Table 2 Effects of thiazide and loop diuretics on proteinuria or albuminuria in subjects with CKD
Study | No. of subjects | Study duration (follow-up) | Renal function and albuminuria (proteinuria) at baseline | Comparison | Outcome measure | Results |
|---|---|---|---|---|---|---|
Thiazide diuretics (thiazide-type/thiazide-like) | Â | Â | Â | Â | Â | Â |
 Buter et al. [61] (1998) | 7 | 12 wk | Creatinine clearance 51–101 mL/min with proteinuria of 1.4–5.6 g/day | Low sodium vs. high sodium vs. high sodium intake plus hydrochlorothiazide, with ACEi | Creatinine clearance, 24-hr proteinuria | Decreased mean 14 mL/min in creatinine clearance Decreased mean 1.7 g/day in 24-hr proteinuria after addition of hydrochlorothiazide to high sodium intake compared with high salt intake alone |
 Uzu et al. [62] (2005) | 25 | 8 wk | Serum creatinine ≤ 1.2 mg/dL with proteinuria of 0.5–3.0 g/day | ACEi vs. ARB, with and without trichlormethiazide | Creatinine clearance, 24-hr proteinuria | No difference in creatinine clearance Decreased 0.48 g/day in proteinuria after addition of thiazide |
 Vogt et al. [63] (2008) | 34 | 36 wk | Creatinine clearance > 30 mL/min with proteinuria of 2–10 g/day | Placebo vs. ARB vs. ARB plus hydrochlorothiazide, during high salt or low salt diet (crossover) | 24-hr proteinuria, serum creatinine | Decreased proteinuria by 56% with adding hydrochlorothiazide and by 70% with combined addition of hydrochlorothiazide and low-sodium diet Same pattern in change of creatinine clearance after adding hydrochlorothiazide |
 Kwakernaak et al. [64] (2014) | 45 | 30 wk | Creatinine clearance 101 ± 47 mL/min/1.73 m2 with mean albuminuria of 711 mg/day | Placebo vs. hydrochlorothiazide, with regular sodium or sodium restriction, during background ACEi (crossover) | Albuminuria, renal function | Decreased mean albuminuria to 393 mg/day by sodium restriction, 434 mg/day by hydrochlorothiazide and 306 mg/day by their combination Creatinine clearance unaffected by sodium restriction but decreased 14 mL/min by the combination |
 Hoshino et al. [65] (2015) | 11 | 12 mo | eGFR 21.5 ± 8.1 mL/min/1.73 m2 with proteinuria 6.7 ± 3.9 g/g | Addition of hydrochlorothiazide to existing antihypertensive medication including loop diuretics | Proteinuria, eGFR | Decreased 4.3 g/g in proteinuria Decreased 8.4 mL/min/1.73 m2 in eGFR after initiation of hydrochlorothiazide |
 Agarwal et al. [35] (2014) | 14 | 12 wk | eGFR 20–45 mL/min/1.73 m2 with mean baseline urine albumin excretion rate 604 mg/g during day and 535 mg/g during night | With vs. without chlorthalidone | Urine albumin to creatinine ratio | Decreased albuminuria by 40–45% Transient increase in plasma creatinine by 0.24 ± 0.14 mg/mL at week 8 (returning to baseline at week 12) in chlorthalidone group |
 CLICK trial [8] (2021) | 160 | 12 wk | eGFR 23.2 ± 4.2 mL/min/1.73 m2 with urine albumin excretion rate 862 mg/g for chlorthalidone and 812 mg/g for placebo | Placebo vs. chlorthalidone | Urine albumin to creatinine ratio, eGFR | Decreased albuminuria by 52% in chlorthalidone group Between-group difference by − 2.2 mL/min/1.73 m2 in eGFR (lower in chlorthalidone group) |
 Marre et al. [66] (2004) | 570 | 1 yr | Creatinine clearance 91.5 ± 29.5 mL/min and urine albumin to creatinine ratio 6.16 mg/mmol in indapamide group; 93.4 ± 29.2 mL/min and urine albumin to creatinine ratio 6.17 mg/mmol in ACEi group | Indapamide sustained release vs. enalapril | Urine albumin to creatinine ratio, creatinine clearance | Improvement to normoalbuminuria by 40% in indapamide group and by 42% in ACEi group without change in creatinine clearance between two groups |
Loop diuretics | Â | Â | Â | Â | Â | Â |
 Esnault et al. [67] (2005) | 18 | 8 wk | Serum creatinine 151.22 ± 63.9 µmol/L with 24-hr proteinuria 3.71 ± 2.1 g/day | Ramipril 5 mg vs. ramipril 10 mg vs. valsartan 160 mg vs. combined of ramipril 5 mg and valsartan 80 mg vs. combined of ramipril 5 mg and valsartan 80 mg plus increased furosemide dosage (20–80 mg) | Urine protein to creatinine ratio, 24-hr proteinuria, serum creatinine | Decreased proteinuria by 18.9% in combined ramipril and valsartan group and by 44.5% in combined ramipril, valsartan and increased furosemide Increased serum creatinine by 7.6% in combined ramipril and valsartan group and by 26.2% in combined ramipril, valsartan and increased furosemide |
 Esnault et al. [68] (2010) | 18 | 18 wk | eGFR 39.2 mL/min/1.73 m2 with 24-hr proteinuria 1.97 g/day | Combined ramipril 5 mg and valsartan 80 mg vs. combined ramipril 10 mg and valsartan 160 mg vs. combined ramipril 5 mg, valsartan 80 mg and increased furosemide dosage | Urine protein to creatinine ratio, 24-hr proteinuria, eGFR | Proteinuria 1.95 g/day by combining low doses of ramipril and valsartan vs. 1.75 g/day by combining higher doses ramipril and valsartan vs. 1.20 g/day by combining lower doses of ramipril and valsartan plus increased furosemide dosage eGFR 40.4 mL/min/1.73 m2 by combining lower doses of ramipril and valsartan vs. eGFR 38.1 mL/min/1.73 m2 by combining higher doses of ramipril and valsartan vs. eGFR 33.4 mL/min/1.73 m2 by combining lower doses of ramipril and valsartan plus increased furosemide dosage |