Q: When (at what GFR) do you change over from hydrochlorothiazide (HCTZ) to loop diuretics? And what should be the starting dose?
The Kidney Disease Outcomes Quality Initiative (KDOQI) guidelines for hypertension and antihypertensive agents in chronic kidney disease1 (CKD) recommend replacing thiazide diuretics with loop diuretics once a patient’s glomerular filtration rate (GFR) falls below 30 mL/min/1.73 m2.
The mechanism of action for thiazide and loop diuretics differs by site of action in the kidney. Thiazide diuretics work in the distal convoluted tubules by inhibiting sodium (Na+)/chloride (Cl-) channels while the action of loop diuretics is exerted by inhibiting Na+/potassium (K+)/2Cl- channels in the thick ascending limb of the loop of Henle.2 Thiazide diuretics, with exception of metolazone, are ineffective in CKD stages 4 and 5 due to thiazide’s inability to reach the site of action.1,3
The initial furosemide dose should be 40 to 80 mg/d by mouth, preferably divided into two doses to minimize rebound sodium reabsorption.1,4 Weekly dose titrations by 25% to 50% may be made based on fluid status, blood pressure, and potassium level.1 Bumetanide and torsemide are loop diuretics that may also be used to therapeutically replace HCTZ when the GFR falls below 30 mL/min/1.73 m2. The relative potency of bumetanide: furosemide: torsemide is 1:40:20, respectively.5 The relative initiating dose equivalency of furosemide 40 mg would be bumetanide 1 mg or torsemide 20 mg.5,6
Finally, metolazone is a thiazide-related diuretic that retains its effectiveness even at GFR below 30 mL/min/1.73 m2.1,6 Metolazone can be initiated at oral doses of 2.5 to 5.0 mg/d and titrated up to 10 to 20 mg/d. Patients with residual renal function, defined as daily urine output exceeding 100 mL, may continue to use metolazone and loop diuretics even after dialysis is initated.5,7 Upon the loss of residual renal function, all diuretics should be discontinued.
Min Sik Shin
PharmD candidate, 2012, College of Pharmacy, University of Illinois at Chicago
Cheryl L. Gilmartin, PharmD
Clinical Assistant Professor, Department of Pharmacy Practice, College of Pharmacy, University of Illinois at Chicago;
Clinical Pharmacist, Ambulatory Pharmacy Services, University of Illinois Hospital and Health Sciences System, Chicago
REFERENCES
1. K/DOQI [Kidney Disease Outcome Quality Initiative] clinical practice guidelines on hypertension and antihypertensive agents in chronic kidney disease. Am J Kidney Dis. 2004;43(5 suppl 1):S1-S290.
2. Reilly RF, Jackson EK. Ch 25. Regulation of renal function and vascular volume. In: Chabner BA, Brunton LL, Knollman BC, eds. Goodman & Gilman’s The Pharmacological Basis of Therapeutics. 12th ed. New York: McGraw-Hill Professional; 2010.
3. Sica DA, Gehr TW. Diuretic use in stage 5 chronic kidney disease and end-stage renal disease. Curr Opin Nephrol Hypertens. 2003;12(5): 483-490.
4. Cohen DL, Townsend RR. Treatment of hypertension in patients with chronic kidney disease. US Cardiology. 2009;6(2):54-58.
5. Wickersham RM, ed. Drug Facts and Comparisons. St. Louis, MO: Wolters Kluwer Health; 2009.
6. Comparison of commonly used diuretics (Detail Document). Pharmacist’s Letter/Prescriber’s Letter. February 2012.
7. DRUGDEX® System [Internet database]. Greenwood Village, Colo: Thomson Reuters (Healthcare) Inc. Updated periodically.
8. National Kidney Foundation. MIPPA Kidney Disease Education Benefit. Your Treatment, Your Choice (2010). www.kidney.org/professionals/KLS/YTYC.cfm. Accessed September 19, 2012.
9. Turner JM, Bauer C, Abramowitz MK, et al. Treatment of chronic kidney disease. Kidney Int. 2012;81(4):351-362.