Background
Methods
Inclusion and exclusion criteria
Data sources and searches
Data extraction and quality assessment
Risk of bias assessment
Statistical analyses
Trial sequential analyses
Results
Basic information regarding the included studies
Study | Patient | Sample size | Intervention (treatment) | Intervention (control) | Follow-up |
---|---|---|---|---|---|
Ballardie 2002 [10] | 18 to 54 years | 38(19/19) | Prednisolone 40 mg/d (reduced to 10 mg/d by 2 year) + cyclophosphamide 1.5 mg/kg/day (adjusted down to the nearest 50 mg) | no immunosuppression | 24 M |
Cheng 2015 [11] | 18–55 years old, hypertension under control, urinary proteins 0.5–3.5 g/24 h, Cr < 265.2 μmol/L | 84(42/42) | leflunomide 20 mg/d + Valsartan | Valsartan | 24 M |
Cruzado 2011 [12] | 18–70 years old, eGFR 30-60 ml/min/1.73m2, proteinuria > 1 g/d; BP > 140/90 mmHg with proteinuria 0.3-1 g/d | 23(14/9) | SRL 1 mg/d (initial) + enalapril (or ACEI) + atorvastatin (or other statin) | Enalapril (or ACEI) + atorvastatin (or other statin) | 12 M |
Frisch 2005 [13] | 18–75 years old, protein> 1 g/d | 32(17/15) | MMF 1000 mg bid +ACEI/ARB | Placebo + ACEI/ARB | 12 M |
Harmankaya 2002 [14] | 13–63 years, mean Ccr 89.2 ± 10.2 ml/min | 43(21/22) | Prednisolone 40 mg/day + azathioprine 100 mg/day | no specific treatment | 60 M |
Hirai 2017 [15] | urinary protein excretion > 0.5 g/day, age > 16 years | 42(21/21) | MZR 150 mg once daily orally in the morning for 12 months + Standard treatment | Standard treatment | 36 M |
Hogg 2015 [16] | 7–70 years old; UPCR > 0.6 g/g (males) or > 0.8 g/g (females); eGFR> 50 mL/min/1.73 m2 (or > 40 mL/min/1.73 m2 in those already receiving ACE or ARB). | 52(25/27) | MMF 25 to 36 mg/kg/d (Max dose of 1 g/d) + lisinopril | lisinopril or placebo 25 to 36 mg/kg/d (Max dose of 1 g/d) | 12 M |
Julian 1993 [17] | Ccr > 25 ml/min/1.73 m2 | 35(17/18) | prednisone | no placebo | 12 M |
Yoshikawa 1999a [18] | < 15 Years old | 78(40/38) | Prednisolone 2 mg/kg/d in three divided doses for a total dose of not more than 80 mg/d for 4w, followed by 2 mg/kg /2d, given as a single dose in the morning of every other day for 4w, 1.5 mg/kg/2d for 4w, and 1 mg/kg/2d for 21 m + azathioprine 2 mg/kg/d in a single morning dose for 24 m + heparin-warfarin + dipyridamole | heparin-warfarin + dipyridamole | 24 M |
Katafuchi 2003 [19] | ≤60 years old, Cr < 1.5 mg/dl(132.6umol/L) | 90(43/47) | prednisolone orally: 20 mg/d for 1 month, followed by 15 mg/d for 1 month, 10 mg/d for 1 month, 7.5 mg/d for 3 months, and 5 mg/d for 18 months + dipyridamole 150–300 mg/day | Dipyridamole 150–300 mg/day | 60 M |
Kim 2013 [20] | 18–70 years old, serum creatinine ≤1.5 mg/dL or eGFR ≥45 ml/min/1.73 m2, UACR 0.3-3 g/g creatinine, BP < 130/80 mmHg | 40(20/20) | Tacrolimus 0.1 mg/kg/day, 8 weeks (maintain trough levels at 5–10 ng/ml) → 0.05 mg/kg/day, 16 weeks (maintain the trough level in 5–10 ng/ml) + RASi(9/20) | RASi(11/20), placebo | 16 W |
Koike 2008 [21] | NA | 48(24/24) | initially treated with 0.4 mg/kg/day of prednisolone (20–30 mg/day) for the first 4 weeks, and the dose was gradually reduced to 10–20 mg on alternate days for the next 12 months, and then 5–10 mg on alternate days for a subsequent year | Dipyridamole or dilazep hydrochloride | 24 M |
Pozzi 1999b [22] | 15–69 years old, urinary protein excretion of 1.0–3.5 g/d, Cr ≤ 133 umol/L (1.5 mg/dL) | 86(43/43) | methylprednisolone intravenously for 3 consecutive days; this course was repeated 2 months and 4 months later. Oral prednisone was given at a dose of 0.5 mg/kg on alternate days for 6 months. | Supportive treatment | 60 M |
Lai 1986 [23] | 14–42 years old, IgAN & NS | 34(17/17) | prednisone/prednisolone 40-60 mg/d, reduce by half after 8 weeks | Supportive therapy | 38 M |
Lv 2009 [24] | 18–65 years old, urinary proteins 1–5 g/d, eGFR> 30 ml/min | 63(33/30) | prednisone: 0.8–1.0 mg/kg/day for 8 weeks, tapered by 5–10 mg every 2 weeks + cilazapril | cilazapril | 48 M |
Lv 2017 [25] | proteinuria> 1 g/d, eGFR: 20 -120 ml/min/1.73m2 | 262(136/126) | oral methylprednisolone (0.6–0.8 mg/kg/d; maximum, 48 mg/d) | placebo | 60 M |
Maes 2004 [26] | > 18 years old, inulin clearance 20–70 mL/min/1.73m2, proteinuria > 1 g/day, BP > 140/90 mmHg, | 34(21/13) | MMF: 2 g/d + ACEI | Placebo (identical lactose-containing capsules) | 36 M |
Manno 2009 [27] | 16–70 years old, proteinuria> 1 g/d, eGFR≥50 ml/min/1.73m2 | 97(48/49) | prednisone: 1.0 mg/kg/day (Max: 75 mg/day) for 2 months, tapered by 0.2 mg/kg/day every month ramipril | ramipril | 5Y |
Rauen 2015 [28] | proteinuria> 0.75 g/d after 6 months support treatment | 162(82/80) | Supportive Care (100%) + Immunosuppression | RASi (77/80) | 36 M |
Shoji 2000 [29] | 15–55 years old, proteinuria less than 1.5 g/d, serum creatinine level less than 1.5 mg/dL | 19(11/8) | prednisolone 0.8 mg/kg of body weight; this was gradually reduced to a daily dose of 0.4 mg/kg of body weight during the first month of therapy, and then tapered to 10 mg very other day for the remainder of the 1 year of therapy | Dipyridamole 300 mg/day | 12 M |
Tang 2005c[30] | urinary proteins> 1 g/d, BP < 125/85 mmHg, Cr < 300umol/L(3.4 mg/dl) | 40(20/20) | MMF 2 g/day (weight ≥ 60 kg), 1.5 g/day (weight < 60 kg) + ACEI/ARB(16:4) | ACEI/ARB (14:6) | 72 W |
Walker 1990 [31] | 24 h pro> 1.0 g/d, 120umol/L < Cr < 200umol/L one or more | 52(25/27) | Cyclophosphamide (1–2 mg/kg/24 h - maximum of 100 mg/24 h and ajusted according to peripheral white cell counts) + dipyridamole +warfarin | no treatment | 2Y |
Wu 2016 [32] | 18–55 years, proteinuria of 0.5–3.5 g/d, serum creatinine < 265 μmol/L, blood pressure between 90/60 and 130/80 mmHg | 399(100/299) | Leflunomide 20 mg/d + telmisartan + clopidogrel placebo | Telmisartan + Leflunomide placebo + clopidogrel placebo & Telmisartan + clopidogrel + Leflunomide placebo & Telmisartan + clopidogrel | 24w |
Xie 2011 [33] | 14–70 years old, urinary protein excretion: 0.5 to 3.5 g/24 h, Cr < 353.6 umol/L | 64(34/30) | MZR 200 mg/d (weight < 50 kg), 250 mg/d (weight > 50 kg), 150 mg/d (Cr > 176.8 umol/L) + losartan | Losartan | 12 M |
Woo 1987 [34] | 48(27/21) | cyclophosphamide 1.5 mg/kg per day+ dipyridamole + warfarin | No treatment | 36 M |
Quality of trials
Effects on proteinuria
Creatinine
eGFR
ESRD
Adverse events of treatment
Main adverse events | No. of studies | Immunosuppressive agent group | Control group | RR (95% CI) | P value | ||
---|---|---|---|---|---|---|---|
FE | RE | FE | RE | ||||
Gastrointestinal | 11 | 38/431 | 8/606 | 2.53 [1.15, 5.55] | 2.42[1.07, 5.45] | 0.02 | 0.03 |
Hematologic | 9 | 16/373 | 6/551 | 2.17 [1.00, 4.68] | 2.0[0.84, 4.77] | 0.05 | 0.12 |
Dermatologic | 7 | 16/273 | 3/463 | 4.09 [1.57, 10.66] | 3.88[1.41, 10.64] | 0.004 | 0.009 |
Hepatotoxicity | 7 | 21/455 | 19/636 | 1.26 [0.72, 2.22] | 1.26[0.70, 2.24] | 0.42 | 0.44 |
Respiratory | 6 | 9/371 | 12/544 | 0.81 [0.37, 1.74] | 0.82[0.37, 1.82] | 0.58 | 0.62 |
Infection | 6 | 189/373 | 114/547 | Not estimable | Not estimable | Not estimable | Not estimable |
Impaired glucose tolerance or diabetes mellitus | 5 | 15/326 | 5/316 | 2.61 [1.04, 6.55] | 2.16[0.77, 6.05] | 0.04 | 0.14 |
Elevation of blood pressure | 4 | 14/193 | 16/389 | 0.96 [0.52, 1.79] | 0.97[0.43, 2.22] | 0.9 | 0.95 |
Malignant | 4 | 4/167 | 2/157 | 1.40 [0.39, 4.98] | 1.33[0.30, 5.93] | 0.61 | 0.71 |
Musculoskeletal | 3 | 5/238 | 3/226 | 1.47 [0.44, 4.93] | 1.37[0.40, 4.71] | 0.53 | 0.62 |
Hyperkalemia | 3 | 2/156 | 11/350 | 0.23 [0.07, 0.71] | 0.3[0.05, 1.98] | 0.01 | 0.21 |
Genitourinary | 3 | 6/59 | 0/56 | 4.59 [0.85, 24.85] | 4.07[0.71, 23.39] | 0.08 | 0.12 |
Death | 2 | 3/218 | 2/206 | 1.42 [0.24, 8.44] | 1.41 [0.23, 8.55] | 0.70 | 0.71 |