Low presription of ACEI/ARB among hypertensive patients who showed two consecutive albuminuria during national health screening program in Korea

Abstract

The ability of renin-angiotensin-aldosterone system (RAAS) suppression to reduce albuminuria is clear. However, chronic suppression of RAAS does not impede the development of cardiorenal damage in all cases. Microalbuminuria is one of the predictors. With high prevalence, patients under chronic treatment show albuminuria or even develop de novo microalbuminuria, but there are not available markers able to predict patients’ evolution. The purpose of the study is to discover a molecular fingerprint in urine associated to albuminuria progression in HBP patients chronically treated, allowing the evaluation of patients’ response to the action of RAAS inhibitors. We have investigated changes in urine proteome and metabolome by using complementary omics approaches. Urine was collected from hypertensive patients under chronic suppression of RAAS, and healthy subjects. Patients were classified as: normoalbuminuric who had remained stable (normonormo), normoalbuminuric who had progressed to microalbuminuria (normo-micro) and microalbuminuric who had remained stable (micro-micro). By differential gel electrophoresis (DIGE), 27 protein spots were found significantly altered (fold change >2, p value <0.05) corresponding to 11 proteins which respond to albuminuria condition with different trends: 2 proteins were altered in all patients versus controls, 3 proteins responded specifically to microalbuminuria and 6 proteins were altered significantly in either normo-normo, normo-micro or micro-micro patients’ group. By nuclear magnetic resonance, 26 metabolite signals showed variation in response to albuminuria finding three different trends: responders to albuminuria progression, responders to HBP condition itself, or responders at intermediate condition (normo-normo or normo-micro) which do not differentiate among control and micro-micro individuals. In conclusion, a specific protein and metabolite fingerprint in urine respond to albuminuria condition and progression in HBP patients under chronic suppression of RAAS.