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Controlled Trial of Antiplatelet Agents in Mesangial IgA Glomerulonephritis
Controlled Trial of Antiplatelet Agents in Mesangial IgA Glomerulonephritis M.K. Chan, MD, FRCP (Edin), S.YL. Kwan, MSSS, MRCP (UK), K.W. Chan, MSSS, MRCPath, and C.K. Yeung, MSSS, FRACP • A trial of antiplatelet therapy (slow-release aspirin and dipyridamole) in mesangial IgA glomerulonephritis was conducted. Vitamin B was given to the control group. Altogether, 38 patients were observed for a mean of 33.2 months. Antiplatelet therapy did not favorably modify the course of mesangial IgA glomerulonephritis. The rate of progression of the disease, measured by the slope of reciprocals of serum creatinine v time plots, correlated significantly with the severity of tissue damage as assessed by an arbitrary morphologic score from renal biopsy specimens. © 1987 by the National Kidney Foundation, Inc. INDEX WORDS: Antiplatelet agents; IgA glomerulonephritis.
M
ESANGIAL IgA glomerulonephritis not infrequently follows a relentlessly downhill course. 1 In our experience, the disease proceeds to end-stage renal failure in 20% to 30% of cases . 2 No effective treatment has been reported. 3 Here we report the results of a controlled trial of antiplatelet agents (a combination of slow-release aspirin and dipyridamole) in patients with biopsyproven mesangial IgA glomerulonephritis. PATIENTS AND METHODS Fifty-two patients with biopsy-proven mesangial IgA glomerulonephritis were randomly allocated to either the treatment group or the control group. Eight patients defaulted within 6 months and another six within 18 months. The treatment group received slow-release aspirin, 650 mg daily, and dipyridamole, 25 to 75 mg thrice daily. The control group received vitamin B complex . By coincidence, there were 19 evaluable patients in each group. On entry into the study, all had blood taken for serum creatinine, albumin, uric acid, calcium, phosphate, IgG, IgA, and IgM. Twenty-four-hour urinary protein excretion was measured and endogenous creatinine clearance determined. The period of observation before the patients were entered for the study was 17.6 ± 2.2 months (mean ± SEM) and the study was conducted for 33.2 ± 1.5 months (mean ± SEM). Blood pressure was monitored and hypertension controlled with antihypertensive agents. Renal biopsy specimens obtained at the time when diagnosis was first made were examined by one of us (KWC), who had no knowledge of the clinical condition of the patients. The histologic changes were arbitrarily graded. Proliferative changes, glomerular sclerosis, and changes in the tubules and the interstitium were graded separately and the score for each morphologic index ranged from 0 to I. The total morphologic score ranged from 0 for normal kidneys to 3 for the most severely affected. Reciprocals of serum creatinine concentrations were plotted against time in months and linear regression analysis was applied. The slope of the regression line was taken as an indication of the rate of change in glomerular filtration . Before the commencement of medication, the number of points used to generate the slopes of the regression line varied from 3 to 7 with a mean of
4, and after the commencement of medications, it varied from 3 to 11 with a mean of7. Statistical analysis was performed on a computer using the Minitab program (Minitab, Inc, University Park, PA). The two-sample t test was used for comparison of differences between treatment and control groups, and the paired t test used to evaluate differences within the same group before and after the commencement of the study.
RESULTS
The demographic data of the two groups of patients are listed in Table 1. The two groups were well matched regarding age, morphologic changes as observed in renal biopsies, renal function profile, and serum immunoglobulins, except that the mean serum IgG was significantly higher in the treatment group than in the control group. Urinary protein excretion and creatinine clearance were comparable between the two groups. There was no statistically significant difference in the rate of deterioration in glomerular filtration between the two groups before the study. The renal function profile at the end of the study and the slopes of the lIcreatinine v time curves of the two groups after the commencement of "treatment" with either vitamin B complex or antiplatelet agents are also shown in Table 1. There was no statistically significant difference in these values between the two groups. Within the same group, no significant difference in the slopes of the plots From the Departments of Medicine and Pathology, Queen Mary Hospital, University of Hong Kong. Address reprint requests to M.K. Chan , MD , Department of Medicine , Queen Mary Hospital, University of Hong Kong, Hong Kong. © 1987 by the National Kidney Foundation , lnc. 0272-6386/87/0903-0005$03.00/0
American Journal of Kidney Diseases, Vol IX, No 5 (May), 1987: pp 417-421
417
418
CHAN ET AL
Table 1.
Demographic and Biochemical Data of Patients With Mesangial IgA Glomerulonephritis Before Commencement of Therapy
No. of patients (sex) Age (yrs) Body weight (kg) Systolic BP (mm Hg) Diastolic BP (mm Hg) Creatinine (mmol/L) Albumin (gIL) Uric acid (mmoI/L) Calcium (mmol/L) Phosphate (mmoI/L) IgG (mg/dL) IgA (mg/dL) 19M (mg/dL) C3 (mg/dL) C4 (mg/dL) 24-h Urine protein (g) Creatinine clearance (mUmin) Morphologic score Slope of (1/Cr v time)
End of Study '
Antiplatelet
Vitamin B
Antiplatelet
Vitamin B
19 (10 M + 9 F) 29.0 ± 2.5 62 .0 ± 1.9 135 ± 4 82 ± 2 0.125 ± 0.017 42 ± 0.7 0.39 ± 0.02 2.38 ± 0.03 1.10 ± 0.05 1307 ± 74 340 ± 26 182 ± 21 108 ± 5 60 ± 5 1.57 ± 0.18 77 ± 6 1.188 ± 0.096 - 0.088 ± 0.054
19 (14 M + 5 F) 27.5 ± 1.9 62.6 ± 2.2 139 ± 4 82 ± 2 0.130 ± 0.015 44 ± 0.9 0.45 ± 0.04 2.36 ± 0.03 1.65 ± 0.53 1085 ± 70§ 306 ± 22 189 ± 19 109 ± 6 61 ± 5 1.72 ± 0.35 73 ± 7 1.139 ± 0.125 0.001 ± 0.031
19 (10 M + 9 F) 31.7 ± 2.6 63.1 ± 2.0 132 ± 4 80 ± 2 0.198 ± 0.056 42 ± 1 0.45 ± 0.03t 2.31 ± 0.04 1.32 ± 0.10:j: NO NO NO NO NO 2.46 ± 0.78 78 ± 9 NO - 0.080 ± 0.084
19 (14 M + 5 F) 30.1 ± 1.8 64.1 ± 2.2 132 ± 4 81 ± 2 0.199 ± 0.052 43 ± 1 0.44 ± 0.03 2.25 ± 0.06 1.28 ± 0.11 NO NO NO NO NO 2.21 ± 0.54 72 ± 8 NO -0.0018 ± 0.0198
All values are in mean ± SEM. Abbreviations: ND, not done; Cr, creatinine . • All parameters listed were values obtained at the end of the study except the slope of (1/Cr v time), which was calculated from values of creatinine concentrations during the period the patients received medications. tOifferent from pre-treatment values, P = .004. :j:Oifferent from pre-treatment values, P = .03. §Oifferent from anti platelet group, P = .04.
was noted after the commencement of treatment, nor was any difference in the mean serum creatinine concentration observed between the two groups at the conclusion of the study. Within each group, there was no significant difference between any of the parameters measured at the start and at the end of the study when the paired t test was applied. The lIcreatinine v time plots for the control group is shown in Fig 1. Three patients had rather rapid deterioration of renal function , ending in end-stage renal failure during the period of observation. Figure 2 shows the IIcreatinine plots of the treatment group. As in the control group , rapid deterioration in renal function occurred in three patients. However, five patients showed a significant improvement in renal function with a readily noticeable increase in the slope of their 1I creatinine v time plots . Since there was no discernible difference between the treatment and the control groups, data from the two groups were pooled and regression analysis applied to see if any parameter correlated with the morphologic scores and the slopes of 11 creatinine v time plots, respectively. A significant correlation between morphologic scores and the
slopes of IIcreatinine v time became apparent (r = - .46, P < .01) (Fig 3) . The latter also correlated, respectively, with serum creatinine (r = - .56, P < .001), serum phosphorus (r = - .49, P < .01), and creatinine clearance (r = - .42, P = .01) measured at the end of the study. Not unexpectedly, the slopes of IIcreatinine v time before the commencement of the study correlated significantly with that observed afterward (r = .65, P < .001) (Table 1). When glomerular sclerosis, glomerular proliferative changes, and tubulointerstitial changes were separately correlated with the slopes of 1/creatinine v time, it appeared that each component contributed more or less equally to the correlation, since r was - .30 for glomerular sclerosis, -.31 for glomerular proliferative changes, - .42 for tubulointerstitial changes, and - .46 for the total morphologic score. DISCUSSION
Attention has been called to the role of platelets in glomerular diseases. 4 Antiplatelet agents have been used to treat mesangiocapillary glomerulonephritis with conflicting results. 5 .6 Mesangial proliferation is the hallmark of IgA glomerulonephritis, and our trial with anti platelet agents was initiated along lines of reasoning similar to
419
ANTI PLATELETS AND IGA GLOMERULONEPHRITIS 20
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Time In months Fig 1. Plot showing reciprocals of serum creatinine against time in patients with mesanglal IgA glomerulonephritis who received vitamin B complex. There was no significant difference between the mean slopes of the plot before and after commencement of therapy (.001 v - .0018, P = not significant).
complex as a control drug partly because it was difficult to obtain placebo for combination drugs and partly because some form of medication was needed to ensure our patients' regular attendance. Although an influence of vitamin B complex on the course of IgA glomerulonephritis cannot be ruled
those used when anti platelet therapy was tried for mesangiocapillary glomerulonephritis. We used a combination of slow-release aspirin and dipyridamole because there is evidence that aspirin and dipyridamole affect platelet function at different sites. 7 We had to resort to the use of vitamin B 20
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Fig 2. Plot showing reciprocals of serum creatinine against time in patients with mesangial IgA glomerulonephritis who received anti platelet therapy. There was no significant difference between the mean slopes of the plot before and after commencement of therapy ( - .088 v - .0080, P = not significant).
CHAN ET AL
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out, such a possibility is most unlikely. While it must be cautioned that our period of observation was rather short (mean 33 .2 months) for a disease that characteristically has a slow downhill course and that a favorable influence of antiplatelet therapy on IgA glomerulonephritis in the long term cannot be excluded, it is fair to conclude that administration of anti platelet agents for almost 3 years confers no benefit on mesangial IgA glomerulonephritis. Our patients were well matched in all aspects except serum IgG. We have no explanation for the fact that the mean serum IgG was significantly higher in the treatment group. Most likely, it was due to some inadequacy in the randomization process. Nevertheless, it is unlikely that this difference could have affected the outcome of the trial since serum immunoglobulins have no prognostic significance 2 .8 in mesangial IgA glomerulonephritis. The fact that the rate of deterioration in glomerular filtration (as determined by the slopes of lIcreatinine v time plots) after the commencement of the study correlated significantly with that observed before the study is consistent with the lack of significant modification of the disease course by the therapy. The small, but significant, increase in uric acid concentration in the group treated with antiplatelet agents is likely the consequence of interference of renal tubular
2.110
3.00
Fig 3. Plot showing a significant inverse correlation between morphologic scores assessed from rena' biopsy specimens and slopes of reciprocals of serum creatinine v time plots.
uric acid excretion by aspirin . That the rate of deterioration of renal function correlated with total morphologic scores indicates that once the damage to the glomeruli is done, the disease tends to pursue its own course . Our findings thus lend further support to earlier reports 9 . 10 that evidence of tubulointerstitial changes on renal biopsy carries a bad prognosis. Our results also suggest that glomerular changes and tubulointerstitial changes contribute more or less equally to the progression of IgA glomerulonephritis. The observation that morphologic changes have a profound influence on the course of IgA glomerulonephritis implies that in therapeutic trials in IgA glomrulonephritis, interpretation of results is difficult , if not impossible, unless renal biopsy changes are comparable for both treatment and control groups.
REFERENCES l. Clarkson AR, Seymour AE , Thomson AJ , et al : IgA nephropathy: A syndrome of uniform morphology, diverse clinical features and uncertain prognosis. Clin Nephrol 8:459-471, 1977 2 . Chan MK, Kwan SYL, Yeung CK, et la: MesangiallgA glomerulonephritis in Hong Kong: A clinical review. Chin Med J (in press) 3. Kincaid-Smith PS : Mesangial IgA nephropathy. Br Med J 290:96-97 , 1985 4 . Cameron JS: Platelets in glomerular disease. Annu Rev Med35: l75-l80, 1984
ANTI PLATELETS AND IGA GLOMERULONEPHRITIS
5. Donadio JU Jr, Anderson CF, Mitchell JC, et al: Membrano proliferative glomerulonephritis. A prospective clinical trial of platelet-inhibitor therapy. N Engl J Med 310:14211426, 1984 6. Cattran DC, Cardella CJ, Roscoe JM, et al: Results of a controlled drug trial in membranoproliferative glomerulonephritis. Kidney Int 27:436-441 , 1985 7. Weiss HJ: Antiplatelet therapy. N Engl J Med 298: 13441346, 1978
421
8. Julian BA, Wyatt RJ, McMorrow RG , et al: Serum complement proteins in IgA nephropathy. Clin Nephrol 20:251258 , 1983 9. Hood SA, Velosa JA, Holley KE , et al: IgA-IgG nephropathy: Predictive indices of progressive disease. Clin Nephrol 16:55-62, 1981 10. D 'Amico G, Ferrano F, Colasanti G, et al: IgAmesangial nephropathy (Berger's disease) with rapid decline in renal function. Clin Nephrol 16:251-257, 1981
M
ESANGIAL IgA glomerulonephritis not infrequently follows a relentlessly downhill course. 1 In our experience, the disease proceeds to end-stage renal failure in 20% to 30% of cases . 2 No effective treatment has been reported. 3 Here we report the results of a controlled trial of antiplatelet agents (a combination of slow-release aspirin and dipyridamole) in patients with biopsyproven mesangial IgA glomerulonephritis. PATIENTS AND METHODS Fifty-two patients with biopsy-proven mesangial IgA glomerulonephritis were randomly allocated to either the treatment group or the control group. Eight patients defaulted within 6 months and another six within 18 months. The treatment group received slow-release aspirin, 650 mg daily, and dipyridamole, 25 to 75 mg thrice daily. The control group received vitamin B complex . By coincidence, there were 19 evaluable patients in each group. On entry into the study, all had blood taken for serum creatinine, albumin, uric acid, calcium, phosphate, IgG, IgA, and IgM. Twenty-four-hour urinary protein excretion was measured and endogenous creatinine clearance determined. The period of observation before the patients were entered for the study was 17.6 ± 2.2 months (mean ± SEM) and the study was conducted for 33.2 ± 1.5 months (mean ± SEM). Blood pressure was monitored and hypertension controlled with antihypertensive agents. Renal biopsy specimens obtained at the time when diagnosis was first made were examined by one of us (KWC), who had no knowledge of the clinical condition of the patients. The histologic changes were arbitrarily graded. Proliferative changes, glomerular sclerosis, and changes in the tubules and the interstitium were graded separately and the score for each morphologic index ranged from 0 to I. The total morphologic score ranged from 0 for normal kidneys to 3 for the most severely affected. Reciprocals of serum creatinine concentrations were plotted against time in months and linear regression analysis was applied. The slope of the regression line was taken as an indication of the rate of change in glomerular filtration . Before the commencement of medication, the number of points used to generate the slopes of the regression line varied from 3 to 7 with a mean of
4, and after the commencement of medications, it varied from 3 to 11 with a mean of7. Statistical analysis was performed on a computer using the Minitab program (Minitab, Inc, University Park, PA). The two-sample t test was used for comparison of differences between treatment and control groups, and the paired t test used to evaluate differences within the same group before and after the commencement of the study.
RESULTS
The demographic data of the two groups of patients are listed in Table 1. The two groups were well matched regarding age, morphologic changes as observed in renal biopsies, renal function profile, and serum immunoglobulins, except that the mean serum IgG was significantly higher in the treatment group than in the control group. Urinary protein excretion and creatinine clearance were comparable between the two groups. There was no statistically significant difference in the rate of deterioration in glomerular filtration between the two groups before the study. The renal function profile at the end of the study and the slopes of the lIcreatinine v time curves of the two groups after the commencement of "treatment" with either vitamin B complex or antiplatelet agents are also shown in Table 1. There was no statistically significant difference in these values between the two groups. Within the same group, no significant difference in the slopes of the plots From the Departments of Medicine and Pathology, Queen Mary Hospital, University of Hong Kong. Address reprint requests to M.K. Chan , MD , Department of Medicine , Queen Mary Hospital, University of Hong Kong, Hong Kong. © 1987 by the National Kidney Foundation , lnc. 0272-6386/87/0903-0005$03.00/0
American Journal of Kidney Diseases, Vol IX, No 5 (May), 1987: pp 417-421
417
418
CHAN ET AL
Table 1.
Demographic and Biochemical Data of Patients With Mesangial IgA Glomerulonephritis Before Commencement of Therapy
No. of patients (sex) Age (yrs) Body weight (kg) Systolic BP (mm Hg) Diastolic BP (mm Hg) Creatinine (mmol/L) Albumin (gIL) Uric acid (mmoI/L) Calcium (mmol/L) Phosphate (mmoI/L) IgG (mg/dL) IgA (mg/dL) 19M (mg/dL) C3 (mg/dL) C4 (mg/dL) 24-h Urine protein (g) Creatinine clearance (mUmin) Morphologic score Slope of (1/Cr v time)
End of Study '
Antiplatelet
Vitamin B
Antiplatelet
Vitamin B
19 (10 M + 9 F) 29.0 ± 2.5 62 .0 ± 1.9 135 ± 4 82 ± 2 0.125 ± 0.017 42 ± 0.7 0.39 ± 0.02 2.38 ± 0.03 1.10 ± 0.05 1307 ± 74 340 ± 26 182 ± 21 108 ± 5 60 ± 5 1.57 ± 0.18 77 ± 6 1.188 ± 0.096 - 0.088 ± 0.054
19 (14 M + 5 F) 27.5 ± 1.9 62.6 ± 2.2 139 ± 4 82 ± 2 0.130 ± 0.015 44 ± 0.9 0.45 ± 0.04 2.36 ± 0.03 1.65 ± 0.53 1085 ± 70§ 306 ± 22 189 ± 19 109 ± 6 61 ± 5 1.72 ± 0.35 73 ± 7 1.139 ± 0.125 0.001 ± 0.031
19 (10 M + 9 F) 31.7 ± 2.6 63.1 ± 2.0 132 ± 4 80 ± 2 0.198 ± 0.056 42 ± 1 0.45 ± 0.03t 2.31 ± 0.04 1.32 ± 0.10:j: NO NO NO NO NO 2.46 ± 0.78 78 ± 9 NO - 0.080 ± 0.084
19 (14 M + 5 F) 30.1 ± 1.8 64.1 ± 2.2 132 ± 4 81 ± 2 0.199 ± 0.052 43 ± 1 0.44 ± 0.03 2.25 ± 0.06 1.28 ± 0.11 NO NO NO NO NO 2.21 ± 0.54 72 ± 8 NO -0.0018 ± 0.0198
All values are in mean ± SEM. Abbreviations: ND, not done; Cr, creatinine . • All parameters listed were values obtained at the end of the study except the slope of (1/Cr v time), which was calculated from values of creatinine concentrations during the period the patients received medications. tOifferent from pre-treatment values, P = .004. :j:Oifferent from pre-treatment values, P = .03. §Oifferent from anti platelet group, P = .04.
was noted after the commencement of treatment, nor was any difference in the mean serum creatinine concentration observed between the two groups at the conclusion of the study. Within each group, there was no significant difference between any of the parameters measured at the start and at the end of the study when the paired t test was applied. The lIcreatinine v time plots for the control group is shown in Fig 1. Three patients had rather rapid deterioration of renal function , ending in end-stage renal failure during the period of observation. Figure 2 shows the IIcreatinine plots of the treatment group. As in the control group , rapid deterioration in renal function occurred in three patients. However, five patients showed a significant improvement in renal function with a readily noticeable increase in the slope of their 1I creatinine v time plots . Since there was no discernible difference between the treatment and the control groups, data from the two groups were pooled and regression analysis applied to see if any parameter correlated with the morphologic scores and the slopes of 11 creatinine v time plots, respectively. A significant correlation between morphologic scores and the
slopes of IIcreatinine v time became apparent (r = - .46, P < .01) (Fig 3) . The latter also correlated, respectively, with serum creatinine (r = - .56, P < .001), serum phosphorus (r = - .49, P < .01), and creatinine clearance (r = - .42, P = .01) measured at the end of the study. Not unexpectedly, the slopes of IIcreatinine v time before the commencement of the study correlated significantly with that observed afterward (r = .65, P < .001) (Table 1). When glomerular sclerosis, glomerular proliferative changes, and tubulointerstitial changes were separately correlated with the slopes of 1/creatinine v time, it appeared that each component contributed more or less equally to the correlation, since r was - .30 for glomerular sclerosis, -.31 for glomerular proliferative changes, - .42 for tubulointerstitial changes, and - .46 for the total morphologic score. DISCUSSION
Attention has been called to the role of platelets in glomerular diseases. 4 Antiplatelet agents have been used to treat mesangiocapillary glomerulonephritis with conflicting results. 5 .6 Mesangial proliferation is the hallmark of IgA glomerulonephritis, and our trial with anti platelet agents was initiated along lines of reasoning similar to
419
ANTI PLATELETS AND IGA GLOMERULONEPHRITIS 20
18
-
18
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-II
0
II
10
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20
211
30
311
40
411
110
Time In months Fig 1. Plot showing reciprocals of serum creatinine against time in patients with mesanglal IgA glomerulonephritis who received vitamin B complex. There was no significant difference between the mean slopes of the plot before and after commencement of therapy (.001 v - .0018, P = not significant).
complex as a control drug partly because it was difficult to obtain placebo for combination drugs and partly because some form of medication was needed to ensure our patients' regular attendance. Although an influence of vitamin B complex on the course of IgA glomerulonephritis cannot be ruled
those used when anti platelet therapy was tried for mesangiocapillary glomerulonephritis. We used a combination of slow-release aspirin and dipyridamole because there is evidence that aspirin and dipyridamole affect platelet function at different sites. 7 We had to resort to the use of vitamin B 20
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Fig 2. Plot showing reciprocals of serum creatinine against time in patients with mesangial IgA glomerulonephritis who received anti platelet therapy. There was no significant difference between the mean slopes of the plot before and after commencement of therapy ( - .088 v - .0080, P = not significant).
CHAN ET AL
420
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out, such a possibility is most unlikely. While it must be cautioned that our period of observation was rather short (mean 33 .2 months) for a disease that characteristically has a slow downhill course and that a favorable influence of antiplatelet therapy on IgA glomerulonephritis in the long term cannot be excluded, it is fair to conclude that administration of anti platelet agents for almost 3 years confers no benefit on mesangial IgA glomerulonephritis. Our patients were well matched in all aspects except serum IgG. We have no explanation for the fact that the mean serum IgG was significantly higher in the treatment group. Most likely, it was due to some inadequacy in the randomization process. Nevertheless, it is unlikely that this difference could have affected the outcome of the trial since serum immunoglobulins have no prognostic significance 2 .8 in mesangial IgA glomerulonephritis. The fact that the rate of deterioration in glomerular filtration (as determined by the slopes of lIcreatinine v time plots) after the commencement of the study correlated significantly with that observed before the study is consistent with the lack of significant modification of the disease course by the therapy. The small, but significant, increase in uric acid concentration in the group treated with antiplatelet agents is likely the consequence of interference of renal tubular
2.110
3.00
Fig 3. Plot showing a significant inverse correlation between morphologic scores assessed from rena' biopsy specimens and slopes of reciprocals of serum creatinine v time plots.
uric acid excretion by aspirin . That the rate of deterioration of renal function correlated with total morphologic scores indicates that once the damage to the glomeruli is done, the disease tends to pursue its own course . Our findings thus lend further support to earlier reports 9 . 10 that evidence of tubulointerstitial changes on renal biopsy carries a bad prognosis. Our results also suggest that glomerular changes and tubulointerstitial changes contribute more or less equally to the progression of IgA glomerulonephritis. The observation that morphologic changes have a profound influence on the course of IgA glomerulonephritis implies that in therapeutic trials in IgA glomrulonephritis, interpretation of results is difficult , if not impossible, unless renal biopsy changes are comparable for both treatment and control groups.
REFERENCES l. Clarkson AR, Seymour AE , Thomson AJ , et al : IgA nephropathy: A syndrome of uniform morphology, diverse clinical features and uncertain prognosis. Clin Nephrol 8:459-471, 1977 2 . Chan MK, Kwan SYL, Yeung CK, et la: MesangiallgA glomerulonephritis in Hong Kong: A clinical review. Chin Med J (in press) 3. Kincaid-Smith PS : Mesangial IgA nephropathy. Br Med J 290:96-97 , 1985 4 . Cameron JS: Platelets in glomerular disease. Annu Rev Med35: l75-l80, 1984
ANTI PLATELETS AND IGA GLOMERULONEPHRITIS
5. Donadio JU Jr, Anderson CF, Mitchell JC, et al: Membrano proliferative glomerulonephritis. A prospective clinical trial of platelet-inhibitor therapy. N Engl J Med 310:14211426, 1984 6. Cattran DC, Cardella CJ, Roscoe JM, et al: Results of a controlled drug trial in membranoproliferative glomerulonephritis. Kidney Int 27:436-441 , 1985 7. Weiss HJ: Antiplatelet therapy. N Engl J Med 298: 13441346, 1978
421
8. Julian BA, Wyatt RJ, McMorrow RG , et al: Serum complement proteins in IgA nephropathy. Clin Nephrol 20:251258 , 1983 9. Hood SA, Velosa JA, Holley KE , et al: IgA-IgG nephropathy: Predictive indices of progressive disease. Clin Nephrol 16:55-62, 1981 10. D 'Amico G, Ferrano F, Colasanti G, et al: IgAmesangial nephropathy (Berger's disease) with rapid decline in renal function. Clin Nephrol 16:251-257, 1981