2. Biopsias de protocolo:utilidad clínica RSC & NCT Diagnóstico precoz Valor predictivo independiente Variable de eficacia en ensayos clínicos

3. Estructura Mediadores de lesión

4. T Renal adaptation after transplantation he kidney and the host

5. Glomerular number (Ng) Disector /fraccinator (n=56) 0.23-1.82 x 10 6 Hughson M et al Kidney Int 2003; 63: 2113

6. Ng and Vg in humans Ng/Vg/BSA Hoy WE et al, Kidney Int Suppl 2003; 83, S31

7. Number of Glomeruli per Kidney (Panel A) and Mean Glomerular Volume (Panel B) in 10 Patients with Hypertension and 10 Matched Normotensive Controls Nephron number in patients with primary hypertension Number of Glomeruli per Kidney (Panel A) and Mean Glomerular Volume (Panel B) in 10 Patients with Hypertension and 10 Matched Normotensive Controls Keller, G. et al. N Engl J Med 2003;348:101-108

8. Ng Vg T Renal adaptation after transplantation he kidney and the host Renal adaptation Alloimmunity Nephrotoxicity Renal quality IS

9. Baseline glomerular size as a predictor SCr glomerular MPA, n=96, follow up 7.5 2.5 Abdi R et al, Transplantation 1998; 66: 329 Timer 2 ________________ 6m0.23 1y0.42 2y0.27 3y0.34 4y0.35 ________________

10. Donor Vg and CrCl June 2000-Dec 2001, N = 77 ( 10 glom, 1 art) Lopes JA et al. Kidney Int 2005; 67: 1595

11. Estimating Ng in vivo

12. Integration of macro and microscopic quantitative renal evaluation Radiology Histology Morfometry New parameters

13. Ng in vivo V cortex MRI V vglom/cortex Vg Biopsy Fulladosa X et al J Am Soc Nephrol 2003 ; 14: 2662

14. Vren and Vcortex by means of a MRI

15. Volumen renal Vren Volumen cortical Vcort

16. V glom/cortex y Vg Fulladosa X et al J Am Soc Nephrol 2003

17. Estimación del número de V cortex * V vglom/cortex Ng =__________________ Vg

18. Characteristics of patients SCr < 200 mmol/l and proteinuria < 1g/24h 4m protocol biopsy (n=39) Mean SD ______________________________________ N39 Donor age38 18 Donor sex (male / female)26 / 13 Recipient age46 14 Recipient sex (male / female)24 / 15 Recipient BSA a (sqm)1.74 0.19 Cold ischemia time (hours)20 5 Delayed graft function (no / yes)37 / 2 Serum Creatinine ( mol/l)123 30 Proteinuria g/day0.38 0.47 ______________________________________ Fulladosa X et al J Am Soc Nephrol 2003; 14: 2662

19. Donor age and Vg & Ng

20. Relationship between Ng and GFR Fulladosa X et al J Am Soc Nephrol 2003; 51: 310

21. Vg is a subordinate measure of Ng Ng is a major determinant of FG 2GFR = 9 Ng

22. ¿Cómo se adaptan los glomérulos post TR?

23. Glomerular enlargement after transplantation (n=41) Donor biopsy Recipient biopsy Vg 04 Alperovich G et al, AJT 2004; 4 : 650

24. Vg after transplantation Vg Donor BiopsyRecipient Biopsyp _______________________________________________ Ah0.15 0.420.29 0.56NS cg0.10 0.300.15 0.36NS ci0.19 0.450.49 0.640.0006 ct0.15 0.420.49 0.670.0002 cv0.02 0.160.19 0.600.087 Vg4.1 1.45.1 2.40.021 _______________________________________________ Alperovich G et al, AJT 2004; 4 : 650

25. De que depende el crecimiento glomerular postrasplante?

26. Donor Vg and Vg -7 -5 -3 1 3 5 7 123456789 VgR - VgD x10 6 3 VgDx10 6 3 R=0.3, p=0.04

27. Glomerular enlargement and CAN n=27 n=14 p=0.017

28. Vg & CrCl at 4m CrCl ml/min Vg (x10 6 3 ) Alperovich G et al, AJT 2004; 4 : 650 R=0.38, p=0.01

29. Glomerular enlargement is a necessary condition to achieve an adequate renal function

30. Glom size and FGS in renal allografts m 18101377 * Bathena. JASN 1993; 4: 1316

31. Epidemiological paradox

32. Vg FG GS ¿GS?

33. Vg, GFR and graft survival n=144 patients, protocol biopsy at 4m Donor age (years)37 16(12 – 76) Donor gender (male/female)101 / 43 Patient age (years)47 13(15 – 72) Patient gender (male/female)95 / 49 Panel reactive antibodies (%)7 18(0 – 100) DR mismatches0.6 0.6(0 – 2) Cold ischemia time (hours)22 5(7 – 38) Delayed graft function (no/yes)121 / 23 Acute rejection (no/yes)114 / 30 Time of protocol biopsy (days)125 52(25 – 261) Serum creatinine ( mol/l)140 44(72– 298) Proteinuria (g/day)0.34 0.28(0.03 – 1.00) Azevedo F et al AJT in press

34. Vg n=144 patients, protocol biopsy at 4m Donor ager=0.23 DGFp=0.01 BMIr=0.17 CsAr=-0.18 CrClr=0.17

35. Vg and graft survival Best cut-off of Vg 4.0 4.5 5.0 5.5 6.0 (x10 6 3 ) RR 2.4, CI 1.03-5.6

36. CrCl and graft survival Best cut-off of CrCl 50 55 60 65 (ml/min) RR 3.3, CI 1.04-11.9

37. Vg, CrCl and Graft Survival n=144 patients protocol biopsy at 4m Multivariate analysis adjusting for donor age, acute rejection, CAN RR IC ___________________________ Vg >5 x 10 6 3 3.31.4-8.0 CrCl <60 ml/min/1.73m2 4.91.4-17.0 ___________________________

38. Vg small CrCl highn=24(17%) Vg small CrCl lown=60(42%) Vg large CrCl highn=20(20%) Vg large CrCl lown=31(21%)

39. Vg, CrCl, GS Vg > 5 & GFR > 60 GS 73% Vg 60GS 95% Vg > 5 & GFR < 60GS 45% Vg < 5 & GFR < 60GS 78% Time (months) 0,2,4,6,8 1 0255075100125150175200

40. Conclusion Vg a surrogate of nephron number an independent predictor of graft survival

41. Acknoledgements Francesc Moreso Xavier Fulladosa Gabriela Alperovich Fabio Azevedo José Antonio Lopes Meritxell Ibernon Montserrat Gomà Marta Carrera Miguel Hueso Josep Maria Cruzado Salvador Gil-Vernet Josep Maria Grinyó