LDL Apheresis in Drug Resistant Nephrotic Syndrome Rodney D Gilbert

Patient JM 14 year old girl, presented 06/07/2015 Severe oedema, hypoalbuminaemia and proteinuria Diagnosis nephrotic syndrome No response to steroids

At Southampton Cushingoid, oedematous Creat 27 µmol/L Albumin 20 g/L U Prot/creat 4029 mg/mmol Total cholesterol 16.3 mmol/L Triglycerides 16.2 mmol/L Renal Biopsy: FSGS (collapsing variety)

Further treatment 1 Tacrolimus (Blood levels 4.3 – 6.4 µg/L) Bezafibrate 200 mg bd Continued twice weekly IV albumin 2 weeks later Plasma albumin 15 g/L UPC 3192 mg/mmol MMF 1 g bd added 2 months later Albumin18 g/L UPC 1371 mg/mmol Cholesterol 14.3 mmol/L TG 7.7 mmol/L

Further treatment 2 Rituximab 1 g IV x 2 doses Remained severely nephrotic, fortnightly IV albumin After 8 months: Albumin 14 g/L UPC 1575 mg/mmol Cholesterol 12.5 mmol/L TG 6.4 mmol/L

09/03/2016 First session on the Liposorber!

LDL apheresis

LDL apheresis Two sessions per week for 3 weeks One session per week for 6 weeks Plasma volumes processed increased to 3,500 ml Last session: Cholesterol 14.2 -> 5.7 mmol/L LDL C 1.92 post treatment Albumin 19 g/L UPC 1365 NOT IN REMISSION!

First UK patient treated with LDL apheresis for nephrotic syndrome A few case reports (no genetics) 2 small series 11 patients: 5 complete remission, 2 partial remission 44 patients: 11 complete remission, 10 partial remission (No genetics) A few reports of post Tx recurrence patients successfully treated

Keeping the customer stratified! Genomic and clinical profiling of a national nephrotic syndrome cohort advocates a precision medicine approach to disease management. Kidney Int April 2017 187 patients with SRNS WES: Genetic cause in 26.2% No response to drugs, rapid deterioration, no recurrence No genetic cause in 73.8% Some responded to CNI, rituximab or MMF Slower deterioration 47.7% recurrence in graft

Planned LDL Apheresis Study Adults and children Patients with SRNS with MCNS or FSGS Drug resistant Native kidneys or transplant recurrence No genetic cause found Watch this space!