Geographic, ethnic, age-related and temporal variation in the incidence of end-stage renal disease in Europe, Canada and the Asia-Pacific region, 1998-2002.

BACKGROUND: Only unbiased estimates of end-stage renal disease (ESRD) incidence and trends are useful for disease control-identification of risk factors and measuring the effect of intervention. METHODS: Age- and sex-standardized incidences (with trends) were calculated for all-cause and diabetic/non-diabetic ESRD for persons aged 0-14, 15-29, 30-44 and 45-64 years in 13 populations identified geographically, and six populations identified by ethnicity. RESULTS: The incidence of ESRD varied most with age, ethnicity and prevalence of diabetes. All non-Europid populations had excess ESRD, chiefly due to rates of type 2 diabetic ESRD that were greater than accounted for by community prevalences of diabetes. Their rates of non-diabetic ESRD also were raised, with contributions from most common primary renal diseases except type 1 diabetic nephropathy and polycystic kidney disease. The ESRD rates generally were low, and more similar than different, in Europid populations, except for variable contributions from type 1 (high in Finland, Sweden, Denmark and Canada) and type 2 (high in Austria and Canada) diabetes. In Europid populations during 1998-2002, all-cause ESRD declined by 2% per year in persons aged 0-44 years, and all non-diabetic ESRD by a similar amount in persons aged 45-64 years, in whom diabetic ESRD had increased by 3% per year. CONCLUSIONS: Increased susceptibility to type 2 diabetes and to kidney disease progression characterizes excess ESRD in non-Europid peoples. The decline in all-cause ESRD in young persons, and non-diabetic ESRD in the middle-aged, probably reflects improving management of progressive renal disease.     

Regional variability in the incidence of end-stage renal disease: an epidemiological approach.

BACKGROUND: Regional variability in the incidence of end-stage renal disease (ESRD) in Austria is reported. Our aim was to investigate the reason for low rates in the state of Tyrol. METHODS: ESRD incidence data were obtained from the Austrian Dialysis and Transplantation Registry. Additional sources were two health interview surveys, the Hospital Discharge Registry, the Mortality Registry and the Drug Wholesale Registry. RESULTS: Between 1995 and 1999, 4811 new cases of ESRD were recorded; the state of Tyrol (T) had a mean annual, age-adjusted incidence of 97.9/1 000 000 population [95% confidence interval (CI) 86.9-109.1], a number significantly lower than that for the rest of Austria [(RA), 120.9 (95% CI 116.9-124.5); P < 0.001]. This was due mainly to a difference in the incidence of ESRD patients with type 2 diabetes mellitus [(DM-2) T = 12.2 (95% CI 8.2-16.2) vs RA = 28.9 (95% CI 27.2-30.6); P < 0.001]. When these patients were excluded, the difference in the overall ESRD incidence disappeared. When data from various registries were analysed for the prevalence of DM, a highly significant correlation was found between ESRD incidence and DM. CONCLUSION: We conclude that the variability in the ESRD incidence in Austria is explained mainly by regional differences in DM-2. Data from similar studies might be useful for predictions concerning resource allocation for ESRD programmes in the future.     

Serum C-peptide concentrations poorly phenotype type 2 diabetic end-stage renal disease patients

BACKGROUND: A homogeneous patient population is necessary to identify genetic factors that regulate complex disease pathogenesis. In this study, we evaluated clinical and biochemical phenotyping criteria for type 2 diabetes in end-stage renal disease (ESRD) probands of families in which nephropathy is clustered. C-peptide concentrations accurately discriminate type 1 from type 2 diabetic patients with normal renal function, but have not been extensively evaluated in ESRD patients. We hypothesized that C-peptide concentrations may not accurately reflect insulin synthesis in ESRD subjects, since the kidney is the major site of C-peptide catabolism and would poorly correlate with accepted clinical criteria used to classify diabetics as types 1 and 2. METHODS: Consenting diabetic ESRD patients (N = 341) from northeastern Ohio were enrolled. Clinical history was obtained by questionnaire, and predialysis blood samples were collected for C-peptide levels from subjects with at least one living diabetic sibling (N = 127, 48% males, 59% African Americans). RESULTS: Using clinical criteria, 79% of the study population were categorized as type 1 (10%) or type 2 diabetics (69%), while 21% of diabetic ESRD patients could not be classified. In contrast, 98% of the patients were classified as type 2 diabetics when stratified by C-peptide concentrations using criteria derived from the Diabetes Control and Complications Trial Research Group (DCCT) and UREMIDIAB studies. Categorization was concordant in only 70% of ESRD probands when C-peptide concentration and clinical classification algorithms were compared. Using clinical phenotyping criteria as the standard for comparison, C-peptide concentrations classified diabetic ESRD patients with 100% sensitivity, but only 5% specificity. The mean C-peptide concentrations were similar in diabetic ESRD patients (3.2 +/- 1.9 nmol/L) and nondiabetic ESRD subjects (3.5 +/- 1.7 nmol/L, N = 30, P = NS), but were 2.5-fold higher compared with diabetic siblings (1.3 +/- 0.7 nmol/L, N = 30, P < 0.05) with normal renal function and were indistinguishable between type 1 and type 2 diabetics. Although 10% of the diabetic ESRD study population was classified as type 1 diabetics using clinical criteria, only 1.5% of these patients had C-peptide levels less than 0.20 nmol/L, the standard cut-off used to discriminate type 1 from type 2 diabetes in patients with normal renal function. However, the criteria of C-peptide concentrations> 0.50 nmol/L and diabetes onset in patients who are more than 38 years old identify type 2 diabetes with a 97% positive predictive value in our ESRD population. CONCLUSIONS: Accepted clinical criteria, used to discriminate type 1 and type 2 diabetes, failed to classify a significant proportion of diabetic ESRD patients. In contrast to previous reports, C-peptide levels were elevated in the majority of type 1 ESRD diabetic patients and did not improve the power of clinical parameters to separate them from type 2 diabetic or nondiabetic ESRD subjects. Accurate classification of diabetic ESRD patients for genetic epidemiological studies requires both clinical and biochemical criteria, which may differ from norms used in diabetic populations with normal renal function.     

Trends in the incidence of renal replacement therapy for end-stage renal disease in Europe, 1990-1999.

BACKGROUND: The epidemiology of renal replacement therapy (RRT) for end-stage renal disease (ESRD) varies considerably worldwide, but we have lacked reliable quantitative estimates of trends in the incidence by age, sex and cause in Europe over the last decade. METHODS: We analysed data from nine countries participating in the ERA-EDTA registry: Austria, Belgium, Denmark, Finland, Greece, The Netherlands, Norway, Spain and UK (Scotland). Adjusted incidence rates for age and sex were studied for 2 year periods between 1990 and 1999. Average annual changes (%) were estimated by Poisson regression. RESULTS: The adjusted incidence rate of RRT increased from 79.4 per million population (pmp) (range: 58.4-101.0) in 1990-1991 to 117.1 pmp (91.6-144.8) in 1998-1999, i.e. 4.8% (3.1-6.4%) each year. This increase did not flatten out at the end of the decade, except in The Netherlands, and was greater in men than women, 5.2 vs 4.0%/year. In most countries, the incidence rate remained stable for those younger than 45 years; it rose by 2.2%/year on average in the 45-64 year age group and by 7.0% among those 65-74 years; it tripled over the decade in those 75 years or older, and by 1998-1999 it ranged from 140.9 to 540.4 pmp between countries. The incidence of ESRD due to diabetes, hypertension and renal vascular disease nearly doubled over 10 years; in 1998-1999, it varied between countries from 10.2 to 39.3 pmp for diabetes, from 5.8 to 21.0 for hypertension, and from 1.0 to 15.5 for renal vascular disease. CONCLUSION: RRT incidence continues to rise but at various rates in the European countries studied, tending to widen the gap between them. This mainly results from enlarging differences in incidence in the elderly and, to a lesser extent, in that due to diabetes, hypertension and renal vascular disease.     

Post-liver transplant acute renal failure: factors predicting development of end-stage renal disease

BACKGROUND: Acute renal failure (ARF) occurs in 5-50% of patients undergoing orthotopic liver transplantation (OLT). The aim of this study was to determine factors that might predict the development of end stage renal disease (ESRD) in patients who had ARF after OLT. METHODS: We studied all OLT recipients between 9/1/1988 through 12/31/2000. RESULTS: A total of 1602 patients underwent OLT during the study period. About 350 patients (22%) developed ARF requiring dialysis post-operatively. One hundred and twenty-three (39.8%) died within a year after OLT. Median follow up was 5.8 yr (range 1-12 yr). Forty-three patients (23%) developed ESRD over median of 3.79 yr (range 1-8 yr). Multivariate logistic regression analysis revealed creatinine levels > 1.7 mg/dL at 1 yr (p < 0.001), cyclosporine as immunosuppression (p = 0.026), and the presence of diabetes pre-OLT (p < 0.001) to be associated with the development of ESRD. The development of ESRD did not decrease patient survival (p = 0.111). ESRD patients who received subsequent kidney transplantation had significantly improved survival rates (p = 0.005). CONCLUSIONS: Serum creatinine levels at 1 yr, cyclosporine as immunosuppression, and the presence of diabetes pre-OLT are independent predictive factors for the development of ESRD. ESRD patients who received kidney transplantation had higher 10-yr survival rates when compared with patients maintained on dialysis.     

The incidence of treated end-stage renal disease in New Zealand Maori and Pacific Island people and in Indigenous Australians.

BACKGROUND: Although Indigenous Australians, New Zealand Maori and Pacific Island people comprise an unduly high proportion of patients treated for end-stage renal disease (ESRD) in the two countries, no population-based age- and disease-specific rates have been published. METHODS: From data provided to the Australia and New Zealand Dialysis and Transplant Registry (ANZDATA), truncated age- and sex-standardized incidence rates were calculated for treated ESRD due to all causes and by primary renal disease, in four broad age groups of Maori, Pacific Island people and all 'other' New Zealanders and Indigenous and non-indigenous Australians, for the period 1992-2001. RESULTS: The incidence of ESRD did not differ in persons aged 0-14 years. In adults, Maori and Pacific Island people had similar rates of ESRD, a little more than half those of Indigenous Australians except in persons aged 65 years and over in whom the rates were nearly equal, but two to ten times the rates in 'other' New Zealanders and non-indigenous Australians. The excess of ESRD in Indigenous Australians was due principally to type II diabetic nephropathy and glomerulonephritis (all common types except lupus nephritis), but was seen also in respect of type I diabetic nephropathy, hypertensive renal disease and analgesic nephropathy, while the excess in Maori and Pacific Island people was confined to type II diabetic nephropathy, hypertensive renal disease and glomerulonephritis (especially lupus nephritis and type I mesangiocapillary glomerulonephritis, but not mesangial IgA disease). CONCLUSIONS: The incidence and pattern of treated ESRD differs quantitatively and qualitatively between Maori, Pacific Island people and other New Zealanders, and Indigenous and non-indigenous Australians.     

Interpreting incidence trends for treated end-stage renal disease: implications for evaluating disease control in Australia

BACKGROUND: Five sources of change modify trends in incidence of treated end-stage renal disease (ESRD): (i) demography; (ii) disease control, comprising prevention and treatment of progressive kidney disease; (iii) competing risks, which encompass dying from untreated uraemia or non-renal comorbidity; (iv) lead-time bias; and (v) classification bias. Thus, rising crude incidence of treated ESRD may conceal effective disease control when there has been demographic change, lessening competing risks, or the introduction of bias. METHODS: Age-specific incidences of treated ESRD in Australia were calculated from Australia and New Zealand Dialysis and Transplant (ANZDATA) Registry data by indigenous/non-indigenous status (all causes) and by primary renal disease (non-indigenous only) for two successive decades, 1982-1991 and 1992-2001. RESULTS: We postulate that less competing risks explained much of the increase in treated ESRD in the elderly and Indigenous Australians. The increase in glomerulonephritic ESRD in non-indigenous Australians could be ascribed mainly to immigration from non-European countries. There was no significant change in incidence of treated ESRD in Indigenous or non-indigenous persons aged less than 25 years, in non-indigenous persons aged 25-64 years for ESRD caused by hereditary polycystic disease or hypertension, or in type 1 diabetics aged over 55 years. End-stage renal disease from analgesic nephropathy had declined. The increase in treated ESRD caused by type 2 diabetic nephropathy appeared to be multifactorial. Lead-time/length bias and less competing risks may have concealed a small favourable trend in other primary renal diseases. CONCLUSION: Whether recent disease control measures have had an impact on incidence of treated ESRD is not yet certain, but seems more likely than implied by previous reports.     

Time trends in the epidemiology of renal transplant patients with type 1 diabetes mellitus over the last four decades.

BACKGROUND: Diabetes mellitus (DM) type 1 is an important contributor to end-stage renal disease (ESRD) among younger transplant recipients. However, little is known about the changes in epidemiological characteristics of this population. Especially, time to reach ESRD may have changed in type 1 diabetic patients referred for transplantation, resulting in higher age at time of grafting. Such time trends may allow anticipating future developments regarding the demand for organ replacement in this patient group. METHODS: We retrospectively analysed 173 patients with type 1 DM undergoing renal transplantation at our institution, stratified into four groups according to year of reaching ESRD (A = 1973-1983, B = 1984-1990, C = 1991-1995 and D = 1996-2002). For each group we determined age at diagnosis of DM, age at time of reaching ESRD and age at time of transplantation. From these data, the interval from diagnosis of DM to ESRD and from ESRD to transplantation was calculated. The results were analysed in relation to gender, year of and age at onset of diabetes. RESULTS: Patients reaching ESRD in more recent years (group D) tended to be both younger at diagnosis of DM and older when reaching ESRD, resulting in higher mean age at transplantation (35.0, 37.5, 39.6 and 41.0 years in groups A, B, C and D, respectively). Accordingly, median duration to ESRD has significantly been prolonged over the last five decades in patients with type 1 DM undergoing renal transplantation (group A: 21.0, B: 20.7, C: 22.3 and D: 28.5 years; P < 0.0001), this finding being more pronounced in female patients. CONCLUSIONS: The results of our analysis are compatible with a change in epidemiology in patients undergoing kidney transplantation. Older age at time of reaching ESRD may impact significantly on the demand for renal grafts, as patients are already clearly older nowadays when being transplanted. From our data it cannot be concluded whether this development is due to a change in the progression of diabetic nephropathy or may simply reflect a change in the selection of type 1 diabetic patients referred for transplantation.     

Coronary artery,aortic wall,and valvular calcification in nondialyzed individuals with type 2 diabetes and renal disease

BACKGROUND: Individuals with end-stage renal disease (ESRD) have highly prevalent and severe vascular and valvular calcification. We undertook this study to test the hypothesis that vascular and valvular calcification begins and is often severe long before diabetic renal disease progresses to ESRD. METHODS: A total of 32 nondialyzed individuals with type 2 diabetes mellitus and diabetic renal disease (albumin excretion rate>30 microg/min) [mean glomerular filtration rate (GFR), 49.8 +/- 6.1 mL/min/1.73 m2] were identified and compared with a group of 18 normoalbuminuric diabetics. We used 3:1 matching to identify 95 nondiabetic controls without renal disease, matched for age, gender, ethnicity, and the presence/absence of dyslipidemia, hypertension, and known coronary artery disease (CAD). RESULTS: Using electron beam computed tomography (CT), the prevalence of coronary artery calcification was significantly greater among diabetic renal disease individuals (prevalence, 94% vs. 59%, P < 0.001; median score, 238 vs. 10, P < 0.001) than the nondiabetic controls. The coronary artery calcification scores were significantly more severe among diabetic renal disease individuals than either the diabetic or nondiabetic controls. Among individuals with diabetic renal disease, the coronary artery calcification and aortic wall calcification scores were several-fold greater among those with known CAD than among those without. There was also a significantly greater prevalence of aortic and mitral valve calcification among diabetic renal disease individuals than nondiabetic controls (aortic, 23% vs. 6%, P = 0.03; mitral, 25% vs. 2%, P < 0.001). Multivariate analysis using all three groups reproduced these findings and also consistently identified age and diabetic renal disease as additional predictors for the presence or severity of coronary artery and aortic wall calcification. CONCLUSION: In this first, systematic analysis among nondialyzed individuals with diabetic renal disease, these data demonstrate that vascular and valvular calcification is present and often severe long before the disease progresses to ESRD. The data also suggest that the coronary artery and aortic wall calcification may represent atherosclerosis.     

Morphological and functional differences in haemostatic axis between kidney transplanted and end-stage renal disease patients

End-stage renal disease (ESRD) is characterized by several atherothrombotic abnormalities, and kidney transplant seems to improve most of them. However, because it is not clear which mechanism is responsible for such improvement, our purpose was to clarify that point.We conducted a cross sectional study involving 30 ESRD patients, 30 ESRD kidney-transplanted patients (Ktx) and 30 healthy controls (C) to evaluate platelet morphology and function, atherothrombotic profile, endothelial abnormalities and cytokine levels involved in the insulin resistance/endothelial dysfunction. (i) Platelet morphology: The ESRD group showed platelet size similar to the other two groups (ESRD=3518x10(3)+/-549x10(3) nm2, C=3075x10(3)+/-197x10(3) nm2, Ktx=2862x10(3)+/-205x10(3) nm2) with similar platelet granules and number. (ii) Platelet surface glycoprotein: The CD41 and P-Selectin were similar between groups. (iii) Platelet intracellular calcium: Resting intracellular calcium was statistically higher in ESRD compared to the C group (ESRD=182.1+/-34.5, Ktx=126.7+/-14.1, C=72.0+/-11.0 nM, P<0.01). (iv) Hypercoagulability markers and natural anticoagulants: The Ktx and ESRD groups showed higher levels of hypercoagulability markers compared to the C group. A reduction in antithrombin activity was evident in ESRD compared to the Ktx group (P=0.03). (v) Endothelial morphology: The ESRD group showed a thickened vessel basal membrane compared to the Ktx and C groups with more endothelial sufference. (vi) Insulin resistance and pro-inflammatory cytokine profile: The ESRD showed a higher homeostasis model assessment provided equations for estimating insulin resistance (HOMA-IR) compared to the Ktx and C groups (ESRD=2.6+/-0.3, Ktx=1.8+/-0.2, C=1.1+/-0.1, P=0.005) and increased soluble tumor neurosis factor alpha (sTNFalpha) (P<0.05) and soluble vascular cell adhesion molecule (sVCAM) levels (P<0.01). Positive correlations were evident among HOMA-IR and sTNFalpha (P<0.001) and sVCAM (P=0.01), respectively. In a small subgroup of ESRD who underwent Ktx (five pts), our findings were confirmed at 1 year of follow-up, suggesting an improvement of almost haemostatic abnormalities. Kidney transplant is associated with a better atherothrombotic profile in ESRD, platelet intracellular calcium and cytokines seem to be most influenced by the transplant, while most morphological abnormalities are retained.     

A multicentre study of registration on renal transplantation waiting list of the elderly and patients with type 2 diabetes.

BACKGROUND: Studies in the USA have shown that some patients (African-Americans, women, the elderly and diabetics) were less likely to receive renal transplants. In order to identify patient characteristics modifying the likelihood of being wait-listed, we studied registration on renal transplantation waiting list (WLR) focusing on elderly (age > or =60 years) and on patients with type 2 diabetes (D2) in three departments of nephrology in the Rh?ne-Alpes county in France. METHODS: In a cohort of 549 patients who reached end-stage renal disease (ESRD) between 1995 and 1998 in these units, we analysed the rates of pre-transplant evaluation (PTE), the duration of PTE, the rates of exclusion from transplantation by PTE and the rates of WLR. With Cox regression model, we identified the characteristics that have independent and significant effects on the likelihood of being registered after the first renal replacement therapy (RRT). RESULTS: In this cohort, 185 patients (33.7%) were wait-listed by 31.03.00 and no patient > or =70 years was evaluated or registered. In univariate analysis, PTE and WLR rates were lower in the elderly (21.5 and 20.0%, respectively) than those <60 years (79.1 and 70.2%, P < 0.001) and in D2 (33.0 and 24.2%) than in non-D2 (65.8 and 60.6%, P < 0.001). The duration of PTE was longer in D2 than in non-D2 (12.7 +/- 11.0 vs 7.5 +/- 7.1 months, P < 0.01). Among patients excluded from PTE, more patients without relevant co-morbidities [e.g. rapidly progressive ESRD, cardiovascular disease (CVD), malignancy] were present in the elderly (> or =70 years: 14.8%; 60-69 years: 17.0%; <60 years: 6.4%) and in D2 (18.0%) than in non-D2 (10.9%). The adjusted relative risks (aRR) of being wait-listed after first RRT were significantly lowered by age and D2 (aRR, 95% CI): 60-64 year olds (0.44%: 0.26-0.75), 65-69 year olds (0.07%: 0.03-0.20) and D2 (0.41%: 0.24-0.69). Other conditions associated with a lower aRR were rapidly progressive ESRD (0.21%: 0.08-0.55), CVD (0.59%: 0.36-0.94), malignancy (0.13%: 0.04-0.46) and psychosis (0.05%: 0.01-0.35). CONCLUSION: Advanced age and D2 were associated with low PTE and WLR rates even after adjustment for other patient characteristics.     

Dyslipidaemia and the progression of renal disease in chronic renal failure patients.

BACKGROUND: Dyslipidaemia is common in patients with chronic renal failure (CRF), and there is increasing evidence to support the role of dyslipidaemia as a contributing factor in the progression of chronic renal disease. However, few prospective studies have been carried out which address the possible relationship between dyslipidaemia and the rate of progression of renal disease in patients with renal failure. METHODS: Between January 1985 and December 1997, we prospectively assessed the risk of CRF progression to dialysis in a cohort of 138 patients. Forty CRF patients reached end-stage renal disease (ESRD) and had to start supportive therapy during the follow-up period [group ESRD(+)]. The remaining 98 CRF patients served as controls [group ESRD(-)]. Potential clinical and laboratory risk factors for more rapid CRF decline to dialysis, including lipid abnormalities and baseline creatinine clearance were determined at the start of the follow-up period. RESULTS: Several significant differences were found in univariate analysis between the two groups of CRF, ESRD(+) and ESRD(-), namely a shorter follow-up period, a lower level of baseline creatinine clearance, a faster rate of creatinine clearance decline, a higher level of serum triglycerides, fibrinogen, total homocyst(e)ine and proteinuria, and a lower level of serum high-density lipoprotein in the ESRD(+) group than in the ESRD(-) group. However, by multivariate Cox analysis proteinuria [relative risk (95% confidence interval) 1.32 (1.16-1.50) for each g/day P = 0.001], baseline creatinine clearance [0.53 (0.40-0.70) for each 10 ml/min, P = 0.001] and chronic interstitial nephritis and hypertensive nephrosclerosis [0.38 (0.17-0.84) for presence, P = 0.005] were the only significant risk factors for CRF progression to dialysis. Hypertriglyceridaemia and male gender were selected in the final model, but were of borderline significance. CONCLUSIONS: These results suggest a limited role for dyslipidaemia in the progression of chronic renal disease to dialysis in CRF patients, in contrast with the powerful influence of proteinuria, baseline creatinine clearance and nephropathy type in predicting this progression.     

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.     

Diabetic end-stage renal disease in the indigenous population of the Commonwealth of the Northern Mariana Islands

The number of cases of treated end-stage renal disease (ESRD) attributable to type 2 diabetes and survival after the onset of renal replacement therapy was examined in the Commonwealth of the Northern Mariana Islands (CNMI). All Chamorros and Carolinians to receive renal replacement therapy for ESRD between January 1982 and December 2002 were identified. Changes in survival over time were examined by dividing the study into three equal periods. Of 180 new cases of ESRD, 137 (76%; 101 Chamorros, 36 Carolinians) were attributed to diabetes. Ninety-nine subjects, 80% of whom had diabetic ESRD, began renal replacement therapy in the last 7 years of the study compared with 81 (72% with diabetic ESRD) in the previous 14 years. All 137 of the diabetic subjects received haemodialysis. During the 21-year study period, 79 of the diabetic subjects receiving dialysis died. The median survival after the onset of haemodialysis was 37 months in the first time period (1982-1988), 47 months in the second period (1989-1995) and 67 months in the third period (1996-2002). The death rate in the first period was 4.3 times (95% CI, 2.1-8.9) as high and the second period was 2.9 times (95% CI, 1.5-5.8) as high as the most recent period, after adjustment for age, sex and ethnicity in a proportional-hazards analysis. The number of diabetic patients in CNMI who are receiving renal replacement therapy is rising rapidly. Considerable improvement in survival after the onset of haemodialysis has occurred over the past 21 years.     

Incidence of end-stage renal disease in overseas-born, compared with Australian-born, non-indigenous Australians

BACKGROUND: Barriers to immigration from non-European sources were relaxed in the 1970s. As a result, more Australians are now of Middle Eastern, Asian or Pacific Islander origin, rather than British or European. Currently, overseas-born persons comprise one-third of non-indigenous Australians with end-stage renal disease (ESRD). METHODS: Using data recorded by the Australia and New Zealand Dialysis and Transplant (ANZDATA) Registry, age-standardized incidence rates were calculated for ESRD due to all causes and to certain primary renal diseases for all non-indigenous Australians who were aged over 15 years when first treated for ESRD between 1993 and 2001. Truncated age-standardized incidence rates were calculated for ESRD due to glomerulonephritis by type. RESULTS: Immigrants from the British Isles and 'rest of Europe' had less, and those from the Pacific Island nations, East/South-East Asia, Indian subcontinent, Middle East and Southern Europe more ESRD from all causes than the Australian-born. Two diseases accounted for most of the excess: Type 2 diabetic nephropathy and glomerulonephritis (the latter not significant for the Indian-born). There was a small excess (not always significant) of hypertensive/arteriopathic renal disease in Asian- and Middle Eastern-born persons. The East/South-East Asian-born had the highest rates of ESRD due to mesangial immunoglobulin A (IgA) disease and lupus nephritis, and the Middle Eastern-born the highest rates from focal sclerosing glomerulonephritis. CONCLUSION: For Australians born in the Pacific Island nations, Asia, the Middle East or Southern Europe, excess prevalence of, and/or susceptibility to, diseases that cause ESRD has more than offset any 'healthy migrant' effect.     

Haematocrit and the risk of developing end-stage renal disease.

BACKGROUND: Anaemia is common in patients with renal failure; however, it is not known whether haematocrit level in the general population is a predictor for developing end-stage renal disease (ESRD). METHODS: A retrospective analysis was conducted to assess the development of ESRD within a population of 71 802 subjects (37 190 men and 34 612 women), 20-99 years, in Okinawa, Japan. Haematocrit data were collected between April 1983 and March 1984 and the subjects were followed forward to the year 2000 whether they were identified in the Okinawa Dialysis Study registry for identification of ESRD. Multivariate logistic analyses were performed to analyse the influence of haematocrit on the development of ESRD after adjusting for age, sex, blood pressure, body mass index, proteinuria and haematuria. In a subgroup of the cohort, similar analyses were repeated adjusting for estimated creatinine clearance by the method of Cockcroft and Gault. RESULTS: The mean (SD) level of haematocrit at the time of screening was 45.3% (3.3%) for men and 38.8% (3.2%) for women. During the 17-year follow-up, 269 patients (171 men and 98 women) were identified with ESRD. The mean time to onset of ESRD was 130.4 (53.6) months. The adjusted odds ratio and 95% confidence interval (CI) for the influence of haematocrit (%) on the development of ESRD was 0.991 and 0.988-0.995 (P<0.0001), suggesting that the lower haematocrit, the greater was the risk of developing ESRD. This finding was repeated in the subgroup analysis that included calculated creatinine clearance (adjusted odds ratio 0.991 and 95% CI 0.984-0.997, P=0.0057). In women, the adjusted odds ratio for haematocrits of 20.0-34.9% was 3.086 (CI 1.770-5.376, P<0.0001) when compared with the reference haematocrits of 35.0-39.9%. In men, the adjusted odds ratio for haematocrits of 25.0-39.9% was 1.927 (CI 1.418-2.625, P<0.0001) when compared with the reference haematocrits of 45.0-49.9%. CONCLUSIONS: Subjects with low haematocrits, <40% for men and <35% for women, have a significantly increased risk of ESRD.     

Genetic analysis of nitric oxide and endothelin in end-stage renal disease.

BACKGROUND: Genetic factors have been implicated in the development of the common aetiologies of end-stage renal disease (ESRD), including renal failure attributed to hypertension, diabetes mellitus, systemic lupus erythematosus and human immunodeficiency virus infection. Nitric oxide (NO) and endothelin are powerful vasoactive mediators involved in inflammation and regulation of vascular tone and blood pressure. We evaluated the role of the neuronal constitutive (NOS1) and endothelial constitutive (NOS3) nitric oxide synthase genes and the endothelin-1 (EDN-1) gene in predisposition to chronic renal failure in African-Americans. METHODS: The study population for the linkage and association analyses in ESRD consisted of 361 individuals from 168 multiplex African-American families. These individuals comprised 207 unweighted sibling pairs concordant for all-cause ESRD. Microsatellite markers NOS1B (NOS1), D7S636 (NOS3) and CPHD1-1/2 (EDN-1) were genotyped in the sample. In addition, a mutation, Glu298Asp, in exon 7 of NOS3 and a 27 bp variable number tandem repeat (VNTR) marker in intron 4 of NOS3 were evaluated in the sibling pairs and in an additional 92 unrelated African-Americans with type 2 diabetes mellitus-associated ESRD (singletons). Association analyses utilized the relative predispositional effect method. Model independent linkage analyses were performed using GeneHunter-plus and MapMaker/SIBS (exclusion analysis) software. RESULTS: Significant evidence for association with ESRD was detected for alleles 7 and 9 of the NOS1 gene (11.9 and 34.2%, respectively, in unrelated probands of ESRD families versus 6.5 and 27.5%, respectively, in race-matched controls, both P:<0.01). These associations were maintained when the unrelated first sibling from each family was used in a case-control comparison and was most pronounced in the non-diabetic ESRD cases. The NOS3 and EDN-1 markers failed to provide consistent evidence for association in the sibling pairs and the diabetic ESRD singletons, although we identified two novel endothelial constitutive NOS4 (ecNOS4) VNTR alleles in African-Americans. Significant evidence for linkage was not detected between the NOS genes or the EDN-1 gene in either all-cause ESRD or when the ESRD sibling pairs were stratified by aetiology (type 2 diabetic ESRD or non-diabetic aetiologies). CONCLUSION: Based upon the consistent allelic associations, we believe that further evaluation of the NOS1 gene in ESRD susceptibility in African-Americans is warranted.     

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.     

Endothelial nitric oxide synthase gene intron 4 polymorphism in patients with end-stage renal disease.

BACKGROUND: Nitric oxide (NO) synthesized by endothelial cell NO synthase (ecNOS) is a potent regulator of intrarenal haemodynamics. A polymorphism in intron 4 of the ecNOS gene is a candidate gene in cardiovascular and renal diseases. We investigated a potential involvement of this polymorphism in chronic renal failure. METHODS: We performed a case-control study involving 706 patients with end-stage renal disease (ESRD) and 321 healthy controls. All subjects were genotyped for the ecNOS4 polymorphism by the polymerase chain reaction followed by agarose gel electrophoresis. RESULTS: The analysis revealed that the frequencies of the ecNOS4 genotypes were significantly different in ESRD patients, both diabetic and non-diabetic, than in controls. In all dialysis patients for aa, ab and bb genotypes the frequencies were, respectively, 6.5, 35 and 58.5% in the patient group, and 1, 25 and 74% in control subjects. The a allele carriers (aa + ab) were more frequent among ESRD patients than in controls (OR 1.95; 95% CI 1.13-3.4; P = 0.0031). No significant association was found when hypertensive ESRD patients were compared with normotensive patients. The distribution of genotypes was similar in both subgroups (P = 0.21). CONCLUSION: There was a significantly higher frequency of the ecNOS4a allele carriers among ESRD patients, both diabetic and non-diabetic, than in control subjects. This suggests that the ecNOS gene polymorphism may be associated with an increased risk of chronic renal failure.     

Different regional dynamics of end-stage renal disease in Japan by different causes

BACKGROUND: We recently showed that there were clear regional differences in the dynamics of end-stage renal disease (ESRD) within Japan, which has an ethnically homogenous population. We speculate on the reason for these regional differences by correlating the regional distributions in the incidence of ESRD due to each of the following individual causes of ESRD: chronic glomerulonephritis (CGN), diabetic nephropathy (DMN) and polycystic kidney disease (PKD). METHODS: The number of ESRD patients entering maintenance dialysis therapy due to individual causes of renal disease in each prefecture was reported annually for a 6-year period by the Japanese Society for Dialysis Therapy. After combining data from several prefectures into 11 geopolitical regions in Japan, the mean annual incidence of ESRD across the 11 regions was correlated among the three causes of ESRD. RESULTS: There were significant regional differences in the incidence of ESRD due to CGN (P<0.0001) and DMN (P=0.0015), the distributions of which were similar to each other across the 11 regions. In contrast, no regional differences were found in the incidence of ESRD due to PKD (P=0.6) as the major genetic disorder of the kidneys, suggesting that genetic backgrounds are relatively uniform throughout Japan. The regional distributions due to PKD were not correlated with those due to other causes: CGN and DMN. CONCLUSION: Risk factors common to nephropathy progression, rather than an underlying disease incidence and genetic predisposition, might contribute to regional differences in the overall ESRD incidence in Japan. Other possibilities such as the prevalence of underlying diseases, and acceptance or rejection rates into treatment programmes must be considered further for better explanations.