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.

The manifestations of renal diseases that precede CKD vary among populations and have changed over time. We investigated biopsy-proven renal diseases in patients from Northwest China over a 10-year period. We retrospectively analyzed data from 3514 renal biopsies performed at our center from January 2014 to December 2023 and compared the presentations (indications for biopsy) and clinicopathological diagnoses during two periods: 2014-2018 vs. 2019-2023. Overall, primary glomerulonephritis (PGN) was the most common pathology (72.23%), followed by secondary glomerulonephritis (SGN, 21.35%), and tubulointerstitial diseases (2.79%). Membranous nephropathy (MN, 26.60%) and IgA nephropathy (IgAN, 24.02%) were the main diagnoses in patients with PGN. The proportion of PGN patients with MN and IgAN was greater during the latter period, but the proportion of those with focal segmental glomerular sclerosis was greater during the earlier period (all P < 0.05).Among SGN patients during the later period, the proportion of those with lupus nephritis (LN) and Henoch-Schönlein purpura nephritis (HSPN) was lower and proportion of those with diabetic nephropathy (DN) was greater (all P < 0.05). This descriptive study in Northwest China showed that NS was the main indication for renal biopsy, PGN was the most common diagnosis, and MN was the predominant type of PGN. The proportions of MN and DN were greater in 2019-2023 than in 2014-2018, but the proportions of LN and HSPN had the opposite pattern. These results provide a foundation for future studies that seek to prevent CKD and improve patient outcomes.

We aimed to evaluate the clinical and genetic characteristics and clinical course of children with persistent proteinuria associated with CUBN variants. Forty-eight children with CUBN variants from 15 pediatric nephrology centers were included. Patients' characteristics, serum creatinine, albumin, hemoglobin, vitamin B12 levels, urinalysis, spot urine protein/creatinine (uPCR), microalbumin/creatinine (uACR), beta-2 microglobulin/creatinine (uBMCR) ratios, estimated glomerular filtration rates (eGFRs), treatments, kidney biopsies, and genetic findings were evaluated. All patients had normal serum albumin and creatinine and preserved eGFR. There was no significant change in eGFR between the first and last visits (p = 0.15), whereas uPCR was lower at the last visit (p = 0.001). Kidney biopsy was performed in 13 (27%); light microscopy was normal in all except one patient with focal segmental glomerulosclerosis (FSGS). Thirty-five patients (72.9%) had ACEi/ARB therapy, which was discontinued in 21 patients without subsequent worsening of proteinuria. Overall, 26 distinct CUBN variants were identified, predominantly in the C-terminal region. The most frequent variant was c.10102A > G (p.Met3368Val). Variant types included 15 (57.7%) missense, 7 (27%) nonsense, 3 (11.5%) splicing, and 1 (3.8%) frameshift variants. In this multicenter, large pediatric cohort, proteinuria associated with CUBN variants generally followed a benign course over short to mid-term follow-up even without sustained ACEi/ARB therapy. Embedding targeted CUBN testing into the evaluation of children with asymptomatic proteinuria and normal kidney function may reduce unnecessary kidney biopsies and prolonged medication, while improving family counseling. We outline a stepwise care pathway → early genetic screening → conservative monitoring with periodic eGFR and proteinuria assessment → consideration of ACEi/ARB discontinuation and recommend prospective validation and cost-effectiveness studies.

Reduced podocyte stiffness is a feature of proteinuric kidney disease.

Oligomeganephronia (OMN) is a rare congenital renal hypoplasia characterized by markedly reduced nephron number with compensatory glomerular hypertrophy. Although typically diagnosed in childhood, adult-onset OMN is uncommon and often under-recognized. A 29-year-old man born at 28weeks of gestation as one of triplets, with a birth weight of 740g, was referred for evaluation of persistent proteinuria. Proteinuria had been intermittently detected for 10years but remained uninvestigated. Three months before admission, the urinary protein-to-creatinine ratio increased to 1.20g/gCr with serum creatinine 1.54mg/dL. He had engaged in regular resistance exercise and consumed protein supplements. On admission, urinary β2-microglobulin was mild elevated, and a discrepancy between creatinine- and cystatin C-based estimated glomerular filtration rate (eGFR) was observed, whereas inulin clearance was preserved. Kidney biopsy revealed markedly enlarged glomeruli, reduced glomerular density, and perihilar variant focal segmental glomerulosclerosis, consistent with OMN with secondary hyperfiltration injury. Treatment with losartan resulted in a rapid reduction in proteinuria and stable renal function over 9months. This case illustrates that latent OMN in individuals born extremely preterm may remain subclinical until additional hyperfiltration stressors precipitate overt renal injury. Early recognition and renin-angiotensin system inhibition can ameliorate proteinuria and stabilize renal function.

Anti-drug antibody (ADA) formation against rituximab (RTX) may affect treatment efficacy, safety, and B-cell depletion kinetics, yet data across different immune-mediated diseases remain limited. We evaluated ADA formation in 1312 blood samples from 300 patients with various autoimmune systemic and kidney-affecting diseases treated by rituximab (RTX) to describe the formation frequency and titers of ADA. ADA positivity was found in 54 patients and typically paralleled B-cell reconstitution. ADAs were significantly more frequent in diagnoses with overall worse response to RTX treatment (membranous nephropathy (MN), systemic lupus erythematosus, focal-segmental glomerulosclerosis (FSGS) and other less frequent diagnoses) compared with standard-response diagnoses (ANCA associated vasculitis (AAV) and minimal change disease). The pattern of ADA formation differed between diagnoses-in AAV ADAs were usually detected in low titers and transiently, in MN ADA titers were higher and more sustained and in FSGS ADA titers were sometimes unmeasurably high and occurred rather early during the treatment. We were not able to evaluate the interference of ADA formation or their titers with clinical response as some of our patients obtained robust response even after formation of unmeasurably high ADA titers. ADA formation frequency and titers markedly differ between different autoimmune diseases, therefore the frequency of their formation and their clinical significance should be evaluated separately in patients with different diagnoses.

PIK3CA-related overgrowth spectrum (PROS) comprises mosaic gain-of-function variants in PIK3CA that lead to segmental overgrowth and complex vascular malformations. Renal involvement has been inconsistently described and mainly includes glomerulomegaly and focal segmental glomerulosclerosis. We report a 39-year-old woman with a phenotypic diagnosis of CLOVES syndrome molecularly supported by a somatic mosaic PIK3CA variant, NM_006218.4:c.1634A > C, p.Glu545Ala, detected in affected hypertrophic tissue. She presented with acute kidney injury and subnephrotic-range proteinuria secondary to left renal vein thrombosis. Imaging revealed intrarenal venous congestion in the setting of extensive abdominal venous malformations. Anticoagulation resulted in complete radiologic and functional recovery. Renal vein thrombosis should be considered as a potentially reversible vascular cause of acute kidney injury and proteinuria in patients with CLOVES syndrome/PROS, particularly in the presence of extensive venous malformations.

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 4months 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 10months 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.

Pathogenic variants in COL4A3, COL4A4, JAG1, and NPHS2 genes in focal segmental glomerulosclerosis: Insights from targeted gene panel sequencing

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 18years 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 26years; median age at glomerular disease diagnosis 33years). Glomerular disease was diagnosed a median of 5years (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.

Anemia is a frequent but often underrecognized complication of primary glomerulonephritis (PGN). This study aimed to determine the prevalence and determinants of anemia in a large multicenter PGN cohort, with particular focus on immunoglobulin A nephropathy (IgAN), and to evaluate its clinical, laboratory, and histopathological correlates. Data were retrieved from the Turkish Society of Nephrology Glomerulonephritis Database (TSN-GOLD). A total of 5,500 patients with biop-valuesy-proven PGN were included, of whom 1,571 (28.6%) had IgAN. Demographic, clinical, laboratory, and histopathological findings were analyzed. Anemia was defined according to World Health Organization criteria. Multivariate logistic regression was used to identify independent risk factors for anemia. The prevalence of anemia was approximately 35% in both the overall PGN cohort and the IgAN subgroup. Patients in the lowest hemoglobin tertile (< 11.8g/dL) were older, had lower eGFR, serum albumin, and total protein, as well as higher serum creatinine, urea, and inflammatory markers. Histologically, mesangial hypercellularity, interstitial inflammation, and particularly tubular atrophy/interstitial fibrosis (T1-T2) were more common in this group. Multivariate analysis identified older age, female sex, lower eGFR, hypoalbuminemia, and advanced tubular atrophy as independent risk factors for anemia. Importantly, PGN subtype was also an independent determinant: compared with IgAN, membranoproliferative GN carried a markedly higher anemia risk, whereas minimal change disease and focal segmental glomerulosclerosis showed lower risk. Anemia is a common and clinically relevant comorbidity in PGN, strongly associated with both functional and structural renal impairment. Beyond reduced kidney function, disease-specific mechanisms contribute to anemia in IgAN, including chronic low-grade inflammation and recurrent hematuria. Recognition of PGN subtype as an independent determinant underscores the need for tailored evaluation and management of anemia in these patients. This study was registered retrospectively in an appropriate clinical trial registry.

ImportanceRecently, proteinuria has been accepted as a surrogate end point for clinical trials in focal segmental glomerulosclerosis (FSGS) ang IgA nephropathy. However, proteinuria has not been evaluated in Apolipoprotein L1 (APOL1)-mediated kidney disease (AMKD).MethodsReal world data (RWD) analysis of 128 patients of African ancestry with APOL1 high risk genotypes, without diabetes, enrolled in the Million Veteran Program (MVP; n=109) or the biorepository at Vanderbilt University (BioVU; n=19), who had urine albumin-creatinine ratio (UACR) >= 420 mg/g (PCR∼0.9 g/g) with a concurrent GFR value. The main predictor was change in the log-UACR at 12 months. The primary outcome was annual GFR slope over 24 months. Secondary outcomes included a kidney composite of a sustained 30% GFR decline, end stage kidney disease (ESKD) or death and ESKD as a single outcome. Linear regression and Cox proportional hazards models were used to assess the effect of changes in UACR and the outcomes.ResultsIn the pooled analysis the mean age was 56.8 (SD 15.5) y, 116 were male (90.6%) and three patients had diagnosis of FSGS at baseline. Mean baseline eGFR was 46.8 (SD 16.1) mL/min/1.73m2, mean baseline UACR was 1240.8 (1107.7) mg/g, mean eGFR slope was - 4.67[-6.00, -3.33] mL/min/1.73m2/year and the geometric mean percentage changes in the UACR at 12 months were -57.5% [-65.0%, -48.4%]. For every 1 unit of log (UACR) increment at 12 months, the annual eGFR slope decreased by -1.80 [-2.56, -1.03] mL/min/1.73m2in the pooled analysis. For every 1 unit of log (UACR) increment at 12 months, the Cox regression showed a 61% increase in the risk of a kidney composite (p=0.002) and a 98% increase in the risk of ESKD (p<0.001). It was estimated that a 50% reduction of UACR at 12 months was associated with a 28% reduction in the kidney composite endpoint (adjusted hazard ratio [aHR]=0.72; 95% confidence interval [CI]:0.59-0.88; p=0.002), and a 38% reduction in the risk of ESKD (aHR=0.62; 95% CI:0.49-0.80; p<0.001).Conclusions and relevanceChanges in UACR at 12 months significantly modify the rate of decline of GFR over 24 months and clinically meaningful endpoints, supporting the use of UACR changes as surrogate endpoint in AMKD.

Immunoglobulin M nephropathy (IgMN) is a pathological term defining glomerulonephritis with IgM deposition. The clinical significance is still a matter of debate. The aim was to evaluate children with IgM nephropathy (IgMN) in terms of clinical and pathological features, along with treatment responses and outcomes. The children with idiopathic nephrotic syndrome (INS) who underwent kidney biopsy at our center (n=41) were evaluated retrospectively. Twenty-one children with IgMN were included. The female to male ratio was 0.9, the median age was 3.5 years in the study group. The mean disease duration and follow-up periods were 11.8 and 11.3years, respectively. At admission, 14% of the patients had hypertension, and 19% had microscopic hematuria. Steroid-dependent nephrotic syndrome (SDNS) was observed in 62% of the patients at admission and 81% at last visit. The patients with IgM (≥2+) depositions had more SDNS than those with IgM (1+). The most common light microscopic diagnosis was mesangial proliferative glomerulonephritis (MesPGN) (47.6%). Focal segmental glomerulosclerosis (FSGS) elevated significantly from 14% at initial biopsy to 57% at follow-up biopsies. Patients who progressed to FSGS mostly had C3 co-deposition, high IgM intensity (≥2+), diagnosis of MesPGN, and SDNS clinic. The most frequently used adjuvant agent was cyclosporine-A (n=19) with mean duration of 68 months. It provided lower relapse rates. Rituximab (n=4) showed 75% remission rate. None of the patients had needed renal replacement treatment. Two patients who were steroid-resistant at admission had FSGS in their first biopsies, acted as multi-drug resistance at follow-up, and ended up in Stage-2 chronic kidney disease (CKD). This study shows IgMN is mainly presented with SDNS clinic and MesPGN pathology. Evolution to FSGS may be related to steroid resistance, MesPGN, high IgM intensity, and C3 co-deposition.

Glomerular diseases are a leading cause of chronic kidney disease (CKD) and kidney failure. Finerenone, a nonsteroidal mineralocorticoid receptor antagonist, reduces the risk of kidney function loss in CKD, but its effects in individuals with CKD due to glomerular diseases are uncertain. To evaluate the efficacy and safety of finerenone in patients with glomerular diseases. Prespecified exploratory subgroup analysis of a phase 3, randomized, double-blind, placebo-controlled trial conducted across 24 countries and regions, focusing on participants with an investigator-reported glomerular disease diagnosis. The overall trial enrolled adults with nondiabetic CKD and an estimated glomerular filtration rate (eGFR) of either (1) at least 25 to less than 60 mL/min/1.73 m2 and urinary albumin to creatinine ratio of at least 200 mg/g to less than 500 mg/g or (2) an eGFR of at least 25 to less than 90 mL/min/1.73 m2 and urinary albumin to creatinine ratio of at least 500 mg/g to less than 3500 mg/g. Finerenone 10 mg or 20 mg taken orally once daily (n = 446) vs matching placebo (n = 457). Annualized rate of eGFR decline (total eGFR slope) from baseline to month 32 (primary outcome of the main trial); percent change in albuminuria to 12 months; and a composite outcome of kidney failure or sustained 40% or more decline in eGFR (prespecified exploratory outcomes). Of 1584 participants, 903 (57.0%) had investigator-reported glomerular disease, including 416 (46.1%) with immunoglobulin A nephropathy, 215 (23.8%) with focal segmental glomerulosclerosis, and 90 (10.0%) with membranous nephropathy. Participants with glomerular disease (mean [SD] age, 51.1 [13.6] years; 362 female [40.1%]; 558 Asian [61.9%]) had a mean eGFR of 48.8 mL/min/1.73 m2 and median urinary albumin to creatinine ratio of 839.6 mg/g. The total eGFR slope up to 32 months was -3.50 mL/min/1.73 m2 per year with finerenone and -4.23 mL/min/1.73 m2 per year with placebo (0.73 mL/min/1.73 m2 per year difference; 95% CI, 0.22-1.24). Finerenone reduced albuminuria at month 12 by 42% (95% CI, 35%-48%) and lowered the risk of kidney failure or 40% or more eGFR decline (7.42 vs 9.60 events per 100 patient-years; hazard ratio, 0.74; 95% CI, 0.57-0.97). In this exploratory analysis, treatment with finerenone slowed kidney function decline, reduced albuminuria, and lowered the risk of kidney failure or substantial loss of kidney function in patients with glomerular diseases. These findings suggest an important role for finerenone in preserving kidney function in this population. ClinicalTrials.gov Identifier: NCT05047263.

Air pollution is increasingly recognized as a risk factor for progression of kidney disease; however, few studies have examined its impact among patients with primary glomerular disorders. To address this knowledge gap, we previously reported positive associations between fine particulate matter ≤ 2.5μm in aerodynamic diameter (PM2.5) and black carbon with kidney disease progression in an observational cohort of children and adults (n = 925) with primary glomerular diseases, namely minimal change disease, focal segmental glomerulosclerosis, membranous nephropathy, and IgA nephropathy. In the current study, we leverage the same cohort to (1) identify additional air pollutants that may be associated with kidney disease progression using data from the National Center for Atmospheric Research (NCAR); (2) determine whether the association between baseline air pollution exposure and kidney disease progression is maintained over a longer follow-up period; and (3) assess whether associations identified in our previously published findings remain when using NCAR pollutant data. In this retrospective cohort study, we obtained air pollutant concentration data from NCAR based on participant residential census tract at enrollment. For each census tract and pollutant, we aggregated daily pollutant concentrations to annual averages. We used Cox proportional hazards models to estimate associations between average baseline pollutant exposure and time to kidney disease progression, defined as a 40% decline in estimated glomerular filtration rate (eGFR) or occurrence of kidney failure (eGFR) < 15 ml/min/1.73 m2) during follow-up. Hazard ratios (HR) represented a doubling of exposure. Use of NCAR data supported our previous findings of adverse effects of PM2.5 and black carbon on the progression of glomerular disease. Moreover, using the NCAR data we identified novel associations with NO2 exposure, HR 1.12 [1.01, 1.26] and specific components of PM2.5, including organic matter, HR 1.17 [1.01, 1.37] and an increased risk of disease progression. When considering a longer follow-up period, associations between baseline exposures and kidney outcomes persisted, but were attenuated suggesting a need for recent, interval-specific risk assessment, inclusion of acute exposures, and enhanced spatial resolution of exposures. Our findings highlight the importance of the systematic assessment including spatial and temporal variation of a broad range of air pollution components to determine the impact of exposure on short- and long-term outcomes in patients with primary glomerular disease (word count: 368).

Chronic kidney disease (CKD) is a major global health burden that disproportionately impacts people of recent African ancestry. The discovery of risk variants in the apolipoprotein L1 (APOL1) gene has transformed the understanding of racial disparities in CKD. In particular, APOL1 variants have been associated with increased risk of focal segmental glomerulosclerosis, virus-associated nephropathy, and other glomerular diseases in Black adults. While approximately 10-15% of Black Americans have a high-risk APOL1 genotype, disease penetrance is variable and is likely mediated by additional genetic and environmental "second hits." Variants in APOL1 have also been implicated in kidney transplant outcomes and pregnancy complications, underscoring its broad clinical relevance. Advances in therapeutic strategies, including small molecule inhibitors of APOL1 pore function, APOL1 antisense oligonucleotides, and JAK-STAT pathway modulation, offer promise for targeted interventions in adult populations. Emerging data in children highlight similar genotype-phenotype associations, with evidence of high-risk APOL1 genotype impacting steroid-resistant nephrotic syndrome and CKD progression. However, pediatric studies remain limited and underpowered, leaving critical gaps in the understanding of disease epidemiology, mechanisms, and long-term outcomes. This review will explore current knowledge of APOL1 kidney disease (AMKD) with a particular focus on pediatric populations and highlight the need for inclusion of children in future studies.

Persistent proteinuria in children is commonly attributed to glomerular diseases; however, atypical clinical features should prompt evaluation for alternative etiologies. We report a 10-year-old boy presenting with persistent isolated non-nephrotic proteinuria without edema, hypoalbuminemia, hypertension, or systemic illness. Renal function and lipid profile were normal. The patient showed no response to corticosteroids and mycophenolate mofetil. Renal biopsy demonstrated focal segmental glomerulosclerosis involving approximately 2% of glomeruli, with negative immunofluorescence and mild podocyte foot process effacement. Genetic testing revealed a homozygous pathogenic mutation in the CUBN gene, confirming tubular proteinuria. Following comprehensive clinicopathological correlation, immunosuppressive therapy was discontinued, and the patient remained clinically stable on conservative management during follow-up.

The relationship between APOL1 risk variants and with preeclampsia and fetal outcomes.