Post Renal Transplant Patient with Headache and Giddiness

History:

24 yrs old male, resident of Chennai who underwent live related renal transplant three years before for his End Stage Renal disease due to presumed chronic glomerulonephritis. His renal donor was his mother and was on regular follow up. His immune suppression consists of tacrolimus, mycophenolate and prednisolone. He was on regular follow up and his renal functions remained normal. He started complaining of on and off headaches and giddiness. He is a non-smoker.

 He was euvolemic with well controlled blood pressure. The only abnormal finding on examination was injected conjunctiva. His blood tests revealed gradually increasing hemoglobin over the last few months with current Hb was 18 grams and hematocrit was 54. His white cell count and platelet counts remained normal. His renal functions were normal so as the ultrasound examination of the transplant kidney. Doppler evaluation of the transplant renal artery was normal.

He is being treated with Enalapril, theophylline and aspirin and his hemoglobin shows declining trend.

Post-transplant erythrocytosis (PTE):

Is one of the common complication post renal transplantation. The incidence varies from 2 to 22 % in different studies. (1) KDIGO – Kidney Disease Improving Global Outcome group defined PTE when the hemoglobin increases >17 grams and /or the hematocrit is > 51 irrespective of the gender of the patient. (2)

It is due to robust erythropoietin production post transplantation. The risk factors for PTE include near normal hemoglobin pre transplantation, male gender, normal graft function, renin angiotensin system, insulin like growth factor. Renal artery stenosis of transplant kidney causes ischemia to the transplant kidney that increases the stimulus for erythropoietin production. Younger donor and recipient age, polycystic kidney disease also predispose to PTE (3)

Mechanism of PTE:

The pre transplant stage has anemia of CKD and a successful renal transplant increases EPO from the transplant kidney. Once the hemoglobin starts increasing the production of erythropoietin should decrease. On the contrary in few patients the EPO production is unchecked resulting in continuous EPO production and erythropoiesis. (4)

N-acetyl-seryl-aspartyl-lysyl-proline (ac-SKDP) is an inhibitor of erythropoiesis. RAAS system inhibits this enzyme and ACEI/ARB augments and degrades ac-SKDP. IGF and androgens directly or through RAAS influences ac-SKDP. (5)

Clinical Presentation: Clinical presentation: PTE generally manifests few months to few years post-transplant in susceptible individuals. The patient may be asymptomatic or may have constitutional symptoms like malaise, giddiness, and headache or with rarely thrombotic complications. Deep venous thrombosis, pulmonary embolism, stroke are common complications and sometimes it can be fatal.

Diagnosis: Persistent elevation of Hb and Hct post-transplant identifies PTE. It is important to exclude other causes of erythrocytosis like renal artery stenosis or certain malignancies. Erythropoietin levels will be high and is not a routine to check its levels. Detailed evaluation for erythrocytosis including those towards excluding polycythemia vera are done, when the patient does not respond to standard treatment.

Treatment:

The first line of treatment consists of ACEI/ARB that decreases the production of red cells. If the hematocrit is high and if the patient gets symptoms phlebotomy is indicated. Theophylline. Mycophenolate and sirolimus because of anti-proliferative effects decrease red cell mass. Antiplatelet drugs offer protection from thrombotic complications. (6)

Stopping these drugs could result in rebound increase in hemoglobin levels.

Conclusions:

PTE is a common complication post renal transplant. Careful monitoring of hemoglobin post-transplant is key to diagnosis. Exclusion of contributing factors and administering the easy therapeutic options could result in lowering the hemoglobin and reducing the complications from PTE.

References:

• Vlahakos DV, Marathias KP, Agroyannis B, Madias NE. Posttransplant erythrocytosis. Kidney Int. 2003;63:1187–1194
• Kidney Disease: Improving Global Outcomes (KDIGO) Transplant Work Group. KDIGO clinical practice guideline for the care of kidney transplant recipients. Am J Transplant. 2009;9 Suppl 3:S1–155
• Alasfar S, Hall IE, Mansour SG, Jia Y, Thiessen-Philbrook HR, Weng FL, Singh P, Schröppel B, Muthukumar T, Mohan S, Malik RF, Harhay MN, Doshi MD, Akalin E, Bromberg JS, Brennan DC, Reese PP, Parikh CR. Contemporary incidence and risk factors of post transplant Erythrocytosis in deceased donor kidney transplantation. BMC Nephrol. 2021;22:26.
• Vlahakos DV, Marathias KP, Agroyannis B, Madias NE. Posttransplant erythrocytosis. Kidney Int. 2003;63:1187–1194.
• Yang Y, Yu B, Chen Y. Blood disorders typically associated with renal transplantation. Front Cell Dev Biol. 2015;3:18
• Pesavento TE. Kidney transplantation in the context of renal replacement therapy. Clin J Am Soc Nephrol. 2009;4:2035