A 12-year-old girl presented with steroid-resistant nephrotic syndrome and was found on kidney biopsy to have membranous nephropathy with a full-house immunofluorescence pattern. At presentation, she had marked hypercholesterolemia, with an LDL-C level of 589 mg/dL, and a family history suggestive of familial hypercholesterolemia. Multiple immunosuppressive therapies resulted in only transient or insufficient improvement in proteinuria, while conventional lipid-lowering agents failed to control hypercholesterolemia. On hospital day 98, evolocumab was initiated for refractory hypercholesterolemia. LDL-C levels declined rapidly, and proteinuria subsequently improved during the clinical course. Corticosteroids were tapered and discontinued. Evolocumab was administered for three doses, and nephrotic remission was achieved during the subsequent clinical course and maintained for nearly 1 year. This case illustrates that evolocumab may be an effective lipid-lowering option for selected pediatric patients with nephrotic syndrome complicated by severe refractory hypercholesterolemia. The subsequent improvement in proteinuria should be interpreted cautiously as a temporal association.

Gut microbiota exert core regulatory effects on systemic metabolic homeostasis and immune balance under physiological and pathological conditions. Marked gut dysbiosis occurs during the progression of chronic kidney disease (CKD), characterized by abnormal enrichment of opportunistic pathogens and depletion of beneficial commensal bacteria. This pathological alteration leads to excessive accumulation of uremic toxins including indoxyl sulfate, p-cresyl sulfate and trimethylamine N-oxide (TMAO), as well as sharp reductions in the synthesis of intestinal protective metabolites such as short-chain fatty acids (SCFAs) and indole-3-aldehyde. The imbalance between harmful and protective metabolites persistently triggers renal inflammatory activation and interstitial fibrosis via activating multiple signaling pathways, including the renin-angiotensin system, oxidative stress, Toll-like receptor 4, aryl hydrocarbon receptor, IκB/NF-κB, Keap1/Nrf2, NLRP3 inflammasome and ferroptosis. This review systematically summarizes the pathological correlations between gut microbiota disturbance and various renal disorders, namely diabetic kidney disease, membranous nephropathy, lupus nephritis, IgA nephropathy, hypertension-associated nephropathy and dialysis-related renal injury, and clarifies the universal mechanisms and disease-specific characteristics underlying gut-kidney axis-mediated progression of different subtypes of kidney diseases. Natural products represented by natural polysaccharides, traditional Chinese medicine formulas and plant polyphenols are capable of remodeling gut microbiota composition, repairing intestinal mucosal barrier function, balancing microbial metabolic profiles and regulating gut-kidney axis homeostasis, thereby exerting renal and multi-organ protective effects in patients with CKD and dialysis-dependent individuals. Targeted modulation of intestinal microecology and intervention against gut-kidney axis dysfunction using natural products provide novel strategies for early prevention and control of CKD, disease progression retardation and prognosis improvement in dialysis patients, and also lay a theoretical foundation for the development and clinical translational application of novel therapeutic targets for kidney diseases.

Primary biliary cholangitis (PBC) is a chronic autoimmune cholestatic liver disease primarily affecting the intrahepatic small bile ducts. Although PBC is mainly a hepatobiliary disease, renal abnormalities have been reported in a subset of patients and should be regarded as uncommon but clinically relevant extrahepatic manifestations. Reported glomerular lesions in patients with PBC include membranous nephropathy, immunoglobulin A nephropathy, crescentic glomerulonephritis, and minimal change disease, although most evidence is derived from case reports and small series. Tubulointerstitial involvement has also been described, most commonly as distal renal tubular acidosis in reported cases and less commonly as Fanconi syndrome; these conditions may reflect immune-mediated tubular dysfunction in selected patients. In addition, metabolic disturbances secondary to cholestasis and tubular injury may increase the risk of nephrolithiasis and nephrocalcinosis, whereas advanced cirrhosis can precipitate hepatorenal syndrome. Limited reports further suggest that cholestatic nephropathy and drug-related nephrotoxicity may contribute to renal impairment in selected patients. From a mechanistic perspective, immune complex deposition, T-cell-mediated inflammation, mitochondrial dysfunction, cholestatic/metabolic disturbances, and gut microbiota dysbiosis have been proposed as potential contributors, but direct causal evidence remains limited. Given the heterogeneity and potential clinical significance of renal manifestations in PBC, early detection, thorough nephrological assessment, and individualized therapeutic strategies are essential.

Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare antineutrophil cytoplasmic antibody-associated vasculitis that typically presents with asthma, eosinophilia and small-to-medium vessel inflammation. Central nervous system infarction is an uncommon complication and typically occurs during active disease. Recurrent stroke despite apparent disease remission is rare and presents a diagnostic challenge.We report a man in his 60s with EGPA who developed recurrent multifocal cerebral infarcts. His initial presentation occurred in the context of marked eosinophilia and systemic inflammation, consistent with active vasculitis. However, subsequent cerebrovascular events occurred despite well-suppressed eosinophil counts and inflammatory markers. His later course was complicated by pulmonary embolism, iliac vein thrombosis, nephrotic-range proteinuria and autoimmune serological abnormalities, raising suspicion of a superimposed prothrombotic state. Renal biopsy, performed in view of nephrotic syndrome and initial autoimmune serology, demonstrated neural epidermal growth factor-like 1 protein membranous glomerulonephritis-to our knowledge a previously unreported association with EGPA.This case highlights the complexity of stroke mechanisms in EGPA and emphasises the importance of reconsidering alternative or additional contributors when cerebrovascular events recur despite apparent disease control.

Podocytes are terminally differentiated visceral epithelial cells that form the outermost layer of the glomerular filtration barrier. Through their foot processes and slit diaphragm structures, podocytes confer selective permeability to the glomerular filtration barrier and play a critical role in maintaining kidney function. Podocyte damage is characterized by foot process effacement, loss of slit diaphragm proteins, reorganization of the actin cytoskeleton, and apoptosis, and plays a central role in the pathogenesis of proteinuric glomerular diseases such as minimal change disease, focal segmental glomerulosclerosis, membranous nephropathy, and diabetic nephropathy. This narrative review examines podocyte biology, the main molecular pathways of podocyte damage (RhoA/ROCK, TGF-β, mTOR, and oxidative stress), the clinical presentations of podocytopathies, and treatment strategies ranging from RAAS blockade, SGLT2 inhibitors, cytoskeletal stabilizers, gene therapy, to regenerative medicine approaches. By highlighting recent findings and translational challenges, the importance of podocyte-focused therapies in glomerular diseases is emphasized. Future studies aim to preserve podocyte integrity and prevent progressive kidney disease through personalized molecular therapies and multidisciplinary research.