Use of Metolazone, a New Diuretic, in Patients with Renal Disease

Abstract

Metolazone, a new diuretic/saluretic/anti-hypertensive agent related to quinethazone, was used to treat 20 patients with impaired renal function. Among eight water loaded hospitalized patients given metolazone 5 mg intra venously, glomerular filtration rate rose in four and diminished slightly in four while urine flow and sodium excretion in creased significantly. In 12 out-patients given long-term oral metolazone (usually 5–10 mg in single daily doses) treatment effectively removed oedema and induced weight loss; in the seven initially hypertensive patients blood pressure decreased also. Plasma renin activity was measured in seven patients before and after several weeks’ metolazone therapy. Activity fell in two patients and rose in five, but the upper limit of normal was exceeded in one only. Renal epithelial cell excretion rates indicated that drug nephrotoxicity was absent. Mean creatinine clearances rose, serum potassium levels fell, and ten patients received oral potassium supplements. Small transient increases in liver enzymes were seen in three patients. Metolazone tended to maintain glomerular filtration rate and renal plasma flow while increasing salt and water losses. A proximal as well as a distal site of action was suggested for the drug, and its anti-hypertensive effect was confirmed.

Thiazides in advanced chronic kidney disease

“…As detailed in Table 1, these early studies included 5 small heterogeneous trials of metolazone in CKD all with a before-and-after design [22][23][24][25][26], and in general GFR was low with 2 trials reporting creatinine clearances for individual subjects as low as 1 mL/min. These studies showed an improvement in reported diuretic or antihypertensive outcomes with metolazone administration, and these early positive results are likely the reason that there is a persistent belief that metolazone is the unique thiazide that is effective in advanced CKD [27].…”

Diuretics

“…The dose in patients with severe renal insufficiency should probably not exceed 20 mg/day (Table 5) (DARGIE et al 1972;CRASWELL et al 1973;PATON and KANE 1977). Secondary action ot related to carbonic anhydrase inhibitory activity, but due to interference with Na phosphate cotransport Primary action related to an ability to interfere with activity of the need be given only once daily or every other day.…”

Metolazone and Its Role in Edema Management

“…Alternatively, metolazone administered with a loop diuretic can be uniquely successful in effecting a diuresis in edematous or diuretic‐resistant patients. Furosemide has been the loop diuretic most commonly administered with metolazone in clinical practice 1–25 . The basis for combination diuretic therapy is the principle of sequential nephron blockade: i.e., the proximal and more primary distal site of action of metolazone bolstering the effect of furosemide within the loop of Henle 26 .…”

“…Chronic renal failure. Metolazone monotherapy has occasionally proved effective in eliciting a diuretic response in advanced renal failure, 9,45–47 which has not always been the case with other thiazide diuretics 48 . A diuretic response has been demonstrable in the presence of an extremely low glomerular filtration rate (GFR), 1,5,7,9,19,27 as well as in patients undergoing maintenance hemodialysis 25,28,47 .…”

“…Metolazone monotherapy has occasionally proved effective in eliciting a diuretic response in advanced renal failure, 9,45–47 which has not always been the case with other thiazide diuretics 48 . A diuretic response has been demonstrable in the presence of an extremely low glomerular filtration rate (GFR), 1,5,7,9,19,27 as well as in patients undergoing maintenance hemodialysis 25,28,47 . The dose(s) of metolazone needed for a satisfactory diuretic response in renal failure have proved surprisingly variable, and typically do not have a defined relationship to the GFR 45–47 ; in this regard doses as high as 100–200 mg have been employed 13,45 …”