title: Vitamin D analogues to target residual proteinuria: potential impact on cardiorenal outcomes.
abstract: Residual proteinuria, the amount of proteinuria that remains during optimally dosed renin-angiotensin-aldosterone system (RAAS) blockade, is an independent risk factor for progressive renal function loss and cardiovascular complications in chronic kidney disease (CKD) patients. Dual RAAS blockade may reduce residual proteinuria but without translating into improved cardiorenal outcomes at least in diabetic nephropathy; rather, dual RAAS blockade may increase the risk of adverse events. These findings have challenged the concept of residual proteinuria as an absolute treatment target. Therefore, new strategies must be explored to address whether by further reduction of residual proteinuria using interventions not primarily targeting the RAAS benefit in terms of cardiorenal risk reduction would accrue. Both clinical and experimental intervention studies have demonstrated that vitamin D can reduce residual proteinuria through both RAAS-dependent and RAAS-independent pathways. Future research should prospectively explore vitamin D treatment as an adjunct to RAAS blockade in an interventional trial exploring clinically relevant cardiorenal end points.
authors.affiliation: Division of Nephrology, Department of Medicine, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Jelmer K
authors.initials: JK
authors.lastname: Humalda
authors.affiliation: Renal Unit at Guy's and St Thomas' NHS Foundation Hospital, London, UK.
authors.forename: David J A
authors.initials: DJ
authors.lastname: Goldsmith
authors.affiliation: Division of Nephrology, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Ravi
authors.initials: R
authors.lastname: Thadhani
authors.affiliation: Division of Nephrology, Department of Medicine, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Martin H
authors.initials: MH
authors.lastname: de Borst
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D059347:Cardio-Renal Syndrome / Q000517:prevention & control*; D006801:Humans; D011507:Proteinuria / Q000188:drug therapy*; D051436:Renal Insufficiency, Chronic / Q000517:prevention & control*; D012084:Renin-Angiotensin System / Q000187:drug effects*; D014807:Vitamin D / Q000627:therapeutic use*
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D014807:Vitamin D
keywords: cardiovascular disease; chronic kidney disease; proteinuria; vitamin D