Table 2.

Non-GFR determinants of serum concentrations of endogenous filtration markers and clinical conditions associated with their variation

	Endogenous Filtration Markers
	Creatinine	Cystatin C	β-2 Microglobulin	β-Trace Protein
Non-GFR determinants
Generation	Muscle mass	All nucleated cells	All nucleated cells	CNS, testis, ovary
Tubular handling	Receptor-mediated tubular secretion (trimethoprim, cimetidine, fenofibrate, ritonavir, dolutegravir), level of GFR, cause of CKD (PKD versus others), antihypertensive agents (diuretics and CCB)	Receptor-mediated uptake and degradation in proximal tubular cells	Receptor-mediated uptake and degradation in proximal tubular cells	Receptor-mediated uptake and degradation in proximal tubular cells
Extrarenal elimination	GI (bacterial creatininase)	Multiple sites	Not known	Liver
Variation in non-GFR determinantsa
Associated clinical conditions	Muscle mass	Fat mass, inflammation (higher CRP, lower serum albumin), smoking, thyroid and corticosteroid hormone	Lymph-proliferative and plasma cell disorders, smoking, inflammation (higher CRP, lower serum albumin), proteinuria	Proteinuria, weight

There are two main methods for use in clinical studies to ascertain the association of race and other factors with the non-GFR determinants of endogenous filtration markers. For metabolites, such as creatinine, which are filtered and excreted in the urine, generation can be ascertained from urinary excretion in the steady state, tubular handling can be ascertained by comparison of urinary clearance with measured GFR, and extrarenal elimination can be ascertained by comparing plasma with urinary clearance. Then, variation in these processes can be assessed among racial groups (however determined) with and without adjustment for other explanatory factors. For low molecular weight proteins, such as cystatin C, which are filtered, reabsorbed, and metabolized with only small quantities excreted in the urine, inferences about variation in non-GFR determinants among racial groups are generally assessed by differences in the measured GFR filtration marker associations with and without adjustment for other factors. However, this latter method does not provide information about which physiologic process is affected. These methods could be supplemented by laboratory studies of the relevant mechanisms. CNS, central nervous system; PKD, polycystic kidney disease; CCB, calcium-channel blocker; GI, gastrointestinal; CRP, C-reactive protein.

^aAdjusted for age, sex, and race.