Improvement of Glycemic Control by CAPD with Intraperitoneal Insulin in a Child with IDDM and ESRD
Joseph T. Flynn, David B. Kershaw, Aileen B.
Sedman, William E. Smoyer, Timothy E. Bunchman
Use of intraperitoneal insulin in diabetic
end-stage renal disease (ESRD) patients receiving
continuous ambulatory peritoneal dialysis (CAPD) is known
to result in improved glycemic control. This route
of insulin administration, although standard in
adult diabetic CAPD patients, has not previously
been reported in children.
A 12-year old boy with ESRD from renal
dysplasia who also had insulin-dependent diabetes
mellitus (IDDM) was treated with CAPD and
intraperitoneal insulin prior to renal transplantation. Diabetes
and renal dysplasia were both diagnosed at 11 weeks
of age. When he reached end-stage he was initially started on hemodialysis via a central line but
was switched to CAPD because of recurrent line
sepsis. His IDDM had been poorly controlled up to that
time. CAPD was performed using 4 exchanges per day
of 1.5% dialysate with a fixed dose of insulin added
to each bag and with adjustments made based on
blood glucose. His glycemic control markedly
improved, with a fall in his glycosylated hemoglobin from
13.6% to 6%. CAPD was continued for 7 months until
a living-related renal transplant was performed.
Two episodes of peritonitis occurred while the
patient received CAPD (1 episode/3.5 patient-months).
We conclude that the use of intraperitoneal
insulin in children with IDDM and ESRD leads to
improved glycemic control. The rate of peritonitis, however,
may be increased in these children.
Diabetes, insulin, children
From:Department of Pediatrics and
Communicable Diseases, University of Michigan, Ann Arbor,
Patients with insulin-dependent diabetes
mellitus (IDDM) who develop end-stage renal disease
(ESRD) may continue to benefit from strict control of
their diabetes in order to avoid or forestall the
development of extrarenal diabetic complications.
Continuous ambulatory peritoneal dialysis (CAPD) with
intraperitoneal insulin administration has been shown
to provide superior glycemic control compared to subcutaneous administration of insulin (1,2), and
is therefore favored by many nephrologists for
these patients (3-6).
These issues are rarely faced in the
management of children with IDDM since they rarely
develop ESRD from diabetic nephropathy during
childhood (7). We recently cared for a child with ESRD
from renal dysplasia who also had IDDM and who
required dialysis prior to renal transplantation. Use of
CAPD with intraperitoneal insulin administration
markedly improved his glycemic control. His clinical
course demonstrates that management approaches used
in adults with IDDM can be successfully adapted
for use in children.
EZ was referred to our service at the age of 9
years for management of renal insufficiency. He had
been diagnosed with IDDM at the age of 11 weeks,
and had had erratic control of his diabetes
throughout early childhood, with numerous hospitalizations
for hypoglycemia and diabetic ketoacidosis. He had
been noted to have "cystic kidneys" on renal
ultrasound in infancy, but at the time of presentation to us a
repeat renal ultrasound revealed small, echogenic
kidneys without large cysts, most consistent with
long-standing renal dysplasia. Glomerular filtration
rate (GFR) at that time was approximately 34 mL/min
per 1.73 m2. Recurrent dehydration secondary to
his high obligate urine output led to placement of
a feeding gastrostomy and institution of
continuous feedings. Despite intensive conservative
management of his renal disease and intensive treatment of
his diabetes, he gradually progressed to ESRD and required initiation of dialysis 2 years after
initial presentation to our center.
Because of family concerns, the initial
dialysis modality selected was hemodialysis (HD), and
a percutaneous tunneled central venous dialysis catheter was placed. The patient received HD
four times per week with good control of his uremia,
but continued poor control of his diabetes (see
Table I). He also developed frequent infections of his
dialysis catheter, which continued to recur even after
removal of his original line and replacement with a new line
a week later. After a symptomatic episode of
Enterobacter sepsis, it was decided to switch him
to peritoneal dialysis (PD), and a Tenckhoff catheter
was placed. His route of insulin administration
was gradually transitioned from subcutaneous to
intraperitoneal as his dialysis volumes were
increased. Eventually he reached a stable CAPD regimen of
four 1.0-L exchanges of 1.5% dialysate (Dianeal®,
Baxter Healthcare Corp., McGaw Park, IL, USA) per
day, with 18 to 23 units of regular insulin added to
each bag. Insulin was added through the injection port
of the bags using sterile technique. Adjustments to
the insulin dose were made based on regular blood-glucose monitoring. The total daily dose of
insulin was divided equally among the four bags, as
is generally recommended (8). Occasional episodes
of hyperglycemia were treated with small doses of regular insulin administered subcutaneously.
On this regimen the patient's clinical
condition stabilized considerably. His appetite and
well-being improved, and he had no further episodes of
dehydration. His total daily insulin dose
increased markedly compared to his pre-CAPD dose, but
this was accompanied by a dramatic improvement in
his glycosylated hemoglobin, reflecting improved
glycemic control (see Table I). He was
successfully maintained on the above regimen for a total
of 7 months, until a living-related renal transplant
was performed. Unfortunately, he developed two
episodes of S. aureus peritonitis while receiving CAPD,
for an overall peritonitis rate of 1 episode per 3.5 months.
At the present time, the patient is doing
well, 15 months after his renal transplant, with a stable
serum creatinine of 1.3 mg/dL. He is receiving
intensive management of his IDDM with twice-daily
subcutaneous insulin injections. On this regimen, his
total daily insulin dose has decreased below what he
was receiving prior to CAPD, and his glycemic
control remains adequate, although he is not as
well-controlled as he was while receiving CAPD (see Table I).
Many complications of IDDM are felt to be
related to hyperglycemia, including retinopathy,
nephropathy, and peripheral neuropathy (9). Given the
recent demonstration of the ability to delay the onset
and/or progression of these complications with
intensive management of IDDM (10), control of blood
glucose has gained greater importance than ever before in
the management of IDDM (11). This same philosophy prevails even after patients have progressed to
ESRD, since they remain at risk for development of all
the extrarenal complications of IDDM (2,4).
Toward this end, diabetics who develop
ESRD are frequently managed with CAPD because of
the possibility of administering insulin continuously
via the intraperitoneal route. Intraperitoneal
insulin administration has been shown to produce
improved glycemic control and improved insulin
sensitivity while avoiding the high circulating insulin levels
and peripheral insulin resistance often seen with
the subcutaneous route of insulin administration
(1,2,4). Although there is a theoretical increased risk
of peritonitis, because of the necessity of
injecting insulin into the dialysate bags, this has not been
a consistent finding in clinical trials (3,8). Side
effects of intraperitoneal insulin administration which
have been commonly reported include
hyperlipidemia (1,12) and subcapsular hepatic steatosis (3). However,
since the clinical significance of these
findings remains unclear, the advantages of
intraperitoneal insulin administration are commonly agreed
to outweigh its disadvantages. Many authors
therefore recommend CAPD with intraperitoneal
insulin administration as a first-line dialysis modality
for diabetic adults who develop ESRD (3,5,6).
In contrast to the high prevalence of IDDM as
a cause of ESRD in adults, children with IDDM
rarely develop ESRD solely due to their diabetes:
among over 3000 children with ESRD reported to the
North American Pediatric Renal Transplant
Cooperative Study (NAPRTCS), only 0.1% listed IDDM as a
cause of ESRD (7). Consequently, experience with
management of children with IDDM on dialysis is
sorely lacking; we could locate no previous reports of a
child with IDDM who had received CAPD, despite an exhaustive literature search.
Although our patient developed ESRD from
a cause other than IDDM, his coexisting IDDM made his management on dialysis similar, if not
identical, to that of an adult with IDDM who develops
ESRD. By adapting adult protocols for CAPD with
intraperitoneal insulin administration, we were able
to achieve a significant improvement in his
glycemic control compared to his pre-CAPD management,
as evidenced by a greater-than-50% reduction of
his glycosylated hemoglobin to a level seen in
normal individuals. His glycemic control on CAPD was
even superior to what he is currently achieving with a
well-functioning renal transplant and intensive
subcutaneous insulin administration.
Similar to what is seen in adults with
diabetic nephropathy, our patient's total daily insulin
dose increased dramatically over his pre-CAPD
insulin dose. CAPD also proved an effective solution to
his long-standing tendency toward dehydration. However, he did have difficulties with
recurrent peritonitis while on CAPD, with a frequency
of peritonitis episodes far greater than that reported
by NAPRTCS for older children in its PD population (7). It cannot be said with certainty whether
this problem was unique to this particular patient,
or whether it represented an inherent flaw in his
management plan, although we suspect the former.
In conclusion, we have presented the first
reported case of a child with ESRD and IDDM treated
with CAPD and intraperitoneal insulin administration.
Our patient demonstrates that the same excellent glycemic
control can be achieved in children treated with
this technique as is seen in adults. Extra
measures designed to minimize the risk of peritonitis may
be justified in these patients.
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Joseph T. Flynn, md, Pediatric Nephrology, Mott
F6865, Box 0297, 1505 Simpson Rd. East, Ann Arbor, MI