We thank the authors of the letter entitled ‘Type of proteinuria might be essential for RAAS-I treatment in children with congenital anomalies of the kidney and urinary tract’ [Citation1] for highlighting the importance of discriminating proteinuria in children with congenital anomalies of the kidney and urinary tract (CAKUT). This adds useful information for the readers of the Special Report article entitled ‘Renin angiotensin aldosterone inhibitors in the treatment of proteinuria in children with congenital anomalies of the kidney and urinary tract: more evidence needed’ [Citation2].
Little is known regarding tubular proteinuria in patients with CAKUT. In fact, even if it is common knowledge that these patients have both tubular and glomerular proteinuria, the current literature principally supports the presence of glomerular proteinuria [Citation3,Citation4].
Moreover, increased urinary excretion of albumin (which is the index of glomerular proteinuria) is considered the most important risk predictor for progression of chronic kidney disease (CKD) [Citation5].
Angiotensin-converting enzyme inhibitors (ACE-I) and/or angiotensin II receptor blockers (ARBs) reduce proteinuria by lowering the intraglomerular pressure and reducing hyperfiltration [Citation6].
As pointed out in the comment [Citation1], these drugs have a significant impact on CKD progression, thanks to the reduction in albuminuria [Citation7].
Even if tubular proteinuria has an undetermined role in the progression of CKD, it could be a sign of congenital tubulo-interstitial dysplasia [Citation8,Citation9] that can be associated with CAKUT. So then, a screening for tubular proteinuria in patients with CAKUT can be useful to identify those patients who have kidney dysplasia and who have a congenital higher risk of developing CKD due to a congenital reduced nephronic mass [Citation10].
Furthermore, considering that renin–angiotensin–aldosterone (RAAS) system activation might be implicated in the kidney damage in patients with CAKUT in an early stage [Citation1,Citation11], patients with CAKUT who have glomerular proteinuria could benefit from RAAS inhibitors. Similarly, patients with mixed (glomerular and tubular) proteinuria could benefit from RAAS inhibitors by the reduction of glomerular quote of proteinuria. The association of ACE-I and ARBs might be a good therapy in patients with mixed proteinuria since it was shown to be safe in children [Citation12] and might have a better effect either on proteinuria and hypertension in comparison with single high-dose treatment [Citation13].
Declaration of interest
The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.
Additional information
Funding
References
- Marcellino A, Lubrano R. Letter to the editor: type of proteinuria might be essential for RAAS-I treatment in children with CAKUT. Expert Rev Clin Pharmacol. 2023. https://www.tandfonline.com/doi/full/10.1080/17512433.2023.2295004?src=recsys
- Rivetti G, Gizzone P, Di Sessa A, et al. Renin angiotensin aldosterone inhibitors in the treatment of proteinuria in children with congenital anomalies of the kidney and urinary tract: more evidence needed. Expert Rev Clin Pharmacol. 2023;16(9):791–798. doi: 10.1080/17512433.2023.2247985
- Matsell DG, Catapang M. Predicting outcomes and improving care in children with congenital kidney anomalies. doi: 10.1007/s00467-020-04677-2/Published
- Stonebrook E, Hoff M, Spencer JD. Congenital anomalies of the kidney and urinary tract: a clinical review. Curr Treat Options Pediatr. 2019;5:223. doi: 10.1007/S40746-019-00166-3
- Tuttle KR. Albuminuria reduction: the holy grail for kidney protection holy grail: a distant, ultimate goal. Kidney Int. 2007;72(7):785–786. doi: 10.1038/sj.ki.5002505
- Momoniat T, Ilyas D, Bhandari S. ACE inhibitors and ARBs: managing potassium and renal function. Cleve Clin J Med. 2019;86(9):601–607. doi: 10.3949/CCJM.86A.18024
- KDIGO. Clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney Int. 2012;33:1–150.
- Narasimhan KL, Mahajan JK, Kaur B, et al. The vesicoureteral reflux dysplasia syndrome in patients with posterior urethral valves. J Urol. 2005;174(4 Part 1):1433–1435. doi: 10.1097/01.JU.0000173129.70381.E9
- Konda R, Kakizaki H, Nakai H, et al. Urinary concentrations of alpha-1-microglobulin and albumin in patients with reflux nephropathy before and after puberty. Nephron. 2002;92(4):812–816. doi: 10.1159/000065462
- Kohl S, Avni FE, Boor P, et al. Definition, diagnosis and clinical management of non-obstructive kidney dysplasia: a consensus statement by the ERKNet Working group on kidney malformations. doi: 10.1093/ndt/gfac207
- Simões Silva A C, Lanza K, Andrade Palmeira V, et al. 2020 update on the renin–angiotensin–aldosterone system in pediatric kidney disease and its interactions with coronavirus. Pediatr Nephrol. 2021;36(6):1407–1426. doi: 10.1007/s00467-020-04759-1/Published
- Mastrangelo A, Brambilla M, Romano G, et al. Single, double and triple blockade of RAAS in Alport syndrome: different tools to freeze the evolution of the disease. J Clin Med. 2021;10(21):4946. doi: 10.3390/JCM10214946
- Lubrano R, Soscia F, Elli M, et al. Renal and cardiovascular effects of angiotensin-converting enzyme inhibitor plus angiotensin II receptor antagonist therapy in children with proteinuria. Pediatrics. 2006;118(3):e833–e838. doi: 10.1542/PEDS.2005-2053