Kidney Week

Abstract: PUB303

ABCC6/MRP6 Gene Mutation with Associated Membranous Nephropathy

Session Information

• Publication Only

Category: Genetic Diseases of the Kidneys

• 1202 Genetic Diseases of the Kidneys: Non-Cystic

Authors

• Patel, Samir Dinesh, University of California Irvine Nephrology Hypertension & Kidney Transplantation, Orange, California, United States

Samir Dinesh Patel, MD, PhD

• Fekrat, Ryan Evan, University of California Irvine Nephrology Hypertension & Kidney Transplantation, Orange, California, United States

Ryan Evan Fekrat

• Dileep, Gayathri, University of California Irvine Nephrology Hypertension & Kidney Transplantation, Orange, California, United States

Gayathri Dileep

• Nguyen, Matthew Duy Thanh Luyen, University of California Irvine Nephrology Hypertension & Kidney Transplantation, Orange, California, United States

Matthew Duy Thanh Luyen Nguyen

• Hanna, Ramy Magdy, University of California Irvine Nephrology Hypertension & Kidney Transplantation, Orange, California, United States

Ramy Magdy Hanna, MD, FASN

Introduction

Multidrug resistant associated protein 6 (ABCC6/MRP6) is found in the liver and kidneys and functions in ATP-dependent export for systemic delivery related to modulators of calcification. Mutation of ABCC6 results in ectopic mineralization characterized in cases of pseudoxanthoma elasticum (PXE) and dystrophic cardiac malfunction (DCC). Neural epidermal growth factor-like 1 protein (NELL-1) has been associated with a rare form of membranous nephropathy (MN) with little proposed mechanistic link. Here we present a 54-year-old female with known ABCC6/MRP6 and NELL1 positive MN with no evidence of serological factor, rheumatoid factor, cryoglobulin, or M-protein abnormality, implying a possible link between ABCC6 mutation and NELL1 positive MN.

Case Description

Our patient is a 54-year-old female with a known ABCC6/MRP6 gene mutation on outside testing presented with initially normal renal function (BUN 6 mg/dl, sCr 0.5 md/dl). However, 24-hour urine collection shows 1.1 grams of protein with findings of an increase in urine protein to 4.4 grams (within nephrotic level range) with a peak UPCR of 7 grams at an outside hospital. Serological testing was negative with exception of isolated low C4. There was no evidence of rheumatoid factor, cryoglobulin, or M-protein abnormalities. Renal biopsy reflects membranous nephropathy, NELL1 positive. glomerulomegaly, mesangial IgM deposits, and mild to moderate arteriosclerosis. She was advised cancer screening for secondary MGN/NELL membranous nephropathy. She currently is on a RAAS inhibitor for blood pressure control. Her proteinuria decreases when on steroids to less than 350 mg.

Discussion

Our case presents as NELL1 positive MN in an adult female with negative findings of most common associations of secondary MN such as sarcoidosis, hematopoietic stem cell therapy (HSCT), autoimmune disease, infection, or malignancy with the additional presentation of ABCC6 mutation and low complement activation and no cancer as of report timing. Negative lipoid acid supplementation and target antigens in cases of secondary MN additionally are not always associated with identifiable causes. In our case, we propose the association of NELL1 positive finding with mutant or aberrant ABCC6-MN in conjunction with negative cancer findings. Supplemental ABCC6/MRP6 therapy may improve prognosis in patients with NELL1-MN.