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

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 type 1 diabetes and 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
patients with diabetes.

Patients with diabetes form a high risk population in which intervention may
offer greater benefits than in low risk populations. Our hypothesis predicts
that patients with diabetes are more susceptible to the blood pressure raising
effects of renal sensing of the acidifying effect of ingestion of
sulphur-containing amino acids than healthy subjects. Patients with diabetes
frequently have mild renal function disturbances and a high prevalence of
hypertension. A cohort of more than 1200 patients with diabetes is visiting at
least once yearly our outpatient clinics. As already mentioned renal function
may be an important mediator of susceptibility for the effect of high intake of
sulphur-containing amino acids on blood pressure, while dietary sodium intake
and urinary mineralocorticoid excretion volume may be other important
determinants.

We will collect data on dietary intake using a dietary diary and a
questionnaire. Questions concerning patient*s lifestyles (e.g. smoking
behaviour, habitual physical activity) will be included as well. Patients with
diabetes will have to be instructed how to collect 24h urine samples and
containers will have to be sent to them. Follow-up of the patients will be
automatic, as diabetic patients visit our outpatient clinics usually 3 times a
year, and at least once a year.

Collection of fresh 24h urine samples will provide us with urine samples from
which amongst others urinary bicarbonate, titratable acidity and ammonia can be
determined in addition to urinary sodium, urea, sulphate, cortisol and
alsosterone. Repeated assessment of blood pressure, body weight, and
assessments in 24h urine collections will not only allow for initial
cross-sectional analyses, but also for prospective analyses of development of
hypertension and changes in blood pressure, in which variation in dietary
sodium intake and other relevant parameters can be taken into account.

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. Samples of 24-hour urine have to be collected by the patients.
During their visit, blood pressure, height and weight will be measured. Fasting
blood samples will be drawn during the venapuncture that is already performed
for regular clinical patient care. No further invasive measurements will be
executed and therefore risks of participation in this study are minimal, if
present at all. 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.