There is a paucity of biomarkers that reliably detect nephrotoxicity. The Predictive Safety Testing Consortium (PSTC) faced several challenges in identifying novel safety biomarkers in the renal setting.The kidney is a major site of organ damage caused by drug toxicity. This frequently manifests during drug development and/or in standard clinical care. Nephrotoxicity resulting from drug exposure has been estimated to contribute to 19-25% of all cases of acute kidney injury (AKI, the currently preferred term for the clinical disorder formerly called acute renal failure) in critically ill patients 1 . Given the societal cost of nephrotoxicity and the insensitivity of current methods to detect it, sensitive methods for prediction of toxicity in preclinical studies and identification of injury in humans are extremely important for patient safety in clinical practice and in all stages of the drug-development process. It is in the interest of patients, physicians, the drug industry and health regulatory bodies to prevent new nephrotoxic drugs from entering the market or, when the medical need dictates use of such an agent, to be able to identify early and best manage nephrotoxicity.This article discusses the purview of the first effort of the PSTC-a collaboration of the biotech and pharmaceutical industry, the US Food and Drug Administration (FDA; Rockville, MD), the European Medicines Agency (EMEA; London, UK) and academia-to facilitate the qualification of renal biomarkers for safety in drug development. It brings together expertise from a variety of disciplines to organize and/or create evidentiary datasets to present to the regulatory agencies for qualification decision-making. Although this first

Inhibition of HSD1 with MK-0916 was generally well tolerated in patients with T2DM and MetS. Although no significant improvement in FPG was observed with MK-0916 compared to placebo, modest improvements in A1C, body weight and blood pressure were observed.

No abstract

No abstract

No abstract

Miglitol monotherapy is effective and safe in NIDDM patients. Compared with glibenclamide, it reduced HbA1c less effectively and caused more gastrointestinal side effects. On the other hand, glibenclamide, unlike miglitol, tended to cause hypoglycemia, hyperinsulinemia, and weight gain, which are not desirable in patients with NIDDM.

Pulse wave velocity (PWV), a measure of arterial stiffness, is an independent risk factor for cardiovascular morbidity and mortality. We investigated the relationship of ambulatory brachial cuff-based oscillometric PWV (oPWV) to two known correlates: age and brachial systolic blood pressure (SBP).In 234 participants in the Masked Hypertension Study, we analyzed 7,284 validated hourly ambulatory SBP and oPWV readings using the Mobil-O-Graph monitor, which employs a proprietary pulse wave analysis (PWA) algorithm to determine oPWV. Carotid-femoral PWV (cfPWV) was also measured. Mixed linear models were developed to estimate oPWV from age and ambulatory SBP.Participants were 34% male, with mean (SD) age 52.8 (9.9) years, SBP 123.8 (18.4) mmHg, and oPWV 7.6 (1.3) m/sec and cfPWV of 7.7 (1.7) m/sec. The relationship of oPWV to age and SBP was:Age uniquely accounted for an estimated 75% of the total variation of oPWV, while SBP uniquely accounted for 20%; these findings were confirmed in an external validation dataset. Together, age and SBP accounted for 99.1% of the total variance of oPWV, but (only) 40.2% of the variance of cfPWV. The correlation between oPWV and cfPWV was 0.58, but was only 0.11 after controlling for age and SBP.We conclude that the Mobil-O-Graph's oPWV is nearly completely explained by age and SBP and its relationship to cfPWV is due to their shared associations with age and SBP.

No abstract