La gestione del rischio nelle nefropatie Roberto Pontremoli

La gestione del rischio … nelle nefropatie Roberto Pontremoli Università degli Studi e IRCCS Ospedale Policlinico San Martino, Genova

Cases and observations, illustrative of renal disease accompanied with the secretion of albuminous urine. Guy's Hospital Reports, 1836, 1: 338379. Richard Bright

“… the obvious structural changes in the heart [in patients with shrunken kidneys] have consisted chiefly of hypertrophy with or without valve disease; and, what is most striking, out of 52 cases of hypertrophy, no valvular disease whatsoever could be detected in 34”

La gestione del rischio … nelle nefropatie • Le dimensioni del problema • Meccanismi patogenetici • Il rene come sensore di rischio CV

CHARES Invecchiamento della popolazione 61 milioni 59. 5 milioni >65 anni 22% 32% >80 anni 7% 10% 2012 2056

LANCET 2015; 385: 117– 171 1990 LANCET 2040 2013 5 CKD 19 CKD 36 CKD 2018; 392: 2052– 2090

JASN 2013, 2167– 2179, 2017 1. 2 million CV deaths attributed to GFR, In 2009 in England 7000 strokes and 12, 000 myocardial infarctions attributable to CKD were registered The resulting cost was £ 176 million Kerr M et al. NDT 2012 GFR responsible for 18. 7 million CV Disability Adjusted Life Years (DALYS) per year

La gestione del rischio … nelle nefropatie • Le dimensioni del problema • Meccanismi patogenetici • Il rene come sensore di rischio CV

Pathogenesis of cardiorenal damage in CKD Traditional and kidney-related RFs Disorder of Nolan, C. R. J Am Soc Nephrol 2005; 16: S 120 -S 127

The Cardiovascular Continuum: Treatment Benefits and Residual Risk at Increasing CV Risk LIFE 10% 10 5% 30% ONTARGETTRANSCEND ALTITUDE of the CVR Along the timecourse 40% 20% continuum the specific weight of different risk factors as well as the relative incidence of a given type 30 20 of event (and its influence on 22. 5 global outcome) vary 37. 5 Risk-benefit ratio varies for 15 different pharmacologic 50% interventions (LLT, RAAS-I, BPLT, Treatment Benefits 50 Glucose lowering) Anti. PLT, -25% CV risk 7. 5 CV risk % in 10 years Modificata da Zanchetti et al. Nat Rev Cardiol 2010; 7: 66 -7. Death

AURORA n=243 n=226 60 Placebo 50 40 Atorvastatin 30 20 Hazard ratio, 0. 92 95% CI 0. 77 -1. 10 P=0. 37 10 0 0 1 2 3 4 5 Cumulative Incidence of the Primary End Point (%) Cumulative incidence of the primary composite end point (%) 4 D Placebo 40 35 30 Rosuvastatin 25 20 15 Hazard ratio, 0. 96 95% CI 0. 84 -1. 11 P=0. 59 10 5 0 0 6 Year No. at Risk Placebo Atorvastatin 636 619 532 515 Annual mortality rate 383 378 252 n=408 n=396 1 2 3 4 5 Years since randomization 136 12% 51 58 19 29 No. at Risk Placebo Rosuvastatin 1384 1390 1163 1152 962 13. 7% 809 826 534 551 153 148

SHARP: Major Atherosclerotic Events Proportion suffering event (%) Placebo Simv/Eze 25 Risk ratio 0. 83 (0. 74 -0. 94) Logrank 2 P=0. 0021 20 15 10 5 0 0 1 2 3 4 5 Years of follow-up The effects of lowering LDL cholesterol with simvastatin plus ezetimibe in patients with chronic kidney disease (Study of Heart and R a randomised placebo-controlled trial. Lancet 2011; 377: 2181 -92.

Causes of death among dialysis patients (2005 -2006) usrds. org

Causes of death among dialysis patients (2005 -2006) Cardiovascular composites 120 100 80 60 40 20 0 usrds. org Arythmia, electric Atherosclerotic

La gestione del rischio … nelle nefropatie • Le dimensioni del problema • Meccanismi patogenetici • Il rene come sensore di rischio CV

16 105, 872 participants from 14 studies with urine ACR 1, 128, 310 participants from 7 studies with urine protein dipstick

Cardiovascular events Cardiovascular death ADVANCE J Am Soc Nephrol 2009

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La gestione del rischio … nelle nefropatie • CKD is a worldwide problem of epidemic dimensions • CKD entails a marked increase in CVD and related costs • Biomarkers of renal function may serve as tool for CVR assessment in GP