CKD strategy for Kidney Transplant Recipients and Donors

Ａｔｓｕｓｈｉ　Ａiｋａｗａ !

Department of Nephrology, Toho University, Faculty of Medicine

9th International IKEA-J Symposium, Mar 1, 2014, Tokyo, Japan

9th International IKEA-J Symposium

Stage in CKD of Kidney Transplant Recipients(K/DOQI = KDIGO Guideline)

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CKD Stage GFR (ml/min/1.73m1T ≧902T 60 ～ 893T 30 ～ 594T 15 ～ 29

5T or D <15

CKD Stage in Kidney Transplant Recipients

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Recipients: n=115 Adult (age≧20 years) ABO Compatible Living Related Donor Kidney Transplantation in Toho University Omori Hospital (1997 ~ 2004) !eGFR (male) = 194 x Cr -1.094 x Age -0.287 eGFR (female) = 0.739 x 194 x Cr -1.094 x Age -0.287

The Rate of CKD Stage in Kidney Transplant Recipients (n = 115)

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0%

25%

50%

75%

100%

1-yr 2-yr 3-yr 4-yr 5-yr 6-yr 7-yr

12%6%5%4%3%3%2%

4%3%

1%

14%10%9%5%7%6%5%

47%51%56%58%52%58%58%

20%25%23%28%36%29%30%

4%6%8%4%3%4%4%

Stage 1T Stage 2TStage 3T Stage 4TStage 5T Stage 5TD

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Survival in Patients with CKD, PD, HD and Transplantation

CKD PD

HD Transplanted

Neovius M, Jacobson SH, Eriksson JK, et al. BMJ Open 2014;4:e004251. doi:10.1136/bmjopen-2013-004251

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Neovius M, Jacobson SH, Eriksson JK, et al. BMJ Open 2014;4:e004251. doi:10.1136/bmjopen-2013-004251

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Mortality Hazard Ratios (95%CI; Log Scale) v.s.

Matched General Population Comparators

CKD n=3032

PD n=724

HD n=1761

Tx n=606

Causes of Graft Failure in Kidney Transplant Recipients(n = 771; 2001~)

9Fact book 2012, Japanese Society for Transplantation

Causes of Death in Kidney Transplant Recipients(n = 356; 2001~)

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InfectionCardiovascular DiseaseNeoplasmaStroke and Cerebral HemorrhageDigestive System DiseaseRespiratory DiseaseAccidentHematopoietic diseaseSuicideOthers

Fact book 2012, Japanese Society for Transplantation

Factors of CKD in Kidney Transplant Recipients• Immunological Factor Donor Specific HLA Antibody Chronic Antibody Mediated Rejection Chronic T Cell Medicated Rejection !

• Non Immunological Factor Metabolic Syndrome Hypertension Hyperglycemia Dyslipidemia Obesity CNI Nephrotoxicity

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DSA Formation in Kidney Transplant Recipients depends on Immunosuppression

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Immunosuppression n %antibody p valueCsA, Aza 536 18.10% Reference

CsA, MMF 533 9.80% 0.000082Tac, Aza 67 13.40% 0.34

Tac, MMF 233 12.90% 0.073

Graft Failure and Death among Kidney Transplant Patients with or without Antibody (1 Yr Follow up)

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Pathology of Advanced CKD in Kidney Transplant Recipients (Chronic Allograft Nephropathy)

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Interstitial fibrosis and tubular atrophy (III ; ct3, ci3)

Intimal thickening in artery (IIIb; cv3)

Arterial hyalinosis (ah3)

Metabolic Syndrome is an Independent Risk Factor of CKD

Metabolic syndrome (MS) Hypertension Hyperglycemia. Dyslipidemia Obesity !The epidemic of MS contributes to the rapid growth of chronic kidney disease (CKD) and end-stage renal disease (ESRD) in US* and Japan**

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* Ann Intern Med. 2004;140 (3):167–74. ** Am J Kidney Dis. 2006;48(3):383–91.

Clinical Guideline of Medical and Pediatric Complications after Kidney Transplantation

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Post-Kidney Transplant Hypertension • BP should be less than 130/80 mmHg in kidney transplant recipients

with CKDT (grade B) • First line anti-hypersensitive drugs should be ACE-I and/or ARB

(grade B)

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Guideline Systoric BP Diastoric BP

EBPG < 130 <80

K/DOQI < 130 <80

Clinical Guideline of CKD

Urinary Protein Neg <130 <80

Urinary Protein Pos <125 <75 Treatment of Hypertension 2009

(Japan) <130 <80

Hypertension Patient & Graft Survival

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BP 10mmHg up RR for Graft Loss 1.12 RR for Graft Loss following Death 1.17 RR for Death 1.18

(Evidence IVa)

New Onset Diabetes Mellitus After Kidney Transplantation(NODAT)

!!!• NODAT is mainly caused by immunosuppressive agents,

such as steroid and CNI (tacrolimus and cyclosporine) !• Minimization or withdrawal of steroid and Monitoring of

blood level of CNI are critically important. !

• NODAT should be managed by a team (transplant physician, endocrinologist for DM, staff Ns, and Dietitian)

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FBS < 130mg/dLBS 2hrs after meal < 180mg/dL

HbA1c < 6.5%

NODAT and DM

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(Evidence IVa)

The risks of Ischemic heart disease are 2.78 times (male) and 5.4 times (female) in kidney Tx recipients with DM, compared to those without DM.

Patient survival is worse in recipients with NODAT than those without NODAT

(Evidence IVa)

Dyslipidemia• LDL-C <120mg/dl !

• LDL-C < 100mg/dl (recipients with CVD) !

• Dyslipidemia should be treated with improvement of life style and then medicine. !

• Statin is first line medicine.

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Fluvastatin

0 1 2 3 4 5 6 7Time (years)

0

10

15

20

Cum

ulat

ive

inci

denc

e (%

)

5

Primary endpoint P = 0.036

PlaceboALERTALERT

extension

ALERT extension: Fluvastatin Significantly Reduced

the Risk of MACEFluvastatin significantly reduced the risk of MACE by 21% in patients receiving Fluvastatin throughout ALERT and the ALERT extension, compared with patients switched from placebo at the start of the extension study

Holdaas H et al: Am J Transplant 5:2929-2936, 2005

21%

Obesity• Check body weight and waist !• Obesity should be improved in terms of life style. !

• BMI < 25kg/m2

!• Gain of body weight < 5% of body weight

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Graft Survival in Non-obese and Obese Transplant Recipients

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• 56 patients had deceased donor kidney transplantation with 28 pairs.

!• one kidney from the pair into

an obese patient • the other kidney into a non-

obese patient.

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eGFR 1 Year after Donation

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Sequential Change of eGFR Following Kidney Transplantation

Clinical Courses in Living Kidney Donors Who Developed ESRD

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ATN

ATN

Survival Rate of A Donor and General Population

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Donor

General Population

Post-Transplantation

Survival Rate

%

No. of Donors

N Eng J Med 360;5: 459~469, 2009

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Brigham Womens

First successful organ donor dies Posted by Elizabeth Cooney December 29, 2010 12:33 PM

Mr.Ronald Lee Herrick, who donated a kidney to his twin brother in 1954 and has died at the age of 79.