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.

Older adult patients with acute-onset minimal change nephrotic syndrome (MCNS) often have difficulties with exercise therapy due to uremia caused by severe generalized edema and acute kidney injury (AKI). Rehabilitation treatment targeting increased light-intensity physical activity (LPA) is typically implemented to address this limitation. An 81-year-old man with suspected MCNS complicated by stage I AKI was admitted to our hospital. The patient's short physical performance battery (SPPB) score was 10 points, while his total physical activity (TPA) was 411 steps per day. To increase his LPA, the patient performed resistance exercises in the sitting position and standing activities with support under supervision five times per week at low load and high frequency. Physical activity education with self-monitoring using an activity meter and check sheet was also implemented during the unmonitored periods. After uremia and other symptoms improved, aerobic and resistance exercises were added. At discharge, the patient's moderate-vigorous physical activity (MVPA) increased from 0.1 to 3.2 minutes per day; his LPA increased from 5.1 to 34.6 minutes per day; and his TPA increased from 411 to 3,233 steps per day. His SPPB score improved from 10 to 12 points, while the motor component of the functional independence measure (FIM) increased from 66 to 82 points, leading to improved activities of daily living (ADL). These results indicate that LPA-focused rehabilitation treatment in older patients with MCNS and AKI is both effective and feasible, potentially contributing to improved physical activity and ADL and facilitating the transition to exercise therapy after clinical improvement.

Relapsing polychondritis (RP) is a rare autoimmune disorder with minimal reported renal involvement. We describe the first case of tip lesion variant of focal segmental glomerulosclerosis (FSGS) in a 60-year-old male with familial RP. The patient initially presented with nephrotic syndrome concomitant with RP, which was diagnosed 17 years ago; renal biopsy revealed minimal change disease at that time. Over the subsequent 17 years, he experienced four RP flares without nephrotic syndrome recurrence until his recent presentation with severe nephrotic syndrome. Repeated renal biopsy confirmed tip lesion variant of FSGS, demonstrating excellent response to corticosteroid therapy with prednisolone 1 mg/kg/day; proteinuria declined from 7g/24h to 0.98g/24h and serum albumin increased from 0.9g/dL to 2.2g/dL within three months. This case underscores the importance of considering FSGS in RP-associated nephrotic syndrome and suggests potential shared immune/genetic mechanisms. To our knowledge, this represents both the first report of tip lesion FSGS in RP and the first documented familial RP case with FSGS development.

Serum protein electrophoresis (SPEP) is commonly used in the diagnostic evaluation of nephrotic syndrome (NS) to rule out monoclonal gammopathies. However, NS itself and various other factors may cause transient bisalbuminemia, resulting in albumin fraction irregularities in capillary SPEP and complicating interpretation. This study proposes a stepwise approach for interpreting albumin fraction irregularities, illustrated through three representative cases of NS. Case 1: a 44-year-old woman with isolated proteinuria, Case 2: a 36-year-old woman with diabetic foot infection, and Case 3: a 58-year-old man with ankylosing spondylitis, all presenting with nephrotic-range proteinuria. On initial SPEP case 1 exhibited a distinct sharp peak, while cases 2 and 3 showed irregular bands between the albumin and α1 regions. A stepwise interpretative approach was applied: First, technical errors were excluded by repeat analysis using alternative capillaries on the same analyzer. Second, potential biochemical interferences were evaluated. Third, SPEP was repeated using freshly collected samples. Fourth, persistent albumin fraction irregularities prompted consideration of biochemical albumin modifications, such as glycosylated or carbamylated forms. Fifth, other causes including drugs, heavy metal toxicity, liver disease, and systemic inflammation were excluded. Finally, additional tests such as immunofixation electrophoresis were performed to rule out monoclonal proteins. In the absence of monoclonal proteins, the condition was interpreted as bisalbuminemia related to NS. Using this approach, transient bisalbuminemia was considered the most likely cause in Cases 1 and 2, whereas the disappearance of the irregular band in Case 3 suggested a preanalytical artifact. Systematic interpretation of albumin fraction irregularities can help distinguish true pathology from benign or artifactual patterns in patients with NS.

Familial Amyloidosis of Finnish type (FAF) is a rare autosomal dominant hereditary amyloidosis associated with genetic variants of gelsolin. This condition is characterized by ophthalmologic abnormalities, progressive cranial neuropathy, and cutis laxa, while renal impairment is rare. We report a gelsolin amyloidosis in a 58-year-old man with nephrotic syndrome and slowly progressive kidney dysfunction, associated with a gelsolin gene mutation (c.480C > A, p.Asn160Lys). Initial renal biopsy showed segmental IgA deposition, moderate mesangial expansion with weak PAS positivity, and parallel bundles of 10 nm fibrils, but only trace Congo red staining. A second biopsy 2 years later revealed IgA-dominant deposition, nodular sclerosis, similar fibrils, glomerular basement membrane lamination, and weakly positive Congo red. The diagnosis of gelsolin amyloidosis was confirmed by mass spectrometry and immunohistochemistry. Clinically, the patient had no neuropathy or family renal disease but presented with gastrointestinal symptoms, and endoscopy confirmed vascular amyloid deposition. Molecular structure analysis suggested that the mutation may loosen the protein structure while preserving its calcium-binding ability. Combining with the literature, we discuss the clinicopathological features and predicted protein functions of mutated gelsolin, aiming to elucidate its pathogenic mechanisms and deepen the understanding of hereditary amyloidosis.

Kidney diseases, including acute kidney injury (AKI), chronic kidney disease (CKD), nephrotic syndrome (NS) and diabetic nephropathy (DN), represent a major global public health concern. Salvianolic acids are water-soluble bioactive components from Salvia miltiorrhiza, among which salvianolic acid A (SAA), salvianolic acid B (SAB) and salvianolic acid C (SAC) are the focus of current research. This review systematically elaborates their renoprotective value, establishes a clear pharmacokinetic-pharmacodynamic (PK-PD) correlation, summarizes multi-target protective effects in multiple kidney disease models, and conducts in-depth horizontal comparisons of efficacy intensity, target affinity and pathway specificity among the three components, key pharmacokinetic parameters including half-life (T1/2), time to peak concentration (Tmax), peak plasma concentration (Cmax), and area under the curve (AUC). Low oral bioavailability, rapid metabolism and insufficient renal distribution are common bottlenecks that restrict therapeutic efficacy, especially long-term anti-fibrotic activity and chronic intervention effects. Accordingly, promising strategies such as kidney-targeted nanodelivery systems and structural modification are proposed, and the mechanism of enhancing efficacy by optimizing pharmacokinetic properties is clarified. This review improves the mechanistic understanding of salvianolic acids, strengthens the horizontal comparison of three components, and supports their further translation into clinical therapies.

Minimal change disease (MCD) is a common cause of nephrotic syndrome in adults. Rituximab, a type I anti-CD20 antibody, is effective in many cases, but up to 40% of patients show an insufficient or transient response. Obesity, a frequent comorbidity, is associated with chronic low-grade inflammation and B-cell dysfunction, which may contribute to suboptimal treatment outcomes. Obinutuzumab, a type II anti-CD20 antibody, induces more profound B-cell depletion than rituximab. We report two obese patients (BMI 32.10 and 42.45 kg/m2) with biopsy-confirmed MCD who had an insufficient response to multiple immunosuppressive therapies, including rituximab. Patient 1 achieved complete remission with corticosteroids and tacrolimus; obinutuzumab (1 g) was added to enable rapid steroid withdrawal due to severe corticosteroid-induced acne. He remained in remission for >26 months after obinutuzumab, with CD19+ B-cell counts showing complete depletion (0 cells/μL), a rise to 103 cells/μL at 9 months (prompting a second dose). Patient 2 received obinutuzumab (1 g) for active disease after rituximab failure. He achieved complete remission but relapsed after immunosuppressant withdrawal. CD19+ B-cells had reconstituted to 75 cells/μL at relapse; a second obinutuzumab dose re-induced depletion (0 cells/μL) and remission, which was maintained at last follow-up. These observations suggest that obinutuzumab may induce and sustain remission in some obese patients with rituximab-insufficient MCD, and that obesity should be considered a potential modifier of treatment response in MCD.

The purpose of this commentary is to review the 2025 Kidney Disease Improving Global Outcomes (KDIGO) clinical practice guidelines on the management of childhood nephrotic syndrome (NS) within the Canadian context and based on current practices across the country.

Proteinuria in children is most often transient or orthostatic. However, the diagnosis and treatment of persistent proteinuria may significantly impact long-term health outcomes, as persistent proteinuria is both a sign of underlying kidney pathology as well as a modifiable risk factor for progression of kidney disease. The differential diagnosis of proteinuria differs depending on whether proteinuria is glomerular or tubular. This article reviews the pathophysiology, evaluation, and management of proteinuria, including an emphasis on the management of idiopathic nephrotic syndrome.