Acute Kidney Injury Complicating Severe Acute Pancreatitis: Clinical Profile and Factors Predicting Mortality.

Introduction: Acute kidney injury (AKI) frequently complicates severe acute pancreatitis (SAP) among the critically ill. We studied clinical profile and risk factors predicting mortality in SAP-AKI. Materials and Methods: We conducted a prospective observational study of 68 patients with SAP-AKI from September 2015 to September 2019. Patient data and outcomes grouped as survivors and deceased were analyzed. Results: SAP-AKI constituted 2.14% (68 of 3,169) of all AKIs with 1.5%, 20.6%, and 77.9% in Kidney Disease Improving Global Outcomes (KDIGO) Stages I, II and III respectively. The mean age was 39.93 ± 11.79 years with males 65 (95.6%). The causes of acute pancreatitis were alcohol addiction 59 (86.8%), highly active antiretroviral therapy 1 (1.4%), hypercalcemia 1 (1.4%), IgG4-related disease 1 (1.4%), and unidentified 6 (8.8%). Complications were volume overload, shock, respiratory failure, and necrotizing pancreatitis in 21 (30.9%), 10 (14.7%), 6 (8.8%), and 14 (20.5%), respectively. Kidney replacement therapy done in 40 (58%), with intermittent hemodialysis 36 (53%) and acute intermittent peritoneal dialysis 4 (6%). The overall mortality was 23 (33.8%), three progressed to chronic kidney disease (thrombotic microangiopathy 2; biopsy inconclusive 1). In 45 survivors, AKI recovered in 22.7 ± 9.6 days. Death occurred within first 6 days. The risk factors associated with in-hospital mortality was necrotizing pancreatitis (odds ratio [OR] = 5.143; 95% confidence interval 1.472-17.972; P = 0.01), circulatory failure (OR = 6.125; P = 0.016), peak creatinine >3 mg/dL (OR = 7.118; P = 0.068), Bedside Index of Severity for Acute Pancreatitis score >3 (OR = 8.472; P = 0.001), need for kidney replacement therapy (OR = 3.764; P = 0.024), KDIGO III (OR = 9.935; P = 0.03). Conclusions: Alcohol addiction was the commonest cause of severe acute pancreatitis. The overall mortality was 33.8%. Necrotizing pancreatitis, circulatory failure, peak creatinine >3 mg/dL, BISAPs >3, KDIGO III, and the need for kidney replacement therapy were independent risk factors for mortality.

A clinical study on the changing dynamics of disease severity, management strategies and outcomes of COVID-19 in patients requiring haemodialysis.

INTRODUCTION: In this observational study, we describe the change in the clinical profile and outcome of Corona Virus Disease 2019 (COVID-19) over the course of the outbreak, among patients requiring dialysis, including chronic haemodialysis therapy. METHODS: This is a single-centre prospective observational study of patients with COVID-19 (as confirmed by RT-PCR) and renal failure requiring haemodialysis. Their clinical profiles and outcomes were analysed, vis-à-vis the changing disease severity. FINDINGS: A total of 483 patients were included, of whom 416 had end-stage renal disease and were on maintenance haemodialysis. Patients who were symptomatic at presentation had significantly higher levels of Neutrophil-lymphocyte ratio (NLR) (p < 0.001), C-reactive protein (CRP) (p < 0.001), lactate dehydrogenase (LDH) (p < 0.001), higher degrees of lung involvement (p < 0.001) and required more respiratory support (p < 0.001). The overall mortality observed was 18.8%. In the late phases of the outbreak, there was a significant increase in disease severity without a statistically significant increase in mortality. Predictors of mortality on univariate analysis were age, diabetes mellitus, acute on chronic kidney disease, presence of symptoms on admission, NLR, CRP, LDH, computed tomography (CT) chest grades 3 and 4, and need for respiratory support; however, only age and the renal syndrome of acute on chronic kidney disease retained significance on multivariate analysis (p0.003 and p0.019, respectively). CONCLUSION: Among patients on haemodialysis, higher mortality was observed in patients who were older, and among those with acute on chronic kidney disease. In the late phase of the outbreak, there was a statistically significant increase in disease severity without a corresponding increase in mortality.

Clinical and Immunological Profile of Anti-factor H Antibody Associated Atypical Hemolytic Uremic Syndrome: A Nationwide Database.

Background: Atypical hemolytic uremic syndrome (aHUS), an important cause of acute kidney injury (AKI), is characterized by dysregulation of the alternative complement pathway. Autoantibodies to factor H (FH), a chief regulator of this pathway, account for a distinct subgroup. While high anti-FH titers predict relapse, they do not correlate well with disease activity and their functional characterization is required. Methods: Of 781 patients <18-year-old of aHUS in the nationwide database from 2007 to 2018, 436 (55.8%) had anti-FH antibodies. Clinical features and outcome of patients managed in the last 6-year (n = 317) were compared to before (n = 119). In plasma samples of 44 patients, levels of serial circulating FH immune complexes (CIC), free FH, soluble terminal complement complex (sC5b-9), sheep red blood cell (SRBC) lysis and epitope specificity (n = 8) were examined. Functional renal reserve, ambulatory hypertension, left ventricular hypertrophy (LVH), and proteinuria were evaluated in a subset. Results: Patients presented with markedly elevated anti-FH titers (10,633.2 ± 998.5 AU/ml). Management varied by center, comprising plasma exchange (PEX; 77.5%) and immunosuppression (73.9%). Patients managed in the last 6-year showed better renal survival at mean 28.5 ± 27.3 months (log rank P = 0.022). Mean anti-FH titers stayed 700-1,164 AU/ml during prolonged follow-up, correlating with CIC. Patients with relapse had lower free-FH during remission [Generalized estimating equations (GEE), P = 0.001]; anti-FH levels ≥1,330 AU/ml and free FH ≤440 mg/l predicted relapse (hazards ratio, HR 6.3; P = 0.018). Epitope specificity was similar during onset, remission and relapse. Antibody titer ≥8,000 AU/ml (HR 2.23; P = 0.024), time to PEX ≥14 days (HR 2.09; P = 0.071) and PEX for <14 days (HR 2.60; P = 0.017) predicted adverse renal outcomes. Combined PEX and immunosuppression improved long-term outcomes (HR 0.37; P = 0.026); maintenance therapy reduced risk of relapses (HR 0.11; P < 0.001). At 4.4±2.5 year, median renal reserve was 15.9%; severe ambulatory, masked and pre-hypertension were found in 38, 30, and 18%, respectively. Proteinuria and LVH occurred in 58 and 28% patients, respectively. Conclusion: Prompt recognition and therapy with PEX and immunosuppression, is associated with satisfactory outcomes. Free-FH predicts early relapses in patients with high anti-FH titers. A significant proportion of impaired functional reserve, ambulatory hypertension, proteinuria and LVH highlight the need for vigilant long-term follow-up.

Association of HLA-DR/DQ alleles and haplotypes with nephrotic syndrome.

BACKGROUND: Nephrotic syndrome (NS) is a debilitating renal problem in children resulting from an interaction between environmental and genetic factors including human leukocyte antigen genes (HLA). The aim of this work was to study the probable link between HLA alleles/haplotypes and NS in south India. METHODS: HLA DRB1*/DQB1* alleles were genotyped in 183 NS (76 steroid sensitive-SSNS; 107 steroid resistant-SRNS) and paediatric healthy controls (PHCs; n = 91) using polymerase chain reaction-sequence specific primers (PCR-SSP). HLA-A/-B genotyping was performed for patients (n = 70) positive for DRB1*07-DQB1*02 haplotype to identify four locus extended haplotype. RESULTS: The following alleles and haplotypes were strongly associated with NS (P < 0.05 as significant): DRB1*07 (SSNS, P < 7.98 × 10(-6) ; SRNS, P < 0.008), DQB1*02 (SSNS, P < 3.99 × 10(-6) ; SRNS, P < 0.002), DRB1*07-DQB1*02 (SSNS, P < 1.32 × 10(-4) ; SRNS, P < 0.010), DRB1*07-DQB1*0301,0304 (DQ7) (SSNS, P < 0.001) and DRB1*03-DQB1*02 (SRNS, P < 0.048). Protective associations were observed for alleles DRB1*10 (SRNS, P < 0.013), DQB1*05 (SSNS, P < 4.34 × 10(-6) ; SRNS, P < 0.01), DQB1*06 (SSNS, P < 0.003), and haplotypes DRB1*10-DQB1*06 (SSNS, P < 0.046; SRNS, P < 0.032) and DRB1*15-DQB1*05 (SSNS, P < 0.018). HLA-A/-B typing of 70 NS cases with two locus haplotype DRB1*07-DQB1*02 (70/183; 38.25%) revealed the presence of an extended haplotype 'A*03-B*07-DRB1*07-DQB1*02' (n = 35; 50%). CONCLUSION: Our study revealed strong susceptible association of DRB1*07 with SRNS and DQB1*02 with SSNS. A gender predominant protective association was observed for DRB1*10 with SRNS females; DQB1*05 with SSNS and SRNS males. Further, the study documented the presence of an extended haplotype and pleiotropic action of DRB1*/DQB1* alleles in immune-mediated aetiology of NS in south India.