Biopsias de protocolo:utilidad clínica RSC & NCT Diagnóstico precoz Valor predictivo independiente...
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Transcript of Biopsias de protocolo:utilidad clínica RSC & NCT Diagnóstico precoz Valor predictivo independiente...
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
Glomerular number (Ng)Disector /fraccinator (n=56)
0.23-1.82 x 106
Hughson M et al Kidney Int 2003; 63: 2113
Ng and Vg in humans
Ng/Vg/BSA
Hoy WE et al, Kidney Int Suppl 2003; 83, S31
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
Ng
Vg
T Renal adaptation after transplantation he kidney and the host
Renal adaptation
AlloimmunityNephrotoxicity
Renal quality IS
Baseline glomerular size as a predictor SCr
glomerular MPA , n=96, follow up 7.52.5
Abdi R et al, Transplantation 1998; 66: 329
Time r2
________________6m 0.231y 0.422y 0.273y 0.344y 0.35________________
Donor Vg and CrClJune 2000-Dec 2001, N = 77 (10 glom, 1 art)
0
20
40
60
80
100
120
140
0 2 4 6 8 10 12 14
Vg (um3 x 106)
CrCl (mL/min)
R=0.30P=0.010
Lopes JA et al. Kidney Int 2005; 67: 1595
Estimating Ng in vivo
Integration of macro and microscopic quantitative renal evaluation
Radiology Histology
Morfometry
New parameters
Ng in vivo
Vcortex MRI
Vvglom/cortex Vg Biopsy
Fulladosa X et al J Am Soc Nephrol 2003 ; 14: 2662
Vren and Vcortex by means of a MRI
Volumen renal VrenVolumen cortical Vcort
Vglom/cortex y Vg
Fulladosa X et al J Am Soc Nephrol 2003
Estimación del número de
Vcortex * Vvglom/cortex Ng = __________________
Vg
Characteristics of patientsSCr < 200 mmol/l and proteinuria < 1g/24h
4m protocol biopsy (n=39)Mean SD ______________________________________ N 39 Donor age 38 18Donor sex (male / female) 26 / 13Recipient age 46 14Recipient sex (male / female) 24 / 15Recipient BSAa (sqm) 1.74 0.19Cold ischemia time (hours) 20 5 Delayed graft function (no / yes) 37 / 2Serum Creatinine (mol/l) 12330Proteinuria g/day 0.38 0.47______________________________________
Fulladosa X et al J Am Soc Nephrol 2003; 14: 2662
Donor age and Vg & Ng
Relationship between Ng and GFR
0
20
40
60
80
100
120
0 0.4 0.8 1.2 1.6
Ng-W&G (x 106)6
GFR
(m
l/m
in)
Fulladosa X et al J Am Soc Nephrol 2003; 51: 310
Vg is a subordinate measure of Ng
Ng is a major determinant of FG
2GFR = 9 Ng
¿Cómo se adaptan los glomérulos post TR?
Glomerular enlargement after transplantation
(n=41)
Donor biopsy Recipient biopsyVg
0 4
Alperovich G et al, AJT 2004; 4 : 650
Vg after transplantationVg
Donor Biopsy Recipient Biopsy p_______________________________________________Ah 0.150.42 0.290.56 NScg 0.100.30 0.15 0.36 NSci 0.190.45 0.49 0.64 0.0006ct 0.15 0.42 0.49 0.67 0.0002cv 0.02 0.16 0.19 0.60 0.087Vg 4.1 1.4 5.1 2.40.021_______________________________________________
Alperovich G et al, AJT 2004; 4 : 650
De que depende
el crecimiento glomerular
postrasplante?
Donor Vg and Vg
-7
-5
-3
-1
1
3
5
7
1 2 3 4 5 6 7 8 9
VgR - VgD x1063
VgDx1063R=0.3, p=0.04
Glomerular enlargement and CAN
- 0,5
0
0,5
1
1,5
2
No CAN CAN
Delta Vg
n=27 n=14
p=0.017
Vg & CrCl at 4mCrCl ml/min
Vg (x1063)
Alperovich G et al, AJT 2004; 4 : 650
R=0.38, p=0.01
Glomerular enlargement is a
necessary condition to achieve
an adequate renal function
Glom size and FGS in renal allografts
0
50
100
150
200
250
Donor
Bx
no FGS
<2y
FGS
<2y
no FGS
>2y
FGS
>2y
Glom diameterm
18 10 13 7 7
*
Bathena. JASN 1993; 4: 1316
Epidemiological paradox
Vg
FG GS
GS GS
¿GS?
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
Vg n=144 patients, protocol biopsy at 4m
Donor age r=0.23DGF p=0.01BMI r=0.17CsA r=-0.18
CrCl r=0.17
Vg and graft survivalBest cut-off of Vg
4.04.55.05.56.0
(x1063)
RR 2.4, CI 1.03-5.6
CrCl and graft survivalBest cut-off of CrCl
50556065
(ml/min)
RR 3.3, CI 1.04-11.9
Vg, CrCl and Graft Survivaln=144 patients protocol biopsy at 4m
Multivariate analysis
adjusting for donor age, acute rejection, CAN
RR IC___________________________Vg >5 x 1063 3.3 1.4-8.0
CrCl <60 ml/min/1.73m2 4.9 1.4-17.0___________________________
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%)
Vg, CrCl, GS
Vg > 5 & GFR > 60 GS 73%
Vg < 5 & GFR > 60 GS 95%
Vg > 5 & GFR < 60 GS 45%
Vg < 5 & GFR < 60 GS 78%
Time (months)0
,2
,4
,6
,8
1
0 25 50 75 100 125 150 175 200
Conclusion
Vga surrogate of nephron number
an independent predictor of graft survival
AcknoledgementsFrancesc MoresoXavier FulladosaGabriela AlperovichFabio AzevedoJosé Antonio LopesMeritxell IbernonMontserrat GomàMarta CarreraMiguel HuesoJosep Maria CruzadoSalvador Gil-VernetJosep Maria Grinyó