Abstract: FR-PO716
Polycythemia and IgA Nephropathy: An Interesting Association
Session Information
- Glomerular Diseases: From Inflammation to Fibrosis - II
November 03, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1401 Glomerular Diseases: From Inflammation to Fibrosis
Authors
- Zariat, Asheen, University of Pennsylvania, Philadelphia, Pennsylvania, United States
- Geara, Abdallah Sassine, University of Pennsylvania, Philadelphia, Pennsylvania, United States
Introduction
IgA nephropathy (IgAN) is often associated with chronic kidney disease (CKD) which usually presents with anemia. We present a case IgAN-associated polycythemia.
Case Description
A 46-year-old patient with known hypertension (HTN) was evaluated for progressive CKD. Serum creatinine (sCr) increased from 1.2 to 1.7 mg/dL over 5-6 years. Urinalysis showed microscopic hematuria and proteinuria of 1g/g of creatinine. A kidney biopsy showed IgAN with an Oxford classification score of M1E0S1T1-C0. He was treated with RAAS blockade and a 6 months course of steroid followed by dapagliflozin and currently with stable sCr and proteinuria of 0.13 g/g.
In conjunction to IgAN, polycythemia was noted for several years with Hematocrit (Ht) levels between 50-60%. The most recent Hemoglobin was 18.6 g/dL with normal platelets and white blood cell counts. Abdominal imaging showed normal sized kidneys and no splenomegaly or hepatomegaly. Polycythemia evaluation was unrevealing. The patient had no smoking history, and sleep study was negative. Genetic testing for Janus kinase 2 (JAK2) mutation as well as other polycythemia-associated mutations was negative, excluding Polycythemia Vera. The final diagnosis from hematology was polycythemia associated with IgAN with a recommendation for observation.
Discussion
The 4-hit hypothesis for IgAN pathogenesis involves galactose-deficient IgA1 targeting the hinge region, being recognized by IgG autoantibodies, leading to immune complexes which deposit in kidney mesangium. High polymeric IgA (pIgA1) and IgA1 complexes can stimulate red blood cell formation in some patients. In vitro study showed that the serum of patients with IgAN and unexplained polycythemia increased the number of erythroid burst forming unit (BFU-E)-derived colonies from human progenitor CD34+ cells. Removal of IgA1 from IgAN-Polycythemia patients normalized the number of colonies. Mice studies have shown that increased expression of Polymeric IgA (pIgA1) was associated with increased hemoglobin levels without raising EPO levels likely by sensitizing cells to Epo through activating the transferrin receptor 1 (TfR1).
We report an interesting association of IgAN and polycythemia that is supported by in vitro findings of polygenic IgA1 stimulating RBC formation. Evaluation for other etiologies of polycythemia needs to be done before considering the IgAN as the plausible etiology of polycythemia.