Search

A 67-year-old man was referred to the renal team following an episode of acute kidney injury on a background of chronic kidney disease. He had a 9-year history of steroid-sensitive arthritis, epigastric pain and isolated submandibular gland enlargement. He was noted to have a raised eosinophil count, total serum protein and total immunoglobulin G4 (IgG4) level as well as a serum hypocomplementaemia. A renal biopsy showed a tubulointerstitial nephritis with lymphoplasmacytic infiltrates, fibrosis and IgG4-positive plasma cells on immunohistochemistry. A diagnosis of IgG4-related disease was made based on clinical presentation and pathology. Renal function improved with glucocorticoids and the patient was successfully transitioned to azathioprine as a steroid-sparing agent.

Granulomatosis with polyangiitis (GPA) is a rare disorder characterised by inflammation of small-sized and medium-sized blood vessels that result in damage to various organ systems, but it most commonly affects the respiratory tract and kidneys. It is one of the few entities that can present with ocular inflammation as well as renal impairment at the same time. We describe a case of a 38-year-old man with conjunctivitis, episcleritis, anterior uveitis as a first manifestation of GPA. His presentation with red eye and anterior uveitis prompted further workup, which revealed acute renal failure (creatinine 442 mmol/L), elevated inflammatory markers (erythrocyte sedimentation rate of 85 mmol/hour and C reactive protein of 72 mg/L), and a c-antineutrophil cytoplasmic antibody titre >8. An urgent renal biopsy was performed demonstrating necrotising crescentic glomerulonephritis, which led to the final diagnosis of GPA. Treatment induction with intravenous methylprednisolone and plasmapheresis followed by an oral prednisone taper and intravenous rituximab infusions leading to resolution of all symptoms and normalisation of kidney function. This report highlights conditions that can present with both ocular inflammation and renal dysfunction with a focus on GPA and its ocular manifestations.

Purpose To describe a case of AA amyloidosis which produced an orbital inflammatory response with a novel presentation. Methods Case report. Results A 24 year-old Caucasian female with a history of intravenous (IV) heroin use was hospitalized for tricuspid valve endocarditis and methicillin resistant Staphylococcus aureus bacteremia, as well as acute renal failure. She received hemodialysis and IV daptomycin and had negative blood cultures for 3 weeks, when she developed sudden bilateral orbital swelling and blurred vision. Visual acuity was 20/200 in the right eye (OD) and 20/400 in the left eye (OS). Examination revealed proptosis, conjunctival chemosis and desiccation, optic disc swelling, creamy choroidal infiltrates and inferiorly located exudative retinal detachments in both eyes (OU). Multimodal imaging demonstrated thickening of the sclera, choroid and choriocapillaris as well as outer retinal disruption, subretinal fluid and deposits of hyperfluorescent debris within the choriocapillaris, outer retina and vitreous. Oral prednisone at 60 mg per day resolved the choroidal infiltrates and exudative detachments. Persistent nephrotic syndrome called for a renal biopsy, which demonstrated AA amyloidosis. Conclusion - Orbital and choroidal AA amyloidosis can induce a local inflammatory response manifesting as orbital swelling, papillitis, posterior scleritis, choroiditis and exudative retinal detachment, which responds to steroid therapy. The underlying pathology is likely a reactive inflammation and vaso-occlusive process involving the choriocapillaris and orbital vasculature to the presence of amyloid fibrils.

A 39-year-old woman was hospitalized for nephrotic syndrome. Laboratory test results showed increased serum creatinine levels and urinary excretions of beta-2-microglobulin, and N-acetyl-beta-D-glucosaminidase. A renal biopsy revealed collapsing focal segmental glomerulosclerosis (FSGS) and acute interstitial nephritis. Despite treatment with pulse steroid followed by oral high-dose glucocorticoids and cyclosporines, heavy proteinuria persisted. After low-density lipoprotein apheresis (LDL-A) therapy was initiated, her proteinuria gradually decreased, leading to complete remission. A repeat renal biopsy after treatment revealed no collapsing glomeruli. Immediate LDL-A should be performed to treat cases of collapsing FSGS poorly responding to other treatments.

Tubular basement membrane (TBM) deposits are very uncommon in non-lupus membranous nephropathy. We report 5 patients with membranous nephropathy and extensive TBM deposits following allogeneic hematopoietic cell transplant. Patients presented with nephrotic syndrome (3 also had acute kidney injury) late post-transplant in association with chronic graft-versus-host disease (cGVHD). Kidney biopsies revealed global subepithelial and extensive TBM immune complex deposits, accompanied by acute tubular injury (n = 4) and tubulointerstitial inflammation (n = 4). Proteomic analysis of glomeruli in 4 cases identified PLA2R in 1, with no significant protein spectra for PLA2R, THSD7A, EX1/2, NELL-1, PCDH7, NCAM1, or SEMA3B detected in the remaining 3. On follow-up (for a mean 42 months), 4 patients had complete and 1 partial remission following prednisone and/or rituximab therapy. We propose that membranous nephropathy with extensive TBM deposits is a distinctive clinicopathologic lesion associated with allogeneic hematopoietic cell transplant. Pathogenesis likely involves cGVHD-driven antibodies against glomerular and TBM components, the identity of which remains to be elucidated.

Objectives IgA nephropathy (IgAN) is the most common primary chronic glomerulonephritis and a major cause of end-stage kidney disease worldwide. Novel biomarkers, including the aberrantly glycosylated IgA1 and glycan-specific antibodies, could be useful in the diagnosis of IgAN. The aim of this study was to assess the cost analysis of IgAN screening using novel biomarkers in addition to the conventional screening compared with conventional screening alone. Methods To estimate the medical expense of each strategy related to renal disease for 40 years, we developed an analytical decision model. The decision tree started at “40 years of age with first-time hematuria.” It simulated 2 clinical strategies: IgAN screening using the novel biomarkers (group N) and conventional screening (group C). The analysis results were presented as medical expenses from a societal perspective. Discounting was not conducted. Results The expected medical expense per person for 40 years was ¥31.2 million (~$291 000) in group N and ¥33.4 million (~$312 000) in group C; hence, expense in group N was lower by ¥2.2 million (~$21 000). In group N, the expected value of IgAN increased by 5.67% points (N 48.44%, C 42.77%) and that of dialysis introduction decreased by 0.85% points (N 19.06%, C 19.91%). In the sensitivity analysis, expenses could be reduced in almost all cases except when renal biopsy using conventional screening was performed at the rate of 73% or higher. Conclusion Screening for IgAN using novel biomarkers would reduce renal disease–related expenses.

Objectives Current treatments are effective only in 30% of lupus nephritis patients emphasizing the need for novel therapeutic strategies. To develop mechanistic hypotheses and explore novel biomarkers, we analyzed the longitudinal urinary proteomic profiles in patients with lupus nephritis undergoing treatment. Methods We quantified 1,000 urinary proteins in 30 patients with lupus nephritis at the time of the diagnostic renal biopsy and after 3, 6, and 12 months. The proteins and molecular pathways detected in the urine proteome were then analyzed with respect to baseline clinical features and longitudinal trajectories. The intrarenal expression of candidate biomarkers was evaluated using single cell transcriptomics of renal biopsies from lupus nephritis patients. Results Our analysis revealed multiple biological pathways including chemotaxis, neutrophil activation, platelet degranulation, and extracellular matrix organization that could be noninvasively quantified and monitored in the urine. We identified 237 urinary biomarkers associated with lupus nephritis as compared to controls without SLE. IL-16, CD163, and TGF-β mirrored intrarenal nephritis activity. Response to treatment was paralleled by a reduction of urinary IL-16, a CD4 ligand with proinflammatory and chemotactic properties. Single cell RNA sequencing independently demonstrated that IL16 is the second most expressed cytokine by most infiltrating immune cells in lupus nephritis kidneys. IL-16 producing cells were found at key sites of kidney injury. Conclusion Urine proteomics may profoundly change the diagnosis and management of lupus nephritis by noninvasively monitor active intrarenal biological pathways. These findings implicate IL-16 in lupus nephritis pathogenesis designating it as a potentially treatable target and biomarker.

Aim of the work: To assess urinary soluble CD163 (sCD136) in systemic lupus erythematosus (SLE) patients compared to healthy controls. In addition to determine its association with different SLE clinical features, laboratory investigations and pathological indices focusing on those suggest renal disease activity. Patients and methods: The study included 58 SLE patients and 30 controls. SLE disease activity index (SLEDAI) was assessed and patients subdivided into active lupus nephritis (ALN) (renal SLEDAI ≥ 4) and no-renal activity (NRA) SLE patients (renal SLEDAI = 0). Urinary sCD163 was measured by Enzyme-Linked Immunosorbent Assay (ELISA). Urine values were normalized to urinary creatinine excretion. Renal biopsies were performed in 21 ALN patients. Results: They were 54 females and 4 males with a mean age 31.8 ± 9.1 years and disease duration 6.2 ± 4.8 years. They were 31 with ALN and 27 NRA SLE patients. Urinary sCD163 level was significantly higher in SLE patients (1.85 ± 0.3) than controls (0.5 ± 0.36, p 0.82 with sensitivity of 90.3%, specificity of 88.89%, p

Infections with neuraminidase-producing bacteria can lead to acute kidney injury (AKI). We herein report a 74-year-old woman who developed AKI in the course of Capnocytophaga infection, a neuraminidase-producing bacterium. A renal biopsy showed tubulointerstitial injury accompanied by specific binding of fluorescence-conjugated peanut lectin to the tubular epithelial cells, suggesting exposure of Thomsen-Friedenreich antigen (T-antigen) on the tubules. Although AKI is often observed in patients infected with Capnocytophaga, little is known about its etiology and associated pathology. This case suggests that tubulointerstitial injury caused by neuraminidase production and resultant T-antigen exposure is a mechanism of Capnocytophaga infection-induced AKI.

Acute kidney injury (AKI) is a common syndrome that has a significant impact on prognosis in various clinical settings. To evaluate whether new evidence supports changing the current definition/classification/staging systems for AKI suggested by the Kidney Disease: Improving Global Outcomes (KDIGO) 2012 Clinical Practice Guideline, the Taiwan AKI-TASK Force, composed of 64 experts in various disciplines, systematically reviewed the literature and proposed recommendations about the current nomenclature and diagnostic criteria for AKI. The Taiwan Acute Kidney Injury (TW-AKI) Consensus 2020 was established following the principles of evidence-based medicine to investigate topics covered in AKI guidelines. The Taiwan AKI-TASK Force determined that patients with AKI have a higher risk of developing chronic kidney disease, end-stage renal disease, and death. After a comprehensive review, the TASK Force recommended using novel biomarkers, imaging examinations, renal biopsy, and body fluid assessment in the diagnosis of AKI. Clinical issues with regards to the definitions of baseline serum creatinine (sCr) level and renal recovery, as well as the use of biomarkers to predict renal recovery are also discussed in this consensus. Although the present classification systems using sCr and urine output for the diagnosis of AKI are not perfect, there is not enough evidence to change the current criteria in clinical practice. Future research should investigate and clarify the roles of the aforementioned tools in clinical practice for AKI.

Rosai-Dorfman-Destombes disease (RDD) is a non-Langerhans cell histiocytosis characterized by the accumulation of histiocytes inside the lymph nodes or extranodally. The association between RDD and IgG4-related disease (IgG4-RD) is discussed. We herein report a case of RDD manifesting as acute tubulointerstitial nephritis mimicking IgG4-RD. The first renal biopsy showed severe tubulointerstitial nephritis with infiltration of S100-positive histiocytes and IgG4-positive plasma cells; storiform fibrosis and obliterative phlebitis were not confirmed. After prednisolone therapy, IgG4-positive cells and S100-positive histiocytes were decreased, but the IgG4/IgG ratio increased despite clinical improvement. These findings indicated extranodal RDD in the kidney presenting as tubulointerstitial nephritis.

Calciphylaxis is commonly associated with end-stage renal disease (ESRD) and renal transplant. We present a rare case of early onset calciphylaxis in a patient presenting with acute kidney injury (AKI) secondary to anti-glomerular basement membrane (anti-GBM) antibody disease. A 65-year-old obese Caucasian woman with type 2 diabetes mellitus and hypertension presented with a 1-month history of painless gross haematuria and worsening lower extremity oedema. Laboratory results indicated AKI and nephrotic-range proteinuria. Anti-glomerular antibodies were elevated. Renal biopsy revealed focal crescentic glomerulonephritis with linear capillary immunoglobulin G staining consistent with anti-GBM antibody disease. She was treated with haemodialysis, plasmapheresis, steroids, bumetanide and cyclophosphamide. Two months later, she developed necrotic lesions on bilateral thighs. Wound biopsy was consistent with calciphylaxis. This case highlights that calciphylaxis, usually seen in patients with chronic kidney disease or ESRD, can manifest in patients with AKI as well.

The objective of this study was to evaluate the correlation between contrast-enhanced ultrasound (CEUS) parameters and histopathological features in patients with diabetic nephropathy (DN). Sixty-two patients with DN (44 men, mean age: 52.61 ± 10.63 y) were enrolled. They underwent renal biopsy for DN at the Department of Ultrasound, PLA Hospital, between May 2017 and February 2020. Renal tissue was obtained by ultrasound-guided percutaneous needle biopsy. CEUS was performed, and time-intensity curves (TICs) and renal perfusion parameters were analyzed. Differences in CEUS parameters were analyzed according to the glomerular classification and interstitial fibrosis-tubular atrophy (IFTA) score. Continuous variables were evaluated using the analysis of variance or Mann-Whitney U-test. Discontinuous variables were compared with the χ2-test. Spearman correlation analyses evaluated associations among quantitative ultrasound perfusion parameters and histopathological characteristics. Peak enhancement (PE), wash-in rate (WiR), wash-in perfusion index (WiPI) and wash-out rate (WoR) of the cortex, and their cortex/medulla ratios, decreased with increasing glomerular classification grade (p < 0.05). The fall time (FT) of the cortex, and their cortex/medulla ratios, increased with increasing glomerular classification grade (p < 0.05). There were no significant differences in the CEUS parameters for different IFTA scores. The perfusion volume-relevant parameters (such as PE, WiR and WiPI) had a negative correlation (p < 0.05), while the perfusion time-relevant parameters (such as RT and FT) had a positive correlation (p < 0.05), with the severity of glomerular lesions, glomerulosclerosis rate and number of Kimmelstiel-Wilson lesions. The CEUS parameters of the cortex could reflect pathological characteristics, especially changes in glomerular lesions.

Amyloidosis is a rare group of diseases characterized by abnormal folding of proteins and extracellular deposition of insoluble fibrils. It can be localized to one organ system or can have systemic involvement. The kidney is the most common organ to be involved in systemic amyloidosis often leading to renal failure and the nephrotic syndrome. The two most common types of renal amyloidosis are immunoglobulin light chain-derived amyloidosis (AL) and reactive amyloidosis (AA). A novel form of amyloidosis (ALECT2) derived from leukocyte chemotactic factor 2 (LECT-2) and primarily involving the kidneys was first described by Benson et al in 2008. The liver was subsequently identified as the second most common organ involved in ALECT2 amyloidosis. LECT-2 is a unique protein that can form amyloid deposits even in its unmutated form. Patients with ALECT2 present with minimal proteinuria in contrast to other forms of amyloidosis especially AL and AA. They may present with slightly elevated serum creatinine. Nephrotic syndrome and hematuria are rare. ALECT2 can be found in association with other types of amyloidosis as well as malignancies or autoimmune diseases. ALECT2 may be confused with amyloidosis associated with light and heavy chain monoclonal gammopathy if the immunofluorescence is positive with anti-light chain and anti-AA sera. The other organs involved are the duodenum, adrenal gland, spleen, prostate, gall bladder, pancreas, small bowel, parathyroid gland, heart, and pulmonary alveolar septa, but consistently uninvolved organs included brain and fibroadipose tissue. A renal biopsy along with characteristic features found on immunohistochemistry and mass spectrometry is diagnostic of ALECT2. ALECT2 should be suspected when all markers for AL and AA are negative. Proper diagnosis of ALECT2 can determine need for supportive care versus more aggressive interventions.

Patients with chronic kidney disease (CKD) are commonly at high risk of tuberculosis (TB). Conversely, TB rarely causes tubulointerstitial nephritis. A 75-year-old Japanese man who was undergoing periodic follow-ups for CKD stage G3aA3 with membranous nephropathy was diagnosed with acute kidney injury (AKI) (estimated glomerular filtration rate [eGFR]: 15 mL/min/1.73 m2) without prerenal AKI. He reported developing recent-onset cough 3 weeks prior to presenting to us. Renal biopsy revealed acute tubulointerstitial nephritis along with known membranous nephropathy. CD4+ helper T cells comprised most lymphocytes in the tubulointerstitium. Results of the interferon-gamma release assay, sputum smear test, polymerase chain reaction (PCR), and culture test were positive for TB. Chest computed tomography revealed thickening of the left bronchial wall; therefore, a diagnosis of early bronchial TB was made; his urine culture and PCR were negative for TB. At four months after TB treatment with no immunosuppressive therapy, his eGFR improved to 50 mL/min/1.73 m2, and based on this progress, the AKI was diagnosed as tuberculosis-associated tubulointerstitial nephritis (TATIN). Although TATIN typically occurs with chronic or miliary tuberculosis, it is very rare in early bronchial TB. Identification of TATIN is important in kidney diseases of unknown etiology, and treatment with anti-TB drugs is necessary.

TAFRO syndrome is a rare systemic inflammatory disorder that is characterized by thrombocytopenia, anasarca, fever, reticulin fibrosis, and organomegaly. Progressive renal involvement is frequently observed in patients with TAFRO syndrome, and the renal histological findings remain limited. A 52-year-old man with thymoma that was detected by chest computed tomography was admitted to our hospital because of dyspnea and abdominal distension. He had a rapid reappearance of pleural and abdominal effusion following repeated puncture with inflammation and kidney involvement on admission. Renal histology showed glomerular lesions denoting diffuse endocapillary proliferative glomerulonephritis, without any crescentic glomeruli, which was diagnosed as thrombotic microangiopathy (TMA)-like glomerulopathy. Together with histological findings of thymoma and progressively emergent thrombocytopenia, the patient was diagnosed with TAFRO syndrome. Corticosteroid and tocilizumab administration ameliorated the renal insufficiency and his clinical condition relevant to TAFRO syndrome, but there was a rapid concomitant appearance of massive proteinuria. A second renal biopsy revealed membranoproliferative glomerulonephritis (MPGN)-like glomerulopathy with de novo sclerosing and crescentic glomeruli development. Patients with TAFRO syndrome show glomerular lesions that are consistent with TMA- or MPGN-like lesions, but their clinical data are similar between the two glomerulopathies. It remains controversial whether the two are a histopathological continuum or distinct diseases. This case shows that glomerular lesions had TMA-like glomerulopathy in the acute stage of TAFRO syndrome, while the histopathology pattern favors MPGN in the chronic stage, as confirmed by repeated renal biopsies. TAFRO syndrome disease activity may not always correspond to that of glomerulopathy that is associated with TAFRO syndrome.

Introduction: Nephrologists have recently recognized the heterogeneity of kidney diseases among patients with diabetes and begun to actively perform percutaneous renal biopsies (PRBs). Nevertheless, the association between diabetes and major bleeding complications of PRB remains unclear. Methods: In this retrospective cohort study using the Diagnosis Procedure Combination database in Japan, we identified patients who underwent an elective PRB from July 2010 to March 2018. The primary outcome was the occurrence of major bleeding complications, defined as red blood cell transfusion within 7 days after PRB or invasive hemostasis after PRB. Multivariable regression analysis was performed to analyze the association between diabetes and major bleeding complications with adjustment for patient and hospital characteristics. Results: We identified 76,302 patients, including 8245 with diabetes. The proportion of PRBs performed for patients with diabetes continuously increased over time. Major bleeding complications occurred in 678 patients (0.9%), including 622 (0.8%) with red blood cell (RBC) transfusion and 109 (0.1%) with invasive hemostasis. Diabetes was significantly associated with major bleeding complications (relative risk [RR] = 2.41; 95% CI 2.00–2.90). Among patients with diabetes, multiagent or insulin treatment had significant association with major bleeding complications (RR = 1.57; 95% CI 1.18–2.10), compared with single-agent diabetes treatment. Conclusion: Diabetes is significantly associated with major bleeding complications of PRBs. Moreover, severity of diabetes has association with increases in major bleeding complications. Thus, nephrologists should carefully judge whether the anticipated benefits outweigh the relatively high risk of major bleeding complications when considering PRB for patients with diabetes.

Background Nephrotic syndrome (NS) is the most frequent glomerular disease among children. Renal biopsy is the most precise procedure for diagnosing and following childhood NS; however, it is an invasive procedure with potential complications. As a result, early non-invasive diagnostic and prognostic indicators and new treatment targets are urgently needed for this disease. Purpose To assess the miR-142-5p expression in peripheral blood as an indicator of the autoimmune processes in children with NS and the role of differential microRNAs (miR) expression and expression panels in diagnosing and predicting the response to steroid treatment in children with NS. Methods Eighty (80) children with NS and 100 subjects matched for age and gender used as controls constitute the study sample in this case-control study. MiR-142-5p, miR-191, miR-181-5p, miR-30a-5p and miR-50a-5p expression are measured in all enrolled children by real-time PCR. We assessed the sensitivity and accuracy of different MicroRNAs panels. Results miR-142-5p, miR-191, miR-181-5p, miR-30a-5p and miR-150a-5p expressions were significantly increased in the children with NS than controls. There was a significant difference in the five mRNAs differential expressions between steroid-resistant and steroid-sensitive children with NS. Of the selected five microRNAs, miR-142a-5p was the best to allow very good discrimination of the children with NS and predict steroid resistance (AUC = 0.965 and 1.00, respectively), suggesting the possible autoimmunity processes' role in the pathogenesis of NS and the resistance to steroids. The (miR-142a-5p with miR-181a-5p and miR-30a-5p) was the best expression panel to diagnose new NS cases and predict steroid resistance. Conclusions microRNAs expressions, either differential or as a panel, are important for early diagnosing childhood NS and may provide a non-invasive clue for the response to steroid treatment in these patients. The (miR-142a-5p, miR-181-5p, and miR-30a-5p) panel was the best one to cover both the diagnosis of the new cases and prediction of response to steroid treatment. Autoimmunity has an important role in NS pathogenesis and resistance to steroid treatment.

OBJECTIVE To determine whether ultrasonographic features in dogs with protein-losing nephropathy (PLN) were associated with renal biopsy findings and compare corticomedullary ratios between dogs with PLN versus non-renal disease. ANIMALS 71 dogs with PLN and 33 dogs without renal disease. PROCEDURES Medical records and archived ultrasonographic images for dogs with PLN that underwent renal biopsy between 2008 and 2018 were reviewed. Corticomedullary ratios were measured. RESULTS In dogs with PLN, median serum creatinine and BUN concentrations and urine-protein-to-creatinine-ratio prior to renal biopsy were 3.4 mg/dL (interquartile range [IQR], 1.2 to 5.3 mg/dL), 80 mg/dL (IQR, 28 to 105 mg/dL), and 11.4 (IQR, 6.4 to 18.3), respectively. Histologic abnormalities within the tubulointerstitial space were associated with cortical echogenicity. Gastric wall thickness > 5 mm was associated with a histologic diagnosis of acute glomerular disease. Dogs with immune complex–mediated glomerular disease were more likely to have abnormal gastric mural architecture. Other ultrasonographic features of the kidneys, liver, and stomach and the presence of ascites did not help to differentiate immune complex–mediated from non-immune complex–mediated glomerular disease, acute from chronic disease, or amyloid from non-amyloid disease or distinguish whether tubulointerstitial disease was present or absent. Median left corticomedullary ratio for 66 dogs with PLN (1.2) was significantly higher than that for the 33 dogs without renal disease (1.0). Clinical Relevance Ultrasonographic features were poorly associated with specific pathological disorders in dogs with PLN. In this study, the corticomedullary ratio was higher in dogs with PLN, indicating the presence of cortical thickening, but the clinical relevance is unknown.

Background/Aims: Anti-phospholipase A2 receptor (PLA2R) autoantibody is the main biomarker of idiopathic membranous nephropathy (IMN). We aimed to find a new cutoff value of anti-PLA2R for patients with IMN and to explore the relevance between this antibody and baseline clinical parameters.Methods: A total of 670 subjects including 374 IMN cases and 296 non-IMN controls were included between January 2017 and January 2020. All clinical parameters were collected at the time of renal biopsy. The levels of anti-PLA2R were detected by a commercial enzyme-linked immunosorbent assay (ELISA) kit. The optimal cutoff value was calculated by a receiver operating characteristic curve and compared in diagnostic efficiency.Results: The optimal cutoff value of anti-PLA2R for IMN was 7.45 RU/mL with the highest Youden index, and the corresponding sensitivity, specificity, positive predictive value and negative predictive value were 80.75%, 97.97%, 98.05% and 80.11%, respectively. Anti-PLA2R levels in IMN patients demonstrated a significant positive correlation with serum creatinine and 24-hour urinary protein, while they showed a negative correlation with serum albumin and estimated glomerular filtration rate.Conclusions: The recommended cutoff value of anti-PLA2R is 7.45 RU/mL using ELISA detection for distinguishing IMN from non-IMN nephropathy. The level of anti-PLA2R is related to baseline renal function in IMN. This new threshold can improve the diagnostic efficiency and facilitate early diagnosis of IMN.

Aim The prevalence of kidney disease and the number of renal biopsies performed in the elderly are increasing with aging of the population. We aimed to analyze the clinicopathological findings of kidney diseases in the elderly (≥ 65 years), in comparison with their younger counterparts (aged 16 - 64 years). Materials and methods The data at the time of renal biopsy were obtained by reviewing medical records and the biopsy reports of the patients retrospectively. The data at the time of renal biopsy were obtained by reviewing medical records and the biopsy reports of the patients who underwent renal biopsy at Bakirkoy Dr. Sadi Konuk Education and Research Hospital. Demographic characteristics, clinical syndrome at presentation, and histopathological diagnosis of all patients were recorded. Results Among the 750 renal biopsies, 93 were performed in elderly patients, which constitutes 12.4% of the biopsies. The mean age of the patients was 71.7 ± 5.4 years, and 62.4% were male. The most common indication for renal biopsy was nephrotic syndrome (NS) in elderly and younger age groups (45.2% vs. 40%). The most frequent histopathological diagnosis was membranous glomerulonephritis (MGN). According to the clinical presentation, MGN (42.8%) was the leading cause of NS, and almost 1/3 of the patients with acute or rapidly progressive renal failure were found to have pauci-immune glomerulonephritis (GN). In comparison with renal biopsy results of younger patients, MGN and pauci-immune GN were more prevalent, but IgA nephropathy, lupus nephritis, and acute tubular necrosis were less common in elderly patients. Conclusion Clinical presentation and the frequency of certain renal pathologies differ with age. The relatively high prevalence of potentially curative kidney diseases in the elderly indicates the importance of renal biopsy in these patients.

Background In Fabry disease, the presence of globotriaosylceramide (GL3) deposits in various kidney cells leads to progressive renal dysfunction. However, kidney biopsy studies in patients with Fabry disease are limited. In the present study, the pathologic findings of patients with Fabry nephropathy receiving enzyme replacement therapy (ERT) and untreated patients without albuminuria were investigated. Methods The present study included 15 patients with Fabry disease who underwent renal biopsy while receiving ERT (group 1: n = 9, age 19–58 years, two males and seven females) or before ERT initiation (group 2: n = 6, age 11–66 years, one male and five females). All patients in group 2 were normoalbuminuric. Results Group 1 showed improved clinical symptoms, such as acroparesthesia. The ERT duration was 1.2 to 8 years and seven of the nine patients showed GL3 deposits in various kidney cells and segmental foot process effacement (FPE) of podocytes. GL3 deposits and FPE were not observed in the two remaining patients in group 1. Group 2 showed segmental FPE and podocyte GL3 deposits. Most patients in group 2 also showed GL3 deposits in the mesangium, endothelium, or tubular epithelium. Conclusion The study results showed that segmental FPE and GL3 deposits can persist in Fabry nephropathy despite ERT. In addition, segmental FPE and GL3 deposits were observed in various kidney cells in normoalbuminuric patients with Fabry disease. These findings indicated that kidney biopsies at baseline and follow-up evaluation of Fabry nephropathy are essential for timely ERT initiation and ERT response assessment.

Background Renal involvement is a common and severe complication of ANCA (antineutrophil cytoplasmic antibody) associated vasculitis (AAV) potentially resulting in a pauci-immune necrotizing and crescentic antineutrophil cytoplasmic antibody (ANCA) glomerulonephritis (GN) with acute kidney injury (AKI), end-stage renal disease (ESRD) or death. We recently described that Bowman’s capsule rupture links glomerular damage to tubulointerstitial inflammation in ANCA-associated glomerulonephritis. Herein we provide a comprehensive histological subtyping of immune cell infiltrates in association with Bowman’s capsule rupture in ANCA GN. Methods A total of 44 kidney biopsies with ANCA GN were retrospectively included in a single-center observational study. Within a renal biopsy specimen, each glomerulus was scored separately for the presence of extensive and focal Bowman’s capsule rupture in injured glomeruli. Infiltrates of neutrophils, eosinophils, plasma cells, and mononucleated cells (macrophages, lymphocytes) were quantified as a fraction of the area of total cortical inflammation. Results Extensive Bowman’s capsule rupture was associated with tubulointerstitial inflammation containing infiltrates of neutrophils, eosinophils and plasma cells. A similar association was observed for the presence of focal Bowman’s capsule rupture, correlating with tubulointerstitial inflammation containing neutrophils, eosinophils and plasma cells. Multiple logistic regression confirmed that extensive Bowman’s capsule rupture correlated with tubulointerstitial inflammation containing neutrophils, and focal Bowman’s capsule rupture correlated with neutrophil and plasma cell infiltration. Furthermore, this association was specifically observed in PR3-ANCA GN. Conclusion To our knowledge, this is the first report linking Bowman’s capsule rupture directly to tubulointerstitial inflammation by immune cell subtypes. This underscores a pathomechanistic link between tubulointerstitial and glomerular lesions in ANCA GN and needs further investigation. Graphical abstract

Fabry disease (FD) is an inherited X-linked lysosomal storage disorder, with hemizygous males being more severely affected than heterozygous females. Herein, we report a rare case of FD in a heterozygous female with a severe phenotype. The patient had obesity and hyperlipidemia and had her first cerebral infarction at the age of 33 years. She underwent renal biopsy and was diagnosed with FD with morphological features of focal segmental glomerulosclerosis nephropathy at the age of 34 years. Her leukocyte alpha-galactosidase A activity was 2.3 Agal/U (normal: >20 Agal/U), and genetic analysis revealed the presence of the classical phenotype. Enzyme replacement therapy (ERT) was initiated at the age of 35 years; however, peritoneal dialysis owing to end-stage renal failure occurred at the age of 37 years. The patient died of a cerebral hemorrhage at the age of 44 years. Her Mainz Severity Score Index at the time of death was 48/76, suggestive of the severe phenotype. Autopsy findings revealed remarkable globotriaosylceramide accumulation on electron microscopy, particularly in the major organs and their vascular smooth muscle cells. Regarding the vertebral arteries which sourced the cerebral hemorrhage, the effects of FD-induced vascular thickening and long-term renal failure-induced atherosclerosis were confirmed. Furthermore, the patient’s vascular sclerosis was modified with acquired factors such as lifestyle-related disease associated with obesity. We recommend intensified treatment for metabolic factors simultaneous with ERT to help in delaying the progression of FD.

To explore the elastic values obtained by shear wave elastography (SWE) in assessing renal fibrosis in chronic kidney disease (CKD). One hundred and twenty-four patients with CKD who underwent renal biopsy were prospectively enrolled between April 2019 and June 2021. SWE was performed to measure the renal cortex stiffness, presented as SWE parameters, including the minimum, mean, and maximum elasticity (namely Emin, Emean, and Emax). Then, the patients with different kidney pathological impairment (mild, moderate, and severe groups) were compared in SWE elasticity and the discriminative capacity was also analyzed. For the pathology impaired grade, SWE parameter was significantly reduced in the moderately and severely impaired group than the mild one. Emax parameter achieved the best discriminative ability toward differentiating moderate–severe impairment from mild one, yielding an area under the curve (AUC) of 0.764 (95%CI: 0.681–0.848). Regarding interstitial fibrosis/tubular atrophy and global glomerular sclerosis, the Emax values were significantly reduced across the group of patients with moderate grade compared to those with mild grade. Patients in severe group were also with reduced elastic value than those in mild one, while the difference was non-significant in interstitial fibrosis/tubular atrophy but a borderline statistical significance was achieved in global glomerular sclerosis. For grade of vessel wall thickening, patients in moderate (33.04 ± 9.86 kPa, P = 0.009) and severe (31.42 ± 9.16 kPa, P

Background Recent clinical reports indicate a correlation between gross hematuria after the coronavirus 2019 (COVID-19) vaccination in patients with glomerulonephritis, especially immunoglobulin A nephropathy (IgAN). Furthermore, healthcare workers in Japan were initially vaccinated with an mRNA vaccine from February 17, 2021, and some of them experienced gross hematuria after receiving the vaccination. Methods We conducted a web-based survey of the councilor members of the Japanese Society of Nephrology (581 members, 382 facilities) to elucidate the relationship between gross hematuria and COVID-19 vaccination. Results In the first survey, 27 cases (female: 22, 81.5%) of gross hematuria were reported after receiving a COVID-19 vaccination. Of them, 19 (70.4%) patients were already diagnosed with IgAN at the occurrence of gross hematuria. Proteinuria appeared in eight of the 14 (57.1%) cases with no proteinuria before vaccination and hematuria in five of the seven (71.4%) cases with no hematuria before vaccination. The second survey revealed that a renal biopsy was performed after vaccination in four cases, all of whom were diagnosed with IgAN. Only one case showed a slightly increased serum creatinine level, and no patients progressed to severe renal dysfunction. Conclusion This study clarified the clinical features of gross hematuria after a COVID-19 vaccination. Because there was no obvious progression to severe renal dysfunction, safety of the COVID-19 vaccination is warranted at least in the protocol of inoculation twice.

IgA nephropathy (IgAN) has been anecdotally reported in association with atypical hemolytic uremic syndrome (aHUS). The association likely portends poor renal outcome, and the possible relationship with complement overactivation has yet to be elucidated. We evaluated a series of IgAN patients with aHUS and reviewed the available literature. Adult patients who received a diagnosis of IgAN and developed aHUS between January 2009 and December 2019 were included in this retrospective review. We identified six IgAN-aHUS patients, all of whom developed end-stage kidney disease. At aHUS presentation all patients had decreased serum C3 levels. Predisposing pathogenetic variants and risk haplotypes for aHUS in CFH gene heterozygosity were documented in four out of six patients. Anti-CFH antibodies were found to be negative in the five tested patients. In the literature we identified 21 case reports involving aHUS-IgAN and six retrospective studies evaluating the presence of TMA at the time of renal biopsy. Hypertension, severe proteinuria, reduced sC3 and a worse renal prognosis were the common features of most cases. Our case series and literature review show that the onset of either aHUS or renal TMA in the course of IgAN are associated with very poor renal outcome. Activation of the alternative pathway revealed by consumption of serum C3 seems to play a major role. Our hypothesis is that the presence of a predisposing factor (e.g. dysregualtion of complement alternative pathway and/or other intrarenal precipitating factors) might be at the heart of aHUS-IgAN pathophysiology.

A 37-year-old African–British man was referred to our hospital for detailed examination because of persistent fever, swelling and pain in both ankle joints, and blurred vision for two months. Inguinal lymph node biopsy showed a large number of epithelioid granulomas without necrosis. Granulomatous anterior uveitis, nephropathy, high serum angiotensin-converting enzyme activity, and high serum-soluble interleukin-2 receptor were observed, and the diagnosis of systemic sarcoidosis was made. His serum creatinine was 1.4 mg/dL and hematuria, leukocyturia, and urine protein were also seen. The renal biopsy finding was mesangial proliferative glomerulonephritis, with no findings of granuloma formation or tubular interstitial nephritis. Immunofluorescence staining showed deposition of IgG, C3, and C1q in the mesangial region. IgG3 was dominant in subclass staining. There was no monoclonality on kappa and lambda staining. Electron microscopy showed predominant deposition in the mesangial region with some subepithelial and endothelial deposition. His hematuria and leukocyturia disappeared with steroid therapy, suggesting sarcoidosis-related nephropathy. A case of systemic sarcoidosis with mesangial proliferative glomerulonephritis showing predominant deposition of IgG in the mesangial region is presented. No cases of such histological findings have been reported so far, and it is necessary to analyze further cases to clarify the pathogenic significance of the renal biopsy findings observed in this case.

Necrobiotic xanthogranuloma (NXG) is a rare non-Langerhans cell histiocytosis with characteristic cutaneous features and rare visceral involvement. More than 80% of individuals with this disease have a detectable paraprotein but the precise pathogenesis remains obscure. A 68-year-old man with known cutaneous necrobiotic xanthogranuloma presented with acute kidney injury and imaging suggestive of bilateral perinephric infiltration. Renal biopsy showed a prominent histiocytic infiltration of renal capsule and cortex with necrobiosis and characteristic 'Touton-type' giant cells suggestive of necrobiotic xanthogranuloma involvement. Kidney function returned to normal and cutaneous lesions improved with a combination of corticosteroid, chlorambucil and rituximab. This case represents only the second reported incidence of kidney involvement by necrobiotic xanthogranuloma and the first with acute kidney injury and pre-mortem histopathology. This report adds to a small body of literature on the diagnosis and management of visceral involvement by this rare disease.

A 33-year-old Japanese man with no significant past medical history was admitted to our hospital for evaluation of weight gain and pitting edema. A laboratory test confirmed nephrotic-range proteinuria. Renal biopsy showed subepithelial deposits, and membranous nephropathy (MN) was diagnosed. Closer examination clarified an active syphilis infection. After renal biopsy, we prescribed amoxicillin for 8 weeks to treat the syphilis infection. Three weeks later, the patient's proteinuria dramatically decreased. This case is of interest because syphilis can become a cause of acute-onset MN in younger adults, and the incidence of syphilis is increasing in Japan. .

Highlights • Fabry is an X-linked lysosomal storage disease with deficiency in α-galactosidase. • This deficiency results in the accumulation of glycosphinogolipids. • Diagnosis is often made by analysis of globotriaosylceramide in fluids and tissues. • Fabry is often misdiagnosed in female patients due to residual enzyme activity. • Lipidomics by LC-HRMS enables identification of new biomarkers in Fabry., Introduction Lipidomics analysis or lipid profiling is a system-based analysis of all lipids in a sample to provide a comprehensive understanding of lipids within a biological system. In the last few years, lipidomics has made it possible to better understand the metabolic processes associated with several rare disorders and proved to be a powerful tool for their clinical investigation. Fabry disease is a rare X-linked lysosomal storage disorder (LSD) caused by a deficiency in α-galactosidase A (α-GAL A). This deficiency results in the progressive accumulation of glycosphingolipids, mostly globotriaosylceramide (Gb3), globotriaosylsphingosine (lyso-Gb3), as well as galabiosylceramide (Ga2) and their isoforms/analogs in the vascular endothelium, nerves, cardiomyocytes, renal glomerular podocytes, and biological fluids. Objectives The primary objective of this study was to evaluate lipidomic signatures in renal biopsies to help understand variations in Fabry disease markers that could be used in future diagnostic tests. Methods Lipidomic analysis was performed by ultra-high pressure liquid chromatography-high-resolution mass spectrometry (UHPLC-HRMS) on kidney biopsies that were left over after clinical pathology analysis to diagnose Fabry disease. Results We employed UHPLC-HRMS lipidomics analysis on the renal biopsy of a patient suspicious for Fabry disease. Our result confirmed α-GAL A enzyme activity declined in this patient since a Ga2-related lipid biomarker was substantially higher in the patient's renal tissue biopsy compared with two controls. This suggests this patient has a type of LSD that could be non-classical Fabry disease. Conclusion This study shows that lipidomics analysis is a valuable tool for rare disorder diagnosis, which can be conducted on leftover tissue samples without disrupting normal patient care.

The authors report a case of a 57-year-old woman who was successfully treated with a percutaneous embolization procedure for a renal arteriovenous fistula that developed as a complication of a kidney biopsy. An acute kidney injury that failed to resolve with medical management prompted further investigation with a renal biopsy. Five hours after the kidney biopsy, the patient became hemodynamically unstable with a blood pressure of 77 of 52 mm Hg. A stat abdominal computed tomography scan without contrast discovered a large left-sided perinephric hematoma that measured up to 11.5 cm with a moderate amount of perinephric blood. An angiogram subsequently demonstrated the presence of an arteriovenous fistula at the inferior pole of the left kidney. Several 2 × 3 mm and 3 × 3 mm coils were deployed into two separate segmental branches of the inferior pole, and the post embolization angiogram confirmed resolution of the previously visualized arteriovenous fistula.

To explore the spectrum, clinicopathological features and prognosis of patients with inflammatory bowel disease (IBD) including Crohn's disease (CD) and ulcerative colitis (UC) with renal involvement. Included in this cross-sectional study were 36 IBD patients, in whom renal biopsy was performed to analyze the histological pattern and prognosis. Renal histopathology was examined by light microscopy and immunofluorescence using the standard procedures. Renal function decline was defined as a twofold increase in serum creatinine (SCr) after biopsy, initiation of dialysis and transplantation. Of the 36 IBD patients (22 UC and 14 CD), renal biopsy was performed in 33 cases. Compared with UC patients, CD patients were significantly younger at presentation and had a higher proportion of chronic renal insufficiency (CRI). The most common renal histological pattern in the 33 biopsy cases was IgA nephropathy (66.6%), followed by membrane nephropathy (9.1%), amyloidosis (9.1%), tubulointerstitial nephritis (9.1%), and membranoproliferative glomerulonephritis (6.1%). Renal function decline occurred in 4 patients (1 with amyloidosis, 1 with TIN and 2 with CRI). Factors associated with renal function decline included CD and a higher SCr level at presentation. Urinalysis and renal function test should be routinely examined in IBD patients. Renal biopsy can provide useful information about the histological patterns and therefore should be considered in IBD patients with renal lesions.

Objective The objective of this study was to validate the diagnosis of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) as the primary cause of end-stage renal disease (ESRD) in the US Renal Data System (USRDS). Methods We identified patients with ESRD in the Mass General Brigham (MGB) health care system who were enrolled in the USRDS. The health records of those with AAV listed as the primary cause of ESRD in the USRDS were reviewed to confirm the diagnosis and estimate positive predictive value (PPV). Sensitivity was estimated by evaluating the primary cause of ESRD listed in the USRDS for patients with ESRD due to AAV in the MGB AAV cohort. Results We identified 89 MGB patients with ESRD due to AAV in the USRDS. Of these, 85 cases were confirmed to be true cases of AAV (PPV = 94%). Among the patients classified as having AAV, 84 (99%) had an ANCA test, which was predominantly myeloperoxidase/P-ANCA (47 [55%]); 36 (42%) had a renal biopsy, and all biopsies were supportive of the diagnosis. The majority (81 [90%]) was identified as AAV by International Classification of Diseases Ninth Revision or International Classification of Diseases 10th Revision codes for granulomatosis with polyangiitis (446.4 or M313.1). Of the 77 MGB AAV cohort patients with ESRD who were linked to the USRDS, 41 (53%) had AAV listed as the cause of ESRD; in the remainder, ESRD was attributed to nonspecific nephritis. Conclusion The diagnosis of AAV as the cause of ESRD in the USRDS has a high PPV; sensitivity was moderate. These findings support the continued use of the USRDS to study ESRD due to AAV.

Renal parenchymal fibrosis is the most important determinant of kidney disease progression and it is determined via biopsy. The aim of this study is to evaluate the renal stiffness noninvasively by magnetic resonance elastography (MRE) and to compare it with clinicopathologic parameters in glomerulonephritis and AA amyloidosis patients. Thirty-four patients with glomerular filtration rate (GFR) over 20 ml/min/1.73m2 had non-contrast MRE prospectively. Kidney stiffness values were obtained from whole kidney, cortex, and medulla. Values were correlated with GFR, albuminuria, proteinuria, and degree of fibrosis that are assessed via renal biopsy. Patients were grouped clinicopathologically to assess the relation between stiffness and chronicity. Mean whole kidney, cortex, and medulla stiffnesses were 3.78 (± 1.26), 3.63 (± 1.25), and 4.77 (± 2.03) kPa, respectively. Mean global glomerulosclerosis was 22% (± 18%) and median segmental glomerulosclerosis was 4% (min–max: 0%–100%). Extent of tubulointerstitial fibrosis was less than 25% in 26 of the patients (76.5%), 25%–50% in 6 of the patients (17.6%), and higher than 50% in 2 of the patients (5.9%). Fourteen patients were defined to have chronic renal parenchymal injury. MRE-derived stiffness values correlated negatively with parameters of fibrosis. Lower stiffness values were observed in patients with chronic renal injury compared to those without (P

Background/Aims: Inflammatory bowel disease (IBD) is a chronic inflammation of the gastrointestinal tract. Some patients with this condition have been reported to present with immunoglobulin A nephropathy (IgAN), a renal complication that can cause end-stage renal failure, but the frequency of this comorbidity has not been described. Thus, the aim of this study was to investigate the frequency of IgAN in patients with IBD.Methods: This study included 620 patients with IBD (338 with ulcerative colitis [UC] and 282 with Crohn’s disease [CD]) from the Hiroshima University Hospital outpatient department. IgAN cases were identified from medical interviews, blood examinations (serum immunoglobulin A), and urinalyses (occult blood, proteinuria). Definitive IgAN cases were diagnosed by renal biopsies, while those detected through the clinical course and test results, but not clinically recommended for renal biopsy, were defined as suspected IgAN.Results: We analyzed 427 cases meeting the inclusion criteria (220 with UC and 207 with CD). The incidence of IgAN across all patients with IBD was 3.0%. The frequency of IgAN was significantly higher in patients with CD (11/207, 5.3%) than in those with UC (2/220, 0.9%) (P< 0.01). Moreover, a significant correlation was found between CD patients with ileostomy or colostomy and a diagnosis of IgAN.Conclusions: Patients with IBD present a high incidence of IgAN, especially those with CD who have undergone ileostomy or colostomy.

Diagnosis of immunoglobulin A nephropathy (IgAN) requires the evaluation of renal biopsy specimens. However, renal biopsy is an invasive procedure and is not frequently performed for various reasons. Thus, recognized noninvasive biomarkers for predicting IgAN progression are urgently needed. In the present study, we included 86 IgAN patients with renal biopsy from June 2015 to May 2016 and had their plasma interleukin-7 (IL-7) level measured with ELISA. The association between the plasma IL-7 level and clinico-pathological characteristics was analyzed. Immunohistochemical staining was used to assay the in situ expression of IL-7 in vivo. Western blotting was performed to examine the production of extracellular matrix, p-mTOR and the markers of autophagy under the treatment of IL-7 after TGF-β1 stimulation in renal tubular epithelial cells. IL-7 was significantly decreased in patients with IgAN compared to healthy subjects (2.3077 vs. 8.6294 pg/mL, P

Lupus podocytopathy (LP) is an uncommon manifestation of systemic lupus erythematosus (SLE) and is not included in the classification of lupus nephritis. The diagnosis of LP is confirmed by the presence of diffuse foot process effacement in the absence of capillary wall deposits with or without mesangial immune deposits in a patient with SLE. Here we describe a 13-year-old female who presented with nephrotic syndrome (NS) seven years after the diagnosis of SLE. The renal function had been stable for seven years since the SLE diagnosis, as manifested by the normal serum creatinine, serum albumin and absence of proteinuria. Renal biopsy showed evidence of minimal change disease without immune complex deposits or features of membranous nephropathy. Renal function was normal. The patient had an excellent response to steroid therapy with remission within two weeks. The patient remained in remission five months later during the most recent follow-up. This report highlights the importance of renal histology to determine the accurate etiology of NS in patients with SLE. Circulating factors, including cytokines such as interleukin 13, may play a role in the pathophysiology of LP and needs to be studied further in future larger studies.

Introduction: Systemic Lupus Erythematosus (SLE) is a disease of thousand faces whose manifestations vary with the interplay of genetic, ethnic, and host factors along with environmental exposures and geographical conditions. Since the first case of SLE reported in India in 1955, many case series have been published from various centers depicting Clinical and Immunological features in the Indian population. This study was undertaken to study the clinical and immunological profile in a tertiary care center in the sub-Himalayan region of northern India. Materials and Methods: This study is a cross-sectional retrospective study conducted at a tertiary care center in the hilly northern state of Himachal Pradesh over a period of 1 year; from 1st June 2017 to 31st May 2018. The records of all patients admitted in the study period with the department of medicine and diagnosed with SLICC 2012 classification criteria were studied to abstract the Clinical and Immunological profile of patients. Results: A total of sixty-nine patients were included in the study. 96% of the subjects were female patients, and 84 % of the patients were in the reproductive age group of 20 – 40 years. Mucocutaneous manifestations were most commonly seen in nearly 89 % of patients followed by musculoskeletal involvement in about 71 %. Hematological involvement was more frequent than reported in the literature. Lupus Nephritis was diagnosed in about 30 % of the patients. Fatigue and synovitis were the most common features, followed by oral ulcers and Acute cutaneous lupus. ANA and ds DNA positivity was 98.5 and 72.4 % respectively. Six cases of MCTD were d=found in the study group. Conclusion: In hospitalized SLE patients admitted in a tertiary care center of the northern hilly state, females of reproductive age group constituted the majority of patients. Mucocutaneous, Musculoskeletal, hematological, and renal involvement was most prevalent. Keywords: SLE, cross-sectional study, Mucocutaneous involvement, Renal Biopsy, Hilly area.

This study aimed to explore the long-term outcomes of mesangial proliferative lupus nephritis (LN class II) and the factors associated with its relapse and histological transformation in Chinese patients. 104 SLE patients with biopsy-proven LN class II were included and divided into proteinuria group (proteinuria ≥ 0.4 g/24 h, with or without microscopic hematuria) and hematuria group (microscopic hematuria with proteinuria

Data on anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) are limited in children. This study is to determine the clinical features and outcomes of childhood-onset AAV. A retrospective study was performed on patients who were diagnosed with AAV before 18 years old in Xiangya Hospital. Their medical records were analyzed by retrospective review. Sixteen patients were diagnosed with AAV before 18 years old in the past 9 years, with an average age of 13.3 ± 3.3 years and 13 of them were female. There were 15 patients with microscopic polyangiitis (MPA) and 1 with Wegener’s granulomatosis. The interval between onset of disease and diagnosis of AAV was 2 (1.5–3) months. Most patients (15/16, 93.8%) had multi-organ involvement, and all patients had renal involvement with 7 (43.8%) patients requiring dialysis at presentation. Eleven patients underwent a renal biopsy, of which mixed class and sclerotic class were the most two common histological types. All patients received immunosuppressive therapy for induction therapy including intravenous administrations of methylprednisolone (MP) pulse therapy for 8 patients. 8 patients (50%) achieved remission after induction therapy. After a median follow-up of 46.3 ± 36.1 months, nine (56.3%) patients progressed to end-stage renal disease (ESRD) and 5 (31.3%) patients died. Childhood-onset AAV showed similar clinical and pathological features compared to those of adults, except that it usually occurs in girls. The most commonly involved organ was the kidney, and it had a high risk of progression to ESRD. Early diagnosis and initiation of appropriate immunomodulatory therapy would be important to improve outcomes.

A 69-year-old woman presented with mild renal dysfunction, proteinuria, and sensorineural hearing loss. A renal biopsy showed focal segmental glomerulosclerosis with thinning of the glomerular basement membrane. There was a positive family history of end-stage kidney disease and hearing loss. Although Alport syndrome was suspected from these features, a genetic test using next-generation sequencer identified a novel missense mutation in LMX1B, c.655C>G: p. (Pro219Ala). In silico analyses predicted the pathogenicity of the mutation. Thus, the present case was diagnosed as LMX1B-associated nephropathy presenting with Alport syndrome-like phenotype, expanding the disease spectrum of LMX1B nephropathy.

Immune check point inhibitors (ICIs) are now increasingly used for cancer therapy. At the same time, by activating the immune system, ICIs induce unique side effects, termed immune-related adverse events (irAEs). Renal irAEs, although uncommon, result in acute tubulointerstitial nephritis. Recently, because of an increase in ICI administration, renal irAEs, including glomerulonephritis, are being increasingly reported. A 69-year-old man presented with nephrotic syndrome after use of the ICI nivolumab. He underwent renal biopsy and was diagnosed with membranous nephropathy (MN) without acute tubulointerstitial nephritis. Immunofluorescence staining was negative for IgG4 and phospholipase A2 receptor (PLA2R), suggesting a malignancy-associated pattern. Oral glucocorticoid therapy was started as the standard treatment for irAEs, which resulted in complete remission of the nephrotic syndrome in 20 months. We suggest his MN was induced or accelerated by immune activation due to nivolumab. It means that ICIs possibly induce not only acute tubulointerstitial nephritis but also nephrotic syndrome due to MN as renal irAEs which is treatable with glucocorticoid.

Fabry disease (FD) is a rare X-linked lysosomal storage disorder caused by mutations in the galactosidase A (GLA) gene that result in deficiency of α-GLA activity, leading to major organ failure and premature mortality. According to different disease courses, FD can be divided into classical and nonclassical phenotypes. The nonclassical FD phenotype is always absent of characteristic symptoms, which makes identifying it challenging. This article presents a 49-year-old man with a 10-year history of proteinuria and decreased glomerular filtration rate. An electrocardiogram showed a complete right bundle branch block and abnormal Q waves in high lateral, accompanied by dramatically elevated ST segment. Consequently, a renal biopsy was performed. Vacuolation was found in many podocytes in light microscopic examinations. Similarly, a myelin-like structure was detected by electron microscopy. Pathological findings were most consistent with FD. Consequently, genetic analysis, p.R301Q (c.902G>A [p.Arg301Gln]), confirmed the FD diagnosis. Angiotensin receptor blocker and traditional Chinese medicine, but not enzyme replacement therapy, were prescribed due to financial constraints. The patient had stabilization of kidney disease 6 months later. The case showed that renal biopsy should be performed in patients with cardiac and renal symptoms, which could contribute toward the correct diagnosis for nonclassical FD type.

Background The associations of focal segmental glomerulosclerosis (FSGS) histological variants with renal outcomes have rarely been investigated comprehensively by clinically relevant subgroups in this modern age. Methods Data on 304 (173 nephrotic and 131 non-nephrotic) patients with biopsy-confirmed FSGS from 2010 to 2013 were analyzed using the Japanese nationwide renal biopsy registry. The primary outcome was a composite of a 30% decline in estimated glomerular filtration rate or progression to end-stage kidney disease 5 years from the biopsy. We compared outcomes of FSGS variants according to the Columbia classification using survival analyses. Subgroup analyses were performed based on nephrotic syndrome (NS), immunosuppression and proteinuria remission (PR; proteinuria Results The distribution of variants was 48% (n = 145) FSGS not otherwise specified, 19% (n = 57) tip, 15% (n = 47) perihilar, 13% (n = 40) cellular and 5% (n = 15) collapsing. The outcome event occurred in 87 patients (29%). No significant differences in the outcome were found among the variants. Subgroup analyses yielded similar results. However, there was a trend toward improved outcome in patients with PR irrespective of variants [hazard ratio adjusted for histological variant and potential confounders (adjusted HR) 0.19 (95% confidence interval 0.10–0.34)]. NS was marginally associated with better outcome compared with non-NS [adjusted HR 0.50 (95% confidence interval 0.25–1.01)]. Conclusions FSGS variants alone might not have significant impacts on the renal outcome after 5 years, while PR could be predictive of improved renal prognosis for any variant. Specific strategies and interventions to achieve PR for each variant should be implemented for better renal outcomes.

В статье приведены данные 10-летних наблюдений авторов по использованию ритуксимаба при хронической болезни почек, вызванной гломерулонефритом, системной красной волчанкой или васкулитом. 27 взрослых пациентов (34 ± 6 лет, 10 (37 %) мужчин, 17 (63 %) женщин; продолжительность почечного заболевания составила 3,2 ± 0,3 года), 2 — с трансплантированной почкой и 6 детей получали ритуксимаб в дозе 1 г дважды с перерывом 2 недели и потом через полгода. Средняя доза ритуксимаба составила 2,4 г на курс лечения на одного больного. 86 % (23) больных была проведена нефробиопсия, 17 % (4) — дважды, 4 % (1) — трижды, CD20-позитивные клетки в нефробиоптате определяли 17 пациентам (74 %). Перед вторым введением ритуксимаба (через 6 месяцев после первого введения) проводилось исследование CD20 в сыворотке крови, при наличии любого количества клеток или сохранении активного процесса доза ритуксимаба составляла повторно по 1 г дважды. У 3 пациентов (11 %) при введении препарата на 2,00 ± 0,25 часа была аллергическая реакция на ритуксимаб. Для контроля артериального давления у гипертензивных пациентов дополнительно назначали торасемид и моксонидин после введения метилпреднизолона. Сопроводительная терапия включала назначение ингибиторов ренин-ангиотензин-альдостероновой системы и мочегонные. Для оценки эффективности терапии ритуксимабом использовали 2 показателя: уровень протеинурии (до начала лечения составил 3,7 ± 1,0 г/сут) и расчетную скорость клубочковой фильтрации (EPI) (до начала лечения — 55,50 ± 3,33 мл/мин). Общая эффективность лечения ритуксимабом в достижении ремиссии составила 74 % среди нефрологических пациентов, однако существенно отличалась при разных нозологических формах: самая высокая наблюдалась при люпус-нефрите (до 80 %), у половины пациентов с фокально-сегментарным гломерулосклерозом и мембранозной нефропатией, и абсолютно неэффективным лечение было при гранулематозе с полиангиитом при синдроме Гудпасчера. Прогностическая значимость выявления CD20 в нефробиоптате для обоснования назначения ритуксимаба требует дальнейших исследований, однако большое количество CD20 является прогностически неблагоприятным фактором. Определение CD20 в крови может быть дополнительным инструментом для обоснования сроков второго/третьего введения ритуксимаба.

AIM to perform a comparative analysis of the results of morphofunctional and morphoanatomical studies for the clinical assessment of the viability of the renal parenchyma. MATERIALS AND METHODS Based on a random sampling method, the results of whole-body PET/CT scan with 18F-FDG glucose in 134 patients with various non-urological disorders were analyzed. However, 13.3% of the participants had concomitant chronic kidney diseases without exacerbation. At the same time, the morphological and anatomical manifestations of chronic kidney disease were studied in 32 patients of the same age and sex in order to evaluate the severity of structural changes in nephron. RESULTS It was found that among individuals undergone to whole-body PET/CT scan with 18F-FDG glucose for various diseases without a urological history and patients with chronic kidney disease, the parenchyma tropism to energy-intensive labeled glucose molecules had certain differences that correlated with morphoanatomical manifestations of structural changes in the nephron in chronic kidney disease. CONCLUSIONS The modern morphofunctional PET/CT study of the whole-body viability with 18F-FDG glucose, including the kidneys, is an advanced diagnostic tool that may supplement the results of morphoanatomical studies and monitor the efficiency of treatment.

Introduction: Clinical indicators or pathological features alone cannot reliably predict renal survival in patients with biopsy-confirmed diabetic nephropathy (DN). Therefore, this analysis sought to develop and validate a predictive model incorporating both clinical and pathological markers to predict renal outcomes in patients with biopsy-confirmed DN. Methods: A predictive nomogram was developed based upon data pertaining to 194 patients with biopsy-confirmed DN. The prognostic relevance of individual clinicopathological variables was assessed through univariate and multivariate Cox regression analyses. A prognostic nomogram was then developed and validated based upon concordance (C)-index values and calibration curves. Internal validation was conducted through bootstrap resampling, while the clinical utility of this model was assessed via a decision curve analysis (DCA) approach. Results: Nephrotic-range 24-h proteinuria, late-stage CKD, glomerular classification III–IV, and IFTA score 2–3 were all identified as independent predictors of poor renal outcomes in DN patients and were incorporated into our final nomogram. Calibration curves revealed good agreement between predicted and actual 3- and 5-year renal survival in DN patients with the C-index value for this nomogram at 0.845 (95% CI: 0.826–0.864). DCA revealed that our nomogram was superior to models based solely upon clinical indicators. Conclusion: A predictive nomogram incorporating clinical and pathological indicators was developed and validated for the prediction of renal survival outcomes in patients with biopsy-confirmed DN. This model will be of value to clinicians, as it can serve as an easy-to-use and reliable tool for physicians to guide patient management based on individualized risk.

Lithium is one of the first-line agents for treating bipolar disorder. Although this agent is highly effective in treating mood disorders, renal toxicity is a frequent side effect. Lithium metabolism is affected by sodium-lithium counter-transporter (SLC-T) in erythrocytes. The high activity of SLC-T can result in decreased urinary lithium clearance and may lead to accumulation of lithium in the distal renal tubular cells, causing lithium toxicity. SLC-T is a genetic marker in primary hypertension (HTN), HTN in pregnancy, diabetic nephropathy, and IgA nephropathy (IgA-N) with HTN. Patients with IgA-N have been reported to have enhanced SLC-T activity and are likely to have considerably lower renal fractional clearance of lithium. Therefore, patients taking lithium for bipolar disorder with coexisting IgA-N can have severe lithium-induced nephropathy and nephrotoxicity even at therapeutic serum levels. Serum lithium levels reflect only extracellular lithium concentration. However, lithium exerts its effects once it has moved to the intracellular compartment. This phenomenon illustrates the reason why patients with significantly elevated serum levels might be asymptomatic. Creatinine clearance is inversely related to the duration of lithium therapy. The degree of interstitial fibrosis on renal biopsy has been known to be associated with the duration of lithium therapy and cumulative dose. We present a case with a past medical history of bipolar disorder treated with lithium for almost 20 years. His family history was significant for HTN. The patient was diagnosed with renal insufficiency of unknown causes, for which he underwent renal biopsy. The renal biopsy showed a typical lithium-induced tubulointerstitial nephritis and a coincidental finding of IgA-N. We suspect a high activity of SLC-T seen in IgA-N, and the adverse effects of lithium on SLC-T activity might cause reduction of urinary lithium clearance and accumulation of lithium in distal renal tubular cells, contributing to nephrotoxicity. There is a lack of the literature on the coexistence of IgA-N and lithium nephrotoxicity. We recommend in patients with concomitant IgA-N, taking lithium, more frequent monitoring of renal functions, and dose adjustments may reduce the risk of lithium-induced nephrotoxicity.

The main objective of this study is to analyze the clinical and pathological features and prognosis of patients with Hepatitis B associated membranous nephropathy (HBV-MN) and idiopathic membranous nephropathy (IMN) complicated with hepatitis B virus (HBV) infection. This study will provide more basis for diagnosis and prognosis evaluation. A total of 50 patients with HBV-MN were included in this study. 56 IMN patients complicated with HBV infection diagnosed during the same period formed the control group. Parameters including blood routine, urine routine and plasma levels of albumin (ALB), serum creatinine (SCR), blood urea nitrogen (BUN), urea acid (UA), total cholesterol (T-CHO), triglycerides (TG), complement C3 and C4, glutamic pyruvic transaminase (ALT), glutamic pyruvic transaminase (AST), 24-h urinary protein quantification (24 h-TP), renal phospholipase A2 receptor (PLA2R) and HBV related markers during the hospitalization and outpatient follow-up study period were collected for all the patients. The proportion of male patients was high in both groups. The average age of the HBV-MN group was 37.2 ± 14.187 years old, it was younger compared with the IMN group (P = 0.003). Nephrotic syndrome was the major clinical manifestation among patients. There was no significant difference between the two groups in the levels of anemia, microscopic hematuria, renal dysfunction, liver dysfunction, liver cirrhosis. The level of serum C3 and C4 in the HBV-MN group was lower compared with the IMN group (P = 0.002, P = 0.014). In the HBV-MN group, serum HBV markers were negative in 6 (12%) patients, 4 patients (8%) were positive for PLA2R in serum, and 5 patients (10%) were positive for PLA2R in renal tissue. Stronger IgG1 and C1q and weaker IgG4 staining were found in HBV-MN group renal tissues (P = 0.003, P = 0.025, and P = 0.001, respectively). There were no statistical differences compared with serum and renal PLA2R between HBV-MN and IMN groups (P = 0.098, P = 0.109). During the 1-year follow-up, there was no significant difference in complete remission rate between the two groups (P = 0.7739). Renal biopsy is crucial to diagnose HBV-MN. IgG subtypes in the HBV-MN group were mainly IgG1 deposition, while those in IMN complicated with HBV infection group were mainly IgG4 deposition. When HBV-associated antigen and PLA2R are present in renal tissue, lower level of serum C3 and C4, high intensity of renal C1q and IgG1 is more supportive of HBV-MN. The positive of PLA2R in serum and renal tissue in differentiating HBV from IMN complicated with HBV infection remains to be discussed.