Post-transplant erythrocytosis treated with RAS blockade

Transplantmedium

A 60-year-old-man with ESRD due to ADPKD, status post deceased donor kidney transplant 1 year ago, presents to establish care with a nephrologist after a recent move out of state. He has not been seen by a nephrologist for 5 months. He has occasional mild headaches, but feels well overall. The headaches are bilateral and not associated with vision changes. He denies recent infections, night sweats, or pruritis. He has no daytime sleepiness. He has a 10-pack-year smoking history, but a CT scan of his chest done as part of his original transplant evaluation was without evidence of lung disease or nodules. His immunosuppressive regimen is tacrolimus, mycophenolate mofetil, and prednisone. His RBC indices were found to be elevated at his most recent transplant nephrology appointments, 5 and 6 months ago. On examination, BP is 124/76 mm Hg, heart rate is 60/min, and oxygen saturation is 99% while breathing room air. He has a normal cardiopulmonary examination. He does not have edema. Laboratory data: WBC count 3400/µL (reference 4000–11,000); hemoglobin 18.1 g/dL (pre-transplant, 11.8) (14–18); platelet count 170,000/µL (150,000–450,000); tacrolimus whole blood trough 7.7 ng/mL (5–10, >3 months after transplant). Evaluation for the V617F or other mutations in the JAK2 gene for the diagnosis of polycythemia vera is negative. Which ONE of the following is the next best step in diagnosis or management?

  1. A.Phlebotomy
  2. B.CT scan of the chest and abdomen
  3. C.LisinoprilCorrect
  4. D.Bone marrow biopsy

Explanation

Prescribing lisinopril is the best management strategy in this patient with post-transplant erythrocytosis (PTE). PTE is defined as a hemoglobin >17 g/dL or a hematocrit >51% for >6 months after transplantation in a patient who had a normal hematocrit previously. It has been reported to occur in 8%–15% of kidney transplant recipients. Risk factors for PTE include male sex, diabetes, retention of native kidneys, and transplant renal artery stenosis. ADPKD is also a risk factor for PTE, as seen in this case. PTE must be distinguished from other causes of erythrocytosis, including hypoxemic lung disease, sleep apnea, heart failure, and malignancy. Secondary causes of erythrocytosis, including renal artery stenosis and renal cell carcinoma, should also be excluded. Myeloproliferative disorders should be ruled out by evaluating for JAK2 gene mutations. Because erythropoietin (EPO) is produced by angiotensin II-sensitive peritubular fibroblasts in the renal interstitium, patients with PTE should be prescribed a moderate dose of ACEI or ARB as initial therapy. If after 4 weeks the hemoglobin remains >17 g/dL, the dose of the drug may be titrated as tolerated. Typically, treatment is successful in >90% of patients within 2–6 weeks. If ACEI/ARB therapy is not tolerated, then azathioprine or a mammalian target of rapamycin inhibitor such as sirolimus may be considered. In refractory cases, in whom secondary screening fails to identify a cause, periodic phlebotomy may be required. Phlebotomy may also be used for sympatomatic patients with signs or symptoms of hyperviscosity syndrome. In this patient, phlebotomy could be considered if medical therapy were ineffective. If EPO levels are elevated, imaging should be considered to evaluate for malignancy. Although this patient was a smoker, his chest CT scan was normal before transplant, so he is unlikely to have chronic obstructive pulmonary disease or other pulmonary causes of erythrocytosis. Thus, a CT scan is not the next best step in management. If polycythemia worsened or progressed while receiving ACEI/ARB therapy for the most likely diagnosis of PTE, then further evaluation could be entertained. Bone marrow biopsies are recommended in patients with clinical suspicion for polycythemia vera (PCV) or another hematologic malignancy, such as easy bleeding or bruising or pruritis. As this patient has no evidence of PCV-associated genetic mutations and does not report other symptoms associated with PCV, a bone marrow biopsy would not be indicated.

Why each option

A.
Phlebotomy is reserved for hyperviscosity symptoms or erythrocytosis refractory to ACE inhibitor or ARB therapy, which succeeds in over 90% of patients.
B.
With a normal pretransplant chest CT, normal oxygen saturation, and a typical PTE profile, imaging is reserved for elevated erythropoietin or failure of ACE inhibitor therapy.
C.
Correct. Hemoglobin above 17 g/dL beyond 6 months after transplant in a man with ADPKD and negative JAK2 indicates post-transplant erythrocytosis, which responds to ACE inhibition.
D.
Marrow biopsy is for suspected polycythemia vera or other marrow disease; negative JAK2 testing and absent pruritus or bleeding make it unnecessary.

Reference: Vlahakos DV, Kidney Int 2003 (post-transplant erythrocytosis); KDIGO 2009 Clinical Practice Guideline for the Care of Kidney Transplant Recipients

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