SMS Medical College and Hospital, Jaipur
Jaipur, Rajasthan | India
Main Specialties: Nephrology
Additional Specialties: Nephrology
Dr. Rajesh Jhorawat did his MBBS from prestigious All India Institute of Medical Sciences (AIIMS) New Delhi, MD from PGI Chandigarh & DM (Nephrology) from SMS Medical College Jaipur.
Dr Jhorawat has Experience in Clinical Immunology (including Transplant Immunology) from SGPGI (Lucknow) & published many papers in index journal. His study & his work have been selected for presentation both in national & international Nephrology Meet.
He is active member of-
Indian Society of Nephrology (ISN)
American Society of Nephrology (ASN)
European Renal Association (ERA - EDTA)
International Society of Nephrology (ISN)
Primary Affiliation: SMS Medical College and Hospital, Jaipur - Jaipur, Rajasthan , India
4PubMed Central Citations
Indian journal of nephrology 28 (1), 41
Indian journal of nephrology 28 (1), 41
The aim of this study was to measure insulin resistance (IR) in dialysis patients and its relation to Vitamin D status and nutritional parameters. We included patients on maintenance dialysis, both hemodialysis and peritoneal dialysis (HD and PD). IR was measured by homeostatic model assessment (HOMA)-IR index defined as fasting serum insulin (μU/L) × fasting blood sugar (mmol/L)/22.5. Baseline Vitamin D levels were measured by chemiluminescence immunoassay (CLIA) method. HOMA-IR index correlated with nutritional parameters such as 7-point subjective global assessment (SGA) and anthropometric measures, for example, body fat percentage, lean body weight (LBW), mid-arm circumference (MAC), and mid-arm muscle circumference (MAMC). A total of 55 patients were studied, of them 74.55% were male with mean age of the study population being 37.44 ± 14.96 years. The prevalence values of Vitamin D deficiency <30 ngm/ml, <20 ngm/ml, and <10 ngm/ml levels were 96.36%, 70.91%, and 23.64%, respectively. Mean HOMA-IR index was 3.14 ± 3.86. The correlation of HOMA-IR with Vitamin D was negative (r = −0.140, 95% confidence interval [CI] = −0.397–0.138 and P = 0.309); however, in subgroup analysis, patients with Vitamin D level <20 ng/ml had significantly high IR compared to those with Vitamin D >20 ng/ml, i.e., 3.74 ± 4.37 and 1.67 ± 1.47, respectively (P = 0.018). The other measured parameter which had a significant positive correlation with IR was serum uric acid (r = 0.303, 95% CI = 0.021–0.534, and P = 0.025). In nutritional assessment, body mass index, MAC, and MAMC had statistically significant positive correlation with HOMA-IR index (P ≤ 0.001, 0.004, and 0.004, respectively) unlike SGA (P = 0.480). The mode of dialysis did not have a significant effect on IR (HD vs. PD, P = 0.227). The majority of the patients on maintenance dialysis are Vitamin D deficient. Low Vitamin D level, especially <20 ng/ml, muscle mass, and high serum uric acid level are likely to have more IR in dialysis-dependent patients.
Despite new advances in the treatment of chronic kidney disease (CKD), it remains an important public health challenge. CKD is a major risk factor for cardiovascular disease, which is the leading cause of mortality in these patients. Cardiac mortality in dialysis patients is more than 10-fold greater than that of the general population. The excess cardiovascular mortality in patients with CKD is not fully explained by traditional risk factors such as hypertension, hypercholesterolemia, and smoking. One of the factors which were neglected in earlier studies was insulin resistance (IR) in CKD. IR which is a central pathogenic mechanism in metabolic syndrome and recognized in CKD patients has been directly associated with increased cardiovascular mortality in many studies.[3,4]
IR can be physiologic (e.g., in pregnancy) or pathologic as in CKD and it is linked to protein energy wasting and malnutrition in dialysis patients.[5,6] Hyperinsulinemic-euglycemic clamp is the gold standard for IR determination because it provides a direct measure of whole-body sensitivity to insulin. Other is oral glucose tolerance test primarily measuring glucose tolerance, which reflects both IR and beta-cell function. However, due to the complexity of these methodologies, more practical methods such as homeostatic model assessment (HOMA) and the quantitative insulin sensitivity check index are widely used in clinical studies.
The role of Vitamin D deficiency in several pathological conditions has been the focus of several investigations in the last few years. The complexity of the biological role of Vitamin D metabolism makes it difficult to clearly delineate the role of Vitamin D cascade in this complex pathophysiology of IR. In CKD, Vitamin D status has been related to IR; however, very limited information is available on dialysis patients and factors affecting IR. We designed this study to assess the IR in dialysis patients and its relation with Vitamin D status.
It was a cross-sectional, observational study.
We included 55 patients both on maintenance hemodialysis and peritoneal dialysis (HD and PD). The inclusion criteria were those who were on regular maintenance dialysis either on PD or HD and had age more than 18 years. Both diabetic and nondiabetic patients were included. The exclusion criteria were as follows:
This study was approved by our local ethics committee and written consent was obtained from all included patients.
We measured blood hemoglobin level, serum creatinine, serum urea, serum calcium, serum phosphorus, serum alkaline phosphatase (ALP), serum albumin, and serum uric acid before starting HD and in the morning before starting PD. The morning fasting blood sugar and blood insulin level were measured. The homoeostasis model (HOMA) was used for the assessment of IR with the following formula:
HOMA-IR (mmol/l × mU/ml) = fasting plasma glucose (mmol/l) × Fasting plasma insulin (mU/ml)/22.5.
25-(OH) Vitamin D level was measured using CLIA system, with Immulite 2000, Advia Centaur XP-Siemens system.
Parameters such as weight (kg), heights (m), body mass index (BMI), mid-arm circumference (MAC), mid-arm muscle circumference (MAMC), total body fat, lean body weight (LBW), and subjective global assessment (SGA) were measured of all included patients [Supplement][10,11,12].
The statistical analyses were carried out using Statistical Package for Social Sciences for Windows version 20 (SPSS Chicago, IL, USA). The univariate analyses were expressed as mean ± standard deviation or percentages. ANOVA was used for comparison of the groups of SGA and their HOMA-IR index. HOMA-IR of two groups was compared using Mann–Whitney test, i.e., male versus females and HD versus PD and the correlation between nonparametric data was estimated using Spearman's coefficient. P < 0.05 was considered statistically significant.
A total of 55 diabetic and nondiabetic patients on dialysis were included in our study. Their demographic and laboratory profile are shown in Table 1. Forty-one (74.55%) patients were male. The mean age was 37.44 ± 14.96 years, height was 166.24 ± 8.66 cm, body weight was 52.81 ± 10.21 kg, LBW was 44.81 ± 7.81 kg, body fat percentage was 14.6 ± 8.80, body fat weight was 8 ± 6.15 kg, fat weight–to-LBW ratio was 0.18 ± 0.14, LBW index was 16.13 ± 2, and BMI was 19.06 ± 3.16. The cause of end-stage renal disease was chronic glomerulonephritis in 15 patients (27.27%), hypertension in seven patients (12.73%), diabetic nephropathy in seven patients (12.73%), polycystic kidney disease in two patients (3.64%), and unknown in 24 (43.64%). The estimated glomerular filtration rate by Cockcroft–Gault formula was 7.82 ± 3.04 ml/min/1.73 m2.
As per SGA, all patients have some degree of malnutrition. Six patients had mild degree of malnutrition (10.9%), 46 patients had moderate degree of malnutrition (83.64%), and three patients had severe degree of malnutrition (5.46%). As per BMI, thirty patients were <19 kg/m2 (54.55%), 23 patients were between 19 and 25 kg/m2 (41.82%), and two were >25 kg/m2 (3.64%). Of 55 patients, 42 were on HD (73.36%) and 13 patients were on PD (23.64%).
Age, hemoglobin level, serum albumin, and serum uric acid had positive correlation with IR; however, only uric acid level had significant association (r = 0.303, 95% confidence interval [CI] 0.021–0.534, P = 0.025) [Table 2]. Duration of dialysis, serum ALP, parathyroid hormone, and Vitamin D level had negative correlation; however, only Vitamin D level < 20 ngm/ml had significantly higher IR (3.743 ± 4.367) compared to those with Vitamin D level >20 ngm/ml (1.673 ± 1.473 (P = 0.018) as shown in Figure 1a.
Of all the measured nutritional parameters as detailed in Table 3, lean BMI (r = 0.375, 95% CI: 0.099–0.669, P = 0.005), MAC (r = 0.377, 95% CI: 0.115–0.586, P = 0.004), MAMC (r = 0.380 95% CI: 0.121–0.579, P = 0.004), and BMI (r = 0.451, 95% CI: 0.231–0.717, P = 0.001) had significant positive association with IR. Body fat percentage did not had strong correlation in our study; however, body fat weight had achieved significant association with IR (r = 0.275, 95% CI: 0.038–0.531, P = 0.041).
The mean HOMA-IR index in mild, moderate, and severe grade malnutrition by SGA was 2.54 ± 1.55, 3.27 ± 4.17, and 2.39 ± 2.05, respectively (P = 0.861). The IR between male and female was 3.12 ± 3.69 and 2.44 ± 2.55, respectively (P = 0.528). HOMA-IR index in HD and PD patients was 3.101 ± 4.223 (P = 0.277) [Figure 1b]. Diabetic patients who were on dialysis had IR similar with that of nondiabetic patients on dialysis in our study (2.774 ± 1.800 vs. 3.194 ± 4.087, P = 0.647).
We studied dialysis patients and majority were male; however, the IR was not different in either gender in our study group (P = 0.528). The mean Vitamin D level was 15.91 ± 7.98 ng/ml and majority were Vitamin D deficient. In our study, the prevalence values of Vitamin D deficiency <10 ng/ml, <20 ng/ml, and <30 ng/ml levels were 23.64%, 70.91%, and 96.36%, respectively. Studies have reported 70%–80% prevalence of Vitamin D deficiency in CKD patients which worsens with deteriorating renal function.[13,14] The mode of dialysis did not affect IR in dialysis patients in our study (P = 0.277). In an earlier study, both HD and PD had shown similar improvement in IR after initiation of dialysis.
The Vitamin D and IR had nonsignificant negative correlation; however, in subgroup analysis, patients with Vitamin D level <20 ng/ml had significantly high IR compared to those with Vitamin D level >20 ng/ml [Figure 1a]. There is also experimental evidence that Vitamin D is related to IR, a condition frequently observed in patients with progressive renal disease. Earlier study by Chonchol and Scragg also support our finding and had shown that renal dysfunction and Vitamin D have independent inverse associations with IR.
Another important association of IR is with serum uric acid level which has been considered as a potential risk factor in the development and progression of CKD. IR has significant positive correlation with serum uric acid (r = 0.303 95% CI: 0.021–0.534, P = 0.025). This is not new in metabolic syndrome patients. However, in our study, this association reflects significance of uric acid in dialysis patients also.
One of the most important predictive factors for survival on dialysis is the presence of malnutrition.[19,20] Moreover, most of the patients in our study were malnourished. The mean BMI was 19.055 ± 3.161 kg/m2 and more than 50% patientshave BMI <19 kg/m2. As measured by SGA, around 80% patients had moderate grade malnutrition. Out of the measured parameters, BMI, MAC, MAMC, and body fat content had significant positive correlation with IR [Figure 2 and Table 2]. This means that muscle mass and body fat have significant associations with IR in dialysis patients. Other studies also have reported significant positive correlation of BMI and body fat with IR.[21,22]
Although the exact mechanism for IR in CKD remains unclear, a postreceptor defect in the insulin-receptor signaling pathway in skeletal muscle is the likely primary abnormality. Siew et al. have highlighted that IR is an important determinant of protein breakdown in CKD. It appears that in CKD patients requiring dialysis, skeletal muscle is the primary tissue which is responsible for IR. In our study, IR increases with skeletal muscle mass; however, in sarcopenic patients, other factors such as metabolic acidosis, inflammation, and oxidative stress might be the main contributors of IR.
There are many limiting factors in our study. First, inflammatory state of the patient which is an important mechanism of IR in CKD has not mean measured and needs a well-controlled study. Second, visceral fat which has been reported in some studies to be related with IR has not been measured in our study. Third, dual-energy X-ray absorptiometry or bioimpedance was not used in our study. Finally, IR was quantified using the surrogate index of HOMA, and these findings need to be confirmed using euglycemic clamp technique.
Serum uric acid and Vitamin D level <20 ng/ml significantly influence the insulin sensitivity in dialysis patients. Anthropometric measures which indicate body muscle mass are more strongly correlated with IR in dialysis patients. It appears that the milieu in CKD is different, where IR is less likely depended on underlying causes and mode of dialysis. However, IR is a potentially modifiable cardiovascular risk factor and more studies are required in the future regarding intervention for preventing IR and its effect on cardiovascular morbidity.
There are no conflicts of interest.
Indian J Med Res 2016 Nov;144:725-729
Indian J Med Res
Background & objectives: Adriamycin though considered as an effective anticancer drug, leads to irreversible cardiomyopathy (CMP) and congestive heart failure (CHF). The aim of this study was to determine the protective effect of carvedilol in adriamycin (ADR)-induced cardiomyopathy (CMP) in cancer patients. Methods: Patients with lymphoreticular malignancy in whom ADR therapy was planned were randomized into two groups: carvedilol and control. Twenty seven patients each were enrolled in carvedilol and control groups. In the carvedilol group, 12.5 mg once daily oral carvedilol was given during six months. The patients were evaluated by echocardiography before and after chemotherapy. Left ventricular ejection fraction (EF) and systolic and diastolic diameters were calculated. Results: At six months of follow up, six patients in the carvedilol group and five in the control group had died. The mean EF (63.19 vs. 63.88%) and fraction shortening (FS) (34 vs. 34.6) of the carvedilol group were similar at follow up, but in the control group, the mean EF (67.27 vs. 60.82%, P=0.003) and FS (38.48 vs. 34.6, P<0.05) at control echocardiography were significantly lower. In carvedilol group, both systolic and diastolic diameters were not changed, but in control group, systolic diameters were significantly increased compared with basal measures (left ventricular end systolic diameter = 28.26±5.50 mm vs. 31.25± 6.50 mm; P< 0.05). Interpretation & conclusions: Prophylactic use of carvedilol in patients receiving anthracycline protected systolic functions of the left ventricle. Carvedilol can be a potential drug which can ameliorate ADRinduced CMP.
Saudi Journal for Health Sciences. 2016 Sep-Dec;5(3):138-41
Saudi Journal for Health Sciences
Context: There has been an unexplained increase in the number of cases with multiorgan dysfunction including acute kidney injury (AKI), attributed to Plasmodium vivax monoinfection. Only a few case reports in literature have published the renal biopsy findings in these patients. Aims: The aim of this study was to evaluate the clinical and histopathologic profile of patients with P. vivax malaria monoinfection and AKI. Settings and Design: A prospective study was performed in a tertiary care hospital in North‑Western India. Subjects and Methods: The study included patients diagnosed with P. vivax monoinfection on peripheral smear blood films and rapid diagnostic test (positive for P. vivax specific lactate dehydrogenase). AKI was defined based on the WHO criteria for complicated malaria, i.e. serum creatinine >265 μmol/l or 3 mg/dl. The patients were initiated on hemodialysis for persistent hyperkalemia, fluid overload, severe metabolic acidosis, or uremic symptoms. Renal biopsy was performed in the presence of active urinary sediments (proteinuria, hematuria) or persistence of renal failure >14 days. Results: A total of thirty patients fulfilled AKI criteria. The patients with AKI were older (mean age 42.1 ± 10.9 years), male, with a longer duration of illness (mean 12.3 ± 10 days) and associated with multisystem dysfunction. The mean serum creatinine was 7.58 ± 3.2 mg/dl, thrombocytopenia was seen in 47%. Thirty percent had severe anemia requiring a blood transfusion. Renal biopsy was performed in six patients for various indications. The most common pattern was acute tubular necrosis (four patients), followed by acute cortical necrosis (1), and thrombotic microangiopathy (one patient). The complete renal recovery was seen in 24 (80%). Two patients became dialysis‑dependent. Conclusions: AKI associated with P. vivax monoinfection is not rare as previously thought. Therefore, it should be considered in the differential diagnosis of any patient presenting with AKI.
Indian J Gastroenterol 2016 Jan 15;35(1):67-71. Epub 2016 Feb 15.
Department of Nephrology, Sawai Man Singh Medical College and Hospital, J L N Marg, Jaipur, 302 004, India.
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Indian journal of pharmaceutical sciences 78 (1), 159
Indian journal of pharmaceutical sciences
Nonsteroid antiinflammatory drugs have been implicated as nephrotoxic drugs, causing both acute and chronic adverse effects that range from reversible ischemia to chronic kidney disease and urothelial tumors to renal cell carcinoma specially papillary subtype. We report one case of collecting duct (Bellini duct) renal cell carcinoma in patient with analgesic-abuse nephropathy. This young individual was suffering from ankylosing spondylitis since the age of 16 years and was consuming diclofenac and paracetamol (acetaminophen) combination for >15 years. He developed hypertension, secondary glomerulopathy, chronic kidney disease and collecting duct renal cell carcinoma.
Jhorawat, et al.: Is AAN a Risk Factor for CDRCC?
Trop Parasitol 2015 Jul-Dec;5(2):127-9
Department of Nephrology, SMS Medical College and Hospital, SMS Hospital, Jaipur, Rajasthan, India.
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Indian J Nephrol 2015 Sep-Oct;25(5):265-8
Department of Nephrology, SMS Hospital and Medical College, Jaipur, Rajasthan, India.
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Nephrology Dialysis Transplanation 30 (suppl_3), iii336-iii337
Nephrology Dialysis Transplanation 30 (suppl_3), iii336-iii337
Indian J Nephrol 2014 Nov;24(6):390-3
Professor and Head, Department of Nephrology, SMS Medical College, Jaipur, Rajasthan, India.
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Indian journal of transplantation 2014 July-September 8(3);75-79
Indian journal of transplantation
Aim To assess the level of hormones in chronic kidney disease (CKD) patients and the effect of renal transplantation (RTx) on these hormones. Materials and methods 17 patients enrolled and levels of 11 hormones i.e. FT3, FT4, TSH, FSH, LH, prolactin, testosterone, cortisol, growth hormone, PTH and insulin were measured in every patient before and at 1st, 3rd and 6th month after RTx with correlation to serum creatinine. Patients with underlying endocrine disorders were excluded. Result At 1st and 3rd month of follow up after RTx, there was no statistical significant change in the hormones level except in PTH, which normalised (Pre transplant levels: 262.542 ± 239.706 and 1 month levels: 101.412 ± 66.615 p = 0.024 at 3rd month level: 113.02 ± 95.960 p = 0.036). At 6th month, along with PTH, LH level decreased significantly (LH level pre-RTx 8.387 ± 4.536 and 3.091 ± 2.139 at 6th month p = 0.024). Levels of other hormones also normalised. Mean serum creatinine at 6th month had increased from its nadir level post RTx (1.149 ± 0.164 mg/dl to 1.386 ± 0.323 mg/dl p = 0.034), due to rise of serum creatinine in 4 patients. FT3, cortisol, prolactin and insulin levels also increased in parallel with serum creatinine, however insulin level correlated significantly (r = 0.759 with 95% CI = 0.015–0.962). Conclusion RTx corrects most of the hormonal disturbances in CKD patients, particularly abnormalities in PTH and LH levels in early post transplant period. Even mild allograft dysfunction significantly affects the hormonal levels in a manner which is similar to the changes seen in CKD.