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 research team, publishing in Health Science Reports, recruited adults with type 2 diabetes from the outpatient department between December 2023 and December 2025, excluding anyone with acute kidney injury, acute infection, active liver disease, malignancy, or use of medications known to distort homocysteine levels, such as methotrexate or antiepileptic drugs. Each participant provided a fasting venous blood sample after eight to twelve hours without food, along with an early-morning urine specimen. Serum homocysteine was quantified by chemiluminescent immunoassay, creatinine by an enzymatic method, and cystatin C by immunoturbidimetry, while kidney function was estimated using the modern 2021 CKD-EPI equation that combines creatinine and cystatin C. Chronic kidney disease was operationally defined as an estimated glomerular filtration rate below 60 mL/min/1.73 m² and/or a urinary albumin-to-creatinine ratio above 30 mg/g.

The cohort was strikingly skewed toward renal disease: 164 of the 201 participants, or 81.6 percent, met the study definition of chronic kidney disease, while only 37 did not. Patients with kidney disease were significantly older, averaging nearly 66 years compared with just over 60 years in the spared group, but sex, body mass index, blood pressure, and HbA1c were statistically indistinguishable between the two groups. What separated them most clearly was biochemistry. Homocysteine averaged 15.93 μmol/L in the kidney disease group versus 10.68 μmol/L among those without, and the diseased group also carried markedly higher creatinine, cystatin C, and albuminuria alongside drastically lower filtration rates.

Perhaps the most visually compelling result was the stepwise climb of homocysteine across the full spectrum of renal impairment. Stratified by filtration rate, mean homocysteine rose from 10.3 μmol/L in patients with preserved function to 15.5 μmol/L at moderate impairment and 20.5 μmol/L in the most advanced stages, a gradient that held with high statistical significance. The same monotonic pattern appeared across albuminuria categories, from 13.4 μmol/L in patients with normal urinary albumin to 16.9 μmol/L in those with heavy protein loss. The authors note that the scatter of values widened considerably at advanced disease, hinting at growing heterogeneity in homocysteine metabolism and clearance as the kidneys fail.

Correlation analysis reinforced the picture. Homocysteine correlated strongly and positively with both creatinine and cystatin C, with coefficients of 0.67 for each, and inversely with estimated glomerular filtration rate at −0.59, while showing only weak associations with age and albuminuria and none at all with blood pressure or glycemic control. That asymmetry is mechanistically telling: it suggests that in this cohort, circulating homocysteine tracks impaired glomerular filtration far more closely than it tracks direct glomerular injury, implying the molecule may largely accumulate because the failing kidney cannot clear it, rather than serving as an independent report of inflammatory damage within the kidney tissue itself.

The predictive mathematics was equally striking. In univariable logistic regression, every 1 μmol/L rise in homocysteine increased the odds of chronic kidney disease by 28 percent. Receiver operating characteristic analysis yielded an area under the curve of 0.79, and a Youden-derived threshold of 11.35 μmol/L delivered balanced performance, with 76 percent sensitivity and 78 percent specificity. Notably, adding age and HbA1c to a multivariable model nudged the area under the curve only to 0.812, and a formal DeLong comparison found that this increment was not statistically significant, meaning homocysteine alone carried nearly all of the discriminative information the combined model offered. Higher homocysteine also remained associated with kidney disease after adjustment for age and glycemic control.

Why would homocysteine and kidney damage be entwined? Experimental work has implicated several converging pathways. Elevated homocysteine promotes the generation of reactive oxygen species, fueling oxidative stress and NF-κB–mediated inflammation that can injure the delicate endothelial cells of the renal microvasculature. It also interferes with DNA methylation, potentially inducing epigenetic changes in gene regulation that reshape renal structure under chronic hyperglycemia, and it has been tied experimentally to glomerulosclerosis, TGF-β1–driven fibrosis, and podocyte apoptosis that increases the leakiness of the glomerular filter. Yet the authors are careful to stress that a cross-sectional design cannot untangle cause from consequence: homocysteine may help drive renal injury, or it may simply accumulate as an innocent bystander of failing clearance.

The team therefore ran a sensitivity analysis using albuminuria alone, independent of the filtration criterion, as the outcome. Homocysteine remained associated with albuminuria, with an odds ratio of 1.08, but its discriminatory power dropped sharply to an area under the curve of 0.628, reinforcing the conclusion that the biomarker’s strongest signal lies in reflecting reduced filtration rather than pinpointing glomerular barrier injury. The authors also caution that the 11.35 μmol/L cutoff was derived and evaluated in the same cohort and, given the marked imbalance between disease groups and the convenience sampling design, should be regarded as exploratory rather than a validated screening threshold pending external confirmation in larger, more representative diabetic populations.

Limitations temper the enthusiasm appropriately. The single-center design, the absence of data on folate and vitamin B12 status, metformin exposure, smoking, alcohol, and dietary protein all leave room for residual confounding, and no longitudinal follow-up was available to test whether rising homocysteine actually precedes declining kidney function. Still, the large sample relative to prior Vietnamese studies and the use of the contemporary creatinine–cystatin C filtration equation lend the findings credibility. The research team proposes clear next steps: prospective cohort studies to establish temporality, interventional trials of homocysteine-lowering strategies such as folate and B-vitamin supplementation, and integrated prognostic models combining homocysteine with emerging biomarkers like NGAL and KIM-1, alongside population-specific thresholds adjusted for age, sex, nutrition, and ethnicity.

If those studies succeed, the implications for a country like Vietnam—and for the many nations riding the same wave of metabolic disease—could be substantial. A homocysteine assay is inexpensive, widely available on automated platforms, and already ordered in cardiovascular workups, meaning the infrastructure to deploy it as an adjunctive kidney risk marker largely exists. For the roughly one in five adults with diabetes who will progress toward kidney failure, an early, easily repeated warning signal that outperforms conventional markers in simplicity and matches them in this cohort’s discrimination would represent a genuinely meaningful advance. For now, the message is one of cautious promise: homocysteine is not yet ready for the clinic as a standalone kidney test, but the evidence that it mirrors diabetic renal decline, stage by stage, has grown decidedly harder to ignore.

Subject of Research: The association between serum homocysteine levels and chronic kidney disease severity in Vietnamese outpatients with type 2 diabetes.

Article Title: Association Between Serum Homocysteine and Chronic Kidney Disease Severity in Vietnamese Outpatients With Type 2 Diabetes: A Cross‐Sectional Study

Article References: Ho, L. N., Van Tran, T., Tran, T. T. T., Le, N. T., Quach, L. H., Thanh, K. M., Tran, H. N., Hoang, H. K., Tran, H. H., & Le, T. Q. (2026). Association Between Serum Homocysteine and Chronic Kidney Disease Severity in Vietnamese Outpatients With Type 2 Diabetes: A Cross‐Sectional Study. Endocrinology, Diabetes & Metabolism, 9(5), Article e70339. https://doi.org/10.1002/edm2.70339

Image Credits: AI Generated

DOI: 10.1002/edm2.70339

Keywords: homocysteine, chronic kidney disease, type 2 diabetes, estimated glomerular filtration rate, albuminuria, biomarker, Vietnam, diabetic kidney disease, cystatin C, ROC analysis, cross-sectional study, renal function

The research, published in The Journal of Antibiotics, focused on CSA-13, the prototype of a family of laboratory-designed molecules called ceragenins. Unlike antimicrobial peptides, which are short chains of amino acids that the innate immune system deploys against invading pathogens, ceragenins are small sterol-based compounds built to reproduce the membrane-disrupting activity of those peptides without the fragility that limits their clinical use. Natural peptides are easily degraded by proteases and can be inactivated by DNA and actin released from dying tissue, conditions abundant in infected lungs. Ceragenins were engineered to sidestep those weaknesses while retaining a positively charged surface that binds to and permeabilizes bacterial membranes, and to additionally modulate inflammatory signaling through pathways involving innate immune receptors.

To test whether CSA-13 could protect the kidneys during pneumonia-induced sepsis, the team, led by Ugur Aksu of Istanbul University together with colleagues at several Turkish institutions and Paul B. Savage of Brigham Young University, worked with female C57/BL6 mice randomly assigned to four experimental groups of six animals each. One group served as a healthy control, while a second was subjected to Pseudomonas pneumonia-induced sepsis and left untreated. The remaining two groups received sepsis induction followed by either a low or a high dose of CSA-13 delivered intraperitoneally, a route that allowed the compound to circulate systemically after the infection had taken hold. The design deliberately modeled a treatment scenario rather than prophylaxis, asking whether the ceragenin could intervene after septic injury had already begun.

The investigators then tracked three interlocking dimensions of sepsis-related renal damage. Renal injury was quantified using plasma cystatin C, a small protein widely regarded as a more sensitive and reliable marker of glomerular filtration than traditional creatinine measurements because it is produced at a constant rate and is not confounded by muscle mass in the same way. Inflammation was assessed by measuring interleukin-6 concentrations in kidney tissue, since IL-6 is a central cytokine amplifier of the septic response and elevated tissue levels correlate with worse outcomes in acute kidney injury. Finally, glycocalyx integrity was evaluated through plasma hyaluronan, a glycosaminoglycan that is shed into the bloodstream when the endothelial glycocalyx—a delicate gel-like layer coating the interior surface of blood vessels—is degraded during systemic inflammation.

The glycocalyx deserves particular attention because it has emerged in recent years as both a diagnostic window and a therapeutic target in sepsis. This carbohydrate-rich coating on endothelial cells acts as a barrier that regulates vascular permeability, limits inappropriate adhesion of leukocytes, and maintains the selective sieving properties of the glomerular filtration barrier in the kidney. During sepsis, enzymes and inflammatory mediators shred the glycocalyx, releasing fragments such as hyaluronan into the circulation and simultaneously leaving the vasculature leaky and prothrombotic. In the kidney, this shedding contributes to the breakdown of filtration barriers that defines acute kidney injury. A therapy that preserves or restores the glycocalyx could therefore interrupt a critical step in the cascade from infection to organ failure, which is precisely what the researchers hoped CSA-13 might achieve.

The results were striking in two of the three domains. Both the low and high doses of CSA-13 successfully restored plasma cystatin C toward normal levels, indicating that kidney function was substantially preserved despite the septic insult. Equally important, tissue levels of interleukin-6, which surged in untreated septic mice, fell back to values indistinguishable from those of healthy controls in animals receiving either dose of the ceragenin. This dual effect—preserving filtration capacity while suppressing a key inflammatory cytokine within the kidney itself—suggests that CSA-13 acts not merely as an antibiotic reducing bacterial load but also as an immunomodulatory agent dampening the local renal inflammatory response that drives tissue damage.

Histological examination reinforced the biochemical findings. Under the microscope, the kidneys of untreated septic mice displayed the expected hallmarks of acute injury, including disruption of cellular architecture and tissue disorganization. In contrast, mice treated with either dose of CSA-13 largely maintained cellular integrity, with renal tissue structure closely resembling that of the healthy control group. The consistency of the protection across both low and high dosing regimens is noteworthy from a translational standpoint, because it hints that effective renoprotection does not require aggressive dosing, a potentially valuable property given that dose-dependent toxicity is a persistent concern with many antimicrobial agents used in critically ill patients.

The one measure that resisted the treatment was glycocalyx degradation. Plasma hyaluronan, the surrogate marker of glycocalyx shedding, remained elevated in septic mice whether or not they received CSA-13, at either dose. The authors’ conclusion was measured: the administration of the ceragenin did not substantially alter hyaluronan levels in infected animals. This finding matters because it delineates the boundary of the compound’s protective reach. CSA-13 appears to safeguard kidney function and cellular structure primarily through antimicrobial and anti-inflammatory mechanisms rather than by directly preserving the endothelial glycocalyx. In practical terms, other therapeutic strategies may still be needed alongside ceragenin therapy to address the vascular barrier failure that accompanies sepsis, and future studies will need to determine whether the persistent hyaluronan elevation reflects ongoing glycocalyx damage that is functionally compensated by other protective effects.

Even with that limitation, the study carries significant implications at a moment when antimicrobial resistance is eroding the effectiveness of the clinical arsenal against Pseudomonas aeruginosa, a notoriously drug-resistant Gram-negative pathogen and a leading cause of hospital-acquired and ventilator-associated pneumonia. Previous work has demonstrated that ceragenins retain activity against multidrug-resistant clinical isolates, function in challenging biological environments such as cystic fibrosis sputum, and show promise in animal models of peritoneal, urinary tract, and intestinal infection, as well as in early clinical studies of ceragenin-coated endotracheal tubes designed to prevent ventilator-associated pneumonia. The present findings extend this evidence base by demonstrating systemic renoprotective and anti-inflammatory effects in the septic context, raising the possibility that ceragenins could one day serve as combination agents that simultaneously control infection and prevent downstream organ damage.

The researchers conclude that intraperitoneal CSA-13 administration decreases renal interleukin-6 levels and protects both kidney function and cellular integrity in pneumonia-induced sepsis, positioning the compound as a candidate component of treatment protocols aimed at preventing acute kidney injury in this setting. Much work remains before such a protocol could reach patients: the current study involved small groups of animals, a single time course, and a single sepsis model, and questions of optimal dosing, timing, safety, and efficacy relative to standard antibiotics are unresolved. Moreover, the authors acknowledge funding support from N8 Medical, Inc., a company with commercial interest in ceragenin technology, and one coauthor serves as a paid consultant, considerations that will warrant scrutiny as the work moves toward independent replication. Nevertheless, the convergence of preserved filtration markers, normalized inflammatory cytokines, and protected tissue architecture paints a coherent and encouraging picture. If subsequent studies confirm these results, ceragenins may carve out a distinctive niche in critical care medicine—molecules conceived as peptide mimics but proving their worth as protectors of the organs that sepsis strikes hardest.

The choice of cystatin C as the primary renal endpoint reflects a broader shift in nephrology toward biomarkers that detect injury earlier than creatinine. Because cystatin C is freely filtered and reabsorbed by proximal tubular cells, rising plasma concentrations can signal declining filtration before conventional tests change, making it particularly valuable in dynamic conditions such as sepsis where hours matter for intervention.

Interleukin-6 likewise carries clinical weight beyond the laboratory. Circulating IL-6 has been associated with progression to severe sepsis and mortality in critically ill patients, and the cytokine drives endothelial activation, capillary leak, and recruitment of inflammatory cells into renal tissue. The observation that kidney tissue IL-6 normalized with treatment, rather than merely declining, suggests the compound interrupted the local amplification loop rather than blunting it partially.

The persistence of elevated hyaluronan despite preserved kidney structure also raises mechanistic questions. Glycocalyx shedding is mediated by enzymes such as heparanase and hyaluronidase activated during inflammation, and their activity may outlast the cytokine surge. Alternatively, hyaluronan released from injured pulmonary tissue could contribute to circulating levels independently of renal vascular damage, a possibility that would reconcile normal histology with unchanged biomarker values.

For Pseudomonas aeruginosa specifically, the findings arrive as the pathogen appears on global watchlists of critical-priority drug-resistant bacteria. Compounds with dual antimicrobial and immunomodulatory activity could reduce reliance on high-dose beta-lactams and aminoglycosides, agents whose nephrotoxicity compounds septic renal injury. Whether ceragenins can deliver that benefit in humans will depend on pharmacokinetic studies and larger, independent animal work before clinical trials become realistic.

Subject of Research: Evaluation of the ceragenin CSA-13 for renoprotection, anti-inflammatory effects, and glycocalyx preservation in a murine model of Pseudomonas pneumonia-induced sepsis.

Article Title: CSA-13 treatment in a murine model of Pseudomonas pneumonia-induced sepsis and its effects on renal injury, inflammation, and glycocalyx derangement

Article References: Aksu, U., Bozkurt-Guzel, C., Erkose-Genc, G., Tok, O. E., Esrefoglu, M., Oyardi, O., & Savage, P. B. (2026). CSA-13 treatment in a murine model of Pseudomonas pneumonia-induced sepsis and its effects on renal injury, inflammation, and glycocalyx derangement. The Journal of Antibiotics. https://doi.org/10.1038/s41429-026-00957-5

Image Credits: AI Generated

DOI: 10.1038/s41429-026-00957-5

Keywords: ceragenin, CSA-13, sepsis, acute kidney injury, Pseudomonas aeruginosa, pneumonia, interleukin-6, cystatin C, glycocalyx, hyaluronan, antimicrobial peptides, renal inflammation