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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. [ABSTRACT FROM AUTHOR]

The primary objective of the current study was to create a mathematical model utilizing fractional-order calculus for the purpose of analyzing the symmetrical characteristics of Wolbachia dissemination among Aedesaegypti mosquitoes. We investigated various strains of Wolbachia to determine the most sustainable one through predicting their dynamics. Wolbachia is an effective tool for controlling mosquito-borne diseases, and several strains have been tested in laboratories and released into outbreak locations. This study aimed to determine the symmetrical features of the most efficient strain from a mathematical perspective. This was accomplished by integrating a density-dependent death rate and the rate of cytoplasmic incompatibility (CI) into the model to examine the spread of Wolbachia and non- Wolbachia mosquitoes. The fractional-order mathematical model developed here is physically meaningful and was assessed for equilibrium points in the presence and absence of disease. Eight equilibrium points were determined, and their local and global stability were determined using the Routh–Hurwitz criterion and linear matrix inequality theory. The basic reproduction number was calculated using the next-generation matrix method. The research also involved conducting numerical simulations to evaluate the behavior of the basic reproduction number for different equilibrium points and identify the optimal CI value for reducing disease spread. [ABSTRACT FROM AUTHOR]

In this paper, the ABC fractional derivative is used to provide a mathematical model for the dynamic systems of substance addiction. The basic reproduction number is investigated, as well as the equilibrium points' stability. Using fixed point theory and nonlinear analytic techniques, we verify the theoretical results of solution existence and uniqueness for the proposed model. A numerical technique for getting the approximate solution of the suggested model is established by using the Adams type predictor‐corrector rule for the ABC‐fractional integral operator. There are several numerical graphs that correspond to different fractional orders. Furthermore, we present a numerical simulation for the transmission of substance addiction in two scenarios with fundamental reproduction numbers greater than and fewer than one. [ABSTRACT FROM AUTHOR]

It is estimated that 50% of patients with coronavirus disease 2019 (COVID-19) have varying degrees of renal involvement. In this clinical biomarker development research, we examined in a retrospective study design the temporal changes in biochemical laboratory parameters in relation to the development of acute kidney injury (AKI). In a sample of 399 patients admitted from May 2020 to May 2021 to a tertiary health care intensive care unit (ICU), the incidence of AKI was 27.3%, and the median time to AKI was on 7th day of ICU admission. Most common etiology of AKI was kidney hypoperfusion. Within 72 h of developmental of low blood pressure, 63.76% developed AKI. The likelihood of AKI was higher in those with elevated serum ferritin, aspartate transaminase, and thrombocytopenia (low platelet count). A cutoff value of 750.3 ng/mL [area under the ROC curve (AUC) = 0.777] for serum ferritin, and 40.05 U/L for alanine aminotransferase (AUC = 0.677) 1 day before development of AKI displayed, respectively, a sensitivity of 76.2% and 64.3%, whereas the specificity was 69.5% and 64.1%, respectively, for these two biochemical predictors. A cutoff value of platelets (152.50 × 109/L [AUC = 0.75]) measured 4 days before development of AKI, displayed 83.3% sensitivity and 16.4% specificity. Taken together, our study thoroughly examined the temporal association of various clinical and laboratory parameters with AKI and prediction models were developed as per results of the time series data. These observations in a tertiary health care setting contribute to ongoing efforts for biomarker discovery and development using routine biochemical tests so as to forecast AKI in patients with COVID-19. [ABSTRACT FROM AUTHOR]

Background. Allograft rejection postkidney transplantation (KTx) is a major clinical challenge despite increased access to a healthcare system and improvement in immunosuppressive (IS) drugs. In recent years, mesenchymal stromal cells (MSCs) have aroused considerable interest in field of transplantation due to their immunomodulatory and regenerative properties. This study was aimed at investigating safety, feasibility, and immunological effects of autologous MSCs (auto-MSCs) and allogeneic MSCs (allo-MSCs) as a complement to IS drug therapy in KTx patients. Methods. 10 patients undergoing KTx with a living-related donor were analysed along with 5 patients in the control group. Patients were given auto-MSCs or allo-MSCs at two time points, i.e., one day before transplant (D-0) and 30 days after transplant (D-30) at the rate of 1.0- 1.5 × 10 6 MSCs per kg body weight in addition to immunosuppressants. Patients were followed up for 2 years, and 29 immunologically relevant lymphocyte subsets and 8 cytokines and important biomarkers were analysed at all time points. Results. Patients displayed no signs of discomfort or dose-related toxicities in response to MSC infusion. Flow cytometric analysis revealed an increase in B regulatory lymphocyte populations and nonconventional T regulatory cells and a decrease in T effector lymphocyte proportions in auto-MSC-infused patients. No such favourable immune responses were observed in all MSC-infused patients. Conclusion. This study provides evidence that auto-MSCs are safe and well tolerated. This is the first ever report to compare autologous and allogeneic MSC infusion in KTx patients. Importantly, our data demonstrated that MSC-induced immune responses in patients did not completely correlate with clinical outcomes. Our findings add to the current perspective of using MSCs in KTx and explore possibilities through which donor/recipient chimerism can be achieved to induce immune tolerance in KTx patients. [ABSTRACT FROM AUTHOR]

Background: Unlike adults, primary membranous nephropathy (PMN) comprises only 1–2% of childhood nephrotic syndrome. The clinical behaviour of PMN in children is not explicit and we report upon clinical presentation and outcome. Methods: This prospective study includes children and adolescents (< 20 years) with biopsy-proven PMN without secondary causes. Anti-PLA2R assessment: before and after completing therapy. Outcome: percentage of patients achieving remission. Results: Study cohort included 48 (M:F ratio 1.1:1) patients and median age 17 (IQR 15–18) years, with 35 (72.9%) PLA2R related. Median interval from symptom onset to presentation was 5 months, where median proteinuria, serum albumin and creatinine were 4.9 g/day, 2.1 g/dL and 0.63 mg/dL, respectively. Forty-seven patients received immunosuppressive therapy, with various agents used as first-line therapy: cyclical CYC/GC (53.1%), CNI/GC (21.3%), rituximab (14.9%), prednisolone alone (4.3%), azathioprine (4.3%) and mycophenolate mofetil (2.1%). Median follow-up was 29 (14, 59) months. At 6 months, 11 (24.4%) and 17 (37.7%) had complete remission (CR) or partial remission (PR), while at last follow-up (median 29 months), 20 (45.4%) and 14 (31.8%) had CR and PR respectively. No significant differences in outcome were observed with different agents. A total of 60% patients treated with rituximab as first line/for relapsing disease, and all cases with resistant disease receiving rituximab had CR or PR at last follow-up. PLA2R antibody presence was associated with clinical outcome. Conclusions: Three-quarters of PMN in children and adolescents is PLA2R related and two-thirds respond to immunosuppressive therapy. Rituximab is a promising agent to manage PMN in children. Anti-PLA2R is associated with clinical outcomes. [ABSTRACT FROM AUTHOR]

Background Complement 3 glomerulopathy (C3G) results from dysfunction of the alternative complement pathway (ACP). No data are available on post-transplant C3G in South Asia. Methods In this study, renal allograft biopsies of C3G patients performed from 2012 to 2017 were analysed for ACP functional assay (APFA), serum complement levels, complement factor H (CFH), complement factor B (CFB) and autoantibodies to CFH and CFB. Limited genetic screening for CFH / CFHR5 genes was carried out. All study patients were also followed up. Results A total of 21 cases of C3G were included, of which 11 had native C3G disease (that is, recurrent C3G). Of these 11 recurrent cases, 7 presented with allograft dysfunction and 4 with proteinuria and renal dysfunction. Early post-transplant recurrence (<1 month) was noted in six patients, whereas recurrence in five patients occurred within 8–17 months of transplant. Biopsies showed mild focal mesangial expansion with or without endocapillary proliferation and thrombotic microangiopathy. Rejection was also noted in six patients. APFA/C3 levels were low in all cases. Serum CFH levels were low [dense deposit disease (DDD), 44%; C3 glomerulonephritis (C3GN), 25%], whereas CFB levels were normal. Autoantibodies to CFH, CFB and C3 nephritic factor were present in 11, 0 and 44% of DDD cases, respectively, and in 17, 17 and 33% of C3GN cases, respectively. Genetic analysis revealed only non-pathogenic CFH gene variants (93%). No novel mutation was found. At follow-up (140 months), stable graft was noted in 28% of cases, progressive renal failure in 19%, graft loss in 34%, and 19% of patients died. Conclusion Post-transplant C3G can present with graft dysfunction and/or proteinuria. Subtle histological findings demand careful interpretation of immunofluorescence results. Autoantibodies to complement pathway regulatory proteins are common, and no novel mutation has been found from limited genetic workup. Clinical outcome is poor. [ABSTRACT FROM AUTHOR]

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 C 0 , 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. [ABSTRACT FROM AUTHOR]

Rituximab is currently used after the conventional agents have failed in the management of steroid‐dependent (SD)/ steroid‐resistant (SR) podocytopathies and have a safer toxicity profile. We report 53 adults with podocytopathies who were managed effectively with CD19‐targeted rituximab therapy. Methods: This was a prospective study carried out at a tertiary care centre in India between January 2014 and June 2019. Adults between 16 and 60 years with SD, frequently relapsing (FR), and SR nephrotic syndrome (NS) due to podocytopathy received rituximab in a CD19‐targeted approach. Primary outcome: Percentage of patients who were in remission at 6 and 12 months. Secondary outcome: Percentage of patients in remission at the last follow‐up, rituximab dose and adverse events of rituximab therapy. Results: Fifty‐three adults with SD/FR/SR NS received CD19‐targeted rituximab. The median age at the time of first rituximab injection was 30.09 ± 13.21 (16.53) years. At the time of first rituximab infusion, all patients were in remission with steroids and/or calcineurin inhibitors (CNIs). Fifty (94.33%) patients were in remission at the end of 6 and 12 months and the last follow‐up (median: 36 months). The mean total dose of rituximab at 1 year was 788.7 ± 128.1 (6 001 100) mg. At last follow‐up (median 36 months), 42 (79%) patients did not require any additional CNI or steroids therapy. No serious adverse events to rituximab were noted. Conclusion: CD19‐targeted rituximab therapy is safe and efficacious in the management of SD/SR adult podocytopathy. Also, rituximab is effective in maintaining remission in treatment naïve adult SD or FR podocytopathy. SUMMARY AT A GLANCE: Among 53 adult patients with podocytopathies, rituximab was safe in inducing remission in 22 patients with steroid‐dependent/steroid‐resistant disease, and effective as maintenance therapy in 23 patients who were treatment naïve or had frequently relapsing disease. [ABSTRACT FROM AUTHOR]

The viable pathogens in the liquid food can be efficiently inactivated using Pulsed Electric Field (PEF) treatment through electroporation. Electroporation depends on applied electric field for causing minute pores on the cell membrane. The electric field application from electrodes play an important role in getting the required inactivation and it varies based on the dimensions and design of electrodes inside the chamber. Parallel plate electrodes provide more uniform electric field in the inactivation area, where all the microbes will be uniformly treated under the same field value. This paper analyses the electric field distribution under two circumstances (i) To find a suitable surface material for titanium electrodes, for future noninvasive PEF applications (ii) Comparative performance of platinum coated and alumina coated titanium electrodes, when a viable pathogen is placed in the inactivation area. Under first circumstance, the electric field distribution through four surface materials such as glass, alumina, quartz and plexiglass was compared and analyzed. The electrodes have a diameter and thickness of 40 mm and 3.5 mm respectively. From the first analysis, it was found that alumina exhibited greater percentage (82%) of electric field in the inactivation area than with other materials. This signifies the suitability of alumina as a coating for titanium electrodes for successful noninvasive PEF applications. Secondly, the inactivation performance of alumina coated titanium electrodes was compared with platinized titanium on Escherichia coli models. From the second analysis, alumina coated electrodes gave equivalent performance with platinized titanium on bacterial inactivation which reconfirmed alumina’s suitability for non invasive PEF applications. The electric field simulations were implemented using ANSYS MAXWELL v 15.0. [ABSTRACT FROM AUTHOR]

Aim: A significant proportion of patients with minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS) are either steroid dependent or steroid resistant, requiring long‐term calcineurin inhibitors (CNI) use. Rituximab has more favourable safety profile. The present study was undertaken to evaluate the efficacy and safety of rituximab in CNI‐dependent patients. Methods: This was a prospective observational study conducted from July 2014 to February 2018. Steroid‐dependent nephrotic syndrome or steroid‐resistant nephrotic syndrome (biopsy proven MCD/FSGS), who were CNI dependent were enrolled. Mean age at enrolment was 22.77 ± 7.45 years. All patients received rituximab at a dose of 375 mg/m2 at entry in the study. CD‐19 levels were monitored monthly and patients having CD‐19 levels >5/μL and/or > 1% received additional low‐dose (100 mg) of rituximab. Results: A total of 24 patients were followed up for 12 months. At the end of 6 and 12 months, 87.5% and 79.16% of the patients achieved remission, respectively. Eight (33.33%) patients developed relapse. The mean dose of rituximab in the first year was 791 mg. The average cost of rituximab in the first year was 487.17$. Rituximab was well‐tolerated, with mild infusion reactions, respiratory tract infection and oral candidiasis in 5 (20.83%), 5 (20.83%) and 1 (4.17%) patient, respectively. Conclusions: CD‐19 targeted rituximab is a safe and cost‐effective agent in remission maintenance in adults with CNI dependent. Over three‐fourths of the patients with CNI‐dependent podocytopathy maintain clinical remission with CD‐19 targeted rituximab therapy. SUMMARY AT A GLANCE: This paper shows that rituximab, a monoclonal antibody‐based therapy that depletes CD‐19 and CD‐20‐positive B cells, may be an alternative approach to maintain remission in calcineurin‐inhibitor dependent podocytopathies. [ABSTRACT FROM AUTHOR]

Abstract: The literature on membranous nephropathy (MN) with monoclonal deposits on immunofluorescence (IF) and their outcome is very scarce. We report our experience of managing five patients with this clinical entity. The mean age of the patients was 33.2 ± 6.55 years. The mean proteinuria, serum albumin and serum creatinine was 5.73 ± 2.17 g/day, 2.86 ± 0.51 g/dL and 1.34 ± 1.19 mg/dL, respectively. None of the patients had a lymphoproliferative disorder. Only one patient had an elevated free light chain ratio. Four (80%) patients were M‐type phospholipase A2 receptor (PLA2R) negative (tissue and serum), and one (20%) was PLA2R related. Three (60%) cases had monoclonal IgG3/k, one IgG3/λ, whereas one patient with PLA2R positivity had an IgG3/IgG4k subtype. Two (67%) patients treated with cyclical cyclophosphamide and steroids (cCYC/GC) achieved complete remission and one patient (33%) with elevated baseline creatinine had a reduction in serum creatinine with persistent proteinuria at the end of the 12th month of follow‐up. One patient with PLA2R positive MN was treated with Rituximab and is in complete remission. The patient with an elevated free light chain at baseline was treated with Bortezomib/Thalidomide/Dexamethasone, had complete remission at 12 months, however, had a progressive rise in creatinine over the next 40 months of follow‐up. The current series, though limited by numbers, documents the efficacy of conventional therapies in non‐malignant associated MN with monoclonal deposits on IF. [ABSTRACT FROM AUTHOR]

Aim: Despite its importance in bone and cardiovascular disease in subjects with kidney disease, there are no data on fibroblast growth factor 23 (FGF23) perturbations in nephrotic syndrome. We evaluated FGF23 and markers of mineral bone metabolism in subjects with untreated NS. Methods: In this cross-sectional study, we measured circulating levels of FGF23, 25-hydroxy vitamin D [25(OH)D], 1,25 di-hydroxy vitamin D [1,25(OH)2D], serum albumin, serum calcium, phosphorus, creatinine and intact parathyroid hormone (iPTH) in 101 patients with adults onset NS and 40 healthy controls. We examined the correlation between FGF23 and markers of mineral bone metabolism. Results: Compared to healthy controls, subjects with NS showed reduced levels of 25(OH)D (21.76 ± 10.18 vs 35.74 ± 40.27 nmol/L, P = 0.001), 1,25(OH)2D (median; 37.80 vs 73.13 pmol/L, P = 0.0001) and FGF23 (37.81 ± 20.42 vs 48.20 ± 11.60 pg/mL, P = 0.004) levels. Serumphosphorus levels were marginally, but significantly higher in subjects with nephrotic syndrome compared to healthy controls (P = 0.004). Serum iPTH levels were significantly higher in subjects with NS compared to healthy controls (52.24 ± 39.58 vs 37.90 ± 14.60 pg/mL, P = 0.028). Conclusions: We conclude that FGF23 is reduced in subjects with NS compared to healthy controls. The reduced levels of Vitamin D, and urinary losses may contribute to lower levels of FGF23 in NS. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 58-year-old non-diabetic female with history of hypertension with swelling of both lower limbs and facial puffiness. Topics discussed include use of antiviral therapy and cyclical cyclophosphamide in the treatment; effects of serum-glomerular dynamics on aPLA2R; and persistence of nephrotic syndrome in the patient.

Background. Antibodies to M-type phospholipase A2 receptor (PLA2R) correlate with clinical activity of primary membranous nephropathy (PMN). Risk alleles in PLA2R1 and HLA-DQA1 genes are associated with PMN. Whether these alleles are associated with the development of anti-PLA2R is unknown. In this prospective study we evaluated anti-PLA2R, enhanced glomerular staining for PLA2R and variations in PLA2R1 and HLA-DQA1 genes in Indian patients with PMN and examined their association with response to treatment. Methods. A total of 114 adult PMN patients were studied. Anti-PLA2R was estimated before treatment and after 6 and 12 months of therapy. Enhanced glomerular staining for PLA2R was assessed on fresh frozen tissue. Genotype analysis was done on recruited patients and 95 healthy controls by Taq- Man assays for six single-nucleotide polymorphisms (SNPs; rs4664308, rs3749119, rs3749117, rs4664308, rs3828323 and rs2187668). Patients were followed up monthly for a period of 12 months. Results. Of 114 patients, 66.7% showed elevated serum anti- PLA2R by ELISA and 64.9% by indirect immunofluorescence. About 75% had enhanced glomerular staining for PLA2R. A total of 82% of patients had PLA2R-related disease. Reduction in serum anti-PLA2R titer had a significant association with remission of nephrotic syndrome (P = 0.0003) at 6 and 12 months. More than 85% of patients showing >90% reduction in the anti- PLA2R titer achieved remission of the nephrotic state, whereas of those showing <50% reduction in titers, 87.5% had persistent nephrotic state. The SNPs rs3749119, rs3749117, rs4664308 in PLA2R1 and rs2187668 in HLA-DQA1 were significantly associated with PMN. The SNP rs2187668 was associated with anti-PLA2R positivity. Patients with a high-risk genotype had higher anti-PLA2R levels. Conclusion. To conclude, anti-PLA2R and enhanced glomerular PLA2R staining are found in more than two-thirds of Indian PMN cases. A reduction in the anti-PLA2R titer correlated with response to therapy. [ABSTRACT FROM AUTHOR]

Aims Immunoglobulin-G4 (IgG4)-related tubulo-interstitial nephritis (IgG4 TIN) could be the first presentation of IgG4-related systemic disease. Most of the data is from the West or Japan and retrospective, with good patient outcome. Methods This study was carried out from April 2011 to July 2013. We report a prospective follow-up of 11 patients who presented with renal dysfunction and had histological diagnosis of IgG4 TIN followed for a minimum period of 1 year or until end-stage renal disease. Results IgG4 TIN constituted 0.28% of total renal biopsies and 6.5% of all tubulointerstitial nephritis. Patient ages ranged between 21 and 71 years with a male predominance. All the patients had renal dysfunction at presentation with a mean serum creatinine of 5.12 mg/dL. Proteinuria was subnephrotic except when there was coexisting membranous glomerulonephritis (36.4%). The mean 24-h urine protien excretion was 1.8 g. Serum IgG4 levels were elevated in 10 (90.9%) patients. Ten (90.9%) patients had renomegaly and one (9.1%) had focal renal mass. Extra-renal manifestations were present in seven (63.6%). Renal histology showed pattern A in five (45.5%), pattern B in four (36.3%) and pattern C in two (18.1%) patients. All but one patient (90.9%) received immunosuppressive therapy. Four (36.3%) achieved complete remission and three (27.2%) progressed to end stage renal disease. Two patients died due to infections while on steroid therapy. One patient with a mass had end stage renal disease for 12 months and did not improve with steroid therapy, and one (pattern C) had progressive chronic kidney disease on follow-up. Conclusion IgG4 TIN in an Indian cohort most often presents with rapidly progressive renal failure and less often has extra-renal organ involvement. On follow-up, patients can experience a more aggressive course with progression to end stage renal disease. [ABSTRACT FROM AUTHOR]

Aim There have been very few studies comparing cyclophosphamide ( CTX) and calcineurin inhibitor based regimens in the management of non-immunosuppressive symptomatic therapy ( NIST) resistant idiopathic membranous nephropathy ( IMN). The present study was aimed at comparing the efficacy and safety of tacrolimus ( TAC)/steroids with cyclical CTX/steroids ( Modified Ponticelli regimen ( MPR)) in patients with IMN. Methods Idiopathic membranous nephropathy patients ( n = 70) with persistent nephrotic syndrome after at least 6 months of antiproteinuric therapy or with complications of nephrotic syndrome were equally randomized to receive TAC with oral prednisolone ( TAC*) or MPR. Antibodies against m-type phospholipase A2 receptor ( PLA2R Ab) were tested for at baseline and, at 6 and 12 months after the start of therapy. The primary end point was achievement of remission and secondary objectives were adverse effects and estimated glomerular filtration rate in both the study groups. Results Intention-to-treat analysis showed that remissions at the end of 6 (74% with TAC* vs. 60% with MPR; P = 0.30) and 12 months (71% with TAC* vs. 77% with MPR; P = 0.78) were comparable. PLA2R Ab titres at 6/12 months correlated with urine protein (r 0.54/0.58) and serum albumin (r −0.49/−0.53) at the end of therapy. Patients on CTX had a significantly higher risk of amenorrhea and while those on TAC had a greater risk of reversible nephrotoxicity. Conclusion In NIST refractory IMN, both TAC* and MPR are comparable, but with different adverse effect profile. PLA2R Ab has a very good association with proteinuria, and should be regularly monitored on clinical follow-up. [ABSTRACT FROM AUTHOR]

Idiopathic membranous nephropathy ( IMN), the commonest cause of adult nephrotic syndrome ( NS), accounts for only a minority of paediatric NS. Antibodies to m-type phospholipase A2 receptor ( PLA2R) are seen in two-thirds of adult IMN cases. PLA2R staining in glomerular deposits is observed in 74% and 45% of adult and paediatric IMN cases, respectively. However, there are no reports of anti- PLA2R in paediatric IMN. We evaluated anti- PLA2R levels and PLA2R in gloemrular deposits in paediatric IMN seen at our center. Five cases were enrolled, all the cases stained for PLA2R in glomeruli and three (60%) had antibodies to PLA2R antigen. There was a parellel reduction in proteinuria and anti- PLA2R titer. The present report suggests that PLA2R has a contributory role in the pathogenesis of paediatric IMN. [ABSTRACT FROM AUTHOR]

To meet the increased customer demands, microgrid evolved. The structure of microgrid changes dynamically due to the intermittent nature of renewable-based generation, status of the distributed generator and opening of breakers for fault/maintenance. Hence, the magnitude of fault current is dynamic in nature. In order to deal with these dynamic changes, this paper addresses an adaptive central microgrid controller-based protection and relay coordination scheme, which revises the relay settings dynamically (both radial and looped configuration) for every change in topology. In the proposed algorithm, the primary relay responds to a fault immediately since the individual relays are given with fault level setting. For any abnormality in the network, the fault location is determined both via local relay and microgrid central controller (MCC). Hence, even though the local relay fails to identify the fault due to high fault impedance, the MCC locates the fault accurately and isolates the minimum faulty part. The coordination between relays is carried out by MCC in a time-graded manner based on microgrid central protection and relay coordination algorithm. The proposed algorithm is tested using Matlab in a microgrid built based on the IEEE 33 bus distribution network. [ABSTRACT FROM AUTHOR]

Introduction Management of adults with steroid-resistant (SR) nephrotic syndrome due to focal segmental glomerulosclerosis (FSGS) is a challenging task. Is tacrolimus (TAC) effective in this situation without serious adverse effects? This prospective study was done to answer this question. Materials and methods In patients with SR nephrotic syndrome due to FSGS, oral TAC (0.1 mg/kg/day) was started targeting a trough level of 5–10 ng/mL along with oral prednisolone (0.15 mg/kg/day) for 48 weeks. In patients with complete remission (CR), TAC dose was reduced to a target of 3–6 ng/mL whereas in partial responders, TAC trough levels were kept at 5–10 ng/mL. TAC was discontinued in those with no remission at 24 weeks and was deemed TAC resistant. Outcome, namely CR and partial remission (PR), was assessed at the end of 24 and 48 weeks. All patients were prospectively followed for 60 weeks. Relapses after CR or PR were recorded; adverse effects, namely nephrotoxicity (>25% rise in creatinine), cosmetic effects, infections and hyperglycemia, were recorded every month. Results A total of 44 SR-FSGS [not otherwise specified 33 (75%), tip lesion 03 (6.8%) and cellular variant 8 (18.1%)] were analyzed. Mean age was 25.16 ± 8.26 (18–51) years. Of 44 patients, CR and PR were achieved in 17 (38.6%) and 06 (13.6%) patients, respectively. TAC resistance was seen in 21 (47.7%) patients. Time taken to achieve remission was 15.2 ± 6 weeks. Five (21.7%) patients with CR had relapse on tapering the dose and seven (30.4%) after stopping TAC. Reversible nephrotoxicity was seen in seven (15.9%) and irreversible in four patients (9%). TAC-related diarrhea was the problem in 10 (22.7%), and infections were seen in 19 patients (43.1%). Impaired fasting glucose and diabetes mellitus were seen in 10 patients (22.7%). Conclusion TAC is an effective agent in the management of SR-FSGS. However, strict renal function and blood sugar monitoring is required due to its potential nephrotoxicity and diabetogenic potential. [ABSTRACT FROM AUTHOR]

This research paper deals with the passivity and synchronization problem of fractional-order memristor-based competitive neural networks (FOMBCNNs) for the first time. Since the FOMBCNNs' parameters are state-dependent, FOMBCNNs may exhibit unexpected parameter mismatch when different initial conditions are chosen. Therefore, the conventional robust control scheme cannot guarantee the synchronization of FOMBCNNs. Under the framework of the Filippov solution, the drive and response FOMBCNNs are first transformed into systems with interval parameters. Then, the new sufficient criteria are obtained by linear matrix inequalities (LMIs) to ensure the passivity in finite-time criteria for FOMBCNNs with mismatched switching jumps. Further, a feedback control law is designed to ensure the finite-time synchronization of FOMBCNNs. Finally, three numerical cases are given to illustrate the usefulness of our passivity and synchronization results. [ABSTRACT FROM AUTHOR]

Kidney transplantation (KT) is only viable renal replacement option for most patients in India. Most patients do not have health insurance and meet treatment expenditure from their own resources. We prospectively evaluated the expenses associated with KT and its impact on the socioeconomic status of families in a public hospital. All direct and indirect expenses incurred by the patients from the time of diagnosis of chronic kidney disease to KT were recorded. Direct expenses included physician fees, cost of drugs and disposables, dialysis, and expenses on investigations and hospitalization. Indirect expenses included travel, food, stay, and loss of income suffered by the family. Educational dropout and financial loss were also recorded. There were 43 males and 7 females between the ages of 12 and 57 years. Direct expenses ranged from US$ 2,151–23,792 and accounted for two-thirds of the total expenses. Pre-referral hospitalization, dialysis and medication accounted for majority of direct expense. Indirect expenses ranged from US$ 226–15,283. Travel expenses and loss of income accounted for most of indirect expense. About 54%, 8%, and 10% of families suffered from severe, moderate, and some financial crisis respectively. A total of 38 families had job losses, and 1 patient and 12 caregivers dropped out of studies. To conclude, KT is associated with catastrophic out-of-pocket expenditure and pushes a majority of the patients who come for treatment to public hospitals into severe financial crisis. Educational dropout and loss of jobs are other major concerns. Systematic efforts are required to address these issues. [ABSTRACT FROM AUTHOR]

Sexual and gonadal dysfunction/infertility are quite common in patients with chronic kidney disease. Forty percent of male and 55% of female dialysis patients do not achieve orgasm. The pathophysiology of gonadal dysfunction is multifactorial. It is usually a combination of psychological, physiological, and other comorbid factors. Erectile dysfunction in males is mainly due to arterial factors, venous leakage, psychological factors, neurogenic factors, endocrine factors, and drugs. Sexual dysfunction in females is mainly due to hormonal factors and manifests mainly as menstrual irregularities, amenorrhea, lack of vaginal lubrication, and failure to conceive. Treatment of gonadal dysfunction in chronic kidney disease is multipronged and an exact understanding of underlying pathology is essential in proper management of these patients. [ABSTRACT FROM AUTHOR]

Keywords: Endosonography; Tuberculosis; Fine needle biopsy; Histoplasmosis EN Endosonography Tuberculosis Fine needle biopsy Histoplasmosis 2204 2206 3 05/18/23 20230601 NES 230601 Histoplasmosis, caused by I Histoplasma capsulatum i , is an uncommon life-threatening infection in immunocompromised patients [[1]]. In tuberculosis (TB) endemic areas like India, TB is the commonest cause of mediastinal lymphadenopathy, even in immunocompromised patients and histoplasmosis is rarely reported [[2]]. [Extracted from the article]

The article presents a case study of 19-year-old-male with swelling of the lower limbs and periorbital puffiness of 2 months' duration. The diagnosis of minimal-change disease (MCD) was made and the patient was started on oral prednisolone. The patient treated with rituximab and results show a favourable effect of rituximab in an adult with CG.

This article interrogates the issue of global asymptotic stability and synchronization analysis of uncertain multi‐agent systems (MASs) with multiple time‐varying delays (discrete and distributed) and impulsive perturbations. In this problem, we prove the existence and uniqueness of the equilibrium point using Brouwer degree properties for the addressed MASs. By applying the approach of Lyapunov–Krasovskii function into the considered system, we achieve the global asymptotic stability and the synchronization criteria by designing the pining control strategy into the MAS. Finally, we provide two numerical calculations along with the computational simulations to check the validity of the theoretical findings reported in this article. [ABSTRACT FROM AUTHOR]

Background The increasing burden of kidney failure (KF) in India necessitates provision of cost-effective kidney replacement therapy (KRT). We assessed the comparative cost-effectiveness of initiating KRT with peritoneal dialysis (PD) or haemodialysis (HD) in the Indian context. Methods The cost and clinical effectiveness of starting KRT with either PD or HD were measured in terms of life years (LYs) and quality-adjusted life years (QALYs) using a mathematical Markov model. Complications such as peritonitis, vascular access–related complications and blood-borne infections were considered. Health system costs, out-of-pocket expenditures borne by patients and indirect costs were included. Two scenarios were considered: Scenario 1 (real-world scenario)—as per the current cost and utilization patterns; Scenario 2 (public programme scenario)—use in the public sector as per Pradhan Mantri National Dialysis Programme (PMNDP) guidelines. The lifetime costs and health outcomes among KF patients were assessed. Results The mean QALYs lived per KF person with PD and HD were estimated to be 3.3 and 1.6, respectively. From a societal perspective, a PD-first policy is cost-saving as compared with an HD-first policy in both Scenarios 1 and 2. If only the costs directly attributable to patient care (direct costs) are considered, the PD-first treatment policy is estimated to be cost-effective only if the price of PD consumables can be brought down to INR70/U. Conclusions PD as initial treatment is a cost-saving option for management of KF in India as compared with HD first. The government should negotiate the price of PD consumables under the PMNDP. [ABSTRACT FROM AUTHOR]

The article presents a case study of 28-year-old primigravida having vaginal bleeding and pain abdomen at 28 week of gestation. Her previous reports shows only blood pressure and no abnormalities. The article discusses microangiopathic haemolysis normal prothrombin and activated thromboplastin times.

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

India is seeing a rapid rise in Coronavirus disease-2019 (COVID-19). Immunosuppression is a possible risk factor for severe COVID-19, although their exact interaction is unclear. A total of 13 cases with active lupus nephritis (LN, with or without extra-renal manifestations) were managed with intense immunosuppression between January 2020 and June 2020 during the COVID-19 pandemic at our center. There were no other comorbidities in any patient. All patients received hydroxychloroquine as a part of standard of care. Vigorous precautionary measures were taken for preventing infection in all. One patient developed acute respiratory distress syndrome but was tested negative for COVID-19. None of the other 12 patients developed symptoms suggestive of COVID-19. We report safe management of patients with active LN with intense immunosuppression along with vigorous precautions amidst the COVID-19 pandemic. The role of hydroxychloroquine along with timely precautions needs to be further explored as protective measures against COVID-19 among systemic lupus erythematosus patients. [ABSTRACT FROM AUTHOR]

This article examines the role of B cells in the development and treatment of primary podocytopathies, specifically minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS). The study focuses on adults with new-onset nephrotic syndrome (NS) caused by primary podocytopathy and compares them to healthy controls. The findings indicate that B cell proportions differ between children and adults, and specific B cell subsets are associated with disease activity and predict response to steroid treatment. These findings have implications for targeted therapies for primary podocytopathies. However, more research is needed to confirm these results. [Extracted from the article]

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. [ABSTRACT FROM AUTHOR]

A letter to the editor in response to the article "Serial monitoring of anti-PLA2R in initial PLA2R-negative patients with primary membranous nephropathy," that

A letter to the editor is presented regarding a study about the role of Tacrolimus (TAC) in patients with nephrotic syndrome (NS) and in the management of steroid-dependent minimal change disease (SDMCD).

The article discusses a study that aims to assess the role of Tacrolimus (TAC) only therapy in patients of nephrotic syndrome due to idiopathic membranous glomerulonephritis (IMGN)-resistant to modified Ponticelli regimen (MPR2). Calcineurin inhibitors (CNIs) have been used in IMGN. TAC is effective in a minority of patients with MPR-resistant IMGN and is associated with significant side-effects as concluded.

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. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented on the use of rituximab therapy for the management of steroid resistant (SR) C1q nephropathy (C1qN) in a 13-year old girl suffering with nephrotic syndrome (NS).

The article presents a case study of a 23-year old man who has fever, shortness of breath and progressive blurring of vision over one week. His light microscopic examination of the kidney tissue shows multiple confluent necrotizing epitheloid cell granulomas that are replacing tubules. He was given a four-drug antituberculosis treatment which helped restore his vision. The article discusses acute interstitial nephritis which accounts for 15-25% of biopsies done for acute kidney injury patients.

Introduction Nearly 220000 patients are diagnosed with end-stage renal disease (ESRD) every year, which calls for an additional demand of 34 million dialysis sessions in India. The government of India has announced a National Dialysis Programme to provide for free dialysis in public hospitals. In this article we estimate the overall cost of performing hemodialysis (HD) in a tertiary care hospital. Second, we assess the catastrophic impact of out-of-pocket expenditures (OOPEs) for HD on households and its determinants. Methods The economic health system cost of HD was estimated using bottom-up costing methods. All resources, capital and recurrent, utilized for service delivery from April 2015 to March 2016 were identified, measured and valued. Capital costs were annualized after accounting for their useful life and discounting at 3% for future years. Sensitivity analyses were undertaken to determine the effect of variation in the input prices and other assumptions on the annual health system cost. OOPEs were assessed by interviewing 108 patients undergoing HD in the study hospital to account for costs from the patient's perspective. The prevalence of catastrophic health expenditures (CHEs) was computed per threshold of 40% of non-food expenditures. Results The overall average cost incurred by the health system per HD session was INR 4148 (US$64). Adjusting for capacity utilization, the health system incurred INR 3025 (US$47) per HD at 100% bed occupancy. The mean OOPE per patient per session was INR 2838 (US$44; 95% confidence interval US$34–55). The major components of this OOPE were medicines and consumables (64.1%). The prevalence of a CHE per HD session was 11.1%. Conclusion Our study findings would be useful in the context of planning for dialysis services, setting provider payment rates for dialysis under various publicly sponsored health insurance schemes and undertaking future cost-effectiveness analysis to guide resource allocation decisions. [ABSTRACT FROM AUTHOR]

Background: Reports on long-term complications of childhood-onset nephrotic syndrome (NS), such as obesity, osteoporosis, growth failure, and hypertension, are mostly from developed countries not representing South Asian ethnicities. Furthermore, data on cardiovascular health among patients with childhood-onset NS are limited. Methods: This was an observational study involving patients attending a tertiary care center. Patients aged 15 years and older were examined for long-term complications and remission of NS at their visit in December 2021. Childhood-onset NS meant onset of NS before 10 years of age. Long-term complications included obesity, growth failure, low bone mineral density (BMD) Z score, hypertension, and increased carotid intima-media thickness (cIMT). Long-term remission was defined as no relapse for the last ≥ 3 consecutive years without immunosuppressive medication to maintain remission. Results: Of 101 patients studied (~ 80% with frequent relapsing (FR)/steroid-dependent (SD) NS), the mean age was 17.6 (± 2.4) years at the time of study. Long-term complications were noted in 89.1% of patients which included one or more of the following: obesity (22.7%), growth failure (31.7%), low BMD Z score (53.5%), hypertension (31.7%), and high cIMT (50.5%). Thirty-nine patients (38.6%) were in long-term remission at the time of the study. Growth failure and low BMD Z scores were less frequent in patients with long-term remission compared to those without long-term remission. Conclusions: In patients with childhood-onset NS (predominantly FR/SDNS) who were studied at ≥ 15 years of age, ~ 90% had long-term complications which included high cIMT in 50%. Only ~ 40% were in long-term remission. [ABSTRACT FROM AUTHOR]