Renal sensing of the acidifying effect of sulphur-containing amino acids: consequences for the relation between protein intake and blood pressure

The kidney as a nutrient sensing organ plays a key role in the relation between
dietary protein intake and blood pressure. Different amino acids may have
opposing effects, dependent on whether they are involved in gluconeogenesis
and/or ureagenesis or whether they are acidifying. Amino acids involved in
gluconeogenesis and/or ureagenesis may have a blood pressure lowering effect,
whereas several pathways may contribute to a blood-pressure raising effect of
acidifying amino acids. Subjects with subclinical renal injury, such as elderly
subjects, subjects with low renal functional mass such as renal transplant
recipients and subjects with obesity-related conditions, such as metabolic
syndrome and type 2 diabetes, will be more susceptible to the blood pressure
raising effects than others. Therefore, safety effects of (increased) intake of
(specific) dietary protein in subjects with compromised renal function need to
be elucidated.

The primary objective of this study is to unravel mechanisms by which dietary
protein (fractions) could influence systolic and diastolic blood pressure in
humans.

The study is designed as an observational epidemiological study.
Cross-sectional and prospective analyses will be performed in a cohort with
renal transplant recipients.

Renal transplant recipients form a very high risk population. Beyond one year
after transplantation, when threats of acute rejection and opportunistic
infections have largely disappeared, cardiovascular disease, high blood
pressure, and gradual decline of renal function unrelated to immunological
rejection are major problems. Rates of cardiovascular death and return to
dialysis are very high. Susceptibility for an effect of high ingestion of
sulphur-containing amino acids on blood pressure would be very high. This
population should also be extremely susceptible to dietary intervention.
Because of their high susceptibility, our hypothesis predicts amongst others
that variation in dietary ingestion of sulphur-containing amino acids within
subjects is associated with variation in blood pressure. This population is
therefore extremely interesting for testing the effects of dietary
intervention.
First we will collect data on dietary intake using the dietary questionnaire.
Each patient visits our outpatient clinic at least once a year, and 24h urine
collections and blood samples are gathered by routine, in combination with
assessment of blood pressure and body weight. This will allow us to perform
cross-sectional analyses initially and prospective analyses on development of
hypertension and changes in blood pressure, in which variation in dietary
sodium intake and other relevant parameters can be taken into account. From the
fresh 24h urine samples to be collected amongst others urinary creatinine,
bicarbonate, titratable acidity and ammonia will be determined in addition to
urinary sodium, urea and sulphate.
Because under steady state conditions intake equals output, assessments of food
substances and metabolites in 24h urine collections reflect dietary intake for
many food components. Potential modification of these relations by sodium
intake and body mass index can also be investigated.

There are no direct benefits for the patients to be included. Participation in
the study is on a free-will base. Patients will not receive any financial
support or priority for treatment of other diseases in the clinic during this
study.
Patients will be asked to fill in questionnaire concerning their dietary intake
and lifestyles. During their visit, blood pressure, height and weight will be
measured and fasting blood samples will be drawn.
Participation is accompanied with only minor risks. Venapunctures can
occasionally cause a local haematoma and some participants may report some
discomfort. All further performed measurements are non-invasive and risks are
therefore minimal.
Since patients will be seen at a regular visit to the outpatient clinic, no
extra costs for transportation to attend in the clinic for the study purpose
are needed.