LDL Apheresis in Drug Resistant Nephrotic Syndrome Rodney

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 – – Albumin 18 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!

ма р- 17 17 ян в- 6 -1 но я 6 н 1 се 6 л 1 ию 16 16 й- ма ма р- 16 ян в- 5 -1 но я 5 н 1 се 5 л 1 ию 4500 4000 3500 3000 2500 2000 1500 1000 500 0 UPC Alb 40 35 30 25 20 15 10 5 0

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!