腹膜透析病人透析早期使用高濃度透析液之後截肢的風險評估

林詩怡 中國醫藥大學附設醫院 腎臟科暨腎臟醫學中心 Oral presentation Annual conference of TSN, 2012 Taichung

Early utilization of hypertonic peritoneal dialysate and subsequent risks of non-traumatic amputation among

peritoneal dialysis patients:

A nationwide retrospective longitudinal study

Shih-Yi Lin1,2_{, Che-Chen Lin, MS}3,4_{, Chung-Chih Lin}2_{, Chi-Jung Chung} 5,6_{, Horng-Che Yeh}2_{, I-Kuan Wang}1,2_,

Background

 _{Non-traumatic extremity amputation places a}

considerable burden on individuals, families, and health care finances.

Background

Compared with the general population, dialysis patients

Background

 _{Diabetes is the strongest risk factor of amputation}

in dialysis patients.

Kid Int 1999; 56, 1524–1533

Diabetes

Non-Diabetes

Background

Clin J Am Soc Nephrol 2009;4: 1637–45.

Cumulative incidence of PVD-related procedures after

the start of dialysis, by baseline history of diabetes. P < 0.001 by log-rank test.

Background

Recent commencement of dialysis is a recognized risk factor

Game FL et al. NDT 2006;21:3207-3210

Background

 _{Risk factors of amputation in hemodialysis patients}

Diabetes

Male

P

Background

 _{Only a few studies have investigated the risk}

factors of amputation in PD patients, and these have had limited sample size

 _{Pliakogiannis et al , 71 diabetic PD patients}

albumin

CAD

neuropathy

Background

 _{In the clinic, we noted that PD patients who}

required hypertonic peritoneal dialysis (HPD) solution soon after the initiation of PD were more likely to require amputation

Hypothesis

Early HPD use is related to future amputation in PD patients

Methods

 Extract a Longitudinal Health Insurance Database

(LHID) from National Health Insurance Research Database (NHIRD) of the National Health

Methods

 Enrolled patients

First diagnosed with ESRD ( ICD-9-CM code 585) and receiving PD.

HPD cohort: received HS (i.e., 7.5% icodextrin

solution or 4.25% dextrose solution)

within the first 6 months of initiating PD . Comparison cohort: other new PD patients

Methods

 Excluded:

(1) who underwent amputation before the index date (2) who registered ESRD but did not have record of PD

(3) who had received HD or had undergone renal transplantation before the index date.

 We followed the cohorts until diagnosis and surgery

for the first amputation (ICD-9-CM 785.4 and 440.24; ICD-9-CM 84.10-84.17) been made, withdrawal from insurance, loss to follow-up, or December 31, 2009.

Methods

 Baseline comorbidities analyzed Diabetes (ICD-9 code 250)

Hypertension (ICD-9 codes 401-405)

Ischemic heart disease (ICD-9 codes 410-414, A270, and A279) Previous foot ulcers (ICD-9 codes 707.1-707.9)

Diabetic neuropathy (ICD-9 codes 353.5, 357.2, 354.0-355.9, 337.1) Peripheral vascular disease (PVD, ICD-9-CM codes 443.89 443.9) Hyperparathyroidism (ICD-9-CM codes 252.0)

Heart failure (ICD-9-CM codes 428) Diabetes duration

Comparison cohort N = 296 (%) HPD cohort N = 203 (%) p-values

Age, mean (SD) years 50.9 (17.0) 56.2 (15.8) 0.0005*

≦30 41 (13.9) 13 (6.4) 0.005 31-50 103 (34.8) 56 (27.6) 51-70 108 (36.5) 94 (46.3) >70 44 (14.9) 40 (19.7) Sex 0.350 Female 170 (57.4) 108 (53.2) Male 126 (42.6) 95 (46.8) Comorbidity Hypertension 247 (83.4) 182 (89.7) 0.049

Ischemic heart disease 81 (27.4) 72 (35.5) 0.054

Diabetes 79 (26.7) 89 (43.8) <0.0001

DM foot ulcer 5 (1.7) 5 (2.5) 0.545

DM neuropathy 13 (4.4) 20 (9.9) 0.016

Heart failure 61 (20.6) 63 (31.0) 0.008

Peripheral vascular disease 5 (1.7) 5 (2.5) 0.5445

Hyperparathyroidism 7 (2.4) 9 (4.4) 0.1976

Follow-up duration, mean (SD) 4.2 (2.9) 3.0 (2.8) <0.0001*

DM duration, mean (SD) 8.5 (4.1) 9.1 (4.0) 0.308*

Patient group Event PYs Rate Crude HR (95% CI)

Adjusted HR (95% CI)

Comparison _{10 1248 8.01} Ref Ref

HPD _{15 608 24.7 3.05(1.36-6.82) 2.48(1.06-5.82)**} Table 2:

Incidence of amputation and multivariate Cox proportional hazards regression analysis measured hazard ratio for PD patients using hypertonic solution

PYs: person-years; rate: incidence rate, per 1000 person-years HR: hazard ratio; CI: confidence interval

HPD cohort had a 2.48-fold increase in the HR of new amputation

Crude HR Adjusted HR HPD Diabetes Rate HR (95%CI) HR (95%CI)

No No 0.97 Ref Ref

No Yes 40.6 44.09(5.50-353.4) 19.45(2.32-162.79)*

Yes No 4.70 4.92(0.45-54.37) 3.57(0.32-39.72)

Yes Yes 71.1 80.67(10.3-631.61) 45.67(5.67-367.75)*

Table 3:

The interaction between diabetes and hypertonic solution for amputation risk

Rate: incidence rate, per 1000 person-years HR: hazard ratio; CI: confidence interval

Model adjusted for age, sex, hypertension, heart failure and ischemic heart disease p value for interaction > 0.05

HPD cohort who had concomitant DM carried the highest risk, with 45.67 times the incidence of

Figure1: Cumulative incidence of amputation in hypertonic solution cohort and comparison cohort Figure1: Cumulative incidence of amputation in hypertonic solution cohort and comparison cohort Figure1:_Figure1

Discussion

 _{Recent commencement of dialysis therapy has been}

recognized as an influential risk factor for lower limb amputation in the DM population

Discussion

 _{Several researchers have studied the}

pathophysiological changes that occur during

hemodialysis, which may contribute to these limb-threatening conditions.

 _{Systemic hypoxemia, microcirculatory}

hypoperfusion, and decreased transcutaneous

oxygen tension of the lower limbs can occur during and after HD; all these factors could lead to limb ischemia and amputation

Aurigemma NM e al. NEJM 1977, 297: 871-73. Bemelmans RHH et al.NDT 2009, 24: 3487-92. Hinchliffe RJ et al. NDT 2006, 21: 1981-3.

Discussion

 _{Although there are no comparable data on PD, it is}

possible that HPD could produce similar effects.

 _{HPD might create a more rapid fluid shift into the}

peritoneal cavity, reducing microcirculatory blood flow and tissue oxygen tension.

 _{PD patients placed on HPD have clinical signs of}

fluid overload, such as hypertension and tissue edema, which may worsen tissue oxygenation status.

Discussion

 _{Li et al found that PD patients have higher incidence}

rates of mesenteric ischemia than HD patients,

indicating that PD therapy might contribute to the advancement of microvascular disease

Discussion

 _{The NHIRD database providing complete data}

about the incidence of amputation ,age, sex, types of dialysis solution, dialysis vintage, and

Discussion

 _{We excluded subjects with previous amputations.}

 _{Excluding patients with past amputation might}

eliminate possible bias with regard to analyzing future amputation and provide a clearer

interpretation of the effect of HPD on limb ischemia.

Discussion

 _{The number of subjects was relatively small,}

Discussion

 _{It is possible that some patients had subclinical}

PVD.

 _{However, we also considered co-morbidities such}

as foot ulcers, heart failure, and cardiovascular risk factors associated with PVD, suggesting that any effect of undiagnosed PVD on our results was

Discussion

 _{Lack precise information about smoking status}

and the calcium and phosphate levels, which might be associated with the risk of future amputation.

 _{However, Pliakogiannis et al reported that time}

average Kt/v, creatinine clearance, serum calcium levels, calcium and phosphate production, and

intact parathyroid hormone level are not associated with amputation in PD patients

Discussion

 _{We also lacked information about the subjects’}

scores on baseline measures of circulatory status, such as the ankle-brachial index (ABI)

 _{Given that ABI is not correlated with the severity}

of peripheral arterial disease among dialysis

patients and would be falsely elevated by arterial calcification, it may be appropriate to overlook ABI in the current study.

Conclusion

 _{Along with diabetes, early utilization of HPD}

is associated with the subsequent risk of amputation in PD patients.

 _{We suggest that PD patients be provided}

intensive education on foot protection and screening for evidence of limb ischemia, especially those who received HPD early.