Blog entry by mohammad katout

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by mohammad katout - Friday, 6 January 2012, 8:35 AM
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An interesting recent single-center retrospective cohort study of pediatric patients (n: 67) with primary FSGS confirmed by biopsy. Kangovi S, Edwards M, Woloszynek S, Mitra N, Feldman H, Kaplan BS, Meyers KE. Renin-angiotensin-aldosterone system inhibitors in pediatric focal segmental glomerulosclerosis. Pediatr Nephrol. 2011 Nov 25. [Epub ahead of print] Start of follow-up was defined as the time of diagnosis of FSGS based on the onset of clinical symptoms such as edema. Patients were classified into two groups based upon initial treatment: RAAS inhibition monotherapy (RIM, 35 patients on angiotensin-converting enzyme inhibitors and/or angiotensin-receptor blockers without immunosuppressive agents) and conventional therapy (CT, 32 patients with steroids and other immunosuppressive agents). The primary endpoint was progression to end-stage renal disease (ESRD). Secondary endpoints were remission of proteinuria, relapse, and death. They analyzed the baseline characteristics of this cohort. Patients in the RIM group were more likely to be African–American, older, and have worse renal function but less proteinuria than patients in the CT group. The authors assumed that the presence of a certain profile of clinical characteristics (older, African–American, low eGFR, sub-nephrotic proteinuria) signaled to nephrologists that the underlying disease was a subtype or later stage of FSGS that, in their center’s experience, responded to RAAS inhibition monotherapy. This belief may have been supported by data that suggest that the Mendoza protocol may not be as effective in African–Americans as it is in Caucasian patients! Patients started on RAAS inhibition monotherapy remained on this modality for a longer period of time and that only 5.7% of patients in the RIM group were switched over to conventional therapy. Authors concluded that patients tolerated RAAS inhibition monotherapy without serious side effects for a relatively long period of time. Second, there was rarely a need to “step up” therapy for patients in the RIM group to conventional immunosuppressive medications.  The authors suggested that RAAS inhibition monotherapy might be more effective than toxic immunosuppressive medications for this subset of pediatric FSGS patients. They suggested that RAAS inhibition monotherapy can be an alternative to conventional therapy, particularly for patients who are poor candidates for immunosuppressive medication Yet, there are several limitations of this study: - relatively small sample size limiting the accuracy of estimates. - 1986-2008 is a long time with changing trends in the decision regarding initial treatment that could have biased the treatment groups (the earlier half of the cohort received care prior to more recent data supporting the role of RAAS inhibition in proteinuric renal diseases!), Moreover, the authors did not correlate the outcome in both groups to genetic mutational analysis in these FSGS patients and never mentioned the percentage of genetically proven FSGS amongst their study children! A prospective randomized controlled trial on a larger number of patients is greatly needed to assess the efficacy of RAAS inhibition monotherapy compared with conventional immunosuppressive therapy in pediatric primary FSGS. Also, it would be interesting to study the clinical decision-making to further understand nephrologists’ reasons for selecting RAAS inhibition monotherapy over conventional therapy.
[ Modified: Thursday, 1 January 1970, 1:00 AM ]