Iranian Journal of Kidney Diseases
Volume:7 Issue: 6, Nov 2013

Metformin, a biguanide drug, is widely prescribed to treat high blood glucose in individuals with type 2 diabetes mellitus. Type 2 diabetes mellitus is a troubling chronic disease and diabetic nephropathy is one of the most important complications of diabetes mellitus. Recent studies suggest that metformin, in addition to its efficacy in treating type 2 diabetes, may also have therapeutic efficacy in other conditions, including diabetic nephropathy or ameliorative property against tubular cell injury. Moreover, metformin significantly decreases albuminuria in patients with type 2 diabetes mellitus. However, the exact mechanisms beyond the effect of metformin on blood glucose are still unknown. Recent studies suggest that the therapeutic effect of metformin is mediated by its action on adenosine monophosphate-activated protein kinase in tissues. Various investigations show that metformin decreases intracellular reactive oxygen species. Metformin protects against tubular injury by restoring the biochemical alterations and regulation of oxidative stress on renal tubules. It also protects podocytes in nephropathy of diabetes. These findings can more strongly potentiate the clinical use of metformin in the prevention of nephropathy of diabetes. In this regard, to better understand the metformin nephroprotective properties, more experimental rat models and clinical studies are needed.

The pediatric kidney transplant recipient differs from the adult recipient in many ways، including immune responsiveness، drug metabolism and clearance، perfusion of transplanted organs، and risk for posttransplant lymphoproliferative disease. Pediatric patients also have special quality of life issues such as cosmetic side effects of medications، stunted growth and sexual maturation، and separation from their peers. Congenital urological anomalies and glomerulosclerosis are the most common causes of pediatric end-stage renal disease. In the pediatric patients، consideration for preemptive transplantation should be first and arteriovenous fistula placement second. Pediatric patients should receive priority for kidneys from deceased donors to shorten the wait time for transplant. Fevers or changes in blood pressure may identify allograft dysfunction weeks before changes in creatinine occur. Thus، monitoring serum creatinine level is a poor indicator of allograft dysfunction in this setting. There is great concern about nonadherence to immunosuppressive therapy as children reach the stage of adolescence. This report highlights these and other important differences in the evaluation and management of the pediatric kidney transplant recipients compared with the adult and provides practical guidance to the practitioners involved in caring for such patients.

Urinalysis is a mandatory diagnostic tool for the evaluation of patients with kidney diseases. A workshop on urinalysis was held for nephrologists in Isfahan, Iran, on October 11-12, 2012. After the presentation of the results of a survey of the nephrology centers of Iran on urine microscopy, the most important aspects of urinalysis were presented and discussed. These included the following: (1) urinalysis by dipstick, which provides results in a few seconds, is simple to use, has a low cost, and is used worldwide for screening purposes, in spite of some limitations; (2) measurement of proteinuria by 24-hour urine collection, which still represents the reference method in spite of limitations due to frequent over or under collection errors; (3) protein-creatinine ratio in a random urine sample, which is recommended by international guidelines as an alternative to the measurement of 24-hour protein excretion; (4) microalbuminuria, which is seen as a marker of systemic endothelial damage; and (5) the urinary sediment, which is underused even among nephrologists in spite of the relevant diagnostic information it can supply in a wide spectrum of kidney diseases.

Fetuin-A (Α2-HS-glycoprotein) is a protein that plays several functions in human physiology and pathophysiology. The role of fetuin-A in type 1 diabetes mellitus (DM) has been less studied. We investigated the serum levels of fetuin-A in type 1 diabetic patients with microalbuminuria. Furthermore, the blocking effect of renin-angiotensin-aldosteron system on serum levels of fetuin-A was assessed. From January 2010 to May 2011, 32 patients with type 1 DM with confirmed microalbuminuria were included in this study in Isfahan, Iran. Serum fetuin-A levels before and 8 weeks after valsartan administration were measured. In addition, serum lipid profile, creatinine, hemoglobin A1c, and urine microalbuminuria were determined. The mean age of participants was 21.65 ± 0.38 years. Before valsartan administration, the mean values of fetuin-A were not significantly different between males and females (64.22 ± 1.77 ng/mL versus 61.39 ± 3.35 ng/mL, respectively). After valsartan administration, serum levels of fetuin-A and urine albumin-creatinine significantly decreased. A negative correlation was observed between serum fetuin-A level after valsartan administration and serum low-density lipoprotein cholesterol level (P =. 007, r = -0.507). Administration angiotensin receptor blockers concomitantly decreases fetuin-A levels and urine albumin levels

Visfatin (also known as pre-B cell colony-enhancing factor) is increased in patients with chronic kidney disease and has been linked with coronary atherosclerosis. Given that it has been reported that visfatin plays a role in endothelial dysfunction in chronic kidney disease patients, we examined associations between visfatin levels and several markers related to atherosclerosis. The association between visfatin and atherosclerotic risk factors was studied in 173 chronic kidney disease patients (130 men and 43 women). Serum levels of visfatin were measured by the enzyme-linked immunosorbent assay. With increasing visfatin tertiles, patients proved to have a larger number of vessels with stenosis and a higher likelihood of coronary artery disease, as well as having incrementally lower estimated glomerular filtration rate and serum albumin and higher total leukocyte, neutrophil, and monocyte counts; high-sensitivity C-reactive protein; and brain natriuretic peptide levels. Visfatin showed significant positive correlations with low-density lipoprotein cholesterol, uric acid, blood urea nitrogen, creatinine, brain natriuretic peptide, E-selectin, total leukocyte count, neutrophil count, and high-sensitivity C-reactive protein, and a significant negative correlation with estimated glomerular filtration rate and albumin. Only E-selectin was independently associated with visfatin in multiple linear regression analysis. This study indicates that plasma visfatin levels are significantly higher in the presence of coronary artery disease and are correlated with E-selectin levels, which suggest that increased plasma visfatin may be involved in the pathogenesis of coronary atherosclerosis in CKD patients.

Low fetuin-A and vitamin D and high monounsaturated fatty acid (MUFA) contents are associated with vascular calcification (VC) in dialysis patients. We aimed to demonstrate the difference in fetuin-A, vitamin D, MUFA, and VC on plain radiography between patients on hemodialysis and peritoneal dialysis (PD). We recruited 31 hemodialysis and 30 PD patients. We examined plain radiography of the feet, hands, pelvis, and lateral lumbar spine and defined significant VC as abdominal aortic calcifications scores of 5 and higher, VC scores of the hands and pelvis of 3 and higher, or arterial media calcifications of the feet on plain radiography. The mean age, dialysis duration, and prevalence of VC on plain radiography were not significantly different in PD patients compared to hemodialysis patients. However, fetuin-A (P <. 001) and MUFA (P =. 001) were significantly higher, whereas serum albumin and 25-hydroxyvitamin D (P <. 001) were significantly lower in PD patients compared to hemodialysis patients. Hemodialysis patients who demonstrated significant VC on plain radiography had longer dialysis vintage, higher prevalence of coronary artery disease, and higher MUFA than patients without significant VC. Peritoneal dialysis patients who demonstrated significant VC on plain radiography had lower fetuin-A levels and higher C-reactive protein than patients without significant VC. Fetuin-A was an independent risk factor related with VC on plain radiography in PD patients. Fetuin-A, 25-hydroxyvitamin D, and MUFA were significantly different, although the prevalence of VC on plain radiography was not different according to dialysis modality.

Increased oxidative stress, inflammation, and malnutrition are present in hemodialysis patients and these factors exacerbate cardiovascular comorbidities. Vitamin E and α-lipoic acid (ALA) may have a protective role against cardiovascular disease risk factors via anti-oxidative and anti-inflammatory properties. The aim of this study was to evaluate the effect of ALA and vitamin E administration (alone or combined) on hemodialysis-induced stress oxidation, inflammation, and malnutrition. In a randomized placebo-controlled trial, we examined the effects of 2-month supplementation by vitamin E and ALA (alone or combined) on biomarkers of lipid peroxidation (malondialdehyde), inflammation (high-sensitivity C-Reactive protein and interleukin-6), and malnutrition (Subjective Global Assessment and body mass index) in 85 hemodialysis patients receiving ALA (600 mg), vitamin E (400 IU), ALA and vitamin E, and placebo. After supplementation, no significant changes were observed in malondialdehyde level; however, there was a decrease in the ALA and vitamin E group during the period of the study. Also, a nonsignificant decrease was seen in the high-sensitivity C-Reactive protein concentration of the interventional groups. Supplementation of vitamin E with and without ALA significantly reduced interleukin-6 concentration. A significant improvement was observed in malnutrition status of all groups. Vitamin E and ALA supplementation, especially their combination, might improve inflammation and malnutrition status, which suggest it as a potential preventive strategy against CVD among end-stage renal disease patients.

The objective of this study was to report the clinical characteristics and outcomes of children with end-stage renal disease under regular hemodialysis in a dialysis unit in Egypt. Ninety children with end-stage renal disease were included in this study and their charts over the past 11 years (from January 2001 to January 2012) were reviewed. The mean age of the patients at the start of hemodialysis was 5.6 ± 1.4 years. The main causes of end-stage renal disease were glomerular diseases (35.6%), unknown etiology (33.3%), and urological problems (17.8%). Hospital admissions were due to hypertensive attacks, cardiac problems, arteriovenous shunt complications, and infections. Only 3 children received a kidney transplant and 24 (26.7%) died during the 11-year follow-up. Eight patients died of heart failure, 5 due to sepsis, and 4 due to unexplained causes. Maintaining an appropriate care for children with end-stage renal disease is quite difficult in developing countries due to factors such as late referral, poor medical service utilization, limitation of financial resources, and limitations to transplantation. As a result, maintaining on hemodialysis for long periods imposes a high risk of complications.

Varicella-zoster virus (VZV) can cause life-threatening disease in immunosuppressed patients, including kidney allograft recipients. This study was designed to evaluate the immune status of the cohort of hemodialysis patients, who could potentially be candidates for kidney transplantation, against VZV, and to determine the correlation between the self-reported history of chickenpox infection and the VZV antibody status in this population. Serologic testing for VZV was performed for 187 patients at different age groups receiving hemodialysis treatment at Hasheminejad Hospital, Tehran. The enzyme immunoassay method was used for determining immunoglobulin G antibodies against VZV. A total of 187 patients, aged 18 to 88 years (mean, 57.5 ± 16.2 years), were examined. Ninety-five patients (50.8%) were men. Overall, 183 patients (97.9%) were found to be seropositive for VZV. No significant correlation was observed between patients'' history of chickenpox disease and seropositivity of VZV. The sensitivity, specificity, and positive and negative predictive values of patients'' self-reported history was 39.3%, 50%, 97.2%, and 1.7%, respectively. Serologic screening for VZV in patients who are candidates for transplantation is essential to determine their immune status prior to transplant surgery. We suggest that this population be considered as the target group for future immunization programs in Iran.

Patients with end-stage renal disease are at a high risk of adverse cardiovascular events. Elevated level of homocysteine is an important risk factor for cardiovascular morbidity and mortality in dialysis patients. There are some strategies for reduction of serum homocysteine level in these patients, including folate and vitamin supplementation. The aim of the present study was to evaluate the effect of omega-3 supplementation on serum homocysteine level in patients on hemodialysis. In a randomized controlled trial, 100 hemodialysis patients were assigned into two groups to receive omega-3 (oral capsule, 3 g/d) or placebo for 2 months. Complete blood count, blood urea nitrogen, serum creatinine, serum lipids, and serum homocysteine levels were measured before the study and after 2 months at the end of study. Of 100 patients, 6 in each group were excluded, and 44 patients in each group completed the study. There were no significant differences regarding the age, sex, and the number of dialysis sessions per week between the two groups. No difference was observed between the two groups in the laboratory investigations at the end of the study, except for a significant reduction in serum homocysteine level in the omega-3 group as compared to the placebo group (P =. 03). Our study showed a significant reduction regulated by omega-3 supplementation in serum homocysteine level which is a cardiovascular risk factor among hemodialysis patients. Omega-3 can be considered as another homocysteine-reducing agent in this population.

Nitric oxide (NO) is one of the endothelium-dependent relaxing factors released by the vascular endothelium. It is decreased in chronic kidney disease. It was found that higher levels of circulating proinflammatory cytokines such as interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), IL-6, and IL-13 are associated with mortality. The aim of our study was to evaluate the disturbance in NO in chronic kideny failure and its relationship with hypertension and inflammatory and nutritional parameters, as indirect indexes of uremic oxidative stress. This study included 31 children consisting of 23 children, aged from 4 to 18 years old, with ESRD, on regular hemodialysis, and 8 children admitted to hospital for other diseases (control group). Predialysis blood samples were tested for IL-1β, TNF-α, and NO, and were compared with the control group. Serum levels of TNF-α and IL-1β were significantly higher in children on hemodialysis as compared to the control group (TNF-α, 104.54 ± 17.31 pg/mL versus 48.19 ± 6.28 pg/mL, P =. 005; IL-1β, 5.35 ± 0.75 pg/mL versus 2.13 ± 0.61 pg/mL, P =. 02; respectively). However, the levels of NO, albeit higher in this group had no significant difference with the controls. The levels of cytokines are high in pediatric patients on hemodialysis, which reflects a state of oxidative stress.

This study aims to determine the prevalence, types, and associated factors for the use of herbal remedies in hemodialysis patients. Two hundred participants were selected by stratified sampling and were systematically interviewed. One hundred and twenty-six patients (63%) had used herbal remedies some time since their initiation of dialysis treatment. The users of herbal remedies had a significantly older age than nonusers, but no other significant differences were observed. The most prevalent complaints that led to herbal remedies use were gastroenterological complaints, flushing, and excessive thirst. Cichorium intybus, Borage officinalis, Mentha longifolia, and Matricaria recutita were the most prevalently used herbs in our patients. More study should be done on safety and efficacy of these herbs for hemodialysis patients.

Necrotizing fasciitis is a rare complication of nephrotic syndrome in children, with a high mortality rate. We report a case with successful outcome with judicious intravenous antibiotics and skin grafting of the bilateral lower thighs.

Primary ciliary dyskinesia is characterized by congenital impairment of mucociliary clearance. Kartagener syndrome (KS) is a clinical variant of primary ciliary dyskinesia which is involved in situs inversus associated with chronic respiratory infections. In addition, glomerular disease in KS syndrome is rare and reported cases are limited. We had a 27-year-old female patient with KS who presented with proteinuria, hematuria, normal kidney function, and a family history of systemic lupus erythematosus. Kidney biopsy showed segmental scar with adhesion to Bowman capsule, which was indicative of focal segmental glomerulosclerosis.

Treatment of steroid-dependent nephrotic syndrome, particularly in patients who have failed to respond to multiple immunosuppressive drugs, remains challenging. Rituximab represents a new off-label therapeutic option. Here, we report the use of rituximab in 7 children with steroid-dependent nephrotic syndrome with various histological backgrounds who failed to maintain remission with other immunosuppression regimens. All patients received rituximab infusion, 750 mg/m2 in 2 doses, 2 weeks apart, and the subsequent doses were adjusted by clinical response. In all patients, complete B-cell depletion was observed after the first course of rituximab. Follow-up for at least 12 months showed sustained remission in 6 children. We conclude that rituximab can reduce the risk of relapses, reduce the burden of immunosuppression, and at least, offer a better control of steroid-dependent nephrotic syndrome with minimal doses of immunosuppressive agents and steroids.