Multiple myeloma disrupts calcium homeostasis by a variety of mechanisms, including bone destruction and resorption. This causes hypercalcemia. When left untreated, hypercalcemia leads to nephrocalcinosis, impairment of kidney function, and eventually renal failure. Some degree of renal dysfunction is common in myeloma patients. Here, we report case studies showing the efficacy and renal safety of the single-nitrogen bisphosphonate, ibandronate, for the treatment of hypercalcemia and/or nephrocalcinosis in multiple myeloma patients hospitalized with acute renal failure. Patients (n = 7) received either one or two intravenous infusions of ibandronate (2–6 mg). Ibandronate was well tolerated in all patients and returned elevated blood calcium levels to normal. Renal function improved for all patients and normalized in 3/7 patients. We conclude that ibandronate is involved in rapidly improving or restoring acute renal function and calcium levels to within the normal range in this patient population. To clarify the exact value of ibandronate, further investigation is warranted in randomized prospective trials.

Keywords:
Acute renal failure, Bisphosphonate, Hypercalcemia, Ibandronate, Multiple myeloma
1.
Berenson J, Hillner B, Kyle R, Anderson K, Lipton A, Yee GC, Biermann JS, American Society of Clinical Oncology Bisphosphonates Expert Panel: American Society of Clinical Oncology clinical practice guidelines: the role of bisphosphonates in multiple myeloma. J Clin Oncol 2002;20:3719–3736.
2.
Bajorunas D: Clinical manifestations of cancer-related hypercalcemia. Semin Oncol 1990;17:16–25.
3.
Goldschmidt H, Lannert H, Bommer J, Ho AD: Multiple myeloma and renal failure. Nephrol Dial Transplant 2000;15:301–304.
4.
Corso A, Zappasodi P, Lazzarino M: Urinary proteins and renal dysfunction in patients with multiple myeloma. Biomed Pharmacother 2002;56:139–143.
5.
Coleman RE, Rubens RD: The clinical course of bone metastases from breast cancer. Br J Cancer 1987;55:61–66.
6.
Body J: Current and future directions in medical therapy: hypercalcemia. Cancer 2000;88(suppl 12):3054–3058.
7.
Knudsen LM, Hjorth M, Hippe E: Renal failure in multiple myeloma: reversibility and impact on the prognosis. Nordic Myeloma Study Group. Eur J Haematol 2000;65:175–181.
8.
Montseny JJ, Kleinknecht D, Meyrier A, Vanhille P, Simon P, Pruna A, Eladari D: Long-term outcome according to renal histological lesions in 118 patients with monoclonal gammopathies. Nephrol Dial Transplant 1998;13:1438–1445.
9.
Ralston SH, Thiebaud D, Herrmann Z, Steinhauer EU, Thurlimann B, Walls J, Lichinitser MR, Rizzoll R, Hagberg H, Huss HJ, Tubiana-Hulin M, Body JJ: Dose-response study of ibandronate in the treatment of cancer-associated hypercalcemia. Br J Cancer 1997;75:295–300.
10.
Pecherstorfer M, Herrmann Z, Body JJ, Manegold C, Degardin M, Clemens MR, Thurlimann B, Tubiana-Hulin M, Steinhauer EU, van Eijkeren M, Huss HJ, Thiebaud D: Randomized phase II trial comparing different doses of the bisphosphonate ibandronate in the treatment of hypercalcemia of malignancy. J Clin Oncol 1996;14:268–276.
11.
Pfister T, Atzpodien E, Bauss F: The renal effects of minimally nephrotoxic doses of ibandronate and zoledronate following single and intermittent intravenous administration in rats. Toxicology 2003;191:159–167.
12.
Heidenreich A, Ohlmann CH: Ibandronate: its pharmacology and clinical efficacy in the management of tumor-induced hypercalcemia and metastatic bone disease. Expert Rev Anticancer Ther 2004;4:991–1005.
13.
Body J, Mancini I: Bisphosphonates for cancer patients: why, how, and when? Support Care Cancer 2002;10:399–407.
14.
Berenson J: Treatment of hypercalcemia of malignancy with bisphosphonates. Semin Oncol 2002;29(suppl 21):12–18.
15.
Clezardin P: The antitumor potential of bisphosphonates. Semin Oncol 2002;29(suppl 21):33–42.
16.
Bounameaux HM, Schifferli J, Montani JP, Jung A, Chatelanat F: Renal failure associated with intravenous diphosphonates. Lancet 1983;i:471.
17.
Zojer N, Keck AV, Pecherstorfer M: Comparative tolerability of drug therapies for hypercalcaemia of malignancy. Drug Saf 1999;21:389–406.
18.
Banerjee D, Asif A, Striker L, Preston RA, Bourgoignie JJ, Roth D: Short-term, high-dose pamidronate-induced acute tubular necrosis: the postulated mechanisms of bisphosphonate nephrotoxicity. Am J Kidney Dis 2003;41:E18.
19.
Markowitz GS, Appel GB, Fine PL, Fenves AZ, Loon NR, Jagannath S, Kuhn JA, Dratch AD, D’Agati VD: Collapsing focal segmental glomerulosclerosis following treatment with high-dose pamidronate. J Am Soc Nephrol 2001;12:1164–1172.
20.
Kunin M, Kopolovic J, Avigdor A, Holtzman EJ: Collapsing glomerulopathy induced by long-term treatment with standard-dose pamidronate in a myeloma patient. Nephrol Dial Transplant 2004;19:723–726.
21.
Markowitz GS, Fine PL, Stack JI, Kunis CL, Radhakrishnan J, Palecki W, Park J, Nasr SH, Hoh S, Siegel DS, D’Agati VD: Toxic acute tubular necrosis following treatment with zoledronate (Zometa). Kidney Int 2003;64:281–289.
22.
Johnson K, Gable P, Kaime EM, Luiken G, Castillos T, Hu J: Significant deterioration in renal function with the new bisphosphonate, zoledronic acid (abstract 296). Proc Am Soc Clin Oncol 2003;22:738.
23.
Chang JT, Green L, Beitz J: Renal failure with the use of zoledronic acid. N Engl J Med 2003;349:1676–1679.
24.
Aredia® (pamidronate): Prescribing information. Novartis Pharma.
25.
Zometa® (zoledronic acid): Prescribing information. Novartis Pharma.
26.
CDER New and Generic Drug Approval 1998–2003: Boniva (ibandronate sodium) Tablets, NDA 21-455, Pharmacology Review Part 2, Pharmacokinetics/Toxicokinetics, http://www.fda.gov/cder/foi/nda/2003/21-455_Boniva_pharmr_P2.pdf.
27.
Bauss F, Endele R, Besenfelder E, Hoelck JP: Ibandronate: serum kinetics, tissue distribution and binding to bone following intravenous bolus injection. Calcif Tissue Int 2002;70:289–290.
28.
Pfister T: Comparative renal effects of two intravenously administered bisphosphonates. Toxicology 2004;196:169–170.
29.
Pecherstorfer M, Diel IJ: Rapid administration of ibandronate does not affect renal functioning: evidence from clinical studies in metastatic bone disease and hypercalcemia of malignancy. Support Care Cancer 2004;12:877–881.
30.
Body JJ, Diel IJ, Lichinitser MR, Kreuser ED, Dornoff W, Gorbunova VA, Budde M, Bergström B, MF 4265 Study Group: Intravenous ibandronate reduces the incidence of skeletal complications in patients with breast cancer and bone metastases. Ann Oncol 2003;14:1399–1405.
31.
Diel IJ, Lichinitser MR, Kreuser ED, Dornoff W, Gorbunova VA, Budde M, Bergström B, MF 4265 study group: Improved quality of life after long-term treatment with the bisphosphonate ibandronate in patients with metastatic bone disease due to breast cancer. Eur J Cancer 2004;40:1704–1712.
32.
Bondronat® (ibandronate): Prescribing information. Roche.
33.
Price PA, Faus SA, Williamson MK: Bisphosphonates alendronate and ibandronate inhibit artery calcification at doses comparable to those that inhibit bone resorption. Arterioscler Thromb Vasc Biol 2001;21:817–824.
34.
Weber CK, Friedrich JM, Merkle E, Prummer O, Hoffmeister A, Mattfeldt T, Frickhofen N: Reversible metastatic pulmonary calcification in a patient with multiple myeloma. Ann Hematol 1996;72:329–332.
35.
Menssen HD, Sakalova A, Fontana A, Herrmann Z, Boewer C, Facon T, Lichinitser MR, Singer CRJ, Euller-Ziegler L, Wetterwald M, Fiere D, Hrubisko M, Thiel E, Delmas PD: Effects of long-term intravenous ibandronate therapy on skeletal-related events, survival, and bone resorption markers in patients with advanced multiple myeloma. J Clin Oncol 2002;20:2353–2359.
36.
Bergner R, Henrich D, Hoffmann M, Ullmann M, Honecker A, Nagel D, Uppenkamp M: Renal safety of ibandronate in multiple myeloma patients with renal deterioration (abstract 83). Cancer Treat Rev 2005;31(suppl 1):S45.
37.
Bergner R, Henrich D, Hoffmann M, Lenz G, Bals M, Ullmann M, Uppenkamp M: High bone binding capacity of ibandronate in haemodialysis patients (abstract 82). Cancer Treat Rev 2005;31(suppl 1):S45.
38.
Barrett J, Bergström B: Pharmacokinetics of intravenous ibandronate in patients with renal function impairment. Presented at Skeletal Complications of Malignancy IV, Bethesda, Maryland, USA, 28–30 April 2005.
39.
Green JR, Seltenmeyer Y, Jaeggi KA, Widler L: Renal tolerability profile of novel, potent bisphosphonates in two short-term rat models. Pharmacol Toxicol 1997;80:225–230.
40.
Troehler U, Bonjour J, Fleisch H: Renal transport of bisphosphonates: accumulation by renal cortical slices enhanced by calcium phosphate ions. J Lab Clin Med 1985;106:23–29.
41.
Kino I, Kato Y, Lin JH, Sugiyama Y: Renal handling of bisphosphonate alendronate in rats. Biopharm Drug Dispos 1999;20:193–198.
42.
Adami S, Zamberlan N: Adverse effects of bisphosphonates: a comparative review. Drug Saf 1996;14:158–170.
43.
Bonefos® (clodronate): Prescribing information. Schering.
© 2006 S. Karger AG, Basel
2006
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