Dr. K. Pressmar

Department of Clinical Medicine IV, Division of Nephrology and Hypertensiology, Friedrich-Alexander University Erlangen-Nuremberg Erlangen, Germany

 

Introduction:

A 43-year-old Caucasian woman was admitted due to increasing serum creatinine from 1.3 to 2.4 mg/dl as assessed in a routine control evaluation one year after renal transplantation. On admission, she felt completely fine showing no clinical problems.
Last medication: tacrolimus (3mg) bid, mycophenolate mofetil (500mg) bid, prednisolone (15mg) od and ramipril (10mg), amlodipine (10mg), metoprolol (150mg), hydrochlothiazid (25mg), tmp/smx (480mg), amphotericine-suspension, risedronate (10mg), pravastatin (40 mg), pantoprazol (80 mg) daily.

Past medical history / clinical course before transplantation:

- 10/1994: Acute presentation with nephrotic syndrome and renal impairment (17 g proteinuria/24 hours, serum creatinine 1.4 mg/dl). Clinically and histologically, primary focal segmental glomerulosclerosis (FSGS) was diagnosed.
- 11/94–03/95: Immunmodulatory therapy using cyclophosphamide and steroids was started, but no positive response was achieved. Within half a year she developed renal failure.
- 03/95-01/03: renal replacement therapy (hemodialysis for 93 months).
- 12/02: renal transplantation of an allogenic cadaveric donor.

Data of renal transplantation

 

Clinical course during the first year after renal transplantation:

Figure A: Clinical course after Transplantation

 

Initial immunosuppressive therapy based on a combination of tacrolimus bid (target level 10-15 ng/ml), low dose rapamycin od (fix dose of 0.5mg), and prednisolone accompanied by TMP/SMX and ganciclovir as prophylaxis of pneumocystis carinii and cytomegaly virus infection, respectively.

Due to delayed graft function, the first renal allograft biopsy was performed on the 9th day after transplantation, presenting a BANFF Ia rejection. The patient was treated with a high dose steroid pulse (250mg/d for three consecutive days followed by tapering within several weeks). Renal dysfunction improved and serum creatinine reached 1.1 mg/dl on day 27 after transplant surgery.

Four months later renal impairment was again noted (S-creatinine 1.6 mg/dl; tacrolimus level 11 ng/ml). The second renal biopsy revealed another BANFF Ia rejection that was successfully treated with another course of high dose steroids and transiently increased levels of tacrolimus (S-creatinine declined to 1.2 mg/dl within 10 days, tacrolimus target level was 13-15 ng/ml).

Half a year after renal transplantation, the patient suddenly developed asymptomatic nephrotic proteinuria (>3.5 g/24 hrs.) associated with impairment of renal function (S-creatinine 2.2 mg/dl; tacrolimus level 10 ng/ml).

The third renal biopsy was performed.

Question 1