Does Excess Protein Cause Kidney Damage?

by Ben Best

An article that appeared on the Sept 9, 1992 issue of THE NEW ENGLAND JOURNAL OF MEDICINE [ 307:652-659 (1982)] states that when renal patients "with serum creatinine concentrations averaging 2.2 mg per decilitre (190 micromole per liter) were maintained on a diet containing 30 to 40 gm of protein per day and were phosphate-restricted, no significant fall in glomerular filtration rate was observed over two years, whereas continued deterioration of renal function characterizes comparable patients whose intake of protein and phosphorus is not restricted."

The paper estimates that the average protein intake in the Western diet is about 100 grams per day. The authors suggest that "augmented intrarenal pressures and flows associated with ad libitum feeding contributes to the age-associated glomerular sclerosis repeatedly observed in laboratory animals and in human beings."

Changing the diet of dogs from carbohydrate to meat was shown to "increase renal blood flow and glomerular filtration rate by as much as 100 per cent." Moreover, "the average filtration rate was about 70 per cent higher in rats maintained on 35 per cent protein chow than in rats fed a diet containing only 6 per cent protein."

One extremely interesting comment made in this paper was "Development of renal lesions in both sexes [of mice and hamsters] can be delayed by making food available on alternate days". To me, it suggests that the difference in mean lifespan between every-other-day feeding and 50% "diet restriction" could be due to kidney function. A paper by Ingram & Reynolds in EVOLUTION OF LONGEVITY IN ANIMALS ( Woodhead & Thompson, Editors, 1987) reported 56% increase in mean lifespan for CRAN mice fed every-other-day as opposed to a 36% increase in mean lifespan for CRAN mice fed 50% normal calories. Quite possibly protected renal function was accounting for over half of the benefit attributed to CRAN. (Dr. Roy Walford fed his animals ad libitum on alternate days to achieve CRAN).

[CRAN refers to Caloric Restriction with Adequate Nutrition. For technical details about CRAN -- plus an account of my personal experiences with CRAN -- see my essays Caloric Restriction with Adequate Nutrition -- Overview and My Practice of Caloric Restriction with Adequate Nutrition .]

But why did CRAN experiments not show particular advantage for protein restriction? Perhaps the benefits (or hazards) of protein restriction are non-linear. That is, there may be a threshold value of kidney burden beyond which there is damage, but before which there is NO damage. The experiment cited above demonstrating renal patients on 30-40 grams of protein per day showing "no significant fall in glomerular filtration rate" over 2 years seems to support this explanation. If protein caused damage in a linear fashion, then at least SOME damage would be expected -- directly proportional to the amount of protein.

One study [AMERCIAN JOURNAL OF KIDNEY DISEASE 27(5):652-662 (1996)] compared kidney patients on a low protein diet (0.73gm/kg/day) with patients on a very low protein diet (0.66 gm/kg/day). It was concluded that for every 0.2 gm/kg/day of protein increase there was a 29% GFR (Glomerular Filtration Rate) decline associated with a 41% prolongation in the time before the patients experienced renal failure. However, another study [NEW ENGLAND JOURNAL OF MEDICINE 330(13):877-884 (1994)] comparing patients on a normal protein diet (1.3 gm/kg/day), a low protein diet (0.58 gm/kg/day) and a very low protein diet (0.28 gm/kg/day) showed only a small benefit for the low protein diet for patients with moderate renal insufficiency and no benefit for very low (as opposed to low) protein diet for patients with severe renal insufficiency. This might indicate a lower limit threshold for a benefit of protein restriction. Except that another study [KIDNEY INT 49(6):1783-1786 (1996)] comparing usual (1.3 gm/kg/day) protein diets with low protein diets (0.58 gm/kg/day) found a 28% lower GFR in the low protein group after 3 years on the diets. It was noted that the low protein group had lower blood pressure. Two other studies on children with chronic renal failure showed no benefit for protein restriction [ARCHIVES OF DISEASES OF CHILDHOOD 68(3):371-375 (1993) and LANCET 349(9059):1117-1123 (1997)], however. Possibly children are less susceptible to blood pressure reduction with reduced dietary protein.

A study of elderly persons not diagnosed with renal disease showed that a GFR change with age was only seen among those who ingested more than one gram of protein per kilogram body weight per day [NEPHROL. DIAL. TRANSPLANT (11 Suppl 9):85-88 (1996)]. A study of vegans and omnivores showed significantly lower GFR in vegans. The omnivores had higher urinary albumin excretion and higher blood pressure [NEPHRON 46(1):37-42 (1987)].

Two animal experiments, one on dogs [LAB. INVEST. 58(2):172-183 (1988)] and one on cats [LAB. INVEST. 70(3):347-357 (1994)] -- in which both dogs & cats had artificially reduced functional kidney mass -- showed fewer renal lesions in the animals with the lower protein diets. Neither of these studies, however, controlled for calories, leaving open the possibility that it was the calorie-reduction associated with the protein-reduction that provided the benefits. A much more careful study of cats [AMERICAN JOURNAL OF VETERINARY RESEARCH 59(5):575-582 (1998)] showed that protein was not associated with glomerular or non-glomerular lesions, but that reduced calories was associated with fewer non-glomerular lesions (but no association with glomerular lesions). Another study on cats [AMERICAN JOURNAL OF VETERINARY RESEARCH 54(10):1653-1662 (1993)] noted that cats on a high protein diet were more likely to suffer from low blood potassium than cats on a low protein diet -- and that this could be corrected with potassium gluconate supplement. There may be an association between blood potassium and blood pressure.

The kind of dietary protein may also be important. Subjects fed 90 grams of meat protein daily showed a significantly greater increase in GFR (stress on the kidney) than was seen for subjects fed 90 grams of milk protein [CLIN. NEPHROL. 27(2):71-75 (1987)]. By contrast, a study with whey protein [NAHRUNG 42(1):12-15 (1998)] showed no significant effects on liver or kidney function.

Studies on rats found that the use of soy protein rather than casein (a milk protein) resulted in markedly less kidney damage (and longer lifespans). This result was attributed to both the antigenic glycoprotein structure of casein and to the favorable lysine/arginine ratio in soy protein [ENDOCRINOLOGY 122:1847-1854 (1988) and JOURNALS OF GERONTOLOGY:BIOLOGICAL SCIENCES 43(1):B5-B12 (1988)]. Soy protein has a lysine/arginine ratio of 1.0, whereas in casein the ratio is 2.0 -- which is why soy stimulates insulin secretion less and is less atherogenic than casein [ANNALS OF NUTRITION AND METABOLISM 28:192-199 (1984) and ATHEROSCLEROSIS 41:429-431 (1982)]. Elderly Fischer 344 rats normally have a high prevalence of fatal nephropathy (kidney disease), but substituting soy protein for casein in the diet reduces the nephropathy considerably [JOURNAL OF GERONTOLOGY; Shimokawa,I; 48(1):B27-B32 (1993))]. A more recent review of the literature reinforces the conclusion that casein can be damaging to the sensitive kidney, whereas soy protein has no such effect [CURRENT OPINION IN NEPHROLOGY AND HYPERTENSION; Lentine,K; 13(3):333-336 (2004) and TOXICOLOGIC PATHOLOGY; Rao,GN; 30(6):651-656 (2002)].

An eleven-year study of 1624 nurses indicated that high protein intake had no effect on kidney function for women with normal kidneys, but that high protein (particularly meat) accelerated decline in kidney function in women with mild kidney impairment [ANNALS OF INTERNAL MEDICINE; Knight,EL; 138(6):460-467 (2003)].

Studies on human subjects (usually without distinguishing the type of protein) indicate that the effects of dietary protein are minimal in nondiabetic patients with no renal injury, but that protein restriction is beneficial for patients with chronic renal failure [AMERICAN JOURNAL OF KIDNEY DISEASES 31(6):1048-1049 (1998) and INTERNATIONAL JOURNAL OF ARTIFICAL ORGANS 20(6):304-308 (1997)]. Most, if not all, of the benefit from low protein diets is attributed to reduction in phosphates, sodium and acid [KIDNEY INTERNATIONAL; Mitch,WE; 57(Suppl.75):S38-S43 (2000)].

A study of diabetic mice showed that soy protein resulted in less kidney damage than casein only for high protein diets -- and suggested that the lower bioavailability of phosphorus in soy (70% of which is in phytic acid) may contribute to the protective effect of soy [JOURNAL OF NUTRITION; Teixeira,SR; 133(3):673-678 (2003)].

Type 2 diabetes (which is associated with obesity) has become the most common cause of end-stage renal disease. Over 90% of obese Zucker rats die from end-stage renal disease, but marked reduction in renal pathology can be achieved with as little as a 7% reduction in calories for male Zucker rats [JOURNAL OF NUTRITION; Stern,JS; 131(3):913S-917S (2001)]. A study of human type 2 diabetes patients showed that restricting carbohydrates and iron in combination with polyphenol (polyphenols extracted from tea) enrichment was nearly 50% more effective than protein restriction in improving renal function and increasing survival [DIABETES; Facchini,FS; 52(5):1204-1209 (2003)].

Although it is tempting to think that the dietary requirements of kidney patients may be a guide for healthy people wanting to avoid kidney disease in advancing years, such thinking may be mistaken. Kidney patients are under nutritional constraints that might lead to poor nutrition when applied to normal people. Potassium provides a good example of this.

It is quite probable that kidney damage from high-protein diets in humans is associated with Advanced Glycation End-products (AGES) produced by cooking meat [CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY; Uribarri,J; 1(6):1293-1299 (2006)]. The type of cooking can make a great difference, with significantly more AGE formation from frying, broiling & grilling as compared to steaming, poaching or boiling [JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY; Uribarri,J; 14(3):728-731 (2003)].

Sodium reduction is often recommmended to prevent high blood pressure (especially in the elderly), but potassium/sodium ratio may be more important than absolute amount of sodium -- such that keeping potassium high may be at least as good a strategy as restricting sodium [AMERICAN JOURNAL OF HYPERTENSION 12(8 Pt 1):849-851 (1999)]. Potassium is also essential for nerve & muscle (including heart) function and for electrolyte balance. A tomato or banana provides about 600mg of potassium and a cup of milk or several large mushrooms provides about 400mg of the estimated 2000mg minimum adult daily potassium requirement. Kidney patients can benefit from potassium (and reduced blood pressure) as much as, if not more, than most people. But potassium is often restricted in kidney patients because a malfunctioning kidney may be unable to excrete potassium. If blood levels of potassium increase without limit, the patient is in danger of fatal cardiac arrest.

Phosphorous is also restricted in kidney patients. For normal people phosphorous is as important as calcium for maintaining healthy bones, but for people with kidney disease high phosphorous can increase the harmful deposition of calcium in the kidney. Kidney patients have an increased requirement for calcium, but restrict dairy products because these foods are high in both calcium & phosphorous (meat is also high in phosphorous). Broccoli is high in both calcium & potassium, but does not have so much phosphorous. [References: HUMAN NUTRITION H.Guthrie & M.Picciano MOSBY (1995) and MODERN NUTRITION IN HEALTH AND DISEASE M.Shils, LEA&FEBIGER (1994)]

Vegetarians can ensure complete protein by combining legumes (peas, beans, peanuts soy, lentils, etc) with grains (wheat, rice, barley, etc) or nuts or seeds. A complete protein is one that includes all nine (eight for adults) of the essential amino acids: threonine, valine, methionine, leucine, isoleucine, phenylalanine, tryptophan and histidine (some histidine synthesis is possible for adults). Grains, nuts & seeds tend to be deficient in isoleucine & lysine, whereas legumes are high in lysine, contain moderate isoleucine and are deficient in tryptophan (except soybean, which is high in tryptophan). Methionine is often low in legumes and higher in grains. Dairy products are mostly complete (egg protein is the standard of completeness) and are very high in lysine. Milk or cheese will complement any grain, nut seed or legume. Legumes typically supply 25% of calories as protein, in contrast to grains which only supply 15%.

A vegetarian diet not only dramatically reduces fat and cholesterol intake, it reduces the amount of concentrated pesticide and chemical toxin found in high food-chain organisms. The World Health Organization has established that an adult requires only 5% of total calories in the form of protein (the same proportion found in human mother's milk -- cow's milk is 15%). Nearly all vegetables, legumes, grains, nuts and even fruit has at least that much protein (a banana's protein is 5% of total calories -- spinach and broccoli have protein nearly 50% of total calories). Most of the original 1971 edition of the book DIET FOR A SMALL PLANET dealt with combining protein, but the 1981 edition was mostly re-written to combat the misimpression that without animal protein one must pay close attention to ensure sufficient percentages of amino acids. Worry that vegetarian diets contain insufficient iron is also mistaken -- spinach, cucumber, lettuce, strawberries and lima beans all have several times the iron per calorie as does lean ground beef. Nonetheless, even the ardent vegetarian John Robbins advocates that vegetarians take Vitamin B12 supplement. (Meat, incidently, is the most common cause of airway obstruction and choking in adults.)

I am now inclined to believe that someone on a lactovegetarian CRAN diet (including adequate potassium) with low blood pressure probably won't achieve much benefit in making special efforts to reduce protein to protect kidneys. As a source of calories, protein is more satiating than carbohydrate. Therefore, a high-protein, low-calorie, lacto-vegetarian diet is an easier CRAN diet to comply with. Moreover, milk products are the major dietary source of calcium for most people. Although cheese has less lactose than milk, most of the potassium is lost with whey during cheesemaking. So skim milk or nonfat yogurt are probably the best dairy products for normal people who are wanting to have a long life with healthy kidneys. And substituting firm tofu for cheese would be a good choice if calcium intake is adequate.