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Introduction: The aim of our study was to clarify the hypothesis that proximal tubule (PT) dysfunction may be responsible for early diabetic nephropathy (DN), independently of preceding glomerular endothelial dysfunction. The pattern of endothelial dysfunction and its potential variability was evaluated in two vascular beds, the kidney and the brain. Methods: A total of 68 normoalbuminuric type 2 diabetes mellitus (DM) patients were enrolled in a cross-sectional study and the following parameters were assessed: urinary albumin:creatinine ratio (UACR), urinary α1-microglobulin, urinary β2-microglobulin, plasma asymmetric dimethyl-arginine (ADMA), serum creatinine, glomerular filtration rate (GFR), C-reactive protein (CRP), fibrinogen, HbA1c; pulsatility and resistance indices in the internal carotid artery and middle cerebral artery and intima-media thickness (IMT) in the common carotid artery; cerebrovascular reactivity was evaluated through the breath-holding test. Results: Plasma ADMA was increased in 12 patients (17.5%), urinary α1-microglobulin in 19 patients (27.9%) and urinary β2-microglobulin in 16 patients (23.5%). Cerebral hemodynamic indices correlated with plasma ADMA, CRP, fibrinogen, duration of DM, HbA1c and GFR. ADMA correlated with fibrinogen, CRP, HbA1c, duration of DM and GFR. There were no correlations between ADMA and UACR, and urinary α1-/β2-microglobulin. Also, no correlations were found between urinary α1-/β2-microglobulin and UACR, HbA1c, duration of DM and GFR. Conclusion: The increase in urinary α1-/β2-microglobulin precedes the stage of albuminuria. It may be assumed that early DN is related to PT dysfunction. Endothelial dysfunction plays a pivotal role in the brain vasculature, while its involvement in the development of early DN is not conditional on the occurrence of albuminuria. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Balkan endemic nephropathy (BEN) is a disease found in Romania and neighboring countries in the Balkan area. In Romania, BEN is most prevalent in Mehedinti County, located in the South of Romania near the Danube River. The etiology of the disease is as yet unknown. One of the current hypotheses concerning BEN etiology is an involvement of aristolochic acid (AA). BEN bears many similarities to aristolochic nephropathy, which is developed due to the use of Chinese herbs as therapeutic remedies in slimming diets. This paper analyzes the involvement of therapeutic remedies based on AA in the BEN found in Mehedinti County, where these herbs have been traditionally used. The presence of AA in the plasma of BEN patients as well as of other subjects, including healthy relatives of these patients and other persons from the BEN-affected area, has been analyzed. No AA was detected in the plasma of the studied subjects. This proves the absence, at the current time, of an AA contribution in the analyzed subjects. Therapeutic remedies based on AA have been used in the BEN-affected area. We were not able to reveal direct relationships between these remedies and either the development of BEN in dialyzed patients or the development of urinary-tract tumors in dialyzed patients with urothelial tumors. Therapeutic remedies based on Aristolochiaclematitis may play a stimulating role in BEN with regard to its development and the development of urinary-tract tumors. There may be a relationship between BEN and cumulative previous exposure to low doses of AA due to the consumption of contaminated foodstuffs, which could add to any contributions by therapeutic remedies. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Diabetic atherosclerosis and microangiopathy parallel diabetic nephropathy. The aim of our study was to evaluate the pattern of endothelial dysfunction in two vascular territories, the kidney and the brain, both affected by diabetic vasculopathic complications. The endothelial variability was evaluated in relation to advanced glycation end-products modified peptides. Methods: Seventy patients with type 2 diabetes mellitus and 11 healthy subjects were assessed concerning urine albumin: creatinine ratio, plasma and urinary advanced glycation end-products, plasma asymmetric dimethyl-arginine, serum cystatin C, intima-media thickness in the common carotid arteries, the pulsatility index, the resistance index in the internal carotid arteries and the middle cerebral arteries, the cerebrovascular reactivity through the breath-holding test. Results: The breath-holding index correlated with asymmetric dimethyl-arginine (R² = 0.151; p < 0.001), plasma advanced glycation end-products (R² = 0.173; p < 0.001), C-reactive protein (R² = 0.587; p < 0.001), duration of diabetes mellitus (R² = 0.146; p = 0.001), cystatin C (R² = 0.220; p < 0.001), estimated glomerular filtration rate (R² = 0.237; p = 0.001). Urine albumin: creatinine ratio correlated with urinary advanced glycation end-products (R² = 0.257; p < 0.001), but not with asymmetric dimethylarginine (R² = 0.029; p = 0.147). Conclusions: In type 2 diabetic patients endothelial dysfunction in the cerebral vessels appears to be dissociated from glomerular endothelial dysfunction in early diabetic nephropathy. Advanced glycation endproducts could impact both the cerebral vessels and the glomerular endothelium. [ABSTRACT FROM AUTHOR]

Background: Advanced glycation end-products have been involved in the pathogenesis of proximal tubule dysfunction which characterizes diabetic tubulopathy., Methods: A total of 76 Type 2 diabetes mellitus patients and 28 healthy controls were evaluated concerning a potential association of glycated peptides with proximal tubule dysfunction by assessing urine albumin:creatinine ratio, urinary alpha1-microglobulin, urinary neutrophil gelatinase-associated lipocalin, plasma and urinary advanced glycation end-products, plasma asymmetric dimethyl-arginine, serum cystatin C. Fully automated chip-nanoelectrospray ionization and high-capacity ion trap multistage mass spectrometry characterized the urinary proteomic profile., Results: The urinary glycated proteins displayed a molecular weight of 15,121.4 Da in normoalbuminuric patients and of 30,180.4 Da in microalbuminuric patients. Urinary alpha1-microglobulin and neutrophil gelatinase-associated lipocalin correlated with urinary advanced glycation end-products (R(2)=0.586; R(2)=0.415), urine albumin: creatinine ratio (R(2)=0.292; R(2)=0.116), estimated glomerular filtration rate (R(2)=0.172; R(2)=0.135), serum cystatin C (R(2)=0.146; R(2)=0.129), but not with asymmetric dimethyl-arginine. In multivariable regression analysis models, the correlations for urinary alpha1-microglobulin and neutrophil gelatinase-associated lipocalin remained significant with urine albumin: creatinine ratio, urinary advanced glycation end-products, estimated glomerular filtration rate (P<0.0001, R(2)=0.674; P<0.0001, R(2)=0.551; P<0.0001, R(2)=0.482)., Conclusions: In patients with Type 2 diabetes mellitus urinary glycated peptides are associated with proximal tubule dysfunction. The proteomic patterns of urinary glycated peptides could differentiate normo- from microalbuminuric patients and may explain a potential relation between the size and the glycation status of glycated peptides, and the extent of proximal tubule dysfunction. The lack of correlation between parameters of endothelial dysfunction and proximal tubule dysfunction cannot exclude glomerular involvement in early diabetic nephropathy.

Our aim was to assess kidney shear wave speed by means of acoustic radiation force impulse (ARFI) elastography in patients without kidney pathology ("normal" patients) and to identify the factors that influence it. We analyzed 91 "normal" patients in whom kidney shear wave speed was assessed by means of ARFI elastography. Five valid ARFI elastographic measurements were obtained in all "normal" patients in both kidneys. In univariate analysis, age (r = -0.370, p = 0.003), gender (female vs. male, r = -0.305, p = 0.003) and measurement depth (r = -0.285, p = 0.01) were significantly correlated with kidney shear wave speed values assessed by ARFI elastography, whereas body mass index, kidney length and renal parenchyma thickness were not correlated. In multivariate analysis, only age (p = 0.006) and gender (p = 0.03) were significantly correlated with kidney shear wave speed values. In conclusion, kidney shear wave speed values assessed by ARFI elastography in "normal" patients are influenced mainly by age and gender and less by measurement depth., (Copyright © 2015 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

Objectives: The pathophysiology of the single kidney is involved in the evolution toward endstage renal disease. Furthermore, most data suggest that the renal function of the donor is maintained after nephrectomy. This study sought to analyze the difference between surgically acquired single kidney and the congenital single kidney, regarding kidney function at a similar moment in time of the existence of a single kidney., Materials and Methods: Two groups were enrolled in this study. Group A consisted of 28 patients with surgically acquired single kidney, time from nephrectomy was 30.23 +/- 10.82 years; mean age, 54.42 +/- 14.99 years. Group B consisted of 20 patients with a congenital single kidney (mean age, 30.3 +/- 10.43 years). We assessed glomerular filtration rate (Modification of Diet in Renal Disease 4 Study Equation) and the presence of classic and nonclassic risk factors for chronic kidney disease., Results: The estimated glomerular filtration rate showed no statistically significant difference between the 2 groups., Conclusions: Our study did not show any influence of surgical nephrectomy on the evolution of kidney function. Kidney function in the surgically acquired single kidney was similar to the kidney function in the congenital single kidney at a comparable time interval. Our results have potential favorable implications for kidney transplant from living donors.

Introduction: The aim of the study was to evaluate cerebral microangiopathy in type 2 noninsulin- dependent diabetes mellitus (NIDDM) patients and to establish potentially conducive factors., Materials and Methods: A group of 34 patients with NIDDM and 31 gender- and agematched normal controls (NC) were assessed by extracranial Doppler ultrasound, in order to evaluate the pulsatility index (PI) and the resistance index (RI) in the internal carotid arteries (ICAs); transcranial Doppler was utilised to assess the same parameters in the middle cerebral arteries (MCAs). All patients underwent screening for favouring factors for cerebral vascular remodelling., Results: Of the 34 NIDDM patients, 21 patients (61.76%) (subgroup A) presented with microangiopathic complications [of these, 19 patients (90.46%) had diabetic nephropathy (DN)] versus 13 NIDDM patients (38.24%) (subgroup B) without complications. In subgroup A, 16 patients (76.19%) had PI >1 and RI >0.7 in the ICAs and MCAs (changes consistent with cerebral microangiopathy) versus 5 patients (35.46%) in subgroup B, and no modifications in NC. Of the 19 patients with DN, 14 patients (73.68 %) had impaired haemodynamic indices. Univariate regression analysis showed the following risk factors for the cerebral haemodynamics changes: fibrinogen (F) (OR = 3.11), C-reactive protein (CRP) (OR = 2.40), duration of DM (OR = 2.40), proteinuria (OR = 1.80), serum creatinine (OR = 1.66). Multivariate regression analysis showed as predictors for impaired haemodynamic indices: duration of DM (HR =1.70), proteinuria (HR = 1.70). The haemodynamic indices in the ICAs correlated with duration of DM (r = 0.87, P <0.0001), F (r = 0.86; P <0.0001), CRP (r = 0.80; P <0.0001); in the MCAs with the duration of DM (r = 0.66, P <0.0001), F (r = 0.38; P <0.0001), CRP (r = 0.88; P <0.0001)., Conclusion: Cerebral microangiopathy has a high prevalence in NIDDM patients. These cerebral vascular changes correlate with the duration of DM, parameters of inflammation, and proteinuria.