Kidney Disease

Am J Kidney Dis 2002 Aug;40(2):265-74
Effect of low-carbohydrate high-protein diets on acid-base balance, stone-forming propensity, and calcium metabolism.
Reddy ST, Wang CY, Sakhaee K, Brinkley L, Pak CY. Department of Internal Medicine, Section of General Internal Medicine, The University of Chicago, IL 60637, USA. sreddy@medicine.bsd.uchicago.edu

  BACKGROUND: Low-carbohydrate high-protein (LCHP) diets are used commonly for weight reduction. This study explores the relationship between such diets and acid-base balance, kidney-stone risk, and calcium and bone metabolism.
  METHODS: Ten healthy subjects participated in a metabolic study. Subjects initially consumed their usual non-weight-reducing diet, then a severely carbohydrate-restricted induction diet for 2 weeks, followed by a moderately carbohydrate-restricted maintenance diet for 4 weeks. Results: Urine pH decreased from 6.09 (Usual) to 5.56 (Induction; P < 0.01) to 5.67 (Maintenance;P < 0.05). Net acid excretion increased by 56 mEq/d (Induction; P < 0.001) and 51 mEq/d (Maintenance; P < 0.001) from a baseline of 61 mEq/d. Urinary citrate levels decreased from 763 mg/d (3.98 mmol/d) to 449 mg/d (2.34 mmol/d; P < 0.01) to 581 mg/d (3.03 mmol/d; P < 0.05). Urinary saturation of undissociated uric acid increased more than twofold. Urinary calcium levels increased from 160 mg/d (3.99 mmol/d) to 258 mg/d (6.44 mmol/d; P < 0.001) to 248 mg/d (6.19 mmol/d; P < 0.01). This increase in urinary calcium levels was not compensated by a commensurate increase in fractional intestinal calcium absorption. Therefore, estimated calcium balance decreased by 130 mg/d (3.24 mmol/d; P < 0.001) and 90 mg/d (2.25 mmol/d; P < 0.05). Urinary deoxypyridinoline and N-telopeptide levels trended upward, whereas serum osteocalcin concentrations decreased significantly (P < 0.01).
  CONCLUSION: Consumption of an LCHP diet for 6 weeks delivers a marked acid load to the kidney, increases the risk for stone formation, decreases estimated calcium balance, and may increase the risk for bone loss. Copyright 2002 by the National Kidney Foundation, Inc.

PMID: 12148098

  ABSTRACT
  Background A low-calcium diet is recommended to prevent recurrent stones in patients with idiopathic hypercalciuria, yet long-term data on the efficacy of a low-calcium diet are lacking. Recently, the efficacy of a low-calcium diet has been questioned, and greater emphasis has been placed on reducing the intake of animal protein and salt, but again, long-term data are unavailable.
  Methods We conducted a five-year randomized trial comparing the effect of two diets in 120 men with recurrent calcium oxalate stones and hypercalciuria. Sixty men were assigned to a diet containing a normal amount of calcium (30 mmol per day) but reduced amounts of animal protein (52 g per day) and salt (50 mmol of sodium chloride per day); the other 60 men were assigned to the traditional low-calcium diet, which contained 10 mmol of calcium per day.
  Results At five years, 12 of the 60 men on the normal-calcium, low-animal-protein, low-salt diet and 23 of the 60 men on the low-calcium diet had had relapses. The unadjusted relative risk of a recurrence for the group on the first diet, as compared with the group on the second diet, was 0.49 (95 percent confidence interval, 0.24 to 0.98; P=0.04). During follow-up, urinary calcium levels dropped significantly in both groups by approximately 170 mg per day (4.2 mmol per day). However, urinary oxalate excretion increased in the men on the low-calcium diet (by an average of 5.4 mg per day [60 µmol per day]) but decreased in those on the normal-calcium, low-animal-protein, low-salt diet (by an average of 7.2 mg per day [80 µmol per day]).
   Conclusions In men with recurrent calcium oxalate stones and hypercalciuria, restricted intake of animal protein and salt, combined with a normal calcium intake, provides greater protection than the traditional low-calcium diet.

  Lipid peroxidation (LP) has recently been suggested to trigger the atherosclerotic process as well as to worsen the progression of renal disease. Autoantibodies against oxidized low-density lipoproteins (Ox-LDLAb) were considered to provide a sensitive marker to detect LDL oxidation in vivo. To date few studies have been reported on Ox-LDLAb levels in patients with different degrees of renal failure. The aim of this study was to evaluate the influences of renal function, dietary manipulation, and lipids on Ox-LDLAb concentrations in uremic patients either on conservative or replacement therapy. Seventy-one patients (42 males, 29 females) aged 60 +/- 19 years with chronic renal failure (CRF) of different etiology and degree were divided into four groups according to serum creatinine levels [sCr(mg/dl)] and diet: CRF I > or = 1.5-3.0, CRF II > 3.0-5.5, and CRF III > 5.5 were all patients on a conventional low-protein diet, while a fourth group included patients on a vegetarian diet supplemented with keto analogues and amino acids (CRF SD >3.0). A further group was represented by patients on dialysis therapy. All patients were examined for Ox-LDLAb, triglycerides (TG), total cholesterol, HDL and LDL cholesterol, and apolipoproteins Apo A1, Apo B, and Lp(a). The results were compared with those of 20 controls (9 males and 11 females) aged 52 +/- 11 years with sCr <1.5 mg/dl. Ox-LDLAb increased, although not significantly, with TG and Lp(a) from the early stages of CRF along with the deterioration of renal function. However, TG and Lp(a) levels were significantly higher in all groups of patients except those on vegetarian diet (CRF SD). This group also showed the lowest Ox-LDLAb levels. No relationship was observed between lipids or apolipoproteins and Ox-LDLAb. Hyperlipidemic patients did not show higher Ox-LDLAb levels than normolipidemics. Our results show a progressive increase of LP as the renal function declines, which may account for the increased risk of cardiovascular disease reported in uremia. Dialysis does not correct significantly the oxidative state observed in patients with end-stage renal disease. Vegan diet, by reducing LP, TG, and Lp(a), is supposed to decrease the risk of cardiovascular disease and worth being reconsidered as an alternative effective therapeutic tool in patients with advanced CRF. Copyright 2001 S. Karger AG, Basel.

PMID: 11244306

  Kidney stones occur in up to 15% of the population. The incidence of stone disease is 0.1-0.4%, i.e. 100 to 400 out of 100,000 people form a kidney stone every year. The recurrence rate is high, reaching 52% within 10 years and 75% within 20 years, respectively. Since urinary supersaturation, the driving force for crystallisation and stone formation, directly depends on nutritional habits, dietary recommendations are an important part of stone treatment. The benefit of urine dilution by means of a high fluid intake (urine volume at least 2.5 L/d) has been established by several studies. On the other hand, incorrect dietary recommendations, such as the restriction of calcium as advocated for decades, can even promote stone formation! Indeed, large prospective trials have clearly demonstrated that the risk for stone formation decreases with increasing daily calcium intake. It is therefore mandatory that low-calcium diet is finally abandoned in patients with calcium kidney stones and replaced by a sufficient calcium consumption, i.e. 1200 mg per day. Furthermore, epidemiological studies confirm that a diet rich in meat protein carries an increased risk for forming upper urinary tract stones; thus, daily protein intake should not exceed 1 g/kg body weight, which corresponds with general recommendations for a healthy diet. Last but not least, more recent studies have shown that the consumption of high quantities of fruits and vegetables may protect against kidney stone formation, since it raises urinary excretion of citrate, an important inhibitor of crystallization. The present review emphasizes on the relations between nutrition and stone formation in the urinary tract and offers convenient and inexpensive measures for the prevention of recurrence of nephrolithiasis.

PMID: 10756693

  Progressive impairment of kidney function is one of the major problems in diabetic patients. Control of glycaemia and blood pressure is the main strategy for preventing or slowing impairment in renal function in this condition. However, contributing factors such as hyperlipidaemia and high protein intake have now been identified, and their control can be regarded as a complementary measure. The role of lipid abnormalities and hypercholesterolaemia in the pathogenesis of glomerular injury has been demonstrated in animal models, and a link between hypercholesterolaemia and diabetic nephropathy has been established in humans. To date, few intervention studies in diabetic patients have shown a slower decline in renal function. Nonetheless, in every study in which follow-up was long enough, cholesterol lowering had a beneficial effect on renal function. Although hypercholesterolaemia may not be the cause of renal injury, it represents an aggravating factor. High serum cholesterol seems to have a similar action on glomerular mesangial cells and endothelial cells. This appears to be analogous to the process of atherosclerosis, as mesangial cells possess binding sites for LDL and oxidised LDL, help recruit macrophages and secrete proliferative factors. Protein intake is another factor that can influence renal deterioration. Two meta-analyses have confirmed the beneficial effect of a low-protein diet in diabetic nephropathy, showing no adverse effects on the glycaemic control. Protein intake even seems to enhance the sensitivity of tissues and liver to insulin. Thus, there appear to be no contraindications to such diets in well-controlled diabetic patients. In short, although glycaemic and blood pressure control are still the main lines of treatment for diabetic patients, lowering blood cholesterol and restricting protein intake represent complementary measures that can help slow renal impairment.

PMID: 10922973

  BACKGROUND: High dietary protein intake is a potential risk factor for nephrolithiasis because of its capacity to increase urinary calcium and to facilitate lithogenesis [stone formaztion] through many other mechanisms.
  OBJECTIVE: Our aim was to verify the effects of moderate protein restriction in hypercalciuric patients.
  DESIGN: We studied 18 patients (10 men and 8 women aged 45.6+/-12.3 y) with idiopathic hypercalciuria and renal calculi. Before and after 15 d of a diet with 0.8 g protein x kg(-1) x d(-1) and 955 mg Ca, all patients were evaluated for the main serum and urinary measures of calcium metabolism as well as for urinary uric acid, oxalate, citrate, and prostaglandin E2.
  RESULTS: Urinary excretion of urea fell after the diet (P < 0.001). Urinary calcium (P < 0.001), uric acid (P < 0.005), oxalate (P < 0.01), and hydroxyproline (P < 0.01) decreased after protein restriction, whereas urinary citrate increased (P < 0.025). Blood pH increased [i.e. less acidic] after the hypoproteic diet (P < 0.05). 1,25-Dihydroxycholecalciferol (calcitriol) concentration fell significantly (P < 0.025) and parathyroid hormone increased (P < 0.001). Creatinine clearance tended to decrease (106.4+/-4.8 compared with 97.5+/-5.7 mL/min) after the diet. The decrease in urinary uric acid after the diet correlated with calcitriol concentration (r = 0.57, P < 0.05) and the decrease in urinary urea correlated positively with that in hydroxyproline excretion (r = 0.58, P < 0.01).
  CONCLUSIONS: In hypercalciuric patients, moderate protein restriction decreases calcium excretion, mainly through a reduction in bone resorption and renal calcium loss; both are likely due to a decreased exogenous acid load. Moreover, dietary protein restriction ameliorates the entire lithogenic profile in these patients.

PMID: 9989691

  PURPOSE: The influence of dietary lipids on nephrolithogenesis is unclear. In the present study, I investigated the role of dietary lipids concerning both the etiology and the prevention of nephrolithiasis using 9-week-old male Wistar rats. METHODS: Study 1: The rats were divided into five groups and reared on standard, low protein, high protein and high cholesterol diets for 23 weeks. Study 2: The effects of cholesterol on nephrolithiasis was examined. The animals were given a 30 intraperitoneal injection of 2 ml of 8.5% calcium gluconate. Study 3: A nephrolithiasis model was prepared by intraperitoneal administration of 40 mg/kg of glyoxylic acid and 0.25 microgram of vitamin D3 daily for 2 weeks. The inhibitory effects of eicosapentaenoic acid (EPA) on nephrolithiasis were studied. RESULTS: Study 1: In the groups given the high protein and high cholesterol diets, an increase in renal osteopontin-mRNA, one of the major matrix ingredients of stones containing calcium, was observed. Study 2: Microlith was more frequently observed in the high cholesterol group than in the standard diet group. Study 3: In the EPA group, lithiasis was less extensively than in the groups administered distilled water or olive oil, and this was assumed to be caused by factors other than inorganic substances such as calcium and oxalic acid in the urine. When the renal tissue specimens in Studies 2 and 3 were examined, initial calcium deposition was found to start from the basement membrane of renal tubular cells and gradually spread throughout the cells. CONCLUSION: These results suggested that cholesterol is a risk factor in nephrolithiasis, and EPA is effective in its prevention. The elimination of hyperlipidemia should be included in dietary instructions for nephrolithiasis patients.

PMID: 9990224

  The course of chronic renal failure is generally progressive and mediated by several factors that operate in combination. Several extrarenal events which may cause transient or permanent deterioration of renal function, are important, because their correction may slow the progression of renal disease e.g. volume disorders, infection, nephrotoxic agents. In progression of chronic renal disease leading factors are hypertension, proteinuria and high protein/phosphorus intake. Number of evidence suggests that ameliorating hypertension, reducing proteinuria slow the progression of chronic renal failure. Clinical studies in diabetic nephropathy demonstrated that the renoprotective effect of ACE inhibitors was independent of their effect of systemic blood pressure. In ESRD patients access for renal replacement therapy should be obtained as early as possible. An A-V fistula may take several weeks to mature especially in diabetic or elderly patients. Early dialysis has been advocated in diabetic patients. In general, patients can start ESRD therapy when residual kidney function drops to 5-10% of normal value. High quality of dialysis should be provided to the uremic patient with respect of successful renal transplantation.

PMID: 9876458

  BACKGROUND: A high-protein diet is one of the maneuvers which produce hypertrophy of kidney mass. The underlying mechanism(s) has not been elucidated. In the present study, we investigated the possibility that a humoral factor may be involved. METHODS: Twenty-eight 3-week-old Charles River rats were studied. Fourteen underwent right nephrectomy and 14 sham operation. Each of these groups was divided into two equal subgroups (n = 7 in each): one maintained on a regular diet (20% protein) and the other on a high-protein diet (60% protein) for 7 days. Following this period the animals were sacrificed. Sera from the animals were added to mesangial cell cultures from kidneys of intact 3-week-old rats, and the thymidine incorporation was assessed. RESULTS: The parameters of kidney mass indicated that the high-protein diet indeed produced kidney hypertrophy. Sera from the sham-nephrectomized animals fed a high-protein diet produced a significantly greater proliferative effect on mesangial cells in culture than sera from the respective animals on a normal-protein diet. Sera from either nephrectomized group or from the high-protein sham-operated group all had similar magnitudes of enhancement of mesangial cell proliferation. CONCLUSION: We conclude that the renal hypertrophy produced by a high-protein diet is mediated, at least in part, by a humoral factor(s).

PMID: 9647501

  OBJECTIVE: Whether the differences in renal function found in vegetarian compared with omnivorous subjects are related to quantity or quality of the protein is unknown. We have studied the renal function of nine normotensive, nonproteinuric type I diabetic patients who were fed in random order for 4 weeks either an animal protein diet (APD) (protein intake 1.1 g . kg-1 . day-1) or a vegetable protein diet VPD (protein intake 0.95 g . kg-1 . day-1). The two diets were isocaloric.
  RESEARCH DESIGN AND METHODS: In a crossover study, we measured glomerular filtration rate (GFR) (inulin clearance), renal plasma flow (RPF) (p-aminohippurate clearance), plasma amino acids, growth hormone, glucagon, insulin-like growth factor I-(IGF-I), and microalbuminuria.
  RESULTS: GFR and RPF were lower with the VPD than with the APD (89.9 +/- 4.1 vs. 105.6 +/- 5.1 ml . min-1 . 1.73 m-2, P < 0.05, and 425.7 +/- 22.2 vs. 477.8 +/- 32.2 ml . min-1 1.73m-2, P < 0.05, respectively). Renal vascular resistance (RVR) was higher with the VPD than with the APD (101 +/- 25 vs. 91 +/- 10 mmHg . min-1 . ml-1, P < 0.05). Filtration fraction (FF) remained unchanged after either diet. Fractional clearance of albumin fell with the VPD to 2.0 +/- 0.65 from 3.4 +/- 1.15 x 10-6 (P < 0.05). At the end of the APD and VPD, the plasma levels of growth hormone and glucagon did not differ significantly. Plasma levels of IGF-I were higher with the APD than with the VPD (1.1 +/- 0.6 vs. 0.9 +/- 0.13 U/ml, P < 0.05). Plasma concentrations of valine and lysine were significantly higher with the APD than with the VPD (234.6 +/- 30.3 vs. 164.5 +/- 25.4 mm1/1, P < 0.05, and 565 +/- 45.1 vs. 430 +/- 56.1 mmol/l, P < 0.05, respectively), whereas plasma valine was strongly correlated to the GFR (r = 0.832, P < 0.01). No differences were found in other amino acids.
  CONCLUSIONS: A VPD has significantly different renal effects from an APD equal in protein intake in normotensive type I diabetic patients. This could be explained partly by differences in plasma concentrations of amino acids and IGF-I.

PMID: 8612436

  The kidney stone-forming risk of a high sodium diet was evaluated by assessing the effect of such a diet on the crystallization of stone-forming salts in urine. Fourteen normal subjects participated in 2 phases of study of 10 days duration each, comprising a low sodium phase (basal metabolic diet containing 50 mmol. sodium per day) and a high sodium phase (basal diet plus 250 mmol. sodium chloride per day). The high sodium intake significantly increased urinary sodium (34 +/- 12 to 267 +/- 56 mmol. per day), calcium (2.73 +/- 1.03 to 3.93 +/- 1.51 mmol. per day) and pH (5.79 +/- 0.44 to 6.15 +/- 0.25), and significantly decreased urinary citrate (3.14 +/- 1.19 to 2.52 +/- 0.83 mmol. per day). Arterialized venous blood bicarbonate and total serum carbon dioxide concentrations decreased significantly during the high sodium diet, whereas serum chloride concentration increased. However, no change in arterialized venous pH was detected. Thus, a high sodium intake not only increased calcium excretion, but also increased urinary pH and decreased citrate excretion. The latter effects are probably due to sodium-induced bicarbonaturia and a significant decrease in serum bicarbonate concentration, respectively. Commensurate with these changes, the urinary saturation of calcium phosphate (brushite) and monosodium urate increased, and the inhibitor activity against calcium oxalate crystallization (formation product) decreased. The net effect of a high sodium diet was an increased propensity for the crystallization of calcium salts in urine.

PMID: 8326549

  OBJECTIVE: To examine and compare the food preferences of patients undergoing maintenance hemodialysis (HD) and continuous ambulatory peritoneal dialysis (CAPD) with those of age- and sex-matched controls. DESIGN: We administered two questionnaires, one assessing preferences for 88 food items (according to a nine-point hedonic scale) and the other assessing factors influencing dietary habits.
  SUBJECTS: Thirty-three patients on HD, 17 patients on CAPD, and 30 control subjects with normal renal function.
  MAIN OUTCOME MEASURES: The 88 foods were grouped into 14 classes to compare preferences. Taste aversions, food preparation details, and psychological and social determinants of food intake were also compared.
  STATISTICAL ANALYSIS: The preference ratings of the HD, CAPD, and control groups were compared using analysis of variance. The dietary habits results were examined using a chi 2 analysis.
  RESULTS: Sweet foods (P = .002), vegetables (P = .003), red meats (P = .010), and fish and poultry (P = .015) were less pleasant for patients on HD than for control subjects. Red meats (P = .019), fish and poultry (P = .032), and eggs (P = .005) were less pleasant for patients on HD than for patients on CAPD. Red meat was the most unpopular food group for all dialysis patients. The most common factor affecting dietary intake was a loss of interest in food and/or cooking.
  CONCLUSION: We conclude that chronic renal failure influences patients' food preferences and food habits. Knowledge of these preferences will help dietitians plan more adequate and enjoyable diets for such patients.

[NOTE: this suggests that the body will try to reject "foods" that cause disease. LF]

PMID: 8409134

  We wished to determine whether different types of dietary protein might have different effects on calcium metabolism and on the propensity for renal stone formation. Fifteen young normal subjects were studied during three 12-day dietary periods during which their diet contained vegetable protein, vegetable and egg protein, or animal protein. While these three diets were constant with respect to Na, K, Ca, P, Mg, and quantity of protein, they had progressively higher sulfur contents. As the fixed acid content of the diets increased, urinary calcium excretion increased [approx 50% - ljf] from 103 +/- 15 ( +/- SEM) mg/day (2.6 +/- 0.4 mmol/day) on the vegetarian diet to 150 +/- 13 mg/day (3.7 +/- 0.3 mmol/day) on the animal protein diet (P less than 0.02). Despite the increased urinary calcium excretion, there was a modest reduction of urinary cAMP excretion and serum PTH and 1,25-dihydroxyvitamin D levels consistent with acid-induced bone dissolution. There was no change in fractional intestinal 47Ca absorption. The inability to compensate for the animal protein-induced calciuric response may be a risk factor for the development of osteoporosis. The animal protein-rich diet was associated with the highest excretion of undissociated uric acid due to the reduction in urinary pH. Moreover, citrate excretion was reduced because of the acid load. However, oxalate excretion was lower than during the vegetarian diet [26 +/- 1 mg/day (290 +/- 10 mumol/day) vs. 39 +/- 2 mg/day (430 +/- 20 mumol/day); P less than 0.02]. Urinary crystallization studies revealed that the animal protein diet, when its electrolyte composition and quantity of protein were kept the same as for the vegetarian diet, conferred an increased risk for uric acid stones, but, because of opposing factors, not for calcium oxalate or calcium phosphate stones.

PMID: 2826524

  1. Studies were carried out on six normal male subjects to determine the short-term effect of increasing the dietary consumption of animal protein on the urinary risk factors for stone-formation, namely, volume, pH, calcium oxalate, uric acid and glycosaminoglycans.
  2. An increase of 34 g/day of animal protein in the diet significantly increased urinary calcium (23%) and oxalate (24%). Total urinary nitrogen increased by an average of 368 mmol/day. The accompanying increase in dietary purine (11 mmol of purine nitrogen/day) caused a 48% increase in the excretion of uric acid.
  3. The overall relative probability of forming stones, calculated from a combination of the risk factors, was markedly increased (250%) throughout the period of high animal protein ingestion.

PMID: 573189