When prescribing medications for patients, it is always advisable to know their estimated glomerular filtration rate (eGFR). The creatinine and blood urea nitrogen (BUN) by themselves are not always good indicators of renal function. If you have doubts, any reliable pharmacy source can guide you to dosing adjustments. Most medications do not require adjustments for eGFR greater than 60 mL/min/1.73m2.
Patients with an eGFR of less than 60 should never be prescribed NSAIDs, and extreme caution is advised with use of aminoglycosides and contrast dyes.
With medications such as ACE inhibitors, which can affect renal function (particularly levels of creatinine and potassium), eGFR should be monitored initially and within two weeks of each dosing adjustment. Other commonly prescribed drugs requiring dosing adjustment in patients with eGFR below 60 include gabapentin, metoclopramide, and ranitidine.1,2
As always, inquire about your patient’s use of complementary and alternative therapies, including herbal remedies, as these often are contraindicated in this population.
Jane S. Davis, CRNP, DNP
Q: I have a patient with CKD stage 4 (GFR, 30 mL/min/1.73m2). My supervising physician said to take him off his hydrochlorothiazide (50 mg qd) and start furosemide. Why do I do this, and at what dose do I start?
Thiazide diuretics work by blocking approximately 40% of sodium chloride reabsorption in the distal convoluting tubule of the nephron. This process increases the fractional excretion of sodium and provides a natriuresis with reduced blood pressure (BP). Thiazides also have a second mode of action in lowering BP by reducing peripheral vascular resistance.5
It is generally thought that thiazides are ineffective in patients with more advanced CKD because of more proximal sodium reabsorption in the nephron. This results in less sodium being delivered to the distal tubule and therefore less thiazide diuretic action in the distal tubule.5
The National Kidney Foundation’s Kidney Disease Outcomes Quality Initiative (K/DOQI)6 recommends that hypertension in CKD be treated with combination therapy: renin-angiotensin system blockade (ACE inhibitor/angiotensin receptor blocker) and thiazide diuretics in patients with CKD stages 1 to 3; and loop diuretics in those with CKD stages 4 and 5. No large study has evaluated thiazide diuretic use in patients with CKD stages 4 and 5. In one small study (n = 7) in which thiazides were compared with loop diuretics, there was similar BP control between the groups, but patients in the thiazide group had superior urinary fractional sodium excretion.5
There is new concern that thiazides may partially contribute to the increased risk for metabolic syndrome or diabetes. Reungjui et al7 have used animal models to demonstrate that the hypokalemic and hyperuricemic effects of thiazides are the culprits for this risk. They recommend managing the potassium and uric acid levels to manage or prevent this risk.
When a change is made from thiazides to loop diuretics, K/DOQI recommends starting furosemide at 40 mg/d and titrating upward as needed for BP and edema control. In my experience, counseling patients to follow a low-sodium diet (the American Heart Association recommends restricting sodium intake to 1500 mg/d) allows for a lower dose of furosemide (20 mg) to be effective.8
Elizabeth Evans, DNP
Renal Medicine Associates, Albuquerque, NM
REFERENCES
1. Gabardi S, Abramson S. Drug dosing in chronic kidney disease. Med Clin North Am. 2005;89(3):649-687.
2. Munar MY, Singh H. Drug dosing adjustments in patients with chronic kidney disease. Am Fam Physician. 2007;75(10):1487-1496.
3. Huerta C, Castellsague J, Varas-Lorenzo C, Garcia Rodriguez LA. Nonsteroidal anti-inflammatory drugs and risk of ARF in the general population. Am J Kidney Dis. 2005;45(3): 531-539.
4. Schneider V, Lévesque LE, Zhang B, et al. Association of selective and conventional nonsteroidal antiinflammatory drugs with acute renal failure: a population-based, nested case-control analysis. Am J Epidemiol. 2006; 164(9):881-889.
5. Loyd J, Wright P. Are thiazide diuretics an effective treatment for hypertension in patients with chronic kidney disease? J Okla State Med Assoc. 2008;101(5):84-85.
6. Kidney Disease Outcomes Quality Initiative (K/DOQI). K/DOQI clinical practice guidelines on hypertension and antihypertensive agents in chronic kidney disease. Am J Kidney Dis. 2004;43(5 suppl 1):S1-S290.
7. Reungjui S, Pratipanawatr T, Johnson RJ, Nakagawa T. Do thiazides worsen metabolic syndrome and renal disease? The pivotal roles for hyperuricemia and hypokalemia. Curr Opin Nephrol Hypertens. 2008;17(5):470-476.
8. Lichtenstein AH, Appel LJ, Brands M, et al. Diet and lifestyle recommendations revision 2006: a scientific statement from the American Heart Association Nutrition Committee. Circulation. 2006;114(1):82-96.
9. Pharmacokinetics. In: Golan DE, Tashjian AH, Armstrong EJ, Armstrong AW, eds. Principles of Pharmacology: The Pathophysiologic Basis of Drug Therapy. 2nd ed. Philadelphia, PA: Lippincott Williams & Wilkins, 2007:31-48.
10. Masters PA, O’Bryan TA, Zurlo J, et al. Trimethoprim-sulfamethoxazole revisited. Arch Intern Med. 2003;163(4):402-410.