Differential early tubular injury in minimal Change disease and Focal segmental Glomerulosclerosis: A Multifaceted analysis.

Pathogenic variants in myosin heavy chain 9 (MYH9), encoding the heavy chain of nonmuscle myosin IIA (NMMIIA), cause autosomal-dominant MYH9-related disease that may include proteinuric kidney disease, macrothrombocytopenia, cataract, sensorineural deafness, and elevated liver enzymes. Whole exome sequencing and segregation analysis were performed in a patient with end-stage renal disease. Histology of kidney and liver biopsies was assessed and blood smears were examined for the presence of Döhle-like bodies. Deformability cytometry and monocyte migration assays were performed. Immortalized podocytes and primary skin fibroblasts of 1 patient were transfected with plasmids containing MYH9 wild type (WT) or the p.(Arg424Gly) variant. Biochemical studies using recombinantly produced proteins were conducted to assess the variant's impact on adenosine triphosphate (ATP) turnover and motor function. We identified the likely pathogenic heterozygous MYH9 variant c.1270C>G, p.(Arg424Gly) in all affected members of a nonconsanguineous family. Typical microscopic findings, such as Döhle-like bodies or NMMIIA conglomerates were absent. Nonetheless, all patients presented with proteinuric kidney disease, elevated liver enzymes, and intermittent thrombocytopenia. The altered protein showed increased ATP turnover in the presence of actin and enhanced motor activity under both unloaded and loaded conditions. We identified a novel fully segregating MYH9 variant causing MYH9-related disease. Based on biochemical findings, we report the first gain-of-function variant of MYH9. We propose that the enhanced intrinsic motor activity of the p.(Arg424Gly) variant is a key contributor to the disease mechanism. Incorporation of the p.(Arg424Gly) variant into nonmuscle myosin IIA filaments and higher-order actomyosin assemblies may, in principle, affect actomyosin dynamics.

The Pathophysiological Mechanism of Beni-koji Choleste-Help or Puberulic Acid-Induced Kidney Injury.

A 3-year-old boy presented with dark-colored urine for 4months. His history was negative for infections, but he was taking oral methylcobalamin treatment for a persistent deficiency. His parents were first-degree cousins, and a female cousin had proteinuria of unknown etiology. A physical examination and laboratory examination revealed no abnormalities except for non-orthostatic nephritic proteinuria and low levels of vitamin B12. Albumin was the main protein in the urine. Kidney biopsy showed nonspecific changes. Genetic analysis identified a homozygous pathogenic AMN mutation, confirming Imerslund-Grâsbeck syndrome (IGS). Angiotensin-converting enzyme inhibitor was prescribed but discontinued due to stable protein levels. After 4years, kidney function remained stable. Imerslund-Grâsbeck syndrome is a rare autosomal recessive disorder that affects vitamin B12 and protein, particularly albumin absorption. While typically presenting with megaloblastic anemia, AMN mutations show variable phenotypes. Proteinuria is resistant to ACE inhibitors, and currently, there is no specific treatment.

Objectives: Illustrate the role of embolization as a therapeutic alternative to surgery for renal bleeding. Clarify the benefits of embolization in preserving renal function. Materials and methods: Retrospective study including observations of 22 patients with hematuria secondary to renal trauma. The cases collected in our study were diagnosed by abdominal angiography and then underwent renal arterial embolization over a period of 4 years from January 2020 to December 2024. Results: Our series was characterized by a predominance of males with a sex ratio of 1.2 and an average age of 35 years. All patients presented with uncontrolled gross hematuria and 41% of cases had hemorrhagic shock. The etiologies were: blunt abdominal renal trauma 36% (n=8), open trauma 32% (n=7), iatrogenic trauma post renal biopsy 22% (n=5), and iatrogenic hematuria after percutaneous lithotomy 10% (n=2). The embolization agents used were: coils 64% (n=14), biological glue 27% (n=6), and a combination of coils and biological glue in 9% (n=2). Our results were satisfactory with immediate cessation of hematuria in all cases, stabilization of hemoglobin, preservation of pre-existing renal function, and near-total preservation of renal parenchyma on imaging control. Conclusion: Embolization of post-traumatic renal hematuria is an effective alternative to surgery, avoiding partial or sometimes total nephrectomy and deterioration of renal function.

Percutaneous ultrasound-guided kidney biopsy remains the reference standard for diagnosing renal allograft dysfunction and for tailoring immunosuppression. Although major complications are uncommon in experienced hands, bleeding-related events and post-biopsy vascular lesions require a rapid, operational imaging and follow-up strategy. This practical guide provides a step-by-step, competency-based workflow for renal transplant biopsy-from indication setting and risk optimisation to room set-up, equipment selection, safe cortical targeting, and specimen adequacy criteria-followed by structured post-biopsy monitoring and discharge counselling. In this study, we will be conducting a comparative analysis of percutaneous, transvenous, and CT-guided approaches. Furthermore, we will be summarising pragmatic thresholds for blood pressure, coagulation parameters, and periprocedural antithrombotic management. A dedicated section integrates contrast-enhanced ultrasound (CEUS) into complication triage when grayscale ultrasound and Doppler are equivocal, defining practical triggers for escalation and follow-up pathways for haematoma, pseudoaneurysm, arteriovenous fistula, and segmental perfusion defects. The translation of imaging findings into actionable clinical decisions, facilitated by a protocolised biopsy technique in conjunction with CEUS-driven problem solving, has been demonstrated to enhance diagnostic confidence and improve safety in routine transplant care.

Anti-glomerular basement membrane (GBM) nephritis is an autoimmune disease which typically presents rapid progressive glomerulonephritis. A subacute course and relapse are rare. We report the case of a 23-year-old woman with no prior medical history, who was referred for proteinuria and elevated serum creatinine (Cr) level of 3.3mg/dL. Two weeks later, upon her visit to our hospital, her creatinine level was 3.2mg/dL. Five months prior, her Cr was 1.2mg/dL. Urinalysis showed 2.3g/gCre of proteinuria and microscopic hematuria. The anti-GBM antibody titer was high at 135 U/mL. Anti-neutrophil cytoplasmic antibody and anti-nuclear antibody were negative. Kidney biopsy revealed crescentic glomerulonephritis with advanced glomerular sclerosis and diffuse linear staining of IgG along the GBM. She received corticosteroids, intravenous cyclophosphamide and 7 sessions of plasma-exchanges. After three months, her Cr improved to 1.9mg/dL and the antibody became undetectable. However, she self-discontinued prednisolone 2months later. Three weeks after discontinuation, she presented with nausea, oliguria. Her Cr level had risen to 9.6mg/dL and the anti-GBM antibody titer was 4.0U/mL. A second kidney biopsy showed progression of glomerulosclerosis, endothelial injury in the arterioles characterized by fibrin deposition, and extensive tubulointerstitial damage. Despite resuming treatment, her kidney function did not recover, and she required maintenance hemodialysis. This case highlights two atypical features of anti-GBM nephritis: subacute progression over 5months, and relapse after antibody negativity triggered by steroid discontinuation. This emphasizes the importance of adherence to immunosuppressive therapy, even after serological remission.

Adenine phosphoribosyltransferase (APRT) deficiency is a rare autosomal recessive disorder of purine metabolism causing 2,8-dihydroxyadenine urinary tract stones and crystal nephropathy. Disease manifestations include acute kidney injury (AKI), progressive chronic kidney disease (CKD), and not infrequently, kidney failure. A significant proportion of affected individuals remainasymptomaticinto adulthood. The diagnosis of APRT deficiency should be considered in all children presenting with renal colic, radiolucent urinary stones and/or AKI, as well as in infants with a history of reddish-brown diaper stain. Indeed, the disorder should be considered in any person with radiolucent urinary stones and in young and middle-aged individuals with progressive CKD, particularly when a kidney biopsy reveals tubulointerstitial nephropathy of unknown cause. The presence of biallelic pathogenic APRT mutations identified through targeted multi-gene panels or single-gene testing confirms the diagnosis of APRT deficiency. As kidney stone analysis can be false-positive, this method can only be considered suggestive of APRT deficiency, and confirmatory testing must be carried out in all cases. Timely diagnosis and treatment with a xanthine oxidoreductase inhibitor, eitherallopurinol or febuxostat, have in several studies, based on different levels of evidence, been found to be both highly effective and safe in APRT deficiency. Appropriate pharmacotherapy significantly reduces kidney stone recurrence, slows CKD progression and appears to prevent the development of kidney failure. The outcome of kidney transplantation in individuals with APRT deficiency is comparable to those withother causes ofkidney failure when allopurinol or febuxostat therapy is initiated before the transplant procedure.

Desmopressin has a theoretical rationale to reduce procedural bleeding risk but results from randomized controlled trials are mixed. PubMed, EMBASE, and Google Scholar were searched on October 27, 2025 to identify studies evaluating Desmopressin administered prior to kidney biopsy. Risk of bias was assessed using the Cochrane Risk of Bias 2.0 tool. Statistical analysis was performed using RevMan software to calculate Odd's Ratios and assess heterogeneity with the I2 statistic. Publication bias was assessed with Egger's test. A sensitivity analysis was performed due to heterogeneity via the leave-one-out method with revised estimated odds presented thereafter. 17 studies including 5394 participants were analyzed. The pooled estimated odds ratio (OR) for total bleeding was 0.89 [0.59 - 1.36], p = 0.60, I2 = 85%. In subgroup analysis the pooled estimated OR for subcutaneous administration was 0.37 [0.21 - 0.65], p < 0.001, I2 = 0%); intravenous administration was 1.47 [1.05 - 2.05], p =0.03, I2 = 61%; intranasal administration was 0.68 [0.30 - 1.56], p = 0.37, I2 = 87%; and estimated glomerular filtration rate (eGFR) <60 ml/min/1.73m2 was 0.74 [0.40 - 1.37 p =0.34, I2 = 81%. After sensitivity analysis the revised OR for intranasal administration was 0.42 [0.31 - 0.59], p <0.001 and for eGFR < 60 was 0.55 [0.38 - 0.81], p = 0.002. The pooled estimated OR for severe hyponatremia was 3.85 (95% CI [2.12 - 7.00], p <0.001, I2 = 33%. Overall there was no reduction in odds of bleeding but with high between-group heterogeneity. There were lower odds of bleeding in the intranasal and subcutaneous administration subgroups. Desmopressin resulted in higher odds of hyponatremia.

Diabetic nephropathy (DN), a leading cause of end-stage kidney disease (ESKD), often progresses despite standard care. Evidence suggests a DN subgroup exhibit overlapping features of primary podocytopathy, potentially responsive to immunosuppression, has not yet systematically studied. We hypothesized that DN patients with biopsy-proven concurrent ultrastructural features of primary podocytopathy will demonstrate superior renal outcomes following immunosuppressive therapy, compared to those with isolated DN pathology. A retrospective analysis was conducted on 88 patients with biopsy-confirmed DN recruited from Peking University First Hospital between 2017 and 2022. The patients were categorized into two groups: Group A (patients with DN and primary podocytopathy) and Group B (patients with DN without primary podocytopathy). Seven patients with diabetes and primary podocytopathy but without DN served as disease controls. Primary podocytopathy was defined by electron microscopy foot process width (FPW) ≥821nm. Patients in Group A had a shorter duration of nephropathy (p=0.005), lower serum albumin levels (p<0.001), and higher proteinuria (p=0.032) than those in Group B. Light microscopy demonstrated milder glomerular lesions in Group A (p<0.001), with most cases classified as Class I or II (63.6%). Electron microscopy showed significantly broader FPW in Group A than in Group B (1310.5±510.1nm vs. 569.1±97.5nm, p<0.001). While Group B showed no such benefit and differed significantly from the control group, patients in Group A benefited from immunosuppressive therapy, with a significantly reduced risk of ESKD. DN with concurrent primary podocytopathy represents a distinct clinical entity characterized by nephrotic-range proteinuria, ultrastructural podocyte effacement, and favorable response to immunosuppressive therapy. Early renal biopsy incorporating FPW assessment enables targeted therapy to mitigate ESKD progression in this high-risk phenotype.

BK polyomavirus (BKV) infection is associated with injury and subsequent graft loss due to the extent of injury or rejection. However, the molecular mechanisms driving injury and subsequent adverse outcomes remain poorly understood. In a cross-sectional study, single-cell RNA sequencing from kidney allograft biopsies was used to assess cell type-specific responses between uninfected controls and two distinct phases of BKV infection: peaking (increasing viral blood titers) and resolving (decreasing viral titers following immunosuppression reduction). Genes upregulated in BK viral nephropathy (BKVN) were enriched for polyomavirus infection hallmarks, including ribosome biogenesis, translation, and energy restructuring. Additionally enriched pathways included wound healing, cellular stress, antigen presentation and immune signaling. Even without BKVN (peaking BK viremia alone), epithelial cells expressed signatures for wound healing, cellular stress, and extracellular matrix remodeling. In vivo tubular cell responses at single-cell resolution were validated against single cell transcriptomic data of BKV infected cells in a cell culture model. Despite similarities, in vivo tubular cells underwent metabolic adaptation favoring fatty acid oxidation and proinflammatory responses not observed in culture models likely due to an absent innate and adaptive immune system. Despite lymphopenia and immunosuppressive therapies, the proportion of recipient derived intrarenal adaptive immune cells was increased in biopsies associated with peaking viremia alongside activation of innate immune responses. Adaptive immune cells exhibited persistent inflammatory signaling and remodeling of energy metabolism during the resolving phase of infection. These not previously reported insights into BKV-associated injury may have implications for clinical management and improved allograft outcomes.

This single-center retrospective cohort study divided 176 adults with biopsy-proven primary glomerulonephritis (GN) between 2014 and 2021 into 4 groups based on cortical interstitial fibrosis (IF) percentage. The primary outcome was disease progression, defined as a ≥ 40 % decline in estimated glomerular filtration rate (eGFR) and/or the need for dialysis. The secondary outcome was complete remission, defined as proteinuria < 300 mg/24 hours. Baseline proteinuria and serum creatinine increased with greater IF severity, while eGFR decreased. Kaplan-Meier analysis showed a higher risk of progression in patients with severe IF. After adjusting for glomerulosclerosis, baseline eGFR, proteinuria, and treatments, IF severity remained an independent predictor of progression (HR 3.15). IF was not independently associated with achieving complete remission. Stratified analyses suggested a stronger association in immunoglobulin-A (IgA) nephropathy, while results for focal segmental glomerulosclerosis (FSGS) and membranous glomerulonephritis (MGN) were inconclusive due to limited statistical power. In summary, the severity of IF on diagnostic biopsy is a strong and independent prognostic factor for disease progression in primary glomerular diseases, supporting its routine standardized assessment to improve risk stratification and personalized patient management.

We previously reported an association between cnm-positive Streptococcus mutans in the oral cavity and IgA nephropathy. However, whether this association is specific to IgA nephropathy among various kidney diseases remains unclear. This study aimed to investigate the presence of cnm-positive S. mutans in patients who underwent a renal biopsy and to evaluate its association with different kidney disease subtypes. We included 294 patients who underwent a renal biopsy and provided informed consent between May 2017 and March 2024 (renal biopsy group). The healthy control group consisted of 81 individuals with an estimated glomerular filtration rate > 60mL/min and no proteinuria. Saliva samples were collected from all participants, stored at - 20°C, and analyzed by polymerase chain reaction to detect S. mutans and cnm-positive S. mutans. Associations between cnm-positive S. mutans and the histopathological diagnosis were subsequently assessed. The prevalence of cnm-positive S. mutans was significantly higher in the renal biopsy group than in the control group (21.8% vs. 11.1%, p < 0.05). Among kidney disease subtypes in the renal biopsy group, a higher prevalence of cnm-positive S. mutans was observed in patients with lupus nephritis (31.6%), membranous nephropathy (29.2%), and IgA nephropathy (23.6%). However, a logistic regression analysis identified a significant association only between cnm-positive S. mutans and IgA nephropathy (p < 0.05). This study suggests that cnm-positive S. mutans is significantly associated with IgA nephropathy.

Children with inflammatory bowel disease (IBD) have an increased risk of developing kidney disorders, which may cause significant kidney function impairment (SKI) or lead to chronic kidney disease (CKD). In this study we aimed to provide insights in causes and diagnoses of SKI cases and to provide recommendations for pediatric gastroenterologists for children with IBD and SKI. Cases of SKI in children with IBD (<19 years) were collected from the international, prospective PIBD-SETQuality Safety Registry. A monthly survey was sent to participating pediatric gastroenterologists to report cases of SKI (defined as an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73m2). Additionally, a panel consisting of 16 members (including experts in pediatric IBD and nephrology) rated the most likely cause of the cases and formulated recommendations for screening, follow-up and referral for children with IBD and SKI. Between November 1, 2016 and December 31, 2023, 42 cases of SKI were eligible for analysis. Tubulo-interstitial nephritis (TIN) was the most common diagnosis (n = 15). Sixteen (38%) cases were confirmed with renal biopsy (10 cases of TIN). Twelve patients developed CKD. IBD medication was the most frequently reported cause (n = 15), however, there was low concordance between panelists about the most likely etiology (Fleiss' kappa 0.143 and 0.102). This is the first prospective study to report cases of SKI in children with IBD. SKI may lead to CKD. Confirming the etiology of the SKI proved to be very challenging. The study provides recommendations for screening and follow-up of SKI in children with IBD.

Kidney biopsies are common diagnostic procedures. Risk factors for biopsy complications in children are not well delineated. The objective of our study is to assess complication rates in pediatric native and transplant kidney biopsies and associated clinical and technical risk factors. Our retrospective study at BC Children's Hospital (Vancouver, Canada) included 402 biopsies performed on 232 patients from 2010-2018. Data were obtained through patient chart review. Minor complications were defined as perinephric hematomas ≥ 2cm or labelled as at least "moderate", arteriovenous fistula, or pseudoaneurysm. Major complications were defined as complication requiring blood transfusion, embolization, or surgery. There were 32 biopsy complications (8%) of which one was a major complication. The most common complication was hematoma in native kidneys, and arteriovenous fistula in transplant kidneys. Complications rates were significantly higher in children < 3years of age (22%, p = 0.046), female patients (11%, p = 0.048), patients with eGFR ≤ 30ml/min/1.73m2 (17%, p = 0.025), hemoglobin < 10g/dL (16%, p = 0.002), vasculitis (15%, p = 0.004), and native kidney biopsies (11%, p = 0.027). Most technical factors such as number of biopsies per patient, cortical tangential vs. perpendicular approach, training level, kidney location, and sedation methods were not associated with increased complication rates. Kidney biopsies are a relatively safe procedure, especially in transplant patients. Specific patient populations (children < 3years, patients with low eGFR, anemia, and vasculitis/SLE) may be at higher risk of complications. Standardization of biopsy protocol and complication definition will enhance consistency of outcome reporting and allow evidence-based improvement in biopsy practices.

Abstract Tubulointerstitial nephritis and uveitis (TINU) syndrome is an uncommon autoimmune disorder. It affects the kidneys and causes eye inflammation. Uveitis in TINU usually presents as bilateral anterior uveitis. The kidney component appears as acute interstitial nephritis. This case study presents the diagnosis of a teenager with both eye and systemic symptoms. Ophthalmologic examination confirmed uveitis. Further investigation then revealed impaired kidney function. Diagnosis was established with a kidney biopsy. This ruled out other systemic diseases. TINU is rare and often not immediately apparent. Clinicians must maintain a high index of suspicion for early recognition and prompt action. Physicians should consider TINU when pediatric patients present with both uveitis and kidney dysfunction. This ensures complete and timely treatment of this complex syndrome.

The prognostic significance of impaired renal function in Waldenström macroglobulinaemia (WM) remains poorly defined. We conducted a nationwide multicentre study to evaluate its clinical characteristics and prognostic impact in symptomatic patients. We analysed 402 symptomatic WM patients, stratified according to renal function at diagnosis (creatinine clearance <60 mL/min/1.73 m2). Renal dysfunction was identified in 119 patients (29.6%). Renal biopsy was performed in 33 cases. Patients with reduced renal function were older (median age 76 vs. 67 years, p < 0.0001), had lower haemoglobin levels (10.8 vs. 11.8 g/dL, p = 0.008) and higher 24-h proteinuria (0.29 vs. 0.20 g, p = 0.04). Comorbidities of renal interest were similarly distributed between groups. Renal dysfunction was associated with inferior median overall survival (139 vs. 203 months, p < 0.001) and progression-free survival (PFS) (80 vs. 106 months, p = 0.002). Among patients aged <70 years, renal dysfunction remained associated with shorter PFS (77 vs. 121 months, p = 0.005). Importantly, worsening renal function did not correlate with increasing age. In this setting, first-line chemoimmunotherapy was associated with improved median PFS. Thus, renal dysfunction at diagnosis may represent an underrecognized, independent adverse prognostic factor in symptomatic WM.

Alport syndrome (AS) is a hereditary nephropathy caused by mutations in the COL4A3 , COL4A4 , and COL4A5 genes. Rare contiguous COL4A5–COL4A6 alterations cause AS with diffuse leiomyomatosis (AS-DL). Case report. A 16-year-old male had mild proteinuria, hematuria, hearing loss and myopia since childhood. Estimated glomerular filtration rate was 82.8 mL/min/1.73 m 2 . Kidney biopsy showed segmental mesangial sclerosis; immunofluorescence was negative. Electron microscopy demonstrated diffuse glomerular basement membrane thinning and podocyte foot-process effacement. Two deceased brothers had end stage kidney disease; the mother had hematuria, uterine myoma, and a benign bladder tumor. A diagnosis of X-linked AS was established according to the Flinter criteria and nephroprotective treatment was initiated. Since 2024, the patient had complained of epigastric symptoms. An endoscopy revealed a 2-cm gastric submucosal lesion. A whole-exome sequencing identified a hemizygous missense variant in COL4A5 and a COL4A6 exon 1–2 deletion, confirming AS-DL. Discussion. This case demonstrates the co-occurrence of AS-DL and shows that early pedigree assessment, combined with integrated clinicopathologic-genetic evaluation in a multidisciplinary framework, enables a timely diagnosis of atypical familial AS-DL and improves clinical management.

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.

Renal dysfunction after allogeneic hematopoietic stem cell transplantation (allo-HSCT) often results from common causes like drug toxicity, infection, or transplant-associated thrombotic microangiopathy (TA-TMA). However, renal graft-versus-host disease (GVHD) may be ignored. We discuss a 49-year-old man who experienced worsening kidney function despite being in hematologic remission and having negative results for infections and autoimmune diseases. A renal biopsy showed chronic tubulointerstitial injury consistent with renal GVHD, along with existing TMA. Treatment with eculizumab did not lead to improvement, likely indicating significant chronic damage. This case highlights the need to maintain clinical suspicion and to perform timely renal biopsies in cases of unexplained kidney dysfunction after transplant.