How to manage hypercalcemia in patients with Chronic Kidney Disease (CKD)?

From the Guidelines

Managing hypercalcemia in CKD patients requires a multifaceted approach targeting the underlying pathophysiology, with the primary goal of reducing morbidity, mortality, and improving quality of life.

Key Considerations

• Identify and address reversible causes such as excessive calcium intake, vitamin D supplementation, or medications like thiazide diuretics.
• Dietary calcium restriction to 800-1000 mg/day is recommended.
• For pharmacological management, discontinue calcium-based phosphate binders and switch to non-calcium alternatives like sevelamer (800-1600 mg with meals) or lanthanum carbonate (500-1000 mg with meals) 1.
• Calcimimetics such as cinacalcet (starting at 30 mg daily, titrating up to 180 mg if needed) effectively lower calcium levels by reducing parathyroid hormone secretion 1.

Severe Cases

• In severe cases (calcium >12 mg/dL or symptomatic), intravenous hydration with normal saline at 100-150 mL/hour should be initiated, with careful monitoring of fluid status given the risk of volume overload in CKD.
• Loop diuretics like furosemide (20-40 mg IV) may be added after adequate hydration to enhance calcium excretion.
• Bisphosphonates can be considered in severe cases, though dosing must be adjusted for kidney function.
• Hemodialysis using a low-calcium dialysate (1.25-1.5 mEq/L) is effective for urgent treatment in dialysis-dependent patients.

Ongoing Management

• Regular monitoring of serum calcium, phosphorus, PTH, and vitamin D levels is essential for ongoing management.
• This approach targets the calcium-phosphate-PTH axis disruption that commonly occurs in CKD, where impaired kidney function leads to mineral metabolism abnormalities 1.

Guideline Recommendations

• The Kidney Disease: Improving Global Outcomes (KDIGO) 2017 clinical practice guideline update suggests avoiding hypercalcemia in adult patients with CKD G3a to G5D (Grade 2C recommendation) 1.
• The guideline also recommends using a dialysate calcium concentration between 1.25 and 1.50 mmol/L (2.5 and 3.0 mEq/L) in patients with CKD G5D (Grade 2C recommendation) 1.

From the FDA Drug Label

Cinacalcet tablets are not indicated for use in patients with CKD who are not on dialysis because of an increased risk of hypocalcemia [see Warnings and Precautions (5.1)]. The recommended starting oral dose of cinacalcet tablets is 30 mg once daily for patients with secondary hyperparathyroidism in patients with Chronic Kidney Disease on Dialysis. For CKD Stage 5: To avoid hypercalcemia only treat patients after their baseline serum calcium has been reduced to 9.5 mg/dL or lower (2.2) with paricalcitol.

Management of Hypercalcemia in CKD:

• For patients with CKD on dialysis, cinacalcet can be used to manage hypercalcemia, with a starting dose of 30 mg once daily.
• For patients with CKD Stage 5, paricalcitol can be used to manage secondary hyperparathyroidism, but only after baseline serum calcium has been reduced to 9.5 mg/dL or lower.
• Cinacalcet is not indicated for patients with CKD who are not on dialysis due to an increased risk of hypocalcemia.
• Monitoring of serum calcium levels is crucial to avoid hypercalcemia and hypocalcemia in patients with CKD 2, 3.

From the Research

Management of Hypercalcemia in CKD Patients

• Hypercalcemia in patients with Chronic Kidney Disease (CKD) is often caused by secondary hyperparathyroidism, which can lead to increased bone turnover and vascular calcification 4.
• Treatment of secondary hyperparathyroidism with vitamin D analogs and calcium-based phosphate binders can sometimes produce hypercalcemia and over-suppression of parathyroid hormone (PTH) 4.
• To manage hypercalcemia in CKD patients, it is essential to reduce PTH levels to a range that supports normal bone turnover and minimizes ectopic calcification 4.

Treatment Options

• Vitamin D analogs, such as paricalcitol and doxercalciferol, can be used to inhibit PTH gene transcription and parathyroid hyperplasia, with less calcemic activity than 1,25-dihydroxyvitamin D3 4.
• Non-calcium-based phosphate binders, such as sevelamer and lanthanum carbonate, can be used to reduce the risk of hypercalcemia with vitamin D therapy 4, 5.
• Cinacalcet, an allosteric activator of the calcium receptor, can be used to reduce PTH and the serum calcium-phosphate product 4, 5, 6.

Hypercalcemia Treatment

• Mild hypercalcemia usually does not require acute intervention, but severe hypercalcemia can be treated with hydration and intravenous bisphosphonates, such as zoledronic acid or pamidronate 7.
• In patients with kidney failure, denosumab and dialysis may be indicated 7.
• Glucocorticoids may be used as primary treatment when hypercalcemia is due to excessive intestinal calcium absorption 7.

Secondary Hyperparathyroidism Management

• Early detection of secondary hyperparathyroidism is critical for effective treatment, and approximately 40% of patients with stage 3 CKD and 80% of patients with stage 4 CKD have secondary hyperparathyroidism 8.
• Appropriate treatment involves suppression of PTH to normal levels with active vitamin D therapy and phosphate binders 8.
• Ergocalciferol or cholecalciferol should be used to correct 25-hydroxyvitamin D levels either before or during active vitamin D therapy 8.