Iranian Journal of Kidney Diseases
Volume:11 Issue: 3, May 2017

Drug-induced nephrotoxicity is one of the most common causes of acute kidney injury. There are various agents that exert nephrotoxic effects through different pathogenic mechanisms. Aminoglycoside antibiotics, chemotherapeutic agents, radiocontrast media, and nonsteroidal anti-inflammatory drugs are among common nephrotoxic agents. In recent years, natural compounds are being increasingly used in the treatment of kidney diseases. Given many reports available on the curative effects of a variety of medicinal plants against drug-associated nephrotoxicity, we aimed to review the protective effects of medicinal plants on certain nephrotoxic drugs.

The pathophysiology of urinary stone formation is complex, involving a combination of metabolic, genetic, and environmental factors. Over the past decades, remarkable advances have been emerged in the understanding of the pathogenesis, diagnosis, and treatment of calcium kidney calculi. For this review, both original and review articles were found via PubMed search on pathophysiology, diagnosis, and management of urinary calculi. These resources were integrated with the author's knowledge of the field. Nephrolithiasis is suggested to be associated with systemic disorders, including chronic kidney insufficiency, hematologic malignancies, endocrine disorders, autoimmune diseases, inflammatory bowel diseases, bone loss and fractures, hypertension, type 2 diabetes mellitus, metabolic syndrome, and vascular diseases like coronary heart diseases and most recently ischemic strokes. This is changing the perspective of nephrolithiasis from an isolated disorder to a systemic disease that justifies further research in understanding the underlying mechanisms and elaborating diagnostic-therapeutic options.

Introduction. Hypertension has been identified as one of the commonest modifiable determinants for chronic kidney disease progression. A variety of antihypertensive drugs are available and their effect on kidney function has been investigated by a large number of randomized controlled trials. Observational studies, although scarcely been used, outpatient can reflect everyday practice, where drug exposures vary over time, and may provide an alternative for detecting longitudinal changes in kidney function.
Materials and Methods. We applied mixed model repeated measures analysis to investigate the effect of antihypertensive drug categories and their combinations on kidney function change over time in a cohort of 779 patients with essential hypertension, using the data from a Greek hypertension outpatient clinic. Antihypertensive drugs were grouped in 5 categories. Their effect was evaluated and their combinations with and without renin-angiotensin-system inhibitors (RASI) to each other. In addition, the combination of RASI with calcium channel blockers (CCBs) was studied.
Results. Diuretics, RASI, CCBs, and beta-blockers had a significant renoprotective and blood pressure lowering effect. Combinations with RASI had a smaller beneficial effect on kidney function compared to CCBs (0.75 mL/min/1.73 m2 per year of drug use versus 0.97 mL/min/1.73 m2). There was no additional effect when combining RASI with CCBs. However, the lowering effect on systolic blood pressure was greater (-0.83 mm Hg per year of drug use, P Conclusions. RASI were found to have a smaller, although significant, renoprotective effect. There was no additional effect on kidney function when combining RASI with CCBs.

Introduction. The aim of the present study was to compare the changing pattern of urine neutrophil gelatinase-associated lipocalin (NGAL) with serum as well as urine creatinine during amphotericin B treatment and determine its accuracy in the early detection of amphotericin B nephrotoxicity.
Materials and Methods. A cohort study was performed during 9 months at 3 hematology-oncology services. Patients aged 15 years and greater with no documented history of acute kidney injury or chronic kidney disease, planned to receive any formulation of amphotericin B for at least 1 week, were included. Serum as well as urine creatinine and urine NGAL were determined on days zero, 3, 5, 7, 10, and 14 of amphotericin B treatment.
Results. Forty patients with the mean age of 38.0 ± 14.1 years were recruited. Eleven of 40 patients (27.5%) developed amphotericin B nephrotoxicity. The overall changes in the mean values of urine NGAL were not significant during amphotericin B treatment, neither within nor between the two groups. The area under the curve of urine NGAL (0.765; 95% confidence interval, 0.588 to 0.962) on day zero was significantly higher than that of serum creatinine (0.464; 95% confidence interval, 0.268 to 0.660; P = .01) for predicting amphotericin nephrotoxicity.
Conclusions. The incremental pattern of urine NGAL during amphotericin B treatment was not significant compared to baseline values. The urine level of NGAL on the first day of amphotericin B administration was more accurate than serum creatinine in predicting acute kidney injury caused by this agent.

Introduction. Prevalence of urinary calculi in children has been increasing in the past years. We performed an analysis of the chemical composition of stones formers of the pediatric population in our geographical area over the years 2005 to 2013.
Materials and Methods. Fourier transform infrared spectroscopy was employed for the determination of the calculus composition of a group of Sicilian children, and metabolic studies were performed to formulate the correct diagnosis and establish therapy.
Results. The prevalence of stone formation was much higher for boys than for girls, with a sex ratio of 1.9:1. The single most frequent component was found to be calcium oxalate monohydrate, and calcium oxalates (pure or mixed calculi) were the overall most frequent components. Calcium phosphates ranked 2nd for frequency, most often in mixed calculi, while urates ranked 3rd. The metabolic disorder most often associated with pure calcium oxalate monohydrate calculi was hypocitraturia, while hyperoxaluria was predominantly associated with calcium oxalate dihydrate calculi.
Conclusions. Mixed calculi had the highest prevalence in our pediatric population. Our data showed that Fourier transform infrared spectroscopy was a useful tool for the determination of the calculi composition.

Introduction. The angiotensin-converting enzyme (ACE) gene insertion or deletion in long-term hemodialysis patients may be associated with corrected QT interval prolongation, leading to fatal arrhythmias. The ACE D allele is known to increase the risk of malignant ventricular arrhythmias and is also associated with increased QT dispersion after myocardial infarction and hypertension. This study aimed to evaluate the relationship between ACE gene polymorphism and QT dispersion in hemodialysis patients.
Materials and Methods. In 70 hemodialysis patients, electrocardiography was performed and QT dispersion was calculated. Corrected QT interval was calculated using Bazett Formula. The ACE gene polymorphism was determined by polymerase chain reaction.
Results. The mean age of the patients was 60 ± 12 years. The mean QT dispersion and corrected QT dispersion were 61.71 ± 21.99 and 73.18 ± 25.51, respectively. QT dispersion inversely correlated with serum calcium and potassium levels and positively correlated with ACE gene polymorphism and residual urine. Calcium level was the predictor factor for QT dispersion. The ACE genotype correlated with QT dispersion, corrected QT dispersion, hemoglobin, and residual urine, and inversely correlated with serum potassium. Corrected QT dispersion correlated with ACE gene polymorphism and residual urine. The DD genotype of ACE had significally greater QT dispersion and corrected QT dispersion than the II and ID genotypes.
Conclusions. Our study showed that the most important parameter affecting corrected QT dispersion was ACE gene polymorphism on the background of D allelle. Patients carrying this allelle need special attention regarding optimal suppression of renin-angiotensin-aldosteron system activity.

Introduction. This study aimed to investigate the effects of erythropoiesis-stimulating agents (ESAs) on intestinal flora in peritoneal fibrosis.
Methods and Methods. Twenty-four Wistar albino rats were divided into 3 groups as the control group, which received 0.9% saline (3 mL/d) intraperitoneally; the chlorhexidine gluconate (CH) group, which received 3 mL/d injections of 0.1% CH intraperitoneally, and the ESA group, which received 3 mL/d injections of 0.1% CH intraperitoneally and epoetin beta (3 doses of 20 IU/kg/wk) subcutaneously. On the 21st day, the rats were sacrificed and the visceral peritoneum samples were obtained from left liver bowel. Blood samples were obtained from abdominal aorta and intestinal flora samples were obtained from transverse colon.
Results. Histopathologically, the CH, ESA, and control groups had peritoneal thickness of 135.4 ± 22.2 µm, 48.6 ± 12.8 µm, and 6.0 ± 2.3 µm, respectively. Escherichia coli was the predominant bacterium in the intestinal flora in the control group. Significant changes in microbial composition of intestinal flora towards Proteus species and Enterobacter species was seen among the groups (P Conclusions. Erythropoiesis-stimulating agents change intestinal flora by a clinically significant amount in experimental peritoneal fibrosis. We consider that ESAs achieve this via regulating intestinal peristaltism.

Cardiovascular and noncardiovascular mortality and morbidity rates of hemodialysis patients are high despite improvement in dialysis delivery.

Hemodialysis patients (n = 532) from 9 hemodialysis facilities were enrolled in this cohort study in September 2012. Causes of death, hospitalization, and hemodialysis exit were recorded during a 28-month follow-up period. A Cox proportional hazard model was used to predict death adjusting for case-mix variables, nutrition variables, bone mineral variables, Kt/V, vascular access, and Charlson comorbidities index.

Patients were 56.0 ± 15.4 years old (57% men). A total of 161 patients (30%) died (17 per 100 patient years), and the most common causes of death were cardiovascular diseases (42%) and infections (25%). Transplantation rate was 7 per 100 patient years and hospitalization frequency was 0.76 per patient year. Based on the multivariable Cox proportional hazard model, the mortality hazard ratio was 1.03 (95% confidence interval [CI], 1.01 to 1.05; P = .007) for age (years), 0.21 (95% CI, 0.11 to 0.40; P

Nutritional factors, comorbidities, vascular access, and abnormal mineral metabolism are the main determinants of mortality and morbidity in hemodialysis patients.

Introduction. Various medication regimens have been used to eradicate Helicobacter pylori in dialysis patients; however, optimal response to treatment is still a challenge. This study aimed to compare response to H pylori eradication in dialysis and nonuremic patients.
Materials and Methods. In a randomized controlled trial, dialysis patients with dyspepsia and confirmed positive endoscopic biopsy for H pylori were compared to nonuremic patients. Participants were randomly assigned to receive clarithromycin or levofloxacin. H pylori eradication was assessed using stool antigen test 4 weeks later.
Results. Forty-four dialysis and 44 nonuremic patients participated in the study. Four dialysis patients and 2 nonuremic patients did not respond to levofloxacin (P = .35). Six dialysis patients and 4 nonuremic patients did not respond to clarithromycin (P = .47).
Conclusions. Response rate to H pylori eradication by clarithromycin and levofloxacin was slightly lower in dialysis patients compare to nonuremic patients. In dialysis patients, response rate to levofloxacin was slightly higher than clarithromycin, but the results were not significantly different.

Introduction. Oxidative stress contributes to delayed graft function (DGF). Glutathione S-transferases (GSTs) are polymorphic genes which produce enzymes with protective effect against oxidative stress. This study aimed to investigate the association between donor's and recipient's GSTM1 and GSTT1 polymorphisms and DGF, creatinine clearance, and oxidative stress parameters in kidney allograft recipients.
Materials and Methods. One hundred and eighty-two donor-recipient pairs were studied. Lipid peroxidation and total antioxidant capacity were measured in the recipient's plasma as the parameters of oxidative stress. Delayed graft function was determined based on at least 10% increase, no change, or less than 10% decrease in the serum creatinine level in 3 consecutive days during the 1st week after transplantation.
Results. Lipid peroxidation was significantly greater in the recipients with DGF (P Conclusions. These results suggest that the donors and recipient's GSTM1 polymorphism may be a major risk factor for oxidative stress and poor kidney allograft transplantation outcomes.

Renal involvement in multiple myeloma has multiple etiologies. Glomerulonephritis rarely occurs in multiple myeloma and numerous case reports in the literature explain their correlation. We report 2 cases of glomerulonephritis, one membranous glomerulonephritis and the other focal segmental glomerulosclerosis, in which multiple myeloma was confirmed after several months in the first case and synchronous with the second. Glomerulonephritis can be an uncommon, but not rare, cause of proteinuria in multiple myeloma.

Renal involvement in Cockayne syndrome is rare and its pathogenesis is yet unknown. We report herein 2 cases (siblings) with Cockayne syndrome type A confirmed by biochemical and molecular assays. The first case was a 13-year-old girl who presented with nephritic syndrome and a rapidly progressive kidney failure. Her younger sister, 7 years old, exhibited hypertension, hyperfiltration, and microalbuminuria. She had hyperreninemia and hyperaldosteronemia without kidney failure or renal arterial stenosis. Renal biopsy, performed the older sister, revealed cystic focal segmental glomerulosclerosis, arteriosclerosis, tubulointerstitial fibrosis, and tubular atrophy. The different clinical phenotypes in the two siblings support the absence of an obvious genotype-phenotype correlation in Cockayne syndrome type A patients. In the older sister, the particular focal glomerular sclerosis and senile lesions assume that kidney disease in Cockayne syndrome may be related to prematurely aging secondary to a defective nucleotide repair.