Association of Mitochondrial Pyruvate Carrier with the Clinical and Histological Features in Lupus Nephritis

Figures & data

Table 1 Comparison of the Clinical and Histologic Features Between the Patients with Proliferative LN and Membranous LN

	Total (n=36)	Proliferative LN (n=18)	Membranous LN (n=18)	P value
Clinical features
Female, n (%)	31 (86.10)	15 (83.33)	16 (88.9)	0.635
Age (years)	39.56±13.39	38.89±15.19	40.22±11.72	0.770
SLE duration (months)	2.00 (1.00, 4.50)	2.50 (1.00, 6.00)	2.50 (1.00, 4.00)	0.518
Hypertension, n (%)	10 (27.80)	6 (33.33)	4 (22.22)	0.463
SBP (mmHg)	130.89±17.21	128.33±15.86	133.44±18.55	0.381
DBP (mmHg)	84.42±10.85	83.17±11.05	85.67±10.81	0.497
Nephrotic syndrome, n (%)	13 (36.10)	4 (22.22)	9 (50.00)	0.087
Hematuria, n(%)	15 (41.70)	9 (50.00)	6 (33.33)	0.310
SLEDAI-2K	10.72±4.98	12.83±5.54	8.61±3.31	0.009
rSLEDAI	8 (4.00, 8.00)	8.00 (4.00, 8.00)	4.00 (4.00, 8.00)	0.098
Cutaneous lupus, n (%)	15 (41.67)	8 (44.44)	7 (38.89)	0.739
Nonscarring alopecia, n (%)	3 (8.33)	3 (16.67)	0 (0.00)	0.074
Oral/nasal ulcers, n (%)	1 (2.78)	0 (0.00)	1 (5.56)	0.317
Arthritis, n (%)	12 (33.30)	7 (38.89)	5 (27.78)	0.486
Serositis, n (%)	0 (0.00)	0 (0.00)	0 (0.00)	0.999
Neurological disorder, n (%)	0 (0.00)	0 (0.00)	0 (0.00)	0.999
Hemolytic anemia, n (%)	26 (72.22)	16 (88.89)	10 (55.56)	0.028
Lymphopenia/leukopenia, n (%)	11 (30.56)	8 (44.44)	3 (16.67)	0.074
Thrombocytopenia, n (%)	6 (16.67)	3 (16.67)	3 (16.67)	0.999
Laboratory assessment
WBC (10^9/L)	5.32±2.71	4.54±2.14	6.09±3.05	0.087
Hemoglobin (g/L)	110.47±19.82	101.78±18.63	119.17±17.37	0.007
Platelet (10^9/L)	185.69±60.87	184.50±53.37	186.89±69.11	0.908
eGFR (mL/min/1.73 m^2)	90.79±35.72	77.58±45.32	104.01±14.26	0.028
Serum cystatin C (mg/L)	1.74±1.11	2.05±1.23	1.11±0.38	0.172
Serum creatinine (µmol/L)	69.60 (54.00, 133.55)	90.35 (56.00, 166.20)	64.50 (51.30, 73.60)	0.009
BUN (mmol/L)	6.16 (4.12, 10.70)	6.53 (4.70, 12.95)	4.98 (3.50, 7.70)	0.103
Uric acid (µmol/L)	374.59±110.83	421.62±92.39	327.57±109.86	0.009
Albumin (g/L)	26.47±7.75	27.11±6.02	25.83±9.30	0.628
Anti-Sm antibodies (+), n (%)	19 (52.80)	10 (55.56)	9 (50.00)	0.742
Anti-dsDNA antibodies (+), n (%)	18 (50.00)	11 (61.11)	7 (38.89)	0.189
Serum IgG (g/L)	13.65±6.26	16.28±6.28	11.03±5.17	0.010
Serum C3 (g/L)	0.70±0.35	0.59±0.35	0.82±0.31	0.047
Serum C4 (g/L)	0.14±0.11	0.12±0.12	0.16±0.10	0.386
Urine protein (g/24h)	2.08 (1.90, 3.71)	2.19 (1.76, 4.23)	4.46 (1.07, 7.31)	0.268
Urine pH	6.07±0.61	6.02±0.74	6.11±0.46	0.667
Urine titratable acid (mmol/L)	17.22±11.68	16.39±13.10	18.06±10.39	0.675
Urine ammonia (mmol/L)	30.81±19.05	26.56±22.35	35.06±14.48	0.185
Biopsy index
Modified NIH activity index	5.33±3.52	6.83±3.854	3.83±2.431	0.046
Endocapillary hypercellularity, n (%)	5 (13.89)	3 (16.67)	2 (11.11)	0.635
Neutrophils/karyorrhexis, n (%)	13 (36.11)	8 (44.44)	5 (27.78)	0.298
Fibrinoid necrosis, n (%)	4 (11.11)	4 (22.22)	0 (0.00)	0.037
Hyaline deposits, n (%)	32 (88.89)	18 (100.00)	14 (77.78)	0.097
Cellular/fibrocellular crescents, n (%)	15 (41.67)	5 (27.78)	10 (55.56)	0.091
Interstitial inflammation, n (%)	16 (44.44)	10 (55.56)	6 (33.33)	0.359
Modified NIH chronicity index	2.06±2.52	2.39±3.05	1.72±1.87	0.435
Total glomerulosclerosis score, n (%)	16 (44.44)	7 (38.89)	9 (50.00)	0.597
Fibrous crescents, n (%)	9 (25.00)	6 (33.33)	3 (16.67)	0.268
Tubular atrophy, n (%)	18 (50.00)	8 (44.44)	10 (55.56)	0.958
Interstitial fibrosis, n (%)	8 (21.05)	6 (33.33)	2 (11.11)	0.117
ISN/RPS class
III, n (%)	6 (15.79)	6 (33.33)	0 (0.00)	<0.001
IV, n (%)	12 (31.58)	12 (66.67)	0 (0.00)	<0.001
V, n (%)	18 (50.00)	0 (0.00)	18 (100.00)	<0.001

Notes: Values for categorical data were given as a number (percent); values for continuous variables were expressed as mean ± standard deviation (normally distributed data) or median (interquartile range) (non-normally distributed data); values for renal histopathology indices were expressed as median (minimum, maximum). A two-tailed P<0.05 was considered statistically significant. Bold values denote statistical significance at the P<0.05 level.

Abbreviations: SLE, systemic lupus erythematosus; SBP, systolic blood pressure; DBP, diastolic blood pressure; SLEDAI-2K, systemic lupus erythematosus disease activity index 2000; rSLEDAI, renal systemic lupus erythematosus disease activity index; WBC, white blood cell; eGFR, estimated glomerular filtration rate; BUN blood urea nitrogen; IgG, immunoglobulin G; C3, complement C3; C4, complement C4; NIH, National Institutes of Health; ISN/RPS, International Society of Nephrology/Renal Pathology Society.

Figure 1 MPC1 expression in kidney tissues of LN. Representative immunohistochemical staining of MPC1 in proliferative LN ((A), n=18), and membranous LN ((B), n=18) groups, respectively. Left column (Magnification×100). Right two columns (Magnification×400). (C) shows a comparison of quantitative analysis of MPC1 expression between proliferative LN and membranous LN using Image-Pro Plus 6.0 software.

Abbreviations: LN, lupus nephritis; IOD, integrated optical density.

Figure 2 MPC2 expression in kidney tissues of LN. Representative immunohistochemical staining of MPC2 in proliferative LN ((A), n=18), and membranous LN ((B), n=18) groups, respectively. Left column (Magnification×100). Right two columns (Magnification×400). (C) shows a comparison of quantitative analysis of MPC2 expression between proliferative LN and membranous LN using Image-Pro Plus 6.0 software.

Abbreviations: LN, lupus nephritis; IOD, integrated optical density.

Table 2 Associations Between MPC and Features of Lupus Nephritis (n=36)

	MPC1		MPC2
	r	P value	r	P value
Clinical features
Gender	0.329	0.050	0.259	0.127
Age (years)	0.098	0.571	0.252	0.137
SLE duration (months)	0.107	0.536	0.057	0.074
Hypertension	−0.209	0.211	−0.078	0.653
Nephrotic syndrome	−0.031	0.859	0.092	0.594
SLEDAI-2K	−0.510	0.001	−0.364	0.029
rSLEDAI	−0.424	0.011	−0.234	0.176
Laboratory assessment
eGFR (mL/min/1.73 m2)	0.484	0.003	0.343	0.041
Serum cystatin C (mg/L)	−0.448	0.145	−0.140	0.665
Serum creatinine (µmol/L)	−0.633	<0.001	−0.525	<0.001
BUN (mmol/L)	−0.487	0.003	−0.526	0.001
Uric acid (µmol/L)	−0.576	<0.001	−0.397	0.017
Albumin (g/L)	0.239	0.161	0.055	0.749
Anti-Sm antibodies (+)	0.340	0.052	0.121	0.484
Anti-dsDNA antibodies (+)	−0.380	0.022	−0.390	0.019
Serum IgG (g/L)	0.028	0.870	0.031	0.857
Serum C3 (g/L)	0.159	0.354	0.130	0.451
Serum C4 (g/L)	0.121	0.481	0.039	0.823
Urine protein (g/24h)	−0.122	0.478	−0.005	0.977
Urine pH	0.244	0.151	0.235	0.167
Urine titratable acid (mmol/L)	0.174	0.309	0.056	0.746
Urine ammonia (mmol/L)	0.391	0.018	0.385	0.020
Biopsy index
Modified NIH activity index	−0.422	0.010	−0.372	0.025
Endocapillary hypercellularity	−0.159	0.356	−0.244	0.152
Neutrophils/karyorrhexis	−0.508	0.002	−0.451	0.006
Fibrinoid necrosis	−0.289	0.087	−0.086	0.619
Hyaline deposits	−0.160	0.351	−0.062	0.720
Cellular/fibrocellular crescents	−0.253	0.137	−0.301	0.075
Interstitial inflammation	−0.167	0.331	−0.133	0.440
Modified NIH chronicity index	−0.082	0.636	−0.060	0.728
Total glomerulosclerosis score	0.012	0.944	0.052	0.761
Fibrous crescents	−0.032	0.853	−0.260	0.125
Tubular atrophy	−0.059	0.734	−0.028	0.870
Interstitial fibrosis	−0.235	0.167	−0.247	0.147

Notes: A two-tailed P<0.05 was considered statistically significant. Bold values denote statistical significance at the P<0.05 level.

Abbreviations: MPC, Mitochondrial pyruvate carrier; SLE, systemic lupus erythematosus; SLEDAI-2K, systemic lupus erythematosus disease activity index 2000; rSLEDAI, renal systemic lupus erythematosus disease activity index; eGFR, estimated glomerular filtration rate; BUN, blood urea nitrogen; IgG, immunoglobulin G; C3, complement C3; C4, complement C4; NIH, National Institutes of Health.

Data Sharing Statement

The datasets analyzed during the current study are available from the corresponding author on reasonable request.