Assessment of Renal Function

In routine clinical practice it is not practical to collect the urine samples that are needed to measure creatinine clearance directly. However creatinine clearance in adult patients can be estimated either from a standard nomogram or from equations such as that proposed by Cockcroft and Gault (23). For meiy creatinine clearance can be estimated from this equation as follows  

The Cockcroft and Gault equation cannot be used to estimate creatinine clearance in pediatric patients because muscle mass has not reached the adult proportion of body weight. Therefore/ Schwartz and colleagues (25/ 26) developed the following equation to predict creatinine clearance in these patients  

For womeii/ this estimate should be reduced by 15%. While this equation estimates creatinine clearance 

From the standpoint of clinical pharmacology/ the utility of using the Cockcroft and Gault equation/ or other methods/ to estimate creatinine clearance stems from the fact that these estimates can alert healthcare workers to the presence of impaired renal function in patients whose creatinine formation rate is reduced. As discussed in Chapter 5, creatinine clearance estimates also can be used to guide dose adjustment in these patients. 

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Streptomycin Adults See footnote8 Children 20-40 mg/kg per day Ototoxicity, neurotoxicity, nephrotoxicity Baseline audiogram, vestibular testing, Romber testing and SCr Monthly assessments of renal function and auditory or vestibular symptoms... 

Laboratory monitoring is performed before initiating therapy and before each cycle of chemotherapy. A complete blood count should be obtained prior to each course of chemotherapy to ensure that hematologic values are adequate. In particular, white blood cell counts and absolute neutrophil counts can be decreased in patients receiving chemotherapy such as irinote-can and 5-FU and increase the risk of infection. Baseline liver function tests and an assessment of renal function should be done prior to and periodically during therapy. Other selected laboratory tests include checking for the presence of protein in the urine in patients receiving oxaliplatin and bevacizumab. 

Buchet JP, Roels H, Bernard A, et al. 1980. Assessment of renal function of workers exposed to inorganic lead, cadmium, or mercury vapor. J Occup Med 22 741-750. 

Maranelli G, Apostoli P. 1987. Assessment of renal function in lead poisoned workers. Occup Environ Chem Hazards 344-348. 

Patients receiving hypouricemic medications should have baseline assessment of renal function, hepatic enzymes, complete blood count, and electrolytes. The tests should be rechecked every 6 to 12 months in patients receiving long-term prophylaxis. 

Urinalysis can help clarify the cause of ARF. Certain laboratory parameters are helpful in the assessment of renal function with ARF (Table 75-2). Urine microscopy gives further information to assist with determination of the etiology of the ARF (Table 75-3). 

Assessment of renal function is not required prior to first administration to man or even during clinical development however, based on the potential implications of acute renal failure and the challenges in assessing it in normal healthy animals or humans, it would make sense to consider a proper assessment of renal function prior to first administration to humans. 

Special patient populations Initial and maintenance dosing should be conservative in patients with advanced age because of the potential for decreased renal function. Base any dosage adjustment on a careful assessment of renal function. Generally, do not titrate elderly, debilitated, or malnourished patients to the maximum dose. Do not initiate metformin IR and ER treatment in patients 80 years of age and older unless measurement of Ccr demonstrates that renal function is not reduced. 

Once the presence of hypertension is established, the question of whether to treat and which drugs to use must be considered. The level of blood pressure, the age of the patient, the severity of organ damage (if any) due to high blood pressure, and the presence of cardiovascular risk factors all must be considered. Assessment of renal function and the presence of proteinuria are useful in... 

Lenle, F, V, and Suit, P (1989). Assessment of renal function by serum creatinine and creatinine clearance Glomerular filtration rate estimated by four procedures. Our. Cfiem. 35, 2,326-2330. 

Duan SB, Wu HW, Luo JA, Liu FY. Assessment of renal function in the early stages of nephrotoxicity induced by iodinated contrast media. Nephron 1999 83(2) 122-5. 

Animal studies suggest that lipid formulations of AmB are effective in the treatment of fungal infections, but usually require higher doses than AmB [143,146, 147,154,155,163,164]. The lack of concomitant assessment of renal function in many of these studies makes it impossible to determine a dose ratio, although most reports confirm that the drug was well tolerated. As... 

E499 Apple, F.S., Benson, P., Abraham, P.A., Rosano, T.G. and Halstenson, C.E. (1989). Assessment of renal function by inulin clearance Comparison with creatinine clearance as determined by enzymatic methods. Clin. Chem. 35, 312-314. E500 Auslander, W. (1989). Die quantitative Analytik mit der Ektachem-Mehrschichtenfilmtechnik. Lab. med. 73, 71, Leserbrief E501 Ayers, G.J., Baldwin, A.J., Fowler, A.M., Goudie, J.H. and Burnett, D. (1989). Theophylline assay on Kodak Ektachem DTSC - Performance and interference by structurally-related compounds and salicylate. Ann. Clin. Biochem. 26, 268-273. 

S98 Gibb, I., Cross, P., Pratt, D. and Hall, R.R. (1985). Rapid ward assessment of renal function by reflectance photometric determination of plasma creatinine. Br.J, Urol. 57, 510-514. 

Data on biological variability are used to assist in the selection of the most appropriate test in a given situation. For example, creatinine clearance and urine creatinme have less intraindividual variation than serum creatinine so that creatinine clearance is a better choice than serum creatinine for initial assessment of renal function in an individual but the lower RCV for serum creatinine make this test better for monitoring individuals. However, the need for a urine collection reduces the practicality of using clearance in the initial assessment of renal function. Studies to determine whether the GFR calculated from the serum creatinine concentration might enhance the utility of the serum measurement still have to be performed. 

Ayatse JOJ, Kwan JTC. Relative sensitivity of serum and urinary retinol binding protein and aj-microglobuhn in the assessment of renal function. Ann CUn Biochem 1991 28 514-6. 

The initial laboratory evaluation is directed toward the assessment of renal function and measurement of serum albumin and magnesium concentrations. Serum intact PTH concentrations are low or inappropriately normal in hypoparathyroidism and elevated in pseudohypoparathyroidism. Vitamin D deficiency is characterized by low serum 25(OH)D> high PTH (secondary hyperparathyroidism), and high serum alkaline phosphatase (ALP). 

Qualitative assessments of renal function, such as x-ray, computed tomography, magnetic resonance imaging, sonography, and biopsy, are useful for determining the etiology and structural aspects of kidney disease. 

Assessment of Renal Function In Liver Disease CLcr estimation in patients with liver disease is problematic. Orlando and coworkers evaluated 10 healthy subjects, 10 patients with mild liver disease, and 10 with severe liver disease, and observed a measured CLcr CL inulin ratio of 1.05, 1.03, and 1.04 for each group, respectively. However, when the CLcr of patients with severe liver disease was estimated using the CG equation the resultant ratio (CLcr using CG CL inulin) was 1.23. Lam and associates likewise noted an overprediction by CG of the measured CLcr in patients with severe disease, by 40% to 100%. 

Luke DR, Halstenson CE, Opsahl JA, et al. Validity of creatinine clearance estimates in the assessment of renal function. Clin Pharmacol Ther... 

Quadri KHM, Bemardini J, Greenberg A, et al. Assessment of renal function during pregnancy using a random urine protein to creatinine ratio and Cockcroft-Gault formula. Am J Kidney Dis 1994 24 416-420. 

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