1. Dyslipidemia after Kidney Transplant
Fasika M. Tedla, MD, MSc
Medical Director of Transplantation
Assistant Professor of Medicine
SUNY Downstate Medical Center

2. Outline Background Basics of lipoprotein biology Pathophysiology
Outcomes of treatment
Non-dialysis CKD
Dialysis
Transplant
Future directions
Summary

3. Prevalence of Cardiovascular Disease in CKD
USRDS 2016 ADR

4. Cardiovascular Disease in CKD
USRDS 2016 ADR 4

5. Background 1850’s:- “…plates of cholesterine” – Virchow 1901 :-
Nerking suggested lipids exist in plasma bound to protein
1950’s:-
Biochemical pathway, lipoprotein quantitation
Framingham and other association studies
J-curve
1980’s:
Cholesterol reduction with sequesterants
?reduction in cardiovascular mortality
1990’s - present
HMG-CoA reductase inhibitors (statins) in tertiary prevention
Statins in secondary prevention
Extension to subpopulations, lower targets

6. Lipoprotein Biology

7. Lipoprotein Biology

8. Lipoprotein Biology

9. The “HDL” Hypothesis
Barter et al. N Engl J Med. 2007;357(21):

10. Lipid Profile in CKD Hemodialysis patients Pre-dialysis CKD
Triglycerides (H)
Total Cholesterol (L/N)
LDL (V, but usually L/N)
HDL (L)
Pre-dialysis CKD
Similar to HD (if no proteinuria)
Progression to HD pattern with declining GFR
de Boer et al. Clin J Am Soc Nephrol. 2008;3(1):

11. Mechanism of Dyslipidemia in CKD

12. Lipoprotein (a) [Lp(a)]
Modified LDL
Higher affinity to macrophages
Homologous to plasminogen
Impairs fibrinolysis
Variable size
Levels
determined by genetics
Stable over time
Associated with CAD
Levels of larger moieties increase in CKD

13. HDL Changes in CKD Vaziri N. Kidney Int. 2009;76(4):437-44.
Holzer M. J Am Soc Nephrol. 2015;26(9):
Bakillah A. Mediators Inflamm. 2015;2015:

14. Changes After Transplant
Complex factors
Proteinuria
Graft dysfunction
New-onset or worsening diabetes
Immunosuppressants
Sirolimus > Cyclosporine > tacrolimus
Mechanism unknown
Impaired activity of lipases
Overall
Lipid profile similar to non-CKD patients
Lp(a) levels decline
HDL function may improve

15. Effect of Statin Therapy: non-dialysis CKD
Study of Heart and Renal Protection (SHARP)
9,200 patients, ~ 1/3 on HD
Simvastatin + ezetimibe vs placebo
10 outcome: major atherosclerotic event (coronary event or death, ischemic stroke or revascularization)
11.3% vs 13.4%
Similar side effects
Subgroup analysis
No difference in MI or coronary death
No difference in HD patients (but so if adjusted for reduction in LDL-C)
Baigent C et al. Lancet. 2011;377(9784):2181.

16. Effect of Statin Therapy: non-dialysis CKD
Outcome
No. Stud.
No. Subj.
RR/MD
All cause M 21
18762
0.81
CV mort. 20
18746
0.8
CV events 5
19363
0.75
Proteinuria (g/24h) 6
311
-0.73
CrCl 11
548 NS
LFTs 10
2282 CK
2299
Navaneethan et al. Cochrane Database Syst Rev. 2009;(2):CD

17. Effect of Statin Therapy: Hemodialysis
Wanner et al. N Engl J Med 2005;353(3):

18. Effect of Statin Therapy: Hemodialysis
Fellstrom et al. N Engl J Med. 2009;360(14):

19. Effect of Statin Therapy: Renal Transplant Recipients
Holdaas et al. Lancet Jun 14;361(9374):

20. Effect of Statin Therapy: Renal Transplant Recipients
Holdaas et al. Am J Transplant. 2005;5(12):

21. Treatment Guidelines KDIGO: NKF/K-DOQI/AST: not recently updated
Treatment for
Non-dialysis CKD
≥ 50
18-59 with known stroke or CAD or 10-yr risk >10%
Dialysis
Continue for dialysis patients already on treatment
Do not start
NKF/K-DOQI/AST: not recently updated
symptomatic coronary disease or stroke after HD start?
Non-obstructive CAD or carotid disease identified on testing?
KDIGO 2013

22. Future Directions Reason for lack of effect in HD:
?agent, duration, subpopulation, target
?CV death due to arrhythmia/CHF
What is the target for lipid lowering in CKD?
β-lipoproteins?
metabolic pathways other than cholesterol
e.g. MTP, HDL pathway, PPAR-α agonists
Effect of treatment in modern era?
Newer ISx
Longer dialysis vintage

23. Summary
Lipoprotein, not simply cholesterol level, associated with atherosclerosis
Both quantitative and qualitative lipoprotein abnormalities
Treatment of Dyslipidemia
of benefit in non-dialysis CKD
Probably of benefit to renal transplant recipients
No evidence for benefit in hemodialysis patients
Statins are safe in CKD or after transplant