Table 2.
Summary data on the association of proteinuria reduction with long-term kidney and patient outcomes from randomized clinical trials in IgA nephropathy
| Study | N | Primary Outcome | Follow-Up (yr) | Baseline Characteristics | Measure of Proteinuria | Change in Proteinuria Significantly Associated with Outcome | ||||
|---|---|---|---|---|---|---|---|---|---|---|
| Race/Ethnicity | Proteinuria g/d | eGFR ml/min per 1.73 m2 | Unadjusted/Univariable Analysis | Adjusted/Multivariable Analysis | Variables Included in Adjusted Analysis | |||||
| Donadio et al. (46) | 106 | Increase ≥50% in serum creatinine | Mean 6.4, median 6.8 | 97% white | Fish oil 2.55±1.71, placebo 3.22±3.21 | Creatinine clearance fish oil 82±30, placebo 81±27 | Proteinuria/24 h | ND | ND | |
| Donadio et al. (47) | 73 | Slope in serum creatinine | Minimum 2 | 92% white | Low-dose fish oil 1.79 (0.76, 2.57), high-dose fish oil 1.52 (0.70, 3.60) | Serum creatinine low-dose fish oil 2.1 (0.7), high-dose fish oil 2.3 (0.7) | Proteinuria/24 h | ND | ND | |
| Katafuchi et al. (48) | 90 | Change in urine protein excretion from baseline | Mean 5.4 | Asian (Japan) | Steroid 2.2±2, control 1.1±0.9 | Creatinine clearance steroid 90.8±27.3, control 90.5±26.1 | UPCR | No | ND | |
| Maes et al. (49) | 34 | Decrease ≥25% in inulin clearance during the 3-yr treatment period | All for 3 yr | >90% white | MMF 1.9±0.3, placebo 1.3±0.4 | Inulin clearance MMF 73±5, placebo 69±7 | Proteinuria/24 h | ND | ND | |
| Frisch et al. (50) | 32 | 50% increase in baseline serum creatinine | Mean 1.3, range 0.1–2.5 | 72% white, 16% Asian, 12% Hispanic | MMF 2.7±1.6, placebo2.7±1.4 | Creatinine clearance MMF 57±28.6, placebo 75±42.3 | Proteinuria/24 h | No | ND | |
| Li et al. (43) | 109 | Time to doubling of baseline serum creatinine level or ESKD | All for 2 yr | Chinese (Hong Kong) | Placebo 2.3±1.7, valsartan 1.8±1.2 | Placebo 87±36, valsartan 87±36 | Proteinuria/24 h | Yes | Yes | Average BP, treatment, proteinuria |
| Lv et al. (37) | 63 | 50% increase in serum creatinine | Mean 2.3, SD 0.6, range 1.3–4 | Chinese | Cilazapril 2.0±0.8, cilazapril and steroid 2.5±0.9 | MDRD cilazapril 101.5, cilazapril and steroid 101.2 | Proteinuria/24 h TA-P was defined as the average of the mean of every 6-mo period of proteinuria measurements | Yes | Yes | “Sex, age, kidney function, hypertension, proteinuria, TA-MAP, TA-P, and treatment” |
| Manno et al. (51) | 97 | Combination of doubling of baseline serum creatinine or ESKD | Median 5, range 3–9 | ND (Italian study) | Ramipril 1.5 (1.4–2.3), prednisolone and ramipril 1.7 (1.2–2.5) | MDRD ramipril 97.5±27.7, prednisolone and ramipril 100.4±26.1 | Proteinuria/24 h | Yes during the first 2 yr of follow-up | ND | |
| Tang et al. (52) | 40 | ESKD and doubling of serum creatinine | 6 yr for all participants | 100% Chinese | MMF 1.8±0.21, control 1.87±0.28 | MMF 52.5±4.40, control 50.0±4.51 | Proteinuria/24 h and ACR changes from baseline to each time point | Yes | Yes | “Age, gender, BP, and histologic score” |
| Pozzi et al. (53) | 207 | 50% increase in serum creatinine | Median 4.9, IQR 3.0–6.4 | Does not state, 27 Swiss and Italian nephrology centers | 2.0 (IQR 1.5–3.0) | MDRD 66 (48–87) | 24 h collection. “Proteinuria over time.” Absolute reduction. | Yes | Yes | Age, sex, systolic BP, antihypertensive medications, RAS blocker, complete remission of proteinuria, treatment group |
| Pozzi et al. (54) | 46 | 50% increase in plasma creatinine from baseline | Median 4.5, IQR 2.9–6.1 | Does not state | 2.4 (IQR 1.5–3.8) | MDRD 25 (20–31), C-G 34 (25–41) | Proteinuria/24 h. Absolute reduction from baseline, 6 mo, 12 mo, then yearly to end of follow-up | Yes | Yes | Sex, proteinuria, antihypertensive medications, RAS blocker, treatment group |
| Rauen et al. (STOP-IgAN) (39) | 162 | UPCR<0.2 g/g and decrease in EPI eGFR of <5 ml/min per 1.73 m2 from baseline eGFR, decrease in the EPI eGFR of at least 15 ml/min per 1.73 m2 from baseline eGFR | 0.5 yr run-in 3-yr for trial | Does not state, 32 German nephrology centers | Supportive 1.6±0.7 g/d, supportive plus immunosuppression 1.8±0.8 g/d | EPI supportive 57.4±24.9, supportive plus immunosuppression 61.1±29.0 | Proteinuria/24 h during the run-in phase, switch to UPCR during the randomized, controlled trial phase | ND | No (RCT) | |
| Lv et al. 2017 (TESTING) (40) | 262 | 40% decrease in eGFR, ESKD, and death due to kidney failure | Median 2.1 yr, no IQR stated for whole study | 95.8% Chinese, 3.1% white, 1.1% Southeast Asian | Methylprednisolone 2.55±2.45, placebo 2.23±1.11 | EPI methylprednisolone 60.0±24.8, placebo 58.6±25.2 | Proteinuria reduction (TA-P). Proteinuria remission defined as <200 mg/24 h and partial proteinuria remission defined as <50% of baseline and <1 g/24 h. | Yes (RCT) | No (RCT) | |
ND, not done; UPCR, urine protein-to-creatinine ratio; MMF, mycophenolate mofetil; MDRD, modification of diet in renal disease equation for estimating GFR; TA-P, time average proteinuria; TA-MAP, time-average mean arterial pressure; ACR, albumin-to-creatinine ratio; IQR, interquartile range; C-G, Cockroft-Gault equation for estimating creatinine clearance; RAS, renin angiotensin system; STOP-IgA, STOP-IgAN trial; EPI, epidemiology collaboration (CKD-EPI) equation for estimating GFR; RCT, randomized, controlled trial.