Why hypocalcemia in chronic renal failure

The combination of features of these two conditions is sometimes referred to as autosomal dominant hypocalcemia with Bartter syndrome or Bartter syndrome type V. There are two types of autosomal dominant hypocalcemia distinguished by their genetic cause. The signs and symptoms of the two types are generally the same.

The prevalence of autosomal dominant hypocalcemia is unknown. The condition is likely underdiagnosed because it often causes no signs or symptoms. Autosomal dominant hypocalcemia is primarily caused by mutations in the CASR gene; these cases are known as type 1.

A small percentage of cases, known as type 2, are caused by mutations in the GNA11 gene. The proteins produced from these genes work together to regulate the amount of calcium in the blood.

Calcium molecules attach bind to the CaSR protein, which allows this protein to monitor and regulate the amount of calcium in the blood.

As a result, calcium levels in the blood remain low, causing hypocalcemia. Calcium plays an important role in the control of muscle movement, and a shortage of this molecule can lead to cramping or twitching of the muscles. Impairment of the processes that increase calcium can also disrupt the normal regulation of other molecules, such as phosphate and magnesium, leading to other signs of autosomal dominant hypocalcemia.

Studies show that the lower the amount of calcium in the blood, the more severe the symptoms of the condition are. This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In most cases, an affected person inherits the mutation from one affected parent. A small number of cases result from new mutations in the gene and occur in people with no history of the disorder in their family.

Genetics Home Reference has merged with MedlinePlus. MEN 2A. Patients with adrenal insufficiency and acromegaly may also develop hypercalcemia and these disorders should be included in the differential diagnosis. The history should focus on other rare causes of hypercalcemia including chronic kidney disease, immobility and the recovery phase of acute renal failure secondary to rhabdomyolysis. Chronic kidney disease CKD usually results in hypocalcemia, but prolonged hyperphosphatemia and low vitamin D levels lead to enhanced parathyroid hormone PTH secretion which can result in hypercalcemia.

This disorder is termed tertiary hyperparathyroidism and is discussed below. Immobility including prolonged bed rest leads to loss of bone minerals and in patients with rapid bone turnover e. During the recovery phase of rhabdomyolysis, the calcium deposited in the tissues mobilizes back into the circulation resulting in hypercalcemia.

Regardless of the etiology of hypercalcemia, the signs and symptoms are similar. However, more severe symptoms may manifest in certain disease states. The severity of the symptoms depend on the level and rate of rise of serum calcium. However, acute rises in serum calcium to these levels may result in discernible symptoms.

Elderly patients are more susceptible to the severe symptoms of hypercalcemia. The most common clinical manifestations of hypercalcemia are shown in Table 2 and are discussed below.

The first symptoms that occur are usually general and nonspecific. They include fatigue, muscle weakness, nervousness, difficulty concentrating and depression. As the hypercalcemia persists, other symptoms begin to manifest and are discussed by systems below. Gastrointestinal symptoms are common in hypercalcemia.

They include nausea, constipation, anorexia and rarely peptic ulcer disease or pancreatitis. Neuropsychiatric manifestations include headache, mild cognitive dysfunction, lethargy and rarely stupor and coma. Conjunctivitis may occur from crystal deposition. Other rare opthalmologic mainfestations include band keratopathy resulting from calcium phosphate deposition in the cornea. Skeletal manifestations include bone pain, osteoarthritis, osteitis fibrosa cystica, and osteoporosis.

Elevated serum calcium causes shortening of the QT interval. Long standing hypercalcemia can result in vascular and valvular calcification.

There are several renal manifestations of hypercalcemia including acute and chronic renal dysfunction, nephrolithiasis and nephrogenic diabetes insipidus. Renal dysfunction rarely occurs with mild hypercalcemia. Long standing hypercalcemia can result in tubulointersitial disease with medullary and cortical deposition of calcium nephrocalcinosis. The nephrocalcinosis can result in a distal type 1 renal tubular acidosis which can predispose patients to the development of kidney stones.

Nephrolithiasis occurs in patients with chronic hypercalcemia. The chronically elevated serum calcium levels leads to increased excretion of calcium into the urine resulting in hypercalciuria and kidney stones.

Kidney stones do not develop in FHH. Key physical exam findings: There are no specific physical examination findings of hypercalcemia except for band keratopathy, which is rare. The physical exam may point to the underlying etiology of the hypercalcemia as there may be manifestations of malignancy, hyperthyroidism, etc. Hypocalcemia occurs when the level of serum ionized calcium falls below 1.

False hypocalcemia occurs from a reduction in the serum albumin which decreases the total serum calcium level but the ionized calcium level remains stable. False hypocalcemia must be excluded before a diagnosis of hypocalcemia can be made by correcting the calcium for the hypoalbuminemia or directly measuring the ionized calcium level. The most commonly used formula for correction is to add 0.

However, it is better to directly measure ionized calcium if this test is available. There are numerous causes of hypocalcemia Table 3. A careful history and physical examination can help identify the underlying cause of the hypocalcemia and should focus on the following key elements:. Hypocalcemia spans all ages and the incidence is equal in males and females. The patient should be asked about recent surgery, as acquired hypoparathyroidism is usually the result of post-surgical damage to the parathyroid glands.

Hypoparathyroidism can occur after parathyroid, thyroid or radical neck surgery e. Neck trauma from accidents, etc. The hypoparathyroidism may be permanent or transient. Transient hypoparathyroidism should resolve in days to months. Bowel surgery is also a cause of hypocalcemia secondary to malabsorption.

The patient may have a history of chronic diarrhea or intestinal disease e. Acute gastroinestinal disease can cause acute hypocalcemia that is usually transient. Autoimmune damage to the parathyroid glands is a cause of acquired hypoparathyroidism.

Thus, it is important to document any autoimmune diseases such as hyperthyroidism in the history. The timing of hypocalcemia is important. Hypocalcemia that has been present for a prolonged period of time suggests hypoparathyroidism or pseudohypoparathyroidism. Family history is very important in the work-up of hypocalcemia as several causes of hypocalcemia are genetic. Polyglandular autoimmune syndrome type 1 is an autosomal recessive disorder in which hypocalcemia is very common.

There are also inherited vitamin D disorders including vitamin D-dependent rickets. Familial isolated hypoparathyroidism is also reported with different modes of inheritance. Mutations in the calcium sensing receptor have been identified in autosomal dominant hypocalcemia. Pseudohypoparathyroidism parathyroid hormone resistance is also a familial disease that causes hypocalcemia as well as short stature, hypothyroidism, hypogonadism and developmental delay.

There are multiple reasons why these patients develop hypocalcemia: acute or chronic kidney disease CKD , medications, transfusions with citrated blood, radiology studies using contrast dyes that may contain ethlyenediaminetetra-acetic acid EDTA , hypomagnesemia and sepsis. Hypocalcemia is a poor prognostic sign in patients with critical illness. Pancreatitis is a frequent cause of hypocalcemia. The hypocalcemia is due to precipitation of calcium in the retroperitoneum. Hypomagnesemia may augment the problem if there is associated alcohol abuse or other history of poor nutritional intake.

Vitamin D deficiency is common in the general population. Most cases of vitamin D deficiency do not result in hypocalcemia unless the deficiency is severe. Patients with CKD and the elderly are more likely to have hypocalcemia as a result of vitamin D deficiency.

Bisphosphonates and calcitonin are common causes of hypocalcemia. Radiocontrast dyes that use EDTA or gadolinium can result in hypocalcemia but it is usually transient. Several chemotherapy agents can cause hypocalcemia cisplatinum, 5-flurouracil and lecovorin. Prolonged therapy with anticonvulsants such as phenytoin and phenobarbital can also lead to hypocalcemia by causing vitamin D deficiency.

Gadolinium based contrast agents cause pseudohypocalcemia as they interfere with the colorimetric assays for calcium. The effect rapidly reverses as the gadolinium is metabolized. The effect is prolonged in patients with CKD as gadolinium is metabolized renally.

Patients are asymptomatic and no treatment is required. The history should be reviewed for recent blood or other blood product transfusions. Citrate is a calcium chelator that is used to prevent coagulation in blood products and results in hypocalcemia. The hypocalcemia resulting from transfusion of blood or plasma is usually mild and patients are asymptomatic. However, significant hypocalcemia can occur in patients receiving large quantities of blood products, such as with plasmapheresis or massive blood transfusions.

Patients with liver failure may also develop symptomatic hypocalcemia as citrate metabolism is impaired. Hungry bone syndrome can occur after thyrotoxicosis or hyperparathyroidism due to a rapid increase in bone formation. Hypocalcemia occurs if the rate of bone formation exceeds the rate of bone resorption. Patient history should be reviewed for metastases to bone. Patients with prostate or breast cancer can have osteoblast metastases that result in hypocalcemia. Acute respiratory alkalosis causes hypocalcemia.

The decrease in hydrogen ion concentration frees up binding sites on albumin and albumin then binds up ionized calcium causing a decrease in serum levels. Infusion of sodium bicarbonate also results in hypocalcemia. The addition of sodium bicarbonate results in a decrease in hydrogen ion concentration which frees up binding sites on albumin.

Albumin then binds ionized calcium and decreases the serum levels. Importantly, in both the above conditions, total serum calcium levels will not change. The diagnosis of hypocalcemia can only be made by checking the ionized calcium level. Ionized calcium levels must be monitored closely during sodium bicarbonate infusions to evaluate for hypocalcemia.

Magnesium depletion can cause hypocalcemia. Hypocalcemia usually occurs when the serum magnesium level falls below 1. Hypomagnesemia results in decreased serum ionized calcium levels by inducing PTH resistance and decreasing PTH secretion. Excessive intake of fluoride can cause hypocalcemia from excessive rates of bone mineralization from formation of calcium difluoride.

Most patients with hypocalcemia are asymptomatic. Rapid or large changes in ionized calcium levels may lead to symptoms which can be life-threatening. The clinical manifestations depend on how severe and how long the hypocalcemia has been present. The key clinical symptoms are shown in Table 4 and are reviewed here. The hallmark of acute hypocalcemia is neuromuscular irritability. The most specific symptoms are perioral numbness and carpodedal spasms of the hands and feet.

Muscle cramps can be extremely painful and may progress to tetany. Seizures may be the only presenting symptom of hypocalcemia. Patients may also present with lethargy and altered mental status, especially if the hypocalcemia is severe.

Tetany usually only occurs when the total serum calcium level falls below 7. Alkalosis worsens tetany. Thus, patients with acute respiratory alkalosis and hypocalcemia are more likely to develop tetany whereas tetany is rare in patients with CKD and hypocalcemia as there is usually concomitant metabolic acidosis. A positive test is ipsilateral contraction of the facial muscles. The spasm presents as flexion of the wrist and metacarpal phalangeal joints, extension of the intraphalangeal joints and adduction of the thumb.

Seizures: Grand mal, petit mal and focal seizures all can occur as a result of hypocalcemia. Patients who develop seizures usually also have tetany, but seizures can occur without tetany. T-waves may also be abnormal. In patients with severe hypocalcemia EKG changes may mimic those of acute anteroseptal injury. If hypomagnesemia is also present the EKG abnormalities may be magnified. Dsyrthymias can be triggered by hypocalcemia.

Serious dysrthymias such as ventricular tachycardia and heart block can occur but are rare. Hypotension may occur as a result of low ionized calcium levels. Acute hypotension can occur following rapid transfusions of citrated blood. Hypocalcemia has also been found to be a cause of refractory hypotension in critically ill patients. Papilledema can occur in patients with hypocalcemia from increased intracranial pressure and usually improves with reversal of the hypocalcemia. Patients with chronic hypocalcemia are often asymptomatic.

However, prolonged hypocalcemia can lead to changes in the skin, bones, eyes and brain. Ectodermal changes are frequently found in patients with chronic hypocalcemia. These include dry skin, coarse hair and brittle nails. Dental abnormalities can occur if the hypocalcemia was present before the age of five.

Alopecia is associated with autoimmune hypoparathyroidism and in some cases of post-surgical hypoparathyroidism. Resolution of the hypocalcemia results in improvement in these disorders. Basal ganglia calcifications occur due to long standing hypoparathyroidism. Patients with these calcifications often develop extrapyramidal symptoms including parkinsonism and other movement disorders such as dystonic spasms and choreoathetosis.

Dementia can also occur secondary to the calcifications. These symptoms may be reversible with treatment of the hypocalcemia. Neurologic symptoms including psychoses, psychoneuroses and impaired intellectual ability have been noted with chronic hypocalcemia. Treatment of the hypocalcemia may improve intelligence but the psychiatric symptoms may not resolve.

Cataracts are common in patients with prolonged hypocalcemia and usually reverse with correction of the hypocalcemia. Skeletal abonormalities are common in patients with chronic hypocalcemia and are related to the underlying cause. Different skeletal abnormalities are seen in hypoparathyroidism, pseudohypoparathyroidism and vitamin D deficiency. Many nonspecific findings such as epidermal changes, mental status changes, etc. The physical exam may point to the underlying etiology of the hypercalcemia as there may be manifestations of pancreatitis, sepsis, renal failure, etc.

Hypercalcemia should be confirmed if there is only one elevated serum calcium level. It is important to remember that the serum calcium level is a poor reflection of overall total body calcium. In the presence of low serum albumin the total serum calcium usually underestimates the amount of ionized calcium. Therefore, in the setting of hypoalbuminemia the total calcium level needs to be corrected for the albumin level.

Once hypercalcemia is confirmed, the next step is to measure the serum intact parathyroid hormone PTH level to differentiate between PTH-related and non-PTH related hypercalcemia Table 1. If the serum PTH level is high this is indicative of primary hyperparathyroidism. If the level of PTH is low or high normal then further laboratory testing should be performed Figure 1.

A high PTH level can also be seen with tertiary hyperparathyroidism. Tertiary hyperparathyroidism develops in patients with end-stage renal disease from hyperfunctioning parathyroid tissue. A high-normal PTH level is still highly suggestive of primary hyperparathyroidism. The next step is to order a 24 hour urine to evaluate calcium excretion. Since malignancy is the most common cause of hypercalcemia the next laboratory test should be measurement of serum PTH-related protein PTHrp.

Most malignancies usually solid tumors cause hypercalcemia through secretion of PTHrp, a condition termed humoral hypercalcemia of malignancy. If the serum PTHrp is high then the patient should be evaluated for malignancy Figure 1. Serum 1,dihydroxyvitamin D should be measured if PTHrp is not elevated.

Lymphoma usually results in hypercalcemia through increased production of 1,dihydroxyvitamin D. Sarcoidosis and other granulomatous diseases also over produce 1,dihydroxyvitamin D. A high serum 1,dihydroxyvitamin D level should prompt further testing for these disorders.

Medications should also be reviewed to ensure the patient is not taking any form of active vitamin D e. Measurement of serum hydroxyvitamin D should be performed if there is a concern for vitamin D intoxication.

An elevated serum hydroxyvitamin D level results from exogenous intake of compounds containing vitamin D. Thus, all medications, including herbal supplements, should be reviewed with the patient. Given the large number of diseases associated with hypercalcemia, one should use patient factors and symptoms to guide further testing. All patients should have a creatinine checked to evaluate for chronic kidney disease CKD as well as any acute kidney dysfunction from hypercalcemia.

Serum phosphate concentration should also be measured. Serum alkaline phosphatase, a measure of bone turnover, can be measured in patients with suspected bone lysis. Serum and urine protein electrophoresis should be measured in patients at risk for multiple myeloma. Testing for other endocrinopathies adrenal insufficiency, pheochromocytoma, and acromegaly should be considered but not routinely performed.

It is reasonable to consider referring the patient to an endocrinologist prior to performing these specialized tests. Imaging studies are helpful for identifying malignancy or granulomatous disease.

The type of imaging performed should be based on clinical suspicion of the underlying disease. Renal imaging should be performed if kidney stones are suspected as it helps guide management of primary hyperparathyroidism discussed below. Imaging studies of the parathyroid gland have no role in the diagnosis of primary hyperparathyroidism but preoperative localization imaging studies are useful in planning the approach for surgery.

Hypocalcemia should be confirmed if there is only one low serum calcium value. In the presence of low serum albumin the total serum calcium usually underestimates the amount of ionized calcium false hypocalcemia.

After hypocalcemia is confirmed the laboratory evaluation should be guided by the medical history and physical examination as the cause of the hypocalcemia may be obvious Table 3. Acute pancreatitis, acute or chronic kidney disease, post-surgical hypoparathyroidism, medication related causes, rhabdomyolysis, and tumor lysis syndrome may be diagnosed or excluded based on the history, physical and routine laboratory measurements creatinine, creatinine kinase, amylase.

The next step is to measure the serum magnesium level to determine its potential contribution to the hypocalcemia. Hypocalcemia should resolve quickly within minutes to hours if hypomagnesemia is the cause of the hypocalcemia.

If the hypocalcemia does not resolve or if the magnesium level is normal or greater then 1. The next step in the evaluation is to check serum intact parathyroid hormone PTH. Low ionized calcium is the strongest stimulus of PTH secretion. In patients with hypocalcemia the PTH should be elevated unless the underlying disorder results in decreased PTH secretion e. Thus, the PTH level gives critical information about the cause of the hypocalcemia.

Figure 3. If the PTH is low it is essentially diagnostic of hypoparathyroidism hereditary or acquired but autosomal dominant hypocalcemia activating mutation of the calcium sensing receptor must be ruled out with further laboratory testing. Chronic hypomagnesemia also results in low or normal PTH. Hungry bone syndrome results from an abrupt decrease in PTH levels post-surgery resulting in increased bone uptake of calcium, magnesium and phosphorus. A serum phosphate level should be checked next.

Serum phosphate is elevated in hypoparathyroidism and autosomal dominant hypocalcemia but is not usually elevated in hypomagnesemia. The phosphate level is usually low in hungry bone syndrome unless the patient has underlying CKD in which the serum phosphate levels are usually normal. It is difficult to distinguish between hypoparathyroidism and autosomal dominant hypocalcemia by laboratory testing alone as both present with hypocalcemia and hyperphosphatemia.

However, urinary calcium excretion is usually normal or increased in autosomal dominant hypocalcemia whereas it is low in hypoparathyroidism. The clinical history of the patient can help to distinguish these two disorders. Previously normal calcium levels essentially rule out autosomal dominant hypocalcemia as the calcium levels are always low in these patients.

Patients with autosomal dominant hypocalcemia also typically develop kidney stones and nephrocalcinosis when treated with vitamin D and calcium supplementation. A history of recent neck surgery is highly suggestive of acquired hypoparathyroidism. The only way to make a definitive diagnosis is by testing for a mutation in the calcium sensing receptor. A high PTH level is the normal response to hypocalcemia secondary hyperparathyroidism.

Thus, an elevated PTH levels is seen in patients with hypocalcemia from acute or chronic kidney disease, pseudohypoparathyroidism, vitamin D deficiency, rhabdomyolysis, tumor lysis syndrome, osteoblastic metastases, sepsis, etc. Further laboratory testing can be used to distinguish vitamin D deficiency from pseudohypoparathyroidism Figure 3.

The serum phosphate level should be checked. If the phosphate level is high this indicates acute or chronic renal failure or pseudohypoparathyroidism. These disorders can be distinguished easily by measuring the serum creatinine as it will be elevated in patients with renal failure and normal in patients with pseudohypoparathyroidism.

A low serum phosphate indicates vitamin D deficiency or osteoblastic metastases and serum hydroxyvitamin D should be checked. If the patient has low hydroxyvitamin D levels, then 1,dihydroxyvitamin D levels should be checked. Hereditary vitamin D-resistant rickets also has low hydroxyvitamin D levels and high 1,dihydroxyvitamin D levels but this disorder can be ruled out in adult patients without a lifelong history of hypocalcemia as it presents in early childhood. Low hydroxyvitamin D levels and low 1,dihydroxyvitamin D levels indicate vitamin D-dependent rickets type 1.

These patients present in the first year of life with profound hypocalcemia and skeletal disease. If the patient does not have vitamin D deficiency or the diagnosis remains unclear, serum alkaline phosphatase should be measured. Patients with osteoblastic metastases will have elevated serum levels of alkaline phosphatase. Imaging studies can then be performed to confirm the presence of metastases. Imaging studies are useful for identifying osteoblastic metastases which can usually be seen on plain films.

In patients with idiopathic hypoparathyroidism or pseudohypoparathyroidism computed tomography CT scans of the head may show basal ganglia calcification. The main goal of therapy is to treat the underlying disorder leading to hypercalcemia discussed below. Whether the patient requires immediate treatment of hypercalcemia depends on the presence of symptoms and the level of serum calcium. They should avoid medications that can cause hypercalcemia and should increase fluid intake to at least 2 liters per day to decrease the risk of kidney stones.

Further therapy should be aimed at the underlying cause of the hypercalcemia. Any offending medications must be stopped.

Patients with a hypercalcemic crisis should be managed initially in the intensive care unit. Immediate treatment of severe hypercalcemia involves conservative therapies saline plus loop diuretics as well as pharmacologic management. The safest and most effective immediate treatment is intravenous volume resuscitation with normal saline to euvolemia, assuming the patient has reasonable cardiac and renal function.

Patients with hypercalcemia are often volume depleted and infusion of saline corrects the volume depletion and thereby reduces the reabsorption of sodium and calcium in the proximal tubule of the kidney. The rate of saline infusion depends on the severity of hypercalcemia and patient factors including cardiac or renal disease.

The patient must be monitored carefully for signs and symptoms of volume overload. Elderly patients are more susceptible to volume overload with rapid infusions of saline. Severe cardiac or renal failure are contraindications to large volume expansion with saline. Infusion of saline is only used to restore euvolemia.

Use of saline after euvolemia is reached is not recommended given the risk of substantial volume overload. Loop diuretics e. This helps minimize the risk of volume overload and substantially increases the urinary excretion of calcium.

The dose of intravenous IV furosemide used should be based on the estimated glomerular filtration rate eGFR of the patient. It is always better to use conservative dosing i. Caution must be taken to ensure that loop diuretics are only given once volume resuscitation is complete as the diuresis will lead to loss of sodium and water. The intake and output of the patient must be monitored carefully as patients will require replacement of the lost salt and water.

Serum electrolytes, especially potassium and magnesium, must be monitored closely as therapy can lead to significant hypokalemia and hypomagnesemia. If conservative therapies fail to decrease the serum calcium level or patients have contraindications to saline therapy then pharmacologic therapies should be used.

Intravenous bisphosphonates are very effective for the treatment of hypercalcemia. Bisphosphonates block osteoclast mediated bone resorption through induction of osteoclast apoptosis. Pamidronate mg IV over 4 hours and zoledronate 4 mg over 15 minutes are usually the agents of choice and are approved in the United States for the treatment of malignancy related hypercalcemia.

Zoledronate is more potent than pamidronate at reversing hypercalcemia. A single dose of these medications usually results in normocalcemia. Decreases in serum calcium levels are seen within 2 to 4 days. Very rare side effects of these mediations are osteonecrosis of the jaw and acute renal failure. These medications should be used with caution in patients with significant renal impairment and the dose must be reduced. We recommend using pamidronate mg IV over 4 hours in patients with renal impairment.

Calcitonin is another option for reducing serum calcium. It has a rapid effect and usually lowers serum calcium within four to six hours by increasing urinary calcium excretion and decreasing bone resorption.

Its use in clinical practice is limited by its short duration of action and the rapid development of tachyphylaxis. It is most useful when used in combination with saline hydration for a rapid reduction in serum calcium in patients with severe hypercalcemia. Calcitonin is usually well tolerated with few side effects.

Glucocorticoids are effective for hypercalcemia resulting from malignancy and excess vitamin D, either endogenous e. The mechanism of action is unclear but may involve decreased intestinal absorption of calcium and suppression of bone resorption. Glucocorticoids are usually given orally starting at 40 to 60 mg per day.

The decrease in serum calcium usually occurs within 1 to 2 days. Plicamycin Mithramycin is a cytostatic drug that inhibits bone resorption. It results in a rapid decline in serum calcium levels within a few hours and its effect lasts several days.

Serious side effects including bone marrow suppression liver and renal toxicity occur and have limited its use in clinical practice. The maximum daily dose is 25 micrograms mcg per kg. Gallium nitrate is another agent that reduces serum calcium via inhibition of bone resorption. It must be infused continuously for four to five days. Nephrotoxicity is a major side effect of gallium nitrate. It is not favored for the treatment of hypercalcemia and has largely been replaced by the bisphosphonates.

Immediate consultation with nephrology is recommended in patients who meet this criteria. As stated earlier, the goal of therapy is to treat the underlying cause of hypercalcemia. The treatment of the most common causes of hypercalcemia is discussed here. Parathyroidectomy is the only definitive cure at this time. Experts agree that patients with symptomatic hyperparathyroidism should undergo parathyroid surgery.

The treatment of asymptomatic primary hyperparathyroidism is more controversial. Patients who do not meet these criteria should be followed closely with yearly measurements of serum calcium and renal function and bone mineral density studies every one to two years.

If their disease progresses they should be referred for surgical intervention. Medical management can be used in patients who are poor surgical candidates or decline surgery. Medical management includes the use of bisphosphonates and calcimimetics e.

Bisphosphonates are useful for treatment of osteopenia in these patients. Calcimimetics are new drugs that activate the calcium sensing receptor on the parathyroid gland and reduce PTH secretion. Results A total of eight CKD patients with symptomatic hypocalcaemia were identified from Dec to Feb aged between 52 and 85 years.

All results including serum phosphate, PTH, ALP, and vitamin D were obtained closest to the time of presentation with hypocalcaemia in patients who were symptomatic or nadir of hypocalcaemia in patients who were asymptomatic and being actively monitored.

Table 1. Baseline clinical data for 8 patients with CKD stages 4 to 5 who were on denosumab treatment. Table 2. Figure 1. Figure 2. A summary of mechanisms for increased risk of hypocalcaemia with denosumab in patients with CKD. Review the indication for denosumab. Review calcium-based phosphate binders and calcitriol supplementation dosing, or initiate this therapy if hypocalcaemic. After denosumab administration : 1 Clearly notify denosumab administration to all clinicians involved to raise awareness of potential hypocalcaemia.

Optimize calcium and calcitriol therapy early to prevent severe hypocalcaemia. Information for patients : 1 Patients with Stage 4—5 CKD should be counselled about the increased risk of hypocalcaemia with denosumab. References S. Cummings, J. Martin, M. McClung et al. Festuccia, M. Jafari, A. Moioli et al. Huynh, S. Baker, A. Stewardson, and D. Block, H. Bone, L. Fang, E. Lee, and D. View at: Google Scholar V. Dave, C. Chiang, J. Booth, and P. Levey and L.

Payne, A. Little, R. Williams, and J. Hu, Q. Xuan, B. Hu, L. Lu, J. Wang, and Y. Gutierrez, T. Isakova, E. Rhee et al. Komaba and M. Ben-Dov, H. Galitzer, V. Lavi-Moshayoff et al.