Predictive Effect of Salt Intake on Patient and Kidney Survival in Non-Dialysis CKD

Competing Risk Analysis in Older Versus Younger Patients Under Nephrology Care

Carlo Garofalo; Michele Provenzano; Michele Andreucci; Antonio Pisani; Luca De Nicola; Giuseppe Conte; Silvio Borrelli


Nephrol Dial Transplant. 2021;36(12):2232-2240. 

In This Article

Abstract and Introduction


Background: The optimal level of salt intake remains ill-defined in non-dialysis chronic kidney disease (CKD) patients under regular nephrology care. This unanswered question becomes critical in older patients who are exposed to higher risk of worsening of cardiorenal disease due to volemic changes.

Methods: In this pooled analysis of four prospective studies in CKD, we compared the risk of all-cause mortality and end-stage kidney disease (ESKD) between patients ≤65 and >65 years of age stratified by salt intake level (<6, 6–8 and >8 g/day) estimated from two measurements of 24-h urinary sodium.

Results: The cohort included 1785 patients. The estimated glomerular filtration rate was 37 ± 21 mL/min/1.73 m2 overall, 41 ± 25 in younger patients and 34 ± 16 in older patients (P < 0.001). The median 24-h urinary sodium excretion was 143 mEq [interquartile range (IQR) 109–182] in all, 147 (112–185) in younger patients and 140 (106–179) in older patients (P = 0.012). Salt intake was ≤6, 6–8 and >8 g sodium chloride/day in 21.9, 26.2 and 52.0% of older patients and 18.6, 25.2 and 56.2% in younger patients, respectively (P = 0.145). During a median follow-up of 4.07 years we registered 383 ESKD and 260 all-cause deaths. In the whole cohort, the risks of ESKD and all-cause death did not differ by salt intake level. In older patients, ESKD risk [multi-adjusted hazard ratio (HR) and 95% confidence interval (CI)] was significantly lower at salt intakes of 6–8 g/day [HR 0.577 (95% CI 0.361–0.924)] and >8 g/day [HR 0.564 (95% CI 0.382–0.833)] versus the reference group (<6 g/day). Mortality risk was higher in older versus younger patients, with no difference across salt intake categories. No effect of salt intake on ESKD and mortality was observed in younger patients.

Conclusions: CKD patients under nephrology care show a moderate salt intake (8.4 g/day) that is lower in older versus younger patients. In this context, older patients are not exposed to higher mortality across different levels of salt intake, while salt intake <6 g/day poses a greater risk of ESKD.


Ageing of the general population is the major determinant of the observed increase of non-communicable chronic disease with higher rates of disabilities and frailty in elderly subjects. In this context, non-dialysis chronic kidney disease (CKD) plays a key role because its prevalence is more than double in individuals >65 years of age.[1,2] Since the epidemiological burden of CKD[3,4] leads to dramatic consequences in terms of social and economic costs, public health interventions aimed at slowing CKD progression and preventing the need for renal replacement therapy become crucial in elderly CKD patients.

In CKD, the mainstay of multifactorial therapy is the prescription of a low salt diet. The World Health Organization recommends a salt intake of <5 g/day in the general population to reduce blood pressure (BP) and cardiovascular (CV) mortality.[5] In a salt-sensitivity condition, such as CKD, a low salt intake is recommended to decrease BP and albuminuria; the latter effect being related to the synergism with renin–angiotensin–aldosterone system (RAAS) inhibitors.[6–9] Indeed, BP and albuminuria are recognized as major determinants of CKD progression.[8–11] However, few data are available on the effect of reducing sodium intake on renal outcome. A recent meta-analysis of randomized controlled trials has shown that a low salt diet is efficacious in reducing BP and albuminuria in CKD patients;[12] however, all included trials were characterized by short-term follow-ups. Long-term effects of low salt intake have been investigated in the large cohort of the Chronic Renal Insufficiency Cohort (CRIC) study and results showed a significant association between the highest quartile of sodium intake and the risk of CKD progression and CV mortality; the outcomes of the lowest quartile did not differ from those of the second and third quartiles.[13,14] However, the CRIC study was performed in middle-aged patients and did not provide evidence in elderly patients.

The gap of knowledge in elderly patients is not trivial because this large subgroup of the CKD population is characterized by impaired renal autoregulation due to atherosclerosis that can be enhanced by the effects of low salt intake on systemic and renal haemodynamics.[15] Indeed, elderly subjects are more susceptible to acute kidney dysfunction due to renal hypoperfusion even when BP levels are within the normal range.[16,17] In this regard, relevant are the signals of the potential risk of all-cause and CV mortality associated with lower salt intake in the general as well as the CKD population.[18–20] In contrast, older patients may be exposed to higher CV risk in the presence of higher salt intake because of the well-known sodium sensitivity of BP and the risk of heart failure.[6,21,22]

Therefore, to gain insights into the association between salt intake level and risks of end-stage kidney disease (ESKD) and mortality by age, we performed an observational study in a cohort of patients with CKD Stages 1–5 under regular nephrology care. The risk of either hard endpoint was compared between patients ≤65 or >65 years of age stratified by salt intake category (<6, 6–8 and >8 g/day).