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.

BACKGROUNDAcute interstitial nephritis (AIN) is a common cause of acute kidney injury (AKI), but the diagnosis may be missed as kidney biopsies are rarely obtained when acute tubular injury (ATI) is suspected.METHODSThe Kidney Precision Medicine Project is a cohort study that obtains kidney biopsies from individuals with AKI, which undergo pathologic and molecular interrogation. We compared ATI and AIN cases among the first 60 AKI participants.RESULTSOn clinicopathologic adjudication, 30 patients (50%) had a primary adjudicated diagnosis of ATI, 13 (22%) patients had AIN, 9 (15%) had diabetic nephropathy, and 3 (5%) had other conditions. There were increased interstitial white blood cells and tubulitis (P < 0.05 for both) in AIN compared with ATI. Prior to biopsy, the treating clinician suspected ATI in 83% of the cases with adjudicated ATI, while the treating clinician suspected AIN in 54% of the cases with AIN. Tissue transcriptomic signatures showed enrichment of proinflammatory signaling and increased expression of CXCL9, a chemokine induced by IFN-γ, in myeloid cells of participants with AIN. CXCL9 localized to inflammatory infiltration in spatial transcriptomic data.CONCLUSIONAdjudication of kidney biopsies revealed distinct pathologic and molecular profiles between ATI and AIN. Kidney biopsy should be considered more frequently in AKI, as AIN is clinically underrecognized.TRIAL REGISTRATIONClinicalTrials.gov NCT04334707.FUNDINGNational Institute of Diabetes and Digestive and Kidney Diseases grants U01DK133081, U01DK133091, U01DK133092, U01DK133093, U01DK133095, U01DK133097, U01DK114866, U01DK114908, U01DK133090, U01DK133113, U01DK133766, U01DK133768, U01DK114907, U01DK114920, U01DK114923, U01DK114933, U24DK114886, UH3DK114926, UH3DK114861, UH3DK114915, and UH3DK114937.

Chronic cough in patients with systemic lupus erythematosus can be difficult to evaluate, especially when initial testing is unrevealing. We report the case of a 33-year-old woman with long-standing systemic lupus erythematosus, biopsy-proven lupus nephritis, prior extrapulmonary pericardial tuberculosis, and no active or passive smoking exposure who developed a persistent dry cough for six months. She was initially treated for gastroesophageal reflux disease with pantoprazole, without meaningful relief. Chest radiography and swallowing assessment were normal. Initial pulmonary function testing in July 2023 was formally interpreted as moderate obstructive airways disease, mild parenchymal restriction, and a moderately severe diffusion defect, without a significant bronchodilator response. High-resolution volumetric computed tomography of the chest with dynamic airway assessment showed no emphysema, bronchiectasis, interstitial lung disease, tracheomalacia, or acute cardiopulmonary process. Her cough improved substantially after inhaled therapy with albuterol and budesonide/glycopyrrolate/formoterol fumarate. Repeat pulmonary function testing in October 2023 showed improved spirometric values, but the forced expiratory volume in one second/forced vital capacity ratio remained preserved, and hemoglobin-adjusted diffusing capacity remained reduced at 64% predicted. This case highlights a diagnostic pitfall: inhaler-responsive chronic cough and a pulmonary function report suggesting obstruction should be evaluated together with post-bronchodilator spirometry, diffusing capacity, imaging, and exposure history. In systemic lupus erythematosus, a persistent cough may be associated with clinically relevant pulmonary function abnormalities even when chest imaging is unrevealing.

The long-term renal implications of conditions leading to male reproductive surgeries remain unclear. This study evaluated the potential causal relationships between genetic liability to undergoing these surgeries and kidney diseases. Genetic variants associated with four surgery-related phenotypes-testicular hydrocele surgery, testicular or scrotal surgery, circumcision, and vasectomy-were selected as instrumental variables. Mendelian randomization, meta-analysis, and exploratory mediation analyses were used to assess associations with 20 kidney outcomes. Results showed genetic liability to testicular hydrocele surgery was associated with higher odds of chronic kidney disease, IgA nephropathy, glomerulonephritis, cystic kidney disease, tubulo-interstitial nephritis, and kidney injury, and with lower odds of benign kidney tumors and renal stones. Genetic liability to testicular or scrotal surgery was associated with increased odds of renal colic, gout, malformations of the renal pelvis or ureters, renal stones, and kidney infections. Genetic liability to circumcision was associated with higher odds of congenital obstructive malformations, hypertensive heart/renal disease, malignant kidney neoplasms, and increased kidney volume, and with lower odds of kidney cysts, benign tumors, and chronic renal failure. Genetic liability to vasectomy was linked to reduced odds of pyelonephritis and malignant kidney neoplasms. Mediation analyses suggested partial contributions of immune and metabolic traits. This study provides evidence that genetic liability to undergoing male reproductive system surgeries-reflecting the underlying biological or pathological indications-is associated with distinct patterns of kidney disease susceptibility. Findings suggest that individuals with underlying conditions predisposing them to testicular hydrocele or scrotal surgery may benefit from attention to long-term kidney health.

Tubulointerstitial nephritis (TIN) with IgM-positive plasma cells (IgMPC-TIN) is an inflammatory disease characterized by the infiltration of IgM and CD138 dual-positive plasma cells into the renal interstitium. Steroid treatment is effective for many cases of IgMPC-TIN. However, the optimal dose and duration of steroid therapy remain poorly understood. In the present case, IgMPC-TIN was diagnosed in a 36-year-old woman with femoral head osteonecrosis. After administration of prednisolone (PSL, 20 mg/day), several markers of disease activity gradually decreased. The PSL dose was tapered to 5 mg/day for one year without TIN recurrence. To avoid exacerbation of bone lesions due to prolonged administration of PSL, cyclosporine was added to PSL. Combination treatment with 5 mg/day PSL and 100-125 mg/day cyclosporine stabilized the TIN. The patient remained stable without recurrence after further reduction and discontinuation of PSL. This case provides original evidence regarding the optimal treatment regimen for patients with IgMPC-TIN who are unsuitable for prolonged PSL administration.

Acute interstitial nephritis (AIN) is an immunologically mediated cause of acute kidney injury (AKI), most often drug-induced, with NSAIDs being a leading culprit. We present a 39-year-old woman who developed biopsy- proven AIN following a single intramuscular dose of ketorolac, an exceptionally short latency likely due to prior sensitization. Despite lacking classic systemic features, she exhibited non-oliguric AKI that improved rapidly with corticosteroids. This case underscores that NSAID-induced AIN can occur even after minimal exposure, highlighting the importance of early recognition, drug withdrawal, and timely steroid therapy to optimize renal recovery.

Sarcoidosis is a multisystemic inflammatory disease of unknown etiology with more frequent lung and lymph node involvement. Despite kidney involvement occurring between 25% and 43%, it may be underdiagnosed, with interstitial granulomatous nephritis and nephrocalcinosis being the most common features, and glomerular disease being less frequent.

Cancer immunotherapies, particularly immune checkpoint inhibitors (ICIs), have proven to be a very effective and well-established type of therapy for advanced malignancies. Although generally considered well tolerated, immune-related adverse events, which can sometimes be severe, do occur. Unlike other types of adverse events, immune-mediated renal toxicity is rare and can occur after significant delay. Diagnosing immune-mediated renal toxicity can often be difficult, due to possible alternative causes of acute kidney injury, especially in this particular patient population. Acute interstitial nephritis is the most common finding in kidney biopsies. In most cases, ICI-mediated nephritis can be treated effectively by discontinuing ICI therapy and initiating corticosteroid therapy. Renal outcomes are generally favorable. Other types of targeted immunotherapy, such as CAR-T-cell or BiTE therapies play a minor role in renal toxicity. However, due to their increase in usage, possible renal adverse effects of these therapies should receive greater attention.

Serum anti-phospholipase A2 receptor (PLA2R) antibody is widely used to diagnose primary membranous nephropathy (MN), but PLA2R positivity also occurs in secondary MN, especially nonsteroidal anti-inflammatory drug (NSAID)-induced MN, leading to a common diagnostic pitfall. We report a 71-year-old female with long-term unsupervised NSAID administration for polymyalgia rheumatica, presenting with recurrent nephrotic syndrome and acute kidney injury. Initial laboratory tests revealed severe hypoalbuminemia (15.7 g/L), elevated serum creatinine (3.98 mg/dL), massive proteinuria (10.24 g/24 h), and positive anti-PLA2R antibody (39.69 U/mL). The etiology of her first nephrotic episode remained unclear, and renal biopsy during disease relapse finally confirmed NSAID-induced secondary MN. Pathological examination demonstrated PLA2R-positive MN with immunoglobulin G1 (IgG1)-predominant immune deposits, moderate (2+) glomerular complement component 1q (C1q) deposition, and concomitant severe acute interstitial nephritis. The patient achieved clinical remission after NSAID discontinuation and treatment with intravenous methylprednisolone combined with rituximab, but disease relapse occurred after inadvertent NSAID re-exposure. This case highlights that PLA2R positivity does not exclude drug-induced secondary MN. IgG subclass profiling and C1q staining are critical complementary biomarkers for precise differential diagnosis and can effectively prevent the common diagnostic pitfall of attributing PLA2R positivity exclusively to primary MN. Permanent NSAID discontinuation remains the cornerstone of disease management.

Interstitial nephritis caused by Infectious Bronchitis Virus (IBV) is a primary cause of mortality in chickens. To investigate whether gut microbiota mediate this effect, chickens were treated with antibiotics to deplete intestinal flora, which exacerbated IBV infection and abolished RIP's protective effect. It was found that fecal microbiota transplantation (FMT) could reduce IBV copy numbers, decrease the production of metabolites, decrease the expression of NLRP3 pathway-related genes and proteins in the kidneys and intestines and increase the expression of tight intestinal junction proteins, and alleviate enteritis and interstitial nephritis. The 16S rRNA sequencing results indicated a significant increase in the abundance of harmful Escherichia_Shigella bacteria following IBV infection. However, in the RIP prevention group and FMT group, there was an increase in the abundance of probiotics such as Faecalibacterium, Lactobacillus, and Bifidobacterium. Furthermore, Lactobacillus reuteri, isolated from the feces of RIP-administered chickens and combined with sodium acetate (NaAc), alleviated interstitial nephritis and was associated with decreased expression of NLRP3 pathway-related molecules, reduced inflammatory factors, and enhanced intestinal tight junction proteins. This study not only confirms the vital role of gut microbiota in the treatment of IBV-induced nephritis but also opens avenues for the development of targeted probiotic therapies in viral infections and kidney diseases.