Bone-Eating Kidney Disease: A Case report

Case Studies 7 min 344

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Created On: 04/02/2020

Bone-Eating Kidney Disease: A Case report

A 31-year-old female patient reported severe pain in the right hand, left forearm, right knee, right hip, and lower back following a fall which sustained for three days. She had reported a history of end-stage renal disease (ESRD) and was on maintenance haemodialysis. Medical records revealed that she had poor compliance with her diet, medications, and dialysis treatments. Laboratory values were significant for marked elevation in serum parathyroid hormone level (1735 pg/mL), as well as hyperphosphatemia and normal serum calcium levels.

These symptoms are most consistent with which of the following disease?

Renal failure
Hyperparathyroidism

In chronic kidney disease (CKD) patients, the levels of parathyroid hormone (PTH) are progressively increased. Several observational studies determined an association between PTH levels at extremes and mortality in CKD patients. It is difficult to observe skeletal symptoms of secondary hyperparathyroidism with early detection and treatment of CKD.

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Key take away

Patient with end-stage renal disease developed severe hyperphosphatemia and hyperparathyroidism. High-dose phosphate binder and a calcimimetic agent were initiated to manage hyperphosphatemia and hyperparathyroidism.

Medical history

The patient reported a history of hypertension, diabetes, and congestive heart failure and end-stage renal disease, for which she was receiving maintenance hemodialysis for the past 15 years. She also had a history of chronic leg pain and disabling peripheral neuropathy which made her wheelchair-bound. The femoral fracture was also reported about a year ago but was managed with the conservative treatment approach.

Examination & lab investigations

Physical examination showed a blood pressure of 153/81 mm Hg and pulse rate of 101 bpm. Tenderness and moderate swelling over the tip of the right index finger and right distal femur was also reported. She found difficulty in the motion of the right knee due to pain. The patient did not report any distal neurovascular deformity in the extremities.

Initial laboratory values were significant for white blood cell count, haemoglobin, platelet count, blood urea nitrogen, and creatinine. Serum intact PTH was found to be significantly elevated with serum phosphate level of 5.7 mg/dL (2.7–4.5 mg/dL) and calcium level of 9.5 mg/dL (8.4–10.2 mg/dL). Lab investigation revealed serum vitamin D levels of 24 ng/mL (>20ng/mL).

Diffuse and decreased osseous mineralisation and a comminuted distal femoral fracture were observed in X-ray findings of the right lower extremity. Similarly, significant diffuse osteopenia was also seen on X-ray of the left upper extremity. The distal phalanx of the index finger was found fractured as per the X-ray study of the right hand. Computed tomography (CT) scan of the pelvis and abdomen showed widespread brown tumors, florid changes of renal osteodystrophy and remarkable diffuse severe demineralisation of the bones, with prominent subligamentous resorption in the sacroiliac joints bilaterally.

Management

The patient was administered with medications including aspirin (81 mg/day), lisinopril (40 mg/day), carvedilol (25 mg twice a day), sevelamer carbonate (800 mg thrice a day with meals), and insulin regimen. The patient did not show compliance with diet, medications and hemodialysis.

The fractures were treated with non-operative treatment due to severe hyperparathyroidism and poor baseline functional status. The patient was not comfortable in undergoing surgical parathyroidectomy. A high-dose phosphate binder (sevelamer carbonate) and also an oral calcimimetic (cinacalcet) were started for management of hyperparathyroidism and hyperphosphatemia.

Discussion

The patients with advanced kidney disease show a decrease in the phosphorus clearance, which in turn decreases the glomerular filtration rate (GFR). Subclinical and postprandial hyperphosphatemia has been observed even in patients with a GFR of greater than 30 mL/min, which may be a significant cause of secondary hyperparathyroidism. Bone resorption (increase in serum concentration of calcium and phosphorous) is caused by osteoclasts which are stimulated by PTH. Additionally, PTH also increases intestinal phosphorus and calcium absorption by stimulating the production of 1,25-dihydroxy vitamin D. Research has reported the negative effect of calcium on the parathyroid hormone through the calcium-sensing receptors. Cinacalcet works mainly by activating calcium-sensing receptors.

The most critical step in the management of hyperthyroidism due to kidney disease starts with optimizing calcium and serum phosphate levels. High PTH levels can be effectively reduced by supplementing calcitriol. But, careful monitoring is required as calcitriol may augment calcium and phosphate absorption from the gut, thereby increasing calcium-phosphate product.

Previous research studies have shown that the severity of secondary hyperparathyroidism even in ESRD patients receiving dialysis is attributed to 25-hydroxyvitamin D levels below 15ng/mL. The addition of calcimimetic drug should be considered in patients with persistently elevated PTH levels despite optimising serum phosphate and calcium levels. The patients with serum calcium lower than 8.4 mg/dL should not receive cinacalcet as it can cause severe hypocalcaemia.

In this case, cinacalcet addition was considered as the patient had serum PTH levels of >1000pg/mL, and the chances of improvement with hyperphosphatemia control alone were low. Surgical parathyroidectomy should be considered if the patients have markedly elevated PTH levels and have unmanageable signs and symptoms. Research has suggested the use of parathyroidectomy in reversing bone resorption and regressing brown tumors completely.

In the present case, all-cause or cardiovascular mortality failed to improve with the use of cinacalcet. Still, the use of cinacalcet may diminish the requirement of parathyroidectomy in ESRD patients.

Learning

Patients with chronic kidney disease, especially those who are on dialysis, are at higher risk of bone fractures and secondary hyperparathyroidism.

Reduction in active vitamin D production, accumulation of phosphate and hypocalcemia may act as stimuli for increased secretion of PTH. Therefore, laboratory measures should be monitored periodically and optimized early in the course of CKD.

Adherence to therapy and appropriate patient education plays a prominent role in the management of bone-eating disease.

References

Moorthi RN, Moe SM. CKD-mineral and bone disorder: core curriculum 2011. Am J Kidney Dis 2011; 58(6): 1022–1036.
Koratala A, Bhatti V. Skeletal findings in secondary hyperparathyroidism. Oxf Med Case Reports 2017; 2017(1): omw097.
Saliba W, El-Haddad B. Secondary hyperparathyroidism: pathophysiology and treatment. J Am Board Fam Med 2009; 22(5): 574–581.
Brown EM, Hebert SC. Calcium-receptor-regulated parathyroid and renal function. Bone 1997; 20: 303–309.
Ghazali A, Fardellone P, Pruna A, et al. Is low plasma 25-(OH)vitamin D a major risk factor for hyperparathyroidism and Looser’s zones independent of calcitriol? Kidney Int 1999; 55: 2169–2177.
Tominaga Y, Uchida K, Haba T, et al. More than 1,000 cases of total parathyroidectomy with forearm autograft for renal hyperparathyroidism. Am J Kidney Dis 2001; 38(4 Suppl. 1): S168–S171.
Arabi A, Khoury N, Zahed L, et al. Regression of skeletal manifestations of hyperparathyroidism with oral vitamin D. J Clin Endocrinol Metab 2006; 91(7): 2480–2483.
Palmer SC, Nistor I, Craig JC, et al. Cinacalcet in patients with chronic kidney disease: a cumulative meta-analysis of randomized controlled trials. PLoS Med 2013; 10(4): e1001436.