As eGFR declines, complications and comorbidities occur more commonly and are more severe. These include:
People with CKD are at increased risk for CVD. Most patients with CKD die of CVD-related complications than progress to ESRD.
Preventive strategies for CVD and CKD overlap. Blood pressure control and glucose control are paramount. Additionally, lipid control may be important to prevent CVD. Low-density lipoprotein (LDL) cholesterol should be lowered with diet, physical activity, and pharmacologic therapy. The target level for LDL cholesterol has not been established specifically for CKD. Inflammation may be a key factor raising cardiovascular risk in CKD.
Non-traditional risk factors for CVD include albuminuria, anemia and abnormal metabolism of calcium and phosphorus. Patients with CKD are in the high-risk category for CVD risk factor management.
Aspirin (acetylsalicylic acid or ASA) therapy is recommended unless otherwise contraindicated for those with CKD.
The National Institute of Diabetes and Digestive and Kidney Disease is funding the Chronic Renal Insufficiency Cohort (CRIC) Study, which is investigating the link between CVD and CKD, examining risk factors for progression of CKD and the occurrence of CVD among patients with CKD. Insights from CRIC are likely to inform revisions to treatment guidelines for risk factor reduction.
Anemia may develop due to inadequate synthesis of erythropoietin by the kidneys, and may worsen as CKD progresses. People with diabetes may present with anemia of CKD earlier than people without diabetes.
Evaluation of anemia includes:
Uncomplicated anemia of CKD is usually normocytic and normochromic. Hemoglobin is the preferred test to assess and monitor for anemia in CKD.
Prior to therapy, other treatable causes of anemia must be ruled out. Iron deficiency should be corrected. Both oral and parenteral iron preparations are available.
Therapy may include erythropoiesis-stimulating agents (ESAs) to increase red blood cell production and prevent the need for transfusion.
A Food and Drug Administration (FDA) black box warning for ESAs was released as a result of recent trials, which showed an increased risk for stroke, blood clot, heart attack, and death when ESAs were prescribed to achieve higher hemoglobin goals (> 11 g/dL). FDA recommends providers consider starting ESA therapy only when the hemoglobin level is less than 10 g/dL and both of the following apply:
FDA requires that a Medication Guide explaining the risks and benefits of ESAs be provided to all patients receiving ESAs. See links below.
A serum albumin level above 4 g/dL prior to initiating Renal Replacement Therapy (RRT) is associated with reduced morbidity and mortality in kidney failure. A spontaneous decrease in food intake or appetite may occur early in CKD and may continue as eGFR declines. Metabolic acidosis, defined as serum bicarbonate level < 22 mEq/L, anemia, and inflammation may increase the risk for malnutrition. Appetite may improve with adequate RRT. To prevent malnutrition, adequate calories are required across the continuum. Diet recommendations for each patient are individualized and will change as CKD progresses. Refer to a registered dietitian as needed.
The interrelationships among vitamin D, calcium, phosphorus, and parathyroid hormone (PTH) are altered in CKD and complex in nature. The mineral and bone disorders may occur when the kidneys fail to maintain serum calcium and phosphorus levels.
The kidneys activate vitamin D [1,25(OH)2D or calcitriol] and maintain serum calcium and phosphorus levels. As kidney function declines, hypovitaminosis D—measured as vitamin 25(OH)D—with hypocalcemia may stimulate PTH secretion by the parathyroid gland. PTH controls serum calcium levels by mobilizing calcium from bone, stimulating renal tubular reabsorption of calcium and stimulating production of active vitamin D to enhance gastrointestinal calcium absorption. PTH may also increase phosphaturia. Hyperplasia of the parathyroid gland may occur.
Depending on the type of mineral and bone disorder, serum calcium, phosphorus, intact PTH (iPTH), and alkaline phosphatase may be normal, decreased, or elevated. A bone biopsy is the gold standard for diagnosing mineral and bone disorders.
Monitor trends in the levels of vitamin 25(OH)D, calcium, phosphorus, and iPTH. Serum phosphorus levels may be normal until CKD is advanced.
Existing guidelines on management of mineral and bone disorders reflect consensus rather than high-grade evidence. Early intervention may help prevent vascular calcification and secondary hyperparathyroidism. Interventions may include use of vitamin D, dietary phosphorus restriction, and use of phosphate-binding medication. If phosphorus binders are used, they are most effective when taken with meals.
Specific recommendations for vitamin D supplementation have not been established for CKD. Monitor for hypercalcemia and hyperphosphatemia when supplementing with vitamin D. Ergocalciferol (vitamin D2) or cholecalciferol (vitamin D3) have been used to replete vitamin D levels in CKD. Active vitamin D (calcitriol) or its analogs (doxercalciferol, paracalcitol, or alfacalidol) are more commonly used in renal replacement therapy.
Calcium acetate and calcium carbonate are commonly prescribed to bind phosphate. These medications should be taken with meals. Calcium citrate is not recommended for CKD patients due to potential increase in aluminum absorption. Other binders, used more often in RRT, are typically composed of resins (sevelamer carbonate) and earth metals (lanthanum carbonate). Phosphorus in food additives may be absorbed more efficiently than phosphorus in food sources. Refer to a registered dietitian knowledgeable in the CKD diet and nutrition to educate the patient about sources of dietary phosphorus.
Patients with CKD, as with other chronic diseases, should be up to date on vaccines. These include:
See CDC for more information on adult vaccination schedules.
Besarab A, Coyne DW. Iron supplementation to treat anemia in patients with chronic kidney disease. Nature Reviews Nephrology. 2010; 6(12):699-710.
Kaysen GA, Johansen KL, Cheng S, Jin C, Chertow GM. Trends and outcomes associated with serum albumin concentration among incident dialysis patients in the United States. Journal of Renal Nutrition. 2008; 18(4):323-331.
Kendrick J, Chonchol MB. Nontraditional risk factors for cardiovascular disease in patients with chronic kidney disease. Nature Clinical Practice Nephrology 2008; 4(12): 672-681.
Kidney Disease: Improving Global Outcomes (KDIGO) CKD-MBD Work Group. KDIGO clinical practice guideline for the diagnosis, evaluation, prevention and treatment of chronic kidney disease-mineral and bone disorder (CKD-MBD). Kidney International. 2009; 76 (Suppl 113): S1-S130.
Kwan BCH. Kronenberg F, Beddhu s, Cheung AK. Lipoprotein metabolism and lipid management in chronic kidney disease. Journal of the American Society of Nephrology. 2007; 18(4):1246-1261.
Martin KJ, Gonzalez EA. Metabolic bone disease in chronic kidney disease. Journal of the American Society of Nephrology. 2007;18(3):875-885.
Moranne O, Froissart M, Rossert J, et al. Timing of onset of CKD-related metabolic complications. Journal of the American Society of Nephrology. 2009; 20(1):164-171.
Navaneethan SD, Palmer SC, Craig JC, Elder GJ, Strippoli GFM. Benefits and harms of phosphate binders in CKD: A systematic review of randomized control trials. American Journal of Kidney Diseases. 2009; 54(4):619-637.
Palmer SC, Hayen A, Macaskill P, et al. Serum levels of phosphorus, parathyroid hormone, and calcium and risks of death and cardiovascular disease in individuals with chronic kidney disease A systematic review and meta-analysis. Journal of the American Medical Association. 2011; 305(11):1119-1127.
Palmer SC, McGregor DO, Craig JC, Elder G, Macaskill P, Strippoli GFM. Vitamin D compounds for people with chronic kidney disease not requiring dialysis (Review). The Cochrane Library 2009, Issue 4. John Wiley & Sons.
Page last updated: February 6, 2013