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Introduction: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) rarely coexist with systemic thrombotic microangiopathy (TMA).The TMA can be in the form of either hemolytic uremic syndrome (HUS) or thrombotic thrombocytopenic purpura (TTP). This review explores the clinical characteristics, histopathological findings, treatment options, and outcomes in patients presenting as AAV with coexisting HUS/TTP. Methods: We conducted a search on the PubMed database and additional searches from January 1998 to September 2022 using the following terms: "ANCA", "Antineutrophil cytoplasmic antibody", "thrombotic thrombocytopenic purpura", "TTP", "thrombotic microangiopathy", "haemolytic uremic syndrome", and "HUS". We excluded articles that described renal-limited TMA. Two authors independently reviewed the full texts and extracted all critical data from the included case reports. Finally, we included 15 cases for this review. Hematological remission and kidney recovery in the form of independence from dialysis was assessed. Results: The median age of the patients was 61 years and a majority of them were females (66.7%). Myeloperoxidase (MPO)-ANCA positivity (66.67%) was more common than proteinase 3 (PR3)-ANCA positivity (33.33%). All patients had laboratory parameters consistent with systemic TMA (HUS or TTP), and only six (out of 11) cases showed histological features of renal TMA. Ten had crescentic glomerulonephritis, and two had advanced degrees of chronicity in histology. Eighty-six percent of cases had hematological remission, and sixty percent of cases became dialysis-independent after treatment. Conclusion: In conclusion, kidney outcome was worse in patients who manifested both AAV and systemic TMA. A paucity of literature regarding this diagnostic quandary calls for avid reporting of such cases.
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There is evidence to suggest that M-type phospholipase A2 (PLA2R) antibodies activate the mannose-binding lectin (MBL) cascade, resulting in glomerular damage and proteinuria in patients with primary membranous nephropathy (PMN). Furthermore, there are few reports indicating that aberrant MBL activation is associated with endothelial dysfunction and accelerated atherosclerosis. While PMN is a common cause of adult nephrotic syndrome, and patients are at increased risk of cardiovascular disease (CVD), there is a lack of research that explores the factors that contribute to this condition. This study aims to determine the MBL levels in PMN and their relation to the clinical activity and endothelial dysfunction in PMN. The MBL levels of 22 biopsy-confirmed PMN patients were assessed at baseline and after 6 months of immunosuppressive therapy. In order to evaluate endothelial dysfunction in PMN patients, flow-mediated vasodilation (FMD) was measured at baseline and after treatment. A total of 22 healthy controls were included in this study to measure MBL levels and FMD. A significant difference was observed between MBL levels in PMN patients and healthy controls (p < .01). MBL levels decreased significantly after immunosuppressive therapy (p = .04). The baseline MBL levels and FMD levels exhibited a strong correlation (Spearman correlation coefficient [ρ] = 0.51: p = .01). In conclusion, the study signals the activation of the MBL cascade and its association with endothelial dysfunction in PMN patients.
Subject(s)
Glomerulonephritis, Membranous , Immunosuppressive Agents , Mannose-Binding Lectin , Vasodilation , Humans , Glomerulonephritis, Membranous/blood , Glomerulonephritis, Membranous/immunology , Glomerulonephritis, Membranous/diagnosis , Pilot Projects , Male , Female , Mannose-Binding Lectin/blood , Middle Aged , Adult , Immunosuppressive Agents/therapeutic use , Biomarkers/blood , Case-Control Studies , Treatment Outcome , Endothelium, Vascular/physiopathology , Up-Regulation , Time FactorsABSTRACT
OBJECTIVES: Respiratory tract infections are life-threatening infections in solid-organ transplant recipients that pose risk to the graft and to the patient. This study was undertaken to examine the clinical and microbiological spectrum of pneumonia in renal transplant recipients. MATERIALS AND METHODS: Of 400 consecutive renal transplant recipients, 87 recipients (21.8%) were hospitalized between November 2014 and October 2016 with pneumonia. We examined demographic profiles and clinical investigations. RESULTS: The median age of patients was 38 years (range, 19-72 y). The mean time of presentation after renal transplant was 18 months (range, 1-174 mo). Most patients (80.5%) were on maintenance immunosuppression with tacrolimus, mycophenolate mofetil, and steroids; 34% of patients had an induction agent. Chronic hepatitis C and hepatitis B infections were found in 12.6% and 2.2% of patients, respectively, and new-onset diabetes in 19.5% of patients. Fever (88%), cough (87%), shortness of breath (68%), and hypotension (33%) were common presenting symptoms. Diarrhea was the most frequent accompanying symptom, found in 9.2% of patients. Cytopenia and graft dysfunction were present in 38.7% and 80.4% of patients. Among infections, fungal infections were the most frequent (30%) followed by mixed infections (20.7%), tuberculosis (12.6%), bacterial (12.6%), and viral (3.5%) infections. Etiology could not be found in 27.6% patients. Mortality rate was 24.1%, with the highest rates for fungal infections (44%), followed by bacterial (25%) and mixed infections (18%). Presence of hypoxia and hypotension at presentation was associated with increased risk of death, whereas use of induction agents, new-onset diabetes posttransplant, diabetes mellitus, and acute kidney injury were not correlated with death or increased duration of hospital stay. CONCLUSIONS: Pneumonia carries high risk of mortality in renal transplant recipients. Fungal and bacterial infections carry high risk of mortality. Despite invasive investigations, a substantial number of patients had unidentified etiology.
Subject(s)
Coinfection , Diabetes Mellitus , Hypotension , Kidney Transplantation , Mycoses , Pneumonia , Humans , Young Adult , Adult , Middle Aged , Aged , Immunosuppressive Agents/adverse effects , Kidney Transplantation/adverse effects , Coinfection/chemically induced , Coinfection/complications , Mycophenolic Acid/adverse effects , Diabetes Mellitus/etiology , Pneumonia/chemically induced , Hypotension/etiology , Transplant Recipients , Graft RejectionABSTRACT
Primary membranous nephropathy (PMN), an autoimmune disease, is the most common cause of nephrotic syndrome in middle-aged non-diabetic adults. PMN pathophysiology includes Th1/Th2 paradigm. The IL-23/IL-17 pathway is implicated in autoimmune kidney disorders, but no study has examined its relationship with PMN. In several unrelated studies, PMN patients reported to have paradoxical IL-17 levels. This manuscript describes the best possible association of IL-23/IL-17 axis with PMN. Biopsy-proven PMN patients and age, gender-matched healthy controls were enrolled. Serum-PLA2R (Euroimmune, Germany), IL-23 and IL-17 (R&D; USA), was measured using ELISA along with biochemical parameters. Appropriate statistical tools were used for analysis. One hundred eighty-nine PMN patients (mean age 41.70 ± 12.53 years) and 100 controls (mean age 43.92 ± 10.93 years) were identified. One hundred forty were PLA2R-related. PMN patients had median proteinuria, serum albumin, and creatinine of 6.12 (3.875, 9.23) g/day, 2.32 (1.96, 2.9) g/dl, and 0.89 (0.7, 1.1) mg/dl, respectively. IL-17, but not IL-23, was significantly increased in PMN patients compared to controls (IL-17, median: 12.07 pg/ml (9.75, 24.56) vs median: 9.75 pg/ml (8.23, 17.03) p = 0.0002); (IL23, median: 6.04 pg/ml (4.22, 10.82) vs median: 5.46 pg/ml (3.34, 9.96) p = 0.142). IL-17 and IL-23 correlated significantly (p 0.05) in PMN patients, and similar trend was seen when grouped into PLA2R-related and -unrelated groups. The levels of IL-23 (p = 0.057) and IL-17 (p = 0.004) were high in MN patients that did not respond to the treatment. The current finding may indicate or suggest the involvement of IL-23/IL-17 PMN pathogenesis. A comprehensive investigation is needed to evaluate IL-23/IL-17 axis with renal infiltrating immune cells, and external stimuli.
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Organ transplantation is the primary therapy for organ failure caused by telomere biology disorder (TBD). We describe the first documented case of simultaneous liver and kidney transplantation (SLKTx) for TBD, although the diagnosis of TBD was reached only three months following SLKTx. The patient was born prematurely, displayed growth retardation, and developed chronic kidney and liver diseases. His pre-SLKTx autoimmune, metabolic, and viral assessments were negative, and persistent pancytopenia (bone marrow cellularity 70-80%) was attributed to renal disease-associated bone marrow changes. Following SLKTx, he was discharged with stable graft function on tacrolimus and prednisolone. Although mycophenolate mofetil was discontinued on the second postoperative day, his pancytopenia persisted. Despite extensive evaluations, including drug, immune, nutritional, and viral assessments, all results were negative. A bone marrow biopsy conducted three months post-transplant revealed significant hypocellularity (40-50%). Whole genome sequencing revealed a likely pathogenic variant of the TINF2 gene. The patient was subsequently treated with danazol. At the nine-month follow-up post-SLKTx, he exhibited stable graft function and improved cell counts while maintaining triple-drug immunosuppression. Given the lack of uniform diagnostic criteria for TBD, healthcare providers must be vigilant with patients presenting with multi-organ failure and persistent cytopenias. Effective pre-transplant screening for TBD can lead to timely diagnoses, better management, and improved post-transplant outcomes.
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This study focuses on the synchronization analysis of Hindmarsh-Rose neurons coupled through a common memristor (coupled mHRN). Initially, we thoroughly examine the synchronization of two mHRNs coupled via a common memristor before exploring synchronization in a network of mHRNs. The stability of the proposed model is analyzed in three cases, demonstrating the existence of a single equilibrium point whose stability is influenced by external stimuli. The stable and unstable regions are investigated using eigenvalues. Through bifurcation analysis and the determination of maximum Lyapunov exponents, we identify chaotic and hyperchaotic trajectories. Additionally, using the next-generation matrix method, we calculate the chaotic number C0, demonstrating the influence of coupling strength on the chaotic and hyperchaotic behavior of the system. The exponential stability of the synchronous mHRN is derived analytically using Lyapunov theory, and our results are verified through numerical simulations. Furthermore, we explore the impact of initial conditions and memristor synapses, as well as the coupling coefficient, on the synchronization of coupled mHRN. Finally, we investigate a network consisting of n number of mHRNs and observe various collective behaviors, including incoherent, coherent, traveling patterns, traveling wave chimeras, and imperfect chimeras, which are determined by the memristor coupling coefficient.
Subject(s)
Nonlinear Dynamics , Synapses , Neurons/physiology , Cluster AnalysisABSTRACT
Introduction: Drug-induced acute kidney injury (DI-AKI) is a frequent adverse event. The identification of DI-AKI is challenged by competing etiologies, clinical heterogeneity among patients, and a lack of accurate diagnostic tools. Our research aims to describe the clinical characteristics and predictive variables of DI-AKI. Methods: We analyzed data from the Drug-Induced Renal Injury Consortium (DIRECT) study (NCT02159209), an international, multicenter, observational cohort study of enriched clinically adjudicated DI-AKI cases. Cases met the primary inclusion criteria if the patient was exposed to at least 1 nephrotoxic drug for a minimum of 24 hours prior to AKI onset. Cases were clinically adjudicated, and inter-rater reliability (IRR) was measured using Krippendorff's alpha. Variables associated with DI-AKI were identified using L1 regularized multivariable logistic regression. Model performance was assessed using the area under the receiver operating characteristic curve (ROC AUC). Results: A total of 314 AKI cases met the eligibility criteria for this analysis, and 271 (86%) cases were adjudicated as DI-AKI. The majority of the AKI cases were recruited from the United States (68%). The most frequent causal nephrotoxic drugs were vancomycin (48.7%), nonsteroidal antiinflammatory drugs (18.2%), and piperacillin/tazobactam (17.8%). The IRR for DI-AKI adjudication was 0.309. The multivariable model identified age, vascular capacity, hyperglycemia, infections, pyuria, serum creatinine (SCr) trends, and contrast media as significant predictors of DI-AKI with good performance (ROC AUC 0.86). Conclusion: The identification of DI-AKI is challenging even with comprehensive adjudication by experienced nephrologists. Our analysis identified key clinical characteristics and outcomes of DI-AKI compared to other AKI etiologies.
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Background and Aim: Primary glomerular disease accounts for one-sixth of all chronic kidney diseases (CKDs) in India. We remain limited in our ability to effectively treat these conditions because of lack of understanding of the disease mechanisms and lack of predictors to identify the clinical course and therapeutic responsiveness. We propose to develop a network of investigators in glomerular diseases, collect information in a systematic fashion to understand the clinical outcomes, answer translational research questions better, and identify and recruit patients for clinical trials. Materials and Methods: This is a prospective, observational study. The Indian TrANslational GlomerulonephrItis BioLogy nEtwork (I-TANGIBLE) cohort will enroll patients (>18 years) with biopsy-proven minimal change disease (MCD), focal segmental glomerulonephritis (FSGS), membranous nephropathy (MN), IgA nephropathy (IgAN), or membranoproliferative glomerulonephritis (MPGN) (immune complex- and complement-mediated), with first biopsy taken within 2 years of enrollment. Patients with estimated glomerular filtration (eGFR) rate <15 ml/min/1.73 m2 for >3 months at the time of screening, kidney transplant or bone marrow transplant recipients, patients with active malignancy, and patients with active hepatitis B/C replication or human immunodeficiency virus (HIV)-I/II will be excluded. Clinical details including history, medication history and details, and family history will be obtained. Consenting patient's blood and urine samples will be collected and stored, aligned to their clinical follow-up. Expected Outcomes: The network will allow accurate ascertainment of disease burden of glomerular diseases across study sites, establishment of the treatment pattern of common glomerular diseases, investigation of medium- and long-term outcomes (remission, relapse, rate of eGFR decline), and building a suitable infrastructure to carry out clinical trials in primary glomerular disease.
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AIM: This cross-sectional survey aimed to determine the prevalence of Interventional Nephrology (IN) practice amongst nephrologists in the Asia-Pacific Region (APR), specifically related to dialysis access (DA). METHODS: The Association of VA and intervenTionAl Renal physicians (AVATAR) Foundation from India conducted a multinational online survey amongst nephrologists from the Asia-Pacific to determine the practice of IN in the planning, creation, and management of dialysis access. The treatment modalities, manpower and equipment availability, monthly cost of treatment, specifics of dialysis access interventions, and challenges in the training and practice of IN by nephrologists were included in the survey. RESULTS: Twenty-one countries from the APR participated in the survey. Nephrologists from 18 (85.7%) countries reported performing at least one of the basic dialysis access-related IN procedures, primarily the placement of non-tunnelled central catheters (n-TCC; 71.5%). Only 10 countries (47.6%) reported having an average of <4% of nephrologists performing any of the advanced IN access procedures, the most common being the placement of a peritoneal dialysis (PD) catheter (20%). Lack of formal training (57.14%), time (42.8%), incentive (38%), institutional support (38%), medico-legal protection (28.6%), and prohibitive cost (23.8%) were the main challenges to practice IN. The primary obstacles to implementing the IN training were a lack of funding and skilled personnel. CONCLUSION: The practice of dialysis access-related IN in APR is inadequate, mostly due to a lack of training, backup support, and economic constraints, whereas training in access-related IN is constrained by a lack of a skilled workforce and finances.
Subject(s)
Nephrology , Humans , Nephrology/education , Renal Dialysis , Cross-Sectional Studies , Catheterization/methods , Asia/epidemiologyABSTRACT
BACKGROUND: Factors associated with pulmonary mucormycosis (PM) among subjects with diabetes mellitus (DM) remain unclear. Following the coronavirus disease (COVID-19)-associated mucormycosis outbreak in India, specific environmental exposures (especially cattle dung exposure) were proposed as possible aetiology. We hypothesized that environmental factors are associated with PM. We compared subjects with DM with (cases) and without PM (controls). METHODS: In this case-control study, for each PM case, we included five unmatched diabetic controls (hospital [n = 2], community [n = 3]) without PM. We collected information on demography, COVID-19 infection, glycated haemoglobin% (HbA1c), the type of house (pucca vs. kutcha) where the participants reside, and other environmental factors. The primary exposure tested was cattle dung exposure (CDE; using cattle dung cakes as fuel or cattle handling). We performed a multivariate logistic regression to explore factors associated with PM and report the association as an adjusted odds ratio (OR) with 95% confidence intervals (CI). RESULTS: We enrolled 39 PM cases and 199 controls (hospital [n = 80], community [n = 119]). CDE (OR 0.68, 95% CI [0.14-3.31]; p = 0.63) was not associated with increased PM in DM. We found male sex (OR 4.07, 95% CI [1.16-14.31]), higher HbA1c (OR 1.51, 95% CI [1.18-16.32]), COVID-19 (OR 28.25, 95% CI [7.02-113.6]) and residence at kutcha house (OR 4.84, 95% CI [1.33-17.52]) associated with PM. CONCLUSION: Cattle dung exposure was not associated with PM in subjects with DM. Instead, male sex, poor glycaemic control, COVID-19 and the type of housing were associated with pulmonary mucormycosis.
Subject(s)
COVID-19 , Diabetes Mellitus , Mucormycosis , Male , Animals , Cattle , Mucormycosis/epidemiology , Case-Control Studies , Glycated Hemoglobin , COVID-19/complications , COVID-19/epidemiology , Diabetes Mellitus/epidemiology , Risk FactorsABSTRACT
BACKGROUND AND AIMS: Most guidelines recommend protein restriction in adults with chronic kidney disease (CKD), with or without diabetes. However, advising protein restriction for every person with CKD is controversial. We aim to arrive at a consensus on this topic, especially among Indian adults with CKD. METHODS: A systematic literature search in the PubMed electronic database was undertaken using specific keywords and MeSH terms until May 1, 2022. All the retrieved literature was circulated and rigorously deliberated upon by the panel members. RESULTS: Seventeen meta-analyses that evaluated the outcomes of protein restriction in adults with CKD, with or without diabetes, met our inclusion criteria and were analyzed. A low-protein diet (LPD) in people with stages 3-5 of CKD (who are not on haemodialysis [HD]) reduces the severity of uremic symptoms and the rate of decline in glomerular filtration rate, leading to a delay in dialysis initiation. However, LPD in patients on maintenance HD may not be desirable because HD-induced protein catabolism may lead to protein-energy malnutrition. Since the average protein intake among Indians is much lower than recommended, this must be taken into consideration before recommending LPD for all Indian adults with CKD, particularly those on maintenance HD. CONCLUSION: It is essential to assess the nutritional status of people with CKD, particularly in countries like India where average daily protein intake is poor, before recommending guideline-directed protein restriction. The prescribed diet, including the quantity and quality of proteins, should be tailored to the person's habits, tastes, and needs.