Trends in incidence of treated end-stage renal disease, overall and by primary renal disease, in persons aged 20-64 years in Europe, Canada and the Asia-Pacific region, 1998-2002

AIMS: To determine if rates of diabetic and non-diabetic end-stage renal disease (ESRD), which had been rising in young and middle-aged adults in all populations up to the mid-1990s, had started to decline, and if so, whether improvement had occurred in respect of each of the principal primary renal diseases causing ESRD. METHODS: Poisson regression of age- and sex-standardized incidence of ESRD for persons aged 20-64 years in 18 populations from Europe, Canada and the Asia-Pacific region, for 1998-2002. RESULTS: In persons from 12 European descent (Europid) populations combined, there was a small downward trend in all-cause ESRD (-1.7% per year, P = 0.001), with type 1 diabetic ESRD falling by 7.8% per year (P < 0.001), glomerulonephritic ESRD by 3.1% per year (P = 0.001), and 'all other non-diabetic' ESRD by 2.5% per year (P = 0.02). The reductions in ESRD attributed to hypertensive (-2.2% per year) and polycystic renal disease (-1.5% per year) and unknown diagnosis (-0.2% per year) were not statistically significant. On the other hand, the incidence of type 2 diabetic ESRD rose by 9.9% per year (P < 0.001) in the combined Europid population, although that of (principally type 2) diabetic ESRD remained unchanged in the pooled data from the four non-Europid populations. CONCLUSION: Recent preventive strategies, probably chiefly modern renoprotective treatment, appear to have been effective for tertiary prevention of ESRD caused by the proteinuric nephropathies other than type 2 diabetic nephropathy, for which the continuing increase in Europid populations represents a failure of prevention and/or a change in the nephropathic potential of type 2 diabetes.     

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.     

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.     

A genome-wide association study for diabetic nephropathy genes in African Americans

A genome-wide association study was performed using the Affymetrix 6.0 chip to identify genes associated with diabetic nephropathy in African Americans. Association analysis was performed adjusting for admixture in 965 type 2 diabetic African American patients with end-stage renal disease (ESRD) and in 1029 African Americans without type 2 diabetes or kidney disease as controls. The top 724 single nucleotide polymorphisms (SNPs) with evidence of association to diabetic nephropathy were then genotyped in a replication sample of an additional 709 type 2 diabetes-ESRD patients and 690 controls. SNPs with evidence of association in both the original and replication studies were tested in additional African American cohorts consisting of 1246 patients with type 2 diabetes without kidney disease and 1216 with non-diabetic ESRD to differentiate candidate loci for type 2 diabetes-ESRD, type 2 diabetes, and/or all-cause ESRD. Twenty-five SNPs were significantly associated with type 2 diabetes-ESRD in the genome-wide association and initial replication. Although genome-wide significance with type 2 diabetes was not found for any of these 25 SNPs, several genes, including RPS12, LIMK2, and SFI1 are strong candidates for diabetic nephropathy. A combined analysis of all 2890 patients with ESRD showed significant association SNPs in LIMK2 and SFI1 suggesting that they also contribute to all-cause ESRD. Thus, our results suggest that multiple loci underlie susceptibility to kidney disease in African Americans with type 2 diabetes and some may also contribute to all-cause ESRD.     

Trends in incidence of end-stage renal disease in Japan, 1983-2000: age-adjusted and age-specific rates by gender and cause.

BACKGROUND: Trends in age-adjusted or age-specific incidence rates of end-stage renal disease (ESRD) have never been examined in Japan, a major ESRD epidemic area. METHODS: A nationwide registry has provided the number of ESRD patients commencing maintenance renal replacement therapy for time period from 1983 to 2000. We computed gender- and age-specific incidence rates of ESRD over 2-year periods, in total or by cause. Age-adjusted incidence rates were calculated using the 1985 Model Population of Japan as the standard. RESULTS: Causes of ESRD in 1999-2000 were, in order of decreasing frequency, diabetic nephropathy, chronic glomerulonephritis, unknown causes, nephrosclerosis and polycystic kidney disease in men, and chronic glomerulonephritis, diabetic nephropathy, unknown causes, nephrosclerosis and polycystic kidney disease in women. The age-adjusted all-cause incidence of ESRD increased until 1995-1996, but has since levelled off in both genders. The age-adjusted rate for diabetic nephropathy has been rapidly increasing, while that for chronic glomerulonephritis has decreased since 1995-1996. The former rate exceeded the latter in 1997-1998 in men. All-cause ESRD has rapidly increased in the eighties age group, whereas the increase slowed down in younger age groups in the late 1990s. The rate for diabetic nephropathy has linearly risen in almost every age group in men, whereas it began to level off in women aged 40-59 years at about 1995. For chronic glomerulonephritis, the rate had already started to decline in the mid-1980s in those aged <45 years. The rate of nephrosclerosis has been increasing independently of age. CONCLUSIONS: The present study shows changes in the epidemiological features of the incidence of ESRD in Japan from 1983 to 2000.     

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.     

Diabetes mellitus, aortic stiffness, and cardiovascular mortality in end-stage renal disease

Cardiovascular mortality is elevated in patients with end-stage renal disease (ESRD), especially in those with diabetes mellitus. Although the higher cardiovascular death rate in diabetic ESRD patients may be the result of more advanced atherosclerotic changes of the arterial wall, this has not been documented previously. Aortic stiffness was compared between ESRD patients with and without diabetes, and the impact of aortic stiffness on cardiovascular mortality was examined in a prospective, observational cohort study. The cohort consisted of 265 ESRD patients on hemodialysis, including 50 diabetic patients studied between June 1992 and December 1998. At baseline, the diabetic ESRD patients had significantly higher aortic pulse wave velocity (PWV), a noninvasive measure of aortic stiffness, than the nondiabetic patients. During a mean follow-up period of 63 mo, 81 deaths, including 36 cardiovascular deaths, were recorded. Kaplan-Meier analysis revealed higher all-cause or cardiovascular mortality rates in the diabetic as compared with the nondiabetic patients and also in those with higher aortic PWV than those with lower aortic PWV. The effect of diabetes on cardiovascular death was significant in the Cox model, including age, years on hemodialysis, gender, smoking, C-reactive protein, hematocrit, and body mass index as covariates. However, when aortic PWV was included as a covariate, the impact of diabetes was no longer significant, whereas aortic PWV was a significant predictor. In a model including 13 covariates, aortic PWV remained a significant predictor for cardiovascular and overall mortality but not for non-cardiovascular death. These results demonstrate that the increased aortic stiffness of the ESRD patients with diabetes mellitus contributed to the higher all-cause and cardiovascular mortality rates.     

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.     

Diabetic renal disease in Pima Indians

Diabetic renal disease is a major source of morbidity and mortality in Pima Indians. Excess mortality in NIDDM occurs principally in those with proteinuria regardless of whether death is due to cardiovascular or renal disease. Diabetes duration is a strong predictor of diabetic renal disease. Additional predictors include blood pressure, severity of diabetes, and, most likely, genetic or shared environmental determinants. The incidence rate of diabetic renal disease in Pima Indians with NIDDM is similar to that reported for subjects with IDDM with equivalent durations of diabetes. These observations suggest that clinical proteinuria and renal failure may occur in patients with NIDDM just as frequently as in those with IDDM. This finding has important implications and suggests that the variations in the frequency and age of onset of NIDDM among different populations and ethnic groups may be primarily responsible for the apparent variations in the frequency of ESRD associated with diabetes in different populations. Furthermore, diabetic renal disease appears to account for virtually all of the excess mortality associated with diabetes among Pima Indians and may perhaps do so in other populations. Improved survival of persons with NIDDM, an increasing incidence of this disease, and a relatively early age of onset in many populations could lead to a dramatic increase in the incidence of ESRD in the future. On the other hand, if diabetic renal disease and its consequences could be prevented, a profound improvement in the longevity and quality of life of those afflicted with diabetes might be possible.     

Perceived health-related quality of life and comorbidity in diabetic patients starting dialysis (CALVIDIA study)

BACKGROUND: Diabetes mellitus (DM) is a widespread prevalent illness, currently the main cause of end-stage renal disease (ESRD). MATERIAL AND METHODS: In a longitudinal, prospective study we compared two cohorts of patients starting dialysis therapy, diabetic and non-diabetic ESRD patients. Perceived health was measured by the Medical Outcomes Study Short-Form 36 (SF-36) questionnaire, functional status by the Karnofsky scale and comorbidity by the Charlson age-comorbidity index. A broad spectrum of variables in relation to diabetes, ESRD, comorbidity and renal replacement therapy (RRT) were studied, as well as the distribution of comorbidity frequencies at dialysis start. RESULTS: Thirty-four Spanish centers included 232 diabetic patients, 43 type 1 and 189 type 2, mean diabetes duration 18 +/- 9 yrs, and five centers included 121 non-diabetic patients. Out of the 232 diabetic patients, 187 patients (81%) started hemodialysis (HD) and 45 patients (19%) started peritoneal dialysis (PD) (vs. 82% and 18%, respectively in non-diabetic patients). Transient vascular access (VA) for starting RRT was required in 54% of the diabetic patients vs. 53% in the nondiabetic patients. When both study groups were compared, diabetic patients required antihypertensive drugs more frequently than non-diabetic patients and showed higher systolic blood pressure (BP), as well as higher cardiovascular (CV) complication incidences, poorer SF-36 physical component summary scores and mental component summary scores and worse Karnofsky scale scores, with the Charlson age-comorbidity score being higher. CONCLUSION: Diabetic patients starting dialysis in Spain are more often type 2 diabetics, have worse perceived health-related quality of life (HRQoL) in relation to non-diabetic patients, worse functional status and higher incidences of prognostic mortality markers.     

Diabetic CKD/ESRD 2010: A Progress Report?

Both in the United States and many regions of the world, chronic kidney disease and end‐stage renal disease (ESRD) in patients with diabetes mellitus have reached epidemic proportions in recent years. The large prevalent diabetic ESRD population in the US involves remarkable risk in African Americans and an increasing population of elderly diabetic patients, including many octogenarians. In the US and globally, over 90% of diabetic ESRD patients have type 2 diabetes. The multinational epidemic of diabetic ESRD has been linked to increases in the prevalence of diabetes in many populations, related to obesity, ageing, and physical inactivity. It is anticipated that the worldwide prevalence of diabetes over the next 20 years will reach a level twice that of the year 2000. The excessive morbidity and mortality of the diabetic ESRD population are well documented. However, the growth in incidence and prevalence rates for diabetic ESRD has remained somewhat stable in the US in recent years, and new data suggest that the incidence of ESRD expressed per diabetic population may finally be declining, suggesting that proven therapies are making “progress on progression.”     

Differences in heart rate variability parameters during the post-dialytic period in type II diabetic and non-diabetic ESRD patients.

BACKGROUND: Heart rate variability parameters were evaluated in 10 healthy subjects, 10 type II diabetic patients and 20 end-stage renal disease (ESRD) patients (11 non-diabetic and nine type II diabetic) undergoing chronic haemodialysis. The study was divided in two phases. METHODS: In the first phase all subjects underwent electrocardiograph (ECG) recording under baseline conditions. In the second phase only ESRD patients underwent haemodialysis and ECG recording. On the day of dialysis and ECG recording the ECG recording was started 1 h before the haemodialysis session (pre-dialytic period), and continued throughout the dialysis (dialytic period), until the morning after (post-dialytic period). RESULTS: Compared with ESRD patients, non-ESRD patients showed the lowest cardiac sympathetic activity. Diabetic patients compared to non-diabetic patients showed a prevalence of cardiac sympathetic activity in the pre-dialytic period (P < 0.01). During the dialytic period in comparison with the pre-dialytic one, a further increase in cardiac sympathetic activity was observed in both diabetic and non-diabetic ESRD patients (P < 0.001). However, in the post-dialysis period the cardiac autonomic nervous system activity remained at the pre-dialytic condition in the diabetic group. In contrast, in the non-diabetic group the cardiac autonomic balance shifted towards a parasympathetic prevalence in the post-dialytic period (P < 0.01). In addition, a significant correlation was found between changes in heart rate variability and changes in plasma urea concentration in the non-diabetic group only (r = 0.65; P < 0.03). CONCLUSIONS: Non-insulin-dependent diabetic uraemic patients undergoing a chronic haemodialysis programme have a severe impairment of heart rate variability. This is probably due to autonomic neuropathy related to the effects of both diabetes and chronic uraemic conditions. In non-diabetic haemodialysis patients uraemia causes similar but reversible changes in heart rate variability compared with the changes caused by diabetes.     

Sickle cell trait is not independently associated with susceptibility to end-stage renal disease in African Americans

Conflicting reports exist as to whether sickle cell trait is a risk factor for the progression of nephropathy. In order to determine whether African Americans with sickle cell trait are at increased risk for kidney disease, we assessed the genetic association between sickle cell trait and end-stage renal disease (ESRD). Hemoglobin S, non-muscle myosin heavy chain 9 (MYH9), and apolipoprotein L1 (APOL1) risk variants were genotyped in 3258 unrelated African Americans: 1085 with non-diabetic ESRD, 996 with type 2 diabetes-associated ESRD, and 1177 controls. Since APOL1 is strongly associated with ESRD in African Americans, interactions between APOL1 and MYH9 risk variants and hemoglobin S were assessed using case-only and case-control centered two-way logistic regression interaction analyses. The sickle cell trait genotype frequencies were 8.7% in non-diabetic ESRD, 7.1% in type 2 diabetes-ESRD, and 7.2% in controls. There was no age-, gender-, and admixture-adjusted significance for sickle cell trait association with non-diabetic ESRD (odds ratio 1.16); type 2 diabetes-ESRD (odds ratio 1.01); or all-cause ESRD (combined non-diabetic and type 2 diabetic-ESRD patients compared to the controls; odds ratio 1.05) in dominant models. In addition, no evidence of APOL1 or MYH9 interactions with sickle cell trait was detected. Hence, sickle cell trait is not associated with diabetic or non-diabetic ESRD in a large sample of African Americans.     

Dialysis in Israel, 1989-2005--time trends and international comparisons.

BACKGROUND: A universal increase in the incidence of renal replacement therapy (RRT) was reported in developed countries during the 1990s, especially among the elderly and diabetic patients. We studied trends in RRT incidence and mortality in Israel between 1989 and 2001-2005. METHODS: The end-stage renal disease (ESRD) registry holds data on all RRT patients in Israel. Age-adjusted incidence rate ratios (RRs) were estimated comparing 2001-2005 with 1989. We compared incidence data between Israel and elsewhere using standardized incidence ratios (SIRs). Survival analysis was conducted by the Kaplan-Meier method and Cox's proportional hazards regression was used to compare survival of diabetic with non-diabetic ESRD patients. RESULTS: The mean incidence rates per million population increased from 99 in 1989-1991 to 179 in 2003-2005. In 2000, Israel was the second leading country for incidence of RRT. Age-adjusted incidence rates increased by 67% [95% confidence interval (CI): 49-87%], from 1989 to 2001, but the trend was attenuated between 2002 and 2005. The increase in incidence was positively associated with age, the largest increase being among the elderly aged > or = 75 years (RR: 3.18, 95%CI: 2.72-3.70). Diabetes accounted for 41% of RRT in 2001 vs only 19% in 1989. There was no increase in 1-year survival between the beginning and the end of the study period. Patients with diabetes-associated RRT had 57% increased risk of 1-year mortality (adjusted HR: 1.57 95% CI: 1.51-1.63). CONCLUSIONS: Despite a similar proportion of RRT attributed to diabetes in Israel and other countries, the age-adjusted incidence in Israel is considerably higher than most countries.     

Kidney transplantation in type 2 diabetic patients: a comparison with matched non-diabetic subjects.

BACKGROUND: Because they generally are older and frequently have co-morbidities, patients with type 2 diabetes mellitus and end-stage renal disease seldom are selected for renal transplantation. Thus, information on transplantation results from controlled studies in this high-risk category of patients is scarce. We have compared the results of kidney transplantations in type 2 diabetic patients with carefully matched non-diabetic subjects. METHODS: All first cadaveric renal transplants performed in type 2 diabetic patients from January 1, 1988 to December 31, 1998 in our centre were included. Non-diabetic controls were individually matched with diabetic patients with respect to year of transplantation, sex, age, selected immunological parameters, and graft cold ischaemia. RESULTS: We included 64 type 2 diabetic and 64 non-diabetic patients who were followed for a mean period of 37+/-27 and 41+/-31 months, respectively, after renal transplantation. Patient survival at 1 and 5 years post-transplant was 85 and 69 vs 84 and 74% (P=0.43, NS), while graft survival rates censored for patient death were 84 and 77 vs 82 and 77% for diabetic and non-diabetic subjects, respectively (P=0.52, NS). With graft survival results not censored for death with functioning graft, no significant change was seen (diabetic vs non-diabetic group: 77 and 54 vs 73 and 61%, P=0.19, NS). Age, but not the presence of diabetes, was the only factor significantly affecting patient survival when both patient groups were pooled. With regard to post-transplant complications requiring hospitalization, there was a significant difference only in the number of patients who had amputations (diabetic vs non-diabetic group: 8 vs 0, P=0.01). CONCLUSIONS: Patient and graft survival after kidney transplantation was similar in type 2 diabetic and matched non-diabetic subjects, with more amputations occurring in the diabetic group. Thus, at a single-centre level renal transplantation results almost equivalent to those in non-diabetic patients may be achieved in type 2 diabetes mellitus.     

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.     

Irbesartan is projected to be cost and life saving in a Spanish setting for treatment of patients with type 2 diabetes, hypertension, and microalbuminuria

OBJECTIVES: The purpose of this study was to project the cumulative incidence of end-stage renal disease (ESRD), life expectancy, and costs in a Spanish setting of treating patients with diabetes, hypertension, and microalbuminuria with either standard hypertension treatment alone or standard hypertension treatment plus irbesartan 300 mg daily. METHODS: A peer-reviewed, published Markov model that simulated progression from microalbuminuria to nephropathy, doubling of serum creatinine, ESRD, and all-cause mortality in patients with hypertension, type 2 diabetes, and microalbuminuria was adapted to a Spanish setting. Two strategies were compared: (1) irbesartan versus (2) standard hypertension care with comparable blood pressure control; both began in diabetic hypertensive subjects with microalbuminuria. Cumulative incidence of ESRD, costs, and life expectancy were projected for a hypothetical cohort of 1000 subjects. Future costs and life expectancy were discounted at 3% yearly. A 25-year time horizon and third party payer perspective were used. RESULTS: When compared to standard blood pressure control, irbesartan was projected to reduce the cumulative incidence of ESRD from (mean +/- standard deviation) 24 +/- 1% to 9 +/- 2%, save 11,082 +/- 2,996 euro, and add 1.40 +/- 0.27 life years per treated patient. The superiority of irbesartan over standard care was robust under a wide range of plausible assumptions. CONCLUSION: Treating patients with hypertension, microalbuminuria, and type 2 diabetes with irbesartan was projected to reduce the incidence of ESRD, extend life, and reduce costs.     

ACE-inhibitor use and the long-term risk of renal failure in diabetes

The incidence of end-stage renal disease (ESRD) owing to diabetes has continued to increase despite the extensive use of angiotensin-converting enzyme (ACE) inhibitors to prevent diabetic nephropathy, primarily from evidence of short-term effectiveness. We assessed the long-term effect of ACE inhibitors on the risk of ESRD. We formed a population-based cohort of all diabetic patients treated with antihypertensive drugs in the Province of Saskatchewan, Canada, between 1982 and 1986. The patients were followed up to the end of 1997 to identify cases of end-stage renal failure. A nested case-control analysis was used with the controls matched to each case on age, diabetes type, and duration of follow-up. The cohort comprised 6102 subjects, of which the 102 cases who developed end-stage renal failure were matched to 4129 controls. Relative to thiazide diuretic use, the adjusted rate ratio of end-stage renal failure associated with the use of ACE inhibitors was 2.5 (95% confidence interval 1.3-4.7), whereas it was 0.8 (95% confidence interval 0.5-1.4) for beta-blockers and 0.7 (95% confidence interval 0.4-1.3) for calcium antagonists. The rate ratio of end-stage renal failure with the use of ACE inhibitors was 0.8 (95% confidence interval 0.3-2.5) during the first 3 years of follow-up, but increased to 4.2 (95% confidence interval 2.0-9.0) after 3 years. ACE-inhibitor use does not appear to decrease the long-term risk of end-stage renal failure in diabetes. Our data suggest instead that ACE inhibitors might actually increase this risk, which may possibly contribute to the continued increasing incidence of ESRD owing to diabetes.     

Patient and technique survival of diabetics on peritoneal dialysis: one-center's experience and review of the literature

BACKGROUND: Diabetes is the leading cause of end-stage renal disease (ESRD). This retrospective study investigated the long-term patient and technique survival and sought to identify the predictors of mortality in diabetic patients receiving PD. METHODS: Patients, aged 17 years or more who commenced home PD between January 31, 1994, and December 31, 2001 were included. Clinical data were available for 358 patients out of 418 total patients who started PD during this period. They were followed until cessation of PD, death, or to January 31, 2003. Survival probabilities were generated according to the Kaplan-Meier method, and multivariate Cox proportional hazards models were used to assess predictors of survival. RESULTS: A total of 358 patients were enrolled in the study. Among them, 139 patients (38.8%) were diabetics. The 1-, 2-, 3- and 5-year patient survival rates were 91%, 76%, 66% and 47% in diabetics and 94%, 89%, 84% and 69% in non-diabetics, respectively. Median actuarial patient survival for diabetic patients (51.8 months; 95% CI 36.0 a 67.5 months) was significantly shorter than that of non-diabetic patients (log rank 14.117, p < 0.001). Death-censored technique survival rates at 1-, 2-, 3- and 5-year were 90%, 83%, 67% and 58% in diabetic, and 94%, 87%, 77% and 70% in non-diabetic patients, respectively. Similar to patient survival, the median technique survival time was significantly shorter for diabetic patients (63.9 months; 95% CI 35.7 - 92.2 months) than that of non-diabetic patients (log rank 4.884, p = 0.027). Multivariate Cox regression analysis showed that advancing age was the only independent predictor of death in the diabetic patients, whereas higher age and wider pulse pressure were associated with mortality in non-diabetic patients. CONCLUSION: Long-term patient and technique survival for diabetic patients on PD seem to be improved compared to our previous report and other studies. The mortality of diabetic patients was predicted predominantly by advancing age. PD remains a viable form of long-term renal replacement therapy for diabetic patients with ESRD.