Clinical Quiz #3:


Clinical Case:

A normotensive 13 year-old boy with chronic renal failure secondary to Nephronophthisis received a deceased donor kidney transplantation. The early post-transplant follow up was characterized by arterial hypertension requiring treatment with two antihypertensive drugs and slow improvement of serum creatinine.

During follow up, he experienced a C4d negative “cellular” rejection, which only partially responded to steroid treatment. Donor specific antibodies (DSA) were repeatedly undetectable. Rejection relapsed twice within one year and finally led to graft loss.

High sensitization against a broad array of human leukocyte antigens (HLA) was demonstrated.

One year later, he received a second deceased donor kidney transplantation. No prohibited antigens were detected and current and historical flow cytometry cross-match were negative. Patient received anti -lymphocyte serum for induction  followed by tacrolimus, mycophenolate and steroid. Renal function rapidly improved after surgery, but in day 10 post-op, a sharp decrease of diuresis and worsening of renal function occurred. According to his previous history, as he was at high risk for antibody-mediated rejection, methylprednisolone pulses plus plasmapheresis were immediately started.
Renal biopsy revealed mild acute humoral rejection with weakly positive peritubular C4d.

HLA-DSA and MICA antibodies were both negative. Renal function slowly improved, 10 plasma-exchange sessions were performed and the boy was discharged with a creatinine of 1.5 mg/dl, no proteinuria and a mild hypertension treated with amlodipine.

Three months later, a moderate but steady increase in plasma creatinine and blood pressure occurred. A second antihypertensive drug was introduced and a new renal biopsy was obtained. Histology was again positive for humoral rejection with weakly positive C4d. HLA-DSA and MICA antibodies were search again and found negative.

Question: What is the most likely diagnosis?

Multiple choice:

  • Anti-Angiotensin Type 1 Receptor “rejection”
  • Unrecognized BK virus nephropathy
  • Steroid resistant cellular rejection
  • Anti DSA humoral rejection


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