Predictors of functional impairment and mortality in patients on maintenance hemodialysis.

INTRODUCTION: Numerous factors impact the mortality and functional abilities of patients with end-stage renal disease (ESRD) receiving maintenance hemodialysis (MHD). We aimed to determine the mortality rate at 1 year of MHD, identify predictors of mortality, and assess functional impairments concerning activities of daily living (ADLs) and instrumental ADL (IADL). METHODS: Our study was prospective, observational cohort study that enrolled patients receiving MHD. We collected demographic, clinical, and laboratory data. We also assessed ADLs and IADLs for daily performance. RESULTS: Our study included 167 patients with a mean age of 51.6 ± 13.1 years, and 56.9% were male. Of these, 80 (47.9%) were diabetic, and 145 (86.8%) were hypertensive. The mortality rate after 1 year of MHD was 10.8%, and cardiovascular causes accounted for over 70% of total deaths. Sudden cardiac death was the most frequent cause (38.9%), followed by cardiogenic shock (22.2%). Older age and low parathormone levels (<300 pg/mL) were significantly associated with higher mortality rates. Mean ADL and IADL scores were 4.5 ± 1.3 and 6.3 ± 2.7, respectively. Eighteen (10.8%) and 56 (33.5%) patients had low ADL and IADL scores, respectively. Although statistically insignificant, a higher proportion of non-survivors exhibited low IADL and ADL scores. Older age, longer diabetes duration, and higher BMI levels were significantly associated with lower IADL scores. CONCLUSIONS: Older age and suppressed PTH levels are predictors of mortality in ESRD patients receiving MHD. These patients require regular follow-ups to rule out cardiovascular morbidity. Functional impairment is prevalent but remains underdiagnosed in MHD patients. It should be monitored regularly to improve quality of life in ESRD.

Indian TrANslational GlomerulonephrItis BioLogy nEtwork (I-TANGIBLE): Design and Methods.

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.

Diabetic with Nephrotic Syndrome: A Case of "Masked" Membranous Nephropathy - A Case Report.

Distinguishing nondiabetic renal disease (NDKD) from diabetic nephropathy (DN) is of paramount importance in choosing treatment modalities and determining renal prognosis. Nearly 40% of the patients with diabetes are likely to have NDKD. We report a case of a patient with diabetes with a massive nephrotic range of proteinuria that was labeled as DN based on LM and IF, but paraffin IF confirmed the presence of masked MN.

Induction with rATG versus No-induction in Deceased Donor Renal Transplantation - A Retrospective Observational Study.

Introduction: Deceased donor renal transplantation (DDRT) poses special immunological challenges; particularly in resource-poor scenarios. There is substantial evidence that rabbit antithymocyte globulin (rATG) is superior to interleukin-2 receptor blocker and placebo among patients at high immunological risk. However, due to the lack of randomized controlled trials, this remains controversial in DDRT maintained on tacrolimus/mycophenolic acid/steroids. Here, in this study, we compared the clinical outcomes of induction with rATG therapy to no-induction therapy. Methods: The study was a single-center, retrospective cohort study. A total of 62 patients were divided into two groups, based on induction immunosuppression; induction with rATG (N = 25) and no-induction group (N = 37). Both groups received tacrolimus/mycophenolate mofetil sodium/prednisolone as maintenance immunosuppression. The main outcomes were incidence of acute rejection (AR) within the first year and graft survival at the end of 1 year. Results: The AR at the end of 1-year was reported as 8% and 27% for the induction and no-induction groups (P = 0.07), respectively. A total of 15 patients died. Patient survival rates at 12 months were 83.8% (no-induction) and 64.0% (induction; P = 0.094). Death-censored graft survival rates, 12 months after transplantation, were similar in both treatment groups (83.7% vs. 83.5%, P = 0.972). The incidence of death with functioning graft was significantly high in the induction group (28% vs. 5.4%, P = 0.045). Conclusion: The incidence of AR was less in patients who received rATG induction compared with patients who did not receive any form of induction. An added advantage of induction with ATG in terms of reduced incidence of AR must be weighed against high incidence of infection, death with functioning graft, and death.

Revisiting Vasculopathy in Lupus Nephritis: A Renal Biopsy Evaluation Study.

Introduction: The classification of lupus nephritis (LN) on biopsy is essentially focused on morphologic changes in glomeruli. Renal vascular lesions are not addressed in detail in current classifications and are often overlooked. We aimed to determine the prevalence of vascular lesions in LN on biopsies and to compare these with biopsies not showing the vasculopathies. Methods: A total of 740 renal biopsies of LN were analysedfor presence of vasculopathies from January 2013 to June 2019. Of these, 527 (71.2%) biopsies showed vascular lesions (vascular group), which were further categorized into known five subtypes according to morphology and immunofluorescence (IF) findings. Remaining 213 (28.8%) biopsies constituted non-vascular group. Clinical, demographic and laboratory parameters were compared between these two groups. Results: The mean age was 27.95 ± 9.8 years and 27.0 ± 9.4 years in the vascular and non-vascular groups respectively with higher M:F (1:2 > 1:7) in vascular group. Majority of vasculopathies (257, 48.7%) were found in biopsies with class IV LN. Haematuria (69.8% vs. 20.1%), proteinuria (100% vs. 62%), anemia (48.3% vs. 3.60%) and hypertension (39.8% vs. 8.46%) were common in group I. Uncomplicated vascular immune deposits (426; 80.8%) were the most common vasculopathy and true vasculitis (4;0.8%) was least common. Activity and chronicity indices (7.35 ± 3 and 2.45 ± 1.5, respectively) were significantly higher in the vascular group. Activity index was highest in uncomplicated vascular immune deposits (7.45 ± 2.8) and chronicity index was highest in non-specific sclerotic vascular lesions (2.7 ± 1.6). Conclusion: Vascular involvement is common in LN. Uncomplicated vascular immune deposits were common vasculopathies whereas true vasculitis was least common. The morphology and IF both need to be carefully screened for the diagnosis of vasculopathies.

Is Age a Limitation for Organ Donation? A Comparison of Elderly and Non-elderly Donors in a Deceased Donor Organ Transplantation Program from South India.

To bridge the gap between demand and supply of organs, deceased donors with extreme ages can be utilized. The object of this study was to compare elderly with non-elderly donors and to assess the predictors of organ utilization or wastage. This was a retrospective chart analysis. Univariate and multivariate logistic regression analysis of cohorts was carried out to predict organ utilization or wastage. Of the 716 deceased donors, 16.2% were elderly (≥60 years) and 83.8% were not elderly (≤59 years). Donors in the elderly cohort were more likely to be diabetic, hypertensive, overweight, and smokers compared with non-elderly donors. They had deranged terminal creatinine and succumbed to cerebrovascular accident or intracerebral hemorrhage. They had a high kidney donor risk index (KDRI) of 1.83 ± 0.46. Those in the younger donor cohort, were more likely to have succumbed to road traffic accident-associated traumatic brain injury, were subjected to more efforts to revive them in the intensive care unit via cardiopulmonary resuscitation, had deranged liver function tests, and had a KDRI of 0.93 ± 0.28. The kidney discard rate (KDR) and liver discard rate (LDR) in the elderly donors was 50% and 8.6%, respectively (vis-a-vis the non-elderly at 13.3 % and 7.5%). The KDR was significantly higher than the LDR in elderly donors. The main reason for this was the high number of "marginal kidneys". We revealed that elderly donors formed a significant proportion of deceased donors. The utilization of the liver from deceased donors was more frequent compared with the kidney.

Vaccine-Induced Thrombotic Thrombocytopenia Due to Coronavirus Disease 2019 Vaccine From a Deceased Donor: A Case Report.

With the rapid and massive vaccination campaign against coronavirus disease 2019 (COVID-19) taking place across the globe, there are increasing reports of thrombotic complications with various COVID-19 vaccines such as the Pfizer-BioNTech mRNA, Moderna mRNA, AstraZeneca Oxford (serum institute), and Johnson & Johnson/Janssen vaccines. We report a case of successful organ donation from an 18-year-old woman who presented with cerebral venous thrombosis caused by vaccine-induced thrombotic thrombocytopenia following the first dose of the COVID-19 vaccine (AstraZeneca, University of Oxford, and Serum Institute of India), which caused brain death. Four recipients received 5 organs, kidneys (2), liver (1), and combined heart and lung (1). All 4 recipients had normal graft function without any thrombotic complications after 16 weeks of transplantation. This is first such case being reported from Asian countries.

Effect of Coronavirus Disease 2019 on Transplantation and Nephrology in India: A Nationwide Report From India.

BACKGROUND: The effect of coronavirus disease 2019 (COVID-19) on a developing nation is sparsely reported and, more importantly, the discrepancies in public and private sectors are underexplored. METHODS: We retrospectively investigated the data on the effect of COVID-19 on renal transplantation between 2019 and 2020 in a nationwide analysis from 8 public and 10 private sector hospitals of India. RESULTS: On comparing the yearly data, the number of living-related transplants and deceased donor transplants declined by 48% (2610 vs 1370) and 49% (194 vs 99), respectively. The outpatient numbers and in-center admissions decreased by 40.4% (616,741 vs 367,962) and 30.8 % (73,190 vs 49,918). respectively. There was no increase in the number of renal or graft biopsies in the COVID-19 era. The number of waitlisted patients on hemodialysis was higher in public (304,898 vs 338,343) when compared with private (163,096 vs 150,292) in the last 2 years. Similarly, the number of waitlisted patients on peritoneal dialysis (4655 vs 3526) was higher in the public sector compared with private sector (932 vs 745). The decline in living transplants during the pandemic was higher in public sectors (58%) compared with the private (49%). However, the decline in deceased donation was higher in private (57.9%) relative to public (50.6%). CONCLUSIONS: COVID-19 has adversely affected the transplantation activities across the Indian transplantation centers, with a disproportionately higher impact on waitlisted patients in public sector programs. A sound prioritization of health care resources is mandated to safeguard the most deprived and high-risk waitlisted patients during the pandemic.

Is Early COVID-19 in Kidney Transplant Recipients Concerning Enough to Halt Transplantation? A Multicenter Comparative Analysis from India.

BACKGROUND: Limited data exist on the incidence and outcome of early coronavirus disease 2019 (COVID-19) in kidney transplantation recipients (KTR). METHODS: A retrospective multicenter research study was conducted across 12 centers in India. We explored the symptomatology, demographic, laboratory findings, and outcome of COVID-19 within 30 days of transplantation. The outcome was compared with the overall KTR and waitlisted patients acquiring COVID-19. RESULTS: The incidence of early COVID-19 was 2.6% (n = 22) for the cumulative 838 renal transplants performed since nationwide lockdown in March 2020 until May 2021. Overall, 1049 KTR were diagnosed with COVID-19 and 2% of those had early COVID-19. The median age of the early COVID-19 cohort was 43 (31-46) years. COVID-19 severity ranged from asymptomatic (18.2%), mild (59.1%), moderate (9.1%), and severe (13.6%). Among clinical symptoms, dyspnea and anosmia were frequent, and in laboratory parameters, neutrophil lymphocyte ratio, high-sensitivity C-reactive protein, and D-dimer were higher in patients requiring oxygen. The mortality in early COVID-19 was not higher than overall KTR (4.5% vs 8.5%; P = 1). COVID-19 severity (23.9% vs 15.7%; P = .0001) and mortality (15.5% vs 8.5%; P = .001) among waitlisted patients (n = 1703) were higher compared with overall KTR. CONCLUSIONS: We report higher burden of COVID-19 in waitlisted patients compared with KTR and a favorable outcome in early COVID-19 in KTR. Our report will help the transplant physicians in dealing with the ongoing dilemma of halting or resuming transplantation in the COVID-19 era.

Arterial Thrombosis Associated with Factor V Leiden Mutation in a Child with Nephrotic Syndrome.

Thromboembolism remains a common complication of nephrotic syndrome (NS) in adults and a less common complication in children. Venous thrombosis is well recognized, but arterial thrombosis occurs less frequently and is seen primarily in children. We report a case of arterial thrombosis associated with factor V Leiden (FVL) mutation in a young girl with NS. Screening for inherited thrombophilias such as FVL mutation may be beneficial for NS patients with thromboembolic vascular events not explained by conventional risk factors.

Gender bias in the genetic vulnerability towards type 2 diabetes and diabetic nephropathy: Role of forkhead box Protein3 transcription factor gene variants.

Forkhead Box Protein3 Transcription Factor (FOXP3) gene is an essential role player in the function and differentiation of regulatory T cells. Polymorphisms/mutations in FOXP3 gene cause Treg cell dysfunction, promote autoimmunity and inflammation. Based on this presumption, we screened 600 subjects from south India (equal number of diabetic (T2DM), diabetic nephropathy (T2DN) and healthy controls) for promoter and intronic (rs3761548C/A and rs2294021C/T) polymorphisms of FOXP3 gene. PCR-RFLP method used for genotyping, revealed an association of promoter SNP for both T2DM (OR = 2.41, 95% C.I = 1.67-3.49; p < 0.0001) and T2DN (OR = 2.16, 95% C.I = 1.45-3.24; p < 0.005). While intronic polymorphism with T2DN (OR = 1.91, 95% C.I = 1.28-2.84; p < 0.05). Further, in females rs3761548C/A showed 2.6 and 5.5-fold; rs2294021C/T showed 2.2- and 2.5-fold predisposition towards T2DM and T2DN respectively. Males exhibited a twofold risk (OR = 2.01, 95% C.I = 1.22-3.30; p < 0.05) towards T2DM with promoter and no association with intronic polymorphism. The combined genotypes in females with AA-CC; AA-TT predisposed and CA-CC; CA-CT protected heading towards T2DM and T2DN respectively, suggesting irrespective of type of allele at intronic locus AA and CA at promoter locus promote or protect the individual for diabetes and diabetic nephropathy, further confirmed by MLR. To our knowledge, the current study is the first of its kind that revealed an association of these polymorphisms of FOXP3 gene and gender influence on T2DM and T2DN among South Indians. Functional and cell-based studies on Treg cells are warranted to confirm our results that help to develop FOXP3/Treg based therapeutic interventions. Lack of data on Treg cells is the limitation of this study.

Anti-glomerular basement membrane disease: A clinicomorphological study of 16 cases.

INTRODUCTION: Antiglomerular basement membrane disease manifests as rapidly progressive glomerulonephritis and alveolar hemorrhage. It encompasses 10-15% of crescentic glomerulonephritis and is associated with poor outcome. In this study, we have elaborated on the clinical details, morphological features, and outcome of anti-GBM glomerulonephritis. MATERIALS AND METHODS: All the consecutive biopsy-proven cases of anti-GBM glomerulonephritis over a period of 4½ years were analyzed, retrospectively. RESULTS: Sixteen cases were diagnosed as anti-GBM glomerulonephritis during the study period. Twelve patients presented with rapidly progressive renal failure of which four patients required hemodialysis at the time of presentation. Goodpasture's syndrome was noted in two patients. Thirteen cases were positive for circulating anti-GBM antibodies and two patients showed double positivity for both anti-GBM antibodies and ANCA. Fifteen biopsies revealed crescentic glomerulonephritis with linear deposition of IgG along the glomerular basement membrane in all the 16 cases. CONCLUSION: Renal biopsy analysis is important in the diagnosis of Anti GBM nephritis. Morphology is an important predictor of disease progression.

Link between ACE I/D Gene Polymorphism and Dyslipidemia in Diabetic Nephropathy: A Case-control Study from Hyderabad, India.

INTRODUCTION: Diabetic nephropathy (DN) is the commonest single cause of end-stage renal failure, and dyslipidemia is a critical risk factor in the occurrence of DN. In the light of recent reports emphasizing the importance of angiotensin I-converting enzyme (ACE) in the modulation of plasma lipids, we sought to evaluate the influence of ACE I/D gene polymorphism with dyslipidemia status among type 2 diabetic (T2D) patients with and without nephropathy in the genetic predisposition and the progression to DN. METHOD: This study comprised of 600 subjects, which include patients with DN, T2D, and healthy controls (HC). Polymerase chain reaction based genotyping of ACE I/D polymorphism was performed and appropriate statistical analysis was done. RESULTS: Out of the 600 subjects, 20 (10%) of the HC, 73 (36.5%) of the T2D group, and 125 (62.5%) of the DN subjects had dyslipidemia. The D allele (0.62) and DD (42.5) genotype frequencies were higher in the DN group in comparison with T2D and HC (P < 0.05). The genotypes also varied among patients with dyslipidemia (χ2 5.04; P < 0.05) but not in the non-dyslipidemia group. Under the co-dominant model, DD genotype conferred a risk of 1.26 (P < 0.001) toward DN, whereas the ID genotype offered protection from DN among the dyslipidemic subjects (OR = 0.05; P < 0.01). In addition, genotype-dependent difference was seen in the plasma lipid levels among study groups. A multiple logistic regression analysis revealed male gender, BMI, HbA1c, TG, HDL, and ACE DD genotype as independent risk factors for the development of DN. CONCLUSION: The study showed a significant predisposing association of ACE DD genotype with DN and protective effect of ID genotype on DN in the dyslipidemia subgroup.

A Clinicopathological Study of 267 Patients with Diabetic Kidney Disease Based on the Renal Pathology Society - 2010 Classification System.

INTRODUCTION: Renal biopsy is primarily indicated in patients with diabetes mellitus (DM) with proteinuria, to diagnose non-diabetic renal disease (NDRD). However, Renal Pathology Society classification (RPSc) - 2010 has classified diabetic nephropathy (DN) into four classes of glomerular lesions with a separate scoring for tubulointerstitial and vascular lesions. Paucity of data from Indian subcontinent prompted us to plan this study to classify DN on biopsy as per the RPSc and correlate the clinical profile with histology. MATERIALS AND METHODS: Patients with DM who underwent renal biopsy for various indications (between Aug 2013 and Nov 2015) were included in the study. DN on histology was classified according to RPSc. Histopathology lesions of DN were correlated with clinical and biochemical profiles. RESULTS: Of the 267 patients studied, 252 (94.3%) were type 2 DM. NDRD alone was seen in 65 (24.34%), DN in 161 (60.3%), and NDRD with DN in 41 (15.3%). The most common indications for biopsy were rapidly progressive renal failure (76.7%) and nephrotic syndrome (16.4%). The most common glomerular class was class IV (43.5%), followed class III (41%), class II (13.3%), and class I (1.9%). The most common NDRD seen was acute interstitial nephritis (AIN) in 20.2% and is frequently associated with class III. Tubulointerstitial chronicity and not the arteriolar chronicity, was correlated with low estimated glomerular filtration rate (eGFR). CONCLUSIONS: Most patients with DN subjected to renal biopsy were in class IV, and AIN was the most common NDRD. Only tubulointerstitial chronicity correlated with low eGFR.

A Rare Case of Acute Kidney Injury Due to Levofloxacin-induced Crystal Nephropathy.

Crystal-induced acute kidney injury (AKI) is caused by the intratubular precipitation of crystals, which results in obstruction and kidney injury. Levofloxacin is commonly used fluoroquinolone antibiotic especially for respiratory and urinary tract infections. It rarely causes any serious adverse events. Several cases of crystal nephropathy after ciprofloxacin use have been reported. Pre-existing renal dysfunction, high dose of the drug, and advanced age are considered as risk factors. To best of our knowledge, only two cases of crystal nephropathy due to levofloxacin use have been reported, we add a new one to it. The patient responded to conservative treatment with complete recovery on follow-up.

Persistent Left Superior Vena Cava in a Hemodialysis Patient.

Awareness of persistent left superior vena cava (PLSVC), a rare congenital variant is helpful to a clinician to avoid the unnecessary complications. We report a case of PLSVC in a patient with chronic kidney disease which was identified following a difficult catheterization into the right internal jugular vein (IJV). The catheterization was attempted through the left IJV and the position of which could not be confirmed with check radiograph and two-dimensional echo. PLSVC was suspected in the computed tomography angiography and was confirmed following digital subtraction angiography.

Monoclonal Gammopathy of Renal Significance Presenting as Cryoglobulinemic Glomerulonephritis: A Case Report and Review of Literature.

Monoclonal gammopathy of renal significance (MGRS) can present with myriad of morphological features. We report a case of MGRS in a 46-year-old man who presented with nephrotic-range proteinuria and renal insufficiency. Renal biopsy showed amorphous eosinophilic periodic acid-Schiff positive deposits in capillary loops and lamda light chain positivity on immunofluorescence, suggestive of cyoglobulinemic glomerulonephritis. Serum cryoglobulins were positive. Serum immunoelectrophoresis and immunofixation showed a M band of 0.5 g/dl of IgG lambda type. Bone marrow showed 8% of plasma cells which confirmed the diagnosis of MGRS.

Revisiting renal amyloidosis with clinicopathological characteristics, grading, and scoring: A single-institutional experience.

INTRODUCTION: Kidney involvement is a major cause of mortality in systemic amyloidosis. Glomerulus is the most common site of deposition in renal amyloidosis, and nephrotic syndrome is the most common presentation. Distinction between AA and AL is done using immunofluorescence (IF) and immunohistochemistry (IHC). Renal biopsy helps in diagnosis and also predicting the clinical course by applying scoring and grading to the biopsy findings. MATERIALS AND METHODS: The study includes all cases of biopsy-proven renal amyloidosis from January 2008 to May 2017. Light microscopic analysis; Congo red with polarization; IF; IHC for Amyloid A, kappa, and lambda; and bone marrow evaluation were done. Classification of glomerular amyloid deposition and scoring and grading are done as per the guidelines of Sen S et al. RESULTS: There are 40 cases of biopsy-proven renal amyloidosis with 12 primary and 23 secondary cases. Mean age at presentation was 42.5 years. Edema was the most common presenting feature. Secondary amyloidosis cases were predominant. Tuberculosis was the most common secondary cause. Multiple myeloma was detected in four primary cases. Grading of renal biopsy features showed a good correlation with the class of glomerular involvement. CONCLUSION: Clinical history, IF, and IHC are essential in amyloid typing. Grading helps provide a subtle guide regarding the severity of disease in the background of a wide range of morphological features and biochemical values. Typing of amyloid is also essential for choosing the appropriate treatment.