David J. Tiller

A randomized, controlled trial of early versus late initiation of dialysis

BACKGROUNDnIn clinical practice, there is considerable variation in the timing of the initiation of maintenance dialysis for patients with stage V chronic kidney disease, with a worldwide trend toward early initiation. In this study, conducted at 32 centers in Australia and New Zealand, we examined whether the timing of the initiation of maintenance dialysis influenced survival among patients with chronic kidney disease.nnnMETHODSnWe randomly assigned patients 18 years of age or older with progressive chronic kidney disease and an estimated glomerular filtration rate (GFR) between 10.0 and 15.0 ml per minute per 1.73 m2 of body-surface area (calculated with the use of the Cockcroft-Gault equation) to planned initiation of dialysis when the estimated GFR was 10.0 to 14.0 ml per minute (early start) or when the estimated GFR was 5.0 to 7.0 ml per minute (late start). The primary outcome was death from any cause.nnnRESULTSnBetween July 2000 and November 2008, a total of 828 adults (mean age, 60.4 years; 542 men and 286 women; 355 with diabetes) underwent randomization, with a median time to the initiation of dialysis of 1.80 months (95% confidence interval [CI], 1.60 to 2.23) in the early-start group and 7.40 months (95% CI, 6.23 to 8.27) in the late-start group. A total of 75.9% of the patients in the late-start group initiated dialysis when the estimated GFR was above the target of 7.0 ml per minute, owing to the development of symptoms. During a median follow-up period of 3.59 years, 152 of 404 patients in the early-start group (37.6%) and 155 of 424 in the late-start group (36.6%) died (hazard ratio with early initiation, 1.04; 95% CI, 0.83 to 1.30; P=0.75). There was no significant difference between the groups in the frequency of adverse events (cardiovascular events, infections, or complications of dialysis).nnnCONCLUSIONSnIn this study, planned early initiation of dialysis in patients with stage V chronic kidney disease was not associated with an improvement in survival or clinical outcomes. (Funded by the National Health and Medical Research Council of Australia and others; Australian New Zealand Clinical Trials Registry number, 12609000266268.)

Uremic Cardiomyopathy — Effect of Hemodialysis on Left Ventricular Function in End-Stage Renal Failure

Left ventricular ejection fraction was measured by radionuclide left ventriculography before and immediately after hemodialysis in 20 uremic patients, 11 of whom presented with congestive heart failure. Ejection fraction and contraction were normal in 15 patients (Group A), six of whom had signs of congestive failure; they were abnormal in five patients (Group B), all of whom were in clinical heart failure. Mean arterial pressure and body weight decreased by a similar amount after dialysis in both groups, and heart rate did not change. In Group A ejection fraction was unchanged by dialysis (0.63 +/- before vs. 0.62 +/- 0.09 after) (mean +/- S.D.), but in Group B it was improved significantly (0.32 +/- 0.04 before vs. 0.44 0.08 after) (P less than 0.01). In three patients in Group B cardiomegaly and ejection fraction returned to normal with long-term hemodialysis. In end-state renal failure, radionuclide left ventriculography can separate patients with circulatory congestion due to fluid overload from patients with left ventricular dysfunction in whom hemodialysis can provide immediate and long-term improvement.

Circulatory adaptation to pregnancy--serial studies of haemodynamics, blood volume, renin and aldosterone in the baboon (Papio hamadryas).

To test the hypothesis that haemodynamic changes in pregnancy precede any significant increase in circulating blood volume, serial haemodynamic studies were performed in eight baboon pregnancies using Swan-Ganz catheterization and arterial cannulation. Simultaneous measurements were made of red cell and plasma volumes, and of plasma renin activity and aldosterone concentration. Haemodynamic changes identified by 4 weeks gestation included significant (P less than 0.01) reductions in right atrial pressure, systemic and pulmonary arterial pressures, and systemic and pulmonary vascular resistance. Stroke volume increased in early pregnancy (P less than 0.01), with a consequent increase in cardiac output. Plasma renin activity and aldosterone concentration were elevated by 4 weeks (P less than 0.01), but plasma volume did not expand until 12 weeks. At no stage in middle or late pregnancy was cardiac filling pressure increased. These results provide the first haemodynamic evidence that pregnancy is a state of reduced effective blood volume associated with vasodilatation from the early weeks.

Factors affecting the utility of the multiple mini-interview in selecting candidates for graduate-entry medical school

Contextu2002 We wished to determine which factors are important in ensuring interviewers are able to make reliable and valid decisions about the non‐cognitive characteristics of candidates when selecting candidates for entry into a graduate‐entry medical programme using the multiple mini‐interview (MMI).

Cost-Effectiveness of Initiating Dialysis Early: A Randomized Controlled Trial

BACKGROUNDnPlanned early initiation of dialysis therapy based on estimated kidney function does not influence mortality and major comorbid conditions, but amelioration of symptoms may improve quality of life and decrease costs.nnnSTUDY DESIGNnPatients with progressive chronic kidney disease and a Cockcroft-Gault estimated glomerular filtration rate of 10-15 mL/min/1.73 m(2) were randomly assigned to start dialysis therapy at a glomerular filtration rate of either 10-14 (early start) or 5-7 mL/min/1.73 m(2) (late start).nnnSETTING & POPULATIONnOf the original 828 patients in the IDEAL (Initiation of Dialysis Early or Late) Trial in renal units in Australia and New Zealand, 642 agreed to participate in this cost-effectiveness study. STUDY PERSPECTIVE & TIMEFRAME: A societal perspective was taken for costs. Patients were enrolled between July 1, 2000, and November 14, 2008, and followed up until November 14, 2009.nnnINTERVENTIONnPlanned earlier start of maintenance dialysis therapy.nnnOUTCOMESnDifference in quality of life and costs.nnnRESULTSnMedian follow-up of patients (307 early start, 335 late start) was 4.15 years, with a 6-month difference in median duration of dialysis therapy. Mean direct dialysis costs were significantly higher in the early-start group (

A Randomized Controlled Trial Of Cyclosporine Withdrawal In Renal-Transplant Recipients: 15-Year Results.

10,777; 95% CI,

EVIDENCE THAT ALTERATIONS IN RENAL METABOLISM AND LIPID PEROXIDATION MAY CONTRIBUTE TO CYCLOSPORINE NEPHROTOXICITY

313 to

Effects of timolol and hydrochlorothiazide on blood-pressure and plasma renin activity. Double-blind factorial trial.

22,801). Total costs, including costs for resources used to manage adverse events, were higher in the early-start group (

Effect of timing of dialysis commencement on clinical outcomes of patients with planned initiation of peritoneal dialysis in the ideal trial

18,715; 95% CI, -

Structure-activity relationships of cyclosporines: toxicity in cultured renal tubular epithelial cells

3,162 to