Does Secretory Clearance Follow Glomerular Filtration Rate in Chronic Kidney Diseases? Reconsidering the Intact Nephron Hypothesis.

Drug-dose modification in chronic kidney disease (CKD) utilizes glomerular filtration rate (GFR) with the implicit assumption that multiple renal excretory processes decline in parallel as CKD progresses. We compiled published pharmacokinetic data to evaluate if GFR predicts renal clearance changes as a function of CKD severity. For each drug, we calculated ratio of renal clearance to filtration clearance (Rnf). Of 21 drugs with Rnf >0.74 in subjects with GFR >90 mL/min (implying filtration and secretion), 13 displayed significant change in Rnf vs. GFR (slope of linear regression statistically different from zero), which indicates failure of GFR to predict changes in secretory clearance. The dependence was positive (n = 3; group A) or negative (n = 10; group B). Eight drugs showed no correlation (group C). Investigated drugs were small molecules, mostly hydrophilic, and ionizable, with some characterized as renal transporter substrates. In conclusion, dosing adjustments in CKD require refinement; in addition to GFR, biomarkers of tubular function are needed for secreted drugs.

Chronic Kidney Disease Alters Vitamin A Homeostasis via Effects on Hepatic RBP4 Protein Expression and Metabolic Enzymes.

Vitamin A, via retinoic acid (RA), is a critical micronutrient. Normally, plasma concentrations are tightly regulated. Concentrations of vitamin A metabolites (13cis-RA, atRA) and relationships between RBP4 and retinoids have never been fully evaluated in adult patients with CKD. We measured retinoid and RBP4 concentrations in plasma and urine from 55 adult patients with CKD and 21 matched healthy subjects. RBP4 and retinol levels were increased approximately twofold in patients with CKD, with a negative correlation between plasma retinol and eGFR (p = 0.006) and plasma RBP4 and eGFR (p = 0.0007). RBP4 renal clearance was higher in patients with CKD than healthy subjects but not associated with eGFR. Circulating concentrations of atRA increased and concentrations of 13cis-RA decreased in subjects with CKD with no change in RA-to-retinol ratio. Increases in circulating retinol, RBP4, and atRA may be due to increased hepatic RBP4 synthesis, retinyl ester hydrolysis, and/or hepatic secretion of RBP4-retinol.

Mineral metabolism disturbances in patients with chronic kidney disease.

BACKGROUND: Kidney disease, especially chronic kidney disease (CKD), is a worldwide public health problem with serious adverse health consequences for affected individuals. Secondary hyperparathyroidism, a disorder characterized by elevated serum parathyroid hormone levels, and alteration of calcium and phosphorus homeostasis are common metabolic complications of CKD that may impact cardiovascular health. MATERIALS AND METHODS: Here, we systematically review published reports from recent observational studies and clinical trials that examine markers of altered mineral metabolism and clinical outcomes in patients with CKD. RESULTS: Mineral metabolism disturbances begin early during the course of chronic kidney disease, and are associated with cardiovascular disease and mortality in observational studies. Vascular calcification is one plausible mechanism connecting renal-related mineral metabolism with cardiovascular risk. Individual therapies to correct mineral metabolism disturbances have been associated with clinical benefit in some observational studies; clinical trials directed at more comprehensive control of this problem are warranted. CONCLUSIONS: There exists a potential to improve outcomes for patients with CKD through increased awareness of the Bone Metabolism and Disease guidelines set forth by the National Kidney Foundation-Kidney Disease Outcomes Quality Initiative. Future studies may include more aggressive therapy with a combination of agents that address vitamin D deficiency, parathyroid hormone and phosphorus excess, as well as novel agents that modulate circulating promoters and inhibitors of calcification.

Racial and ethnic differences in incident myocardial infarction in end-stage renal disease patients: The USRDS.

African Americans have a greater risk of cardiovascular disease (CVD) than Caucasians in early chronic kidney disease; however, limited data describe racial and ethnic differences in the risk of incident myocardial infarction (MI) among patients with end-stage renal disease (ESRD). We conducted a prospective, observational cohort study among 271 102 incident dialysis patients receiving renal replacement therapy enrolled in the United States Renal Data System (USRDS) for whom Medicare was the primary insurer between 1995 and 2000. The incidence and risk of any MI (non-fatal or fatal) estimated by Cox proportional hazards models was the primary outcome of interest. Of those with prevalent CVD at baseline (118 708), 14 849 had an incident non-fatal MI compared with 9926 events for those without prevalent CVD (152 394). Patients with prevalent CVD had higher crude rates of combined fatal and non-fatal MI (99.3/1000 person-years vs 42.9/1000 person-years) compared with those without prevalent CVD. Among those with prevalent CVD, African Americans (adjusted relative risk (aRR)=0.65, 95% confidence interval (CI):0.62-0.68), Asian Americans (aRR=0.74, 95% CI: 0.66-0.83), and Hispanics (aRR=0.72, 95% CI: 0.68-0.77) were 26-35% less likely to have an incident MI compared to Caucasians. Similarly, among those without prevalent CVD, racial/ethnic minorities were 26-42% less likely to have an incident MI compared to Caucasians. We conclude that in a national setting where comparable access to dialysis and associated medical care, exist, racial/ethnic minorities were found to have a lower risk of non-fatal and fatal MI than Caucasians.

Commentary on "A methodology for identifying married couples in Medicare data".

Authors of an article appearing recently in Demography propose a retrospective method to identify husband-wife pairs in administrative records. Although their premise is correct, they over-state the power of their methodology. The error stems from a misunderstanding of how persons entitled to both primary and secondary social security benefits are classified in program data. A retrospective look four years after the reference data shows that the number of pairs is increased by less than 10%, not by more than 50%, as the authors claim.

Effect on benefits of earnings at ages 65 or older, 1995.

A major policy issue for the Social Security program is the treatment of earnings of persons who have attained retirement age. This article discusses the retirement test and recomputation of benefit provisions, and provides statistical data for 1995. In 1995, about 806,000 persons aged 65-70 had significant earnings resulting in the withholding of benefits by the retirement test. About 1,659,000 persons aged 65 or older realized an increase in their benefit amount because of their earnings.

A description of the extreme aged population based on improved Medicare enrollment data.

The mortality and size of the extreme aged population can be studied most accurately with Medicare enrollment data from the Social Security Administration's Master Beneficiary Record after certain types of questionable records are eliminated. With the improved data base we find that mortality rates at the very old ages are higher than published rates, we are more confident of the reality of the race crossover, and we can estimate the number of centenarians more accurately. Furthermore, a large matched-records study shows close agreement on age at death between the Master Beneficiary Record and the death certificate.

Seasonality of birth: two findings from the decennial census.

PIP: The enigmatic seasonality of births in the US has been analyzed extensively, but gaps in the knowledge of this phenomenon exist along dimensions not accessed by the national vital registration system. Live births in the US have for some time followed a pattern of spring trough and summer peak--at least since the initiation of the national birth registration system in 1933. The pattern is known to be more pronounced for the South than for other regions and for blacks than for whites. In this study it has been shown that this pattern existed as far back as the 1890's, and currently is more pronounced for lower than for higher socioeconomic groups. These findings come from an analysis of census population data, rather than vital registration data. In this way census data have been used in an innovative way to address 2 aspects of the phenomenon which had heretofore not been adequately treated.^ieng

Mortality by nativity.

This note reports the reversal of the mortality-nativity relationship in the United States. In the first half of the twentieth century, mortality among foreign-born Americans was greater than among (white) native Americans. Data for 1980 show that now mortality among the foreign-born is markedly lower than among native Americans.