Histological and clinical evaluation of marginal donor kidneys before transplantation: Which is best?

Table 1 Descriptive table of selected clinical scoring system

Score	Authors	Variables included in risk score	Score grades	Outcome
Expanded criteria donor	Port et al[58], 2002	Donor age	SCD	Relative risk of graft failure compared to SCD
		Cerebrovascular accident as cause of death	ECD	RR>1.7
		Serum creatinine> 1.5mg/dL
		History of hypertension
Deceased donor score	Nyberg et al[65], 2003	Age		5-year graft survival
		History of hypertension	A (0-9 points)	Grade A 82%
		Creatinine clearance	B (10-19 points)	Grade B 79%
		HLA mismatch	C (20-29 points)	Grade C 72%
		Cause of death	D (30-39 points)	Grade D 65%
Donor risk score (DRS)	Schold et al[67], 2005	Donor risk factors		5-year graft survival
		Race	I	Grade I 76.7%
		Age	II	Grade II 73.6%
		History of hypertension	III	Grade III 66.3%
		History of diabetes	IV	Grade IV54.8%
		Cause of death	V	Grade V 47.6%
		History of hypertension
		History of diabetes
		Cause of death
		HLA-Dr mismatch
		CMV mismatch
		Cold ischemia time
DGF nomogram	Irish et al[70], 2003	Donor risk factors	Continuous point score	Delayed graft function
		Age
		Serum creatinine
		History of hypertension
		Cause of death
		Donor after cardiac death
		Recipient risk factors
		Peak PRA
		Race
		Gender
		History of diabetes mellitus
		Previous transplant
		Pretransplant dialysis
		Pretransplant transfusions
		Combined transplantation
		HLA mismatch
		Cold ischemia time
KDRI	Rao et al[71], 2009	Donor risk factors	KDRI quintile	5-year graft survival
		Age	0.45-0.79	82%
		Race	0.80-0.96	79%
		Height	0.97-1.15	NA
		Weight	1.16-1.45	NA
		History of hypertension	>1.45	63%
		History of diabetes
		Cause of death
		Serum creatinine
		Hepatitis C
		Donation after cardiac death
		HLA-B mismatch
		HLA-DR mismatch
		Cold ischemia time
		Double or en bloc transplant
Donor-only KDRI	OPTN[72], 2014	Donor risk factors		5-year graft survival
		Age	<0.6	80%
		Race	0.61-0.79	78%
		Height	0.80-0.99	74%
		Weight	1.00-1.19	66%
		History of hypertension	1.20-1.59	59%
		History of diabetes	1.60-1.99	52%
		Cause of death	>1.99	44%
		Serum creatinine
		Hepatitis C
		Donation after cardiac death

ECD: Expanded criteria donor; KDRI: Kidney donor risk index; OPTN: The Organ Procurement and Transplantation Network; SCD: Standard criteria donor.

Table 2 Histological score according Karpinski

Histological score
Glomerular score	0 = no globally sclerosed glomeruli
	1 = < 20% global glomerulosclerosis
	2 = 20-50% global glomerulosclerosis
	3 = > 50% global glomerulosclerosis
Tubular score	0 = absent
	1 = < 20% of tubules affected
	2 = 20-50% of tubules affected
	3 = > 50% of tubules affected
Interstitial score	0 = absent
	1 = < 20% of cortical parenchyma replaced by fibrous connective tissue
	2 = 20-50% of cortical parenchyma replaced by fibrous connective tissue
	3 = > 50% of cortical parenchyma replaced by fibrous connective tissue
Vascular score	0 = absent
	1 = increased wall thickness but to a degree that is less than the diameter of the lumen
	2 = wall thickness that is equal or slightly greater than the diameter of the lumen
	3 = wall thickness that far exceeds the diameter of the lumen, with extreme narrowing

Table 3 Maryland Aggregate Pathology Index scoring system for pre-transplant kidney biopsies

	HR (95%CI)	P value	MAPI points
			Absent	Present
Arteriolar hyalinosis	3.93 (2.02-7.64)	<0.0001	0	4
PGF (any)	4.09 (1.65-10.14)	0.002	0	3
Scar (any)	2.58 (1.24-5.38)	0.01	0	3
GS > 15%	1.87 (1.17-2.99)	0.009	0	2
WLR interlobular arteries > 0.5	2.05 (1.21-3.47)	0.008	0	2

MAPI: Maryland Aggregate Pathology Index; WLR: Wall to lumen ratio; CI: Confidence interval.

Table 4 Cox Multivariate analysis showing association of Maryland Aggregate Pathology Index score and clinical parameters to risk of graft failure

	HR (95%CI)	P value
MAPI	1.21 (1.05-1.40)	0.008
Donor age	1.03 (1.00-1.07)	0.096
Cold ischemia (h)	3.66 (0.77-17.40)	0.102
Donor history of hypertension	1.62 (0.67-3.97)	0.287
Donor terminal creatinine> 1.5 mg/dL	1.34 (0.43-4.18)	0.611
CVA as cause of donor death	0.98 (0.35-2.73)	0.973

CVA: Cerebrovascular accident; MAPI: Maryland Aggregate Pathology Index.

Table 5 Studies on molecular markers measured in 0-h biopsies (up to 2011)

Ref.	Pats	f/u	Findings/timing of biopsy-technology
Hoffmann et al[28], 2002	24	1 h	IRI injury ass w increased adhesion, chemotaxis, apoptosis, monocyte recruitment/activation transcripts.Post-reperfusion/RT-PCR
Hauser et al[29],2004	36	1	Increased Communication, apoptosis, inflammation
Kainzet al[30],2004	10	1	DD kidneys distinctly different transcripts in the TI but not in the G compartment compared to LD. End of CIT/microarrays
Avihingsanon et al[31],2005	75	6	15 selected genes associated with outcomes, included DGF, REJ and 6 mofunction. Post-reperfusion/RT-PCR
Kainzet al[32],2007	31	12	Increased immunity, signal transduction, oxidative stress response associated with lower 1-year function
Park et al[33],2007	15	12	Increased inflammation and immune response at 1-year in uncomplicated grafts
Mas et al[34],2008	33	3	Increased immunity, inflammation and apoptosis genes associated with DGF. End of CIT/microarrays
Mueller et al[35],2008	87	12	Increased acute phase, complement, chemochines and reduced metabolism, transporters in DD versus LD, transcriptome identifies risk for DGF better than clinical ± histological markers. Post-reperfusion/ microarrays
Perco et al[36], 2009	82	12	Increasedimmunity/defense, communication, apoptosis in damaged kidneys, CADI score + clinic explained 14%, 3 biomarkers 28% of 1-year creatinine variability. End of CIT/ microarrays
Naesens et al[37], 2009	28	36	Complement genes differ between LD and DD and are associated with early and late function. End of CIT and post-transplant/ microarrays
Bodonyi-Kovacs et al[38], 2010	75	48	Pre-selected genes associated with 2-year graft function. Post-reperfusion/ RT-PCR
Cravedi et al[39], 2010	49	12	LDvs DD differ by inflammation, donor age and ITGB2 prognostic for 1-year function. Post-reperfusion/RT-PCR

f/u:Follow up in months; IRI:Ischemia-reperfusion injury; DD:Deceased donor; LD:Living donor; IGF:Immediate graft function; DGF:Delayed graft function; REJ:Rejection; CIT: Cold ischemia time; TI:Tubulointerstitial; G:Glomerular.

Table 6 Donor and transplant factors and corresponding hazard ratios for graft failure

	Hazard ratio	95%CI	P value
Donor parameter
Age	1.013	1.011-1.015	< 0.0001
Afro American race	1.20	1.13-1.27	< 0.0001
Serum creatinine	1.25	1.17-1.23	< 0.0001
Hypertensive	1.13	1.08-1.19	< 0.0001
Diabetic	1.14	1.04-1.24	0.0040
Cause of Death	1.09	1.04-1.14	0.0002
Height	0.96	0.94-0.97	< 0.0001
Weight	0.98	0.97-0.99	0.0003
Donation after cardiac death	1.14	1.02-1.28	0.0246
HCV positive	1.27	1.13-1.43	< 0.0001
Transplant parameter
HLA-DR mismatch	0.88	0.84-0.92	< 0.0001
Cold ischemia time	1.005	1.003-1.008	< 0.0001
En bloc transplant	0.70	0.57-0.84	0.0002
Double kidney transplant	0.86	0.75-1.00	0.0494

HLA:Human leukocyte antigen; HCV:Hepatitis C virus.

Table 7 Genes included in the study

ID	Symbol	Gene description	CADI-12 correlation	P value
3954887	CHCHD 10	Coiled-coil-helix-coiled-coil-helix domain containing 10	0.404	2.85 x 10-5
4019160	KLHL 13	Kelch-like family member 13 (Drosophila)	0.369	1.49 x 10-4
3326826	FJX1	Four jointed box 1 (Drosophila)	0.367	1.60 x 10-4
3120343	MET	Met proto-oncogene (hepatocyte growth factor receptor)	0.352	3.01 x 10-4
2864449	SERUNC5	Seine incorporator 5	0.318	0.0012
2567583	RNF149	Ring finger protein 149	0.280	0.0046
2879105	SPRY4	Sprout homolog 4 (Drosophila)	0.270	0.0062
3776504	TG1F1	TGFB-induced factor homeobox 1	0.244	0.0140
2898441	KAAG1	Kidney associated antigen 1	0.240	0.0154
3361971	ST5	Suppression of tumorigenity 5	0.232	0.0197
2459352	WNT9A	Wingless-type MMTV integration site family member 9A	0.212	0.0332
3021696	ASB15	Ankrin repeat and SOCS box-containing 15	-0.263	0.0079
3193339	RXRA	Retinoid X receptor alpha	-0.300	0.0023

CADI-12: Chronic allograft damage index at 12 mo.