Background Recurrence of focal segmental glomerulosclerosis (rFSGS) remains a major complication and a challenge to study treatment efficacy due to lack of granular data in a sufficient sample size. Aggregated data from electronic health records can provide such data. Methods We applied computational phenotypes to data from 11 large pediatric health systems in the USA, to identify treatments used and remission outcomes in children with rFSGS after renal transplantation. Additional data were collected by chart review. We performed both linear and non-linear multivariable Cox regression analyses with penalized splines to allow for time-varying predictors. Based on effect sizes from the hazard ratios, we then calculated a sample size needed for a future randomized clinical trial. Results Plasmapheresis was used in 101/107 (94%) patients, followed by anti-CD20 agents in 84 (78%), Low-Density-Lipoprotein (LDL)-apheresis in 22 (20%) and CTLA4Igs in 8 (7%). In linear multivariable models, complete remission was associated with more plasmapheresis sessions. In non-linear models, more doses or sessions of all the above treatments were associated with complete remission or any remission (partial or complete). Penalized spline curves for complete or any remission showed greatest yield within 5 doses of anti-CD20 agents but increasing yield with more doses/sessions of CTLA4Igs or LDL-apheresis. Based on observed hazard ratios, a prospective randomized trial of plasmapheresis vs LDL-apheresis would require 155 participants to have 80% power. Conclusions Increased doses/sessions or additional therapies for rFSGS associated with more favorable outcomes. Non-linear modelling identified when further increases did not improve outcomes.

Background and objective Thyroid dysfunction is a well-recognised but under-investigated complication of chronic kidney disease (CKD). While the overall prevalence of hypothyroidism in CKD is documented, its association with specific clinical variables, particularly including gender, haemoglobin (Hb), and azotaemia, has not been systematically characterised in populations from the Indian subcontinent. Hence, this study was designed to identify the correlates of thyroid dysfunction in CKD patients on conservative management. Methods A cross-sectional observational study was conducted involving 100 CKD patients (age ≥ 18 years) attending the outpatient and inpatient wards of Dr. Baba Saheb Ambedkar Medical College and Hospital (Dr. BSAH), New Delhi, between 2019 and 2021. Patients on dialysis, those with nephrotic syndrome, pregnancy, liver disease, or medications known to alter thyroid function were excluded. CKD was staged using the Kidney Disease: Improving Global Outcomes (KDIGO) criteria and the four-variable Modification of Diet in Renal Disease (MDRD) formula. Serum free triiodothyronine (FT3), free thyroxine (FT4), and thyroid-stimulating hormone (TSH) were measured by an enzyme-linked immunosorbent assay (ELISA). Statistical analysis was performed using IBM SPSS Statistics version 20 (IBM Corp., Armonk, NY), employing the chi-square test, one-way analysis of variance (ANOVA), the independent samples t-test, the Pearson correlation, and binary odds ratio (OR) calculation. Results The mean age of the cohort was 51.32 ± 11.89 years; 72 (72%) were male and 28 (28%) female. CKD stage 5 was the most common stage (44 (44%)). Total hypothyroidism prevalence was 46% (subclinical hypothyroidism (SCH): 24 (24%), overt hypothyroidism (OH): 22 (22%), low T3 syndrome: nine (9%)). Female patients had a significantly higher hypothyroidism rate (20 (71.4%) vs 26 (36.1%); χ[2] = 10.335, OR = 4.42, 95% CI: 1.71-11.44, p = 0.003) and higher mean TSH (5.84 vs 4.41 μIU/ml; t = -2.116, p = 0.036). Overt hypothyroidism was associated with the lowest Hb (7.97 g/dl; ANOVA F = 6.349, p = 0.001) and the highest blood urea (152.03 mg/dl; ANOVA F = 3.24, p = 0.024). Hb correlated negatively with TSH (r = -0.236, p = 0.018) and positively with estimated glomerular filtration rate (eGFR) (r = 0.516, p < 0.001). Advanced CKD stage 5 was significantly associated with a higher risk of hypothyroidism (OR = 2.60, 95% CI: 1.15-5.85, p = 0.034). Comorbidities (type 2 diabetes mellitus (T2DM), hypertension (HTN)) and age were not significantly associated with thyroid dysfunction. Conclusions Female gender and advanced CKD stage show the strongest associations with hypothyroidism in this cohort. Overt hypothyroidism is associated with more severe anaemia and higher azotaemia, beyond what is explained by CKD stage alone. These findings support targeted thyroid function testing in CKD patients; prospective studies are warranted to establish the clinical benefit of such a strategy.

Complement dysregulation is frequently implicated in the thrombotic microangiopathy (TMA) known as atypical hemolytic uremic syndrome (aHUS). Diacylglycerol kinase epsilon (DGKE) mutations encode a non-complement regulatory protein, and pathogenic variants in DGKE define a distinct form of aHUS. Indeed, the DGKEgene encodes a key enzyme involved in intracellular signaling. While eculizumab and other anti-C5 monoclonal antibodies are widely used in complement-related aHUS, their relevance in DGKE-associated forms remains controversial. We report a case of a patient followed from the age of eight months for suspected aHUS. Genetic testing, performed only at the age of 13 years, revealed a homozygous DGKE mutation (c.412T>C; p.C138R), despite a typical presentation, including hemolytic anemia, thrombocytopenia, and acute kidney injury. Due to severe disease progression and a fatal family history, empirical eculizumab therapy was initiated. Although the treatment resulted in a stable overall clinical status, relapses manifested as isolated nephrotic-range proteinuria (without hemolysis) on two occasions during treatment interruptions. Complement C3 levels remained consistently within the normal range. In this case, eculizumab did not prevent disease relapses, which occurred in the absence of complement activation. The persistence of proteinuria despite C5 blockade further highlights this distinction. The lack of genetic testing options has led to overtreatment in this patient with that type of mutation, with additional costs associated with the drug (eculizumab) and an increased risk of life-threatening infectious complications for the patient.

Waldenström macroglobulinemia (WM) is a rare CD20-positive B-cell non-Hodgkin lymphoma. It is characterized by lymphoplasmacytic infiltration in the bone marrow and abnormal monoclonal IgM secretion. WM complicated by renal amyloidosis is uncommon but associated with rapid progression of organ damage. Accurate identification of pathogenic factors and individualized treatments are essential to improve prognosis. This paper reports the case of a 75-year-old female who initially presented with facial edema and bilateral lower-extremity edema lasting 2 days. Additional symptoms included foamy urine, frequent urination, and urgency. Laboratory tests revealed significant proteinuria (24-h urinary protein, 6.11 g), hypoalbuminemia (serum albumin, 20.07 g/L), and impaired renal function (serum creatinine, 129.90 μmol/L; eGFR, 45.2 mL/min/1.73 m2). Immunofixation electrophoresis detected monoclonal IgM-λ immunoglobulin in both serum and urine. Bone marrow biopsy demonstrated clonal lymphoplasmacytic infiltration (32%), and genetic testing revealed a positive MYD88-L265P mutation (mutation frequency, 28.5%). Renal biopsy indicated diffuse deposition of λ light chains predominantly in the glomerular mesangium. Ultrastructural examination revealed amyloid fibrils, confirming the diagnosis of AL λ - type amyloid nephropathy. Chemotherapy with rituximab, cyclophosphamide, and dexamethasone (RCD regimen), combined with symptomatic supportive therapy, resulted in temporary improvement of clinical symptoms and laboratory parameters. However, the disease progressed rapidly. The patient died on Jan 28, 2024, approximately 3 months after discharge, due to multiple organ failure involving cardiac, renal, and respiratory dysfunction. Based on relevant literature and the Chinese Expert Consensus on Diagnosis and Treatment of Lymphoplasmacytic Lymphoma (LPL)/WM (2022 Edition) [Abstract 3], this paper discusses diagnostic criteria, differentiation of pathogenic components, treatment strategies, and prognostic factors. These findings may provide clinical guidance for similar rare cases.

[This corrects the article DOI: 10.3389/fped.2026.1737399.].

The proprotein convertase subtilisin/kexin 9 (PCSK9) protein is well known for its role in the regulation of plasma cholesterol levels. We previously showed that the initiation of hypercholesterolemia in nephrotic syndrome is related to PCSK9 secreted by the cortical collecting duct (CCD), whereas the established phase is due to PCSK9 secreted by the liver. In this study, we investigated whether early neutralization of circulating CCD-secreted PCSK9 could prevent sustained hypercholesterolemia. We showed that PAN rats, a widely used animal model that mimics nephrotic syndrome phenotype of human minimal change disease (MCD), developed increased levels of PCSK9 of CCD origin prior to peak proteinuria. CCD-secreted PCSK9 followed an increase in the transcription factor sterol regulatory element-binding protein 2 (SREBP2) expression, while both SREBP2 and PCSK9 were unmodified and reduced, respectively, in the liver. Treatment of PAN rats with anti-PCSK9 antibodies administrated at or shortly after the onset of proteinuria prevented the development of significant and sustained hypercholesterolemia through the course of PAN. These data confirm that PCSK9 secreted from the kidney initiates the development of hypercholesterolemia in MCD and suggest that early depletion of PCSK9 during the initial stages of MCD prevents sustained hypercholesterolemia.

Libman-Sacks endocarditis (LSE), characterized by sterile valvular vegetations, is a recognized complication of systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS). However, its occurrence as the initial manifestation of previously undiagnosed autoimmune disease is uncommon and may create significant diagnostic uncertainty. A 27-year-old female presented to the emergency department with acute-onset exertional dyspnea, cough, and severe anemia, with a history of three consecutive first-trimester miscarriages. Initial evaluation revealed severe mitral regurgitation with valvular masses, raising suspicion for infective endocarditis. Further workup demonstrated elevated inflammatory markers, autoimmune hemolytic anemia, nephrotic-range proteinuria, and positive autoimmune serology, including antinuclear antibodies, anti-double-stranded DNA, anticardiolipin IgG, anti-β2-glycoprotein I IgG, and lupus anticoagulant. Transthoracic echocardiography showed severe mitral regurgitation with valvular masses and reduced left ventricular ejection fraction, while transesophageal echocardiography confirmed Libman-Sacks vegetations. Computed tomography of the chest revealed diffuse alveolar hemorrhage. The patient was diagnosed with new-onset SLE and APS, presenting with LSE and multisystem involvement. Management included pulse methylprednisolone therapy, hydroxychloroquine, cyclophosphamide, therapeutic anticoagulation, and plasma exchange for alveolar hemorrhage, resulting in clinical improvement with resolution of hemoptysis and improvement in cardiac function. This case is particularly notable because severe valvular disease led to the initial recognition of previously undiagnosed SLE and APS in the setting of simultaneous pulmonary, hematologic, renal, and obstetric manifestations. It highlights the importance of considering autoimmune etiologies in young patients with unexplained valvular heart disease, particularly in the presence of suggestive systemic features.