Clinical Profile and Outcome in Long-term Hemodialysis: A Comparative Study of Hospital-based Versus Standalone Units.

Introduction: Chronic hemodialysis (CHD) remains the most "resorted to" renal-replacement option in India. Pursuit for accessible and affordable dialysis has resulted in setting up standalone centers (SACs). We need more Indian data on the profile of CHD population and outcome of SAC compared to hospital-based units (HBUs). Material and Methods: We analyzed the clinical profile of patients on CHD for >5 years, compared the outcome between HBU and SAC, and analyzed the factors associated with mortality. Patients initiated between January 1, 2006 and December 31, 2012 and who have survived 5 years on CHD at HBU or SAC were enrolled and followed up prospectively for 2 years. Their clinical and biochemical profile, comorbidities, long-term complications, and mortality were analyzed. Results: The study included 137 patients, 41 (30%) from HBU and 96 (70%) from SACs. In both groups, the patients were predominantly male, aged 51-70 yrs, diabetic, unplanned initiation through catheters, and had average-dialysis vintage between 83 and 85 months. SAC had more patients with hemoglobin (> 11 gm/dL) and hyperparathyroidism with elevated SAP levels (P < 0.05). Both groups had comparable iron stores, serum calcium, and phosphorus. Comparable between groups, infections, coronary artery disease, and access complications accounted for most hospitalizations and sudden cardiac death and sepsis accounted for most mortality. A trend of better survival was seen in SAC. Multivariate analysis showed anemia, DM and hospitalizations were associated with mortality. Conclusion: We conclude that the outcomes of long-term CHD at SACs are not inferior to HBUs. Anemia, diabetes, and hospitalizations were associated with overall mortality. Benefits of SACs in cost, QOL, and employment opportunities need to be studied in the Indian context.

Management strategies and outcomes in renal transplant recipients recovering from COVID-19: A retrospective, multicentre, cohort study.

Background: There is an enormous knowledge gap on management strategies, clinical outcomes, and follow-up after kidney transplantation (KT) in recipients that have recovered from coronavirus disease (COVID-19). Methods: We conducted a multi-center, retrospective analysis in 23 Indian transplant centres between June 26, 2020 to December 1, 2021 on KT recipients who recovered after COVID-19 infections. We analyzed clinical and biopsy-confirmed acute rejection (AR) incidence and used cox-proportional modeling to estimate multivariate-adjusted hazard ratios (HR) for predictors of AR. We also performed competing risk analysis. Additional outcome measures included graft loss, all-cause mortality, waiting time from a positive real-time polymerase test (RT-PCR) to KT, laboratory parameters, and quality of life in follow-up. Findings: Among 372 KT which included 38(10·21%) ABO-incompatible, 12(3·22%) sensitized, 64(17·20%) coexisting donors with COVID-19 history and 20 (5·37%) recipients with residual radiographic abnormalities, the incidence of AR was 34 (9·1%) with 1(0·26%) death censored graft loss, and 4(1·07%) all-cause mortality over a median (interquartile range) follow-up of 241 (106-350) days. In our cox hazard proportional analysis, absence of oxygen requirement during COVID-19 compared to oxygen need [HR = 0·14(0·03-0·59); p-value = 0·0071], and use of thymoglobulin use compared to other induction strategies [HR = 0·17(0·03-0.95); p-value = 0·044] had a lower risk for AR. Degree of Human leukocyte antigen (HLA) DR mismatch had the highest risk of AR [HR = 10.2(1·74-65·83); p-value = 0·011]. With competing risk analysis, with death as a competing event, HLA DR mismatch, and oxygen requirement continued to be associated with AR. Age, gender, obesity, inflammatory markers, dialysis vintage, steroid use, sensitization and ABO-incompatibility have not been associated with a higher risk of AR. The median duration between COVID-19 real time polymerase test negativity to transplant was 88(40-145) days (overall), and ranged from 88(40-137), 65(42-120), 110(49-190), and 127(64-161) days in World Health Organization ordinal scale ≤ 3, 4, 5, and 6-7, respectively. There was no difference in quality of life, tacrolimus levels, blood counts, and mean serum creatinine assessed in patients with a past COVID-19 infection independent of severity. Interpretation: Our findings support that the outcomes of KT after COVID-19 recovery are excellent with absence of COVID-19 sequelae during follow-up. Additionally, there does not seem to be a need for changes in the induction/immunosuppression regimen based on the severity of COVID-19. Funding: Sanofi.

ABO-incompatible transplantation without conventional induction immunosuppression (IL-2RB or depleting agents).

Transplantation across the ABO blood group (ABOI-Tx) has facilitated to increase in donor pool for living donor kidney transplantation. Increased risk of rejection despite augmented immunosuppression has been the concern for many transplant programs in initiating an ABOI-TX program. The benefits of induction immunosuppression on long-term graft survival in immunologically low-risk individuals are still not clear. Increased immunosuppression of ABOI-Tx recipients before transplantation could provide an opportunity to transplant without induction with IL2-R blockers or Lymphocyte depleting agents. The aim of our study is to analyze the outcome of our series of 25 consecutive ABOI-Tx patients who underwent transplantation without routine thymoglobulin or IL2R-blocker induction. Our study is a prospective observational study for the first 25 consecutive patients who had undergone ABOI-Tx from two tertiary care centers in Kerala, India, having the same IS protocol. Anti-A and anti-B titers ≤1:512 by Gel-method (Biorad) were accepted for desensitization. Patients underwent CDC-crossmatch, Flow-crossmatch, and Luminex-anti-HLA-antibody-screen. Desensitization regimen included- Rituximab 200 mg on Day-21, Triple IS Prednisolone 10 mg, mycophenolate mofetil 1000 mg, and Tacrolimus 0.06 mg/bodywt from Day-14 and Plasma-exchange (PLEX) 3-4 sessions from day -7 to attain titer of 1:8 before transplantation. Transplantation was done without induction IS. Twenty-five patients underwent ABOI-Tx from both centers. Twenty recipients were male. The average age was 34.5 ± 8 years with follow-up of 503 ± 120 days. Eight donors were spouse, 13 were parents and three siblings. The average age of the donor was 46.3 ± 10.5 years. Twenty-two patients have normal functioning transplant with creatinine 1.23 ± 0.2 mg/dL. Kaplan-Meier analysis showed patient survival of 91.2% and death censored graft survival of 95.6% at 36 months. Two patients were lost; one on the postoperative day (POD)-3 due to ACS and second on POD-22 due to sepsis. One graft loss occurred due to posttransplant HUS. Of the functioning 22 allograft-recipients, one had cellular rejection, which resolved with pulse steroids; one developed HUS due to CNI, which recovered with PLEX and switch to non-CNI based IS. One patient developed AMR on POD-4, which was completely reversed with PLEX, intravenous immunoglobulin (IVIG), and augmentation of IS. Three patients had CMV viremia and another three patients had BKV viremia, all resolved with treatment and tailoring of IS. Achieving acceptable anti-A/B titers prior to transplantation is the most critical step in ABOI-Tx. Avoidance of induction IS can reduce cost and infectious complications. Our data showed that there is no increased incidence of rejections in the first post-transplant year for immunologically low-risk individuals from histocompatibility standpoint undergoing ABOI-Tx without induction immunosuppression.

Paying for Hemodialysis in Kerala, India: A Description of Household Financial Hardship in the Context of Medical Subsidy.

INTRODUCTION: Many low- and middle-income countries are implementing strategies to increase dialysis availability as growing numbers of people reach end-stage renal disease. Despite efforts to subsidize care, the economic sustainability of chronic dialysis in these settings remains uncertain. We evaluated the association of medical subsidy with household financial hardship related to hemodialysis in Kerala, India, a state with high penetrance of procedure-based subsidies for patients on dialysis. METHODS: Patients on maintenance hemodialysis at 15 facilities in Kerala were administered a questionnaire that ascertained demographics, dialysis details, and household finances. We estimated direct and indirect costs of hemodialysis, and described the use of medical subsidy. We evaluated whether presence of subsidy (private, charity, or government-sponsored) was associated with lower catastrophic health expenditure (defined as ≥40% of nonsubsistence expenditure spent on dialysis) or distress financing. RESULTS: Of the 835 patients surveyed, 759 (91%) reported their households experienced catastrophic health expenditure, and 644 (77%) engaged in distress financing. Median dialysis-related expenditure was 80% (25th-75th percentile: 60%-90%) of household nonsubsistence expenditure. Government subsidies were used by 238 (29%) of households, 139 (58%) of which were in the lowest income category. Catastrophic health expenditure was present in 215 (90%) of households receiving government subsidy and 332 (93%) without subsidy. CONCLUSIONS: Provision of medical subsidy in Kerala, India was not associated with lower rates of household financial hardship related to long-term hemodialysis therapy. Transparent counseling on impending costs and innovative strategies to mitigate household financial distress are necessary for persons with end-stage renal disease in resource-limited settings.

Spectrum of biopsy-proven renal diseases: A single center experience.

Kidney biopsy is one of the most important tools in the assessment of kidney disease as histopathological diagnosis promotes evidence-based practice in Nephrology. This study included 271 consecutive percutaneous kidney biopsies (145 males and 126 females) performed at EMS Memorial Cooperative Hospital, Perinthalmanna, Kerala, India, from September 2009 to March 2016. Among the biopsy-proven renal diseases (BPRD), primary glomerular diseases (PGD) were the most common (77.78%) followed by secondary glomerular diseases (SGD) (12.22%) and tubulointerstitial diseases (10%). The IgA nephropathy (IgAN) was the most common PGD and majority had mesangial hypercellularity (M1) (93.54%), tubular atrophy (T1 or T2 68.25%), and the most common pattern was M1, E0, S0, and T1, suggesting that patients of Indian subcontinent have aggressive disease type, unlike western literature. The focal segmental glomerulosclerosis (FSGS) was the second most common PGD and the majority were of not otherwise specified type. FSGS, membranous nephropathy and minimal change disease were the three most common causes for PGD causing nephrotic syndrome. Diabetic nephropathy and lupus nephritis were the two most common biopsy-proven SGDs. Among the patients of diabetes mellitus who underwent renal biopsy with suspicion of nondiabetic renal disease (NDRD), 58.33% had NDRD, 16.67% had DN+ NDRD, and 26.67% had DN alone. This study shows the changing pattern BPRD in comparison to earlier studies. This study also confirms the aggressive nature of IgAN in Indian patients and underlines the importance of renal biopsy in patients of DM.

Case Report: Application of whole exome sequencing for accurate diagnosis of rare syndromes of mineralocorticoid excess.

Syndromes of mineralocorticoid excess (SME) are closely related clinical manifestations occurring within a specific set of diseases. Overlapping clinical manifestations of such syndromes often create a dilemma in accurate diagnosis, which is crucial for disease surveillance and management especially in rare genetic disorders. Here we demonstrate the use of whole exome sequencing (WES) for accurate diagnosis of rare SME and report that p.R337C variation in the HSD11B2 gene causes progressive apparent mineralocorticoid excess (AME) syndrome in a South Indian family of Mappila origin.

Caregiver burden among nocturnal home hemodialysis patients.

Recent studies have suggested improvements in quality of life (QOL) in patients on quotidian dialysis compared with conventional hemodialysis. Few studies have focused on the burden and QOL in caregivers of patients with end-stage renal disease (ESRD) on nocturnal home hemodialysis (NHD). We aim to assess the caregivers' burden, QOL, and depressive symptoms and to compare these parameters with their patients' counterparts. Cross-sectional surveys were sent to 61 prevalent NHD patients and their caregivers. Surveys assessed demographics, general self-perceived health using the 12-Item Short Form Health Survey (SF-12) and the presence of depression using the Beck Depression Inventory. Subjective burden on caregivers was assessed by the Caregiver Burden scale and was compared with perceived burden by the patients. Thirty-six patients and 31 caregivers completed the survey. The majority of caregivers were female (66%), spouse (81%) with no comorbid illness (72%). Their mean age was 51 ± 11 years. Patients were mostly male (64%) with a median ESRD vintage of 60 months (interquartile range [IQR], 18-136 months) and a mean age of 52 ± 10 years. Compared to caregivers, patients had lower perceived physical health score but had similar mental health score. Depression criteria were present in 47% of patients and 25% of caregivers. Total global burden perceived by either caregivers or patients is relatively low. Although there is a relatively low global burden perceived by caregivers and patients undergoing NHD, a significant proportion of both groups fulfilled criteria for depression. Further innovative approaches are needed to support caregivers and patients performing NHD to reduce the intrusion of caring for a chronic illness and the risk of developing depression.

Delayed graft function and the risk of death with graft function in living donor kidney transplant recipients.

BACKGROUND: The link between delayed graft function (DGF) and death with graft function (DWGF) in living donor kidney transplant recipients presently is unknown. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: 44,630 adult living donor kidney recipients (first transplants only) in the US Renal Data System from January 1, 1994, to December 31, 2004. PREDICTOR: DGF, defined as the need for dialysis therapy in the first week after transplant. OUTCOME: Time to DWGF. MEASUREMENTS: Kaplan-Meier curves were constructed to assess the impact of DGF on DWGF. Recipients with DGF were 1:1 propensity score matched to those without DGF, and time-dependent Cox proportional hazards models were used to examine factors associated with DWGF. Subgroup and sensitivity analyses also were conducted. RESULTS: DWGF occurred in 3,878 patients during 3.9 years' (median) follow-up. In patients with DGF, survival with graft function at 1, 3, 5, and 10 years was 91.9%, 86.8%, 81.6%, and 61.7%, respectively (in patients without DGF, these values were 98.0%, 95.2%, 91.6%, and 80.1%, respectively; P < 0.001 compared with the DGF group). In a fully adjusted time-dependent Cox model, HRs for DWGF in patients with DGF (vs without DGF) were 6.55 (95% CI, 4.78-8.97), 3.55 (95% CI, 2.46-5.11), 2.07 (95% CI, 1.53-2.81), and 1.48 (95% CI, 1.26-1.73) at 0-1, 1-3, 3-12, and longer than 12 months posttransplant, respectively. Propensity score analysis showed similar results. Inferences were unchanged after adjustment for kidney function and acute rejection at 6 months and 1 year posttransplant. Cardiovascular and infectious causes of DWGF were more prevalent in patients with DGF. The association was more marked in female recipients and robust to various sensitivity analyses. LIMITATIONS: The impact of lesser decreases in early graft function could not be evaluated. CONCLUSIONS: DGF is associated with an increased risk of DWGF in living donor kidney recipients. The mechanisms underlying this relation require further study.