Salt sensitivity and hypertensive nephropathy: a link to be discovered

Objective: Sodium sensitivity is defined as a change in blood pressure depending on sodium intake, which is present in about 30% of the adult population. According to blood pressure variation in salt load test we can classify the population in 3 categories: sodium sensitive (SS), sodium resistant (SR), inverse sodium sensitivity (ISS), based on, respectively, an increase, a non-significant variation or a decrease in the blood pressure values following the administration of sodium. It is reported that SS subjects have, independently from other risk factors, an increased risk of cardiovascular diseases. Moreover, SNPs located in genes related with Na+ metabolism, aldosterone synthesis and tubular sodium reabsorption in the kidney are related to salt sensitivity phenotype. The aim of this study is to analyze the relationship between sodium sensitivity and the development of hypertensive kidney damage in patients with primary hypertension. Design and method: A cohort of 712 naïve hypertensive patients were classified for salt-sensitivity using acute saline test (NaCl 308 mEq / 2h / iv).127 patients (follow-up > 5 years- median 11) were selected for the present analysis (SS, n = 40; 0 SR, n = 46; RSS, n = 41). We analyzed annual decline of the eGFR (CDK-EPI) (Delta-eGFR) and development of microalbuminuria (MicrAlb) as renal outcome. Moreover, genetic polymorphism involved in salt sensitive hypertension has been investigated. Results: No differences in Delta-eGFR was observed among the groups. However, SR subjects develop earlier microalbuminuria (p = 0.002) even with an adequate pressure control. Genotypes analysis revealed: polymorphism in CYP11B2 and NEDD4L to be protective against decline in eGFR. For microalbuminuria HSD3B1 and ADD3 seem to be a risk factors, whereas KL, PKD and TRPC6 polymorphism result protective factors. Conclusions: Unexpectedly these finding suggests that SR patients are more at risk of developing hypertensive nephropathy than other groups of patients. Moreover genotypes associated with salt sensitivity play different and complex role in kidney damage in hypertension. Improvement in salt sensitivity testing and standardization will be needed to allow all this pathophysiological knowledge to be translated in a clinical setting