Papers by Ashok Kumar Yadav
Clinical Journal of the American Society of Nephrology, 2021
Clinical Kidney Journal, 2021
Background Chronic kidney disease (CKD) is an important cause of morbidity and mortality worldwid... more Background Chronic kidney disease (CKD) is an important cause of morbidity and mortality worldwide. There is a lack of information on epidemiology and progression of CKD in low–middle income countries. The Indian Chronic Kidney Disease (ICKD) study aims to identify factors that associate with CKD progression, and development of kidney failure and cardiovascular disease (CVD) in Indian patients with CKD. Methods ICKD study is prospective, multicentric cohort study enrolling patients with estimated glomerular filtration rate (eGFR) 15–60 mL/min/1.73 m2, or >60 mL/min/1.73 m2 with proteinuria. Clinical details and biological samples are collected at annual visits. We analysed the baseline characteristics including socio-demographic details, risk factors, disease characteristics and laboratory measurements. In addition, we compared characteristics between urban and rural participants. Results A total of 4056 patients have been enrolled up to 31 March 2020. The mean ± SD age was 50.3 ...
JCR: Journal of Clinical Rheumatology, 2019
The aim of this study was to assess endothelial dysfunction in acute and convalescent phases of K... more The aim of this study was to assess endothelial dysfunction in acute and convalescent phases of Kawasaki disease (KD) using automated edge detection software. Methods: This was a case-control study to assess the flow-mediated dilatation (FMD) of brachial artery (BA) in patients with KD during acute phase and at least 3 months after diagnosis. A 10-MHz multifrequency linear array probe attached to a high-resolution ultrasound machine (PHILIPS Medical System-IU22) was used to acquire the images. Automated edge detection software was used to assess BA diameter. Results: A total of 16 children with KD and 16 healthy children were enrolled in the study. Mean ± SD maximum BA diameter was found to be significantly low during the acute stage of KD (2.56 ± 0.36 mm) as compared with the convalescence phase (2.93 mm ± 0.31) and in healthy controls (2.95 mm ± 0.56). The mean ± SD percentage change in the FMD was found to be significantly low in the acute phase of KD (12.32 ± 6.2) as compared with the convalescence phase of KD (17.99 ± 8.13) and healthy controls (26.88 ± 12.76). The mean ± SD percentage change in the FMD was also found to be significantly low in the convalescence phase of KD as compared with healthy controls. Conclusions: The FMD of the BA is significantly reduced in patients during the acute and convalescence phase of KD as compared with normal healthy children. The endothelial dysfunction was present even in patients who had no obvious coronary artery abnormalities during the acute stage.
Kidney international reports, 2017
Fibroblast Growth Factor 23 (FGF23) in untreated Nephrotic syndrome
Nephrology (Carlton, Vic.), Jan 14, 2017
Despite its importance in bone and cardiovascular disease in subjects with kidney disease, there ... more Despite its importance in bone and cardiovascular disease in subjects with kidney disease, there is no data on fibroblast growth factor 23 (FGF23) perturbations in nephrotic syndrome. We evaluated FGF23 and markers of mineral bone metabolism in subjects with untreated NS. In this cross-sectional study, we measured circulating levels of FGF23, 25-hydroxy vitamin D [25(OH)D], 1,25 di-hydroxy vitamin D [1,25(OH)2 D], serum albumin, serum calcium, phosphorus, creatinine and intact parathyroid hormone (iPTH) in 101 patients with adults onset NS and 40 healthy controls. We examined the correlation between FGF23 and markers of mineral bone metabolism. Compared to healthy controls, subjects with NS showed reduced levels of 25(OH)D (21.76 ± 10.18 vs 35.74 ± 40.27 nmol/l, p = 0.001), 1,25(OH)2 D (median; 37.80 vs 73.13 pmol/l, p < 0.0001) and FGF23 (37.81 ± 20.42 vs 48.20 ± 11.60 pg/ml, p = 0.004) levels. Serum phosphorus levels were marginally, but significantly higher in subjects with ne...
BMC nephrology, Feb 1, 2018
Accurate estimation of glomerular filtration rate (GFR) is important for diagnosis and risk strat... more Accurate estimation of glomerular filtration rate (GFR) is important for diagnosis and risk stratification in chronic kidney disease and for selection of living donors. Ethnic differences have required correction factors in the originally developed creatinine-based GFR estimation equations for populations around the world. Existing equations have not been validated in the vegetarian Indian population. We examined the performance of creatinine and cystatin-based GFR estimating equations in Indians. GFR was measured by urinary clearance of inulin. Serum creatinine was measured using IDMS-traceable Jaffe's and enzymatic assays, and cystatin C by colloidal gold immunoassay. Dietary protein intake was calculated by measuring urinary nitrogen appearance. Bias, precision and accuracy were calculated for the eGFR equations. A total of 130 participants (63 healthy kidney donors and 67 with CKD) were studied. About 50% were vegetarians, and the remainder ate meat 3.8 times every month. Th...
Background: Accurate estimation of glomerular filtration rate (GFR) is important for diagnosis an... more Background: Accurate estimation of glomerular filtration rate (GFR) is important for diagnosis and risk stratification in chronic kidney disease and for selection of living donors. Ethnic differences have required correction factors in the originally developed creatinine-based GFR estimation equations for populations around the world. Existing equations have not been validated in the vegetarian Indian population. We examined the performance of creatinine and cystatin-based GFR estimating equations in Indians. Methods: GFR was measured by urinary clearance of inulin. Serum creatinine was measured using IDMS-traceable Jaffe's and enzymatic assays, and cystatin C by colloidal gold immunoassay. Dietary protein intake was calculated by measuring urinary nitrogen appearance. Bias, precision and accuracy were calculated for the eGFR equations. Results: A total of 130 participants (63 healthy kidney donors and 67 with CKD) were studied. About 50% were vegetarians, and the remainder ate meat 3.8 times every month. The average creatinine excretion were 14.7 mg/kg/day (95% CI: 13.5 to 15.9 mg/kg/day) and 12.4 mg/kg/day (95% CI: 11.2 to 13.6 mg/kg/day) in males and females, respectively. The average daily protein intake was 46.1 g/day (95% CI: 43.2 to 48.8 g/day). The mean mGFR in the study population was 51.66 ± 31.68 ml/min/1.73m 2. All creatinine-based eGFR equations overestimated GFR (p < 0.01 for each creatinine based eGFR equation). However, eGFR by CKD-EPI Cys was not significantly different from mGFR (p = 0.38). The CKD-EPI Cys exhibited lowest bias [mean bias: −3.53 ± 14.70 ml/min/1.73m 2 (95% CI:-0.608 to −0.98)] and highest accuracy (P 30 : 74.6%). The GFR in the healthy population was 79.44 ± 20.19 (range: 41.90–134.50) ml/min/1.73m 2. Conclusion: Existing creatinine-based GFR estimating equations overestimate GFR in Indians. An appropriately powered study is needed to develop either a correction factor or a new equation for accurate assessment of kidney function in the Indian population.
Background & objectives: Uromodulin, a UMOD gene encoded glycoprotein is synthesized exclusively ... more Background & objectives: Uromodulin, a UMOD gene encoded glycoprotein is synthesized exclusively in renal tubular cells and released into urine. Mutations lead to uromodulin misfolding and retention in the kidney, where it might stimulate cells of immune system to cause inflammation and progression of kidney disease. Genome-wide association studies (GWAS) have identified UMOD locus to be associated with hypertension and diabetic nephropathy (DN). In this study, we investigated the association between rs4293393 variation in UMOD gene and susceptibility to kidney disease in individuals with type 2 diabetes mellitus (T2DM).
Aim: Despite its importance in bone and cardiovascular disease in subjects
Background: Accurate estimation of glomerular filtration rate (GFR) is important for diagnosis an... more Background: Accurate estimation of glomerular filtration rate (GFR) is important for diagnosis and risk stratification in chronic kidney disease and for selection of living donors. Ethnic differences have required correction factors in the originally developed creatinine-based GFR estimation equations for populations around the world. Existing equations have not been validated in the vegetarian Indian population. We examined the performance of creatinine and cystatin-based GFR estimating equations in Indians. Methods: GFR was measured by urinary clearance of inulin. Serum creatinine was measured using IDMS-traceable Jaffe's and enzymatic assays, and cystatin C by colloidal gold immunoassay. Dietary protein intake was calculated by measuring urinary nitrogen appearance. Bias, precision and accuracy were calculated for the eGFR equations. Results: A total of 130 participants (63 healthy kidney donors and 67 with CKD) were studied. About 50% were vegetarians, and the remainder ate meat 3.8 times every month. The average creatinine excretion were 14.7 mg/kg/day (95% CI: 13.5 to 15.9 mg/kg/day) and 12.4 mg/kg/day (95% CI: 11.2 to 13.6 mg/kg/day) in males and females, respectively. The average daily protein intake was 46.1 g/day (95% CI: 43.2 to 48.8 g/day). The mean mGFR in the study population was 51.66 ± 31.68 ml/min/1.73m 2. All creatinine-based eGFR equations overestimated GFR (p < 0.01 for each creatinine based eGFR equation). However, eGFR by CKD-EPI Cys was not significantly different from mGFR (p = 0.38). The CKD-EPI Cys exhibited lowest bias [mean bias: −3.53 ± 14.70 ml/min/1.73m 2 (95% CI:-0.608 to −0.98)] and highest accuracy (P 30 : 74.6%). The GFR in the healthy population was 79.44 ± 20.19 (range: 41.90–134.50) ml/min/1.73m 2. Conclusion: Existing creatinine-based GFR estimating equations overestimate GFR in Indians. An appropriately powered study is needed to develop either a correction factor or a new equation for accurate assessment of kidney function in the Indian population.
Please cite this article as: Yadav AK, Kumar V, Banerjee D, Gupta KL, Jha V, Effect of vitamin D ... more Please cite this article as: Yadav AK, Kumar V, Banerjee D, Gupta KL, Jha V, Effect of vitamin D supplementation on serum sclerostin levels in chronic kidney disease, Journal of Steroid Biochemistry and Molecular Biology (2010), https://doi.Highlights: Serum sclerostin level correlated with 25(OH) D at baseline in CKD Subjects. Cholecalciferol supplementation did not lead to change in serum sclerostin. Change in serum sclerostin level at 16 weeks correlated with change in eGFR and change in serum uric acid. Abstract Vitamin D deficiency, cardiovascular disease and abnormal bone mineral metabolism are common in chronic kidney disease (CKD). Abnormal bone mineral metabolism has been linked to vascular calcification in CKD. Sclerostin has emerged as an important messenger in cross talk between bone-vascular axis. We analyzed sclerostin in subjects who participated in the randomized, double blind, placebo controlled trial investigating the effect of cholecalciferol supplementation on vascular function in non-diabetic CKD stage G3-4 and vitamin D ≤20ng/ml [CTRI/2013/05/003648]. Patients were randomized (1:1) to receive either two directly observed oral doses of 300,000 IU of cholecalciferol or matching placebo at baseline
Journal of steroid biology and molecular biology
Vitamin D deficiency is common and associated with mortality in chronic kidney disease (CKD) pati... more Vitamin D deficiency is common and associated with mortality in chronic kidney disease (CKD) patients. Cardiovascular disease (CVD) is the commonest cause of mortality in CKD patients. In a randomized, double blind, placebo controlled trial, we have recently reported favorable effects of vitamin D supplementation on vascular & endothelial function and inflammatory biomarkers in vitamin D deficient patients with non-diabetic stage 3–4 CKD (J Am Soc Nephrol 28: 3100–3108, 2017). Subjects in the placebo group who had still not received vitamin D after completion of the trial received two oral doses 300,000 IU of oral cholecalciferol at 8 weeks interval followed by flow mediated dilatation (FMD), pulse wave velocity (PWV), circulating endothelial and inflammatory markers (E-Selectin, vWF, hsCRP and IL-6), 125 (OH) 2 D, iPTH and iFGF-23 assessment at 16 weeks. 31 subjects completed this phase of the study. Last values recorded in the preceding clinical trial were taken as baseline values. Serum 25(OH)D and 1,25(OH) 2 D increased and FMD significantly improved after cholecalciferol supplementation [mean change in FMD%: 5.8% (95% CI: 4.0–7.5%, p < 0.001]. Endothelium independent nitroglycerine mediated dilatation, PWV, iPTH, iFGF-23 and IL-6 also showed favorable changes. The data further cement the findings of beneficial effects of correction of vitamin D deficiency on vascular function.
Use of active forms of vitamin D is advocated in patients with chronic kidney disease (CKD) for t... more Use of active forms of vitamin D is advocated in patients with chronic kidney disease (CKD) for treatment of mineral bone disease because of the presumption that native forms of vitamin D would not undergo significant activation to calcitriol, the most active biological form of vitamin D. We present secondary analysis looking at bone turnover in subjects who completed the randomized, double blind, placebo-controlled trial investigating the effect of cholecalciferol supplementation on vascular function in nondiabetic CKD stage G3G4 and vitamin D 20 ng/mL (Clinical Trials Registry of India: CTRI/2013/05/003648). Patients were randomized (1:1) to receive either two directly observed oral doses of 300,000 IU of cholecalciferol or matching placebo at baseline and 8 weeks. Of the 120 subjects enrolled, 58 in the cholecalciferol group and 59 in the placebo group completed the study. At 16 weeks, the serum 25(OH)D and 1,25(OH) 2 D levels increased in the cholecalciferol group but not in the placebo group (between-group difference in mean change: 23.40 ng/mL; 95% CI, 19.76 to 27.06; p < 0.001, and 14.98 pg/mL; 95% CI, 4.48 to 27.18; p ¼ 0.007, respectively). Intact parathyroid hormone (iPTH) decreased in the cholecalciferol group (between-group difference in mean change –100.73 pg/mL (95% CI, –150.50 to –50.95; p < 0.001). Serum total and bone-specific alkaline phosphatase (SAP, BAP) and serum C-terminal cross-linked collagen type I telopeptides (CTX-1) were significantly reduced in cholecalciferol group (between group difference for change in mean: –20.25 U/L; 95% CI, –35.14 to –5.38 U/L; p ¼ 0.008 for SAP; –12.54 U/L; 95% CI, –22.09 to –2.98 U/L; p ¼ 0.013 for BAP; and –0.21 ng/mL; 95% CI, –0.38 to –0.05 ng/mL; p ¼ 0.05 for CTX-1). Correlation analysis showed significant correlation of D25(OH)D with DiPTH (r ¼ –0.409, p < 0.0001), D1,25(OH) 2 D (r ¼ 0.305, p ¼ 0.001), DSAP (r ¼ –0.301, p ¼ 0.002), DBAP (r ¼ –0.264, p ¼ 0.004), and DCTX-1 (r ¼ –0.210, p ¼ 0.0230). Cholecalciferol supplementation corrects vitamin D deficiency and is effective in lowering serum intact parathyroid hormone and bone turnover markers in early stages of CKD.
Vitamin D deficiency associates with mortality in patients with CKD, and vitamin D supplementatio... more Vitamin D deficiency associates with mortality in patients with CKD, and vitamin D supplementation might mitigate cardiovascular disease risk in CKD. In this randomized, double-blind, placebo-controlled trial, we investigated the effect of cholecalciferol supplementation on vascular function in 120 patients of either sex, aged 18–70 years, with nondiabetic CKD stage 3–4 and vitamin D deficiency (serum 25-hydroxyvitamin D #20 ng/ml). We randomized patients using a 1:1 ratio to receive either two directly observed oral doses of cholecalciferol (300,000 IU) or matching placebo at baseline and 8 weeks. The primary outcome was change in endothelium-dependent brachial artery flow-mediated dilation at 16 weeks. Secondary outcome measures included changes in pulse wave velocity and circulating biomarkers. Cholecalciferol supplementation significantly increased endothelium-dependent brachial artery flow-mediated dilation at 16 weeks, whereas placebo did not (between-group difference in mean change: 5.49%; 95% confidence interval, 4.34% to 6.64%; P,0.001). Intervention also led to significant favorable changes in pulse wave velocity and circulating IL-6 levels. Thus, in nondiabetic patients with stage 3–4 CKD and vitamin D deficiency, vitamin D supplementation may improve vascular function. This study is registered with the Clinical Trials Registry of India (no.: CTRI/2013/05/003648).
This study aims to determine risk factors for CKD progression and CVD development in Indian peopl... more This study aims to determine risk factors for CKD progression and CVD development in Indian people through the international comparisons to determine ethnic and geographical differences. Authors also apply the bio-repository to discover biomarkers and explore genetic risk factors in this study. ABSTRACT: Aim: The rate and factors that influence progression of chronic kidney disease
Aim Despite its importance in bone and cardiovascular disease in subjects with kidney disease, th... more Aim Despite its importance in bone and cardiovascular disease in subjects with kidney disease, there is no data on fibroblast growth factor 23 (FGF23) perturbations in nephrotic syndrome. We evaluated FGF23 and markers of mineral bone metabolism in subjects with untreated NS. Methods In this cross-sectional study, we measured circulating levels of FGF23, 25-hydroxy vitamin D [25(OH)D], 1,25 di-hydroxy vitamin D [1,25(OH) 2 D], serum albumin, serum calcium, phosphorus, creatinine and intact parathyroid hormone (iPTH) in 101 patients with adults onset NS and 40 healthy controls. We examined the correlation between FGF23 and markers of mineral bone metabolism.
BACKGROUND & OBJECTIVES: CNDP1 gene, present on chromosome 18q22.3-23, encodes carnosinase, the r... more BACKGROUND & OBJECTIVES: CNDP1 gene, present on chromosome 18q22.3-23, encodes carnosinase, the rate-limiting enzyme in hydrolysis of carnosine to ß-alanine and L-histidine. Linkage of CTG trinucleotide (leucine) repeat polymorphism in CNDP1 gene with diabetic nephropathy has been observed in several populations. However, this association is conflicting and population-dependent. We investigated this association in type 2 diabetes mellitus (T2DM) patients with and without nephropathy in north India.METHODS: A total of 564 individuals [199 T2DM without nephropathy (DM), 185 T2DM with nephropathy (DN) and 180 healthy individuals (HC)] were enrolled. CNDP1 CTG repeat analysis was done by direct sequencing of a 377 base pair fragment in exon 2.RESULTS: The most frequent leucine (L) repeats were 5L-5L, 6L-5L and 6L-6L. 5L-5L genotype frequency was reduced in DN (24.3%) as compared to DM (34.7%, P=0.035) and HC (38.4%, P=0.005). Similarly, 5L allele frequency was lower in DN (46.8%) as compared to DM (57.3%, P=0.004) and HC (60.5%, P<0.001). The genotype and allelic frequencies were similar in DM and HC groups. No gender specific difference was observed in the genotype or allelic frequencies between groups.INTERPRETATION & CONCLUSIONS: Compared to healthy individuals and those with diabetes but no kidney disease, patients with diabetic nephropathy exhibited lower frequencies of 5L-5L genotype and 5L allele of CNDP1 gene, suggesting that this allele might confer protection against development of kidney disease in this population.
Kidney International (2016) 90, 905-906; http://dx.Kidney International (2016) 90, 906-907; http:... more Kidney International (2016) 90, 905-906; http://dx.Kidney International (2016) 90, 906-907; http://dx.
A prospective study of collapsing focal segmental glomerulosclerosis.
Collapsing focal segmental glomerulosclerosis (cFSGS) is characterized by rapid progression to en... more Collapsing focal segmental glomerulosclerosis (cFSGS) is characterized by rapid progression to end-stage renal disease (ESRD). We evaluated the clinicopathological spectrum of cFSGS and compared its clinical behavior to steroid and tacrolimus (TAC)-resistant noncollapsing focal segmental glomerulosclerosis (FSGS). All patients (>14 years) diagnosed with cFSGS were enrolled in the study. Staining for differentiated podocyte markers such as WT 1, PAX and KI67 were performed in all patients. The outcome and histological features of cFSGS was compared with a prospectively followed cohort of steroid and TAC-resistant noncollapsing FSGS. The study included 22 cFSGS patients and 19 cases of steroid and TAC-resistant FSGS. Complete remission, partial remission, steroid resistance, progression to ESRD and death were observed in 13.6%, 4.5%, 27.3%, 36.4% and 18.2% patients, respectively. Patients with cFSGS had higher serum creatinine and more advanced tubulointerstitial changes compared to resistant FSGS. Twenty-six percent of therapy resistant noncollapsing FSGS progressed to ESRD after two years of stopping TAC. However, there was no difference in progression to ESRD between cFSGS and therapy-resistant noncollapsing FSGS at the end of two years. Glomerular collapse in the setting of FSGS is poorly responsive to treatment and has a high rate of progression to ESRD. The long-term prognosis of cFSGS and steroid and TAC-resistant FSGS are similar.
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Papers by Ashok Kumar Yadav