Renal drug clearance

The renal drug clearance is influenced by alterations in glomerular filtration rate and tubular reabsorption or secretion rate. 

For women, the result should be multiplied by 0.85 (because of reduced muscle mass). It must be emphasized that this estimate is, at best, a population estimate and may not apply to a particular patient. If the patient has normal renal function (up to one third of elderly patients), a dose corrected on the basis of this estimate will be too low—but a low dose is initially desirable if one is uncertain of the renal function in any patient. If a precise measure is needed, a standard 12- or 24-hour creatinine clearance determination should be obtained. As indicated above, nutritional changes alter pharmacokinetic parameters. A patient who is severely dehydrated (not uncommon in patients with stroke or other motor impairment) may have an additional marked reduction in renal drug clearance that is completely reversible by rehydration. 

Leabman MK, Giacomini KM. Estimating the contribution of genes and environment to variation in renal drug clearance. Pharmacogenetics 2003 13 581-584. 

The renal drug clearance, as the major excretion route, is influenced to different extents by urine flow, urine pH and plasma protein binding. The extent of sensitivity to these parameters depends on the nature of compounds and mechanisms involved in its renal elimination (e.g. glumerular filtration, active secretion, passive re-absorption). Thus, interindividual variation in these parameters together with renal function determines the overall renal clearance, The urine flow is sensitive to individual fluid intake and administration of diuretic drugs. Interindividual differences in urine pH are mainly related to differences in diet and physical activity. 

Because GFR is usually decreased in patients with cirrhosis and assessments-based creatinine clearance can greatly overestimate renal drug clearance, drugs with considerable renal elimination and those with a narrow therapeutic range should be prescribed with caution [10]. 

Burt H, Neuhoff S, Lu G, Jamei M, Tucker GT, Rostami-Hodjegan A (2012) Simulation of the effect of urine pH on renal drug clearance using a novel population based mechanistic kidney model (Mech KiM). Paper presented at the Gordon research conference—drug metabolism, Holderness, NH, 8-13 July 2012... 

Salazar DE, Corcoran GB. Predicting creatinine clearance and renal drug clearance in obese patients from estimated fat-free body mass. Am J Med 1988 84 1053-1060. 

Alterations in one or more of the three renal processes (filtration, secretion, or reabsorption) secondary to reductions in functional nephron mass may have a dramatic effect on the pharmacokinetics of a drug. A reduction in glomerular filtration rate results in a decrease in renal drug clearance. For drugs that are extensively renally secreted (CLr >300 mL/min), the loss of filtration clearance (up to 120 mL/min) will have less of an impact than for those primarily dependent on GFR. 

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