Proteinuria in predicting adverse outcomes in women with severe features of pre-eclampsia from a developing country: A prospective cohort study.

OBJECTIVE: To study the adverse maternal and perinatal outcomes in women with severe pre-eclampsia (SPE) among different ranges of proteinuria. METHODS: This prospective cohort study was conducted in Jawaharlal Institute of Postgraduate Medical Education and Research, India. After obtaining informed written consent, the 202 singleton women fulfilling the criteria of severe features of pre-eclampsia were stratified based on the value of urine protein-creatinine ratio (UPCR) as mild, moderate, severe, and massive proteinuria during pregnancy. Clinical outcomes were assessed and patients were followed up until 12 weeks postpartum to identify persistent proteinuria and hypertension. RESULTS: Of the 202 women with SPE, adverse maternal outcomes were seen in 34.65% (n = 70) and adverse perinatal outcomes in 75.74% (n = 153). The demographic and clinical factors were similar among women with increasing severity of proteinuria, except for mean systolic blood pressure, serum creatinine and total serum protein. UPCR was found to have a significant correlation with composite adverse perinatal outcome (P < 0.001) and individual outcomes of neonatal intensive care unit admission for >48 h (P = 0.01) and neonatal sepsis (P = 0.02) but not adverse maternal outcomes (P = 0.201). The optimum UPCR cutoff for adverse perinatal outcomes was 1.6 (sensitivity, 73.2%; specificity, 52.7%). In addition, 14.85% of the women had a persistently elevated UPCR and 3.96% had hypertension at 3 months postpartum. CONCLUSION: In women with SPE, severe and massive proteinuria were related to composite adverse perinatal outcome but not composite adverse maternal outcome. Moreover, antenatal 24-h proteinuria was significantly associated with persistent proteinuria. Significant proteinuria in women with SPE poses a risk for chronic renal dysfunction, requiring follow-up.

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.

Characteristics and Outcome of Biopsy-proven Malignant Hypertension with Severe Kidney Injury: A Retrospective Study.

BACKGROUND: Although malignant hypertension begets multiple target organ damage, there is limited data on patients with severe renal injury and evident malignant hypertension in renal histopathology. METHODS: We assessed the baseline demographic, histopathological findings and clinical outcomes in this retrospective analysis of patients with biopsy-proven malignant hypertension. RESULTS: Thirty cases were analysed, the mean age of patients was 40 ± 11.5 years, 28 (93.3%) were males and the average systolic and diastolic blood pressures at hospitalisation were 197.04 ± 24.14 and 117.41 ± 18.31 mmHg, respectively. Severe retinopathy was seen in 10 (33.3%). The median eGFR at admission was 6.3 (IQR 4.4-9.15) mL/min and 21 (72.4%) needed dialysis. Nine (30%) cases with glomerular crescents were having the primary glomerular disease (7 IgAN, 1 C3 glomerulonephritis, 1 membranoproliferative glomerulonephritis) and 17 (56.6%) had thrombotic microangiopathy. Three-month ESRD free survival was 34.5% (n = 10) and the ESRD cohort had more incidence of dialysis requiring kidney injury at presentation (94.4% vs. 40% in the non-ESRD cohort). Patient survival at 1 year was 50%. Isolated malignant hypertension, differed from others with regard to lesser incidence of severe retinopathy, less glomerular sclerosis (29.61 ± 15.86 vs. 48.45% ± 30.78; P = 0.03), absence of crescents (P = 0.02), more incidence of tuft wrinkling (100% vs. 35%, P = 0.00) and total vessel occlusion (P = 0.02). CONCLUSION: Clinicopathologically, accelerated essential hypertension differs from hypertension of glomerular disease. Degree of kidney injury at presentation is risk predictor for long-term morbidity in malignant hypertension.

Cholemic Nephrosis: An Autopsy Study of a Forgotten Entity.

OBJECTIVE: The aim of the study is to do a clinicopathologic study of post mortem kidney biopsies with significant deposition of bilirubin pigment within tubular epithelial cells and in the lumen of distal tubules as a bile cast. MATERIAL AND METHOD: All post mortem specimens with acute tubular necrosis, with the presence of bile casts in tubules or bile pigment deposition in the tubular epithelium during the period 2015-2018 were examined for gross and histopathology along with biochemical parameters and viral markers. RESULTS: Bile casts with sloughed renal tubular epithelial cells and occasional macrophages were present in the distal convoluted tubule in 78.6% of biopsies (11/14). The plugging of distal convoluted tubule with casts was similar to that seen in myeloma and myoglobin cast nephropathies. Bilirubin pigment deposition was present in 35.7% (5/14) of cases. The frequency of bile casts in each biopsy was variable and it did not have any association with serum bilirubin levels or etiology of liver dysfunction. A striking difference from earlier studies is the high number of toxin-induced liver damage including six cases of paraquat and 2 cases of yellow phosphorus poisoning. CONCLUSION: This study proves importance of the bile cast nephropathy as a reason for kidney injury, especially with varied hepatotoxic etiologies, especially paraquat and yellow phosphorus.

Role of Urinary Beta 2 Microglobulin and Kidney Injury Molecule-1 in Predicting Kidney Function at One Year Following Acute Kidney Injury.

BACKGROUND: There is only limited information on the utility of urinary biomarkers in predicting long-term kidney function following acute kidney injury (AKI). The current study assessed whether urinary beta 2 microglobulin/creatinine (B2M/creat) and kidney injury molecule-1/creatinine (KIM-1/creat) ratios, measured in the early recovery phase of AKI, are predictive of kidney function at one year. METHODS: This is a prospective study done in a tertiary care centre in South India, from March 2017 to December 2018. Adult patients who survived an episode of AKI were followed up for one year (n=125). B2M/creat and KIM-1/creat ratio were measured at two weeks and three months following AKI. RESULTS: In the AKI survivors, the B2M/creat ratio at 2 weeks [18.3mg/g (IQR 2.3, 52.9)] and KIM-1/creat ratio [1.1 µg/g (IQR 0.5, 4.0) at two weeks were higher compared to healthy controls [B2M/creat ratio 0.35 mg/g (0.17,0.58) and KIM-1/creat ratio 0.40 µg/g (0.23,1.00); P=<0.001]. After adjusting for covariates, the eGFR and urinary B2M/creat ratio at two weeks following AKI were predictive of eGFR at one year (P<0.001). KIM-1/ creat ratios were not predictive of eGFR at one year. A urinary B2M/creat ratio of 10.85 at two weeks following AKI had an 85.5% sensitivity (95% CI 74, 93) and 64.3% (95% CI 53, 75) specificity to predict CKD at one year. An eGFR cutoff of 60 mL/min/1.73 m2 at two weeks had a sensitivity of 81.8% (95% CI 69, 90) and specificity of 71.4% (95% CI 60, 81) for predicting CKD. The presence of either one criteria (urinary B2M/creat ratio >10.85 (mg/g) or eGFR <60 mL at two weeks) had a sensitivity of 100% (95% CI 94%, 100%) in predicting CKD at one year. CONCLUSION: An eGFR <60 mL/min/1.73m2 and elevated urinary B2M/creat ratio at two weeks following AKI is predictive of low eGFR at one year. Urinary KIM-1/creat ratios do not predict CKD progression.

Erratum: Prognosis and long-term outcomes of acute kidney injury due to snake envenomation.

[This corrects the article DOI: 10.1093/ckj/sfz055.][This corrects the article DOI: 10.1093/ckj/sfz055.].

Prognosis and long-term outcomes of acute kidney injury due to snake envenomation.

BACKGROUND: Snakebite is a common occupational hazard in tropical countries. To date, the literature on snakebite-related acute kidney injury (AKI) has been limited by retrospective study designs, lack of uniformity in case definitions of AKI and limited follow-up. This study aims to identify the in-hospital outcomes and long-term changes in kidney function that follow haemotoxic envenomation. METHODS: All adult patients admitted with AKI following haemotoxic envenomation from January 2016 to June 2017 were recruited and followed up until July 2018. Predictors of in-hospital mortality was assessed. Long-term follow-up data on kidney function were collected from survivors. RESULTS: In total, 184 patients with haemotoxic envenomation and AKI were recruited. The mean age of the subjects was 42.2 years [95% confidence interval (CI) 40.3-44.7]. The majority were male (71.2%). The mortality of patients with haemotoxic envenomation was 21.5%. The mortality was considerably higher in patients with Kidney Disease: Improving Global Outcomes (KDIGO) Stage 3 AKI [relative risk (RR) 4.45 (95% CI 1.14-17.42)] and those who met KDIGO urine output criteria [RR 20.45 (95% CI 2.84-147.23)]. A Cox regression model identified mechanical ventilation [odds ratio (OR) 5.59 (95% CI 2.90-10.81)], hypotension [OR 2.48 (95% CI 1.31-4.72)] and capillary leak syndrome [OR 2.02 (95% CI 1.05-3.88)] as independent predictors of mortality. Long-term follow-up data were available for 73 patients. A total of 21 patients (28.7%) developed adverse renal outcomes (glomerular filtration rate <60 mL/min/1.73 m2, urine albumin excretion >30 mg/g and new-onset hypertension or prehypertension). CONCLUSIONS: AKI resulting from snake envenomation is associated with considerable risk of mortality. The greater the AKI stage the greater the likelihood of mortality. One-third of patients with AKI developed long-term complications like chronic kidney disease, prehypertension and hypertension over the follow-up period.

Utility of Urinary Neutrophil Gelatinase Associated Lipocalin (NGAL) in Decompensated Cirrhosis.

BACKGROUND AND AIMS: Renal failure occurring in the setting of cirrhosis increases mortality by more than threefold. Serum creatinine, the conventional marker for renal dysfunction has inherent limitations in identifying and categorizing renal dysfunction in patients with chronic liver disease (CLD). Neutrophil gelatinase associated lipocalin (NGAL) is a novel biomarker which gets upregulated as early as 2-6 hours following the insult to renal tubules. In this study, we aim to check the utility of uNGAL to identify the different phenotypes of renal dysfunction in patients with CLD. We also intend to assess the utility of NGAL to predict 90-day transplant-free survival in patients with CLD. METHODS: A total number of 120 adult patients, with cirrhosis of liver were recruited. Those with pre-existing renal parenchymal disease, receiving nephrotoxic medications, spontaneous bacterial peritonitis, septic shock, proteinuria, hematuria, urinary tract infection and anuria were excluded. Urine samples for NGAL was measured at admission and at 48 hours thereafter. Patients were followed up for 90 days post admission. RESULTS: Among the study population, 16 patients (13.3%) had normal kidney function, 43 (35.8%) had prerenal azotemia and 54 (45%) had Hepatorenal Syndrome (HRS - AKI) and 7 (5.8%) had acute tubular necrosis (ATN). Urinary NGAL (uNGAL) levels were considerably lower in patients with normal kidney function and prerenal azotemia. An uNGAL level of 124 ng/ml on admission could distinguish severe forms of renal injury, with a sensitivity of 86% and specificity of 84%. The non survivors had higher uNGAL levels at admission [209.6 ng/ml (118.7-376.8) vs. 123 (33.6-344.3); P = 0.013].The receiver operated curves for uNGAL and serum creatinine at admission did not show any significant difference for predicting 90 day mortality (AUC for uNGAL: 0.632 vs 0.580 for serum creatinine; difference in AUC 0.053, P value 0.17). CONCLUSION: uNGAL levels are elevated in patients with HRS-AKI and ATN. A higher uNGAL level at admission was suggestive of severe renal dysfunction. An elevated uNGAL on admission is associated with inferior survival. However, uNGAL is not superior to serum creatinine in predicting 90-day mortality.

Reliability of Anthropometry-Based Equations Compared to Dual Energy Absorptiometry for Assessing Body Composition in Predialysis Chronic Kidney Disease-A Longitudinal Study.

OBJECTIVES: Skinfold thickness measurements for assessing body composition are reported to have good reproducibility compared to the reference method of dual energy absorptiometry (DXA). In the current study, we compared the level of agreement between body composition measured with DXA and skinfold thickness (SFT) in CKD Stage 3 and 4, at 2 occasions, 6 months apart. METHODS: Body composition was assessed in 177 Indian patients with CKD Stage 3 and 4 using DXA and anthropometry (SFT). The body fat mass obtained by the 2 methods was compared by paired t-test, intraclass correlation coefficients, regression analysis, and Bland-Altman plots. A linear regression analysis was done to identify the patient-related parameters which would account for the intermethod differences between DXA and SFT. RESULTS: Compared to DXA, SFT underestimated the fat mass at baseline as well as 6 months [DXA vs. SFT at entry: 15.85 kg (95% confidence interval, CI 15.07-16.65) vs. 13.71 kg (95% CI 13.21-14.32), P < .001; at 6 months: 16.13 (95% CI 15.33-16.93) vs. 13.85 (95% CI 13.25-14.45), P < .001]. The intraclass correlation coefficients at entry and 6 months were 0.894 (0.857-0.921) and 0.896 (0.860-0.923), respectively. The intermethod differences between DXA and SFT at baseline and 6 months were comparable: 2.08 kg (95% CI 1.66-2.5) at baseline versus 2.27 kg (95% CI 1.83-2.71) at 6 months, P = 0.200. Gender and body mass index turned out to be the significant predictors of intermethod differences at base line and exit (P < .001). CONCLUSIONS: SFT-based measurements show good reproducibility compared to DXA over a period of 6 months. However, SFT systematically underestimates the fat mass by 2 Kg compared to DXA.

Correction of metabolic acidosis improves muscle mass and renal function in chronic kidney disease stages 3 and 4: a randomized controlled trial.

BACKGROUND: Metabolic acidosis (MA) is associated with a loss of muscle mass and faster deterioration of kidney function in patients with chronic kidney disease (CKD). A few single-centre randomized trials have reported favourable outcomes following correction of MA. Additional good quality evidence on the safety and efficacy of alkali supplementation is required in epidemiologically different patient subsets with CKD. METHODS: A single-centre, open-label, randomized, prospective parallel-group study was conducted to assess the effect of correction of MA on body composition and kidney function. A total of 188 patients with CKD stages 3 and 4, with venous bicarbonate levels <22 mEq/L were randomized. The intervention arm received standard care as per Kidney Disease: Improving Global Outcomes (KDIGO) 2012 guidelines along with oral sodium bicarbonate supplementation to maintain venous bicarbonate levels at 24-26 mEq/L, whereas the control group received standard care alone. The mid-arm muscle circumference (MAMC), lean body mass (LBM) and estimated glomerular filtration rate (eGFR) were compared between the groups at the end of 6 months. RESULTS: The intervention arm showed a higher LBM {36.8 kg [95% confidence interval (CI) 36.5-37.1] versus 36 [35.7-36.4]; P = 0.002} and MAMC [22.9 cm (95% CI 22.8-23) versus 22.6 (22.5-22.7); P = 0.001] when compared with the control group. The GFR in the intervention arm was higher [32.74 mL/1.73 m2 (95% CI 31.5-33.9) versus 28.2 (27-29.4); P ≤ 0.001]. A rapid decline in GFR was documented in 39 (41.5%) patients in the control arm and 19 (20.2%) patients in the intervention arm (P = 0.001). CONCLUSIONS: Alkali supplementation to increase venous bicarbonate levels to 24-26 mEq/L is associated with preservation of LBM and kidney function in patients with CKD stages 3 and 4.

Manifest interstitial and vascular pathology in anti-neutrophil cytoplasmic antibody-associated renal disease.

Rapidly progressive renal failure in anti-neutrophil cytoplasmic antibody (ANCA)- associated renal disease customarily implies crescentic glomerulonephritis with approximately 50% of the glomeruli will have crescents. The tubulointerstitial inflammation is often proportionate to the glomerular inflammation and may have granulomatous pattern adjacent to the glomeruli or an inflamed vessel. A 77-year-old male with rapidly progressive renal failure was myeloperoxidase-ANCA positive, and renal histopathology revealed thrombotic microangio-pathy, significant interstitial inflammation, interstitial granulomas, and arteritis. Pathology is unique for the paucity of the classical crescents and the myriad of extraglomerular features. His renal function improved and stabilized after induction with cyclophosphamide and maintenance with azathioprine.

Short-term Changes in Urine Beta 2 Microglobulin Following Recovery of Acute Kidney Injury Resulting From Snake Envenomation.

INTRODUCTION: Urine ß2 microglobulin (ß2m) is a validated marker to diagnose sepsis and toxin-related acute kidney injury (AKI). In the current study, we used urine ß2m as a potential marker to identify persistent tubular dysfunction following a clinical recovery from snake venom-related AKI. METHODS: A total of 42 patients who developed AKI following hemotoxic envenomation were followed up for a period of 6 months. Urine albumin excretion, estimated glomerular filtration rate (eGFR), and urine ß2m levels were measured at 2 weeks, 3 months, and 6 months following discharge. RESULTS: At the end of 6 months of follow-up, 6 patients (14.3 %) progressed to chronic kidney disease (CKD) (eGFR < 60 ml and/or urine albumin excretion > 30 mg/d). The urine ß2m levels were 1590 µg/l (interquartile range [IQR] 425-5260), 610 µg/l (IQR 210-1850), 850 µg/l (IQR 270-2780) at 2 weeks, 3 months, and 6 months, respectively (P = 0.020). The levels of urine ß2m in the study population at the end of 6 months remained significantly higher compared with the levels in healthy control population (850 µg/l [IQR 270-2780] vs. 210 µg/l [IQR 150-480]; P = 0.001). The proportion of patients with urine ß2m levels exceeding the 95th percentile of control population (>644 µg/l) during the 3 follow-up visits were 70.7% (n = 29), 48.8 % (n = 20), and 51.2% (n = 21). Similar trends were noticed in a sensitivity analysis, after excluding patients with CKD. CONCLUSIONS: Urine ß2m levels remain persistently elevated in approximately half of the individuals who recover from AKI due to snake envenomation.

Functional Status in Hemodialysis - A Comparative Study with FIM, ADLQ and 7D5L Instruments.

There is only limited information on the functional status (FS) of patients receiving hemodialysis (HD) from developing countries where the etiology of chronic kidney disease (CKD) and demographic profile are different. The study aims to assess the FS in patients with CKD using three validated generic instruments. A total of 116 adult patients on HD with a dialysis vintage >3 months were enrolled. FS was assessed using three generic tools - Functional Independence Measure (FIM) (scores 18-126), Seven domains and five levels (7D5L) (scores 0-28), and Activities of Daily Living Questionnaire (ADLQ) (scores 0-6) scales. A higher FIM and ADLQ scores and lower 7D5L score indicated good FS. The mean age of patients was 41.28 ± 15.44 years. About 77.6% were males and 80.2% were unemployed. About 67.2% were receiving twice-weekly HD, and 28.4% were receiving thrice-weekly dialysis. The mean scores were 119.05 ± 11.42 with FIM, 6.44 ± 4.26 with 7D5L, and 5.51 ± 1.19 with ADL instruments. More than 80% showed full functional independence with ADLQ instrument. With FIM, the overall scores showed a tendency for functional independence, but the subdomains involving locomotion/mobility were impaired to a greater extent. The proportion of patients with full independence was less with 7D5L. We observed an inferior FS in individuals <40 years. Patients on HD were functionally independent as assessed by FIM and ADLQ instruments. However, 7D5L appeared to be better in identifying mild to moderate limitations in daily activities. The domains involving motor tasks seem to be affected to a greater extent. The current scales for assessing FS do not incorporate a time-dependent component.

Persistent Metabolic Acidosis on Regular Hemodialysis or Peritoneal Dialysis.

Metabolic acidosis is known to have adverse consequences in patients with chronic kidney disease (CKD) including protein-energy wasting, inflammation, bone disease, and disturbance in endocrine function. Unlike in the management of patients with predialysis CKD, bicarbonate levels were not being routinely monitored in dialysis patients at our center. The KDOQI guidelines recommend serum bicarbonate levels ≥22 mEq/L in patients on dialysis. We measured the predialysis serum bicarbonate levels in 100 adult patients on regular hemodialysis (HD) and 41 adult patients on peritoneal dialysis (PD). We also studied the extent of rise in serum bicarbonate levels from predialysis levels after HD in our patients. Predialysis serum bicarbonate level was <22 mEq/L in 73% of patients on HD and 12% of patients on PD. The serum bicarbonate levels remained <22 mEq/L at the end of HD in 41% of patients on HD. Thirty-nine percent of patients were on a HD schedule of thrice a week, and 93% of PD patients performed three PD exchanges a day. The dialysate bicarbonate level was 34 mEq/L. There was a significant increase in serum bicarbonate levels with HD, but the mean postdialysis bicarbonate level was 23.45 mEq/L. A very high proportion of our patients on HD continued to have uncorrected metabolic acidosis, with metabolic acidosis persisting in the immediate postdialysis period in a significant number of patients. Predialysis serum bicarbonate level needs to be monitored in patients on HD. There is an urgent need to modify HD prescription to ensure better correction of metabolic acidosis in our HD population. Compared to HD, the proportion of patients having persistent metabolic acidosis is significantly lower in PD.