IL DANNO RENALE ACUTO NEL PAZIENTE CON NEFROPATIA CRONICA

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1 IL DANNO RENALE ACUTO: ATTUALITA E PROSPETTIVE Cuneo 11 novembre 2010 IL DANNO RENALE ACUTO NEL PAZIENTE CON NEFROPATIA CRONICA Angelo Perego Nefrologia e Dialisi Ospedale Vittorio Emanuele III Monselice (PD) ULSS 17 Veneto Gruppo di Studio S.I.N. Trattamenti Depurativi in Area Critica

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3 Acute Kidney Injury Acute Kidney Injury is increasingly particularly in elderly people Age related incidence rose from 17 per million per year in adults under 50 to 949 per million per year in the age group. Recent prospective studies report an overall incidence of acute kidney injury of almost 500 per million per year and an incidence of A.K.I. needing dialysis of more than 200 per million per year. This is double the UK incidence of end stage renal disease needing dialysis and places high demands on healthcare resources.

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8 The risk of acute renal failure in patients with chronic kidney disease C Y Hsu, J D Ordoñez, G M Chertow, D Fan, C E McCulloch and A S Go Kidney Int 74: , 2008 Compared with patients with an estimated GFR of 60 ml/min or greater, the relative risk of dialysis-requiring AKI in those with an estimated GFR of ml/min is about 20.

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11 Clin J Am Soc Nephrol 5: , 2010

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14 Fibrosis and Nephron Loss the Renal Response to Injury CHRONIC RENAL FAILURE Aging, Diabetes, Hypertension, Atherosclerosis Consequences Functional Decrease in GFR Proteinuria Structural Glomular basement membrane changes Expanded mesangial matrix Glomerulosclerosis Tubulo-interstitial fibrosis Nephron loss

15 Nephron loss means reduction in the kidney functional reserve and sometimes GFR lowering

16 Riserva Funzionale Renale Nelle fasi precoci di molte nefropatie il VFG è mantenuto a livelli normali o lievemente ridotti- grazie a fenomeni di iperattività (iperfiltrazione) nei nefroni superstiti L Iperfiltrazione riduce ed azzera la Riserva Funzionale Renale e produce un danno renale progressivo

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19 Riserva funzionale renale VFG (dopo stimolo) VFG (basale)

20 The impact of ageing on Kidney Renal Mass: Decreased Renal Functional Reserve: Decreased Renal Filtration Fraction: Increased Responsiveness to sodium balance: Impaired Ability to excrete water load: Delayed Maximal urinary concentrating ability: Decreased Rise in osmotic sensitivity of ADH release: Impaired Free Water Clearance + Multiple drug therapy +A lifetime of accumulated disease and comorbidities

21 Copyright 2009 American Physiological Society Pechman, K. R. et al. 2009;

22 Fig. 1. Relationship between renal perfusion pressure and urine flow rate (top) or sodium excretion rate (bottom) in anesthetized sham control or postischemia-reperfusion (I/R) rats with neural and hormonal influences on the kidney controlled Copyright 2009 American Physiological Society Pechman, K. R. et al.2009;

23 Copyright 2009 American Physiological Society Pechman, K. R. et al. Am J Physiol Regul Integr Comp Physiol 297: R1358-R ; doi: /ajpregu

24 Fig. 6. Relationship between sodium intake by intravenous infusion of isotonic saline and mean arterial blood pressure (top), creatinine clearance rate (middle), and albumin excretion rate (bottom) in sham or I/R rats 35 days after surgery Pechman, K. R. et al. Am J Physiol Regul Integr Comp Physiol 297: R1358-R ; doi: /ajpregu Copyright 2009 American Physiological Society

25 Fig. 1. Schematic diagram to illustrate how tubules regenerating after acute injury may fail to differentiate and exhibit profibrotic paracrine activity before they become atrophic Venkatachalam, M. A. et al. Am J Physiol Renal Physiol 298: F1078-F ; doi: /ajprenal Copyright 2010 American Physiological Society

26 Fig. 2. Left: hypothetical scheme for relationships between signaling activity in regenerating tubule cells and downstream signaling events in the interstitium: inflammation, fibroblast proliferation, and capillary rarefaction Venkatachalam, M. A. et al. Am J Physiol Renal Physiol 298: F1078-F ; doi: /ajprenal Copyright 2010 American Physiological Society

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