Clinical Trial Comparing the Efficacy and Safety of Regional Citrate Anticoagulation Versus Heparin in CRRT.

Introduction: Heparin continues to be the most common modality of anticoagulation in CRRT. The increased risk of hemorrhagic complications associated with its use led to the emergence of regional citrate anticoagulation (RCA) as an alternative. However, the perceived complexities associated with its use and the risk of metabolic derangements have prevented it from being adopted on a larger scale. Thus, we conducted a prospective study to compare the efficacy and safety of RCA versus heparin. Methods: Adult patients admitted to our ICU (November 2018-November 2019) with renal insufficiency and requiring CRRT were included in the study. It was an open-label study with 25 patients each being allotted to the heparin and citrate groups. Our primary outcome was the filter life span. Secondary outcomes included metabolic derangements, bleeding episodes, and patient survival. The starting dose of citrate was 2.0 mmol/L. Results: The mean filter life span was 32.84 h in the citrate group and 30.40 h in the heparin group (p-value = 0.47). In a significant proportion of the cases, CRRT was terminated for non-filter clotting-related reasons (64% in citrate vs. 32% in heparin). Kaplan-Meir analysis was done to overcome this confounder; the filter lifespan was estimated to be 46.94 h in citrate and 40.05 h for the heparin group (p-value = 0.29). No significant metabolic derangements or bleeding episodes were noted in either group. Overall patient survival was higher in the citrate group at 52% versus 32% (p-value = 0.15) in the heparin group. Conclusion: No significant difference in filter lifespan or risk of metabolic derangements was noted. A trend toward higher patient survival rates in the citrate group was noted, which warrants further evaluation in future trials.

Practice of dialysis access interventional nephrology procedures in the Asia-Pacific region: Getting lay of the land.

AIM: This cross-sectional survey aimed to determine the prevalence of Interventional Nephrology (IN) practice amongst nephrologists in the Asia-Pacific Region (APR), specifically related to dialysis access (DA). METHODS: The Association of VA and intervenTionAl Renal physicians (AVATAR) Foundation from India conducted a multinational online survey amongst nephrologists from the Asia-Pacific to determine the practice of IN in the planning, creation, and management of dialysis access. The treatment modalities, manpower and equipment availability, monthly cost of treatment, specifics of dialysis access interventions, and challenges in the training and practice of IN by nephrologists were included in the survey. RESULTS: Twenty-one countries from the APR participated in the survey. Nephrologists from 18 (85.7%) countries reported performing at least one of the basic dialysis access-related IN procedures, primarily the placement of non-tunnelled central catheters (n-TCC; 71.5%). Only 10 countries (47.6%) reported having an average of <4% of nephrologists performing any of the advanced IN access procedures, the most common being the placement of a peritoneal dialysis (PD) catheter (20%). Lack of formal training (57.14%), time (42.8%), incentive (38%), institutional support (38%), medico-legal protection (28.6%), and prohibitive cost (23.8%) were the main challenges to practice IN. The primary obstacles to implementing the IN training were a lack of funding and skilled personnel. CONCLUSION: The practice of dialysis access-related IN in APR is inadequate, mostly due to a lack of training, backup support, and economic constraints, whereas training in access-related IN is constrained by a lack of a skilled workforce and finances.

Role of haptoglobin 2-2 genotype on disease progression and mortality among South Indian chronic kidney disease patients.

BACKGROUND: Haptoglobin (HP), a plasma glycoprotein, binds to free hemoglobin and prevents the loss of iron and kidney damage. The variations of HP gene affect its enzyme activity, resulting in varied antioxidant, angiogenic and anti-inflammatory properties. HP 2-2 genotype showed 3.84 fold increased risk for the development of CKD in Taiwan population. With this background, the present work focused to conduct a prospective case-control study in South Indian population to evaluate whether the HP variants are associated to nondialysis (ND) (CKD stages 1-4) and ESRD (CKD stage 5) conditions. METHODS AND RESULTS: Totally 392 CKD patients (nondialysis, ND; n = 170, end-stage renal disease, ESRD; n = 222) and 202 healthy individuals were enrolled. The blood samples collected from the patients were used to determine biochemical parameters and HP genotyping. Gene frequency and biochemical parameters were statistically analyzed for disease association. Results showed that HP 2-2 genotypes were significantly associated with ND and ESRD disease development compared to controls. Higher HP2-2 genotype frequency showed an increased hazard ratio for overall disease progression among ND patients (hazard ratio = 3.86; 95% CI 1.88 to 7.93; P = 0.0002). Survival analysis also showed that non-HP2-2 patients have a statistically significantly decreased risk for mortality compared to patients with the HP2-2 genotype (ESRD patients hazard ratio = 4.05; P = 0.04). CONCLUSION: The present study confirms that HP2-2 polymorphism is statistically associated with the risk of CKD incidence, progression, and mortality among South Indians. Concluding our results, the HP2-2 genotype could be an independent predictor of all-cause mortality and disease progression in patients with CKD.

Abdominal aortic calcification as prognostic marker in continuous ambulatory peritoneal dialysis.

BACKGROUND: Patients with chronic kidney disease (CKD) on dialysis are at high risk of cardiovascular complications and mortality. We investigated the prognostic role of presence and severity of abdominal aortic calcification (AAC) detected by a simple lateral lumbar X-ray as a risk marker in CAPD. MATERIALS AND METHODS: A prospective study was undertaken in 45 patients on CAPD (continuous ambulatory peritoneal dialysis). Lateral lumbar films of consented patients were checked for the presence of AAC at the level of L1 - L4 lumbar vertebrae. The severity of aortic calcification was graded as per Antero-Posterior Severity Score (APSS). These APSS grades were correlated with the patient's demographic, biochemical, and echocardiographic findings. The patients were followed up prospectively for one year. RESULTS: 45 patients formed the study group. Mean standard deviation (SD) age and body mass index (BMI) were 57.2 (11.9) years and 25.8 (4.7) kg/m2, respectively. Males constituted 62% of the cohort. Average duration of dialysis was 34.3 months. Diabetic kidney disease was seen in 75%. The prevalence of AAC was 47%. AAC was positively correlated with age of patient (r = 0.378; p = 0.01). No correlation with BMI, diabetes, hypertension, dialysis vintage, serum calcium, phosphorus, and PTH was seen; whereas a trend towards negative correlation with alkaline phosphatase was seen. Mitral valve calcification had a significant association with APSS severity. Patients with severe APSS (≥ 4) had poor survival, with an average survival of 37 months (Log-rank test p = 0.026). ROC analysis showed that APSS 3 predicted 1-year mortality with a specificity of 89% and sensitivity of 62% (AUC = 0.73) (p = 0.007). CONCLUSION: Abdominal aortic calcification was present in 47% of our CAPD patients. A simple lateral pelvic skiagram can be utilized as a cost-effective tool in prediction of All-cause mortality and cardiac valvular calcification.

GSTM1-null allele predicts rapid disease progression in nondialysis patients and mortality among South Indian ESRD patients.

Chronic kidney disease (CKD) is one of the main causes of early death in humans worldwide. Glutathione S-Transferases (GSTs) are involved in a series of xenobiotics metabolism and free radical scavenging. The previous studies elucidated the interlink between GST variants and to the development of various diseases. The present case-control study performed to ascertain whether GST polymorphisms are associated with the incidence and advancement of CKD. From the Southern part of India, a total of 392 CKD patients (nondialysis, ND; n = 170, end-stage renal disease, ESRD; n = 222) and 202 healthy individuals were enrolled. Patients were followed-up for 70 months. Serum biochemical parameters were recorded, and the extraction of DNA was done from the patient's blood samples. To genotype study participants, multiplex PCR for GSTM1/T1 was performed. Statistical analysis was carried out to analyze the relationship between gene frequency and sonographic grading, as well as biochemical parameters for disease development. The GSTM1-null genotype showed threefold increased risk (OR = 2.9304; 95% CI 1.8959 to 4.5296; P < 0.0001) to CKD development and twofold increased risk (OR = 1.8379; 95% CI 1.1937 to 2.8299; P = 0.0057) to ESRD progression. During the mean follow-up of 41 months study, multivariate Cox regression analysis revealed that GSTM1-null genotype has 4 times increased the risk for all-cause rapid disease progression to ESRD among ND patients and 3.85-fold increased risk for death among ESRD patients. Survival analysis revealed that patients with GSTM1-present allele showed a significantly diminished risk of mortality compared to patients bearing the GSTM1-null allele among ESRD patients with a hazard ratio of 4.6242 (P < 0.0001). Thus, present data confirm that GSTM1-null genotype increased the risk for all-cause rapid disease progression to ESRD among ND patients. Based on our results, GSTM1-null genotype could be considered as a significant predictor for causing mortality among CKD patients when compared to all other variables.

Diabetic kidney disease patients on hemodialysis: a retrospective survival analysis across different socioeconomic groups.

BACKGROUND: Diabetic kidney disease is the leading cause of stage 5 chronic kidney disease (CKD) in India. Renal replacement therapy (RRT) is accessible to very few patients because of socioeconomic deprivation. We studied the effect of diabetes and socioeconomic status on the outcome of patients on maintenance hemodialysis (MHD). METHODS: We retrospectively analyzed the outcome of 897 patients (629 males/268 females; mean age ± standard deviation 48.69 ± 14.27 years) initiated on MHD from 2003 to 2009 at five dialysis centers in south India. There were 335 type 2 diabetic patients and 562 non-diabetic patients. Group 1 comprised the self-paying patients (518 patients) and Group 2 included the TANKER Foundation charity dialysis patients (379 patients). We compared the 5-year survival rates of Group 1 versus Group 2 and also those of diabetic versus non-diabetic patients, using the Kaplan-Meier survival estimator. RESULTS: Of the 897 patients, 166 patients survived, 350 died, 234 were lost to follow-up, 137 had renal transplantation and 10 patients were transferred to peritoneal dialysis. The 5-year survival rates after censoring were 20.7 and 38.2% for diabetic and non-diabetic patients, respectively (P < 0.001). The survival rate of diabetic patients was significantly lower, compared with non-diabetic patients, in Group 2 (P < 0.001), but not significantly lower in Group 1 (P = 0.226). CONCLUSIONS: Diabetic patients have poor survival rates on MHD, especially those from poor socioeconomic groups. Due to scarce RRT facilities and poor survival rates of diabetic patients, prevention, early detection and management of diabetic CKD patients should be the way to go forward.

Vascular Access Creation and Care--Perspective From India.

India has one of the fastest growing economies in the world and is home to nearly one sixth of world's population. Chronic diseases such as diabetes mellitus and hypertension are common. Kidney disease is a known complication of these chronic diseases and is on the rise. Improving affordability with advanced care delivery has led to the increasing use of maintenance hemodialysis. Along with this hemodialysis comes the inevitable need for vascular access. Interventional nephrology in India is a fast-evolving discipline and promises to be a critical component of hemodialysis care in the future. This review provides a background on the current state of the CKD burden in India and the various vascular access options in use currently. In addition, we describe the experience of 2 centers in western and southern India in managing vascular access needs in hopes that they will serve as a model of the proliferation of vascular access care throughout India and in other developing countries.

Granulomatous interstitial nephritis due to tuberculosis-a rare presentation.

Granulomatous interstitial nephritis (GIN) is an uncommon form of acute interstitial nephritis. We report a young male who presented to us with a rapidly progressing renal failure and massive proteinuria. A renal biopsy revealed GIN, and we were able to demonstrate the presence of tuberculous DNA in the biopsy specimen. The patient was started on anti-tuberculous therapy and steroids besides 11 sessions of hemodialysis. He recovered and is currently doing well. This case highlights an uncommon manifestation of renal tuberculosis, namely massive proteinuria, acute renal failure, and granulomatous interstitial lesions.

Analysis of polymorphism in renin angiotensin system and other related genes in South Indian chronic kidney disease patients.

BACKGROUND: Several Renin Angiotensin System (RAS) polymorphisms alter the homeostasis to an abnormal state. Similarly, other genes such as Nephrin (NPHS1) and Podocin (NPHS2) contribute to the loss of renal function during renal diseases. In Indian population, studies in RAS and other renal specific gene polymorphisms in Chronic Kidney Disease (CKD) patients are scanty. METHODS: We examined 118 CKD patients and 98 control subjects for the occurrence of common polymorphisms in angiotensin converting enzyme insertion/deletion (ACE; I/D), angiotensinogen (AGT; M235T), chymase (CMA; -1903G>A), angiotensin receptor type-1 (AGTR1-1166A>C), methylene tetrahydrofolate reductase (MTHFR; 677C>T), nephrin (NPHS1; R1160X) and podocin (NPHS2; R291W and R229Q). RESULT: Significant association was observed in AGT-M235T polymorphism between CKD patients and controls. The frequency of TT genotype was higher in CKD patients when compared with controls (0.39 vs. 0.14; chi(2)=20.3, P<0.001). ACE-DD genotype showed a higher level of systolic pressure with a median of 166 mmHg (P<0.05) when compared to II and ID genotypes. Two heterozygous conditions of NPHS2-R229Q polymorphism were found among 105 CKD patients. No significant associations were found in genotype frequencies in other above polymorphisms between CKD patients and controls. CONCLUSION: Asian Indian population with AGT-TT genotypes may have a higher relative risk towards CKD with odds ratio (OR) 3.98 (95% CI=1.92-8.25; P=0.0002).

Hair dye poisoning and the developing world.

Hair dye poisoning has been emerging as one of the important causes of intentional self harm in the developing world. Hair dyes contain paraphenylene-diamine and a host of other chemicals that can cause rhabdomyolysis, laryngeal edema, severe metabolic acidosis and acute renal failure. Intervention at the right time has been shown to improve the outcome. In this article, we review the various manifestations, clinical features and treatment modalities for hair dye poisoning.

Niacin and analogs for phosphate control in dialysis--perspective from a developing country.

Hyperphosphatemia is an important modifiable risk factor in the dialysis population because it is linked to increased mortality. Existing phosphate-reducing agents either increase the risk of vascular calcification or are costly with high pill burden. Niacin shows promise as a cheap drug with low pill burden and a novel mode of action. Niacin and its metabolite nicotinamide inhibit the small intestinal sodium-phosphate cotransporter. Approximately 50% of intestinal phosphate absorption occurs through this route under physiological conditions. Studies performed on the dialysis population with niacin and nicotinamide have shown significant phosphate reduction with lowering of the calcium-phosphorus product. The well documented increase in serum HDL levels may also offer survival benefits. Side-effects include flushing, which is controlled with aspirin, diarrhea, and thrombocytopenia, which may be treatment-limiting. Niacin is cheap and phosphate reduction can be achieved by administration of one or two tablets per day. These factors will boost compliance in developing countries. Further basic research and large-scale clinical trials are needed in this field.

Emphysematous prostatitis in renal transplant.

Urinary tract infections are common following renal transplant. The spectrum varies from asymptomatic bacteriuria to septicemia. Gas-producing infections of the urinary tract are rare but tend to have a grave prognosis when they do occur. We report a 57-year-old gentleman who underwent a renal transplant 20 months earlier. He presented to us with fever and dysuria. Clinical examination revealed a febrile and ill-looking patient with severe graft tenderness. An emergency pelvic CT scan revealed presence of emphysematous prostatitis, cystitis and pyelitis. Urine and blood cultures grew E. coli. Endoscopic abscess drainage was done and antibiotics given but he succumbed to his illness due to multiorgan failure within 48h. This is the first reported case of emphysematous prostatitis in a renal allograft recipient.

Extended release nicotinic acid - a novel oral agent for phosphate control.

BACKGROUND: Hyperphosphatemia is common in hemodialysis patients. Recent animal studies show that nicotinamide inhibits the sodium dependent phosphate co-transport in the small intestine and thereby reduces serum phosphorus levels. Nicotinic acid which is the prodrug of nicotinamide is widely used as antihyperlipidemic agent. We examined in a prospective study whether it reduces serum phosphorus levels in hemodialysis patients. METHODS: Patients who were on maintenance hemodialysis were enrolled in to the study if their predialysis serum phosphorus was more than 6 mg/dl. During the pre-trial run in period of 1 week all phosphate binders were stopped. A single dose of extended release nicotinic acid (375 mg) tablet was given with meal. Repeat measurements of serum calcium, phosphorus and alkaline phosphatase were carried out after 8 weeks. Then the drug was stopped in a subgroup of patients and serum phosphorus remeasured after 2 weeks. RESULTS: There were 34 patients with varied etiological spectrum of end stage renal disease. They were on hemodialysis for a mean period of 8.7 months. Serum phosphorus levels changed significantly from a pre treatment level of 7.7 +/- 1.5 mg/dl to post treatment level of 5.6 +/-1 mg/dl (p < 0.001). There was no significant variance across age groups, sex, disease categories and dialysis duration. The calcium level increased from 8.1 +/- 1.0 to 8.5 +/- 1.0 mg/dl (p < 0.015). The serum alkaline phosphatase level decreased significantly from 107+/-66 IU/l to 82+/-46 IU/l (p < 0.001 ). There was a significant reduction of calcium phosphate product from 63.1 + 15.1 mg2 to 48.7 +/- 10.9 mg2/dl2 (p < 0.001). Oral nicotinic acid was well tolerated. Mild pruritus was encountered in 2 patients. CONCLUSION: Oral nicotinic acid may emerge as a safe, low cost yet powerful agent for phosphorus control in dialysis patients.