Renal complications from bisphosphonate treatment

More than 10 years ago evidence emerged that bisphosphonate therapy especially in malignant bone diseases is associated with renal complications. The nature of renal injury from bisphosphonates has become clearer in recent years.

Pamidronate can rarely cause (collapsing) focal segmental glomerular sclerosis with the nephrotic syndrome and renal insufficiency. This renal complication has also been observed with other bisphosphonates but only in isolated cases. Other types of renal injury include transient but self-limited rises in creatinine, and, very rarely, acute tubular necrosis causing acute renal failure. The frequency of the latter two complications appears to follow the potency of different bisphosphonates. Although thus far no tubular transport for bisphosphonates has been identified (renal excretion appears to be only by glomerular ultrafiltration), the occurrence of tubular cell injury gives rise for the possibility that these cells can take up bisphosphonates. In patients receiving bisphosphonates monitoring of serum creatinine before and after intravenous (i.v.) dosing or periodically with oral bisphosphonates is advised.

Renal complications with bisphosphonates are rare but creatinine monitoring, especially with i.v. bisphosphonates is strongly advised. The mechanisms by which bisphosphonates can cause renal insufficiency are still elusive and opportunities for research include the discovery of potential mechanisms of tubular cell uptake of bisphosphonates.