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BACKGROUND: Renal ischemia-reperfusion injury (IRI) induces inflammatory reaction damaging kidney. Pentoxifylline (PTX) given before IRI attenuates inflammation and prevents ischemic acute kidney injury (iAKI). Given that in clinical settings IRI is not always predictable, we aimed to assess whether PTX administration during or shortly after IRI affects the course of iAKI in the rat. METHODS: In 58 male 10-week-old Sprague-Dawley rats, 14 days after right nephrectomy, a 45-minute clamping of solitary renal pedicle was conducted. PTX 100 mg/kg body weight or 0.9% NaCl 1 mL were given subcutaneously either 60 minutes before renal ischemia, 1 minute into ischemia, or 60 minutes after clamp release. Creatinine clearance (ClCr; mL/min/kg body weight), fractional excretions of sodium (FENa [%]) and potassium (FEK [%]), and urine protein/ClCr ratio (Uprot/ClCr [mg/1 mL ClCr]) at 48 hours after IRI were compared between PTX-treated animals and respective controls (Mann-Whitney U test). RESULTS: Kidney function was improved in rats given PTX before IRI compared with controls: ClCr 2.10 ± 0.44 versus 1.03 ± 0.18; FENa 0.16 ± 0.12 versus 0.84 ± 0.55; FEK 40.3 ± 13.0 versus 75.5 ± 17.9, respectively (all P < .001). There was no difference in proteinuria: Uprot/ClCr 0.004 ± 0.002 versus 0.004 ± 0.002. Conversely, the analyzed parameters did not differ between animals administered PTX during IRI and controls: ClCr 0.42 ± 0.34 versus 0.73 ± 0.43; FENa 2.98 ± 2.71 versus 3.16 ± 3.05; FEK 280.1 ± 155.7 versus 206.2 ± 154.1; and Uprot/ClCr 0.031 ± 0.029 versus 0.029 ± 0.031, respectively, nor between rats given PTX after IRI and controls: ClCr 0.29 ± 0.38 versus 0.40 ± 0.47; FENa 4.25 ± 3.55 versus 3.80 ± 3.94; FEK 284.9 ± 117.5 versus 243.0 ± 150.6; and Uprot/ClCr 0.044 ± 0.018 versus 0.055 ± 0.061, respectively. CONCLUSIONS: PTX given only before, and not at the time of renal ischemia or after reperfusion, alleviates subsequent iAKI in the rat. This implicates usefulness of PTX in the clinical settings of expected renal ischemia, like kidney transplantation, and suggests potential benefits of PTX in peritransplant period foremost with donor pretreatment.

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INTRODUCTION: High blood pressure and arterial stiffness contribute independently to cardiovascular mortality in uremic patients. High blood pressure is an established risk factor for chronic allograft nephropathy, recently named interstitial fibrosis/tubular atrophy (IF/TA). We sought to assess whether heart afterload determinants: arterial stiffness and vascular resistance or impedance accelerate kidney graft failure upon long-term observation. METHODS: Using a noninvasive method of blood pressure waveform analysis, (HDI/PulseWave/CR-2000), we studied 160 consecutive kidney transplant recipients, who were at least 3 months after transplantation, for systolic (SBP), diastolic, and mean blood pressure; pulse rate; systemic vascular resistance and impedance as well as large and small artery compliance. The associations of the hemodynamic parameters with relative increases in serum creatinine for every year of graft survival (ΔCreat) were assessed using multiple linear regression analysis. Relationships between systemic hemodynamics and kidney graft loss due to IF/TA were evaluated by Cox regression analysis, including serum creatinine, time after transplantation, delayed graft function, human leukocyte antigen mismatch, panel-reactive antibodies, cold ischemia time, donor age glomerular filtration rate as well as prescribed cardiovascular and immunosuppressive drugs. RESULTS: Over 6.6±0.4 years of follow-up, excluding four noncompliant patients, 11 patients died and 32 lost their kidney grafts, including 25 due to IF/TA. ΔCreat (10.3%±22.0%/y) was independently and positively associated with the initial SBP (ß=0.26; P=.001) and serum creatinine values (ß=0.16; P=.04). The risk of graft loss due to IF/TA was greater among patients with an increased serum creatinine (relative risk [RR]=59.5 per nlog-unit increase; P<.001) or higher SBP (RR=51.1 per nlog-unit increase; P=.04). Besides SBP, no other hemodynamic parameter was associated with graft failure. CONCLUSIONS: The rate of kidney graft function deterioration and risk of transplant loss due to IF/TA are not independently influenced by systemic arterial compliance, resistance, or impedance. SBP appears to be the key circulatory parameter independently affecting the progression of IF/TA, and should be a therapeutic target.

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Chronic kidney disease coexists with metabolic syndrome and this relationship may be apparent before overt manifestations of cardiovascular disease. To investigate early stages of the natural history of associations between renal function and metabolic syndrome, we phenotyped 1572 young (mean age=18.4 years), apparently healthy men for metabolic risk factors and estimated their creatinine clearance based on the Cockcroft-Gault equation. High metabolic risk (clustering of at least three metabolic risk factors) was revealed in 8.7% (137) of the subjects and was associated with a 6.9-fold increase in the odds of glomerular hyperfiltration (95% confidence interval (CI): 3.9-11.5) when compared to reference (from none to two metabolic risk factors). Overweight, elevated blood pressure, and low high-density lipoprotein (HDL) cholesterol increased the multivariate-adjusted odds ratio of glomerular hyperfiltration to 6.6 (95% CI: 3.8-11.6), 1.8 (95% CI: 1.0-3.0), and 2.5 (95% CI: 1.5-4.3), respectively. Systolic and diastolic blood pressures clustered together with leptin in the factor analysis and this blood pressure-adiposity component correlated with estimated creatinine clearance (r=0.329, P<0.0001) and explained on its own 10.2% of the variance in the estimated renal function. Our data reveal the silent epidemics of metabolic risk among young, apparently healthy men. Furthermore, the results indicate that high metabolic risk is associated with glomerular hyperfiltration before overt manifestations of cardiovascular disease.

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AIMS: Only one-third of Type 1 diabetes patients develop diabetic nephropathy, and a genetic predisposition is postulated. To obtain more insight into processes that lead to diabetic nephropathy, messenger RNA expression profiles of peripheral blood mononuclear cells from patients with and without diabetic nephropathy were compared. METHODS: We studied seven male patients with Type 1 diabetes and proteinuria and 12 male patients with Type 1 diabetes and normoalbuminuria after at least 20 years of diabetes duration. The expression of genes was examined using the microarray method with Human Genome U133A Arrays (Affymetrix, Santa Clara, CA, USA). We analysed the expression of all candidate genes suggested to be involved in the pathogenesis of diabetic nephropathy in previously published articles. Altogether, expression of 198 genes was analysed. RESULTS: We found that thrombospondin 1 (THBS1) and cyclooxygenase 1(COX1) genes were over-expressed in patients with diabetic nephropathy, and matrix metalloproteinase 9 (MMP9) and cyclooxygenase 2 (COX2) genes had lower expression in diabetic nephropathy. For other genes, we did not observe different expression between patients with and without diabetic nephropathy,or the expression was too low for analysis. CONCLUSIONS: The different gene expression pattern in peripheral blood mononuclear cells in patients with diabetic nephropathy might indicate an important pathway in the pathogenesis of this complication.

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Accumulated clinical data suggest that non-diabetic nephropathy complicating type 1 diabetes mellitus is rare, accounting for 2-3% of unselected diabetic patients with proteinuria. In contrast, non-diabetic kidney disease is a common finding in patients with type 2 diabetes mellitus. Joint analysis of available data on prevalence of non-diabetic kidney disease among type 2 diabetic patients revealed that non-diabetic nephropathy was evident on kidney biopsy approximately in 22% of European and 26.7% of Asian patients with type 2 diabetes mellitus. Therefore, kidney biopsy may become a useful diagnostic option among proteinuric patients with type 2 diabetes mellitus. However, it is generally agreed that renal biopsy cannot be used as a routine diagnostic test in all type 2 diabetic patients with proteinuria. Diabetic subjects that may benefit form kidney biopsy should be rather identified on a case-by-case basis. Absence of diabetic retinopathy, particularly used in combination with acanthocyturia, may come useful in decisions about kidney biopsy in type 2 diabetic patients.

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BACKGROUND: Results of epidemiological studies have suggested that a hereditary predisposition to the development of chronic renal failure exists, and that such predisposition might be independent from underlying etiology of kidney disease. On the other hand, high blood pressure contributes substantially to a faster rate of progression of renal damage, regardless of underlying etiology of kidney disease. In this study we tested whether GNB3 C825T polymorphism, previously reported to be associated with hypertension, contributes to predisposition to end-stage renal disease (ESRD). METHODS: GNB3 polymorphism was genotyped in 247 family trios: offspring affected with ESRD and both parents, and transmission/disequilibrium test was used to establish the allele-phenotype association. Among the examined offspring, 47 patients had ESRD in the course of type 1 diabetes and diabetic nephropathy, 120 had primary glomerulonephritis and 80 had interstitial nephritis. We observed no significant differences between the GNB3 C and T allele transmission from heterozygous parents to affected offspring. RESULTS: In the overall group of examined patients, the C:T allele transmission (%) was 48:52, while in patients with diabetic nephropathy, chronic glomerulonephritis and chronic interstitial nephritis the transmission was (%) 50:50, 48:52 and 48:52, respectively. CONCLUSION: The results of our study suggest that GNB3 C825T polymorphism does not contribute substantially to the increased risk of the development of ESRD.

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The pathogenesis of hypertension in diabetes type 1 and type 2 is different. Diabetic nephropathy is regarded as the most essential factor contributing to the development of hypertension in patients with diabetes mellitus type 1. Obesity, insulin resistance and hyperinsulinaemia are responsible for hypertension in diabetes mellitus type 2. In both types of diabetes, hypertension is involved in fast progress of diabetic renal disease. Antihypertensive treatment in diabetic patients should include: non-pharmacological interventions, drug-therapy, regular blood pressure monitoring, educational efforts. ACE-inhibitors, calcium antagonists, diuretics, beta-blockers, angiotensin II receptor antagonists and alpha 1-blockers are used as antihypertensive agents in diabetic patients. Neutral endopeptidase inhibitors are the new, promising therapeutic option.

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BACKGROUND: Because of the heterogeneous aetiology of kidney diseases, interactions between multiple genetic and environmental factors are thought to be involved in the process of progression to end-stage renal disease (ESRD). Raised blood pressure remains a well-established, independent risk factor for a more rapid decline of renal function in various kidney diseases. The aim of the study was to investigate the role of the human SA gene Pst1 polymorphism in the development and/or progression of chronic renal failure (CRF). METHODS: This polymorphism was genotyped in a group of 247 family trios (offspring affected with end-stage renal disease, and both parents): 120 with primary chronic glomerulonephritis, 80 with interstitial nephritis, and 47 with diabetic nephropathy. Transmission/disequilibrium test (TDT) was used to evaluate allele transmission from heterozygous parents to affected offspring. RESULTS: SA gene Pst1 allele transmission did not differ from random proportion of 50:50, with no significant variation in the slope of reciprocal serum creatinine over time between patients with SA Pst1 A1A1, A1A2, and A2A2 genotypes. In addition, no impact of this marker on the rate of progression of CRF in the course of diabetes mellitus, interstitial nephritis, and chronic glomerular nephritis was shown. CONCLUSION: Results of the study suggest no major role of SA gene polymorphism in promoting renal damage. However, the limited numbers of patients having both parents alive included in the analysis might have resulted in insufficient power to detect a minor impact of this polymorphism, especially if such effect is confined to a certain aetiology of CRF.

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BACKGROUND: The XbaI polymorphism in the glucose transporter GLUT1 gene has been implicated in the development of diabetic nephropathy in Chinese type 2 diabetes patients. METHODS: To examine whether the XbaI polymorphism is involved in the development of diabetic nephropathy in Caucasian type 2 diabetes patients, a large case control study was performed. The study group of 444 patients with type 2 diabetes consisted of three subgroups: 162 patients with normoalbuminuria (only patients with duration of type 2 diabetes of at least 10 years after diagnosis); 150 with microalbuminuria; and 132 subjects with persistent proteinuria or chronic renal failure (CRF). The polymerase chain reaction (PCR)-based genotyping of the XbaI polymorphism was performed in each subject. RESULTS: The genotype distribution in the subgroups showed an increased frequency of the (+/+) genotype in patients with microalbuminuria (41%; OR 1.40, 95% CI, 0.89 to 2.24) and proteinuria/CRF (47%; OR 1.82, 95% CI, 1.13 to 2.93, P = 0.013) when compared with normoalbuminuria (33%). No difference in the genotype distribution was observed between type 2 diabetes patients and healthy controls. CONCLUSIONS: The results of this study in Caucasian patients with type 2 diabetes indicate that the XbaI(-) allele in the GLUT1 gene protects against the development of diabetic nephropathy. Our results are in contrast to the case control study in Chinese patients with type 2 diabetes in which the presence of the XbaI(-) allele appeared to have a strong association with the development of diabetic nephropathy.

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This paper estimates the excretory kidneys activity in women with pregnancy complicated by EPH-gestosis and in women with a physiological pregnancy by denoting albuminuria, beta-2-microglobulinuria and beta-2-microglobulin in blood serum. It was claimed that the excretion of albumins with urine increases considerably in women with a pregnancy complicated by EPH-gestosis before the delivery in comparison with women with a pregnancy of a physiological course. The increase of albumins excretion with urine in a labour in two groups of tested pregnant women was also noticed. However, the increase in excretion of albumins with urine during delivery was much bigger in the group of women with pregnancy complicated by EPH-gestosis in comparison to the group of women with a physiological course of pregnancy. The albumins size before delivery as well as during the next 48 hours after the delivery did not differ statistically in both groups of tested women. Beta-2-microglobulin concentration in blood serum was bigger in the group of pregnant women with EPH-gestosis than women with a physiological pregnancy during the whole period of research. Bigger excretion of beta-2-microglobulin with urine was noticed among women with pregnancy complicated by EPH-gestosis before delivery, during delivery and during the next 48 hours after the delivery in relation to the group of women with a physiological pregnancy.

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BACKGROUND: Several studies have suggested that the same genetic factors may be involved in the predisposition to both essential hypertension and diabetic nephropathy, but the molecular mechanism underlying this predisposition still remains unclear. In particular, the role of genes involved in blood-pressure regulation and angiotensin II action is still controversial. This study examines a possible association between angiotensinogen M235T and chymase gene CMA/B polymorphisms with the presence of nephropathy in type II diabetic Caucasians. METHODS: For the purposes of the study, 323 microalbuminuric and 127 overt proteinuric cases, together with 243 normoalbuminuric controls with long-duration diabetes were selected from a group of 941 type II diabetic patients with established renal status. RESULTS: No differences in the genotype distributions or allele frequencies of the examined polymorphisms between the study groups were observed. The study groups were also stratified by gender, diabetes duration, level of glycaemic control, body mass index, hypertension, and retinopathy status, but still no distortion in the distributions of genotypes of any of the examined polymorphisms in any of the strata was shown. CONCLUSIONS: Our study provided evidence against an association between angiotensinogen M235T or chymase gene CMA/B polymorphisms and the presence of incipient or overt nephropathy in Caucasian patients with type II diabetes.

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BACKGROUND: There is substantial evidence that hereditary factors contribute to the predisposition to diabetic nephropathy. On the other hand, it has been suggested that genetics of diabetic nephropathy and hypertension may overlap. Recently, a C to T substitution (C825T) in the gene encoding for the guanine-nucleotide-binding protein beta(3) subunit (GNB3) was identified, and this molecular variant was found to be associated with enhanced activation of G proteins and increased risk of the development of hypertension. The aim of the study was to test whether GNB3 C825T polymorphism contributes to the development of incipient or overt nephropathy or hypertension in type 2 diabetic patients. METHODS: GNB3 genotype was determined in 130 type 2 diabetic patients with overt proteinuria or chronic renal failure, 155 diabetic patients with microalbuminuria and 163 control subjects with normoalbuminuria and known type 2 diabetes duration of at least 10 years. RESULTS: No differences in GNB3 genotype distributions or allele frequencies between the study groups were found. Also, no differences between normotensive and hypertensive patients were demonstrated. CONCLUSION: The study provided evidence against the major impact of the GNB3 C825T polymorphism on the increased risk of the development of nephropathy or hypertension in type 2 diabetic patients.

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BACKGROUND: Chronic renal failure (CRF) is a complex phenotype that results from an underlying kidney disease and superimposing environmental and genetic factors. The aim of our study was to evaluate the role of polymorphisms in the genes encoding for components of the renin-angiotensin system (RAS) in the development and/or progression of CRF. METHODS: Two hundred forty-seven family trios (patients with CRF and both parents; 120 with primary chronic glomerulonephritis, 80 with interstitial nephritis, and 47 with type 1 diabetes with nephropathy) were examined, and transmission/disequilibrium test (TDT) was used to evaluate allele transmission from heterozygous parents to affected offspring. RESULTS: The D allele of the angiotensin I-converting enzyme (ACE) gene insertion/deletion polymorphism was transmitted significantly more frequently than expected for no association among all examined trios and in the subgroup of patients with interstitial nephritis. The angiotensinogen 235T allele was transmitted significantly more frequently to patients with CRF than expected for no association, but the effect was seen only in patients with interstitial nephritis. The presence of the DD or ID genotype was associated with a faster rate of decline of renal function, which was not observed for the angiotensinogen M235T polymorphism. For chymase gene and angiotensin II receptor type 1 gene, allele transmission did not deviate significantly from a random proportion of 50:50%. CONCLUSIONS: The results of this study suggest that ACE gene insertion/deletion and angiotensinogen M235T polymorphisms contribute to the increased risk for the development of CRF, but the magnitude of the effect within subsets of patients with specific etiologies of CRF must be evaluated further.

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Doctors' and medical students' attitude to the primary prevention of hypertension is important, as this community is responsible for medical education. The level of acceptance for some antihypertensive strategies was assessed in 180 doctors and 300 medical students (263 women and 217 men). The study consisted of reading and filling the anonymous questionnaires. The necessity of primary prevention of hypertension in absolutely essential in medical education.

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Chronic renal failure (CRF) is a complex phenotype, which results from the underlying kidney disease and superimposing environmental and genetic factors. The aim of the study was to evaluate the role of angiotensin converting enzyme gene Pst 1 polymorphism in the development and/or progression of CRF. 247 family trios (patients with CRF and both parents): 120 with primary chronic glomerulonephritis, 80 with interstitial nephritis and 47 with diabetic nephropathy were examined, and transmission/disequilibrium test (TDT) was used to evaluate allele transmission from heterozygous parents to affected off-spring. No significant deviation from random transmission of the examined ACE gene Pst 1 alleles was observed, as well as no impact of this marker on the rate of progression of chronic renal failure.

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The aim of the study was to determine serum concentration of complement component C4 and IgA, IgG, IgM immunoglobulins in hypertensive patients and healthy controls as well as to assess the interrelationships regarding some immunological and clinical data in the study group. The study group consisted of 81 hypertensive patients (with secondary forms of hypertension excluded), 44 females and 37 males (mean age 51.2 +/- 14.5 years). The control group comprised 34 healthy volunteers, 19 females and 15 males (mean age 47.5 +/- 15.3 years). C4, IgA, IgG, IgM serum concentrations were evaluated with turbidymetry. C4 serum concentration was significantly higher in hypertensive patients when compared to the controls. No significant differences in IgA, IgG, IgM serum concentrations existed between the groups. The duration of hypertension correlated positively with C4 serum concentration. Elevated C4 serum concentration may be one of the markers of immunological disturbances existing in hypertensive patients. IgA, IgG, IgM immunoglobulins do not seem to be directly associated with essential hypertension.

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The aim of the study was to assess the prevalence of headaches and analgesic use in hypertensive patients and to evaluate the relationship between taking analgesic drugs and adherence to antihypertensive therapy. 754 consecutive hypertensive patients (446 women and 308 men, aged 18-89 years, median age--58 years) from 7 out-patient centres participated in the study. Anonymous questionnaires consisted of 13 simple questions concerning demographic parameters (age, gender), clinical data (the duration of hypertension and antihypertensive therapy), the history of headache and use of analgesics were distributed among the participants. Among the hypertensives participating in the study, 82.9% (625) reported headaches. Analgesics were used by 65.3% (408) of hypertensive patients with headaches. There was significant, positive linear correlation between the history of headaches and the duration of analgesic use in hypertensive patients. The rate of non-compliance was significantly higher among patients with headaches who reported regular use of analgesics when compared to non-users of analgesics. There were statistically more non-compliants among patients taking more than 1 type of analgesics than in hypertensives reporting use of only 1 analgesic drug. The prevalence of headaches and the rate of analgesic use is considerably significant among hypertensive patients. Analgesic consumption seems to be a risk factor for non-adherence to antihypertensive medication.

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