Volume 68, Issue 2, Pages 802-812 (August 2005) Mycophenolate mofetil alleviates persistent proteinuria in IgA nephropathy  Sydney Tang, Joseph C.K. Leung, Loretta Y.Y. Chan, Y.U.N. H.O.I. Lui, Colin S.O. Tang, C.H.I. Hang Kan, Y.I.U. Wing Ho, K.A.R. Neng Lai  Kidney International  Volume 68, Issue 2, Pages 802-812 (August 2005) DOI: 10.1111/j.1523-1755.2005.00460.x Copyright © 2005 International Society of Nephrology Terms and Conditions

Figure 1 Patient recruitment and randomization. Abbreviations are: IgAN, IgA nephropathy; ACEI, angiotensin-converting enzyme inhibitors; ARB, angiotensin receptor blockers; MMF, mycophenolate mofetil. Kidney International 2005 68, 802-812DOI: (10.1111/j.1523-1755.2005.00460.x) Copyright © 2005 International Society of Nephrology Terms and Conditions

Figure 2 Probability of achieving remission of proteinuria (complete or partial) in IgA nephropathy (IgAN) subjects. Complete remission was defined as a value for urinary protein excretion that was below 0.3 g/24 hours; partial remission was defined as a decline in urinary protein excretion by 50% or more over baseline value but exceeding 0.3 g/24 hours. In the mycophenolate mofetil (MMF) group, 80% of the patients experienced a ≥50% reduction in proteinuria, as compared to 30% in the control group. All patients in both groups completed the entire 72-week follow-up period. Bottom panel shows the cumulative number of patients who had gone into remission at each interval. Kidney International 2005 68, 802-812DOI: (10.1111/j.1523-1755.2005.00460.x) Copyright © 2005 International Society of Nephrology Terms and Conditions

Figure 3 Percentage change in urinary protein excretion over time. Error bars are means ± SE. MMF is mycophenolate mofetil. Kidney International 2005 68, 802-812DOI: (10.1111/j.1523-1755.2005.00460.x) Copyright © 2005 International Society of Nephrology Terms and Conditions

Figure 4 Serial changes in peripheral blood lymphocyte count. In the control group, there was no significant change in lymphocyte count throughout the study period. In the mycophenolate mofetil (MMF)-treated group, there was progressive drop in lymphocyte count during the 24 weeks of treatment, followed by a rebound after treatment cessation. *P = 0.014; †P = 0.001; ‡P < 0.001 versus baseline value. The treatment effect on lymphocyte count at week 24 was greater in patients who received MMF than in those who did not (-22.5 ± 3.9 vs. +0.5 ± 4.5%) (P < 0.001). Error bars are means ± SE. Kidney International 2005 68, 802-812DOI: (10.1111/j.1523-1755.2005.00460.x) Copyright © 2005 International Society of Nephrology Terms and Conditions

Figure 5 Rate of change in renal function. The rates of change in serum creatinine (circles) and creatinine clearance (triangles) over the study period were calculated for each patient by linear regression analysis. The median change in serum creatinine was -0.013mg/dL in the mycophenolate mofetil (MMF) group and +0.108mg/dL in the control group (P = NS). The median change in creatinine clearance rates were -3.76mL /min/1.73m2 of body surface area in the MMF group and -1.0mL /min/1.73m2 in the control group (P = NS). Plus signs are the median values for each category. Kidney International 2005 68, 802-812DOI: (10.1111/j.1523-1755.2005.00460.x) Copyright © 2005 International Society of Nephrology Terms and Conditions

Figure 6 Systolic and diastolic blood pressure changes according to treatment group. Between-group differences for both systolic and diastolic blood pressures were not statistically significant at each time point. MMF is mycophenolate mofetil. Kidney International 2005 68, 802-812DOI: (10.1111/j.1523-1755.2005.00460.x) Copyright © 2005 International Society of Nephrology Terms and Conditions

Figure 7 Fluctuations in urine sodium excretion rates throughout the study period. MMF is mycophenolate mofetil. Kidney International 2005 68, 802-812DOI: (10.1111/j.1523-1755.2005.00460.x) Copyright © 2005 International Society of Nephrology Terms and Conditions

Figure 8 Binding to cultured mesangial cells by polymeric IgA (pIgA) isolated from patients and healthy subjects (A), and serum interleukin-6 (IL-6) concentration in patients and healthy subjects (B). (A) Polymeric IgA was isolated from IgA nephropathy (IgAN) patients at baseline, weeks 24, 48, and 72, and its binding to cultured glomerular mesangial cells was determined by flow cytometry and expressed as mean fluorescent intensity (MFI). The binding of pIgA isolated from 15 healthy volunteer subjects was also determined for comparison. *P < 0.001; †P = 0.028; ‡P = 0.016 vs. healthy subjects; §P = 0.002 vs. baseline; #P = 0.05; ¶P = 0.004;∥P = 0.047 vs. corresponding time points in group 2 (control IgAN subjects). Error bars are means ± SE. (B) Serum IL-6 concentration was assayed at baseline, weeks 24, 48, and 72. The mean serum IL-6 level (3.61 ± 0.5 pg/mL) of the 15 healthy volunteer subjects was also determined for comparison. *P < 0.001; †P = 0.005; ‡P = 0.041; **P = 0.048 vs. healthy subjects; §P = 0.001; ¶P = 0.003 vs. baseline; #P = 0.005;∥P = 0.008 vs. corresponding time points in group 2 (control IgAN subjects). *P < 0.001; †P = 0.005; ‡P = 0.04 vs. healthy subjects. Error bars are means ± SE. Kidney International 2005 68, 802-812DOI: (10.1111/j.1523-1755.2005.00460.x) Copyright © 2005 International Society of Nephrology Terms and Conditions