Association of CTG repeat polymorphism in carnosine dipeptidase 1 (CNDP1) gene with diabetic nephropathy in north Indians.

Background & objectives: CNDP1 gene, present on chromosome 18q22.3-23, encodes carnosinase, the rate-limiting enzyme in hydrolysis of carnosine to β-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.

The live kidney donor: Do we now understand the risks better.

Grams ME, Sang Y, Levey AS, Matsushita K, Ballew S, Chang AR, Chow EK, Kasiske BL, Kovesdy CP, Nadkarni GN, Shalev V, Segev DL, Coresh J, Lentine KL, Garg AX; Chronic Kidney Disease Prognosis Consortium. (Division of Nephrology, Johns Hopkins University School of Medicine, Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, and the Departments of Surgery and Epidemiology, Johns Hopkins University, Baltimore; Division of Nephrology, Tufts Medical Center, Boston; Division of Nephrology, Geisinger Medical Center, Danville, Pennsylvania; Department of Medicine, Hennepin County Medical Center, University of Minnesota, Minneapolis; Memphis Veterans Affairs Medical Center and University of Tennessee Health Science Center, Memphis; Division of Nephrology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, USA; Medical Division, Maccabi Healthcare Services and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; Centers for Abdominal Transplantation and Outcomes Research, Saint Louis University, St Louis; Departments of Medicine and Epidemiology and Biostatistics, Western University, and the Institute for Clinical Evaluative Sciences, London, Ontario, Canada). Kidney-failure risk projection for the living kidney-donor candidate. N Engl J Med 2016;374:411–21.

Effect of mesenchymal stem cells transplantation on glycaemic profile & their localization in streptozotocin induced diabetic Wistar rats.

Background & objectives: Bone marrow is a rich source of adult stem cells that can differentiate into various cell types. Administration of mesenchymal stem cells (MSCs) in irradiated diabetic rat model has transiently shown to decrease blood glucose level. This study examines the effect of high dose and multiple injections of MSCs on glycemic profile, their localization and regeneration of islet in diabetic Wistar rat. Methods: The study was carried out in male Wistar rats categorized into three groups (n=6, in each group): Group 1 as control, group 2 streptozotocin (STZ) (50 mg/kg) induced diabetic group and group 3 experimental group; 5-bromo-2-deoxyuridine (BrdU) labelled allogenic MSCs were injected in the non-irradiated diabetic rat of the experimental group through tail vein. The blood glucose profile was subsequently monitored at regular intervals. Rats were sacrificed on day 45 and pancreas was examined for localization of BrdU labelled stem cells by immunofluorescence and islet-neogenesis by immunohistochemistry . Results: There was a significant reduction in blood glucose level after administration of MSCs in the experimental group (p<0.001). The presence of BrdU labelled MSCs in islet suggested their localization in the pancreas. Co-expression of anti-BrdU and anti-insulin antibody indicated trans-differentiation / fusion into insulin producing cells evidenced by significant increase in total number of islet (p=0.004) and insulin positive cells (p<0.0001) in experimental group. Interpretation & conclusions: Our results showed that the MSCs administration in non-irradiated diabetic Wistar rat reduced hyperglycaemia and was accompanied by increased islet-neogenesis, possibly through trans- differentiation/fusion.

Utility of adenosine deaminase (ADA), PCR & thoracoscopy in differentiating tuberculous & non-tuberculous pleural effusion complicating chronic kidney disease.

Background & objectives: Pleural effusion is a common occurrence in patients with late-stage chronic kidney disease (CKD). In developing countries, many effusions remain undiagnosed after pleural fluid analysis (PFA) and patients are empirically treated with antitubercular therapy. The aim of this study was to evaluate the role of adenosine deaminase (ADA), nucleic acid amplification tests (NAAT) and medical thoracoscopy in distinguishing tubercular and non-tubercular aetiologies in exudative pleural effusions complicating CKD. Methods: Consecutive stage 4 and 5 CKD patients with pleural effusions underwent PFA including ADA and PCR [65 kDa gene; multiplex (IS6110, protein antigen b, MPB64)]. Patients with exudative pleural effusion undiagnosed after PFA underwent medical thoracoscopy. Results: All 107 patients underwent thoracocentesis with 45 and 62 patients diagnosed as transudative and exudative pleural effusions, respectively. Twenty six of the 62 patients underwent medical thoracoscopy. Tuberculous pleurisy was diagnosed in six while uraemic pleuritis was diagnosed in 20 subjects. The sensitivity and specificity of pleural fluid ADA, 65 kDa gene PCR, and multiplex PCR were 66.7 and 90 per cent, 100 and 50 per cent, and 100 and 100 per cent, respectively. Thoracoscopy was associated with five complications in three patients. Interpretation & conclusions: Uraemia remains the most common cause of pleural effusion in CKD even in high TB prevalence country. Multiplex PCR and thoracoscopy are useful investigations in the diagnostic work-up of pleural effusions complicating CKD while the sensitivity and/or specificity of ADA and 65 kDa gene PCR is poor.

Transplantation in the times of HIV infection: Thinking outside the box.

Muller E, Barday Z, Mendelson M, Kahn D. (Transplant Unit, Department of Surgery; Division of Nephrology, Department of Medicine; Division of Infectious Diseases and HIV Medicine, Department of Medicine; and the Department of Surgery, University of Cape Town, Groote Schuur Hospital, Cape Town, South Africa.) HIV-positive-to-HIV-positive kidney transplantation––results at 3 to 5 years. N Engl J Med 2015;372: 613–20.

Risk of pre-eclampsia after kidney donation: Primum non nocere.

Altruistic donation of a kidney, a paired organ, has been seen as an acceptable way of giving a new lease of life to patients with end-stage kidney failure. Living donors must undergo a stringent process of evaluation and meet several criteria to be labelled as ‘healthy’ before they can be accepted in a transplant programme. Concerned that the care of the donor needed to be standardized, the Transplantation Society organized the Amsterdam Forum on the Care of the Living Donor,1 which provided guidance on how to work-up living donors. Thanks to some recent publications based on long-term follow-up of living donors and comparison with carefully selected healthy nondonor cohorts, the safety of live kidney donation is being investigated afresh. In this publication of the Ontario, Canada-based Donor Nephrectomy Outcomes Research (DONOR) network, Garg and colleagues matched 85 women who donated a kidney between 1992 and 2010 with 510 healthy non-donor women from the general population in a ratio of 1:6. They collected data on 131 and 788 pregnancies in the two groups, respectively, after cohort entry. The groups were well-matched with respect to age, age at entry into the cohort, rural/urban residency, income, number of pregnancies before entry and time to first pregnancy. They found that in-hospital diagnosis of pre-eclampsia and gestational hypertension was more common among donors (11% v. 5%, odds ratio 2.5, 95% CI 1.2–5, p=0.01). The difference was present for both components separately as well (odds ratio, 2.5 for gestational hypertension and 2.4 for pre-eclampsia). There was no difference, however, in the rates of low birth-weight (8% and 7%) or preterm deliveries (6% and 4%). There were no maternal deaths

Attitude and knowledge of healthcare workers in critical areas towards deceased organ donation in a public sector hospital in India

Background. The attitude of healthcare workers towards organ donation can either facilitate or hinder the process of organ donation. We assessed the attitude of healthcare workers employed in intensive or emergency care units of our hospital towards organ donation, and the influence of various factors on willingness for self-organ donation after death. Methods. All doctors, paramedical workers, nursing staff and other staff members working in six distinct intensive or emergency care units in the hospital were requested to fill a completely anonymous, voluntary and self-administered questionnaire. Younger individuals, women and nurses constituted a majority of the study population. Results. The questionnaire completion rate was 99%. About 55% of the study population were agreeable to donating organs after death and 27% were undecided. The factors that positively influenced their willingness to donate organs after death were favourable attitude of the spouse, religious beliefs supporting organ donation, knowledge of hospital’s organ transplant programme, personal experience of the organ donation scenario, having ever donated blood or involvement in social activities, willingness to become an eye donor and willingness to become a living kidney donor. Conclusion. A largely favourable attitude towards organ donation was seen in our study population. However, the study reflects incomplete knowledge leading to confusion and thus, desire to know more among participants with respect to various aspects regarding organ donation. The factors identified that positively influence decisions regarding organ donation can be used as direct interventions.

Referral pattern of patients with end-stage renal disease at a public sector hospital and its impact on outcome.

Background. Late referral of patients with chronic kidney disease (CKD) to a nephrologist has been shown to be associated with greater morbidity and adverse clinical outcomes. Methods. We did a prospective cross-sectional study of 2490 consecutive, newly diagnosed patients with end-stage renal disease (ESRD) referred to the Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh over 2 years. The referral pattern was classified on the basis of the interval between first visit to a nephrologist and initiation of renal replacement therapy (RRT). If the patient reported later to a nephrologist, the disease would have progressed more, and the time interval to initiation of RRT would thus be shorter. A time interval of <3 months was classified as late referral (LR), 3–12 months as intermediate referral (IR) and >12 months as early referral (ER). The demographic and clinical characteristics and co-morbid conditions were compared, and factors associated with LR and outcomes were evaluated. Results. About 75% of patients were referred late. Poor socioeconomic status, low level of education and reduced access to reimbursement of treatment costs contributed to LR. The aetiology of ESRD could not be established in a larger number of LR patients as compared to the other groups. LR patients had a higher prevalence of uraemic complications and required emergency dialysis more frequently. A higher proportion of LR patients were lost to follow up because they could not afford to continue dialysis. Early mortality was higher in the ER group than in the other groups. ER patients were older, more likely to have diabetic nephropathy and a higher burden of co-morbid conditions. They were also more likely to choose continuous ambulatory peritoneal dialysis or undergo transplantation. Only 28% of all patients continued RRT beyond 3 months. Conclusion. A large majority of patients with ESRD in India seek medical attention late, usually in advanced stages of CKD with uraemic complications. LR is more frequent in younger patients and those with non-diabetic kidney disease, and is associated with poor socioeconomic status, lack of education and poor outcomes.

Nephrotic syndrome and recurrent pulmonary oedema in bilateral atherosclerotic renal artery stenosis: resolution following renal angioplasty and stenting.

Hypertension and episodic pulmonary oedema are known complications of bilateral renovascular disease. However, significant proteinuria has not been reported in this setting. We describe a patient who presented with recurrent pulmonary oedema and nephrotic syndrome, and was found to have bilateral renal artery stenosis. Percutaneous angioplasty and stenting led to a complete resolution of both, confirming a causal relationship. This is perhaps the first report documenting the rare combination of nephrotic syndrome and flash pulmonary oedema due to bilateral renal artery stenosis.

Pathological spectrum of cytomegalovirus infection of renal allograft recipients-an autopsy study from north India.

This is a retrospective study of autopsy material to highlight the histo-morphological changes in cytomegalovirus (CMV) infection amongst renal allograft recipients. Nineteen out of 80 patients (23.75%) autopsied during a seventeen-year period (1985-2001) had CMV infection. Pulmonary infection was present in 14 out of 19 cases of which four had isolated lung involvement. Likewise, there were two cases each of isolated oesophageal and renal involvement; one case with isolated colonic involvement. The other 10 cases had multi-organ involvement and the organs involved were kidneys (4), esophagus (6), stomach (1), colon (5), adrenals (3), pancreas (3), liver (1) and spleen (1). Pulmonary infection with CMV was associated with acute pneumonitis in 3 cases and lymphocytic interstitial pneumonitis in 9 instances. Four out of 6 cases had acute tubulo-interstitial nephritis induced by CMV and only two cases had no significant inflammatory response. Glomerular involvement in the form of CMV inclusions in the glomeruli was present in only one case. Gastrointestinal CMV infection (15) presented as acute necrotizing ulceration because of predominant endothelial involvement. Post transplant survival period varied from one month to three years, with majority (14) of the patients having survived for less than one year.

Viral infections of renal allografts--an immunohistochemical and ultrastructural study.

Viral infections have been recognized as an integral part of both graft injury and rejection. On routine histology, viral infections are diagnosed only when fully established, by the presence of viral inclusions or cytopathic effect. Although renal transplants are routinely done in many centres in India, the incidence of viral infections is largely unkown. This study was aimed at detecting 5 viral infections namely, cytomegalovirus (CMV), BK polyoma Virus (BKV), Herpes Simplex Virus1 and 2 (HSV1 and 2) and Epstein Barr Virus (EBV) in renal biopsies from 321 renal allograft patients, using immunohistochemical and electron microscopic studies. Sixty two biopsies were selected from a total of 414 (belonging to 321 patients) for immunostaining on the basis of features suspicious of viral infections in hematoxylin and eosin stained sections. Immunostaining confirmed CMV infection in 8 biopsies, BKV infection in 31 biopsies and HSV1 in only 2 biopsies. HSV2 and EBV were not detected in any biopsy. Two biopsies showing CMV immunopositivity and 5 of BKV were further processed for electron microscopy, which supported the diagnoses. Thus, the study highlights the prevalence of BKV and CMV infections in renal transplant patients having graft dysfunction, to be 9.3% and 1.9%, respectively. Besides, only one case each was diagnosed as CMV infection and BKV infection in routine histopathological reporting, establishing the importance of immunohistochemical studies in early diagnosis of these viral infections.

Respiratory paralysis in Sjogren syndrome with normal renal function.

We report a 28-year-old woman who presented with quadriparesis and respiratory failure, and had severe hypokalaemia and distal renal tubular acidosis. She recovered completely on potassium and alkali supplementation. Biopsy and scintigraphy of the minor salivary glands confirmed the presence of Sjogren syndrome. A 6-month course of prednisolone did not correct the distal renal tubular acidosis.