Shifts in Intestinal Metabolic Profile Among Kidney Transplantation Recipients with Antibody-Mediated Rejection

Figures & data

Table 1 Comparisons of Demographic and Clinical Characteristics Between Recipients with AMR and Controls

Variable	KT-AMR (n = 30)	KT-SRF (n = 35)	ESRD (n = 21)	KT-AMR vs KT-SRF P value	KT-AMR vs ESRD P value	KT-SRF vs ESRD P value
Age, years	33.77 ± 7.2	38.69 ± 8.864	39.52 ± 10.54	NS	NS	NS
Male gender, n (%)	90%	80%	71.4%	NS	NS	NS
BMI	22.64 ± 3.193	23.01 ± 2.977	22.9 ± 2.524	NS	NS	NS
Diabetes mellitus, n (%)	3 (10%)	4 (11.4%)	2 (9.5%)	NS	NS	NS
Hypertension, n (%)	27 (90%)	29 (82.8%)	20 (95.2%)	NS	NS	NS
Scr, μmol/L	341.9 ± 178	90.17 ± 18.29	820 ± 240.9	<0.0001	0.0041	<0.0001
BUN, mmol/L	17.47 ± 6.917	6.569 ± 1.145	22.17 ± 7.578	<0.0001	NS	<0.0001
UA, μmol/L	385.1 ± 142.4	335.9 ± 58.41	352.9 ± 116.9	NS	NS	NS
CO2, mmol/L	26.22 ± 30.83	23.43 ± 2.069	21.96 ± 4.066	0.0028	NS	NS
ALB, g/L	38.06 ± 3.824	45.24 ± 3.895	43.18 ± 5.98	<0.0001	0.0053	NS
TBA, μmol/L	4.147 ± 4.186	5.014 ± 2.579	2.719 ± 1.619	NS	NS	0.0014
LDH, U/L	269.6 ± 111	230.7 ± 64.67	215.6 ± 66.12	NS	NS	NS
ALP, U/L	115.6 ± 87.13	92.26 ± 49.2	94.57 ± 83.38	NS	NS	NS
HGB, g/L	96.9 ± 17.71	139 ± 15.93	98.86 ± 25.92	<0.0001	NS	<0.0001
WBC, ×10^9/L	5.399 ± 2.846	5.857 ± 1.365	5.653 ± 1.863	NS	NS	NS
PLT, ×10^9/L	182.7 ± 65.65	191.3 ± 50.43	181.4 ± 69.66	NS	NS	NS
CRP, mg/L	5.544 ± 7.388	1.515 ± 2.043	3.812 ± 7.151	0.0023	NS	NS
U-protein, -/±/+/++/+++	0/0/4/10/16	27/4/3/1/0	0/0/2/4/15	<0.0001	NS	<0.0001
Induction therapy, Thymoglobuline, n (%)	30 (100%)	35 (100%)	21 (100%)	NS	-	-
Maintenance Therapy
Tacrolimus, n (%)	30 (100%)	35 (100%)	21 (100%)	NS	-	-
Mycophenolate mofetil, n (%)	30 (100%)	35 (100%)	21 (100%)	NS	-	-
Prednisone, n (%)	30 (100%)	35 (100%)	21 (100%)	NS	-	-
DSAs, n (%)	16 (45.7%)	0 (0%)	-	-	-	-
Time after transplantation to fecal collection (years)	5.3 (4.15–6.2)	5.6 (4.3–6.5)	-	NS	-	-

Notes: Data for age were expressed as median (min-max) and other continuous variables were expressed as median (interquartile range), while categorical variables were reported as counts.

Abbreviations: KT-AMR, kidney transplantation recipients with AMR; KT-SRF, kidney transplantation recipients with stable renal functions; ESRD, patients with end-stage renal disease; BMI, body mass index; Scr, serum creatinine; BUN, blood urea nitrogen; UA, uric acid; CO2, carbon dioxide; CysC, serum cystatin C; ALB, albumin; TBA, total bile acid; LDH, lactate dehydrogenase; ALP, alkaline phosphatase; HGB, hemoglobin; WBC, white blood cell; PLT, platelet; CRP, C-reactive protein; U-protein, urine protein; DSAs, donor‐specific antibodies; NS, not significant (P < 0.05).

Figure 1 Differences in intestinal metabolic profiles among the KT-AMR, KT-SRF, and ESRD groups. (A) PCA score plots in the ESI+ mode; (B) PCA score plots in the ESI- mode; (C) OPLS-DA score plots in the ESI+ mode (KT-AMR vs ESRD); (D) OPLS-DA score plots in the ESI+ mode (KT-AMR vs KT-SRF); (E) OPLS-DA score plots in the ESI+ mode (KT-SRF vs ESRD); (F) OPLS-DA score plots in the ESI- mode (KT-AMR vs ESRD); (G) OPLS-DA score plots in the ESI- mode (KT-AMR vs KT-SRF); (H) OPLS-DA score plots in the ESI- mode (KT-SRF vs ESRD).

Abbreviations: KT-AMR, kidney transplantation recipients with AMR; KT-SRF, kidney transplantation recipients with stable renal functions; ESRD, patients with end-stage renal disease.

Figure 2 Differential intestinal metabolites among the KT-AMR, KT-SRF, and ESRD groups. (A) Wayne figures of overlapping and different metabolites among groups; (B) the heatmap of 14 differential intestinal metabolites in both the ESRD group and the KT-SRF group compared the KT-AMR group.

Abbreviations: KT-AMR, kidney transplantation recipients with AMR; KT-SRF, kidney transplantation recipients with stable renal functions; ESRD, patients with end-stage renal disease.

Figure 3 Receiver operating characteristic (ROC) curves of potential metabolic biomarkers. (A) ROC curves of metabolites to discriminate between the KT-AMR and ESRD groups; (B) ROC curves of metabolites to discriminate between the KT-AMR and KT-SRF groups; (C) ROC curves of the combination of metabolic biomarkers using logistic regression models to discriminate between the KT-AMR and KT-SRF groups; (D) ROC curves of metabolites to discriminate between the KT-SRF and ESRD groups.

Abbreviations: AUC, the total area under the ROC curve; KT-AMR, kidney transplantation recipients with AMR; KT-SRF, kidney transplantation recipients with stable renal functions; ESRD, patients with end-stage renal disease.

Figure 4 Metabolic pathway enrichment analysis. The top 10 enrichment pathways were represented by bubble charts. (A) ROC curves of microbial biomarkers. (A) Pathway enrichment analysis of differential metabolites between the KT-AMR and ESRD groups; (B) pathway enrichment analysis of differential metabolites between the KT-AMR and KT-SRF groups; (C) pathway enrichment analysis of differential metabolites between the KT-SRF and ESRD groups.

Abbreviations: KT-AMR, kidney transplantation recipients with AMR; KT-SRF, kidney transplantation recipients with stable renal functions; ESRD, patients with end-stage renal disease.