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Effect of Allopurinol on CKD and CVD
- 1. Department of Medicine Division of Nephrology Journal Club Sridhar Reddy Allam, MD, MPH Nephrology Fellow Mount Sinai School of Medicine July 14, 2010
- 2. Clin J Am Soc Nephrol. June, 2010
- 3. BACKGROUND
- 6. Dr. Alexander Gutman and Dr.Tsai-Fan Yu
- 10. Adverse outcomes with Hyperuricemia
- 11. D. Feig, D. Kang and R. Johnson 2008:359;1811-21 Adverse effects of Hyperuricemia
- 12. Hyperuricemia and renal outcomes Authors Methods Outcome Reference Iseki et al Population cohort of 48177 individuals HR for ESRD is 2.0 in men, 5.7 in women AJKD 2004 Lee et al 1952 subjects with pre-hypertension Strong association with microalbuminuria Hypertension 2006 Madero et al 840 patients from MDRD study HR for all cause mortality 1.6, CV mortality 1.5, ESRD 1.2 AJKD 2009 Chonchon et al 5808 patients in Cardiovascular Health Study cohort Association with higher prevalence and progression of CKD AJKD 2007 Akalin & Winston 307 renal transplant recipients at MSSM from 2001-2004 Strong association with new CV events and development of CAN Transplantation 2008
- 13. J-shaped mortality relationship for uric acid in patients with CKD5 Suliman et al, AJKD 2006: 48;761-771
- 16. D. Feig, D. Kang and R. Johnson 2008:359;1811-21 Risk of hypertension with Hyperuricemia
- 17. Kang, D.-H. et al. J Am Soc Nephrol 2002;13:2888-2897 Morphology of preglomerular vessels in RK and RK+OA rats RK RK+OA RK+OA PAS SMA+PCNA
- 18. Mazzali, M. et al. Hypertension 2001;38:1101-1106 Reduction of uric acid levels was associated with BP control and protection of interstitial injury OPN Collagen
- 19. D. Feig, D. Kang and R. Johnson 2008:359;1811-21 Proposed mechanism of uric acid mediated adverse effects
- 20. Effect of treatment of Hyperuricemia Authors Methods Outcome Reference Siu et al RCT of 54 patients with CKD: 12 months of Allopurinol Stable renal function in 84% in AP group vs. 54% in control group AJKD 2006 Kanbay et al 48 patients with GFR > 60 given 3 months of Allopurinol Improvement in BP and GFR Int Urol Nephrol 2007 Talaat et al Allopurinol withdrawn in 50 patients with CKD stages 3 and 4 Worsening of GFR and HTN in patients not on RAAS blockers Am J Nephorl 2007 Fieg et al RCT of Allopurinol in 30 adolescents with newly diagnosed HTN Reduction of BP JAMA 2008
- 21. Feig, D. I. et al. JAMA 2008;300:924-932 Blood Pressure Response of Adolescents to Allopurinol and Placebo
- 22. Serum creatinine trend over 12 months in patients treated with Allopurinol vs. control (n=25) Siu et al, AJKD 2006: 47(1); 51-59
- 23. Clin J Am Soc Nephrol. June, 2010
- 24. Hypothesis Allopurinol attenuates progression of CKD and lowers cardiovascular risk
- 32. RESULTS
- 35. No effect of Allopurinol on Blood Pressure control
- 36. Allopurinol attenuated GFR decline
- 37. GFR change in Allopurinol group vs. control group Cox regression analysis (adjusting for age, gender, diabetes, RAAS blockade, CRP, CKD etiology and albuminuria) revealed statistically significant benefit with Allopurinol
- 38. Allopurinol decreased the levels of inflammatory markers
- 39. Allopurinol group had less cardiovascular events
- 40. Allopurinol treatment lowered the risk of cardiovascular events by 71% Cox regression analysis confirmed independent benefit of Allopurinol treatment on cardiovascular risk
- 45. Thank You….
Notes de l'éditeur
- Morphology of preglomerular vessels in the RK and RK+OA rats. Compared with RK rats (A, x400, PAS; D, x400, PCNA+ -SMA double-staining), there was marked wall thickening with smooth muscle cell (SMC) proliferation in RK+OA rats (B, x400, PAS; E, x400, PCNA+ -SMA double-staining). Occasional arteries in RK+OA rats showed an increase in SMC number, migration of SMC into intima consistent with an obliterative arteriopathy (C, x400, PAS). Perivascular adventitial fibrosis was also prominent in RK+OA rats (F, x400, Collagen III immunostaining).
- Reduction of uric acid levels was associated with BP control and protection of interstitial injury (experiment IV). Rats were placed on LS/OA diet (OA 2%) for 7 weeks and then matched on the basis of uric acid level and BP into 3 groups: (1) OA 2%, (2) withdrawal of OA but continuation of the LS diet (OA withdrawal), and (3) the addition of allopurinol (150 mg/L drinking water) with continuation of the OA 2% diet (allopurinol). Panel A shows the BP, and panel B shows the uric acid levels. * P <0.05 vs other groups. Control of uric acid and BP levels was associated with a reduction in the tubulointerstitial injury index, as shown by OPN (magnification, x200; C through E) and type III collagen (magnification, x100; F through H) immunostaining. Panels C and F show kidneys after OA (2%) was continued for 11 weeks, panels D and G show kidneys after OA withdrawal, and panels E and H show kidneys from OA-treated rats that received allopurinol.