Renal Function Assessment

Review for the Family Practitioner

Value

Family practitioners measure renal function parameters routinely in the primary care of patients. The benefits for patient management include:

  • Quantification of renal function
  • Identification and quantification of degree of renal impairment
    • Mild: 60-89 mls/min
    • Moderate: 30-59 mls/min
    • Severe: <30 mls/min (1)
  • Recognition of patients who require referral to tertiary care (a)
  • Follow-up monitoring
  • Medication usage: drug choices and dosing. (b)

(a) Referral to a Nephrologist

If a serum creatinine is above the lab upper value of normal, the primary care physician should first confirm the value with a second test and then investigate for reversible causes. The Canadian Society of Nephrology and the American Society of Nephrology recommend referral of patients identified with an estimated glomerular filtration rate of 30 mls/minute or less. (1,2) A rapidly changing creatinine (> 20%) or newly diagnosed serum creatinine > 300 µmol/l are also criteria for urgent referral. (2,3,4). In the presence of nephrotic or nephritic syndrome, homeostatic imbalance or systemic diseases that cause progressive renal disease, patients will require referral regardless of absolute value of measured glomerular filtration rate.

Family physicians should initiate strategies for 3 levels of renal dysfunction as outlined in Figure 1. (3, 4) In particular, the use of angiotensin converting enzyme inhibition or angiotensin receptor blockade therapy in diabetics or proteinuric disease should be considered. If initiated, the electrolytes and creatinine should be checked within several days of the initiation and again a week later. Serum creatinine increase of 20-30% with introduction of antihypertensive medications may occur in a patient with chronic renal insufficiency. If it remains stable at the new level, this should not be viewed as a contraindication as the benefit is for preservation of renal function. (5)

(b) Drugs

The dosage and choice of drug may be altered by renal impairment. Decreases in renal excretion of many drugs require dosage adjustments to avoid toxicity. Alternate agents may also be indicated at certain levels of dysfunction. The monographs in the Compendium of Pharmaceuticals and Specialties describe the pharmacokinetics of the drugs including excretion and give recommendations for dosing in renal impairment based on glomerular filtration rate. i.e.: Glucophage (metformin) monograph defines a Creatinine of in 136 in males and 124 in females as a contraindication due to potential for life threatening lactic acidosis complication. (6) A handbook on drug dosing in renal impairment is also available from the American Society of Nephrology. (7)

Methods

The gold standard for identification of glomerular filtration rate is inulin clearance. Exogenous excretion of radioisotopes such as iothalmate or DPTA radioisotope excretion are alternative measures. These tests are not practical as they are not readily available, cumbersome and costly. (3)

Other more common methods for estimation of the glomerular filtration rate include: (1) serum creatinine, (2) creatinine clearance estimated by serum creatinine, (3) creatinine clearance in a 24-hour urine collection. The use of these methods will be discussed. The calculation of the latter two will be described.

(1) Serum creatinine is dependant primarily on muscle metabolism and ingestion of meat products (creatine to creatinine). The creatinine level can be altered by muscle mass changes (decrease in elderly), liver disease (decreased muscle mass and creatine, decrease), malnutrition (decrease), large protein meat intake (increase), exercising (increase) and renal failure (increase). Medications (i.e. cimetidine, trimethoprim) can increase creatinine by inhibition of creatinine secretion. Other medications or ketoacidosis can interfere with the creatinine assay (increase). (3)

The value of the serum creatinine is that the test is easy, readily available, cheap. It can be used for follow-up monitoring of patients with previously determined creatinine clearance. The glomerular filtration rate is inversely related with serum creatinine. As the serum creatinine rises, the glomerular filtration rate is decreased. A graph of the change in serum creatinine can be used and measures that fall off the curve can indicate a potentially reversible cause of renal dysfunction. A stable creatinine in a patient with stable weight and diet can be assumed to have stable renal function. However, if there are changes in muscle mass, liver function or decreased nourishment, a stable creatinine indicates there is renal function decline.

(2) Estimation of creatinine clearance from serum values can be performed by various formulas. The most common formula was derived by Cockcroft and Gault and corrects for age, weight and gender. (8) It is the recommended method of calculation in the guidelines by the Canadian Society of Nephrology. (2) This formula should be used for steady state creatinine values only. The formula was (3) Tested against 24-hour collection and DTPA clearance and had a good correlation of 0.82. (8, 9) The value of this measure is that it requires only measurement of serum creatinine, and can be calculated by hand.

The Cockcroft Gault Formula (2,8,9):

(4) 24-hour urine can be ordered to measure creatinine clearance. The creatinine in the urine is measured and compared to a serum creatinine measured within 24 hours of the urine. Creatinine is both filtered at the glomerulus and secreted by the proximal tubule in the kidney. Therefore, unlike inulin, excretion overestimates the true glomerular filtration rate due to the secreted portion.

This method more accurately determines creatinine clearance particularly in malnourished patients. The disadvantage is the cumbersome nature of the test that results often in no collection or inaccurate collection. The patient must be educated carefully to discard the first morning urine specimen, to collect all other urination for the day of collection, through the night and the first specimen of the following day. The amount of creatinine in the 24 hour collection can be compared to an expected amount of creatinine production based on the size of the patient to determine the completeness of the collection: 177-221 mol/kg in males and 133-177 kg/kg in females based on lean body weight. (10)

Formula for creatinine clearance calculation in mls/min from 24-hour urine requires several corrections.

Creatinine/24 hours = 2.7 liters x 4.6 mmol/l = 12.42 mmol Cr
Adequate collection: 133-177 umol/kg = 10.64-14.16 g expected 24 hour Cr

As our patient population ages and requires more medications , and as we use more medications that are potentially toxic to the kidney, Creatinine Clearance has become an important issue for all Family Physicians to consider when prescribing drug therapy.

- Tammy Keough-Ryan

Thanks to Dr. Tom Hewlett is a staff nephrologist at the Cape Breton Regional Hospital in Sydney , Nova Scotia, for reviewing the draft copy of this article.

References:
  1. K/DOQI Clinical Practice Guidelines on Chronic Kidney Disease. AJKD 2002; 39(2) S.1: S1-S266.
     
  2. Churchill DN, Blake PG, Jindal KK, Tofflemire EB, Goldstein MB. Chapter 1: Clinical practice guidelines for initiation of dialysis. J Am Soc Nephrol 1999; 10:S287-S321.
     
  3. Mendelssohn DC, Barrett BJ, Brownscombe LM, Ethier J, Greenberg DE, Kanani SD, Levin A, Tofflemire EB. Elevated levels of serum creatinine: Recommendations for management and referral. CMAJ 1999; 161(4): 413-7. Comment 1999; 161(10): 1237-8.
     
  4. Anonymous. Elevated levels of serum creatinine. Guidelines for management and referral. Canadian Society of Nephrology. CanFamPhysician 2000; 46: 661-663.
     
  5. Palmer BF. Renal Dysfunction complicating the treatment of hypertension. NEngJMed 2002; 347:1256-1261.
     
  6. Canadian Pharmacists Association. Compendium of Pharmaceuticals and Specialties 2002. Repchinsky C. Editor. Webcom Ltd. Toronto, Canada.
     
  7. Aronoff GR, Berns JS, Brier TA, Morrison G, Singer I, Swan SK, Bennett WM. Drug prescribing in renal failure. Dosing guidelines for adults. Fourth Edition 1999. American College of Physicians, Philadelphia, Pennsylvania.
     
  8. Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron 1976; 16:31-41.
     
  9. Gault MH, Longerich LL, Harnett JD, Wesolowski C. Predicting glomerular function from adjusted serum creatinine. Nephron 1992; 62:249-256.
     
  10. Rose BD. Clinical Physiology of Acid-Base and Electrolyte Disorders Fourth Edition 1994. Jeffers JD, Navrozov M, editors, Smith S. McGraw-Hill, Inc., New York, USA.
     

Figure 1: Approaches to the diagnosis and treatment of patients with elevated levels of serum creatinine, at 3 stages of disease: newly discovered elevation of creatinine level (A), progressive renal failure (B) and just before end-stage disease (C). The creatinine values and time course are hypothetical and are intended for illustrative purposes only.

Reprinted with permission from DC Mendelssohn. CMAJ 1999; 161(4):413.

You can search for abstracts of the above references by following this link: PubMed

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