Ali Riza Odabas

Anti‐proteinuric effects of combination therapy with enalapril and losartan in patients with nephropathy due to type 2 diabetes

The benefits of angiotensin‐converting enzyme inhibitors and angiotensin II (ATII) receptor antagonist therapy of diabetic nephropathy (DNP) are thought to be largely the result of attenuation of ATII effects on proteinuria. The aim of the study was to ascertain whether there is the additive anti‐proteinuric effect of enalapril plus losartan in DNP. Twenty‐two patients with DNP were studied. Patients were randomly assigned to enalapril 10 mg/day (11 patients) or losartan 50 mg/day (11 patients) administered in a single oral dose in the morning for 12 weeks. and then, in 10 patients (five patients from enalapril group and five patients from losartan group), combination therapy (10 mg/day enalapril and 50 mg/day losartan) was started and continued for 12 weeks. In 12 patients, initial drugs dosages were doubled (six patients 20 mg/day enalapril and six patients 100 mg/day losartan), and monotherapy was continued for 12 weeks. Blood pressure and proteinuria were measured before and after therapy. Adverse effects were recorded at every visit. Proteinuria decreased by 33% with enalapril and losartan administered alone (p < 0.05). Co‐administration of enalapril and losartan decreased proteinuria by a greater extent compared with enalapril and losartan administered alone (51%, p < 0.05). This proteinuria level was significantly lover than the proteinuria level of 12 weeks therapy with enalapril and losartan alone. The decrease of proteinuria was 37% in double‐dose monotherapy group (p < 0.05). Reduction of mean arterial blood pressure (MAP) in co‐administration of enalapril and losartan was higher than enalapril and losartan administered alone (p < 0.05). Combination of enalapril and losartan decreased proteinuria and MAP by a greater extent compared with enalapril and losartan administered alone. We have found that proteinuria reduction induced by combined therapy is maintained throughout short‐term follow‐up; a greater anti‐proteinuric response was observed in the patients with DNP.

Changes in frequency and etiology of acute renal failure in pregnancy (1980 – 1997)

In recent years, the incidence of acute renal failure (ARF) in pregnancy has decreased in developed countries. This cause of this decline has been reported to be liberalized abortion laws and improved prenatal care. The aim of this study was to determine if the incidence and etiology of ARE in pregnancy in our population had undergone similar changes. Between January 1, 1980 and January 1 1997 the number of the patients with ARF was 487. In 74 (15%) of these patients, the etiology of ARF was associated with pregnancy. The frequency of ARF in pregnancy was 17.4% between January 1980 and August 1985, 15.4% between September 1985 and November 1989, 13.5% between December 1989 and January 1997. The differences between the frequencies were not statistically significant (p > 0.5). In the present series, the various disorders leading to ARF in pregnancy were abortion (30%), HELP syndrome and pre-eclampsia (14%), pre-eclampsia or eclampsia (12%), postpartum hemorrhage (15%), fetal death (12%), abruption placentae (6%) and placentae previa (1%).

Lowering Uric Acid With Allopurinol Improves Insulin Resistance and Systemic Inflammation in Asymptomatic Hyperuricemia

Background Hyperuricemia is an independent predictor of impaired fasting glucose and type 2 diabetes, but whether it has a causal role in insulin resistance remains controversial. Here we tested the hypothesis that lowering uric acid in hyperuricemic nondiabetic subjects might improve insulin resistance. Methods Subjects with asymptomatic hyperuricemia (n = 73) were prospectively placed on allopurinol (n = 40) or control (n = 33) for 3 months. An additional control group consisted of 48 normouricemic subjects. Serum uric acid, fasting glucose, fasting insulin, HOMA-IR (homeostatic model assessment of insulin resistance), and high-sensitivity C-reactive protein were measured at baseline and at 3 months. Results Allopurinol-treated subjects showed a reduction in serum uric acid in association with improvement in fasting blood glucose, fasting insulin, and HOMA-IR index, as well as a reduction in serum high-sensitivity C-reactive protein. The number of subjects with impaired fasting glucose significantly decreased in the allopurinol group at 3 months compared with baseline (n = 8 [20%] vs n = 30 [75%], 3 months vs baseline, P < 0.001). In the hyperuricemic control group, only glucose decreased significantly and, in the normouricemic control, no end point changed. Conclusions Allopurinol lowers uric acid and improves insulin resistance and systemic inflammation in asymptomatic hyperuricemia. Larger clinical trials are recommended to determine if lowering uric acid can help prevent type 2 diabetes.

Obstructive sleep apnea syndrome and chronic kidney disease: a new cardiorenal risk factor

Abstract Clinical and experimental studies revealed that sleep apnea might be an insidious risk factor for the progression of kidney disease and development of cardiovascular events by exacerbating well-known risk factors, namely hypertension, type 2 diabetes mellitus and obesity. Furthermore, sleep apnea also has a negative impact on endothelial function. Therefore, sleep apnea might be defined as a new cardiorenal risk factor. In this review, we aimed to summarize the evidences supporting the complex inter-relations between sleep apnea and development and progression of chronic kidney disease.

Genotype–Phenotype Correlation in Patients with Familial Mediterranean Fever in East Anatolia (Turkey)

AIMS Familial Mediterranean fever (FMF) is an autosomal recessive hereditary disease. Clinical symptoms and findings (phenotypes) seen in this disease are generally fever, abdominal pain, and arthritis. Amyloidosis is also a significant complication. Phenotype-genotype correlations in FMF have not been conclusively resolved. The aims of this study were to find the most frequent mutation/genotype of FMF, as well as to investigate the role of genetic factors on the phenotype and on the development of amyloidosis in a population living in East Anatolia (Turkey). This study included 105 adult patients with FMF. DNA samples were obtained from peripheral blood lymphocytes of the patients. Mutations of the Mediterranean fever (MEFV) gene were analyzed with an FMF Strip Assay test kit (ViennaLab Labordiagnostika GmbH, Vienna, Austria). Patients were separated according to genotypes, and phenotypes were compared statistically by the chi-square test. RESULTS The most frequent mutation was M694V (53%) and the most frequent genotype was M694V/M694V (26%). In total, 81% of the patients experienced abdominal pain, 76% had fever, and 22% had arthritis. Fever and arthritis were determined in similar ratios to other genotypes (76% and 19%, respectively) in the M694V/M694V genotype (74% and 29%, respectively) (p > 0.50 and p > 0.20, respectively). However, the patients without the M694V/M694V genotype (86%) had a higher abdominal pain ratio than did the patients with the M694V/M694V genotype (67%) (p <0.05). Renal amyloidosis was determined in 33% of both M694V/M694V and M680I(G/C)/M680I(G/C) homozygous groups and in 12% of the heterozygous groups (p < 0.02 and p < 0.00002, respectively). In other words, homozygous groups had higher ratios of renal amyloidosis. CONCLUSIONS The most frequent mutation in FMF was M694V and the most frequent genotype was M694V/M694V. Fever, abdominal pain, arthritis, and renal amyloidosis were determined not only in patients with M694V/M694V genotype but also in other genotypes. Therefore, genotypes may not predict phenotypes in FMF. Renal amyloidosis was seen more frequently in homozygous genotypes.

Effect of Losartan Treatment on the Proteinuria in Normotensive Patients Having Proteinuria due to Secondary Amyloidosis

Secondary amyloidosis (AA amyloidosis) is a well known cause of nephrotic syndrome and renal failure. Several studies in patients with nephrotic syndrome have suggested a beneficial effect of angiotensin-converting enzyme inhibitors (ACEI). Angiotensin II (ATII) receptor antagonists effect on the long term is not known. In this study, we intended to study the effect of losartan, as an ATII receptor antagonist, on proteinuria and renal functions in patients with normotensive secondary amyloidosis. In total 44 patients with biopsy proven AA amyloidosis associated with nephrotic proteinuria were included. The first group of patients (n=22) was treated with losartan 50 mg/day. The second group of patients (n=22) did not receive any specific antiproteinuric treatment. Urinary protein loss was effectively lowered by losartan from 4.38±1.0 to 2.8±0.61 g/day (p<0.0001), whereas the control group showed a slight fall in proteinuria as 4.21±1.06 to 4.12±1.07 g/day (p = 0.176). Hypoalbuminemia improved significantly from 2.52±0.69 to 2.78±0.46 g/dl (p = 0.004), in the losartan group, whereas serum albumin had fallen in the control group from 2.44±0.57 to 2.27±0.41 (p = 0.041). Serum creatinine increased in the control group from 1.52±0.42 to 2.39±0.51 mg/dl (p<0.0001), and in the losartan group from 1.59±0.50 to 1.84±0.6 mg/dl (p<0.001), after 24 months of treatment. The ATII receptor blocker losartan is effective in protecting against the progression of nephropathy due to AA amyloidosis. Symptomatic treatment of proteinuria with losartan is therefore to be considered, especially with severe proteinuria even in normotensive patients.

High frequency of aspirin resistance in patients with nephrotic syndrome

BACKGROUND Aspirin has a beneficial role in prevention of cardiovascular and thromboembolic events. Patients may experience thromboembolic events despite aspirin treatment, a phenomenon called aspirin resistance. We evaluated the frequency of aspirin resistance and its correlation with clinical and biochemical parameters among patients with nephrotic syndrome (NS). METHODS A total of 83 patients (50 males, 33 females, age range 18-79 years) with NS using aspirin 100 mg/day were included in the study. Demographic information and aetiology of NS based on the histology of a renal biopsy were recorded for each patient. Blood samples were drawn to investigate the association of aspirin resistance with inflammation and thrombotic risk factors. Aspirin resistance was defined as a normal collagen/epinephrine closure time<159 s using a platelet function analyzer (PFA-100). RESULTS Aspirin resistance was determined in 51 patients (61.4%). The number of patients exposed to azathioprine therapy was significantly higher in the aspirin-sensitive group (P=0.043), whereas patients exposed to cyclosporine therapy were significantly higher in the aspirin-resistant group (P=0.017). More patients in the aspirin-resistant group were on angiotensin-converting enzyme inhibitor therapy compared with the aspirin-sensitive group (P=0.024). The aspirin-resistant group showed significantly higher serum low-density lipoprotein cholesterol (LDL-C) (151±47 versus 104±21 mg/dL; P<0.001), triglyceride levels (192±116 versus 134±82 mg/dL; P=0.015) and glomerular filtration rates (91.8±43.0 versus 74.0±35.6 mL/min/1.73 m2; P=0.044) compared with the aspirin-sensitive group. In multivariate analysis, LDL-C was the only parameter associated independently with aspirin resistance [odds ratio (OR) 1.04, 95% confidence interval (CI) 1.02-1.06; P=0.004]. CONCLUSIONS A significant number of patients with NS are resistant to aspirin therapy. Serum LDL-C level is closely associated with aspirin resistance in NS.

Real-time ultrasound guided placement of temporary internal jugular vein catheters: Assessment of technical success and complication rates in nephrology practice

Aim:  Internal jugular vein (IJV) catheterization is often required to gain access for haemodialysis. Use of ultrasound guidance has reduced the complication rates of this procedure. We hypothesized that nephrologists may perform IJV cannulation with a high technical success and low immediate complication rates under real‐time ultrasound guidance.

Severe Alloimmune Hemolytic Anemia after Renal Transplantation

Alloimmune hemolytic anemia is a rare complication following allogeneic organ transplantation. Despite that some other drugs have also been reported, in the majority of cases this complication has been associated with cyclosporine therapy. We here present a case of severe alloimmune hemolytic anemia due to ABO minor incompatibility after renal transplantation in a patient treated with tacrolimus.

Alkaptonuria: A Case Report

Alkaptonuria is a rare, autosomally recessive, metabolic disorder caused by a deficiency in homogentisic acid oxidase. It results in accumulation and deposition of homogentisic acid in cartilage, eyelids, forehead, cheeks, axillae, genital regions, nail beds, buccal mucosa, larynx, tympanic eardrum, and the tendons. We report a 33‐year‐old woman who presented with alkaptonuria and ochronotic pigment deposited in articular cartilage and cartilage of the ear and sclera.