A Study of Prevalence of Renal Function Abnormalities and Their Association with the Individual Components of Metabolic Syndrome.

INTRODUCTION: Metabolic syndrome (MetS) is one of the most important emerging pandemics of the 21st century and is associated with renal dysfunction in a significant number of subjects, the association of which is shown to be of greater significance in the South Asian population. AIMS AND OBJECTIVES: The prevalence of renal dysfunction in patients with MetS is the primary outcome. The secondary outcome is to assess the strength and significance of the association between the individual components of MetS and the presence of renal dysfunction. MATERIALS AND METHODS: This is a hospital-based cross-sectional observational study conducted for 2 years in a tertiary care hospital in India. A total of 100 diagnosed subjects of MetS were taken as cases and underwent relevant blood tests. Data were collected and analyzed in a Statistical Package for the Social Sciences (SPSS) v29 sheet. RESULTS: Over a period of 18 months, 100 subjects with MetS were documented, among which 66% had albuminuria, with microalbuminuria being 24% and the rest being macroalbuminuria. Among the same subjects, 30% had an estimated glomerular filtration rate (eGFR) <60 mL/minute/1.73m2. Waist circumference (WC) [measured by the National Institutes of Health (NIH) protocol] had the strongest association with increased albuminuria (r = 0.540; p-value < 0.001) as well as reduced eGFR (r = 0.460; p-value < 0.001). CONCLUSION: All the components of MetS, for example, increased WC, hypertension, increased fasting glucose, raised triglyceride (TG), and low high-density lipoprotein (HDL), have statistically significant correlations with increased urine albumin-to-creatinine ratio (ACR) and decreased eGFR, signifying glomerular injury and renal dysfunction, respectively.

Intravenous cyclophosphamide vs rituximab for the treatment of early diffuse scleroderma lung disease: open label, randomized, controlled trial.

Objectives: SSc is characterized by fibrotic changes in the skin and lung, and the mainstay of treatment has been CYC. B cell involvement suggests that rituximab (RTX) may also be of therapeutic benefit. The aim of the study was to compare the efficacy and safety of RTX compared with CYC in retarding the progression of interstitial lung disease and skin manifestations of primary SSc. Methods: We randomly assigned 60 patients of dcSSc, age 18-60 years with skin and lung involvement, to monthly pulses of CYC 500 mg/m2 or RTX 1000 mg × 2 doses at 0, 15 days. Primary outcomes were forced vital capacity (FVC) percent predicted at 6 months. Secondary outcomes were: absolute change in litres (FVC-l) at 6 months; modified Rodnan skin scores at 6 months, 6-min walk test, Medsgers score and new onset or worsening of existing pulmonary hypertension by echocardiographic criteria. Results: The FVC [%mean (s.d.)] in the RTX group improved from 61.30 (11.28) to 67.52 (13.59), while in the CYC group it declined from 59.25 (12.96) to 58.06 (11.23) at 6 months (P = 0.003). The change of FVC was 1.51 (0.45) l to 1.65 (0.47) l in the RTX group, compared with 1.42 (0.49) to 1.42 (0.46) l in the CYC group. The mRSS changed from 21.77 (9.86) to 12.10 (10.14) in the RTX group and 23.83 (9.28) to 18.33 (7.69) in the CYC group after 6 months. Serious adverse events were more common in the CYC group. Conclusion: RTX is a safe and effective alternative to CYC in the primary therapy of skin and lung manifestations of scleroderma. Trial registration: Clinical Trials Registry - India, www.ctri.nic.in, CTRI/2017/07/009152.

Efficacy of Febuxostat for Slowing the GFR Decline in Patients With CKD and Asymptomatic Hyperuricemia: A 6-Month, Double-Blind, Randomized, Placebo-Controlled Trial.

BACKGROUND: Hyperuricemia is a putative risk factor for the progression of chronic kidney disease (CKD). We hypothesized that control of asymptomatic hyperuricemia may slow disease progression in CKD. STUDY DESIGN: This was a single-center, double-blind, randomized, parallel-group, placebo-controlled study. SETTING & PARTICIPANTS: Eligible participants were adults from Eastern India aged 18 to 65 years with CKD stages 3 and 4, with asymptomatic hyperuricemia. INTERVENTION: The intervention group received febuxostat, 40mg, once daily for 6 months, while the placebo group received placebo; both groups were followed up for 6 months. OUTCOMES: The primary outcome was the proportion of patients showing a >10% decline in estimated glomerular filtration rate (eGFR) from baseline in the febuxostat and placebo groups. Secondary outcomes included changes in eGFRs in the 2 groups from baseline and at the end of the study period. RESULTS: 45 patients in the febuxostat group and 48 in the placebo group were analyzed. Mean eGFR in the febuxostat group showed a nonsignificant increase from 31.5±13.6 (SD) to 34.7±18.1mL/min/1.73m(2) at 6 months. With placebo, mean eGFR decreased from a baseline of 32.6±11.6 to 28.2±11.5mL/min/1.73m(2) (P=0.003). The difference between groups was 6.5 (95% CI, 0.08-12.81) mL/min/1.73m(2) at 6 months (P=0.05). 17 of 45 (38%) participants in the febuxostat group had a >10% decline in eGFR over baseline compared with 26 of 48 (54%) from the placebo group (P<0.004). LIMITATIONS: Limitations of this study included small numbers of patients and short follow-up, and ∼10% of the randomly assigned population dropped out prior to completion. CONCLUSIONS: Febuxostat slowed the decline in eGFR in CKD stages 3 and 4 compared to placebo.

A Randomized Controlled Trial Comparing Remission Induction with Modified Multitarget Therapy with Intravenous Cyclophosphamide in Proliferative Lupus Nephritis.

Introduction: Therapy of proliferative lupus nephritis (PLN) is yet to be optimized. Standard of care for induction consists of intravenous (IV) cyclophosphamide (CYC) and steroids, which shows an improved outcome, but end-stage renal disease (ESRD) progression, increased mortality, and therapy-related adverse effects remain a major concern. The other treatment reported to induce early remission was the multitarget therapy comprising tacrolimus, mycophenolate, and steroid, but infections were high in the multitarget therapy. Considering azathioprine as a potentially safer and effective alternative anti-B-cell therapy, modified multitarget therapy (MMTT) was planned replacing mycophenolate with azathioprine. Material and Methods: A single-center, 24-week, open-label, randomized controlled trial comprising adults of age 18-65 years with biopsy-proven PLN was carried out. The intervention groups were 1) MMTT: tacrolimus 0.075 mg/kg/day and azathioprine 2 mg/kg/day and 2) IV CYC group with a starting dose of 0.75 (adjusted to 0.5-1.0) g/m2 every 4 weeks for 6 months. Both groups received 3 days of pulse methylprednisolone followed by a tapering course of oral prednisone therapy. Results: Among 100 randomized patients, 48 were in MMTT arm and 52 were in IV CYC arm. At the end of 24 weeks, overall remission (complete and partial) was comparable in both the arms: MMTT (86.36%) and IV CYC (87.75%). There was comparable proteinuria reduction and systemic lupus erythematosus disease activity index (SLEDAI) score improvement with recovery of complement level C3 in both groups. Major adverse events were numerically more in the IV CYC group, including one death from pneumonia. Conclusion: The MMTT arm is as effective as IV CYC in improving short-term outcome in PLN, with a comparable safety profile.

Long-term renal outcome of snake bite and acute kidney injury: a single-center experience.

BACKGROUND: Snake bite can cause acute kidney injury (AKI) through multiple mechanisms. Many of these patients have severe kidney injury requiring renal replacement therapy. The long-term outcome of survivors of such severe AKI is not known. METHODS: We prospectively followed up 60 patients who developed dialysis-requiring severe AKI following snake bite and had survived the hospital stay. RESULTS: A total of 25 (41%) patients showed persistent renal involvement in the form of renal dysfunction, proteinuria, or hypertension at a mean period of follow-up of 45 months. Totally 5% of the patients progressed to end-stage renal disease (ESRD) while 20% had glomerular filtration rate (GFR) <45 mL/min. CONCLUSIONS: Long-term outcome of snake bite and AKI is not benign with a significant percentage of patients continuing to have features of persistent renal damage.

Renin-angiotensin blocker use is associated with improved cardiovascular mortality in Indian patients with mild-moderate chronic kidney disease-findings from the ICKD study.

Introduction: Angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB) are the antihypertensive drug class of choice in patients with chronic kidney disease (CKD). Head-to-head comparisons of the renal or non-renal outcomes between ACEI/ARB users and nonusers have not been conducted in all population groups. We examined the renal and cardiovascular outcomes in users and nonusers enrolled in the Indian Chronic Kidney Disease (ICKD) Study. Methods: A total of 4,056 patients with mild-moderate CKD were studied. Patients were categorized as ACEI/ARB users or nonusers. Major adverse kidney events [ESKD (end stage kidney disease), ≥50% decline in eGFR and kidney death], all-cause mortality, and cardiovascular mortality were analyzed over a median follow-up period of 2.64 (1.40, 3.89) years between the two groups. Results: Out of a total of 4,056 patients, 3,487 (87%) were hypertensive. The adjusted sub-hazard ratio (SHR) and 95 % CI for ACEI /ARB users was 0.85 (0.71, 1.02) for MAKE, 0.80 (0.64, 0.99) for a 50% decline in eGFR, and 0.72 (0.58, 0.90) for ESKD. For cardiovascular mortality, ACEI/ARB users were at lower risk (SHR = 0.55, 95% CI: 0.34, 0.88). Diuretic users were at increased risk of all-cause mortality (HR = 1.95, 95% CI: 1.50, 2.53) and cardiovascular mortality (adjusted SHR = 1.73, 95% CI: 1.09, 2.73). There was non-significant association between the use of other antihypertensives and any of the end points. Discussion: ACEI/ARB use is associated with slower rate of decline in eGFR in those with CKD stage 1-3. ACEI/ARB users had a significantly lower risk of renal outcomes, and cardiovascular mortality.

Remote Ischemic Preconditioning for Prevention of Contrast-Induced Acute Kidney Injury in Patients of CKD Stage III and IV Undergoing Elective Coronary Angiography: A Randomized Controlled Trial.

INTRODUCTION: Contrast-induced acute kidney injury (CI-AKI) is a serious complication of coronary angiography (CA). The aim of this randomized, parallel group, single blind, sham-controlled trial was to assess the safety and efficacy of the remote ischemic preconditioning on the prevention of CI-AKI. METHODS: Patients of 18-80 years of age with CKD 3 and 4, who were admitted for elective coronary angiography in a tertiary care hospital in eastern India were randomized in a 1:1 ratio to standard care with ischemic preconditioning (n = 45; intermittent arm ischemia through 4 cycles of 5-min inflation and 5-min deflation of a blood pressure cuff) or with standard care and sham ischemic preconditioning (n = 42). Overall, both study groups were at moderate risk of developing CI-AKI according to the Mehran risk score. The primary endpoint was the incidence of CI-AKI, defined as an increase in serum creatinine ≥25% or ≥0.5 mg/dL above baseline at 48 h after contrast medium exposure. RESULTS: CI-AKI occurred in 8 patients (19.04%) in the control group and 2 (4.4%) in the remote ischemic preconditioning group (odds ratio, 0.198, 95% confidence interval, 0.087 to 0.452; P = 0.04). No major adverse events were related to remote ischemic preconditioning. CONCLUSIONS: This study indicates that remote ischemic preconditioning is a simple and well-tolerated procedure, which reduces the incidence of CI-AKI in CKD 3 and 4 patients undergoing coronary angiography.

Effect of Chronotherapy of Antihypertensives in Chronic Kidney Disease: A Randomized Control Trial.

INTRODUCTION: There is a higher prevalence of non-dipping pattern in hypertensive chronic kidney disease (CKD) patients. Nocturnal hypertension has been shown to predict cardiovascular mortality and morbidity and is often superior to daytime blood pressure. We studied the effect of shifting or adding antihypertensive to night time on blood pressure profile of CKD III-IV patients. METHODS: In this single-center, prospective, randomized controlled trial, eligible participants were adults from eastern India aged 18-65 years with CKD stages 3 and 4, with a non-dipping pattern on ambulatory blood pressure monitor (ABPM). The intervention group received all the antihypertensives in the night time whereas the standard care group continued to take the medication in the morning. Both groups were followed up for 1 year. The primary outcome was the number of patients changed from non-dippers to dippers in the standard care group and intervention group. Secondary outcomes included a change in estimated glomerular filtration rate (eGFR) and change in the cardiac structure. RESULTS: 39 patients in the intervention group and 36 patients in the standard care group were analyzed. 10 patients (26%) reverted to dipping pattern in the intervention group as compared to none in the standard care group. Mean changes in eGFR were -2.55 and -0.18 mL/min/1.73 m2 in the standard care and intervention group at the end of the study, respectively. Between-group difference in eGFR was significant at 1 year (5.22 [95% CI, 4.3-6.1] ml/min/1.73 m2); (P = 0.03). The cardiac structure showed no significant changes in either group. CONCLUSIONS: Bedtime administration of antihypertensives reverted non-dippers to dippers and slowed the decline in eGFR in CKD stages 3 and 4 compared to morning administration of antihypertensives.

Prescription Practices in Patients With Mild to Moderate CKD in India.

INTRODUCTION: Patients with chronic kidney disease (CKD) require multiple medications. There is no information on prescription patterns or the use of evidence-based therapies for management of CKD from low-middle-income countries. Using baseline data from the Indian CKD (ICKD) cohort, we describe the drug prescription practices in patients with mild to moderate CKD. METHODS: The ICKD study is a prospective, observational cohort study of mild to moderate kidney disease across 11 centers in India. We analyzed all the prescriptions captured at enrollment in the ICKD study. Drugs were categorized into 11 different groups. We provide descriptive data on prescription details and evaluate the appropriateness of medication use. RESULTS: Complete prescription data were available in 3966 out of 4056 (97.8%) subjects enrolled in the ICKD database. Most patients had stage 3 CKD, 24.9% had diabetic kidney disease, 87% had hypertension, and 25.5% had moderate to severe proteinuria. Renin-angiotensin-aldosterone system blockers were prescribed in less than half (47.9%) and in 58.8% of patients with proteinuric CKD. Metformin was prescribed in 25.7% of diabetic subjects with CKD. Only 40.4% of patients were taking statins; 31.1% and 2.8% subjects with anemia were receiving iron and erythropoiesis-stimulating agents, respectively. CONCLUSION: This study highlights the missed opportunities for improving outcomes through appropriate prescriptions of drugs in patients with CKD. There is need for dissemination of evidence-based guidelines and institution of sustainable implementation practices for improving the overall health of patients with CKD.

Granulomatous Interstitial Nephritis - A Series of Six Cases.

Granulomatous interstitial nephritis is an uncommon variant accounting for about 6% of all tubulointerstitial nephritis. The etiology can be drugs such as antibiotics and nonsteroidal anti-inflammatory drugs and infections such as tuberculosis, sarcoidosis, and fungal infections. Renal biopsy remains the gold standard for establishing the diagnosis. Here, we present a series of six cases of granulomatous interstitial nephritis, of which two cases were associated with lupus nephritis and another two cases with crescentic glomerulonephritis. Focal segmental glomerulosclerosis and mesangiosclerosis with chronic tubulointerstitial nephritis were detected in the rest of the cases. Most of the patients presented with features of nephrotic syndrome. Urine analysis showed albuminuria in all cases. In renal biopsy, interstitial epithelioid cell granuloma was a constant feature along with which there were foci of necrosis and moderate fibrosis in few cases. But none of our cases had any relevant history of prolonged drug intake. Tuberculosis and fungal infections were also ruled out. Thereby in this case series, we subgroup all the cases into two category four cases associated with granulomatous nephritis and two cases with idiopathic granulomatous nephritis.

The changing face of pregnancy-related acute kidney injury from eastern part of India: A hospital-based, prospective, observational study.

This study was initiated to look into the etiologies, prevalence, and outcome of pregnancy-related acute kidney injury (PRAKI) in a tertiary care hospital. Women admitted with PRAKI from January 2015 to December 2016 were included in the study. All patients were investigated and treated and followed up for the next six months.. For statistical analysis, Chi- square test and analysis of variance were performed to analyze the data. Multivariate analysis was applied to compare the risk of nonrecovery of renal function in different etiologies of PRAKI. During the study period, 81 patients were admitted with PRAKI, of whom 68 (84%) received hemodialysis (HD). A total of 449 patients including all cases of AKI underwent HD from January 2015 to June 2016. The incidence of dialysis requiring PRAKI was 68 out of the 449 patients (15%). Sixty-eight (84%) patients required dialysis support while the most common cause was sepsis (49%), with the second being pregnancy-associated atypical hemolytic-uremic syndrome (P-aHUS) (17%) followed by obstetric hemorrhages (16%). There was a significant reduction of first-trimester AKI (8.6%) compared to a previous study published from this institute (19.3%). The maternal mortality (25%) and fetal mortality (23.5%) were high. Nearly 39% of the patients had complete recovery of renal function. This study revealed significant PRAKI burden due to a largely preventable cause, puerperal sepsis. Renal survival was poor in P- aHUS. The gaps in the obstetric care may be identified for the improvement of fetomaternal outcome.

Nonmedical Factors and Health-Related Quality of Life in CKD in India.

BACKGROUND AND OBJECTIVES: Patient-reported outcomes have gained prominence in the management of chronic noncommunicable diseases. Measurement of health-related quality of life is being increasingly incorporated into medical decision making and health care delivery processes. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: The Indian Chronic Kidney Disease Study is a prospective cohort of participants with mild to moderate CKD. Baseline health-related quality of life scores, determined by the standardized Kidney Disease Quality of Life 36 item instrument, are presented for the inception cohort (n=2919). Scores are presented on five subscales: mental component summary, physical component summary, burden, effect of kidney disease, and symptom and problems; each is scored 0-100. The associations of socioeconomic and clinical parameters with the five subscale scores and lower quality of life (defined as subscale score <1 SD of the sample mean) were examined. The main socioeconomic factors studied were sex, education, occupation, and income. The key medical factors studied were age, eGFR, diabetes, hypertension, and albuminuria. RESULTS: The mean (SD) subscale scores were physical component summary score, 43±9; mental component summary score, 48±10; burden, 61±33; effects, 87±13; and symptoms, 90±20. Among the socioeconomic variables, women, lower education, and lower income were negatively associated with reduced scores across all subscales. For instance, the respective ß-coefficients (SD) for association with the physical component summary subscale were -2.6 (-3.4 to -1.8), -1.5 (-2.2 to -0.7), and -1.6 (-2.7 to -0.5). Medical factors had inconsistent or no association with subscale scores. The quality of life scores also displayed regional variations. CONCLUSIONS: In this first of its kind analysis from India, predominantly socioeconomic factors were associated with quality of life scores in patients with CKD.

A Cross-sectional Prospective Study of Asymptomatic Urinary Abnormalities, Blood Pressure, and Body Mass Index in Healthy School Children.

INTRODUCTION: Screening school children for urinary abnormalities is an inexpensive task but is not commonly undertaken in India. Although debated in western countries, its utility in early diagnosis of kidney disorders has been proved by studies from Asia. We examined the prevalence of asymptomatic urinary abnormalities (AUA), obesity, and hypertension in school children and analyzed data to identify potential risk factors among those detected with such abnormalities. METHODS: Children and adolescents 8 to 18 years of age of either gender, attending 14 public schools in West Bengal, were screened prospectively from July 2013 to July 2016 for detecting asymptomatic urinary abnormalities by a spot urine test using a dipstick. Sociodemographic profile, medical examination (weight, height, and blood pressure), and questionnaire-based data were recorded. RESULTS: A total of 11,000 children were screened. Of these, data from 9306 children were available for AUA, obesity, and hypertension. The prevalence rate was 7.44% (95% confidence interval [CI] = 6.91%-7.97%) for at least 1 AUA. Isolated hematuria was present in 5.2% (95% CI 4.75%-5.65%), whereas isolated proteinuria was present in 1.9% (95% CI = 1.62%-2.18%). The prevalence of prehypertension was 13.43% (95% CI = 12.74%-14.12%) and that of hypertension and abnormal body mass index was 4.05% (95% CI = 6.43%-7.47%) and 38.67 (95% CI = 37.68%-39.66%) respectively. DISCUSSION: The prevalence rates of AUA were comparable with those in some Asian countries but higher than in most developed countries. Of children and adolescents 8 to 18 years of age, those 13 to 18 years had significantly more high risk factors such as AUA, hypertension, and obesity.

Herpes labialis in patients with Russell's viper bite and acute kidney injury: a single center experience.

Snake bite is an important health hazard in tropical countries and is associated with significant morbidity and mortality. Herpes labialis is a common ailment caused by the Herpes simplex virus. There is no published data showing any association between the snake bite and development of Herpes labialis. Here, we present a series of patients who developed Herpes labialis after Russell's viper bite and had acute kidney injury. We attempted to find whether snake bite is an immunosuppressed state and whether it could have pre-disposed the patients to the development of these lesions.