Pathological diagnosis of Alport syndrome.

Alport syndrome (AS) is a hereditary nephritis characterized by structural abnormalities in the glomerular basement membrane resulting from pathogenic variants in the COL4A3, COL4A4, and COL4A5 genes. Conventional pathological evaluations reveal nonspecific light microscopic changes and diagnostic clues can be obtained through electron microscopy. Type IV collagen staining elucidates distinct patterns based on AS inheritance, aiding in subtype classification. However, limitations arise, particularly in autosomal dominant cases. Genetic testing, particularly next-generation sequencing, gains prominence due to its ability to identify diverse mutations within COL4A3, COL4A4, and COL4A5.

The contribution of the sphingosine 1-phosphate signaling pathway to chronic kidney diseases: recent findings and new perspectives.

Chronic kidney disease (CKD) is a multifactorial condition with diverse etiologies, such as diabetes mellitus, hypertension, and genetic disorders, often culminating in end-stage renal disease (ESRD). A hallmark of CKD progression is kidney fibrosis, characterized by the excessive accumulation of extracellular matrix components, for which there is currently no effective anti-fibrotic therapy. Recent literature highlights the critical role of sphingosine 1-phosphate (S1P) signaling in CKD pathogenesis and renal fibrosis. This review provides an in-depth analysis of the latest findings on S1P metabolism and signaling in renal fibrosis and in specific CKDs, including diabetic nephropathy (DN), lupus nephritis (LN), focal segmental glomerulosclerosis (FSGS), Fabry disease (FD), and IgA nephropathy (IgAN). Emerging studies underscore the therapeutic potential of modulating S1P signaling with receptor modulators and inhibitors, such as fingolimod (FTY720) and more selective agents like ozanimod and cenerimod. Additionally, the current knowledge about the effects of established kidney protective therapies such as glucocorticoids and SGLT2 and ACE inhibitors on S1P signaling will be summarized. Furthermore, the review highlights the potential role of S1P as a biomarker for disease progression in CKD models, particularly in Fabry disease and diabetic nephropathy. Advanced technologies, including spatial transcriptomics, are further refining our understanding of S1P's role within specific kidney compartments. Collectively, these insights emphasize the need for continued research into S1P signaling pathways as promising targets for CKD treatment strategies.

Clinical Characteristics, Pathological Features and Treatment Outcomes of Children With Nephrotic Syndrome at Princess Marina Hospital, Botswana.

Objective. Despite the remarkable progress made in the understanding and treatment of childhood nephrotic syndrome (NS), a lot is still unknown about its epidemiology in many African countries. This study sought to determine the clinicopathological features and treatment outcomes of children with NS at the largest tertiary hospital in Botswana. Methods. A retrospective study of 26 children with NS treated from 2009 to 2014 was conducted. Results. Mean age at presentation was 5.96 ± 3.06. Hematuria was found in 92.3%, low C3 in 26.7%, high creatinine in 19.2% and hypertension in 46.2% of the patients. 92.3% had primary NS out of which 23.1% had familial NS. HIV, tuberculosis and hepatitis B infections were diagnosed in 3.85%, 9.09% and 4.16% respectively. 69.2% had steroid-resistant nephrotic syndrome, focal segmental glomerulosclerosis (SRNS-FSGS). Conclusion. The frequency of primary SRNS-FSGS and familial SRNS appears to be much higher in Botswana highlighting the possibility of genetic causes.

IgA Nephropathy Secondary to COVID-19 Infection - A Case Report.

We present a case of a 73-year-old African American lady with COVID-19 infection who developed acute Kidney Injury (AKI) and significant proteinuria. Renal biopsy showed IgA nephropathy. Patient was eventually diagnosed with IgA nephropathy secondary to COVID Infection. This unique case highlights the complexity of renal involvement in COVID-19. Notably, the onset of IgA nephropathy in the patient occurred several weeks after her COVID-19 diagnosis, deviating from the typical synpharyngitic presentation. This article contributes to the growing body of evidence regarding renal complications associated with COVID-19 and highlights the need for vigilance in assessing and managing renal conditions in COVID-19 patients, especially when atypical presentations occur.

The dual role of lipids in chronic kidney disease: Pathogenic culprits and therapeutic allies.

Chronic kidney disease (CKD) is a significant health burden, with rising incidence and prevalence, attributed in part to increasing obesity and diabetes rates. Lipid accumulation in the kidney parenchyma and chronic, low-grade inflammation are believed to significantly contribute to the development and progression of CKD. The effect of dysregulated kidney lipid metabolism in CKD progression, including altered cholesterol and fatty acid metabolism contribute to glomerular and tubular cell injury through the activation of oxidative stress and inflammatory signalling cascades. In contrast, classes of endogenous specialized pro-resolving lipid mediators (SPMs) have been described that act to limit the inflammatory response and promote the resolution of inflammation. This review highlights our current understanding of how lipids can cause damage within the kidney, and classes of protective lipid metabolites that offer therapeutic benefits.

Lipoprotein Apheresis: Utility, Outcomes, and Implementation in Clinical Practice: A Scientific Statement From the American Heart Association.

Despite the availability of multiple classes of lipoprotein-lowering medications, some high-risk patients have persistent hypercholesterolemia and may require nonpharmacologic therapy. Lipoprotein apheresis (LA) is a valuable but underused adjunctive therapeutic option for low-density lipoprotein cholesterol and lipoprotein(a) lowering, particularly in children and adults with familial hypercholesterolemia. In addition to lipid lowering, LA reduces serum levels of proinflammatory and prothrombotic factors, reduces blood viscosity, increases microvascular myocardial perfusion, and may provide beneficial effects on endothelial function. Multiple observational studies demonstrate strong evidence for improved cardiovascular outcomes with LA; however, use in the United States is limited to a fraction of its Food and Drug Administration-approved indications. In addition, there are limited data regarding LA benefit for refractory focal segmental glomerulosclerosis. In this scientific statement, we review the history of LA, mechanisms of action, cardiovascular and renal outcomes data, indications, and options for treatment.

Transcriptome meta-analysis and validation to discovery of hub genes and pathways in focal and segmental glomerulosclerosis.

BACKGROUND: Focal segmental glomerulosclerosis (FSGS), a histologic pattern of injury in the glomerulus, is one of the leading glomerular causes of end-stage renal disease (ESRD) worldwide. Despite extensive research, the underlying biological alterations causing FSGS remain poorly understood. Studying variations in gene expression profiles offers a promising approach to gaining a comprehensive understanding of FSGS molecular pathogenicity and identifying key elements as potential therapeutic targets. This work is a meta-analysis of gene expression profiles from glomerular samples of FSGS patients. The main aims of this study are to establish a consensus list of differentially expressed genes in FSGS, validate these findings, understand the disease's pathogenicity, and identify novel therapeutic targets. METHODS: After a thorough search in the GEO database and subsequent quality control assessments, seven gene expression datasets were selected for the meta-analysis: GSE47183 (GPL14663), GSE47183 (GPL11670), GSE99340, GSE108109, GSE121233, GSE129973, and GSE104948. The random effect size method was applied to identify differentially expressed genes (meta-DEGs), which were then used to construct a regulatory network (STRING, MiRTarBase, and TRRUST) and perform various pathway enrichment analyses. The expression levels of several meta-DEGs, specifically ADAMTS1, PF4, EGR1, and EGF, known as angiogenesis regulators, were analyzed using quantitative reverse transcription polymerase chain reaction (RT-qPCR). RESULTS: The identified 2,898 meta-DEGs, including 665 downregulated and 669 upregulated genes, were subjected to various analyses. A co-regulatory network comprising 2,859 DEGs, 2,688 microRNAs (miRNAs), and 374 transcription factors (TFs) was constructed, and the top molecules in the network were identified based on degree centrality. Part of the pathway enrichment analysis revealed significant disruption in the angiogenesis regulatory pathways in the FSGS kidney. The RT-qPCR results confirmed an imbalance in angiogenesis pathways by demonstrating the differential expression levels of ADAMTS1 and EGR1, two key angiogenesis regulators, in the FSGS condition. CONCLUSION: In addition to presenting a consensus list of differentially expressed genes in FSGS, this meta-analysis identified significant distortions in angiogenesis-related pathways and factors in the FSGS kidney. Targeting these factors may offer a viable strategy to impede the progression of FSGS.

To biopsy or not to biopsy a teenager with typical idiopathic nephrotic syndrome? Start steroids first.

It is well known that minimal change disease (MCD) and focal segmental glomerulosclerosis are the most common histopathology findings in children with idiopathic nephrotic syndrome. Moreover, several studies demonstrated that MCD is associated with high steroid-responsiveness and a low incidence of kidney failure, suggesting that routine kidney biopsy is not warranted. Over time, the indications for performing a kidney biopsy have become increasingly stringent, aiming to limit unnecessary invasive procedures in the paediatric population. The most recent guidelines state that a kidney biopsy is not usually necessary at disease onset. Still, it should be performed in case of atypical features suggestive of systemic diseases or glomerulonephritis and in case of steroid-resistance, to assess the different differential diagnoses, regardless of patient age. Moreover, it has been shown that the best prognostic marker in childhood nephrotic syndrome is response to treatment and that kidney histology is not accurate in predicting prognosis. Furthermore, a kidney biopsy is not necessary to predict the relapsing course. Notably, kidney biopsy is an invasive procedure and may lead to significant complications. Finally, novel non-invasive biomarkers have been validated or are in the process of being approved to guide differential diagnoses and thus limit the need for kidney biopsies in patients with typical nephrotic syndrome. In the following sections, we aim to explain why initiating steroid treatment as the initial approach in teenagers with typical nephrotic syndrome is a reasonable strategy. Additionally, we explore how kidney biopsy indications may be alleviated in this population.

Aberrant localization of ß1 integrin in podocyte cytoplasm of primary FSGS with cellular lesion.

Podocyte detachment is a major trigger in pathogenesis of focal segmental glomerulosclerosis (FSGS). Detachment via ß1 integrin (ITGB1) endocytosis, associated with endothelial cell injury, has been reported in animal models but remains unknown in human kidneys. The objectives of our study were to examine the difference in ITGB1 dynamics between primary FSGS and minimal change nephrotic syndrome (MCNS), among variants of FSGS, as well as between the presence or absence of cellular lesions (CEL-L) in human kidneys, and to elucidate the pathogenesis of FSGS. Thirty-one patients with primary FSGS and 14 with MCNS were recruited. FSGS cases were categorized into two groups: those with CEL-L, defined by segmental endocapillary hypercellularity occluding lumina, and those without CEL-L. The podocyte cytoplasmic ITGB1 levels, ITGB1 expression, and degrees of podocyte detachment and subendothelial widening were compared between FSGS and MCNS, FSGS variants, and FSGS groups with and without CEL-L (CEL-L( +)/CEL-L( -)). ITGB1 distribution in podocyte cytoplasm was significantly greater in CEL-L( +) group than that in MCNS and CEL-L( -) groups. ITGB1 expression was similar in CEL-L( +) and MCNS, but lower in CEL-L( -) compared with others. Podocyte detachment levels were comparable in CEL-L( +) and CEL-L( -) groups, both exhibiting significantly higher detachment than the MCNS group. Subendothelial widening was significantly greater in CEL-L( +) compared with CEL-L( -) and MCNS groups. The findings of this study imply the existence of distinct pathological mechanisms associated with ITGB1 dynamics between CEL-L( +) and CEL-L( -) groups, and suggest a potential role of endothelial cell injury in the pathogenesis of cellular lesions in FSGS.

PPAR-α Insufficiency Enhances Doxorubicin-Induced Nephropathy in PPAR-α Knockout Mice and a Murine Podocyte Cell Line.

Peroxisome proliferator-activated receptor-alpha (PPAR-α) and its exogenous activators (fibrates) promote autophagy. However, whether the deleterious effects of PPAR-α deficiency on doxorubicin (DOX)-induced podocytopathy are associated with reduced autophagy remains to be clarified. We investigated the mechanisms of PPAR-α in DOX-induced podocytopathy and tubular injury in PPAR-α knockout (PAKO) mice and in a murine podocyte cell line. DOX-treated PAKO mice showed higher serum levels of triglycerides and non-esterified fatty acids and more severe podocytopathy than DOX-treated wild-type mice, as evidenced by higher urinary levels of proteins and podocalyxin at 3 days to 2 weeks and higher blood urea nitrogen and serum creatinine levels at 4 weeks. Additionally, there was an increased accumulation of p62, a negative autophagy marker, in the glomerular and tubular regions in DOX-treated PAKO mice at Day 9. Moreover, DOX-treated PAKO mice showed more severe glomerulosclerosis and tubular damage and lower podocalyxin expression in the kidneys than DOX-treated control mice at 4 weeks. Furthermore, DOX treatment increased p-p53, an apoptosis marker, and cleaved the caspase-3 levels and induced apoptosis, which was ameliorated by fenofibrate, a PPAR-α activator. Fenofibrate further enhanced AMPK activation and autophagy under fed and fasting conditions. Conclusively, PPAR-α deficiency enhances DOX-induced podocytopathy, glomerulosclerosis, and tubular injury, possibly by reducing autophagic activity in mouse kidneys.

How Stem and Progenitor Cells Can Affect Renal Diseases.

Stem and progenitor cells have been observed to contribute to regenerative processes in acute renal failure and chronic kidney disease. Recent research has delved into the intricate mechanisms by which stem and progenitor cells exert their influence on kidney diseases. Understanding how these cells integrate with the existing renal architecture and their response to injury could pave the way for innovative treatment strategies aimed at promoting kidney repair and regeneration. Overall, the role of stem and progenitor cells in kidney diseases is multifaceted, with their ability to contribute to tissue regeneration, immune modulation, and the maintenance of renal homeostasis. Here, we review the studies that we have available today about the involvement of stem and progenitor cells both in regenerative therapies and in the causes of renal diseases, as well as in natural healing mechanisms, taking into account the main kidney disorders, such as IgA nephropathy, lupus nephritis, diabetic nephropathy, C3 glomerulopathy, focal segmental glomerulosclerosis, idiopathic membranous nephropathy, anti-glomerular basement membrane glomerulonephritis, and ANCA-associated crescentic glomerulonephritis. Moreover, based on the comprehensive data available in the framework of the specific kidney diseases on stem cells and renal progenitors, we hypothesize a possible role of adult renal progenitors in exacerbating or recovering the illness.

Altered Endoplasmic Reticulum Integrity and Organelle Interactions in Living Cells Expressing INF2 Variants.

The cytoskeleton mediates fundamental cellular processes by organizing inter-organelle interactions. Pathogenic variants of inverted formin 2 (INF2) CAAX isoform, an actin assembly factor that is predominantly expressed in the endoplasmic reticulum (ER), are linked to focal segmental glomerulosclerosis (FSGS) and Charcot-Marie-Tooth (CMT) neuropathy. To investigate how pathogenic INF2 variants alter ER integrity, we used high-resolution live imaging of HeLa cells. Cells expressing wild-type (WT) INF2 showed a predominant tubular ER with perinuclear clustering. Cells expressing INF2 FSGS variants that cause mild and intermediate disease induced more sheet-like ER, a pattern similar to that seen for cells expressing WT-INF2 that were treated with actin and microtubule (MT) inhibitors. Dual CMT-FSGS INF2 variants led to more severe ER dysmorphism, with a diffuse, fragmented ER and coarse INF2 aggregates. Proper organization of both F-actin and MT was needed to modulate the tubule vs. sheet conformation balance, while MT arrays regulated spatial expansion of tubular ER in the cell periphery. Pathogenic INF2 variants also induced mitochondria fragmentation and dysregulated mitochondria distribution. Such mitochondrial abnormalities were more prominent for cells expressing CMT-FSGS compared to those with FSGS variants, indicating that the severity of the dysfunction is linked to the degree of cytoskeletal disorganization. Our observations suggest that pathogenic INF2 variants disrupt ER continuity by altering interactions between the ER and the cytoskeleton that in turn impairs inter-organelle communication, especially at ER-mitochondria contact sites. ER continuity defects may be a common disease mechanism involved in both peripheral neuropathy and glomerulopathy.

Autophagic inhibitor ROC-325 ameliorates glomerulosclerosis and podocyte injury via inhibiting autophagic flux in experimental FSGS mice.

BACKGROUND: Autophagy plays an important role in the pathogenesis of focal segmental glomerulosclerosis (FSGS). Podocyte-specific Yes-associated protein (YAP) deletion mice, referred to as YAP-KO mice, is considered a new animal model to study the underlying mechanism of FSGS. ROC-325 is a novel small-molecule lysosomal autophagy inhibitor that is more effective than chloroquine (CQ) and hydroxychloroquine (HCQ) in suppressing autophagy. In this study, we sought to determine the therapeutic benefit and mechanism of action of ROC-325 in YAP-KO mice, an experimental FSGS model. METHODS AND RESULTS: YAP-KO mice were treated with ROC-325 (50 mg/kg, p.o.) daily for one month. Our results revealed that albuminuria, mesangial matrix expension, and focal segmental glomerulosclerosis in YAP-KO mice were significantly attenuated by ROC-325 administration. Transmission electron microscopy and immunofluorescence staining showed that ROC-325 treatment significantly inhibited YAP-KO-induced autophagy activation by decreasing autophagosome-lysosome fusion and increasing LC3A/B and p62/SQSTM. Meanwhile, Immunofluorescence staining revealed that preapplication of ROC-325 in podocyte with YAP-targeted siRNA and mRFP-GFP-LC3 adenovirus markedly suppressed autophagic flux in vitro, suggesting that autophagy intervention may serve as a target for FSGS. CONCLUSIONS: These results showed that the role of autophagic activity in FSGS mice model and ROC-325 could be a novel and promising agent for the treatment of FSGS.

To biopsy or not to biopsy a teenager with idiopathic nephrotic syndrome? Biopsy first.

Kidney biopsy plays a crucial role in the diagnosis and management of several glomerular diseases. While it is generally considered a routine and safe procedure in children, it should be conducted with the primary objective of addressing the following question: do the prognosis and treatments vary based on the findings of kidney biopsy? In children presenting with idiopathic nephrotic syndrome (INS), guidelines suggest to consider kidney biopsy for individuals older than 12 years, primarily due to the possible increased incidence of different glomerulonephritis compared to younger patients, who predominantly manifest with minimal change disease. However, these guidelines also advocate for uniform therapeutic strategies, typically steroids, irrespective of the age or histological findings. Whether the age of more than 12 years may be a recommendation for performing kidney biopsy at presentation of INS is debatable. Instead, kidney biopsy could be reserved for steroid-resistant cases. On the other hand, when kidney biopsy is performed in INS, particularly in focal segmental glomerulosclerosis, histology may reveal additional lesions, that are strongly associated with a poorer response to treatment and worse clinical outcomes. Therefore, current guidelines on treatments of nephrotic syndrome may appear overly restrictive, despite the relevant findings provided by kidney biopsy. Therefore, in the present manuscript, which is part of a pro-con debate on the management of nephrotic syndrome in adolescents, we emphasize the potential role of performing a kidney biopsy before initiating corticosteroid treatment.

Safety and efficacy of sparsentan versus irbesartan in focal segmental glomerulosclerosis and IgA nephropathy: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Sparsentan has shown positive effects on managing different subtypes of glomerulonephritis. The recent results of trials require a pooled analysis to validate these results. AIM: We aim to assess the safety and efficacy of sparsentan versus irbesartan for patients with IgA nephropathy and focal glomerulosclerosis (FSGS). METHODS: We conducted a systematic review and meta-analysis of randomized controlled trials retrieved by systematically searching PubMed, Web of Science, Scopus, and Cochrane through March 2024. We used Review Manager v.5.4 to pool dichotomous data using risk ratio (RR) and continuous data using mean difference (MD) with a 95% confidence interval (CI). RESULTS: Three studies with a total of 884 patients were included. Sparsentan was superior to irbesartan in improving urine protein to creatinine ratio (UP/C) (ratio of percentage reduction 0.66, 95% CI [0.58 to 0.74], P < 0.001); as well as the proportion of patients achieved complete and partial remission of proteinuria (RR = 2.57, 95% CI [1.73 to 3.81], P < 0.001) and (RR = 1.63, 95% CI [1.4 to 1.91], P < 0.001) respectively. Regarding the effect on the glomerular filtration rate, the results estimate did not favor either sparsentan or irbesartan (MD = 1.98 ml/min per 1.73mm2, 95% CI [-1.05 to 5.01], P = 0.2). There were no significant differences in adverse events except for hypotension, which showed higher rates in the sparsentan group (RR = 2.02, 95% CI [1.3 to 3.16], P = 0.002). CONCLUSION: Sparsentan is effective and has a good safety profile for treating FSGS and patients with IgA nephropathy. However, more well-designed RCTs against ARBs, ACE inhibitors, and steroids with larger sample sizes are needed to get conclusive evidence.

Differing sensitivities to angiotensin converting enzyme inhibition of kidney disease mediated by APOL1 high-risk variants G1 and G2.

Apolipoprotein L1 (APOL1) variants G1 and G2 contribute to the excess risk of kidney disease in individuals of recent African ancestry. Since disease mechanisms and optimal treatments remain controversial, we study the effect of current standard-of-care drugs in mouse models of APOL1 kidney disease. Experiments were performed in APOL1 BAC-transgenic mice, which develop proteinuria and glomerulosclerosis following injection with a pCpG-free IFN-γ plasmid. Proteinuric, plasmid injected G1/G1 and G2/G2 mice were randomized to drug treatment or no treatment. Lisinopril, dapagliflozin, and hydralazine were administered in drinking water starting day seven. The urine albumin/creatinine ratio was measured twice weekly, and the kidneys examined histologically with the focal segmental glomerulosclerosis score computed from periodic acid-Shiff-stained sections. The angiotensin converting enzyme inhibitor lisinopril, at standard dose, reduced proteinuria by approximately 90-fold and reduced glomerulosclerosis in the APOL1 G1/G1 BAC-transgenic mice. These effects were independent of blood pressure. Dapagliflozin did not alter disease progression in either G1/G1 or G2/G2 mice. Proteinuria reduction and glomerulosclerosis in G2/G2 BAC-transgenic mice required lisinopril doses two times higher than were effective in G1/G1 mice but achieved a much smaller benefit. Therefore, in these BAC-transgenic mouse models of APOL1 disease, the anti-proteinuric and anti-glomerulosclerotic effects of standard dose lisinopril were markedly effective in G1/G1 compared with G2/G2 APOL1 mice. Comparable reduction in blood pressure by hydralazine treatment provided no such protection. Neither G1/G1 nor G2/G2 mice showed improvement with the sodium-glucose cotransporter-2 inhibition dapagliflozin. Thus, it remains to be determined if similar differences in ACE inhibitor responsiveness are observed in patients.

Rituximab in Steroid-Dependent Podocytopathies.

Introduction: Rituximab (RTX) has been reported as an effective treatment alternative in primary forms of minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS) associated with steroid dependence and frequent relapses. However, the optimal RTX regimen and the outcomes of further doses of RTX remain unclear. This study aimed to evaluate the use of induction and maintenance RTX therapy for adults with primary podocytopathies. Methods: We performed a retrospective case series on adult patients with steroid-dependent podocytopathies who received an induction RTX therapy. Maintenance therapy was performed at physician's discretion. Remission and relapse rates, concomitant corticosteroids and immunosuppressants use, B-cell depletion and adverse events were analyzed. Results: Fourteen patients (mean age at start of RTX 29.1 ± 21.9 years) with MCD (n = 7) or FSGS (n = 7) were treated with 2 doses of 1,000 mg 2 weeks apart (n = 13) or four doses of 375 mg/m2 (n = 1) of RTX. At last follow-up (mean 47.3 ± 101.7 months), 10 patients were in complete remission and two remained in partial remission. A reduction in the number of relapses, number of patients under corticosteroids and immunosuppressants, and dose of prednisolone was observed when compared to baseline (14 [100%] vs. 5 [35.7%]; 8/14 [57.1%] vs. 4/12 [33.3%]; 13/14 [92.9%] vs. 7/12 [58.3%]; 20 mg/day vs. 5.25 mg/day, respectively). Maintenance RTX therapy was used in 6 patients, with sustained complete remission. Infusion reactions were observed in 4 patients (one required treatment withdrawal). Conclusions: Our findings support the use of RTX for a steroid-free remission in podocytopathies and suggest that maintenance RTX is well-tolerated and associated with prolonged remission. Further studies are needed to confirm its efficacy and safety and establish the optimal induction and maintenance RTX regimen in steroid-dependent podocytopathies.

Rituximab (RTX) seems to be an effective treatment alternative in primary forms of MCD and FSGS, particularly in cases of steroid dependence and frequent relapses. Our findings support the use of RTX for a steroid-free remission in podocytopathies and suggest that maintenance RTX is well-tolerated and associated with prolonged remission. Further studies are needed to confirm its efficacy and safety and establish the optimal induction and maintenance RTX regimen in steroid-dependent podocytopathies.

Unveiling Renal Lipid Deposition: A Rare Case of Hepatic Glomerulosclerosis Resembling Lecithin-Cholesterol Acyltransferase (LCAT) Deficiency Post Liver Transplantation.

Hepatic glomerulosclerosis, a renal complication of liver cirrhosis, presents challenges in diagnosis and management. This case report discusses the rarity of kidney biopsy findings resembling lecithin-cholesterol acyltransferase (LCAT) deficiency post liver transplantation. We present the case of a patient with end-stage liver disease (ESLD) from alcohol-related cirrhosis, who underwent orthotopic liver transplantation (OLT) with persistent proteinuria after transplantation. Kidney biopsy revealed features of hepatic glomerulopathy resembling both IgA nephropathy (IgAN) and LCAT deficiency. The histopathological similarities between hepatic glomerulosclerosis and LCAT deficiency suggest a potential link between liver disease and lipid deposition in the kidneys. The clinical course and outcomes of such renal alterations post liver transplantation remain uncertain, highlighting the need for further research in glomerular pathology in the context of liver transplantation. This case underscores the importance of kidney biopsy in ESLD patients and the necessity for more attention to glomerular pathology post liver transplantation, especially in the current era of increasing liver transplantation rates.

National Unified Renal Translational Research Enterprise: Idiopathic Nephrotic Syndrome (NURTuRE-INS) study.

Background: Idiopathic nephrotic syndrome (INS) is a heterogenous disease and current classification is based on observational responses to therapies or kidney histology. The National Unified Renal Translational Research Enterprise (NURTuRE)-INS cohort aims to facilitate novel ways of stratifying INS patients to improve disease understanding, therapeutics and design of clinical trials. Methods: NURTuRE-INS is a prospective cohort study of children and adults with INS in a linked biorepository. All recruits had at least one sampling visit collecting serum, plasma, urine and blood for RNA and DNA extraction, frozen within 2 hours of collection. Clinical histology slides and biopsy tissue blocks were also collected. Results: A total of 739 participants were recruited from 23 centres to NURTuRE-INS, half of whom were diagnosed in childhood [n = 365 (49%)]. The majority were white [n = 525 (71%)] and the median age at recruitment was 32 years (interquartile range 12-54). Steroid-sensitive nephrotic syndrome (SSNS) was the most common clinical diagnosis [n = 518 (70%)]. Of patients diagnosed in childhood who underwent a kidney biopsy, for SSNS (n =103), 76 demonstrated minimal change disease (MCD), whereas for steroid-resistant nephrotic syndrome (n =80), 21 had MCD. Almost all patients diagnosed in adulthood had a kidney biopsy [n = 352 (94%)]; 187 had MCD and 162 had focal segmental glomerulosclerosis. Conclusions: NURTuRE-INS is a prospective cohort study with high-quality biosamples and longitudinal data that will assist research into the mechanistic stratification of INS. Samples and data will be available through a Strategic Access and Oversight Committee.