Controlled trial of antiplatelet agents in mesangial IgA glomerulonephritis. Effects of dipyridamole on the short-term evolution of glomerulonephritis. Hong Kong study using valsartan in IgA nephropathy (HKVIN): a double-blind, randomized, placebo-controlled study. [The effect of diphenylhydantoin on IgA nephropathy]. ACEI/ATRA therapy decreases proteinuria by improving glomerular permselectivity in IgA nephritis. The effects of dual blockade of the renin-angiotensin system on urinary protein and transforming growth factor-beta excretion in 2 groups of patients with IgA and diabetic nephropathy. Low-dose losartan therapy reduces proteinuria in normotensive patients with immunoglobulin A nephropathy. Treatment of IgA nephropathy with eicosapentanoic acid (EPA): a two-year prospective trial. [Prospective, multi-centered, randomized and controlled trial on effect of Shenle Capsule in treating patients with IgA nephropathy of Fei-Pi qi-deficiency syndrome]. [Multicentered, randomized, controlled clinical trial on patients with IgA nephropathy of Qi-yin deficiency syndrome type]. Effects of angiotensin-converting enzyme inhibitor, angiotensin II receptor antagonist and calcium antagonist on urinary podocytes in patients with IgA nephropathy. The antiproteinuric effect of angiotensin antagonism in human IgA nephropathy is potentiated by indomethacin. Sodium cromoglycate therapy in IgA nephropathy: a preliminary short-term trial. Efficacy of tonsillectomy pulse therapy versus multiple-drug therapy for IgA nephropathy. Prednisolone co-administered with losartan confers renoprotection in patients with IgA nephropathy. Beneficial effects of olmesartan and temocapril on urinary liver-type fatty acid-binding protein levels in normotensive patients with immunoglobin A nephropathy. Treatment of IgA nephropathy with omega-3-polyunsaturated fatty acids: a prospective, double-blind, randomized study. Interim evidence of the renoprotective effect of the angiotensin II receptor antagonist losartan versus the calcium channel blocker amlodipine in patients with chronic kidney disease and hypertension: a report of the Japanese Losartan Therapy Intended for Global Renal Protection in Hypertensive Patients (JLIGHT) Study. Effect of fluvastatin on proteinuria in patients with immunoglobulin A nephropathy. Coadministration of losartan and enalapril exerts additive antiproteinuric effect in IgA nephropathy. [Clinical study on dan shao tang in treating IgA nephropathy of deficiency of yin with damp-heat symptom]. ACE inhibition reduces proteinuria in normotensive patients with IgA nephropathy: a multicentre, randomized, placebo-controlled study. Vitamin E therapy in IgA nephropathy: a double-blind, placebo-controlled study. [Clinical observation on treatment of IgA nephropathy with Huobahuagen Tablets and irbesartan]. [A prospective controlled study of sairei-to in childhood IgA nephropathy with focal/minimal mesangial proliferation. Japanese Pediatric IgA Nephropathy Treatment Study Group]. [The effects of angiotensin-converting enzyme inhibitor on IgA nephropathy and the influencing factors]. Treatment of severe IgA nephropathy with omega-3 fatty acids: the effect of a "very low dose" regimen. Controlled trial of phenytoin therapy in IgA nephropathy. Effect of angiotensin-converting enzyme and calcium channel inhibition on progression of IgA nephropathy. [Effects of Astragalus injection on renal tubular function in patients with IgA nephropathy]. Low-dose combination therapy with temocapril and losartan reduces proteinuria in normotensive patients with immunoglobulin a nephropathy. Early intensive therapy for clinical remission of active IgA nephropathy: a three-year follow-up study. Treatment of IgA nephropathy with ACE inhibitors: a randomized and controlled trial.
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. The aim of the present study is to evaluate the effect of dipyridamole (300 mg/day) versus placebo in a double-blind randomized trial on membranous glomerulonephritis (M-GMN), mesangial IgA glomerulonephritis (IgA-GMN), and segmentary and focal hyalinosis glomerulonephritis (SFH-GMN) during the first 3 months of treatment. In the case of M-GMN, proteinuria dropped by 60% of the basal value in patients treated with dipyridamole; in the case of IgA-GMN it dropped by 65-70%; and in the case of SFH-GMN it dropped by 40% of the basal value. Inhibition of proteinuria in M-GMN was correlated to platelet response, and above all, to the ADP-induced platelet aggregation in whole blood. Previous studies showed that angiotensin-receptor blocker (ARB) therapy decreased proteinuria and possibly slowed the rate of renal function decline in patients with chronic proteinuric nephropathies. We performed a double-blind, randomized, placebo-controlled, multicenter study on the ARB valsartan in the treatment of patients with immunoglobulin A (IgA) nephropathy.
                From 6 centers, we recruited 109 patients with IgA nephropathy who had either: (1) proteinuria with protein greater than 1 g/d and serum creatinine level less than 2.8 mg/dL (< 250 micromol/L), or (2) serum creatinine level of 1.4 to 2.8 mg/dL (120 to 250 micromol/L) regardless of degree of proteinuria. Patients were randomly assigned to administration of either valsartan, 80 mg/d (titrated up to 160 mg/d for blood pressure control), or placebo for 104 weeks. Additional antihypertensive therapy was allowed to achieve a target blood pressure of 140/90 mm Hg. The primary end point was doubling of serum creatinine level or dialysis-dependent renal failure. Secondary outcomes included change in proteinuria and decrease in glomerular filtration rate (GFR).
                There were 54 patients in the treatment group and 55 patients in the placebo group. Baseline clinical characteristics were similar between groups, although the treatment group had a marginally greater baseline GFR (87 +/- 36 versus 78 +/- 38 mL/min/1.73 m2 [1.45 +/- 0.60 versus 1.30 +/- 0.63 mL/s/1.73 m2];P = 0.29) and less proteinuria (protein, 1.8 +/- 1.2 versus 2.3 +/- 1.7 g/d; P = 0.21) than the placebo group. Average blood pressures during the study were 92.7 +/- 10.6 mm Hg in the treatment group and 100.9 +/- 9.1 mm Hg in the placebo group (P < 0.001). During the study period, 4 patients in the placebo group and 1 patient in the treatment group reached the primary end point (log-rank test, P = 0.18). Proteinuria decreased significantly in the treatment group (protein, 1.8 +/- 1.2 to 1.2 +/- 1.2 g/d; P = 0.03), but did not change in the placebo group. With multiple linear regression models, valsartan treatment resulted in a 33.0% decrease in proteinuria (95% confidence interval, 10.9 to 55.1) after adjusting for other confounding factors. There was a significant decrease in mean rate of GFR decrease in the valsartan-treated group (-5.62 +/- 6.79 mL/min/y [-0.09 +/- 0.11 mL/s/y]) compared with the placebo group (-6.98 +/- 6.17 mL/min/y [-0.12 +/- 0.10 mL/s/y]) throughout the study period after adjustment for average blood pressure and proteinuria (P = 0.014).
                Valsartan significantly decreases proteinuria and slows renal deterioration in patients with IgA nephropathy after adjustment for confounding factors, notably blood pressure. The long-term benefit of valsartan needs to be confirmed with additional studies. Seventeen patients with verified diagnosis of IgA nephropathy (15 men and 2 women) were divided into two groups using random selection. The group receiving treatment consisted of 9 persons, the control group was made up of 8 persons. The former group were given diphenylhydantoin in doses of 2-3 mg/kg/day for a period of 6 months. After the termination of the course of treatment, the authors found a drop in the levels of serum immunoglobulins A, G, complement components C3, C4, circulating immunocomplexes, and decreased haematuria, and, in contrast, increased levels of serum creatinine. No undesirable effects of diphenylhydantoin were noted. It has been postulated that angiotensin-converting enzyme inhibitor/angiotensin receptor antagonist (ACEI/ATRA) may decrease proteinuria in patients with glomerulonephritis by its action on the glomerular basement membrane. We therefore studied the relationship between the response of patients with IgA nephritis (IgAN) to ACEI/ATRA therapy by decreasing proteinuria and its effect on the selectivity index (SI) in these patients.
                Forty-one patients with biopsy-proven IgAN entered a control trial, with 21 in the treatment group and 20 in the control group. The entry criteria included proteinuria of 1 g or more and/or renal impairment. Patients in the treatment group received ACEI/ATRA or both with three monthly increases in dosage. In the control group, hypertension was treated with atenolol, hydrallazine, or methyldopa. The following tests were performed at three monthly intervals: serum creatinine, total urinary protein, SI, sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), and low molecular weight (LMW) proteinuria.
                After a mean duration of therapy of 13 +/- 5 months, in the treatment group, there was no significant change in serum creatinine, proteinuria, or SI, but in the control group, serum creatinine deteriorated from 1.8 +/- 0.8 to 2.3 +/- 1.1 mg/dL (P < 0.05). Among the 21 patients in the treatment group, 10 responded to ACEI/ATRA therapy determined as a decrease in proteinuria by 30% (responders), and the other 11 did not respond (nonresponders). Among the responders, SI improved from a mean of 0.26 +/- 0.07 to 0.18 +/- 0. 07 (P < 0.001), indicating a tendency toward selective proteinuria. This was associated with an improvement in serum creatinine from mean 1.7 +/- 0.6 to 1.5 +/- 0.6 mg/dL (P < 0.02) and a decrease in proteinuria from a mean of 2.3 +/- 1.1 to 0.7 +/- 0.5 g/day (P < 0. 001). After treatment, proteinuria in the treatment group (1.8 +/- 1. 6 g/day) was significantly less than in the control group (2.9 +/- 1. 8 g/day, P < 0.05). The post-treatment SI in the responder group (0. 18 +/- 0.07) was better than that of the nonresponder group (0.33 +/- 0.11, P < 0.002). Eight out of 21 patients in the treatment group who had documented renal impairment had improved renal function compared with two in the control group (chi2 = 4.4, P < 0. 05). Of the eight patients in the treatment group who improved their renal function, three normalized their renal function compared with one from the control group.
                Our data suggest that ACEI/ATRA therapy may be beneficial in patients with IgAN with renal impairment and nonselective proteinuria, as such patients may respond to therapy with improvement in protein selectivity, decrease in proteinuria, and improvement in renal function. ACEI/ATRA therapy probably modifies pore size distribution by reducing the radius of large unselective pores, causing the shunt pathway to become less pronounced, resulting in less leakage of protein into the urine. The therapeutic benefits of dual blockade of the renin-angiotensin system (RAS) have been inconsistent on renal function and proteinuria. To know the contribution of the heterogeneity of study subjects to such inconsistency, we evaluated the effects of dual blockade of RAS in 2 groups of selected renal diseases, IgA and diabetic nephropathy. To avoid confounding by the blood pressure-reducing effects, angiotensin II receptor antagonists (ATRAs) were added on the patients with long-term, optimally controlled blood pressure taking ACE inhibitors. Twenty-four-hour urinary protein excretion rate and urinary TGF-beta1 level were measured as surrogate markers of renal injury.
                We conducted a prospective crossover trial with 14 IgA and 18 type-2-diabetic nephropathy patients showing moderate degree of proteinuria (> or = 1.0 g/day) and renal dysfunction (creatinine clearance 25 - 75/ml/min). Four to 8 mg once-daily dose of candesartan and placebo were alternatively added on ramipril dose of 5 - 7.5 mg/day for 16 weeks.
                All baseline data except for the age factor were statistically the same between the 2 disease groups. Twenty-four-hour mean arterial blood pressures were 91.2 +/- 1.6 and 92.3 +/- 1.8 mmHg in IgA and diabetic nephropathy patients respectively at baseline (p = NS). Mean arterial pressure did not change by the addition of candesartan or placebo in both groups. The addition of candesartan (combination) reduced 24-hour urinary protein excretion rate in IgA nephropathy patients with a mean change of -12.3 +/- 4.5%, which is significantly greater compared to a mean change of -0.1 +/- 3.3% after the addition of placebo (placebo) (mean difference 12.4 +/- 5.0, 95% CI 1.2 - 23.5; p < 0.05). Urinary TGF-beta1 level was reduced considerably by the combination therapy, with a -28.9 +/- 6.0% decrease, which was significantly different to that by the placebo, with +4.3 +/- 12.4% (33.3 +/- 13.5, 3.2 - 63.3; p < 0.05). In diabetic nephropathy patients, the addition of candesartan did not reduce 24-hour urinary protein excretion rate. Mean changes of 24-hour urinary protein excretion rate were -0.8 +/- 4.7% by the combination therapy and +0.5 +/- 6.1% by placebo (mean difference 1.3 +/- 4.7, 95% CI -6.8 - 13.5; p < NS). The level of urinary TGF-beta1 was reduced by the combination therapy, with -14.3 +/- 9.5% decrease, but it did not reach statistical significance compared to placebo of +0.7 +/- 15.5% (15.0 +/- 13.5, -14.4 - 44.5; p < NS). The changes in 24-hour urinary protein excretion rate and urinary TGF-beta1 level were neither correlated with each other, nor with the change in mean arterial pressure. Significant changes in the renal function were not detected during the study period.
                Definite beneficial effects of dual blockade of RAS on proteinuria and TGF-beta1 excretion were found in IgA nephropathy patients, which was independent of blood pressure-reducing effect. With our 16-week trial, such benefits were not observed in type 2 diabetic nephropathy. The reduction in urinary TGF-beta1 level suggests that the combination therapy may provide additional renoprotection through the antisclerosing effects. Based on our results, for a proper interpretation the therapeutic effects of the combination therapy should be evaluated separately according to the underlying renal disease. The present study was designed to assess the antiproteinuric effects of a low dose of an angiotensin II-receptor blocker, losartan, in normotensive patients with immunoglobulin A (IgA) nephropathy. We performed a prospective, controlled trial of losartan (12.5 mg/d) therapy to assess the effects on mild proteinuria and renal function. The study subjects were 18 normotensive and proteinuric patients with IgA nephropathy in the losartan group and 18 IgA nephropathy patients treated with antiplatelet agents in the control group. We prospectively evaluated blood pressure, proteinuria, renal function, and biochemical parameters before and after 12 months of therapy. Blood pressure was kept constant during the 12-month period. Serum creatinine levels and estimated glomerular filtration rate did not significantly change during the 12 months in any of the patients studied. Systolic and diastolic blood pressures did not differ significantly between the losartan and control groups. However, low-dose losartan significantly reduced proteinuria from 0.8+/-0.5 g/d at baseline to 0.4+/-0.4 g/d at 12 months (p=0.006). Proteinuria was significantly lower at 12 months in the losartan group than in the control group (p=0.04). In addition, urinary N-acetyl-beta-D-glucosaminidase (NAG) levels in the losartan group at 12 months were significantly lower than those in the control group (p=0.009). Our data suggest that low-dose losartan therapy for normotensive patients with IgA nephropathy could reduce the amount of urinary protein and NAG excretion without affecting systemic blood pressure. Thirty-seven patients with biopsy proven mesangial IgA nephropathy were prospectively allocated to either two years of treatment with eicosapentanoic acid (EPA) 10 g per day or no treatment. At entry treated and untreated patients with renal dysfunction (Group A) or patients with normal serum creatinine less than 0.12 mmol/l (Group B) did not differ in serum creatinine, creatinine clearance, urinary protein excretion, or quantitative urinary red cell counts. Compliance with EPA therapy was excellent as assessed by plasma fatty acid profiles. At the end of the trial creatinine clearance in treated patients had gone from 80 +/- 16 to 57 +/- 17 ml/min (p less than 0.05) and in untreated patients from 76 +/- 18 to 55 +/- 14 (p less than 0.05). There were no beneficial effects in either Group A or Group B patients. The only two patients who had improvement in renal function were in the EPA treatment group. Although no side effects of treatment were noted, EPA does not alter the course of established mesangial IgA nephropathy. To observe the effect and safety of Chinese compound Shenle Capsule (SC) in treating IgA nephropathy patients of Fei-Pi qi-deficiency syndrome (FPQD).
                A prospective, multi-centered, randomized, double-blinded, double-mimetic, controlled trial was conducted in 70 IgA nephropathy patients of FPQD syndrome, who were randomly assigned to two groups treated with SC and fosinopril respectively for 12 weeks. The changes of TCM syndrome score, 24 h urine protein quantity (UP), serum creatinine (SCr), hepatic function before and after treatment and the adverse reaction were observed.
                Compared with those before treatment, the level of UP and the TCM syndrome scores decreased significantly in both groups (P < 0.05 or P < 0.01), while the level of albumin increased significantly after treatment, and the level of total cholesterol, triglycerid and renal function remained unchanged (P > 0.05). There was no significant difference in all the above parameters between the two groups. According to the curative criterion for Chinese medicine and Western medicine, the total effective rate was 83.3% and 66.7% respectively in the SC treated patients, 82.4% and 58.8% respectively in the fosinopril treated patients, showing insignificant difference between them. In addition, no severe adverse event was found.
                SC treatment showed effects similar to that of fosinopril in reducing proteinuria and improving TCM syndrome in IgA nephropathy patients of FPQD syndrome, and could be well tolerated by patients. To evaluate the effect and safety of Chinese medicine Compound Shenhua Tablet (SHT) on IgA nephropathy patients of TCM Qi-yin deficiency syndrome type, by using angiotensin-converting enzyme inhibitors (ACEI) fosinopril as the positive control.
                Adopting prospective, multicentered, double-blinded, double-dummy, randomized, controlled trial design, 131 patients with IgA nephropathy of Qi-yin deficiency syndrome type were assigned to two groups, the 65 patients in the treated group (SHG) and the 66 in the control group treated with SHT and fosinopril respectively for 12 weeks. The indexes of efficacy, including TCM syndrome scores, urinary protein, serum creatinine, urea nitrogen and endogenous creatinine clearance rate, as well as the indexes of safety, including liver function and occurrence of adverse events were observed.
                There was no significant statistical difference between the two groups in aspects of baseline demographic characteristics and clinical figures, including gross hematuria, hypertension, incidence of renal insufficiency, total course of disease, urinary protein, TCM syndrome score, renal pathological Katafuchi score, glomerular score, tubular-interstitial score, vascular score and Lee grading. Afte 12 weeks of treatment, the content of 24-h urinary protein significantly decreased by 0.26 +/- 0.95 g/24 h and 0.26 + 0.92 g/24 h respectively in the two groups, showing significant difference in comparing with baseline, but insignificant difference between the two groups (P > 0.05); the scores of TCM dominant syndromes in them decreased by 2.52 +/- 2.34 scores and 1.74 +/- 2.12 scores respectively with significant difference as compared with baseline (P < 0.01), and in comparison between groups (P < 0.05). No significant change in levels of serum creatinine, urea nitrogen, endogenous creatinine clearance rate in both groups was found (P > 0.05). Scores of TCM accompanied syndromes in the two groups was significantly decreased (P < 0.01), but the difference between them was insignificant (P > 0.05). No severe adverse event occurred during treatment, and the occurrence in the two groups was similar.
                SHT, just like the positive control medicine fosinopril, can effectively decrease the proteinuria and improve clinical syndrome of IgA nephropathy patients of Qi-yin deficiency syndrome type, and shows no serious adverse reaction. The urinary podocyte is postulated to be a marker for estimation of the severity of active glomerular injury and a predictor of disease progression in children with glomerulonephritis. Non-dihydropyridine calcium antagonist, including verapamil, reduce proteinuria to an extent similar to that of the angiotensin-converting enzyme inhibitor (ACEI), including trandolapril, but to a greater extent than other antihypertensives. Angiotensin (Ang) II receptor antagonists, including candesartan cilexetil, show potent and long-term preventive effects against the progression of renal injury. The aim of the present study is to assess whether verapamil, trandolapril and candesartan cilexetil affect proteinuria and urinary podocytes in patients with IgA nephropathy. Thirty-two normotensive patients aged 18-54 years with biopsy-proven IgA nephropathy, nonnephrotic proteinuria (1-3 g/day), and normal renal function (creatinine clearance >80 ml/min) were studied. Twenty patients with diffuse mesangial proliferative glomerulonephritis (non-IgA PGN) and 20 healthy controls were also included in this study. The number of urinary podocytes in patients with advanced IgA nephropathy (n = 16) was significantly higher than that in patients with the disease in the mild stage (n = 16) (p < 0.01) or in patients with non-IgA PGN (p < 0.01). Urinary podocytes were not detected in healthy controls. The 32 patients with IgA nephropathy were randomly divided into four treatment groups: those treated with verapamil (120 mg/day, n = 8); those treated with trandolapril (2 mg/day, n = 8); those treated with candesartan cilexetil (8 mg/day, n = 8), and those given a placebo (n = 8). Treatment continued for 3 months. Antiproteinuric response in the trandolapril group was similar to that in the candesartan cilexetil group (-38 vs. -40%). The action of trandolapril or candesartan cilexetil was greater than that of verapamil (p < 0.01). Reduction in the number of urinary podocytes from baseline was significantly greater in patients treated with trandolapril or candesartan cilexetil than in patients treated with verapamil (p < 0.01). However, there was no difference between patients treated with trandolapril and those treated with candesartan cilexetil. Proteinuria and urinary podocytes were unaffected in the placebo group. These data suggest that urinary podocytes may be a marker of disease activity in adult patients with IgA nephropathy and that trandolapril and candesartan cilexetil are more effective than verapamil in reducing the number of podocytes.
                Copyright 2000 S. Karger AG, Basel Evidence is available from animal and human studies that protein traffic through the glomerular capillary has a pathogenetic role in subsequent renal damage and that angiotensin-converting enzyme (ACE) inhibitors appear superior to other drugs in lowering proteinuria and the rate of renal function decline. This study compares the effect of ACE inhibition or angiotensin II (AngII) receptor blockade on urinary protein excretion and renal hemodynamics in 20 patients with IgA glomerulonephritis randomized to receive enalapril (20 mg/d) or irbesartan (100 mg/d) for 28 d in a double-blind study with two parallel groups. This study also evaluated whether addition of indomethacin (75 mg twice a day) to each of the two treatments resulted in a more potent antiproteinuric effect. Enalapril alone reduced total protein excretion (61% change from baseline) and fractional clearance of albumin without changes in GFR and minor elevation in renal plasma flow. Also, patients randomized to receive the AngII receptor antagonist irbesartan for 28 d had lower proteinuria (55% change from baseline) and fractional clearance of albumin at the end of the treatment period with similar renal hemodynamic changes. When indomethacin was added to enalapril treatment, a further significant reduction in urinary proteins and fractional albumin clearance was observed. In patients given irbesartan, the addition of indomethacin further reduced proteinuria and fractional clearance of albumin. The combined therapy with enalapril or irbesartan and indomethacin did not significantly affect GFR and renal plasma flow compared with baseline. These findings indicate that in patients with IgA glomerulonephritis the antiproteinuric effect of blocking AngII activity by either ACE inhibitors or AngII receptor antagonists is potentiated by indomethacin, an effect that occurred without impairment of renal function. Sodium cromoglycate (SCG), an antiallergic agent, is an effective drug in an experimental model for IgA nephropathy. The present report concerns a preliminary trial of patients with IgA nephropathy and proteinuria (greater than 1.0 g/d), which was conducted to determine the therapeutic value of SCG. Thirty patients were divided into two groups: one group (n = 15) was given oral SCG (1,200 mg/d) for 16 weeks after an observation of 4 weeks (SCG group), and the other group (n = 15) was observed without the changes of prescription (control group). No fluctuations were noted in proteinuria during the observation period in both groups. Proteinuria in the SCG group slowly decreased throughout the time course; however, a significant reduction was observed at 16 weeks as compared with that of the control group. On the other hand, no significant changes were noted in creatinine clearance (Ccr), serum albumin (s-alb), serum IgA (s-IgA), and IgA-CIC between groups. Five of 15 patients, designated "responders", showed a reduction in proteinuria of more than 50% of the pre-value (average value of observations period). The responder and nonresponder groups were comparable in clinical and histopathological data at the beginning of the trial. Nevertheless, no significant correlations arose concerning any point. Short-term SCG therapy may be beneficial in reducing proteinuria in some patients with IgA nephropathy. Allergic reactions may participate in the pathogenesis of this disease. We evaluated the efficacy of tonsillectomy plus pulse prednisolone, warfarin, and dipyridamole including methylprednisolone pulse (tonsillectomy plus pulse therapy), versus prednisolone, warfarin, and dipyridamole including mizoribine (PWDM) for the treatment diffuse IgA nephropathy (IgAN) in children. The patients were randomly assigned to be treated by tonsillectomy plus pulse therapy for 2 years (Group A, n=16) or PWDM for 2 years (Group B, n=16). The clinical features and pathological findings in both groups were analyzed prospectively. The mean urinary protein excretion after 6 months of treatment in both groups had decreased significantly compared with pre-therapy. The activity index (AI) in both groups was lower at the time of the second biopsy than at the time of the first biopsy. The chronicity index (CI) in Groups A and B did not differ between the first and second biopsy. At the latest follow-up examination none (0%) of the patients in either group had renal insufficiency. None of the patients in Group A, but six patients in Group B experienced an acute exacerbation of IgAN as a result of tonsillitis (P<0.05). In conclusion, although there was no untreated control group in this study, the results suggested that tonsillectomy plus pulse therapy is as effective as PWDM in ameliorating proteinuria and histological severity in IgAN patients and in preventing acute exacerbation of IgAN by tonsillitis. Treatment options for progressive IgA nephropathy are limited.
                We performed a small, randomized controlled trial to evaluate the effects of prednisolone (PSL, 30 mg/dL, gradually tapered to 5 mg/dL over two years) plus 50 mg/day of losartan (LST, an angiotensin II receptor blocker) or PSL alone on IgA nephropathy. We separated 38 patients (age, 33 +/- 11 years; creatinine clearance, 103 +/- 31 mL/min; proteinuria, 1.6 +/- 0.5 g/day) into two groups that were treated with either PSL plus LST or PSL alone, and compared the proteinuria and creatinine clearance after two years. Baseline and histopathological data did not significantly differ between the two groups.
                Two years of treatment in both groups significantly decreased proteinuria compared with baseline, and PSL plus LST (from 1.6 +/- 0.6 to 0.3 +/- 0.1 g/day, p < 0.05) was more effective than PSL alone (from 1.6 +/- 0.3 to 0.5 +/- 0.1 g/day, p < 0.05). Creatinine clearance in both groups was similar at the start of study but significantly differed at the end of the study (PSL plus LST, 104.3 +/- 36.4 to 100.4 +/- 38.9 mL/min; PSL alone, 103.4 +/- 28.5 to 84.8 +/- 34.3 mL/min, p < 0.05).
                Combined therapy with PSL plus LST appears to be more effective than PSL alone in reducing proteinuria and protecting renal function in patients with IgA nephropathy. Liver-type fatty acid-binding protein (L-FABP) is a clinical biomarker of tubulointerstitial damage, which plays an essential role in the progression of chronic kidney disease (CKD), including immunoglobin A (IgA) nephropathy. The effect of combination therapy with the angiotensin receptor blocker (ARB) and the angiotensin-converting enzyme inhibitor (ACEI) on CKD has not been elucidated.
                Twenty-four normotensive patients with IgA nephropathy were randomly assigned to receive olmesartan 10 mg/day, temocapril 2 mg/day, or combination therapy with both drugs. Urinary levels of L-FABP as well as 8-hydroxydeoxyguanosine (8-OHdG) and protein excretion were measured before and after 3 months of treatment. The chronicity index and activity index were also assessed by histopathologic findings.
                Urinary levels of L-FABP and 8-OHdG were higher in patients with IgA nephropathy than in age-matched and sex-matched healthy controls (122.5 +/- 25.5 v 6.4 +/- 3.8 mug/g.creatinine, P < .001; and 22.6 +/- 4.4 v 4.8 +/- 1.4 ng/mg.creatinine, P < .01, respectively). Urinary levels of L-FABP were correlated with those of 8-OHdG (baseline, P = .0001; after 3 months, P = .008) and the severity of proteinuria (baseline, P = .0015; after 3 months, P = .0001). The percent reductions in urinary levels of L-FABP and 8-OHdG, protein excretion, and activity index after 3 months were greater in the combination therapy group, compared with each monotherapy group of olmesartan (P < .05) and temocapril (P < .05).
                The data suggest that a combination therapy of ARB plus ACEI has a greater beneficial effect on renal injury compared with monotherapy using ARB or ACEI in normotensive patients with IgA nephropathy. In several studies diets supplemented with fish oil containing a high proportion of omega-3-polyunsaturated fatty acids (w-3-PUFA) have been shown to produce beneficial effects, such as a reduction in blood pressure, lipid levels and inflammation, all of which may affect the course of IgA nephropathy. However, the results of hitherto published studies concerning IgA nephropathy have been inconclusive. We therefore carried out a prospective, randomized, placebo-controlled six-month study with a higher daily dose of w-3-PUFA than used in previous studies. Thirty-two adult patients with biopsy-proven IgA nephropathy and proteinuria completed the study: 15 were assigned to a fish-oil product with a high percentage of w-3-PUFA (K 85, with 55% eicosapentenoic and 30% docosahexenoic acid) and 17 to corn oil, 6g daily of either oil. At the start, no significant differences were found between the two groups (K85: 3 females/12 males, mean age 39 years (range 22-64), corn oil: 4 females/13 males, age 42 years (range 26-68). By six months, supplements of K85 resulted in a slight but significant reduction in glomerular filtration rate (GFR) compared to the start: 51Cr-EDTA: 63 +/- 22 to 59 +/- 21 ml/min/1.73 m2 (p < 0.05), creatinine clearance: 91 +/- 31 to 79 +/- 25 ml/min (p < 0.01), s-creatinine: 131 +/- 39 to 139 +/- 39 mumol/l, whereas no change in GFR was observed in the corn oil group. The urinary total protein and red blood cell excretions were not affected in any of the groups.(ABSTRACT TRUNCATED AT 250 WORDS) Insufficiency of renal function and high blood pressure influence each other and eventually result in life-threatening endstage renal disease. It has been proposed that proteinuria per se is a determinant of the progression of chronic kidney disease (CKD). The therapeutic strategy for patients with proteinuric CKD and hypertension should therefore be targeted with a view not merely toward blood pressure reduction but also toward renoprotection.
                We examined the effect of the angiotensin (AT)1 receptor antagonist losartan and the calcium channel blocker amlodipine, throughout a period of 12 months, on reduction of blood pressure and renoprotection. This was done by assessing amounts of urinary protein excretion, serum creatinine (SCr), and creatinine clearance (CCr) in patients with hypertension (systolic blood pressure [SBP] > or = 140 mmHg or diastolic blood pressure [DBP] > or = 90 mmHg) and CKD (male, body weight [BW] > or = 60 kg: 1.5 < or = SCr < 3.0 mg/dl; female or male BW < 60 kg: 1.3 < or = SCr < 3.0 mg/dl), manifesting proteinuria of 0.5 g or more/day. Losartan was administered once daily at doses of 25 to 100 mg/day, and amlodipine was given once daily at 2.5 to 5 mg/day. No antihypertensive combination therapy was allowed during the first 3-month period.
                A 3-month interim analysis revealed that, despite there being no difference in blood pressure between the two groups, there was a significant reduction in 24-h urinary protein excretion in the losartan group ( n = 43), but there was no change in the amlodipine group ( n = 43). Analysis of stratified subgroups with proteinuria of 2 g or more/day and less than 2 g/day showed that losartan lowered proteinuria by approximately 24% in both subgroups, while amlodipine lowered proteinuria by 10%, but only in the subgroup of less than 2 g/day (NS). SCr and CCr did not change throughout the period of 3 months in either group. No severe or fatal adverse event was experienced in either group during the study period.
                Losartan appeared to be efficacious for renoprotection in patients with proteinuric CKD and hypertension, with the mechanism being independent of its antihypertensive action. 3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors are established drugs for the treatment of hypercholesterolemia, but several studies have shown that benefits obtained with these drugs are not causally related only to regression of cholesterol lowering. Moreover, in experimental models of progressive renal disease, statins have reduced the extent of glomerulosclerosis. This study evaluated the antiproteinuric effect of a daily dose of 40 mg fluvastatin for 6 months in moderately proteinuric patients with immunoglobulin A nephropathy, stable renal function, and no indicators of poor long-term prognosis. The effects of therapy were evaluated on the basis of 24-hour proteinuria (total proteinuria and albuminuria), albuminemia, creatinine clearance, cholesterol, and triglyceride values. Renal function remained stable in all patients. A significant decrease in proteinuria was observed after 6 months of therapy and persisted for all the observations. An increase in serum albumin was observed after 6 months of therapy. This study suggests that there is an antiproteinuric effect of HMG-CoA reductase inhibitors in moderately proteinuric patients with immunoglobulin A nephropathy. Angiotensin-converting enzyme (ACE) inhibitors and AT1-receptor antagonists (ARAs) are widely administered to reduce urinary protein loss and slow the progression of proteinuric nephropathy to end-stage renal failure. Our group recently observed that the combination of ACE inhibitors and ARAs may have an additive antiproteinuric effect, which may occur because ACE inhibitors do not completely reduce angiotensin II (Ang II) production. Ang II is also produced by chymase. Thus, combination therapy better antagonizes the effects of Ang II. The purpose of this study is to ascertain whether the additive antiproteinuric effect of ACE inhibitors plus ARAs is dose dependent and related to the drug-induced reduction in systemic blood pressure. Therefore, enalapril (E; 10 mg/d) and losartan (LOS; 50 mg/d) were randomly administered alone and then in association; initial dosages were doubled when drugs were administered alone and in association. To determine the influence of the drug-dependent effect on reducing blood pressure and the reduction in urinary proteinuria, both ambulatory and office blood pressures were recorded. E and LOS administered alone reduced proteinuria by the same extent; no further reduction was observed when E and LOS alone were administered at a doubled dose. When E and LOS were coadministered, proteinuria decreased by a greater extent compared with E and LOS alone; an additional reduction in proteinuria was observed when combined therapy doses were doubled. The reduction in proteinuria was not correlated with clinical through blood pressure; however, reductions in diastolic and mean ambulatory blood pressures significantly correlated with the decrease in proteinuria, as well as with creatinine clearance. In conclusion, this study shows that combination therapy with E and LOS has an additive dose-dependent antiproteinuric effect that is likely induced by the drug-related reduction in systemic blood pressure. In normotensive proteinuric patients, it is likely that even a small reduction in systemic blood pressure may affect intraglomerular hemodynamics by a great extent because efferent arteriole regulation is hampered more completely by the coadministration of ACE inhibitors and ARAs. To explore the effect of Dan Shao Tang(DST) in treating IgA nephropathy(IgAN) of deficiency of Yin with damp-heat symptom.
                90 patients with IgAN of deficiency of Yin with damp-heat symptom were randomly divided into two groups. 50 patients in treatment group were treated with DST and western medicine and 40 patients in control group were treated only with western medicine. The effects and changes of the indexes including renal function, hematuria, proteinuria, blood IgA before and after treatment were observed.
                After six months treatment, the general effective rate in treatment group was 70.00%, which was markedly higher than that in control group(37.50%, P < 0.01). Treatment group is obviously better than control group on decreasing hematuria, proteinuria, blood IgA and improving renal function(P < 0.05).
                DST is effective on IgAN of deficiency of Yin with damp-heat symptom. A multicentre, randomized, placebo-controlled study was performed in 39 adult patients with biopsy-proven IgA nephropathy with the aim of comparing the effects of the ACE inhibitor fosinopril and placebo on proteinuria. All patients had normal blood pressure and normal renal function. Proteinuria ranged from 1.0 to 2.5 g/24 h. After a 3-month run-in period, fosinopril and placebo were randomly administered in two 4-month sequences separated from cross-over treatment by a 1-month interval. The mean values of creatinine clearance did not change during either the placebo or the treatment sequences. The mean values of mean arterial pressure (MAP) were significantly lower during the fosinopril sequence (90.4 +/- 9.0 mmHg) than in basal conditions (92.8 +/- 9.1 mmHg) (P = 0.034). The mean basal values of proteinuria were 1.74 +/- 0.84 g/24 h. They were unchanged during the placebo sequence (1.79 +/- 1.20) and fell to 1.37 +/- 0.98 g/24 h after 4 months of fosinopril treatment. Using a multivariate statistical analysis, the treatment effect by time on proteinuria was significantly evident only in the fosinopril sequence (Wilks test, P = 0.033). Changes in protein excretion were not correlated with changes in MAP, baseline plasma renin activity, and urinary sodium excretion. This controlled study shows that fosinopril can significantly reduce proteinuria even in normotensive patients with IgA nephropathy. Obviously, the results of treatment with ACE inhibitors on long-term renal prognosis remain to be elucidated. IgA nephropathy is the world's most common primary glomerulonephropathy. Recent evidence in a rat model implicated excessive production of oxygen-free radicals in the pathogenesis and suggested that vitamin E-treatment ameliorated progression. We studied this antioxidant therapy on the glomerular filtration rate (GFR), proteinuria and hematuria in biopsy-proven IgA nephropathy in children. The duration of treatment or placebo was 2 years, with vitamin E treatment consisting of 400 IU/day in children weighing <30 kg, and twice that dose for those >30 kg. We measured GFR at entry, midpoint and exit. At baseline and at 4-month intervals after randomization, urinary protein/creatinine ratios and urinalysis were examined. The mixed model procedure with log transformation was used in data analysis to test treatment difference as well as the potential time effect. Fifty-five patients were randomized and 38 completed at least 1 year of follow-up. At entry, the clinical characteristics were not different between the treatment and placebo groups. There was a trend toward better preservation of GFR in vitamin E-treated versus placebo patients, 127+/-50 vs. 112+/-31 ml/min/1.73 m(2), respectively ( P=0.09). The urinary protein/creatinine ratio was significantly lower in the vitamin E-treated group vs. placebo; 0.24+/-0.38 vs. 0.61+/-1.37 ( P<0.013). However, there was no difference in the prevalence of hematuria between the groups. Vitamin E treatment in our study patients was associated with significantly lower proteinuria, but no effect on hematuria. While there was a trend toward stabilization of GFR in the vitamin E-treated patients, long-term treatment and follow-up are needed to determine whether antioxidant therapy is associated with preservation of renal function in IgA nephropathy. To observe the effects of Huobahuagen Tablets combined with irbesartan on the risk factors of IgA nephropathy.
                Sixty-two patients diagnosed as IgA nephropathy were randomly divided into control group and treatment group. Thirty patients in the control group were treated with Huobahuagen Tablets (5 tablets po t.i.d.), and 32 patients in the treatment group were treated with irbesartan (150 to 300 mg po q.d.), besides the same treatment as the control group. After 3 months of treatment, the levels of blood pressure (BP), 24 h urine protein (Upr), urinary red blood cells (URBC), blood triglycerides (TG), total cholesterol (TC), albumin (Alb), alanine transaminase (ALT), white blood cells (WBC) and serum creatinine (Scr) were observed.
                After treatment, the levels of Upr, URBC and Scr in both groups were decreased, as compared with those before treatment (P<0.05 or P<0.01), and the levels of BP, Upr, URBC and Scr in the treatment group were lower than those in the control group (P<0.01). The levels of Alb in both groups were increased, as compared with those before treatment (P<0.05 or P<0.01), and the level of Alb in the treatment group was higher than that in the control group (P<0.05).
                Huobahuagen Tablets, when used together with irbesartan, may improve the renal function of the patients with IgA nephropathy and slow the deterioration of the disease by reducing BP, Upr, URBC and Scr. To determine the effect of the Chinese herbal medicine, Sairei-to (TJ-114) in children with newly diagnosed IgA nephropathy showing focal/minimal mesangial proliferation, we undertook a prospective controlled study. One hundred and one patients were randomly assigned to receive Sairei-to for 2 years (group 1) or no drug for 2 years (group 2). Forty-six of the 50 patients in group 1 and 48 of the 51 patients in group 2 completed their trial. At entry, the two groups of patients did not differ in the clinical, laboratory and pathologic findings. At the end of the trial, urinary protein excretion and hematuria were significantly reduced in group 1, but were unchanged in group 2. Twenty-one group 1 patients (46%) had normal urine, but only 5 group 2 patients (10%) had normal urine at the end of the trial (p < 0.001). Blood pressure and creatinine clearance were normal at the end of the trial in all but one group 2 patient, who developed chronic renal failure. The present study demonstrates that 2-year Sairei-to treatment early in the course of disease is effective in children with IgA nephropathy showing focal/minimal mesangial proliferation. OBJECTIVE To investigate the effects of angiotensin-converting enzyme inhibitor (ACEI) on IgA nephropathy(IgAN) and the factors influencing the therapeutic effects. METHODS 131 cases with IgAN diagnosed by renal biopsy were randomly divided into two groups: ACEI group (benazepril 10 mg/d) and non-ACEI group as control. The pathological changes in the kidney were analyzed using Lee SMK. RESULTS After 1 month treatment of ACEI, the levels of proteinuria and serum cholesterol decreased significantly, meanwhile those of serum albumin and total protein increased obviously in patients with IgAN(P < 0.05). The proteinuria level at the 3rd month after treatment was lower than that at the 1st month, but was same as that at the 18th month. While in the control group the proteinuria level increased and the clearance of creatinine decreased continuously during the observation (P < 0.05). The effects correlated positively with mesangial proliferation and negatively with course of the disease glomerular sclerosis in glomerulus and changes of small arterioles in the kidney. Normal blood pressare normal renal function I approximately II degree of Lee SMK I degee of interstitial changes minimal changes of small arterioles and mild glomerular sclerosis predicted better response to ACEI treatment than hypertension renal insufficiency V degree of Lee SMK IV degee of interstitial changes severe changes of small arterioles and massive glomerular sclerosis. CONCLUSIONS It is suggested that benezepril could definitely reduce the excretion of urinary protein and protect renal function of patients with IgAN and should be used as earlier as possible. Mesangial prolife ration glomerular sclerosis in glomerulus changes of small arterioles in kidney and course of the disease are the major influencing factors of ACEI treatment on IgAN. The effect of a "very low dose" of purified omega-3 fatty acids (PFA) in the progression of severe IgA nephropathy (IgAN) was tested, in a randomized, prospective, controlled trial.
                Fourteen patients were assigned to receive a "very low dose" of PFA (0.85 g EPA and 0.57 g PHA) and 14 patients were treated symptomatically and used as controls. Both groups were similar in terms of serum creatinine (Scr) and glomerular filtration rate (GFR) at baseline. Patients were treated for 4 years. The primary end-points were an increase of 50% or more in Scr or a decrease of 50% or more in GFR at the end of the study.
                During treatment, 1 patient (7%) in the PFA group and 6 (43%) in the control group had an increase of 50% or more in their Scr (p<0.01). Also, 1 patient (7%) in the PFA group and 7 (50%) in the control group had a decrease of 50% or more in GFR (p<0.007). The mean annual change in Scr was 0.2 mg/dL in the PFA group and 1.0 mg/dL in the control group (p<0.01). The mean annual change in GFR was -1.4 mL/min in the PFA group and -3.0 mL/min in the control group (p <0.001). One patient in the PFA group (7%) and 6 patients in the control group (43%) (p<0.01) developed end-stage renal disease during the period of observation.
                A "very low dose" of PFA is also effective in slowing renal progression in high-risk patients with IgAN and particularly those with advanced renal disease. IgA nephropathy, a condition thought to cause slowly progressive renal damage, is frequently associated with high serum IgA levels. As phenytoin sodium lowers serum IgA concentrations, a controlled trial of therapy with this drug was conducted over a two-year period in patients with IgA nephropathy. Despite significant depression of serum IgA concentrations in the treatment group, there was no significant change in any other clinical, biochemical or pathological parameter, in either control or treatment groups. Indeed, there was evidence for a slow progression of renal damage in both groups. These observations suggest that the elevated serum IgA concentrations in IgA nephropathy are not of primary pahtogenetic significance but are rather a consequence of a basic abnormality in antigen processing and IgA production. nan To investigate the relationship between the renal tubular function and the severity of tubulo interstitial lesion and the effects of Astragalus Injection (AI) on renal tubular function in patients with IgA nephropathy (IgAN).
                Sixty-seven patients with IgAN were randomly divided into the control group and the astragalus group, both received dipyridamole and benazepril orally, while the astragalus group treated with AI by intravenous dripping additionally. The indices for renal tubular function, including protein in blood and urine, urinary retinol binding protein (RBP) and N-acetyl-beta-D-glucosaminidase (UNAG), were detected. Area of glomerular Bowman capsule, renal tubules, and capillary were measured with color magic image analysis system type CMIAS2000.
                Urinary RBP and UNAG were correlated with tubulointerstitial lesion. Urine protein concentration decreased, blood albumin increased remarkably and renal tubular function improved after treatment in the astragalus group, with the improvement significantly different to those in the control group respectively.
                The severity of tubulointerstitial lesion was positively related to urinary RBP concentration, and astragalus injection has obvious effect on IgAN. This study investigates the ability of low doses of angiotensin-converting-enzyme inhibitors, in combination with angiotensin II receptor blockers, to exert antiproteinuric effects in normotensive and proteinuric outpatients with immunoglobulin A (IgA) nephropathy confirmed by biopsy. We performed a prospective, randomized, 6-month study of the effects of temocapril 1 mg (n=10), losartan 12.5 mg (n=10), and both (n=11) on mild-to-moderate proteinuria 0.76+/-0.35 g/day (range, 0.4 to 1.6 g/day) and renal function. The study subjects comprised 31 normotensive and proteinuric outpatients with IgA nephropathy accompanied by normal, or mild-to-moderately reduced but stable renal function (glomerular filtration rate>50 ml/min) without steroid or immunosuppressive therapy. We prospectively evaluated blood pressure, proteinuria, renal function and biochemical parameters before and after 6 months of therapy. The combination therapy significantly reduced proteinuria (63.2%) compared with either temocapril or losartan alone (41.3% and 36.6%, respectively, p=0.04 and 0.01, respectively). Blood pressure was most decreased in the group that received combination therapy. The reduced proteinuria did not correlate with reduced systolic or diastolic blood pressure or mean arterial pressure in any of the groups. The glomerular filtration rate fell during the first 3 months of combined therapy, but became reversible after a further 3 months of therapy. The combination significantly decreased angiotensin II (p <0.01), and this decrease was greater than that by either drug alone. In conclusion, the effectiveness of the combined therapy may have been at least partly due to the greater inhibition of the action of angiotensin II in patients with IgA nephropathy. This strategy apparently reduced mild-to-moderate proteinuria in patients with normotensive IgA nephropathy. To achieve clinical remission, intensive therapy in active IgA nephropathy was conducted on a trial basis. Forty-five patients with active IgAN in which cellular crescents were present were divided into two groups. The patients in one group (Group A, N = 19) were treated with a combined regimen of steroid pulse, cyclophosphamide (4 months), dipyridamole (36 months) and warfarin. The patients in the other group (Group B, N = 26) were treated with tonsillectomy in addition to the same regimen as Group A. Three years after the initiation of treatment, proteinuria and hematuria had significantly decreased in both groups, and the renal function in Group B was significantly improved. Remission of proteinuria and hematuria was achieved in five patients (26.3%) and eight patients (42.1%), respectively, in Group A, and 14 patients (53.8%) and 20 patients (76.9%), respectively, in Group B. These results indicate that early intensive therapy combined with tonsillectomy in active IgAN is potentially of great benefit from both the medical and socioeconomic points of view. Some retrospective studies have suggested a beneficial influence of angiotensin-converting enzyme (ACE) inhibitors on the progression of IgA nephropathy (IgAN), but prospective and controlled studies demonstrating this effect are lacking. Forty-four patients with biopsy-proven IgAN, proteinuria > or = 0.5 g/d, and serum creatinine (SCr) < or = 1.5 mg/dl were randomly assigned either to receive enalapril (n = 23) or to a control group (n = 21) in whom BP was controlled with antihypertensives other than ACE inhibitors. Primary outcome was renal survival estimated by a 50% increase in baseline SCr. Secondary outcomes were the presence of a SCr > 1.5 mg/dl at the last visit and the evolution of proteinuria. Baseline clinical findings were similar at baseline between enalapril-treated and control group, and there were no differences in BP control during follow-up. Mean follow-up was 78 +/- 37 mo in the enalapril group and 74 +/- 36 mo in the control group. Three patients (13%) in the enalapril group and 12 (57%) in the control group reached the primary end point (P < 0.05). Kaplan-Meier renal survival was significantly better in enalapril group than in control group: 100% versus 70% after 4 yr and 92% versus 55% after 7 yr (P < 0.05). Three patients in the enalapril group (13%) and 11 (52%) in the control group showed SCr > 1.5 mg/dl at the last visit (P < 0.05). Proteinuria significantly decreased in the enalapril group, whereas it tended to increase in the control group (P < 0.001 between groups). In conclusion, ACE inhibitors significantly improve renal survival in proteinuric IgAN with normal or moderately reduced renal function.
IgAN remains a disease in search of adequately powered RCTs to reliably inform clinical practice. More and better evidence is needed to understand the magnitude of benefit and the possible risks of anti-hypertensive or more specifically of ACEi/ARB therapy alone or in combination and which specific types of patients with the IgAN might have the greatest potential for benefit. For other non-immunosuppressive therapies, where neither benefit nor significant harm has yet to be demonstrated, there remains some justification for further exploration of the potential benefits.