Prognosis in CKD Can we do anything about it? Rodney D Gilbert

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1 Prognosis in CKD Can we do anything about it? Rodney D Gilbert

2 A diagnosis of end stage renal failure implies what degree of loss of life expectancy? A. 10% B. 20% C. 30% D. 40% E. 50% F. 60% 38% 22% 16% 14% 5% 5% 10% 20% 30% 40% 50% 60%

3 Which of the following is true for those with CKD?

4 Cola drinks have many health benefits A. True B. False 87% 13% True False

5 A diet rich in meat is beneficial because of the iron content A. True B. False 76% 24% True False

6 CKD patients: the most we can achieve is get them ready for transplant by CKD stage 5 A. True B. False 86% 14% True False

7 Exercise has a beneficial effect in slowing the progression of CKD A. True B. False 73% 27% True False

8 Life expectancy with CKD Study in Alberta, Canada: No change in life expectancy with egfr >60 Progressive decline in life expectancy as egfr declines

9 Life expectancy aged 30 Estimated GFR Gende r > Male Female

10 Figure 4.5. Unadjusted KM survival in paediatric patients <16 years old starting RRT between 2000 and 2013, by age at start UK Renal Registry 18th Annual Report

11 UK Population Survival

12 CKD is bad for you! Hazard ratio for death compared with functioning graph 6.3 But can we do anything about it?

13 Can we prevent CKD? A. Yes B. No C. Maybe 53% 26% 21% Yes No Maybe

14 Can we slow down progression of CKD? A. Yes B. No C. Maybe 95% 0% 5% Yes No Maybe

15 Can we prevent CKD? Figure 4.3. Primary renal disease percentage in incident and prevalent paediatric patients in 2014 for whom a causative diagnosis was reported

16 Preventable CKD Diabetic nephropathy: 16% of ESRD in the UK Type 2 diabetes almost entirely preventable

17 How can we slow the rate of Obesity Hypertenision Proteinuria Vitamin D Acidosis Phosphate Anaemia Dietary fibre Exercise progression?

18 Obesity Risk factor for hypertension, hyperinsulinism and diabetes Strong dose-response relationship between obesity and CKD Paediatric nephrology patients had consistently higher BMI than general population over 2 decades in Canada Transplants from obese donors have lower GFR than from lean patients

19 Hypertension Hypertension is an indepenent risk factor for progression of CKD Control of BP slows progression RAAS inhibitors first line BP should be below 75 th centile, not just normal range (if possible) HOTKID study currently examining effect of tighter BP control (<40 th vs <75 th centile) on cardiovascular outcome

20 Proteinuria Proteinuria is an independent predictor of renal progression Pharmacological treatment improves renal outcomes BP control improves proteinuria RAAS inhibitors Vitamin D supplements

21 Vitamin D Not just about bones! Transcription factor: 3% of genome regulated by vit D; 1% highly regulated Suppresses renin gene, reduces BP, reduces LVH, regulates inflammatory response, improves insulin sensitivity, reduces proteinuria

22 Acidosis Dietary acid load mainly determined by intake of animal protein High renal acid load correlates with incident CKD Acidosis causes autophagic cell death of proximal tubular cells Bicarb can slow down rate of progression of CKD

23 Phosphate High-normal phosphate associated with higher mortality even with normal renal function In CKD, increases bone disease and vascular calcification Phosphate intake tends to parallel protein intake Note: processed meats, COLA DRINKS

24 Anaemia Renal hypoxia promotes renal fibrosis Managing anaemia improves oxygen delivery Improves quality of life

25 ACE inhibitors Reduce blood pressure Reduce proteinuria Downregulate TGF-beta production Upregulate Nephrin production Enhance renal survival

26 Diet, fibre and the microbiome High dietary fibre is associated with decreased inflammation and all-cause mortality in CKD Higher intake of plant protein was associated with lower FGF23 and higher Bicarbonate levels Higher fibre intake associated with lower p- cresol, p-cresyl sulfate, indoxyl sulphate & IL-6 levels Plant phosphates have lower bio-availability

27 Diet Balanced diet Appropriate energy intake Adequate fibre (beyond infancy) Limited phosphate Limited animal protein Probably improves renal outcomes and survival

28 Exercise Higher exercise levels associated with slower decline in GFR (adults) 3 studies in adults showed improved egfr after 12 weeks of exercise (1 swimming, 1 aerobics, 1 walking and cycling) 4 week course of regular walking reduced inflammatory markers

29 A diagnosis of end stage renal failure implies what degree of loss of life expectancy? 30% A. 10% 25% B. 20% 20% C. 30% D. 40% 13% E. 50% 5% 8% F. 60% 10% 20% 30% 40% 50% 60%

30 Which of the following is true for CKD? A. Cola drinks have many health benefits B. A diet rich in meat is beneficial because of the iron content C. CKD patients: the most we can achieve is get them ready for transplant by CKD stage 5 D. Exercise has a beneficial effect in slowing the progression of CKD Cola drinks have many he... 0% A diet rich in meat is ben... 0% CKD patients: the most w... 0% Exercise has a beneficial e %

31 Conclusion CKD is VERY bad for you Many of the interventions have a direct beneficial effect on renal function and progression Aim to avoid ESKD wherever possible Transplant first, wherever possible