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Background:Many studies have shown that transforming growth factor(TGF)-beta has a major role in renal scarring in many renal diseases and hypertension.Objectives:The primary aim of this study was to investigate both the relationship between hypertension and serum and urinary levels of TGF-beta[2] (a more sensitive isoform for glomeruli than TGF-beta[1]), and the effects of combination therapy with perindopril + indapamide on microalbuminuria, which becomes an early indicator of hypertensive benign nephropathy, and serum and urinary TGF-beta[2] levels in patients with mild to moderate essential hypertension. In addition, we examined the possible relationship between TGF-beta[2] gene polymorphism and essential hypertension.Methods:This study was conducted at the Department of Nephrology, Medical Faculty, Gazi University, Ankara, Turkey. Patients aged >/=18 years with newly diagnosed mild to moderate essential hypertension (systolic/diastolic blood pressure [SBP/DBP] >120/>80 mm Hg) who had not previously received antihypertensive treatment were included in the study. Patients with stage I hypertension received perindopril 2 mg + indapamide 0.625 mg (tablet), and patients with stage lI hypertension received perindopril 4 mg + indapamide 1.125 mg (tablet). All study drugs were given OD (morning) PO with food for 6 months. Serum and urinary TGF-beta[2] and creatinine levels and serum and urinary albumin levels were measured before and after perindopril + indapamide administration. Amplified DNA fragments of the TGF-beta[2] primer region were screened using amplification refractory mutation system polymerase chain reaction analysis, and the number of ACA repeats was confirmed by DNA sequencing. Genetic studies were performed using a commercial TGF-beta[2] kit.Results:Forty patients were enrolled in the study, and 38 patients (27 women, 11 men; mean [SD] age, 46.3 [6.5] years) completed it. SBP and DBP were significantly decreased from baseline with perindopril/indapamide (both, P < 0.001). Microalbuminuria and urinary TGF-beta[2] levels also decreased significantly from baseline (P = 0.04 and P < 0.001, respectively), whereas the serum TGF-beta[2] level did not change significantly. Three patients, all of whom were found to have TGF-beta[2] gene mutations, had increased urinary TGF-beta[2] levels despite good blood pressure control.Conclusions:The results of this study in patients with mild to moderate hypertension suggest that, despite good clinical control of blood pressure, the persistence of microalbuminuria and high urinary TGF-beta[2] levels might predict renal impairment. When treating these patients, genetic tendencies and possible polymorphisms on the TGF-beta[2] locus should be kept in mind. [ABSTRACT FROM AUTHOR] more...

Fabry Disease (FD) is an X-linked lysosomal storage disease that emerges as a result of the mutations in the galactosidase A gene encoding alpha-galactosidase. The peripheral nervous system (PNS) involvement manifests itself as acroparesthetic complaints due to the small-fiber involvement. Our goal was to assess the PNS involvement of 14 patients with FD both clinically and electrophysiologically besides the other systemic features. 14 patients (11 female and 3 male) of the same family whose enzyme level and genetic mutation analysis confirmed the FD diagnosis were evaluated retrospectively in terms of systemic and neurological findings of the FD. Neurological examination and nerve conduction studies were performed to evaluate the PNS involvement. PNS involvement was more common in females. Eight of the patients had acroparesthesia. The neurological examinations of all patients were normal. Two patients presented sensory axonal polyneuropathy, one of whom had no acroparesthesia. Other patients with acroparesthesia had normal nerve conduction studies. There was no significant relationship between the presence of acroparesthesia and the results of conduction studies (p > 0.05). Acroparesthetic complaints in patients with normal results were attributed to small-fiber involvement. Since small-diameter nerve fibers cannot be evaluated by routine conduction studies, especially in the early stages of FD, these studies may be normal. Early diagnosis through the symptoms such as acroparesthesia may contribute to the survival of the patient by preventing and/or delaying the development of renal, cardiac, and cerebrovascular diseases, which are the main causes of morbidity and mortality. more...

Fabry disease, an X-linked lysosomal storage disorder, is caused by α-galactosidase A deficiency and leads to accumulation of glycospinhgolipids in most tissues, with life-theratening consequences in the kidney, heart, and cerebrovascular system. Enzyme replacement therapy is available as 2 different preparations: agalsidase alfa and agalsidase beta. Enzyme replacement therapy is started as soon as the diagnosis is confirmed, but there is no data available in the literature about its safety during preganacy. Herein, we described 2 patients with Fabry disease who received agalsidase beta during their pregnancy. This report is important as the data about enzyme replacement therapy during pregnancy is restricted with case reports. more...

Background: The aim of our study was to delineate the demographic and clinical properties of primary glomerular diseases of adult population in our country in the light of global knowledge., Methods: All over the country, a total of 25 centers entered data between May 2009 and July 2012 to the database created by 'Glomerulonephritis Study Group' of Turkish Society of Nephrology. Demographic and clinical characteristics, specific diagnoses of glomerular diseases and biopsy findings recorded to the database were analyzed., Results: Among the 1,274 patients, who had renal biopsy within the defined time period, 55 % were male and 45 % were female. The mean age was 40.8 ± 14.6 years. The most frequent indication for biopsy was nephrotic syndrome (57.8 %), followed by nephritic syndrome including rapidly progressive glomerulonephritis (16.6 %) and asymptomatic urinary abnormalities (10.8 %). The most frequent primary glomerular disease was membranous nephropathy (28.8 %), followed by focal segmental glomerulosclerosis (19.3 %) and IgA nephropathy (17.2 %)., Conclusion: The presented study displayed important data about the epidemiology of primary glomerular diseases among adults in our country. The predominance of membranous nephropathy in contrast to other countries, in which the most frequent etiology is IgA nephropathy, seems to be due to differences in the indications for renal biopsy. more...

Background: Acidosis is associated with protein-energy malnutrition, inflammation, and bone disease, and low bicarbonate levels have been implicated in higher mortality rates in chronic kidney disease. Recently, the concentration of serum pregnancy-associated plasma protein-A (PAPP-A) has become accepted as a prognostic marker in hemodialysis patients. This study determined the relationship between PAPP-A and bicarbonate levels in these patients., Methods: The study enrolled 65 hemodialysis patients (41 males, 24 females) and 26 control subjects (11 males, 15 females). Serum PAPP-A, intact parathormone (iPTH), calcium, phosphorus (P), and bicarbonate levels were measured. Correlations between PAPP-A and bicarbonate, iPTH, calcium, and phosphorus were evaluated., Results: Median PAPP-A levels were significantly higher in hemodialysis patients [15.1 (<0.03-158.8) ng/ml] than in control subjects [6.6 (<0.03-16.4) ng/ml] (P < 0.05). There were statistically significant correlations between serum PAPP-A and bicarbonate, iPTH, and P in hemodialysis patients but not in control subjects., Conclusion: Elevation of serum PAPP-A has been found in hemodialysis patients and its significant correlation with bicarbonate suggests that it may be a prognostic factor., (© 2014 Wiley Periodicals, Inc.) more...

Extracorporeal shockwave lithotripsy (ESWL) has dramatically changed the treatment of urinary lithiasis and has been the first treatment option for the majority of patients for more than two decades. Despite its significant benefits, it induces acute renal injury that extends from the papilla to the outer cortex. We evaluated the severity of the inflammatory response to ESWL by measuring the urinary excretion of the cytokines TNF-α, IL-1α, and IL-6. The study included 21 selected patients and 14 control subjects. All patients underwent the same ESWL procedure (2,500 shockwaves at 100 shockwaves/min and 0.039 J from the lithotripter). Urine TNF-α, IL-1α, and IL-6 levels were measured using standard ELISA kits. In the study population (patients and controls), we did not detect TNF-α in the urine samples. The levels of both IL-1α (2.5 pg/ml) and IL-6 (3.8 pg/ml) measured before ESWL were not significantly different from the control group (2.5 and 5.2 pg/ml, respectively; p > 0.05). Twenty-four hours after ESWL, in contrast to IL-1α (4 pg/ml), urine IL-6 (19.7 pg/ml) increased significantly (p < 0.05). Fourteen days after ESWL, IL-1α increased to 5 pg/ml, while IL-6 (7 pg/ml) decreased to the control level. Urine cytokine levels may be used to evaluate the inflammatory response to ESWL. After ESWL, IL-6 levels increased in the early phase, while IL-1α levels increased later. These two markers may be used to measure the severity of inflammation. In contrast to IL-1α and IL-6, urine TNF-α excretion was not increased by ESWL. We believe that the inflammatory response to ESWL can be detected by the urinary excretion of IL-1α for up to 14 days. more...

Background: Obesity and related disorders have a high prevalence all over the world. Increased C-reactive protein (CRP) value in obese individuals and its potential adverse effects have been reported. Here we have investigated the relationship between CRP levels and renal functions in nondiabetic, nonhypertensive, overweight, and obese individuals. The aim of this study was to evaluate the predictive value of CRP levels on future severe renal disease., Methods: One hundred sixty individuals were included in the study. They were grouped as normal weight, overweight, and obese. Anthropometric measurements, renal function tests, and serum hsCRP values were obtained. Mean values were compared and correlation analysis was performed., Results: Significant differences were detected between the groups according to body mass index, waist circumference (WC), and body fat percentage. There was a significant difference with respect to creatinine clearance (CC). Difference in the mean urinary albumin excretion (UAE) was significant between normal-weight and overweight subjects. There was a linear increase in serum CRP values in parallel to the increase in body weight; mean values were significant between groups. A positive correlation was detected between CC and body mass index and WC, and there were significant correlations between CRP and anthropometric measurements, CC and UAE., Conclusions: This study showed that increased CRP levels in nondiabetic, nonhypertensive, overweight, and obese individuals could possibly associated with impaired renal functions that might be originating from endothelial dysfunction. Determination of cutoff levels of CRP, as in cardiovascular diseases, may be useful for early estimation and prevention of renal diseases. more...

Background: Pregnancy-associated plasma protein A (PAPP-A) was recently described as a new marker of cardiovascular events and of inflammation in uremic patients. The aim of this study was to determine levels of PAPP-A in chronic dialysis patients and its possible relationships with renal osteodystrophy., Methods: A total of 99 adult chronic hemodialysis patients, 14 peritoneal dialysis patients and 41 control subjects were included in the study. Serum PAPP-A, intact parathormone (iPTH), calcium, phosphorus and alkaline phosphatase (ALP) were measured. The correlations between PAPP-A and iPTH, calcium, phosphorus and ALP were determined., Results: PAPP-A levels were significantly higher in peritoneal dialysis [4.5 (3.2-6.7) mU/L, median (interquartile range)], and hemodialysis patients [4.7 (3.8-6.5) mU/L] in comparison to control subjects [3.4 (3.0-5.0) mU/L] (p<0.05). In hemodialysis patients, post-dialysis PAPP-A levels [6.2 (4.7-9.4) mU/L] were significantly higher than pre-dialysis levels [4.7 (3.8-6.5) mU/L] (p<0.05). There was a weak but statistically significant positive correlation between serum PAPP-A and iPTH (r=0.216; p=0.041) and ALP (r=0.205; p=0.044) in the hemodialysis group. Correlation between the duration of dialysis therapy and PAPP-A levels was also significant (r=0.267; p=0.008) in the hemodialysis group., Conclusions: PAPP-A levels are elevated in acute coronary syndromes and are closely related to inflammation and oxidative stress. We conclude that PAPP-A levels are increased in dialysis patients and may reflect a greater degree of chronic inflammation than osteodystrophy in uremic patients. more...

Objective: To describe the benefit of ursodeoxycholic acid (UDCA) for the initiation and completion of a successful pregnancy in a previously infertile woman with primary biliary cirrhosis., Design: Case report., Setting: A university hospital with relevant departments., Patient(s): A 29-year-old woman with primary biliary cirrhosis and failure to conceive for 6 years., Intervention(s): Establishment of diagnosis with a liver biopsy, pretreatment of patient with UDCA before conception, and continuation of UDCA after first trimester until term. UDCA was used in the second pregnancy again after the first trimester., Main Outcome Measure(s): Achievement of a safe conception and full-term pregnancy., Result(s): Two consecutive successful pregnancies, a healthy 3,250-g male infant and a healthy 3,000-g female infant. The second conception occurred in a period without the use of UDCA, implicating a latent beneficial effect of either UDCA or the previous pregnancy via some possible immune mechanism., Conclusion(s): Ursodeoxycholic acid could help achieve conception in infertile women with primary biliary cirrhosis. The use of UDCA after the first trimester is shown to be safe in two consecutive pregnancies. Although it cannot be conclusive, the unintentional use of UDCA in the first 20 days after conception did not result in any teratogenicity in the first child. more...

Atherosclerosis is a disease of the arterial wall, with increasing wall thickness representing an early event in the progression of the disease. It has been suggested that iron overload, as assessed by increased serum ferritin concentration, may be a risk factor for atherosclerosis. The aim of this study was to investigate the relationship between the influence of intravenous (IV) iron therapy and ferritin levels and carotid intima media thickness (C-IMT) in dialysis patients. Sixty patients (51 +/- 14) years were divided into two groups according to their IMT obtained by ultrasound; group I (high risk) and group II (low risk). The parameters assessed were serum creatinine, urea, calcium, phosphorus, hemoglobin, albumin, uric acid, iron, ferritin, and lipid levels. Thirty-eight patients (88%) in group I and 5 patients (12%) in group II received IV iron therapy while 5 patients (29%) in group I and 12 patients (71%) in group II (P < 0.001) did not receive IV iron therapy. Ferritin levels were higher in group I than in group II (581 +/- 303 and 306 +/- 224) (P < 0.001). C-IMT measurements correlated with serum ferritin and with the intravenous iron dose received during the 24 months preceding the study (r = 0.315, P = 0.015; r = 0.471, P = 0.001). The findings indicate that IV iron therapy and elevated serum ferritin levels may cause an increase in the incidence of atherosclerosis. more...

Chronic allograft dysfunction (CAD) is the most common cause of allograft failure in the long-term, and current immunologic strategies have little effect on this condition. The renin-angiotensin system (RAS) plays important roles progression of chronic renal disease. It is thought that plasminogen activator inhibitor-1 (PAI-1) functions in the RAS, in addition to involvement in thrombotic risk and fibrosis. This study investigated possible links between angiotensinogen (AGT) genotypes (M235T/MM, MT, TT) and PAI-1 genotypes (4G4G, 4G5G, 5G5G) and CAD assessments of both types of polymorphism were performed in 82 renal allograft recipients. One hundred healthy subjects were also investigated for AGT polymorphism, and 80 healthy subjects for PAI-1 polymorphism. Genotypes were determined using polymerase chain reaction (PCR) sequence-specific primers, and PCR followed by restriction fragment length polymorphism analysis. Kidney recipients with CAD had significantly lower frequencies of the MM genotype and the M allele than the recipients without CAD (p < 0.05 and <0.001). The transplant recipients with CAD also had significantly lower frequencies of the 5G5G genotype and the 5G allele than those without CAD (p < 0.001 and <0.05). Determination of AGT M235T and PAI-1 genotypes prior to transplantation may help identify patients who at risk for chronic renal transplant dysfunction. more...

We determined the sensitivity, specificity, receiver operating characteristics and correlation between cystatin C (cysC) and two widely used markers of renal function, creatinine clearance and serum creatinine, in 244 patients (84 diabetics, 84 hypertensive and 76 healthy subjects). Renal failure was defined as creatinine clearance of less than either 80 or 60 mL/min. Variables were evaluated for two definitions of renal failure and compared between patient groups. Correlation coefficients with cysC were -0.87 for creatinine clearance and 0.92 for creatinine in patients with hypertension; -0.90 for creatinine clearance and 0.97 for creatinine in diabetics; and -0.61 for creatinine clearance and 0.94 for creatinine in the control group. The receiver operating characteristic curves with a cut-off value of 60 mL/min were similar for creatinine and cysC, while at 80 mL/min they were 0.626 for creatinine and 0.813 for cysC levels. We classified the patients into three groups with respect to creatinine clearance (1, >80 mL/min; 2, 60-80 mL/min; 3, <60 mL/min). Mean creatinine (p<0.0001) and cysC (p<0.0001) levels were significantly different between all the groups. Sensitivity, specificity and predictive values were higher for cysC levels, particularly in diabetics and hypertensive patients. The current study suggests that cysC is preferable for detecting temporal changes in renal function in the early stages of renal insufficiency. more...

Background: Oxidative stress is an important risk factor for the development and progression of several complications in hemodialysis patients. The aim of this study was to evaluate the effects of two different dialysis membranes on oxidative stress and selenium status., Methods: Forty long-term dialysis patients and 20 age-matched healthy controls were enrolled into our study. Serum malondialdehyde (MDA) and selenium (Se) concentrations, and glutathione peroxidase (GSH-Px) activities were determined before and after hemodialysis (HD) using a hemophan (H) or a polysulfone (PS) membrane., Results: MDA levels in the HD patients were significantly higher than those in the control group (p < 0.001). GSH-Px activity and selenium concentrations were significantly lower in HD patients compared to the control group (p < 0.001). MDA levels were significantly increased (p < 0.05); GSH-Px activity and selenium concentrations were significantly reduced (p < 0.001) in the PS membrane group compared to H membrane group after HD., Conclusions: Comparing with H membrane, PS membrane caused more oxidative stress and lower levels of Se in HD patients. more...

This prospective study was designed to evaluate the effects of hyperthyroidism on flow-volume loops in nonasthmatic 20 patients with hyperthyroidism. Thyroid related hormones (Total T3, Total T4 and TSH), thyroid gland volumes with ultrasonography, circumference of neck values and flow-volume loops were obtained at the beginning and after three months of antithyroid treatment. Propylthiouracil treatment was followed by a statistically significant decrease in thyroid gland volume and circumference of neck (p< 0.001 and p< 0.001, respectively). The most significant result was improvement of maximum midexpiratory flow rate (MMEFR) after propylthiouracil therapy for three months (p= 0.003). Increases in mean forced expiratory flow after 25% of FVC has been exhaled (FEF25), mean forced expiratory flow after 75% of FVC has been exhaled (FEF75) values were found consistent with the overall improvement in expiratory flow parameters (p= 0.044, p= 0.012 respectively). In conclusion, we speculated that improvement of expiratory flow parameters might be the earlier changes in flow volume loops of patients who were treated with propylthiouracil for hyperthyroidism. more...