Kidney Function

Background:: Validated prediction scores are required to assess the risks of end-stage renal disease (ESRD) and death in individuals with chronic kidney disease (CKD).Study Design:: Prospective cohort study with validation in a separate cohort.Setting & Participants:: Cox regression was used to assess the relevance of baseline characteristics to risk of ESRD (mean follow-up, 4.1 years) and death (mean follow-up, 6.0 years) in 382 patients with stages 3-5 CKD not initially on dialysis therapy in the Chronic Renal Impairment in Birmingham (CRIB) Study. Resultant risk prediction equations were tested in a separate cohort of 213 patients with CKD (the East Kent cohort).Factors:: 44 baseline characteristics (including 30 blood and urine assays).Outcomes:: ESRD and all-cause mortality.Results:: In the CRIB cohort, 190 patients reached ESRD (12.1%/y) and 150 died (6.5%/y). Each 30% lower baseline estimated glomerular filtration rate was associated with a 3-fold higher ESRD rate and a 1.3-fold higher death rate. After adjustment for each other, only baseline creatinine level, serum phosphate level, urinary albumin-creatinine ratio, and female sex remained strongly (P < 0.01) predictive of ESRD. For death, age, N-terminal pro-brain natriuretic peptide, troponin T level, and cigarette smoking remained strongly predictive of risk. Using these factors to predict outcomes in the East Kent cohort yielded an area under the receiver operating characteristic curve (ie, C statistic) of 0.91 (95% CI, 0.87-0.96) for ESRD and 0.82 (95% CI, 0.75-0.89) for death.Limitations:: Other important factors may have been missed because of limited study power.Conclusions:: Simple laboratory measures of kidney and cardiac function plus age, sex, and smoking history can be used to help identify patients with CKD at highest risk of ESRD and death. Larger cohort studies are required to further validate these results.

Background:: Clinical trials in kidney transplantation are beginning to include markers of kidney function as end points now that traditional outcomes, such as acute rejection, become increasingly rare events. The frequency and type of kidney function end points used are unknown.Study Design:: Systematic review.Setting & Population:: Randomized controlled trials in adult kidney transplant recipients reported in 5 major general medical journals and 5 major subspecialty journals in nephrology and transplantation between January 2003 and November 2008.Selection Criteria:: Inclusion of at least one kidney function end point at least 1 month posttransplant.Results:: 133 (79%) of 169 randomized trials identified used a kidney function end point. Of these, 37 (28%) used one or more measures of kidney function as the primary end point, and 81 (61%), as a secondary end point. For the primary end point, 21 (57%) trials used a creatinine-based estimated glomerular filtration rate (eGFR), 18 (49%) used serum creatinine level, and 7 (19%) used measured GFR. Overall, eGFR was an end point in 81 (61%) trials, and measured GFR, in 12 (9%) trials.Limitations:: This review is limited by the poor quality of the included trials, with many not defining either primary or secondary end points.Conclusions:: Measures of kidney function are used commonly as surrogate end points in kidney transplant trials, with eGFR becoming more frequently used over time. Further data are needed to properly validate these surrogate end points and fully understand their limitations when designing and interpreting randomized trials.

Background:: Little is known about disability in early-stage chronic kidney disease (CKD).Study Design:: Cross-sectional national survey (National Health and Nutrition Examination Survey 1999-2006).Setting & Participants:: Community-based survey of 16,011 noninstitutionalized US civilian adults (aged ≥20 years).Predictor:: CKD, categorized as no CKD, stages 1 and 2 (albuminuria and estimated glomerular filtration rate [eGFR] ≥60 mL/min/1.73 m2), and stages 3 and 4 (eGFR, 15-59 mL/min/1.73 m2).Outcome:: Self-reported disability, defined by limitations in working, walking, and cognition and difficulties in activities of daily living (ADL), instrumental ADL, leisure and social activities, lower-extremity mobility, and general physical activity.Measurements:: Albuminuria and eGFR assessed from urine and blood samples; disability, demographics, access to care, and comorbid conditions assessed using a standardized questionnaire.Results:: Age-adjusted prevalence of reported limitations generally was significantly greater with CKD: for example, difficulty with ADL was reported by 17.6%, 24.7%, and 23.9% of older (≥65 years) and 6.8%, 11.9%, and 11.0% of younger (20-64 years) adults with no CKD, stages 1 and 2, and stages 3 and 4, respectively. CKD also was associated with greater reported limitations and difficulty in other activities after age adjustment, including instrumental ADL, leisure and social activities, lower-extremity mobility, and general physical activity. Other demographics, socioeconomic status, and access to care generally only slightly attenuated the observed associations, particularly in older individuals; adjustment for cardiovascular disease, arthritis, and cancer attenuated most associations such that statistical significance no longer was achieved.Limitations:: Inability to establish causality and possible unmeasured confounding.Conclusion:: CKD is associated with a higher prevalence of disability in the United States. Age and other comorbid conditions account for most, but not all, of this association.