Role of the procurement biopsy in the assessment of kidneys from marginal donors

1. Role of the procurement biopsy in the assessment of kidneys from marginal donors Eva Pokorna Institute for Clinical and Experimental Medicine, Prague Czech Republic

2. Renal transplant biopsy is the gold standard for evaluation of graft dysfunction, establishment of diagnosis and for patient treatment Procurement renal biopsy or „zero hour“ biopsy is still discussed. Their diagnostic meaning is compared with the increasing of the cost and with risk of potential complications.

3. Organ shortage is basic limit of transplant medicine. One possibility for increasing number of kidneys available to transplants is to enlarge indication criteria of cadaver donor and to consider as suitable donor over 60 years and donors with diagnosis of arterial hypertension… Donor renal biopsy can play the important role inthe indication of these marginal donors

4. Cadaver kidney donors in IKEM1993-2009donor age (median)

5. Since1993we performed donor renal biopsy as the routine method 1200 donor biopsies The first it was providedprospective study of a consecutive series of 200 donors. Kidneys of these donors had transplanted to 387 recipients

6. The aim of study Identification of clinical and morphological factors affecting onset of function level of function 36-month graft survival Definition of procedure in indication of „marginal donors“

7. Method of donor biopsy wedge excision from the renal cortex after perfusion and retrieval of the kidneys punction method (biopsy gun)

8. wedge excision Safety method Large specimen (46±23 glomeruli) x Percentage of glomerulosclerosis varies depending of the cortical depth Subcortical part has more incidence of glomerulosclerosis Small caliber arterial branches

9. Punction method (biopsy gun) risk method bleeding in urinary tract small specimen (aprox. 8 glomeruli) Glomerulosclerosis only limited meaning x Large caliber arterial branches Gaber et al:glomerulosclerosis as a determinant of posttransplant function of older donor renal allografts Transplantation60:334, 1995 Kaplan et al: Age-related incidence of sclerotic glomeruli in human kidneys. AmJPathol 80:227, 1975 Pokorna et al: Proportion of glomerulosclerosis in procurement wedge renal biopsy cannot alone discriminate for acceptance of marginal donors. Transplantation 69:36, 2000

10. Schema Anatomy of vescular supply: no existence of collaterals!! any block = infarct Damage of glm has deep impact of interst. and medulla

11. Morphology of vascular nephrosclerosis

12. Status of vessels (arteries, arteriolies) has main impact on the fate of renal graft Kidney without capsulla

17. Representative sample Wedge excision – 5 mm in depth % glomerulosclerosis depends on the depth of renal cortex Subcortical part – higher incidence of GS The important role plays sample size – number of catching glomeruli Cca 25 glm 1 vessel higher calibre (artery) Lopes et al:Evalution of pre-implantation kidney biopsies: Comparison of Banff criteria to a morphometric approach. Kidney Int 2005, 67: 1595

18. One kidney x both kidneys Correlation between left and right kidneys: Glomerulosclerosis r=0.88, p<0.0001 Vascular changes r=0.93, p<0.0001 Intertitial sclerosis r=0.86, p<0.0001 Tubular changes r=0.92, p<0.0001 Sample size – more than 14 glm and exclusion of presence of cortical scar Pokorna et al: Proportion of glomerulosclerosis in procurement wedge renal biopsy cannot alone discriminate for acceptance of marginal donors. Transplantation 69:36, 2000 Lopes et al:Evalution of pre-implantation kidney biopsies: Comparison of Banff criteria to a morphometric approach.Kidney Int 2005, 67: 1595

20. Remuzzi score 1999, J AmSocNephrol 10:2591-2598 Global glmsclerosis (1,2,3, 20%, 50%, >50%) Tubular atrophy Interstitial fibrosis Vascular changes (narrowing of luminas of arteries and arteriolies)

21. Remuzzi score Remuzzi score has very disadvantageous (inapplicable for marginal donors) criteria of vascular changes(almost every time is 3) Remuzzi: 3 • cv 0, ah 2

28. 50 45 40 35 % of glomerulosclerosis 30 25 20 15 10 5 0 0 10 20 30 40 50 60 70 80 Age (years) Age and glomerulosclerosis r = 0.57 P < 0.001

29. Morphological changes Pokorna et al: Proportion of glomerulosclerosis in procurement wedge renal biopsy cannot alone discriminate for acceptance of marginal donors. Transplantation 69:36, 2000 Lopes et al:Evalution of pre-implantation kidney biopsies: Comparison of Banff criteria to a morphometric approach. Kidney Int 2005, 67: 1595

30. Glomerulosclerosis (GS)Does exist limit?

31. Glomerulosclerosis (GS)Does exist limit? Only limited data of results of graft transplants with severe glomerulosclerosis Worse survival of grafts with GSmore than 20% Gaber et al, Transplantation 1995, 60:334 Only 8 kidneys Sample - 6 glomeruli Limit for acceptance15% GS Rather et al, Surgery 1996, 119:372

32. Glomerulosclerosis (GS)Does exist limit? Donors older than 60 years and with GS more than 15% - tx both kidneys Andrés et al, Transplantation 2000, 69(10):260 x Remuzzi, Transplantation 2000, 69(10):2000 Polemic, nonconvincing results, chronic changes affect both kidneys, „wasting of organs“ Donors older than 55 years or with history of HT or DM and with GS more than 15% - tx both kidneys Jerius, J Urology 2000, 163: 423

33. Pokorna et al: Proportion of glomerulosclerosis in procurement wedge renal biopsy cannot alone discriminate for acceptance of marginal donors. Transplantation 69:36, 2000

34. 77 biopsies of cadaver donors Wedge excision Min 10 glomeruli and 1 artery Evaluated glomeruli (GS%), interstitium (ci), tubuli (ct), vessels (cv, ah)

35. Results Significant correlation between donor age and GS, interstitial fibrosis and vascular changes Morphological changes vs. DGF Vascular changes (cv) P = 0.013 Glomerulosclerosis P = 0.024 cg, ci, ct, ah n.s. Similar impact on the level of function (GFR 3 months, graft survival)

36. UNOS 3444 renal transplant with donor biopsy Evaluated only glomerulosclerosis (not noticed method of biopsy, sample size – number of glomeruli Calculated ClCr of donor (Cockcroft-Gault) correlated and %GS do not correlated with 1 year graft survival and with level of function Grafts of donors with GS more than 20% and donor CrCl more than 80 ml/min have good prognosis

37. Conclusion„Procurement“or „zero-hour“ biopsy Representativ sample size, catching structures, scare? Evaluation of all structures – not only isolated glomerulosclerosis To consider next factors donor age history renal function (admission level of SCr) macroskopy of kidneys – size, symmetry, finding of renal arteries

38. ConclusionProcurement or „zero-hour“ biopsies Crucial role to asses pre-existing donor disase Confirmation sample for recipient graft biopsy (transfer changes from donor, de-novo changes due to calcineurin inhibitors toxicity, chronic rejection, recurrence of kidney disease..) Help to classify graft pathology more precisely Limited meaningfor decision whever or not to accept a kidney donor Does not criteria for exclusion kidneys for tx

39. ConclusionMARGINAL DONORS Alocation of these kidneys? Older recipient? Risk factors of recipients retransplantation, PRA Effort of short CIT Pulsatil perfusion? Modification of immunosuppression?