We report an 11-year-old boy with chronic kidney disease (CKD) stage 3 due to right multicystic dysplastic kidney and contralateral dysplasia who developed poststreptococcal acute glomerulonephritis (PSAGN) that rapidly progressed to kidney failure despite intensive immunosuppressive treatment. He presented with oliguria, macrohematuria, heavy proteinuria, hypocomplementemia, and an elevated antistreptolysin O titer. Initial kidney biopsy revealed diffuse endocapillary proliferation with prominent C3 deposition, subepithelial humps, and positive staining for nephritis-associated plasmin receptor (NAPlr), consistent with PSAGN. Kidney dysfunction persisted despite the administration of methylprednisolone pulse therapy, prednisolone, cyclosporine, and mycophenolate mofetil. A second biopsy at 4 months revealed focal segmental glomerulosclerosis, diffuse foot process effacement, and negative staining for NAPlr, suggesting transition from a glomerular inflammatory process to a hyperfiltration-driven structural injury. Comprehensive genetic analysis did not identify any pathogenic variants associated with bilateral dysplastic kidney. Peritoneal dialysis was initiated on day 182, and living donor kidney transplantation was performed 10 months after nephritis onset, with favorable early outcomes. This case highlights that PSAGN superimposed on CKD with reduced nephron mass may result in rapid kidney function deterioration despite aggressive treatment.

Focal segmental glomerulosclerosis (FSGS) involves glomerular scarring and podocyte injury. FSGS treatment typically involves the use of corticosteroids and immunosuppressants. In patients with steroid-resistant FSGS, however, no ideal treatment exists. Extracorporeal therapies such as plasma exchange and low-density lipoprotein apheresis (LDL-A) may be promising options for managing lipid-mediated nephrotoxicity found in patients with steroid-resistant FSGS. Unfortunately, these extracorporeal techniques are inaccessible in many low- and middle-income countries (LMICs) due to high costs and infrastructure challenges. The use of extracorporeal therapies for FSGS management was evaluated at a single center. Additionally, a literature search was conducted across multiple databases to identify studies that explored FSGS treatment modalities in LMICs. Eligibility was assessed based on discussion of viability, efficacy, and application of therapies. At a single center, we found that double filtration plasmapheresis (DFPP) with the Evaflux filter was the most frequently used and most effective method of extracorporeal therapy for FSGS in terms of remission. The development of improvements in extracorporeal therapy, such as modified double filtration plasmapheresis (DFPP), may offer cost improvements due to reduced fluid replacement, which may lead to increased use in LMICs. Twinning programs and governmental intervention may be used to address the gaps in FSGS care in LMICs. Future efforts involve expanding access to plasmapheresis in the management of FSGS, especially in resource-limited settings.

Focal segmental glomerulosclerosis (FSGS) is a major cause of nephrotic syndrome and end-stage kidney disease (ESKD). Many cases are attributable to pathogenic variants in podocyte-related genes, such as inverted formin 2 (INF2). However, no specific treatment exists for hereditary FSGS, and experimental platforms that faithfully model podocyte injury remain limited. Therefore, in this study, we developed an injury model by generating induced pluripotent stem cells (iPSCs) from a patient with INF2-associated FSGS and differentiating them into kidney organoids. Podocytes were validated by immunofluorescence staining for podocyte-specific markers. We induced podocyte injury in this model using puromycin aminonucleoside (PAN) in a dose-dependent manner. Injury severity was quantified by measuring podocalyxin fluorescence intensity. Cyclosporine A (CsA) or voclosporin (VCS) was administered as a 1-h pretreatment before PAN exposure to evaluate their podocyte-protective effects. The kidney organoids exhibited well-defined podocyte marker expression, confirming successful differentiation. PAN exposure caused a significant and concentration-dependent reduction in podocalyxin fluorescence, indicating robust induction of podocyte injury in organoids harboring the INF2 variant. Pretreatment with CsA or VCS significantly attenuated PAN-induced podocyte injury and preserved podocyte marker expression. CsA and VCS reduced podocyte injury to similar extents. In conclusion, we established a patient-specific kidney organoid model of INF2-associated FSGS that reliably recapitulated podocyte vulnerability to toxic injury. This platform demonstrated that calcineurin inhibitors, including the novel agent VCS, exert direct podocyte-protective effects in a genetic FSGS background and provide a practical system for mechanistic studies and therapeutic screening.

Nephrologists often order genetic testing panels to clarify diagnoses in patients with diverse presentations of kidney disease. This was not the case 10 years ago, prior to the current era of precision medicine. In the past, elevated blood sugars and blood pressures were felt to be the primary factors that initiated diabetic and mislabeled "hypertensive" nephropathy. In addition, the markedly higher incidence rates of kidney failure in African Americans relative to European, Asian, and Hispanic Americans were poorly understood. This changed with recognition of marked familial aggregation of kidney failure, particularly in the African American population. The 2010 discovery of the apolipoprotein L1 gene (APOL1) association with chronic kidney disease demonstrated that two coding variants in a single gene caused more than 35% of kidney failure in African Americans. APOL1 explained ancestry-based disparities in incidence rates of nephropathy, as well as outcomes after kidney transplantation and live kidney donation. This manuscript reviews the APOL1 discovery and its resultant changes in our understanding of kidney disease susceptibility. Mechanisms of APOL1 injury in kidney cells and novel therapies are reviewed with an emphasis on gaps in existing knowledge and future directions.

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) and primary focal segmental glomerulosclerosis (FSGS) are distinct glomerular diseases that rarely occur together. When present concurrently, they may produce overlapping nephritic and nephrotic features that complicate diagnosis and management. We report a case of a 63-year-old man who presented with four weeks of progressive anasarca and several months of cognitive changes, blurry vision, and paresthesia. Investigations demonstrated nephrotic-range proteinuria (8.25 g per day), hypoalbuminemia, hematuria, acute kidney injury, and hypertension. Kidney biopsy demonstrated two concurrent pathologies: FSGS with complete podocyte foot process effacement and pauci-immune glomerulonephritis with focal active crescents. Serology confirmed proteinase 3 antibody (PR3)-ANCA positivity, establishing active AAV alongside primary FSGS. Treatment included pulse intravenous methylprednisolone followed by oral prednisone and rituximab for induction and maintenance of AAV. Because nephrotic syndrome persisted, calcineurin inhibitor therapy was initiated for steroid-resistant FSGS (cyclosporine followed by tacrolimus). Adjunctive antiproteinuric therapies included renin-angiotensin system blockade, sodium-glucose cotransporter-2 inhibition, and later a nonsteroidal mineralocorticoid antagonist. The patient eventually achieved partial remission with resolution of his nephrotic syndrome and undetectable PR3 titers. After 2.5 years of follow-up, kidney function stabilized at an estimated glomerular filtration rate (eGFR) of 29 mL/min/1.73 m2 with persistent urine albumin-to-creatinine ratio (ACR) of 163 mg/mmol despite maximal antiproteinuric therapy. Long-term complications included diabetes mellitus related to immunosuppression. This case illustrates the rare coexistence of primary FSGS and PR3-positive AAV requiring simultaneous treatment, with differing responses to therapy. It highlights the challenges of assessing treatment response in dual glomerular pathology while balancing aggressive immunosuppression against systemic toxicity. Incorporation of the patient perspective in this case report highlights the lived experience and burden of managing concurrent FSGS and AAV.

Takayasu arteritis (TAK) is a large-vessel vasculitis in which glomerulonephritis is a rare complication with a poorly characterized clinical and histopathological profile. Patients with biopsy-proven glomerulonephritis were retrospectively identified from a single-center TAK cohort followed between 2014 and 2022. A systematic review of PubMed/MEDLINE, Scopus, and Web of Science for articles published up to December 2025 was conducted in parallel, excluding studies involving patients younger than 18 years and cases with confounding autoimmune conditions or non-classifiable biopsy findings. This case-based review was reported in accordance with the CABARET and PRISMA 2020 standards. Among 72 patients with TAK, three (4.2%) had biopsy-proven glomerulonephritis. The systematic review yielded 31 articles describing 39 additional cases (84.6% female; median age at TAK diagnosis 26 years; median age at glomerular disease diagnosis 33 years). Glomerular disease was diagnosed a median of 5 years (IQR 0-11) after TAK and most often presented as asymptomatic proteinuria or nephrotic syndrome. Mesangial proliferative glomerulonephritis was the most common subtype (35.9%), followed by AA amyloidosis (30.8%), membranoproliferative glomerulonephritis (12.8%), focal segmental glomerulosclerosis (10.3%), and membranous nephropathy (7.7%). Renal artery stenosis was absent in 69.2% of cases. Corticosteroids were used in 92.3% of cases and biologic agents in 10.3%. Glomerulonephritis is a rare but clinically significant late complication of TAK, characterized by a distinct histopathological spectrum dominated by mesangial lesions, AA amyloidosis, and membranoproliferative glomerulonephritis. Routine proteinuria screening in patients with TAK, including during clinical remission, is warranted to enable early detection and timely management.

This narrative review examines acute and chronic kidney injury following COVID-19 infection and vaccination, discussing the mechanism of SARS-CoV-2 entry into host cells through the ACE2 receptor - highly expressed in renal tissues - facilitating the viral invasion. Viral RNA has been detected in the urine of patients infected with SARS-CoV-2, suggesting direct renal involvement. The incidence of acute kidney injuriy (AKI) among hospitalized COVID-19 patients was particularly higher in the early stages of the pandemic and largely varied by 29%-46%, depending on population studied and COVID-19 wave. Pathological findings include acute tubular injury (ATI), collapsing glomerulopathy, and focal segmental glomerulosclerosis. Major risk factors for AKI comprise older age, male sex, diabetes, hypertension, cardiovascular disease, and preexisting Chronic Kidney Disease (CKD). AKI significantly increases mortality of COVID-19 patients, particularly in advanced stages of renal failure. CKD is also associated with severe COVID-19 outcomes, including increased hospitalization, intensive care admission, and mortality. Patients with CKD show a dose-dependent relationship between disease stage and adverse patient outcomes. This review further addresses renal complications following COVID-19 vaccination, which, although rare, encompass various immune-mediated glomerular diseases. Minimal Change Disease (MCD) is most frequently reported after COVID-19 vaccination, followed by IgA nephropathy, membranous nephropathy, anti-glomerular basement membrane (anti-GBM) nephritis, and ANCA-associated vasculitis. These conditions commonly present with hematuria, proteinuria, or nephrotic syndrome, and many respond to corticosteroid or immunosuppressive therapy. Other less frequent renal complications include thrombotic microangiopathy, acute tubulointerstitial nephritis, and IgG4-related nephritis. In conclusion, both COVID-19 infection and vaccination can be associated with a spectrum of renal manifestations ranging from AKI to CKD and immune-mediated glomerulopathies. Awareness, early detection, and multidisciplinary management are essential to reduce renal morbidity and improve patient outcomes.

Mantle cell lymphoma (MCL) rarely causes glomerular disease. While immune complex-mediated and infiltrative lesions predominate, podocytopathies are exceptionally rare. We report a case of reversible focal segmental glomerulosclerosis (FSGS) occurring in the setting of blastoid-variant MCL, highlighting the paraneoplastic nature of the podocyte injury. A 69-year-old man presented with nephrotic syndrome and dialysis-dependent acute kidney injury (AKI). Kidney biopsy revealed FSGS. Subsequent diagnostic evaluation uncovered blastoid-variant MCL. Following lymphoma-directed chemotherapy, nephrotic syndrome resolved and renal function recovered, supporting a paraneoplastic mechanism of podocyte injury. This case underscores that MCL can induce a reversible paraneoplastic podocytopathy mimicking primary FSGS. Recognition of this entity is crucial to avoid unnecessary immunosuppression and to prompt early evaluation for underlying malignancy. Treating the neoplasm can result in renal recovery, emphasizing the functional connection between tumor activity and podocyte injury.