Nephrology

Healthcare in India and violence against doctors: The missing links Sanjay Kumar Agarwal Indian Journal of Nephrology 2019 29(4):221-231

Reset osmostat: Facts and controversies J Feder, JM Gomez, F Serra-Aguirre, CG Musso Indian Journal of Nephrology 2019 29(4):232-234 Reset osmostat (RO) consists of a change in the normal plasma osmolality threshold (reduction or increase), which consequently induces chronic dysnatremia (hyponatremia or hypernatremia). Although the early papers on RO state that hyponatremic patients with this condition are usually not symptomatic, the current view is that most patients with hyponatremia are symptomatic and should be treated. RO has been associated with a myriad of clinical conditions and has clear diagnostic criteria which are crucial to arrive at the correct diagnosis and treatment.

Risk Factors for 3-Year-Mortality and a Tool to Screen Patient in Dialysis Population MA Bujang, PX Kuan, FE Sapri, WJ Liu, R Musa Indian Journal of Nephrology 2019 29(4):235-241 Introduction: Clinical parameters especially co-morbidities among end stage renal disease (ESRD) patients are associated with mortality. This study aims to determine the risk factors that are associated with mortality within three years among prevalent patients with ESRD. Methods: This is a cohort study where prevalent ESRD patients' details were recorded between May 2012 and October 2012. Their records were matched with national death record at the end of year 2015 to identify the deceased patients within three years. Four models were formulated with two models were based on logistic regression models but with different number of predictors and two models were developed based on risk scoring technique. The preferred models were validated by using sensitivity and specificity analysis. Results: A total of 1332 patients were included in the study. Majority succumbed due to cardiovascular disease (48.3%) and sepsis (41.3%). The identified risk factors were mode of dialysis (P < 0.001), diabetes mellitus (P < 0.001), chronic heart disease (P < 0.001) and leg amputation (P = 0.016). The accuracy of four models was almost similar with AUC between 0.680 and 0.711. The predictive models from logistic regression model and risk scoring model were selected as the preferred models based on both accuracy and simplicity. Besides the mode of dialysis, diabetes mellitus and its complications are the important predictors for early mortality among prevalent ESRD patients. Conclusions: The models either based on logistic regression or risk scoring model can be used to screen high risk prevalent ESRD patients.

Vitamin D, 1,25-Dihydroxyvitamin D, FGF23, and graft function after renal transplantation Sonia Mehrotra, Raj Kumar Sharma, Manas R Patel Indian Journal of Nephrology 2019 29(4):242-247 Vitamin-D has immuno-modulatory properties besides its role in mineral and bone disorder (MBD) and could have a role in allograft outcome. Fifty-two chronic kidney disease patients on dialysis going for transplantation were prospectively studied before and after renal transplantation. FGF23, 25(OH) vitamin D, 1,25-Dihydroxyvitamin D, PTH, serum Ca, serum PO4, and e-GFR status were evaluated. Vitamin D deficiency was seen in 25.0% of recipients before transplant (26.09 ± 12.19 ng/mL) and in 48.1% at 6 months post-transplant (23.36 ± 15.11 ng/mL). 1,25-(OH)2D levels before transplant were 102.37 ± 108.44 pmol/L, which were less than control (143.30 ± 108.0 pmol/L) and decreased further to 46.20 ± 42.11 pmol/mL at 3 months and started increasing to 78.37 ± 60.12 pmol/mL at 6 months post-transplantation without vitamin D supplementation. The prevalence of hypophosphatemia after transplantation was 32.0%, hyperkalemia was 12.0%, elevated intact PTH levels at 3 and 6 months after transplant were seen in 66.7% and 30.8% patients, respectively. FGF-23 levels were high in 72.5% of patients before transplant (495.94 ± 690.68 pg/mL) and decreased to normal levels at 3 months post-transplant (31.63 ± 14.17 pg/m) (control 32.07 ± 9.78 pg/mL). Serum intact PTH levels were 379.54 ± 281.27 pg/mL before transplant and came down to 103.96 ± 68.34 at 3 months and 69.87 ± 116.03 at 6 months post-transplantation. There was trend of higher e-GFR at 1 year post-transplant in patients without vitamin D deficiency (levels ≥30 ng/mL). The dysregulated mineral metabolism continues in post-transplant despite improvement in renal function and normalization of FGF-23.

Evaluation of iron status in patients of chronic kidney disease - A study to assess the best indicators including serum transferrin receptor assay Manu Venkatesan, Shilpi Saxena, Arun Kumar Indian Journal of Nephrology 2019 29(4):248-253 Anemia is an early complication of chronic kidney disease (CKD). The iron deficiency is an important contributor, more so in the Indian population. As routine standalone iron tests do not accurately reflect the actual status in the complex environment of CKD, there is a need to study better indicators. Serum iron, ferritin, total iron-binding capacity (TIBC), and serum transferrin receptor (sTfR) levels were estimated in 100 primary iron deficiency anemia (IDA) patients (controls-Group 1) and 68 newly diagnosed CKD cases. The CKD patients were divided into two groups: Serum ferritin <=100 μg/L (Group 2) and >100 μg/L (Group 3). The values of percentage saturation, log of ferritin (log_ferritin), and the ratio of sTfR to log ferritin (sTfR/log_f or sTfR index) were calculated. The CKD cases were further divided depending on ferritin cut-offs of 30, 50, 70, and 100 μg/L and statistically analyzed including ROC and AUC, to choose the best diagnostic parameter for accurate assessment of iron status in CKD cases. The mean serum ferritin was 11.34 μg/L, 28.70 μg/L, and 281.81 μg/L, and the mean sTfR was 2.34 μg/ml, 1.82 μg/ml, and 1.28 μg/ml in Groups 1, 2, and 3. Among all groups, the difference was found to be significant for serum iron, log_ferritin, and sTfR/log_f. The sTfR and sTfR/log_f showed good discrimination between IDA and Anemia of chronic disease in CKD cases, but sTfR/log_f gave the best discrimination at all cut-off levels of ferritin. At a ferritin cut-off of 50 μg/L, the sTfR/log_f value of 0.83 had a sensitivity of 93.5% and specificity of 95.45%, and at a ferritin cut-off 100 μg/L, the same value of 0.83 had a sensitivity of 95.5% and specificity of 86.5%. The ratio of sTfR/log_f is the best indicator for assessing iron status in CKD.

Community acquired AKI: A prospective observational study from a tertiary level hospital in Southern India Ramesh Kaaviya, Mehalingam Vadivelan, Nathan Balamurugan, Sreejith Parameswaran, Molly Mary Thabah Indian Journal of Nephrology 2019 29(4):254-260 Introduction: Pattern of acute kidney injury (AKI) differs vastly from region to region in India. Moreover, prospective data on community-acquired AKI (CAAKI) using the KDIGO criteria for AKI are limited. Our objective was to study the etiology, clinical characteristics, and short-term outcome of CAAKI in adults. Methods: This was a prospective observational study in the medical wards of a tertiary care hospital. Patients fulfilling the 2012 KDIGO AKI criteria of community acquired acute kidney injury (CAAKI) were included. Patients who developed AKI 48 hours after admission, those hospitalized >48 hours elsewhere, and patients with chronic kidney disease were excluded. The study did not include obstetric or surgical cases of AKI. Serum creatinine and urine output was monitored. Daily progress, in particular development of hypotension, oliguria, acute respiratory distress syndrome, sepsis, and renal replacement therapy, was noted. Results: Of 186 CAAKI patients (mean age, 46.13 ± 15.2 years), 86/186 was infective etiology, 93/186 was non-infective etiology, 7/186 was due to intrinsic renal pathology. Pyelonephritis 33/186 (17.7%) was the most common infective etiology, and snakebite in 49 (26.3%) was the most common non-infective etiology; 28/186 (15.1%) died. On logistic regression, hypotension, mechanical ventilation, thrombocytopenia, and anuria were associated with mortality. Conclusions: Acute pyelonephritis and snakebite-related AKI emerged as the two most common medical causes of CAAKI in our region. Such environmental and infectious causes that largely are preventable causes of AKI are also associated with significant morbidity and mortality.

Influence of CYP3A5 and ABCB1 polymorphism on tacrolimus drug dosing in South Indian renal allograft recipients M Edwin Fernando, Manokaran Sellappan, ND Srinivasa Prasad, Sujit Suren, K Thirumalvalavan Indian Journal of Nephrology 2019 29(4):261-266 Introduction: Tacrolimus blood levels are influenced by polymorphisms involving Cytochrome 3A subfamily (CYP3A5) and P-Glycoprotein (ABCB-1) genes. However, their role in transplant outcomes was less studied in South Indian population. We studied the prevalence and impact of these polymorphisms in renal transplant recipients from South India. Methods: An analysis of CYP3A5, ABCB1 genotype done in 101 renal transplant recipients by polymerase chain reaction was correlated with blood tacrolimus trough levels (CLIA method), weight, concentration/dose (L/D) ratio, incidence of biopsy proven early acute rejections, and tacrolimus toxicity. Results: Prevalence of CYP3A5*1/*1, *1/*3 and *3/*3 and ABCB1 (3435C>T) TT, CT, CC genotypes were 12 (11.9%), 48 (47.5%), 41 (40.6%) and 16 (15.8%), 45 (44.6%), 40 (39.6%), respectively. Mean tacrolimus level, median concentration/dose (L/D) ratio were significantly lower in homozygous (CYP3A5*1/*1-6.01 ng/mL; 48.99 ng/mL/mg/kg/day) and heterozygous expresser group (CYP3A5*1/*3-5.84 ng/mL; 68.93 ng/mL/mg/kg/day) when compared with nonexpresser group [CYP3A5*3/*3-7.46 ng/mL (P < 0.001);181.3 ng/mL/mg/kg/day (P < 0.05]. No significant differences observed between the ABCB1 genotypic groups. Incidence of early acute rejections (30% vs. 9.76%; P 0.016) and tacrolimus-related toxicity (14.6% vs. 5%; P 0.039) were significantly higher in CYP3A5 expressers and nonexpressers, respectively. No correlation observed between the ABCB1 polymorphisms between rejection episodes or tacrolimus renal toxicity. Among 101 patients, 40.6% were non-expressers (poor metabolizers) (*3/*3). Conclusions: CYP3A5 polymorphisms correlated with tacrolimus dose requirements and blood levels, incidence of early acute rejection, and tacrolimus nephrotoxicity. CYP3A5 polymorphism analysis prior to renal transplant will aid more precise early tacrolimus dose calculation to balance between rejection and toxicity.

The effectiveness of personal hygiene practices on non-cuffed central vein catheter-related infection in patients undergoing hemodialysis: A randomized controlled trial Geetanjali Loomba, Manju Dhandapani, Sukhpal Kaur, Sandhya Ghai, Manisha Biswal, Raja Ramachandran, Krishan Lal Gupta Indian Journal of Nephrology 2019 29(4):267-271 Infection of the internal jugular vein (IJV) catheter continues to be a common cause of death in patients with end-stage renal disease undergoing hemodialysis (HD). The present study aimed to evaluate the effectiveness of personal hygiene on the incidence of IJV catheter-related bloodstream infection (CRBSI). A randomized, controlled, parallel, and non-inferiority trial was conducted on patients initiated on maintenance HD via right IJV catheter. Patients were randomly allocated to control and intervention group via computer-generated random table. Intervention package for the intervention group included hand washing (2–4 hourly and whenever visibly dirty), feet washing (12 hourly), and axillary shave (at any point during the study, no hair growth in axilla). Patients were provided with a pamphlet and reinforced to continue package till IJV catheter was in situ. Patients were followed up twice a week for one month from the date of catheter insertion for the incidence of CRBSI. The primary outcome of the study was percentage of patients free from CRBSI. On intention-to-treat analysis, the percentage of patients without CRBSI was 53.7% and 29.3% in the intervention and control arm, respectively [P = 0.04; 25.12% (1.43–45.28%)]. Positive blood cultures were higher in control (73.3%) as compared to the intervention group (28.6%) (P = 0.19). Personal hygiene interventions are an effective method to reduce the incidence of CRBSIs among population undergoing maintenance HD via non-cuffed IJV catheter.

To study the impact of donor nephrectomy on blood pressure as measured by ambulatory blood pressure monitoring and renal function Raj K Yadav, Dipankar Bhowmik, Arunkumar Subbiah, Sushma Yadav, Soumita Bagchi, Sandeep Mahajan, Sanjay K Agarwal Indian Journal of Nephrology 2019 29(4):272-277 Prospective living kidney donors need meticulous evaluation prior to kidney donation. Ambulatory blood pressure monitoring (ABPM) is considered the reference standard for diagnosing hypertension. With no prior study available in India in this context, we undertook this study to evaluate the utility of ABPM in kidney donors and effect of donor nephrectomy on renal function. This was a prospective observational study involving healthy prospective kidney donors between 18 and 70 years with normal office blood pressure measurements (OBPM). Detailed clinical and biochemical parameters were recorded. OBPM and 24-hour ABPM was done preoperatively and 3 months following donor nephrectomy. There were 51 donors with a mean age of 46.1 ± 11.3 years, of which 40 (78.4%) were females. Preoperatively, three (5.8%) donors were hypertensive on ABPM but normal on OBPM (P = 0.08). Three months post nephrectomy, hypertension was present in seven (13.7%) donors by ABPM, while only two (3.9%) donors were diagnosed as hypertensive by OBPM (P = 0.02). Median pre-nephrectomy proteinuria was 70 mg (10 mg–180 mg) with a mean estimated glomerular filtration rate (eGFR) using the Modification of Diet in Renal Disease (MDRD) formula of 86.86 ± 19.1 ml/min. Six donors developed >300 mg/day proteinuria, and 17 (33.3%) had a 24-hour urinary protein excretion greater than 150 mg/day. Mean serum creatinine (0.79 ± 0.11 vs 1.03 ± 0.16 mg/dl) significantly increased post donation, more so in donors >55 years of age (1.14 ± 0.25 mg/dl). Our study shows that in transplant donors, ABPM is better for diagnosing hypertension, which otherwise remains masked in 10% of the donors on routine OBPM. Significance of post-nephrectomy hypertension and increasing proteinuria needs further evaluation.

Efficacy and safety of canagliflozin in kidney transplant patients Mita Shah, Zaheer Virani, Prashant Rajput, Bharat Shah Indian Journal of Nephrology 2019 29(4):278-281 Introduction: There is no report of efficacy and safety of canagliflozin, a sodium glucose cotransporter 2 (SGLT2) inhibitor in post kidney transplant patients with diabetes. Materials and Methods: A pilot study was undertaken in stable renal transplant recipients with preexisting diabetes or new onset diabetes after transplantation (NODAT) to look at the efficacy of SGLT2 inhibitor, cangliflozin. With the introduction of canagliflozin (100 mg), the dose of insulin and/or other oral hypoglycemic agents was reduced if the blood sugar control improved. The parameters monitored were body weight, blood pressure (BP), serum creatinine, HbA1c, and tacrolimus trough level. Safety was assessed by adverse event (AE) reports. Each patient was followed for a minimum period of 6 months. Results: The study included 24 (23 males and 1 females) stable kidney transplant patients with diabetes. The mean age of the patients was 53.8 ± 7.12 years. The mean body weight of study subjects was 78.6 ± 12.1 kg before and 76.1 ± 11.2 kg 6 months after starting canagliflozin (P < 0.05). The mean systolic and diastolic BP (mm Hg) was 142 ± 21 and 81 ± 9 before and 134 ± 17 and 79 ± 8, 6 months after starting canagliflozin, respectively (P < 0.05 for systolic BP). There was no significant change in creatinine level (mg/dL). It was 1.1 ± 0.2 before and 1.1 ± 0.3 after starting canagliflozin. The tacrolimus level (ng/mL) was 6.7 ± 3.7 before and 6.1 ± 2, 6 months after starting canagliflozin. The mean HbA1c before was 8.5 ± 1.5%. At 6 months, it was 7.6 ± 1%. Hypoglycemia was not seen. There was no increase in infections. Conclusion: Canagliflozin provided reductions in body weight, BP, HbA1c, and the requirement of other hypoglycemic agents without any hypoglycemic episodes and without significant AEs.