Evaluation of the modification of diet in renal disease study equation in a large diverse population.

Glomerular filtration rate (GFR) estimates facilitate detection of chronic kidney disease. Performance of the Modification of Diet in Renal Disease (MDRD) Study equation varies substantially among populations. To describe the performance of the equation in a large, diverse population, estimated GFR (eGFR) was compared to measured GFR (mGFR) in a cross-sectional analysis of 5504 participants in 10 studies that included measurements of standardized serum creatinine and urinary clearance of iothalamate. At eGFR <60 ml/min per 1.73 m(2), the MDRD Study equation had lower bias and higher precision than at eGFR > or =60 ml/min per 1.73 m(2). The accuracy of the equation, measured by the percent of estimates that fell within 30% of mGFR, was similar for eGFR values above or below 60 ml/min per 1.73 m(2) (82% and 84%, respectively). Differences in performance among subgroups defined by age, sex, race, diabetes, transplant status, and body mass index were small when eGFR was <60 ml/min per 1.73 m(2). The MDRD Study equation therefore provides unbiased and reasonably accurate estimates across a wide range of subgroups when eGFR is <60 ml/min per 1.73 m(2). In individual patients, interpretation of GFR estimates near 60 ml/min per 1.73 m(2) should be interpreted with caution to avoid misclassification of chronic kidney disease in the context of the clinical setting.

Impact of creatinine calibration on performance of GFR estimating equations in a pooled individual patient database.

BACKGROUND: Variation in performance of glomerular filtration rate (GFR) estimating equations is related to variation in calibration of the creatinine assay across clinical laboratories. STUDY DESIGN: Cross-sectional analysis. SETTING & PARTICIPANTS: 6 research studies and 4 clinical populations including 5,504 participants who had GFR measured using urinary clearance of iothalamate. MEASUREMENTS: Standardized serum creatinine values obtained by means of calibration to the Cleveland Clinic Research Laboratory using frozen specimens, a calibration panel, and/or survey results from the College of American Pathologists. PREDICTOR: Noncalibrated serum creatinine assayed in research and clinical laboratories compared with standardized serum creatinine. OUTCOME: Difference between measured GFR versus GFR estimated from the Modification of Diet in Renal Disease (MDRD) Study and Cockcroft-Gault equations. RESULTS: For a noncalibrated serum creatinine value of 1 mg/dL (88.4 micromol/L), standardized serum creatinine value was 0.07 mg/dL (6.2 micromol/L) less than noncalibrated values. In the pooled data set, for the MDRD Study equation, calibration improved median percentage of difference between measured and estimated GFR from 9.0% (interquartile range [IQR], 28%) to 5.8% (IQR, 28%) and improved the percentage of estimates within 30% of measured GFR (P30) from 80% to 83%. The effect of calibration was greater at higher levels of GFR and varied across studies. For the Cockcroft-Gault equation, calibration worsened the median percentage of difference from -2.0% (IQR, 38%) to -11.4% (IQR, 39%), and the P30, from 74% to 69%. LIMITATIONS: College of American Pathologist samples were used for calibration of clinical populations; calibration factors do not account for drift over time in the serum creatinine assay; calibration cannot account for variation in assay performance among individuals. CONCLUSION: Calibration improves the performance of the MDRD Study equation. After calibration, larger errors remain for GFR estimates greater than 60 mL/min/1.73 m2 (>1 mL/s/1.73 m2).

Mice lacking ghrelin receptors resist the development of diet-induced obesity.

Ghrelin is the endogenous ligand for the growth hormone secretagogue receptor (GHSR; ghrelin receptor). Since its discovery, accumulating evidence has suggested that ghrelin may play a role in signaling and reversing states of energy insufficiency. For example, ghrelin levels rise following food deprivation, and ghrelin administration stimulates feeding and increases body weight and adiposity. However, recent loss-of-function studies have raised questions regarding the physiological significance of ghrelin in regulating these processes. Here, we present results of a study using a novel GHSR-null mouse model, in which ghrelin administration fails to acutely stimulate food intake or activate arcuate nucleus neurons. We show that when fed a high-fat diet, both female and male GHSR-null mice eat less food, store less of their consumed calories, preferentially utilize fat as an energy substrate, and accumulate less body weight and adiposity than control mice. Similar effects on body weight and adiposity were also observed in female, but not male, GHSR-null mice fed standard chow. GHSR deletion also affected locomotor activity and levels of glycemia. These findings support the hypothesis that ghrelin-responsive pathways are an important component of coordinated body weight control. Moreover, our data suggest that ghrelin signaling is required for development of the full phenotype of diet-induced obesity.