Resolving an 80-yr-old controversy: the beginning of the modern era of renal physiology.

Marcello Malpighi discovered the glomerulus that bears his name in the 17th century, but it was not until the middle of the 19th century, in 1842, that William Bowman in London published his studies of the histological structure of the glomerulus and proposed that urine formation begins with glomerular secretion. At nearly the same time in Marburg, Carl Ludwig, unaware of Bowman's findings, proposed that urine formation begins with glomerular filtration followed by tubule reabsorption. The controversy lasted 80 yr.

Medication adherence assessment in a clinical trial with centralized follow-up and direct-to-patient drug shipments.

Background: Assessment of adherence to study medications is a common challenge in clinical research. Counting unused study medication is the predominant method by which adherence is assessed in outpatient clinical trials but it has limitations that include questionable validity and burdens on research personnel.

Purpose: To compare capsule counts, patient questionnaire responses, and plasma drug levels as methods of determining adherence in a clinical trial that had 2056 participants and used centralized drug distribution and patient follow-up.

Homocysteine lowering and cognition in CKD: the Veterans Affairs homocysteine study.

Background: Individuals with advanced chronic kidney disease (CKD) and end-stage renal disease (ESRD) have high plasma total homocysteine (tHcy) levels, which may be a risk factor for cognitive impairment. Whether treatment with high-dose B vitamins to decrease high tHcy levels improves cognition in persons with kidney disease is unknown.

Study Design: Randomized controlled trial.

Effect of the MTHFR C677T and A1298C polymorphisms on survival in patients with advanced CKD and ESRD: a prospective study.

Background: Abnormalities in the gene regulating methylenetetrahydrofolate reductase (MTHFR) are associated with increased homocysteine levels and increased mortality in normal and chronic kidney disease (CKD) populations.

Study Design: Gene association study.

Setting & Participants: This was a substudy of 677 patients from 21 Veterans Affairs medical centers participating in a randomized clinical trial (Homocysteinemia in Kidney and End-Stage Renal Disease [HOST]) of the effect on all-cause mortality of vitamin-induced lowering of plasma homocysteine levels.

Effect of homocysteine lowering on mortality and vascular disease in advanced chronic kidney disease and end-stage renal disease: a randomized controlled trial.

Context: High plasma homocysteine levels are a risk factor for mortality and vascular disease in observational studies of patients with chronic kidney disease. Folic acid and B vitamins decrease homocysteine levels in this population but whether they lower mortality is unknown.

Objective: To determine whether high doses of folic acid and B vitamins administered daily reduce mortality in patients with chronic kidney disease.

Design and statistical issues in the homocysteinemia in kidney and end stage renal disease (HOST) study.

The Homocysteine Study (HOST) Veterans Affairs Cooperative Studies Program No. 453, is a prospective, randomized, two arm, double blind study of patients with end stage renal disease (ESRD) or advanced chronic kidney disease (ACKD, defined as an estimated creatinine clearance of 30 ml/min or less). Its primary objective is to determine whether administration of high doses of three vitamins, folic acid, vitamin B6 and vitamin B12, to lower the high plasma homocysteine levels, will reduce all cause mortality.

Countercurrent exchange in the renal medulla.

The microcirculation of the renal medulla traps NaCl and urea deposited to the interstitium by the loops of Henle and collecting ducts. Theories have predicted that countercurrent exchanger efficiency is favored by high permeability to solute. In contrast to the conceptualization of vasa recta as simple "U-tube" diffusive exchangers, many findings have revealed surprising complexity.