1 / 40

Biopsias de protocolo:utilidad clínica

Biopsias de protocolo:utilidad clínica. RSC & NCT. Diagnóstico precoz Valor predictivo independiente Variable de eficacia en ensayos clínicos. Estructura. Mediadores de lesión. T Renal adaptation after transplantation he kidney and the host.

juan
Download Presentation

Biopsias de protocolo:utilidad clínica

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

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

  2. Estructura Mediadores de lesión

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

  4. Glomerular number (Ng)Disector /fraccinator (n=56) 0.23-1.82 x 106 Hughson M et al Kidney Int 2003; 63: 2113

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

  6. 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 hypertensionNumber 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

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

  8. Baseline glomerular size as a predictor SCrglomerular MPA , n=96, follow up 7.52.5 Time r2 ________________ 6m 0.23 1y 0.42 2y 0.27 3y 0.34 4y 0.35 ________________ Abdi R et al, Transplantation 1998; 66: 329

  9. CrCl (mL/min) 140 R=0.30 P=0.010 120 100 80 60 40 20 0 0 2 4 6 8 10 12 14 Vg (um3 x 106) Donor Vg and CrClJune 2000-Dec 2001, N = 77 (10 glom, 1 art) Lopes JA et al. Kidney Int 2005; 67:1595

  10. Estimating Ng in vivo

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

  12. Ng in vivo Vcortex MRI Vvglom/cortex Vg Biopsy Fulladosa X et al J Am Soc Nephrol 2003 ; 14: 2662

  13. Vren and Vcortex by means of a MRI

  14. Volumen renal VrenVolumen cortical Vcort

  15. Vglom/cortexy Vg Fulladosa X et al J Am Soc Nephrol 2003

  16. Estimación del número de Vcortex * Vvglom/cortexNg = __________________ Vg

  17. Characteristics of patientsSCr < 200 mmol/l and proteinuria < 1g/24h4m protocol biopsy (n=39) Mean  SD ______________________________________ N 39 Donor age 38 18 Donor sex (male / female) 26 / 13 Recipient age 46 14 Recipient sex (male / female) 24 / 15 Recipient BSAa (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/day 0.38  0.47 ______________________________________ Fulladosa X et al J Am Soc Nephrol 2003; 14: 2662

  18. Donor age and Vg & Ng

  19. 120 100 80 GFR (ml/min) 60 40 20 0 0 0.4 0.8 1.2 1.6 6 Ng-W&G (x 106) Relationship between Ng and GFR Fulladosa X et al J Am Soc Nephrol 2003; 51: 310

  20. Vg is a subordinate measure of NgNg is a major determinant of FG2GFR = 9 Ng

  21. ¿Cómo se adaptan los glomérulos post TR?

  22. Glomerular enlargement after transplantation(n=41) Vg Recipient biopsy Donor biopsy 0 4 Alperovich G et al, AJT 2004; 4 : 650

  23. Vg after transplantationVg Donor Biopsy Recipient Biopsy p _______________________________________________ Ah 0.150.42 0.290.56 NS cg 0.100.30 0.15 0.36 NS ci 0.190.45 0.49 0.64 0.0006 ct 0.15 0.42 0.49  0.67 0.0002 cv 0.02 0.16 0.19 0.60 0.087 Vg 4.1 1.4 5.1 2.4 0.021 _______________________________________________ Alperovich G et al, AJT 2004; 4 : 650

  24. De que depende el crecimiento glomerular postrasplante?

  25. Donor Vg and dVg VgR - VgD x106m3 7 5 3 1 -1 -3 -5 R=0.3, p=0.04 VgDx106m3 -7 1 2 3 4 5 6 7 8 9

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

  27. Vg & CrCl at 4m CrCl ml/min R=0.38, p=0.01 Vg (x1063) Alperovich G et al, AJT 2004; 4 : 650

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

  29. mm * 18 10 13 7 7 Glom size and FGS in renal allografts Bathena. JASN 1993; 4: 1316

  30. Epidemiological paradox

  31. FG GS ¿GS? GS GS  Vg

  32. Vg, GFR and graft survivaln=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 mismatches 0.6  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

  33. Vgn=144 patients, protocol biopsy at 4m Donor age r=0.23 DGF p=0.01 BMI r=0.17 CsA r=-0.18 CrCl r=0.17

  34. Vg and graft survivalBest cut-off of Vg 4.0 4.5 5.0 5.5 6.0 (x1063) RR 2.4, CI 1.03-5.6

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

  36. Vg, CrCl and Graft Survivaln=144 patients protocol biopsy at 4mMultivariate analysisadjusting for donor age, acute rejection, CAN RR IC ___________________________ Vg >5 x 1063 3.3 1.4-8.0 CrCl <60ml/min/1.73m2 4.9 1.4-17.0 ___________________________

  37. Vg small CrCl high n=24 (17%) Vg small CrCl low n=60 (42%) Vg large CrCl high n=20 (20%) Vg large CrCl low n=31 (21%)

  38. Vg < 5 & GFR > 60 GS 95% Vg < 5 & GFR < 60 GS 78% Vg > 5 & GFR > 60 GS 73% Vg > 5 & GFR < 60 GS 45% Vg, CrCl, GS 1 ,8 ,6 ,4 ,2 0 Time (months) 0 25 50 75 100 125 150 175 200

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

  40. 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

More Related