Overhydration is a risk factor for hypertension and left ventricular hypertrophy in peritoneal dialysis patients. Recently, a high prevalence of subclinical overhydration was observed in peritoneal dialysis patients. Aim of the present open-label randomized study was to assess the effect of a icodextrin 7.5% solution on fluid status [extracellular water (ECW) bromide dilution], blood pressure regulation (24-hour ambulatory measurements) and echocardiographic parameters during a study period of 4 months, and to relate the effect to peritoneal membrane characteristics (dialysate/plasma creatinine ratio). Forty peritoneal dialysis patients (22 treated with icodextrin, 18 controls) were randomized to either treatment with icodextrin during the long dwell or standard glucose solutions. Thirty-two patients (19 treated with icodextrin, 13 controls] completed the study. The use of icodextrin resulted in a significant increase in daily ultrafiltration volume (744 +/- 767 mL vs. 1670 +/- 1038 mL; P = 0.012) and a decrease in ECW (17.5 +/- 5.2 L vs. 15.8 +/- 3.8 L; P = 0.035). Also the change in ECW between controls and patients treated with icodextrin was significant (-1.7 +/- 3.3 L vs. +0.9 +/- 2.2 L; P = 0.013). The effect of icodextrin on ECW was not related to peritoneal membrane characteristics, but significantly related to the fluid state of the patients (ECW:height) (r = -0.72; P < 0.0001). Left ventricular mass (LVM) decreased significantly in the icodextrin-treated group (241 +/- 53 grams vs. 228 +/- 42 grams; P = 0.03), but not in the control group. In this randomized open-label study, the use of icodextrin resulted in a significant reduction in ECW and LVM. The effect of icodextrin on ECW was not related to peritoneal membrane characteristics, but was related to the initial fluid state of the patient.

We conclude that in patients with severe heart failure, high dose furosemide administered as a continuous infusion is more efficacious than bolus injection and causes less ototoxic side effects.

Objective We studied the synergism between high-dose furosemide and hydrochlorothiazide in patients with severe congestive heart failure and impaired renal function show ing diuretic resistance to a daily dose of furosemide of at least 250 mg. Design and setting An open study. A general hospital in The Netherlands.Methods In 20 patients with severe congestive heart failure (stage III-IV according to the New York Heart Association) with an oedematous mass of more than 5 kg and a proven diuretic resistance to high-dose furosemide, hydrochlorothiazide (25-100 mg daily) was added to the medication for 3-12 days, leaving the other medica tion unchanged. After correction of the hydration state, hydrochlorothiazide was withdrawn. Variables included body weight, serum electrolytes, renal function and natriuresis.Results Addition of hydrochlorothiazide resulted in a mean (it standard deviation) body weight reduction of 6*7 ± 3*3 kg per patient. Mean daily urine volume increased from 1899 dt 958 ml to 3065 ± 925 ml (P<0*001). Fractional sodium excretion increased significantly from 3-5 ±3-2% to 11*5 ± 9*0% (P<0-001), The most important side effect of this combination therapy appeared to be hypokalaemia. Mean endogenous creatinine clearance decreased (not significantly) from 32*7 ± 22*5 m l. min ~ 1 . 1*73 m " 2 to 27*6 ± 22-5 ml . min" 1 , 1*73 m~2.Conclusions Addition of hydrochlorothiazide to highdose furosemide is a powerful diuretic tool, even in patients with a significantly reduced renal function. Because of its potentially dangerous side effects (hypokalaemia), it should be used in a carefully controlled

The Nijmegen Biomedical Study is a population-based cross-sectional study conducted in the eastern part of the Netherlands. As part of the overall study, we provide reference values of estimated glomerular filtration rate (GFR) for this Caucasian population without expressed risk. Age-stratified, randomly selected inhabitants received a postal questionnaire on lifestyle and medical history. In a large subset of the responders, serum creatinine was measured. The GFR was then measured using the abbreviated Modification of Diet in Renal Disease (MDRD) formula. To limit possible bias, serum creatinine was calibrated against measurements performed in the original MDRD laboratory. The study cohort included 2823 male and 3274 female Caucasian persons aged 18-90 years. A reference population of apparently healthy subjects was selected by excluding persons with known hypertension, diabetes, cardiovascular-or renal diseases. This healthy study cohort included 1660 male subjects and 2072 female subjects, of which 869 of both genders were 65 years or older. The median GFR was 85 ml/min/1.73 m 2 in 30-to 34-year-old men and 83 ml/min/1.73 m 2 in similar aged women. In these healthy persons, GFR declined approximately 0.4 ml/min/year. Our study provides age-and gender-specific reference values of GFR in a population of Caucasian persons without identifiable risk.

Furosemide delivery rate in the nephron has been reported to be one of the major determinants of diuretic response. In a randomized, crossover double-blind study in eight healthy volunteers, we tested this hypothesis by comparing continuous intravenous infusion of furosemide (infusion rate, 4 mg/hr) during 8 hours after administration of an intravenous loading dose of 8 mg (total dose, 40 mg) with an intravenous bolus injection of 40 mg furosemide. During the study days subjects were rehydrated with isovolumetric amounts of fluid. Mean total urinary volume (Vw), sodium (U,,), potassium, and chloride excretion after 8 and 24 hours were significantly greater after treatment with continuous furosemide infusion when compared with bolus injection, whereas total urinary furosemide excretion showed no differences ( V , , bolus versus V , infusion, 5270 versus 6770 mV8 hours; UNa bolus versus UNa infusion, 314 versus 430 mmoV8 hours; bothp < 0.001). These findings strongly support the concept of the furosemide delivery rate into the nephron as a determinant of diuretic efficiency. (CLIN PHARMACOL THER 1992;s 1:440-4).