Association between attributed cause of end-stage renal disease and risk of death in Brazilian patients receiving renal replacement therapy

BACKGROUND: Studies conducted in several countries have indicated that the survival of patients undergoing renal replacement therapy (RRT) depends on the attributed cause of end-stage renal disease (ESRD). OBJECTIVES: This study was conducted to evaluate the association between attributed cause of ESRD and mortality risk in RRT patients in Brazil. METHODS: We analyzed 88,881 patients from the Brazilian Ministry of Health Registry who were undergoing RRT between April 1997 and July 2000. Cox proportional hazards models were used to estimate the relative risk (RR) of death in patients with ESRD secondary to diabetes mellitus (DM), polycystic kidney disease (PKD), and primary glomerulopathies (GN) compared with a reference group comprised of patients with ESRD caused by hypertensive nephropathy. Patient's age, gender, and length of time (years) in RRT before inclusion in the registry (vintage) were included in the adjusted Cox model. RESULTS: Compared with the reference group, the mortality risk was 27% lower in patients with PKD (RR=0.73, 95% CI: 0.65-0.83, p<0.0001); 29% lower in patients with GN (RR=0.71, 95% CI: 0.68-0.74, p<0.0001); and 100% greater in DM patients (RR=2.00, 95% CI: 1.92-2.10, p<0.0001). These relative risks remained statistically significant after adjustment for age, gender, and length of time in RRT before inclusion in the registry. CONCLUSIONS: Our data indicate that compared with the patients with hypertensive nephrosclerosis as attributed cause of ESRD, patients undergoing RRT in Brazil with idiopathic glomerulopathy and polycystic kidney disease have a lower risk of mortality, and patients with diabetes mellitus have a greater risk of mortality.     

Egypt Information, Prevention, and Treatment of Chronic Kidney Disease (EGIPT-CKD) programme: prevalence and risk factors for microalbuminuria among the relatives of patients with CKD in Egypt

Chronic kidney disease (CKD) is increasingly recognized as a public health problem, and is linked to the risk of development of cardiovascular disease (CVD) and end-stage renal disease (ESRD) with their attendant morbidity, mortality and increased healthcare costs. There is still paucity of data on the prevalence and risk factors for microalbuminuria (MA) and CKD in the Middle East. We report a cross-sectional study of the prevalence and risk factors for MA in the relatives of patients with CKD from a community-based screening programme in Egypt. The study was conducted among participants of the Egypt Information, Prevention, and Treatment of Chronic Kidney Diseases (EGIPT-CKD) Program, a population-based screening program for MA and CKD in Damanhour, Egypt. The screening tools included a questionnaire collating information on demographics, lifestyle, medical and family history of diabetes mellitus, hypertension and CKD. The prevalence of MA was 10.6% in the population screened. The prevalence was 6.2% in the non-diabetic and non-hypertensive subjects. The prevalence of albuminuria increases with age (P = 0.001 for trend). The prevalence was higher in the subjects with diabetes, hypertension, obesity or CVD. There was also a higher burden of MA subjects with low educational attainment (16% vs 5.6%; P = 0.001) and also those with a positive history of smoking (15.7% vs 8.1%; P = 0.01). The independent predictor variables associated with the presence of MA in a mutually adjusted logistic regression model were age (OR = 1.055, 95% CI: 1.01-1.10), mean arterial blood pressure (OR = 1.04, 95% CI: 1.102-1.07) and personal history of CVD (OR = 2.34, 95% CI: 2.31-18.1). In this study, we determined the prevalence and risk factors for those having MA among the first-degree relatives of ESRD patients of the EGIPT-CKD program in Damanhour, Lower Egypt.     

Association Between Attributed Cause of End-Stage Renal Disease and Risk of Death in Brazilian Patients Receiving Renal Replacement Therapy

Background. Studies conducted in several countries have indicated that the survival of patients undergoing renal replacement therapy (RRT) depends on the attributed cause of end-stage renal disease (ESRD). Objectives. This study was conducted to evaluate the association between attributed cause of ESRD and mortality risk in RRT patients in Brazil. Methods. We analyzed 88,881 patients from the Brazilian Ministry of Health Registry who were undergoing RRT between April 1997 and July 2000. Cox proportional hazards models were used to estimate the relative risk (RR) of death in patients with ESRD secondary to diabetes mellitus (DM), polycystic kidney disease (PKD), and primary glomerulopathies (GN) compared with a reference group comprised of patients with ESRD caused by hypertensive nephropathy. Patient's age, gender, and length of time (years) in RRT before inclusion in the registry (vintage) were included in the adjusted Cox model. Results. Compared with the reference group, the mortality risk was 27% lower in patients with PKD (RR = 0.73, 95% CI: 0.65–0.83, p< 0.0001); 29% lower in patients with GN (RR = 0.71, 95% CI: 0.68–0.74, p< 0.0001); and 100% greater in DM patients (RR = 2.00, 95% CI: 1.92–2.10, p< 0.0001). These relative risks remained statistically significant after adjustment for age, gender, and length of time in RRT before inclusion in the registry. Conclusions. Our data indicate that compared with the patients with hypertensive nephrosclerosis as attributed cause of ESRD, patients undergoing RRT in Brazil with idiopathic glomerulopathy and polycystic kidney disease have a lower risk of mortality, and patients with diabetes mellitus have a greater risk of mortality.     

Prevalence and characteristics of a family history of end-stage renal disease among adults in the United States population: Reasons for Geographic and Racial Differences in Stroke (REGARDS) renal cohort study

This report describes the prevalence and characteristics of people with a family history of ESRD in a first-degree relative (FH-ESRD). This is a cross-sectional study of individuals in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort, a population-based sample of US residents who are 45 yr and older. FH-ESRD was ascertained at baseline among 12,030 participants of the cohort, and multivariate logistic regression was used to identify characteristics that were independently associated with FH-ESRD. FH-ESRD was reported by 9.5% of participants. Individual characteristics that were independently associated with FH-ESRD included black race (odds ratio [OR] 2.14; 95% confidence interval [CI] 1.82 to 2.53); female gender (OR 1.28; 95% CI 1.08 to 1.51); a history of diabetes (OR 1.22; 95% CI 1.02 to 1.47); a 1-SD change in the log of the C-reactive protein level (OR 1.10; 95% CI 1.01 to 1.19); and World Health Organization body mass index weight categories normal (OR 2.11; 95% CI 0.66 to 6.79), overweight (OR 2.64; 95% CI 0.82 to 8.42), and obese (OR 3.48; 95% CI 1.09 to 11.1) compared with underweight. Black but not white individuals with FH-ESRD were more likely to have an estimated GFR <60 ml/min per 1.73 m(2). There is a high prevalence of FH-ESRD among US adults, and the prevalence of FH-ESRD was higher among lack individuals. Individuals with a positive family history were more likely to have diabetes and to be obese. If confirmed, then these findings suggest that individuals with FH-ESRD may benefit from interventions to improve the detection and treatment of chronic kidney disease risk factors such as diabetes and obesity.     

Kidney stone disease and risk factors for coronary heart disease

BACKGROUND: We conducted a case-control study to examine the impact of coronal heart disease (CHD) risk factors on calcium oxalate (CaOX) stone formation. METHODS: Variables included body mass index (BMI), current alcohol use, smoking habit, hypertension, hypercholesterolemia, diabetes mellitus, and hyperuricemia. Data suf fi cient for analysis were obtained for 181 CaOX stone formers and 187 controls. RESULTS: Seven of 181 stone formers (3.9%) had a history of CHD compared with none of 187 control subjects (P = 0.007). In univariate logistic regression analysis, smoking habit (OR 4.41, 95% CI 2.85-6.84, P < 0.0001), hypertension (OR 4.24, 95% CI 2.61-6.91, P < 0.0001), hypercholesterolemia (OR 3.03, 95% CI 1.77-5.20, P < 0.0001) and BMI (OR 1.10, 95% CI 1.04-1.17, P = 0.007) reached statistical signi fi cance. In a multivariate logistic regression analysis, smoking habit (OR 4.29, 95% CI 2.68-6.86, P < 0.0001), hypertension (OR 3.57, 95% CI 2.11-6.07, P < 0.0001), and hypercholesterolemia (OR 2.74, 95% CI 1.51-5.00, P = 0.001) reached statistical signi fi cance, while BMI (OR 1.06, 95% CI 0.99-1.12, P = 0.09) did not. CONCLUSIONS: CaOX stone formers are signi fi cantly associated with several CHD risk factors, including smoking habit, hypertension, hypercholesterolemia, and obesity.     

Evaluation of aortic arch calcification in hemodialysis patients

BACKGROUND: In the general population, aortic arch calcification (AAC) is related to cardiovascular (CV) disease. Vascular calcifications are common findings in dialysis patients; therefore, we carried out a retrospective study evaluating which risk factors are associated to AAC in stable hemodialysis (HD) patients. METHODS: Standard posterior-anterior chest radiographs, performed the day after the midweek HD session in 132 patients (mean age 65 +/- 12 yrs) who had been on renal replacement therapy (RRT) for 33 months (range 1-471), were analyzed. Cardiothoracic ratio (CTR) was also calculated. RESULTS: AAC was detected in 51% of patients. They were older (68 +/- 8 vs. 62 +/- 14 yrs; p = 0.003), were on RRT for longer (51 (range 2-471) vs. 22 (range 1-195) months; p = 0.0001), had greater CTR (54 (32-71) vs. 50% (40-65); p = 0.034) and higher prevalence of peripheral vascular disease (PVD) (40 vs. 17%; p = 0.049), whilst body weight was lower (62 +/- 14 vs. 68 +/- 14 kg; p = 0.04) than those without AAC. On the contrary, sex, diabetes frequency, smoking habit, history of hypertension and hyperphosphatemia, cerebrovascular and ischemic heart disease (IHD), blood pressure (BP) and antihypertensive therapy, lipids, albumin, degree of anemia, calcium, phosphate and their product were no different between the two groups. Logistic regression analysis showed that age (odds ratio (OR) 1.069 95% confidence interval (95% CI) 1.02-1.11; p = 0.003), length of time on RRT (OR 1.02 95% CI 1.01-1.03; p = 0.0002), calcium-phosphate product (OR 1.03 95% CI 1.007-1.07; p = 0.016), systolic BP (OR 1.03 95% CI 1.005-1.06; p = 0.02) and PVD (OR 3.08 95% CI 1.17-8.06; p = 0.02) were independently associated to AAC. CONCLUSIONS: We conclude that AAC is related to atherosclerosis and to renal failure-related CV risk factors. A careful evaluation of a frequently performed investigation is useful in CV disease risk stratification in HD patients.     

Higher risk for renal failure in first-degree relatives of white patients with end-stage renal disease: a population-based study

To explore the possibility that hereditary factors increase the risk for end-stage renal disease (ESRD), 669 patients with ESRD in the province of Newfoundland, Canada from 1987 to 1993 were studied. Detailed family histories were obtained from 584 (87%) consecutive probands and 499 spousal control subjects. Diseases with a Mendelian pattern of inheritance accounted for 8.4% of the cases; 4.5% of the cases were caused by autosomal dominant polycystic kidney disease (ADPKD). Glomerulonephritis was the original cause of renal failure in 25% of the probands, diabetes mellitus (DM) in 20%, unknown in 14%, interstitial kidney disease in 11%, other disease in 12%, multifactorial in 4%, and hypertension in 5%. In the group without a Mendelian pattern of inheritance, 28% of the probands had a first-, second-, or third-degree relative with renal failure associated with death or dialysis versus 15% of the controls. Compared with 0.4% of the control group, 1.2% of the first-degree relatives of probands developed renal failure (odds ratio [OR]=3.0; 95% confidence interval [CI], 1.7 to 5.2). No difference was observed when risks were compared for second-degree relatives, but a highly significant increased risk was observed for third-degree relatives (OR=2.1; 95% CI, 1.2 to 3.4). The highest rates of affected first-degree relatives occurred in probands with hypertensive renal failure (2.3%), DM (1.6%), and interstitial kidney disease (1.6%). The annual provincial incidence of ESRD, registered with the Canadian Organ Replacement Registry (CORR) from 1981 to 1993 was 79 per million, excluding the 8% of patients with Mendelian inherited disease. The similar rate of ESRD in first-degree relatives of probands without Mendelian inherited disease was 297 per million. We conclude that not only is the contribution of Mendelian inherited diseases to ESRD high, but there is also an increased risk for renal failure in first-degree relatives of probands without a Mendelian inherited renal disease in a white population.     

Predictive value of cytokine gene polymorphisms for the development of end-stage renal disease

BACKGROUND: Cytokines play a crucial role in different immunopathological conditions. Cytokine secretion is reported to be determined by polymorphisms in the cytokine genes. Since TNF-alfa and IL-10 are involved in regulation of inflammation, and TGF-beta 1 can induce fibrosis and renal insufficiency - dominant features of end-stage renal disease (ESRD), we explored the hypothesis that polymorphisms of these cytokine genes may be possible genetic susceptibility factors for the progression of renal failure. METHODS: We studied the IL-10 (-1082), TNF-alfa (-308), TGF-beta 1 (codon 10;25) gene single nucleotide polymorphisms in 118 healthy donors and 103 patients with ESRD (44 hemodialysis patients with diabetic nephropathy and 59 hemodialysis patients with glomerulonephritis) using PCR-SSP. RESULTS: Significant associations of ESRD with the TGF-beta 1 (codon 10) TT (odds ratio [OR] = 5.31; 95% confidence interval [95% CI], 3.77-7.02; p<0.001) and IL-10 (-1082) GG (OR=2.35; 95% CI, 1.67-3.15; p<0.01) genotypes were found. Statistical analysis of genotype frequencies made separately for the underlying renal disease (diabetes or glomerulo-nephritis) revealed the same linkage trend: TGF-beta 1 (codon 10) TT and IL-10 (-1082) GG were associated with type 2 diabetic nephropathy (p<0.001 and p<0.05, respectively) and chronic glomerulonephritis (p<0.001 and p<0.01, respectively). No significant differences in the TNF-alfa , TGF-beta 1 (codon 25) genotype distribution between healthy controls and patients with diabetic nephropathy- or glomerulonephritis-associated ESRD were detected. CONCLUSIONS: Carriage of the TGF-beta 1 (codon 10) TT and IL-10 (-1082) GG genotypes may increase susceptibility to ESRD in German patients with type 2 diabetes or glomerulonephritis.     

Predictors of cardiovascular events in patients with type 2 diabetic nephropathy and hypertension: a case for albuminuria

Individuals with type 2 diabetes and nephropathy represent a particularly high-risk group for both adverse cardiac as well as renal events. Using the Irbesartan in Diabetic Nephropathy Trial (IDNT) cohort, our objective was to determine baseline characteristics of individuals with type 2 diabetic nephropathy and hypertension predictive for cardiac events. IDNT identified 1715 individuals with type 2 diabetic nephropathy and hypertension having serum creatinine of 1.0 to 3.0 mg/dL and urinary albumin excretion rates > or = 900 mg/day. A cardiovascular (CV) composite was used consisting of CV death, nonfatal MI, hospitalization for heart failure, stroke, amputation, and coronary and peripheral revascularization. Using multivariable Cox regression analysis, 41 baseline characteristics determined a priori were analyzed for their potential relationship to risk of experiencing a CV event. Of the 1715 individuals, 518 (30.2%) had at least one of the CV composite end points. Older age, male gender, longer duration of diabetes, history of cardiovascular disease, history of CHF, high urinary albumin:creatinine ratio, and low serum albumin were strong predictors for CV events; of these, prior history of CVD (RR 2.00, 95% CI 1.63-2.45; P < 0.0001) and high urinary albumin:creatinine ratio (RR 1.29 per natural log unit, 95% CI 1.13-1.48; P = 0.0002) at baseline were highly predictive for cardiovascular events. In conclusion, among individuals with hypertension and diabetic nephropathy, both the degree of albuminuria and lower serum albumin levels provide additional prognostic information concerning cardiovascular risk, in addition to traditional coronary risk factors.     

Association of Human Leukocyte Antigen Haplotypes With End-Stage Renal Disease in Vietnamese Patients Prior to First Transplantation

IntroductionThe prevalence of chronic kidney failure is significantly increasing in Vietnam, causing a burden for health care. This study assessed the relationship of HLA-A, -B, and –DRB1 alleles with end-stage renal disease (ESRD).MethodA retrospective, cross-sectional study and a comparative study using secondary data analysis were conducted on 196 ESRD patients and 187 controls from 2009 to 2017. The patient and donor profiles were collected from medical records, including age, sex, etiology of renal failure, and HLA phenotypes. HLA-A*, -B*, and -DRB1* typing were done by polymerase chain reaction-sequence specific primers.ResultThe most frequent HLA alleles in Vietnamese patients with ESRD were HLA-A*02, -A*11, -B*15, -B*46, -DRB1*04, -DRB1*09, and -DRB1*12. The haplotypes HLA-A*0233 (odds ratio [OR] = 0.40, 95% CI: 0.15–0.98) had a negative association for ESRD. The haplotypes HLA-B*1515 (OR = 4.14, 95% CI: 1.52–11.26) and HLA-DRB1*1212 (OR = 2.01, 95% CI: 1.06–3.81) had a positive association for ESRD. The haplotypes HLA-B*1515 (OR = 4.69, 95% CI: 1.69–13.03) and -DRB1*1212 (OR = 2.15, 95% CI: 1.10–4.21) had a positive association for ESRD related to glomerulonephritis. The HLA-B*1557 (OR = 17.34, 95% CI: 2.70–11.49) had a positive association for ESRD related to hypertension.ConclusionThe haplotypes of HLA class I and II had significant relationships with ESRD. The results of our study should be confirmed in further investigations.     

Prognostic indicators of IgA nephropathy in the Chinese--clinical and pathological perspectives.

BACKGROUND: IgA nephropathy is the most common primary glomerulonephritis in the world. Up to 30% of patients can progress to end-stage renal disease (ESRD) in 10 years. METHODS: We studied 168 Chinese patients with IgA nephropathy followed for an average of 7.4 years in our hospital and tried to identify the clinical and pathological data that were associated with the prognosis of the disease. Clinical features at the time of renal biopsy were reviewed. Severity of histological involvement was scored semi-quantitatively as grade 1-3. RESULTS: There was a female preponderance in our cohort of patients (male:female ratio 1:1.5). The average age at biopsy was 32.9+/-10.0 years. Forty-seven of the 168 patients (28.0%) were hypertensive and 47 of 136 patients (34.6%) had a family history of hypertension. A high histological grade of IgA nephropathy was associated with hypertension at presentation, family history of hypertension, a higher serum creatinine, total cholesterol and 24-h urine protein excretion, and a lower serum albumin level. During the follow-up period, four patients died and another 24 progressed to ESRD. The renal survival was 92.0% at 1 year, 87.5% at 5 years and 81.8% at 10 years. With univariate analysis, hypertension at presentation, family history of hypertension, renal impairment at presentation (plasma creatinine >120 micromol/l), high cholesterol, proteinuria >1 g/day and high histological grading were associated with poor prognosis. With multivariate analysis, hypertension at presentation, family history of hypertension, renal impairment at presentation, proteinuria >1 g/day and histological grading were independent predictors of renal survival. The relative risks of renal failure for patients were 9.60 (95% confidence interval 4.02-22.92) with hypertension, 1.56 (1.16-2.02) with a family history of hypertension, 15.38 (6.40-36.93) with renal impairment and 5.93 (3.07-11.46) with every increase of one histological grade. Male patients did not show a more adverse outcome compared with females. CONCLUSIONS: Our results suggest that renal biopsy remains useful, even in clinically trivial disease, because of its distinct value in prognosis and risk stratification. The long-term prognosis of IgA nephropathy in Chinese patients is guarded. The prognostic importance of family history of hypertension has not been widely recognized and requires further study.     

Clinicopathological findings in patients with gastric adenocarcinoma with familial aggregation.

BACKGROUND/AIMS: The clinicopathological characteristics of gastric cancer (GC) with a positive family history of site-specific GC have not been well discussed. The aim of this study was to estimate the risk of familial aggregation of GC in a hospital-based case-control study and to analyze the clinicopathological characteristics of GC with familial aggregation of GC. METHODS: Our series was comprised of 926 histologically confirmed patients with GC (588 males and 338 females) and 2,052 non-cancer outpatients between 1985 and 1996. The odds ratios (ORs), as estimators of relative risks, together with the corresponding 95% confidence intervals (CIs) for a family history of GC and for a family history of other cancers were calculated. Moreover, the clinicopathological findings of patients with GC who had a GC family history were compared with those of patients with GC who had no GC family history. RESULTS: A positive family history of GC was associated with a statistically significant increase in the risk of GC (OR = 2.15; 95% CI = 1.77-2.63), while no association was observed between the risk of GC and a family history of other cancers (OR = 1.11; 95% CI = 0.91-1.36). The incidence of a multifocal occurrence of GCs was higher in patients with a family history of GC (19.4%) than in patients without a family history of GC (12%, p = 0.005). The risk (OR) of occurrence of multiple cancers in the stomach in patients who had a family history of GC was 1.77 (95% CI = 1.19-2.64). CONCLUSIONS: Our results suggest that a family history of GC seemed to be a risk factor for the development of GC. Further, a family history of GC was found to be associated with a multifocal occurrence of GC.     

Anemia and end-stage renal disease in patients with type 2 diabetes and nephropathy

BACKGROUND: Diabetic nephropathy is the leading cause of end-stage renal disease (ESRD). Anemia is common in diabetics with nephropathy; however, the impact of anemia on progression to ESRD has not been carefully examined. METHODS: We studied the relationship between baseline hemoglobin concentration (Hb) and progression of diabetic nephropathy to ESRD in 1513 participants enrolled in Reduction in Endpoints in NIDDM with the Angiotensin II Antagonist Losartan study and followed for an average of 3.4 years. Multivariate Cox proportional hazards models were used to analyze the relationship between Hb and ESRD, after adjusting for predictors for ESRD. Analyses were performed with Hb stratified by quartile: first quartile <11.3 g/dL, second quartile 11.3 to 12.5 g/dL, third quartile 12.6 to 13.8 g/dL, and fourth quartile >/=13.8 g/dL (reference) and as a continuous variable. RESULTS: Baseline hemoglobin concentration was correlated with subsequent development of ESRD. After adjustment for predictors of ESRD, the hazard ratios for the first, second, and third Hb quartiles were 1.99 (95% CI, 1.34-2.95), 1.61 (95% CI 1.08-2.41), and 1.87 (95% CI 1.25-2.80). With hemoglobin as a continuous variable, the adjusted hazard ratio was 0.90 (95% CI 0.84-0.96, P= 0.0013). The average increase in adjusted relative risk was 11% for each 1 g/dL decrease in hemoglobin concentration. CONCLUSION: Our data suggest that even mild anemia, Hb <13.8 g/dL increases risk for progression to ESRD. Hemoglobin is an independent risk factor for progression of nephropathy to ESRD in type 2 diabetes.     

Frequency and determinants of erectile dysfunction in Italy

OBJECTIVE: To analyze the prevalence and risk factors for erectile dysfunction (ED) in Italy in a cross-sectional study. METHODS: Eligible for the study were men aged 18 years or more, randomly identified by 143 general practitioners among their registered patients during the period January 1996 to February 1997. ED was defined as the impossibility to achieve and maintain an erection sufficient for satisfactory sexual performance. RESULTS: Of the 2, 010 men interviewed, 257 (12.8%) reported ED. The prevalence increased with age, from 2% in men aged 18-39 to 48% in those >70 years (tested for trend, p = 0.0001). A history of cardiopathy, diabetes, hypertension, neuropathy, thrombotic/hemorrhagic stroke, peripheral vascular disorders, pelvic/medullary injury and pelvic surgery/radiation all increased the risk of ED. The association of hypertension and diabetes tends to increase the risk of ED. In comparison with nondiabetic and nonhypertensive men, the odds ratio (OR) was 1.4 (95% confidence interval (CI), 0.7-3.2) for hypertensive men without diabetes, 4.6 (95% CI, 1.6-13.7) for diabetic men without hypertension and 8.1 (95% CI, 1.2-55.0) for men with diabetes and hypertension. In comparison with never smokers, the OR of ED was 1.7 (95% CI, 1.2-2.4) for current smokers and 1.6 (95% CI, 1.1-2.3) for ex-smokers and increased with duration of the habit. CONCLUSIONS: The study offers a quantitative estimate of the prevalence of ED and of its main risk factors in Italian men.     

Modifier genes play a significant role in the phenotypic expression of PKD1

BACKGROUND: Polycystic kidney disease type 1 (PKD1) is characterized by extreme variation in the severity and progression of renal and extrarenal phenotypes. There are significant familial phenotype differences; but it is not clear if this is due to differences in PKD1 mutations, differences in genetic background, or both. METHODS: A total of 315 affected relatives (83 PKD1 families) without end-stage renal disease (ESRD) were evaluated for disease markers, including renal volume, creatinine clearance, proteinuria, liver cysts, and hypertension. Of these patients, 19% progressed to ESRD within 1 to 10 years after the initial examination. Nested analysis of variance was used to investigate interfamilial and intrafamilial differences in these phenotypes. Heritability analyses were used to estimate the effect of the genetic background on phenotypic variability. The age of onset of ESRD was also analyzed with an additional 389 family members from the same PKD1 families without clinical evaluation but with data on age of onset of ESRD (or age without ESRD). RESULTS: There were significant phenotype differences between patients with the same mutation and different genetic backgrounds. The phenotypic variation between patients with different mutations and different genetic backgrounds was not significantly greater than the variation between patients with the same mutation and different genetic backgrounds. However, when the 389 family members were included, both the mutation and modifier genes had significant effects on the age of onset of ESRD. Inherited differences in genetic background were estimated to account for 18% to 59% of the phenotypic variability in PKD1 disease markers in patients prior to ESRD and in the subsequent progression to ESRD (43% heritability) in the 315 patients who were clinically evaluated. CONCLUSION: Modifier loci in the genetic background are important factors in inter- and intrafamilial variability in the phenotypic expression of PKD1. The extreme intrafamilial phenotype differences are consistent with the hypothesis that one or a few modifier genes have a major effect on the progression and severity of PKD1.     

Relationship between GSTs gene polymorphism and susceptibility to end stage renal disease among North Indians

BACKGROUND AND OBJECTIVE: Glutathione-S-transferase (GST) is the superfamily of genes that provides protection to the cells against reactive oxygen species and plays a vital role in phase II of biotransformation of many substances. Overexpression of GST (EC 2.5.1.18) has been documented in the erythrocytes of patients with chronic renal failure, which may be of clinical relevance. Keeping this background in mind, we have investigated the relationship between human GST gene polymorphism in end stage renal disease (ESRD) patients. DESIGN AND METHODS: We have assessed 184 patients with ESRD and 569 age-and sex-matched controls from North India. The GSTT1 and GSTM1 null genotypes were identified by polymerase chain reaction (PCR). GSTP1-313 A/G mutation was determined by PCR followed by restriction enzyme digestion. RESULTS: The gene frequency of GSTM1, GSTT1, and GSTP1 polymorphism were evaluated. We observed that GSTM1 null genotype was present in 46.74% of the ESRD patients while GSTT1 null genotype was present in 58.7% of the ESRD subjects. The genotypic distribution of GSTP1 was Ile(105)/Ile(105) in 47.3%, Ile(105)/Val(105) in 30.97% and Val(105)/Val(105) in 21.74% of ESRD patients. There was a significant association of null alleles of the GSTM1 (p = 0.0386; OR = 1.445, 95% CI = 1.033-2.021) and GSTT1 (p < or = 0.0001; OR = 4.568, 95% CI = 3.215-6.492) and in the -313 G alleles (Val) of the GSTP1 gene (p = 0.0032; OR = 1.956, 95% CI = 1.265-3.024) with end stage renal disease. The combined analysis of the three genotypes showed a further increased risk to ESRD (p < or = 0.0001; OR = 9.01, 95% CI = 5.55-14.626). Interpretations and CONCLUSIONS: The null / low polymorphism of the detoxifying enzymes GSTT1, GSTM1, and GSTP1 are associated with the risk of developing ESRD in North Indian patients.     

Association of endothelial nitric oxide synthase gene intron 4 polymorphism with end-stage renal disease

BACKGROUND: Nitric oxide (NO) released from endothelial cells is related to the maintenance of physiological vascular tone. The impairment of endothelial NO generation brought about by gene polymorphism is considered one of the deterioration factors in progressive renal disease. In the endothelial nitric oxide synthase (eNOS) intron 4 polymorphism, the presence of the aa genotype has been associated with cardiovascular and renal disease. The aim of this study was to investigate the presence of eNOS gene intron 4 polymorphism in patients with end-stage renal disease (ESRD). METHODS: A total of 114 patients and 94 controls were studied. DNA specimens were extracted from blood and amplified by polymerase chain reaction. The alleles were separated by agarose gel electrophoresis. Genotype distribution and allele frequencies were compared between groups using the chi-squared test. RESULTS: Statistical analysis revealed that the frequency of the eNOS4 genotype aa was significantly different in ESRD patients and in controls (P=0.016, OR=2.07, CI 95%: 1.14-3.74). There was also a statistically significant difference between ESRD patients and controls regarding allele carriers (P=0.004; OR=2.26; CI 95%: 1.29-3.96). When the frequencies of allele carriers in the diabetic nephropathy group and in the control group were compared, a significant difference was found (P=0.034, OR=2.28; CI 95%: 1.04-5.00). CONCLUSION: This study showed a strong correlation between eNOS4a polymorphism and end-stage renal disease.     

Prevalence and risk factors for early postoperative infection after liver transplantation

OBJECTIVES: To analyze factors related to the development of infection soon after a liver transplant. PATIENTS AND METHOD: Retrospective study of 1000 liver transplants in adults between 1991 and 2004. Pre-, intra- and postoperative variables of recipients were analyzed in 2 groups according to whether infection did or did not develop. RESULTS: Infection developed in 151 patients. Bacterial infections were the most common type. Significant risk factors for infection in the multivariate analysis were sex (odds ratio [OR], 0.54; 95% confidence interval [CI], 0.33-0.90); Child-Pugh stage (OR, 1.89; 95% CI, 1.29-2,77); hepatitis C virus cirrhosis (OR, 0.58; 95% CI, 0.34-0.99); post-reperfusion syndrome (OR, 1.82; 95% CI, 1.03-3.21); vena cava preservation technique (OR, 0.43; 95% CI, 0.22-0.84); history of diabetes mellitus (OR, 2.38; 95% CI, 1.34-4.22); respiratory distress syndrome (OR, 6.60; 95% CI, 1.16-37.45); pulmonary edema (OR, 2.36; 95% CI, 1.44-3.86); renal dysfunction (OR, 3.25; 95% CI, 1.89-5.60); acute renal insufficiency (OR, 20.24; 95% CI, 9.88-41.46); neurological alterations (OR, 3.36; 95% CI, 1.94-5.821); postoperative bleeding (OR, 2.80; 95% CI, 1.32-5.97); graft dysfunction (OR, 2.07; 95% CI, 1.21-3.53); primary graft failure (OR, 0.07; 95% CI, 0.01-0.33). CONCLUSION: Infection is a serious complication that continues to be difficult to control. Certain risk factors can be improved with careful management (kidney failure, pulmonary edema) or appropriate donor-recipient matching (initial dysfunction). Others, however, are inherent to the procedure (post-reperfusion syndrome, sex) or to immunosuppression, which acts as a true mediator of infection with regard to both its appearance and its clinical manifestation.     

Association of endothelial nitric oxide synthase Glu298Asp polymorphism with end-stage renal disease

BACKGROUND: Impairment of nitric oxide generation caused by gene polymorphism is considered as a major factor in the deterioration of progressive renal disease, including diabetic nephropathy and hypertension. The aim of the present study was to examine the Glu298Asp polymorphism of endothelial nitric oxide synthase (eNOS) in patients with end-stage renal disease (ESRD). METHODS: The Glu298Asp polymorphism in exon 7 was determined in 100 ESRD patients who were maintained on hemodialysis at Dr. Soetomo Hospital, Surabaya, Indonesia, and in a control group of 100 unrelated healthy individuals. In the patient group, 39 patients had Type 2 diabetes mellitus (DM), 44 hypertension (HT) and 17 miscellaneous conditions. The mean length of time from onset of ESRD to the start of this study was 24.37 +/- 32.37 months (Mean +/- SD). RESULTS: The positivity of Glu298Asp in the ESRD group was significantly higher than that in the control group (p < 0.0001). The odds ratio for this group was 4.57 (95% confidence interval 2.52 - 8.31). The positivity of 298Asp in Type 2 DM ESRD with subgroup was significantly higher than that in healthy controls (p < 0.0001). The positivity of 298Asp in the subgroup of patients with HT-derived ESRD was also significantly higher (males p < 0.036, females p < 0.005) than that in healthy control group. Homozygotes with glutamate to aspartate substitution at nucleotide position 7702 showed a single band at 457 bp. CONCLUSION: It appears that Glu298Asp may be a predisposing factor in DM-derived and HT-derived ESRD.     

Meta-analysis of the relationship between ACE I/D gene polymorphism and end-stage renal disease in patients with diabetic nephropathy

Aims: Diabetic nephropathy (DN) is the major cause for end‐stage renal disease (ESRD) and the pathogenesis for DN developing into ESRD is not clear at present. Results from published studies on the relationship between angiotensin‐converting enzyme (ACE) insertion/deletion (I/D) gene polymorphism and ESRD risk in DN patients are still conflicting. This meta‐analysis was performed to evaluate the association between ACE I/D gene polymorphism and ESRD risk in DN patients. Methods: Association studies were identified from the databases of PubMed, Embase and Cochrane Library on 1 October 2011, and eligible investigations were identified and synthesized using the meta‐analysis method. Results were expressed using odds ratios (OR) for dichotomous data and 95% confidence intervals (CI) were also calculated. Results: Twelve studies reporting the relation between ACE I/D gene polymorphism and ESRD risk in DN patients were identified. In overall populations, there was a notable association between D allele or DD genotype and ESRD susceptibility (D: OR = 1.32, 95% CI: 1.11–1.56, P = 0.002; DD: OR = 1.67, 95% CI: 1.25–2.21, P = 0.0004). In the sub‐group analysis according to ethnicity, D allele or DD genotype was associated with ESRD risk in Asians. In Caucasians, the association of DD genotype with ESRD risk was observed, but the D allele was not. Furthermore, ACE I/D gene polymorphism was associated with ESRD risk in patients with DN due to diabetes mellitus type 2, but the association was not found for patients with DN due to diabetes mellitus type‐1. Conclusions: Our results indicate that D allele or DD homozygous is associated with the ESRD susceptibility in DN patients. However, more investigations are required to further this association.