Search Results (561)

Nephrotic syndrome (NS) is characterized by proteinuria, hypoalbuminemia, edema, and hyperlipidemia. Apart from the traditional causes of NS, such as minimal change disease, focal segmental glomerulosclerosis, diabetes, infections, malignancies, autoimmune conditions, and nephrotoxic agents, there are also rare causes of NS, whose knowledge is of the utmost importance. The aim of this article was to highlight the less well-known causes that have a significant impact on diagnosis and treatment. Genetic syndromes such as Schimke immuno-osseous dysplasia, familial lecithin-cholesterol acyltransferase deficiency with two clinical variants (fish-eye Disease and the p.Leu364Pro mutation), lead to NS through mechanisms involving podocyte and lipid metabolism dysfunction. Congenital disorders of glycosylation and Nail–Patella Syndrome emphasize the role of deranged protein processing and transcriptional regulation in glomerular injury. The link of NS with type 1 diabetes, though rare, suggests an etiology on the basis of common HLA loci and immune dysregulation. Histopathological analysis, particularly electron microscopy, shows mainly podocyte damage, mesangial sclerosis, and alteration of the basement membrane, which aids in differentiating rare forms. Prompt recognition of these novel etiologies by genetic analysis, renal biopsy, and an interdisciplinary panel is essential to avoid delays in diagnosis and tailored treatment. Full article

Introduction: Renal malacoplakia is a rare chronic granulomatous disease, often associated with immunosuppression and persistent Gram-negative infections, particularly Escherichia coli. Case Presentation: We present a case involving a 31-year-old woman with hypertension, gestational diabetes, and prior uterine curettage after labor induction for preeclampsia at 23 weeks. She developed urinary sepsis post-procedure. Imaging revealed bilateral nephromegaly, while laboratory tests showed acute kidney injury (KDIGO stage III), anemia, and thrombocytopenia. Blood and urine cultures grew Escherichia coli. Renal biopsy confirmed malacoplakia, demonstrating PAS-positive Michaelis–Gutmann bodies and Von Hansemann cells. The patient responded to prolonged antibiotic therapy and supportive care. Discussion and Conclusion: This case highlights the importance of considering renal malacoplakia in patients with atypical urinary tract infections and nephromegaly, particularly in obstetric settings. Histopathological confirmation is essential, and timely treatment with intracellularly active antibiotics can lead to favorable outcomes. Early diagnosis is critical to prevent irreversible renal damage. Full article

A 10-year-old intact female Bichon Frise presented with multiple firm skin nodules on all four limbs. The nodules progressively increased in number and size over seven months. Diagnostic tests included cytology of fine-needle aspirates, histopathology of skin biopsies, radiography, and abdominal ultrasonography. Cytology revealed spindle-shaped mesenchymal cells and extracellular matrix components, and histopathology confirmed ND characterized by mature collagen deposition without evidence of malignancy. Ultrasonography detected multiple kidney cysts bilaterally, although their exact nature (benign or malignant) could not be confirmed histologically. Genetic analysis was performed, revealing no mutation in the traditionally implicated FLCN gene but multiple nonsynonymous mutations in the BRCA2 gene. This case suggests a potential association between BRCA2 gene mutations and the development of ND with renal cystic lesions, broadening the known genetic causes beyond the commonly reported FLCN mutation. Regular genetic screening and close monitoring of dermatological and renal conditions in atypical breeds are recommended. To the best of current knowledge, this is the first case report demonstrating ND and renal cysts associated with BRCA2 mutations in a Bichon Frise. Full article

Background/Objectives: Thousands of nephrectomies are performed annually in the United States, but the short-term metabolic effects of surgically induced renal ischemia remain unclear. The conventional metabolic markers used to characterize post-surgical renal function, such as creatinine and GFR, are measured in the serum but do not provide metabolic information about the renal parenchyma itself. We aimed to characterize the immediate metabolic effects of surgical ischemia on renal parenchyma within a temporal framework. Methods: Timed renal parenchyma biopsies were collected from eight patients undergoing nephrectomy for renal cell carcinoma both prior to and after ligation of the renal hilum. These samples were ground, extracted, and analyzed using nuclear magnetic resonance (NMR) spectroscopy to measure changes in lactate, succinate, glucose, alanine, and glycine levels. Results: Due to experimental limitations, we were only able to draw limited conclusions from three patients. Of the five remaining patients, all had significant increases in lactate and succinate levels as a function of time, though the degree to which these increases occurred varied between each patient. Glucose levels generally decreased in the renal parenchyma but did not necessarily correlate with lactate production, assuming all glucose underwent fermentation to lactate in a hypoxic environment. Alanine and glycine levels did not change in a predictable pattern across patients. Conclusions: There are significant changes in lactate, glucose and succinate levels within minutes of the onset of renal ischemia in human patients. The degree of change in the metabolites analyzed varied significantly between patients. The length of surgical ischemia must be considered during surgical procurement of tumor specimens for metabolomic analysis. Full article

Background and Clinical Significance: Although dietary supplements have often been deemed safe, some have been linked to drug-induced nephropathy due to their diverse ingredients. The aim of this report is to enhance clinical awareness of a novel and emerging cause of Fanconi syndrome due to red yeast rice supplements and to contribute new histopathological and clinical data. Case Presentation: We report two cases of renal dysfunction and Fanconi syndrome associated with the use of red yeast rice supplements. Both patients presented with renal impairment accompanied by elevated markers of tubular injury, hypouricemia, hypokalemia, and glucosuria, consistent with Fanconi syndrome. Following the discontinuation of the red yeast rice supplement and initiation of steroid therapy, Fanconi syndrome resolved, however, moderate renal dysfunction persisted. Urinary NGAL levels improved after treatment in both cases. KIM-1 normalized in one case but remained elevated in the other. Uromodulin recovery was complete in one case and partial in the other. Renal biopsy revealed mild tubulointerstitial nephritis, with notable shedding of proximal tubular epithelial cells. Immunohistochemical analysis demonstrated reduced expression of URAT-1, Na-K ATPase, and Na-Pi IIa in some tubules. Conclusions: These findings suggest that renal injury induced by red yeast rice supplements is mediated by direct proximal tubular necrosis caused by a harmful substance in the supplement, resulting in persistence of tubular dysfunction. Full article

Molecular testing in renal cell carcinoma (RCC) has allowed for a better understanding of the biology of both sporadic and hereditary diseases, where genetic testing is currently recommended in the guidelines for a select population with risk factors. Historically, screening, surveillance, and management decisions were based solely on clinicopathologic data; however, we now know that molecular profiling can enhance decision making, altering the treatment plan, approach, or selection of systemic therapy and enhancing the delivery of precision oncologic care. Advances and the increasing availability of next-generation sequencing technologies have improved the identification of germline and somatic variants in key RCC-associated genes. Given the molecular heterogeneity of RCC, these modern methods can identify unique genetic events that occur in a single individual, allowing for distinction between a metachronous tumor from metastases. Separate four-tier systems have been proposed to categorize germline and somatic variants according to their clinical significance, which should be highlighted. Additionally, emerging technologies, such as liquid biopsy, show potential for enhancing precision oncology in RCC. With this said, challenges, such as variant interpretation, ethical considerations, and accessibility, persist. This review examines the molecularly defined RCC, genetic testing methodologies currently available, their current clinical applications, limitations, and future directions. Full article

Glomerular diseases are a major cause of chronic kidney disease worldwide, yet epidemiological data from Eastern Europe, and Romania in particular, remain scarce. This study aimed to characterize the spectrum of biopsy-proven glomerulopathies in Romania through a multicenter national registry over a 10-year period. We retrospectively analyzed 4047 native kidney biopsies performed between 2014 and 2023 across four national nephrology reference centers. Patient demographics, clinical presentation, and histopathological diagnoses were collected and categorized into primary and secondary glomerular diseases, glomerulosclerosis, tubulointerstitial nephropathies, hereditary nephropathies, and vascular nephropathies. The mean patient age was 48 years, 54.8% were male, and 51.4% presented with nephrotic-range proteinuria. The most common primary glomerulopathies were membranous nephropathy (16.7%), immunoglobulin A nephropathy (15.6%), focal segmental glomerulosclerosis (8.8%), and membranoproliferative glomerulonephritis (10%). Among secondary glomerular diseases, lupus nephritis (9.3%), diabetic nephropathy (8.5%), and vasculitis (7.7%) were most frequent. Marked inter-center variability was observed, with a notably high prevalence of membranous nephropathy in Iași (31.1%). Over the study period, the incidence of focal segmental glomerulosclerosis increased while immunoglobulin A nephropathy declined. This study provides the first nationwide epidemiological assessment of biopsy-proven glomerular disease in Romania, revealing both similarities and distinctive differences compared to patterns reported in other European countries. Full article

Background: Acute phosphate nephropathy (APN) is an underrecognized cause of acute kidney injury (AKI), typically associated with the use of oral sodium phosphate (OSP)-based bowel preparations. It is characterized by calcium phosphate crystal deposition within the renal tubules and may result in permanent renal impairment. Despite known risks, phosphate-containing solutions are still widely used without sufficient risk stratification. Methods: We retrospectively evaluated 517 native kidney biopsies performed in our nephrology clinic between 2017 and 2022. Among these, 12 patients with unexplained AKI and recent colonoscopy history were identified. In nine cases, non-specific tubular deposits on routine staining prompted further histochemical analysis. All had a history of recent OSP-based bowel cleansing. The use of von Kossa staining confirmed calcium phosphate deposition, consistent with APN. Results: Out of 517 kidney biopsies performed during the study period, 9 patients were diagnosed with APN based on histopathological findings following recent colonoscopy and OSP-based bowel cleansing. The mean age was 58.7 years, and three were female. Hypertension was present in seven patients, diabetes mellitus in three, and epilepsy in two; one patient had no comorbidities. Baseline renal function was normal (mean serum creatinine 0.86 mg/dL) and increased to 1.76 mg/dL at three months post-exposure. All biopsies revealed tubulointerstitial calcium phosphate deposits and interstitial inflammation; mesangial hypercellularity was observed in five cases, tubular atrophy in three, and acute tubular necrosis in one. All samples stained positive with von Kossa staining. Over time, all patients developed chronic kidney disease, and one progressed to end-stage renal disease requiring dialysis. Conclusions: In patients presenting with unexplained AKI and recent OSP-based bowel preparation, APN should be considered in the differential diagnosis. When routine histology is inconclusive, definitive diagnosis may require special histochemical staining. Risk-based restrictions on phosphate-containing agents are warranted to reduce preventable kidney injury. Full article

Background/Objectives: Cowden syndrome (or PTEN hamartoma tumor syndrome) (CS/PHTS) belongs to a group of inherited disorders associated with the development of multiple hamartomas. The clinical presentation of patients may include dysmorphic facial features, macrocephaly, developmental delay, and multiple benign and malignant tumors of various localizations. At the same time, only thyroid cancer is thought to have an increased risk in childhood. Skin lesions in CS/PHTS occur in 90–100% of patients and include multiple tricholemmoma, papilloma, acral keratosis, pigmentation changes, as well as rarer forms like vascular malformations, fibromas, neuromas, melanoma, and basal cell carcinoma. Methods: Next-generation sequencing and Sanger sequencing were used to search for PTEN genetic variants. A histological and immunohistochemical examination of tumor biopsies and skin lesions was performed. Results: A total of 13 patients from six families with CS/PHTS, including 10 children, were described. Seven pediatric patients belonged to families with paternal transmission of the PTEN pathogenic variants, while three others were de novo cases. Atypical manifestations in CS/PHTS were diffuse large B-cell lymphoma in one adult, a renal cell carcinoma, three germ cell tumors, and a linear epidermal nevus in pediatric patients. A literature review of the identified pathogenic variants in the PTEN gene was performed, assessing their clinical significance and analyzing the traditional and modified diagnostic criteria as applied to the pediatric population. Conclusions: Taking into account the low incidence of CS/PHTS, the data presented significantly expand our current understanding of this disease and guide physicians to consider a wider range of possible malignant neoplasms in pediatric patients with CS/PHTS. Full article

Background/Objectives: Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis is a rare autoimmune disease marked by small-vessel inflammation. Pulmonary and renal manifestations are believed to critically influence prognosis, but detailed regional data are lacking. This study aimed to determine the prevalence and prognostic impact of pulmonary and renal involvement in AAV patients in the Thrace region of Türkiye. Methods: A retrospective cohort study was conducted on 78 biopsy-proven AAV patients followed between 2018 and 2025. Demographic, clinical, laboratory, and outcome data were analysed. Logistic regression identified predictors of relapse and mortality. Results: The cohort included 44 granulomatosis with polyangiitis, 30 microscopic polyangiitis, and 4 eosinophilic granulomatosis with polyangiitis patients; 40 were pr3-ANCA positive and 33 MPO-ANCA positive. Pulmonary involvement was observed in 71.8% and renal involvement in 74.4%, and overall mortality was 20.5%. All deaths occurred in patients with pulmonary involvement (28.6% vs. 0%, p = 0.048). Relapse was higher in those with pulmonary (17.9% vs. 4.5%, p = 0.048) and renal (15.5% vs. 5%, p = 0.056) involvement. Multivariate analysis showed that pulmonary involvement (OR 3.82, p = 0.002), renal involvement (OR 4.73, p = 0.013), and rituximab treatment (OR 10.79, p = 0.049) predicted relapse; elevated CRP (OR 1.01, p = 0.003), creatinine (OR 1.42, p = 0.028), hypoalbuminaemia (OR 0.24, p = 0.046), renal (OR 2.86, p = 0.031), and pulmonary (OR 3.21, p = 0.003) involvement predicted mortality. Conclusions: Pulmonary and renal involvement are highly prevalent and represent the strongest predictors of relapse and mortality in AAV patients in this regional cohort. Recognising these risks is essential to guide early interventions and improve patient outcomes. Full article

Background and Clinical Significance: Kidney transplantation remains the most effective method of renal replacement therapy. Living donor transplantation offers several advantages—reduced cardiovascular risk, better graft survival, and preemptive intervention. However, donor obesity is a growing concern, as it is usually associated with perioperative and long-term complications, which can affect donor eligibility. Bariatric surgery is a standard recommendation for patients with a BMI over 35 kg/m². There are limited data on the use of pharmacological agents for weight reduction in kidney donors. This case presents a successful conservative treatment with GLP-1 receptor agonist in an obese woman wishing to donate a kidney to her son. Case Presentation: We are presenting the case of a 63-year-old woman with grade II obesity who was initially denied being a kidney donor to her son because of her weight. Under these circumstances, she underwent comprehensive lifestyle modification in the cardio-obesitology clinic (caloric restriction, physical activity, and pharmacological treatment with liraglutide). During the 3-month follow-up, she decreased her BMI to 33.4 kg/m², and subsequent examinations confirmed no surgical contraindications to donating a kidney. Despite hematuria, biopsy and genetic testing revealed a benign carrier condition of Alport syndrome, which, without proteinuria or renal impairment, allowed successful kidney donation. Conclusions: This case demonstrates that conservative pharmacological treatment for body weight reduction with GLP-1 receptor agonists may be an alternative to bariatric surgery for selected obese kidney donor candidates. The presented case highlights the importance of a multidisciplinary and personalized approach. Full article

Renal cell carcinoma (RCC) is a major global health issue with an increasing incidence and mortality rate. Current diagnostic methods are either invasive or limited in their ability to accurately differentiate between benign and malignant tumours and to predict early treatment response. This can lead to incorrect diagnosis, delayed treatment, patient anxiety, and suboptimal outcomes. RCC subtypes are known to exhibit distinct metabolic alterations, for example in glucose metabolism. These metabolic phenotypes offer potential targets for non-invasive imaging techniques to improve diagnosis and treatment, but current clinically available metabolic imaging tools such as ¹⁸F-FDG-PET and ^99mTc-sestamibi SPECT have limitations. Therefore, new approaches are required to assess this metabolism, and novel metabolic MRI techniques including hyperpolarised [1-¹³C]pyruvate MRI and deuterium metabolic imaging offer promising alternatives. These techniques are non-radioactive, demonstrate spatial metabolic heterogeneity, and can probe metabolic flux beyond tracer uptake. This review aims to explore the potential of metabolic MRI in the clinical management of RCC by (1) summarising current clinical guidelines; (2) reviewing metabolic heterogeneity across RCC subtypes; (3) discussing the potential of metabolic MRI to advance the understanding of in vivo metabolism; (4) and finally suggesting future directions for research in this field. Full article

Background/Aim: Fibrillary glomerulonephritis (FGN) is a rare glomerular disease characterized by non-amyloid fibrillary deposits in the glomeruli and positive staining for DNAJB9. There is currently no treatment of choice, and the poor prognosis highlights the need for further research. We aimed to investigate the clinical and pathological characteristics and outcomes of FGN patients from a tertiary nephrology center. Methods: A retrospective cohort study of eleven patients diagnosed with FGN between 2016 and 2025, based on kidney biopsy and DNAJB9 positivity, was used. Partial response was defined as a ≥50% reduction in proteinuria with stable renal function. Results: At diagnosis, nine patients had nephrotic-range proteinuria, and eight had microscopic hematuria. Mean serum creatinine was 1.6 mg/dL, and mean proteinuria was 3.78 g/24 h. Comorbidities included SLE (n = 1), sarcoidosis (n = 1), and lung cancer (n = 1). The most common histological pattern was mesangial proliferative (n = 6). DNAJB9 staining was positive in five patients. All patients received RAAS blockade and immunosuppression (e.g., corticosteroids, rituximab). Partial response occurred in 73% with a median follow-up of 24 months, with 80% showing >50% proteinuria reduction. One patient died during follow-up; no patients progressed to ESRD or required dialysis. Conclusions: FGN is clinically diverse and lacks a standard treatment. The small sample size limits generalizability. Full article

Background: Fibrillary glomerulonephritis (FGN) is a rare and poorly understood kidney disease characterized by the deposition of non-amyloid fibrils in the glomeruli. Its clinical heterogeneity and high rate of progression to end-stage renal disease (ESRD) pose significant diagnostic and therapeutic challenges. This case series aims to enhance awareness of FGN and emphasizes the need for further research to improve patient outcomes. Case Reports: We reviewed the clinical, histopathological, and therapeutic data of three patients with FGN diagnosed by kidney biopsy. The cases included variations in clinical presentation from nephrotic syndrome to rapidly progressive glomerulonephritis (RPGN). Diagnostic methods incorporated light microscopy, immunofluorescence, and electron microscopy, with the integration of DnaJ homolog subfamily B member 9 (DNAJB9) staining for confirmation. Patient 1 showed a more favorable response to rituximab, achieving complete remission (CR) at 6 months and maintaining CR after 3 years. Patient 2 showed only partial remission after 2 years following treatment with rituximab. Patient 3 presented with RPGN and rapidly progressed to ESRD despite aggressive immunosuppressive therapy. Discussion: DNAJB9 has emerged as both a specific and sensitive biomarker in patients with FGN and has facilitated accurate differentiation from other glomerulopathies. This series underscores the variability in clinical outcomes and responses to therapy as well as the importance of early and accurate diagnosis. Conclusions: FGN remains a diagnostic and therapeutic challenge due to its rarity and heterogeneity. Advances in biomarkers like DNAJB9 have improved diagnostic accuracy, distinguishing FGN from similar conditions such as immunotactoid glomerulopathy. Further research into pathophysiological mechanisms and targeted therapies is essential to optimize management and outcomes for affected patients. Full article

Objective: The American Urological Association recommends ablation as an alternative treatment option for T1a RCC smaller than 3 cm. Our objective is to describe our technique and evaluate the outcomes of radiofrequency ablation (RFA) for biopsy-proven T1a RCC measuring 3–4 cm, compared to outcomes for tumors <3 cm. Materials and Methods: A single-center, retrospective review included patients with solitary, de novo, biopsy-proven T1a RCC who underwent RFA between January 2001 and December 2020. Using propensity score matching, patients with 3–4 cm lesions (Group A) were matched with patients with lesions less than 3 cm (Group B) based on the pathology, grade, duration of follow-up, another primary malignancy, age, and sex. Survival outcomes were estimated using the Kaplan and Meier product-limit estimator, and both groups were compared. Results: A total of 122 patients were included in the matched analyses. Eight patients were missing data on disease recurrence, leaving 114 patients with data on RFS and DFS (55 patients in Group A and 59 patients in Group B). The median tumor size in groups A and B was 3.3 cm and 2.2 cm, respectively. There was no statistically significant difference in the complication rate (p = 0.11) and local recurrence at the ablation site (p = 0.15). There was no statistically significant difference in overall survival (p = 0.93), recurrence-free survival (p = 0.45), or disease-free survival (p = 0.37). The metastasis-free survival and cancer-specific survival were 100% in both groups. Conclusions: RFA is a highly effective modality for the treatment of 3–4 cm T1a RCC, with long-term favorable oncologic and survival outcomes. Full article