Reply
Sir,Our intention was to raise awareness of the potentially deleterious effect of a high-protein diet on progression in patients with renal disease. The impact of a high protein diet on normal kidneys, however, is not necessarily as clear-cut as put forward by Dr Manninen. The statement that a high protein diet should be used to ‘prevent’ renal functional decline is incorrect. In the short term, a high protein diet does lead to an increase in renal blood flow and an increase in glomerular filtration rate (GFR) [1,2]. This increase, however, termed hyperfiltration, does not represent a true sustained ‘improvement’ in renal function, but rather reflects a physiologic recruitment of renal functional reserve to offload the increased metabolic burden posed by a high-protein diet [1].
Conversely, hyperfiltration in the setting of renal ablation in rats may be attenuated by a low-protein diet, and renal disease progression halted or delayed [1,3,4]. The increase in single nephron GFR occurring after a high-protein meal is associated with glomerular hypertension, a pivotal factor in the final common pathway of progressive renal failure [4,5]. In contrast to the finding of Lacroix et al. [6], Hostetter et al. [2], did find evidence of increased glomerulosclerosis and proteinuria in normal rats fed a high-protein diet for 4 and 8 months. In addition, in rats with increasing degrees of renal mass ablation, a high protein diet resulted in progressive, several-fold increases in proteinuria and glomerulosclerosis, which worsened over time [2]. In all groups, rats on a high-protein diet had a higher GFR compared to those on a normal protein diet reflecting the hyperfiltration [2]. Differences in animal strain may account for these authors’ conflicting observations, which should raise further caution in extrapolation to humans. Interestingly, in both studies the high- and low-protein diets were isocaloric, a factor that may not always be the case in humans. People tend to take popular dietary advice to the extreme and may feel it is acceptable to consume protein ad libitum, regardless of calorie intake, as long as carbohydrates are avoided.
Although data in humans are not highly conclusive, Knight et al. [7] also found that in women with mild renal insufficiency a higher protein diet may accelerate loss of renal function. The human studies reporting lack of gross harm of high-protein diets cited by Dr Manninen should be regarded with a healthy skepticism, as the ability to detect renal dysfunction in the early 1800s, or a study of 7 days duration, cannot address long-term effects on renal function. It should be noted too that these reports included subjects with high-protein intake in the setting of high calorie expenditure (early explorers and body builders), which may offset a potentially negative impact of a high-protein diet on the kidney. Calorie restriction itself has been demonstrated to play a role in attenuating renal disease progression [8]. Manninen's letter does not fit the demographic we wish to target. Many people desperate for weight loss are often obese, diabetic, hypertensive and have, or are at high risk for, renal disease. These people tend to be sedentary. As we stated previously [9], the potential metabolic benefits in terms of weight loss, glucose and lipid control may outweigh the potential renal hazards of a high protein diet, but this remains to be demonstrated in clinical trials. In the interim, we strongly suggest that patients with renal dysfunction follow such high-protein, low-carbohydrate diets under close supervision of a dietician for guidance in appropriate food choices, attention to caloric intake and a healthy exercise programme.
Brigham and Women's Hospital Boston, MA USA Email: vluyckx{at}partners.org
References
- Brenner BM, Meyer TW, Hostetter TH. Dietary protein intake and the progressive nature of kidney disease: the role of hemodynamically mediated glomerular injury in the pathogenesis of progressive glomerular sclerosis in aging, renal ablation, and intrinsic renal disease. N Engl J Med 1982; 307: 652–6592[Web of Science][Medline]
- Hostetter TH, Meyer TW, Rennke HG, Brenner BM. Chronic effects of dietary protein in the rat with intact and reduced renal mass. Kidney Int 1986; 30: 509–5173[Web of Science][Medline]
- Hostetter TH, Olson JL, Rennke HG et al. Hyperfiltration in remnant nephrons; a potentially adverse response to renal ablation. Am J Physiol 1981; 241: F85–F934[Medline]
- Zatz R. Haemodynamically mediated glomerular injury; the end of a 15-year-old controversy? Curr Opin Nephrol Hypertens 1996; 5: 468–4755[CrossRef][Medline]
- Simons JL, Provoost AP, Anderson S et al. Modulation of glomerular hypertension defines susceptibility to progressive glomerular injury. Kidney Int 1994; 46: 396–4046[Web of Science][Medline]
- Lacroix M, Gaudichon C, Martin A et al. A long-term high-protein diet markedly reduces adipose tissue without major side-effects in Wistar male rats. Am J Physiol 2004; 287: R934–R9427
- Knight EL, Stampfer MJ, Hankinson SE et al. The impact of protein intake on renal function decline in women with normal renal function or mild renal insufficiency. Ann Intern Med 2003; 138: 460–4678
[Abstract/Free Full Text] - Reisin E, Harris KY, Azar S et al. A low-calorie unrestricted protein diet attenuates kidney damage in uninephrectomized spontaneously hypertensive rats. Am J Nephrol 1999; 19: 433–4409[Medline]
- Luyckx VA, Mardigan TA. High-protein diets may be hazardous for the kidneys. Nephrol Dial Transplant 2004; 19: 2678
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