A population-based assessment of the familial component of chronic kidney disease mortality

BACKGROUND/AIM: While the familial nature of chronic kidney disease (CKD) has been recognized, it has primarily been defined from studies of first-degree relatives of selected sets of cases. The goal of this study is an evaluation of the familial clustering of end-stage renal disease (ESRD) and CKD mortality using a population-based genealogy of Utah. This is the first population-based analysis of the familial component of ESRD and non-ESRD CKD. METHODS: We have defined two distinct patient groups for this analysis, using individuals with death certificates in the Utah Population Database indicating ESRD (n = 192) and non-ESRD CKD (n = 335) as the cause of death. Two measures of familiality were used: (1) relative risk (RR) of CKD or ESRD death in relatives of cases and (2) an average relatedness statistic, i.e., the Genealogical Index of Familiality. RESULTS: The RR for dying with ESRD among the first-degree relatives of individuals dying with ESRD is estimated to be 10.1 (p = 0.0007, 95% confidence interval CI 2.76-25.95), but is not significantly elevated among second-degree relatives. The RR for dying with non-ESRD CKD among first- and second-degree relatives of individuals dying with non-ESRD CKD was 3.89 (p = 0.0051, 95% CI 1.43-8.46) and 3.11 (p = 0.04, 95% CI 0.85-7.95), respectively. The Genealogical Index of Familiality statistic demonstrated that the individuals dying with ESRD are significantly more related than expected in this population (p = 0.013); significant excess relatedness was also observed for individuals dying with non-ESRD CKD (p = 0.006), suggesting a familial component for both, with evidence for common environmental and genetic effects. CONCLUSION: The results of this analysis of individuals dying with ESRD and non-ESRD CKD supports a significant and independent familial component to both conditions, suggesting a heritable factor playing a role.     

Survival differences between peritoneal dialysis and hemodialysis among "large" ESRD patients in the United States

BACKGROUND: It has been hypothesized that peritoneal dialysis compared to hemodialysis may be less effective in large patients with end-stage renal disease (ESRD). METHODS: We tested this hypothesis in a cohort of 134,728 new ESRD patients who were initiated on dialysis from May 1, 1995 to July 31, 1997 using data from United States Renal Data System (USRDS). Cox regression models evaluated the association of body mass index (BMI) in quintiles (8.8-20.9, 20.9-23.5, 23.5-26.1, 26.1-30.0, 30.0-75.2 kg/m(2)) with mortality over 2 years in peritoneal dialysis and hemodialysis patients separately, while time-dependent models evaluated the relative risk (RR) of death by modality for each BMI quintile. RESULTS: For hemodialysis, the adjusted RR of death was greatest for patients with BMI 30.0 (RR = 0.97, 95% CI 0.96-0.99 for diabetic and RR = 0.97, 95% CI 0.95-0.98 for nondiabetic patients) compared with the referent (23.5-26.1; RR = 1.00). For peritoneal dialysis, the RR of death was also higher for patients with a BMI <20.9 (RR = 1.20, 95% CI 1.00-1.43 for diabetic and RR = 1.39, 95% CI 1.19-1.64 for nondiabetic patients) but no survival advantage was associated with higher BMI values. The RR of death (peritoneal dialysis/hemodialysis) for each BMI quintile was 0.99, 1.12, 1.26 (P < 0.01), 1.15 (P < 0.01), and 1.44 (P < 0.0001) for diabetic and were 1.07, 1.01, 0.96, 1.04, and 1.22 (P < 0.01) for nondiabetic patients, respectively. CONCLUSION: We conclude that body size modifies the impact of dialysis modality on mortality risk among new ESRD patients in the United States. The selection of hemodialysis over peritoneal dialysis was associated with a survival advantage in patients with large body habitus.     

Impact of dialysis modality on survival of new ESRD patients with congestive heart failure in the United States

BACKGROUND: It is hypothesized, but not proven, that peritoneal dialysis might be the optimal treatment for end-stage renal disease (ESRD) patients with established congestive heart failure (CHF) through better volume regulation compared with hemodialysis. METHODS: National incidence data on 107,922 new ESRD patients from the Center for Medicare and Medicaid Services (CMS) Medical Evidence Form were used to test the hypothesis that peritoneal dialysis was superior to hemodialysis in prolonging survival of patients with CHF. Nonproportional Cox regression models evaluated the relative hazard of death for patients with and without CHF by dialysis modality using primarily the intent-to-treat but also the as-treated approach. Diabetics and nondiabetics were analyzed separately. RESULTS: The overall prevalence of CHF was 33% at ESRD initiation. There were 27,149 deaths (25.2%), 5423 transplants (5%), and 3753 (3.5%) patients lost to follow-up over 2 years. Adjusted mortality risks were significantly higher for patients with CHF treated with peritoneal dialysis than hemodialysis [diabetics, relative risk (RR) = 1.30, 95% confidence interval (CI) 1.20 to 1.41; nondiabetics, RR = 1.24, 95% CI 1.14 to 1.35]. Among patients without CHF, adjusted mortality risk were higher only for diabetic patients treated with peritoneal dialysis compared with hemodialysis (RR = 1.11, 95% CI 1.02 to 1.21) while nondiabetics had similar survival on peritoneal dialysis or hemodialysis (RR = 0.97, 95% CI 0.91 to 1.04). CONCLUSION: New ESRD patients with a clinical history of CHF experienced poorer survival when treated with peritoneal dialysis compared with hemodialysis. These data suggest that peritoneal dialysis may not be the optimal choice for new ESRD patients with CHF perhaps through impaired volume regulation and worsening cardiomyopathy.     

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.     

Forearm reactive hyperemia and mortality in end-stage renal disease

BACKGROUND: Reports on the general population indicated that decreased endothelial-mediated vasodilation has a prognostic impact on cardiovascular (CV) morbidity and mortality. Flow-dependent vasodilation of conduit arteries and ischemia-induced forearm reactive hyperemia are impaired in end-stage renal disease (ESRD). Whether deterioration of vasodilator function in ESRD patients has a prognostic impact has not been documented. The aim of this study was to determine whether the impaired forearm postischemic vasodilation is an independent predictor of mortality in ESRD patients, independently from CV end-organ damages, which are usually associated with decreased vasodilatory response. METHODS: Common carotid artery intima-media thickness (CCA-IMT), aortic stiffness (pulse wave velocity-PWV), and LV mass (LVM) were determined for 78 stable ESRD patients on hemodialysis. Forearm postischemic vasodilation [flow debt repayment (FDR)] was measured by venous plethysmography. All-cause mortality served as the outcome variable over a median follow-up of 60 +/- 27 months. RESULTS: Twenty-four deaths occurred (16 of CV origin). According to Cox regression adjusted for age, CCA-IMT, LVM, and PWV, all-cause mortality was independently associated with decreased FDR (RR 0.69 for every 10% increase; 95% CI 0.56-0.85; P= 0.0006) and increased aortic PWV (RR 1.16 for 1 m/s increase; 95% CI 1.04-1.29; P= 0.0091). CONCLUSION: Our data indicate that lower postischemic forearm reactive hyperemia is associated with all-cause mortality of ESRD patients, independently of the presence of end-organ damage such as LVH or arteriosclerosis.     

Comparison of mortality risk for dialysis patients and cadaveric first renal transplant recipients in Ontario, Canada

In population-based studies, renal transplantation has been shown to improve survival compared to dialysis patients awaiting transplantation in the United States. However, dialysis mortality in the United States is higher than in Canada. Whether transplantation offers a survival advantage in regions where dialysis survival is superior to that in the United States is uncertain. This study examines a cohort of 1156 patients who started end-stage renal disease (ESRD) therapy and were wait-listed for cadaveric renal transplantation in the province of Ontario, Canada between January 1, 1990 and December 31, 1994. Patients were followed from wait-listing for renal transplant (n = 1156), to cadaveric first renal transplant (n = 722), to death, or to study end (December 31, 1995). The annual crude mortality rates for wait-listed dialysis patients and transplanted patients were 5.0 and 3.4%, respectively. In Cox proportional hazards models, mortality in wait-listed patients was associated with increased age and diabetes, but not time from onset of ESRD to wait-listing. Factors associated with death following transplantation include older age, diabetes, and longer time spent on the waiting list before transplantation. In a time-dependent Cox regression model, the relative risk of death after transplantation compared to dialysis varied in a time-dependent manner. Covariates associated with increased risk included older age, diabetes, and time from onset of ESRD to wait-listing. The average relative risk (RR) of dying was 2.91 (95% confidence interval [CI], 1.34 to 6.32) in the first 30 d after transplantation, but was significantly lower 1 yr after transplantation (RR 0.25; 95% CI, 0.14 to 0.42), indicating a beneficial long-term effect when compared to wait-listed dialysis patients. This long-term benefit was most evident in subgroups of patients with diabetes (RR 0.38; 95% CI, 0.17 to 0.87) and glomerulonephritis (RR 0.13; 95% CI, 0.04 to 0.39) as the cause of ESRD. The survival advantage associated with renal transplantation is evident in this cohort of patients with a lower wait-listed dialysis mortality than that reported previously in the United States. The magnitude of the treatment effect is consistent across studies.     

Prognostic importance of clinic and home blood pressure recordings in patients with chronic kidney disease

Blood pressure (BP) measured only in the clinic substantially misclassifies hypertension in patients with chronic kidney disease (CKD). The role of out-of-clinic recordings of BP in predicting end-stage renal disease (ESRD) and death in patients with CKD is unknown. A prospective cohort study was conducted in 217 Veterans with CKD. BP was measured at home and in the clinic by 'routine' and standardized methods. Patients were followed over a median of 3.5 years to assess the end points of total mortality, ESRD or the composite outcome of ESRD or death. Home BP was 147.0+/-21.4/78.3+/-11.6 mmHg and clinic BPs were 155.2+/-25.6/84.7+/-14.2 mmHg by standardized method and 144.5+/-24.2/75.4+/-14.7 mmHg by the 'routine' method. The composite renal end point occurred in 75 patients (34.5%), death in 52 patients (24.0%), and ESRD in 36/178 patients (20.2%). One standard deviation (s.d.) increase in systolic BP increased the risk of renal end point by 1.27 (95% confidence interval (CI) 1.01-1.60) for routine clinic measurement, by 1.69 (95% CI 1.32-2.17) for standardized clinic measurement and by 1.84 (95% CI 1.46-2.32) for home BP recording. One s.d. increase in home systolic BP increased the risk of ESRD by 1.74 (95% CI 1.04-2.93) when adjusted for standardized clinic systolic BP, proteinuria, estimated glomerular filtration rate, and other risk factors. In patients with CKD, BPs obtained at home are a stronger predictor of ESRD or death compared to BPs obtained in the clinic. Systolic home BP is an independent predictor for ESRD.     

Phenotypic and genotypic risk factors for cardiovascular events in an incident dialysis cohort

Cardiovascular disease (CVD) remains the major cause of death in patients with end-stage renal disease (ESRD). Traditional risk factors do not explain the high prevalence of CVD in this population, and other non-traditional cardiovascular (CV) risk markers have now been described. Therefore, the potential relationship between CVD and phenotypic and genotypic risk markers was investigated prospectively in incident dialysis patients cohort. The 279 patients (244 on hemodialysis, 35 on peritoneal dialysis) within the Diamant Alpin Dialysis Cohort Study were investigated. Phenotypic and genotypic parameters were determined at dialysis initiation, patients monitored over a 2-year period, and CV events (morbidity and mortality) recorded. Globally, 82 CV events occurred and 26 patients (9.3%) died from CVD, whereas 28 (10%) died from non-CV causes. Previous CV events were strongly predictive of CV events occurrence, whatever patients had had one (hazard ratio (HR) 2, 95% confidence intervals (CI) 1.1-3.5) or more (HR 3.9, 95% CI 2.1-7.1) CV accidents before starting dialysis. Both lipoprotein(a) (HR 1.67, 95% CI 1-2.5) and total plasma homocysteine at cutoff 30 micromol/l (HR 1.7, 95% CI 1.1-2.8) were independent predictors of CV events outcome. In the subgroup of patients with homocysteine < 30 micromol/l, methylenetetrahydrofolate reductase (MTHFR) TT was the sole biological parameter predictive of CV event outcome (HR 2.5, 95% CI 1.1-10, P = 0.03). ESRD patients who enter chronic dialysis with a previous CV event, high total homocysteinemia levels, or MTHFR 677TT genotype must be considered at high risk of incident CV events.     

The impact of early-diagnosed new-onset post-transplantation diabetes mellitus on survival and major cardiac events

The impact of early-diagnosed new-onset post-transplantation diabetes mellitus (PTDM) on cardiovascular (CV) disease is not well described. The objectives of the present prospective single-center observational study were to assess the long-term effects of early-diagnosed new-onset PTDM on major cardiac events (MCE; cardiac death or nonfatal acute myocardial infarction) and patient survival. Diabetic status and CV risk factors were assessed in 201 consecutive renal allograft recipients 3 months after transplantation (baseline) during a period of 16 months (1995-96). Follow-up data until January 1, 2004 were obtained from the Norwegian Renal Registry. The 8-year (range 7-9 years) cumulative incidence of MCEs was 7% (nine out of 138) in recipients without diabetes, 20% (seven out of 35) in patients with new-onset PTDM and 21% (six out of 28) in patients with diabetes mellitus before transplantation (DM). Proportional hazards regression analyses (forward stepwise regression) revealed that patients with PTDM had an approximately three-fold increased risk of MCEs as compared with nondiabetic patients (hazard ratio (HR)=3.27, 95% confidence interval (CI)=1.22-8.80, P=0.019). A total of 61 patients (30%) died. Eight-year patient survival was 80% in the nondiabetic group, 63% in the PTDM group and 29% in the DM group, respectively. Pretransplant diabetes (HR=5.09, 95% CI=2.60-9.96, P<0.001), age (HR=1.03, 95% CI=1.01-1.05, P=0.016), cytomegalovirus (CMV) infection (HR=2.66, 95% CI=1.27-5.53, P=0.009), and creatinine clearance (HR=0.98, 95% CI=0.96-1.00, P=0.046), but not PTDM (HR=1.20, 95% CI=0.58-2.49, P=0.621), were independent predictors of death in the multiple Cox regression model. Early-diagnosed PTDM is a predictor of MCEs, but not of all-cause mortality, the first 8 years after renal transplantation.     

HMG-CoA reductase inhibitors are associated with reduced mortality in ESRD patients.

BACKGROUND.: Patients with end-stage renal disease (ESRD) suffer from markedly higher rates of cardiovascular disease than the general population. Although therapy with 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors ("statins") has been demonstrated to reduce the mortality from cardiovascular disease in patients without ESRD, only 10% of patients on dialysis are treated with these medications by day 60 of ESRD. We determined whether the use of statins is associated with a reduction in cardiovascular-specific death and total mortality in ESRD patients. METHODS: Data were analyzed from the U.S. Renal Data System Dialysis Morbidity and Mortality Wave-2 study, a cohort of randomly selected patients who were initiating dialysis in 1996. Information about the use of statins as well as other baseline characteristics was abstracted from the patients' dialysis records by dialysis personnel. Cox proportional hazards models were developed to determine the association between use of statins at baseline and subsequent risk of mortality, with adjustment for known mortality risk factors. RESULTS: Follow-up data were available for 3716 patients through July 1998. At baseline, 362 (9.7%) of patients were using statins. These patients had a mortality rate of 143/1000 person-years, compared with a rate of 202/1000 person-years for patients not using statins. Statin use was independently associated with a reduced risk of total mortality [relative risk (RR)=0.68, 95% confidence interval (CI)=0.54, 0.87] as well as cardiovascular-specific mortality (RR=0.64, 95% CI=0.45, 0.91). In contrast, the use of fibrates was not associated with reduced mortality (RR=1.29). CONCLUSIONS: Statin use was associated with a reduction in cardiovascular-specific death and total mortality in patients on dialysis.     

Risk factors for hip fracture among patients with end-stage renal disease

BACKGROUND: Although bone disease is well described among end-stage renal disease (ESRD) patients, little attention has been paid to the occurrence of fracture. We sought to identify factors that are associated with hip fracture among ESRD patients. METHODS: Data from patients who participated in the United States Renal Data System Dialysis Morbidity and Mortality Study Wave 1 were used for this study. Hip fractures occurring among these patients between 1993 and 1996 were identified from Medicare claims data available from the United States Renal Data System. Cox proportional hazards models were used to estimate the risk of hip fracture associated with demographic and medical variables. RESULTS: Of the 4952 patients included in this analysis, 103 sustained a hip fracture. In the multivariate analysis, age (per increasing decade, RR = 1.40, 95% CI 1.20, 1.64), female gender (RR = 2.26, 95% CI 1.48, 3.44), race (blacks compared with whites, RR = 0.58, 95% CI 0.37, 0.91), body mass index (per 1 unit increase, RR 0.89, 95% CI 0.86, 0.93), and the presence of peripheral vascular disease (RR 1.94, 95% CI 1.29, 2.92) were independently associated with hip fracture. Serum intact parathyroid hormone (iPTH), aluminum, diabetes, and bicarbonate levels did not appreciably influence the risk of hip fracture. CONCLUSIONS: Demographic and other characteristics that predict risk of hip fracture in the population at large also do so in ESRD patients. However, we could identify no characteristics of ESRD or its treatment that were independently related to hip fracture incidence.     

Family history of end-stage renal disease among hemodialyzed patients in Poland

BACKGROUND: In previous reports of end-stage renal disease (ESRD) patients, family history of ESRD was associated with race, younger age, higher education levels and ESRD etiology. This study aimed to analyze how often Polish caucasian dialysis patients reported relatives with ESRD, and to evaluate which risk factors are associated with family history of ESRD. METHODS: 4808 ESRD patients provided data about renal disease etiology, diabetes and hypertensive status of first- and second-degree relatives, socioeconomic status and education level. RESULTS: Reported ESRD etiologies were: chronic glomerular disease, 19.4 %; diabetic nephropathy, 11.3%; interstitial nephritris, 11.2%; hypertension, 7.8%; polycystic kidney disease (PKD), 7.1%; other or no response, 40.0%. Positive ESRD family history was reported by 745 patients (15.5%); positive history of diabetes, 932 (19.4%); hypertension, 1904 (39%). Positive ESRD family history according to kidney disease etiology was: PKD, 53.1%; glomerulonephritis, 12%; diabetic nephropathy, 11.9%; hypertension, 11.8%; interstitial nephritis, 10.8%. PKD as ESRD etiology (odds ratio (OR) 8.06, 95% confidence interval (CI) 6.35-10.23, p < 0.0001), positive family history of diabetes (OR 1.64, 95% CI 1.34-1.99, p < 0.0001) and positive history of hypertension (OR 1.64, 95% CI 1.39-1.95, p < 0.0001), were independently associated with positive ESRD history. Patients with later ESRD onset had a less frequent positive ESRD family history: for ESRD < 45 yrs, 16% (OR 1.0); 45-64 yrs, 14.4% (OR 0.83, 95% CI 0.70-0.99); > or = 65 yrs, 9.2 % (OR 0.5, 95% CI 0.35-0.72). CONCLUSIONS: Results of our study strongly support the contention that familial predisposition contributes to ESRD development.     

The differential impact of risk factors on mortality in hemodialysis and peritoneal dialysis

BACKGROUND: While the survival ramifications of dialysis modality selection are still debated, it seems reasonable to postulate that outcome comparisons are not the same for all patients at all times. Trends in available data indicate the relative risk of death with hemodialysis (HD) compared to peritoneal dialysis (PD) varies by time on dialysis and the presence of various risk factors. This study was undertaken to identify key patient characteristics for which the risk of death differs by dialysis modality. METHODS: Analyses utilized incidence data from 398,940 United States Medicare patients initiating dialysis between 1995 and 2000. Proportional hazards regression identified the presence of diabetes, age, and the presence of comorbidity as factors that significantly interact with treatment modality. Stratifying by these factors, proportional and nonproportional hazards models were used to estimate relative risks of death [RR (HD:PD)]. RESULTS: Of the 398,940 patients studied, 11.6% used PD as initial therapy, 45% had diabetes mellitus (DM), 51% were 65 years or older, and 55% had at least one comorbidity. Among the 178,693 (45%) patients with no baseline comorbidity, adjusted mortality rates in nondiabetic (non-DM) patients were significantly higher on HD than on PD [age 18-44: RR (95% CI) = 1.24 (1.07, 1.44); age 45-64: RR = 1.13 (1.02, 1.25); age 65+: RR = 1.13 (1.05, 1.21)]. Among diabetic (DM) patients with no comorbidity, HD was associated with a higher risk of death among younger patients [age 18-44: RR = 1.22(1.05, 1.42)] and a lower risk of death among older patients [age 45-64: RR = 0.92 (0.85, 1.00); age 65+: RR = 0.86 (0.79, 0.93)]. Within the group of 220,247 (55%) patients with baseline comorbidity, adjusted mortality rates were not different between HD and PD among non-DM patients [age 18-44: RR = 1.19 (0.94, 1.50); age 45-64: RR = 1.01 (0.92, 1.11); age 65+: RR = 0.96 (0.91, 1.01)] and younger DM patients [age 18-44: RR = 1.10 (0.92, 1.32)], but were lower with HD among older DM patients with baseline comorbidity [age 45-64: RR = 0.82 (0.77, 0.87); age 65+: RR = 0.80 (0.76, 0.85)]. CONCLUSION: Valid mortality comparisons between HD and PD require patient stratification according to major risk factors known to interact with treatment modality. Survival differences between HD and PD are not constant, but vary substantially according to the underlying cause of ESRD, age, and level of baseline comorbidity. These results may help identify technical advances that will improve outcomes of patients on dialysis.     

Nocturnal blood pressure and 24-hour pulse pressure are potent indicators of mortality in hemodialysis patients

BACKGROUND: Cardiovascular (CV) complications are the leading cause of mortality in hemodialysis patients. The role of arterial hypertension on the prognosis of CV in hemodialysis patients is not as clear as in the general population. The purpose of this study was to investigate the prognostic role of ambulatory blood pressure (BP) on CV mortality in treated hypertensive hemodialysis patients. METHODS: Fifty-seven treated hypertensive hemodialysis patients (56.87 +/- 16.22 years, 30 men) were prospectively studied. All patients initially underwent an ambulatory BP monitoring between two dialysis sessions. The outcome event studied was CV death; kidney transplantation and deaths not related to CV disease were censored. RESULTS: The duration of follow-up was 34.4 +/- 20.39 months, during which 10 CV and 8 non-CV fatal events occurred. In the 10 patients who died from CV complications, age, previous CV events, ambulatory systolic BP, ambulatory pulse pressure (PP), and life-long smoking level were significantly higher, and the office diastolic BP was lower at the time of inclusion than in those who did not die from CV complications (N = 47). Based on Cox analysis and after adjustment for age, sex, and previous CV events, a low office diastolic BP [relative risk (RR) 0.49, 95% CI, 0.25 to 0.93, P = 0.03], an elevated 24-hour PP (RR 1.85, 95% CI, 1.28 to 2.65, P = 0.009), and an elevated nocturnal systolic BP (RR 1.41, 95% CI, 1.08 to 1.84, P = 0.01) were predictors of CV mortality (RR associated with a 10 mm Hg increase in BP and in PP). CONCLUSION: This study demonstrates that nocturnal BP and 24-hour PP are independent predictors of CV mortality in treated hypertensive hemodialysis patients. Randomized trials are needed to investigate whether nocturnal BP and 24-hour PP are superior to office BP as targets for antihypertensive therapy in this high-risk group.     

Familial risk of prostate cancer in Iceland

OBJECTIVE: To estimate the risk of prostate and other types of cancer among relatives of Icelandic men diagnosed with prostate cancer over a 5-year period. PATIENTS AND METHODS: The risk ratio (RR) was used to estimate the risk among relatives of 371 patients with prostate cancer, all of whom lived in Iceland and were diagnosed when alive over a 5-year interval (1983-7). Information on cancer incidence was obtained from the population-based Icelandic Cancer Registry, and information on families from a comprehensive genealogical database covering the population of Iceland. RESULTS: First-degree male relatives were at a 1.7-fold greater age-adjusted risk of prostate cancer (1832 men; 95% confidence interval, CI, 1.28-2.34). The risk was independent of proband's age at diagnosis. First-degree male relatives of patients who died from prostate cancer were at a statistically significantly greater risk of the disease (784 men; RR 2.17; 95% CI 1.34-3.53) and relatives of patients with incidental disease (T1a) were at a greater risk but not statistically significant so (261; RR 1.86; 95% CI 0.75-4.58). Female first-degree relatives were not at greater risk of breast cancer. The risk of kidney cancer was higher in first- and second-degree female relatives, with an RR (n, CI) of 2.50 (1780, 1.10-5.66) and 2.67 (5534, 1.04-6.81), respectively. The risk of kidney cancer was not statistically significantly greater in male relatives. CONCLUSION: Family history is a risk factor for prostate cancer in Icelandic men. The risk is potentially higher for relatives of patients who die from the disease. Female relatives are not at greater risk of breast cancer but they may be at greater risk of kidney cancer.     

Cause-specific Mortality Risks of Anesthesiologists

Background: The health-related effects of the operating room environment are unclear. The authors compared mortality risks of anesthesiologists to those of internal medicine physicians between 1979 and 1995.

Methods: The Physician Master File database, a listing of all US physicians, was used to identify anesthesiologists and general internists. The cohort of internists (n = 40,211) was a stratified random sample of all internists, frequency-matched to the cohort of anesthesiologists (n = 40,242) by gender, decade of birth, and US citizenship. The National Death Index was used to confirm death status and to determine specific causes of death. Mortality risks, adjusted for age, gender, and race, were compared using the Cox proportional hazards regression model.

Results: The standardized mortality ratios for all physicians were well below 1.0, except for suicide. The all-cause mortality ratios, and the risks of death caused by cancer and heart disease, did not differ between anesthesiologists and internists. Anesthesiologists had an increased risk of death from suicide (rate ratio [RR] = 1.45, 95% confidence interval [CI] = 1.07 - 1.97), drug-related death (RR = 2.79, 95% CI = 1.87 - 4.15), death from other external causes (RR = 1.53, 95% CI = 1.05 - 2.22), and death from cerebrovascular disease (RR = 1.39, 95% CI = 1.08 - 1.79). Male anesthesiologists had an increased risk of death from HIV (RR = 1.82, 95% CI = 1.09 - 3.02) and viral hepatitis (RR = 7.98, 95% CI = 1.0 - 63.84). Although the risk to anesthesiologists of drug-related deaths was highest in the first 5 years after medical school graduation, it remained increased over that of internists throughout the career.     

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.     

The Impact of Chronic Obstructive Pulmonary Disease and Smoking on Mortality and Kidney Transplantation in End-Stage Kidney Disease

Background: Chronic obstructive pulmonary disease (COPD) and tobacco use are leading causes of morbidity and mortality. The prevalence and clinical impact of COPD on mortality and kidney transplantation among patients who begin dialysis therapy is unclear. Methods: We explored the clinical impact of COPD and continued tobacco use on overall mortality and kidney transplantation in a national cohort study of US dialysis patients. National data on all dialysis patients (n = 769,984), incident between May 1995 and December 2004 and followed until October 31, 2006, were analyzed from the United States Renal Data System. Prevalence and period trends were determined while multivariable Cox regression evaluated relative hazard ratios (RR) for death and kidney transplantation. Results: The prevalence of COPD was 7.5% overall and increased from 6.7 to 8.1% from 1995-2004. COPD correlated significantly with older age, cardiovascular conditions, cancer, malnutrition, poor functional status, and tobacco use. Adjusted mortality risks were significantly higher for patients with COPD (RR = 1.20, 95% CI 1.18-1.21), especially among current smokers (RR = 1.28, 95% CI 1.25-1.32), and varied inversely with advancing age. In contrast, the adjusted risks of kidney transplantation were significantly lower for patients with COPD (RR = 0.47, 95% CI 0.41-0.54, for smokers and RR = 0.54, 95% CI 0.50-0.58, for non-smokers) than without COPD [RR = 0.72, 95% CI 0.70-0.75, for smokers and RR = 1.00 for non-smokers (referent category)]. Conclusions: Patients with COPD who begin dialysis therapy in the US experience higher mortality and lower rates of kidney transplantation, outcomes that are far worse among current smokers.     

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.     

Cause-specific mortality risks of anesthesiologists

BACKGROUND: The health-related effects of the operating room environment are unclear. The authors compared mortality risks of anesthesiologists to those of internal medicine physicians between 1979 and 1995. METHODS: The Physician Master File database, a listing of all US physicians, was used to identify anesthesiologists and general internists. The cohort of internists (n = 40,211) was a stratified random sample of all internists, frequency-matched to the cohort of anesthesiologists (n = 40,242) by gender, decade of birth, and US citizenship. The National Death Index was used to confirm death status and to determine specific causes of death. Mortality risks, adjusted for age, gender, and race, were compared using the Cox proportional hazards regression model. RESULTS: The standardized mortality ratios for all physicians were well below 1.0, except for suicide. The all-cause mortality ratios, and the risks of death caused by cancer and heart disease, did not differ between anesthesiologists and internists. Anesthesiologists had an increased risk of death from suicide (rate ratio [RR] = 1.45, 95% confidence interval [CI] = 1.07 - 1.97), drug-related death (RR = 2.79, 95% CI = 1.87 - 4.15), death from other external causes (RR = 1.53, 95% CI = 1.05 - 2.22), and death from cerebrovascular disease (RR = 1.39, 95% CI = 1.08 - 1.79). Male anesthesiologists had an increased risk of death from HIV (RR = 1.82, 95% CI = 1.09 - 3.02) and viral hepatitis (RR = 7.98, 95% CI = 1.0 - 63.84). Although the risk to anesthesiologists of drug-related deaths was highest in the first 5 years after medical school graduation, it remained increased over that of internists throughout the career. CONCLUSIONS: Substance abuse and suicide represent significant occupational hazards for anesthesiologists. New methods to combat substance abuse among anesthesiologists should be developed.