A Preemptive Living Donor Renal Transplant in an HIV Positive Patient from an HIV Positive Donor.

With recent advances in the treatment of human immunodeficiency virus (HIV), renal transplantation is no longer considered a contraindication in properly selected HIV-positive patients. Several studies have demonstrated comparable patient and graft outcomes between HIV-negative and HIV-positive renal transplant recipients. Most of the information on outcomes of HIV-positive to HIV-positive transplantation is based on data from deceased donors. There are only a handful of case reports about living donor renal transplantation in an HIV-positive patient from an HIV-positive donor. Furthermore, there is no report in the world of preemptive living donor renal transplantation in this setting. Here, we report a case of successful preemptive renal transplantation in an HIV-positive recipient from an HIV-positive living donor performed at our center.

An Unusual Presentation of Multiple Myeloma.

Multiple myeloma commonly presents as anemia, renal failure, bone pain, and infections. Presentation with epistaxis is extremely rare, and hence myeloma as the etiologic factor is seldom considered. We report the case of a patient who initially presented with recurrent epistaxis and then with myasthenia. It was only when he developed acute kidney injury 4 months after the initial presentation with epistaxis that a diagnosis of multiple myeloma was made.

Retrospective Diagnosis of Nail-patella Syndrome.

A 37 years old female presented with asymptomatic nephrotic range proteinuria due to focal segmental glomerulosclerosis (FSGS). She was treated with steroids and mycophenolate mofetil to which there was no response and progressed to advanced chronic kidney disease. When her brother who was being evaluated as a potential donor, for renal transplant, was found to have proteinuria and a genetic study for the steroid-resistant nephrotic syndrome was done. This revealed mutation in the LMX1B gene. It is then that a diagnosis of nail-patella syndrome (NPS) was made. She underwent a successful renal transplant with her father as a donor and is doing well.

Evidence of the Effectiveness of Pictorial Health Warnings on Cigarette Packaging in Nepal.

BACKGROUND: Tobacco Control Act of 2010 mandates government to implement at least 75% pictorial health warnings (PHWs) on tobacco packaging that was enforced in 2013. The purpose of the study was to assess the effectiveness of PHWs and its impact to the policy change. METHODS: A cross-sectional study was conducted in 9 cities between September 2014 and March 2015. Direct interviews were made among 2250 randomly selected individuals. The effectiveness of PHWs were measured as perceived: i) scariness; ii) quit motivation iii) convincing youth not to start smoking; iv) encouraging ex-smokers to remain as quitters; v) building public awareness. Logistic regression analysis was used to determine the factors associated with the effectiveness of PHWs. RESULTS: Of the 2250 participants, 29.8% (670) were current smokers, 8.6% (193) were ex-smokers and 97.6% believed that smoking was addictive. PHWs made 83% of the participants scared. Participants believed that PHWs would be effective in motivating smokers to quit (80.2%), in convincing youth not to start smoking (86.8%), in encouraging ex-smokers to remain as quitters (89.1%) and in building public awareness on the dangers of smoking (94%). PHWs made 58% of the current smokers intended to quit smoking and reduced their daily intake of cigarettes from 11 to 5 on average.  Current smokers preferred to purchase loose cigarettes rather than a pack. The covariates significantly associated with the effectiveness of PHWs were current smokers, ex-smokers and addiction. CONCLUSION: PHWs were found important to motivate smokers to quit smoking, to reduce consumption of cigarettes and to prevent relapse in ex-smokers. Evidence from the study had triggered policy changes which included enlargement of the size of PHW to 90% and the release of a notification to ban selling of loose cigarettes. Thus, the warning messages with pictures are required to be improved and rotated.

Crystalline Nephropathy due to APRT Deficiency: A Preventable Cause of Renal and Renal Allograft Failure.

Adenine phosphororibosyl transferase (APRT) deficiency, a rare inborn error of metabolism is inherited as an autosomal recessive trait. It presents with 2,8-dihydroxyadenine (2,8-DHA) crystal nephropathy and recurrent nephrolithiasis and often progresses to end stage renal disease (ESRD). After transplant, it can recur in the allograft. If APRT deficiency is recognized early, renal failure can be prevented, arrested or reversed in native kidney and in allograft by treatment with allopurinol, which inhibits xanthine oxidase and reduces 2,8-DHA formation. We report two cases of APRT deficiency from our center. DNA sequencing of APRT gene performed in one of the cases revealed a pathogenic variant in Exon1 of APRT gene (c.3G>C; p.Met1). This variant affects the translation initiation codon and results in a start loss. The variant has previously been reported in two cases with APRT deficiency.

Role of low protein diet in management of different stages of chronic kidney disease - practical aspects.

BACKGROUND: Chronic kidney disease (CKD) is a worldwide public health problem and more so in India. With limited availability and high cost of therapy, barely 10 % of patients with incident end stage renal disease (ESRD) cases get treatment in India. Therefore, all possible efforts should be made to retard progression of CKD. This article reviews the role of low protein diet (LPD) in management of CKD subjects and suggests how to apply it in clinical practice. DISCUSSION: The role of LPD in retarding progression of CKD is well established in animal experimental studies. However, its role in human subjects with CKD is perceived to be controversial based on the modification of diet in renal disease (MDRD) study. We believe that beneficial effect of LPD could not be appreciated due to shorter duration of follow-up in the MDRD study. Had the study been continued longer, it may have been possible to appreciate beneficial effect of LPD. It is our contention that in all cases of CKD that are slowly progressive, LPD can significantly retard progression of CKD and delay the need for renal replacement therapy (RRT). To be able to apply LPD for a long period, it is important to prescribe LPD at earlier stages (1,2,3) of CKD and not at late stage as recommended by KDIGO guidelines. Many clinicians are concerned about worsening nutritional status and hence reluctant to prescribe LPD. This actually is true for patients with advanced CKD in whom there is spontaneous decrease in calorie and protein intake. In our experience, nutritional status of patients in early stages (1,2,3) of CKD is as good as that of healthy subjects. Prescribing LPD at an early stage is unlikely to worsen status. The role of LPD in retarding progression of CKD is well established in animal experimental studies. Even in human subjects, there is enough evidence to suggest that LPD retards progression of CKD in carefully selected subjects. It should be prescribed to those with good appetite, good nutritional status and a slowly progressive CKD at an early stage (stage 1,2,3). It may also be prescribed at stage 4 & 5 of CKD if the appetite and nutritional status are good.

The Changing Role of Dietary Protein Restriction in Management of Chronic Kidney Disease (CKD).

In the last 5 to 6 decades there has been a marked variation in use of dietary protein restriction (DPR) in treatment of patients with chronic kidney disease (CKD). Before availability of renal replacement therapy (RRT), DPR restriction was widely practised in uraemic patients to reduce generation of nitrogenous waste products and ameliorate uraemic symptoms. With availability of RRT, the interest in DPR was lost. There was a resurgence of interest in DPR when animal experimental studies suggested that DPR can retard the progression of CKD. Then there was concern about worsening nutritional status with DPR. This article reviews how the role of DPR in treatment of CKD as perceived by physicians has varied over the years and suggests a strategy that should be followed in India considering that RRT is available to a very small percentage of cases developing end stage kidney disease (ESKD).

Prevalence of Chronic Kidney Disease and the Incidence of Acute Kidney Injury in Patients with Coronary Artery Disease in Mumbai, India.

BACKGROUND AND OBJECTIVE: To determine the prevalence of chronic kidney disease (CKD) and incidence of acute kidney injury (AKI) in patients with coronary artery disease (CAD) demonstrated on coronary angiography. MATERIALS AND METHODS: Totally, 125 patients admitted to Lilavati Hospital and Research Centre, Mumbai, with CAD were included in the study. RESULTS: Left anterior descending artery was the major vessel involved (40%), followed by a circumflex artery (21.6%). 49 out of 125 (39.2%) were found to have underlying CKD. 69% (34) of these CKD patients developed AKI. 21 out of 34 patients who developed AKI required hemodialysis. Only 47.1% (16 out of 34) of CKD patients had complete recovery, 29% had partial recovery, and 23% had no recovery of their renal function from AKI. Statistically significant number of patients in CKD group had no recovery from AKI as compared to non-CKD group (23.5% vs. 0%). CONCLUSION: Our study concludes that there is a very high prevalence of CKD (39.2%) in patients with CAD and AKI is a very important complication (38.4%) in these patients. Considering such a high prevalence of CKD, nephrology referral must be considered in patients with abnormal urinalysis, spot urinary protein to creatinine ratio and in patients whose creatinine clearance is <60 ml/min.

A single arm, prospective, open label, multicentre study for evaluation of efficacy and safety of IV CERA for treatment of chronic renal anaemia in dialysis patients not currently treated with ESA.

INTRODUCTION: CERA, a continuous erythropoietin receptor activator, has reported effective correction of anaemia in international clinical trials. OBJECTIVE: Objective of this study was to evaluate efficacy and safety of CERA in Indian patients who were on dialysis and has not received erythropoiesis stimulating agent (ESA) therapy in last 8 weeks. METHODS: In this open label, single arm, prospective, multi-centre study, 189 patients on dialysis, having Haemoglobin (Hb) between 8 - 10 g/dL and not receiving any ESA for last 8 weeks were included at 14 centers across India. CERA was given intravenous (IV) at the dose of 0.6 microg/kg every two weeks. Primary end point of the study was mean change in Hb concentration from baseline to end of the treatment period (TP) of 16 weeks. RESULTS: Mean change of Hb from baseline to end of TP was 2.11 +/- 1.37 g/dL and 2.08 +/- 1.29 g/dL in intent to treat (ITT) and per protocol (PP) population respectively. Mean time to achieve Hb response was 6.10 +/- 3.87 weeks and 6.16 +/- 3.92 weeks in ITT and PP populations respectively. Out of 68 adverse events (AEs) seen during study period, 33 were serious adverse events (SAEs). As per investigators all SAEs were related to underlying disease and not to the study medication. CONCLUSION: It is concluded that CERA administered once in two weeks in dialysis patients effectively corrected chronic kidney disease (CKD) related anaemia and was well tolerated with no significant untoward effect directly related to drug therapy in Indian population.

Burden and predictors of hypertension in India: results of SEEK (Screening and Early Evaluation of Kidney Disease) study.

BACKGROUND: Hypertension (HTN) is one of the major causes of cardiovascular morbidity and mortality. The objective of the study was to investigate the burden and predictors of HTN in India. METHODS: 6120 subjects participated in the Screening and Early Evaluation of Kidney disease (SEEK), a community-based screening program in 53 camps in 13 representative geographic locations in India. Of these, 5929 had recorded blood pressure (BP) measurements. Potential predictors of HTN were collected using a structured questionnaire for SEEK study. RESULTS: HTN was observed in 43.5% of our cohort. After adjusting for center variation (p < 0.0001), predictors of a higher prevalence of HTN were older age ≥ 40 years (p < 0.0001), BMI of ≥ 23 Kg/M2 (p < 0.0004), larger waist circumference (p < 0.0001), working in sedentary occupation (p < 0.0001), having diabetes mellitus (p < 0.0001), having proteinuria (p < 0.0016), and increased serum creatinine (p < 0.0001). High school/some college education (p = 0.0016), versus less than 9th grade education, was related with lower prevalence of HTN. Of note, proteinuria and CKD were observed in 19% and 23.5% of HTN subjects. About half (54%) of the hypertensive subjects were aware of their hypertension status. CONCLUSIONS: HTN was common in this cohort from India. Older age, BMI ≥ 23 Kg/M2, waist circumference, sedentary occupation, education less, diabetes mellitus, presence of proteinuria, and raised serum creatinine were significant predictors of hypertension. Our data suggest that HTN is a major public health problem in India with low awareness, and requires aggressive community-based screening and education to improve health.

Recurrent hyponatremia in an elderly patient with a cystic pituitary gland.

A 71-year-old male with a long history of diabetes and hypertension was admitted with mild azotemia and recurrent hyponatremia. He was diagnosed with a pituitary gland cystic tumor. On careful evaluation, his hyponatremia was found to be due to cerebral salt wasting. The patient made a full recovery following treatment for cerebral salt wasting.

Design of Allele Specific PCR for Rapid Detection of CYP3A5 (A6986G) and Mdr-1 (C3435T) Polymorphisms.

Single nucleotide polymorphisms in CYP3A5 (A6986G) and MDR-1 (C3435T) genes have been shown to be associated with the pharmacokinetics of tacrolimus in case of renal transplant recipients. Knowing these genotypes of the recipients before undergoing transplantation, is therefore essential for physicians to adjust the starting dose of tacrolimus in order to avoid drug induced nephrotoxicity. We have designed an allele specific PCR method for easier and rapid detection of these polymorphisms. 20 Indian renal transplant recipients on tacrolimus who developed nephrotoxicity within 1 month of transplantation and 58 Indian non-transplant subjects having the risk factors for kidney disease i.e. hypertension or diabetes or the family history of these, have been studied for these SNPs by allele specific PCR method. The data suggest that the heterozygosity of CYP3A5 and mutant allele frequency of MDR-1 SNP is higher in transplant patients as well as in general population.

Mycophenolate induced diarrhoea.

Mycophenolate (MMF) has arisen as an important addition in the immunosuppression armamentarium. GI disturbances (diarrhea) and bone marrow suppression are its main side effects requiring dose reduction or even withdrawal. The mechanism of diarrhoea is unknown, although some theories have been postulated. We evaluated three of our patients on MMF who came to us with chronic diarhoea. Their evaluation consisted of CBC, stool routine examination, stool culture, endoscopy and biopsy. Histopathologic examination in all three cases showed villous atrophy. All of them improved with discontinuation of MMF and addition of folic acid suggesting that diarrhoea was related to MMF. Since this complication is seen in only a few cases, we can hypothesize that it may be due to lower levels of the enzyme inosine monophosphate dehydrogenase (IMPDH)--the site of action of MMF.

Squamous cell carcinoma of tongue in a renal transplant recipient.

The overall incidence of malignancies in post renal transplant recipients is reported to be approximately 5 to 6%. Malignancies are significant complications after transplantation. Common malignancies include malignancies of the skin and post-transplant lymphoproliferative disorder (PTLD). Squamous cell carcinoma of the tongue is very rare. We present a case of squamous cell carcinoma of the tongue developing nine years after renal transplantation, in a 30-year-old man. He underwent left hemiglossectomy initially and then modified neck dissection. His graft function continues to remain stable.

Mycophenolate mofetil: a promising immunosuppressive agent.

With avaibility of newer immunosuppressive agents, incidence of acute graft rejection has decreased. Mycophenolate mofetil is one such new drug, now available in the Indian market It has been found to be useful in prevention and treatment of acute and chronic rejection after transplantation. Besides transplant it has been used successfully in primary and secondary glomerulopathies (e.g. SLE) and other autoimmune diseases. The drug is well tolerated with side effects limited mainly to gastrointestinal system in the form of epigastric pain, vomiting and diarrhoea.