Overview and Risk Factors
The condition termed "chronic kidney disease" (CKD) is a progressive syndrome of renal insufficiency and failure in which the kidneys lose their ability to filter blood, concentrate the urine, excrete wastes, and maintain electrolyte balance. Formerly called chronic renal failure, CKD is an important public health issue that has been increasing in incidence and prevalence worldwide and consumes disproportionate healthcare resources in the United States. CKD is also a major independent risk factor for cardiovascular mortality.
About 75% of CKD cases are due to diabetes mellitus and/or hypertension. Other common etiologies include glomerulonephritis, renal cystic disease, congenital urologic disorders, urinary obstruction, multiple myeloma, amyloidosis, analgesic abuse, and atheroemboli.
While biochemical and hormonal abnormalities occur early, few symptoms occur until about 75% of kidney function has been lost. Initial presentation includes fluid retention, hypertension, anemia, and electrolyte disturbances. As kidney function is further compromised, overt signs of uremia occur: shortness of breath, nausea, vomiting, anorexia, weight loss, encephalopathy, asterixis, pruritis, and pericarditis.
African Americans have a significantly higher rate of CKD than other racial groups. This is partly due to higher rates of hypertension in this group. Other factors associated with increased risk include:
- Older age.
- Family history.
- Urinary tract disorders that may increase the risk of kidney damage: urinary tract infections, urolithiasis, urinary tract obstruction.
- Systemic medical disorders that may increase the risk of kidney damage: diabetes mellitus, hypertension, autoimmune disorders (eg, systemic lupus erythematosus), systemic infections.
- Nephrotoxic medications (eg, nonsteroidal anti-inflammatory drugs, contrast dye).
- Tobacco smoking.
Diagnosis and Treatment
The National Kidney Foundation has developed guidelines for classifying chronic kidney disease based on glomerular filtration rate (GFR):
- Stage 1: Normal GFR (> 90 ml/min/1.73 m2 for adults) with persistent albuminuria or structural abnormalities.
- Stage 2: GFR between 60-89 ml/min/1.73 m2 with persistent albuminuria or structural abnormalities.
- Stage 3: GFR between 30-59 ml/min/1.73 m2.
- Stage 4: GFR between 15-29 ml/min/1.73 m2.
- Stage 5 (end-stage renal failure): GFR < 15 ml/min/1.73 m2.
Further testing to determine the underlying etiology may include urinalysis; renal imaging including ultrasound and CT scan; and renal biopsy.
Because the kidneys are essential to regulating electrolyte and acid-base balance, CKD leads to chemistry disorders such as hyperkalemia, hyperphosphatemia, hypocalcemia, and metabolic acidosis.
Treatment for CKD aims to reduce the high cardiovascular mortality rate in this high-risk population and to slow disease progression. It is also important to address the underlying etiology, treat related conditions to reduce cardiovascular risk, and replace lost kidney function via dialysis or transplant when uremia develops.
In patients with diabetes mellitus or hypertension, control of blood glucose and blood pressure is very important. The rate of fall of GFR can be reduced or even halted with aggressive blood pressure and glucose control. Angiotensin-converting enzyme (ACE) inhibitors and angiotensin-receptor blockers (ARBs) are especially helpful blood pressure medications for diabetic patients, because they are kidney-protective.
Specific treatments for underlying disorders should be applied. In some cases, addressing the underlying etiology will retard or halt the loss of kidney function.
Sodium restriction and/or diuretics are usually needed to combat fluid retention.
Anemia is common in CKD patients due to the loss of renal erythropoietin production and should be treated with supplemental iron (if iron deficiency is also present) and synthetic erythropoietin to reach a target hemoglobin of 11-12 g/dL. Phosphate binders and dietary phosphorus restriction are indicated to keep phosphate <4.5 mg/dL.
Exercise can benefit patients with CKD. Resistance training in particular helps reduce the catabolic effects of a low-protein (0.6g/kg/day) diet,1 whereas aerobic exercise may help control blood pressure and lipid levels.2
Ultimately, dialysis or kidney transplantation will be necessary for patients who progress to end-stage kidney failure.
Managing CKD presents a nutritional challenge. Patients with CKD frequently have risk factors for atherosclerosis (hypertension, insulin resistance, and dyslipidemia), which would benefit from a fat-, sodium-, and sugar-restricted (but high-fiber) diet. But these patients also commonly present with malnutrition,3 which calls for a less restricted meal plan. The right kind of diet, as described below, can help control blood pressure, cholesterol, and the buildup of nitrogenous waste products in the blood, and may prevent cardiovascular events. Dietary changes can also slow progression to end-stage kidney disease. The following dietary factors may be clinically important.
Low Total and Animal Protein
A prolonged high-protein intake is accompanied by an increase in GFR,4 which in turn may cause intraglomerular hypertension and eventual loss of renal function.5 In women with mild renal insufficiency, those with the highest protein intake had a 3.5-fold risk for developing a ≥15% decrease in GFR, compared with those eating the least protein. This effect was attributed to nondairy animal (not vegetable) sources of protein.5
Evidence for the benefit of a low-protein diet is not conclusive. Some studies suggest that restricting protein intake to 0.6-0.75 g/kg/day may help delay the need for renal replacement therapy.6,7 The Modification of Diet in Renal Disease (MDRD) study did not reveal significant benefit. However, a later meta-analysis of five studies (including the MDRD Study A) reported a roughly 35% lower risk for renal failure or death on a low-protein diet8. A more recent review based on eight trials and including a total of 1524 patients indicated that, although the optimal protein intake remains unknown, reducing protein intake in individuals with CKD (and without diabetes) may reduce mortality from this disease by 31%, compared with higher or unrestricted protein intake.9
In patients with severely limited renal function, very low-protein diets (0.3 g vegetable protein/kg/day) supplemented with essential amino acids and keto analogs can correct metabolic acidosis, secondary hyperparathyroidism, resistance to insulin, and decreased Na(+)-K(+)-ATPase activity.10 Animal products are also a major source of cholesterol-raising saturated fat; avoiding animal products helps reduce elevated cholesterol levels (see below).
Patients with CKD are often salt-sensitive, responding to elevated intakes of sodium chloride with increases in glomerular filtration and proteinuria.11 Blood pressure is a known determinant of CKD progression, and sodium restriction is an important part of blood pressure control in kidney disease.12 Although additional clinical trials are required, evidence indicates that patients with chronic renal failure who adhere to low-salt diets have half the rate of decline in GFR as those who follow high-sodium diets.13
Low-protein diets may increase the risk for deficiency of thiamine, riboflavin, and especially pyridoxine, and vitamin C levels are also often low in CKD patients. In CKD patients not on dialysis, 5 mg per day of pyridoxine and 30 to 50 mg per day of vitamin C have been suggested.14 No standard recommendations for amounts of thiamine or riboflavin exist for this group of patients.
Vitamin D Supplementation
Deficiency of vitamin D is present early in the course of CKD, and correction may prevent activation of key pathogenic mechanisms in cardiovascular disease (eg, inflammation, myocardial cell hypertrophy and proliferation, and the renin-angiotensin system).15
A Diet High in Fiber and Low in Saturated Fat and Cholesterol
Most patients with chronic kidney disease die from cardiovascular causes before developing end-stage renal disease.16 In a significant number of patients, pharmacologic (ie, statin) reduction of serum lipids preserves GFR and reduces proteinuria.17 Studies show that a vegetarian diet has similar effects on lipids and decreases proteinuria.18,19
Dietary and supplemental sources of fiber may be helpful for reducing the buildup of nitrogenous waste products in the blood that cause many symptoms of uremia. Fiber may act through several mechanisms, including the adsorption and excretion of metabolic wastes and stimulation of colonic bacterial proliferation and subsequent incorporation of excess nitrogenous compounds.20 Although further clinical trials are needed, preliminary data indicate that high-fiber diets21 and fiber-supplemented diets22 both cause fecal nitrogen loss. Decreases in serum urea equal to 17% and 19% after 8 and 12 weeks of fiber supplementation, respectively, have been found with certain types of fiber, such as ispaghula husk.22
A High-Calorie Diet
Protein-calorie malnutrition in CKD may result from loss of appetite and poor food intake. In turn, these may be caused by uremia, unpalatable therapeutic diets, lack of adequate dialysis, psychosocial or economic factors, and leptin-induced anorexia and metabolic acidosis.14 Malnutrition-related consequences of metabolic acidosis include proteolysis; negative nitrogen balance; impairments of insulin activity, glucose utilization, and albumin synthesis; and a reduction in insulin-like growth factors (eg, IGF-1).14 Protein-energy deficit is associated with poor clinical outcome and mortality in chronic kidney disease, and the low albumin concentration that is a marker for this condition is a strong predictor of death in this population. Nutritional assessment is essential in these patients.
Omega-3 fatty acid supplements. Omega-3 fatty acid supplements are under study for their role in a form of primary glomerulonephritis called immunoglobulin A nephropathy. Some results have been encouraging, at least for some patient subgroups.26 Nevertheless, more study is required before omega-3 fatty acids can be considered an effective treatment for IgA nephropathy.
Diet: Low protein (0.3-0.6 g/kg ideal body weight, and dependent on residual kidney function); low-sodium, high-fiber, low saturated fat and cholesterol.
Nutrition Consultation: Registered dietitian to determine appropriate energy and protein requirements.
What to Tell the Family
CKD increases the risk for both cardiovascular events and end-stage disease that requires dialysis. The control of high blood pressure through sodium restriction and medication is central to preventing the progression of CKD. However, the addition of other dietary changes (restricting total and animal protein intake, and following a high-fiber diet) may help by reducing urea, cholesterol, and blood glucose levels. Lifestyle changes such as quitting smoking and getting regular exercise may improve disease management.
1. Castaneda C, Gordon PL, Uhlin KL, et al. Resistance training to counteract the catabolism of a low-protein diet in patients with chronic renal insufficiency. A randomized, controlled trial. Ann Intern Med. 2001;135:965-976.
2. Johansen, KL. Exercise and chronic kidney disease: current recommendations. Sports Med. 2005;35:485-499.
5. 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;138:460-467.
6. Lentine K, Wrone EM. New insights into protein intake and progression of renal disease. Curr Opin Nephrol Hypertens. 2004;13:333-336.
8. Pedrini MT, Levey AS, Lau J, Chalmers TC, Wang PH. The effect of dietary protein restriction on the progression of diabetic and nondiabetic renal diseases: a meta-analysis. Ann Intern Med. 1996;124:627-632.
9. Fouque D, Laville M, Boisselle JP. Low protein diets for chronic kidney disease in non diabetic adults. Cochrane Database Syst Rev. 2006;(2):CD001892.
10. Aparicio M, Chauveau P, Combe C. Are supplemented low-protein diets nutritionally safe? Am J Kidney Dis. 2001;37:S71-S76.
11. Weir MR, Fink JC. Salt intake and progression of chronic kidney disease: an overlooked modifiable exposure? A commentary. Am J Kidney Dis. 2005;45:176-188.
16. Chan CM. Hyperlipidemia in chronic kidney disease. Ann Acad Med Singapore. 2005;34:31-35.
18. Azadbakht L, Shakerhosseini R, Atabak S, et al. Beneficiary effect of dietary soy protein on lowering plasma levels of lipid and improving kidney function in type II diabetes with nephropathy. Eur J Clin Nutr. 2003;57:1292-1294.
19. Jibani MM, Bloodworth LL, Foden E, et al. Predominantly vegetarian diet in patients with incipient and early clinical diabetic nephropathy: effects on albumin excretion rate and nutritional status. Diabet Med. 1991;8:949-953.
20. Bliss DZ. Dietary fiber in conservative management of chronic renal failure.
Pediatr Nephrol. 2004;19:1069-1070.
22. Bliss DZ, Stein TP, Schleifer CR, et al. Supplementation with gum arabic fiber increases fecal nitrogen excretion and lowers serum urea nitrogen concentration in chronic renal failure patients consuming a low-protein diet. Am J Clin Nutr. 1996;63:392-398.
26. Appel GB, Waldman M. The IgA nephropathy treatment dilemma. Kidney Int. 2006; 69:1939-1944.