Immunoglobulin A Deposits In Renal Allografts: A Prospective Longitudinal Single-Center Study.

AIMS AND BACKGROUND: To describe the prevalence of IgA deposits (IgAD) in renal allografts in a cohort of renal transplant recipients and to analyze their management strategies and histopathology. To assess graft function and proteinuria after 1 year of follow-up. MATERIALS AND METHODS: A prospective longitudinal follow-up study was carried out in VPS Lakeshore Hospital and Research Centre, Kochi, Kerala, over a period of 5 years (July 2015 to June 2020). Kidney transplant recipients with allograft biopsies that reported IgAD on immunofluorescence were included in the study. Light microscopy and immunofluorescence studies were performed. Mesangial hypercellularity (M); segmental glomerulosclerosis (S); endocapillary hypercellularity (E); tubular atrophy/interstitial fibrosis (T); crescents (C) (MEST-C) Scoring was done in patients with pathogenic IgAD. Treatment strategies included increased baseline steroid dosage, rituximab administration, and plasma exchange. Clinical details and management strategies were analyzed, and patients were followed up for 1 year after diagnosis. Changes in graft function (S. Creatinine) and proteinuria (Urine Protein/Creatinine ratio) were analyzed. Clinico-pathologic correlation with the MEST-C scores was also done. RESULTS: Out of 1036 kidney transplants done in the study period, 760 graft biopsies were performed. Sixty-four cases had post-transplant deposition of IgA (8%). The mean age was 45 ± 11.25SD years. The study had 51 men and 13 women. Induction immunosuppression comprised rabbit antithymocyte globulin in 29 (45%) patients and basiliximab in 35 (54%). Maintenance immunosuppression in all comprised tacrolimus, mycophenolate mofetil, and steroids. There were 2 groups: group A (pathogenic IgAD) and group B (incidental IgAD). Group A had 46 cases (71.9%), out of which 8 had "active" IgA nephropathy (endocapillary proliferation, crescents, and IgA vasculitis), and 38 had "inactive" IgAD. In patients with active deposits, 3 had cellular crescents (18%, 30%, and 23%), all 8 had endocapillary proliferation, and 2 had vasculitis. Group B had 18 cases (28.1%), comprising T cell-mediated rejections (5), antibody-mediated rejection (8), BK virus nephropathy (1), and interstitial fibrosis and tubular atrophy (4). In group A, 22 (47.8%) presented with graft dysfunction, 8 (17.3%) with isolated proteinuria, and 14 (30.4%) patients presented with a combination. Two (4.3%) patients had neither. Fourteen (30.4%) patients presented within 1 month of renal transplant. In patients of group A, at the end of 1 year of treatment, the mean S. Creatinine reduced to 1.68 mg/dL from 1.84 mg/dL, and the mean protein/creatinine ratio reduced from 1.2 to 0.5 (±1.17). In patients with "active IgA" lesions, at the end of 1 year of treatment, the mean S. Creatinine increased slightly to 1.68 mg/dL (±0.47SD) from 1.48 mg/dL (±0.52SD), and the mean protein/creatinine ratio reduced from 2.32 (±1.56SD) to 1.05 (±1.70SD). In the 16 patients with IgAD and proteinuria, at the end of 1 year of treatment, the mean S. Creatinine decreased to 1.41 ± 0.32 SD mg/dL from 1.47±0.37SD mg/dL and the mean protein/creatinine ratio reduced from 1.12 ± 1.31 SD to 0.39±0.75 SD. In the remaining 22 patients with acute tubular injury, at the end of 1 year, the mean S. Creatinine decreased to 1.920.32 SD mg/dL from 2.10.8SD mg/dL, and the mean protein/creatinine ratio reduced from 1.1 ± 1.31 SD to 0.66 ± 1.45 SD. In the MEST-C scoring analysis, all scores were 0 in 20 (43.4%) biopsies, only M1 score in 11 (23.9%) biopsies, only E1 score in 10 biopsies (21.7%), S1 in 13 (28.2%) cases. CONCLUSION: Immunoglobulin A deposits occur commonly after transplant; these may represent recurrence, de novo IgA, or donor-derived IgAD. Although commonly benign, some may cause significant graft dysfunction and graft loss. IgAD can present as varying combinations of graft dysfunction and proteinuria. Active IgA pathologies may occur early in the post-transplant course, may have significant graft dysfunction, and need proactive management. There is a correlation between segmental sclerosis and proteinuria. Evidence for the efficacy of Rituximab, plasma exchange, and prolonged courses of steroids is wanting; however, some benefits are possible. Long-term follow-up is essential.

A Rare Cause of Encephalopathy Post Renal Transplant: BK Polyoma Virus Encephalitis.

BK polyoma virus (BKV) belongs to Polyomaviridae family. It is a double-stranded DNA virus. Only a few cases of BKV-associated neurological disease in renal transplant recipients have been reported. BKV related central nervous system (CNS) infection may often remain unrecognized in immunocompromised patients. Here, we are reporting a case of BKV encephalitis post renal transplantation for the awareness of all physicians regarding this entity.

A profile of metabolic acidosis in patients with sepsis in an Intensive Care Unit setting.

CONTEXT: Metabolic acidosis is frequently found in patients with severe sepsis. An understanding of types of acidosis in sepsis and their evolution over the course of treatment may give us insight into the behavior of acid-base balance in these patients. AIMS: To describe at Intensive Care Unit (ICU) admission and over the first 5 days the composition of metabolic acidosis in patients with sepsis and to evaluate and compare acidosis patterns in survivors and nonsurvivors. SETTINGS AND DESIGN: A prospective study conducted at Amrita Institute of Medical Sciences, Kochi, Kerala, in the Department of Internal Medicine. SUBJECTS AND METHODS: Seventy-five consecutive patients admitted in the medical ICU with sepsis and metabolic acidosis were assessed. Arterial blood gas and serum electrolytes were measured during the first five days of admission or until death, renal replacement or discharge supervened. STATISTICAL ANALYSIS: To test the statistical significance of the difference in mean values of different study variables at day 1 and last day between survivors and non survivors, Mann-Whitney U-test was applied. To test the statistical significance of the difference in mean changes in different study parameters from day 1 to last day, paired t-test was done in the survivor group and Mann-Whitney U-test in the non survivor group. RESULTS: Regardless of survival status, on day 1 of admission, 37 had High Anion Gap metabolic acidosis (HAGMA), 21 had predominant lactic acidosis (LA), 8 had Normal anion gap metabolic acidosis (NAGMA), and 9 had both HAGMA and LA [Figure 1]. When we compared this to the last day, 25 had HAGMA, 3 had LA, 3 had both HAGMA and LA, and 22 patients had resolution of acidosis. Sixty-four patients survived for up to 5 days of admission. Fifteen of these patients underwent hemodialysis on the day of admission itself in view of HAGMA. The remaining 49 comprised of HAGMA (31), Lactic acidosis (12), and a combination (6) on day 1. On the last day in this group, 25 had HAGMA, 2 had LA, and 22 patients had resolution of acidosis. In survivors, over the observation period, changes seen were: mean pH: 7.25-7.34 (P < 0.001), mean serum bicarbonate: 13.9 mEq to 17.2 mEq (P < 0.001), and mean serum lactate: 3.18-1.9 (P = 0.002). The changes in serum albumin and pCO2 were not significant. Eleven patients in the study population succumbed. Seven patients underwent hemodialysis on day 1 and the remaining four were followed up for more than 1 day. On day 1, 7 had lactic acidosis and 5 had HAGMA. Over the observation period, changes seen were mean pH: 7.15-7.14, mean serum lactate: 6.3-7.3 mEq. CONCLUSIONS: In patients with sepsis and septic shock, high anion gap metabolic acidosis is the dominant blood gas anomaly. Fall in lactate levels over the first 5 days of admission is a good prognostic marker of survival. Evolution of the blood gas profile over time suggests that a fall in lactate levels and a rise in bicarbonate levels correlate with a better outcome. The role of the anion gap as a prognostic marker holds promise and further studies are needed in this regard.