Table 1. Characteristics of Included RCTs.
| Study | Location | N | Mean age (range) | Diabetestype | Microalbuminuria definition | BP categories | Intervention(s) | Follow-up (months) |
|---|---|---|---|---|---|---|---|---|
| ABCD-2V (Estacio) 2006 [28] | USA | 129 | 56.1 (40–81) | 2 | UAER 20–200 μg/min | Normotensive | Valsartan 80 mg/d, then valsartan 160 mg/d then HCTZ 12.5 mg/d, 25 mg/d, then metoprolol 50 mg/d, 100 mg twice a day; placebo | 22.8 |
| Atmaca 2006 [29] | Turkey | 26 | 55.1 (36.7–73.5)* | 2 | UAER 30–300 mg/d | Normotensive | Lisinopril 10 mg/d, losartan 50 mg/d, lisinopril 10 mg/d + losartan 50 mg/d | 12 |
| Bojestig 2001 [30] | Sweden | 55 | 39.6 (20.3–58.9)* | 1 | Urine albumin to creatinine ratio 2.5–25 mg/mmol | Normotensive | Ramipril 1.25 mg/d, ramipril 5 mg/d, placebo | 48 |
| CALM (Mogensen) 2000 [31] | Multi-national | 199 | 60.0 (30–75) | 2 | Urine albumin to creatinine ratio 2.5–25 mg/mmol | Hypertensive | Lisinopril 20 mg/d, candesartan 16 mg/d, lisinopril 20 mg/d + candesartan 16 mg/d | 3 |
| ESTIMATE-A (Kojima) 2013 [32] | Japan | 40 | 68.1 (20–75) | 2 | UAE> 30 mg/g creatinine and serum creatinine <1.5 mg/dl for men and <1.2 mg/dl for women | Hypertensive | Telmisartan 40–80 mg/d + TCMZ 1 mg/d, telmisartan 40–80 mg/d + TCMZ 1 mg/d + amlodipine 5 mg/d | 6 |
| EUCLID (Chaturvedi) 1997 [33] | UK | 530 | 33.0 (20–59) | 1 | UAER 20–200 μg/min | Hypertensive | Lisinopril 10–20 mg, placebo | 24 |
| Fogari 1997a [34] | Italy | 50 | 53.9 (51.6–56.1)* | 2 | UAER 30–300 mg/d;serum creatinine<1.4 mg/dl | Hypertensive | Amlodipine 10 mg/d, enalapril 20 mg/d | 12 |
| Fogari 1997b [34] | Italy | 45 | 57.1 (54.7–59.5)* | 2 | UAER 30–300 mg/d;serum creatinine> = 1.3 mg/dl | Hypertensive | Benazepril 10 mg/d, benazepril 10 mg/d + amlodipine 5 mg/d | 6 |
| Fogari 2000 [35] | Italy | 254 | 68.3 (60–75) | 2 | UAER 30–300 mg/d;serum creatinine<1.3 mg/dl | Hypertensive | Amlodipine 5–10 mg/d, fosinopril 10–20 mg/d, placebo | 24 |
| Fogari 2002 [36] | Italy | 453 | 62.5 (44.4–80.7)* | 2 | UAER 30–300 mg/d;serum creatinine<1.5 mg/dl | Hypertensive | Fosinopril 10–30 mg/d, amlodipine 5–15 mg/d, fosinopril 10–30 mg/d + amlodipine 5–15 mg/d | 48 |
| Fogari 2005 [37] | Italy | 121 | 60.3 (47.2–73.3)* | 2 | UAER 30–300 mg/d;serum creatinine<1.4 mg/dl | Hypertensive | Manidipine 10 mg/d, lisinopril 10 mg/d | 24 |
| Fogari 2007 [38] | Italy | 174 | 55.7 (40–65) | 2 | UAER 30–300 mg/d | Hypertensive | Candesartan 16 mg/d + manidipine 10–20 mg/d, candesartan 16 mg/d + HCTZ 12.5–25 mg/d | 6 |
| Fogari 2012 [39] | Italy | 109 | 65.0 (30–75) | 2 | UAER 30–300 mg/d | Hypertensive | Valsartan 160 mg/d + amlodipine 5 mg/d + canrenone 25–50 mg/d, valsartan 160 mg/d + amlodipine 5 mg/d + HCTZ 12.5–25 mg/d | 6 |
| Fogari 2013 [40] | Italy | 176 | 60.8 (25–75) | 2 | UAER 200–300 mg/d | Hypertensive | Imidapril 10–20 mg/d, ramipril 5–10 mg/d | 6 |
| JAPAN-IDDM (Katayama) 2002 [41] | Japan | 79 | 30.9 (20–50) | 1 | UAER>30 mg/d | Hypertensive | Captopril 37.5 mg/d, imidapril 5 mg/d, placebo | 17.8 |
| Jerums 2001 [42] | Australia | 33 | 30.8 (16–65) | 1 | UAER 20–200 μg/min;serum creatinine<200 μmol/l | Normotensive | Perindopril 2–8 mg/d, nifedipine 20–80 mg/d, placebo | 67.2 |
| Josefsberg 1995 [43] | Canada | 21 | 53.0 (37–68) | 2 | UAER 20–200 μg/min | Hypertensive | Nitrendipine 10–40 mg/d, enalapril 5–20 mg/d | 7.5 |
| Kohlmann 2009 [44] | Multi-national | 110 | 63.3 (45–81) | 2 | Urine albumin to creatinine ratio 2.5–25 mg/mmol for men and 3.5–25 mg/mmol for women | Hypertensive | Manidipine 10 mg/d + delapril 30 mg/d, losartan 50 mg/d + HCTZ 12.5 mg/d | 12 |
| Lacourciere 2000 [45] | Canada | 103 | 58.5 (38.8–78.2)* | 2 | UAER 20–350 μg/min;serum creatinine<1.7 mg/dl | Hypertensive | Losartan 50 mg/d, enalapril 5–10 mg/d | 12 |
| Li 2015 [46] | China | 98 | 58.6 (38.8–78.3)* | 2 | UAER 20–200 μg/min, GFR 50–120 ml/min, serum creatinine 50–100 μmol/l | Mixed | Tangshen formula, placebo | 6 |
| MARVAL (Viberti) 2002 [47] | UK | 368 | 58.0 (35–75) | 2 | UAER 20–200 μg/min;normal serum creatinine | Mixed | Valsartan 80 mg/d, amlodipine 5 mg/d | 6 |
| Muirhead 1999 [48] | Canada | 122 | 56.0 (35.9–76.2)* | 2 | UAER 20–300 μg/min;GFR > = 60 ml/min | Mixed | Valsartan 80 mg/d, valsartan 160 mg/d, captopril 75 mg/d, placebo | 12 |
| Melbourne Diabetic Nephropathy Study Group (Doyle) 1991 [49] | Australia | 43 | 50.0 (18–66) | 1 and 2 | UAER 20–200 μg/min;serum creatinine<2.3 mg/dl | Separate normotensive and hypertensive cohorts | Perindopril 2–8 mg/d, nifedipine 10–40 mg twice daily | 12 |
| Nakamura 2002 [50] | Japan | 60 | 56.5 (37.6–75.4)* | 2 | UAER 20–200 μg/min | Normotensive | Trandolapril 2 mg/d, candesartan 8 mg/d, trandolapril 2 mg/d + candesartan 8 mg/d, placebo | 18 |
| Perez-Maraver 2005 [51] | Spain | 36 | 60.4 (45.6–75.2)* | 2 | UAER 30–300 μg/min | Hypertensive | Captopril 25 mg/12 h-50 mg/8 h, captopril 25 mg/12 h-50 mg/8 h + diltiazem 120 mg/d | 24 |
| Poulsen 2001 [52] | Denmark | 21 | 32.4 (18.0–52.2)* | 1 | UAER 20–70 μg/min | Normotensive | Lisinopril 20 mg/d, placebo | 24 |
| PREMIER (Mogensen) 2003 [53] | Multi-national | 481 | 59.6 (40–75) | 2 | UAER 20–500 μg/min, serum creatinine<1.6 mg/dl | Hypertensive | Perindopril 2–8 mg/d + 0.625–2.5 mg/d indapamide, enalapril 10–40 mg/d | 12 |
| Sano 1994 [54] | Japan | 48 | 63.5 (50–76) | 2 | UAER 20–500 μg/min, serum creatinine<140 μmol/l | Normotensive | Enalapril 5 mg/d, placebo | 48 |
| Sato 2003 [55] | Japan | 50 | 63.3 (43.1–83.6)* | 1 and 2 | UAE 30–300 mg/g creatinine,GFR< = 60 ml/min | Separate hypertensive and normotensive cohorts | ACEI (trandolapril 1.5 mg/d or enalapril 7.5 mg/d), candesartan 7.1 mg/d | 11 |
| Schnack 1994 [56] | Austria | 15 | 37.9 (29.9–45.9)* | 1 | UAER 30–300 mg/d;serum creatinine<1.4 mg/dl | Normotensive | Nifedipine 30 mg/d, placebo | 12 |
| Sengul 2006 [57] | Turkey | 145 | 57.2 (40–65) | 2 | UAER 30–300 mg/d;creatinine< = 1.7 mg/dl | Hypertensive | Lisinopril 20 mg/d, telmisartan 80 mg/d, lisinopril 20 mg/d + telmisartan 80 mg/d (following lisinopril monotherapy), lisinopril 20 mg/d + telmisartan 80 mg/d (following telmisartan monotherapy) | 7 |
| Shigihara 2000 [58] | Japan | 30 | 62.9 (56.0–69.7)* | 2 | Microalbuminuria | Hypertensive | ACEI (enalapril 7.0 mg/d, trandolapril 1.6 mg/d, or imidapril 9.2 mg/d), ACEI (enalapril 5.3 mg/d, trandolapril 1.6 mg/d, or imidapril 5 mg/d) + amlodipine 7.0 mg/d | 3 |
| Takebayashi 2006 [59] | Japan | 37 | N/R | 2 | UAE>30 mg/g creatinine | Mixed | Spironolactone 50 mg/d, amlodipine 2.5 mg/d | 3 |
| Tan 2002 [60] | China | 80 | 54.5 (35.6–73.4)* | 2 | UAER 20–200 μg/min | Mixed | Losartan 50 mg/d, placebo | 6 |
| Tutuncu 2001 [61] | Turkey | 34 | 55.6 (38.7–72.5)* | 2 | UAER 30–300 mg/d | Normotensive | Enalapril 5 mg/d, losartan 50 mg/d, enalapril 5 mg/d + losartan 50 mg/d | 12 |
| Weil 2013 [62] | USA | 78 | 42.1 (22.3–61.9)* | 2 | ACR 30–300 mg/g;serum creatinine <1.4 mg/dl | Mixed | Losartan 50–100 mg/d, placebo | 70.8 |
| Viberti 1994 [63] | Multi-national | 92 | 31.5 (18–54) | 1 | UAER 20–200 μg/min;serum creatinine<150 μmol/l | Normotensive | Captopril 100 mg/d, placebo | 24 |
| Zandbergen 2003 [64] | Netherlands | 147 | 57.7 (34.4–81.0)* | 2 | UAER 20–200 μg/min; serum creatinine< = 1.7 mg/dl | Normotensive | Losartan 50–100 mg/d, placebo | 2.5 |
*Age range estimated from the reported standard deviations (SDs) [65].
Abbreviations: UAE, urine albumin excretion; UAER, urine albumin excretion rate; ACR, albumin-to-creatinine ratio; GFR, glomerular filtration rate; ACEI, angiotensin-converting enzyme inhibitor; HCTZ, hydrochlorothiazide; TCMZ, trichlormethiazide