- Email: [email protected]
Clinical Approaches to Assessing and Managing Nursing Home Residents with Chronic Kidney Disease
PHARMACY COLUMN
Barbara J. Zarowitz
Clinical Approaches to Assessing and Managing Nursing Home Residents with Chronic Kidney Disease Barbara J. Zarowitz, PharmD, FCCP, BCPS, CGP, FASCP Impairment of renal function has been estimated to be present in as many as 60% of nursing home residents and measured to be present in 39%, despite normal serum creatinine values.1,2 Additionally, the prevalence increases with age such that in adults 85 years of age or older, as many as 96% have moderate renal impairment (i.e., creatinine clearance [CrCl] \60 mL/min).2 More severe limitation in renal function, as represented by CrCl \30 ml/min may be present in as many as 40% of nursing home residents aged 95 or older.1 Figure 1 demonstrates the relationship between increasing age and increasing prevalence of renal impairment. Several important factors should be taken into consideration in the assessment of older nursing home residents believed to have chronic kidney disease, including those with normal serum creatinine. The consequences of believing that renal function is normal in the face of a normal serum creatinine can lead to prescribing of inappropriate medication doses; missed opportunities to decrease further progression of chronic kidney disease through protective therapy; exposure to potential nephrotoxins; missed coincident diagnoses such as anemia, iron deficiency, and hyperparathyroidism; and missed opportunities to decrease medication cost avoidance through dose-reduction of renally excreted medications. A brief discussion of these considerations follows, with an emphasis on practical management approaches for older patients with chronic kidney disease. First, how should renal function be assessed in older nursing home residents? Serum creatinine alone can be misleading as noted earlier, because it can appear normal, yet because of decreased production of creatinine in persons with reduced mobility or muscle wasting and decreases in dietary protein, functional capability of the
118
kidneys may have deteriorated and can remain undetected.3 Therefore, measurement or calculation of CrCl or glomerular filtration rate (GFR) from standard equations is recommended.3,4 Figure 2 provides the 2 preferred equations: Modi fication of Diet in Renal Disease (MDRD) used to calculate GFR for staging chronic kidney disease and the Cockcroft-Gault equation used to calculate CrCl for drug dosing. Many laboratories automatically calculate GFR by MDRD as part of each serum creatinine analysis. Although neither equation is perfectly accurate in the older nursing home population, these are the best of available methods for reliability and consistency. CrCl slightly overpredicts GFR because creatinine is both filtered and secreted into the distal renal tubules, thereby giving the appearance of higher function but usually within a few mL/min of estimated GFR. With increasing age over 60 years, MDRD decreases in accuracy in the prediction of GFR. In accordance with the recommendations of the National Kidney Foundation Kidney Disease Outcome and Quality Initiative (KDOQI), assessment of renal function for staging of chronic kidney disease should be performed using the MDRD equation.5 Although there are numerous modifications of the Cockcroft-Gault equation that are used in practice to avoid overdosing the frail elderly patient, none has been validated against measured CrCl in the nursing home population. The use of serum creatinine (SCr) rounded to 1.0 and the lesser of actual body weight (ABW) or ideal body weight (IBW) has been validated in critically ill medical patients.6,7 In the absence of estimates of CrCl measured against a gold standard, it is prudent to use a conservative estimate of CrCl through the use of the modified Cockcroft-Gault equation in the best interest of resident safety.
Geriatric Nursing, Volume 30, Number 2
80
Percent of Patients
<30 (Men)
<30 (Women)
30-59 (Men)
30-59 (Women)
60
40
20
0 65-69
70-74
75-79
80-84
85-89
90-94
95+
Age (years)
Figure 1. Prevalence of low glomerular filtration rate in nursing home elderly—Cockcroft-Gault. Graphic depicts results noted in reference 1 and refers to the method outlined in reference 4.
In Table 1 of Ftag 329: ‘‘Potentially Unnecessary Drugs,’’ of the State Operations Manual: Guidance to Surveyors of Long Term Care Facilities, several renally eliminated medications are outlined with suggested monitoring (see Table 1 of this article).8 These medications are frequently the subject of surveyor inquiry. Additionally, numerous other medications prescribed commonly in nursing home residents are at least partially eliminated by the kidneys, including low-molecular-weight heparins, cephalosporin and carbapenem antibiotics, memantine, venlafaxine, paroxetine, mirtazapine, bupropion, ramipril, atenolol, simvastatin, rosuvastatin, pravastatin, and histamine-2 antagonists.9-11 A study was performed to determine whether dosing guidelines based on CrCl for renally excreted drugs were being applied to long-term care residents.12 Residents aged older than 65 years from 4 long-term care facilities in southern Ontario who had been prescribed a medication from a list of renally excreted drugs commonly prescribed in long-term care facilities had their charts reviewed to look for appropriate prescribing. The investigators found that approximately 1 in 3 prescriptions (34.1%) were considered inappropriate for the calculated CrCl of the residents. Overall, 42.3% of the residents who were prescribed a drug under review received at least 1 inappropriate prescription based on CrCl. Logistic regression found that age (odds ratio [OR] 5 1.06 per year; 95% confidence interval [CI], 1.03– 1.09, P 5 .001), weight (OR 5 0.96/kg; 95% CI,
Geriatric Nursing, Volume 30, Number 2
0.94–0.98, P \ .001), the total number of prescribed medications (OR 5 1.10; 95% CI, 1.04– 1.17, P 5 .001), and the number of physicians prescribing in the facility (OR 5 1.02; 95% CI, 1.003– 1.044, P 5 .03) were predictive for receiving an inappropriate prescription based on renal function. The authors concluded that renal function is often overlooked when prescribing renally excreted drugs to older long-term care residents. Calculation of CrCl before initiating therapy may help to avoid excessive exposure in instances in which the medication has associated toxicity and reduce cost when a lower dose or less frequent dosage administration may result in cost savings. Excessive dosing and higher cost is more common in parenterally administered medications, such as enoxaparin and
Abbreviated MDRDStudy Equation (Preferred Method) GFR (mL/min/1.73 m2) = 186.3 SCr -1.154 Age-0.203 0.742 (if female) 1.210 (if African American)
Modified Cockcroft-Gault Equation CrCl= (mL/min)
(140 –age) IBW (ABW if
0.85 if female
Figure 2. Equations for estimating glomerular filtration rate. CrCl 5 creatinine clearance; MDRD 5 Modification of Diet in Renal Disease; SCr 5 serum creatinine in mg/dL.
119
120
Table 1. Renally Eliminated Medications Outlined in F3298 as Potentially Unnecessary Medication
F329 Medication Issues of Particular Relevance
Aminoglycosides and vancomycin
Use should be limited to confirmed or suspected bacterial infections.
Nitrofurantoin
It is not the drug of choice for UTIs or prophylaxis of UTIs for patients with a GFR of \ 60 ml/min.
Fluoroquinolones
NSAIDs and COX IIs
Metformin products
Geriatric Nursing, Volume 30, Number 2
Chlorpropamide and glyburide Lithium Angiotensinconverting enzymes inhibitors and angiotensin receptor blockers
Should be avoided with patients with prolonged QTc intervals or in patients on antiarrhythmic agents. May affect glucose control in the elderly if they are on quinolones and have impaired renal function. Indicated for inflammatory conditions.Interactions with aspirin. Adverse events include GI bleeding, worsening renal function, and CNS side effects
Metformin has been associated with development of lactic acidosis, which is more likely to occur with elevated serum creatinine, abnormal creatinine clearance, age . 80 years, radiologic studies with iodinated contrast dyes, congestive heart failure requiring pharmacologic management, and acute or chronic metabolic acidosis with or without coma. Glyburide added to chlorpropamide as potentially unnecessary. Both drugs have long half-lives and increased risks for hypoglycemia in older persons. Should be avoided in patients with electrolyte abnormalities (sodium depletion). Should be avoided in patients with significant renal and cardiovascular disease. Monitoring of serum potassium is necessary. May cause angioedema, persistent chronic cough, or worsen renal failure. Potential for life-threatening potassium concentrations when used in combination with potassium supplements or potassium-sparing diuretics, including spironolactone.
Suggested Monitoring Guidance for SOM Issues and Concerns Monitor renal function. Monitor for signs of ototoxicity. Monitor renal function before initiation of therapy. Monitor pulmonary function tests and for peripheral neuropathy if administered long term. Monitor renal function before initiation of therapy. For diabetic patients, monitor blood glucose.
Monitor for GI bleeding (especially with asprin). Renal function should be tested yearly at a minimum if these medications are given on a scheduled dosage. Perform renal function tests for patients being initiated or maintained on metformin.
Alternative antidiabetic agents are recommended. If continued, monitor for signs of hypoglycemia Monitor serum lithium concentrations and renal function every 6 months. Monitor serum potassium and creatinine. Monitor for potential adverse consequences.
Geriatric Nursing, Volume 30, Number 2
Digoxin
Indicated for only the following: congestive heart failure, atrial fibrillation, paroxysmal supra-ventricular tachycardia, or atrial flutter. Use with caution in patients with impaired renal function. Dosage in older patients should ordinarily not exceed 0.125 mg/day except when used for atrial arrhythmia and ventricular rate. Close monitoring of both renal function and serum digoxin concentration. Adverse consequences may occur even with therapeutic concentrations. May interact with many other medications; may cause significant bradycardia, fatigue, nausea and vomiting, anorexia, weight loss, delirium, and cardiac arrhythmia.
Monitor serum digoxin concentrations, renal function, potential adverse consequences, and potential drug interactions.
CNS 5 central nervous system; COX 5 cyclooxygenase inhibitor; GFR 5 glomerular filtration rate; GI 5 gastrointestinal; NSAID 5 nonsteroidal anti-inflammatory drug; SOM 5 State Operations Manual; UTI 5 urinary tract infection.
Table 2. Dosage Reduction and Cost Savings of Selected Medications MedicationGeneric (Brand)
Normal Renal Function(CrCl . 60 mL/min) Dosage
Enoxaparin(Lovenox)† Daptomycin(Cubicin)‡ Imipenem/ cilastatin(Primaxin)x Levofloxacin(Levaquin)
40 mg/day 300 mg/d IV(6 mg/kg) 2 g/day divided as 500 mgq 6 hours 750 mg/day
CrCl 5 creatinine clearance; IV 5 intravenous. *Average wholesale price. † For hip replacement surgery. ‡ For Staphylococcus aureus in a 50 kg adult. x For body weight of 50–59 kg and moderately severe infection.
Cost*/day $34.09 $148.98 $169.64 $26.08
Severe Renal Impairment(CrCl \ 30 mL/min) Dosage 30 mg/d 300 mg every other day IV 1 g/day divided as 250 mg q 6 hours 750 mg every other day
Cost*/day
Savings Cost*/10 days
$25.58 $74.49 $86.72
$85.10 $744.90 $867.20
$13.04
$130.40
121
Table 3. Medications Associated with Causing or Worsening Renal Impairment Drug(s)
Type of Chronic Injury
Chinese herbs, cisplatin, ifosfamide Analgesics (antipyretic, NSAIDs) Carmustine Parenteral gold, Penicillamine
Interstitial fibrosis, tubular atrophy Papillary necrosis, interstitial nephritis Interstitial fibrosis, tubular atrophy, glomerulosclerosis Proteinuria, membranous glomerulonephritis, minimal change disease, immune complex mesangial glomerulonephritis Polyuria, interstitial fibrosis, tubular atrophy Interstitial fibrosis, tubular atrophy, glomerulosclerosis Vascular disease (fibrin thrombi, glomerular necrosis), interstitial fibrosis, tubular atrophy Tubulointerstitial nephritis Interstitial fibrosis, tubular atrophy, afferent arteriolopathy
Lithium Lomustine, streptozotocin Mitomycin C Propylthiouracil Tacrolimus, cyclosporine NSAID 5 nonsteroidal anti-inflammatory drug.
antibiotics. Table 2 depicts recommended dosage reduction and approximate cost savings for selected medications. Using average wholesale prices, significant savings in drug price can occur by appropriately adjusting the dose for the degree of renal impairment. Therefore, not only will dosage adjustment potentially avoid unnecessary adverse drug events, but facilities will realize savings in their medication expenditures. There are some medications and supplements that are associated with worsening renal function (Table 3).13 It is wise to avoid or minimize exposure to potential nephrotoxins in older nursing home residents who are at increased risk of renal impairment. Finally, when GFR or CrCl falls below 60 mL/ min, residents should be assessed for the presence of preventative therapy and identification of early consequences of chronic kidney disease, which can include anemia, malnutrition, hyperparathyroidism, hyperphosphatemia, vitamin D deficiency, and other bone and mineral disturbances.5 Angiotensin-converting enzymes and angiotensin receptor blockers are recommended to delay the progression of nephropathy in diabetic residents and those with proteinuria secondary to hypertension or chronic kidney disease. Given that diabetes and hypertension are the most common causes of chronic kidney disease, progression of renal impairment can be mitigated by attainment of good glucose, blood pressure, and lipid control. Residents can be screened for anemia and hyperparathyroidism by laboratory analysis of hemoglobin and intact
122
parathyroid hormone and treated when appropriate. In summary, there are many clinically appropriate considerations when renal function declines to \ 60 mL/min in nursing home residents. The first and most important is the need to assess renal function by calculation or measurement of GFR/CrCl rather than relying on SCr. Medications/supplements that may contribute to worsening of renal impairment or cause renal failure should be discontinued when possible. Identify medications that are eliminated primarily through the kidneys and then adjust dosages accordingly. Evaluate the resident for underlying causes and adverse consequences of chronic kidney disease. Initiate preventative therapies known to delay the progression of renal impairment when appropriate. Initiate therapy to treat the adverse consequences of chronic kidney disease. With the implementation of these basic considerations, we can improve the individualization of therapy and care of residents with chronic kidney disease.
References 1. Garg AX, Papaioannou A, Ferko N, et al. Estimating the prevalence of renal insufficiency in seniors requiring long-term care. Kid Inter 2004;65:646-53. 2. Giannelli SV, Patel KV, Windham BG, et al. Magnitude of underascertainment of impaired kidney function in older adults with normal serum creatinine. J Am Geriatr Soc 2007;816-23.
Geriatric Nursing, Volume 30, Number 2
3. Levey AS, Bosch JP, Lewis JB, et al. A more accurate method to estimate glomerular filtration rate from serum creatinine: A new prediction equation. Modification of Diet in Renal Disease Study Group. Ann Intern Med 1999; 130:461-70. 4. Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron 1976;16:31-41. 5. K/DOQI. Clinical Practice Guidelines for Chronic Kidney Disease: Evaluation, classification, and stratification. Kidney Disease Outcome Quality Initiative. Am J Kid Dis 2002;39:S1-246. 6. Zarowitz BJ, Robert S, Peterson EL. Prediction of glomerular filtration rate using aminoglycoside clearance in critically ill medical patients. Ann Pharmacother 1992; 26:1205-10. 7. Robert S, Zarowitz BJ, Peterson EL, Dumler F. Predictability of creatinine clearance estimates in critically ill patients. Crit Care Med 1993;21:1487-95. 8. State Operations Manual. Appendix PP: Guidance to surveyors of long-term care facilities. Rev 22. 12–15-06. F329 x483.25(l) Unnecessary Drugs, Centers for Medicaid & Medicare, Department of Health and Human Services. Available at www.cms.hhs.gov/transmittals/downloads/ R22SOMA.pdf. Cited January 11, 2009.
Geriatric Nursing, Volume 30, Number 2
9. Clinical Pharmacology On-Line. Tampa, FL: Gold Standard Inc., January 2009. Available at www. clinicalpharmacology.com/. Cited January 11, 2009. 10. Geriatric Pharmaceutical Care Guidelines. Covington, KY: Omnicare, Inc.; 2008. 11. Gilbert DN, Moellering RC, Eliopoulos GM, et al. The Sanford guide to antimicrobial therapy 2008. 38th edition. Hyde Park, VT: Antimicrobial Therapy Inc. 2008. 12. Papaioannou A, Clarke JA, Campbell G, et al. Assessment of adherence to renal dosing guidelines in long-term care facilities. J Am Geriatr Soc 2000;48:1470-3. 13. Tisdale JE, Miller DA. Drug induced diseases. Bethesda, MD: American Society of Health-System Pharmacists; 2005. BARBARA J. ZAROWITZ, PharmD, FCCP, BCPS, CGP, is chief clinical officer and vice president of professional services at Omnicare, Inc., Livonia, MI, and adjunct professor of Pharmacy Practice College of Pharmacy and Allied Health Sciences Wayne State University, Detroit, MI. 0197-4572/09/$ - see front matter Ó 2009 Mosby, Inc. All rights reserved. doi:10.1016/j.gerinurse.2009.01.001
123
Barbara J. Zarowitz
Clinical Approaches to Assessing and Managing Nursing Home Residents with Chronic Kidney Disease Barbara J. Zarowitz, PharmD, FCCP, BCPS, CGP, FASCP Impairment of renal function has been estimated to be present in as many as 60% of nursing home residents and measured to be present in 39%, despite normal serum creatinine values.1,2 Additionally, the prevalence increases with age such that in adults 85 years of age or older, as many as 96% have moderate renal impairment (i.e., creatinine clearance [CrCl] \60 mL/min).2 More severe limitation in renal function, as represented by CrCl \30 ml/min may be present in as many as 40% of nursing home residents aged 95 or older.1 Figure 1 demonstrates the relationship between increasing age and increasing prevalence of renal impairment. Several important factors should be taken into consideration in the assessment of older nursing home residents believed to have chronic kidney disease, including those with normal serum creatinine. The consequences of believing that renal function is normal in the face of a normal serum creatinine can lead to prescribing of inappropriate medication doses; missed opportunities to decrease further progression of chronic kidney disease through protective therapy; exposure to potential nephrotoxins; missed coincident diagnoses such as anemia, iron deficiency, and hyperparathyroidism; and missed opportunities to decrease medication cost avoidance through dose-reduction of renally excreted medications. A brief discussion of these considerations follows, with an emphasis on practical management approaches for older patients with chronic kidney disease. First, how should renal function be assessed in older nursing home residents? Serum creatinine alone can be misleading as noted earlier, because it can appear normal, yet because of decreased production of creatinine in persons with reduced mobility or muscle wasting and decreases in dietary protein, functional capability of the
118
kidneys may have deteriorated and can remain undetected.3 Therefore, measurement or calculation of CrCl or glomerular filtration rate (GFR) from standard equations is recommended.3,4 Figure 2 provides the 2 preferred equations: Modi fication of Diet in Renal Disease (MDRD) used to calculate GFR for staging chronic kidney disease and the Cockcroft-Gault equation used to calculate CrCl for drug dosing. Many laboratories automatically calculate GFR by MDRD as part of each serum creatinine analysis. Although neither equation is perfectly accurate in the older nursing home population, these are the best of available methods for reliability and consistency. CrCl slightly overpredicts GFR because creatinine is both filtered and secreted into the distal renal tubules, thereby giving the appearance of higher function but usually within a few mL/min of estimated GFR. With increasing age over 60 years, MDRD decreases in accuracy in the prediction of GFR. In accordance with the recommendations of the National Kidney Foundation Kidney Disease Outcome and Quality Initiative (KDOQI), assessment of renal function for staging of chronic kidney disease should be performed using the MDRD equation.5 Although there are numerous modifications of the Cockcroft-Gault equation that are used in practice to avoid overdosing the frail elderly patient, none has been validated against measured CrCl in the nursing home population. The use of serum creatinine (SCr) rounded to 1.0 and the lesser of actual body weight (ABW) or ideal body weight (IBW) has been validated in critically ill medical patients.6,7 In the absence of estimates of CrCl measured against a gold standard, it is prudent to use a conservative estimate of CrCl through the use of the modified Cockcroft-Gault equation in the best interest of resident safety.
Geriatric Nursing, Volume 30, Number 2
80
Percent of Patients
<30 (Men)
<30 (Women)
30-59 (Men)
30-59 (Women)
60
40
20
0 65-69
70-74
75-79
80-84
85-89
90-94
95+
Age (years)
Figure 1. Prevalence of low glomerular filtration rate in nursing home elderly—Cockcroft-Gault. Graphic depicts results noted in reference 1 and refers to the method outlined in reference 4.
In Table 1 of Ftag 329: ‘‘Potentially Unnecessary Drugs,’’ of the State Operations Manual: Guidance to Surveyors of Long Term Care Facilities, several renally eliminated medications are outlined with suggested monitoring (see Table 1 of this article).8 These medications are frequently the subject of surveyor inquiry. Additionally, numerous other medications prescribed commonly in nursing home residents are at least partially eliminated by the kidneys, including low-molecular-weight heparins, cephalosporin and carbapenem antibiotics, memantine, venlafaxine, paroxetine, mirtazapine, bupropion, ramipril, atenolol, simvastatin, rosuvastatin, pravastatin, and histamine-2 antagonists.9-11 A study was performed to determine whether dosing guidelines based on CrCl for renally excreted drugs were being applied to long-term care residents.12 Residents aged older than 65 years from 4 long-term care facilities in southern Ontario who had been prescribed a medication from a list of renally excreted drugs commonly prescribed in long-term care facilities had their charts reviewed to look for appropriate prescribing. The investigators found that approximately 1 in 3 prescriptions (34.1%) were considered inappropriate for the calculated CrCl of the residents. Overall, 42.3% of the residents who were prescribed a drug under review received at least 1 inappropriate prescription based on CrCl. Logistic regression found that age (odds ratio [OR] 5 1.06 per year; 95% confidence interval [CI], 1.03– 1.09, P 5 .001), weight (OR 5 0.96/kg; 95% CI,
Geriatric Nursing, Volume 30, Number 2
0.94–0.98, P \ .001), the total number of prescribed medications (OR 5 1.10; 95% CI, 1.04– 1.17, P 5 .001), and the number of physicians prescribing in the facility (OR 5 1.02; 95% CI, 1.003– 1.044, P 5 .03) were predictive for receiving an inappropriate prescription based on renal function. The authors concluded that renal function is often overlooked when prescribing renally excreted drugs to older long-term care residents. Calculation of CrCl before initiating therapy may help to avoid excessive exposure in instances in which the medication has associated toxicity and reduce cost when a lower dose or less frequent dosage administration may result in cost savings. Excessive dosing and higher cost is more common in parenterally administered medications, such as enoxaparin and
Abbreviated MDRDStudy Equation (Preferred Method) GFR (mL/min/1.73 m2) = 186.3 SCr -1.154 Age-0.203 0.742 (if female) 1.210 (if African American)
Modified Cockcroft-Gault Equation CrCl= (mL/min)
(140 –age) IBW (ABW if
0.85 if female
Figure 2. Equations for estimating glomerular filtration rate. CrCl 5 creatinine clearance; MDRD 5 Modification of Diet in Renal Disease; SCr 5 serum creatinine in mg/dL.
119
120
Table 1. Renally Eliminated Medications Outlined in F3298 as Potentially Unnecessary Medication
F329 Medication Issues of Particular Relevance
Aminoglycosides and vancomycin
Use should be limited to confirmed or suspected bacterial infections.
Nitrofurantoin
It is not the drug of choice for UTIs or prophylaxis of UTIs for patients with a GFR of \ 60 ml/min.
Fluoroquinolones
NSAIDs and COX IIs
Metformin products
Geriatric Nursing, Volume 30, Number 2
Chlorpropamide and glyburide Lithium Angiotensinconverting enzymes inhibitors and angiotensin receptor blockers
Should be avoided with patients with prolonged QTc intervals or in patients on antiarrhythmic agents. May affect glucose control in the elderly if they are on quinolones and have impaired renal function. Indicated for inflammatory conditions.Interactions with aspirin. Adverse events include GI bleeding, worsening renal function, and CNS side effects
Metformin has been associated with development of lactic acidosis, which is more likely to occur with elevated serum creatinine, abnormal creatinine clearance, age . 80 years, radiologic studies with iodinated contrast dyes, congestive heart failure requiring pharmacologic management, and acute or chronic metabolic acidosis with or without coma. Glyburide added to chlorpropamide as potentially unnecessary. Both drugs have long half-lives and increased risks for hypoglycemia in older persons. Should be avoided in patients with electrolyte abnormalities (sodium depletion). Should be avoided in patients with significant renal and cardiovascular disease. Monitoring of serum potassium is necessary. May cause angioedema, persistent chronic cough, or worsen renal failure. Potential for life-threatening potassium concentrations when used in combination with potassium supplements or potassium-sparing diuretics, including spironolactone.
Suggested Monitoring Guidance for SOM Issues and Concerns Monitor renal function. Monitor for signs of ototoxicity. Monitor renal function before initiation of therapy. Monitor pulmonary function tests and for peripheral neuropathy if administered long term. Monitor renal function before initiation of therapy. For diabetic patients, monitor blood glucose.
Monitor for GI bleeding (especially with asprin). Renal function should be tested yearly at a minimum if these medications are given on a scheduled dosage. Perform renal function tests for patients being initiated or maintained on metformin.
Alternative antidiabetic agents are recommended. If continued, monitor for signs of hypoglycemia Monitor serum lithium concentrations and renal function every 6 months. Monitor serum potassium and creatinine. Monitor for potential adverse consequences.
Geriatric Nursing, Volume 30, Number 2
Digoxin
Indicated for only the following: congestive heart failure, atrial fibrillation, paroxysmal supra-ventricular tachycardia, or atrial flutter. Use with caution in patients with impaired renal function. Dosage in older patients should ordinarily not exceed 0.125 mg/day except when used for atrial arrhythmia and ventricular rate. Close monitoring of both renal function and serum digoxin concentration. Adverse consequences may occur even with therapeutic concentrations. May interact with many other medications; may cause significant bradycardia, fatigue, nausea and vomiting, anorexia, weight loss, delirium, and cardiac arrhythmia.
Monitor serum digoxin concentrations, renal function, potential adverse consequences, and potential drug interactions.
CNS 5 central nervous system; COX 5 cyclooxygenase inhibitor; GFR 5 glomerular filtration rate; GI 5 gastrointestinal; NSAID 5 nonsteroidal anti-inflammatory drug; SOM 5 State Operations Manual; UTI 5 urinary tract infection.
Table 2. Dosage Reduction and Cost Savings of Selected Medications MedicationGeneric (Brand)
Normal Renal Function(CrCl . 60 mL/min) Dosage
Enoxaparin(Lovenox)† Daptomycin(Cubicin)‡ Imipenem/ cilastatin(Primaxin)x Levofloxacin(Levaquin)
40 mg/day 300 mg/d IV(6 mg/kg) 2 g/day divided as 500 mgq 6 hours 750 mg/day
CrCl 5 creatinine clearance; IV 5 intravenous. *Average wholesale price. † For hip replacement surgery. ‡ For Staphylococcus aureus in a 50 kg adult. x For body weight of 50–59 kg and moderately severe infection.
Cost*/day $34.09 $148.98 $169.64 $26.08
Severe Renal Impairment(CrCl \ 30 mL/min) Dosage 30 mg/d 300 mg every other day IV 1 g/day divided as 250 mg q 6 hours 750 mg every other day
Cost*/day
Savings Cost*/10 days
$25.58 $74.49 $86.72
$85.10 $744.90 $867.20
$13.04
$130.40
121
Table 3. Medications Associated with Causing or Worsening Renal Impairment Drug(s)
Type of Chronic Injury
Chinese herbs, cisplatin, ifosfamide Analgesics (antipyretic, NSAIDs) Carmustine Parenteral gold, Penicillamine
Interstitial fibrosis, tubular atrophy Papillary necrosis, interstitial nephritis Interstitial fibrosis, tubular atrophy, glomerulosclerosis Proteinuria, membranous glomerulonephritis, minimal change disease, immune complex mesangial glomerulonephritis Polyuria, interstitial fibrosis, tubular atrophy Interstitial fibrosis, tubular atrophy, glomerulosclerosis Vascular disease (fibrin thrombi, glomerular necrosis), interstitial fibrosis, tubular atrophy Tubulointerstitial nephritis Interstitial fibrosis, tubular atrophy, afferent arteriolopathy
Lithium Lomustine, streptozotocin Mitomycin C Propylthiouracil Tacrolimus, cyclosporine NSAID 5 nonsteroidal anti-inflammatory drug.
antibiotics. Table 2 depicts recommended dosage reduction and approximate cost savings for selected medications. Using average wholesale prices, significant savings in drug price can occur by appropriately adjusting the dose for the degree of renal impairment. Therefore, not only will dosage adjustment potentially avoid unnecessary adverse drug events, but facilities will realize savings in their medication expenditures. There are some medications and supplements that are associated with worsening renal function (Table 3).13 It is wise to avoid or minimize exposure to potential nephrotoxins in older nursing home residents who are at increased risk of renal impairment. Finally, when GFR or CrCl falls below 60 mL/ min, residents should be assessed for the presence of preventative therapy and identification of early consequences of chronic kidney disease, which can include anemia, malnutrition, hyperparathyroidism, hyperphosphatemia, vitamin D deficiency, and other bone and mineral disturbances.5 Angiotensin-converting enzymes and angiotensin receptor blockers are recommended to delay the progression of nephropathy in diabetic residents and those with proteinuria secondary to hypertension or chronic kidney disease. Given that diabetes and hypertension are the most common causes of chronic kidney disease, progression of renal impairment can be mitigated by attainment of good glucose, blood pressure, and lipid control. Residents can be screened for anemia and hyperparathyroidism by laboratory analysis of hemoglobin and intact
122
parathyroid hormone and treated when appropriate. In summary, there are many clinically appropriate considerations when renal function declines to \ 60 mL/min in nursing home residents. The first and most important is the need to assess renal function by calculation or measurement of GFR/CrCl rather than relying on SCr. Medications/supplements that may contribute to worsening of renal impairment or cause renal failure should be discontinued when possible. Identify medications that are eliminated primarily through the kidneys and then adjust dosages accordingly. Evaluate the resident for underlying causes and adverse consequences of chronic kidney disease. Initiate preventative therapies known to delay the progression of renal impairment when appropriate. Initiate therapy to treat the adverse consequences of chronic kidney disease. With the implementation of these basic considerations, we can improve the individualization of therapy and care of residents with chronic kidney disease.
References 1. Garg AX, Papaioannou A, Ferko N, et al. Estimating the prevalence of renal insufficiency in seniors requiring long-term care. Kid Inter 2004;65:646-53. 2. Giannelli SV, Patel KV, Windham BG, et al. Magnitude of underascertainment of impaired kidney function in older adults with normal serum creatinine. J Am Geriatr Soc 2007;816-23.
Geriatric Nursing, Volume 30, Number 2
3. Levey AS, Bosch JP, Lewis JB, et al. A more accurate method to estimate glomerular filtration rate from serum creatinine: A new prediction equation. Modification of Diet in Renal Disease Study Group. Ann Intern Med 1999; 130:461-70. 4. Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron 1976;16:31-41. 5. K/DOQI. Clinical Practice Guidelines for Chronic Kidney Disease: Evaluation, classification, and stratification. Kidney Disease Outcome Quality Initiative. Am J Kid Dis 2002;39:S1-246. 6. Zarowitz BJ, Robert S, Peterson EL. Prediction of glomerular filtration rate using aminoglycoside clearance in critically ill medical patients. Ann Pharmacother 1992; 26:1205-10. 7. Robert S, Zarowitz BJ, Peterson EL, Dumler F. Predictability of creatinine clearance estimates in critically ill patients. Crit Care Med 1993;21:1487-95. 8. State Operations Manual. Appendix PP: Guidance to surveyors of long-term care facilities. Rev 22. 12–15-06. F329 x483.25(l) Unnecessary Drugs, Centers for Medicaid & Medicare, Department of Health and Human Services. Available at www.cms.hhs.gov/transmittals/downloads/ R22SOMA.pdf. Cited January 11, 2009.
Geriatric Nursing, Volume 30, Number 2
9. Clinical Pharmacology On-Line. Tampa, FL: Gold Standard Inc., January 2009. Available at www. clinicalpharmacology.com/. Cited January 11, 2009. 10. Geriatric Pharmaceutical Care Guidelines. Covington, KY: Omnicare, Inc.; 2008. 11. Gilbert DN, Moellering RC, Eliopoulos GM, et al. The Sanford guide to antimicrobial therapy 2008. 38th edition. Hyde Park, VT: Antimicrobial Therapy Inc. 2008. 12. Papaioannou A, Clarke JA, Campbell G, et al. Assessment of adherence to renal dosing guidelines in long-term care facilities. J Am Geriatr Soc 2000;48:1470-3. 13. Tisdale JE, Miller DA. Drug induced diseases. Bethesda, MD: American Society of Health-System Pharmacists; 2005. BARBARA J. ZAROWITZ, PharmD, FCCP, BCPS, CGP, is chief clinical officer and vice president of professional services at Omnicare, Inc., Livonia, MI, and adjunct professor of Pharmacy Practice College of Pharmacy and Allied Health Sciences Wayne State University, Detroit, MI. 0197-4572/09/$ - see front matter Ó 2009 Mosby, Inc. All rights reserved. doi:10.1016/j.gerinurse.2009.01.001
123