So why have CKD stages I and II at all?!

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1 So why have CKD stages I and II at all?! Structural / genetic abnormalities e.g. APKD Significant proteinuria Nephrotic range Microscopic haematoproteinuria in the absence of infection e.g. vasculitis?!! Isolated haematuria without Urological cause e.g. TBM disease

2 Nephrotic syndrome Oedema Hypertension Hypoalbuminaemia Hypercholesterolaemia Multiple underlying causes Needs renal biopsy to delineate Death from DVT / PE Encapsulated bacterial infections (pneumococcal pneumonia) Swelling isn t just heart failure! Urine dipstix showing proteinuria -> urine Protein/Creatinine Ratio PCR >1000 refer!

3 CKD stage III (egfr 30-59) Attention to BP control and proteinuria reduction Modification of other CVS risk factors Address secondary renal effects Anaemia Hyperparathyroidism

4 CKD stage IV (egfr 15-30) Active focus on arresting further decline Ongoing specific treatment of underlying disease(s) Aggressive BP and proteinuria control egfr < 20 Decisions about treatment options, including conservative management Preparation for dialysis if appropriate Patient involvement in decision making Access creation Workup for renal transplantation Including pre-emptive transplantation

5 Blood pressure control Lv et al CMAJ Aug;185(11):949-57, meta-analysis of 11 RCTs, ~9000 patients with CKD

6 ACEI and ARB combinations MHRA guidance June 2014 Increased risk of hyperkalaemia, hypotension and impaired renal function Particularly in diabetics Sick day rules Applies to renin inhibitor Aliskiren as well Small proportion of (usually nephrotic) patients where we still use the combination

7 CKD stage V (egfr < 15) Dialysis Decision to dialyse combination measured parameters patient symptoms Type of dialysis and patient choice Conservative management Evidence of dialysis benefit in older age group questionable at best Patient choice with focus on highly informed decision making

8 CKD key points on referring Stages IV and V refer if not already known to us Stage III probably refer! Discuss if unsure or ask GP to consider referring Satge I / II refer if: genetic renal disorder nephrotic haematoproteinuria

9 Outline Acute Kidney Injury Chronic Kidney Disease End Stage Kidney Disease (CKD V) Renal Transplantation

10 ESKD Renal Replacement Therapy Haemodialysis Peritoneal Dialysis Renal Transplantation

11 CVS mortality in ESKD Levey et al AJKD 1998

12 Dialysis survival Trade off of higher proportion of time spent in hospital RR acute admission = 1.6 (p<0.05) Hussain J A et al. Palliat Med 2013;27:

13 Dialysis in the elderly Hussain J A et al. Palliat Med 2013;27:

14 Outline Acute Kidney Injury Chronic Kidney Disease End Stage Kidney Disease (CKD V) Renal Transplantation

15 CVS mortality in ESKD Renal Tx Levey et al AJKD 1998

16 Pre-emptive Renal Transplantation p<0.009 Kevin et al N Engl J Med 2001; 344:

17 Renal Transplantation Donor types changing Increasing Donations after Cardiac Death Live Donations Increasing altruistic donation Paired exchange system ABOi and HLAi transplantation

18 Renal transplant activity and type Slide courtesy of Niaz Ahmad

19 Type of Transplant Renal transplants in Leeds: Paradigm shift % 80% LD DCD DBD 60% 40% 20% 0% Year of Transplant Slide courtesy Dr CG Newstead and Mr N. Ahmad

20 Live donors paired exchange system A X B C X D

21 Renal transplant immunosuppression Novel agents Alemtuzumab Anti CD52 - Cytolytic to T cells, sustained lymphopenia for 7-9 months Steroid avoidance regimes Bortozemib Plasma cell inhibitor - treatment for antibody mediated rejection Betalacept Maintenance immunosuppressant dogged by increased CNS lymphoma Eculizumab Complement inhibitor ahus, PNH, potential future use in transplantation

22 Outline Acute Kidney Injury Chronic Kidney Disease End Stage Kidney Disease (CKD V) Renal Transplantation

23 Renal

24 Questions? Useful links UK Renal Association British Transplant Society

25 Renal Medicine An Update Dr. Matthew Welberry Smith Consultant Nephrologist St. James University Hospital, Leeds

26 ABOi and HLAi transplantation

27 ABOi and HLAi transplantation: Mechanisms of rejection - AMR B Plasma cell Antibodies (DSA) Complement mediated target tissue destruction

28 Treating AMR B Plasma cell Antibodies (DSA) Complement mediated target tissue destruction e.g. eculizumab Rituximab Bortezomib Immunoadsorption Plasmapheresis Fehr & Gaspert Transpl Int Jun;25(6):623-32

29 Specific Renal Diseases - Membranous Commonest cause of nephrotic syndrome in non-diabetic adults (~30% of renal biopsies done for nephrosis) Primary and secondary forms Aetiology of primary form? unclear for 50 years+ 80% have IgG4 auto-antibodies to PLA2R Levels correlate with severity Levels may predict response to treatment May predict recurrence post transplantation

30 Specific Renal Diseases - APKD Adult Polycystic Kidney Disease Commonest genetic renal disorder Commonest form autosomal dominant with variable penetrance Arresting cyst growth and GFR decline? Tolvaptan (maybe) Octreotide (maybe) mtor inhibitors (no)