LAUSR

The amount of proteinuria continues to be one of the parameters that best correlates with the development of renal failure in any glomerular pathology. This circumstance is especially relevant when the analysis is limited to IgA nephropathy (IgAN). Although there is no prospective evidence, the influence of proteinuria on renal evolution has been strongly tested in retrospective studies with a very high number of patients after long follow-up periods [1–3]. There is a broad agreement in the nephrological world that treatment with blockade of the renin-angiotensin-aldosterone system (RAAS) is the chosen treatment in patients with IgAN and proteinuria greater than 0.5–1 g/day and arterial hypertension [4]. There are very few randomized, controlled trials (RCT) in IgAN, even though it is the most common glomerular disease worldwide. However, these few studies have shown a significantly better renal survival in patients treated in this way, provided that the targets of proteinuria and blood pressure are achieved [5–7]. The early antiproteinuric effect of blockade RAAS and its recognized local activity have shown a clear renal benefit in the pediatric population. In this issue of the Pediatric Nephrology, Shima et al. [8] report the first RCT that compares the effectiveness and safety of lisinopril in monotherapy versus the combination of lisinopril and losartan in children with IgAN and mild proteinuria. This is a Japanese multicenter study (19 hospitals) prospective, open-label, and randomized (1:1, adjusted by age) phase II controlled conducted between 2005 and 2010 in 63 pediatric patients with biopsy-proven IgA nephropathy and mild proteinuria. The primary end-point was the rate of disappearance of proteinuria between the monotherapy group (group A) and the combination group (group B) after a follow-up of 749 and 743 days, respectively. At the end of the study, no significant differences were observed in the disappearance of proteinuria between the two groups (group A, 89.3% vs. group B, 89%) without differences in safety either. The authors concluded that the combination of lisinopril with losartan does not provide any benefit to treatment with lisinopril alone. However, it is important to highlight that the inclusion criteria of patients can qualify these results. Only patients with mild proteinuria and renal biopsy showing minimal or focal mesangial proliferation (less than 80% glomeruli with moderate or severe mesangial cell proliferation) were included. All the enrolled patients showed an estimated glomerular filtration rate (eGFR) greater than 60 ml/min/1.73 m and the percentage of patients with urinary protein excretion to creatinine ratio (uP/Cr) greater than 0.5 g/g was 42.9% in group A and of 34.5% in group B. As a relevant data, complete remission was reached in 32.2% of patients in group A and in 45% in group B (defined as the disappearance of hematuria, a ratio uP/Cr < 0.2 g/g and eGFR > 60 ml/min/ 1.73 m). One of the things that IgAN suffers is that there is no consistent data on the number of patients who achieved a spontaneous remission. This same group published its experience with a large series of 555 patients, of which 57 (10.3%) achieved spontaneous remission without receiving any medication. These patients showedminor glomerular abnormalities or focal mesangial proliferation. In this study, the authors advise that physicians should consider the possibility of spontaneous remission and wait for the use of relatively aggressive immunosuppressive treatments in IgAN patients with minor glomerular abnormalities or focal mesangial proliferation [9]. Our group observed remission in 37.6% of 141 patients with * Eduardo Gutiérrez [email protected]