*Purpose: An unusual presentation of acute kidney injury with nephrotic range proteinuria following zoledronate in a normal functioning transplant kidney.

*Methods: 61-year-old lady with history of ESRD due to diabetic nephropathy status post kidney transplant 3 years ago with stable allograft function on immunosuppressant’s tacrolimus and mycophenolate mofetil, presented to the ER with frothy urine and elevated blood pressure of 1 day. History significant for receiving IV zoledronate therapy for osteoporosis one week ago. Her physical examination was unremarkable. Labs were remarkable for stage II nonoliguric AKI. Patient’s creatinine trended up to 2.57 from baseline 0.8. Estimated GFR was 19 from baseline 75. UA showed grade 1 proteinuria, protein to creatinine ratio 7.5. Monoclonal study and immunofixation with urine and protein electrophoresis was normal. Urine sodium of 86. HLA antibody and BK nephropathy negative. Tacrolimus level was 6.7. Kidney biopsy showed mild interstitial fibrosis and tubular atrophy. Electron microscopy showed mild podocyte foot process effacement with no evidence of transplant glomerulopathy. Immunofluorescence showed no immune complex deposition.

*Results: AKI due to zoledronate is typically seen 7-9 days after therapy; this patient’s clinical course corresponded to the infusion timeline accordingly. An evaluation of all the available data suggested zoledronate induced nephrotoxicity in our patient, she was monitored in the hospital till her creatinine started to trend down by day 3. Follow up in 1 week showed that her creatinine returned to baseline at 0.88, urine protein to creatinine ratio <0.21.

*Conclusions: Nephrotoxicity is a potential limiting factor to the use of intravenous bisphosphonates. Literature shows, the severity of renal toxicity ranges from transient elevations in serum creatinine to segmental glomerulosclerosis with signs of acute renal failure. Extensive protocol exists for intravenous bisphosphonate therapy, which includes measuring serum creatinine prior to infusion and adjusting the dose as per GFR and monitoring renal function after the treatment. Intermittent evaluation of proteinuria is also recommended at 3-6 month intervals. Zoledronate is not recommended for use in patients with a creatinine clearance < 30 mL/minute, and the dose should be adjusted for CrCl values 30-60. Acute kidney injury in a kidney with normal GFR is virtually unknown. Patients with transplant kidneys will need cautious use of medications like zoledronate irrespective of the GFR.

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