Search Results (280)

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

IgA nephropathy is the most common primary glomerulonephritis, with pathohistological changes described by the Oxford classification, while the Banff classification is used in transplant pathology. This study included 253 patients with IgA nephropathy in native kidneys, divided into the pediatric (n = 105) and adult (n = 148) groups. It aimed to examine clinical, and Oxford and Banff morphological parameters in relation to age, correlations of clinical data with pathohistological parameters, and predictors of the disease outcome. Pediatric patients more frequently presented with macroscopic hematuria, while adults showed higher urea and creatinine levels, and lower eGFR. Examining Oxford classification parameters, chronic glomerular and tubulointerstitial lesions were more common in adults. Banff parameters revealed more frequent chronically active glomerular, inflammatory, chronic tubulointerstitial, and vascular lesions in adults. All inflammatory, chronic tubulointerstitial, and vascular parameters correlated with serum urea levels, eGFR and CKD stage in adults, while less frequent in pediatric patients. Tubulointerstitial Oxford and Banff parameters were strong predictors of CKD and proteinuria progression in children, while such predictors were fewer in adults; segmental glomerulosclerosis predicted hematuria progression in adults. Banff parameters (cg, t, ti, i, i-IFTA, ptc, cv), not in Oxford classification, significantly predict outcomes and are recommended for incorporation into IgA nephropathy reports. Full article

Focal and segmental glomerulosclerosis (FSGS) describes a histological pattern of injury seen by light microscopy in kidney biopsy specimens and is the end result of various injuries to the podocyte. Our understanding of this disease entity has evolved greatly since it was first described, with particular focus on changes in the classification of FSGS as a disease entity and expansion in our understanding of the underlying pathophysiology. The incidence and prevalence of FSGS and FSGS-associated end-stage kidney disease (ESKD) have increased globally, particularly in the United States; it is now the most common primary glomerular disorder in those with ESKD. APOL-1 is likely responsible for this epidemiological trend in kidney disease in the US and is an important focus of clinical trials and potential targeted therapies. Currently, the goal of treatment in FSGS is to achieve remission of proteinuria and to prevent progression to ESKD. Remission is achieved by using immunosuppressive therapies in primary FSGS, but treatment in secondary and genetic FSGS is largely supportive. Recurrent FSGS (rFSGS) post-transplantation remains a significant clinical challenge to nephrologists; current monitoring and treatment strategies are based on retrospective meta-analysis and observational studies with no clear consensus as to the optimum approach. Emerging therapies are focused on developing more targeted interventions in genetic and secondary FSGS. This review article aims to comprehensively explore this multifaceted disease entity. Full article

Unilateral renal agenesis (URA) is a urinary tract congenital anomaly characterized by a congenital absence or early developmental arrest of only one kidney. In the presence of a normal contralateral kidney, URA is typically considered a condition of minimal clinical significance as the solitary kidney often undergoes hypertrophy and can sufficiently perform the needed renal function after birth. However, postnatal studies suggest that URA has a significant association with other urinary and extra-urinary anomalies and may have implications for long-term health. This descriptive review focuses on the perinatal aspects of URA, emphasizing the main ultrasound findings to establish the prenatal diagnosis and to guide perinatal management. The pediatric implications of this diagnosis, particularly the high prevalence of long-term complications including hypertension, proteinuria, and a decreased glomerular filtration rate, are also briefly reviewed. URA is consistently associated with other ipsilateral urogenital anomalies. In females, there is a significant association with uterine anomalies that has significant implications for subsequent reproductive function. In males, the prevalence of both urinary and genital anomalies is also increased, which may also have implications for future fertility. Prenatal ultrasound offers the possibility of early diagnosis and parental counseling, which may result in timely intervention to reduce contralateral renal damage, prevent severe urogenital manifestations and co-morbidities, and improve fertility and the quality of life. Full article

Background: GLP-1 receptor agonists (GLP-1 RAs) lower glucose and reduce cardiovascular events in type 2 diabetes, with noted renal benefits. Few studies directly compare GLP-1 RAs. This study aims to compare the effects of semaglutide and dulaglutide on renal function decline and proteinuria reduction in diabetic patients. Methods: The present study was conducted at Wanfang Hospital, Taipei Medical University. Diabetic patients using either semaglutide or dulaglutide for more than 1 year in the outpatient department from 1 January 2022 to 30 September 2024 were enrolled retrospectively. The outcome events in the present study included a decline in the estimated glomerular filtration rate (eGFR), an increase in the urine albumin–creatinine ratio (UACR), and patient death. Results: A total of 268 patients on dulaglutide and 747 on semaglutide were included. Baseline eGFR levels were similar in both groups. After 12 months, eGFR levels did not significantly decline in both groups. However, the dulaglutide group showed significantly higher UACR increases than the semaglutide group (p < 0.01). More death events also occurred in the dulaglutide group (p < 0.01). Multivariate logistic regression revealed a higher risk of UACR increase with dulaglutide (p < 0.01). Subgroup analysis found dulaglutide associated with higher UACR in patients younger than 60, males, those with hypertension, without heart failure, those using angiotensin receptor blockers, biguanides, and statins, and those not using sodium-glucose cotransporter-2 inhibitors. Conclusions: Dulaglutide and semaglutide had comparable effects on slowing eGFR decline. However, dulaglutide was less effective in reducing UACR, particularly in the subgroups mentioned above. Full article

SHROOM3 encodes an actin-binding protein involved in kidney development and has been associated with chronic kidney disease through genome-wide association studies. However, its regulatory role in proteinuric kidney diseases and its mechanistic contributions to podocyte homeostasis remain poorly defined. Here, we analyzed single-cell transcriptomic datasets and the Nephroseq database to delineate SHROOM3 expression patterns in proteinuric kidney diseases. Using podocyte-specific SHROOM3 knockout mice and an Adriamycin (ADR)-induced nephropathy mouse model, we demonstrated that glomerular SHROOM3, specifically in podocytes, was upregulated following ADR treatment during the acute injury phase but downregulated in chronic kidney disease. Clinically, the glomerular SHROOM3 expression positively correlated with glomerular filtration rates in focal segmental glomerulosclerosis patients. Genetic ablation of SHROOM3 in podocytes exacerbated ADR-induced proteinuria, diminished podocyte markers (nephrin, podocin, and WT1), and accelerated glomerulosclerosis. In vitro, SHROOM3 deficiency impaired podocyte size and adhesion, concomitant with the downregulation of focal adhesion molecules (talin1, vinculin, and paxillin) and stress fiber regulators (synaptopodin and RhoA), as well as calpain activation and RhoA inactivation. Our findings reveal a critical role for SHROOM3 in maintaining podocyte integrity and suggest its therapeutic potential in mitigating proteinuric kidney disease progression. 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

IgA nephropathy (IgAN) is an inflammatory glomerular disease caused by the production of galactose-deficient IgA1 (Gd-IgA1), which induces the formation of autoantibodies and IgA immune complexes (IgAICs) that are ultimately deposited in the mesangium. This event triggers mesangial cell proliferation, cytokine release and complement activation, and both glomerular and interstitial damage, eventually leading to kidney function decline. Persisting proteinuria is the most relevant marker of disease progression. Systemic corticosteroids (CSs), a powerful anti-inflammatory approach, have shown kidney protective effects in early trials involving patients with IgAN at risk of progression with persistent proteinuria. However, later studies raised concerns regarding severe adverse events associated with high doses of methylprednisolone and questioned the long-term benefits. As a result, the KDIGO 2021 guidelines recommended limiting CS therapy to selected patients who accepted the high risk of adverse events. The treatment landscape shifted when reduced doses of methylprednisolone, combined with Pneumocystis pneumonia prophylaxis, demonstrated similar kidney protection compared to full methylprednisolone doses with fewer adverse events. An innovative approach involves a targeted budesonide formulation acting on Peyer’s patches, the main site of Gd-IgA1 production. This treatment showed benefits comparable to systemic CSs, with valuable limitations of adverse events. Several new drugs targeting key pathogenetic events of IgAN are under investigation, with promising results published in recent months. These new therapies target B cell activation (and subsequent Gd-IgA1 production), the complement cascade triggered by IgAIC deposition and the endothelin system, a key amplifier of kidney damage that contributes to the chronicity of IgAN. 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/Objectives: While sodium–glucose cotransporter 2 (SGLT2) inhibitors have demonstrated additional non-glycemic benefits for renal protection in individuals with type 2 diabetes, less evidence is available for those with type 1 diabetes (T1D). To determine whether the adjunctive use of the SGLT2 inhibitor ipragliflozin confers kidney protection in individuals with T1D, we retrospectively analyzed data from a real-world cohort examined at 25 centers in Japan. Methods: We enrolled 359 subjects aged 20–74 years with T1D (IPRA group: 159 ipragliflozin users; control [CTRL] group: 200 non-users). The primary outcome was changes in the estimated glomerular filtration rate (eGFR) from baseline to 24 months after the initiation of ipragliflozin. The secondary outcomes were all other changes, including the urinary albumin–creatinine ratio (UACR) and urinary protein–creatinine ratio (UPCR). Results: The IPRA group’s eGFR decline slopes were 0.79 mL/min/1.73 m²/year milder than the CTRL group’s after propensity score matching, but this difference was not significant. The subjects complicated by chronic kidney disease (CKD) defined as UACR ≥ 30 mg/g and/or UPCR ≥ 0.5 g/g and/or eGFR < 60 mL/min/1.73 m² showed changes in UPCR (g/g) from baseline to 24 months that were significantly lower in the IPRA group (−0.27 ± 1.63) versus the CTRL group (0.18 ± 0.36) (p = 0.016). No significant increase in adverse events (including severe hypoglycemia and hospitalization due to ketosis/ketoacidosis or cardiovascular diseases) was observed in the IPRA group. Conclusions: Adjunctive treatment with ipragliflozin exerted potential renal benefits by decreasing proteinuria in T1D subjects with CKD. Further investigations are required to determine whether its additional benefits exceed the increased risk of ketoacidosis. Full article

Extracellular vesicles (EVs) may play a role in preeclampsia (PE)-associated glomerular damage. We herein investigated the role of PE plasma EVs in triggering a detrimental crosstalk between glomerular endothelial cells (GEC) and podocytes (PODO). Clinical and laboratory variables were examined at T0 (diagnosis), T1 (delivery), and T2 (one month after delivery) in 36 PE patients and 17 age-matched controls. NanoSight and MACSPlex evaluated EV concentration, size, and phenotype. GEC and PODO were stimulated with plasma EVs to study viability, reactive oxygen species (ROS) production, permeability to albumin, endothelial-to-mesenchymal transition, and Endothelin-1 release. EV size and concentration were higher in PE than in healthy controls and in severe than in mild forms of disease. At T0, higher EV concentration correlated with proteinuria, blood pressure, uric acid, and liver enzyme levels. PE-EVs originated from leukocytes, endothelial cells, platelets, and the placenta and induced GEC and PODO damage as shown by the reduction of viability, increased ROS release, and albumin permeability. Co-culture experiments demonstrated that PE-EVs mediated a deleterious intraglomerular crosstalk through Endothelin-1 release from GEC able to down-regulate nephrin in PODO. In conclusion, we observed in PE plasma a peculiar pattern of EVs able to affect GEC and PODO functions and to induce proteinuria through Endothelin-1 involvement. Full article

Sodium-glucose cotransporter 2 (SGLT2) inhibitors, initially developed for glycaemic control in type 2 diabetes, have demonstrated substantial renal and cardiovascular protective effects across various chronic kidney diseases (CKD), including glomerulonephritis. Beyond their established haemodynamic and metabolic benefits, recent evidence points to additional mechanisms of action potentially relevant to immune-mediated kidney diseases, such as the modulation of inflammation, immunometabolism, and oxidative stress. Randomised clinical trials (DAPA-CKD and EMPA-KIDNEY) and real-world observational studies consistently show that SGLT2 inhibitors reduce proteinuria and slow estimated glomerular filtration rate (eGFR) decline in patients with glomerulonephritis, including IgA nephropathy and focal segmental glomerulosclerosis. These benefits may extend to patients with stable immunosuppression. Further data are needed in this subgroup. Importantly, SGLT2 inhibitors display a favourable safety profile, even among those with immunosuppressed status. Again, further evidence is awaited in this respect. Despite these promising findings, unanswered questions remain regarding their efficacy in nephrotic syndrome, early-stage disease, and in comparison or combination with other supportive therapies. Overall, the evolving evidence supports the inclusion of SGLT2 inhibitors as a key component of supportive therapy in glomerulonephritis, with potential benefits extending beyond proteinuria reduction. Full article

Dietary exposure to a high dose of cadmium (Cd) ≥ 100 µg/day for at least 50 years or a lifetime intake of Cd ≥ 1 g can cause severe damage to the kidneys and bones. Alarmingly, however, exposure to a dose of Cd between 10 and 15 µg/day and excretion of Cd at a rate below 0.5 µg/g creatinine have been associated with an increased risk of diseases with a high prevalence worldwide, such as chronic kidney disease (CKD), fragile bones, diabetes, and cancer. These findings have cast considerable doubt on a “tolerable” Cd exposure level of 58 µg/day for a 70 kg person, while questioning the threshold level for the Cd excretion rate of 5.24 µg/g creatinine. The present review addresses many unmet challenges in a threshold-based risk assessment for Cd. Special emphasis is given to the benchmark dose (BMD) methodology to estimate the Cd exposure limit that aligns with a no-observed-adverse-effect level (NOAEL). Cd exposure limits estimated from conventional dosing experiments and human data are highlighted. The results of the BMDL modeling of the relationship between Cd excretion and various indicators of its effects on kidneys are summarized. It is recommended that exposure guidelines for Cd should employ the most recent scientific research data, dose–response curves constructed from an unbiased exposure indicator, and clinically relevant adverse effects such as proteinuria, albuminuria, and a decrease in the estimated glomerular filtration rate (eGFR). These are signs of developing CKD and its progression to the end stage, when dialysis or a kidney transplant is required for survival. Full article

Background: Acute rejection (AR) in kidney transplant (KT) recipients remains a significant challenge for short- and long-term graft survival even in the most recent years characterized by extended criteria donors and older and more comorbid recipients. Methods: We analyzed risk factors and outcomes of AR in 339 KT recipients treated at St. Orsola-Malpighi Hospital, Bologna (Italy), between 1 January 2019 and 31 December 2021. Demographic, immunological, and transplant data (type, cold ischemia time, complications) were recorded with a follow-up period of up to 24 months. Key outcomes included estimated glomerular filtration rate (eGFR), 24 h proteinuria, delayed graft function (DGF), biopsy-proven AR, and graft loss. Results: During the first year after transplant, 57 AR episodes occurred: 19 antibody-mediated rejections (AMR), 18 borderline T cell-mediated rejections (TCMR), 18 TCMR, 2 mixed AMR/TCMR, and 11 graft losses. AR was linked to older donor age (59.9 ± 12.8 vs. 55.5 ± 15.1, p = 0.040), longer cold ischemia time (690 vs. 570 min, p = 0.044), higher DGF rates (61.40% vs. 39.57%, p = 0.002), and lower eGFR (39 vs. 52 mL/min, p = 0.003). AR was consistently prevalent in patients who underwent an AB0-incompatible (AB0-i) transplant (8.8% vs. 2.5%, p = 0.020). HLA matching was strongly associated with a reduced risk of AMR (HLA-DR: OR 0.35, HLA-A: OR 0.33, HLA-C: OR 0.35), while DGF was linked to a higher risk (OR 4.04). TCMR risk was associated with donor age (OR 1.05). The development of post-transplant donor-specific antibodies (DSAs) at 24 months showed no significant association with AR (AMR: p = 0.769; TCMR: p = 0.938). The decline in eGFR over time (24 months) did not differ between patients with and without AR (difference, −0.69 mL/min/year; Standard Error, 0.92; p = 0.452). Similarly, 24 h proteinuria change over time did not differ between patients with and without AR (difference, −0.12 g/24 h; Standard Error, 0.28; p = 0.657). Conclusions: Understanding the risk factors of AR is crucial to identifying KTs at more risk of rejection and to guiding targeted therapeutic decisions. In the most recent era of extended criteria donors and more vulnerable recipients, early diagnosis and prompt and tailored treatment of AR play a critical role in stabilizing renal function over time. Full article

Background: The COVID-19 (coronavirus disease 2019) pandemic has presented a serious challenge to nephrologists, since it can lead to severe kidney injury in the form of acute tubular necrosis, with many patients requiring renal replacement therapy. This is predominantly seen in people who develop severe respiratory manifestations like ARDS (acute respiratory distress syndrome) from the viral infection, a cytokine storm or septic shock with unstable hemodynamics. It also presents with various glomerular injuries, mainly collapsing glomerulopathy in high-risk APOL1 (Apolipoprotein L1) genotype patients, thrombotic microangiopathy-related renal failure due to hyper coagulopathy and occasionally pauci-immune glomerulonephritis due to immune dysregulation. All the glomerular disorders that are caused by COVID-19 infection have been described under the designation COVAN (COVID-19-associated nephropathy). Proteinuria is a predominant presentation in glomerular disorders. Gross hematuria and AKI without any respiratory symptoms from COVID-19 infection have not been described so far in the literature. We are presenting one such rare case here. Methods: We have encountered a rare case of gross hematuria and severe acute renal failure. His serological work up was negative for all autoimmune etiologies that can cause Glomerulonephritis. He was found to have infection-related crescentic glomerulonephritis due to active COVID-19 infections discovered via kidney biopsy. He tested positive for SARS-CoV-2 but didn’t have any clinical respiratory symptoms. He has responded well to treatment with a steroid taper and antiviral medication (Remdesivir). This is a very rare renal manifestation of COVID-19 infection. Results: COVID-19 infection can result in crescentic glomerulonephritis. This can be diagnosed by kidney biopsy which shows extensive c3 deposits, tubuloreticular inclusion bodies along with crescentic lesions. This responds to treatment with steroids and Antiviral agents. Conclusions: Crescentic Glomerulonephritis should be considered as a possible etiology for severe acute kidney injury with hematuria in patients with active covid-19 infection without any respiratory symptoms. Kidney biopsy helps in diagnosing it and responds to treatment with steroids and antivirals. Full article