Nephronophthisis is an autosomal recessive disorder, meaning a child must inherit a defective copy of the responsible gene from both parents to develop the disease. It is caused by mutations in genes that encode components of the primary cilium, a tiny antenna-like structure projecting from nearly every cell in the body, making nephronophthisis part of a broader family of conditions known as ciliopathies. Within the kidney, defective ciliary signaling disrupts the architecture of the renal tubules, leading to chronic tubulointerstitial inflammation, fibrosis, and the eventual formation of cysts at the corticomedullary junction. Despite its name, which references the cysts, nephronophthisis is not primarily a cystic disease in the way polycystic kidney disease is; its hallmark is progressive scarring that silently destroys filtering capacity. It is a leading genetic cause of end stage renal disease in children and adolescents worldwide.

The clinical signature of nephronophthisis is notoriously subtle in its early stages. Classic textbook features include polydipsia, excessive thirst, and polyuria, the production of abnormally large volumes of dilute urine, both stemming from the kidney’s impaired ability to concentrate urine. Anemia, growth retardation, and fatigue often follow as renal function declines. What makes the disease so dangerous is precisely how quietly it progresses: many children reach advanced chronic kidney disease before anyone notices, because the surviving nephrons compensate for the damaged ones for years. Type 1 nephronophthisis, caused by defects in the NPHP1 gene, is the most common form and typically follows a juvenile course, with most patients reaching kidney failure within the first two decades of life.

The girl in this report arrived at medical attention almost by accident. She was admitted after a visit for abdominal pain, during which laboratory testing revealed renal dysfunction that no one had suspected. Her serum creatinine, a waste molecule that accumulates when the kidneys fail to filter blood adequately, measured 101.7 micromoles per liter, and her estimated glomerular filtration rate, the standard measure of kidney filtering capacity, stood at 45.2 milliliters per minute per 1.73 square meters of body surface area. Those numbers placed her in stage 3 chronic kidney disease, a level at which many adults already feel unwell. Yet this child had none of the classic thirst and urination symptoms that usually announce nephronophthisis. The only urinary clue was a relatively low urine specific gravity, a laboratory measure indicating that her kidneys could not concentrate urine properly, a finding easily overlooked in a child with other complaints.

Her history held another thread: a long-standing pattern of enuresis, or bedwetting, and daytime urinary incontinence. That symptom pointed the clinical team toward a completely different diagnostic territory, one involving the nervous system rather than inherited kidney disease. Magnetic resonance imaging of her spine revealed separation of the cauda equina, the bundle of nerve roots at the base of the spinal cord, from the filum terminale, the fibrous strand that anchors the cord to the tailbone. This finding is characteristic of a tethered cord, a condition in which the spinal cord is abnormally anchored and stretched as a child grows. Tethered cord is one of the important causes of neurogenic bladder in children, a dysfunction in which the bladder fails to store or empty urine properly because its nerve supply is compromised.

Here the diagnostic picture grew genuinely tangled. A neurogenic bladder can, over time, drive secondary chronic kidney disease by generating high pressures, incomplete emptying, and recurrent infections that scar the kidneys. Abdominal computed tomography in this patient showed mild bladder wall thickening, measured at 4 millimeters under adequate bladder distension, a finding consistent with chronic bladder strain. Yet a voiding cystourethrogram, an X-ray study in which contrast dye is instilled into the bladder while the child urinates, detected no vesicoureteral reflux, the backward flow of urine toward the kidneys, and no structural abnormalities. In other words, the anatomical evidence that the tethered cord was actively damaging her kidneys was thin. The team faced a genuine diagnostic fork: was this a primary genetic kidney disease, a secondary kidney injury from bladder dysfunction, or both?

The answer came from genetic testing, which identified a homozygous pathogenic deletion of exons 1 through 20 of the NPHP1 gene. That is a devastating molecular finding: essentially the entire functional span of the gene was missing from both of her chromosomes, leaving her cells unable to produce the normal ciliary protein. Large homozygous deletions of this kind are the most common disease-causing mechanism in NPHP1-related nephronophthisis. The result settled the central question. This child carried a primary, inherited, progressive kidney disease, and the tethered cord, while real and requiring treatment, was at minimum not the sole explanation for her failing kidneys. The co-occurrence of the two conditions had, to the authors’ knowledge, never been reported before.

Management proceeded on both fronts. The girl underwent neurosurgical intervention to release the tethered cord, the standard treatment aimed at preventing further neurological and bladder deterioration. But her kidneys did not stabilize. Over the following five months, her renal function progressed rapidly from stage 3 chronic kidney disease to pre-end stage renal disease, the threshold at which dialysis or transplantation becomes necessary. The authors of the report suggest that this trajectory underscores a critical clinical lesson: the presence of an identifiable secondary injury factor, such as a neurogenic bladder, can create a seductive diagnostic shortcut, leading clinicians to attribute all renal decline to that factor while an underlying genetic disease continues its silent advance. In this case, the tethered cord was found and treated, yet the primary disease ran its course regardless.

The broader message of the report reaches well beyond this single patient. Nephronophthisis is genetically heterogeneous, with more than twenty implicated genes, and its phenotype can be modified by additional syndromic features ranging from retinal degeneration to liver fibrosis. Distinguishing a primary ciliopathy from secondary kidney injury requires a level of suspicion that, the authors argue, should translate into early genetic testing for children with unexplained chronic kidney disease, even when a plausible alternative cause has already been identified. Modern sequencing has made such testing faster and more accessible than ever, and a molecular diagnosis carries consequences that imaging alone cannot deliver: it clarifies prognosis, informs the risk to future siblings, shapes decisions about transplant timing, and can reveal extrarenal manifestations that demand surveillance. For a seven-year-old whose kidneys failed in months, the genetic answer arrived, but the case stands as a warning written in real time. When a child’s kidneys fail without explanation, one diagnosis should never be allowed to end the search.

Subject of Research: A pediatric case report of genetically confirmed nephronophthisis type 1 co-occurring with tethered cord and rapid progression to end stage renal disease

Article Title: A case report of nephronophthisis type 1 (NPHP1) complicated with tethered cord in a pediatric patient: clinical phenotype and rapid progression to end stage renal disease

Article References: Deng, H., Fan, S., Jiang, Y., Yang, L., & Wang, W. (2026). A case report of nephronophthisis type 1 (NPHP1) complicated with tethered cord in a pediatric patient: clinical phenotype and rapid progression to end stage renal disease. BMC Pediatrics. https://doi.org/10.1186/s12887-026-07771-w

Image Credits: AI Generated

DOI: 10.1186/s12887-026-07771-w

Keywords: nephronophthisis, NPHP1, tethered cord, chronic kidney disease, end stage renal disease, pediatric nephrology, genetic testing, ciliopathy, neurogenic bladder, case report, autosomal recessive, renal dysfunction

The pituitary gland does not act alone. It sits at the receiving end of signals from the hypothalamus, releasing hormones such as adrenocorticotropic hormone, thyroid-stimulating hormone, growth hormone, follicle-stimulating hormone, luteinizing hormone, and prolactin in carefully calibrated pulses. Each of these axes is closed by a feedback loop: hormones produced downstream—cortisol from the adrenal glands, thyroid hormones from the thyroid, sex steroids from the gonads—circulate back and restrain further pituitary output. The review’s central argument is that chronic kidney disease perturbs this system in two ways at once. It can act directly on the hypothalamus and pituitary, and it can alter the downstream hormones themselves, which then feed back incorrectly and push pituitary secretion out of alignment.

The pathological backdrop matters. Chronic kidney disease is defined by abnormal kidney structure or function and is characterized histologically by chronic inflammation, tubular atrophy, vascular rarefaction, glomerulosclerosis, and interstitial fibrosis. As the disease progresses, the kidney loses its ability to clear waste, activate vitamin D, and regulate mineral balance. Clinical observations compiled in the review suggest the endocrine consequences are broad: altered cortisol dynamics measurable even in hair samples, thyroid dysfunction across multiple stages of kidney disease, gonadal dysfunction that worsens with disease severity, elevated prolactin linked in population cohorts to cardiovascular risk, and diagnostic confusion in children with chronic renal failure who present with features of Cushing’s disease.

At the top of the review’s mechanistic list sit the uremic toxins—compounds that a healthy kidney would excrete but that accumulate in the blood when filtration fails. Chief among them are indoxyl sulfate, p-cresol, p-cresyl sulfate, and trimethylamine N-oxide, the latter a gut microbial metabolite increasingly implicated in cardiovascular disease. These molecules are not inert waste. Experimental studies show they damage hippocampal neurons and disrupt synaptic transmission, and a growing body of work indicates they perturb the blood-brain barrier, the selective gate that normally shields the brain from circulating solutes. In rodent models, uremic toxin-driven blood-brain barrier disruption mediated by aryl hydrocarbon receptor activation produces cognitive impairment, and elevated urea itself has been shown to promote abnormal proliferation of oligodendrocyte precursor cells in the amygdala, driving anxiety-like behavior. If the barrier becomes leaky, toxins and inflammatory signals gain access to hypothalamic and pituitary tissue that would otherwise be protected.

Inflammation provides a second, overlapping route of attack. Chronic kidney disease sustains a state of low-grade systemic inflammation, with elevated interleukin-6, tumor necrosis factor alpha, and C-reactive protein documented in dialysis patients and in those with diabetic kidney disease. Cytokines are well known to modulate hypothalamic-pituitary function; studies dating back decades show they can stimulate or suppress the secretion of pituitary hormones depending on context. More recent animal work adds a striking cellular mechanism: lipopolysaccharide-induced necroptosis activates the hypothalamic-pituitary-adrenal axis in piglets, and in models of subarachnoid hemorrhage, microglia-derived ADAM9 drives pyroptosis— inflammatory cell death—of growth hormone-releasing hormone neurons via the Mad2L2-JNK-caspase-1 pathway. In other words, inflammatory signaling can kill the very hypothalamic neurons that instruct the pituitary to release growth hormone.

Mineral imbalance and the fibroblast growth factor 23–Klotho axis form a third pillar of the proposed mechanism. In chronic kidney disease, phosphate retention drives a compensatory surge of FGF23 from bone, while levels of its obligate co-receptor Klotho fall. This axis is classically associated with secondary hyperparathyroidism and mineral bone disorder, but the review highlights evidence that its reach extends to the brain and the pituitary itself. FGF23 protein has been localized in the rat hypothalamus, alpha-Klotho levels correlate with remission after pituitary surgery for acromegaly, and Klotho has been shown to participate in growth hormone signaling. Altered Klotho has also been linked to hypothyroidism in older adults, to central precocious puberty in girls, and to male and female reproduction, suggesting that the kidney-driven collapse of this signaling system could feed directly into pituitary regulation.

The review also emphasizes the renin-angiotensin-aldosterone system and the enzyme pair 11β-hydroxysteroid dehydrogenase types 1 and 2, which interconvert active cortisol and inactive cortisone. As kidney function declines, type 2 insufficiency progresses, blunting the kidney’s ability to inactivate cortisol and protect mineralocorticoid receptors. The result is a distorted cortisol economy: altered cortisol dynamics in chronic kidney disease have been linked to mortality, and vasopressin—another hormone entangled with renal water balance—has been shown to potentiate the action of corticotropin-releasing hormone on pituitary corticotropes through a protein kinase C-dependent mechanism. Copeptin, a stable surrogate marker for vasopressin, even predicts future kidney disease, underscoring how tightly renal physiology and pituitary stress hormones are interwoven.

Perhaps the most contemporary strand of the review concerns circulating microRNAs and the kidney-gut-brain axis. MicroRNAs—short non-coding RNAs that travel in the bloodstream and fine-tune gene expression—are established players in pituitary disease, with distinct signatures reported in acromegaly, Cushing’s syndrome, hyperprolactinemia, and invasive pituitary tumors. Kidney disease also reshapes the circulating microRNA landscape, raising the possibility that renal-derived microRNAs could modulate hypothalamic and pituitary gene programs. Meanwhile, gut dysbiosis in kidney disease alters the production of short-chain fatty acids, metabolites that influence the central nervous system and have been shown in animal studies to regulate the hypothalamic-pituitary-gonadal axis and reverse obesity-induced precocious puberty. Uremic toxins of gut origin, including indoxyl sulfate, have even been shown in ex vivo studies to alter thyroid gland morphology and function, and TMAO can trigger premature ovarian insufficiency through mitochondrial apoptosis in granulosa cells—effects that would feed back onto pituitary gonadotropin secretion.

The clinical stakes are considerable. Growth impairment in children with chronic kidney disease involves suppressor of cytokine signaling 2 and is treated with recombinant human growth hormone, yet long-term growth hormone use has itself been associated with acute kidney damage, and the FGF23-Klotho axis responds to such treatment in pediatric patients. Pubertal luteinizing hormone levels track with declining glomerular filtration rate in children, hypogonadism and erectile dysfunction are common in hemodialysis patients, and testosterone therapy has been linked to reduced risks of acute kidney injury and cardiovascular events in diabetic men with hypogonadism. Conversely, successful renal transplantation can normalize prolactin and sex hormone levels, and menopausal hormone therapy has been associated with better renal survival in postmenopausal women—observations that reinforce the bidirectional dialogue between kidney and pituitary. Single-cell RNA sequencing analyses have even suggested structured cell-cell interaction patterns along a pituitary-kidney axis, lending molecular weight to what clinicians have long observed.

The authors are careful to frame their work as a synthesis of mechanistic plausibility rather than proof of causation, echoing an older question in the literature about whether pituitary dysfunction in kidney disease is the chicken or the egg. Still, the convergence of evidence—from uremic toxin effects on the blood-brain barrier, to cytokine-driven death of hypothalamic neurons, to the collapse of Klotho signaling and the reshaping of the gut microbiome—makes a compelling case that the pituitary should join the list of organs endangered by chronic kidney disease. If validated in prospective studies, the framework could change how endocrine abnormalities in kidney patients are interpreted and treated, transforming what are often dismissed as epiphenomena of renal failure into actionable targets for therapy.

Subject of Research: Mechanisms by which chronic kidney disease may dysregulate pituitary hormone secretion

Article Title: Chronic kidney disease as a potential risk factor for pituitary hormone dysregulation: a review of the underlying mechanisms

Article References: Singh, N. A., Kalita, J. K., Biswas, S., Nath, B., Khanna, K., & Sen, S. (2026). Chronic kidney disease as a potential risk factor for pituitary hormone dysregulation: a review of the underlying mechanisms. Molecular Biology Reports, 53(1), Article 1704. https://doi.org/10.1007/s11033-026-12931-3

Image Credits: AI Generated

DOI: 10.1007/s11033-026-12931-3

Keywords: chronic kidney disease, pituitary hormones, hypothalamic-pituitary axis, uremic toxins, FGF23-Klotho signaling, inflammation, blood-brain barrier, microRNAs, gut-kidney-brain axis, cortisol, thyroid dysfunction, neuroendocrinology

Diabetic nephropathy develops when prolonged exposure to high blood sugar damages the delicate filtering units of the kidneys, the glomeruli. Clinically, it announces itself through rising levels of albumin in the urine and a gradual decline in the estimated glomerular filtration rate, the standard measure of kidney function. Because the condition often progresses silently for years before symptoms appear, clinicians have long sought biomarkers that could flag patients at risk before irreversible damage sets in. Inflammation has been a prime suspect: hyperglycemia triggers the production of pro-inflammatory cytokines, and these signaling molecules in turn promote the fibrosis, thickening of basement membranes, and vascular dysfunction that characterize the failing diabetic kidney.

The research team, led by Olimjan Nazirkulov of the Institute of Immunology and Human Genomics of the Academy of Sciences of the Republic of Uzbekistan, together with colleagues from Samarkand State Medical University, Tashkent State Medical University, and Kimyo International University, recruited 227 patients with type 2 diabetes. Of these, 95 had no microvascular complications, while 132 had diabetic nephropathy. The investigators collected demographic, clinical, laboratory, and medication data, and measured hs-CRP and IL-6 concentrations in the blood. The study protocol was approved by the Institutional Review Board of the Institute of Immunology and Human Genomics, and all participants provided written informed consent in accordance with the Declaration of Helsinki.

The differences between the two groups were striking. Patients with diabetic nephropathy had a median hs-CRP concentration of 7.50 milligrams per liter, compared with 4.54 milligrams per liter in patients without microvascular complications. Their median IL-6 levels were similarly elevated, at 13.30 picograms per milliliter versus 8.40 picograms per milliliter. Both differences were highly statistically significant, with P values below 0.001. Beyond the inflammatory markers, the nephropathy group was also older, had lived with diabetes for longer, and more frequently suffered from hypertension, all factors known to compound kidney risk.

To determine whether these inflammatory markers carried independent predictive weight, the researchers constructed five multivariable logistic regression models, progressively adjusting for potential confounders. In the fully adjusted model, each unit increase in hs-CRP was associated with a 31 percent higher odds of diabetic nephropathy, with an adjusted odds ratio of 1.31 and a 95 percent confidence interval of 1.07 to 1.59. IL-6 proved an even stronger signal: each unit increase carried a 50 percent higher odds of nephropathy, with an adjusted odds ratio of 1.50 and a confidence interval of 1.31 to 1.72. Longer diabetes duration, hypertension, and higher fasting plasma glucose levels were also independently associated with the complication.

Perhaps the most technically compelling result concerns how much the inflammatory markers improved risk prediction. The researchers evaluated model discrimination using receiver operating characteristic (ROC) curve analysis and pairwise comparisons of the area under the curve (AUC). A clinical model built on conventional risk factors alone achieved an AUC of 0.814, already respectable performance. When hs-CRP and IL-6 were added, the AUC climbed to 0.943, a substantial gain that pushed the model into the range of excellent discrimination. Because such gains can be inflated by overfitting, the team performed internal validation using 1,000 bootstrap resamples; the optimism-corrected AUC remained at 0.921, indicating that the improvement was robust rather than a statistical artifact.

Calibration, the question of whether a model’s predicted probabilities match observed outcomes, was assessed through calibration plots, Brier scores, and the Hosmer–Lemeshow test, providing a methodologically thorough evaluation that goes beyond the discrimination statistics often reported in isolation. Group comparisons in the study were performed using the Mann–Whitney U test for continuous variables and the chi-square test for categorical variables, appropriate choices given that biomarker distributions in biological samples are typically skewed. Statistical significance was defined as a P value below 0.05 throughout.

The study’s setting matters. Central Asian populations have been markedly underrepresented in diabetes research, and evidence linking inflammatory biomarkers to diabetic nephropathy has come overwhelmingly from East Asian, European, and North American cohorts. By demonstrating that the hs-CRP and IL-6 associations hold in an Uzbekistani patient population, the researchers provide a valuable data point from a region where diabetes prevalence is rising and nephrology resources are often stretched. The work also benefited from institutional support, with the authors acknowledging the Samarkand Branch of the Republican Specialised Scientific and Practical Medical Centre of Endocrinology and the Institute of Immunology and Human Genomics for organizational and technical assistance. The study received no specific external funding, and the authors declare no competing interests.

Mechanistically, the findings fit a coherent biological narrative. IL-6 is a pleiotropic cytokine released by immune cells, adipose tissue, and damaged endothelium; it drives hepatic production of CRP, which is why the two markers tend to rise together. In the diabetic kidney, IL-6 signaling has been implicated in mesangial cell proliferation, increased vascular permeability, and the activation of fibrotic pathways that progressively scar the glomeruli. hs-CRP, meanwhile, serves as a stable, easily measured readout of systemic inflammatory burden. The fact that both markers remained significant after adjustment for glycemic control, blood pressure, and diabetes duration suggests that inflammation captures risk information that conventional clinical variables miss, consistent with the hypothesis that inflammatory pathways contribute actively to nephropathy rather than simply reflecting it.

The authors are careful to frame their conclusions appropriately. As a cross-sectional study, the work captures a single moment in time and cannot establish whether elevated hs-CRP and IL-6 precede kidney damage or accompany it; reverse causation, in which declining kidney function itself drives inflammation, remains a plausible alternative explanation. The researchers note that prospective and externally validated studies are needed to determine the clinical utility of hs-CRP and IL-6 before the markers can be considered for routine clinical risk assessment. Still, the magnitude of the associations, the near doubling of model performance, and the bootstrap-validated robustness make a strong case that these inexpensive, widely available blood tests deserve a place in future longitudinal trials. If those trials confirm the signal, a simple pair of measurements could one day help clinicians identify which of their diabetic patients needs the closest kidney surveillance, years before dialysis becomes the only option.

Subject of Research: Associations of inflammatory biomarkers hs-CRP and IL-6 with diabetic nephropathy in type 2 diabetes patients

Article Title: Associations of hs-CRP and interleukin-6 with diabetic nephropathy in patients with type 2 diabetes mellitus: a cross-sectional study from Uzbekistan

Article References: Nazirkulov, O., Abdullayeva, N., Ziyadullaev, S., Tulyaganova, D., Kodirov, A., Kadirov, J., Eshbayeva, K., Ishonhajaev, H., Akhmedov, A., Nasretdinova, M., Samibaeva, U., & Ruzimurodov, N. (2026). Associations of hs-CRP and interleukin-6 with diabetic nephropathy in patients with type 2 diabetes mellitus: a cross-sectional study from Uzbekistan. BMC Endocrine Disorders. https://doi.org/10.1186/s12902-026-02515-4

Image Credits: AI Generated

DOI: 10.1186/s12902-026-02515-4

Keywords: type 2 diabetes, diabetic nephropathy, hs-CRP, interleukin-6, inflammation, chronic kidney disease, biomarkers, risk prediction, Uzbekistan, cross-sectional study, logistic regression, microvascular complications

The SoBic study, as the trial is known, enrolled patients with stage 3 to 4 chronic kidney disease whose serum bicarbonate concentrations were 21 mmol/L or below, a threshold that defines clinically relevant metabolic acidosis in this population. Participants were randomly assigned to one of two open-label treatment arms: one targeting a serum bicarbonate of approximately 24 ± 1 mmol/L, near the lower bound of the normal laboratory range, and the other targeting approximately 20 ± 1 mmol/L, a level that corrects the most dangerous acidity while avoiding aggressive alkalinization. Sodium bicarbonate doses were titrated individually against repeated blood measurements, and the investigators tracked the estimated glomerular filtration rate, the standard measure of kidney filtering capacity, over 104 weeks. In total, 58 subjects were randomized, of whom 49 completed the full follow-up; two participants died and four began dialysis during the study period, reflecting the serious trajectory of advanced kidney disease even under close specialist care.

The treatment separation achieved by the protocol was substantial and well documented. The median sodium bicarbonate dose in the higher-target intervention group reached 6.7 grams per day, with an interquartile range of 4.2 to 8.4 grams, doses that are meaningful in daily clinical terms and comparable to those used in prior observational and interventional work. Roughly 70 percent of participants in each arm successfully reached their assigned bicarbonate target, and the resulting between-group difference in serum bicarbonate averaged 3.57 mmol/L at week 47 and 3.64 mmol/L at week 104, with confidence intervals comfortably excluding zero. In other words, this was not a trial that failed because the intervention failed to change the biology being measured. The acid-base chemistry of the blood was genuinely and durably shifted between the two groups, giving the comparison real biological teeth.

What that shift did not produce was a difference in kidney trajectory. Across the two years of follow-up, the estimated glomerular filtration rate declined by a mean of 5.8 ml/min per 1.73 m², a figure consistent with the expected progression of stage 3 to 4 disease. The difference in eGFR change between the high-target and low-target groups was −0.98 ml/min per 1.73 m², with a 95 percent confidence interval spanning −3.08 to 1.12 and a p-value of 0.648. That interval includes both a modest benefit and a modest harm, but its center sits essentially at zero, and the authors concluded that targeting higher serum bicarbonate concentrations was not associated with a clinically meaningful benefit in patients with advanced chronic kidney disease and overt metabolic acidosis. For a field accustomed to thinking of acid retention as an active driver of scarring, the result is a sobering recalibration.

The biological rationale for the original hypothesis was never frivolous. Metabolic acidosis in chronic kidney disease arises because damaged nephrons lose the ability to excrete the daily acid generated by protein metabolism, and the resulting low bicarbonate, low pH environment has been linked in laboratory and animal models to increased ammoniagenesis, activation of the complement cascade, stimulation of endothelin production, and promotion of interstitial fibrosis. Observational cohorts repeatedly showed that patients with lower bicarbonate levels progress faster to kidney failure, and smaller interventional studies, including trials of oral sodium bicarbonate in earlier-stage disease, suggested possible slowing of decline. Those converging lines of evidence were strong enough to earn alkaline therapy a firm place in international guidelines, which recommend correcting bicarbonate below roughly 22 mmol/L. What the observational data could never settle, however, was whether low bicarbonate was a cause of progression or simply a marker of more severe underlying disease.

That distinction is precisely where randomized trials earn their authority, and the SoBic result illustrates why. By randomly assigning the target rather than letting disease severity dictate it, the Vienna team severed the confounding that has plagued the field. The outcome suggests that, at least in patients who already have advanced disease and established acidosis, the residual acidity that remains at a 20 mmol/L target does not measurably accelerate scarring compared with near-normal levels. It remains possible that earlier correction, before substantial nephron mass is lost, could still matter; the trial was designed and powered for stage 3 to 4 patients, not for the large population of stage 1 to 2 individuals with mild acid-base abnormalities. It is also possible that the two-year window, while respectable, is too short to reveal a divergence that accumulates over a decade of progression.

The study’s limitations deserve honest framing alongside its strengths. With 58 randomized participants and 49 completers, SoBic is a small trial, and its confidence intervals, while centered on zero, cannot exclude effects of up to roughly 3 ml/min per 1.73 m² in either direction. The open-label design, unavoidable given the nature of the intervention, means that neither participants nor clinicians were blinded, although the primary endpoint of eGFR decline is a laboratory measurement far less susceptible to expectation effects than symptom-based outcomes. The mortality and dialysis initiation that occurred during follow-up, while consistent with the natural history of the enrolled population, further reduced the analytical sample. The authors and the funding structure, which came from a Vienna municipal medical-science fund with study medication provided free of charge by the manufacturer and no role for the manufacturer in the study’s conduct or reporting, present the work transparently as a targeted hypothesis test rather than a definitive practice-changing mega-trial.

Even so, the clinical implications are immediate and practical. Guidelines currently recommend correcting serum bicarbonate in chronic kidney disease, but they have been notably silent on how high to push it. SoBic provides the first direct randomized evidence that a target near 20 mmol/L achieves the recognized goals of acidosis correction without sacrificing any measurable kidney protection relative to a more aggressive 24 mmol/L target. For patients, that could mean fewer grams of sodium bicarbonate per day, and with that a reduced sodium load, a real consideration in a population where volume overload and hypertension are constant management challenges. Large bicarbonate doses bring sodium into the circulation, and the trial’s higher-target arm was effectively also a higher-sodium arm, a trade-off that clinicians weighing the result will want to keep in view.

The broader lesson resonates well beyond nephrology. Metabolic acidosis joins a growing list of biomarkers, from uric acid to homocysteine to C-reactive protein in other contexts, whose strong observational associations with disease progression have evaporated or diminished under randomized scrutiny. Association, the trial reminds us, is a hypothesis, not a mechanism. The Vienna team’s careful dose titration, their verification that the bicarbonate gap was genuinely achieved and sustained, and their null result on the hard endpoint of filtration decline together form a model of how to interrogate a guideline-supported practice that has never been properly stress-tested. For the millions of people living with chronic kidney disease worldwide, the message is not that bicarbonate therapy is useless; correction of overt acidosis remains standard care with documented symptomatic and nutritional rationale. The message is narrower and sharper: once acidosis is corrected to a reasonable degree, chasing a higher number on the chemistry panel does not buy additional kidney years. In a specialty where every pill and every millimole of sodium counts, that is a finding worth taking seriously.

Subject of Research: Sodium bicarbonate treatment targets for metabolic acidosis in stage 3–4 chronic kidney disease

Article Title: A randomized trial of high versus low serum bicarbonate targets and glomerular filtration rate decline in stage 3–4 chronic kidney disease

Article References: Gaggl, M., Aigner, C., Repitz, A., Riesenhuber, S., Sliber, C., Madern, M., Gleiss, A., Fraunschiel, M., Schmidt, A., & Sunder-Plassmann, G. (2026). A randomized trial of high versus low serum bicarbonate targets and glomerular filtration rate decline in stage 3–4 chronic kidney disease. Scientific Reports. https://doi.org/10.1038/s41598-026-68492-9

Image Credits: AI Generated

DOI: 10.1038/s41598-026-68492-9

Keywords: chronic kidney disease, metabolic acidosis, sodium bicarbonate, serum bicarbonate, glomerular filtration rate, eGFR decline, randomized trial, SoBic study, nephrology, alkaline supplementation, kidney function, clinical guidelines

The instrument, named the CKD-Malnutrition Knowledge, Attitude and Practice scale, or CKD-MKAP, was described in a study published in the journal Nursing Open. Its development followed a multiphase quantitative design grounded in the well-established KAP framework of behavioural change theory, which holds that accurate perceived knowledge fosters positive attitudes, which in turn translate into effective dietary practices. The team began by synthesising a comprehensive literature review of clinical nutrition guidelines for kidney disease with qualitative findings from previously published semi-structured interviews with thirteen Chinese patients who had experienced malnutrition. Those interviews explored what patients actually knew about malnutrition, how they perceived their own nutritional status, and what barriers and motivators shaped their eating habits. Mapping those lived experiences onto the three KAP domains produced an initial pool of thirty-eight candidate items covering everything from awareness of symptoms and risk factors to beliefs about diet therapy and concrete self-management behaviours such as regular weighing and protein intake.

Refining that raw item pool required the structured judgement of experts. The researchers convened a Delphi panel of fifteen specialists, including ten nephrology experts, three clinical nutrition specialists and two psychometricians, drawn from eight institutions across five regions in two countries. More than eighty percent of the panellists had over a decade of clinical or research experience. Across two email-based consultation rounds conducted between May and July 2023, response rates reached 89.5 percent and 93.75 percent respectively, and the calculated authority coefficient of 0.77 signalled a high degree of expert reliability. Items were evaluated using boundary value methods incorporating full-score frequency, arithmetic means and coefficients of variation, with predefined statistical thresholds determining survival. Eleven items fell during the Delphi phase, including questions about regional and religious food cultures and a query on whether oral supplements could replace ordinary food, leaving a preliminary twenty-seven-item scale.

Before formal validation, a pilot study with twenty kidney disease patients tested the draft instrument for clarity and acceptability. Every participant completed the questionnaire, reported that the items were clear and easy to understand, and finished in eight to fourteen minutes, with no revisions requested. The team then moved to the main psychometric evaluation, distributing 330 questionnaires and analysing 303 valid responses collected between July and November 2023. The sample was predominantly male at 63.7 percent, with a mean age of 48.26 years, and spanned the full range of kidney disease severity, from early-stage patients to the 32 percent already at stage five. Crucially, the sample was randomly split into two independent subsamples of 152 and 151 participants, one for exploratory factor analysis and one for confirmatory factor analysis, a cross-validation strategy designed to ensure that the scale’s structure would hold up beyond the data that shaped it.

The statistical machinery behind the validation was considerable. Content validity was assessed with item-level and scale-level content validity indices, and the results were striking: item-level values ranged from 0.93 to 1.00 across all three domains, comfortably above the accepted threshold of 0.83, while the scale-level average reached 0.99. For the dichotomous Perceived Knowledge domain, classical test theory came into play, with difficulty indices expected between 0.31 and 0.60 and discrimination indices above 0.20. Seven of the eight knowledge items performed well, but one item asking simply whether patients knew what malnutrition was showed suboptimal difficulty and discrimination and was deleted. Exploratory factor analysis, using principal-axis factoring with oblique rotation, extracted a single dominant factor for both the Attitude domain, explaining 69.87 percent of variance with a Kaiser-Meyer-Olkin value of 0.931, and the Practice domain, explaining 61.84 percent of variance, a clean structure that aligned precisely with the theoretical KAP framework.

Confirmatory factor analysis then put the emerging structure through a harsher test. Because the data violated assumptions of multivariate normality, the researchers applied the robust maximum likelihood estimator to the Attitude and Practice models and the weighted least squares mean and variance adjusted estimator to the categorical knowledge items. The initial knowledge model fit poorly, and one item asking about the relationship between malnutrition and chronic renal disease, with a factor loading of just 0.304, was removed, dramatically improving fit indices to a comparative fit index of 0.978 and a standardised root mean residual of 0.061. The attitude and practice models required theoretically justified post hoc correlations among residuals of conceptually related items, such as those concerning professional nutritional interventions, before achieving acceptable fit. The final attitude model reached a comparative fit index of 0.982 and the practice model 0.976, both well above the 0.90 benchmark, with root mean square error of approximation values of 0.077 and 0.071 respectively.

The finished instrument is deliberately lean: twenty-five items across three dimensions, scored separately rather than summed. The Perceived Knowledge domain contains six yes-or-no items yielding scores from zero to six, covering nutritional status awareness, symptoms, risk factors, consequences, daily protein requirements and prevention. The Attitude domain uses nine items on a five-point Likert scale from strong disagreement to strong agreement, spanning beliefs about the importance of nutrition, the value of optimism and self-control, and the role of diet therapy in treatment. The Practice domain asks patients how often they perform ten behaviours, from prioritising nutrition intake and measuring weight regularly to consuming high-quality protein and adhering to dietary recommendations, on a frequency scale from never to always. Reliability figures were strong, with Cronbach’s alpha values of 0.740 for knowledge, 0.970 for attitude and 0.958 for practice, and composite reliability estimates of 0.743, 0.968 and 0.957. Discriminant validity was confirmed through the Fornell-Larcker criterion, with the square roots of average variance extracted for each domain exceeding all inter-construct correlations, which ranged from 0.443 to 0.585.

The clinical logic of the scale is straightforward but powerful. Because many malnourished Chinese kidney patients receive inadequate nutritional education, a brief questionnaire that separates what patients know from what they believe and what they actually do allows nurses and physicians to pinpoint the weakest link. A patient with solid knowledge but poor practices, for example, may benefit far more from behavioural counselling than from another informational pamphlet. The researchers also compared their instrument against existing alternatives, noting that a recently developed seventy-seven-item nutritional KAP questionnaire for non-dialysis patients reported domain alpha values of 0.861, 0.816 and 0.612, whereas the twenty-five-item CKD-MKAP achieves comparable or superior reliability with far less respondent burden, an important consideration for busy wards and outpatient clinics.

The authors are candid about the limits of their work. The validation sample came from a single city in northwest China, raising questions about generalisability across the country’s enormous regional and cultural diversity. Test-retest reliability was not assessed, so temporal stability remains unknown, and the scale’s responsiveness to change has yet to be demonstrated, meaning it cannot yet be formally adopted as an outcome measure for evaluating educational interventions without further longitudinal psychometric testing. The post hoc residual correlations in the attitude and practice models, while theoretically justified, were not independently cross-validated and may hint at local dependence or hidden subdimensions that larger studies should investigate. No formal a priori power analysis was conducted, though the observed strong communalities and factor loadings compensate for the modest sample sizes.

Even with those caveats, the arrival of a culturally adapted, psychometrically validated malnutrition KAP scale fills a genuine gap. Previously available Chinese tools examined isolated KAP dimensions or lacked rigorous validation, while international scales carry assumptions shaped by foreign socioeconomic and dietary contexts that limit their applicability to Chinese patients, whose food culture, linguistic nuances and healthcare experiences differ substantially. By embedding items rooted in the actual reported experiences of Chinese patients and then subjecting them to Delphi consensus, item analysis, exploratory and confirmatory factor analysis, the team has produced an instrument that is short enough for routine clinical use yet statistically robust. If subsequent multicentre validation confirms its stability across regions, the CKD-MKAP could become a standard part of nursing assessments for kidney patients, turning the quiet epidemic of protein-energy wasting into a measurable, targetable and ultimately preventable problem.

Subject of Research: Development and psychometric validation of a malnutrition knowledge, attitude and practice scale for chronic kidney disease patients in China

Article Title: Development and Validation of CKD‐MKAP: A Malnutrition Perceived Knowledge, Attitude, and Practice (KAP) Scale for Patients With Chronic Kidney Diseases (CKD) in China

Article References: Zhu, S., Yusoff, H., Cheng, K. Y., Yusoff, D. M., Feng, X., Zheng, W.-K., & Chen, H. (2026). Development and Validation of CKD ‐ MKAP : A Malnutrition Perceived Knowledge, Attitude, and Practice ( KAP ) Scale for Patients With Chronic Kidney Diseases ( CKD ) in China. Nursing Open, 13(10), Article e70925. https://doi.org/10.1002/nop2.70925

Image Credits: AI Generated

DOI: 10.1002/nop2.70925

Keywords: chronic kidney disease, malnutrition, KAP scale, psychometric validation, nursing, protein-energy wasting, Delphi method, factor analysis, China, nutritional assessment, scale development, patient education

HbA1c is a familiar number to anyone living with diabetes. It reflects the average blood glucose level over the preceding two to three months, because glucose binds irreversibly to haemoglobin in red blood cells in proportion to its concentration in the bloodstream. A value below 5.7 percent is considered normal, while 6.5 percent or above meets the diagnostic threshold for diabetes. The research team, led by Soo-Hyun Sung of Wonkwang University and corresponding authors Kwang-Il Park of Gyeongsang National University and Young Woo Kim of Dongguk University, used this marker together with treatment status to define four phenotypes. P1 describes people on no treatment or lifestyle modification alone whose HbA1c remains below 7 percent, the conventional target for glycaemic control. P2 captures those who have reached their target while taking oral glucose-lowering medication. P3 covers people with HbA1c between 7 and 9 percent who are not yet on insulin, and P4 is the most severe category, comprising anyone using insulin or whose HbA1c has risen to 9 percent or higher.

The dataset behind the analysis is substantial. From the survey years 2015 through 2024, the researchers identified 8,702 adults aged 30 or older who met at least one of four criteria for diabetes: a physician diagnosis, current use of glucose-lowering medication, a fasting glucose of 126 milligrams per decilitre or more, or an HbA1c of 6.5 percent or above, combined with a measured HbA1c value. Because KNHANES uses a complex, stratified, multistage sampling design, the team applied survey weights and design-based statistical methods throughout, ensuring that their estimates reflect the Korean adult population rather than the quirks of the sample. The weighted distribution across the four phenotypes came out as 24.8 percent in P1, 34.3 percent in P2, 28.9 percent in P3, and 12.0 percent in P4.

The headline finding is not the distribution itself but its sudden rearrangement. A formal change-point analysis, which tests whether a time series is better explained by a single trend or by two segments separated by an abrupt shift, selected 2022 as the break point for both the P2 and P3 phenotypes. The selection was not marginal. The year 2022 was chosen by both the design-based Akaike information criterion, a statistic that penalises model complexity, and the maximum Wald statistic, and it reappeared in 97.1 percent and 97.7 percent of 1,000 design-based bootstrap replicates for P2 and P3 respectively. Critically, a discrete level shift fitted the data better than a gradual change in slope, suggesting a step change rather than a slow drift in the composition of the diabetes population.

The magnitude of the shift is striking. The share of people in the treated, at-target phenotype P2 rose from 28.2 percent during 2015 to 2021 to 46.8 percent during 2022 to 2024, a relative increase of 66 percent, equivalent to 18.6 percentage points. After adjustment for covariates, the prevalence ratio for belonging to P2 in the later period was 1.49, with a 95 percent confidence interval of 1.31 to 1.69. Over the same interval, P1 and P3 both declined, with adjusted prevalence ratios of 0.81 and 0.68 respectively, both statistically significant, while P4, the insulin-treated or severely hyperglycaemic group, remained essentially unchanged. In practical terms, the population appears to have migrated from the untreated and above-target categories into the well-controlled, orally treated category, while the most severe group held steady.

Here the study delivers its most important caveat. The year 2022 is also the first year of KNHANES cycle IX, a redesign of the survey program. The authors are explicit that the observed discontinuity cannot be attributed to genuine changes in diabetes care within this study design, because a change in survey methodology, sampling frame, or measurement procedures would produce exactly the kind of step change they detected. This is a recurring challenge in repeated cross-sectional surveillance: when the instrument changes, the signal and the artefact become difficult to disentangle. The researchers therefore frame their temporal finding as a description of a redistribution in the data, one whose clinical interpretation requires confirmation from other data sources and survey designs.

The analysis of correlates, the factors associated with belonging to one phenotype rather than another, also carries a methodological twist. Because the reference category P1 is dominated by screen-detected cases, 88 percent of its members had never been previously diagnosed, comparisons against it can generate associations that reflect diagnostic status rather than biology. When the researchers restricted the analysis to previously diagnosed participants, most of the associations seen in the full sample shrank or vanished. Reduced kidney function, defined as an estimated glomerular filtration rate below 60, was the only association with the insulin-treated or markedly hyperglycaemic phenotype that retained its full magnitude, with an odds ratio of 2.67 and a confidence interval of 1.27 to 5.62. This makes physiological sense: declining renal function is both a complication of long-standing diabetes and a factor that shapes treatment decisions, often pushing clinicians toward insulin-based regimens.

Reported dyslipidaemia, the presence of abnormal blood lipid levels, persisted as a correlate of the P2 and P3 phenotypes but at roughly half its full-sample strength, with an odds ratio of 1.79 in the diagnosed-only analysis. Meanwhile, the inverse associations with obesity and alcohol consumption that appeared in the full sample disappeared entirely once the comparison was restricted to diagnosed individuals, a pattern the authors attribute to the composition of the screen-detected reference group. In the full sample, reported descriptively because of this reference-group problem, the corresponding estimates for reduced kidney function were considerably larger, at 3.09 for both comparisons. The lesson is a general one for observational diabetes research: who ends up in your comparison group can manufacture or erase associations, and screening status is a powerful hidden variable.

The robustness work behind the paper is unusually thorough for a survey analysis. A sensitivity analysis using multiple imputation, a statistical technique that fills in missing covariate values by drawing from their predicted distributions, reproduced every complete-case estimate closely, with the largest discrepancy amounting to just 0.17 on the odds-ratio scale. The temporal findings survived three alternative classification rules, and the estimated change-point remained 2022 under each of them. Of 42 interaction tests examining whether the associations differed across subgroups, none remained significant after correction for the false discovery rate, the expected proportion of false positives among declared findings. These checks do not eliminate the survey-redesign confound, but they do indicate that the reported patterns are not artefacts of missing data or arbitrary analytical choices.

The authors are careful about what their classification does and does not claim. The four phenotypes describe where people currently sit on the combined axes of glycaemic control and treatment intensity; they are not a prognostically validated staging system, and the scheme’s ability to predict complications, cardiovascular events, or mortality remains to be tested in longitudinal and independent populations. Still, the study offers a template for how national surveillance data can be mined more intelligently. By replacing the blunt controlled-versus-uncontrolled dichotomy with a composite phenotype that respects the heterogeneity of the diabetes population, and by subjecting temporal trends to formal change-point analysis with bootstrap validation, the researchers have shown both the promise and the peril of such approaches. The 2022 discontinuity in Korean diabetes data may eventually prove to reflect real changes in care, new drug classes such as SGLT2 inhibitors and GLP-1 receptor agonists reshaping treatment patterns, or simply the fingerprint of a redesigned survey. Until that question is resolved with independent evidence, the study stands as a rigorous description of a population in flux, and a reminder that in health statistics, the measuring instrument is itself part of the measurement.

Subject of Research: Glycaemic–treatment phenotypes of diabetes and their temporal change among Korean adults

Article Title: Glycaemic–treatment phenotypes of diabetes and their correlates among Korean adults: a repeated cross-sectional analysis of the Korea National Health and Nutrition Examination Survey, 2015–2024

Article References: Sung, S.-H., Lee, J., Park, H.-G., Lee, J.-H., Sung, H.-K., Lee, S.-U., Yang, J.-H., Park, K.-I., & Kim, Y. W. (2026). Glycaemic–treatment phenotypes of diabetes and their correlates among Korean adults: a repeated cross-sectional analysis of the Korea National Health and Nutrition Examination Survey, 2015–2024. BMC Endocrine Disorders. https://doi.org/10.1186/s12902-026-02573-8

Image Credits: AI Generated

DOI: 10.1186/s12902-026-02573-8

Keywords: diabetes, HbA1c, KNHANES, phenotype classification, change-point analysis, glycaemic control, insulin treatment, chronic kidney disease, dyslipidaemia, South Korea, survey methodology, epidemiology

The research, published in BMC Cancer by Lei Wang of Chongqing University Three Gorges Hospital, Hao Sun of the Second Affiliated Hospital of Shandong First Medical University and Taizhou People’s Hospital, and colleagues, examined a question that sits at the intersection of oncology and nephrology, a field sometimes called onco-nephrology. Clinicians can estimate filtration rate from serum creatinine, a muscle-derived waste product, or from cystatin C, a small protein produced steadily by nearly all nucleated cells. Because creatinine levels are influenced by muscle mass, diet, and other non-kidney factors, while cystatin C is thought to be less dependent on body composition, the two markers can yield different answers. When the cystatin C-based estimate falls substantially below the creatinine-based one, a situation researchers call large negative discordance, it may flag hidden kidney impairment that the creatinine number alone would miss.

Whether a history of cancer makes such discordance more likely had remained unclear. Cancer and its treatments can reshape body composition, deplete muscle, and alter inflammation, all of which can perturb creatinine independently of true filtration capacity. At the same time, some malignancies and therapies may affect cystatin C production or clearance. The Chinese team set out to quantify the association in a real-world screening population rather than in hospitalized patients, drawing on adults who attended single-visit health examinations with linked questionnaire data at centers in Chongqing, Shandong, and Jiangsu between January and July 2026.

The analytic cohort was deliberately restricted to people whose kidneys looked healthy by the usual screening standard: participants needed both a creatinine and a cystatin C measurement, an ascertainable cancer history, complete covariate data, plausible laboratory values, and a creatinine-based eGFR of at least 60 milliliters per minute per 1.73 square meters, the conventional threshold below which chronic kidney disease is generally staged. The investigators recalculated eGFR from the original measurements using creatinine alone, cystatin C alone, and both markers together. The primary outcome, large negative discordance, was defined as a cystatin C-based estimate at least 30 percent lower than the creatinine-based estimate. Prevalence ratios were estimated with modified Poisson regression using robust variance, and the team layered on an unusually thorough set of sensitivity analyses: center-specific and pooled models, alternative discordance definitions, continuous differences between the estimates, migration across GFR categories, subgroup analyses, overlap weighting, and an age-spline analysis.

Among 3,491 participants, 257, or 7.36 percent, reported a physician-diagnosed history of cancer. The headline finding was stark at the crude level: large negative discordance occurred in 14.79 percent of participants with a cancer history compared with 4.79 percent of those without, a difference the authors report as statistically significant with a P value below 0.001. In other words, roughly one in seven cancer survivors whose creatinine-based estimate suggested preserved kidney function had a cystatin C-based estimate at least 30 percent lower, a pattern seen in fewer than one in twenty of their cancer-free counterparts.

Adjustment for other characteristics softened but did not erase the signal. In the fully adjusted pooled model, cancer history remained associated with a higher prevalence of large negative discordance, with a prevalence ratio of 1.53 and a 95 percent confidence interval of 1.08 to 2.17, corresponding to a P value of 0.018. The association was also visible on a continuous scale: cancer history was linked to an adjusted relative eGFR difference that was 2.73 percentage points lower, with a confidence interval spanning -4.46 to -1.00 and a P value of 0.002. When the team relaxed the discordance threshold to 20 percent or used an absolute difference of -15 milliliters per minute per 1.73 square meters, similar patterns emerged, lending the result a degree of robustness across how the phenomenon is defined.

The geographic texture of the data, however, complicates any simple interpretation. When Chongqing and Shandong were combined, the adjusted prevalence ratio was 1.22 with a confidence interval of 0.78 to 1.89 and a P value of 0.383, meaning the association was not statistically distinguishable from no association at those two centers. In Jiangsu, by contrast, the prevalence ratio climbed to 2.40 with a confidence interval of 1.37 to 4.18 and a P value of 0.002, a substantially stronger effect. The formal test for a center-by-cancer-history interaction was not significant, with a P value of 0.212, but the authors are careful to warn that this nonsignificant interaction should not be read as proof that the effect is equivalent across centers. Absence of a statistically significant interaction is not the same as presence of equivalence, particularly in a cohort of this size.

Not every analytic approach supported the association. Crude downward migration across GFR categories, in which participants appeared to shift into a worse kidney-function category when cystatin C was used instead of creatinine, was substantially attenuated after multivariable adjustment, and the overlap-weighted and adjusted category-migration analyses were described as less precise or null. The authors are explicit about the limits of their design: this is a cross-sectional study, so it cannot establish that cancer or its treatments cause the discordance, nor can it determine which of the two estimates is closer to a directly measured glomerular filtration rate. The study also cannot establish that participants with discordant estimates actually had impaired kidney function; it shows only that the two markers disagreed more often in people with a cancer history.

Why might cancer survivors show this pattern? The study itself does not identify a mechanism, but the biology offers plausible candidates. Creatinine is generated by muscle, and cancer survivors frequently have reduced muscle mass due to the disease, its treatments, or lifestyle changes, which would lower creatinine and inflate the creatinine-based eGFR, making it look as though the kidneys are filtering better than they are. Cystatin C, meanwhile, is less tied to muscle but can be influenced by inflammation, thyroid function, obesity, and possibly malignancy itself. If cancer history shifts the balance of these non-GFR determinants, the two formulas would part ways more often. Disentangling which marker, if either, is telling the truth in this population would require studies comparing both estimates against measured GFR using tracer or clearance methods, which this study did not perform.

The practical takeaway, according to the authors, is one of caution rather than alarm. Among adults with a creatinine-based eGFR of 60 or above attending routine health examinations at three Chinese centers, cancer history was associated with greater negative discordance between the cystatin C- and creatinine-based estimates in the pooled adjusted analysis, with estimates varying across centers. When a kidney-function estimate is clinically consequential, for example when it will guide drug dosing, contrast imaging decisions, or nephrology referral in an adult with a history of cancer, the findings suggest that relying on a single filtration marker should be done cautiously. Measuring both creatinine and cystatin C, or confirming an uncertain estimate with a direct measurement of filtration rate, may be prudent in exactly the situations where the number will change management. As cancer survival continues to improve worldwide and the population of long-term survivors grows, the humble eGFR calculation, and the assumptions baked into it, may deserve closer scrutiny than a single number on a lab report usually receives.

Subject of Research: Association between cancer history and discordance between creatinine- and cystatin C-based estimated glomerular filtration rate in health-examination adults

Article Title: Cancer history and creatinine-cystatin C eGFR discordance across three Chinese health-examination centers

Article References: Wang, L., Sun, H., Yao, X., Xiang, H., Tan, H., Wei, D., & Gong, X. (2026). Cancer history and creatinine-cystatin C eGFR discordance across three Chinese health-examination centers. BMC Cancer. https://doi.org/10.1186/s12885-026-16998-w

Image Credits: AI Generated

DOI: 10.1186/s12885-026-16998-w

Keywords: cancer history, cystatin C, creatinine, eGFR discordance, estimated glomerular filtration rate, kidney function, onco-nephrology, cross-sectional study, chronic kidney disease, health examination, China, BMC Cancer

The central argument of the review is that digital health technologies have demonstrated strong clinical potential yet have not fully transcended traditional intervention paradigms. Mobile applications, wearable sensors, telemedicine platforms, and machine learning models have each shown benefits in isolated settings, but the authors contend that the real transformation will come from integrating these components into coherent systems that connect patients, clinicians, and health records. The rapid digitalisation of healthcare, accelerated in recent years, has created the infrastructure for such integration, and the review evaluates whether the clinical evidence has kept pace with the technological enthusiasm.

One of the most striking findings concerns risk prediction. For decades, cardiometabolic risk has been estimated using tools such as the Framingham Risk Score, SCORE, QRISK3, and the more recent PREVENT equations, which combine a handful of variables—age, sex, blood pressure, cholesterol, smoking status, and diabetes—into a statistical estimate. Machine learning models, by contrast, can extract high-dimensional patterns from multimodal data streams, including electronic medical records, electrocardiograms, retinal images, genomic profiles, and continuous physiological measurements from wearables. The review highlights evidence that AI approaches can outperform these traditional risk models, particularly when they incorporate data types that classical equations cannot use, such as polygenic risk scores derived from single nucleotide polymorphisms, or subtle features extracted from routine electrocardiograms that correlate with future atrial fibrillation, left ventricular dysfunction, and other silent cardiac conditions.

Technical performance in these studies is typically quantified using metrics such as the area under the receiver operating characteristic curve, or AUROC, and the area under the precision-recall curve, alongside calibration measures like the Brier score. The review notes that models reporting strong discrimination in retrospective datasets often degrade when deployed in real-world clinical environments, a phenomenon driven by differences in patient demographics, data collection practices, and measurement standards between development and deployment settings. This gap between benchmark performance and clinical utility is a recurring theme, and the authors identify rigorous, real-world validation as the first of three priorities for future investment.

Beyond prediction, the review examines how artificial intelligence is being embedded into clinical decision support systems through integration with electronic medical records. When a model can read a patient’s longitudinal record—laboratory trends such as estimated glomerular filtration rate, alanine aminotransferase, and glycated haemoglobin, alongside medication histories and clinical notes processed by natural language processing—it can generate individualised recommendations at the point of care. In nephrology, for example, AI-assisted systems have been explored for predicting kidney function decline and optimising the timing of erythropoietin stimulating agent therapy. In hepatology, machine learning models incorporating genetic variants such as PNPLA3, TM6SF2, and APOL1 have been used to stratify liver disease risk in patients with obesity and diabetes. In diabetes research, unsupervised clustering of clinical and genetic data has reproduced and refined the now widely cited subtyping of the disease into five clusters, ranging from severe autoimmune diabetes to mild age-related diabetes, each with distinct trajectories and treatment responses.

The review also documents the contribution of consumer-facing digital health tools. Photoplethysmography signals from smartwatches and fitness bands, transdermal optical imaging, and smartphone-based screening have enabled continuous, passive monitoring of heart rhythm, blood pressure trends, and physical activity. Randomised trials of app-based coaching, remote monitoring, and technology-assisted hybrid cardiac rehabilitation show improvements in patient engagement, medication adherence, and selected clinical outcomes. Telemedicine has expanded access to specialist care for patients in rural and underserved regions, a benefit that became particularly visible during recent global health disruptions. These tools successfully promote engagement, improve outcomes, and enhance access—the three achievements the review credits to the current generation of digital health innovations.

Yet the same technologies that promise to democratise care risk deepening existing inequities. The review identifies inequality in digital health access as a significant barrier to sustained implementation. Wearables and smartphones are less prevalent among older adults, low-income populations, and communities in low- and middle-income countries, precisely the groups that carry a disproportionate burden of cardiometabolic disease. Algorithmic bias compounds this problem: models trained on datasets dominated by particular ethnic or socioeconomic groups may perform poorly when applied to others, generating inaccurate risk estimates and potentially misdirecting care. Generalisability across diverse demographics is therefore not a peripheral concern but a central test of whether these systems can serve whole populations rather than privileged subsets.

Data privacy and governance present a second cluster of challenges. Health data flowing through consumer devices and cloud platforms falls under a patchwork of regulations, including the Health Insurance Portability and Accountability Act in the United States, the General Data Protection Regulation in Europe, and the Asia Pacific Economic Cooperation Privacy Framework. The review argues that robust regulatory frameworks are essential to ensure that AI tools are safe, effective, and accountable before they influence clinical decisions. A third priority is the adoption of explainable artificial intelligence, or XAI. Deep learning models often operate as opaque systems whose internal reasoning cannot be inspected by clinicians, which undermines trust and complicates error analysis. Explainable approaches that surface the features driving a prediction—a specific electrocardiographic pattern, a laboratory trend, a genetic variant—allow clinicians to verify that a model is reasoning sensibly and to identify spurious associations before they cause harm.

The authors also situate these technologies within the broader shift toward precision medicine in cardiometabolic health. Traditional categories such as metabolically healthy obesity, metabolically unhealthy normal weight, and the homoeostasis model assessment of insulin resistance are being re-examined through the lens of high-dimensional data, allowing finer stratification of patients who superficially resemble one another but follow very different disease courses. Combining polygenic risk scores with clinical and behavioural data streams could, in principle, allow prevention strategies to be tailored to an individual’s specific risk architecture rather than applied uniformly. The review suggests that this convergence of genomics, sensing technology, and machine learning is where the greatest transformative potential lies, both for prevention and for treatment.

Taken together, the review offers a measured but optimistic verdict. Artificial intelligence and digital health innovations have already demonstrated that they can promote patient engagement, improve clinical outcomes, and enhance healthcare access in cardiometabolic medicine. However, the authors conclude that realising their transformative potential will require deliberate investment in three areas: rigorous validation in real-world settings rather than curated datasets, the adoption of explainable AI to make algorithmic reasoning transparent to clinicians and patients, and robust regulatory frameworks that safeguard privacy and equity while allowing innovation to proceed. If those conditions are met, the tools described in this synthesis could move from promising prototypes to standard components of cardiometabolic prevention and care, reshaping a field that currently accounts for an enormous share of global morbidity and mortality.

Subject of Research: Artificial intelligence and digital health innovations for cardiometabolic disease prevention and management

Article Title: Reimagining cardiometabolic health through artificial intelligence and digital health innovations

Article References: Tiong, K. I. L., Abd Rahman, N. E., Lee, Y.-H., Chan, W.-K., Lim, S.-K., Boey, V. W.-F., Lui, J. N., Tae, S.-K., & Lim, L.-L. (2026). Reimagining cardiometabolic health through artificial intelligence and digital health innovations. BMC Medicine. https://doi.org/10.1186/s12916-026-05196-x

Image Credits: AI Generated

DOI: 10.1186/s12916-026-05196-x

Keywords: artificial intelligence, digital health, cardiometabolic disease, cardiovascular disease, diabetes, chronic kidney disease, MASLD, machine learning, clinical decision support, explainable AI, algorithmic bias, risk prediction

The research team, led by Leonard D. Browne and Austin G. Stack of the University of Limerick, together with colleagues at University College Cork, the University of Bristol and partner hospitals, performed a retrospective cross-sectional study of every hospital discharge in the Republic of Ireland recorded in 2022. They used the Hospital In-Patient Enquiry database, known as HIPE, which captures demographic, clinical and administrative information on all admissions to Irish public hospitals. To isolate the specific contribution of chronic kidney disease, the researchers excluded infant admissions and cases in which dialysis or kidney transplantation were the principal reason for the stay, since those represent the treatment of established kidney failure rather than the broader disease spectrum.

The headline figures are striking. A total of 35,409 hospitalisations involving 24,110 individual patients were linked to chronic kidney disease, accounting for 422,738 bed-days and €320.3 million in expenditure. The mean length of stay was 11.9 days, far longer than the typical acute admission, which reflects the complexity of patients whose failing kidneys interact with heart disease, diabetes, infection and other organ dysfunction. Men accounted for the majority of admissions at 58.9 percent and a similar share of costs at 59.9 percent, while patients aged 75 to 84 years represented the largest single group, responsible for 30.0 percent of admissions and 30.8 percent of total expenditure.

Perhaps the most consequential finding for health service planners is the dominance of emergency admissions. Some 71.2 percent of kidney disease-related hospitalisations arrived through emergency departments rather than planned pathways, and 69 percent of the patients held medical cards, an Irish means-tested entitlement that signals substantial socioeconomic disadvantage. Emergency-driven care is inherently more expensive and less efficient than scheduled management, and its predominance suggests that many patients are reaching hospital only after their condition has deteriorated to a crisis point, rather than being stabilised through earlier outpatient intervention.

The study also mapped the clinical company that chronic kidney disease keeps. Among patients whose records carried a CKD code, diabetic nephropathy was the most common accompanying diagnosis at 49.5 percent, followed by tubulo-interstitial diseases at 9.1 percent, other disorders of the kidney and ureter at 6.7 percent, and glomerular diseases at 4.3 percent. That nearly half of these hospitalised patients had diabetes-related kidney damage underscores the entanglement of two of the fastest-growing chronic disease epidemics, and it points directly at prevention opportunities in diabetes management.

When chronic kidney disease appeared as a secondary diagnosis rather than the principal reason for admission, the pattern of primary conditions was revealing. Standardised to rates per 100,000 population, the leading principal diagnoses were disorders of the urinary system at 6,442, acute kidney failure at 3,764, type 1 diabetes at 2,540, type 2 diabetes at 2,489, heart failure at 2,362, other sepsis at 2,199, acute lower respiratory infections at 1,831, and unspecified pneumonia at 1,710. In other words, kidney disease shadows the conditions that fill acute medical wards: infections, cardiac decompensation and metabolic crises. This is the clinical signature of a multisystem disease, one in which declining renal function amplifies risk across the cardiovascular, immune and metabolic systems.

To move beyond simple description, the researchers applied formal statistical modelling. They used generalised linear models to examine associations between patient characteristics and continuous outcomes such as length of stay and cost, and multivariate logistic regression to probe the odds of inpatient death. Three factors emerged as independent drivers of worse outcomes across the board: increasing age, higher scores on the Elixhauser comorbidity index, a widely used weighted measure that tallies the burden of coexisting conditions, and the presence of acute kidney injury, the abrupt deterioration of renal function that frequently complicates hospital stays in patients with pre-existing chronic disease.

The independent association of acute kidney injury with longer stays, higher costs and greater mortality carries a specific clinical message. Acute kidney injury is often preventable through careful medication management, adequate hydration and vigilant monitoring during illness, and patients with chronic kidney disease are particularly vulnerable to it. The finding suggests that inpatient care pathways specifically designed to protect vulnerable kidneys, sometimes called kidney-sparing protocols, could yield measurable savings in both bed-days and lives. It also reinforces the idea that chronic kidney disease should not be managed in isolation but integrated within broader chronic disease programmes that address diabetes, cardiovascular risk and infection prevention together.

The financial arithmetic gives the findings their policy weight. At €320.3 million for a single year, kidney disease-related hospitalisation represents a substantial slice of Irish acute hospital spending, and the concentration of that spending in older, multimorbid patients means the burden is likely to grow as the population ages. The authors argue that integrating chronic kidney disease management within existing chronic disease programmes, alongside preventive strategies and optimised inpatient care pathways, offers realistic opportunities to ease the broader healthcare burden and improve patient outcomes. Earlier detection and management in primary care, they suggest, could shift care away from expensive emergency admissions.

The study was supported with funding from the Health Research Board under a grant examining disparities in health outcomes of chronic kidney disease between men and women in the Irish health system, and it used strictly controlled anonymised files provided by the Healthcare Pricing Office through the National Kidney Disease Surveillance System. Ethical approval was granted by the University Hospital Limerick Research Ethics Committee, with the requirement for explicit consent waived because the dataset was fully anonymised. The authors declare no competing interests. For a country grappling with hospital overcrowding and rising chronic disease, the message of this analysis is unambiguous: the kidneys may be small organs, but the cost of ignoring their failure is written in hundreds of thousands of bed-days and hundreds of millions of euro every year.

Subject of Research: Hospitalisation burden, mortality and costs of chronic kidney disease in Ireland

Article Title: The Hospital Burden of Chronic Kidney Disease in Ireland: A National Analysis of Healthcare Utilisation, Mortality and Costs

Article References: Browne, L. D., O’Keeffe, L. M., Buckley, C. M., Eustace, J. A., & Stack, A. G. (2026). The Hospital Burden of Chronic Kidney Disease in Ireland: A National Analysis of Healthcare Utilisation, Mortality and Costs. BMC Health Services Research. https://doi.org/10.1186/s12913-026-15681-x

Image Credits: AI Generated

DOI: 10.1186/s12913-026-15681-x

Keywords: chronic kidney disease, hospitalisation, healthcare costs, acute kidney injury, Ireland, HIPE database, diabetic nephropathy, inpatient mortality, length of stay, multimorbidity, health services research, emergency admissions

The research, led by Satoshi Kozawa, Kyoji Urayama, and Kengo Tejima together with senior author Thomas N. Sato and colleagues at Karydo TherapeutiX, the Advanced Telecommunications Research Institute International, and Nara Medical University in Japan, set out to answer a question that has long been neglected. Salivary proline-rich proteins, abbreviated sPRPs, are secreted in large quantities by the salivary glands and are known to contribute to oral lubrication and to the formation of the protective enamel pellicle. Beyond these local roles, however, their physiology has remained poorly characterized, and their behavior in systemic disease has been almost entirely unexplored.

To probe what these proteins might be doing in chronic kidney disease, the team turned first to mouse models. They used a unilateral nephrectomy model, in which one kidney is surgically removed, combined with a high-phosphate diet to accelerate renal stress, and they also studied mice lacking fibroblast growth factor 23, or FGF23, a bone-derived hormone that is central to phosphate homeostasis and rises dramatically as kidney function declines. The result was striking: expression of the genes encoding salivary proline-rich proteins was upregulated by the high-phosphate diet in the CKD model, and the expression was positively regulated by FGF23. In other words, the salivary glands appear to respond to a systemic mineral-metabolism signal that is itself driven by failing kidneys.

Single-cell RNA sequencing provided the anatomical foundation for this observation. By profiling gene expression cell by cell in both mouse and human salivary gland tissue, the researchers identified the specific cell types that produce the proline-rich proteins, confirming that the signal they were tracking originates from defined secretory populations within the glands rather than from contaminating blood or inflammatory cells. This cell-level resolution matters, because it anchors the biomarker story in a plausible biological mechanism: a hormone from the bone-kidney axis acting on salivary gland cells to change what they secrete.

The most consequential finding, however, came from the human data. Analyzing samples from 1,023 human subjects, the team discovered that salivary proline-rich proteins are present not only in saliva, where everyone expected them, but also in serum, where they had not been appreciated as measurable analytes. This is the sense in which the authors call them non-canonical biomarkers: proteins named for their salivary origin turn out to circulate in blood, and their blood levels, rather than their salivary levels, carry the clinical information.

That distinction proved critical. When the researchers correlated protein measurements with standard kidney function indices, it was serum sPRP levels, not salivary sPRP levels, that tracked with the canonical CKD biomarkers eGFR and ePTFp. The latter abbreviation, estimated proximal tubule fluid phosphate concentration, is a newer index that estimates the phosphate concentration in the fluid processed by the kidney’s proximal tubules, capturing aspects of tubular phosphate handling that eGFR alone cannot. The finding that serum sPRPs associate with both indices suggests they reflect a dimension of kidney physiology that spans filtration and tubular function.

To understand what dimension that might be, the investigators took a proteome-wide view. Using two large-scale affinity-based proteomic platforms, Olink and SomaScan, they examined how the entire serum proteome associates with serum sPRP levels, with eGFR, and with ePTFp. The analysis revealed that each of the three measures captures both common and distinct molecular signatures of chronic kidney disease, and that the signatures associated with serum sPRPs correspond predominantly to the features shared by eGFR and ePTFp. In mechanistic terms, the sPRP signal appears to represent the systemic biology that both standard indices see, rather than a redundant copy of either one.

Specificity is the make-or-break question for any proposed biomarker, and this is where the study delivers its most provocative number. The team compared the serum sPRP-associated proteomic signatures against a comprehensive panel of serum biomarkers spanning 59 non-CKD human diseases. Of the 1,685 signature features examined, 1,106, or 65.64 percent, showed no association with any of the 59 other diseases. The authors interpret this as evidence that serum sPRPs reflect potentially CKD-specific systemic mechanisms, a degree of disease specificity that few candidate biomarkers achieve when tested against broad disease panels.

The practical implication is not that saliva-based kidney tests are around the corner, but rather that a third measurement axis could complement the two that clinicians already use. The authors conclude that eGFR, ePTFp, and serum sPRPs are complementary, each capturing overlapping but non-identical information about CKD biology, and that combining them could improve both mechanistic studies of the disease and, potentially, diagnosis and treatment. Because the sPRP signal is regulated by FGF23 and responsive to dietary phosphate, it may be particularly informative in the mineral and bone disorder that complicates advanced kidney disease, where phosphate handling is a central therapeutic target.

There are caveats worth keeping in view. The human parotid gland tissue used for single-cell sequencing came from a single patient undergoing cancer surgery, and the cohort enrolled patients already diagnosed with kidney disease, cardiovascular disease, diabetes, or hypertension, so prospective validation in general populations will be needed before serum sPRP measurements enter clinical practice. Several of the authors are employees of Karydo TherapeutiX, which files patents related to the work, and the article was released as an early-access version subject to further edits. Even so, the study opens an unexpected window: proteins long treated as mere saliva lubricants, governed by a bone-kidney hormone and modulated by dietary phosphate, turn out to circulate in blood and to carry a molecular fingerprint of kidney failure that is largely invisible to other diseases. It is a reminder that biomarker discovery sometimes means looking again at molecules so familiar that no one thought to ask what they were doing outside their assigned tissue.

Subject of Research: Serum salivary proline-rich proteins as biomarkers of chronic kidney disease

Article Title: Salivary proline-rich proteins are non-canonical serum biomarkers of chronic kidney disease

Article References: Kozawa, S., Urayama, K., Tejima, K., Nakanishi, M., Nakagawa, Y., Eriguchi, M., Watanabe, M., Kosugi, T., Kirita, T., Tsuruya, K., Saito, Y., Kuro-o, M., & Sato, T. N. (2026). Salivary proline-rich proteins are non-canonical serum biomarkers of chronic kidney disease. Clinical Proteomics. https://doi.org/10.1186/s12014-026-09640-1

Image Credits: AI Generated

DOI: 10.1186/s12014-026-09640-1

Keywords: salivary proline-rich proteins, chronic kidney disease, biomarkers, FGF23, eGFR, ePTFp, proteomics, Olink, SomaScan, single-cell RNA sequencing, saliva, serum