Effects of Donor-Recipient Age Difference in Renal Transplantation, an Investigation on Renal Function and Fluid Proteome

Figures & data

Table 1 Characteristics and Renal Function of the Patients

Group	Mean Age* (Years, Surgery Day)	Median Age (Years, Surgery Day)	Mean Age Difference* (Years)	Median Age Difference (Years)	Mean Post-Transplantation Time* (Years)	Median Post-Transplantation Time (Years)	Sex (M:F)	Body Weight* (kg)	Serum Creatinine* (mmol/L)	BUN* (mmol/L)	eGFR* (mL/min)
Young recipient	27±7.42	28	24±2.24	24	5.4±1.82	8	4:1	62.6±8.91	106.24±2.73^a	5.87±2.4^a	75.54±10.3^a
Old donor	52.8±7.6	52	24±2.24	24	5.4±1.83	8	3:2	77±6.48	91.64±17.87^a	5.88±0.9^a	73.54±18.04^a
Old recipient	53.6±9.45	50	23.6±3.85	23	8.2±3.7	10	4:1	71.8±15.99	106.34±24.72^b	6.88±3.08^b	64.46±18.23^b
Young donor	30±10.75	24	23.6±3.85	23	8.2±3.7	10	0:5	65.8±15.39	66.78±6.78^b	4.63±1.15^b	101.20±14.28^b

Notes: *All values are means ± SEMs. ^aNo significantly difference from recipients to donors (p>0.05). ^bSignificantly difference from recipients to donors (p<0.05).

Abbreviations: BUN, blood urea nitrogen; eGFR, estimated glomerular filtration rate.

Table 2 Distinct Serum Proteins in Old Donor/Young Recipient Group

GI Number	Name	Entry Name (UniProt)	Accession Number (UniProt)	IEP	Molecular Weight	Protein Name	Expression
429,836,859	MEGF8	MEGF8_HUMAN	Q7Z7M0	6.45	303,100	Multiple epidermal growth factor-like domains protein 8 isoform 1 precursor	Down
371,502,106	PROZ	PROZ_HUMAN	P22891	5.68	47,053	Vitamin K-dependent protein Z isoform 1 precursor	Down
32,130,518	APOC2	APOC2_HUMAN	P02655	4.64	11,283	Apolipoprotein C-II precursor	Down
4,503,625	F10	FA10_HUMAN	P00742	5.68	54,731	Coagulation factor X isoform 1 preproprotein	Down
4,502,161	APOC4	APOC4_HUMAN	P55056	9.19	14,553	Apolipoprotein C-IV precursor	Down
4,505,047	LUM	LUM_HUMAN	P51884	6.16	38,429	Lumican precursor	Down
27,754,776	FCN3	FCN3_HUMAN	O75636	6.2	32,902	Ficolin-3 isoform 1 precursor	Down
41,393,602	C1S	C1S_HUMAN	P09871	4.85	76,684	Complement C1s subcomponent isoform 1 preproprotein	Down
66,347,875	C1R	C1R_HUMAN	P00736	5.89	80,199	Complement C1r subcomponent precursor	Down
70,778,918	ITIH2	ITIH2_HUMAN	P19823	6.4	106,463	Inter-alpha-trypsin inhibitor heavy chain H2 precursor	Down
4,504,383	HGFAC	HGFA_HUMAN	Q04756	6.99	70,681	Hepatocyte growth factor activator isoform 2 preproprotein	Up
4,757,826	B2M	B2MG_HUMAN	P61769	6.06	13,714	Beta-2-microglobulin precursor	Up
4,503,689	FGA	FIBA_HUMAN	P02671	5.7	94,973	Fibrinogen alpha chain isoform alpha-E preproprotein	Up
70,906,439	FGG	FIBG_HUMAN	P02679	5.37	51,511	Fibrinogen gamma chain isoform gamma-B precursor	Up
268,840,382	IL1RAP	IL1AP_HUMAN	Q9NPH3	6.71	78,602	Interleukin-1 receptor accessory protein isoform 3 precursor	Up
261,337,165	LTBP1	LTBP1_HUMAN	Q14766	5.62	186,768	Latent-transforming growth factor beta-binding protein 1 isoform LTBP-1L precursor	Up
61,744,477	SLC3A2	4F2_HUMAN	P08195	4.91	68,101	Cell-surface antigen heavy chain isoform b	Up

Table 3 Distinct Serum Proteins in Young Donor/Old Recipient Group

GI Number	Name	Entry Name (UniProt)	Accession Number (UniProt)	IEP	Molecular Weight	Protein Name	Expression
91,823,274	ENPP2	ENPP2_HUMAN	Q13822	8.5	105,200	Ectonucleotide pyrophosphatase/phosphodiesterase family member 2 isoform 1 preproprotein	Down
40,255,005	PLXDC2	PXDC2_HUMAN	Q6UX71	5.99	59,583	Plexin domain-containing protein 2 isoform 1 precursor	Down
61,744,477	SLC3A2	4F2_HUMAN	P08195	4.91	68,101	4F2 cell-surface antigen heavy chain isoform b	Down
4,557,321	APOA1	APOA1_HUMAN	P02647	5.56	30,777	Apolipoprotein A-I isoform 1 preproprotein	Down
115,529,484	CD109	CD109_HUMAN	Q6YHK3	5.59	161,689	CD109 antigen isoform 1 preproprotein	Down
156,627,579	CLEC3B	TETN_HUMAN	P05452	5.52	22,536	Tetranectin isoform 1precursor	Down
115,298,678	C3	CO3_HUMAN	P01024	6.02	187,148	Complement C3 preproprotein	Down
156,119,625	ITIH1	ITIH1_HUMAN	P19827	6.31	101,389	Inter-alpha-trypsin inhibitor heavy chain H1 isoform a preproprotein	Down
29,171,717	GPLD1	PHLD_HUMAN	P80108	5.91	92,336.45	Phosphatidylinositol-glycan-specific phospholipase D precursor	Up
291,190,772	GP1BA	GP1BA_HUMAN	P07359	5.87	71,540	Platelet glycoprotein Ib alpha chain precursor	Up
31,317,307	PCSK9	PCSK9_HUMAN	Q8NBP7	6.14	74,286	Proprotein convertase subtilisin/kexin type 9 preproprotein	Up
295,821,193	SAA1	SAA1_HUMAN	P0DJI8	6.28	13,532	Serum amyloid A-1 protein preproprotein	Up

Table 4 IPA Pathways of Distinct Serum Proteins in Old Donor/Young Recipient Group

Ingenuity Canonical Pathways	-Log(p-value)	Ratio	Molecules
Acute Phase Response Signaling	8.57	0.0353	C1R, ITIH2, C1S, FGA, IL1RAP, FGG
Extrinsic Prothrombin Activation Pathway	6.63	0.188	F10, FGA, FGG
LXR/RXR Activation	5.66	0.0331	APOC4, APOC2, FGA, IL1RAP
Coagulation System	5.57	0.0857	F10, FGA, FGG
Intrinsic Prothrombin Activation Pathway	5.33	0.0714	F10, FGA, FGG
Role of Tissue Factor in Cancer	3.92	0.0244	F10, FGA, FGG
FXR/RXR Activation	3.89	0.0238	APOC4, APOC2, FGA
Complement System	3.41	0.0541	C1R, C1S
LPS/IL-1 Mediated Inhibition of RXR Function	3.18	0.0136	APOC4, APOC2, IL1RAP
TR/RXR Activation	2.57	0.0204	F10, FGA
Neuroprotective Role of THOP1 in Alzheimer’s Disease	2.4	0.0168	C1R, HGFAC
Atherosclerosis Signaling	2.35	0.0157	APOC4, APOC2
IL-12 Signaling and Production in Macrophages	2.23	0.0137	APOC4, APOC2
Production of Nitric Oxide and Reactive Oxygen Species in Macrophages	1.99	0.0103	APOC4, APOC2
Clathrin-mediated Endocytosis Signaling	1.97	0.0101	APOC4, APOC2
Lipid Antigen Presentation by CD1	1.69	0.0385	B2M
Cytotoxic T Lymphocyte-mediated Apoptosis of Target Cells	1.6	0.0312	B2M

Table 5 IPA Pathways of Distinct Serum Proteins in Young Donor/Old Recipient Group

Ingenuity Canonical Pathways	-Log(p-value)	Ratio	Molecules
LXR/RXR Activation	2.7	0.0156	APOA1, SAA1
FXR/RXR Activation	2.64	0.0146	APOA1, SAA1
Acute Phase Response Signaling	2.45	0.0116	APOA1, SAA1
Phospholipases	1.43	0.0139	GPLD1

Figure 1 GO terms of distinct serum proteins in old donor/young recipient group.

Figure 2 GO terms of distinct serum proteins in young donor/old recipient group.

Table 6 Distinct Urinary Proteins in Old Donor/Young Recipient Group

Gene Name	Entry Name (UniProt)	Accession Number (UniProt)	IEP	Molecular Weight	Protein Name	Expression
ART3	NAR3_HUMAN	Q13508	5.71	43,923	Ecto-ADP-ribosyltransferase 3	Up
CA4	CAH4_HUMAN	P22748	7.68	35,032	Carbonic anhydrase 4	Up
RBP4	RET4_HUMAN	P02753	5.76	23,010	Retinol-binding protein 4	Up
BCAM	BCAM_HUMAN	P50895	5.53	67,404	Basal cell adhesion molecule	Up
VPS4B	VPS4B_HUMAN	O75351	6.75	49,302	Vacuolar protein sorting-associated protein 4B	Down
VTA1	VTA1_HUMAN	Q9NP79	5.86	33,879	Vacuolar protein sorting-associated protein VTA1 homolog	Down
PRDX6	PRDX6_HUMAN	P30041	6	25,034	Peroxiredoxin-6	Up
BROX	BROX_HUMAN	Q5VW32	7.55	46,476	BRO1 domain-containing protein BROX	Down
LDHB	LDHB_HUMAN	P07195	5.71	36,638	L-lactate dehydrogenase B chain	Up
SERPINA3	AACT_HUMAN	P01011	5.33	47,650	Alpha-1-antichymotrypsin	Up
TPP1	TPP1_HUMAN	O14773	6.01	61,247	Tripeptidyl-peptidase 1	Down
SERPINA1	A1AT_HUMAN	P01009	5.37	46,736	Alpha-1-antitrypsin	Up

Table 7 Distinct Urinary Proteins in Young Donor/Old Recipient Group

GI Number	Gene Name	Entry Name (UniProt)	Accession Number (UniProt)	IEP	Molecular Weight	Protein Name	Expression
331,999,954	KRT4	B4DRS2_HUMAN	B4DRS2	6.25	56,013	Keratin, type II cytoskeletal 4	Down
131,412,225	KRT13	K1C13_HUMAN	P13646	4.91	49,427	Keratin, type I cytoskeletal 13	Down
61,743,954	AHNAK	AHNK_HUMAN	Q09666	5.8	628,973	Neuroblast differentiation-associated protein AHNAK	Down
5,902,072	SERPINB3	SPB3_HUMAN	P29508	6.35	44,434	Serpin B3	Down
4,557,581	FABP5	FABP5_HUMAN	Q01469	6.59	15,033	Fatty acid-binding protein, epidermal	Down
74,271,845	A2ML1	B3KVV6_HUMAN	B3KVV6	5.51	161,139	Alpha-2-macroglobulin-like protein 1 isoform 1 precursor	Down
260,436,922	SBSN	SBSN_HUMAN	Q6UWP8	6.5	60,540	Suprabasin isoform 1 precursor	Down
183,227,678	PARK7	PARK7_HUMAN	Q99497	6.32	19,891	Protein/nucleic acid deglycase DJ-1	Down
193,794,814	ALDOA	ALDOA_HUMAN	P04075	8.3	39,420	Fructose-bisphosphate aldolase A	Down
4,503,117	CSTB	CYTB_HUMAN	P04080	6.96	11,139	Cystatin-B	Down
4,502,101	ANXA1	ANXA1_HUMAN	P04083	6.57	38,714	Annexin A1	Down
4,503,065	CRYM	CRYM_HUMAN	Q14894	5.06	33,775	Ketimine reductase mu-crystallin	Down
4,758,950	PPIB	PPIB_HUMAN	P23284	9.42	23,742	Peptidyl-prolyl cis-trans isomerase B	Down
440,918,691	AOC1	AOC1_HUMAN	P19801	6.68	87,238	Amiloride-sensitive amine oxidase [copper-containing] isoform 1 precursor	Up
39,725,934	SERPINF1	PEDF_HUMAN	P36955	5.97	46,312	Pigment epithelium-derived factor	Up
197,116,348	ACPP	PPAP_HUMAN	P15309	6.54	48,336	Prostatic acid phosphatase	Up
189,163,542	SERPINA1	A1AT_HUMAN	P01009	5.37	46,736	Alpha-1-antitrypsin	Up
110,611,235	COL18A1	COIA1_HUMAN	P39060	5.45	153,766	Collagen alpha-1(XVIII) chain	Up
4,557,287	AGT	ANGT_HUMAN	P01019	5.87	53,154	Angiotensinogen	Up
70,906,435	FGB	FIBB_HUMAN	P02675	8.54	55,928	Fibrinogen beta chain	Up
115,298,678	C3	CO3_HUMAN	P01024	6.02	187,148	Complement C3	Up
50,659,080	SERPINA3	AACT_HUMAN	P01011	5.33	47,650	Alpha-1-antichymotrypsin	Up
4,502,133	APCS	SAMP_HUMAN	P02743	6.1	25,387	Serum amyloid P-component	Up
31,652,249	LBP	LBP_HUMAN	P18428	6.23	53,383	Lipopolysaccharide-binding protein	Up
4,504,489	HRG	HRG_HUMAN	P04196	7.09	59,578	Histidine-rich glycoprotein	Up
4,503,635	F2	THRB_HUMAN	P00734	5.63	70,036	Prothrombin	Up
4,502,511	C9	CO9_HUMAN	P02748	5.43	63,173	Complement component C9	Up
119,372,298	PGA3	PEPA3_HUMAN	P0DJD8	4.22	41,976	Pepsin A-3 preproprotein	Up

Table 8 IPA Pathways of Distinct Urinary Proteins in Old Donor/Young Recipient Group

Ingenuity Canonical Pathways	-Log(p-value)	Ratio	Molecules
Acute Phase Response Signaling	3.99	0.0176	SERPINA3, SERPINA1, RBP4
Neuroprotective Role of THOP1 in Alzheimer’s Disease	2.71	0.0168	TPP1, SERPINA3
LXR/RXR Activation	2.69	0.0165	SERPINA1, RBP4
FXR/RXR Activation	2.66	0.0159	SERPINA1, RBP4
Atherosclerosis Signaling	2.65	0.0157	SERPINA1, RBP4
IL-12 Signaling and Production in Macrophages	2.53	0.0137	SERPINA1, RBP4
Pyruvate Fermentation to Lactate	2.47	0.167	LDHB
Production of Nitric Oxide and Reactive Oxygen Species in Macrophages	2.29	0.0103	SERPINA1, RBP4
Clathrin-mediated Endocytosis Signaling	2.27	0.0101	SERPINA1, RBP4
Glutathione Redox Reactions I	1.87	0.0417	PRDX6
Coagulation System	1.71	0.0286	SERPINA1
Triacylglycerol Degradation	1.53	0.0189	PRDX6
Heparan Sulfate Biosynthesis (Late Stages)	1.38	0.0133	PRDX6
Heparan Sulfate Biosynthesis	1.35	0.0122	PRDX6

Table 9 IPA Pathways of Distinct Urinary Proteins in Young Donor/Old Recipient Group

Ingenuity Canonical Pathways	-Log(p-value)	Ratio	Molecules
Acute Phase Response Signaling	16	0.0647	C3, APCS, C9, SERPINF1, SERPINA3, SERPINA1, FGB, LBP, HRG, F2, AGT
LXR/RXR Activation	8	0.0496	C3, C9, SERPINF1, SERPINA1, LBP, AGT
FXR/RXR Activation	6.24	0.0397	C3, C9, SERPINF1, SERPINA1, AGT
Coagulation System	4.89	0.0857	SERPINA1, FGB, F2
Intrinsic Prothrombin Activation Pathway	4.65	0.0714	FGB, COL18A1, F2
Extrinsic Prothrombin Activation Pathway	3.71	0.125	FGB, F2
Complement System	2.97	0.0541	C3, C9
Hepatic Fibrosis/Hepatic Stellate Cell Activation	2.76	0.0164	LBP, COL18A1, AGT
Neuroprotective Role of THOP1 in Alzheimer’s Disease	1.98	0.0168	SERPINA3, AGT
Role of Tissue Factor in Cancer	1.95	0.0163	FGB, F2
Sucrose Degradation V (Mammalian)	1.93	0.111	ALDOA
Atherosclerosis Signaling	1.92	0.0157	SERPINA1, COL18A1
p70S6K Signaling	1.89	0.0152	F2, AGT
NAD Phosphorylation and Dephosphorylation	1.77	0.0769	ACPP
Guanosine Nucleotides Degradation III	1.77	0.0769	ACPP
Urate Biosynthesis/Inosine 5ʹ-phosphate Degradation	1.74	0.0714	ACPP
Glutaryl-CoA Degradation	1.71	0.0667	PARK7
Parkinson’s Signaling	1.68	0.0625	PARK7
Adenosine Nucleotides Degradation II	1.66	0.0588	ACPP
Histamine Degradation	1.61	0.0526	AOC1
Purine Nucleotides Degradation II (Aerobic)	1.59	0.05	ACPP
Clathrin-mediated Endocytosis Signaling	1.56	0.0101	SERPINA1, F2
Tryptophan Degradation III (Eukaryotic)	1.51	0.0417	PARK7
NAD Salvage Pathway II	1.47	0.0385	ACPP
Glycolysis I	1.47	0.0385	ALDOA
Gluconeogenesis I	1.47	0.0385	ALDOA
LPS/IL-1 Mediated Inhibition of RXR Function	1.47	0.00905	FABP5, LBP
Actin Cytoskeleton Signaling	1.45	0.00881	LBP, F2

Figure 3 GO terms of distinct urinary proteins in old donor/young recipient group.

Figure 4 GO terms of distinct urinary proteins in young donor/old recipient group.