Link Between Hypercalcemia and Renal Failure

Introduction

Hypercalcemia can occur due to excessive bone breakdown, increased calcium retention in the kidneys, excessive absorption of calcium in the intestines, or may be due to all these factors. It can also lead to acute renal failure (ARF) or high blood pressure and may worsen the tubular necrosis often present in ARF cases. According to studies, the association between ARF and hypercalcemia was related in almost all cases (cancer, multiple myeloma, vitamin D intoxication, and leprosy). The levels of ionized serum calcium and creatinine levels were increased after treatment. All patients experienced a progression of nonoliguric acute renal failure. It is expected to find low calcium levels in patients with ARF. High calcium levels in the context of ARF typically suggest additional health issues, which was the case for all eight patients examined in this study. Renal function improved for all patients as their serum calcium levels decreased. This article explains the link between hypercalcemia and renal failure.

What Is Hypercalcemia?

The condition in which the body's calcium levels are too high is hypercalcemia. The calcium levels are increased in the blood. The normal blood calcium level ranges from 8.5-10.5 milligrams per deciliter. Hypercalcemia occurs when blood calcium levels are higher than 12 mg/dl. Patients with mild hypercalcemia, where calcium levels are above normal but less than 12 mg/dL (3 mmol/L), might not show any symptoms, or they could experience general symptoms like constipation, tiredness, and depression. In cases of moderate hypercalcemia, with serum calcium levels between 12 to 14 mg/dL (3 to 3.5 mmol/L), individuals may not have significant issues if the condition is long-standing. However, a sudden increase in these levels can lead to severe symptoms such as increased urination and thirst, dehydration, loss of appetite, nausea, muscle weakness, and altered mental status.

The following are the symptoms of hypercalcemia:

• Fatigue.

• Lethargy.

• Pain in the abdomen.

• Loss of appetite.

• Nausea with vomiting.

• Constipation.

• Feeling thirsty.

• Pain in bone.

• Kidney stones.

• Increased urine volume.

• Mental confusion.

Calcium ions are crucial in regulating various bodily functions, such as muscle movement, secretion processes, and nerve cell activity. Parathyroid hormone (PTH) controls plasma calcium levels by influencing bone resorption and the excretion of calcium by the kidneys, while dietary calcium is absorbed in the intestine through the action of 1.25-dihydroxycholecalciferol. Hypercalcemia may occur due to increased bone resorption, renal calcium retention, excessive absorption of calcium in the intestines, or a mix of these factors. Patients with acute renal failure (ARF) often exhibit low calcium levels, with reductions in both ionized calcium and total plasma calcium. High calcium levels may indicate additional health issues.

Hypercalcemia can lead to high blood pressure, increase renal vascular constriction, and worsen tubular necrosis, which is commonly seen in ARF cases. There are many causes of hypercalcemia, with primary hyperparathyroidism and cancer (both with and without metastases) being the most prevalent. Other factors that can cause high calcium levels include sarcoidosis, tuberculosis, other granulomatous diseases, milk-alkali syndrome, excessive intake of vitamins D and A, prolonged inactivity, certain medications, and the recovery stage of rhabdomyolysis.

What Is Renal Failure?

Renal failure refers to the condition when the kidneys are unable to filter waste and excess fluid from the blood. The glomerulus filtration rate (GFR) becomes low. Acute renal failure (ARF) can occur over a period of time, but chronic renal failure develops over a longer period.

The following are the symptoms of renal failure:

• Fatigue.

• Weakness.

• Reduced amount of urination.

• Breath shortness.

• Swelling in legs, ankles, or feet.

• Vomiting and nausea.

What Is the Link Between Hypercalcemia and Renal Failure?

According to studies, cancer-related hypercalcemia is more commonly seen, as evidenced by one instance of non-Hodgkin’s lymphoma, one poorly differentiated tumor, and two multiple myeloma cases. The remaining four cases involved hypercalcemia due to hyperparathyroidism, vitamin D overdose, sarcoidosis, and leprosy, each accounting for one case.

Generally, the literature cites malignant tumors, primary hyperparathyroidism, prolonged inactivity, excessive intake of vitamins A or D, thiazide diuretics, granulomatous diseases, chronic kidney disease, milk-alkali syndrome, Addison’s disease, familial hypocalciuric hypercalcemia, and inherent bone disorders like Paget’s disease as leading causes of hypercalcemia.

Cancer is the most frequent cause of hypercalcemia in hospital settings, particularly lung squamous cell carcinoma and blood-related cancers such as Hodgkin’s disease and lymphomas with B and T cells, along with bone metastases. In the two cancer patients from this report, acute renal failure showed improvement after lowering serum calcium levels.

While PTH-related protein secretion by various tumors accounts for many instances of cancer-induced hypercalcemia, not all cases are explained by this mechanism. Tumors commonly linked to PTH-related protein production include non-small cell lung carcinoma, breast cancer, esophageal squamous cell carcinoma, and T- or B-cell lymphoma. Blood cancers less frequently produce PTH-related protein.

Hypercalcemia is commonly associated with multiple myeloma and can lead to kidney damage, particularly in cases involving light chain and IgD myeloma. In a study of 56 myeloma patients with severe kidney failure, about 43 % had an identifiable cause for their renal failure, often hypercalcemia or the use of nonsteroidal anti-inflammatory drugs.

Primary hyperparathyroidism is the leading cause of hypercalcemia within the general population. It typically results from a single adenoma in approximately 85% of instances, while 10% to 15% of cases are due to hyperplasia of all four parathyroid glands, and less than 2% are caused by carcinoma.

Hypercalcemia may sometimes reduce glomerular filtration, leading to acute renal failure, which is reversible upon normalization of calcium levels. In the reported case of hyperparathyroidism, glomerular filtration improved, as evidenced by reduced serum creatinine levels concurrent with decreasing calcium levels.

In cases where hypercalcemia is present without an apparent cause and is accompanied by renal dysfunction and low plasma PTH levels, it may suggest the possibility of self-treatment with calcium and alkali-containing antacid preparations, previously referred to by the now obsolete term “milk-alkali syndrome.” Although rare, vitamin D toxicity is a recognized cause of hypercalcemia and also results in low plasma PTH levels. This hypercalcemia is caused by increased bone resorption, and treatment may involve bisphosphonates.

Conclusion

Hypercalcemia occurs when there is excessive calcium in the blood. This condition can cause kidney damage or renal failure. A person with chronic kidney disease can also develop hypercalcemia. Sometimes, too much calcium or vitamin D causes hypercalcemia. The treatment of hypercalcemia includes dialysis, and sometimes other treatments can also help cure it. The treatment can cure hypercalcemia, but once the kidney is damaged, it’s irreversible.