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Journal of Peking University (Health Sciences) ›› 2022, Vol. 54 ›› Issue (5): 1038-1046. doi: 10.19723/j.issn.1671-167X.2022.05.034

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Efficacy of plasma exchange in severe crescentic IgA nephropathy: A multicentered, cohort study

Zi WANG1,Jun-jun ZHANG2,Li ZUO3,Yue WANG4,Wen-ge LI5,Hong CHENG6,Guang-yan CAI7,Hua-ying PEI8,Li-hua WANG9,Xu-jie ZHOU1,Su-fang SHI1,Li-jun LIU1,Ji-cheng LV1,*(),Hong ZHANG1   

  1. 1. Renal Division, Peking University First Hospital; Institute of Nephrology, Peking University; Key Laboratory of Renal Disease, Ministry of Health of China; Key Laboratory of CKD Prevention and Treatment, Ministry of Education of China, Research Units of Diagnosis and Treatment of lmmune-Mediated Kidney Diseases, Chinese Academy of Medical Sciences, Beijing 100191, China
    2. Department of Nephrology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China
    3. Department of Nephrology, Peking University People's Hospital, Beijing 100044, China
    4. Department of Nephrology, Peking University Third Hospital, Beijing 100191, China
    5. Department of Nephrology, China-Japan Friendship Hospital, Beijing 100029, China
    6. Division of Nephrology, Beijing Anzhen Hospital, Capital Medical University, Beijing 10029, China
    7. Department of Nephrology, Chinese PLA General Hospital, Beijing 100853, China
    8. Renal Division, Department of Medicine, The Second Hospital of Hebei Medical University, Shijiazhuang 050000, China
    9. Renal Division, Shanxi Medical University Second Affiliated Hospital, Taiyuan 030001, China
  • Received:2022-06-07 Online:2022-10-18 Published:2022-10-14
  • Contact: Ji-cheng LV E-mail:chenglv@263.com
  • Supported by:
    the National Natural Science Foundation of China(81322009);the National Natural Science Foundation of China(81270795);the Clinical Characteristic Applied Research Fund of Capital(Z161100000516005)

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Abstract:

Objective: To evaluate the efficacy of plasma exchange therapy on crescentic IgA nephropathy (IgAN). Methods: A retrospective analysis was performed in a cohort of patients with crescentic IgAN from January 2012 to September 2020 at 9 sites across China. Clinical and pathological data, as well as therapeutic regimens, were collected. In order to minimize the effect of potential confounders in baseline characteristics, propensity score matching using a 1 ∶1 ratio nearest neighbor algorithm was performed between the adjunctive plasma exchange therapy group and the intensive immunosuppressive therapy group. The primary outcome was end-stage of kidney disease (ESKD). Kaplan-Meier method was used to compare the difference in renal survival between the two groups. Results: A total of 95 crescentic IgAN patients with acute kidney disease were included in this study, including 37 (38.9%) patients receiving adjunctive plasma exchange therapy, and 58 (61.1%) patients receiving intensive immunosuppressive therapy. In the whole cohort, the baseline eGFR was 12.77 (7.28, 21.29) mL/(min·1.73 m2), 24-hour urinary protein quantification was 5.9 (4.0, 8.9) g, and crescent percentage was 64.71% (54.55%, 73.68%). In the study, 23 patients in each group were matched after propensity score matching The median follow-up time was 7 (1, 26) months. As a whole, 29 patients (63.0%) reached ESKD, including 16 patients (69.6%) in the adjunctive plasma exchange therapy group and 13 (56.5%) patients in the intensive immunosuppressive therapy group.. There were no stastical difference between the two groups in terms of baseline eGFR [14.30 (9.31, 17.58) mL/(min·1.73 m2) vs. 11.45 (5.59, 20.79) mL/(min·1.73 m2)], 24-hour urinary protein (7.4±3.4) g vs. (6.6±3.8) g, crescent percentage 64.49%±13.23% vs. 66.41%±12.65% and the proportion of patients received steroid therapy[23 (100.0%) vs. 21 (91.3%)] (All P>0.05). Kaplan-Meier survival analysis demonstrated that there was no significant difference in renal survival rate between the two groups (Log-rank test, P=0.933). Conclusion: The adjunctive plasma exchange therapy in addition to conventional intense immunosuppressive therapy did not additionally improve the prognosis of crescentic IgA nephropathy.

Key words: Glomerulonephritis, IgA nephropathy, Crescentic glomerulonephritis, Plasma exchange therapy

CLC Number: 

  • R692

Table 1

Demographic and clinical characteristics of 95 patients with crescentic IgA nephropathy"

Items Total population
(n=95)		 PLEX+IS group
(n=37)		 IS group
(n=58)		 P
Age/years, M(P25, P75) 32 (23, 55) 40 (23, 59) 31 (22, 46) 0.262
Male, n(%) 58 (61.1) 22 (59.5) 36 (62.1) 0.799
Time of follow-up/months, M(P25, P75) 10 (1, 27) 6 (0, 24) 15 (2, 33) 0.087
Course of disease/months, M(P25, P75) 3.0 (1.0, 8.0) 3.0 (1.0, 12.0) 2.8 (1.0, 7.3) 0.652
Prodromic infection, n(%) 35 (36.84) 17 (45.95) 18 (31.03) 0.072
Auria or oligouria, n(%) 14 (14.74) 8 (21.62) 6 (10.34) 0.131
Gross hematuria, n(%) 20 (21.05) 5 (13.51) 15 (25.86) 0.150
Hypertension history, n(%) 73 (76.84) 32 (86.49) 41 (70.69) 0.075
Dialysis prior to RB, n(%) 30 (31.58) 19 (51.35) 11 (18.97) 0.001
ACEi/ARB use prior to RB, n(%) 19 (20.00) 7 (18.92) 12 (20.69) 0.833
Steroids use prior to RB, n(%) 31 (32.63) 16 (43.24) 15 (25.86) 0.099
IS use prior to RB, n(%) 14 (14.74) 7 (18.92) 7 (12.07) 0.397
MAP/mmHg, ${\bar x}$±s 107.3±11.5 109.3±12.3 105.9±10.9 0.172
Hb/(g/L), ${\bar x}$±s 103.2±23.2 99.2±17.9 105.7±25.8 0.152
ESR/(mm/h), M(P25, P75) 34.0 (23.0，61.5) 41.0 (25.8，57.8) 31.5 (19.0，67.8) 0.706
Urine RBC/(/μL), M(P25, P75) 395. 3 (117.1，1 483.0) 670.1 (142.7，1 932.6) 354.7 (105.9，801.9) 0.055
24-hour proteinuria/g, M(P25, P75) 5.9 (4.0，8.9) 5.7 (4.0，7.8) 6.3 (3.8，9.1) 0.556
Scr/(μmol/L), M(P25, P75) 380.8 (254.0, 616.6) 472.2 (340.7，641.1) 309.8 (184.4，556.7) 0.026
eGFR/[mL/(min·1.73m2)], M(P25, P75) 12.77 (7.28，21.29) 9.38 (6.81，14.94) 16.06 (7.54，32.35) 0.035
Alb/(g/L), M(P25, P75) 29.9 (25.2，33.5) 28.7 (25.3，32.9) 30.4 (24.9，34.6) 0.514
IgG/(g/L), M(P25, P75) 7.20 (5.43，10.95) 7.20 (5.44，10.80) 7.25 (5.25，11.05) 0.751
IgA/(g/L), M(P25, P75) 2.86 (2.01，3.82) 2.87 (1.71，3.91) 2.85 (2.08，3.69) 0.774
IgM/(g/L), M(P25, P75) 0.72 (0.57，1.11) 0.72 (0.59，0.91) 0.81 (0.55，1.48) 0.234
C3/(g/L), M(P25, P75) 0.82 (0.65，1.05) 0.74 (0.61，0.87) 0.86 (0.69，1.18) 0.008
C4/(g/L), M(P25, P75) 0.27 (0.20，0.33) 0.24 (0.19，0.32) 0.28 (0.21，0.35) 0.250
CRP/(g/L), M(P25, P75) 3.28 (1.07，9.21) 4.29 (1.39，9.69) 1.58 (0.65，7.28) 0.116
Global sclerosis/%, M(P25, P75) 0 (0，9.10) 0 (0，9.11) 0 (0，9.10) 0.526
Ischemic sclerosis/%, M(P25, P75) 1.79 (0，11.76) 6.25 (0，11.81) 0 (0，11.82) 0.563
Crescents/%, M(P25, P75) 64.71 (54.55，73.68) 65.00 (54.42，76.08) 63.87 (55.30，73.81) 0.878
Total crescents/%, M(P25, P75) 68.75 (60.00，81.82) 69.23 (61.11，84.92) 67.91 (59.84，80.88) 0.410
ACEi/ARB use post to RB, n(%) 28 (29.47) 13 (35.14) 15 (25.86) 0.334
Steroids use post to RB, n(%) 86 (90.53) 34 (91.89) 52 (89.66) 0.717
Steroid impulse post to RB, n(%) 67 (70.53) 24 (64.86) 43 (74.14) 0.268
IS use post to RB, n(%) 49 (51.58) 19 (51.35) 30 (51.72) 0.989

Figure 1

Study flow diagram for recruiting patients AKD, acute kidney disease; TMA, thrombotic microangiopathy; GBM, glomerular basement membrane; ANCA, anti-neutrophil cytoplasmic antibodies; PLEX, plasma exchange therapy."

Table 2

Demographic and clinical characteristics of 46 patients with crescentic IgA nephropathy after PSM"

Items Total population
(n=46)		 PLEX+IS group
(n=23)		 IS group
(n=23)		 P
Age/years, ${\bar x}$±s 38±18 37±18 39±19 0.769
Male/% 31 (67.4) 16 (69.6) 15 (65.2) 0.753
Time of follow-up/months, M(P25, P75) 7 (1，26) 9 (3，27) 2 (0，22) 0.212
Course of disease/months, M(P25, P75) 2.0 (1.0，6.3) 4.0 (1.0，12.0) 2.0 (1.0，5.0) 0.073
Prodromic infection/% 17 (37.0) 9 (39.1) 8 (34.8) 0.760
Auria or oligouria/% 5 (10.9) 3 (13.0) 2 (8.7) 0.639
Gross hematuria/% 12 (26.1) 4 (17.4) 8 (34.8) 0.184
Hypertension history/% 34 (73.9) 19 (82.6) 15 (65.2) 0.184
Dialysis prior to RB/% 13 (28.3) 6 (26.1) 7 (30.4) 0.743
ACEi/ARB use prior to RB/% 9 (19.6) 6 (26.1) 3 (13.0) 0.270
Steroids use prior to RB/% 16 (34.8) 12 (52.2) 4 (17.4) 0.014
IS use prior to RB/% 7 (15.2) 6 (26.1) 1 (4.3) 0.042
MAP/mmHg, ${\bar x}$±s 110.3±11.7 109.9±12.2 110.7±11.4 0.813
Hb/(g/L), ${\bar x}$±s 103.8±21.6 107.2±16.7 100.5±25.6 0.296
ESR/(mm/h), M(P25, P75) 45.4±22.2 45.7±21.9 44.4±24.8 0.901
Urine RBC/(/μL), M(P25, P75) 466.4 (141.8，1 390.5) 554.4 (140.1，1 728.9) 457.0 (134.0，1 000.0) 0.733
24-hour proteinuria/g, M(P25, P75) 7.0±3.6 7.4±3.4 6.6±3.8 0.502
Scr/(μmol/L), M(P25, P75) 377.6 (283.3，633.7) 352.8 (309.0，522.3) 451.0 (258.7，775.0) 0.374
eGFR/[mL/(min·1.73m2)], M(P25, P75) 12.74 (7.27，18.85) 14.30 (9.31，17.58) 11.45 (5.59，20.79) 0.318
Alb/(g/L), M(P25, P75) 28.3±5.6 27.8±5.5 28.7±5.8 0.627
IgG/(g/L), M(P25, P75) 7.12(5.74，10.30) 7.13(5.71，10.42) 6.41(5.00，10.01) 0.849
IgA/(g/L), M(P25, P75) 2.86(2.04，3.54) 2.79(1.70，3.69) 3.00(2.13，3.45) 0.107
IgM/(g/L), M(P25, P75) 0.75±0.32 0.76±0.34 0.74±0.31 0.864
C3/(g/L), M(P25, P75) 0.83±0.26 0.78±0.26 0.89±0.24 0.165
C4/(g/L), M(P25, P75) 0.26±0.09 0.25±0.08 0.27±0.11 0.525
CRP/(g/L), M(P25, P75) 6.68±7.15 6.89±6.50 6.28±8.58 0.823
Global sclerosis/%, M(P25, P75) 0(0，8.33) 0(0，10.00) 0(0，7.69) 0.694
Ischemic sclerosis/%, M(P25, P75) 8.82±9.97 8.11±10.03 9.54±10.07 0.484
Crescents/%, M(P25, P75) 65.45±12.83 64.49±13.23 66.41±12.65 0.617
Total crescents/%, M(P25, P75) 71.08±13.00 71.03±14.04 71.12±12.20 0.981
ACEi/ARB use post to RB, n(%) 9 (19.6) 6 (26.1) 3 (13.0) 0.270
Steroids use post to RB, n(%) 44 (95.7) 23 (100.0) 21 (91.3) 0.153
Steroid impulse post to RB, n(%) 34 (73.9) 17 (73.9) 17 (73.9) 1.000
IS use post to RB, n(%) 23 (51.1) 13 (59.1) 10 (43.5) 0.295

Figure 2

Cumulative survival curves of paients in the PLEX group and the control group There were no significanly difference betweeen two groups (Cox-mantel Log-rank test, P=0.933). PLEX, plasma exchange therapy."

Table 3

Efficacy of PLEX on primary and secondary outcomes"

Outcomes PLEX+IS group, n(%) IS group, n(%) HR (95%CI) P
Primary outcomes
  ESKD 16 (69.6) 13 (56.5) 0.959 (0.458－2.010) 0.912*
Second outcomes
  All cause of death 2 (8.7) 1 (4.3) 1.048 (0.899－1.221) 0.555
  ESKD at 6 months 8 (34.8) 10 (43.5) 0.867 (0.544－1.382) 0.546
  ESKD at 12 months 10 (43.5) 10 (43.5) 1.000 (0.602－1.660) 1.000
  Dialysis-free at 3 months 3 (50.0) 2 (28.6) 1.429 (0.565－3.611) 0.447
  Dialysis-free at 12 months 1 (16.7) 1 (14.3) 1.029 (0.644－1.643) 0.909

Figure 3

Landmark analysis for the cumulative survival of paients in the PLEX group and the control group There were no significanly difference betweeen two groups before 12 months and afterwards (Cox-mantel Log-rank test, P=0.641, P=0.369). PLEX, plasma exchange therapy."

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