Abstract
The measurement of glomerular filtration rate by the clearance of inulin or creatinine has evolved over the past 50 years into an estimated value based solely on plasma creatinine concentration. We have examined some of the misconceptions and misunderstandings of the classification of renal disease and its course, which have followed this evolution. Furthermore, renal plasma flow and tubular function, which in the past were estimated by the clearance of the exogenous aryl amine, para-aminohippurate, are no longer measured. Over the past decade, studies in experimental animals with reduced nephron mass and in patients with reduced renal function have identified small gut-derived, protein-bound uremic retention solutes ("uremic toxins") that are poorly filtered but are secreted into the lumen by organic anion transporters (OATs) in the proximal renal tubule. These are not effectively removed by conventional hemodialysis or peritoneal dialysis. Residual renal function, urine produced in patients with advanced renal failure or undergoing dialysis treatment, may represent, at least in part, secretion of fluid and uremic toxins, such as indoxyl sulfate, mediated by proximal tubule OATs and might serve as a useful survival function. In light of this new evidence of the physiological role of proximal tubule OATs, we suggest that measurement of renal tubular function and renal plasma flow may be of considerable value in understanding and managing chronic kidney disease. Data obtained in normal subjects indicate that renal plasma flow and renal tubular function might be measured by the clearance of the endogenous aryl amine, hippurate.
Highlights
WHEN NEPHROLOGY EMERGED IN the period 1940 –1960, its main attraction was the strong foundation of renal physiology that underlies the understanding of clinical disorders
Since creatinine is produced in muscles at a fairly constant rate, it was reasoned that glomerular filtration rate (GFR) could be estimated from measurement of creatinine, corrected for body size and age, in a single blood sample [32]
It was assumed that renal tubular function declined in parallel with glomerular filtration [3]
Summary
WHEN NEPHROLOGY EMERGED IN the period 1940 –1960, its main attraction was the strong foundation of renal physiology that underlies the understanding of clinical disorders. There is increasing evidence that the most life-threatening consequences of advanced renal disease, uremic cardiomyopathy characterized by heart failure, arrhythmias, and sudden death [36], are likely related to the accumulation of uremic solutes that are protein-bound and, not filtered or readily dialyzable, but rather are actively secreted by transporters in the proximal renal tubule [44].
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