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: In my orthopedic practice, we have a woman we are treating conservatively for low back pain (NSAIDs, muscle relaxants, and physical therapy). Her primary care provider told her that she cannot take the NSAIDs because of her kidney disease (she has chronic kidney disease [CKD] stage 3). Is there a safe dose of NSAIDs that she can use, or do I need to start narcotics? I would rather not do that!
Unfortunately, all NSAIDs increase the risk for acute kidney injury (AKI) and may exacerbate progression to chronic renal failure, particularly when large doses are taken chronically.3,4 Increased incidence of renal injury with NSAIDs has been seen in patients with existing CKD, hypertension, diabetes, and frequent hospitalizations.3 Most renal damage associated with NSAIDs is related to inhibition of prostaglandin synthesis (discussed below), but NSAIDs can also cause other types of kidney injury, such as interstitial nephritis, analgesic nephropathy, and membranous nephropathy. NSAID use is also associated with hyperkalemia, hyponatremia, and edema (sodium retention).
The primary mechanism of NSAID nephrotoxicity is inhibition of prostaglandin synthesis in the setting of decreased renal perfusion.3 Prostaglandins induce vasodilation of the afferent arterioles to maintain renal perfusion (and consequently GFR). If renal perfusion or effective fluid volume decreases (as in dehydration, diuretic therapy, heart failure, and cirrhosis), renal perfusion is maintained by increasing prostaglandin synthesis. NSAIDs block prostaglandin synthesis, therefore blunting this protective mechanism. Blocking prostaglandin with NSAIDs when renal perfusion is decreased can cause an AKI.
AKI can occur in patients with or without CKD, and it is associated with increased morbidity and mortality. AKI due to NSAID use may progress to end-stage renal disease if the NSAID is not stopped promptly. When NSAIDs are discontinued, renal function most often stabilizes, but residual renal insufficiency is likely to be permanent. In some patients, even after discontinuing the NSAID, the AKI progresses to more advanced kidney disease.
All NSAIDs carry the same risk for acute and chronic kidney disease, with little evidence to suggest that some are safer than others. Higher doses are more likely to cause renal damage, but dosing to prevent renal damage has not been defined. Indomethacin and ketorolac have most frequently been associated with AKI. If appropriate for the patient, acetaminophen 650 mg taken three times daily (scheduled, not “as needed”) can provide pain relief with less risk for kidney injury.
Additionally, narcotic medications are often necessary when treating severe pain in patients with high risk for NSAID-associated kidney injury.
Catherine Wells, DNP, ACNP, CNN-NP
University of Mississippi Health Care, Division of Nephrology, Jackson
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.