Search

Copyright of Namık Kemal Tıp Dergisi is the property of Galenos Yayinevi Tic. LTD. STI and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Introduction: People with Tuberculosis (TB) infection may present with glomerulonephritis (GN). The range of presentations, renal pathologies, and clinical outcomes are uncertain. Whether clinical features that establish if GN etiology is medication or TB related, and possible benefits of immunosuppression remain uncertain. Methods: A scoping review was completed, searching MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Web of Science and Conference Abstracts from Inception to December, 2023. The study population included patients with TB infection who developed GN and underwent renal biopsy. All data regarding presentation, patient characteristics, renal pathology, management of TB and GN, and outcomes were summarized. Results: There were 62 studies identified, with 130 patients. These cases included a spectrum of presentations including acute kidney injury, nephrotic syndrome and hypertension, and a range of 10 different renal pathology diagnoses. Cases that included immunosuppression and outcomes ranged from complete remission to long-term dialysis dependence. The presence of granulomas (4/4, 100%), anti-glomerular basement membrane disease (3/3, 100%), amyloidosis (75/76, 98.7%), and focal segmental glomerulosclerosis (2/2, 100%) were specific for GN being TB-infection related. On the other hand, minimal change disease was specific for anti-TB therapy related (7/7, 100%). While patients with more aggressive forms of GN commonly were prescribed immunosuppression, this study was unable to confirm efficacy. Only rifampin or isoniazid were implicated in drug-associated GN. Discussion: This study provides a clear rationale for renal biopsy in patients with TB and GN, and outlines predictors for the GN etiology. Thus, this study establishes key criteria to optimize diagnosis and management of patients with TB and GN. [ABSTRACT FROM AUTHOR]

IgA nephropathy (IgAN) is considered the most common primary glomerulonephritis worldwide with a predilection for Asian-Pacific populations and relative rarity in those of African descent. Perhaps 20%-50% of patients progress to kidney failure. The pathogenesis is incompletely understood. Mesangial deposition of immune complexes containing galactose-deficient IgA1 complexed with anti-glycan IgG or IgA antibodies results in mesangial cell activation and proliferation, inflammatory cell recruitment, complement activation, and podocyte damage. Diagnosis requires a biopsy interpreted by the Oxford criteria. Additional pathologic features include podocytopathy, thrombotic microangiopathy, and C4d staining. Biomarkers predicting adverse outcomes include proteinuria, reduced GFR, hypertension, and pathology. Acceptable surrogate endpoints for therapeutic trials include ongoing proteinuria and rate of eGFR decline. The significance of persisting hematuria remains uncertain. The mainstay of therapy is supportive, consisting of lifestyle modifications, renin-angiotensin inhibition (if hypertensive or proteinuric), sodium-glucose-transporter 2 inhibition (if GFR reduced or proteinuric), and endothelin-receptor antagonism (if proteinuric). Immunosuppression should be considered for those at high risk after maximal supportive care. Corticosteroids are controversial with the most positive results observed in Chinese. They carry a high risk of serious side effects. Similarly, mycophenolate may be most effective in Chinese. Other immunosuppressants are of uncertain benefit. Tonsillectomy appears efficacious in Japanese. Active areas of investigation include B-cell inhibition with agents targeting the survival factors BAFF and APRIL and complement inhibition with agents targeting the alternate pathway (Factors B and D), the lectin pathway (MASP-2), and the common pathway (C3 and C5). Hopefully soon, the who and the how of immunosuppression will be clarified, and kidney failure can be forestalled. [ABSTRACT FROM AUTHOR]

Immunoglobulin A (IgA) vasculitis, or Henoch‐Schonlein purpura, is the most common systemic vasculitis in children, clinically presenting as palpable purpura in combination with arthritis, gastrointestinal involvement, or kidney injury. Subcutaneous edema is reported in patients with IgA vasculitis, and it commonly affects the lower extremities, especially around joints. Here, we report a case of IgA vasculitis with a rare presentation of edema isolated to the periorbital area in a 7‐year‐old boy, who subsequently developed crescentic glomerulonephritis with nephrotic range proteinuria. Isolated periorbital edema is an uncommon cutaneous feature of IgA vasculitis. [ABSTRACT FROM AUTHOR]

Posttransplant malignancies are an important complication of solid organ transplantation. Kidney transplant recipients are at particularly high risk of cancer development. The most relevant risk factors of carcinogenesis are the use of immunosuppressive agents and oncogenic viral infections. Additionally, immune dysregulation caused by these factors may predispose to various types of organ damage. Paraneoplastic glomerular diseases are one of the most interesting and understudied cancer manifestations. The appropriate diagnosis of paraneoplastic glomerular damage can be challenging in kidney transplant recipients, due to factors inherent to concomitant medication and common comorbidities. Recent advances in the field of molecular and clinical nephrology led to a significant improvement in our understanding of glomerular diseases and their more targeted treatment. On the other hand, introduction of novel anticancer drugs tremendously increased patients' survival, at the cost of kidney-related side effects. Our review aims to provide insights into diagnosis and treatment of paraneoplastic glomerular diseases, with a special attention to kidney transplant recipients. [ABSTRACT FROM AUTHOR]

This article discusses the relationship between Tlr5 deficiency and lupus-like disease in mice. The study found that Tlr5 deficiency actually worsened lupus symptoms in female mice, leading to increased proteinuria and glomerulonephritis. The study suggests that Tlr5 deficiency may modulate host-microbiota interactions to exacerbate lupus. Additionally, the article provides a list of references to various scientific articles related to the gut microbiota and its potential role in autoimmune diseases, specifically lupus. [Extracted from the article]

Introduction: Anti-GBM diseases with IgA deposition in the mesangial region are rarely described. The factors influencing renal prognosis in patients with anti-GBM disease combined with mesangial IgA deposition are unknown. Methods: We searched the pathological reports of the First Affiliated Hospital of Zhengzhou University from 2015 to 2023 and found that a total of 72 patients with the anti-GBM disease and 25 patients combined with mesangial IgA deposition. We studied the clinical and pathological features, renal prognosis, and the factors affecting renal prognosis in patients with anti-GBM disease combined with mesangial IgA deposition. Results: Their median age was 44 years, and their age distribution was unimodal. The proportion of oliguria or anuria in patients with anti-GBM disease combined with mesangial IgA depositionwas significantly lower than that in patients with classic anti-GBMdisease (13.04 vs. 42.31%, p=0.030). Their 24-hour urinary protein excretion was significantly higher [median:3.25 vs. 1.12g/24h, Interquartile range(IQR):1.032~3.945 vs. 0.63~1.79g/24h, p=0.020], serum creatinine (SCr) level at the initial diagnosis was lower(median:456.0 vs. 825.5mmol/L, IQR:270.0~702.0 vs. 515.8~1231.2mmol/L, p=0.002), peak SCr level was lower (median: 601.0 vs. 907.2mmol/L, IQR: 376.5~937.0 vs. 607.0~1361.2mmol/L, p=0.007), and their serum complement 3(C3) level was higher(median: 1.275 vs. 1.015g/L, IQR:1.097~1.462 vs. 0.850~1.220g/L, p=0.027). They had better renal outcomes during follow-up (p<0.001). After adjustment for hypertension, oliguria or anuria, and crescents%, IgA deposition in themesangial region was still an independent protective factor (p=0.003) for ESRD in anti-GBM patients. Hypertension (p=0.026) and SCr levels at initial diagnosis (p=0.004) were risk factors for renal prognosis in patients with anti-GBM disease combined with mesangial IgA deposition. Discussion: Patients with anti-GBM disease combined with mesangial IgA deposition have less severe renal impairment and better renal prognosis than patients with classic anti-GBM disease. [ABSTRACT FROM AUTHOR]

Adipocytokines are substances with endocrine functions produced by adipose tissue, playing crucial roles in regulating metabolic functions and inflammatory processes. Dysregulation of fatty tissue's endocrine functions and dysregulation of the production of adipocytokines such as adiponectin, leptin, fibroblast-stimulating factor, and others can lead to a low-grade systemic inflammation and an insulin resistance in patients. These conditions contribute to the pathophysiology of type 2 diabetes mellitus, atherosclerosis, arterial hypertension, metabolic syndrome, and other disorders. Conversely, these metabolic disorders exert feedback-regulatory effects on adipocytokines and their functions. Glomerulonephritis encompasses a group of immune-mediated diseases characterized by inflammation of the glomeruli. Diagnosis can involve examining urine sediment, detecting autoantibodies, and identifying immune complexes in the blood. However, a kidney biopsy is required for definitive confirmation of glomerulonephritis and is considered the gold standard and a necessity in diagnosis. Affecting the level of adipocytokines could be one of the new strategies for the pharmacological treatment of many diseases. Given a better understanding of their functions and molecular targets, adipocytokines may herald the emergence of new diagnostic approaches (1, 2). Monitoring the level of adipocytokines could contribute to a better patient management and thus become an auxiliary tool for predicting and diagnosing diseases. [ABSTRACT FROM AUTHOR]

Background The importance of albuminuria as opposed to proteinuria in predicting kidney outcomes in primary immunoglobulin A nephropathy (IgAN) is not well established. Methods From 2010 to 2012, 421 patients with biopsy-proven IgAN have been enrolled into the German Chronic Kidney Disease (GCKD) cohort, a prospective observational cohort study (N  = 5217). Adjudicated endpoints include a composite kidney endpoint (CKE) consisting of eGFR decline >40%, eGFR <15 ml/min/1.73 m2 and initiation of kidney replacement therapy; the individual components of the CKE; and combined major adverse cardiac events (MACE), including non-fatal myocardial infarction, non-fatal stroke and all-cause mortality. The associations between the incidence of CKE and baseline factors, including demographics, laboratory values and comorbidities were analysed using the Cox proportional hazards regression model. Results The mean age of IgAN patients at baseline was 51.6 years (± 13.6) and 67% were male. The patient-reported duration of disease at baseline was 5.9 ± 8.1 years. Baseline median urine albumin:creatinine ratio (UACR) was 0.4 g/g [interquartile range (IQR) 0.1–0.8] and mean eGFR was 52.5 ± 22.4 ml/min/1.73 m2. Over a follow-up of 6.5 years, 64 (15.2%) patients experienced a >40% eGFR decline, 3 (0.7%) reached eGFR <15 ml/min/1.73 m2, 53 (12.6%) initiated kidney replacement therapy and 28% of the patients experienced the CKE. Albuminuria, with reference to <0.1 g/g, was most associated with CKE. Hazard ratios (HRs) at UACRs of 0.1–0.6 g/g, 0.6–1.4 g/g, 1.4–2.2 g/g and >2.2 g/g were 2.03 [95% confidence interval (CI) 1.02–4.05], 3.8 (95% CI 1.92–7.5), 5.64 (95% CI 2.58–12.33) and 5.02 (95% CI 2.29–11-03), respectively. Regarding MACE, the presence of diabetes [HR 2.53 (95% CI 1.11–5.78)] was the most strongly associated factor, whereas UACR and eGFR did not show significant associations. Conclusion In the GCKD IgAN subcohort, more than every fourth patient experienced a CKE event within 6.5 years. Our findings support the use of albuminuria as a surrogate to assess the risk of poor kidney outcomes. [ABSTRACT FROM AUTHOR]

Background The anti-neutrophil cytoplasmic antibody (ANCA) renal risk score (ARRS) for predicting renal survival in ANCA-associated vasculitis (AAV) had not previously been validated in adults over 65 years of age and presenting impairments associated with an aging kidney, a high cardiovascular comorbidity burden and prevalent microscopic polyangiitis. Methods We retrospectively studied a cohort of 192 patients over 65 years of age [median (interquartile range) age: 73 (68–78) years], including 17.2% with renal-limited vasculitis, 49.5% with microscopic polyangiitis and 33.3% with granulomatosis with polyangiitis, at six centres in northern France. The primary study endpoint was the cumulative incidence of end-stage kidney disease (ESKD, maintenance of dialysis for at least 3 months) at 12 months, with death considered as a competing event. Results The median serum creatinine concentration at diagnosis was 300 (202–502) µmol/L, and 48 (25.0%) patients required dialysis at presentation. The ARRS was high in 43 (22.4%) patients, medium in 106 (55.2%) and low in 43 (22.4%). The cumulative incidence of ESKD at 12 months was 0% in the low-risk group, 13.0% (interquartile range 7.6–20.0) in the medium-risk group and 44.0% (29.0–58.0) in the high-risk group (P <.001). In the subgroup of 149 patients presenting a medium or high score, the ARRS had a C-index of 0.66 (0.58–0.74) for the prediction of ESKD at 12 months; this rose to 0.86 (0.80–0.90) when dialysis status at diagnosis was included. Conclusion The ARRS was a poor predictor of kidney survival at 12 months among patients over 65 years of age with renal AAV involvement—especially in the high ARRS group. The addition of dialysis status at diagnosis as an additional clinical parameter might improve the predictive performance of the ARRS. [ABSTRACT FROM AUTHOR]

Background: Pauci-immune necrotizing glomerulonephritis (PING) is commonly associated with the presence of antineutrophilic cytoplasmic antibodies (ANCAs) but a significant number of patients do not have these antibodies. The significance of ANCA-negativity in the context of Berden's classification of PING is not known. Methods: A retrospective analysis was conducted on all patients with histopathological diagnosis of idiopathic PING irrespective of ANCA status diagnosed between January 1998 to December 2018 and followed up at renal clinic for > 12 months. All biopsies were reclassified by Berden's classification. Clinicopathological characteristics and renal outcomes of ANCA-positive and ANCA-negative patients were compared. Results: Out of 134 patients, 66 (49.5%) were ANCA-negative. The mean age was 34.76 ± 13.3 years. Compared with the ANCA-positive patients, ANCA-negative patients had significantly greater prevalence of nephrotic-range proteinuria (74.23% Vs 57.9%, P = 0.036) with less extra-renal manifestations (P < 0.05)). On histology, focal and crescentic classes dominated with less number of globally sclerosed glomeruli (2.7% Vs 5.07%, P = 0.02) and more mesangial proliferation (22.7% Vs 4.41%, P = 0.002) in the ANCA-negative group, whereas sclerotic was predominant in the ANCA-positive group (P = 0.05). More patients achieved complete and partial recovery in ANCA-negative patients (42.4% Vs 20.5%, P < 0.05) with better renal survival (27.27% Vs 16.17%, log-rank test: P = 0.03) and less patient mortality (13.63% vs 30.8%, log-rank test: P = 0.04) at 2 years. Conclusion: Our study confirms high prevalence of ANCA negativity among our cohort and this group presents with isolated renal involvement with better renal and patient survival. The ANCA-positive group showed significantly more patients in the sclerotic class, lower 2-year renal survival, and higher 2-year mortality as compared to the ANCA-negative group. However, the complete and partial responses to treatment were significantly better in the ANCA-negative group. Key Points •This study shows a high prevalence of ANCA negativity in cases of PING in Pakistani population, as almost half of patients in this study did not have these antibodies. •This negativity is more prevalent in the Asian populations but its significance in the context of Berden's classification of PING is unknown. •ANCA-negative group exhibited less severe phenotype and better outcomes compared with ANCA-positive group. [ABSTRACT FROM AUTHOR]

Background: Extrahepatic manifestations in patients with primary biliary cholangitis (PBC) are frequently observed recently. We aimed in this study to explore the clinicopathological characteristics and prognosis of glomerulonephritis in patients with PBC. Methods: Consecutive PBC patients admitted to Peking Union Medical College Hospital from January 2002 to May 2019 were retrospectively enrolled. PBC patients with other autoimmune diseases which may have nephritis were excluded. Structured interview, systemic rheumatologic examination, and laboratory tests were conducted for each patient. Literature about patients with PBC and glomerulonephritis was reviewed and summarized. Results: Among the 330 PBC patients enrolled, glomerulonephritis were identified in 10 patients (3.0%). Eight (80.0%) were females and 2 (20.0%) were males. The mean age was 58.4 ± 9.5 years old. Membranous nephropathy (MN) was revealed in 4 patients, IgA nephropathy (IgA N) in 2 patients, minimal change disease (MCD) in 2 patients, mesangial proliferative glomerulonephritis in 1 patient, and renal amyloidosis in 1 patient. Compared to the literature reviewed, 10 cases of MN, 1 case of MCD, 1 case of IgA N, and 1 case of acute poststreptococcal glomerulonephritis (APSGN) were observed. Conclusions: Glomerulonephritis may not be a well-recognized feature of PBC and is not a rare complication and deserved to be routinely screened in clinical practice. As MN is the most common form of glomerulonephritis in PBC patients and PBC can be asymptomatic at an early stage, patients presented with MN should be screened for PBC, so to avoid cirrhosis. Key Points • Patients with primary biliary cholangitis (PBC) can be complicated with glomerulonephritis, and membranous nephropathy (MN) is the most common form. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Antinuclear antibody‐negative full‐house lupus nephritis though previously reported, is fairly uncommon. Some patients go on to develop antibodies later in the disease course. The presence of RO‐52 antibody in this case suggests an underlying immunological cause. Swift management based on strong clinical suspicion can be life‐saving to the patient. Lupus nephritis (LN) is a serious complication of systemic lupus erythematosus (SLE) and is more likely to progress to end‐stage renal disease (ESRD). With the recent EULAR/ACR criteria mandating antinuclear antibody (ANA) positivity as an entry criterion, clinicians are faced with a diagnostic dilemma in diagnosing cases of seronegative SLE. We present the case of a 25‐year‐old female who presented with photosensitive malar rash, hair loss, oral ulcers, menorrhagia, and kidney dysfunction, suggestive of SLE. Her ANA tests were negative, raising doubts about the diagnosis. Biopsy was delayed owing to anemia and thrombocytopenia, and clinical judgment led to the patient being diagnosed with LN, with prompt treatment resulting in significant improvement. Renal biopsy subsequently confirmed the case as diffuse class IV LN with full‐house nephropathy. This case highlights the limitations of relying solely on ANA positivity in diagnosing LN and underscores the need for a comprehensive diagnostic approach for SLE that incorporates clinical features, immunological markers, and patient demographics. ANA‐negative SLE patients demand heightened clinical suspicion, especially when other diagnostic parameters align with the disease. Swift intervention with immunosuppressive therapy, as seen in this case, can be life‐saving. [ABSTRACT FROM AUTHOR]

Renal involvement in inflammatory bowel disease is rather uncommon. This study aims to describe the spectrum of renal involvement in pediatric patients with IBD and reduce delay in detection and management. This is a retrospective study of the renal function of all patients, aged <18 years, who have been followed for IBD in our pediatric gastroenterology department from January 2019 till January 2023. From the 75 IBD patients included in this study 16 % had renal manifestations. The urinalysis revealed proteinuria in 7 patients, proteinuria and hematuria in 3 and proteinuria and glycosuria in 2 patients. All 12 patients with abnormal urinalysis underwent further investigation in order to determine the cause of renal damage and the results are as follows: 2 patients had glomerulonephritis and in other 2 patients renal damage was due to medication adverse effect, 1 had pyelonephritis in combination with chronic active tubulointerstitial nephritis and another 1 had thin basement membrane disease. Three patients had IBD-related dependent renal involvement and 1 resulted in chronic renal failure due to amyloidosis. It is important for all clinicians to be aware of the possibility of renal manifestations in IBD patients for the early diagnosis and prevention of these manifestations and complications. [ABSTRACT FROM AUTHOR]

Scabies is a parasitic infestation of the skin with high prevalence in crowded spaces. In some instances, scabies becomes the underlying factor for complicated skin-borne opportunistic pathogens infections in both children and adults. Geographic area and socio-economic factors are determinants of the endemic pattern of this disease. Currently, the treatment of scabies has been under special attention. A combination of oral therapy with Ivermectin and sulfur-based ointments are the gold standard. However, caution is required in patients with kidney impairment. The renal involvement in children with scabies is mainly caused by acute glomerulonephritis. The severity of the nephritic syndrome can lead to other complications. Also, Ivermectin possesses a nephrotoxic effect. Severe hypertension can lead to neurological complications. The aim of our case report is to present two unusual complications in brothers with scabies. We report the cases of two brothers with scabies who presented with severe skin infection that developed acute post infectious glomerulonephritis (APIGN). In addition, one of the brothers presented with posterior reversible encephalopathy syndrome (PRES). The other one developed acute tubule-interstitial acute kidney injury following Ivermectin administration. The evolution of skin lesions was favorable, and kidney function returned to normal in both brothers. [ABSTRACT FROM AUTHOR]

Canine leishmaniasis (CanL) caused by Leishmania infantum commonly progresses with renal and ophthalmic lesions associated with active systemic disease. As chronic inflammation related to immune complex deposits is a pathophysiological factor in the development of both glomerulonephritis and uveitis, we aimed to evaluate renal and ocular histopathological lesions and analyze whether they were related to each other and the clinical degree of the disease. For that, we evaluated 15 dogs from CanL-endemic areas. L. infantum PCR-positive dogs were studied according to disease severity into two different groups: Group-1 (G1) had data from seven dogs with mild to moderate CanL and no history of treatment, and G2 was formed with eight dogs with severe to terminal disease that had not responded to CanL treatment. Histopathological analysis of kidneys showed higher frequencies and intensities of glomerular basement membrane thickening (p = 0.026), deposits in glomeruli (p = 0.016), epithelial necrosis (p = 0.020), tubular dilatation (p = 0.003) and interstitial fibrosis (p = 0.04) in G2 dogs than in G1 dogs. Surprisingly, the histopathology of eye bulbs showed a higher frequency and intensity of retinitis (p = 0.019) in G1 dogs than in G2 dogs. The comparative analysis showed that there was no correspondence between histopathological findings in kidneys versus eyes in milder or more severe CanL. Our findings suggested that (1) clinically undetectable eye alterations can be more precocious than those in kidneys in the development of CanL, and (2) the lower frequency of eye lesions and higher frequency of renal lesions in dogs with terminal disease even after treatment indicate that therapy may have been effective in reducing CanL-associated ophthalmic disease but not proportionally in reducing kidney disease. [ABSTRACT FROM AUTHOR]

Aim: Post-infectious glomerulonephritis (PIGN) is an acute glomerulonephritis, often develops after infections with nephritogenic strains of group A beta hemolytic streptococcus. Patients may present with mild findings such as asymptomatic microscopic hematuria and non-nephrotic proteinuria or they may present with severe findings such as macroscopic hematuria, nephrotic range proteinuria, edema, hypertension, and acute kidney injury. In this paper, we aimed to present the laboratory and clinical findings of patients who applied to pediatric nephrology clinic in a short period of six months and were followed up with the diagnosis of PIGN. Materials and Methods: The medical records of 30 patients who were followed up in Adana City Training and Research Hospital with the diagnosis of PIGN in a six-month period (between October 2022 and March 2023) were evaluated retrospectively. The clinical, laboratory and treatment data of the patients were recorded. Results: Acute nephritic syndrome was the most common clinical presentation with 22 patients (73.3%) followed up with PIGN. Four (13.3%) of the patients presented with nephrotic syndrome, two (6.7%) with rapidly progressive glomerulonephritis, and two (%6.7) with hypertensive encephalopathy. Kidney biopsy was performed in 3 patients, two of whom presented with rapidly progressive glomerulonephritis and one whose complement 3 level remained low beyond 8 weeks. The pathological diagnosis of these patients was reported as diffuse proliferative glomerulonephritis. Conclusion: Although PIGN usually occurs as a benign nephritis, it should be kept in mind that patients whose diagnosis is delayed and not treated appropriately may present with poor clinical

Abstract Introduction People with Tuberculosis (TB) infection may present with glomerulonephritis (GN). The range of presentations, renal pathologies, and clinical outcomes are uncertain. Whether clinical features that establish if GN etiology is medication or TB related, and possible benefits of immunosuppression remain uncertain. Methods A scoping review was completed, searching MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Web of Science and Conference Abstracts from Inception to December, 2023. The study population included patients with TB infection who developed GN and underwent renal biopsy. All data regarding presentation, patient characteristics, renal pathology, management of TB and GN, and outcomes were summarized. Results There were 62 studies identified, with 130 patients. These cases included a spectrum of presentations including acute kidney injury, nephrotic syndrome and hypertension, and a range of 10 different renal pathology diagnoses. Cases that included immunosuppression and outcomes ranged from complete remission to long-term dialysis dependence. The presence of granulomas (4/4, 100%), anti-glomerular basement membrane disease (3/3, 100%), amyloidosis (75/76, 98.7%), and focal segmental glomerulosclerosis (2/2, 100%) were specific for GN being TB-infection related. On the other hand, minimal change disease was specific for anti-TB therapy related (7/7, 100%). While patients with more aggressive forms of GN commonly were prescribed immunosuppression, this study was unable to confirm efficacy. Only rifampin or isoniazid were implicated in drug-associated GN. Discussion This study provides a clear rationale for renal biopsy in patients with TB and GN, and outlines predictors for the GN etiology. Thus, this study establishes key criteria to optimize diagnosis and management of patients with TB and GN.

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.

Left ventricular thrombus (LVT) is a severe consequence that typically follows acute myocardial infarction (MI) and can occur in nonischemic cardiomyopathies. In patients who have experienced an ST-segment elevation acute myocardial infarction (STEMI), LVT is seen up to 15% of the time; for patients without an ischemic cardiomyopathy, it is only 2% to 36% of the time. According to Virchow's triad, the cornerstone of LVT formation includes endothelial injury, blood stasis, and hypercoagulability. However, LVT increases morbidity and mortality in patients with both ischemic and nonischemic cardiomyopathies by increasing the risk of stroke or systemic embolism. Studies on nonischemic etiology are limited, and the majority of LVT case series concentrate on ischemic cardiomyopathies. We present this case with the nonischemic cardiomyopathies caused by LVT. Specifically, the patient underwent coronary artery assessment using photon-counting computed tomography, which is among the most advanced systems worldwide.

In China, most of the patients who underwent kidney transplants have unknown causes of end-stage renal disease (uESRD). However, little is known regarding the incidence of graft glomerulonephritis (GN) and graft survival in kidney transplant recipients (KTRs) with uESRD. In this retrospective cohort study, 473 of the 565 KTRs who underwent kidney transplantation (KTx) from 2015 to 2020 were included. We mainly observed the occurrence of graft GN between uESRD group and definitively diagnosed GN group, and repeatedly compared after propensity score matching (PSM). The median follow-up was 50 months in 473 KTRs, and about 75% of KTRs of native kidney disease of unknown etiology. The total cumulative incidence of graft GN was 17%, and no difference was observed between the definitively diagnosed GN group and the uESRD group (p = 0.76). Further, PSM analysis also showed no difference in the incidence of graft GN between the 2 groups. Multivariable analysis disclosed males (p = 0.001), younger age (p = 0.03), and anti-endothelial cell anti-body (AECA) positive pre-KTx (p = 0.001) were independent risk factors for graft GN. The incidence of graft GN was similar between uESRD and definitively diagnosed GN group. The allograft survival was also similar between two groups. [ABSTRACT FROM AUTHOR]

Lupus, a systemic autoimmune disease shaped by gene-environment interplay, often progresses to endstage renal failure. While subchronic systemic exposure to bacterial lipopolysaccharide (LPS) triggers autoimmunity and glomerulonephritis in lupus-prone mice, it is unknown if inhaling LPS, which is common in certain occupations, can similarly trigger lupus. Here we determined how subchronic intranasal (IN) LPS instillation influences autoimmunity and glomerulonephritis development in lupusprone NZBWF1 female mice. Briefly, mice were IN-instilled with vehicle or E. coli lPs (0.8 μg/g) twice weekly for 5 wk, followed by necropsy. For systemic comparison, additional cohorts of mice were injected with LPS intraperitoneally (IP) using identical doses/timing. lungs were assessed for inflammatory and autoimmune responses and then related to systemic autoimmunity and glomerulonephritis. IN/LPS exposure induced in the lung: i) leukocyte infiltration, ii)mRNa signatures for cytokines, chemokines, IFN-regulated, and cell death-related genes, iii) ectopic lymphoid tissue formation, and IV)diverse IgM and IgG autoantibodies (AAbs). Pulmonary effects coincided with enlarged spleens, elevated plasma IgG aabs, and inflamed igG-containing kidney glomeruli. in contrast, IP/LPS treatment induced systemic autoimmunity and glomerulonephritis without pulmonary manifestations. Taken together, these preclinical findings suggest the lung could serve as a critical nexus for triggering autoimmunity by respirable LPS in genetically predisposed individuals. [ABSTRACT FROM AUTHOR]

Context: Membranous glomerulonephritis (MGN) is a leading cause of nephrotic syndrome in adults. Diosgenin (DG) has been reported to exert antioxidative and anti-inflammatory effects. Objective: to investigate the renoprotective activity of DG in a cationic bovine serum albumin-induced rat model of MGN. Materials and methods: Fourty male sprague-Dawley rats were randomized into four groups. the MGN model was established and treated with a DG dose (10 mg/kg) and a positive control (TPCA1, 10 mg/kg), while normal control and MGN groups received distilled water by gavage for four consecutive weeks. at the end of the experiment, 24 h urinary protein, biochemical indices, oxidation and antioxidant levels, inflammatory parameters, histopathological examination, immunohistochemistry and immunoblotting were evaluated. Results: DG significantly ameliorated kidney dysfunction by decreasing urinary protein (0.56-fold), serum creatinine (SCr) (0.78-fold), BUN (0.71-fold), TC (0.66-fold) and TG (0.73-fold) levels, and increasing ALB (1.44-fold). DG also reduced MDa (0.82-fold) and NO (0.83-fold) levels while increasing the activity of sOD (1.56-fold), cat (1.25-fold), glutathione peroxidase (GPx) (1.55-fold) and GSH (1.81-fold). Furthermore, DG reduced Keap1 (0.76-fold) expression, Nrf2 nuclear translocation (0.79-fold), and induced NQO1 (1.25-fold) and HO-1 (1.46-fold) expression. additionally, DG decreased IL-2 (0.55-fold), tNF-α (0.80-fold) and IL-6 (0.75-fold) levels, and reduced protein expression of NF-κB p65 (0.80-fold), iKKβ (0.93-fold), p-iKKβ (0.89-fold), ICAM-1 (0.88-fold), VCAM-1 (0.91-fold), McP-1 (0.88-fold) and e-selectin (0.87-fold), and also inhibited the nuclear translocation of NF-κB p65 (0.64-fold). Discussion and conclusions: the results suggest a potential therapeutic benefit of DG against MGN due to the inhibition of the NF-κB pathway, supporting the need for further clinical trials. [ABSTRACT FROM AUTHOR]

IgA nephropathy (IgAN) is a genetically complex multifactorial trait. Over the past decade, population-based genome-wide association studies (GWAS) have identified more than 30 IgAN risk loci, providing novel perspectives on both the epidemiology of the disease and its underlying molecular mechanisms. In addition, the association between IgAN and galactose-deficient IgA1 (Gd-IgA1) presented another avenue for genetic exploration due to the heritability of the elevated serum Gd-IgA1 levels. These endeavors also yielded and enabled refinement of polygenic risk scores, which may help identify specific groups of individuals at significantly increased risks, leading to stratifications of medical treatments. In this review, we aim to explore the existing evidence for genetic causation in IgAN. We summarize the state of genetic research in IgAN and how it has led to the reformulation of the new pathogenesis model and novel therapeutic targets. [ABSTRACT FROM AUTHOR]

A 14-year-old patient presents with hematuria and proteinuria. Clinical evaluation reveals a positive anti-nuclear antibody titer, positive anti-double stranded DNA antibody and hypocomplementemia. Systemic lupus erythematosus (SLE) is diagnosed based on the 2019 EULAR/ACR (European League Against Rheumatism/American College of Rheumatology) classification criteria (Aringer et al. Arthritis Rheumatol 71:1400–1412, 2019). A kidney biopsy is performed that confirms the presence of immune complex glomerulonephritis, ISN-RPS (International Society of Nephrology/Renal Pathology Society) class IV (Bajema et al. Kidney Int 93:789–796, 2018). According to the latest clinical practice guidelines (Rovin et al. Kidney Int 100:753–779, 2021; Fanouriakis et al. Ann Rheum Dis 83:15–29, 2023), there are alternatives to treating this patient with cyclophosphamide. But what if this patient also presented with oliguria and volume overload requiring intensive care and dialysis? What if this patient also presented with altered mental status and seizures, and was diagnosed with neuropsychiatric lupus? What if this patient was also diagnosed with a pulmonary hemorrhage and respiratory failure? The clinical practice guidelines do not address these scenarios that are not uncommon in patients with SLE. Moreover, in some countries worldwide, patients do not have the privilege of access to biologics or more expensive alternatives. The purpose of this review is to evaluate the contemporary options for initial treatment of nephritis in patients with SLE. [ABSTRACT FROM AUTHOR]

One of the urgent problems of medicine is to clarify the pathogenetic mechanisms of glomerulonephritis (GN) with refractory nephrotic syndrome (NS). In 30% of cases, refractory NS has a genetic nature. The role of human histocompatibility system (HLA) genes in the development of refractory NS has not been sufficiently studied. The purpose of this study was to study the association of two-locus haplotypes of HLA class II gene alleles with GN manifested by refractory NS. The typing of HLA class II genes in 136 patients with NS was performed by polymerase chain reaction (PCR), which included the identification of 13 alleles of the DRB1, 8 – DQA1, and 12 – DQB1 loci. The cohort of the examined patients was divided into two groups: a group of patients with refractory NS and a group of patients with rare relapses, with a lack of refractoriness to the therapy. Persons of Chuvash nationality were selected for the study. In the studied groups of patients, the values of the nonequilibrium coupling of alleles (D) were determined to identify characteristic two-locus haplotypes and their frequency according to the formulas of Piazza A. and coauthors. To assess the association of refractory NS with HLA haplotypes, relative risk values (RR) were calculated using the formula Woolf B. and Haldane J. The statistical significance of the association was assessed using the twosided Fisher exact method for four-field tables (PF). The highest value of RR was found in the haplotype HLA-DRB1*11(05)-DQA1*0301. Its value was 42.1 (PF = 0.005). Another statistically significant value was the RR value of the haplotype HLA-DRB1*15(02)-DQB1*0602-8, equal to 0.2 (PF = 0.004). As a result of the study, the haplotype DRB1*11(05)-DQA1*0301, associated with an increased risk of refractory NS, and the protective haplotype DRB1*15(02)-DQB1*0602-8, reducing the risk of refractory NS were found in the HLA genotype of individuals in the Chuvash population.

Abstract Rationale & objective Glomerulonephritis (GN) is a leading cause of chronic kidney disease (CKD). Major adverse cardiovascular events (MACE) are prolific in CKD. The risk of MACE in GN cohorts is multifactorial. We investigated the prognostic significance of routine cardiac biomarkers, Troponin I and N-terminal pro-BNP (NT-proBNP) in predicting MACE within 5 years of GN diagnosis. Study Design Retrospective cohort study. Setting & participants Data were obtained from TriNetX, a global federated health research network of electronic health records (EHR). Exposure or predictor Biomarker thresholds: Troponin I: 18 ng/L, NT-proBNP: 400 pg/mL. Outcomes Primary outcome: Incidence of major adverse cardiovascular events (MACE). Secondary outcome: was the risk for each individual component of the composite outcome. Analytical Approach 1:1 propensity score matching using logistic regression. Cox proportional hazard models were used to assess the association of cardiac biomarkers with the primary and secondary outcomes, reported as Hazard Ratio (HR) and 95% confidence intervals (CI). Survival analysis was performed which estimates the probability of an outcome over a 5-year follow-up from the index event. Results Following PSM, 34,974 and 18,218 patients were analysed in the Troponin I and NTproBNP cohorts, respectively. In the Troponin I all cause GN cohort, 3,222 (9%) developed composite MACE outcome HR 1.79; (95% CI, 1.70, 1.88, p

Abstract IgA Nephropathy (IgAN) is the most prevalent glomerular disease worldwide. Complement system activation is crucial in its pathogenesis. Few studies correlated serum C3 and C4 with disease activity and prognosis. This retrospective study investigated the prognostic value of serum complement at the time of diagnosis in patients with IgAN. Specifically we evaluated whether adding serum C3 and C4 levels to established predictive models-one based on variables related to chronic kidney disease (CKD) progression and another incorporating variables from the International IgA Prediction Tool (IntIgAPT)-enhances the accuracy of outcome prediction. A composite renal outcome was defined as 50% decline in eGFR or onset of kidney failure. 101 patients were stratified according to baseline C3 levels in three groups (Low, Medium and High). During a median follow-up of 54 months, the Low group exhibited higher incidence of primary outcome (16.3 events vs 2.9 and 1.7 events × 100 pts/year, p = 0.0026). Model-1 (M1), consisting of CKD progression variables, and Model-3 (M3), comprising IntIgANPT variables, were implemented with baseline C3 and C4 to create Model-2 (M2) and Model-4 (M4), respectively. M2 demonstrated better predictive performance over M1, showing higher discrimination (lower AIC and BIC, higher C-index and NR2). Similarly, M4 outperformed M3, showing enhanced outcome prediction when C3 and C4 levels were added. Implementation of serum C3 and C4 can enhance prediction accuracy of already-validated prognostic models in IgAN. Lower C3 and higher C4 levels were associated with poorer prognosis, highlighting a more 'Complement-Pathic' subset of patients.

Abstract Background IgA nephropathy (IgAN) is a common primary glomerulonephritis leading to end-stage renal disease. Living donor kidney transplantation (LDKT) is considered a favorable treatment option, but IgAN recurrence rates and the impact on outcome is unclear. In the present study, we retrospectively analyzed the rate of IgAN recurrence, risk factors and clinical outcomes in LDKT recipients. Methods We analyzed 193 adult patients who received a LDKT between 2011 and 2017 of which 32 (16.7%) had IgAN as underlying disease. Demographic data and clinical outcomes, especially regarding IgAN recurrence, were evaluated. Mean follow-up period was 102.13 months in the IgAN group vs. 97.27 months in the control group. Results Among the IgAN cohort, five (15.63%) experienced IgAN recurrence. Patients with IgAN underwent LDKT at a significantly younger age (p

Introduction: Anti-glomerular basement membrane (GBM) disease is a rare cause of glomerulonephritis usually mediated by IgG antibodies and is associated with ANCA-associated glomerulonephritis in up to 50% of cases. IgA-mediated anti-GBM disease is extremely rare and presents diagnostic difficulties as circulating IgA antibodies will not be detected by standard serological tests for anti-GBM disease. Case Presentation: We present the case of a 67-year-old man with rapidly progressive glomerulonephritis requiring haemodialysis at presentation. Serological testing was positive for anti-myeloperoxidase and negative for IgG anti-GBM antibodies. Kidney biopsy revealed necrotizing crescentic glomerulonephritis with linear staining of IgA along the GBM. He was treated with a combination of immunosuppression and plasma exchange and was able to become dialysis-independent. Conclusion: To our knowledge, this is the first documented “double-positive” IgA anti-GBM disease and ANCA-associated glomerulonephritis.

Aim: Kidney disease is common in older adults due to age-related structural and functional changes in the kidneys, higher rates of chronic disease, and increased drug use. As societies age, there is a rise in the prevalence of renal disease and the number of kidney biopsies being performed in older patients. This study aimed to investigate renal biopsy indications, complications, pathology results, and subsequent treatment among older adults in Turkey. Materials and Methods: We retrospectively analyzed data from patients aged 65 and over who underwent renal biopsy in a university nephrology department between 2004 and 2023. The patients’ demographic information, chronic comorbidities, biopsy indications, pre-biopsy laboratory values, post-biopsy complications, pathology results, and post-biopsy treatments were obtained by reviewing their medical records and biopsy reports. Results: A total of 66 patients were included in the study. The median age was 73.0 years (IQR: 68.8-79.0 years) and 66.7% of the patients were men. The most common comorbidities were hypertension (83.3%), diabetes mellitus (24.3%), coronary artery disease (22.7%), and chronic kidney disease (21.2%). The most common indication for renal biopsy was nephrotic-range proteinuria (56.1%), followed by acute kidney injury (24.2%). When the pathology results were examined, primary glomerulonephritis (62.1%) was the most common result, followed by secondary glomerulonephritis (21.2%) and tubulointerstitial nephritis (12.1%). The most common histopathological diagnoses in primary glomerulonephritis were membranous glomerulonephritis (39.4%) and focal segmental glomerulosclerosis (12.1%), while those in secondary glomerulonephritis were secondary amyloidosis (9.1%) and lupus nephritis (4.5%). After biopsy, 54.5% of the patients received immunosuppressive therapy and 34.8% received renal replacement therapy. No post-biopsy complications were observed. Conclusion: Although the most common indication for kidney biopsy in older adults is nephrotic-range proteinuria. Kidney biopsy is the gold standard method for the diagnosis of renal parenchymal diseases and is a safe procedure in older patients, with low complication rates. Kidney biopsy should not be avoided in geriatric patients if deemed clinically necessary.

Abstract Objective To investigate the expression and significance of Fractalkine (CX3CL1, FKN) in serum and renal tissue of myeloperoxidase and anti-neutrophil cytoplasmic antibody associated vasculitis (MPO-AAV) rats. Methods Thirty Wistar-Kyoto (WKY) rats were randomly divided into: Control group, MPO-AAV group (400 µg/kg MPO mixed with Freund’s complete adjuvant i.p), MPO-AAV + Anti-FKN group (400 µg/kg MPO mixed with Freund’s complete adjuvant i.p), anti-FKN group (1 µg/ rat /day, i.p) after 6 weeks. MPO-AAV associated glomerulonephritis model was established by intraperitoneal injection of MPO + Freund’s complete adjuvant with 10 mice in each group. The concentration of MPO-ANCA and FKN in serum was detected by Enzyme-linked immunosorbent assay (ELISA). Hematoxylin-eosin (HE) staining was used to detect pathological changes of kidney tissue. Western blot and immunofluorescence staining were used to detect the expression and localization of FKN protein in kidney tissue. Renal function test indicators: 24-hour urinary protein (UAER), blood urea nitrogen (BUN), serum creatinine (Scr). The expression levels of p65NF-κB and IL-6 was detected by Immunohistochemical assays. Results Compared with the control group, the serum MPO-ANCA antibody expression level in the MPO-AAV group was significantly increased (P

Background: Disseminated septicemia and endocarditis are extremely rare complications of Pasteurella infection and are mainly seen in patients with associated major comorbidities. Clinical Description: A 13-year-old boy, who had undergone surgery for congenital heart disease in early childhood, presented with prolonged fever, gross hematuria, and oliguria. The child was found to be conscious and febrile, with tachycardia, pallor, and edema. There was a systolic murmur in the left upper sternal border with hepatosplenomegaly. Management and Outcome: Routine investigations revealed anemia, low serum albumin, and progressively worsening renal functions, with urinalysis showing significant proteinuria and red cells. Serial blood cultures showed growth of Pasteurella multocida. Echocardiography showed vegetation in conduit (homograft) connecting the right ventricle with the pulmonary artery. Despite intravenous antibiotics, the clinical condition did not improve, so the conduit was removed surgically, following which the child recovered. Conclusion: This case creates awareness regarding infective endocarditis in a child being caused by a rare organism P. multocida, involving a surgically created conduit. The case also highlights the importance of timely surgical removal of the source combined with a prolonged course of antibiotics in a successful recovery.

Abstract IgA nephropathy progresses to kidney failure, making early detection important. However, definitive diagnosis depends on invasive kidney biopsy. This study aimed to develop non-invasive prediction models for IgA nephropathy using machine learning. We collected retrospective data on demographic characteristics, blood tests, and urine tests of the patients who underwent kidney biopsy. The dataset was divided into derivation and validation cohorts, with temporal validation. We employed five machine learning models—eXtreme Gradient Boosting (XGBoost), LightGBM, Random Forest, Artificial Neural Networks, and 1 Dimentional-Convolutional Neural Network (1D-CNN)—and logistic regression, evaluating performance via the area under the receiver operating characteristic curve (AUROC) and explored variable importance through SHapley Additive exPlanations method. The study included 1268 participants, with 353 (28%) diagnosed with IgA nephropathy. In the derivation cohort, LightGBM achieved the highest AUROC of 0.913 (95% CI 0.906–0.919), significantly higher than logistic regression, Artificial Neural Network, and 1D-CNN, not significantly different from XGBoost and Random Forest. In the validation cohort, XGBoost demonstrated the highest AUROC of 0.894 (95% CI 0.850–0.935), maintaining its robust performance. Key predictors identified were age, serum albumin, IgA/C3, and urine red blood cells, aligning with existing clinical insights. Machine learning can be a valuable non-invasive tool for IgA nephropathy.

Introduction: Diabetic kidney disease (DKD) affects 30–40% of patients with diabetes. The prevalence of nondiabetic kidney disease (NDKD) in patients with type 2 diabetes mellitus (T2D) in Egypt is unknown. This study aimed to assess the prevalence of NDKD in patients with T2D in Egypt. Methods: In this cross-sectional study, we searched the data of patients with T2D who underwent a native kidney biopsy between January 2010 and December 2020 in a kidney pathology laboratory in Egypt. Results: Of 12,006 patients who underwent kidney biopsy, 677 patients had T2D. NDKD was found in 285 patients (42.7%), DKD in 220 patients (33%), and mixed DKD and NDKD in 162 patients (24.3%). The total prevalence of NDKD was 67% in patients with T2D in our study group. Membranous nephropathy was the most common histopathological disease in patients with NDKD (20.6%) followed by acute tubular injury (ATI) (19.2%) and focal segmental glomerulosclerosis (15.2%). The presence of ATI in a kidney biopsy was associated with a significantly higher mean serum creatine level (p < 0.001). Minimal change disease was associated with a significantly higher proteinuria level (p < 0.001). In binary logistic regression analysis, combining NDKD and mixed groups, the duration of diabetes was a negative predictor of NDKD, with a longer duration decreasing the likelihood of NDKD. Conclusion: NDKD is prevalent among patients with T2D who underwent a kidney biopsy. Kidney biopsy remains the gold standard for diagnosing NDKD in patients with T2D.

Abstract Background IgA nephropathy (IgAN) is a common cause of chronic kidney disease (CKD) and end-stage renal disease (ESRD). Outcomes are highly variable and predicting risk of disease progression at an individual level is challenging. Accurate risk stratification is important to identify individuals most likely to benefit from treatment. The Kidney Failure Risk Equation (KFRE) has been extensively validated in CKD populations and predicts the risk of ESRD at 2 and 5 years using non-invasive tests; however, its predictive performance in IgAN is unknown. The Oxford classification (OC) describes pathological features demonstrated on renal biopsy that are associated with adverse clinical outcomes that may also inform prognosis. The objective of this systematic review is to compare the KFRE with the OC in determining prognosis in IgAN. Methods A systematic review will be conducted and reported in line with PRISMA guidelines (PRISMA-P checklist attached as Additional file 1). Inclusion criteria will be cohort studies that apply the KFRE or OC to determine the risk of CKD progression or ESRD in individuals with IgAN. Multiple databases will be searched in duplicate to identify relevant studies, which will be screened first by title, then by abstract and then by full-text analysis. Results will be collated for comparison. Risk of bias and confidence assessments will be conducted independently by two reviewers, with a third reviewer available if required. Discussion Identifying individuals at the highest risk of progression to ESRD is challenging in IgAN, due to the heterogeneity of clinical outcomes. Risk prediction tools have been developed to guide clinicians; however, it is imperative that these aids are accurate and reproducible. The OC is based on observations made by specialist renal pathologists and may be open to observer bias, therefore the utility of prediction models incorporating this classification may be diminished, particularly as in the future novel biomarkers may be incorporated into clinical practice. Systematic review registration PROSPERO CRD42022364569

Rationale & objective: Glomerulonephritis (GN) is a leading cause of chronic kidney disease (CKD). Major adverse cardiovascular events (MACE) are prolific in CKD. The risk of MACE in GN cohorts is multifactorial. We investigated the prognostic significance of routine cardiac biomarkers, Troponin I and N-terminal pro-BNP (NT-proBNP) in predicting MACE within 5 years of GN diagnosis. Study Design: Retrospective cohort study. Setting & participants: Data were obtained from TriNetX, a global federated health research network of electronic health records (EHR). Exposure or predictor: Biomarker thresholds: Troponin I: 18 ng/L, NT-proBNP: 400 pg/mL. Outcomes: Primary outcome: Incidence of major adverse cardiovascular events (MACE). Secondary outcome: was the risk for each individual component of the composite outcome. Analytical Approach: 1:1 propensity score matching using logistic regression. Cox proportional hazard models were used to assess the association of cardiac biomarkers with the primary and secondary outcomes, reported as Hazard Ratio (HR) and 95% confidence intervals (CI). Survival analysis was performed which estimates the probability of an outcome over a 5-year follow-up from the index event. Results: Following PSM, 34,974 and 18,218 patients were analysed in the Troponin I and NTproBNP cohorts, respectively. In the Troponin I all cause GN cohort, 3,222 (9%) developed composite MACE outcome HR 1.79; (95% CI, 1.70, 1.88, p < 0.0001). In the NTproBNP GN cohort, 1,686 (9%) developed composite MACE outcome HR 1.99; (95% CI, 1.86, 2.14, p < 0.0001). Limitations: The data are derived from EHR for administrative purposes; therefore, there is the potential for data errors or missing data. Conclusions: In GN, routinely available cardiac biomarkers can predict incident MACE. The results suggest the clinical need for cardiovascular and mortality risk profiling in glomerular disease using a combination of clinical and laboratory variables. [ABSTRACT FROM AUTHOR]

Introduction: Leaky gut has been linked to autoimmune disorders including lupus. We previously reported upregulation of anti-flagellin antibodies in the blood of lupus patients and lupus-prone mice, which led to our hypothesis that a leaky gut drives lupus through bacterial flagellin-mediated activation of toll-like receptor 5 (TLR5). Methods: We created MRL/lpr mice with global Tlr5 deletion through CRISPR/Cas9 and investigated lupus-like disease in these mice. Result: Contrary to our hypothesis that the deletion of Tlr5 would attenuate lupus, our results showed exacerbation of lupus with Tlr5 deficiency in female MRL/lpr mice. Remarkably higher levels of proteinuria were observed in Tlr5-/- MRL/lpr mice suggesting aggravated glomerulonephritis. Histopathological analysis confirmed this result, and Tlr5 deletion significantly increased the deposition of IgG and complement C3 in the glomeruli. In addition, Tlr5 deficiency significantly increased renal infiltration of Th17 and activated cDC1 cells. Splenomegaly and lymphadenopathy were also aggravated in Tlr5-/- MRL/lpr mice suggesting impact on lymphoproliferation. In the spleen, significant decreased frequencies of regulatory lymphocytes and increased germinal centers were observed with Tlr5 deletion. Notably, Tlr5 deficiency did not change host metabolism or the existing leaky gut; however, it significantly reshaped the fecal microbiota. Conclusion: Global deletion of Tlr5 exacerbates lupus-like disease in MRL/lpr mice. Future studies will elucidate the underlying mechanisms by which Tlr5 deficiency modulates host-microbiota interactions to exacerbate lupus. [ABSTRACT FROM AUTHOR]

IgA Nephropathy (IgAN) is the most prevalent glomerular disease worldwide. Complement system activation is crucial in its pathogenesis. Few studies correlated serum C3 and C4 with disease activity and prognosis. This retrospective study investigated the prognostic value of serum complement at the time of diagnosis in patients with IgAN. Specifically we evaluated whether adding serum C3 and C4 levels to established predictive models-one based on variables related to chronic kidney disease (CKD) progression and another incorporating variables from the International IgA Prediction Tool (IntIgAPT)-enhances the accuracy of outcome prediction. A composite renal outcome was defined as 50% decline in eGFR or onset of kidney failure. 101 patients were stratified according to baseline C3 levels in three groups (Low, Medium and High). During a median follow-up of 54 months, the Low group exhibited higher incidence of primary outcome (16.3 events vs 2.9 and 1.7 events × 100 pts/year, p = 0.0026). Model-1 (M1), consisting of CKD progression variables, and Model-3 (M3), comprising IntIgANPT variables, were implemented with baseline C3 and C4 to create Model-2 (M2) and Model-4 (M4), respectively. M2 demonstrated better predictive performance over M1, showing higher discrimination (lower AIC and BIC, higher C-index and NR2). Similarly, M4 outperformed M3, showing enhanced outcome prediction when C3 and C4 levels were added. Implementation of serum C3 and C4 can enhance prediction accuracy of already-validated prognostic models in IgAN. Lower C3 and higher C4 levels were associated with poorer prognosis, highlighting a more 'Complement-Pathic' subset of patients. [ABSTRACT FROM AUTHOR]

Introduction: Anti-glomerular basement membrane (GBM) disease is a rare cause of glomerulonephritis usually mediated by IgG antibodies and is associated with ANCA-associated glomerulonephritis in up to 50% of cases. IgA-mediated anti-GBM disease is extremely rare and presents diagnostic difficulties as circulating IgA antibodies will not be detected by standard serological tests for anti-GBM disease. Case Presentation: We present the case of a 67-year-old man with rapidly progressive glomerulonephritis requiring haemodialysis at presentation. Serological testing was positive for anti-myeloperoxidase and negative for IgG anti-GBM antibodies. Kidney biopsy revealed necrotizing crescentic glomerulonephritis with linear staining of IgA along the GBM. He was treated with a combination of immunosuppression and plasma exchange and was able to become dialysis-independent. Conclusion: To our knowledge, this is the first documented “double-positive” IgA anti-GBM disease and ANCA-associated glomerulonephritis. [ABSTRACT FROM AUTHOR]

Hepatitis C virus (HCV) can cause a range of kidney diseases. HCV is the primary cause of mixed cryoglobulinaemia, which leads to cryoglobulinaemic vasculitis and cryoglobulinaemic glomerulonephritis (GN). Patients with acute cryoglobulinaemic vasculitis often exhibit acute kidney disease due to HCV infection, which typically progresses to acute kidney injury (AKI). HCV also increases the risk of chronic kidney disease (CKD) and the likelihood of developing end-stage renal disease (ESRD). Currently, direct-acting antiviral agents (DAAs) can be used to treat kidney disease at different stages. This review focuses on key findings regarding HCV and kidney disease, discusses the impact of DAAs, and highlights the need for further research and treatment. [ABSTRACT FROM AUTHOR]

Podocyte infolding glomerulopathy (PIG) is a rare pathological entity, diagnosed by electron microscopic demonstration of diffuse infolding of the podocytes into the glomerular basement membranes. We report the first case from United Kingdom exhibiting typical ultrastructural features of PIG in a male with Type II diabetes mellitus, hypertension and common variable immune deficiency. Renal biopsy revealed phospholipase A2 receptor (PLA2R) immunostain positive membranous nephropathy (MN) but no serum PLA2R antibodies. Diffuse infolding of the podocytes into the glomerular basement membranes along with pathognomonic microspherular and microtubular intra basement membrane clusters distributed diffusely and globally were noted on electron microscopy, diagnostic of PIG. We postulate a shared pathomechanistic link between PIG and MN, highlighting the overlapping features of both conditions. [ABSTRACT FROM AUTHOR]

Background: With the availability of whole slide digital scanners, fairly accurate glomerular diameter (GD) measurements are now possible on light microscopy. The value of these measurements in prognosis and diagnosis of immunoglobulin A nephropathy (IgAN) have not been studied widely. IgAN is a major cause of end-stage renal disease (ESRD) worldwide, and its progression is currently assessed using Oxford scores, serum creatinine, and 24-h urinary protein. We aimed to correlate the mean and maximum GDs with serum creatinine, 24-h urinary protein, and Oxford scores in patients with IgAN. Materials and Methods: One hundred biopsies of IgAN with a minimum of eight viable glomeruli were collected along with data of their 24-h proteinuria, serum creatinine, and Oxford scores. The slides were scanned using the Philips IntelliSite Pathology Solution-Ultra Fast Scanner. Mean GD of each glomerulus was calculated as the mean of two measurements, that is, the maximal diameter of the glomerulus and the maximal chord perpendicular to the maximal diameter. Maximum GD was also recorded for each case. The Spearman rho/Pearson R correlation coefficient was used to make this correlation. P-values <0.05 were considered statistically significant. Results: The mean age of the patients was 34.67 ± 12.03 years, and they showed a male preponderance. The overall mean GD was 151.82 ± 28.69 μm, and maximum GD was 205.40 ± 32.76 μm. No statistically significant correlation was observed between the mean or maximum GD and the 24-h proteinuria, serum creatinine levels, and Oxford scores. Conclusion: GD in IgAN does not correlate with proteinuria, serum creatinine, or Oxford scores. [ABSTRACT FROM AUTHOR]

Secondary amyloidosis may complicate inherited dermatoses, but recessive dystrophic epidermolysis bullosa (RDEB) complicated by renal amyloidosis is rare. We report a case of a 12-year-old male child with RDEB presenting with progressive generalized anasarca for 20 days. Kidney biopsy showed diffuse expansion of mesangial matrix by pale acellular Periodic Acid-Schiff (PAS)-negative amorphous material, which was congophilic on Congo red stain and gave apple green birefringence on polarization and extending along the glomerular basement membrane, suggestive of amyloidosis. Genetic analysis showed a compound heterozygous pathogenic variant in the COL7A1 gene with autosomal recessive inheritance. [ABSTRACT FROM AUTHOR]