Thioctic acid/unithiol

Abstract

NELL1-positive membranous nephropathy: case report A 56-year-old man developed NELL1-positive membranous nephropathy (MN) during off label therapy with thioctic acid and unithiol for amyotrophic lateral sclerosis (ALS) [routes and doses not stated]. The man was admitted because of a new-onset nephrotic syndrome (NS) 25 years following successful kidney transplantation (KTx) with serum creatinine of 152 μmol/L, proteinuria of 4041 mg/g, estimated glomerular filtration (eGFR CKD-EPI ) of 54 mL/min/1.73 m2 , creatinine and serum albumin 23.8 g/L. His immunosuppressive regimen included tacrolimus and mycophenolate mofetil. Twelve months before the admission, he was diagnosed ALS with bulbar onset. Because of ALS, riluzole was started. After 6 months, he refused riluzole therapy and was started on an unapproved therapeutic attempt (off label use). Then, a daily chelation therapy with thioctic acid [α-lipoic acid] and unithiol [dimercaptopropane sulfonate] was started 8 weeks before first NS diagnosis. Histological examination showed both KM55 (antibody against galactose-deficient IgA1)-positive IgA nephropathy and subepithelial immune deposits, which were characteristics for MN. Strong glomerular positivity for NELL1 was observed. Electron microscopy showed foot process effacement and subepithelial localisation of electron-dense deposits that confirmed the histological diagnosis of post-transplant NELL1-positive MN. Because of lack of commercially available assays, a NELL1-immunoblotting under non-reducing conditions was established to first analyse if NELL1 antibodies were there in his serum at the time of MN diagnosis. Thus, a positivity for NELL1 total IgG antibodies as well as for the IgG subclasses IgG1, IgG3 and IgG4 was found. Subsequently, NELL1-specific IgG4 antibodies in the serum and IgG4 staining of the kidney biopsy were positive. His serum 31 months prior to the MN diagnosis was taken for the analysis and no NELL1 antibodies were noticed in the serum at that time. Because neither native kidney biopsy material nor medical records pertaining to his primary renal disease were available, the MN was classified as a de novo disease. Based on the findings, a diagnosis of NELL1-positive MN associated with thioctic acid and unithiol was confirmed. The man received captopril followed by irbesartan combined with further supportive measures such as torasemide and atorvastatin. Thereafter, thioctic acid and unithiol were discontinued, while the immunosuppressive regimen was not changed. At a follow-up time of 4 months, partial remission of proteinuria was observed that was regarded as decreased proteinuria, normal serum albumin levels and normal serum creatinine. Partial remission of proteinuria was supplemented by vanishing of circulating NELL1 antibody in the serum.