The reservecapacity of the peritoneum with the NO donor sodium nitroprusside during peritoneal dialysis

Peritoneal membrane failure is associated with an increase in the effective
peritoneal vascular surface area, which is reflected by transport of small
solutes. Its efficacy is determined by peritoneal blood volume. Therefore, the
effective peritoneal vascular surface area can be influenced by vasoactive
substances and the number of vessels perfused. This can be illustrated by the
U-shaped time course for peritoneal solute transport, as described previously
by Parikova et al. The initial high values suggest the influence of vasoactive
substances. The subsequent decrease is followed by an increase, suggesting
neoangiogenesis, a more permanent peritoneal membrane alteration. However,
neoangiogenesis is not significantly related with the duration of PD, although
significantly more vessels are present in patients with membrane failure.
Furthermore, an increase in interindividual variability is present in
peritoneal solute transport and ultrafiltration capacity with the duration of
PD. This makes it rather difficult to predict which patients will develop
marked peritoneal membrane failure.
The Peritoneal Biopsy Study Group reported that vasculopathy was positively
correlated with the duration of PD. A prevalence of 29% was present in patients
less than 2 years on PD and a prevalence of 77% in patients treated with PD
between 4 and 6 years. Vasculopathy was defined as the presence of
subendothelial hyalinization eventually causing luminal narrowing or
obliteration of peritoneal vessels. It is considered a risk factor for
neoangiogenesis and fibrosis of the peritoneal membrane. It is also conceivable
that it causes an increase in the stiffness of the peritoneal vessels and a
decrease in the intraluminal diameter of the vessel. Therefore, it is
hypothesized that the presence of vasculopathy results in a decreased capacity
of the peritoneal vessels to vasodilate, a so-called decreased
*reservecapacity* of the peritoneal membrane. It was observed that
intraperitoneal administration of the vasodilator sodium nitroprusside caused
an increase in peritoneal transport of small solutes in stable PD patients.
This has been shown for intermittent PD and also for continuous ambulatory PD.
A difference in peritoneal protein transport was found between short-term and
long-term PD patients in a study of Park et al. However, in this study a large
intra-individual variability was present. With the methodology used by Imholz
et al., low intra-individual variation coefficients are present.

The objective is to analyze whether a difference in reservecapacity is present
between short-term and long-term PD patients. In case the reservecapacity of
the peritoneum is significantly lower in the long-term compared to short-term
PD patients, a peritoneal function test with the addition of sodium
nitroprusside can be used as an additional tool in long-term PD patients who
are likely to develop marked peritoneal membrane failure.

It will be an observational open-label study.

2 standardized peritoneal function tests with a maximal interval of 2 weeks
will be performed in all patients who are included in the study: one peritoneal
function test with the addition of 4.5mg/L sodium nitroprusside and one
peritoneal function test without sodium nitroprusside. The sequence of the 2
tests will be randomized, but not blinded. This will be done in patients < 1
year on PD treatment and > 3 years on PD treatment. It will be observed what
differences in study parameters are present between the peritoneal function
test with and without sodium nitroprusside in both patient groups.

The peritoneal function test without the intervention will be part of the
regular yearly assessment of the peritoneal function. Patient burden can be
considered to be low, as the SPA with the addition of sodium nitroprusside does
not differ from the regular SPA in terms of data collection No side effects
have been described previously by adding sodium nitroprusside to the SPA.
Therefore, the burden for the patient consists of one additional peritoneal
function test for which the patient has to visit the Academic Medical Center.
At present it is very difficult to predict which patient will develop marked
peritoneal membrane failure. With the results of the present study we
hypothesize that we gain more insight in the peritoneal pathophysiology.
Furthermore, determination of the reservecapacity of the peritoneal membrane by
means of a nitroprusside SPA could be a valuable diagnostic tool to predict
which patient will develop severe peritoneal membrane failure.