Glomerular Filtration Rate Fails to Increase following Protein Ingestion in Hypothalamo-Hypophyseal-Deficient Adults

Abstract

Oral protein loads are known to induce an increase in glomerular filtration rate (GFR) in man and animals. The mechanism underlying this phenomenon is currently unknown. In order to study the possible role of growth hormone (GH) or other hypothalamo-hypophyseal (HH) factors in the response of GFR to a protein meal, we studied 4 chronically GH- or HH-defîcient adults and age-matched controls, free of renal disease, before and after ingestion of a large protein meal (red cooked meat). GFR, measured by inulin clearance and corrected for body surface area, was 18.5% lower during basal conditions (89.1 ± 6.0 ml/min) in the GH- or HH-deficient population when compared to controls (109.7 ± 9.1 ml/min), but this difference did not achieve statistical significance for this small patient population (p > 0.1, < 0.2). For a 3-hour postprandial period, mean GFR increased by 25.3% in the control population (136.8 ± 10.7 ml/min; p < 0.01), while mean GFR failed to increase in the GH- or HH-deficient patients (86.8 ± 10.9 ml/min; p > 0.10). Male control subjects, not pretreated with diethylstilbestrol, had no change in GH levels (p > 0.2). However, 1 female control was found to increase GH levels 10 times preprandial levels. These studies suggest that HH factors other than GH are mediators of the augmentation of GFR following a large protein load in human adults.

Increase in Renal Plasma Flow and Glomerular Filtration Rate during Growth Hormone Treatment May Be Mediated by Insulin-Like Growth Factor I

“…The evidence is as follows: First, with GH deficiency or in the absence of detectable levels of plasma IGF I, RPF and GFR were abnormally low, even when adjusted for the small body surface area of the patient. Low RPF and GFR in GH-deficient adults have been observed in other studies [1,2,8], Second, after the injection of GH, there was a large increase in plasma GH, to supraphysiological levels; however, RPF and GFR did not change in association with the elevated GH levels. This confirms previously reported data that GH infusion does not in crease RPF and GFR acutely [5].…”

“…These data are consistent with the thesis that the low ERPF and GFR in GH deficiency is due to the lack of synthesis of IGF I rather than the deficiency in GH per se. The data are also consistent with a stimulatory effect of IGF I on ERPF and GFR.Renal plasma flow (RPF) and glomerular filtration rate (GFR) are known to be low in growth hormone (GH)-deficient patients as compared to normal adults even when values are corrected for body surface area [ 1,2], In contrast, RPF and GFR are elevated in acromegal ics and fall rapidly after hypophysectomy, before a de crease in kidney size can be demonstrated [3,4], From these observations it has been inferred that GH may increase RPF and GFR. However, a short-term intrave nous infusion of GH failed to increase renal hemody namics in normal subjects [5], whereas repetitive daily intramuscular injections of GH for several days in nor mals [6,7] and hypopituitary patients [8] resulted in a significant rise in RPF and GFR.…”

Peptide hormones and the regulation of sodium excretion.

“…In four GH-deficient adults, GFR failed to increase after a large protein meal compared with the rise seen in four normal subjects. 123 However, plasma GH concentration did not increase in three of the four normal subjects after feeding, indicating that some abnormality other than impaired GH secretion accounted for the lack of effect of protein feeding in the GH-deficient subjects. In another study, GH secretion was stimulated by arginine infusion in normal and GH-deficient subjects.…”

“…Insulinlike growth factors I and II bear close structural similarity to insulin, and their actions are also similar in many target tissues. 150 Insulinlike growth factor I has recently been implicated as the mediator of GH-related increases in GFR and renal plasma flow, 123 and further studies will be needed to clarify the effects of these peptides as well as insulin itself on renal hemodynamics and sodium excretion.…”

Insulin resistance underlies the elevated cardiovascular risk associated with kidney disease and glomerular hyperfiltration

“…Both short-term and long-term animal protein ingestion elevate RPF and GFR in healthy subjects (Bergstrom et al, 1985;Bosch et al, 1983Bosch et al, , 1984Bosch et al, , 1986Brandle et al, 1996;Brouhard et al, 1987;Castellino et al, 1986;Chan et al, 1988;Fioretto et al, 1988;Hostetter, 1986;Jones et al, 1987;Kleinman and Glassock, 1986;Nakamura et al, 1990Nakamura et al, , 1991Pullman et al, 1954;. In contrast, vegetable protein intake does not intensify glomerular workload, regardless of the quantity ingested (Anderson et al, 1999;Bosch et al, 1983;Dhaene et al, 1987;Jenkins et al, 2001;Jones et al, 1985Jones et al, , 1987Kitazato et al, 2002;Kontessis et al, 1990;Nakamura et al, 1989Nakamura et al, , 1990Nakamura et al, , 1991Nakamura et al, , 1993Wiseman et al, 1987).…”