Impact of Candesartan on Achieving Remission in Patients with Active IgA Nephropathy

Methodology and Course of the Study

A total of 77 patients (56% women; average age 36 years) with active IgA nephropathy treated at 1 university and 2 community hospitals on the Japanese island of Okinawa were enrolled in the study between April 2007 and December 2011. The inclusion criteria were as follows:

• protein/creatinine ratio in urine (proteinuria) ≥ 57 mg/mmol
• serum creatinine ≤ 133 µmol/l
• active glomerular lesions defined by the presence of necrosis, crescents, or red blood cell count in urine ≥ 10 per field of view for at least 3 months

The exclusion criteria were as follows:

• contraindication for the use of candesartan
• use of RAS (renin-angiotensin system) inhibitors in the 4 weeks prior to study initiation
• diabetes mellitus
• severe hypertension defined as systolic blood pressure (BP) ≥ 200 mmHg or diastolic BP ≥ 100 mmHg
• recent diagnosis of cardiovascular disease

Patients were randomized into 2 groups: 37 patients in the control group were treated conventionally with steroid pulses (methylprednisolone at a dose of 0.5 g 3 times a week for 3 weeks), followed by oral prednisolone for 6 months and tonsillectomy. Forty patients took candesartan in addition to this therapy for the first 6 months at an initial dose of 2–8 mg/day, gradually titrated according to proteinuria (not blood pressure) up to a maximum dose of 12 mg/day. For patients in both groups who did not achieve remission at 12 months, candesartan was administered for an additional 12 months.

The evaluated parameters were the proportion of patients who achieved remission of proteinuria (< 40 mg/mmol) and hematuria (< 5 red blood cells in the field of view) at 6, 12, and 24 months, as well as the progression of proteinuria, erythrocyturia, urine angiotensinogen (a biomarker of renal RAS activity), and estimated glomerular filtration rate (eGFR).

Results

There were no significant differences between the two groups regarding patient age, initial proteinuria, systolic blood pressure, and eGFR.

Comparable proportions of patients in the control group and the group taking candesartan achieved remission at all evaluated time intervals: at 6 months 37.8 vs. 35% (p = 0.80), at 12 months 48.7 vs. 38.5% (p = 0.37), and at 24 months 71.4 vs. 51.3% (p = 0.08). Thus, a positive effect of candesartan titration on IgA nephropathy remission was observed in both groups between 12 and 24 months.

Initial proteinuria was comparable in both groups (115 mg/mmol in the control group vs. 110 mg/mmol in the group randomized to take candesartan; p = 0.97). A decrease in proteinuria was observed in both groups at 6 months, but it remained significantly higher in the control group (24 vs. 12 mg/mmol; adjusted p = 0.005). At 12 and 24 months, proteinuria was comparably low in both groups.

Erythrocyturia was significantly lower in the control group at all evaluation points. In both groups, urine angiotensinogen levels significantly decreased after 6 and 24 months, despite a transient increase at 12 months in patients who initially took candesartan (which was discontinued at 6 months per study design). No significant changes in eGFR were observed in either group at 24 months. Both systolic and diastolic blood pressure was well controlled in all patients, and no serious adverse effects were observed.

Conclusion

No positive effect of concomitant use of candesartan and steroids on achieving remission (regardless of BP values) was demonstrated in the initial phase of treatment for active IgA nephropathy. However, adding candesartan might be beneficial for patients who do not achieve remission with conventional steroid therapy.

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Source: Kohagura K., Arima H., Miyasato H. et al. Add-on effect of angiotensin receptor blockade (candesartan) on clinical remission in active IgA nephropathy patients treated with steroid pulse therapy and tonsillectomy: a randomized, parallel-group comparison trial. Kidney Blood Press Res 2018; 43 (3): 780–792, doi: 10.1159/000489914.