Controlled Diet Studies of Intestinal Phosphorus Absorption in Chronic Kidney Disease
Elizabeth R Stremke
10.25394/PGS.12014814.v1
https://hammer.purdue.edu/articles/thesis/Controlled_Diet_Studies_of_Intestinal_Phosphorus_Absorption_in_Chronic_Kidney_Disease/12014814
<p>Chronic kidney disease
(CKD) affects approximately 37 million American adults with many more at risk
for disease development. Elevated serum phosphorus and related abnormalities in
phosphorus homeostasis due to progressive loss of kidney function are primary
driving forces behind cardiovascular dysfunction and mortality in CKD patients.
Intestinal phosphorus absorption is an understudied aspect in phosphorus
homeostasis. Despite this lack of information, current therapies focus on
reducing intestinal phosphorus absorption via the use of oral phosphate binders
and dietary phosphorus restriction. Abnormalities in phosphorus-regulating hormones
are already present in early stages of CKD, including elevated FGF23 and
decreased 1,25-dihydroxyvitamin D, which should have the effect of reduced
phosphorus absorption. However, rodent studies suggest that intestinal
phosphorus absorption remains at inappropriately normal levels in CKD, despite
perturbations in phosphorus homeostatic hormones. In these works, we studied
intestinal phosphorus absorption in patients with CKD, with a particular
emphasis on controlled diet studies, and on method of intestinal phosphorus
absorption assessment. </p>
<p> In our first study, we assessed the variation
and reliability of 24-hour urinary phosphorus excretion, a presumed biomarker
of intestinal phosphorus absorption, in N=8 moderate-stage CKD patients. Here
we found a high degree of variability in 13-consecutive measures of 24-hour
urine phosphorus measures in patients consuming a controlled diet. We also
found that at least two measures of 24-hour urine phosphorus is required for a
reliable measure. Lastly, we found that in these moderate CKD subjects, 24-hour
urine phosphorus is not related to net phosphorus absorption. However, this
does not preclude the existence of a relationship in interventional studies
assessing direct methods of intestinal phosphorus absorption suppression (i.e.
efficacy studies of phosphorus binders) and urinary phosphorus excretion.</p>
<p>Next, we assessed
fractional intestinal phosphorus absorption in N=8 moderate-stage CKD patients
compared to N=8 healthy adults matched for age, sex, and race. In this study,
we administered the radioisotopic tracer, 33-Phosphorus, via oral and
intravenous routes, staggered by exactly 25-hours. This mimics the
gold-standard method of dual-administration of two different isotopes. In our
study, the use of a single isotope is a safer method as 33-Phosphorus is lower
energy compared to 32-Phosphorus, a higher energy isotope used in some previous
studies of end-stage kidney disease. Our results showed that fractional
intestinal phosphorus absorption was similar between CKD patients and healthy
adults, as we hypothesized. These findings were despite significantly lower
values of serum 1,25D in CKD patients compared to healthy adults.</p>
<p>Lastly, we considered the
effect of adherence to a low-phosphorus diet on serum phosphorus
area-under-the-curve during the intradialytic period in hemodialysis patients.
In this secondary analysis of a placebo-arm of a drug trial that included a controlled
diet, we examined the post-dialytic serum phosphorus rebound in N=13
hemodialysis patients. We found that, compared to previous reports in the
literature, adhering to a low-phosphorus diet in hemodialysis patients may
delay the serum phosphorus rebound in the intradialytic period. In our study,
only 2 of 13 patients had returned to their pre-dialysis serum phosphorus
values at 24-hours post-dialysis and 4 of 13 at 48-hours. Importantly, all
patients were not using phosphate binder medications for the duration of the
study. These data show a potential benefit of adherence to a low phosphorus
diet for phosphorus control, even in the absence of phosphate binder medications.
However, longer studies of a controlled low phosphorus diet compared with a
normal phosphorus diet on serum phosphorus rebound in the intradialytic period is
needed to substantiate these findings.</p>
<p>The results from our
studies are foundational in the understanding phosphorus absorption in moderate
CKD. This knowledge will be critical for the development of translational interventions
to limit phosphorus burden at earlier stages of the disease, thus limiting
additional risk for disease progression and mortality.</p>
2020-03-22 14:58:21
phosphorus
phosphorus absorption
CKD
chronic kidney disease
renal nutrition
Nutrition and Dietetics not elsewhere classified
Nutritional Physiology