Plasma oxalic acid level, renal oxalate deposition and renal transplant function

Primary hyperoxaluria is an inborn metabolic disorder and is characterized by
overproduction of oxalic acid, which precipitates as oxalate in various organs,
especially in the kidney because this is the organ responsible for excretion of
oxalix acid. It always leads to renal insufficiency. Secondary hyperoxaluria
may be by caused by increased absorption as in gastro-intestinal disorders or
by decreased excretion as in renal insufficiency. Hemodialysis patients may
have very high oxalic acid levels: levels as high as those of patients with
primary hyperoxaluria can be found. Dialysis can decrease the level but
normalization is not achieved. Moreover, within 48 hours after dialysis the
level returns to pre-dialysis values. After renal transplantation the new
kidney graft starts to excrete oxalic acid and very high concentrations of
oxalic acid can be found in the urine. This may lead to oxalate deposition and
renal graft function deterioration or even loss.
In patientes with secundary hyperoxaluria because of gastro-intestinal disease
(besides their renal insufficiency), graft survival is known to be very bad and
in many centres these patients are declined for transplantation. Ten of these
patients have recently been transplanted in our centre with a protocol that
aimed at lowering pre-transplant oxalic acid levels by intensive hemodialysis
and low-oxalic acid diet. All were succesfull.
In a population of patients transplanted in the Erasmus MC in 2014-2015 we
studied all for cause kidney biopsies for the presence of oxalate crystals
within 3 months after kidney transplantation. 388 patients had been
transplanted during that period of whom 149 had had a kidney biopsy. Oxalate
crystals were present in 26 patients (17%) with a kidney biopsy. The patients
without a biopsy had the best graft survival (1% had failed after 1 year),
patients with a biopsy without oxalate functioned in between (8% of the kidneys
had failed after 2 years). Patients with oxalate in their biopsy had the worst
transplant survival (After 2 years, 30% of the kidneys had failed) (resp
p=0.001 and p=0.018 compared to both other groups). The role of plasma and
urine oxalic acid levels is unknown because they were not determined. Our
present study aims at the relationship between oxalic acid levels before kidney
transplantation and the occurrence of oxalate deposits in the kidney and
decreased renal transplant survival. If high levels at transplantation play a
role, measures to decrease these levels pre transplantation in order to prevent
unnecessary loss of transplant kidneys may be indicated. This can easily be
realized by re-institution of hemodialysis treatment shortly before
transplantation to decrease levels. Over the years, the indications for
dialysis shortly before transplantation have been liberated and it occurs that
patients* last dialysis session was a few days before transplantation. In that
period, the plasma oxalic acid could have risen considerably. Simple measures
for improvement could consist of dialysis shortly before transplantation (a few
hours) possibly combined with oxalic acid-restricted diet before
transplantation.

Primary Objective:
* Study the relationship between the pre-transplant plasma oxalic acid level
and the risk of oxalate deposition in for cause renal transplant biopsies
within 6 months after renal transplantation.
Secondary Objective(s):
* Track down the relationship between oxalic acid intake and dialysis status on
the one hand and plasma oxalic acid levels on the other.
* Study the relationship between the pre-transplant plasma oxalic acid level
and graft function and graft loss at 6 months and at 1 year after renal
transplantation.
Study the relationship between oxalate deposition in the graft and graft
function and graft loss at 6 months and at 1 year after renal transplantation.
* The aim is therefore to evaluate the indication for oxalic acid lowering
therapy shortly before transplantation.

This is an observational cohort study.
On the day of transplantation the patient will be asked to fill in a
questionnaire on renal function replacement therapy and on food habits (oxalic
acid content).
Shortly before transplantation (1-2 hours) 1 blood sample will be drawn to
determine plasma oxalic acid value in a cohort of patients. In a small part of
patients, where renal function is delayed and dialysis will be restarted after
transplantation, another blood sample will be taken before start dialysis.
The relationship will be studied between the value of oxalic acid and post
transplant oxalate deposition in the kidneys with for cause renal transplant
biopsy within 6 months after transplantation. It will also be correlated to
renal function and graft survival at 6 months and 1 year after transplantation.
A subsidy for determination of 400 samples was obtained. The number of patients
that will be included depends on the number of patients that need 2 oxalic acid
determinations (delayed graft function occurs in roughly 5% of patients).
Between 275-325 patients can be included than.

Inclusion will be performed in the pre transplant outpatient setting.
The study actions will be performed during admission for transplantation. On
the day of/before transplantation a questionnaire must be filled in (about 25
minutes)
One hour before transplantation 10 cc blood will be drawn while the patient is
already in the operating room.
In patients in whom dialysis has to be re started during admission for
transplantation another one-time 10 cc blood sample will be drawn for oxalic
acid determination.