Article Figures & Data
Figures
- Figure 1.
Network of evidence. A solid line denotes a direct comparison between 2 basic nodes; a dashed line denotes an indirect comparison between 2 functional nodes. The relative effect of 2 therapies as shown by an indirect contrast denoted by a dashed line, for example, Cyclo versus Aza, can be determined using this network through head-on comparisons that have already been done. The number of all possible pairwise comparisons in this case is 6. Numbers on the outer edges denote the study number in Table 2. Aza: azathioprine; Cyclo: cyclophosphamide; MMF: mycophenolate mofetil; Pred: prednisone alone.
- Figure 2.
Caterpillar plots of conventional (frequentist) metaanalysis of the 12 studies included. A. Two comparisons of 5 studies, using serum creatinine < 132 µmol/l as the outcome measure for renal remission.
B. Six comparisons of the 12 studies, using proteinuria < 0.5 g/day as the outcome measure for renal remission. For the M-H method used to combine OR see the Cochrane Handbook16. Aza: azathioprine; Cyclo: cyclophosphamide; MMF: mycophenolate mofetil; Tac: tacrolimus; Pred: prednisone alone; M-H: Mantel-Haenszel test.
Tables
No. Study Citation Arm Serum Creatinine Proteinuria Response Arm Size Response Arm Size 1 Appel, 2009 18 CYC 125 185 50 185 MMF 130 185 44 185 2 Chan, 2005 19 CYC 23 31 MMF 24 33 3 Chen, 2011 20 CYC 33 39 15 39 Tac 38 42 22 42 4 Donadio, 1972 21 AZA 2 7 Prednisone alone 2 9 5 Donadio, 1976 17 CYC 4 19 Prednisone alone 2 20 6 El-Shafey, 2010 22 CYC 5 23 5 23 MMF 6 24 6 24 7 Ginzler, 2005 23 CYC 4 69 4 69 MMF 16 71 16 71 8 Hahn, 1975 24 AZA 8 11 Prednisone alone 8 10 9 Li, 2012 9 CYC 6 20 MMF 9 20 Tac 9 20 10 Miyasaka, 2009 25 Tac 4 27 Prednisone alone 1 33 11 Ong, 2005 26 CYC 3 25 MMF 5 19 12 Ren, 2007 27 CYC 3 12 3 12 Tac 6 13 6 13 -
The outcome used is the number of renal remissions, as defined by serum creatinine < 132 µmol/l; proteinuria < 0.5 g/day. Response: no. responses in each arm; arm size: sample size of each arm; MMF: mycophenolate mofetil; CYC: cyclophosphamide; Tac: tacrolimus; AZA: azathioprine.
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No. Study Citation Region Sample Size Induction (weeks) Biopsy Class (%) Baseline Features (mean ± SD) Complete Renal Remission Definition 1 Appel GB, 2009 18 International (ALMS) 370 24 III, III/V (15.7), IV, IV/V (68.1), V (16.2) sCr (µmol/l, same below): 100.6 ± 1.1; urine protein/creatinine ratio: 4.1 ± 3.7 Return to normal sCr, proteinuria ≤ 0.5 g/day, and inactive urinary sediment (≤ 5 white and ≤ 5 erythrocytes per HPF, and a reading of < ++ on dipstick and absence of RBC casts) 2 Chan TM, 2005 19 China (Hong Kong) 64 24 IV, IV/V (100) sCr: 112.9 ± 57.0; proteinuria (g/24 h, same below): 5.32 ± 3.94 Proteinuria < 0.3 g/day, normal urinary sediment, normal serum albumin, and improved or stable renal function 3 Chen W, 2011 20 China (southern) 81 24 III (3.7), IV (71.6), V (11.1), III/V, IV/V (13.6) sCr: 82.88 ± 102.54; proteinuria: 1.50 ± 1.40 Proteinuria < 0.3 g/day with normal urinary sediment, normal serum albumin (≥ 35 g/l), and stable kidney function (normal sCr or ≤ 15% above baseline values) 4 Donadio Jr JV, 1972 21 North America (Mayo) 16 24 III, IV (100) Proteinuria: 3.39 ± 3.36 Proteinuria < 0.5 g/day, inactive urine sediments (≤ 8 erythrocytes per HPF and absent of RBC casts) 5 Donadio Jr JV, 1976 17 North America 39 24 IV (100) Proteinuria: 5.11 ± 3.50 Proteinuria < 0.5 g/day 6 El-Shafey EM, 2010 22 North Africa 47 24 III (31.9), IV (68.1) sCr: 137.15 ± 50.24; proteinuria: 2.03 ± 1.05 Normal sCr, reduction in proteinuria < 0.5 g/day and urinary sediment < 5 erythrocytes per HPF, without RBC casts 7 Ginzler EM, 2005 23 North America (NYC) 140 24 III (15.7), IV (54.3), V (19.3), III/V, IV/V (10.7) sCr: 94.58 ± 44.64; proteinuria: 4.25 ± 3.30 The return to within 10% of normal values of sCr, proteinuria (< 0.33–0.4 g/day), and urine sediment 8 Hahn BH, 1975 24 North America (Missouri) 24 24 III (15), II (25), V (15), IV/V (45) Proteinuria ≤ 0.2 g/day; OR inactive urine sediments (≤ 6 erythrocyte per HPF), OR normal renal function (sCr clearance > 80 ml/min) 9 Li X, 2012 9 China (eastern) 60 24 III, IV(66.7), III/V, IV/V (20), V(13.3) sCr: 77; proteinuria: 3.57 Proteinuria < 0.3 g/day, normal urine sediment, serum albumin> 35 g/l and stabilization (± 15%) or improvement in sCr at 24 weeks 10 Miyasaka N, 2009 25 Japan (Tokyo) 63 28 III (17.5), IV (30.2), V (27.0), II (4.8) sCr: 61.19 proteinuria: 1.55 Proteinuria < 0.3 g/day 11 Ong LM, 2005 26 Southeastern Asia (Malaysia) 44 24 III (6.8), III/V (2.3), IV (61.4), IV/V (29.5) sCr: 95.08 ± 38.95; proteinuria: 2.48 ± 1.54 Stabilization or improvement in renal function, urinary sediment < 10 erythrocytes per HPF and proteinuria < 0.3 g/day 12 Ren H, 2007 27 China (eastern) 25 24 IV (100) sCr < 265.2; proteinuria > 2.0 Proteinuria < 0.4 g/day, no active urinary sediment (< 10 erythrocytes per HPF), serum albumin > 35 g/l, and normal sCr -
RBC: red blood cell; sCr: serum creatinine; HPF: high power field.
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Prior Outcome Agents, no., name AZA MMF Prednisone Alone Tacrolimus Flat Serum creatinine 3 CYC 1.70 (0.51, 6.87) 2.16 (0.38, 13.36) MMF 1.25 (0.13, 10.51) Flat Proteinuria 4 CYC 0.33 (0.01, 8.06) 1.50 (0.73, 3.64) 0.37 (0.02, 4.36) AZA 4.59 (0.18, 145.22) 1.09 (0.15, 7.90) MMF 0.24 (0.01, 3.04) Flat Proteinuria 5 CYC 0.31 (0.02, 3.60) 1.46 (0.81, 3.04) 0.34 (0.05, 1.90) 1.96 (0.80, 5.11) AZA 4.76 (0.38, 75.76) 1.09 (0.18, 6.91) 6.34 (0.53, 92.51) MMF 0.23 (0.03, 1.38) 1.34 (0.43, 3.90) Pred 5.69 (1.03, 41.32) Sceptical Serum creatinine 3 CYC 1.01 (0.60, 1.63) 1.30 (0.68, 2.34) MMF 1.30 (0.57, 2.73) Sceptical Proteinuria 5 CYC 0.97 (0.52, 1.78) 0.91 (0.62, 1.38) 0.92 (0.55, 1.56) 0.98 (0.61, 1.58) AZA 0.94 (0.46, 1.97) 0.95 (0.46, 1.94) 1.01 (0.47, 2.17) MMF 1.01 (0.52, 1.94) 1.08 (0.57, 1.96) Pred 1.07 (0.55, 2.04) -
Agent in columns is the numerator; agent in rows is the denominator. Outcome: serum creatinine < 132 µmol/l; or proteinuria < 0.5 g/day. Model convergence: empirical measures for chain convergence were excellent; Gelman-Rubin statistic R = 1.00 for each node consistently. The model converged. MMF: mycophenolate mofetil; Pred: prednisone alone; CYC: cyclophosphamide; Tac: tacrolimus; AZA: azathioprine
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Prior Outcome Agents CYC AZA MMF Pred Tacrolimus Flat Serum creatinine 3 Rank 3 (1, 3) 2 (1, 3) 1 (1, 3) 1 0.03 0.39 0.59 2 0.25 0.50 0.26 3 0.73 (0.00, 1.00) 0.12 (0.00, 1.00) 0.16 (0.00, 1.00) Flat Proteinuria 4 Rank 2 (1, 4) 3 (1, 4) 1 (1, 3) 3 (1, 4) 1 0.08 0.14 0.72 0.07 2 0.64 0.08 0.18 0.10 3 0.16 0.29 0.09 0.47 4 0.12 (0.00, 1.00) 0.49 (0.00, 1.00) 0.02 (0.00, 0.00) 0.36 (0.00, 1.00) Flat Proteinuria 5 Rank 3 (2, 5) 4 (1, 5) 2 (1, 4) 5 (2, 5) 1 (1, 3) 1 0.01 0.06 0.26 0.01 0.67 2 0.12 0.05 0.56 0.03 0.24 3 0.68 0.06 0.14 0.05 0.08 4 0.13 0.31 0.04 0.51 0.01 5 0.06 (0.00, 1.00) 0.52 (0.00, 1.00) 0.01 (0.00, 0.00) 0.41 (0.00, 1.00) 0.00 (0.00, 0.00) Sceptical Serum Creatinine 3 Rank 2 (1, 3) 2 (1, 3) 1 (1, 3) 1 0.10 0.21 0.69 2 0.48 0.36 0.16 3 0.42 (0.00, 1.00) 0.43 (0.00, 1.00) 0.15 (0.00, 1.00) Sceptical Proteinuria 5 Rank 3 (1, 5) 3 (1, 5) 4 (1, 5) 4 (1, 5) 3 (1, 5) 1 0.15 0.29 0.13 0.17 0.26 2 0.32 0.16 0.16 0.17 0.19 3 0.33 0.14 0.20 0.16 0.18 4 0.17 0.17 0.25 0.22 0.19 5 0.03 (0.00, 1.00) 0.25 (0.00, 1.00) 0.27 (0.00, 1.00) 0.27 (0.00, 1.00) 0.18 (0.00, 1.00) -
Agent in columns is ranked; rank in rows indicates the probability for a rank; rank is a comprehensive measure. Outcome: serum creatinine < 132 µmol/l; or proteinuria < 0.5 g/day. Model convergence: empirical measures for chain convergence were excellent; Gelman-Rubin statistic R = 1.00 for each node consistently. The model converged. sCr: serum creatinine; MMF: mycophenolate mofetil; Pred: prednisone alone; CYC: cyclophosphamide; Tac: tacrolimus; AZA: azathioprine.
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