NELL 1 Staining in Primary Membranous Nephropathy – A Case Report

History

Mr. S. 45 years presented with gross edema for 2 months. He did not have history of oliguria, hematuria, breathlessness, arthralgia, fever or any other constitutional symptoms. He gave history of passing frothy urine. He was evaluated and found to have nephrotic range of proteinuria (8 grams per day), normal renal chemistry (urea 20 mg% and creatinine – 1.0 mg %), Hypoproteinemia (serum proteins 6 gm% and albumin 3.2 gm%) and hypertriglyceridemia with normal sized kidneys on ultra-sonogram.

He gave history of taking indigenous medications for his eczema.

He was diagnosed to have NEPHROTIC SYNDROME and towards defining the histology he underwent renal biopsy.

Renal Biopsy

Revealed 15 glomeruli with normal cellularity and thickened capillary walls with spike formation. There were no vascular, tubular or interstitial changes. Immuno florescence staining was negative for PLA2R (Phospholipase A2 receptor) staining but showed linear IgG positivity along the glomerular basement membrane and NELL1 (Neural Epidermal GROWTH FACTOR like protein1) along the glomerular basement membrane. (!)

Fig 1- a) LM showing thickening of glomerular basement membrane
Fig 1- b) silver staining showing spike formation
Fig 1- c & d) immunofluorescence staining showing IGg1 & NELL1 positivity along the glomerular basement membrane

Discussion

Membranous Nephropathy is the commonest type of Nephrotic syndrome in adults. It could be primary or idiopathic or it can be secondary to vasculitis (especially Systemic Lupus Erythematosus), infections (Hepatitis B), malignancy associated or drug induced (gold, penicillamine and native medications)

Primary membranous nephropathy is identified by the presence of PLA2R antibody OR THSD7A (Thrombospondin) staining on the glomeruli. NELL1 staining is generally believed to be associated with malignancy associated MN. But this patient currently has no evidence of malignancy.

He gives history of Native medicine intake for his eczema and there are few reports of NELL1 positive MN in those who took indigenous medications.

Malignancy associated MN defining criteria:

1. The onset of glomerulonephritis and malignancy should occur within 2 years of onset between each other
2. Treatment of malignancy should cure the glomerulonephritis
3. Recurrence of the malignancy, should cause the glomerulonephritis to recur
4. The same antigen should be expressed in malignancy as well as in the kidneys

Currently our patient has no evidence of malignancy but we have to wait to see if he manifests evidence of malignancy on follow up.

Reference:

1. Tiffany N. Caza et al.NELL1 is a target antigen in malignancy associated membranous nephropathy. KI Vol 99, issue 4, P967-976, April01,2021V

Dr. R. Balasubramaniyam
Chief Nephrologist
Kauvery Hospital Chennai