Chronic kidney disease (CKD) is a term that refers to abnormalities of kidney structure or function with implications for health. The diagnosis generally requires a duration of at least 3 months. The disease is typically a progressive syndrome in which the kidneys lose their ability to filter blood, concentrate urine, excrete wastes, and maintain electrolyte balance. CKD is an important public health issue that consumes major global health care resources. The worldwide prevalence of renal dysfunction is estimated to be between 11% and 13%.
CKD is a major independent risk factor for cardiovascular mortality, with more severe forms being equivalent to existing coronary artery disease (CAD) in their ability to predict cardiovascular death. CAD is the most common cause of death in CKD patients; they are more likely to die from cardiovascular disease than they are to progress to end stage renal disease.
The two most common contributors to CKD are diabetes and hypertension, collectively accounting for 7 out of every 10 new cases. Less common causes include glomerulonephritis, renal cystic disease, congenital urologic disorders, urinary obstruction, multiple myeloma, amyloidosis, analgesic abuse, and atheroembolic disease.
CKD may occur quickly or may develop over years with few, if any, symptoms until residual renal function is no longer sufficient to maintain homeostasis. Presenting signs and symptoms can include anorexia, weakness, malaise, fatigue, pruritus, nausea, vomiting, and altered mental status. Other signs of CKD can include fluid retention, hypertension, anemia, and electrolyte disturbances. Severe renal dysfunction can present as uremia, a condition which often affects the central nervous system, causing decreased mental status and, in some patients, seizures. There is no specific level of renal dysfunction at which uremia occurs, but once present, it necessitates dialysis.
Other risk factors:
Urinary tract disorders that may increase the risk of kidney damage: urinary tract infections, urolithiasis, chronic urinary tract obstruction.
Systemic medical disorders that increase the risk of kidney damage: diabetes mellitus, hypertension, overweight and obesity, excessive alcohol use, autoimmune disorders (e.g., systemic lupus erythematosus), systemic infections (e.g., HIV, hepatitis C), atherosclerosis.
Nephrotoxic medications (e.g., nonsteroidal anti-inflammatory drugs, radio-contrast dye, aminoglycoside antibiotics).
Initial diagnosis of CKD is made when the GFR is noted to be lower than normal, often estimated via measurement of serum creatinine and other variables. The testing needs to be repeated and renal function must be in a steady state over at least 3 months in order to determine that the renal disease is chronic, rather than just acutely changed.
Testing to determine the underlying etiology typically includes urinalysis with examination of sediment under microscope; renal imaging, initially with ultrasound; and renal biopsy in cases of unclear etiology. Urinary protein excretion should be checked, either with spot urine-creatinine or with 24-hour collection. Excessive protein excretion is a marker for structural damage to the kidney.
Because the kidneys regulate electrolyte and acid-base balance, CKD can lead to hyperkalemia, hyperphosphatemia, hypocalcemia, and metabolic acidosis. Laboratory studies should include a complete metabolic panel as well vitamin D and intact parathyroid hormone levels.
There are currently no recommendations from the United States Preventive Services Task Force to screen asymptomatic individuals without chronic disease.
The National Kidney Foundation has developed guidelines for classifying chronic kidney disease based on estimated glomerular filtration rate (eGFR). There are several methods of calculating eGFR. Some are more accurate when predicting a lower GFR while others are better used for estimating GFR in patients without advanced renal disease. The following stages are used to classify abnormal kidney function:
CKD incidence has been increasing since the 1980s, with the most growth seen in stage 3, according to the most recent United States Renal Data System study. Prevalence increases with age. Studies have shown that more than half of patients over 80 years old have stage 3 CKD or higher.
Treatment for CKD aims to slow disease progression and reduce cardiovascular mortality. It is important to address the underlying etiology and to treat associated conditions, such as anemia, hyperparathyroidism, hyperphosphatemia, hypertension, and acidosis. Decreased proteinuria is associated with reduced cardiovascular mortality. Dialysis may be used to compensate for lost kidney function when appropriate. Patients should be assessed by a nephrologist for the possibility of renal transplant. In patients who continue to progress and a need for hemodialysis is anticipated, an arteriovenous fistula should be placed and given time to mature prior to being needed. This is typically done while patients are in CKD stage 4.
Common indications for dialysis include development of uremia, fluid overload that is no longer responsive to diuretics, and severe electrolyte abnormalities. Care should be taken with elderly patients who have limited life expectancy, as dialysis can lead to a significant decline in functional status.
Dyslipidemia should be assessed and, if present, treated.
In patients with diabetes mellitus or hypertension, aggressive blood glucose and blood pressure control can slow or even halt the decline in GFR. Angiotensin-converting enzyme (ACE) inhibitors may be especially helpful blood pressure medications for diabetic patients, because they are kidney-protective. In diabetic patients without significant albuminuria, ACE inhibitors can prevent progression to diabetic kidney disease. The same may be true for angiotensin-receptor blockers (ARBs), although evidence is more limited. ACE inhibitors can cause transient increases in serum potassium concentrations, so routine monitoring is essential and dietary potassium may need to be limited.
Specific treatments for underlying disorders should be applied. In some cases, addressing the underlying etiology will slow or halt the loss of kidney function.
Sodium restriction and/or diuretics may be needed to combat fluid retention.
Anemia is common in CKD patients due to the loss of renal erythropoietin production. It is important to investigate other causes of anemia. Supplemental iron should be used if iron deficiency is also present. Once iron stores are adequate, synthetic erythropoietin (EPO) may be used to reach a target hemoglobin of 10 to 11 g/dL. Some studies indicate that EPO administration does not improve mortality directly. However, since it does reduce the need for transfusions in CKD stages 3-5, mortality is improved as a result of fewer opportunities for transfusion-related side effects.
Dietary phosphorus restriction should be the initial step to manage elevated phosphorous levels. As the disease progresses, the addition of phosphate binders may become necessary to keep phosphate values within a normal range as the kidney may no longer be excreting sufficient amounts. Phosphate is not removed sufficiently with dialysis.
Corrected calcium levels should be monitored, and if found to be low, may be supplemented as needed. Vitamin D levels should be assessed and are often low in CKD patients since the kidneys play a vital role in vitamin D synthesis. Supplements may be given only after phosphate levels are controlled since vitamin D increases phosphate reabsorption in the GI tract.
Exercise can help patients with CKD. Resistance training reduces the catabolic effects of a low-protein (0.6g/kg/d) diet, whereas aerobic exercise may help control blood pressure and lipid levels.
Ultimately, dialysis or kidney transplantation will be necessary for patients who progress to end-stage kidney failure. Early referral to a nephrologist, no later than onset of CKD stage 4 or when the likelihood of renal replacement therapy within one year is 10%-20%, has been shown to reduce mortality. Other circumstances that warrant early referral include sudden rapid change in eGFR, increased albuminuria, recurrent renal stones, or persistent electrolyte abnormalities. While trying to preserve residual renal function, it is important to avoid nephrotoxic medications and provide renal dosing of essential medications when possible.
Diets commonly consumed in Western countries are important contributors to CKD and its progression, through its contributing an excess of calories, high amounts of dietary acid and saturated fat from animal products, sodium, phosphorus, and refined sugars and lack of fruits, vegetables, and other foods high in fiber and nutritional antioxidants. Such diets contribute to the hypertension, insulin resistance, and dyslipidemia that patients with CKD experience. Patients with progressive CKD also commonly present with malnutrition, which calls for a meal plan high enough in calories to prevent excessive weight loss. The right kind of diet, as described below, can help reduce progression of CKD, control blood pressure and cholesterol, and may prevent cardiovascular events. The following dietary factors are clinically significant in patients with CKD.
Loss of excess weight. Obesity is an independent risk factor for the development and progression of CKD. Both dietary and surgical interventions that promote loss of excess weight reduce proteinuria and blood pressure. Other obesity-related diseases, including metabolic syndrome and nonalcoholic fatty liver disease, are also significantly associated with microalbuminuria, proteinuria, and an increased risk for CKD. ,  However, among patients with established CKD, obesity is associated with greater survival (discussed below).
High dietary acid load is directly related to CKD progression, bone loss and sarcopenia and is predictive of end-stage renal disease (ESRD) in patients with CKD. Diets rich in animal protein are acid-producing and have also been found to increase the risk for CKD progression and ESRD when compared with diets lower in acid load. Animal products are a chief source of saturated fat in human diets, and the intake of saturated fat has been associated with hyperalbuminuria, conferring a 33% greater risk in persons with the highest compared with lowest level of intake. Conversely, a higher dietary ratio of plant to animal protein has been associated with significantly reduced mortality in those CKD patients with lower eGFR values. A systematic review and meta-analysis found that individuals with the highest protein intake had significantly greater eGFR, compared with those eating the least protein; however, these effects have been attributed to nondairy animal (not vegetable) sources of protein. Conversely, several meta-analyses have shown the benefit of vegan, low-protein diets (LPD) for reducing CKD progression and shown their ability to defer the need for dialysis by roughly 1 year. LPDs have also resulted in reductions in secondary hyperparathyroidism, insulin resistance, hyperlipidemia, blood pressure, aldosterone, and endothelin.
Evidence indicates that patients with CKD are more salt-sensitive than the general population, and higher sodium intakes are associated with a decline in eGFR. The efficacy of drugs (e.g., ACE inhibitors) that reduce blood pressure and proteinuria is inhibited by higher sodium intakes. A recent Cochrane review concluded that reducing salt intake decreases proteinuria and blood pressure.
Hyperphosphatemia is a well-known contributor to bone disease in patients with CKD and is an independent risk factor for mortality in patients with stages 3 and 4 CKD. Phosphates added as preservatives to both red and white meats contribute 300-500 mg of phosphorus per day, 80% of which is absorbed in the GI tract; by comparison, absorption of phosphate from plant foods does not exceed 30%-40%. Patients with CKD are advised to limit dietary phosphorus to 800-1000 mg/day and to avoid phosphorus-containing food additives, but these are found in high quantities when consuming processed foods (including prepared frozen foods, dry food mixes, packaged meats, bread and baked goods, soups and yogurt), which can contribute an additional 700-800 mg of phosphorus per day.
Patients with CKD are at risk for deficiency of both vitamins and minerals, including B-vitamins, vitamin K, magnesium, and selenium. This is due in part decreased appetite and a decreased sense of smell and taste, leading to decreased food intake. A substantial proportion of patients with stages 4 and 5 CKD have thiamin-insufficient or deficient status, and a low-protein diet increases the number of patients with biochemical indicators of riboflavin deficiency. Biochemical indications of pyridoxine deficiency have also been found, and a high percentage of CKD patients have been found to have vitamin K deficiency.
Low intake of magnesium also poses a number of problems for patients with CKD. Several studies have established hypomagnesemia as an independent predictor of kidney function decline, and as an independent predictor of future negative cardiovascular outcomes and mortality in CKD patients. Low magnesium levels in CKD patients are closely linked with vascular changes seen, including increased intima-media thickness, arterial stiffness and vascular calcification through increases in inflammation, oxidative stress, vasoconstriction, and hypertension. Selenium is required for synthesis of plasma glutathione peroxidases (GSH-Px) that are synthesized in the kidney. Levels of both are significantly decreased in CKD patients, and supplemental selenium is required to increase GSH-Px in these patients. No standard nutrient recommendations exist for CKD patients.
According to the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines, vitamin D supplementation is indicated when patients with CKD have levels less than 30 ng/mL Vitamin D deficiency in CKD patients must be avoided in order to reduce a significantly greater risk for doubling of serum creatinine, ESRD, anemia, vascular calcification, cardiovascular events, cardiovascular mortality, and all-cause mortality.
Most individuals with chronic kidney disease die from cardiovascular causes before developing end-stage renal disease. The dyslipidemia of CKD is characterized by elevated plasma triglycerides and VLDL cholesterol (VLDL-C) and reduced HDL cholesterol (HDL-C) concentrations, which, along with proteinuria, are improved by a vegetarian diet. , Another benefit of a vegetarian diet is a high intake of fruits and vegetables. These can lower net acid excretion by approximately a third, which is comparable to administration of 0.5 mEq/kg/day of sodium bicarbonate, an amount clinically used to buffer metabolic acidosis. High fruit and vegetable intakes are also associated with a significant reduction in mortality in CKD patients when compared with low intakes. Dietary and supplemental sources of fiber can also be helpful, and a recent systematic review and meta-analysis concluded that dietary fiber supplementation significantly reduces serum urea and creatinine. High dietary fiber intake is associated with reduced mortality in patients with CKD.
Protein-energy wasting (PEW) is associated with poor clinical outcome and mortality in CKD and is multifactorial. Although reduced food intake due to anorexia and dietary restrictions are obvious contributors, uremia-induced alterations such as increased energy expenditure, persistent inflammation, acidosis, and endocrine changes such as lower levels of testosterone and thyroid hormone, resistance to insulin, growth hormone (GH), and IGF-1, and elevated levels of glucocorticoids are also significant contributors. Although correct implementation of protein-restricted diets does not induce protein-energy wasting, a relaxation in dietary restriction is warranted for patients with a significant degree of PEW.
Several reports have noted the toxic effects of Averrhoa carambola in patients with both CKD and end-stage renal failure on dialysis. The primary symptoms are neurological and include hiccoughing, vomiting, asthenia, paresis, muscle twitching, insomnia, mental confusion, convulsion, and coma. The outcome is fatal in some cases despite hemodialysis. The cause is thought to be tubular obstruction by calcium oxalate crystals as well as apoptosis of renal tubular epithelial cells.
Consultation with a nephrologist.
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 low-cholesterol diet
Nutrition consultation by registered dietitian to determine appropriate energy and protein requirements
CKD increases the risk for heart problems and further loss of kidney function. The family can help the patient make the dietary changes that will help preserve health. These include limiting sodium, restricting total and animal protein intake and following a high-fiber diet. If the patient smokes cigarettes, the family can help with the quitting process. Family members can also encourage regular exercise. All of these lifestyle changes are good for everyone involved.
When necessary, family members can also monitor medication use, to be sure that conditions such as high blood pressure and diabetes are well controlled.