Chronic Kidney Disease in Primary Care

Duaine D. Murphree, MD; Sarah M. Thelen, MD

Disclosures

J Am Board Fam Med. 2010;23(4):542-550. 

In This Article

Complications of Chronic Kidney Disease

The prevalence of the complications of chronic kidney disease increases with each stage of the disease. According to the National Health and Nutrition and Examination Survey III database,[15] the prevalence of complications for a patient with stage 1 chronic kidney disease is 0.28, and it rises to an average of 1.71 in stage 4. Therefore, it is recommended that screening for anemia, bone metabolism abnormalities, and metabolic acidosis be performed once the GFR is <60 mL/min/1.73m2 (stage 3).[3] The interval for each screening test varies by the stage of chronic kidney disease. Table 4 provides an overview of the screening recommendations from the National Kidney Foundation. If a complication is identified, the interval shortens to follow the success of treatment interventions.

Anemia of Chronic Kidney Disease

The National Kidney Foundation[3] recommends that patients have at least an annual complete blood count as a screening for anemia. This recommendation leaves room for more frequent assessments in patients who are at higher risk or have had a decline in their hemoglobin but have remained within the normal range.[3] The presence of anemia in a patient with chronic kidney disease requires further evaluation to elucidate the underlying cause of the anemia. Erythropoietin is produced by the kidney and stimulates production of reticulocytes in the bone marrow. As kidney function declines, the production of erythropoietin declines and anemia results. In addition, chronic kidney disease is a pro-inflammatory condition that can result in anemia of chronic disease. Furthermore, nutritional deficiencies may be present and the assessment of iron, folate, and vitamin B12 levels should be made when clinically indicated. The minimal work-up suggested for a patient with anemia includes the complete blood count indices, reticulocyte count, serum ferritin, and transferrin saturation (TSAT). The reticulocyte count can be used to calculate the reticulocyte index, which provides essential information regarding the capability of the bone marrow to compensate for the anemia. The serum ferritin is a measurement of the total body iron stores and is considered low when <25 ng/mL in men and <12 ng/mL in women. The TSAT is a measurement of the adequacy of iron for erythropoiesis and is considered low when <16%. Classically, the anemia associated with chronic kidney disease is a normocytic, normochromic anemia with a normal ferritin and TSAT.

The target hemoglobin level for patients with anemia from chronic kidney disease is between 11.0 and 12.0 g/L. It is recommended by the National Kidney Foundation that hemoglobin should not be above 13.0 g/L because this has been shown to be associated with increased incidence of cardiovascular mortality.[3] There are several erythropoietin analogs that can be given either subcutaneously or intravascularly for the treatment of this anemia. Patients being treated with these agents require monthly assessments of hemoglobin levels because dose adjustments are frequently needed to maintain the hemoglobin at the target of 11.0 to 12.0 g/L. Work-up and treatment of any associated iron-deficiency anemia should be done in conjunction with this treatment because the effectiveness of the erythropoietin is dependent on iron as a building block for hemoglobin synthesis.

Bone Metabolism Abnormalities

The National Kidney Foundation[3] recommends that patients be screened for bone metabolism abnormalities with assessment of intact parathyroid hormone (PTH), phosphorus, and calcium at regular intervals, as directed by the stage of their kidney disease (Table 4). These measurements should be done more frequently if the patient has an abnormality for which they are receiving treatment. The target values for phosphorus and intact PTH vary by stage of kidney disease whereas the target for calcium is the normal laboratory range (Table 5). Assessment of bone density with a dual energy radiograph absorptiometry scan for patients with chronic kidney disease is only recommended by the National Kidney Foundation for those patients with fractures or with known risk factors for osteoporosis. The US Preventative Services Task Force[16] agrees with this recommendation and does not list chronic kidney disease as a specific indication for osteoporosis screening.

Bone metabolism abnormalities are initially caused by elevations in phosphorus; renal excretion is impaired by the declining GFR. To compensate for the hyperphosphatemia, the parathyroid gland increases release of PTH. PTH has several effects on the kidney. It increases the absorption of calcium in the ascending limb of Henle, increases renal excretion of phosphorous by blocking reabsorption in the proximal tubule, and it activates 1-hydroxylase, which converts vitamin D to its active form: 1,25 hydroxyl vitamin D. PTH also acts on bone in conjunction with vitamin D by increasing the release of calcium and initiating the activation and proliferation of osteoclasts. Vitamin D has additional effects of increasing gut absorption of calcium and phosphorus as well as having a mild inhibitory effect on the release of PTH from the parathyroid gland. Secondary hyperparathyroidism is the compensatory increase in parathyroid production of PTH in response to the hypocalcemia and hyperphosphatemia caused by the declining renal function. Vitamin D deficiency results when the elevated PTH is unable to sufficiently stimulate the hydroxylation of 25-OH vitamin D to its active form, resulting in a deficiency. Therefore, an elevated PTH level can signify secondary hyperparathyroidism, vitamin D deficiency, or both.

When serum phosphorus levels are elevated above the recommended range as determined by the patient's kidney disease stage, then treatment must be initiated. The first component of treatment is to restrict dietary phosphorus to 800 to 1000 mg/day and to monitor blood work monthly to ensure the treatment is successful.[3] If dietary adjustments alone are not sufficient then treatment with phosphate binders should be initiated. There are 2 broad categories of phosphate binders: calcium-based and noncalcium-, nonaluminum-, nonmagnesium-based phosphate binders. Both are effective in the treatment of secondary hyperparathyroidism. If calcium-based phosphate binders are used then, to avoid hypercalcemia, the total daily dose of elemental calcium in the medication should not exceed 1500 mg.[3]

When serum intact PTH levels are elevated, either secondary hyperparathyroidism or vitamin D deficiency may be contributing. Therefore, before the initiation of treatment with dietary phosphate restriction and possibly phosphate binders, the serum level of 25-hydroxy vitamin D should be measured. If it is normal (>30 ng/mL) the screening should be repeated annually; however, if it is <30 ng/mL, supplementation with vitamin D2 (erocalciferol) should be initiated.[3] Once the GFR declines into the level of stage 4 chronic kidney disease, there is significant decreased conversion of 25-hydroxy vitamin D to the active form of 1,25-hydroxy vitamin D. Therefore, patients with stages 4 and 5 chronic kidney disease require replacement with 1,25-hydroxy vitamin D (calcitriol) or an active analog (paricalcitriol or doxecalciferol).[17] Treatment of vitamin D deficiency can result in an elevation of calcium and/or phosphate, and these values must be monitored during treatment. If hypercalcemia >10.2 mg/dL develops then treatment should be discontinued. Hyperphosphatemia can be treated with phosphate binders; however, if this does not successfully maintain target phosphate levels, vitamin D therapy may need to be discontinued.

The diagnosis of tertiary hyperparathyroidism should be considered in patients with known, long-standing secondary hyperparathyroidism who have become resistant to treatment. Tertiary hyperparathyroidism involves hypertrophy of the parathyroid glands that has developed into an autonomous adenoma. Treatment of tertiary hyperparathyroidism may require surgical parathyroidectomy.

Metabolic Acidosis The National Kidney Foundation[3] recommends that patients with chronic kidney disease be screened for metabolic acidosis by an assessment of total CO2 at varying frequency intervals per their stage of kidney disease (Table 4). The target total CO2 is 22 mmol/L. When the level falls below 22 mmol/L, treatment with supplemental alkali salts should be considered.

Cardiovascular Risk

Family physicians must be aware that chronic kidney disease has been recognized as an independent risk factor for cardiovascular disease. Therefore, this patient population must be aggressively managed to prevent cardiovascular events. The modifiable risk factor of hyperlipidemia is of particular importance. Patients with chronic kidney disease frequently have multiple lipid abnormalities; however, low-density lipoproteins should be the primary target, with attention paid to the non–high-density lipoprotein levels if the triglycerides are elevated to >200. The National Kidney Foundation and the National Cholesterol Education Program Adult Treatment Panel (ATP III) differ on their recommendations for chronic kidney disease patients. The National Kidney Foundation[3] considers chronic kidney disease to be a coronary heart disease equivalent, placing all chronic kidney disease patients in the high-risk group as defined in the ATP III guidelines. However, the ATP III[18] does not include chronic kidney disease in its calculation of hyperlipidemia goals. Given this information, it is prudent to have an minimum density lipoprotein goal of >100 mg/dL for all patients with chronic kidney disease and an optional goal of <70 mg/dL, depending on the patient's additional risk factors or known cardiovascular disease status.

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