Table 1.
Series and case reports of NELL1 MN patients.
| Series/reference | # | Location | % of MN biopsies | Age, sex | Clinical associations and conditions |
Biopsy findings in NELL1 MN | Treatment | Outcomes |
|---|---|---|---|---|---|---|---|---|
| Sethi et al. KI 2020 (12) | 34 | US, France, Belgium | 16% of PLA2R neg MN | 63; 52% male | 12% with malignancy, others presumed primary |
Segmental in 18%, EM stage I or II in all | NA | NA |
| Caza et al. KI 2020 (13) | 91 | US | 3.8% of PLA2R and THSD7A neg MN | 67; 58% male | 33% with malignancy, 24% diabetes 2% IBD |
Incomplete in 93%, IgG1 (co)dominant in 96%, 24% mes deposits | RAAS blockade in 54%, IS in 25% | At 10 months, 61% remission (34% CR, 27% PR); 39% no remission |
| Wang et al. CJASN 2021 (27) | 15 | China | 35% of PLA2R and THSD7A neg MN | 49; 73% female | 0% malignancy | IgG4 (co)dominant in 67% | IS in 83% | At 25 months, 92% in remission (33% CR) |
| Kudose et al. KI 2021 (28) | 5 | US | 29% of segmental MN* | 58; 4/5 female | 1/5 malignancy | Segmental | RAAS blockade in 5/5, no IS | All in remission (3 CR, 2 PR) |
| Kudose et al. KIR 2021 (29) | 2 | US | 2/9 of GVHD-associated MN | 66; 2/2 male | 2/2 GVHD, 0 active malignancy | Segmental, TBM deposits | NA | NA |
| Munch et al. AJT 2021 (30) | 1 | Germany | NA | 56; 1/1 male | Allograft NELL1 MN, 25 years post-transplant. New ALS, started on LA and DMPS 8 weeks prior | Concurrent IgA nephropathy; no rejection | LA and DMPS cessation, RAAS blockade | At 4 months, PR |
| Spain et al. KI 2021 (31) | 4 | US | NA | 60; 4/4 female | 4/4 on LA 2 with multiple sclerosis, 1 celiac disease, 0 malignancy |
Segmental in 4/4 | LA cessation in 4/4, RAAS blockade in 4/4. No IS | At 9 months, all in remission (2 CR, 2 PR) |
| Caza et al. KI 2021 (32) | 115 | US | NA | Of 15 on LA: 68; 60% female | 13% on LA (1/15 also with active malignancy). 8/15 on LA had diabetes | NELL1 MN | 12/13 on LA remained on drug. IS in 4/15 on LA | At 14 months, remission in 11/15 on LA (7/15 CR, 4 PR); 27% no remission |
| Miller et al. Ped Neph 2022 (33) | 1 | US | 4% adolescent non-lupus MN# | 16; 1/1 female | 1/1 obesity | IgG1 dominant, EM stage 1 | NA | CR in 1/1 |
| Iwakura et al. Sci Rep 2022 (34) | 4 | Japan | 8.5% of secondary MN, 1.5% of primary MN | 69; 4/4 male | 2/4 with RA, 1 NSAIDs, 0 malignancy | IgG4+ in 1/4 | IS in 2/4 | At 6 months CR in 2/3 |
| Dinesh et al., Glom dz 2022 (35) | 1 | US | 2/5 HIV-associated MN | 65; 1/1 male | Treated HIV with undetectable viral load | Segmental, “full house” IF | RAAS blockade | At 7 months, CR |
| Kurien et al. KI 2022 (36) | 64 | India, US | 34% of all MN; 88% TIM-associated MN | TIM-MN: 41; 63% female | 91% on TIM; 9/9 of TIM-MN patients had elevated blood mercury levels. ~2% malignancy, 0% autoimmune disease. In TIM-MN: 26% diabetes | NELL1 MN | TIM cessation, RAAS blockade in most. IS in 24% | For TIM-MN, at 3.5 months, remission in 74% (46% CR, 28% PR) |
| Tsuji et al. medRxiv 2022 (37) | 16 | Japan | 13% of MN; 79% of RA-associated MN (56% of RA-MN on bucillamine) | 75; 69% male | 31% autoimmune disease including 19% RA on bucillamine, 13% malignancy, 63% diabetes | IgG1 dominant; DN in 10%; EM stage I or II in 90% | IS in 44%, RAAS in 31% | At 9 months, 77% remission |
| Miyazaki et al. KIR 2023 (38) | 10 | Japan | 4.5% of MN | NA | 6/10 with RA, 3 on bucillamine, 1 on adalimumab, 1 HCV | NELL1 MN | For 3 on bucillamine, all discontinued drug, IS in 1 | For 3 on bucillamine with follow up, all in remission |
| Takahashi-Kobayashi et al. KIR 2023 (39) | 8 | Japan | 9.1% of MN | NA | 1/8 RA on bucillamine, 1 IgG4 related disease | NELL1 MN | NA | NA |
| Sethi CKJ 2023 (40) and Zubidat et al. KIR 2023 (41) | (review) | US | (review) | (review) | NELL1+ in 4/19 tested cases of sarcoidosis associated MN, 2/8 HBV, 1 HCV, 4 NSAIDs, 3 auto-immune disease, 1 IVIG, 1 HSCT^ | NELL1 MN | NA | NA |
| Santoriello et al. KIR 2023 (42) | 1 | US | NA | 53; 1/1 male | Tiopronin, no malignancy | Segmental | Tiopronin cessation | At 6 months, PR in 1/1 |
| Zhu et al. Kid Dis 2023 (43) | 58 | China | 43% of segmental MN* | 40; 78% female | 9% TB, 7% malignancy | Segmental, EM stage I or II in 93%, 7% mesangial deposits | NA | At 12 months, 71% remission (7/14 CR, 3/14 PR), 29% no remission |
| Sultan et al. Clin Tox 2023 (44) | 3 | India | NA | 3/3 female same family, ages 17, 19, 39 | Skin lightening cream with high mercury content; elevated blood mercury levels; hypothyroidism | NELL1 MN | IS in 2/3 | Remission in 2/3 |
| Nimkar et al. KIR 2023 (45) | 1 | US | NA | 71; male | History of malignancy but NED; on CPI | Weak PLA2R staining | Pembrolizumab cessation | At 2 months, in remission |
| Avasare et al. KIR 2024 (26) | 70 | US | NA | 66; 53% male | 36% on LA, 23% autoimmune disease, 27% diabetes, 27% NSAIDs, 10% recent malignancy | Segmental in 55%; EM stage I or II in 82%; IgG1 (co)-dominant in 86%; mesangial deposits in 16% extra-glomerular deposits in 12%, DN in 8% | IS in 29%. For 25 on LA: LA cessation in 88%, IS in 4% | At 11 months, 72% remission (52% CR). For 25 on LA: 88% remission (72% CR) |
ALS, amyotrophic lateral sclerosis; Bucillamine, similar chemical structure to D-penicillamine; CPI, immune checkpoint inhibitor; CR, complete remission; DMPS, dimercaptopropane sulfonate; DN, diabetic glomerulopathy; EM, electron microscopy; GVHD, graft vs host disease; HBV, Hepatitis B virus; HCV, Hepatitis C virus; HIV, human immunodeficiency virus; HSCT, hematopoietic stem cell transplant; IBD, inflammatory bowel disease; IF, immunofluorescence; IS, immunosuppression; LA, lipoic acid; MN, membranous nephropathy; NA, Not applicable or not available; NED, no evidence of disease; Neg, negative; NELL1, neural epidermal growth factor like 1; NSAID, non-steroidal anti-inflammatory; PLA2R, Phospholipase A2 receptor; PR, partial remission; RAAS, renin-angiotensin system; RA, rheumatoid arthritis; TB, tuberculosis; TBM, tubular basement membrane; THSD7A, thrombospondin type 1 domain-containing 7A; TIM, traditional indigenous medications, the most common of which was Swasa Kalpa which had very elevated mercury content. Tiopronin: thiol agent for cystinuria.
Listed age is mean or median, as provided by study. Results given in % in case series with ≥ 10 patients, and as fractions when <10 patients present.
*segmental MN was 2.5% of MN in Kudose et al. and 0.51% of adult MN in Zhu et al.
#NELL1 positive in 1/25 MN biopsies from adolescents aged 13-20.
^associations described in review article.