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.

Key words

Diabetes, insulin, children

From:

Department of Pediatrics and Communicable Diseases, University of Michigan, Ann Arbor, Michigan, USA.

Introduction


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.

Case report


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).

Discussion


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.

References


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Corresponding author:
Joseph T. Flynn, md, Pediatric Nephrology, Mott F6865, Box 0297, 1505 Simpson Rd. East, Ann Arbor, MI 48109-0297, USA.