As eGFR declines, complications and comorbidities occur more commonly and are more severe. These include:
- Cardiovascular Disease (CVD) and dyslipidemia
- anemia due to impaired erythropoiesis and low iron stores
- mineral and bone disorders
- depression and decreased functional status
Cardiovascular Disease (CVD)
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:
- Complete blood count (CBC)
- Iron studies (serum iron, total iron binding capacity [TIBC], percent transferrin saturation [TSAT], and serum ferritin)
- Peripheral blood smear
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:
- Rate of hemoglobin decline shows the patient may require a red blood cell transfusion and reduction of risk of alloimmunization and/or other red blood cell transfusion-related risk is a goal.
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.
Mineral and Bone Disorders
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.
- Secondary hyperparathyroidism is associated with high bone turnover. Hypercalcemia, hyperphosphatemia and elevated levels of iPTH, and alkaline phosphatase may be seen. Vascular calcification is associated with secondary hyperparathyroidism in CKD.
- Osteomalacia results in low bone turnover, with hypercalcemia and normal to decreased serum phosphorus, iPTH, and alkaline phosphatase.
- Adynamic bone disease results in low bone turnover and may be characterized by normal to low iPTH and alkaline phosphatase. Serum calcium and phosphorus may be normal to elevated.
- Mixed bone disease, as the name implies, has features of both low and high bone turnover.
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.
Vitamin D Supplements
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:
- Influenza vaccine.
- Pneumococcal vaccine: may need to be repeated based on age, diabetes status, and other clinical factors.
- Hepatitis B series given day 1, 1 month, and 6 months. Aim to complete the series before the patient's immune response is compromised by progressive kidney disease.
See CDC for more information on adult vaccination schedules.