Chronic kidney disease: common, harmful, and treatable--World Kidney Day 2007.
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Biomedical subjects
Publications and source records attributed to Allan J Collins.
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BACKGROUND: This study investigates provider practices regarding recombinant human erythropoietin (rHuEPO) dose when patient hemoglobin levels exceeded National Kidney Foundation-Dialysis Outcomes Quality Initiative target levels and reached 13 g/dL or greater (>or=130 g/L). METHODS: The study population (N = 167,796) was hemodialysis patients prevalent on January 1, 2003, who were on renal replacement therapy at least 90 days with Medicare as primary payer and rHuEPO claims in 2 or more consecutive months. Patient characteristics were obtained from the Centers for Medicare & Medicaid Services (CMS) Medical Evidence Report, and comorbid conditions were determined from Medicare claims. Providers and rHuEPO claims were linked by using CMS-assigned provider numbers and the CMS Annual End-Stage Renal Disease Facility Survey. Between-provider differences in patient characteristics were examined by using chi-square test, and provider effect on appropriate response, by using logistic regression. RESULTS: DaVita's percentage of monthly claims for patients with hemoglobin levels of 13 g/dL or greater (>or=130 g/L; 16.7%) and mean monthly rHuEPO dose (54,299 units) were highest. Dialysis Clinic Inc's percentage of such claims (2.0%) and mean monthly dose (38,687 units) were lowest. Dialysis Clinic Inc, Fresenius, and Renal Care Group had the highest percentage of recommended dose adjustments (mean, 70% of units); hospital-based units had the lowest (59%). By adjusted odds ratio, adjustments were 20% more likely for Dialysis Clinic Inc, Fresenius, and Renal Care Group compared with DaVita, National Nephrology Associates, hospital-based units, and independents (17% to 28% less likely). CONCLUSION: rHuEPO dose reduction practices are dependent on specific dialysis providers and whether units are hospital based or independent.
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Although prevention of metabolic bone disease is a principal component of management of end-stage renal disease, the clinical epidemiology of long-bone fractures is not completely understood. Hospital discharge claims from 1994 through 1999 for 7159 subjects in the Dialysis Morbidity and Mortality Study were used to quantify incidence and risk factors of long-bone fractures and to test the hypothesis that long-bone fractures are associated with cardiovascular and infectious events and death in patients receiving hemodialysis. The incidence of long-bone fractures was 16.93 per 1000 patient-years, with the femoral neck being the most common site (59.8%); multivariate analysis revealed greater risk with older age, female gender, diabetes, more years receiving dialysis, and cardiovascular disease, and lower risk with African American race, increasing body mass index, parathyroid hormone values in the fourth quintile (227.1-538.0 pg/mL), and renal transplantation during followup. Postfracture mortality rates were 522.57 per 1000 patient years (versus 215.35 in the overall population). Time-dependent analysis suggested the adverse prognosis of long-bone fractures was related to subsequent congestive heart failure, stroke, pulmonary embolism, pneumonia, and septicemia. Long-bone fractures are common in patients receiving dialysis; their adverse prognostic implications may be linked to major cardiovascular and infectious events.
BACKGROUND: Temporal trends regarding the epidemiology of atherosclerotic renovascular disease (ARVD) in dialysis populations are poorly defined. METHODS AND RESULTS: United States Renal Data System data were used to identify patients aged 67 years or older at dialysis inception between 1996 and 2001 (n=146,973). Medicare claims in the preceding 2 years were used to identify ARVD and revascularization procedures. Prior ARVD rose from 7.1% to 11.2% between 1996 and 2001 (adjusted odds ratio [AOR], 1.68). Other associations included hypertensive end-stage renal disease (ESRD; AOR, 2.21), ESRD network (AOR, 0.44 in network 17 versus 1.00 in network 1), peripheral vascular disease (AOR, 1.65), black race (AOR, 0.44), urologic cause of ESRD (AOR, 0.57), age >85 years (AOR, 0.58), substance dependency (AOR, 0.62), and inability to ambulate or transfer (AOR, 0.67). The proportion of ARVD patients undergoing revascularization rose from 14.6% to 16.7% between 1996 and 2001 (AOR, 1.27). Other associations included hypertension (AOR, 2.10), ESRD network (AOR, 2.07 for network 13 versus 1.00 in network 1), age >85 years (AOR, 0.53), and black race (AOR, 0.54). The rise in ARVD was not reflected in the proportion of patients with renovascular disease listed as cause of ESRD on the Medical Evidence Report at dialysis inception (5.5% in 1996, 5.0% in 2001). CONCLUSIONS: ARVD diagnoses have become more common in older patients beginning dialysis therapy. The association of demographic factors including age, race, and geographic residence with utilization patterns suggests possible barriers to care.
Adiponectin is presumed to possess antiatherogenic and cardioprotective properties. Limited data exist on the relationship between adiponectin and mortality in the earlier stages of chronic kidney disease. The Modification of Diet in Renal Disease study was a randomized, controlled trial that was conducted between 1989 and 1993. Adiponectin was measured in frozen samples that were obtained at baseline (N = 820). Survival status and cause of death, up to December 31, 2000, were obtained from the National Death Index. Multivariable Cox models were used to examine the relationship of adiponectin with all-cause and cardiovascular mortality. Mean +/- SD age was 52 +/- 12 yr, and mean +/- SD glomerular filtration rate (GFR) rate was 33 +/- 12 ml/min per 1.73 m2. Eighty-five percent of participants were white, and 60% were male. Mean +/- SD adiponectin was 12.8 +/- 8.0 mug/ml. Triglycerides, insulin resistance, glucose, body mass index, GFR, C-reactive protein, and albumin were inversely related and proteinuria and HDL cholesterol were directly related to adiponectin. During the 10-year follow-up period, 201 (25%) participants died of any cause, and 122 (15%) from cardiovascular disease. In multivariable adjusted Cox models, a 1-mug/ml increase in adiponectin was associated with a 3% (hazard ratio 1.03; 95% confidence interval 1.01 to 1.05; P = 0.02) increased risk for all-cause and 6% (hazard ratio 1.06; 95% confidence interval 1.03 to 1.09; P < 0.001) increased risk for cardiovascular mortality. High, rather than low, adiponectin is associated with increased mortality in this cohort of patients with chronic kidney disease stages 3 to 4. Further studies are necessary to confirm this association and to elucidate the underlying mechanisms.
BACKGROUND AND PURPOSE: Clinical trials have illustrated warfarin's protective effect on stroke risk in patients with atrial fibrillation (AF). The current study investigated temporal trends in AF prevalence, warfarin use, and its relation to stroke risk in Medicare patients with AF from 1992 to 2002. METHODS: The Medicare 5% sample for 1992 to 2002 was used to create 1-year cohorts of patients with Medicare as primary payer throughout the year. International Classification of Diseases, Ninth Revision, Clinical Modification codes were used to identify AF, ischemic and hemorrhagic stroke, and comorbid conditions. A previously validated surrogate measure, prothrombin/international normalized ratio claims, was used to identify warfarin use. Cox proportional hazards regression was used to examine time to stroke with warfarin use as a time-dependent variable. RESULTS: Among Medicare patients aged > or = 65 years, AF prevalence increased from 3.2% in 1992 to 6.0% in 2002 with higher prevalence in older subsets of the study population. Among patients with AF, warfarin use increased significantly (P< or = 0.001) for each year examined, from 24.5% in 1992 to 56.3% in 2002. Stroke rates per 1000 patient-years declined from 46.7 in 1992 to 19.5 in 2002 for ischemic stroke but remained fairly steady for hemorrhagic stroke (range, 1.6 to 2.9). Time-to-event modeling confirmed a protective association of warfarin against ischemic stroke among Medicare patients with AF. CONCLUSIONS: This analysis represents an observational validation of stroke prevention in AF trials. The significant increase in warfarin use among patients with AF illustrates diffusion of trial evidence into clinical practice.
The incidence of ESRD is increasing rapidly. Limited information exists regarding early markers for the development of ESRD. This study aimed to determine over 25 yr the risk for ESRD associated with proteinuria, estimated GFR (eGFR), and hematocrit in men who did not have identified kidney disease and were randomly assigned into the Multiple Risk Factor Intervention Study (MRFIT). A total of 12,866 men who were at high risk for heart disease were enrolled (1973 to 1975) and followed through 1999. Renal replacement therapy was ascertained by matching identifiers with the United States Renal Data System's data; vital status was from the National Death Index. Men who initiated renal replacement therapy or died as a result of kidney disease were deemed to have developed ESRD. Dipstick urine for proteinuria, eGFR, and hematocrit were related to development of ESRD. During 25 yr, 213 (1.7%) men developed ESRD. Predictors of ESRD were dipstick proteinuria of 1+ or > or =2+ (hazard ratio [HR] 3.1 [95% confidence interval (CI) 1.8 to 5.4] and 15.7 [95% CI 10.3 to 23.9] respectively) and an eGFR of <60 ml/min per 1.73 m(2) (HR 2.4; 95% CI 1.5 to 3.8). Correlation between eGFR and serum creatinine was 0.9; the risk for ESRD with a 1-SD difference of each was identical (HR 1.21). Bivariate analysis demonstrated a 41-fold increase in ESRD risk in those with an eGFR <60 ml/min per 1.73 m(2) and > or =2+ proteinuria (95% CI 15.2 to 71.1). There was no association between hematocrit and ESRD. Other baseline measures that independently predicted ESRD included age, cigarette smoking, BP, low HDL cholesterol, and fasting glucose. Among middle-aged men who were at high risk for cardiovascular disease but had no clinical evidence of cardiovascular disease or significant kidney disease, dipstick proteinuria and an eGFR value <60 ml/min per 1.73 m(2) were strong predictors of long-term development of ESRD. It remains unknown whether intervention for proteinuria or early identification of those with chronic kidney disease reduces the risk for ESRD.
BACKGROUND: The relationship between total homocysteine (tHcy) and outcomes has not been investigated in patients with chronic kidney disease stages 3 to 4. METHODS AND RESULTS: The Modification of Diet in Renal Disease Study was a randomized, controlled trial of 840 patients. Serum tHcy was measured in frozen samples collected at baseline (n=804). Survival status and cause of death were obtained from the National Death Index. To evaluate its association with all-cause and cardiovascular disease (CVD) mortality, tHcy was evaluated both as tertiles (<14.7, 14.7 to 19.5, > or =19.6 micromol/L) and as a continuous variable (per 10/micromol/L). Participants had a mean age of 52+/-12 years and glomerular filtration rate (GFR) of 33+/-12 mL/min per 1.73 m2; 60% were male, and 85% were white. During a median follow-up of 10 years, 195 (24%) died from any cause, and 118 (15%) from CVD. The level of GFR was lower and proteinuria higher in the highest tHcy tertile. There was no association between the highest tertile of tHcy and all-cause (hazard ratio [HR]; 95% confidence interval [CI[, 1.32, 0.94 to 1.85) or CVD (HR; 95% CI, 1.50, 0.96 to 2.34) mortality in univariate analyses; this association was further attenuated by adjustment for GFR (HR; 95% CI all-cause, 1.04, 0.72 to 1.51; CVD, 1.20, 0.73 to 1.95). There was no association between tHcy as a continuous variable and all-cause (0.98, 0.83 to 1.16) or CVD (1.04, 0.85 to 1.27) mortality. CONCLUSIONS: Hyperhomocystinemia does not appear to be a risk factor for all-cause or CVD mortality in the Modification of Diet in Renal Disease Study. Prior studies demonstrating an association between tHcy and CVD risk may have inadequately adjusted for the confounding effects of kidney function.
This study's objective was to determine the incidence and mortality of acute renal failure (ARF) in Medicare beneficiaries. Data were from hospitalized Medicare beneficiaries (5,403,015 discharges) between 1992 and 2001 from the 5% sample of Medicare claims. For 1992 to 2001, the overall incidence rate of ARF was 23.8 cases per 1000 discharges, with rates increasing by approximately 11% per year. Older age, male gender, and black race were strongly associated (P < 0.0001) with ARF. The overall in-hospital death rate was 4.6% in discharges without ARF, 15.2% in discharges with ARF coded as the principal diagnosis, and 32.6% in discharges with ARF as a secondary diagnosis. In-hospital death rates were 32.9% in discharges with ARF that required renal dialysis and 27.5% in those with ARF that did not require dialysis. Death within 90 d after hospital admission was 13.1% in discharges without ARF, 34.5% in discharges with ARF coded as the principal diagnosis, and 48.6% in discharges with ARF as a secondary diagnosis. Discharges with ARF were more (P < 0.0001) likely to have intensive care and other acute organ dysfunction than those without ARF. For discharges both with and without ARF, rates for death within 90 d after hospital admission showed a declining trend. In conclusion, the incidence rate of ARF in Medicare beneficiaries has been increasing. Those of older age, male gender, and black race are more likely to have ARF. These data show ARF to be a major contributor to morbidity and mortality in hospitalized patients.
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BACKGROUND: Haemoglobin levels in haemodialysis patients could represent unknown comorbidities, more severe levels of known comorbidities, as well as therapeutic choice. Thus, integrating factors predictive of anaemia with actual haemoglobin levels might improve prognostic discrimination. METHODS: We retrospectively studied 93,087 patients who started haemodialysis between 1998 and 2000. Clinical and treatment factors from months 4 through 9, derived from Medicare claims, were used to develop propensity scores for anaemia (mean haemoglobin <11 g/dl). Tertiles of propensity scores were interacted with five levels of actual mean haemoglobin to form 15 groups, ranging from low (anaemia) probability with (mean) haemoglobin <10 g/dl to high probability with haemoglobin >or=13 g/dl. Cox proportional hazards regression evaluated mortality and first hospitalization among these groups. RESULTS: The anaemia propensity score improved overall prognostic discrimination. Propensity score adjustment significantly improved prediction of mortality (P<0.0001) after covariate adjustments including haemoglobin. For mortality, the highest and lowest adjusted hazard ratios (AHR) appeared in these groups, respectively: high probability with haemoglobin <10 g/dl (AHR 1.64 [1.54, 1.75], P<0.0001), and low probability with haemoglobin 12 to <13 g/dl (AHR 0.79 [0.74, 0.85], P<0.0001). Higher haemoglobin levels were associated with lower mortality even after propensity score adjustment. Similar patterns resulted for first hospitalization; however, the interaction was significant only for hospitalization (P = 0. 0212). CONCLUSIONS: Integrating factors predictive of anaemia improves overall prognostic discrimination. Propensity score adjustment refines the prognostic association of haemoglobin levels in haemodialysis patients.
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Infectious complications in individuals with chronic kidney disease (CKD) pose a significant source of morbidity and mortality. The overall scope of major infectious complications has, however, received little attention even though some of these events may be preventable. We reviewed infectious hospitalization rates in the CKD and end-stage renal disease (ESRD) populations, comparing them with the non-CKD and non-ESRD groups. We also reviewed preventive vaccination rates for influenza, pneumonia, and pneumococcal pneumonia to assess areas of potential improvement. We reviewed the medical literature and present findings based on hospitalization rates for pneumonia, sepsis/bacteremia, and urinary tract infections in the Medicare CKD, ESRD, and non-CKD populations. Vaccination rates were determined from submitted claims for services with specific codes for the vaccinations. Regardless of the primary cause for the development of CKD, primary kidney disease or secondary to hypertension, diabetes mellitus, or other chronic condition, patient outcomes after the development of infections were 3 to 4 times worse than in the non-CKD population. Influenza vaccination rates were 52%, far less than the target of 90%. Pneumococcal pneumonia vaccination rate was only 13.5%, far less than recommended. CKD is associated with significant major infectious complications, which occur at rates 3 to 4 times the general population. Providers can improve prevention by using fewer dialysis catheters and increasing vaccination rates for influenza and pneumococcal pneumonia.
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BACKGROUND: The long-term effect of a low-protein diet on the progression of chronic kidney disease is unknown. We evaluated effects of protein restriction on kidney failure and all-cause mortality during extended follow-up of the Modification of Diet in Renal Disease Study. METHODS: Study A was a randomized controlled trial from 1989 to 1993 of 585 patients with predominantly nondiabetic kidney disease and a moderate decrease in glomerular filtration rate (25 to 55 mL/min/1.73 m(2) [0.42 to 0.92 mL/s/1.73 m(2)]) assigned to a low- versus usual-protein diet (0.58 versus 1.3 g/kg/d). We used registries to ascertain the development of kidney failure (initiation of dialysis therapy or transplantation) or a composite of kidney failure and all-cause mortality through December 31, 2000. We used Cox regression models and intention-to-treat principles to compute hazard ratios for the low- versus usual-protein diet, adjusted for baseline glomerular filtration rate and other factors previously associated with the rate of decrease in glomerular filtration rate. We estimated hazard ratios for the entire follow-up period and then, in time-dependent analyses, separately for 2 consecutive 6-year periods of follow-up. RESULTS: Kidney failure and the composite outcome occurred in 327 (56%) and 380 patients (65%), respectively. After adjustment for baseline factors, hazard ratios were 0.89 (95% confidence interval [CI], 0.71 to 1.12) and 0.88 (95% CI, 0.71 to 1.08), respectively. Adjusted hazard ratios for both outcomes were lower during the first 6 years (0.68; 95% CI, 0.51 to 0.93 and 0.66; 95% CI, 0.50 to 0.87, respectively) than afterward (1.27; 95% CI, 0.90 to 1.80 and 1.29; 95% CI, 0.94 to 1.78; interaction P = 0.008 and 0.002, respectively). Limitations include lack of data for dietary intake and clinical conditions after conclusion of the trial. CONCLUSION: The efficacy of a 2- to 3-year intervention of dietary protein restriction on progression of nondiabetic kidney disease remains inconclusive. Future studies should include a longer duration of intervention and follow-up.
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