Perit Dial Int
27(Supplement_2):
190-195
2007
© 2007 International Society for Peritoneal Dialysis
Part 5: PD in Pediatric, Elderly, and Diabetic
Patients |
PERITONEAL DIALYSIS IN PATIENTS WITH DIABETES: ARE THE BENEFITS GREATER THAN THE DISADVANTAGES?
Satoru Kuriyama
Division of Nephrology, Saiseikai Central Hospital, Tokyo, Japan
Correspondence to: S. Kuriyama, Division of Nephrology, Saiseikai Central
Hospital, 1-4-17, Mita, Minato-ku, Tokyo 108-0073 Japan.
kuriyamas{at}jikei.ac.jp
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ABSTRACT
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Diabetic nephropathy has been increasing in prevalence in recent years,
and it is now the dominant cause of end-stage renal disease (ESRD) worldwide.
Because diabetes is frequently associated with multiple complications,
nephrologists must be alert to the selection of dialysis modality so as to
reduce the accompanying risks. The present review addresses whether the
benefits of peritoneal dialysis are greater than its disadvantages in diabetic
patients. The answer is quite positive: for most diabetic patients, peritoneal
dialysis offers multiple benefits.
KEY WORDS: Diabetes; survival; diabetic retinopathy; icodextrin.
Since the late 1990s, the occurrence of diabetic nephropathy has been
steadily increasing; this condition is now the dominant cause of end-stage
renal disease (ESRD) in many countries. The increasing prevalence of diabetic
nephropathy is primarily attributable to the growing numbers of people who
have type 2 diabetes mellitus
(1).
In the late 1970s, dialysis for patients with diabetes, who frequently have
advanced cardiovascular complications, could provide only a limited benefit
because of technical problems and insufficient options for medical treatment.
As a result, patient survival at that time was poor. However, improvements in
medical technologies and medicines, advances in the treatment of coronary
artery disease and in critical care medicine, and introduction of earlier
initiation of renal replacement therapy have combined to improve outcomes,
with the result that dialysis for diabetic patients is now a widely accepted
standard clinical practice.
The many improvements made to continuous ambulatory peritoneal dialysis
since its introduction in 1975 have made this modality an alternative to
hemodialysis (HD). In fact, peritoneal dialysis (PD) may provide several
advantages for diabetic patients. Both dialysis modalities are suitable for
most diabetic patients, but in contrast to the utilization of HD, utilization
of PD is still very low in many countries—including Japan, where PD had
only a 3.6% penetration rate at the end of 2005
(2).
The present paper reviews the relevant literature, summarizes the clinical
experience of PD in diabetic patients, and then discusses whether the benefits
of PD in patients with diabetes are greater than the potential
disadvantages.
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PERITONEAL DIALYSIS IN DIABETIC PATIENTS
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In diabetic patients with ESRD, multiple complications such as
hypertension, ischemic heart disease, left ventricular hypertrophy,
arrhythmia, orthostatic hypotension, arteriosclerosis obliterans, diabetic
retinopathy, hyperglycemia, and dyslipidemia exist even before the
pre-dialysis stage. In addition to the rapid and intermittent removal of
solutes and water, the extracorporeal circulation inherent to HD can
frequently be associated with dialysis-induced hypotension, coronary ischemia,
and arrhythmia, possibly leading to a worsening of cardiovascular status in
these patients. Consequently, the choice of HD is not always favorable for
them. The infrequent occurrence of dialysis-induced hypotension in PD is one
of the great advantages of that modality. In addition, the lack of a need to
create an arteriovenous fistula, which increases cardiac overload,
accelerating heart failure, may also be a potential benefit of PD in patients
with diabetes.
Table 1 lists other
potential benefits of PD in diabetic ESRD patients. One of the most important
of these, with a significant impact on patient outcome, is superior
preservation of residual renal function (RRF). The reports listed in
Table 2 show that the decline
in RRF is 24%–80% faster in patients on HD than in those on PD
(7). In addition, Moist et
al. suggested that risk factors for losing RRF were selection of HD as
the dialysis modality, diabetic nephropathy, non-white race, female sex, and
longer follow-up (Figure 1).
Based on that report, the combination of diabetes and HD might be concluded to
further augment the risk. Thus, taking advantage of a "PD first"
approach appears to be a rational way to maximize the maintenance of RRF.
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TABLE 1 Potential Benefits of Peritoneal Dialysis (PD) in the Treatment of
End-Stage Renal Disease Patients with Diabetes
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Freedom from a dialysis machine and the related avoidance of anticoagulants
are additional advantages that favor PD in diabetic patients. Lower risk of
contracting certain blood-borne diseases [hepatitis C virus (HCV), for
example] constitutes another benefit of PD. The prevalence of anti-HCV
antibodies in patients on dialysis has been reported to be substantially lower
in PD patients than in HD patients
(8).
The effect of dialysis on diabetic retinopathy has special importance.
Table 3 summarizes results with
respect to progression of retinal lesions in diabetic patients on either HD or
PD in a Japanese study. Notably, no patients in the PD group showed worsening
of diabetic retinopathy during the 1-year observation period. During the same
period, approximately 20% of HD patients showed substantial progression of
diabetic retinopathy. This difference may be related to a more stable
hemodynamic status and a lack of exposure to heparin in the PD patients.
Despite the above-mentioned advantages, PD is also associated with certain
negative factors inherent to the use of this modality in patients with
diabetes. Continuous glucose absorption from glucose-containing PD solutions
may lead to hyperglycemia, obesity, hyperlipidemia, and increased peritoneal
permeability because of the accumulation of glucose degradation products
(10). Encapsulating peritoneal
sclerosis, peritonitis, and exit-site infection are other complications
specific to PD. However, no evidence shows that the occurrence of these
complications is greater in patients with diabetes than in those without.
With respect to modality selection in diabetic patients, the individual
history of diabetes and any accompanying comorbidities must be considered.
Therapy that is more individualized and linked to the concept of integrated
ESRD care allows for the two dialysis modalities and kidney transplantation
all to be considered at each phase of active ESRD treatment
(11).
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SURVIVAL RATE COMPARISON: PD VERSUS HD IN DIABETIC PATIENTS, PD IN DIABETIC VERSUS NONDIABETIC PATIENTS
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In a review of the literature comparing the survival of diabetic ESRD
patients on PD and HD, Passadakis and Oreopoulos
(12) showed the great
disparity in the results. In some studies, the overall survival rates of
diabetic patients on PD and HD were similar, but in other reports, a more
favorable outcome was associated with one of the two modalities. These mixed
outcomes are potentially explained by heterogeneity in the patients'
backgrounds, including sex, age, age at onset of diabetes, duration of
diabetes, year of dialysis start, duration of dialysis, and severity of
comorbid conditions, and by the statistical techniques used to analyze the
data. Some reports have indicated that diabetic patients on PD have a higher
mortality than do those on HD, with the exception that the mortality
difference in younger patients (<55 years of age) is small and
insignificant
(13,14).
Based on data from the Canadian Organ Replacement Register, Fenton et
al. (15) found that,
after adjusting for age, primary diagnosis, comorbid conditions, and center
size, the overall (all-patient) mortality risk for PD was 73% that for HD. The
lower mortality in PD patients was concentrated in the first 3–4 years
of treatment. Diabetic patients up to 64 years of age undergoing PD had a
mortality rate of 0.73 relative to patients on HD, and in age-matched
nondiabetic patients, the PD/HD mortality ratio was 0.54, suggesting that the
beneficial effect can be accentuated by PD treatment and the absence of
diabetes mellitus.
Vonesh and Moran (16)
analyzed the U.S. Renal Data System (USRDS) data and found that the PD:HD
death rate ratio varied by age and sex. For male diabetic patients on PD,
there was little or no difference in the mortality risk between HD and PD. For
diabetic patients under 50 years of age, PD was associated with a
significantly lower risk of death than was HD. In contrast, older female PD
patients with diabetes had a significantly higher risk of death than did those
on HD. Furthermore, more recent reports from Holland, Denmark, and Canada
(17–19)
have shown that PD in diabetics is associated with survival equal to that in
HD for the first 2–3 years. Collins et al. showed that, in the
United States, the modality risk in diabetic PD patients under 55 years of age
was lower than that in similar patients on HD, but that the risk of all-cause
death for female diabetic patients 55 years of age or older was higher in
those on PD (20). More
recently, however, HD in the United States has been associated with better
survival in diabetic patients over 45 years of age during the first 2–3
years on dialysis (21).
The most recent large-scale, long-term study, which included more than 400
patients, showed that the best survival occurred in nondiabetic patients on PD
(Figure 2). The survival rate
of diabetic patients on PD was equal to that of nondiabetic patients on HD.
Notably, diabetic patients on HD had the worst survival rate. This inferior
survival of HD patients with diabetes may have been attributable to the faster
decline of RRF in that population, because the choice of the HD modality in
the presence of diabetes may have accelerated the loss of RRF.
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Figure 2 — Patient survival: hemodialysis (HD) versus peritoneal dialysis
(PD), diabetic versus nondiabetic.
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Several studies have compared survival rates between diabetic and
nondiabetic patients (21). In
general, the presence of diabetes mellitus is always associated with worse
results, which may be even worse in patients with ESRD. According to the
USRDS, 5-year survival is lower in both diabetic men and women than in their
nondiabetic peers (22). A
10-year survey found no significant difference in survival between diabetic
and nondiabetic patients on PD. The survival rate for patients 55 years of age
and older with diabetes was significantly lower than that for nondiabetic
patients in the same age group
(21).
Based on the foregoing data, it may be concluded that PD offers equal or
better survival in diabetic patients than HD does, especially during the early
years on dialysis.
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STRATEGIES TO IMPROVE CLINICAL OUTCOMES IN DIABETIC PATIENTS ON PD
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Aside from the choice of PD as an RRF-preserving modality, other factors
that may improve the prognosis in diabetic patients on dialysis should be
taken into consideration.
Because diabetes mellitus is a progressive disease with refractory
hypertension and hyperglycemia, the guidelines on chronic kidney disease (CKD)
from the Kidney Disease Outcomes Quality Initiative concluded that control of
blood sugar and blood pressure are two major determinants of improved patient
outcome in CKD, including outcome in diabetic patients
(23). In the WEB study,
Nakayama et al. (24)
reported that a substantial number of PD patients are overhydrated.
Effective fluid removal is undoubtedly a crucial predictor of patient
survival. Indeed, Ates et al.
(25) demonstrated a clear
relationship between relative risk of death and 24-hour ultrafiltration (UF)
volume. The icodextrin in newly available PD solutions enhances fluid removal
and is indicated for patients with UF loss. Net UF volume, urea clearance, and
creatinine were significantly increased with icodextrin
(26,27).
The benefits of icodextrin use in diabetic patients were recently studied
by Paniagua et al. in a prospective, randomized controlled trial in
60 diabetic patients undergoing PD
(28, Paniagua R, personal
communication). These authors showed that icodextrin significantly reduces
extracellular water volume, thereby leading to a significant reduction in both
systolic and diastolic blood pressure. Moreover, they demonstrated that
icodextrin, as compared with conventional glucose solution, reduces blood
glucose concentration, a finding that was accompanied by a concomitant
improvement in HbA1c and a reduction in insulin dosage. This result may
reflect reduced glucose reabsorption through the peritoneal membrane with the
use of icodextrin. Furthermore, a particularly interesting finding was that
icodextrin was associated with a delay in the decline of glomerular filtration
rate and urine volume over a 6-month observation period (Paniagua R,
unpublished data).
An increase in solute transport with time on dialysis is commonly preceded
by increased peritoneal exposure to hypertonic glucose solution. This increase
in peritoneal permeability leads to UF loss
(29). In a 2-year prospective
multicenter study in Europe
(27), investigators found that
UF and dialysate-to-plasma ratio of creatinine both remain stable over time in
patients using icodextrin; in patients on glucose-only solution, peritoneal
permeability was substantially increased. That result suggests that icodextrin
did not affect peritoneal permeability and that it acted in a protective way
on the peritoneum (Figure
3).
Together, the data from these trials suggest that introduction of
icodextrin for diabetic patients can be useful in both treating and preventing
hypervolemia, hyperglycemia, and increased peritoneal permeability. Icodextrin
may also help preserve RRF. Table
4 summarizes the potential benefits of icodextrin. These benefits
are clinically important, and they justify common use of the new solutions in
diabetic patients.
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CONCLUSIONS
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The answer to the question posed in the title of this
article—"Peritoneal dialysis in patients with diabetes: Are the
benefits greater than the disadvantages?"—is obviously yes for
most diabetic patients, because, as outlined, PD offers cardiovascular,
retinal, metabolic, renal, and peritoneal benefits. In addition, the
advantages of PD are accentuated with the use of icodextrin.
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ABSTRACT
PERITONEAL DIALYSIS IN DIABETIC...
