Functional Reserve of the Kidney

Abstract

An exploration of the normal limits of physiologic responses and how these responses are lost when the kidney is injured rarely occurs in clinical practice. However, the differences between "resting" and "stressed" responses identify an adaptive reactiveness that is diminished before baseline function is impaired. This functional reserve is important in the evaluation of prognosis and progression of kidney disease. Here, we discuss stress tests that examine protein-induced hyperfiltration, proximal tubular secretion, urea-selective concentration defects, and acid retention. We discuss diseases in which these tests have been used to diagnose subclinical injury. The study and follow-up of abnormal functional reserve may add considerable understanding to the natural history of CKD.

Keywords: kidney disease.

Figure 1.

Protein-induced hyperfiltration results from the complex interplay of systemic hormonal changes (glucagon, vasopressin, IGF, somatostatin, growth factor, increased urea synthesis by the liver) that induce in the kidney functional changes that drive a reduction in the tubuloglomerular feedback (TGF) restraint of the GFR, with similar afferent and efferent glomerular arteriolar vasodilation. The reduction on the sodium concentration in the urine reaching the macula densa, which inhibits the TGF, results from the interplay of increased proximal reabsorption of sodium, increased urinary urea concentration, and robust activity of the sodium-potassium-chloride cotransporter 2 (NKCC2) in the thick ascending limb of the loop of Henle. Prostaglandins, kinins, and angiotensin participate in the functional changes in a manner incompletely understood. The results are a reduction in renal vascular resistance, and comparable increments in renal blood flow and GFR that maintain a stable filtration fraction.

Figure 2.

Kidney tubular functional reserve is independent of GFR changes. Data show tubular functional response 30 minutes after an intravenous bolus load of 88.4 μmol creatinine/kg body wt that achieved maximal stimulation of creatinine secretion (see text). (A) GFR, tubular secretion of creatinine (TScr), and TScr per milliliter of GFR (TScr/GFR) in healthy individuals. The lack of significant GFR changes is in contrast with the six-fold increase in TScr. (B) Comparison of the response of TScr in normal individuals, patients with sickle cell disease (SCD), kidney donors (KDonors), and transplanted patients (KTx; 4–164 months after transplantation) of comparable age. Data demonstrate the independence of stimulated TScr from GFR (inulin or iodine-125–iothalamate clearance). Drugs that interfere with creatinine secretion were suspended before the studies. Figure drawn from data in Rodriguez-Iturbe et al. (51) and Herrera et al. (50). GFR=mean±SEM; TScr=mean±95% confidence interval (normal individuals versus those with SCD and KTx; P<0.01).