Differentiation of Cyclosporine Nephrotoxicity from Renal Allograft Rejection

Favor Cyclosporine Toxicity

Favor Renal Allograft Rejection

often > 6 weeks post transplant

often < 4 weeks post transplant

concomitant nephrotoxic drugs

retransplant patient

donor > 50 years of age, donor hypotensive, prolonged preservation of donor kidney, prolonged anastomosis time, prolonged initial nonfunction

antidonor immune response

afebrile without graft swelling or tenderness

fever > 37.5°C with graft swelling and tenderness

cyclosporine trough serum levels > 200 ng/mL

cyclosporine trough serum level < 150 ng/mL

rise in serum creatinine gradual (< 0.15 mg/dL per day); plateau < 25% above baseline

rise in serum creatinine rapid (> 0.3 mg/dL per day); plateau > 25% above baseline

BUN to creatinine ratio >= 20

BUN to creatinine ratio < 20

arteriolopathy on renal biopsy

endovasculitis on renal biopsy

tubular atrophy, isometric vacuolization and isolated calcifications on renal biopsy

glomerulitis and tubulitis on renal biopsy

no or minimal edema on renal biopsy; diffuse interstitial fibrosis

interstitial edema and hemorrhage on renal biopsy

mild focal infiltrates on renal biopsy

diffuse inflammatory mononuclear cell infiltrate on renal biopsy

intracapsular pressure < 40 mm Hg on manometry

intracapsular pressure > 40 mm Hg on manometry

graft cross sectional area unchanged on ultrasound

graft cross sectional area increased, with AP diameter >= transverse diameter

MRI appearance normal

MRI shows loss of distinct cortico-medullary junction with swelling

radionuclide scan shows normal or generally decreased perfusion

radionuclide scan shows patchy arterial flow

radionuclide scan shows a decrease in tubular function > decrease in perfusion

radionuclide scan shows a decrease in tubular function < decrease in perfusion; increased uptake of Indium 111 labeled platelets or Tc-99m in colloid

responds to decrease in cyclosporine dose

responds to an increase in steroids or antilymphocyte globulin