The Role of Renal Response to Amino Acid Infusion and Oral Protein Load in Normal Kidneys and Kidney With Acute and Chronic Disease

Francis B. Gabbai


Curr Opin Nephrol Hypertens. 2018;27(1):23-29. 

In This Article

Abstract and Introduction


Purpose of review: High protein intake and hyperfiltration have been a focus of major interest as potential mechanism(s) of progression of renal disease. This review will examine: the renal response to a protein meal or amino acid infusion and its use to test the renal functional reserve (RFR); new methods to evaluate RFR; the use of RFR in various pathophysiologic conditions.

Recent findings: The renal response to protein/amino acid infusion involves several mechanisms, including nitric oxide, insulin, glucagon, arginine vasopressin, urea, the renal N-Methyl-D-Aspartate Glutamate receptor and modulation of the activity of the tubuloglomerular feedback system. Dose–response studies to evaluate RFR suggest the presence of a potential ceiling. The utilization of a noninvasive technique such as Doppler ultrasonography is trying to simplify the measurement of RFR and to bring this test into different clinical settings. There is increased interest in the presence or absence of RFR in patients with acute kidney injury, hypertension, chronic kidney disease, and its potential long-term implication regarding renal function.

Summary: The renal response to protein may help us understand the relationship between hyperfiltration, progression of renal disease, and other conditions (overall mortality, cardiovascular complications, and so on) currently being explored.


Protein intake and intravenous infusion of amino acids leads to renal vasodilation with consequent increases in renal plasma flow (RPF) and glomerular filtration rate (GFR).[1,2] This normal renal hyperemic response to protein loading has attracted the interest of many investigators as a mean to evaluate renal functional reserve (RFR).[2,3] RFR is defined as the difference between baseline GFR (bGFR) and GFR values achieved under stimulated GFR (sGFR) conditions by amino acid or a protein load. Absence of RFR has been interpreted as evidence of the presence of hyperfiltration. Studies by Neuringer and Brenner[4] approximately 40 years ago proposed that glomerular hypertension led to hyperfiltration and those hyperbaric conditions constitute a major mechanism of injury and progressive loss of nephrons. The progressive loss of glomeruli secondary to hyperfiltration has been proposed as one of the mechanisms to explain the progression of chronic kidney disease (CKD). As will be discussed in more detail, the role of hyperfiltration and RFR have been a focus of renewed interest in the renal literature in the setting of diabetic kidney disease, the obesity epidemic, and the use of high protein diet for weight loss, and the potential role of hyperfiltration as a risk factor for morbidity and mortality.[5,6–9]

The review will focus on recent publications regarding: mechanisms involved in the renal response to a protein meal or to single amino acid infusion; methodologies to measure or estimate RFR; RFR in various pathophysiologic conditions [acute kidney injury (AKI), hypertension, CKD]; hyperfiltration as a risk factor for morbidity and mortality.