Introduction: Monoclonal immunoglobulin deposition disease (MIDD) is a rare monoclonal gammopathy of renal significance (MGRS) characterized by linear, non-organized deposition of immunoglobulin fragments along glomerular, tubular, and vascular basement membranes. While light and heavy chain MIDDs are more frequently reported, IgM-associated MIDD is exceedingly rare, with only a few cases documented. Case Presentation: We report a 71-year-old man who presented with seronegative rapidly progressive glomerulonephritis (RPGN) and sub-nephrotic-range proteinuria. Initial serologies were negative for autoimmune and infectious causes. A monoclonal workup revealed an IgM κ paraprotein, prompting further evaluation. Kidney biopsy demonstrated diffuse crescentic glomerulonephritis (81%), linear IgM κ deposits, and arteriolar thrombotic microangiopathy (TMA). Bone marrow studies confirmed lymphoplasmacytic lymphoma with an MYD88 L265P mutation, consistent with Waldenström’s macroglobulinemia (WM). Conclusion: This case represents the first reported instance of IgM κ MIDD presenting with both crescentic GN and TMA in the setting of WM, defining a uniquely aggressive dual-injury renal phenotype. It highlights the diagnostic challenge of seronegative RPGN, in which MIDD should be included in the differential diagnosis. The case underscores the importance of integrated histopathology and hematologic genomics in identifying rare MGRS entities, recognizing that severe kidney injury may evolve rapidly despite appropriate management.

Introduction: Follow-up for hematuria, often found incidentally on urinalysis, is critical as it may be an early sign of glomerular disease or malignancy. We evaluated nephrology and urology referral patterns for outpatients with hematuria, and factors associated with nephrology and urology referrals. Methods: This retrospective, observational cohort study leveraged electronic health record data from a large, regional health care system in Pennsylvania, USA. Outpatients with hematuria (≥1+ blood) on dipstick urinalysis from January 1, 2022, to September 30, 2022, without nephrology/urology appointments in the prior 10 years or prior genitourinary cancer were enrolled. The primary objective evaluated the proportion of outpatients with hematuria who had nephrology or urology referrals or appointments within 6 months following initial presentation. Secondary objectives evaluated concurrent proteinuria and follow-up testing patterns. Results: The mean (standard deviation) age of the 5,475 outpatients with hematuria on urinalysis was 60.5 (20.8) years, and most were female (78.0%). Overall, 774/5,475 (14.1%) patients with hematuria had a nephrology or urology referral/appointment within 6 months following presentation. Urine microscopy was performed at time of hematuria detection for 3,324/5,475 (60.7%) patients, of whom 2,388 (71.8%) had ≥3 red blood cells (RBCs) per high-power field (HPF). Repeat urinalysis was performed for 1,582/5,475 (28.9%) patients. Increased referral likelihood was associated with male sex (odds ratio: 2.3; 95% confidence interval [CI]: 1.9–2.7) and ≥30 RBCs/HPF on microscopy (odds ratio: 1.7; 95% CI: 1.3–2.1). Of 4,952 patients with proteinuria data, 2,375 (48.0%) had hematuria and ≥1+ protein on urinalysis, and 373/2,375 (15.7%) had nephrology (n = 58; 2.4%) and/or urology (n = 332; 14.0%) referrals within 6 months. Conclusion: This study provides insight into current outpatient hematuria management patterns. The low referral rates, particularly with concurrent hematuria and proteinuria, highlight opportunities to improve management moving forward.

Recent years have seen an explosion of interest in the pathogenesis and therapy of immunoglobulin A nephropathy (IgAN). Large cohort studies have facilitated improvements in disease classification and prognosis, including the establishment and validation of a standard pathological classification, the Oxford classification. Landmark treatment studies published in the past several years have solidified a basic therapeutic approach, emphasizing the value of adding immunomodulatory drugs to supportive care for aggressive disease. There are currently a large number of therapies with diverse mechanisms of action in active development for IgAN, promising at least to enhance our understanding of key pathogenic pathways and, at best, to eventually prove useful in slowing or stopping the progression of IgAN. In this cutting-edge feature, we use a clinical case to review and discuss the current standard of care in the diagnosis and treatment of IgAN, as well as to highlight emerging approaches to treatment.

Introduction: Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a systemic condition usually affecting small blood vessels, commonly causing kidney disease. It has a reported incidence of around 20–25 per million per year. AAV includes both granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA). Here, we describe the epidemiology of this condition at our renal centre over a 23-year period, compare GPA and MPA and compare the overall cohort by era of diagnosis. Methods: We identified all patients with AAV with renal involvement between January 2000 and December 2022 through our biopsy database and electronic patient record. The cohort after exclusions totaled 278. We collected demographic data, baseline laboratory values, treatment received and outcomes including progression to renal replacement therapy (RRT), relapse rates and mortality. We performed subgroup analysis comparing those with GPA and MPA, and created 4 groups by era of diagnosis. Results: Median age of the cohort was 63.5 years (interquartile range [IQR] 52–72), 52.5% were male and 92.4% White. GPA was seen in 49.3% and MPA in 42.1%. There was advanced renal disease at presentation with median eGFR 18 mL/min/1.73 m2 (IQR 9–38) and 54 (19.4%) required RRT at presentation. Relapse occurred in 23%, progression to RRT in 26.6% and 1-year mortality was 3.2%. Median follow-up duration was 54 months (IQR 22–98). Those with GPA were younger, had higher incidence of ENT disease at presentation, were more likely to relapse and had greater 1- and 5-year survival. Mortality rate per hundred person years improved from 2010 onwards. Conclusions: This is one of the largest retrospective observational studies conducted on AAV. We demonstrate that there were more cases of GPA (49.2%) compared to MPA (42.1%) presenting to our centre; comorbidity rates were high; there was advanced renal disease at presentation and mortality rate appeared to improve in the more recent eras.

Introduction: Focal segmental glomerulosclerosis (FSGS) and IgA nephropathy (IgAN) are progressive kidney conditions associated with substantial clinical burden. However, limited research has explored the lived experiences of individuals affected by these conditions. The DEFINE study aimed to address this gap by examining day-to-day impacts of FSGS and IgAN on personal and professional lives, emotional wellbeing, time, and finances. Methods: DEFINE was a multi-country qualitative study involving adults with primary FSGS or IgAN, and adult care providers of adults or children with these conditions. Participants were recruited from Germany, Spain, the UK, and the US. All were invited to complete a pre-task survey and to join virtual focus groups. Thematic analysis was conducted to identify key themes and insights. Results: Thirty-two participants completed the pre-task survey and 26 attended the focus groups. Fatigue was the most burdensome symptom, affecting daily activities, social life, and employment, yet was often overlooked in clinical care. Dietary restrictions and reduced physical activity further limited quality of life, compounded by inconsistent guidance. Emotional impacts, such as sadness and anxiety, were commonly reported, driven by the condition’s effect on daily life and fear of disease progression. Many patients reported reduced work hours or ceased employment due to symptoms or condition management. Care providers also made professional adjustments, although some reported greater workplace flexibility. Financial strain was reported across all regions, including medical costs, dietary expenses, medical-related travel, and lost income. Participants highlighted the value of peer support, self-advocacy, and access to specialist healthcare professionals (HCPs). Conclusion: DEFINE highlights the wide-ranging burdens of FSGS and IgAN on patients and care providers. Findings underscore the need for holistic, patient-centered care that recognizes lived experience and provides consistent lifestyle guidance and emotional support. Greater collaboration among HCPs, industry, and patient organizations is essential to improve self-management and quality of life.

Introduction: Corticosteroids are commonly used in severe post-infectious glomerulonephritis (PIGN), but the optimal dosing and long-term outcomes remain unclear. This study investigated the association between cumulative corticosteroid dosage and mortality in patients with biopsy-proven PIGN. Methods: This retrospective cohort study included adult patients (≥18 years) with biopsy-proven PIGN from the King Chulalongkorn Memorial Hospital registry (1996–2023), excluding those with concurrent infections or conditions affecting prognosis. Clinical and histopathological data were collected. The primary outcome was kidney failure (estimated glomerular filtration rate of <15 mL/min/1.73 m2 or long-term kidney replacement therapy). Time-to-event analysis compared outcomes between steroid-treated and untreated patients. Univariable logistic regression and multivariable Cox models identified mortality predictors. Receiver operating characteristic curves identified the optimal cumulative prednisolone dosage, and Kaplan-Meier analysis compared survival between steroid dosage groups. Results: Among 7,005 kidney biopsies, 73 patients with PIGN were analyzed. Over a median follow-up of 15.6 years, 15% died and 15% developed kidney failure. Steroids were used in 62% of patients and were associated with higher rate of skin/soft tissue infections (26% vs. 11%, p = 0.03). Despite similar baseline characteristics, multivariable Cox regression showed that steroid use was independently associated with lower mortality (HR 0.08, 95% CI: 0.01–0.61, p = 0.02). Kaplan-Meier analysis demonstrated significantly lower overall survival in patients receiving cumulative prednisolone ≥73 mg/kg or no steroids, with the best survival observed in those receiving <73 mg/kg (log-rank test, p = 0.02). Steroid-related adverse events included cushingoid appearance (11%) and osteopenia (4%). Conclusion: Corticosteroids improve survival in PIGN, but cumulative doses ≥73 mg/kg increase mortality risk. Low-dose corticosteroids may be beneficial in severe PIGN, but further research is needed to refine dosing strategies.

Introduction: Novel molecular tools have the potential to improve current clinical and histology-based risk classification systems for various medical renal diseases including glomerulonephritis (GN). We aimed to assess the utility of gene expression for improving biopsy-based risk prediction in patients with GN with and without crescent formation. Methods: This retrospective case-control study used NanoString nCounter to measure the expression of 54 previously described inflammation, nephron injury, endothelium, and crescent-related genes in 335 archival, formalin-fixed paraffin-embedded native kidney biopsies, including a 288-biopsy discovery cohort representing a broad spectrum of crescentic GN subtypes, and an independent 47-biopsy validation cohort focused on ANCA-associated crescentic GN. Clinical, histologic, and gene expression data were compared. Results: Discovery cohort analysis demonstrated increased expression of 13 genes in crescentic GN cases that developed end-stage renal disease (ESRD) versus those that did not (false discovery rate <0.05). Within the 75-biopsy subset of ANCA-associated crescentic GN cases in the discovery cohort, this 13-gene set was found to be independently predictive of ESRD in multivariate Cox proportional hazards regression analysis (p = 0.015), with significant differentiation of high and low risk patients in the Kaplan-Meier renal survival analysis (log-rank test, p = 0.002). However, validation cohort analysis did not demonstrate significant improvement in risk stratification with the 13-gene set when compared with established clinicopathologic models. Conclusion: These results suggest that biopsy-based gene expression may provide the opportunity for improved risk stratification in crescentic GN; however, the genes evaluated in this study appear to have limited added clinical utility over existing risk scores.

Introduction: Membranous nephropathy (MN) is a leading cause of nephrotic syndrome in adults. NELL1 accounts for approximately 10% of MN cases and is emerging as a distinct subtype often linked to secondary conditions, such as malignancies and drugs. Here, we describe a case of MN in a patient with metastatic papillary thyroid carcinoma. Case Presentation: A 78-year-old man with metastatic papillary thyroid carcinoma and a distant history of treated syphilis presented with nephrotic syndrome. A renal biopsy revealed segmental MN with positive NELL1 staining, while the thyroid carcinoma tissue also demonstrated NELL1 staining at weak to moderate intensity. The patient was managed conservatively without immunosuppression due to the lack of oncologic treatment options and syphilis was treated with doxycycline due to positive serologies, though active infection was not suspected. Follow-up showed stabilization of renal function and marked reduction in proteinuria. Conclusion: NELL1-positive MN is increasingly recognized for its association with malignancy. The patient achieved partial remission with supportive, non-immunosuppressive therapy. Clinicians should maintain a high index of suspicion for secondary conditions when NELL1-positive MN is encountered. This case report reviews secondary NELL1 associations and underscores the diagnostic challenges in MN when multiple potential secondary causes exist.

Plain Language SummarySickle cell disease is inherited from a patient’s parents, leading to an abnormal red blood cell shape. There are many genetic types of this disease, and some are thought to be associated with a milder disease with fewer symptoms and complications. One serious complication of sickle cell disease is kidney damage, known as sickle cell nephropathy. In this study, we looked at patients with a specific genetic type called the Arab-Indian haplotype, which is common in parts of the Middle East and South Asia. It is often referred to as a milder form of sickle cell disease, and there is limited information about whether it has similar kidney changes to the more severe forms. We have found that the changes caused by sickle cell disease in the Arab-Indian haplotype are similar to those of the more severe form of the disease. These changes suggest that despite the reported milder form of the disease, the underlying disease process is similar. This supports the idea that treatments used for more severe forms might also benefit patients with the Arab-Indian type. However, more research is needed to confirm this across different populations.