Table 2.

Summary data on the association of proteinuria reduction with long-term kidney and patient outcomes from randomized clinical trials in IgA nephropathy

StudyNPrimary OutcomeFollow-Up (yr)Baseline CharacteristicsMeasure of ProteinuriaChange in Proteinuria Significantly Associated with Outcome
Race/EthnicityProteinuria g/deGFR ml/min per 1.73 m2Unadjusted/Univariable AnalysisAdjusted/Multivariable AnalysisVariables Included in Adjusted Analysis
Donadio et al. (46)106Increase ≥50% in serum creatinineMean 6.4, median 6.897% whiteFish oil 2.55±1.71, placebo 3.22±3.21Creatinine clearance fish oil 82±30, placebo 81±27Proteinuria/24 hNDND
Donadio et al. (47)73Slope in serum creatinineMinimum 292% whiteLow-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 hNDND
Katafuchi et al. (48)90Change in urine protein excretion from baselineMean 5.4Asian (Japan)Steroid 2.2±2, control 1.1±0.9Creatinine clearance steroid 90.8±27.3, control 90.5±26.1UPCRNoND
Maes et al. (49)34Decrease ≥25% in inulin clearance during the 3-yr treatment periodAll for 3 yr>90% whiteMMF 1.9±0.3, placebo 1.3±0.4Inulin clearance MMF 73±5, placebo 69±7Proteinuria/24 hNDND
Frisch et al. (50)3250% increase in baseline serum creatinineMean 1.3, range 0.1–2.572% white, 16% Asian, 12% HispanicMMF 2.7±1.6, placebo2.7±1.4Creatinine clearance MMF 57±28.6, placebo 75±42.3Proteinuria/24 hNoND
Li et al. (43)109Time to doubling of baseline serum creatinine level or ESKDAll for 2 yrChinese (Hong Kong)Placebo 2.3±1.7, valsartan 1.8±1.2Placebo 87±36, valsartan 87±36Proteinuria/24 hYesYesAverage BP, treatment, proteinuria
Lv et al. (37)6350% increase in serum creatinineMean 2.3, SD 0.6, range 1.3–4ChineseCilazapril 2.0±0.8, cilazapril and steroid 2.5±0.9MDRD cilazapril 101.5, cilazapril and steroid 101.2Proteinuria/24 h TA-P was defined as the average of the mean of every 6-mo period of proteinuria measurementsYesYes“Sex, age, kidney function, hypertension, proteinuria, TA-MAP, TA-P, and treatment”
Manno et al. (51)97Combination of doubling of baseline serum creatinine or ESKDMedian 5, range 3–9ND (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±26.1Proteinuria/24 hYes during the first 2 yr of follow-upND
Tang et al. (52)40ESKD and doubling of serum creatinine6 yr for all participants100% ChineseMMF 1.8±0.21, control 1.87±0.28MMF 52.5±4.40, control 50.0±4.51Proteinuria/24 h and ACR changes from baseline to each time pointYesYes“Age, gender, BP, and histologic score”
Pozzi et al. (53)20750% increase in serum creatinineMedian 4.9, IQR 3.0–6.4Does not state, 27 Swiss and Italian nephrology centers2.0 (IQR 1.5–3.0)MDRD 66 (48–87)24 h collection. “Proteinuria over time.” Absolute reduction.YesYesAge, sex, systolic BP, antihypertensive medications, RAS blocker, complete remission of proteinuria, treatment group
Pozzi et al. (54)4650% increase in plasma creatinine from baselineMedian 4.5, IQR 2.9–6.1Does not state2.4 (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-upYesYesSex, proteinuria, antihypertensive medications, RAS blocker, treatment group
Rauen et al. (STOP-IgAN) (39)162UPCR<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 eGFR0.5 yr run-in 3-yr for trialDoes not state, 32 German nephrology centersSupportive 1.6±0.7 g/d, supportive plus immunosuppression 1.8±0.8 g/dEPI supportive 57.4±24.9, supportive plus immunosuppression 61.1±29.0Proteinuria/24 h during the run-in phase, switch to UPCR during the randomized, controlled trial phaseNDNo (RCT)
Lv et al. 2017 (TESTING) (40)26240% decrease in eGFR, ESKD, and death due to kidney failureMedian 2.1 yr, no IQR stated for whole study95.8% Chinese, 3.1% white, 1.1% Southeast AsianMethylprednisolone 2.55±2.45, placebo 2.23±1.11EPI methylprednisolone 60.0±24.8, placebo 58.6±25.2Proteinuria 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.