Renal Functional Reserve and Renal Recovery after Acute Kidney Injury

Abstract

Renal functional reserve (RFR) represents the capacity of the kidney to increase glomerular filtration rate (GFR) in response to certain physiological or pathological stimuli or conditions. Once baseline GFR is determined, RFR can be assessed clinically after an oral protein load or intravenous amino acid infusion. In clinical practice, baseline GFR displays variable levels due to diet or other factors. RFR is the difference between peak ‘stress' GFR induced by the test (p.o. or i.v.) and the baseline GFR. In clinical scenarios where hyperfiltration is present (high baseline GFR due to pregnancy, hypertension or diabetic nephropathy, in solitary kidney or kidney donors), RFR may be fully or partially used to achieve normal or supranormal renal function. Since commonly used renal function markers, such as GFR, may remain within normal ranges until 50% of nephrons are lost or in patients with a single remnant kidney, the RFR test may represent a sensitive and early way to assess the functional decline in the kidney. RFR assessment may become an important tool to evaluate the ability of the kidney to recover completely or partially after a kidney attack. In case of healing with a defect and progressive fibrosis, recovery may appear complete clinically, but a reduced RFR may be a sign of a maladaptive repair or subclinical loss of renal mass. Thus, a reduction in RFR may represent the equivalent of renal frailty or susceptibility to insults. The main aim of this article is to review the concept of RFR, its utility in different clinical scenarios, and future perspective for its use.

Biomarkers of acute kidney injury: the pathway from discovery to clinical adoption

“…At the initial stage of critical illness, stressed cells are not injured, but continuation of the injurious processes leads to tubular cell injury. Subclinical AKI occurs when biochemical or anatomical evidence of injury exists but the classic criteria of AKI are not met [175,[178][179][180].…”

Glomerular and Tubular Kidney Stress Test: New Tools for a Deeper Evaluation of Kidney Function

“…Serum creatinine (sCr) tends to remain normal even in presence of a solitary kidney when 1 of the 2 organs is removed [5]. In CKD sCr is still within normal range in the presence of a progressive nephron loss (up to 50%).…”

“…In normal subjects, baseline GFR (bGFR) tends to change throughout the day depending on physiological requirements. GFR can also increase from baseline due to stimuli such as acute oral protein load or intravenous amino acid infusion [3,4,5]. This capacity to increase GFR in response to a stimulus is known as glomerular RFR (RFR-G).…”

“…In presence of appropriate stimuli, patients with intact nephron mass can in fact increase glomerular filtration rate (GFR) and tubular secretion (TS) [2,3,4]. The difference between maximal functional capacity and baseline function represents the renal functional reserve (RFR) [5,6]. The ability to test this reserve may represent an excellent diagnostic possibility to unveil subclinical disease or silent loss of nephron mass [7,8].…”

Cell Cycle Arrest Biomarkers: New Weapons for A New Battle

“…Even a subclinical (creatinine negative) injury, that may appear to be negligible, can produce a significant parenchymal damage [11]. This may be underestimated due to the presence of a significant renal functional reserve in the kidney and the absence of clinical signs and symptoms [12]. The injury, however, reduces the functioning renal mass and produces a progressive increase in kidney frailty with a remarkable susceptibility to future injuries.…”