Ambar Khaira

Spectrum of renal involvement in paroxysmal nocturnal hemoglobinuria: report of three cases and a brief review of the literature.

Renal involvement in paroxysmal nocturnal hemoglobinuria (PNH) is usually clinically not apparent but, in cases with clinical involvement, varies from reversible acute dysfunction to chronic irreversible damage. We report two cases of acute kidney injury and one case of chronic kidney disease due to PNH. In all three cases a diagnosis of PNH was made after detection of renal dysfunction. The renal involvement was documented on both histology and on imaging studies. Finally, we briefly review the main literature data on renal involvement in PNH.

Depression and Marital Dissatisfaction among Indian Hemodialysis Patients and Their Spouses: A Cross-Sectional Study

Aim: Interaction of patient in marital dyad may have bearing on long-term patient outcome. Depression, subjective stress, and marital discord have been reported in healthy spouses of patients with end-stage renal disease (ESRD). Depressed patients on dialysis along with their spouses can function as depressed dyad. We looked at the incidence and factors associated with depression and marital stress among Indian hemodialysis patients and their spouses. Methods: A total of 49 (32 males, 17 females) patients on maintenance hemodialysis and their spouses were independently administered Beck Depression Inventory (BDI), Revised Dyadic Adjustment Scale, and self-rated subjective quality-of-life scale. Their demographic parameters, socioeconomic status, and type of family (nuclear or joint) were also noted. Results: About 57.1% of patients were depressed compared with 42.8% of spouses (p = 0.133). In both patients and spouses, BDI correlated with quality of life and perceived marital stress. About 36.7% of patients and 24.4% of spouses reported marital stress (p = 0.69). Male spouses had more marital stress compared with female spouses (p < 0.0001). Depression and marital stress in patients and spouses was not associated with socioeconomic status, literacy levels, and employment. Depression in patients had direct correlation with depression in spouse (r = 0.572, p < 0.0001) and degree of marital dissatisfaction in spouse (r = 0.623, p < 0.0001). Patients living in nuclear family were more depressed and had more marital stress. Conclusion: Married ESRD patients and their spouses function as a complex psychosocial dyad with significant two-way interactions. Social support, as is seen in joint families, leads to significantly lesser depression and better marital understanding.

Endothelial Function and Oxidative Stress in Chronic Kidney Disease of Varying Severity and the Effect of Acute Hemodialysis

Aim: Oxidative stress (OS) and endothelial dysfunction are implicated in accelerated atherosclerosis in chronic kidney disease (CKD). We assessed endothelial function, OS, and carotid intimal medial thickness (CIMT) and their correlates in 44 CKD stage 5 patients (group III) before and after hemodialysis (HD), 40 patients of CKD stages 3 and 4 (group II), and 25 matched controls (group I). Methods: OS was measured by serum concentration of antioxidants; vitamin C and fractional reducing ability of plasma (FRAP) and pro-oxidant; thiobarbituric acid reactive substances (TBARS). Ultrasonography of carotid artery for CIMT and of brachial artery for flow-mediated dilatation (endothelium-dependent dilatation, EDD) was done. Results: TBARS increased significantly with severity of CKD. Antioxidants FRAP and vitamin C were significantly lower in CKD patients as compared with controls, but there was no significant difference between groups II and III. EDD decreased significantly with severity of CKD, whereas CIMT though higher in CKD patients as compared with controls was not significantly different between groups II and III. After a session of HD as compared with predialysis, levels of TBARS decreased, whereas those of FRAP, vitamin C, and EDD increased. On multivariate analysis, there was negative correlation of TBARS with glomerular filtration rate (GFR), serum albumin, hemoglobin, and EDD. Vitamin C had positive correlations with GFR, serum albumin, hemoglobin, and EDD. EDD had direct correlation with GFR, whereas CIMT correlated negatively with EDD. Conclusions: Endothelial dysfunction and OS occur early in CKD, are closely related to each other and structural atherosclerosis, and are proportional to decline in GFR.

Renal allograft tuberculosis: report of three cases and review of literature

Renal transplant recipients are prone to a variety of infections due a persistent immunodepleted state. Incidence of tuberculosis in this population is much higher compared with the general population. While pulmonary tuberculosis still remains the commonest form in this population, renal allograft tuberculosis is very rare. We report two cases of isolated allograft tuberculosis and one case of allograft tuberculosis with coexistent pleuro-pulmonary and bone marrow involvement. All three cases had presented with pyrexia of unknown origin, wherein despite extensive investigations the cause was not found. In two cases the diagnosis was confirmed on histology. Two cases responded to non-rifampicin-based modified antitubercular treatment and one to conventional four-drug Rifampicin-based regimen. Graft function improved in two cases while in one case the graft was lost. Tuberculosis involving the renal allograft is a potential cause for graft dysfunction/loss and requires a high index of suspicion for diagnosis. Timely detection and early institution of therapy can help save the renal allograft.

Profile of hospital admissions following acute poisoning from a major teaching hospital in North India.

A retrospective analysis of 584 cases of acute poisoning admitted with a medical emergency to the Department of Medicine, GTB Hospital, Delhi, over a three-year period. The patients were analysed with respect to the age, sex, mode of poisoning, type of poison consumed and mortality. Of these, 42.63% were aged 20–30 years. Poisoning was used as a suicidal agent by 63.8% of the patients. The nature of the poison could not be ascertained in 15.92% of patients. Sedatives were involved in 13.36%. Aluminium phosphide poisoning was found in 11.82%. The overall mortality was estimated to be 13.18% with 53.2% being caused by the consumption of aluminium phosphide. There has been a change in the nature of poisons consumed and the number of cases of aluminium phosphide poisoning is declining. However, aluminium phosphide poisoning still remains a major threat as it carries a high mortality rate.

Bardoxolone methyl: a targeted antioxidant.

Diabetic nephropathy is a potential consequence of mitochondrial dysfunction and localized tissue oxidative stress. A number of pathways that generate reactive oxygen species (ROS), such as glycolysis, specific defects in the polyol pathway, uncoupling of nitric oxide synthase, xanthine oxidase, NAD(P)H oxidase, and advanced glycation, have been identified as potential major contributors to the pathogenesis of diabetic chronic kidney disease (CKD). 1 Nrf2 is an active transcription factor for the expression of mRNA that codes for synthesis of a host of cytoprotective molecules. These molecules include enzymes that directly destroy ROS, as well as enzymes that synthesize small molecules such as glutathione that scavenges potentially destructive electrophiles. Animal models have suggested the role of genetic deficiency of Nrf2 in pathogenesis and histology of renal disease including glomerulosclerosis. Also, Nrf2 activation is suppressed in animal models of CKD. 2,3 In search for a specific, well-tolerated agent for the therapeutic induction of Nrf2, a new class of compounds—synthetic oleanane triterpenoids (SO), specifically the methyl ester of 2-cyano-3, 12-dioxooleana-1,9(11)-dien-28-oic acid (bardoxolone methyl) as the most potent representative of this group of molecules, is being focused. The cytoprotective effects are believed to be mediated by binding of the SO to the inhibitory protein Keap1, which then releases its partner, Nrf2 transcription factor, that results in the upregulation of several antioxidant genes including NAD(P)H: quinone oxidoreductase 1, thioredoxin, catalase, superoxide dismutase, and heme oxygenase. This results in the reduction of intracellular ROS and proinflammatory activity of the nuclear factor kappa-light-chain-enhancer of activated B cells pathway, thereby restoring redox homeostasis in areas of inflammation. 4 A recent, phase 2a, multicenter, openlabel study in 20 patients with moderate to severe diabetic CKD showed an apparent increase in kidney function following relatively short-term treatment with bardoxolone methyl with no life-threatening adverse events. 5 Apart from diabetes, SO have been used favorably in experimental animal models of kidney injury caused by toxic agents, cystic fibrosis, and emphysema induced by cigarette smoke, disease states characterized by hyperactivity of the immune system, cancer, including prevention and treatment, Parkinson’s disease, Huntington’s disease, and Alzheimer’s disease. 6 To conclude, bardoxolone methyl and other SO could form the basis of therapies halting the progression of CKD and may be even reversing them. Larger studies are needed to confirm beneficial effect of this drug. Internists should be ready to greet this drug with next sunrise.

Oxidative stress, endothelial function, carotid artery intimal thickness and their correlates among chronic peritoneal dialysis patients

We evaluated important nontraditional cardiovascular risk factors, endothelial function and oxidative stress (OS) among stable peritoneal dialysis (PD) patients. Their association with carotid intimal medial thickness (CIMT) was also assessed. Thirty-eight adult patients (13 diabetics, 20 males) on PD for >6 months and 15 age and sex-matched controls were studied. Duration of dialysis (DOD), residual urine output (UO), weekly Kt/V urea, detailed biochemical and lipid profile were noted. OS was measured by serum concentration of antioxidants; vitamin C and ferric reducing ability of plasma (FRAP) and pro-oxidant; thiobarbituric acid-reactive substances (TBARS). High-resolution ultrasonography was used to determine CIMT and flow-mediated dilatation of brachial artery [endothelium-dependent dilatation (EDD)] and dilatation subsequent to nitrate spray [endothelium-independent dilatation (EID)]. Mean age, DOD, UO and Kt/V of study population were 49.3 ± 11.6 years, 19.4 ± 11.8 months, 508.2 ± 422.9 ml/day and 1.73 ± 0.24, respectively. As compared to controls PD patients had higher CIMT (0.46 ± 0.05 vs 0.50 ± 0.07 mm, P = 0.003) and TBARS (1.5 ± 0.4 vs 5.1 ± 2.3 nM/ml, P < 0.001) but lower Vitamin C (1.7 ± 0.3 vs 0.6 ± 0.2 mg%, P < 0.001), FRAP (990.8 ± 78.1 vs 328.7 ± 183.5 μM/L, P < 0.001) and EDD (26.2 ± 5.4 vs 9.8 ± 4.6 %, P < 0.001). TBARS correlated positively with DOD and negatively with hemoglobin. Vitamin C and FRAP correlated positively with serum albumin. EDD correlated positively with UO, Kt/V and hemoglobin. CIMT correlated negatively with Kt/V and hemoglobin. Among themselves CIMT correlated negatively with EDD and vitamin C. EDD correlated positively with vitamin C, while FRAP correlated positively with vitamin C and negatively with TBARS. PD patients have higher OS, poorer endothelial function and higher structural atherosclerosis. These parameters are closely linked to each other, hemoglobin, DOD, residual UO, serum albumin and small solute clearances.

Aliskiren as an antiproteinuric add-on therapy in primary membranous nephropathy

To the Editor: The management of subnephrotic proteinuria in membranous nephropathy is challenging. We retrospectively analyzed fifteen biopsy-proven membranous nephropathy adults with proteinuria of 1–3 g/day (mean 2.4 g/day) and mean serum creatinine of 0.8 mg/day. Secondary causes were ruled out. All the cases were on conservative therapy receiving angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB). The mean blood pressure was 124/ 82 mm/Hg and mean serum potassium was 4.0 meq/l. Aldosterone antagonists or receptor blockers were not used. After six months of ACEI and ARB, nine cases were still proteinuric in the range of 1–3 g/day. Aliskiren (150 mg/day) was added and titrated to a maximum tolerated dose of 300 mg/day. Three months later, in eight cases mean blood pressure was 120/76 mm/Hg and mean proteinuria decreased to \500 mg/day which was independent of the systemic blood pressure-lowering effect of the drug (Table 1). The cases were followed for additional three months. The benefits continued and there was no relapse of the disease or worsening of renal functions. None of the cases developed side-effects needing the drug to be stopped. This is a preliminary analysis of the use of aliskiren in membranous nephropathy. It highlights the fact that despite adequate blood pressure control and use of ACEI and ARB, there is a need to block renin angiotensin pathway by other steps. Aliskiren interferes with first and rate-limiting step in renin enzyme cascade. The high specificity of renin for its substrate reduces likelihood of unwanted interactions and side-effects. Preliminary data in humans show that aliskiren reduces blood pressure and proteinuria [1]. It has also been found useful in hypertensive diabetics with proteinuria [2]. The antiproteinuric benefit is likely to be related to both lowering of intraglomerular pressure and the anti-inflammatory/antiproliferative effects of the drug. Our analysis has some limitations. The types of ACEI and ARB were based on the physician’s preference and aldosterone blockade was not achieved in any of the cases. Second, we had a small sample size and short duration of follow up. A larger randomized controlled trial is needed to fully explore the benefits of aliskiren in proteinuric diseases. To conclude, aliskiren has proved a useful adjunct to the combination of ACEI and ARB in management of membranous nephropathy and the benefits may possibly be extrapolated to other glomerular diseases. Ankur Gupta, act as guarantor for the other authors.

Chronic diarrhea caused by Hymenolepis nana in a renal transplant recipient.

To the Editor: The occurrence of parasitic infections of the gastrointestinal tract is well known in renal transplant recipients. Some of the infections manifest as chronic diarrhea and pain in the abdomen; the seemingly easy diagnosis often proves difficult. We describe here a 50-year-old live related renal transplant recipient on prednisolone 10 mg/day, mycophenolate mofetil 1,500 mg/day and tacrolimus 2 mg/day with a baseline serum creatinine of 1.3 mg/dl 3 months posttransplant. He was admitted with a painful abdomen and increased frequency of stools for the past 4 weeks. Stools were watery, occurring four to five times per day, and were without mucus. On examination, the patient was dehydrated with a blood pressure of 106/60 mmHg. Systemic examination was noncontributory except for diffuse abdominal tenderness. Investigations showed hemoglobin 13.5gm/dl, leukocyte count 13,200/mm, blood urea 94 mg/dl, serum creatinine 2.2 mg/dl and tacrolimus trough level 8.5 ng/ml. Blood culture was sterile. Ultrasound of the abdomen was normal. Initial stool microscopy was normal. He was given intravenous fluids, levofloxacin 250 mg/day and metronidazole 500 mg thrice daily. Antibiotics were stopped after 5 days as there was no response. Mycophenolate mofetil was changed to mycophenolate sodium preparation, and his frequency of stool decreased to two to three times/day for the next 3 days, but again his diarrhea worsened. A viral screen, including cytomegalovirus PCR, hepatitis B surface antigen, anti-hepatitis C antibody, IgM anti-hepatitis A and E antibodies, and ELISA for HIV were negative. Stool examination for clostridium difficile toxin was negative. Sigmoidoscopic biopsy showed mucosa with focal extension of chronic inflammation in the lamina propia and mild edema without any evidence of infection or viral inclusion bodies. A repeat stool microscopy showed eggs of Hymenolepis nana (H. nana) in simple wet mount preparation. No other parasite or pathogenic bacteria were found by either stool examination or culture. Nitazoxanide 500 mg twice daily for 3 days was given along with praziquantel 25 mg/kg body weight once. The patient’s condition improved over the next couple of days, and repeat stool samples were negative for H. nana. Renal functions returned to baseline within a week. H. nana can cause troublesome diarrhea in renal transplant recipients. A simple detailed stool analysis can diagnose it. In one of the studies, 4.5% renal transplant recipients were positive for parasitic infections, of which 0.3% had ova related to H. nana [1]. Immunosuppression breaks the balance between the agent and the host. In laboratory models, cyclosporine reduces survival, growth and fecundity in a wide range of protozoans and helminths [2], but this has not been reported with tacrolimus and needs evaluation. However, the role of H. nana as an opportunistic infection is unclear and requires more We certify that a written consent for publication of the case has been obtained from the patient.

Gatifloxacin-induced severe hyperglycaemia and ketoacidosis in a non-diabetic renal transplant recipient.

Gatifloxacin has been reported to cause dysglycaemia, especially in the elderly and in diabetics. In this communication, we describe a case of a non-diabetic renal transplant recipient who came to us in a state of diabetic ketoacidosis following the use of gatifloxacin for a urinary tract infection.