Kidney Function as Risk Factor and Predictor of Cardiovascular Outcomes and Mortality Among Older Adults.

RATIONALE & OBJECTIVE: Estimated glomerular filtration rate (eGFR) and urinary albumin-creatinine ratio (UACR) are associated with cardiovascular events in the general population but their utility among older adults is unclear. We investigated the associations of eGFR and UACR with stroke, myocardial infarction (MI), and death among older adults. STUDY DESIGN: Population-based cohort study. SETTING & PARTICIPANTS: 1,581 participants (aged≥70 years) in the Berlin Initiative Study (BIS) without prior stroke or MI. EXPOSURES & PREDICTORS: Serum creatinine- and cystatin C-based eGFR, UACR categories, and measured GFR (n=436). OUTCOMES: Stroke, MI, and all-cause mortality. ANALYTICAL APPROACH: HRs and 95% CIs derived from multivariable-adjusted Cox proportional hazards models for association analyses. Net reclassification improvement (NRI) and C statistic differences comparing the predictive benefit of kidney measures with a traditional cardiovascular risk model. RESULTS: During a median follow-up of 8.2 years, 193 strokes, 125 MIs, and 531 deaths occurred. Independent of UACR, when GFR was estimated using the creatinine- and cystatin C-based BIS equation, eGFR of 45 to 59mL/min/1.73m2 (vs eGFR>60mL/min/1.73m2) was associated with stroke (HR, 2.23; 95% CI, 1.55-3.21) but not MI or all-cause mortality. For those with eGFR<45mL/min/1.73m2, the HRs were 1.99 (95% CI, 1.23-3.20) for stroke, 1.38 (95% CI, 0.81-2.36) for MI, and 1.57 (95% CI, 1.20-2.06) for mortality. Compared with UACR<30mg/g, UACR of 30 to 300mg/g was not associated with stroke (HR, 0.91; 95% CI, 0.63-1.33) but was associated with MI (HR, 1.65; 95% CI, 1.09-2.51) and all-cause mortality (HR, 1.63; 95% CI, 1.34-1.98). Prediction analysis for stroke showed significant positive NRI for eGFR calculated using the cystatin C-based Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation and the creatinine- and cystatin C-based BIS and Full Age Spectrum equations. UACR demonstrated significant positive NRIs for MI and mortality. LIMITATIONS: eGFR and UACR categorization based on single assessments; lack of cause-specific death data. CONCLUSIONS: eGFR of 45 to 59mL/min/1.73m2 without albuminuria was associated with stroke but not MI or all-cause mortality in older adults. In contrast, UACR of 30 to 300mg/g was associated with MI and all-cause mortality but not with stroke. Furthermore, cystatin C-based eGFR improved risk prediction for stroke in this cohort of older adults.

Prevalence of reduced kidney function and albuminuria in older adults: the Berlin Initiative Study.

BACKGROUND: Although CKD is said to increase among older adults, epidemiologic data on kidney function in people ≥70 years of age are scarce. The Berlin Initiative Study (BIS) aims to fill this gap by evaluating the CKD burden in older adults. METHODS: The BIS is a prospective population-based cohort study whose participants are members of Germany's biggest insurance company. This cross-sectional analysis (i) gives a detailed baseline characterization of the participants, (ii) analyses the representativeness of the cohort's disease profile, (iii) assesses GFR and albuminuria levels across age categories, (iv) associates cardiovascular risk factors with GFR as well as albuminuria and (v) compares means of GFR values according to different estimating equations with measured GFR. RESULTS: A total of 2069 participants (52.6% female, mean age 80.4 years) were enrolled: 26.1% were diabetic, 78.8% were on antihypertensive medication, 8.7% had experienced a stroke, 14% a myocardial infarction, 22.6% had cancer, 17.8% were anaemic and 26.5% were obese. The distribution of comorbidities in the BIS cohort was very similar to that in the insurance 'source population'. Creatinine and cystatin C as well as the albumin:creatinine ratio (ACR) increased with increasing age. After multivariate adjustments, reduced GFR and elevated ACR were associated with most cardiovascular risk factors. The prevalence of a GFR <60 mL/min/1.73 m 2 ranged from 38 to 62% depending on the estimation equation used. CONCLUSIONS: The BIS is a very well-characterized, representative cohort of older adults. Participants with an ACR ≥30 had significantly higher odds for most cardiovascular risk factors compared with an ACR <30 mg/g. Kidney function declined and ACR rose with increasing age.

International Network of Chronic Kidney Disease cohort studies (iNET-CKD): a global network of chronic kidney disease cohorts.

BACKGROUND: Chronic kidney disease (CKD) is a global health burden, yet it is still underrepresented within public health agendas in many countries. Studies focusing on the natural history of CKD are challenging to design and conduct, because of the long time-course of disease progression, a wide variation in etiologies, and a large amount of clinical variability among individuals with CKD. With the difference in health-related behaviors, healthcare delivery, genetics, and environmental exposures, this variability is greater across countries than within one locale and may not be captured effectively in a single study. METHODS: Studies were invited to join the network. Prerequisites for membership included: 1) observational designs with a priori hypotheses and defined study objectives, patient-level information, prospective data acquisition and collection of bio-samples, all focused on predialysis CKD patients; 2) target sample sizes of 1,000 patients for adult cohorts and 300 for pediatric cohorts; and 3) minimum follow-up of three years. Participating studies were surveyed regarding design, data, and biosample resources. RESULTS: Twelve prospective cohort studies and two registries covering 21 countries were included. Participants age ranges from >2 to >70 years at inclusion, CKD severity ranges from stage 2 to stage 5. Patient data and biosamples (not available in the registry studies) are measured yearly or biennially. Many studies included multiple ethnicities; cohort size ranges from 400 to more than 13,000 participants. Studies' areas of emphasis all include but are not limited to renal outcomes, such as progression to ESRD and death. CONCLUSIONS: iNET-CKD (International Network of CKD cohort studies) was established, to promote collaborative research, foster exchange of expertise, and create opportunities for research training. Participating studies have many commonalities that will facilitate comparative research; however, we also observed substantial differences. The diversity we observed across studies within this network will be able to be leveraged to identify genetic, behavioral, and health services factors associated with the course of CKD. With an emerging infrastructure to facilitate interactions among the investigators of iNET-CKD and a broadly defined research agenda, we are confident that there will be great opportunity for productive collaborative investigations involving cohorts of individuals with CKD.

Prevalence and correlates of gout in a large cohort of patients with chronic kidney disease: the German Chronic Kidney Disease (GCKD) study.

BACKGROUND: Reduced kidney function is a risk factor for hyperuricaemia and gout, but limited information on the burden of gout is available from studies of patients with chronic kidney disease (CKD). We therefore examined the prevalence and correlates of gout in the large prospective observational German Chronic Kidney Disease (GCKD) study. METHODS: Data from 5085 CKD patients aged 18-74 years with an estimated glomerular filtration rate (eGFR) of 30-<60 mL/min/1.73 m(2) or eGFR ≥60 and overt proteinuria at recruitment and non-missing values for self-reported gout, medications and urate measurements from a central laboratory were evaluated. RESULTS: The overall prevalence of gout was 24.3%, and increased from 16.0% in those with eGFR ≥60 mL/min/1.73 m(2) to 35.6% in those with eGFR <30. Of those with self-reported gout, 30.7% of individuals were not currently taking any gout medication and among gout patients on urate lowering therapy, 47.2% still showed hyperuricaemia. Factors associated with gout were serum urate, lower eGFR, advanced age, male sex, higher body mass index and waist-to-hip ratio, higher triglyceride and C-reactive protein (CRP) concentrations, alcohol intake and diuretics use. While lower eGFR categories showed significant associations with gout in multivariable-adjusted models (prevalence ratio 1.46 for eGFR <30 compared with eGFR ≥60, 95% confidence interval 1.21-1.77), associations between gout and higher urinary albumin-to-creatinine ratio in this CKD population were not significant. CONCLUSIONS: Self-reported gout is common among patients with CKD and lower GFR is strongly associated with gout. Pharmacological management of gout in patients with CKD is suboptimal. Prospective follow-up will show whether gout and hyperuricaemia increase the risk of CKD progression and cardiovascular events in the GCKD study.

An efficient approach for glomerular filtration rate assessment in older adults.

AIMS: Assessment of glomerular filtration rate (GFR) is crucial because the GFR value defines the stage of chronic kidney disease and determines the adjustment of drug dosage. The aim was to investigate a new method for the accurate determination of GFR in older adults based on the combination of an exogenous filtration marker, iohexol, and an endogenous marker, serum creatinine or cystatin C. METHODS: We combined variables for the estimation of GFR with a reduced set of measurements of the marker iohexol. In a population-based sample of 570 subjects (≥70 years old) from the Berlin Initiative Study (BIS), we investigated the following: (i) the BIS1 and BIS2 equations based on age, gender and serum creatinine with or without serum cystatin C; (ii) equations based on one or two iohexol measurements; and (iii) equations based on the combination of variables from BIS1 or BIS2 with iohexol measurements. The reference standard was based on eight iohexol measurements. The cut-off value of 60 ml min(-1) (1.73 m)(-2) was chosen to assess accuracy. Equations were constructed using a learning sample (n = 285) and an independent validation sample (n = 285). RESULTS: Misclassification rates were 17.2% (BIS1), 11.6% (BIS2), 14.7% [iohexol measurement at 240 min (iohexol240 )], 7.0% (iohexol240 combined with variables included in BIS1) and 6.7% (iohexol240 combined with variables included in BIS2). Misclassification rates did not decrease significantly after inclusion of two or three iohexol measurements. CONCLUSIONS: Combined strategies for the determination of GFR lead to a relevant increase of diagnostic validity.

Two novel equations to estimate kidney function in persons aged 70 years or older.

BACKGROUND: In older adults, current equations to estimate glomerular filtration rate (GFR) are not validated and may misclassify elderly persons in terms of their stage of chronic kidney disease. OBJECTIVE: To derive the Berlin Initiative Study (BIS) equation, a novel estimator of GFR in elderly participants. DESIGN: Cross-sectional. Data were split for analysis into 2 sets for equation development and internal validation. SETTING: Random community-based population of a large insurance company. PARTICIPANTS: 610 participants aged 70 years or older (mean age, 78.5 years). INTERVENTION: Iohexol plasma clearance measurement as gold standard. MEASUREMENTS: GFR, measured as the plasma clearance of the endogenous marker iohexol, to compare performance of existing equations of estimated GFR with measured GFR of the gold standard; estimation of measured GFR from standardized creatinine and cystatin C levels, sex, and age in the learning sample; and comparison of the BIS equations (BIS1: creatinine-based; BIS2: creatinine- and cystatin C-based) with other estimating equations and determination of bias, precision, and accuracy in the validation sample. RESULTS: The new BIS2 equation yielded the smallest bias followed by the creatinine-based BIS1 and Cockcroft-Gault equations. All other equations considerably overestimated GFR. The BIS equations confirmed a high prevalence of persons older than 70 years with a GFR less than 60 mL/min per 1.73 m2 (BIS1, 50.4%; BIS2, 47.4%; measured GFR, 47.9%). The total misclassification rate for this criterion was smallest for the BIS2 equation (11.6%), followed by the cystatin C equation 2 (15.1%) proposed by the Chronic Kidney Disease Epidemiology Collaboration. Among the creatinine-based equations, BIS1 had the smallest misclassification rate (17.2%), followed by the Chronic Kidney Disease Epidemiology Collaboration equation (20.4%). LIMITATION: There was no validation by an external data set. CONCLUSION: The BIS2 equation should be used to estimate GFR in persons aged 70 years or older with normal or mild to moderately reduced kidney function. If cystatin C is not available, the BIS1 equation is an acceptable alternative. PRIMARY FUNDING SOURCE: Kuratorium für Dialyse und Nierentransplatation (KfH) Foundation of Preventive Medicine.

Age and the Course of GFR in Persons Aged 70 and Above.

BACKGROUND AND OBJECTIVES: In older adults, data on the age-related course of GFR are scarce, which might lead to misjudgment of the clinical relevance of reduced GFR in old age. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: To describe the course of eGFR in older adults and derive reference values in population-based individuals, we used the longitudinal design of the Berlin Initiative Study (BIS) with a repeated estimation of GFR over a median of 6.1 years of follow-up. In 2069 community-dwelling older individuals (mean inclusion age 80 years, range 70-99), GFR was estimated biennially with the BIS-2 equation, including standardized creatinine and cystatin C levels, sex, and age. We described the crude and adjusted course using a mixed-effects model and analyzed the influence of death on the GFR course applying joint models. GFR slopes were compared using GFR equations on the basis of creatinine and/or cystatin C. RESULTS: We observed a decreasing, thus nonlinear, eGFR decline with increasing age in a population of old adults. The estimated 1-year slope for ages 75 and 90 diminished for men from -1.67 to -0.99 and for women from -1.52 to -0.97. The modeled mean eGFR for men aged ≥79 and women ≥78 was below 60 ml/min per 1.73 m2. Multivariable adjustment attenuated slopes only minimally. Taking death into account by applying joint models did not alter the nonlinear eGFR decline. Using eGFR equations on the basis of creatinine only showed linear slope patterns in contrast to nonlinear patterns for equations including cystatin C. CONCLUSIONS: The eGFR decline depended on sex and age and changed only marginally after multivariable adjustment but decelerated with increasing age. Equations including cystatin C demonstrated a nonlinear slope challenging the previously assumed linearity of the decline of eGFR in old age.

The Berlin initiative study: the methodology of exploring kidney function in the elderly by combining a longitudinal and cross-sectional approach.

Epidemiologic data on incidence, prevalence and risk factors for chronic kidney disease (CKD) and its progression to kidney failure in people > or =70 years are scarce. This lack may have two reasons: First, the issue has only recently gained importance by the changing demographics characterized by an aging society. Secondly, a validated method for estimating kidney function in terms of glomerular filtration rate (GFR) in the elderly is still lacking. In this paper we describe the methodology of a combined longitudinal and cross-sectional approach of a population based study which will start in January 2010. The aims of the study are to identify prevalent and incident cases of CKD as well as co-morbidities and associated risk factors for progression of disease in this specific age-group. To assess prevalence, a new GFR estimation equation is to be developed. In a longitudinal approach a population based, age stratified sample of 2,000 subjects > or =70 years will be randomly drawn from a data base of a large health insurance company. Interview, physical examination, and preliminary estimation of GFR, based on serum creatinine will be performed. The entire cohort will be followed over the course of 2 years. In a cross-sectional approach a subsample of 600 subjects will be defined based on preliminary GFR values. Kidney function will be determined by measuring plasma clearance of an exogenous filtration marker (Iohexol). A new GFR-equation will be developed and validated using Iohexol clearance as gold standard to estimate GFR accurately and precisely. Data of 2,000 subjects will be used to estimate prevalence of CKD.

Educational level as a determinant of access to and outcomes after kidney transplantation in the United States.

BACKGROUND: Disparities in access to kidney transplantation exist, yet few studies investigated educational level as a determinant of access to and outcomes after kidney transplantation. STUDY DESIGN: Prospective cohort study. SETTINGS & PARTICIPANTS: Nationally representative sample of incident US dialysis patients, in which 3,245 patients reported their educational level. PREDICTOR: Educational level, categorized as some high school, high school graduate, some college, and college graduate. OUTCOMES & MEASUREMENTS: Access to kidney transplantation was defined as time from first dialysis treatment to: (1) the day of being wait-listed and (2) first kidney transplantation. Outcomes after kidney transplantation were: (3) all-cause mortality and graft failure ([4] all-cause and [5] death censored). Using Cox regression, we studied the relationship between predialysis educational level and access to and outcomes after kidney transplantation. RESULTS: During follow-up, 692 patients were wait-listed and 670 underwent kidney transplantation. Of those, 164 died and 241 lost their allograft (121 from nondeath causes). After multivariate adjustment, college graduates experienced 3 times greater rates of wait-listing (hazard ratio, 2.81; 95% confidence interval, 2.21 to 3.58) or kidney transplantation (hazard ratio, 3.06; 95% confidence interval, 2.38 to 3.92) compared with patients without a high school degree (P for trend across educational level for both outcomes < 0.001). Although mortality was not associated with educational level, increased rates of death-censored allograft loss were observed with less education (P for trend = 0.03). LIMITATIONS: Not a randomized study. CONCLUSION: The latter finding is novel and important and requires confirmation. Its possible mechanisms (eg, adherence to immunosuppressants) warrant additional study.

Blood pressure measures and risk of chronic kidney disease in men.

BACKGROUND: High blood pressure (BP) has been associated with a decrease in kidney function. However, it remains unclear which BP measure best predicts impaired kidney function. METHODS: We compared systolic blood pressure (SBP), diastolic blood pressure (DBP), pulse pressure (PP) and mean arterial pressure (MAP) in predicting risk of chronic kidney disease (CKD). We prospectively followed 8093 male participants in the Physicians' Health Study, without a known history of kidney disease at baseline, who provided BP values on the baseline and 24-month questionnaires, and for whom we had creatinine measures after 14 years of follow-up. Reported BP was averaged from both questionnaires. The main outcome was CKD, defined as an estimated glomerular filtration rate <60 mL/min/1.73 m(2). We used multivariable-adjusted logistic regression to evaluate the association between BP measures and CKD and compared models using the likelihood ratio test. RESULTS: After 14 years of follow-up, 1039 men (12.8%) had CKD. An increase of 10 mmHg had corresponding multivariable-adjusted odds ratios (95% confidence intervals) of 1.11 (1.03-1.19) for SBP, 1.11 (1.00-1.23) for MAP, 1.14 (1.05-1.25) for PP and 1.05 (0.93-1.17) for DBP. SBP and PP were the strongest predictors of chronic kidney function, with equal predictive abilities. Combining BP measures did not add significantly to the prediction. CONCLUSIONS: Increases in SBP, PP and MAP were significantly associated with CKD. SBP may be the most clinically useful predictor of CKD, since no further calculations are required.

Prognostic associations between lipid markers and outcomes in kidney transplant recipients.

BACKGROUND: Hyperlipidemia is highly prevalent in kidney transplant recipients, but the prognostic significance for mortality and allograft survival in these patients has not been established sufficiently. METHODS: We prospectively enrolled 733 kidney transplant recipients between 1996 and 1998. Clinical information was collected and blood was drawn for laboratory evaluation. Information on the previous transplantation procedures and organ donor were obtained from the Eurotransplant Foundation database. We used the Austrian Dialysis and Transplantation Registry for follow-up. Using multivariate proportional hazard regression, independent relations of fasting plasma triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol levels to risk for death from any cause and risk for kidney allograft loss were examined. RESULTS: During a median follow-up of 6.1 years, 154 patients died and 260 kidney allografts were lost. After careful multivariate adjustment, there were no significant associations between TG and TC levels and patient mortality. Patients in the highest quartile of TG and TC levels had no difference in risks for mortality compared with patients in the lowest quartile of these parameters (hazards ratio, 0.81; 95% confidence interval, 0.51 to 1.28; hazards ratio, 0.68; 95% confidence interval, 0.42 to 1.10, respectively). Similarly, no associations were found with allograft loss. Further analysis of associations between high-density lipoprotein cholesterol or low-density lipoprotein cholesterol categories and patient mortality or kidney allograft loss did not show associations. CONCLUSION: Elevated levels of TC or its subfractions and elevated TG levels are not associated with increased risk for patient mortality or allograft loss in these kidney transplant recipients.

Alcohol consumption and the risk of renal dysfunction in apparently healthy men.

BACKGROUND: Moderate alcohol consumption has been consistently associated with beneficial health effects on cardiovascular disease. In contrast, the association between alcohol consumption and renal dysfunction is less clear. METHODS: We conducted a prospective cohort study of 11,023 initially healthy men who provided blood samples 14 years after a baseline assessment of alcohol consumption. We categorized alcohol consumption into 1 or fewer, 2 to 4, 5 to 6, and 7 or more drinks per week. The main outcome measures were elevated creatinine levels (defined as > or = 1.5 mg/dL [> or = 133 micromol/L]) and reduced estimated glomerular filtration rates (defined as < or = 55 mL/min). We used logistic regression to calculate multivariable-adjusted odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: After 14 years, 473 men (4.3%) had elevated creatinine levels and 1296 (11.8%) had reduced glomerular filtration rates. Compared with men who consumed no more than 1 drink per week, men who consumed 2 to 4 drinks weekly had a multivariable-adjusted OR of 1.04 (95% CI, 0.81-1.32), men who consumed 5 to 6 drinks per week had an OR of 0.92 (95% CI, 0.68-1.25), and men who consumed at least 7 drinks weekly had an OR of 0.71 (95% CI, 0.55-0.92) (P = .01 for trend across categories). Similar associations were observed between alcohol consumption and decreased glomerular filtration rates. Hypertension, diabetes mellitus, and cholesterol level did not attenuate these effects. CONCLUSIONS: In this large cohort of apparently healthy men, alcohol consumption was not associated with an increased risk of renal dysfunction. Instead, these data suggest an inverse relationship between moderate alcohol consumption and the risk of renal dysfunction.

Smoking and the risk of hemorrhagic stroke in men.

BACKGROUND AND PURPOSE: Smoking is an established risk factor for ischemic stroke and subarachnoid hemorrhage (SAH), but the impact of smoking on intracerebral hemorrhage (ICH) is less clear. METHODS: Prospective cohort study among 22,022 US male physicians participating in the Physicians' Health Study. Incidence of stroke was measured by self-report and confirmed by medical record review. We used Cox proportional-hazards models to evaluate the association of smoking with risk of total hemorrhagic stroke, ICH, and SAH. We categorized smoking into 4 groups: never, past, or current smokers of <20 or of >or=20 cigarettes per day. RESULTS: During 17.8 years of follow-up, 108 ICHs and 31 SAHs occurred. Never smokers and past smokers had equal rates of ICH and SAH. Current smokers of <20 cigarettes per day had multivariable-adjusted relative risks of 1.65 (95% CI, 0.61 to 4.50) for total hemorrhagic stroke, 1.60 (95% CI, 0.50 to 5.07) for ICH, and 1.75 (95% CI, 0.24 to 13.09) for SAH when compared with never smokers. Current smokers of >or=20 cigarettes had relative risks of 2.36 (95% CI, 1.38 to 4.02) for total hemorrhagic stroke, 2.06 (95% CI, 1.08 to 3.96) for ICH, and 3.22 (95% CI, 1.26 to 8.18) for SAH when compared with never smokers. CONCLUSIONS: This prospective study suggests an increased risk of total hemorrhagic stroke, ICH, and SAH in current cigarette smokers with a graded increase in risk that depended on how many cigarettes were smoked. The effect of smoking on ICH is of about the same magnitude as the effect of smoking on ischemic stroke. Our results add to the multiple health benefits that can be accrued by abstaining from cigarette smoking.

Knowledge and attitude regarding organ donation among medical students and physicians.

BACKGROUND: There is a discrepancy between demand and supply of donor organs for kidney transplantation. Health care providers can influence the willingness to donate or hold an organ donor card. It is unclear how educated current and future health care professionals are about organ donation and what constitutes their attitude toward this topic. METHODS: The authors conducted a cross-sectional survey among 1136 medical students and physicians to evaluate the knowledge about and attitude toward organ donation and transplantation at a large academic medical center in Germany. The authors used a 28-item questionnaire that included items on knowledge, attitude, and demographics. RESULTS: Only 8% of the respondents felt sufficiently prepared for approaching relatives of potential organ donors. Knowledge about and attitude toward organ donation were highly associated with increasing level of medical education. In multivariate analyses, knowledge (odds ratio [OR], 1.17; 95% confidence interval [CI], 1.08-1.25), attitude (OR, 1.03; 95% CI, 1.02-1.04), and level of education (OR for preclinical students, 0.39; 95% CI, 0.20-0.76 compared with physicians) were significantly associated with the likelihood of holding an organ donor card, whereas age, gender, and personal experience with renal replacement therapy were not. CONCLUSIONS: Higher medical education is associated with greater knowledge about and a more positive attitude toward organ donation. Health care professionals with a higher education level are more likely to hold an organ donor card and also feel more comfortable in approaching relatives of potential organ donors. Educating health care professionals about the organ donation process appears to be an important factor in maximizing the benefits from the limited organ donor pool.

Access to kidney transplantation among the elderly in the United States: a glass half full, not half empty.

BACKGROUND AND OBJECTIVES: Few elderly ESRD patients are ever wait-listed for deceased-donor transplantation (DDTX), and waiting list outcomes may not reflect access to transplantation in this group. Our objective was to determine longitudinal changes in access to transplantation among all elderly patients with ESRD, not just those wait-listed for DDTX. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Using data from the US Renal Data System, we determined changes in the adjusted likelihood of transplantation from any donor source as an indicator of access to transplantation among all incident ESRD patients aged 60 to 75 years between 1995 and 2006. RESULTS: Access to transplantation doubled between 1995 and 2006 despite an apparent decrease in the likelihood of DDTX after wait-listing. A threefold increase in the likelihood of living-donor transplantation, including a 1.5-fold increase in living-donor transplantation after wait-listing, was a key factor that led to increased access to transplantation. When a lead-time bias related to the increased practice of placing patients on the waiting list before dialysis initiation in more recent years was accounted for, there was no decrease in the likelihood of DDTX after wait-listing. The likelihood of receiving a DDTX after placement on the waiting list was maintained by a threefold increase in expanded-criteria-donor transplantation and a 26% reduction in the risk for death on the waiting list. CONCLUSIONS: Although transplantation remains infrequent, elderly patients were twice as likely to undergo transplantation in 2006 versus 1995. Elderly patients with ESRD should not be dissuaded from pursuing transplantation.

Prognostic associations of serum calcium, phosphate and calcium phosphate concentration product with outcomes in kidney transplant recipients.

Disturbances in calcium and phosphate metabolism have been linked to increased mortality in hemodialysis patients, but not in kidney transplant recipients (KTR). We enrolled 733 KTR from the Vienna General Hospital into this study. Detailed demographic, clinical, laboratory, and transplant-related information was collected at baseline. We used the Austrian Dialysis and Transplantation Registry for follow-up. Using multivariate proportional hazard regression, we examined the independent associations between serum calcium, serum phosphate, and calcium phosphate (CaPO(4)) product with the outcomes of death from any cause and kidney allograft loss. Over a median follow-up of >6 years, 154 patients died and 259 kidney allografts were lost. Associations with serum calcium, phosphate concentrations, and CaPO(4) product concentrations were found for allograft loss, but not for patient mortality. Patients in the highest quintile of phosphate concentration and CaPO(4) product had an increased risk for allograft loss compared with patients in the lowest quintile of these parameters (hazards ratio, HR = 2.15; 95% confidence interval, CI: 1.36-3.40 and HR = 1.72; 95% CI: 1.10-2.71, respectively). High calcium levels were associated with a reduced risk for allograft loss. Results were even more pronounced for death-censored allograft loss. High concentrations of serum phosphate and CaPO(4) product were associated with an increased risk for allograft loss in these KTR, whereas high serum calcium concentrations seemed to lower the risk.

A J-shaped association between high-sensitivity C-reactive protein and mortality in kidney transplant recipients.

In kidney transplant recipients (KTR), C-reactive protein (CRP) has been shown to be associated with increased mortality, but data on this association within the high-sensitivity (hs) range of CRP (<5 mg/l) are lacking. We prospectively studied 710 prevalent and stable KTR over >6 years. We thawed frozen plasma and measured baseline hs-CRP using an ultrasensitive assay. Detailed clinical and demographic baseline characteristics were available for study. We stratified patients by quartile of hs-CRP within the hs range (<5 mg/l), and also included KTRs whose hs-CRP was above the hs range (>5-10 and >10 mg/l). We used multivariate proportional hazards models to test for independent associations. After careful multivariate adjustment, we found a J-shaped association between hs-CRP and mortality. Compared with KTR whose hs-CRP was in the second lowest quartile of hs-CRP (0.06-1.26 mg/l), patients in the lowest quartile (<0.06 mg/l) had more than twice their mortality risk (HR = 2.07; 95% CI: 1.05-4.07), as did patients whose hs-CRP was > or =2.44 mg/l (all HRs >2.27). No association was found between hs-CRP and death-censored allograft loss. In contrast to the general population, the association between hs-CRP and mortality in KTRs is not linear, but J-shaped, suggesting that KTRs with very low hs-CRP may also be at increased risk of death.

Cholesterol and the risk of renal dysfunction in apparently healthy men.

Despite extensive knowledge about abnormal lipid patterns in patients with end-stage renal disease, the association between cholesterol and the development of renal dysfunction is unclear. We evaluated this association in a prospective cohort study among 4,483 initially healthy men participating in the Physicians' Health Study who provided blood samples in 1982 and 1996. Main outcome measures were elevated creatinine, defined as >/= 1.5 mg/dl (133 micromol/L), and reduced estimated creatinine clearance, defined as /= 240 mg/dl), HDL (<40 or >/= 40 mg/dl), total non-HDL cholesterol, and the ratio of total cholesterol to HDL. We used logistic regression to calculate age- and multivariable adjusted odds ratios as a measure for the relative risk. After 14 yr, 134 men (3.0%) had elevated creatinine and 244 (5.4%) had reduced creatinine clearance. The multivariable relative risk for elevated creatinine was 1.77 (95% confidence interval [CI], 1.10 to 2.86) for total cholesterol >/= 240 mg/dl, 2.16 (95% CI, 1.42 to 3.27) for HDL <40 mg/dl, 2.34 (95% CI, 1.34 to 4.07) for the highest quartile of total cholesterol/HDL ratio (>/= >6.8), and 2.16 (95% CI, 1.22 to 3.80) for the highest quartile of non-HDL cholesterol (>/= 196.1). Similar although smaller associations were observed between cholesterol parameters and reduced creatinine clearance. Elevated total cholesterol, high non-HDL cholesterol, a high ratio of total cholesterol/HDL, and low HDL in particular were significantly associated with an increased risk of developing renal dysfunction in men with an initial creatinine <1.5 mg/dl.