Effects of Intensive Low-Salt Diet Education on Albuminuria: CJASN e-Journal Club

This month’s CJASN e-journal club was hosted at the Department of Nephrology at the Royal Infirmary of Edinburgh. It discussed a trial designed to investigate the efficacy of an intensive low salt diet intervention (weekly 30 minutes phone feedback by a dietary consultant) on albuminuria in non-diabetic hypertensive patients already on an ARB. This study is an open-label, case-control, randomized clinical trial based in South Korea. 

It is important to note that selected patients were a relatively healthy, homogenous population with good blood pressure control and an already low urinary sodium excretion. Very few were active smokers and many took regular exercise. All RAAS antagonists and diuretic agents were stopped for an 8 week run in and blood pressure was controlled with alternative agents. At week 0, Olmesartan was then commenced, and at 8 weeks, subjects were randomised to control or intensive education groups. 
The primary endpoint was the decrement in albuminuria by week 16 and was reached in the intensive salt reduction group. They demonstrated a significant reduction in albuminuria (278 mg/d to 178 mg/d) compared to the conventional therapy group (258 mg/d to 231 mg/d). There was a greater reduction in urinary sodium excretion in the intensive education group than the conventional group, but no change in blood pressure or renal function. In subgroup analyses, the authors examined those that received a reduction of > 25% of their dietary salt and those who did not, irrespective of treatment group. Notably, only 60% of those who achieved this reduction came from the intensive group. 

Overall this is an interesting, well-performed study which successfully demonstrates that lower salt excretion correlates with lower albuminuria. This occurred despite no effect on BP in a cohort with already excellent BP control. It may be better to interpret this as a “proof of concept” that salt restriction in humans could influence albuminuria. For clinical practice however, there are issues around the generalizability of these findings to everyday patients, given this was a highly selected, compliant group of patients. Also, as we know in the nephrology community from previous trials, an improvement in a relatively soft endpoint like albuminuria will not necessarily translate into improvements in renal/cardiovascular events or mortality. 

Check out the full text of the paper, our complete post and discussion over at the CJASN eJC website.

Authored by Eoin O’Sullivan & Paul Phelan

High Salt-Intake and Autoimmunity

The incidence of auto-immune diseases has dramatically increased in the past 50 years and the concern that environmental exposures have contributed to this increase is broadly suspected. However, it is very hard to pin-point to an individual factor. 

Very intriguing observations were just published at Nature linking a high-salt intake to increased auto-immunity. The authors demonstrate that a high-salt diet increased the severity of experimental autoimmune encephalomyelitis (*EAE) - a mouse model of multiple sclerosis . The authors proposed that high salt-intake induces serum glucocorticoid kinase 1 (SGK1), which than promotes IL-23R expression and enhances TH17 ** cell differentiation in vitro and in vivo. SGK1 has has been shown to govern Na transport and salt (NaCl) homeostasis in other cells. Mice lacking this kinase in their T cells have impaired expression of IL-17-family cytokines and of a receptor for another cytokine molecule, IL-23, which stabilizes the TH17 cell phenotype.

Though salt might not be the trigger of autoimmunity, the possibility that high-salt intake might exacerbate auto-immunity is very provoking and would encourage even more the emergent initiation of trials evaluating the efficacy of low salt-diet in the development of auto-immune diseases and other potential diseases related to inflammation, such as coronary heart disease. 

Based on recent computer-generated data suggesting all the potential benefits of lowering salt consumption, this discussion is very pertinent.  

Above the diagram from the Editorial of Nature discussing the findings and below some additional explanations about the mouse model and Th17 cells. One caveat is that effect of high sodium on human cells was only shown in vitro...

* EAE: Experimental autoimmune encephalomyelitis. An animal model of the human autoimmune disease multiple sclerosis. EAE is experimentally induced in animals by immunization with myelin or with peptides derived from myelin. The animals develop a paralytic disease with inflammation and demyelination in the brain and spinal cord.

** TH17 cells (T helper 17 cells). A subset of CD4+ T helper cells that produce interleukin-17 (IL-17) and that are thought to be important in inflammatory and autoimmune diseases. Their generation involves IL-6, IL-21 and IL-23, as well as the transcription factors RORgt (retinoic-acid-receptor-related orphan receptor-gt) and STAT3 (signal transducer and activator of transcription 3).