Hypertension: from basic research to clinical practice

Mulè, Giuseppe, Castiglia, Antonella, Cusumano, Claudia, Scaduto, Emilia, Geraci, Giulio, Altieri, Dario, Di Natale, Epifanio, Cacciatore, Onofrio, Cerasola, Giovanni, Cottone, Santina, Giuseppe Mulè, Antonella Castiglia, Claudia Cusumano, Emilia Scaduto, Giulio Geraci, Dario Altieri, Epifanio Di Natale, Onofrio Cacciatore, Giovanni Cerasola, Santina Cottone

The kidney is one of the major target organs of hypertension.Kidney damage represents a frequent event in the course of hypertension and arterial hypertension is one of the leading causes of end-stage renal disease (ESRD).ESRD has long been recognized as a strong predictor of cardiovascular (CV) morbidity and mortality. However, over the past 20 years a large and consistent body of evidence has been produced suggesting that CV risk progressively increases as the estimated glomerular filtration rate (eGFR) declines and is already significantly elevated even in the earliest stages of renal damage. Data was supported by the very large collaborative meta-analysis of the Chronic Kidney Disease Prognosis Consortium, which provided undisputable evidence that there is an inverse association between eGFR and CV risk. It is important to remember that in evaluating CV disease using renal parameters, GFR should be assessed simultaneously with albuminuria.Indeed, data from the same meta-analysis indicate that also increased urinary albumin levels or proteinuria carry an increased risk of all-cause and CV mortality. Thus, lower eGFR and higher urinary albumin values are not only predictors of progressive kidney failure, but also of all-cause and CV mortality, independent of each other and of traditional CV risk factors.Although subjects with ESRD are at the highest risk of CV diseases, there will likely be more events in subjects with mil-to-moderate renal dysfunction, because of its much higher prevalence.These findings are even more noteworthy when one considers that a mild reduction in renal function is very common in hypertensive patients.The current European Society of Hypertension (ESH)/European Society of Cardiology (ESC) guidelines for the management of arterial hypertension recommend to sought in every patient signs of subclinical (or asymptomatic) renal damage. This was defined by the detection of eGFR between 30 mL/min/1.73 m(2) and 60 mL/min/1.73 m(2) or the presence of microalbuminuria (MAU), that is an amount of albumin in the urine of 30-300 mg/day or an albumin/creatinine ratio, preferentially on morning spot urine, of 30-300 mg/g.There is clear evidence that urinary albumin excretion levels, even below the cut-off values used to define MAU, are associated with an increased risk of CV events. The relationships of MAU with a variety of risk factors, such as blood pressure, diabetes and metabolic syndrome and with several indices of subclinical organ damage, may contribute, at least in part, to explain the enhanced CV risk conferred by MAU. Nonetheless, several studies showed that the association between MAU and CV disease remains when all these risk factors are taken into account in multivariate analyses. Therefore, the exact pathophysiological mechanisms explaining the association between MAU and CV risk remain to be elucidated. The simple search for MAU and in general of subclinical renal involvement in hypertensive patients may enable the clinician to better assess absolute CV risk, and its identification may induce physicians to encourage patients to make healthy lifestyle changes and perhaps would prompt to more aggressive modification of standard CV risk factors.