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BACKGROUND: Leveraging the Accelerating Medicines Partnership (AMP) Lupus Nephritis (LN) dataset, we evaluated longitudinal patterns, rates, and predictors of response to standard-of-care therapy in patients with lupus nephritis. METHODS: Patients from US academic medical centers with class III, IV, and/or V LN and a baseline urine protein/creatinine (UPCR) ratio ≥ 1.0 (n = 180) were eligible for this analysis. Complete response (CR) required the following: (1) UPCR  50% reduction in UPCR; (2) normal serum creatinine or, if abnormal, ≤ 125% of baseline; and (3) prednisone dose ≤ 15 mg/day. RESULTS: Response rates to the standard of care at week 52 were CR = 22.2%; PR = 21.7%; non-responder (NR) = 41.7%, and not determined (ND) = 14.4%. Only 8/180 (4.4%) patients had a week 12 CR sustained through week 52. Eighteen (10%) patients attained a week 12 PR or CR and sustained their responses through week 52 and 47 (26.1%) patients achieved sustained PR or CR at weeks 26 and 52. Week 52 CR or PR attainment was associated with baseline UPCR > 3 (ORadj = 3.71 [95%CI = 1.34-10.24]; p = 0.012), > 25% decrease in UPCR from baseline to week 12 (ORadj = 2.61 [95%CI = 1.07-6.41]; p = 0.036), lower chronicity index (ORadj = 1.33 per unit decrease [95%CI = 1.10-1.62]; p = 0.003), and positive anti-dsDNA antibody (ORadj = 2.61 [95%CI = 0.93-7.33]; p = 0.069). CONCLUSIONS: CR and PR rates at week 52 were consistent with the standard-of-care response rates observed in prospective registrational LN trials. Low sustained response rates underscore the need for more efficacious therapies and highlight how critically important it is to understand the molecular pathways associated with response and non-response.

Proteasome inhibitors (PIs) are crucial in treating multiple myeloma but carry a risk of thrombotic microangiopathy (TMA), especially with carfilzomib use. This systematic review includes 44 studies with 115 cases of PI-induced TMA, where carfilzomib was implicated in 101 cases. Treatment approaches varied: 28 patients received supportive care, 43 underwent therapeutic plasma exchange (TPE), 9 were treated exclusively with eculizumab (ECU), and 13 received both TPE and ECU. Notably, eculizumab significantly improved outcomes for patients unresponsive to initial TPE, achieving complete remission in seven cases. The need for dialysis emerged as a significant predictor of outcomes, often indicating a poor prognosis. For patients suspected of having PI-TMA, it is advisable to discontinue the offending medication promptly, even without definitive laboratory confirmation. In cases where diagnosis is challenging, kidney biopsy may assist if conditions permit. Comprehensive evaluation of the complement system, including genetic mutations, function, and associated complement inhibitory factor antibodies, should be included in the assessment of PI-TMA. Early administration of eculizumab may be beneficial in cases of suspected complement abnormalities or suboptimal response to initial treatments. Highlights: This review systematically addresses for the first time the clinical manifestations, treatments, and prognostic outcomes associated with PI-related TMA. Based on existing research, it is proposed that activation of the complement pathway may be the underlying mechanism of PI-TMA, with further elaboration provided. A comprehensive management model for PI-TMA has been proposed. [ABSTRACT FROM AUTHOR]

Introduction: Diabetic Kidney Disease (DKD) is a major complication of Diabetes Mellitus (DM). Renal biopsy is the gold standard for the diagnosis and management of many renal diseases. Renal Interstitial Fibrosis and Tubular Atrophy (IFTA), as well as the number of obsolescent glomeruli, are prognostic factors associated with Diabetic Nephropathy (DN). Aim: To describe the renal biopsy profile of patients with DM presenting with renal disease and to determine the significance of IFTA scoring and the number of obsolescent glomeruli in predicting DKD and its severity. Materials and Methods: This cross-sectional study was conducted over a period of three years, from 2019 to 2022, involving a total of 189 patients selected through purposive sampling. Patients with DM who presented with renal disease and required renal biopsy to confirm the diagnosis were admitted to the Department of General Medicine and Nephrology at Kempegowda Institute of Medical Sciences Hospital and Research Centre, Bengaluru, Karnataka, India. The biopsy reports were obtained and analysed. Data were analysed using Statistical Package for the Social Sciences (SPSS) version 20.0 and results were expressed using descriptive and inferential statistics. A p-value of <0.05 was considered statistically significant. Results: The mean age of the participants was 53.02±11.00 years, with an age range from 21 to 81 years. Among the subjects, 78.3% were males and 21.7 were females. Based on the renal biopsy findings, DN was the most common condition, found in 127 subjects (67.6%). Nearly 50.0% of those with DN had Class IV chronic DN, followed by Class III (42.5%). Chronic interstitial nephritis was the most common Non Diabetic Kidney Disease (NDKD), accounting for 24.6% of cases. IFTA scoring was significantly associated with DKD and there was a significant positive correlation between the severity of IFTA scores and the number of obsolescent glomeruli with the class of DKD. A unit rise in the IFTA score and the number of obsolescent glomeruli increased the risk of having severe DKD (Class III and Class IV) by 4.32 times and 1.24 times, respectively, compared to those with less severe forms (Class I and II) (p<0.05). Conclusion: The IFTA scoring and the number of obsolescent glomeruli were found to be significant independent predictors of the severity of DKD. [ABSTRACT FROM AUTHOR]

Objective: Unusual clinical course Background: Focal segmental glomerulosclerosis (FSGS) very rarely occurs in patients with multiple myeloma. Much more common are renal impairments secondary to monoclonal light-chain tubulopathy, AL amyloidosis, light-chain deposition disease, and the so-called monoclonal gammopathy of renal significance. Case Report: We report the case of a 79-year-old myeloma patient without noticeable medical problems but with a long history of myeloma treatment beginning 13 years ago. In the ninth line of therapy, he was successfully treated with belamaf mafodotin, an anti-BCMA monoclonal antibody coupled to monomethyl auristatin F. After 1.5 years of treatment, without any eye toxicity, and while he was in complete hematologic remission, he experienced a very severe COVID-19 infection followed 1 month later by a nephrotic syndrome. The renal biopsy revealed a FSGS not otherwise specified. He was successfully treated symptomatically. One and a half years later, and without treatment for 1 year, he is still in hematologic remission, with a remaining renal insufficiency. Conclusions: Our patient had a particularly long response to belamaf mafodotin of more than 2.5 years, which is still ongoing. This is particularly remarkable because the very unusual acute renal impairment was not myeloma related. This is a very rare case of FSGS in a myeloma patient, potentially linked to a COVID-19 infection considering the chronology of the events and the immunosuppressive status secondary to the malignancy and its treatment. [ABSTRACT FROM AUTHOR]

The morphologic finding of transplant glomerulitis (g) forms important evidence of microvascular injury. Besides antibody-mediated rejection (ABMR), this morphological feature is also seen in acute cellular rejection (ACR) and vasculitis but not included in the grading criteria for cellular rejection. A systematic review was thus conducted to summarize the current evidence and shed light on the quantum of impetus to be given to this finding when encountered during evaluation of renal biopsies. Out of a total of 13 studies selected, 06 studies supported the histologic finding of glomerulitis in ACR and non-DSA ABMR morphologies with variable incidence ranging from 15 to 21%. Seven studies supported glomerulitis as an independent prognostic marker for graft outcome at 1 year post transplant with or without DSA with highest HR reported of 4.52 and lowest being 01. Reviewing the present literature revealed interesting insights into occurrence, nature, molecular expression, role in glomerular injury and long-term outcomes with glomerulitis. It is recommended to approach the treatment of such lesions with heightened caution, as there appear to be elevated rates of graft failure, delayed graft function and Transplant glomerulopathy. [ABSTRACT FROM AUTHOR]

Introduction: CD44 is a transmembrane glycoprotein implicated in tissue inflammation and fibrosis. We investigated its role in kidney inflammation and fibrosis in a murine model of lupus nephritis (LN), and the clinico-pathological association of serum CD44 level in patients with biopsy-proven Class III/IV ± V LN. Methods: NZB/W F1 mice were treated with control IgG or anti-CD44 monoclonal antibody for 4 weeks and disease parameters assessed. Serum CD44 level in LN patients was determined by ELISA. Control groups included healthy subjects and patients with non-renal SLE or non-lupus renal disease. Results: CD44 expression was absent in the normal kidney, but it was expressed in proximal and distal tubular epithelial cells and infiltrating cells in renal biopsies from patients with active proliferative LN. ScRNA-Seq datasets confirmed that CD44 was predominantly expressed in tubular cells and all immune cells identified in LN patients including tissue resident, inflammatory and phagocytic macrophages, Treg cells, effector and central memory CD4+ T cells, resident memory CD8+ T cells and naïve and activated B cells. Treatment of NZB/W F1 mice with anti-CD44 antibody preserved kidney histology and reduced proteinuria, tubulo-interstitial infiltration of CD3+, CD4+ and CD19+ immune cells, and mediators of kidney fibrosis compared to Control mice. Longitudinal studies showed that serum CD44 level increased prior to clinical renal flare by 4.5 months and the level decreased after treatment. ROC curve analysis showed that CD44 level distinguished patients with active LN from healthy subjects and patients with quiescent LN, active non-renal lupus, and non-lupus CKD (ROC AUC of 0.99, 0.96, 0.99 and 0.99 respectively). CD44 level correlated with leukocyte infiltration and interstitial inflammation scores in active LN kidney biopsies. Discussion: Our findings suggest that CD44 plays a pathogenic role in renal parenchymal inflammation and fibrosis in active LN and monitoring CD44 may facilitate early diagnosis of flare. [ABSTRACT FROM AUTHOR]

Background: Chronic kidney disease (CKD) is a significant clinical challenge in Sri Lanka. The present study presents histopathological diagnoses from native renal biopsies in Kandy District, 2011–2020. Methods: Reports of 5,014 renal biopsies principally performed at Kandy Teaching Hospital over 2011–2020 were reviewed. After exclusions for post-kidney transplant biopsies (1,572) and those without evident pathology (347), 3,095 biopsies were included. The predominant histopathological entities were grouped and categorised according to diagnosis and stratified by age and sex. Results: The main histopathological entities (all biopsies) were tubulointerstitial nephropathy (TIN) 25% (n = 760), glomerulonephritis (GN) 15% (467), lupus nephropathy 14% (429), focal segmental glomerular sclerosis (FSGS) 10% (297), and IgA nephropathy (IgAN) 8% (242). For adult women ≥ 15 years, the main histopathological entities were lupus nephropathy 24% (325), TIN 17% (228), and GN 16% (217). For adult men ≥ 15 years, the main histopathological entities were TIN 34% (449), GN 14% (180), and IgAN 10% (125). The proportion of TIN in the present study was higher than international studies of a similar size. Conclusion: This is the largest study of renal biopsies reported from Sri Lanka to date. TIN was the most common diagnosis in adults ≥ 15 years at 25%. Notable sex differences showed TIN was the most common histopathology in men (34%) but not in women (17%). No previously published similar study of this size has found TIN as the predominant diagnosis amongst renal biopsies in men. Further research is required into the possible causes of these observations in Sri Lanka. Clinical Trial Number. Not applicable. [ABSTRACT FROM AUTHOR]

Type I interferons (IFN-Is) are important players in the immunopathogenesis of systemic lupus erythematosus (SLE). Pathogenic events in patients with SLE are potent triggers of IFN-I induction, yet IFN-I may induce or initiate the immunopathogenesis leading to these events. Because blocking IFN-I is effective in some clinical manifestations of SLE patients, concerns about the efficacy of anti-IFN-I therapy in patients with lupus nephritis remain. Tissues from kidney biopsies of patients with lupus nephritis revealed infiltration of various immune cells and activation of inflammatory signals; however, their correlation with renal damage is not clear, which raises serious concerns about how critical the role of IFN-I is among the potential contributors to the pathogenesis of lupus nephritis. This review addresses several issues related to the roles of IFN-I in SLE, especially in lupus nephritis, including (1) the contribution of IFN-I to the development and immunopathogenesis of SLE; (2) evidence supporting the association of IFN-I with lupus nephritis; (3) therapies targeting IFN-I and IFN-I downstream signaling molecules in SLE and lupus nephritis; (4) findings challenging the therapeutic benefits of anti-IFN-I in lupus nephritis; and (5) a perspective associated with anti-IFN-I biologics for lupus nephritis treatment. In addition to providing clear pictures of the roles of IFN-I in SLE, especially in lupus nephritis, this review addresses the lately published observations and clinical trials on this topic. [ABSTRACT FROM AUTHOR]

Chronic graft-versus-host disease (GVHD) is a major complication after allogeneic hematopoietic stem cell transplantation (HSCT). Chronic GVHD may have atypical manifestations affecting non-classical organs. The diagnosis in patients with atypical manifestations of chronic GVHD is particullarly challenging, and there is a lack of knowledge regarding their pathogenesis and treatment. We reported a case who developed post-HSCT nephrotic syndrome and portal hypertensive ascites, which are both rare and atypical manifestations of chronic GVHD. Kidney biopsy revealed membranous nephropathy and renal thrombotic microangiopathy with glomerular immune deposits, suggesting antibody-mediated kidney injury. Treatment with ruxolitinib resulted in remission of both nephrotic syndrome and ascites, suggesting a role of cytokines in the pathogenesis. This case highlighted the awareness of nephrotic syndrome and portal hypertensive ascites as atypical manifestations of chronic GVHD, and the efficacy of ruxolitinib for the two manifestations. [ABSTRACT FROM AUTHOR]

Background: Onconephrology is a growing discipline that aims to improve the management of patients with cancer and kidney disease. If kidney histology is an essential key, the anatomopathological data remain weak although essential to this complex management. Methods: Patients with active cancer who had a kidney biopsy (KB) between 2014 and 2020 were included, and their clinicobiological and histological data were analyzed retrospectively. Results: Our cohort consisted of 154 patients (83 women) with a mean age of 58 years. One hundred twelve patients presented with proteinuria, 95 with acute kidney injury, and 59 with arterial hypertension. Histologically, interstitial fibrosis was found in 74% of KBs, tubular atrophy in 55.1%, arteriolar hyalinosis in 58.4%, and fibrous endarteritis in 54.4%. Regarding the main acute lesions, thrombotic microangiopathy (TMA) was found in 29.9% of biopsies, acute tubular necrosis (ATN) in 51.3%, and acute interstitial nephritis in 24.8%. The etiological diagnosis most often made was the nephrotoxicity of anticancer drugs (87 patients), followed by a pre-renal (15 patients) and kidney disease unrelated to cancer (13 patients). Sixty-seven patients presented with at least 2 associated diagnoses reflecting the complexity of kidney damage in cancer. Different clusters were found, highlighting that immunotherapy and anti-VEGF were the most commonly involved drugs. Conclusions: During onconephrology practice, kidney toxicity of treatments is the most common etiology. Several mechanisms can be involved, underscoring the importance of kidney biopsy and the complexity of its management. Chronic histological lesions were very common. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the prognostic importance of sex in lupus nephritis (LN). Methods: A retrospective cohort of 1048 biopsy-confirmed LN patients, diagnosed between January 1, 1996, and December 31, 2018, was analyzed. Demographics, clinical characteristics, laboratory findings, and renal pathology were assessed. The primary outcome was mortality, and the secondary outcomes included doubling of serum creatinine and end-stage renal disease (ESRD). Sex-associated risks were evaluated using Cox regression models. Results: Among the1048 patients, 178 (17%) were male and 870 (83%) were female. Male patients exhibited more aggressive features: higher blood pressure, earlier disease onset, and elevated levels of serum creatinine (Scr), uric acid, blood urea nitrogen. Intriguingly, male patients also displayed more severe histopathological alterations, such as more total crescents, cellular crescents formations, higher level of glomerular leukocyte infiltration and Activity Index (AI), even when overall renal pathology was comparable between sexes. During a median follow-up of 112 months, mortality was registered in 141 patients (15.3%). Mortality rates were conspicuously higher in males (24.2% males vs. 13.4% females, p = 0.0029). Secondary outcomes did not show significant sex differences. Cox regression analysis highlighted male, age of renal biopsy, eGFR, and Chronicity Index (CI) as independent risk factors for survival in LN patients. Notably, infections emerged as the leading cause of mortality among LN patients, with a significant higher rate in male patients. Conclusion: In our cohort with LN, there was a higher rate of all-cause mortality and proportion of infection-related death in male. Recognizing and further exploring these sex disparities is crucial for optimized LN patients care. [ABSTRACT FROM AUTHOR]

Systemic lupus erythematosus (SLE) is an autoimmune disorder that often leads to kidney injury, known as lupus nephritis (LN). Although renal biopsy is the primary way to diagnose LN, it is invasive and not practical for regular monitoring. As an alternative, several groups have proposed urinary extracellular vesicles (uEVs) as potential biomarkers for LN, as recent studies have shown their significance in reflecting kidney-related diseases. As a result, we developed a flow cytometry approach that allowed us to determine that LN patients exhibited a significantly higher total uEV concentration compared to SLE patients without kidney involvement. Additionally, an analysis of different-sized uEV subsets revealed that microvesicles ranging from 0.3 to 0.5 μm showed the most promise for distinguishing LN. These findings indicate that evaluating uEV concentration and size distribution could be a valuable diagnostic and monitoring tool for LN, pending further validation in more comprehensive studies. [ABSTRACT FROM AUTHOR]

BACKGROUND. The HIV Organ Policy Equity (HOPE) Act allows individuals living with HIV to accept organs from donors with HIV. This practice widens the pool of available organs, but also presents important virological issues, including the potential for HIV superinfection of the recipient, viral persistence in the kidney, and loss of virological control. METHODS. We addressed these issues by performing in-depth longitudinal viral sequence analyses on urine, blood, and urinederived renal epithelial cells from 12 recipients of HIV+ kidney allografts. RESULTS. We amplified donor-derived HIV-1 env sequences in 5 out of 12 recipients after transplant. These donor-derived env sequences were amplified from recipient urine, urine-derived renal epithelial cells, and plasma between 12 and 96 hours after transplant and remained detectable up to 16 days after transplant. Env sequences were also detected in kidney biopsies taken from the allografts before implantation in 6 out of the 12 transplant cases, indicating the presence of donor virus within the organ. One recipient had a viremic episode 3.5 years after transplantation as a result of antiretroviral therapy (ART) interruption. Only recipient strain viral sequences were detected in blood, suggesting that the donor virus, if still present, was not reactivated during the temporary ART withdrawal. CONCLUSIONS. This study demonstrates that the HIV env sequences in a donor kidney can be amplified from biopsies taken from the allograft before implantation and can be detected transiently in blood and urine samples collected from the organ recipients after transplantation. FUNDING. National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) grant number R01DK131497. [ABSTRACT FROM AUTHOR]

Introduction: Fibrillary glomerulonephritis (FGN) is a rare form of glomerular disease that accounts for less than 1 percent of all renal biopsies. It is characterized by pathognomonic electron microscopy findings of fibrillar deposits in the mesangium and glomerular capillary walls. FGN was initially considered to be an idiopathic disorder. However, approximately 30–50 percent of patients have a secondary cause, including a history of malignancy in up to 23% of cases. Chronic lymphocytic leukemia (CLL) is a rare cause of FGN, with limited data and poor prognosis. Case Presentation: In this report, we present the case of a 69-year-old male who was diagnosed with CLL in 2013 and was initially managed conservatively. In 2016, he developed nephrotic syndrome and renal impairment. Renal biopsy showed FGN, and treatment was targeted to the CLL with bendamustine and rituximab, which led to partial remission of nephrotic syndrome and improvement in renal function. After 3 years of clinical remission, the nephrotic syndrome relapsed, and he underwent a repeat renal biopsy confirming ongoing FGN. A bone marrow biopsy confirmed CLL relapse, and the patient was treated with ibrutinib (a tyrosine kinase inhibitor). The patient achieved a significant organ response and sustained remission. Conclusion: This case highlights the success of treating a potentially identifiable cause of FGN and highlights that even at relapse, treatment can confer benefits and help prevent end-stage renal failure. [ABSTRACT FROM AUTHOR]

Background: There is a need to develop accurate and reliable non-invasive methods to evaluate chronic kidney disease (CKD) status and assess disease progression. Given it is recognized that dysregulation in metabolic pathways occur from early CKD, there is a basis in utilizing metabolomic biomarkers to monitor CKD progression. Volatile Organic Compounds (VOCs), a form of metabolomic biomarker, are gaseous products of metabolic processes in organisms which are typically released with greater abundance in disease conditions when there is dysregulation in metabolism. How urinary VOCs reflect the abnormal metabolic profile of patients with CKD status is unknown. Our study aimed to explore this. Methods: Individuals aged 18–75 years undergoing kidney biopsy were included. Pre-biopsy urine samples were collected. All biopsy samples had an interstitial fibrosis and tubular atrophy (IFTA) grade scored by standardized assessment. Urine supernatant was extracted from residue and sampled for stir bar sorptive extraction followed by Gas chromatography–mass spectrometry (GC-MS) analysis. Post-processing of GC-MS data separated complex mixtures of VOCs based on their volatility and polarity. Mass-to-charge ratios and fragment patterns were measured for individual VOCs identification and quantification. Linear discriminant analysis (LDA) was performed to assess the ability of urinary VOCs in discriminating between IFTA 0 ('no or minimal IFTA' i.e. <10%, IFTA), IFTA 1 ('mild IFTA' i.e. 10–25% IFTA) and IFTA ≥ 2 ('moderate or severe IFTA' i.e. >25% IFTA). Linear regression analysis adjusting for age, sex, estimated glomerular filtration rate, diabetes mellitus (DM) status, and albuminuria was conducted to determine significantly regulated urinary VOCs amongst the groups. Results: 64 study participants (22 individuals IFTA 0, 15 individuals IFTA 1, 27 individuals IFTA ≥ 2) were included. There were 34 VOCs identified from GC-MS which were statistically associated with correct classification between the IFTA groups, and LDA demonstrated individuals with IFTA 0, IFTA 1 and IFTA ≥ 2 could be significantly separated by their urinary VOCs profile (p < 0.001). Multivariate linear regression analysis reported 4 VOCs significantly upregulated in the IFTA 1 compared to the IFTA 0 group, and 2 VOCs significantly upregulated in the IFTA ≥ 2 compared to the IFTA 1 group (p < 0.05). Significantly upregulated urinary VOCs belonged to one of four functional groups - aldehydes, ketones, hydrocarbons, or alcohols. Conclusions: We report novel links between urinary VOCs and tubulointerstitial histopathology. Our findings suggest the application of urinary VOCs as a metabolomic biomarker may have a useful clinical role to non-invasively assess CKD status during disease progression. [ABSTRACT FROM AUTHOR]

Proteinuria selectivity index (PSI) is a potential tool for histological classification and prediction of treatment response in nephrotic syndrome, but evidence is insufficient. Clinical relevance of fractional excretion of sodium (FENa) in nephrotic syndrome remains largely unexplored. This multicenter retrospective study included patients with nephrotic syndrome who underwent kidney biopsy between January 2012 and June 2022. Optimal cutoffs for predicting complete remission based on PSI and FENa were determined using receiver operating characteristic curves. Patients were divided into two groups using these cutoffs and followed until complete remission. Of the 611 patients included, 177 had minimal change disease (MCD), 52 had focal segmental glomerulosclerosis (FSGS), and 149 had membranous nephropathy (MN). Median (interquartile range) PSI were 0.14 (0.09–0.19) for MCD, 0.33 (0.23–0.40) for FSGS, and 0.20 (0.14–0.30) for MN. FENa were 0.24 (0.09–0.68), 1.03 (0.50–2.14), and 0.78 (0.41–1.28). Patients with low PSI and FENa had a higher incidence of complete remission. Cox regression analyses demonstrated that both parameters were associated with achieving complete remission (HR 2.73 [95% CI 1.97–3.81] and HR 1.93 [95% CI 1.46–2.55], respectively). PSI and FENa may be useful for histological classification and predicting remission in nephrotic syndrome. [ABSTRACT FROM AUTHOR]

Introduction: Malakoplakia is a rare and chronic granulomatous disease that is pathologically characterized by the presence of Michaelis-Gutmann bodies and large macrophage clusters. Malakoplakia of the renal parenchyma is especially rare. In this report, we describe the long-term prognosis of a patient who was diagnosed with and treated for renal parenchymal malakoplakia in infancy. Case Presentation: Seventeen years after malakoplakia onset, the patient presented to us with worsening proteinuria. Computed tomography revealed structural abnormalities in the kidney, and focal segmental glomerulosclerosis (FSGS) was diagnosed based on renal biopsy findings. No Michaelis-Gutmann bodies were observed in von Kossa-stained biopsy specimens. Regular outpatient monitoring during the next 9 years showed gradual deterioration of renal function and a moderately high protein/creatinine ratio. Conclusion: Our findings suggest that structural changes due to malakoplakia can cause FSGS. Moreover, structural changes indicate the healing of malakoplakia in infancy and the disappearance of its characteristic lesions over time. Owing to its long-term observation period, this unique case provides new insights into the outcomes of patients with renal parenchymal malakoplakia. [ABSTRACT FROM AUTHOR]

Objective This retrospective study evaluated tolvaptan's efficacy, safety, and predictive indicators in managing volume overload in chronic kidney disease (CKD) patients. Methods CKD patients with volume overload, treated with loop diuretics alone or with tolvaptan at Zhongda Hospital, Southeast University, from 1 March 2022 to 31 December 2023, were included. Patients were divided into loop diuretic (Group C) and loop diuretic combined with tolvaptan (Group T) cohorts. Primary outcomes included volume control, changes in weight, urine output, and laboratory parameters within 1 week post-medication. Adverse events such as hypernatremia and hyperkalemia, etc. were recorded. We further conducted immunohistochemical staining of renal biopsy tissues to investigate the roles of aquaporin-2 (AQP2) in the collecting duct and plasma albumin in predicting the efficacy of tolvaptan. Results Of 174 CKD patients with volume overload, 108 (67.07%) were male. Group C and Group T each comprised 87 patients. At baseline, no significant differences in urine output and weight were noted. By day 3, Group T exhibited a greater increase in urine output (P  < .001) and weight reduction (P  < .001). At day 7, Group T maintained more significant diuretic effects (P  < .001). More Group C patients required ultrafiltration therapy (P  = .040). Adverse event rates did not significantly differ. Notably, AQP2 expression in the collecting duct may predict tolvaptan responsiveness, while plasma albumin did not affect efficacy. Conclusion Tolvaptan showed efficacy and safety in managing volume overload in CKD patients. The expression of AQP2 in the collecting duct could predict tolvaptan's efficacy. This study protocol was approved by the Ethics Committee of Zhongda Hospital Affiliated to Southeast University (Approval No. 2023ZDSYLL180-P01, Clinical Trial Registration No. ChiCTR2300075274, Trial Registration Link: https://www.chictr.org.cn/guide.html). [ABSTRACT FROM AUTHOR]

The discovery of the target antigen M-type phospholipase A2 receptor (PLA2R) with the possibility to detect anti-PLA2R antibodies in serum as well as the identification of several other antigens, overall accounting for almost all cases of membranous nephropathy, paved the way to a revolutionary change in the classification of membranous nephropathy. Serum anti-PLA2R autoantibody titers have been found to be highly specific diagnostic and prognostic biomarkers. Therefore, a positive test for anti-PLA2R serology in patients who present with nephrotic syndrome, normal kidney function, and no evidence of another process to account for proteinuria is believed to suffice to make a diagnosis of primary membranous nephropathy, thus removing the need for a renal biopsy. While technological advances will likely allow this proposal to prevail in the near future, the reasons why renal biopsy could still remain a critical tool for the management of membranous nephropathy in real life are discussed. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Acute Coxiella burnetti (Q fever) infection is known to activate the autoimmune inflammatory response. We report a rare case of glomerulonephritis associated with the Coxiella infection. An elderly male first presented with recurrent fevers of unknown origin and was subsequently diagnosed with Q fever infection and treated with doxycycline. He represented 2 months later with an acute kidney injury and active urinary sediment. Renal biopsy demonstrated a mesangiopathic pattern with staining for both C1q and IgM, raising possibilities of infection‐related glomerulonephritis, C1q nephropathy and lupus nephritis. This case demonstrates glomerulonephritis as a complication of Q fever infection and the differential diagnosis and workup up that needs to be considered in cases of chronic Q fever. [ABSTRACT FROM AUTHOR]

There have been exciting advances in our knowledge of primary glomerular diseases and nephrotic syndromes in recent years. Beyond the histological pattern from renal biopsy, more precise phenotyping of the diseases and the use of modern nephrogenetics helps to improve treatment decisions and sometimes also avoid unnecessary exposure to potentially toxic immunosuppression. New biomarkers have led to easier and more accurate diagnoses and more targeted therapeutic decisions. The treatment landscape is becoming wider with a pipeline of promising new therapeutic agents with more sophisticated approaches. This review focuses on all aspects of entities that are associated with nephrotic syndromes with updated information on recent advances in each field. This includes podocytopathies (focal segmental glomerulosclerosis and minimal-change disease), membranous nephropathy, membranoproliferative glomerulonephritis, IgA nephropathy, fibrillary glomerulonephritis, amyloidosis, and monoclonal gammopathy of renal significance in the context of the nephrotic syndrome, but also renal involvement in systemic diseases, diabetic nephropathy, and drugs that are associated with nephrotic syndromes. [ABSTRACT FROM AUTHOR]

Background: Kidney biopsy is the standard of care for the diagnosis of various kidney diseases. In particular, chronic histopathologic lesions, such as interstitial fibrosis and tubular atrophy, can provide prognostic information regarding chronic kidney disease progression. In this study, we aimed to evaluate historadiological correlations between CT-based radiomic features and chronic histologic changes in native kidney biopsies and to construct and validate a radiomics-based prediction model for chronicity grade. Methods: We included patients aged ≥ 18 years who underwent kidney biopsy and abdominal CT scan within a week before kidney biopsy. Left kidneys were three-dimensionally segmented using a deep learning model based on the 3D Swin UNEt Transformers architecture. We additionally defined isovolumic cortical regions of interest near the lower pole of the left kidneys. Shape, first-order, and high-order texture features were extracted after resampling and kernel normalization. Correlations and diagnostic metrics between extracted features and chronic histologic lesions were examined. A machine learning-based radiomic prediction model for moderate chronicity was developed and compared according to the segmented regions of interest (ROI). Results: Overall, moderate correlations with statistical significance (P < 0.05) were found between chronic histopathologic grade and top-ranked radiomic features. Total parenchymal features were more strongly correlated than cortical ROI features, and texture features were more highly ranked. However, conventional imaging markers, including kidney length, were poorly correlated. Top-ranked individual radiomic features had areas under receiver operating characteristic curves (AUCs) of 0.65 to 0.74. Developed radiomics models for moderate-to-severe chronicity achieved AUCs of 0.89 (95% confidence interval [CI] 0.75–0.99) and 0.74 (95% CI 0.52–0.93) for total parenchymal and cortical ROI features, respectively. Conclusion: Significant historadiological correlations were identified between CT-based radiomic features and chronic histologic changes in native kidney biopsies. Our findings underscore the potential of CT-based radiomic features and their prediction model for the non-invasive assessment of kidney fibrosis. [ABSTRACT FROM AUTHOR]

Background: Behcet's disease (BD) is an inflammatory disorder of unknown cause that is characterized by recurrent oral aphthous ulcers, genital ulcers, uveitis, and skin lesions. Local vasculitis can cause damage to the visceral system, but it is rare in kidney patients, especially those with IgA nephropathy (IgAN). In China, a small number of related cases have been reported. Here we present a case of co-occurrence of BD and IgAN. Case presentation: : An 18-year-old female who presented with a history of recurrent oral ulcers was found ten years ago. Four years later, the patient presented with reddish nodules on the skin of both lower limbs and then presented with vulvar ulcers. This patient was clinically diagnosed with Behcet's disease after left calf skin biopsy and presented severe proteinuria and hematuria during this period. IgAN was diagnosed after percutaneous renal biopsy. The patient was treated with hormonal, anti-inflammatory, immunomodulatory, kidney protective, and protein-lowering urine agents. After 3 years of follow-up, the patient reappears oral ulcers, reddish nodules on the skin of both lower limbs and renal dysfunction. Conclusions: BD is less common in China and is clinically prone to missed diagnosis and misdiagnosis. BD with IgAN is rarer. We should regularly pay attention to the routine urine and renal function of BD patients for early detection and treatment and to prevent further progression of the disease. [ABSTRACT FROM AUTHOR]

Background: Fibronectin glomerulopathy (FNG) is a rare autosomal dominant glomerulopathy that can lead to nephrotic syndrome. Here we report the case of an elderly patient diagnosed with FNG, exhibiting nephrotic-range proteinuria, with a 2-year follow-up. Case presentation: A 75-year-old Korean female visited the nephrology clinic after experiencing generalized edema for 2 months. Her serum creatinine was 1.36 mg/dL, and urine protein-to-creatinine ratio was 3.99 g/g. Kidney biopsy revealed mesangial and subendothelial dense deposits, and immunohistochemistry for fibronectin showed strong positivity in the glomerulus. The patient's family history included non-specific renal disease in her mother and two siblings. Genetic testing of the fibronectin 1 (FN1) gene showed Y973C mutation. She received conservative treatment, including angiotensin II receptor blockers (ARB). Two years after biopsy, the patient has preserved renal function and reduced proteinuria. Conclusion: We report the case of a 75-year-old patient with nephrotic-range proteinuria, who was diagnosed with FNG, and found to harbor a FN1 gene mutation. In this case, conservative treatment including ARB yielded reduction of proteinuria and preservation of renal function. [ABSTRACT FROM AUTHOR]

Background: Research biopsies have great potential to advance scientific knowledge by helping to establish predictors of favourable or unfavourable outcomes in kidney transplantation. We evaluated punch and core biopsies of different sizes to determine the optimal size for clinical use. Methods: A total of 54 punch biopsies and 18 core needle biopsies were retrieved by three transplant surgeons. Each surgeon obtained three separate 2 mm, 3 mm and 4 mm punch biopsy samples and three 23 mm (length) core needle biopsies from two pig kidneys. Results: 4 mm punch biopsies yielded the greatest amount of protein (2.11 ± 0.41 mg) with good reproducibility between surgeons and biopsy types (Coefficient of Variation ∼ 22.13%). All surgeons found 2 mm biopsies technically challenging to obtain and sample processing was difficult due to the sample size. Shotgun proteomics identified 3853 gene products with no significant difference in the quantitative proteome of 2 mm and 3 mm punch biopsies. However, the expression of 158 Kidney enriched genes, was higher in bigger and deeper 4 mm punch and core needle biopsies compared to 2 mm biopsy. Only 80% of 2 mm biopsies demonstrated the presence of glomeruli, whereas glomeruli were present in 100% of all other biopsy sizes. Conclusions: The 2 mm punch biopsy has been shown to be challenging to use and frequently provides inadequate tissue for histology and proteomics while 3 mm research biopsies were the smallest size that were technically obtainable with adequate tissue for molecular studies. [ABSTRACT FROM AUTHOR]

Background: Kidney biopsy is an important investigation in nephrology and facilitates the diagnosis of many conditions. It is an invasive procedure with the risk of significant complications, which limits its usage. There is minimal literature on how patients experience a kidney biopsy. Identifying and addressing barriers to access may expand opportunities for diagnosis and treatment. We hypothesise that patients experience kidney biopsy differently, depending on each individual's circumstances. Methods: Ten participants, who had undergone a total of twenty-three kidney biopsies were recruited through purposive sampling. They were interviewed about how they experienced the procedure, how they felt it had impacted their own medical care and about potential barriers and facilitators to access for other patients. A descriptive phenomenological approach was utilised and thematic analysis was applied to responses. Results: Three main themes emerged: Unforeseen health concerns discovered, resilience and re-evaluation and the need for a patient-centred approach to biopsy. The experience of pain and discomfort varied amongst patients, but there was a significant emotional and psychological toll associated with kidney biopsy. All patients felt that the procedure had a positive impact on their treatment course through increased diagnostic information for them and their healthcare team. Further information in advance and the presence of trusted healthcare staff were identified as facilitators to kidney biopsy. Conclusion: Kidney biopsy is experienced differently by patients. Improved information in advance by trusted healthcare professionals may reduce patient-related barriers to biopsy access. [ABSTRACT FROM AUTHOR]

Gastric cancer ranks fourth among the most commonly diagnosed cancers, with over a million new cases diagnosed worldwide each year. Acute and chronic kidney damage are common in patients with malignant diseases and are associated with increased risk of complications and mortality. Rarely, acute renal insufficiency may result from bilateral infiltration of renal parenchyma by tumor cells from another organ. We present a case of a patient with clinical suspected gastric cancer and metastases to the kidneys leading to acute renal failure requiring hemodialysis. Despite gastric biopsies, no tumor cells were found, while histopathological examination of enlarged intra-abdominal lymph node biopsy material confirmed adenocarcinoma of signet ring cell originating from the digestive system. Stomach cancer was identified as the most likely primary site after the kidney biopsy was performed. To the best of our knowledge, no case of gastric cancer leading to kidney metastases and acute renal failure requiring renal replacement therapy was yet described. Multidisciplinary collaboration among oncologists, urologists, radiologists, pathologists, and nephrologists is essential for the optimal treatment outcome of these patients, who generally have a poor prognosis. [ABSTRACT FROM AUTHOR]

Kidney complications can occur due to infective endocarditis, one of which is glomerulonephritis. Most often, an immune complex or complement‐mediated glomerulonephritis is seen on kidney biopsy. In a minor subset of cases, pauci‐immune glomerulonephritis may be present. Most often, such patients will demonstrate the presence of antineutrophil cytoplasmic antibodies (ANCA) on serologic testing. A growing number of cases of ANCA‐associated glomerulonephritis due to Bartonella endocarditis have been reported. This type of endocarditis can present diagnostic difficulties given that these patients are often culture negative. Herein, we report a challenging case of ANCA‐negative pauci‐immune glomerulonephritis showing florid crescents on biopsy that was associated with Bartonella endocarditis. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to investigate the correlation between podocyte related biomarker cofilin-1 and renal function, and explore the value of cofilin-1 in predicting the risk of renal adverse prognosis in IgA nephropathy (IgAN). Methods: Patients with primary IgAN diagnosed by initial renal biopsy performed in our hospital from January 2019 to February 2022 were included. This study was a prospective cohort study. All IgAN patients were detected the expression of cofilin-1 and other related biomarkers (RhoA, NGAL) in urine by enzyme-linked immunosorbent assay (ELISA) and follow-up at least 6 months. We also collected baseline clinicopathologial data of IgAN. The decreased renal function group was defined as baseline eGFR < 60 ml/min/1.73m2. Logistic and Cox regression model were used to analyze the correlation among cofilin-1 and renal prognosis. Results: 133 IgAN patients were included, with a male-to-female ratio of 1.25:1 and an age of 37.67 ± 13.78 years, as well as an average of eGFR was 71.63 (40.42,109.33) ml/min/1.73m2. 56 patients (42.1%) had decreased renal function at baseline, with the average of eGFR was 34.07 (16.72, 49.21) ml/min/1.73 m2. 12 of which developed to renal adverse prognosis. The average of follow-up time was 22.035 ± 8.992 months. The multivariate regression analysis showed that increased urinary cofilin-1 was an independent risk factor associated with baseline renal function decline and renal adverse prognosis in IgAN patients (P < 0.05). ROC curves showed great efficacy of urinary cofilin-1 levels in diagnosing baseline renal function decline and predicting renal adverse prognosis (the area under the ROC curve was 0.708 and 0.803). Conclusion: Cofilin-1 as a novel biomarker of podocyte lesion is closely related to renal function decline in IgAN. Cofilin-1 has certain clinical value in predicting the risk of renal adverse prognosis. Podocyte fusion affects the renal prognosis of IgAN. [ABSTRACT FROM AUTHOR]

Introduction. To explore the construction of a diagnostic prediction model of diabetic nephropathy (DN) in type 2 diabetic patients for prognostic risk prediction and observe the therapeutic effect of Epalrestat combined with Dapagliflozin on DN. Methods. The study consisted of two phases, phase I: A retrospective analysis was conducted on the case information and clinical treatment related data of a total of 460 patients who underwent kidney biopsy from June 2018 to June 2021. They were randomly divided into validation queue and training queue. The predictive factors of the diagnostic prediction model were obtained through multivariate logistic regression. Phase II: An interventional study of 94 patients with DN admitted between January 2022 and August 2023 was conducted, and they were randomized into a control group (n = 47) receiving Dapagliflozin and a research group (n = 47) receiving Epalrestat combined with Dapagliflozin. The glucose metabolism, renal function, and treatment safety of the two groups before and after treatment were compared. In addition, the adverse reactions during the treatment of the two groups were counted. Results. In the phase I of the study, the DN risk model established showed a good performance in the diagnosis and risk assessment of patients with DN and could provide certain reference opinions for future clinical practice. In the phase II of the study, the research group showed better glucose metabolism and renal function than the control group after treatment (P < .05), but no statistical difference was identified between groups in the incidence of adverse reactions (P > .05). Conclusion. Epalrestat combined with Dapagliflozin is significantly effective in the treatment of DN, which can effectively improve glucose metabolism and renal function in DN patients. [ABSTRACT FROM AUTHOR]

Objective: Interstitial fibrosis/tubular atrophy (IFTA) is a common, irreversible, and progressive form of chronic kidney allograft injury, and it is considered a critical predictor of kidney allograft outcomes. The extent of IFTA is estimated through a graft biopsy, while a non-invasive test is lacking. The aim of this study was to evaluate the feasibility and accuracy of an MRI radiomic-based machine learning (ML) algorithm to estimate the degree of IFTA in a cohort of transplanted patients. Approach: Patients who underwent MRI and renal biopsy within a 6-month interval from 1 January 2012 to 1 March 2021 were included. Stable MRI sequences were selected, and renal parenchyma, renal cortex and medulla were segmented. After image filtering and pre-processing, we computed radiomic features that were subsequently selected through a LASSO algorithm for their highest correlation with the outcome and lowest intercorrelation. Selected features and relevant patients' clinical data were used to produce ML algorithms using 70% of the study cases for feature selection, model training and validation with a 10-fold cross-validation, and 30% for model testing. Performances were evaluated using AUC with 95% confidence interval. Main results: A total of 70 coupled tests (63 patients, 35.4% females, mean age 52.2 years) were included and subdivided into a wider cohort of 50 for training and a smaller cohort of 20 for testing. For IFTA ≥ 25%, the AUCs in test cohort were 0.60, 0.59, and 0.54 for radiomic features only, clinical variables only, and a combined radiomic–clinical model, respectively. For IFTA ≥ 50%, the AUCs in training cohort were 0.89, 0.84, and 0.96, and in the test cohort, they were 0.82, 0.83, and 0.86, for radiomic features only, clinical variables only, and the combined radiomic–clinical model, respectively. Significance: An ML-based MRI radiomic algorithm showed promising discrimination capacity for IFTA > 50%, especially when combined with clinical variables. These results need to be confirmed in larger cohorts. [ABSTRACT FROM AUTHOR]

Key Clinical Message: A T217M heterozygous mutation in the SLC22A12 gene caused renal hypouricemia; this patient with IgA nephropathy had no findings other than IgA nephropathy on renal biopsy. Hypouricemia was susceptible to oxidative stress, but IgA nephropathy in the patient with hypouricemia could be treated with steroid pulse therapy without adverse events. [ABSTRACT FROM AUTHOR]

We present two cases of middle‐aged men who developed Fanconi syndrome and renal dysfunction after consuming "foods with functional claims (FFC)" containing red yeast rice. In the first case, the patient had consumed an FFC for 1 year and another FFC suspected to have contained nephrotoxin for 3 weeks; kidney biopsy performed during the acute phase of renal injury showed severe acute tubular necrosis and tubular cell regeneration. He achieved near‐complete recovery 40 days after the FFC was discontinued. In the second case, the patient had consumed FFC for 4 years and stopped 70 days prior to presentation; kidney biopsy revealed significant tubular recovery, persistent tubular injuries, and interstitial fibrosis. Although the manifestations of Fanconi syndrome subsided, mild renal dysfunction persisted. These cases suggest that FFC with nephrotoxins may induce Fanconi syndrome owing to acute tubular necrosis. Recovery is possible after discontinuing the FFC; while short‐term ingestion of FFC allows for tubular regeneration, its long‐term ingestion may cause irreversible damage and lead to chronic kidney disease. Long‐term follow‐up is crucial for preventing further renal deterioration. [ABSTRACT FROM AUTHOR]

Background: C4d deposits are present in a substantial proportion of patients with IgA nephropathy (IgAN), indicating the activation of the lectin pathway (LP) of the complement system. It seems that patients with activated LP have worse renal prognosis. The aim of this study was to investigate the prevalence and prognostic significance of C4d in our cohort of patients with primary IgA nephropathy (pIgAN). Methods: Patients with pIgAN were recruited from a hospital register of kidney biopsies of the Department of Nephrology and Dialysis, Dubrava University Hospital, Zagreb. Additional immunohistochemistry staining for C4d was performed on paraffin-embedded kidney tissue, and patients were stratified into being C4d positive or C4d negative. The clinical and histologic features of patients were analyzed and compared regarding C4d positivity. The primary outcome was defined as kidney failure (KF), and predictor variables of KF and renal survival were analyzed. Results: Of a total of 95 patients with pIgAN included in the study, C4d was present in 43 (45.3%). C4d-positive patients had a higher value of systolic (p = 0.039) and diastolic (p = 0.006) blood pressure at diagnosis as well as higher 24 h proteinuria (p = 0.018), serum urate (p = 0.033), and lower eGFR (p < 0.001). C4d-positive patients had worse renal survival (p < 0.001), higher rates of disease progression to KF (p < 0.001), and higher proteinuria (p < 0.001) and lower eGFR (p < 0.001) at the last follow-up. Glomerular C4d was an independent predictor of disease progression to KF (HR = 5.87 [0.95 CI 1.06–32.44], p = 0.032). Conclusions: C4d is an independent predictor of disease progression in patients with pIgAN. C4d may be used as an additional marker of progressive disease course in IgAN. The therapeutic implications of C4d status in IgAN, particularly in terms of complement inhibitors application, are not yet known. [ABSTRACT FROM AUTHOR]

Purpose: To assess the crescentic status of IgA nephropathy (IgAN) non-invasively using a superb microvascular imaging (SMI)-based radiomics machine learning (ML) model. Patients and Methods: IgAN patients who underwent renal biopsy from June 2022 to October 2023, with two-dimensional ultrasound (US) and SMI examinations conducted one day prior to the renal biopsy. The patients selected were divided randomly into a training group and a test group in a 7:3 ratio. Radiomic features were extracted from US and SMI images, then radiomic features were constructed and ML models were further established using logistic regression (LR) and extreme gradient boosting (XGBoost)XGBoost to determine the crescentic status. The utility of the proposed model was evaluated using receiver operating characteristics, calibration, and decision curve analysis. The SHapley Additive exPlanations (SHAP) was utilized to explain the best-performing ML model. Results: A total of 147 IgAN patients were included in the study, with 103 in the training group and 44 in the test group.Among them, the US-SMI based XGBoost model achieved the best results, with an the area under the curve (AUC) of 0.839 (95% CI,0.756– 0.910) and an accuracy of 78.6% in the training group.In the test group, the AUC was 0.859 (95% CI,0.721– 0.964), and the accuracy was 81.8%, significantly surpassing the ML model of a single modality and the clinical model established based on occult blood. Additionally, the decision curve analysis (DCA) demonstrated that the XGBoost model provided a higher overall net benefit in the both groups. Conclusion: The SMI radiomics ML model has the capability to accurately predict the crescentic status of IgAN patients, providing effective assistance for clinical treatment decisions. [ABSTRACT FROM AUTHOR]

Systemic chronic inflammation may cause kidney injury as a result of an impaired immune response and pro-inflammatory cytokine overload due to various factors that prevent the resolution of inflammation. Therefore, it is important to determine pro-inflammatory cytokine levels by renal biopsy and to investigate treatment modalities in systemic chronic inflammation-related kidney injury. We aimed to investigate the therapeutic effect of methylprednisolone on extra-renal systemic chronic inflammation-induced renal tissue damage in terms of histopathological alterations and immunohistochemically on tumor necrosis factor-α, interleukin-1β, and interleukin-6 levels. The mice used in this study were divided into three equally sized groups (n: 10). Group I (control) received 0.3 mL 0.9% NaCl, and group II received 0.3 mL complete Freund's adjuvant-casein emulsion intraperitoneally for systemic chronic inflammation induction. Group III received methylprednisolone 10 mg/kg intramuscularly after intraperitoneal injection of 0.3 mL complete Freund's adjuvant-casein emulsion. Injections were administered on days 1 and 14 of the study, and the experiment was ended 5 week after the second injections following the development of systemic chronic inflammation. Finally, kidney tissues were examined histopathologically and immunohistochemically for tumor necrosis factor-α, interleukin-1β, and interleukin-6 levels. While normal renal histology was observed in group I, glomerulonephritis and tubulointerstitial nephritis findings were detected in group II and group III. Methylprednisolone treatment decreased the histopathologic lesions observed in group III. Immunostaining with anti-tumor necrosis factor-α, interleukin-1β and interleukin-6 showed severe immunopositivity in group II and mild immunopositivity in group III, whereas they were immunonegative in group I. Our study provides histopathological and immunohistochemical evidence supporting the decreasing effect of methylprednisolone on tumor necrosis factor-α, interleukin-1β, and interleukin-6 levels in kidney tissue against SCI-induced renal damage due to excessive pro-inflammatory cytokine overload. [ABSTRACT FROM AUTHOR]

Introduction: Malakoplakia is a rare and chronic granulomatous disease that is pathologically characterized by the presence of Michaelis-Gutmann bodies and large macrophage clusters. Malakoplakia of the renal parenchyma is especially rare. In this report, we describe the long-term prognosis of a patient who was diagnosed with and treated for renal parenchymal malakoplakia in infancy. Case Presentation: Seventeen years after malakoplakia onset, the patient presented to us with worsening proteinuria. Computed tomography revealed structural abnormalities in the kidney, and focal segmental glomerulosclerosis (FSGS) was diagnosed based on renal biopsy findings. No Michaelis-Gutmann bodies were observed in von Kossa-stained biopsy specimens. Regular outpatient monitoring during the next 9 years showed gradual deterioration of renal function and a moderately high protein/creatinine ratio. Conclusion: Our findings suggest that structural changes due to malakoplakia can cause FSGS. Moreover, structural changes indicate the healing of malakoplakia in infancy and the disappearance of its characteristic lesions over time. Owing to its long-term observation period, this unique case provides new insights into the outcomes of patients with renal parenchymal malakoplakia.

Cyntia Camilo Franco Borges Zago,1 Bruna de Freitas Oliveira,1 Giovanna Uehara,1 Ana Laura Carvalho da Silva,1 Laura Penna Rocha,1 Fabiano Bichuette Custódio,2 Liliane Silvano Araújo,1 Crislaine Aparecida da Silva,1 Marlene Antônia Reis,1 Juliana Reis Machado1 1Kidney Research Center-Department of Pathology, Genetics and Evolution, Federal University of Triângulo Mineiro, Uberaba, Minas Gerais, Brazil; 2Department of Clinical Medicine, Federal University of Triângulo Mineiro, Uberaba, Minas Gerais, BrazilCorrespondence: Juliana Reis Machado, Kidney Research Center – Department of Pathology, Genetics and Evolution, Federal University of Triângulo Mineiro, Uberaba, Minas Gerais, Brazil, Tel +55 (34) 3700-6450, Email juliana.patologiageral@gmail.comPurpose: In the kidneys, Systemic Lupus Erythematosus leads to Lupus Nephritis (LN), a form of glomerulonephritis. There is evidence that patients with LN may present activation of specific pathways for podocyte injury. This injury can occur through different mechanisms such as loss of podocyte adhesion to the glomerular basement membrane, cell death or dedifferentiation. Podocyturia with consequent podocytopenia has been described in some nephropathies such as LN, highlighting the importance of studying podocyte injuries in this condition. Evaluating in situ morphological characteristics of podocytes becomes relevant for a better understanding of the processes involved in their pathogenesis. This study investigated podocytes in different classes of LN in renal biopsies performed by the Kidney Research Center at the Federal University of Triângulo Mineiro.Patients and Methods: Twenty control cases and 29 biopsy cases diagnosed with LN were selected, divided according to the histopathological classes of the disease. Podocyte density was assessed through immunohistochemistry for Wilms tumor 1 protein and the evaluation of foot process effacement was performed by transmission electron microscopy.Results: Podocyte density was lower in the LN and this reduction was observed in all analyzed classes when compared to the control group. More foot process effacement was observed in the LN group, with more effacement in classes I/II and class IV compared to the control group. The class IV group showed more foot process effacement than the class III group and presented higher proteinuria levels compared to the classes I/II group. A strong, positive, and significant correlation was observed between the activity index and foot process effacement in the class IV group.Conclusion: Podocytes play an important role in the development of LN, and possibly, injuries to these cells are more closely related to the inflammatory/diffuse proliferative cellular process developed in class IV LN.Keywords: podocyte density, foot processes effacement, activity index, renal biopsy

Abstract Background Chronic kidney disease (CKD) is a significant clinical challenge in Sri Lanka. The present study presents histopathological diagnoses from native renal biopsies in Kandy District, 2011–2020. Methods Reports of 5,014 renal biopsies principally performed at Kandy Teaching Hospital over 2011–2020 were reviewed. After exclusions for post-kidney transplant biopsies (1,572) and those without evident pathology (347), 3,095 biopsies were included. The predominant histopathological entities were grouped and categorised according to diagnosis and stratified by age and sex. Results The main histopathological entities (all biopsies) were tubulointerstitial nephropathy (TIN) 25% (n = 760), glomerulonephritis (GN) 15% (467), lupus nephropathy 14% (429), focal segmental glomerular sclerosis (FSGS) 10% (297), and IgA nephropathy (IgAN) 8% (242). For adult women ≥ 15 years, the main histopathological entities were lupus nephropathy 24% (325), TIN 17% (228), and GN 16% (217). For adult men ≥ 15 years, the main histopathological entities were TIN 34% (449), GN 14% (180), and IgAN 10% (125). The proportion of TIN in the present study was higher than international studies of a similar size. Conclusion This is the largest study of renal biopsies reported from Sri Lanka to date. TIN was the most common diagnosis in adults ≥ 15 years at 25%. Notable sex differences showed TIN was the most common histopathology in men (34%) but not in women (17%). No previously published similar study of this size has found TIN as the predominant diagnosis amongst renal biopsies in men. Further research is required into the possible causes of these observations in Sri Lanka. Clinical Trial Number. Not applicable.

Background: The Renal Pathology Society developed a universal pathological classification of diabetic nephropathy in 2010. Some research has been conducted to validate this classification's ability to predict the outcome. However, the clinical implications of these pathological abnormalities are still being investigated. Objectives: In this study, we aimed to demonstrate the clinical reflections of these lesions to better understand the underlying mechanisms. Methods: Data of 119 patients with biopsy proven diabetic nephropathy from a single center were included in the study. Pathology specimens were reclassified according to 2010 criteria suggested by the RPS. Results: Diabetic retinopathy was more frequently present in patients with advanced glomerular class, IFTA score, interstitial inflammation score, arteriolar hyalinosis score, arteriosclerosis score, and in patients with exudative lesions present (p < 0.05). The proteinuria levels of patients with advanced glomerular classes and exudative lesions were significantly higher, and serum albumin levels were lower (p < 0.05). Hematuria occurrence was more frequent in glomerular class III and IV patients and in patients with advanced arteriolar hyalinosis (p < 0.05). Conclusion: This large, single center, retrospective study reveals that diabetic retinopathy is associated with glomerular and arteriolar lesions but not with interstitial lesions. Proteinuria and hematuria were independent predictors of glomerular lesions, but not other renal lesions. Nevertheless, prospective studies which include all the confounding clinical factors are required to reach a conclusion on the relationship of hematuria and renal lesions. [ABSTRACT FROM AUTHOR]

Calcium oxalate (CaOx) crystal deposition in acute kidney injury (AKI) patients is under recognized but impacts renal outcomes. This study investigates its determinants and effects. We studied 814 AKI patients with native kidney biopsies from 2011 to 2020, identifying CaOx crystal deposition severity (mild: <5, moderate: 5–10, severe: >10 crystals per section). We assessed factors like urinary oxalate, citrate, urate, electrolytes, pH, tubular calcification index, and SLC26A6 expression, comparing them with creatinine-matched AKI controls without oxalosis. We analyzed how these factors relate to CaOx severity and their impact on renal recovery (eGFR < 15 mL/min/1.73 m2 at 3-month follow-up). CaOx crystal deposition was found in 3.9% of the AKI cohort (32 cases), with 72% due to nephrotoxic medication-induced tubulointerstitial nephritis. Diuretic use, higher urinary oxalate-to-citrate ratio induced by hypocitraturia, and tubular calcification index were significant contributors to moderate and/or severe CaOx deposition. Poor baseline renal function, low urinary chloride, high uric acid and urea nitrogen, tubular SLC26A6 overexpression, and glomerular sclerosis were also associated with moderate-to-severe CaOx deposition. Kidney recovery was delayed, with 43.8%, 31.2%, and 18.8% of patients having eGFR < 15 mL/min/1.73 m2 at 4, 12, and 24-week post-injury. Poor outcomes were linked to high urinary α1-microglobulin-to-creatinine (α1-MG/C) ratios and active tubular injury scores. Univariate analysis showed a strong link between this ratio and poor renal outcomes, independent of oxalosis severity. In AKI, CaOx deposition is common despite declining GFR. Factors worsening tubular injury, not just oxalate-to-citrate ratios, are key to understanding impaired renal recovery. [ABSTRACT FROM AUTHOR]

Lipoprotein glomerulopathy (LPG) is a rare disorder characterized by the development of glomerular lipoprotein thrombosis. LPG exhibits familial aggregation, with mutations in the apolipoprotein E (APOE) gene identified as the leading cause of this disease. This study aimed to investigate APOE gene mutations and the clinicopathological features in eleven LPG patients. Clinicopathological and follow-up data were obtained by extracting DNA, followed by APOE coding region sequencing analysis. This study analyzed clinical and pathological manifestations, gene mutations, treatment and prognosis. The mean age of the eleven patients was 33.82 years. Among them, five had a positive family history for LPG, ten presented with proteinuria, four exhibited nephrotic syndrome, and six presented with microscopic hematuria. Dyslipidemia was identified in ten patients. In all renal specimens, there was evident dilation of glomerular capillary lumens containing lipoprotein thrombi, and positive oil red O staining was observed in frozen sections of all samples. APOE gene testing revealed that one patient had no mutations, while the remaining ten patients exhibited mutations in the APOE gene, with three patients presenting with multiple mutations simultaneously. Following the confirmation of LPG diagnosis, treatment with angiotensin-converting enzyme inhibitor (ACEI)/angiotensin receptor blocker (ARB) was initiated, and the disease progressed slowly. LPG is histologically characterized by lamellated lipoprotein thrombi in glomeruli, and kidney biopsy is essential for diagnosis. Mutations in the APOE gene are the leading cause of LPG. This study revealed clinicopathological characteristics and APOE gene mutations in patients with LPG, which helps us better understand the disease. [ABSTRACT FROM AUTHOR]

While renal biopsy remains the preferred diagnostic method for assessing proteinuria, hematuria, or renal failure, laparoscopic renal biopsy (LRB) can serve as an alternative for high-risk patients when percutaneous kidney biopsy (PKB) is not recommended. This study was aimed to evaluate the safety of LRB. In study 1, Fourteen patients from January 2021 to January 2023 had a LRB taken for various indications, such as morbid obesity, abnormal kidney construction, uncontrolled hypertension, and coagulopathy. We also conducted a Meta-analysis of the success rate and complication rate of previous LRB in study 2. All the patients completed biopsies and adequate renal tissues were obtained. The success rate was 100%. The median number of glomeruli obtained was 22.5 (range:12.0, 45.0). The complication rate was 7.1% (urinary tract infection). There were no significant differences between levels of hemoglobin, serum creatinine, and urinary NAGL before and after surgery. In the meta-analysis, the success rate of operation, satisfactory rate of sample, and complication rate of surgery were 99.9%, 99.1%, and 2.6% respectively. LRB can achieve a good success rate and specimen retrieval and does not increase the risk of complications for high-risk patients. It can present as one of the alternative methods for patients with glomerular diseases. [ABSTRACT FROM AUTHOR]

No study has validated, compared and adapted scoring systems for prognosis prediction based on donor kidney core biopsy (CB), with less glomeruli than wedge biopsy. A total of 185 donor kidney CB specimens were reviewed using seven scoring systems. The association between the total score, item scores, score-based grading, and allograft prognosis was investigated. In specimens with less than ten glomeruli (88/185, 47.6%), scoring systems were modified by adjusting weights of the item scores. The Maryland aggregate pathology index (MAPI) score-based grading and periglomerular fibrosis (PGF) associated with delayed graft function (DGF) (Grade: OR = 1.59, p < 0.001; PGF: OR = 1.06, p = 0.006). Total score, score-based grading and chronic lesion score in scoring systems associated with one-year and 3-year eGFR after transplantation. Total-score-based models had similar predictive capacities for eGFR in all scoring systems, except MAPI and Ugarte. Score of glomerulosclerosis (GS), interstitial fibrosis (IF), tubular atrophy (TA), and arteriolar hyalinosis (AH) had good eGFR predictive capacities. In specimens with less than ten glomeruli, modified scoring systems had better eGFR predictive capacities than original scoring systems. Scoring systems could predict allograft prognosis in paraffin-embedded CB with ten more glomeruli. A simple and pragmatic scoring system should include GS, IF, TA and AH, with weights assigned based on predictive capacity for prognosis. Replacing GS scores with tubulointerstitial scores could significantly improve the predictive capacity of eGFR. The conclusion should be further validated in frozen section. [ABSTRACT FROM AUTHOR]

Idiopathic membranous nephropathy (IMN) with deposits of phospholipase A2 receptor (PLA2R) antigen in glomerular tissue (GAg+) but no circulating serum PLA2R antibody (SAb−) has been reported. However, little is known about the clinicopathological characteristics and prognosis of this subtype. A total of 74 IMN patients with GAg + identified by kidney biopsy were enrolled in this study. We categorized patients into two groups based on the presence or absence of serum PLA2R antibody. Data on clinical features, pathological features, and outcomes were collected. Kaplan–Meier analysis of complete remission (CR) and partial remission (PR) comparing SAb−/GAg + and SAb+/GAg + patients. Cox proportional hazards models was used to examine factors associated with CR and PR. Among 74 IMN patients, 14 were SAb−/GAg+. Compared with SAb+/GAg + patients, SAb−/GAg + patients presented with higher levels of albumin, lower levels of cholesterol and low density lipoprotein cholesterol (all p <.01), but similar pathological manifestations of kidney biopsy. Multivariate logistic analyses indicated that low albumin (0.79 [95%CI: 0.66–0.95], p =.01) and high cholesterol (1.81 [95%CI: 1.02–3.19], p =.04) were correlated with seropositivity of PLA2R antibody. SAb−/GAg + patients exhibited a significantly higher probability of CR (p =.03) than patients who were SAb+/GAg+. However, no difference was found in the PR rate. Cox regression analyses showed that compared to SAb+/GAg + patients, SAb−/GAg + was more predictive of complete remission (4.28 [95%CI: 1.01–18.17], p =.04). IMN with PLA2R staining on kidney biopsy but without serum PLA2R antibody has milder clinical manifestations and a better prognosis. [ABSTRACT FROM AUTHOR]

Background: Light-chain proximal tubulopathy (LCPT) is a rare disease characterized by the accumulation of monoclonal light chains within proximal tubular cells. This study aimed to investigate the clinical characteristics of LCPT from a single Chinese nephrology referral center.Methods: Patients with kidney biopsy-proven isolated LCPT between 2016 and 2022 at Peking University First Hospital were retrospectively included. Clinical data, kidney pathological type, treatment, and prognosis were analyzed.Results: Nineteen patients were enrolled, the mean age at diagnosis was 57 ± 11 and the sex ratio was 6/13 (female/male). Mean proteinuria was 2.44 ± 1.89 g/24 hr and the mean estimated glomerular filtration rate (eGFR) at the point of biopsy was 59.640 ± 27.449 ml/min/1.73 m2. κ-restriction (84%) was dominant among LCPTs. An abnormal free light chain ratio was observed in 86% of the patients. Proximal tubulopathy with cytoplasmic inclusions accounted for the majority (53%), followed by tubulopathy associated with interstitial inflammation reaction (26%), proximal tubulopathy without cytoplasmic inclusions (16%), and proximal tubulopathy with lysosomal indigestion/constipation (5%). One patient presented with acute kidney injury and 16 patients presented with chronic kidney disease. Regarding follow-up, patients received bortezomib-based or R-CHOP chemotherapy or supportive treatment only. The mean follow-up time was 22 ± 16 months, and the mean eGFR was 63.098 ± 27.439 ml/min/1.73 m2 at the end of follow-up. These patients showed improved or stable kidney function.Conclusions: This is the first case series report of LCPT in four different pathological types in northern China. Clone-targeted chemotherapy may help preserve the kidney function in these patients. [ABSTRACT FROM AUTHOR]

Introduction: Membranoproliferative glomerulonephritis (MPGN) is a pattern of injury seen on kidney biopsy, with various underlying etiologies. The component types, including complement-mediated MPGN, are relatively rare. This study presents longitudinal real-world data over 20 years in a tertiary renal center in the UK. Methods: All patients with an MPGN pattern on kidney biopsy between 2000 and 2020 were identified. After applying exclusion criteria, 38 patients remained. Data including patient demographics, details of the renal histology from the kidney biopsy, baseline laboratory results, treatments received, and clinical outcomes including renal replacement therapy and death were collected from the organization’s electronic patient record. Results: Twenty-eight of the cohort had immune complex-mediated MPGN, and 10 had complement-mediated MPGN (8 with C3 glomerulonephritis and 2 with dense deposit disease). Median follow-up was 72 months. Median age was 61 years. Overall, 60.5% were female, and 92.1% white. At presentation, median eGFR was 31.5 mL/min/1.73 m2 and uPCR 394 mg/mmol. Here, 78.9% received renin-angiotensin-aldosterone system inhibitors and 71.1% received any immunosuppression. In total, 47.4% progressed to ESKD and 50% died during follow-up. Conclusions: The study found an older patient population than typically reported. Poor outcomes were observed in the overall cohort with progression to ESKD and mortality both at almost 50%. This may be influenced by the older patient population. Individualized management of patients with an MPGN biopsy finding is paramount, with comprehensive evaluation for triggers and complement abnormalities. Going forward, registry enrolment and collaborative studies may enhance knowledge and outcomes.

Introduction: Drug-induced tubulointerstitial injury is a common cause of renal impairment. Since the mechanisms of drug-induced tubular injury are diverse, various treatment approaches are needed according to the pathogenesis. Renal biopsy is indispensable to determine not only the pathological diagnosis, but also the underlying mechanism, and to guide appropriate treatment. Most recently, one of the red yeast supplements has been widely highlighted as a novel cause of tubular damage, mainly in Japan and Asia. However, neither detailed pathological findings nor the mechanism of renal impairment has been sufficiently reported. Case Presentation: Two cases of renal impairment after taking red yeast supplement internally are presented. Both cases showed renal dysfunction with low uric acid, potassium, and phosphorus levels, characteristic features of Fanconi syndrome. The renal biopsy findings of both cases showed severe injury to the proximal tubules with mild inflammatory cell infiltration. The proximal tubules exhibited diffuse loss of the brush border, flattening, and tubular lumen dilation. Immunofluorescence showed no deposition of immunoglobulin and complement in the glomeruli and tubules. Electron microscopic findings indicated proximal tubular damage without crystal deposition. Moreover, immunohistochemistry using the proximal tubular marker CD10 and a marker for distal tubules including the loop of Henle, E-cadherin, collectively demonstrated that the focus of renal injury in both cases was mainly the proximal tubules. Conclusions: The red yeast rice supplement itself, its metabolized product, or other unknown contaminant components might directly induce proximal tubulopathy rather than an allergic reaction-related tubulointerstitial nephritis.