Journal of the American Society of Nephrology : JASN
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J. Am. Soc. Nephrol. · Jul 2006
Review Meta AnalysisStatins for improving renal outcomes: a meta-analysis.
Statins frequently are used to prevent cardiovascular events. Several recent studies suggest that statins also may have renal benefits, although this is controversial. This systematic review and meta-analysis were performed to assess the effect of statins on change in kidney function and urinary protein excretion. ⋯ In subgroup analysis, the benefit of statin therapy was statistically significant in studies of participants with cardiovascular disease (0.93 ml/min per yr slower than control subjects; 95% CI 0.10 to 1.76) but was NS for studies of participants with diabetic or hypertensive kidney disease or glomerulonephritis. The standardized mean difference for the reduction in albuminuria or proteinuria as a result of statin therapy was statistically significant (0.58 units of SD greater in statin recipients; 95% CI 0.17 to 0.98). Statin therapy seems to reduce proteinuria modestly and results in a small reduction in the rate of kidney function loss, especially in populations with cardiovascular disease.
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J. Am. Soc. Nephrol. · Jun 2006
Racial differences in the prevalence of chronic kidney disease among participants in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) Cohort Study.
The racial disparity in the incidence of ESRD exemplified by the three- to four-fold excess risk among black compared with white individuals in the United States is not reflected in the prevalence of less severe degrees of impaired kidney function among black compared with white individuals. The four-variable Modification of Diet in Renal Disease study equation was used to evaluate the black-to-white prevalence of impaired kidney function with increasing severity of impairment among participants in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study, a nationally representative, population-based cohort of individuals who are 45 yr and older. An estimated GFR (eGFR)<60 ml/min per 1.73 m2 was present in 43.3% of the 20,667 REGARDS participants and was slightly less prevalent among black than white patients (33.7 versus 49.9%; prevalence odds ratio 0.51; 95% confidence interval [CI] 0.48 to 0.54). ⋯ After controlling for other patient characteristics, the black-to-white odds ratio was 0.42 (95% CI 0.40 to 0.46) at an eGFR of 50 to 59 ml/min per 1.73 m2 and increased to 1.73 (95% CI 1.02 to 2.94) at an eGFR of 10 to 19 ml/min per 1.73 m2. The disparity in prevalence of impaired kidney function among white compared with black patients reversed as the severity of impaired kidney function increased. Factors that are responsible for the increasing prevalence of severely impaired kidney function among black patients remain to be determined.
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J. Am. Soc. Nephrol. · May 2006
Randomized Controlled Trial Multicenter StudyAssociation of single measurements of dipstick proteinuria, estimated glomerular filtration rate, and hematocrit with 25-year incidence of end-stage renal disease in the multiple risk factor intervention trial.
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). ⋯ 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.
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J. Am. Soc. Nephrol. · Apr 2006
Development of lithium-induced nephrogenic diabetes insipidus is dissociated from adenylyl cyclase activity.
In antidiuresis, vasopressin (AVP) occupation of V2 receptors in renal collecting ducts activates adenylyl cyclase, resulting in increased intracellular cAMP levels, which activates protein kinase A (PKA). PKA phosphorylates both the cAMP responsive element binding protein, which induces aquaporin-2 (AQP2) transcription, and AQP2, which then is translocated to the apical membrane, allowing urine concentration. Lithium treatment often causes nephrogenic diabetes insipidus (NDI), which coincides with decreased AQP2 expression and which generally is ascribed to reduced adenylyl cyclase activity. ⋯ In vivo, kidney tissue of rats with lithium-induced NDI indeed generated less dDAVP-induced cAMP than that of controls, but this could be due to elevated blood AVP levels in rats with lithium-induced NDI. Indeed, Brattleboro rats, which lack endogenous AVP, with clamped blood dDAVP levels, showed no difference in dDAVP-generated cAMP generation between kidneys of rats with lithium-induced NDI and control rats. In conclusion, the first proper cell model to study lithium-induced NDI was developed, and it was demonstrated that the lithium-induced downregulation of AQP2 and development of NDI occur independent of adenylyl cyclase activity in vitro and in vivo.
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J. Am. Soc. Nephrol. · Mar 2006
Comparative StudyMortality risk stratification in chronic kidney disease: one size for all ages?
Current National Kidney Foundation Kidney Disease Outcomes Quality Initiative staging criteria for chronic kidney disease (CKD) are intended to apply to all age groups. However, it is unclear whether different levels of estimated GFR (eGFR) have the same prognostic significance in older and younger patients. The study cohort was composed of Department of Veterans Affairs (VA) patients who were aged 18 to 100 yr and had at least one outpatient serum creatinine measurement between October 1, 2001, and September 30, 2002 (n=2583,911). ⋯ The association of eGFR with mortality was weaker in the elderly than in younger age groups: Whereas severe reductions in eGFR were associated with an increased risk for death in all age groups, "very" moderate reductions in eGFR (50 to 59 ml/min per 1.73 m2) were associated with an increased adjusted risk for death only among patients who were younger than 65 yr. Age-related attenuation of the association of eGFR with mortality was also present among women and black patients. In the clinical setting, mortality risk stratification in elderly patients should not be based on the same eGFR cut points as for younger age groups and would benefit from finer categorization of the 30- to 59-ml/min per 1.73 m2 eGFR group.