Dr. K. Pressmar

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

 

Proteinuria following renal transplantation appears in 10-40% and is associated with poorer allograft survival.

Proteinuria <six months duration is frequently associated with acute rejection, pyelonephritis or intercurrent systemic disease.

Proteinuria >six months duration occurs with chronic allograft nephropathy or chronic rejection, CNI-toxicity, vascular events (atheroembolic, venous thrombosis), diabetic nephropathy, reflux nephropathy, light chain deposition disease or glomerulonephritis.

Recurrent acute rejections as well as CNI-toxicity contribute to the development of chronic allograft nephropathy even within such a short period as three to six months after renal transplantation as indicated by protocol biopsies. (1)

Atheroembolic events, renal vein thrombosis, light chain deposition disease and de novo diabetic nephropathy are relatively rare causes of proteinuria after renal transplantation.
In our case, the degree and rapid development of proteinuria is suggestive of recurrence of FSGS. Primary FSGS recurs in about 15% of adults after renal transplantation. Moreover, post-transplant FSGS is associated with an increased risk of acute rejection episodes in the early transplant-period. (2)

Light microscopy of the third renal biopsy documented again a combination of focal aggressive interstitial cellular rejection (BANFF Ia) and signs of focal calcifications as an expression of calcineurin-inhibitor toxicity.
Electron microscopy revealed podocyte foot process fusion suggestive of the recurrence of primary focal segmental glomerulosclerosis.

Figure B: Course after transplantation combined with therapeutic interventions

In view of FSGS recurrence, plasma exchange therapy was initiated and remission defined as proteinuria < 0.5g/24 hrs. was achieved within 9 sessions. At the same time, the patient was switched from sirolimus to mycophenolate mofetil (500 mg bid), while tacrolimus (target level around 10 ng/ml) was continued.

However, proteinuria of the nephrotic range relapsed within three months after plasma exchange therapy, however serum creatinine kept stable around 1.5 mg/dl. The fourth renal biopsy demonstrated again acute interstitial cellular rejection (BANFF Ia) associated with discrete signs of glomerulosclerosis.
Immunosuppressive medication was increased again (tacrolimus target level around 10-13 ng/ml) and another course of pulse steroids started. Within a few days, proteinuria was below 0.5 g/24 hrs.

Only a few weeks later, now exactly one year after renal transplantation, the patient was again hospitalized, since serum creatinine had been steadily increased up to 2.3mg/dl, meanwhile proteinuria was still below 0.5 g/24hrs.

The fifth renal biopsy was done.

Figure C: renal histology. (Courtesy of Dr. V. Câmpean and Prof. K. Amann)

Question 2