EBM病例討論報告

臨床場景 (clinical scenario)

Name: 朱 x 穎 Sex: femaleAge : 64 year-oldDate of admission: 98/10/30

Chief complaint General weakness and arrived OPD.

High BP was noted and arranged admission.

Past History Hypertension with poor medication control Diabetes mellitus type 2 Chronic kidney disease stage 4 without

regular follow up at our hospital for 2 years Hypothyroidism, thyroidectomy history

Current medication from clinic

Adalat* 高 *OROS 30mg(Nifedipine) 1# qd Glidiab (Glipizide) 5mg 1# qd Eltroxin ( L-Thyroxin sod ) 1# qd Ca.Carbonate(CaCO3)Ca:40% 自費 1# tid

981106 981103 981031 Urea N 104.1 103.2 117.1 Creatinine 9.87 9.21 9.14 NA 137 140 141 K 4 .2 4.4 4.3

Management Plan

Antihypertensive treatment Anti-diabetic medication Low protein diet Follow up renal function Health education for chronic kidney disease and

prepare for haemodialysis

On 98/11/01, her son arrived and asked for her mother condition. He was a designer and his friend was worked at x x 醫藥科技股份有限公司 . His friend suggested to use Kremezin for her mother to delay the initiation of dialysis. He also blame us that there was no such medication at our hospital.

Problem

Chronic kidney disease, stage 5Diabetes mellitusHypertension

Background

Chronic kidney disease with diabetes mellitus and hypertension

Treatment guideline: Blood pressure control Blood glucose control Low protein diet…etc.

Foregound question

What is the Kremezin?Is it effective in treatment of chronic kidney

disease?Can really it delay the initiation of dialysis

in CKD patient?

AST-120 (Kremezin; Kureha Corporation, Tokyo)

Spherical adsorptive carbon ( 活性碳 ) for chronic kidney disease.

An oral adsorbent, is widely used in Japan as a treatment for chronic kidney disease.

1977 開始研發 AST-120 is effective in removing uremic

toxins from the gastrointestinal tract.

延後需要開始洗腎的時間改善尿毒症候群Oral use6g/day, t.i.d useDevelopmental history in Korea

2005 二月上市場Developmental history in US and Europe

2007 六月 phage III 臨床識驗計劃

Question by PICOT:

P: Chronic kidney disease, stage 4~5I : Conventional Tx without AST-120C: Conventional Tx with AST-120O: Delay the initiation of dialysisT: Undefined

搜尋最有用的資料

PubMed

SUMsearch

Google

Cochrane Library

ACP journal club

Evidence-Based Medicine(BMJ)

Up to date

ACP medicine

ACP pier

Ovid

Key word: Chronic kidney disease AST-120

No result about AST-120

搜尋 ACP Journal Club

Key word: Chronic kidney diseaseAST-120

Nephron Clinical Practice ISSN: 1660-2110 Publisher Information: Karger AGAllschwilerstrasse 10Basel CH-4055Switzerland

Prospective Randomized Study Evaluating theEfficacy of the Spherical Adsorptive CarbonAST-120 in Chronic Kidney Disease Patients withModerate Decrease in Renal Function

Tatsuya Shoji, Akira Wada, Kazunori Inoue Daisuke Hayashi, Kodo Tomida, Yoshiyuki Furumatsu Tetsuya Kaneko, Noriyuki Okada, Yoshifumi Fukuhara Enyu Imai, Yoshiharu Tsubakihara

Department of Nephrology, Osaka General Medical Center, Department of General Internal Medicine,National Hospital Organization Osaka National Hospital, and department of Nephrology, Osaka UniversityGraduate School of Medicine, Osaka , Japan

Aims: We studied whether adding the spherical adsorptive carbon AST-120 to conventional treatments is effective in inhibiting progression of chronic kidney disease (CKD) at the stage of moderate, decrease in renal function

Methods:

43 CKD patients with moderately impaired renal function indicated by glomerular filtration rate (GFR) of 20–70 ml/min as measured by non-radiolabeled iothalamate clearance method.

26 patients showing a decrease of GFR by 5 ml/min during a 1-year observation period were randomized to receive ongoing treatments only (control group, 12 cases) or with AST-120 co-administered with ongoing treatment (AST-120 group, 14 cases).

The intervention period was 1 year and the change in GFR was the primary evaluation variable.

Procedures, Measurements and Outcome

The AST-120 group took AST-120 6 g/day divided into three fractions. For both groups, dietary and blood pressure managements were conducted as routine medical care.

The target of dietary management was protein 0.8 g/kg ideal body weight, calorie 35 kcal/kg ideal body weight and salt < 7 g/day.

The target of blood pressure management was systolic blood pressure <140 mm Hg and diastolic blood pressure < 90 mm Hg.

Results: The mean changes of GFR per month

( GFR) in the intervention period were not significantly different between both groups.

However, when comparing the GFR in the observation and intervention periods for each group, the rate of decline in GFR was significantly retarded (p < 0.001) in the AST-120 group while no significant difference was observed in the control group.

Study design. Entry criteria * : aged 18–70 years at entry, GFR of 20–70 ml/min at entry, and change of GFR < –5 ml/min/year during the observation period. GFR was measured using the modified plasmaiothalamate clearance method.

In the normal protein diet subgroup, decline of GFR was significantly retarded (p = 0.016) in the intervention period compared to the observation period in the AST-120 group (7 cases),

No significant difference was observed before and after intervention in the control group (n = 7)

In the low protein diet group also, decline of GFR was significantly inhibited (p = 0.016) in the intervention period compared to the observation period in the AST-120 group (7 cases).

No significant difference was observed before and after intervention in the control group (n = 5) ( fig. 6 ).

No significant changes in GFR were observed before and after intervention in the control group, whereas the GFR was

significantly improved after intervention compared to the observation period in the AST-120 group.

Conclusion:

These results suggest that co-administration of AST-120 with conventional treatments retards decline in renal function in CKD patients with moderate decrease in renal function.

However, the number of cases in this study was limited (especially if there were less than 10 cases each in subgroup study) and further comparative study with a larger number of cases is required to validate the present results.

證據等級

沒有經過完整評讀醫學文獻的專家意見 5

Case-series(poor quality :cohort / case-control studies) 4

Individual case-control studies 3b

SR of case-control studies 3a

Outcome research / ecological studies 2c

單篇 cohort 及低品質的 RCT 2b

用多篇世代研究所做成的綜合性分析 2a

All or none 1c

單篇 RCT( 有較窄的信賴區間 ) 1b

用多篇 RCT[ 註 1] 所做成的綜合性分析 (SR[ 註 2] of RCTs) 1a

與 [ 治療 / 預防 / 病因 / 危害 ] 有關的文獻 Level

搜尋 DynaMed

Key word:Chronic kidney disease

搜尋到的文章內容摘要 Effect of a carbonaceous oral adsorbent

on the progression of CKD: a multicenter, randomized, controlled trial.

Am J Kidney Dis. 2009 Sep;54(3):459-67.

Epub 2009 Jul 17 Akizawa T, Asano Y, Morita S, Wakita T,

Onishi Y, Fukuhara S. Department of Nephrology, Showa University

School of Medicine, Tokyo, Japan.

BACKGROUND:

The carbonaceous oral adsorbent AST-120 slows the deterioration of kidney function in patients with advanced chronic kidney disease (CKD).

STUDY DESIGN:

Randomized controlled trial. Setting & Participants: 75 medical

facilities. 460 patients with CKD with serum

creatinine (sCr) concentrations less than 5.0 mg/dL (not undergoing dialysis).

INTERVENTION:

Random assignment to either a low-protein diet and antihypertensive medication in the control group or that treatment combined with AST-120 (6 g/d).

OUTCOMES & MEASUREMENTS:

Composite primary end point >>> 1. Doubling of sCr level 2. Increase in sCr level to 6.0 mg/dL or more 3. Need for dialysis or transplantation, or

death.

Secondary outcomes: 1. Adverse events and changes in estimated

creatinine clearance (CCr) rate 2. Proteinuria (protein in milligrams per day) 3. Quality of life.

RESULTS: Mean sCr level was 2.66 mg/dL and estimated CCr

was 22.4 mL/min in both groups. During 56 weeks, numbers of primary end-point

events (43 for control versus 42 for AST-120) and event-free survival (P = 0.9) did not differ between groups.

Gastrointestinal adverse events were less common in the control group than the AST-120 group (2 versus 32 events).

Estimated CCr decreased more in the control group than in the AST-120 group

(-0.15 versus -0.12 mL/min/y; P = 0.001). Median proteinuria changed from protein of 1,162 to

1,167 mg/d in the control group versus 1,102 to 906 mg/d in the AST-120 group (P = 0.2).

CONCLUSION:

AST-120 did not substantially slow the progression of kidney disease in patients with moderate to severe CKD during 1 year.

證據等級

沒有經過完整評讀醫學文獻的專家意見 5

Case-series(poor quality :cohort / case-control studies) 4

Individual case-control studies 3b

SR of case-control studies 3a

Outcome research / ecological studies 2c

單篇 cohort 及低品質的 RCT 2b

用多篇世代研究所做成的綜合性分析 2a

All or none 1c

單篇 RCT( 有較窄的信賴區間 ) 1b

用多篇 RCT[ 註 1] 所做成的綜合性分析 (SR[ 註 2] of RCTs) 1a

與 [ 治療 /預防 /病因 /危害 ] 有關的文獻 Level

搜尋 Studies,Pubmed

Key word:

AST-120 and chronic kidney disease

搜尋結果

Most of the paper and journals are

From 2004—2007Only from Japanese journalsSome of the study : animal (rat)

studyLow level of evidence (no control

group)

Appraisal ( 嚴格評讀）

對找到的文章進行 critical appraisal

A: Does this paper answer your question? Yes.

A: Is the author an expert of the field?

Yes. Is there any conflict of interest

not mentioned

Method: 證據等級 ( 針對這篇 )

Level 與 [治療 /預防 /病因 /危害 ]有關的文獻 1a 用多篇 RCT 所做成的綜合性分析 (SR of RCTs)

1b 單篇 RCT( 有較窄的信賴區間 )

1c All or none

2a 用多篇世代研究所做成的綜合性分析 2b 單篇 cohort 及低品質的 RCT

2c Outcome research / ecological studies

3a SR of case-control studies

3b Individual case-control studies

4 Case-series(poor quality :cohort / case-control studies)

5 沒有經過完整評讀醫學文獻的專家意見

Patients included into the study met the following criteria: CKD with serum creatinine (sCr)

concentrations less than 5.0 mg/dL (not undergoing dialysis).

But my patient has creatinine level of 9.0

Pateint

Intervention and Comparasion

A low-protein diet and antihypertensive medication in the control group without AST-120

That treatment combined with AST-120 (6 g/d).

Outcome

Endpoint: Need for dialysis or death

Time

1 year

將 study的結果應用在病人 There are many study in AST-120 for

chronic kidney disease in Japan, most of them are animal studys or phase III study. There was no high level of evidence that AST-120 can delay the dialysis in chronic kidney disease.

Apply~~結合醫學倫理方法將 study的結果應用在病人身上

醫療現況Nowadays, health information is advanced

among the local people and most of the patient searched the information about the disease and treatment in the internet.

But a little knowledge has challenge the professionals. But we need to solve the problem of the patient and answer their quires.

病人意願

If certain medication or treatment that can really cure the disease, everyone will eagerly buy and use it even though it is how expensive.

No one will like the long time dialysis for her life.

生活品質

Because of chronic kidney disease, she need to visit OPD or clinic frequently to access her renal function that is deteriorated or not.

One day, dialysis is started, she needed to come to dialysis center for hemodialysis or home peritoneal dialysis.

If AST-120 can really delay the dialysis, she will try it by selfpaid.

社會脈絡

由於還無法解決主訴除了洗腎之外，繼續住院或出院需要評估，以避免回家後危險。

病患家庭經濟穩定，較無受限於經濟壓力。

Thanks!