Table 1:

Clinicopathologic features of patients taking lipoic acid with confirmed and suspected NELL1-associated membranous nephropathy

	Patient 1	Patient 2	Patient 3	Patient 4	Patient 5
Clinical findings at presentation
Age, sex, race	56F, Asian, non-Hispanic	74F, White, non-Hispanic	66F, White, non-Hispanic	41F, White, non-Hispanic	71F, White, non-Hispanic
Setting of proteinuria	Pilot Phase 2 RCT (NCT01188811)	Multi-site Phase IIb RCT (NCT03161028)	Multi-site Phase IIb RCT (NCT03161028)	Outpatient glomerular disease clinic	Outpatient glomerular disease clinic
Reason for taking LA	Secondary progressive MS, no treatment	Secondary progressive MS, no treatment	Primary progressive MS, no treatment	Arthritis, weight loss, metabolic syndrome	Joint pain, general wellness
Co-morbid conditions	HTN	Asthma, basal cell carcinoma, melanoma, osteoporosis	COPD, depression, HTN, migraine	Asthma, Celiac disease	HTN, smoldering multiple myeloma, transient VWF deficiency
LA dose	1200mg LA daily	1200mg LA daily	1200mg LA daily	600 mg LA daily	1200mg LA daily
Exposure to LA	Onset 6 months, biopsy 9 months	Onset 3 months, biopsy 9 months	12 months	6 months (inconsistent use)	Over 3 years
Serologies (ANA and PLA2R Antibody)	ANA positive (1:320, speckled), PLA2R not tested	ANA not tested, PLA2R negative	ANA not tested, PLA2R not tested	ANA negative, PLA2R negative	ANA negative, PLA2R negative
Creatinine at peak proteinuria (mg/dL)	0.6	0.6	0.7	0.74	0.67
Proteinuria	19 g/g PCR	2.1 g/g ACR	4.4 g/g ACR	5.5g/g PCR	4.5 g/g PCR
Reason for biopsy	Nephrotic syndrome with leg edema	Asymptomatic proteinuria	Nephrotic range proteinuria	Nephrotic syndrome	Nephrotic syndrome in setting of smoldering myeloma
Kidney biopsy
Light microscopy	Membranous	Membranous	No biopsy performed	Membranous	Membranous
Immunofluorescence (IF)	Segmental capillary wall deposits, IgG1 dominant	Segmental capillary wall deposits, polyclonal IgG		Segmental capillary wall deposits of polyclonal IgG, by paraffin IF	Segmental capillary wall deposits, IgG1 dominant, PLA2R-negative
Electron microscopy	Segmentally distributed subepithelial deposits	Segmentally distributed subepithelial deposits with rare basement membrane spikes		Not available	Segmentally distributed subepithelial and focal mesangial deposits
Glomerular antigen	NELL1+	NELL1+		NELL1+	NELL1+
Clinical outcome
Intervention	LA cessation; furosemide, lisinopril	LA cessation; losartan, spironolactone	LA cessation alone	LA cessation; furosemide, losartan	LA cessation; furosemide, losartan
Creatinine at time of proteinuria resolution (mg/dL)	0.6	0.7	0.7	0.78	0.60
Proteinuria at last follow-up	Resolution proteinuria at 7 months off LA	Resolution proteinuria at 12 months off LA	Resolution proteinuria at 3 months off LA	Partial remission (0.66g/g Cr) at 7 months off LA; Monitoring ongoing	Partial remission (0.66g/d) at 8 months, Complete resolution at 11 months off LA

ACR denotes urine albumin to creatinine ratio, ANA anti-nuclear antigen, COPD chronic obstructive pulmonary disease, dsDNA double stranded DNA, g gram, HTN hypertension, IgG immunoglobulin G, LA lipoic acid, MS multiple sclerosis, NELL1 neural epidermal growth factor-like 1 protein, anti-phospholipase A2 receptor PLA2R, PCR urine protein creatinine ratio, and VWF von Willebrand Factor