The research, conducted at Fayoum University Hospitals and published in BMC Pediatrics, followed 41 children aged one to twelve years who were diagnosed with PSGN between January 2024 and April 2025. Rather than relying on a single test, the team assembled a multimodal cardiac assessment that combined clinical examination, laboratory work, conventional electrocardiography, standard echocardiography, and tissue Doppler imaging, a more sensitive technique that measures the velocity of myocardial motion directly. Each patient was then tracked for twelve weeks after diagnosis, allowing the investigators to distinguish between changes that persisted and those that faded as the kidney disease resolved.

The most striking electrical finding involved the QTc interval, the heart-rate-corrected measure of the time it takes for the ventricles to depolarize and repolarize with each heartbeat. Prolonged QTc was identified in 13 of the 41 children, with a median value of 431 milliseconds in the affected group. Prolongation of this interval matters because it reflects delayed electrical recovery of the heart muscle, a state that can in extreme cases predispose to dangerous rhythm disturbances. What made the finding particularly informative was its pattern of correlations with mechanical performance: longer QTc values were significantly associated with weaker systolic function, showing a negative correlation with ejection fraction (r = -0.40, P = 0.009) and with fractional shortening (r = -0.38, P = 0.01), and a positive correlation with estimated systolic pulmonary artery pressure (r = 0.36, P = 0.02).

That last correlation hints at a second dimension of cardiac involvement: the pulmonary circulation. Elevated pressure in the pulmonary arteries during PSGN is biologically plausible, since the fluid retention, hypertension, and neurohumoral activation that accompany acute glomerulonephritis can increase left-sided filling pressures and, secondarily, pulmonary venous pressure. The echocardiographic follow-up data support this interpretation. By twelve weeks, the children showed a statistically significant decrease in estimated systolic pulmonary artery pressure (P = 0.001), alongside significant reductions in interventricular septum thickness (P = 0.003) and left ventricular end-diastolic diameter (P = 0.01). In other words, the structural and hemodynamic signatures of the acute phase, a thicker septum and a more dilated left ventricle working against higher pressures, largely receded as the nephritis subsided.

Valve function also came under scrutiny. Ten of the children, or 24.4 percent, exhibited mild mitral regurgitation, the backward leakage of blood through the mitral valve during systole, and one child, 2.4 percent, had moderate regurgitation. Mitral regurgitation in this setting is most likely functional rather than structural, arising when ventricular dilation or altered loading conditions stretch the valve annulus and prevent complete leaflet coaptation. Its prevalence in the acute phase, and the absence of any reported structural valve disease, fits the overall picture of a heart that is temporarily stressed by the circulatory consequences of renal inflammation rather than one that is intrinsically diseased.

Perhaps the most technically sophisticated part of the study involved the myocardial performance index, or MPI, also known as the Tei index. This Doppler-derived parameter combines systolic and diastolic time intervals, dividing the sum of isovolumetric contraction time and isovolumetric relaxation time by the ejection time, to yield a single global measure of ventricular efficiency. Because it integrates both filling and pumping performance, MPI can detect subtle myocardial dysfunction that conventional ejection fraction misses. At diagnosis, 30 of the children had an elevated right ventricular MPI and 17 had an elevated left ventricular MPI, indicating that both sides of the heart were affected. The right ventricle’s involvement is notable, since it is often overlooked in kidney-related cardiac assessments yet is directly exposed to changes in pulmonary vascular resistance and volume status.

The twelve-week follow-up brought encouraging news on this front as well. The researchers observed significant decreases in isovolumetric contraction time in both ventricles (right ventricle, P = 0.03; left ventricle, P = 0.01) and significant reductions in MPI for both chambers (P < 0.001 for each). Taken together with the shrinking septal thickness and ventricular dimensions, the data sketch a coherent trajectory: a subclinical, functional cardiac impairment that is detectable at the height of the illness and substantially reversible within three months. The authors characterize these changes as transient, but they are careful to note that transient does not mean trivial, particularly during the acute phase when the myocardium may be operating with reduced reserve.

Why would a kidney disease affect the heart at all? The mechanisms proposed for PSGN-related cardiac involvement converge on hemodynamic and inflammatory pathways. Acute nephritic syndrome produces sodium and water retention, expanding intravascular volume and raising blood pressure, which increases the workload on both ventricles. Activation of the renin-angiotensin-aldosterone system and sympathetic nervous system adds vasoconstriction and inotropic stress. Meanwhile, the immune complexes and inflammatory mediators that damage the glomeruli circulate systemically and may have direct effects on the myocardium and coronary microcirculation. Fluid overload can also raise pulmonary venous pressures, straining the right ventricle, which the elevated MPI values in this cohort appear to reflect. None of these mechanisms requires permanent structural damage, which is consistent with the reversibility observed at follow-up.

The clinical implications are pragmatic rather than alarming. The authors suggest that QTc prolongation, a cheap and universally available measurement from a standard electrocardiogram, may serve as an initial screening tool for myocardial involvement in children with PSGN, while the myocardial performance index can be reserved as a more advanced measure when greater sensitivity is needed. Both, they emphasize, must be interpreted within the relevant clinical context, since QTc is influenced by electrolytes, medications, and autonomic tone, and MPI is affected by loading conditions and heart rate. In selected patients, particularly those with severe hypertension, significant fluid overload, or concerning symptoms, the findings argue for a lower threshold for advanced cardiac investigation during the acute phase.

For a disease long regarded as a straightforward kidney problem with an excellent prognosis, the study adds a nuanced caveat: the heart participates in the acute illness more often than bedside examination alone would reveal, and simple, noninvasive tools can detect that participation early. The children in this cohort recovered cardiac function within twelve weeks, and the study did not report persistent impairment, but the acute-phase findings, prolonged repolarization, reduced systolic indices, valve leakage, elevated pulmonary pressures, and biventricular dysfunction on tissue Doppler, suggest that clinicians managing PSGN should watch more than the urine. As streptococcal infections remain ubiquitous and PSGN continues to affect children across much of the world, the message from Fayoum is that a twelve-lead electrocardiogram and a careful echocardiogram may deserve a place in the routine evaluation of these young patients, at least until the storm has fully passed.

Subject of Research: Transient cardiac dysfunction in children with acute poststreptococcal glomerulonephritis

Article Title: Cardiac changes in children with post-streptococcal glomerulonephritis: a prospective observational study

Article References: Hussein, S. K., Darwish, M. Y., & Elnour, S. I. A. (2026). Cardiac changes in children with post-streptococcal glomerulonephritis: a prospective observational study. BMC Pediatrics, 26(1), Article 925. https://doi.org/10.1186/s12887-026-07396-z

Image Credits: AI Generated

DOI: 10.1186/s12887-026-07396-z

Keywords: poststreptococcal glomerulonephritis, PSGN, pediatrics, cardiology, echocardiography, QTc prolongation, myocardial performance index, tissue Doppler imaging, mitral regurgitation, pulmonary artery pressure, kidney disease, streptococcal infection

The review, led by Lotte M.G. Hulskotte and colleagues in the Netherlands, systematically searched PubMed and Embase for evidence on drug–drug and food–drug interactions and pharmacodynamic adverse effects of all thirty SMIs approved by the US Food and Drug Administration and the European Medicines Agency for non-small cell lung cancer, from long-standing agents such as erlotinib and crizotinib to newcomers including zongertinib, sevabertinib and sunvozertinib. The searches, initiated in October 2025 and finalised in July 2026, were supplemented with regulatory documents from both agencies, and the authors applied a pragmatic hierarchy of evidence ranking pharmacokinetic studies and meta-analyses above phase 1/2 trials, observational data, label information and expert opinion.

At the heart of the pharmacokinetic problem lies chemistry. Most SMIs are weakly basic, lipophilic molecules whose absorption depends delicately on the acidity of the stomach. When acid-reducing agents such as proton pump inhibitors raise gastric pH, the drugs shift toward a less soluble, non-ionised form that dissolves poorly, cutting systemic exposure. The magnitude is striking: selpercatinib exposure fell by roughly 70 percent when omeprazole was given in the fasted state, and sotorasib lost 57 percent of its exposure with omeprazole even when taken with food. Erlotinib, co-administered with esomeprazole, lost nearly half its area under the curve. Bioequivalence standards allow exposure to vary only within 80 to 125 percent of the reference value, so deviations of this size translate directly into subtherapeutic concentrations, lost efficacy and, ultimately, disease progression.

Liver enzymes provide the second major axis of interaction. Most SMIs are metabolised primarily by cytochrome P450 iso-enzymes, above all CYP3A, so potent inducers such as rifampicin can collapse drug levels while inhibitors such as itraconazole can push them to toxic heights. Rifampicin cut adagrasib exposure by 95 percent, while itraconazole raised repotrectinib exposure nearly sevenfold. Compounding the problem, several agents are themselves auto-inducers or auto-inhibitors of CYP enzymes — dabrafenib, encorafenib, lorlatinib and osimertinib induce their own clearance, while adagrasib, ceritinib and taletrectinib inhibit it — meaning that single-dose interaction studies may not predict steady-state behaviour. Transporters such as P-glycoprotein and breast cancer resistance protein add further complexity, although their intestinal contribution is generally considered minor.

Food, by contrast, can be an ally. High-fat meals delay gastric emptying, increase bile flow and create a lipophilic environment that enhances solubilisation of many of these drugs. Alectinib is the poster child: a high-fat meal raised its systemic exposure by roughly 230 to 250 percent, and a clinical crossover study showed that 35 percent of patients failed to reach the alectinib exposure threshold when taking the drug with low-fat yoghurt, compared with only 5 percent eating a continental breakfast or lunch. This very property has been exploited therapeutically — ceritinib’s approved dose fell from 750 mg fasted to 450 mg with food after feeding studies showed comparable exposure with less gastrointestinal toxicity, and the FDA has required a post-marketing evaluation of taletrectinib dosing with food for the same reason. Food also reduced inter-individual variability for several agents, improving predictability of therapeutic exposure.

The interplay between food and acid suppression, however, is drug-specific and sometimes counterintuitive. Selpercatinib’s PPI-induced exposure loss is largely rescued by co-administration with a meal. Sotorasib behaves in the opposite way, losing even more exposure when food and a PPI are combined. For erlotinib, an acidic glass of cola partially reversed the damage done by esomeprazole, restoring roughly 40 percent of lost exposure. The authors conclude that when PPI use is unavoidable, clinicians should weigh the individual pharmacokinetics of each SMI, considering food co-administration, acidic beverages or staggered dosing as mitigation strategies.

Turning to the drugs’ intrinsic toxicities, the review paints a landscape where class effects mask considerable agent-to-agent variation. Corrected QT interval prolongation, which can degenerate into dangerous arrhythmias, affects the entire class but is most pronounced with adagrasib, ceritinib, crizotinib, encorafenib, osimertinib and taletrectinib, with median increases exceeding ten milliseconds and the highest rates of clinically significant prolongation seen with adagrasib, encorafenib, taletrectinib, entrectinib and selpercatinib. Because the effect is largely exposure-dependent, any interaction that raises drug levels also raises arrhythmia risk. Others, including alectinib, gefitinib, capmatinib and the newer HER2 inhibitors, showed no clinically meaningful QTc changes. Management centres on electrocardiographic monitoring, correction of concomitant QT-prolonging factors, and dose interruption or discontinuation when the QTc exceeds 500 milliseconds.

Pneumonitis, the non-infectious inflammation of lung tissue that can prove fatal, occurs with most SMIs but clusters around particular agents. Brigatinib carried the highest trial incidence at 9 percent of all-grade events, with an unusual early onset within the first week — the rationale for its mandatory one-week 90 mg lead-in dose before escalation. Pralsetinib affected about 12 percent of patients including one fatal case, while adagrasib, capmatinib, ensartinib and sunvozertinib each produced events in 5 to 6 percent. Strikingly, ethnicity emerged as an independent risk factor: all-grade interstitial lung disease was reported in up to 15 percent of Japanese patients on gefitinib and 17 percent on osimertinib. Rechallenge after pneumonitis remains fraught — one real-world study found a 50 percent twelve-month recurrence rate when patients were rechallenged with osimertinib itself, versus 15 percent with alternative EGFR inhibitors.

Among the quieter but increasingly recognised toxicities is weight gain. NTRK inhibitors cause weight gain in 53 percent of patients, likely through on-target inhibition of TRKB, a hypothalamic receptor governing appetite, with entrectinib reaching roughly 66 percent incidence. Among ALK inhibitors, lorlatinib produced all-grade weight gain in up to 81 percent of patients, with grade 3 events in up to 23 percent and a median gain of 4.5 kilograms in a prospective study; alectinib added an average 9 centimetres of waist circumference over a year. The irony is acute for alectinib, whose absorption depends on high-fat meals. Management spans lifestyle counselling, systematic weight monitoring and, where needed, GLP-1 receptor agonists — though even here caution is warranted, as semaglutide was recently shown to reduce alectinib exposure by 32 percent.

Further distinguishing the class, EGFR inhibitors uniquely damage the ocular surface — keratitis in 1 to 3 percent of patients and conjunctivitis up to 24 percent with dacomitinib — because EGFR sustains corneal epithelium and tear production, while BRAF/MEK combinations bring uveitis and retinal pigment epithelial detachment, the latter affecting roughly 30 percent of patients on encorafenib plus binimetinib. Central neurotoxicity, including cognitive disorders in up to a third of patients on capmatinib, entrectinib, lorlatinib and repotrectinib, peripheral neuropathy in up to 44 percent on lorlatinib, dabrafenib-driven pyrexia in 39 percent of combination-treated patients, severe stomatitis with second-generation EGFR inhibitors, and hepatotoxicity necessitating intra-class switches — erlotinib after gefitinib injury, adagrasib after sotorasib injury — complete the picture. The authors’ overarching message is that safe prescribing of these transformative drugs demands equal attention to what patients eat, what else they swallow, and which specific molecule sits in the capsule: pharmacokinetic–pharmacodynamic associations remain under-studied, and filling that gap could enable personalised dosing that maximises efficacy while sparing patients avoidable harm.

Subject of Research: Pharmacokinetic and pharmacodynamic considerations for prescribing small molecule kinase inhibitors in non-small cell lung cancer

Article Title: Pharmacological considerations for prescribing of small molecule inhibitors in patients with non-small cell lung cancer

Article References: Hulskotte, L. M., Veerman, G. M., Lanser, D. A., Reyners, A. K., van Schaik, R. H., Dingemans, A.-M. C., Taxis, K., Mathijssen, R. H., & Jansman, F. G. (2026). Pharmacological considerations for prescribing of small molecule inhibitors in patients with non-small cell lung cancer. eClinicalMedicine, 100, Article 104199. https://doi.org/10.1016/j.eclinm.2026.104199

Image Credits: AI Generated

DOI: 10.1016/j.eclinm.2026.104199

Keywords: non-small cell lung cancer, small molecule inhibitors, drug-drug interactions, pharmacokinetics, CYP3A, proton pump inhibitors, food-drug interactions, QTc prolongation, pneumonitis, weight gain, ocular toxicity, targeted therapy