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Topic Review
Maj. Chaken Maniyan M.D.
Division of Nephrology,
Department of Medicine
Phramongkutklao Hospital
17.2.2017
Outcome and complication of
kidney transplantation
Outline
§Outcome of kidney transplantation
§Complication & medical management of KTRs
§ Post transplant diabetes mellitus
§ Hypertension
§ Dyslipidemia
§ Electrolyte disturbance
§ Bone disease
§ Recurrent diseases
§ Malignancy
§ Failing kidney & allograft nephrectomy
Difficulties are opportunities
, said Dr. Murray
1954, First Kidney transplantation by
Joseph E. Murray at Brigham Hospital
in Boston for identical Twin
(Richard and Ron Herrick)
1990	Noble	prize
Risk of death of kidney transplantation
compare to dialysis
Wolfe RA, Ashby VB, Milford EL, et al: N Engl J Med 341:1725–1730, 1999.
Timeline of kidney transplantation,
threats, and opportunities
Adnan Sharif, Solomon Cohney et al , Lancet Diabetes Endocrinol 2016; 4: 337–49
One-year deceased donor kidney allograft survival and
rejection episodes over time
on
Comprehensive Clinical Nephrology, 5th Edition
Highlight 2016 USRDS annual report
2016 ANNUAL DATA REPORT, VOL 2, ESRD,
Trends in incidence rate of treated ESRD
(per million population/year), by country, 2001-2014
2016 ANNUAL DATA REPORT, VOL 2, ESRD,
Ten countries having the
highest % rise in ESRD
Percent distribution of type of RRT modality
by country, 2001-2014
2016 ANNUAL DATA REPORT, VOL 2, ESRD,
Assessing Allograft Outcomes in
Kidney Transplantation
§Main outcome :Allograft survival
§Surrogate outcomes
§Allograft function (SCr level)
§Patient survival
§Rejection episodes
§Days of hospitalization
§Quality of life indices
Brenner and Rector's The Kidney, 10th edition
Short term outcome
§ 0-12 month after kidney transplantation
§ Main causes of allograft loss
§Acute rejection
§Thrombosis
§Primary non-function kidney
§Patient death
Brenner and Rector's The Kidney, 10th edition
Long term outcome
§ After 12 month after kidney transplantation
§ Main causes of allograft loss
§Patient death
§Chronic allograft injury (CAI)
§Late acute rejection
§Recurrent disease
Brenner and Rector's The Kidney, 10th edition
Before 5 years After 5 years
Causes of death with functioning graft in Thailand
Causes of allograft loss in Thailand
Factors associated with allograft survival
§ Donor factors
§ Recipient factors
§ Donor – recipient interaction factors
§ Recurrent disease
§ Proteinuria
Brenner and Rector's The Kidney, 10th edition
Donor factors
§Donor source: deceasedVS living donor
§Donor age
§Donor gender
§Donor ancestry and ethnicity
§Cold ischemia time
§Expanded criteria donors
§Donation after cardiac death (DCD)
Brenner and Rector's The Kidney, 10th edition
Expanded Criteria Donors
§60 years or older
§50 to 59 with two of the following criteria
§ (1) CVA as cause of death
§ (2) history of hypertension
§ (3) Serum creatinine >1.5 mg/dL
KDIGO Guideline for the Care of Kidney Transplant Recipients American Journal of Transplantation 2009; 9 (Suppl 3): S42–S43
Recipients factors
§Recipient age
§Recipient race and ethnicity
§Recipient gender
§Recipient sensitization
§Acute rejection
§Recipient immunosuppression
§Recipient compliance
§Recipient cause of ERSD
§Recipient hypertension
Brenner and Rector's The Kidney, 10th edition
Donor – recipient interaction factors
§ Delayed graft function
§ Human leukocyte antigen matching
§ Cytomegalovirus status of donor and recipient
§Timing of transplantation
§ Center effect
Brenner and Rector's The Kidney, 10th edition
2015 Thai Transplant Society Annual Report
Kidney Transplantation Rate
2000-2015
2015 Thai Transplant Society Annual Report
Cumulative KTRs among hospitals
1994-2015
2015 Thai Transplant Society Annual Report
Living donor and recipient ages
1994-2015
2015 Thai Transplant Society Annual Report
Cold Ischemic Time 1994-2014
2015 Thai Transplant Society Annual Report
Deceased Donor Characteristic
1996-2014
2015 Thai Transplant Society Annual Report
DFG Rate , SCr at discharge day
1994-2012
Patient Survival Rate by 1994-2015
2015 Thai Transplant Society Annual Report
Improving allograft survival outcome
§ Maximizing organs available for KT
§ National campaign
§ Education of medical staff/ family members
§ Expanded criteria donor and DCD
§ Maximize life span of donated organs
§Criteria used for allocation of deceased donor
§Youngest and healthiest, maximizing the life years
from transplantation (LYFT) gained
§Maximized the early marker of allograft injury
Brenner and Rector's The Kidney, 10th edition
Biopsy gene expression to
identify KTRs at risk of chronic injury
O’Connell PJ, Zhang W, Menon MC, et al. Lancet 2016; 388: 983–93.
Outline
§Outcome of kidney transplantation
§Complication & medical management of KTRs
§ Post transplant diabetes mellitus
§ Hypertension
§ Dyslipidemia
§ Electrolyte disturbance
§ Bone disease
§ Recurrent diseases
§ Malignancy
§ Failing kidney & allograft nephrectomy
PTDM : Impact
Adnan Sharif & Keshwar Baboolal , Nature Reviews Nephrology 8, 34-42 (January 2012)
Pathophysiology of post-transplant DM
Adnan Sharif, Solomon Cohney et al L, ancet Diabetes Endocrinol 2016; 4: 337–49
Cardiometabolic risk profi le of
immunosuppression
Adnan Sharif, Solomon Cohney et al L, ancet Diabetes Endocrinol 2016; 4: 337–49
Toxicity profiles of immunosuppressive
medications
KDIGO Guideline for the Care of Kidney Transplant Recipients American Journal of Transplantation 2009; 9 (Suppl 3): S42–S43
Risk factor for NODAT
Non-modifiable Potentially modifiable Modifiable
Ethnicity (non-
Caucasian) Infections
HCV
CMV
Immunosuppressive
Therapy
Age >40 years-old • Tacrolimus
Male gender • Cyclosporine
Donor's gender (M) IGT (pretransplantation) • Corticosteroid
Family history of DM • Sirolimus
HLA Obesity
HLA (mismatches)
Cadaveric donor
OPTN/UNOS database, Am J Kidney Dis. 2010 Dec;56(6):1127-39.
NODAT : Screening
§Screening all nondiabetic KTRs with FPG, OGTT,
and/or HbA1c (1C) at least:
§weekly for 4 weeks (2D)
§every 3 months for 1 year (2D)
§annually, thereafter (2D)
§Screening after starting, or increasing CNIs, mTORi
or corticosteroids. (2D)
KDIGO Guideline for the Care of Kidney Transplant Recipients American Journal of Transplantation 2009; 9 (Suppl 3): S42–S43
NODAT : Screening
§ Criteria for the diagnosis of diabetes
§FPG ≥126 mg/dL (7.0 mmol/L) OR
§S/S of hyperglycemia and CBG ≥ 200 mg/dL OR
§Two-hour glucose ≥200 mg/dL during OGTT
§ glucose load (75 g anhydrous glucose dissolved in water)
KDIGO Guideline for the Care of Kidney Transplant Recipients American Journal of Transplantation 2009; 9 (Suppl 3): S42–S43
Risk factor of NODAT
KDIGO Guideline for the Care of Kidney Transplant Recipients American Journal of Transplantation 2009; 9 (Suppl 3): S42–S43
Management of PTDM
§ Dietary modification
§ Lifestyle modifications
§ Adjustment or modification in immunosuppressive meds
§Rapid steroid taper, steroid-sparing or steroid avoidance
protocols
§Tacrolimus to cyclosporine conversion therapy
§Pharmacologic therapy
§Screening for microalbuminuria
§Regular ophthalmologic exam
§Regular foot care
Brenner and Rector's The Kidney, 10th edition
Management of NODAT
§ Modifying immunosuppressive regimen to reverse
diabetes, after weighing risk of rejection and other
potential adverse effects. (Not Graded)
§ Target HbA1c 7.0–7.5%
§ Avoid HbA1c ≤ 6.0%, esp if hypoglycemic (Not Graded)
§ Aspirin (65–100 mg/day) use for 1o prevention of
CVD be based on patient preferences balancing the
risk for ischemic/bleeding (2D)
KDIGO Guideline for the Care of Kidney Transplant Recipients American Journal of Transplantation 2009; 9 (Suppl 3): S42–S43
Pharmacological management of
diabetes in KTRs
KDIGO Guideline for the Care of Kidney Transplant Recipients American Journal of Transplantation 2009; 9 (Suppl 3): S42–S43
Medications for diabetes control in
first 6 months post-transplant
2014 ANNUAL DATA REPORT, VOL 2, ESRD,
Strategies to prevent and treat PTDM
§ Steroid minimization
§ Avoidance of tacrolimus
§ Lifestyle modification
Brenner and Rector's The Kidney, 10th edition
Rapid Steroid Withdrawal after Renal
Transplantation (Harmony Trial)
Oliver Thomusch et al , Lancet Volume 388, 17 December 2016
Cumulative probability of post-transplantation diabetes mellitus
Aspirin in Diabetes
§Use aspirin 75–162 mg/day as 2nd prevention in DM history
of ASCVD (grade B)
§Consider as1ry prevention in diabetes who increased CV
risk (grade C)
§ Aged > 50 years with least one risk factor
§ Family history of premature ASCVD
§ Hypertension
§ Dyslipidemia
§ Smoking
§ Albuminuria
§And are not at increased risk of bleeding
American Diabetes Association Standards of Medical Care in Diabetes 2017
Outline
§Outcome of kidney transplantation
§Complication & medical Management of KTRs
§ Post transplant diabetes mellitus
§ Hypertension
§ Dyslipidemia
§ Electrolyte disturbance
§ Bone disease
§ Recurrent diseases
§ Malignancy
§ Failing kidney & allograft nephrectomy
Hypertension after KT
§ Prevalence of hypertension 60-80%.
§ Causes include
§Steroids
§CNIs
§Weight gain
§Allograft dysfunction
§Native kidney disease
§TRAS
Brenner and Rector's The Kidney, 10th edition
FAVORIT (Folic Acid for Vascular Outcome
Reduction in Transplantation) trial
Carpenter MA et al, J Am Soc Nephrol. 2014 Jul;25(7):1554-62
Key:
1.Each increase of 20 mm Hg in SBP
↑32% CV events
↑13% death
2. Each drop of 10 mm Hg in DBP
from baseline 70 mmHg
↑ 31% CV events and death
Hypertension
§ Maintaining SBP at <130 mmHg and DBP <80
mmHg in adults (2C)
§To treat hypertension (Not Graded): use any class
of antihypertensive agent;
§monitor closely for adverse effects and
§drug–drug interactions
§When urine protein excretion ≥1 g/day à ACE-I
or ARB as first-line therapy.
KDIGO Guideline for the Care of Kidney Transplant Recipients American Journal of Transplantation 2009; 9 (Suppl 3): S42–S43
Intervention
§ Nonpharmacologic :
§ Weight loss,
§ Reduced sodium intake,
§ Reduced alcohol intake,
§ Treatment of OSA
§ Increased exercise
§ Pharmacologic :
§Minimized steroids and CNIs
§Antihypertensive drug therapy is still frequently
required.
Brenner and Rector's The Kidney, 10th edition
Major antihypertensive agent in KTRs
KDIGO Guideline for the Care of Kidney Transplant Recipients American Journal of Transplantation 2009; 9 (Suppl 3): S42–S43
§ CCB may be preferred as first line agents for
hypertensive kidney transplant recipients.ACEi have
some detrimental effects in kidney transplant recipients.
More high quality studies reporting patient centred
outcomes are required.
Outline
§Outcome of kidney transplantation
§Complication & medical Management of KTRs
§ Post transplant diabetes mellitus
§ Hypertension
§ Dyslipidemia
§ Electrolyte disturbance
§ Bone disease
§ Recurrent diseases
§ Malignancy
§ Failing kidney & allograft nephrectomy
Dyslipidemia after KT
§Prevalence of DLP after transplant is very high
§Causes :
§Steroids
§CNIs (cyclosporine > tacrolimus)
§Sirolimus
§Minimizing steroid dosage and switching cyclosporine
to tacrolimus
§Dose of a statin should be reduced by 50% (CNIs
increase statin levels)
Brenner and Rector's The Kidney, 10th edition
Toxicity profiles of immunosuppressive
medications
KDIGO Guideline for the Care of Kidney Transplant Recipients American Journal of Transplantation 2009; 9 (Suppl 3): S42–S43
Effect of fluvastatin on cardiac outcomes in renal transplant
recipients: a multicentre, randomised, placebo-controlled trial
Hallvard Holdaas et al , Lancet 361 : 2024 –2031, 2003
ALERT Trial
32%. Risk reduction with
fluvastatin for
primary endpoint
risk ratio 0·83 [CI 0.64–1.06
p=0·139
§ Statins may reduce CV events in KTRs
transplant recipients, although treatment effects are
imprecise.
§Statin treatment has uncertain effects on
overall mortality, stroke, kidney function,
and toxicity outcomes in kidney transplant
recipients.
Dyslipidemia
§ Measure a complete lipid profile in all adult
§ 2–3 months after transplantation;
§ 2–3 months after a change in treatment
§ at least annually, thereafter
§Evaluate 2nd causes of dyslipidemia
§If fasting TG ≥500 mg/dL
§LSM and a triglyceride lowering agent
§If LDL-C ≥100 mg/dL treat to reduce LDL-C to <100
mg/dL
KDIGO Guideline for the Care of Kidney Transplant Recipients American Journal of Transplantation 2009; 9 (Suppl 3): S42–S43
Outline
§Outcome of kidney transplantation
§Complication & medical Management of KTRs
§ Post transplant diabetes mellitus
§ Hypertension
§ Dyslipidemia
§ Electrolyte disturbance
§ Bone disease
§ Recurrent diseases
§ Malignancy
§ Failing kidney & allograft nephrectomy
Biochemical Abnormalities in KTR
After KT – 12 mo After 12 mo
GFR rapid change Stable graft function achieved.
Hypophosphatemia Normalized phosphate
Mild hypercalcemia Normalized Calcium
PTH decrease significantly in 3 mo PTH typically stabilizes at elevated
values
Low levels of 1,25(OH)2D
typically do not reach normal
values until 18 mo
KDOQI guideline : Evaluation and Treatment of Chronic Kidney Disease-Mineral and Bone Disorder
Hypercalcemia & Hypophosphatemia
§ Hypercalcemia after KT
§persistent hyperparathyroidism
§calcium and vitamin D supplement
§Hypophosphatemia after KT
§common in early post KT period
§reduced PO4 absorption (vitamin D depletion)
§urinary phosphate wasting(high FGF-23 and PTH)
§tubular effects of CNIs, sirolimus, and high-dose
steroids
Brenner and Rector's The Kidney, 10th edition
§ reserve oral phosphate when < 1-1.5 mg/dL or
symptomatic hypophosphatemia.
Hyperkalemia
§Mild hyperkalemia is common
§Principle cause is
§CNI-induced impairment of tubular potassium
secretion.
§Poor allograft function
§High potassium intake
§ACEIs and β-blockers
Outline
§Outcome of kidney transplantation
§Complication & medical Management of KTRs
§ Post transplant diabetes mellitus
§ Hypertension
§ Dyslipidemia
§ Electrolyte disturbance
§ Bone disease
§ Recurrent diseases
§ Malignancy
§ Failing kidney & allograft nephrectomy
Bone disease after KT
Incidence
Persistent secondary hyperparathyroidism 50%
Post-transplant osteoporosis 44% (28–88%)
Symmetric bone pain syndrome 11%
Spontaneous femoral head necrosis/ localized
osteonecrosis b2M amyloidosis
3%
Hypercalcaemia 50% in 3 months
15% in 2 years
Hypophosphataemia 90% in 4 months
40% in 1 year
Hypomagnesaemia 40%
H. Sperschneider and G. Stein et al, Nephrol Dial Transplant (2003) 18: 874–877
Persistent 2nd hyperparathyroidism
§Residual hyperparathyroidism can persist for years.
§Main risk factors for hyper PTH
§Pretransplant iPTH level
§Dialysis vintage
§Inadequate vitamin D stores
§Poor allograft function (de novo 2nd hyperparathyroidism)
Indications for parathyroidectomy (postKT)
§ Severe symp. Hypercalcemia which failure in
medication
§ Persistent, moderately severe hypercalcemia
(serum calcium level ≥ 12.5 mg/dL) >1 year
§ Calcific uremic arteriolopathy (calciphylaxis)
Brenner and Rector's The Kidney, 10th edition
Post-transplantation Osteoporosis
Rapid loss of vertebral BMD after KT
Julian BA, Laskow DA, Dubovsky J, et al:. N Engl J Med 325:544– 550, 1991.
Risk factors for fracture after KT
Pre transplantation
CKD-MBD
History of fracture
Advanced age
Chronic illness
Malnutrition
Vitamin D deficiency
Immobilization
Hyperparathyroidism
Hypogonadism
Medications: Steroid
Smoking/ Alcohol
Maalouf NM and Shane E. J Clin Endocrinol Metab 2015; 90:2456.
Post transplantation
Immunosuppressive regimens
-Glucocorticoids
-CNI (cyclosporine, tacrolimus)
Chronic illness
Poor nutrition
Vitamin D deficiency
Immobilization
Hypogonadism
Lifestyle factors
Smoking
Alcohol abuse
Inactivity
Pathophysiology of bone loss and fractures
before and after transplantation
Antoine Bouquegneau ,et al : Clin J Am Soc Nephrol 2016.
Effect of steroid in bone loss
Ebeling PR. Et al , J Clin Endocrinol Metab. 2009 May. 94(5):1483-90
Post KT- Osteoporosis definition
Effect of CsA in bone loss
§CsA results in accelerated bone turnover, with
both increased formation and resorption.
Post KT- Osteoporosis
§ If eGFR > 30 mL/min/1.73m2
§ measuring BMD in first 3 months if
§Receive corticosteroids
§Risk factors for osteoporosis as in general
population. (2D)
KDIGO Guideline for the Care of Kidney Transplant Recipients American Journal of Transplantation 2009; 9 (Suppl 3): S42–S43
§In first 12 mo after KT , eGFR > 30 mL/min/1.73 m2 and
low BMD,
§We suggest
§Vitamin D (calcitriol/alfacalcidiol) OR
§Bisphosphonates be considered. (2D)
§Consider bone biopsy to guide treatment , before
bisphosphonates use due to the high incidence of
adynamic bone disease. (Not Graded)
§Insufficient data to guide treatment after the first 12
months. (Not Graded)
Post KT- Osteoporosis
KDIGO Guideline for the Care of Kidney Transplant Recipients American Journal of Transplantation 2009; 9 (Suppl 3): S42–S43
§CKD stages 4–5T
§ BMD testing not be performed routinely
§ BMD does not predict fracture risk as it does in
the general population
Post KT- Osteoporosis
KDIGO Guideline for the Care of Kidney Transplant Recipients American Journal of Transplantation 2009; 9 (Suppl 3): S42–S43
§Treatment with a bisphosphonate, vitamin D sterol or
calcitonin after kidney transplantation may protect
against immunosuppression-induced reductions in BMD
and prevent fracture.
Hyperuricemia and gout
§ Suggest treating hyperuricemia in KTRs when
there are complications, such as gout, tophi, or uric
acid stones. (2D)
§colchicine for treating acute gout, with
appropriate dose reduction for reduced kidney
function and concomitant CNI use. (2D)
§ Avoiding allopurinol in patients receiving
azathioprine. (1B)
KDIGO Guideline for the Care of Kidney Transplant Recipients American Journal of Transplantation 2009; 9 (Suppl 3): S42–S43
Outline
§Outcome of kidney transplantation
§Complication & medical Management of KTRs
§ Post transplant diabetes mellitus
§ Hypertension
§ Dyslipidemia
§ Electrolyte disturbance
§ Bone disease
§ Recurrent diseases
§ Malignancy
§ Failing kidney & allograft nephrectomy
Recurrent primary disease
§The risk of recurrence by prevalence
§FSGS
§IgA
§MPGN
§HUS
§Primary oxalosis
§Fabry’s disease
§Lupus nephritis
§AntiGBM disease
KDIGO Guideline for the Care of Kidney Transplant Recipients American Journal of Transplantation 2009; 9 (Suppl 3): S42–S43
Screening for recurrent diseases
KDIGO Guideline for the Care of Kidney Transplant Recipients American Journal of Transplantation 2009; 9 (Suppl 3): S42–S43
Recurrent disease : FSGS
§ Sporadic recurrence is approximately 30%
§ Risk factors for recurrence
§Recurrent FSGS in a previous KT (strongest risk)
§white recipient
§younger recipient (6-15 yr)
§rapidly progressive FSGS in native kidneys
§diffuse mesangial proliferation on histology
§Treatment options: plasmapheresis or, high-dose
CyclosporinA ,ACEIs,
KDIGO Guideline for the Care of Kidney Transplant Recipients American Journal of Transplantation 2009; 9 (Suppl 3): S42–S43
§ Incidence of recurrence varies from 13% to 53%
§ Single-nucleotide polymorphisms in IL-10 and
TNF-alpha genes shown to predict recurrence risk
§ACEI/ARBs reduce proteinuria and preserve
kidney function in recurrent IgAN
§Use of ATG as induction therapy was associated
with a reduction in recurrence risk from 41% to 9%
when compared to IL2 receptor antagonists
KDIGO Guideline for the Care of Kidney Transplant Recipients American Journal of Transplantation 2009; 9 (Suppl 3): S42–S43
Recurrent disease : IgAN
Survival without recurrence and induction
therapy in IgAN recipients
Berthoux F, et al.. Transplantation 2008; 85: 1505–1507.
Outline
§Outcome of kidney transplantation
§Complication & medical Management of KTRs
§ Post transplant diabetes mellitus
§ Hypertension
§ Dyslipidemia
§ Electrolyte disturbance
§ Bone disease
§ Recurrent diseases
§ Malignancy
§ Failing kidney & allograft nephrectomy
Vaccination
§ Approved, inactivated vaccines, by general schedules ,except HBV
vaccination. (1D)
§ ideally prior to KT and HBsAb titers 6–12 weeks after course (2D)
§ annual HBsAb titers. (2D)
§ revaccination if Ab titer falls below 10 mIU/ mL. (2D)
§ Avoiding vaccinations, in first 6 months after KT (except influenza vaccination, )
(2C)
§Additional vaccine : epidemiological risk
§ Rabies, (2D)
§ Tick-borne meningoencephalitis, (2D) •
§ Japanese B encephalitis—inactivated, (2D)
§ Meningococcus, (2D)
§ Pneumococcus, (2D)
KDIGO Guideline for the Care of Kidney Transplant Recipients American Journal of Transplantation 2009; 9 (Suppl 3): S42–S43
Contraindicated vaccinations after KT
Varicella zoster
BCG
Smallpox
Intranasal influenza
Live oral typhoidTy21a and other newer vaccines
Measles (except during an outbreak) /Mumps/Rubella
Oral polio
Live Japanese B encephalitis vaccine
Yellow fever
KDIGO Guideline for the Care of Kidney Transplant Recipients American Journal of Transplantation 2009; 9 (Suppl 3): S42–S43
Cancer after Kidney Transplantation
§ Overall incidence of cancer in KTRs recipients is
greater than in dialysis patients and general population
§ Mechanism
§1) inhibits normal tumor surveillance mechanisms,
allowing unchecked proliferation of “spontaneously
occurring” neoplastic cells
§2) immunosuppression allows uncontrolled
proliferation of oncogenic viruses
§3) factors related to primary kidney disease or the
ESRD milieu (acquired renal cystic disease) might
promote neoplasia.
Brenner and Rector's The Kidney, 10th edition
§ Routine use of CNIs increased risk of skin cancers
§ Sirolimus has antineoplastic effects
§ Everolimus effective in treatment of RCC
Cancer after Kidney Transplantation
Brenner and Rector's The Kidney, 10th edition
Cancers categorized by SIR for kidney
transplant patients and cancer incidence
KDIGO Guideline for the Care of Kidney Transplant Recipients American Journal of Transplantation 2009; 9 (Suppl 3): S42–S43
Viral-associated cancers
KDIGO Guideline for the Care of Kidney Transplant Recipients American Journal of Transplantation 2009; 9 (Suppl 3): S42–S43
Posttransplant Lymphoproliferative
Disorder (PTLD)
§ Can occur early after KT and high morbidity and mortality
§ 90% are non-Hodgkin’s lymphomas
§ Extranodal, GI tract, and CNS lymphoma is more common
§ Most cases occur in first 24 months after transplant
§Risk factors include
§(1) EBV- positive donor and EBV-negative recipient
§(2) CMV-positive donor and CMV-negative recipient
§(3) pediatric recipient
§(4) aggressive immunosuppression, esp with
antilymphocyte antibody or tacrolimus.
KDIGO Guideline for the Care of Kidney Transplant Recipients American Journal of Transplantation 2009; 9 (Suppl 3): S42–S43
Clinical and Pathologic Spectrum PTLD
Brenner and Rector's The Kidney, 10th edition
EBV and PTLD
§Monitoring high-risk (donor EBV +/recipient-) NAT
PCR(2C):
§once in 1st week after KT(2D);
§then at least monthly for 3–6 months then q 3 months
until the end of the first post-transplant year (2D)
§after treatment for ac rejection. (2D)
§EBV-seronegative pts with increasing EBV load à
immunosuppressive medication reduced. (2D)
§ We recommend that patients with EBV disease, including
PTLD, have a reduction or cessation of immunosuppressive
medication. (1C)
KDIGO Guideline for the Care of Kidney Transplant Recipients American Journal of Transplantation 2009; 9 (Suppl 3): S42–S43
Smoking
§ General populationà strong evidence smoking
causes CVD, cancer, chronic lung disease and
premature death
§In KTRs, cigarette smoking is associated with CVD
and cancer.
KDIGO Guideline for the Care of Kidney Transplant Recipients American Journal of Transplantation 2009; 9 (Suppl 3): S42–S43
Pharmacological therapies for
smoking cessation in KTRs
Class Drug Consideration
Nicotine replacement Nicotine gum, inhaler,
nasal spray, lozenge and
patch
combinations with other
nicotine and non-
nicotine replacement
agents
Antidepressant Bupropion SR Monitor CsA blood
levels and increase CsA
dose as needed
a4b2 nicotinic receptor
partial agonist
Varenicline Caution : including
depression and suicidal
ideationa
KDIGO Guideline for the Care of Kidney Transplant Recipients American Journal of Transplantation 2009; 9 (Suppl 3): S42–S43
Outline
§Outcome of kidney transplantation
§Complication & medical Management of KTRs
§ Post transplant diabetes mellitus
§ Hypertension
§ Dyslipidemia
§ Electrolyte disturbance
§ Bone disease
§ Recurrent diseases
§ Malignancy
§ Failing kidney & allograft nephrectomy
Allograft nephrectomy
§Indication
§ Allograft failure with symptomatic rejection
fever, malaise, hematuria, and graft pain
§ Infarction due to thrombosis
§ Severe infection e.g. emphysematous pyelonephritis
§ Allograft rupture
Brenner and Rector's The Kidney, 10th edition
Failing kidney
§ Preparation for dialysis
§ Immunosuppression weaned gradually
§prevent acute rejection, resulting in transplanted
nephrectomy
§ Listed again for another transplant if no contraindication
Brenner and Rector's The Kidney, 10th edition
Thank you for your attention

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Kidney transplantation outcome complication chaken

  • 1. Topic Review Maj. Chaken Maniyan M.D. Division of Nephrology, Department of Medicine Phramongkutklao Hospital 17.2.2017 Outcome and complication of kidney transplantation
  • 2. Outline §Outcome of kidney transplantation §Complication & medical management of KTRs § Post transplant diabetes mellitus § Hypertension § Dyslipidemia § Electrolyte disturbance § Bone disease § Recurrent diseases § Malignancy § Failing kidney & allograft nephrectomy
  • 3. Difficulties are opportunities , said Dr. Murray 1954, First Kidney transplantation by Joseph E. Murray at Brigham Hospital in Boston for identical Twin (Richard and Ron Herrick) 1990 Noble prize
  • 4. Risk of death of kidney transplantation compare to dialysis Wolfe RA, Ashby VB, Milford EL, et al: N Engl J Med 341:1725–1730, 1999.
  • 5. Timeline of kidney transplantation, threats, and opportunities Adnan Sharif, Solomon Cohney et al , Lancet Diabetes Endocrinol 2016; 4: 337–49
  • 6. One-year deceased donor kidney allograft survival and rejection episodes over time on Comprehensive Clinical Nephrology, 5th Edition
  • 7. Highlight 2016 USRDS annual report 2016 ANNUAL DATA REPORT, VOL 2, ESRD,
  • 8. Trends in incidence rate of treated ESRD (per million population/year), by country, 2001-2014 2016 ANNUAL DATA REPORT, VOL 2, ESRD, Ten countries having the highest % rise in ESRD
  • 9. Percent distribution of type of RRT modality by country, 2001-2014 2016 ANNUAL DATA REPORT, VOL 2, ESRD,
  • 10. Assessing Allograft Outcomes in Kidney Transplantation §Main outcome :Allograft survival §Surrogate outcomes §Allograft function (SCr level) §Patient survival §Rejection episodes §Days of hospitalization §Quality of life indices Brenner and Rector's The Kidney, 10th edition
  • 11. Short term outcome § 0-12 month after kidney transplantation § Main causes of allograft loss §Acute rejection §Thrombosis §Primary non-function kidney §Patient death Brenner and Rector's The Kidney, 10th edition
  • 12. Long term outcome § After 12 month after kidney transplantation § Main causes of allograft loss §Patient death §Chronic allograft injury (CAI) §Late acute rejection §Recurrent disease Brenner and Rector's The Kidney, 10th edition
  • 13. Before 5 years After 5 years Causes of death with functioning graft in Thailand
  • 14. Causes of allograft loss in Thailand
  • 15. Factors associated with allograft survival § Donor factors § Recipient factors § Donor – recipient interaction factors § Recurrent disease § Proteinuria Brenner and Rector's The Kidney, 10th edition
  • 16. Donor factors §Donor source: deceasedVS living donor §Donor age §Donor gender §Donor ancestry and ethnicity §Cold ischemia time §Expanded criteria donors §Donation after cardiac death (DCD) Brenner and Rector's The Kidney, 10th edition
  • 17. Expanded Criteria Donors §60 years or older §50 to 59 with two of the following criteria § (1) CVA as cause of death § (2) history of hypertension § (3) Serum creatinine >1.5 mg/dL KDIGO Guideline for the Care of Kidney Transplant Recipients American Journal of Transplantation 2009; 9 (Suppl 3): S42–S43
  • 18. Recipients factors §Recipient age §Recipient race and ethnicity §Recipient gender §Recipient sensitization §Acute rejection §Recipient immunosuppression §Recipient compliance §Recipient cause of ERSD §Recipient hypertension Brenner and Rector's The Kidney, 10th edition
  • 19. Donor – recipient interaction factors § Delayed graft function § Human leukocyte antigen matching § Cytomegalovirus status of donor and recipient §Timing of transplantation § Center effect Brenner and Rector's The Kidney, 10th edition
  • 20. 2015 Thai Transplant Society Annual Report Kidney Transplantation Rate 2000-2015
  • 21. 2015 Thai Transplant Society Annual Report Cumulative KTRs among hospitals 1994-2015
  • 22. 2015 Thai Transplant Society Annual Report Living donor and recipient ages 1994-2015
  • 23. 2015 Thai Transplant Society Annual Report Cold Ischemic Time 1994-2014
  • 24. 2015 Thai Transplant Society Annual Report Deceased Donor Characteristic 1996-2014
  • 25. 2015 Thai Transplant Society Annual Report DFG Rate , SCr at discharge day 1994-2012
  • 26. Patient Survival Rate by 1994-2015 2015 Thai Transplant Society Annual Report
  • 27. Improving allograft survival outcome § Maximizing organs available for KT § National campaign § Education of medical staff/ family members § Expanded criteria donor and DCD § Maximize life span of donated organs §Criteria used for allocation of deceased donor §Youngest and healthiest, maximizing the life years from transplantation (LYFT) gained §Maximized the early marker of allograft injury Brenner and Rector's The Kidney, 10th edition
  • 28. Biopsy gene expression to identify KTRs at risk of chronic injury O’Connell PJ, Zhang W, Menon MC, et al. Lancet 2016; 388: 983–93.
  • 29. Outline §Outcome of kidney transplantation §Complication & medical management of KTRs § Post transplant diabetes mellitus § Hypertension § Dyslipidemia § Electrolyte disturbance § Bone disease § Recurrent diseases § Malignancy § Failing kidney & allograft nephrectomy
  • 30. PTDM : Impact Adnan Sharif & Keshwar Baboolal , Nature Reviews Nephrology 8, 34-42 (January 2012)
  • 31. Pathophysiology of post-transplant DM Adnan Sharif, Solomon Cohney et al L, ancet Diabetes Endocrinol 2016; 4: 337–49
  • 32. Cardiometabolic risk profi le of immunosuppression Adnan Sharif, Solomon Cohney et al L, ancet Diabetes Endocrinol 2016; 4: 337–49
  • 33. Toxicity profiles of immunosuppressive medications KDIGO Guideline for the Care of Kidney Transplant Recipients American Journal of Transplantation 2009; 9 (Suppl 3): S42–S43
  • 34. Risk factor for NODAT Non-modifiable Potentially modifiable Modifiable Ethnicity (non- Caucasian) Infections HCV CMV Immunosuppressive Therapy Age >40 years-old • Tacrolimus Male gender • Cyclosporine Donor's gender (M) IGT (pretransplantation) • Corticosteroid Family history of DM • Sirolimus HLA Obesity HLA (mismatches) Cadaveric donor OPTN/UNOS database, Am J Kidney Dis. 2010 Dec;56(6):1127-39.
  • 35. NODAT : Screening §Screening all nondiabetic KTRs with FPG, OGTT, and/or HbA1c (1C) at least: §weekly for 4 weeks (2D) §every 3 months for 1 year (2D) §annually, thereafter (2D) §Screening after starting, or increasing CNIs, mTORi or corticosteroids. (2D) KDIGO Guideline for the Care of Kidney Transplant Recipients American Journal of Transplantation 2009; 9 (Suppl 3): S42–S43
  • 36. NODAT : Screening § Criteria for the diagnosis of diabetes §FPG ≥126 mg/dL (7.0 mmol/L) OR §S/S of hyperglycemia and CBG ≥ 200 mg/dL OR §Two-hour glucose ≥200 mg/dL during OGTT § glucose load (75 g anhydrous glucose dissolved in water) KDIGO Guideline for the Care of Kidney Transplant Recipients American Journal of Transplantation 2009; 9 (Suppl 3): S42–S43
  • 37. Risk factor of NODAT KDIGO Guideline for the Care of Kidney Transplant Recipients American Journal of Transplantation 2009; 9 (Suppl 3): S42–S43
  • 38. Management of PTDM § Dietary modification § Lifestyle modifications § Adjustment or modification in immunosuppressive meds §Rapid steroid taper, steroid-sparing or steroid avoidance protocols §Tacrolimus to cyclosporine conversion therapy §Pharmacologic therapy §Screening for microalbuminuria §Regular ophthalmologic exam §Regular foot care Brenner and Rector's The Kidney, 10th edition
  • 39. Management of NODAT § Modifying immunosuppressive regimen to reverse diabetes, after weighing risk of rejection and other potential adverse effects. (Not Graded) § Target HbA1c 7.0–7.5% § Avoid HbA1c ≤ 6.0%, esp if hypoglycemic (Not Graded) § Aspirin (65–100 mg/day) use for 1o prevention of CVD be based on patient preferences balancing the risk for ischemic/bleeding (2D) KDIGO Guideline for the Care of Kidney Transplant Recipients American Journal of Transplantation 2009; 9 (Suppl 3): S42–S43
  • 40. Pharmacological management of diabetes in KTRs KDIGO Guideline for the Care of Kidney Transplant Recipients American Journal of Transplantation 2009; 9 (Suppl 3): S42–S43
  • 41. Medications for diabetes control in first 6 months post-transplant 2014 ANNUAL DATA REPORT, VOL 2, ESRD,
  • 42. Strategies to prevent and treat PTDM § Steroid minimization § Avoidance of tacrolimus § Lifestyle modification Brenner and Rector's The Kidney, 10th edition
  • 43. Rapid Steroid Withdrawal after Renal Transplantation (Harmony Trial) Oliver Thomusch et al , Lancet Volume 388, 17 December 2016 Cumulative probability of post-transplantation diabetes mellitus
  • 44. Aspirin in Diabetes §Use aspirin 75–162 mg/day as 2nd prevention in DM history of ASCVD (grade B) §Consider as1ry prevention in diabetes who increased CV risk (grade C) § Aged > 50 years with least one risk factor § Family history of premature ASCVD § Hypertension § Dyslipidemia § Smoking § Albuminuria §And are not at increased risk of bleeding American Diabetes Association Standards of Medical Care in Diabetes 2017
  • 45. Outline §Outcome of kidney transplantation §Complication & medical Management of KTRs § Post transplant diabetes mellitus § Hypertension § Dyslipidemia § Electrolyte disturbance § Bone disease § Recurrent diseases § Malignancy § Failing kidney & allograft nephrectomy
  • 46. Hypertension after KT § Prevalence of hypertension 60-80%. § Causes include §Steroids §CNIs §Weight gain §Allograft dysfunction §Native kidney disease §TRAS Brenner and Rector's The Kidney, 10th edition
  • 47. FAVORIT (Folic Acid for Vascular Outcome Reduction in Transplantation) trial Carpenter MA et al, J Am Soc Nephrol. 2014 Jul;25(7):1554-62 Key: 1.Each increase of 20 mm Hg in SBP ↑32% CV events ↑13% death 2. Each drop of 10 mm Hg in DBP from baseline 70 mmHg ↑ 31% CV events and death
  • 48. Hypertension § Maintaining SBP at <130 mmHg and DBP <80 mmHg in adults (2C) §To treat hypertension (Not Graded): use any class of antihypertensive agent; §monitor closely for adverse effects and §drug–drug interactions §When urine protein excretion ≥1 g/day à ACE-I or ARB as first-line therapy. KDIGO Guideline for the Care of Kidney Transplant Recipients American Journal of Transplantation 2009; 9 (Suppl 3): S42–S43
  • 49. Intervention § Nonpharmacologic : § Weight loss, § Reduced sodium intake, § Reduced alcohol intake, § Treatment of OSA § Increased exercise § Pharmacologic : §Minimized steroids and CNIs §Antihypertensive drug therapy is still frequently required. Brenner and Rector's The Kidney, 10th edition
  • 50. Major antihypertensive agent in KTRs KDIGO Guideline for the Care of Kidney Transplant Recipients American Journal of Transplantation 2009; 9 (Suppl 3): S42–S43
  • 51. § CCB may be preferred as first line agents for hypertensive kidney transplant recipients.ACEi have some detrimental effects in kidney transplant recipients. More high quality studies reporting patient centred outcomes are required.
  • 52. Outline §Outcome of kidney transplantation §Complication & medical Management of KTRs § Post transplant diabetes mellitus § Hypertension § Dyslipidemia § Electrolyte disturbance § Bone disease § Recurrent diseases § Malignancy § Failing kidney & allograft nephrectomy
  • 53. Dyslipidemia after KT §Prevalence of DLP after transplant is very high §Causes : §Steroids §CNIs (cyclosporine > tacrolimus) §Sirolimus §Minimizing steroid dosage and switching cyclosporine to tacrolimus §Dose of a statin should be reduced by 50% (CNIs increase statin levels) Brenner and Rector's The Kidney, 10th edition
  • 54. Toxicity profiles of immunosuppressive medications KDIGO Guideline for the Care of Kidney Transplant Recipients American Journal of Transplantation 2009; 9 (Suppl 3): S42–S43
  • 55. Effect of fluvastatin on cardiac outcomes in renal transplant recipients: a multicentre, randomised, placebo-controlled trial Hallvard Holdaas et al , Lancet 361 : 2024 –2031, 2003 ALERT Trial 32%. Risk reduction with fluvastatin for primary endpoint risk ratio 0·83 [CI 0.64–1.06 p=0·139
  • 56. § Statins may reduce CV events in KTRs transplant recipients, although treatment effects are imprecise. §Statin treatment has uncertain effects on overall mortality, stroke, kidney function, and toxicity outcomes in kidney transplant recipients.
  • 57. Dyslipidemia § Measure a complete lipid profile in all adult § 2–3 months after transplantation; § 2–3 months after a change in treatment § at least annually, thereafter §Evaluate 2nd causes of dyslipidemia §If fasting TG ≥500 mg/dL §LSM and a triglyceride lowering agent §If LDL-C ≥100 mg/dL treat to reduce LDL-C to <100 mg/dL KDIGO Guideline for the Care of Kidney Transplant Recipients American Journal of Transplantation 2009; 9 (Suppl 3): S42–S43
  • 58. Outline §Outcome of kidney transplantation §Complication & medical Management of KTRs § Post transplant diabetes mellitus § Hypertension § Dyslipidemia § Electrolyte disturbance § Bone disease § Recurrent diseases § Malignancy § Failing kidney & allograft nephrectomy
  • 59. Biochemical Abnormalities in KTR After KT – 12 mo After 12 mo GFR rapid change Stable graft function achieved. Hypophosphatemia Normalized phosphate Mild hypercalcemia Normalized Calcium PTH decrease significantly in 3 mo PTH typically stabilizes at elevated values Low levels of 1,25(OH)2D typically do not reach normal values until 18 mo KDOQI guideline : Evaluation and Treatment of Chronic Kidney Disease-Mineral and Bone Disorder
  • 60. Hypercalcemia & Hypophosphatemia § Hypercalcemia after KT §persistent hyperparathyroidism §calcium and vitamin D supplement §Hypophosphatemia after KT §common in early post KT period §reduced PO4 absorption (vitamin D depletion) §urinary phosphate wasting(high FGF-23 and PTH) §tubular effects of CNIs, sirolimus, and high-dose steroids Brenner and Rector's The Kidney, 10th edition
  • 61. § reserve oral phosphate when < 1-1.5 mg/dL or symptomatic hypophosphatemia.
  • 62. Hyperkalemia §Mild hyperkalemia is common §Principle cause is §CNI-induced impairment of tubular potassium secretion. §Poor allograft function §High potassium intake §ACEIs and β-blockers
  • 63. Outline §Outcome of kidney transplantation §Complication & medical Management of KTRs § Post transplant diabetes mellitus § Hypertension § Dyslipidemia § Electrolyte disturbance § Bone disease § Recurrent diseases § Malignancy § Failing kidney & allograft nephrectomy
  • 64. Bone disease after KT Incidence Persistent secondary hyperparathyroidism 50% Post-transplant osteoporosis 44% (28–88%) Symmetric bone pain syndrome 11% Spontaneous femoral head necrosis/ localized osteonecrosis b2M amyloidosis 3% Hypercalcaemia 50% in 3 months 15% in 2 years Hypophosphataemia 90% in 4 months 40% in 1 year Hypomagnesaemia 40% H. Sperschneider and G. Stein et al, Nephrol Dial Transplant (2003) 18: 874–877
  • 65. Persistent 2nd hyperparathyroidism §Residual hyperparathyroidism can persist for years. §Main risk factors for hyper PTH §Pretransplant iPTH level §Dialysis vintage §Inadequate vitamin D stores §Poor allograft function (de novo 2nd hyperparathyroidism)
  • 66. Indications for parathyroidectomy (postKT) § Severe symp. Hypercalcemia which failure in medication § Persistent, moderately severe hypercalcemia (serum calcium level ≥ 12.5 mg/dL) >1 year § Calcific uremic arteriolopathy (calciphylaxis) Brenner and Rector's The Kidney, 10th edition
  • 68. Rapid loss of vertebral BMD after KT Julian BA, Laskow DA, Dubovsky J, et al:. N Engl J Med 325:544– 550, 1991.
  • 69. Risk factors for fracture after KT Pre transplantation CKD-MBD History of fracture Advanced age Chronic illness Malnutrition Vitamin D deficiency Immobilization Hyperparathyroidism Hypogonadism Medications: Steroid Smoking/ Alcohol Maalouf NM and Shane E. J Clin Endocrinol Metab 2015; 90:2456. Post transplantation Immunosuppressive regimens -Glucocorticoids -CNI (cyclosporine, tacrolimus) Chronic illness Poor nutrition Vitamin D deficiency Immobilization Hypogonadism Lifestyle factors Smoking Alcohol abuse Inactivity
  • 70. Pathophysiology of bone loss and fractures before and after transplantation Antoine Bouquegneau ,et al : Clin J Am Soc Nephrol 2016.
  • 71. Effect of steroid in bone loss Ebeling PR. Et al , J Clin Endocrinol Metab. 2009 May. 94(5):1483-90
  • 72. Post KT- Osteoporosis definition
  • 73. Effect of CsA in bone loss §CsA results in accelerated bone turnover, with both increased formation and resorption.
  • 74. Post KT- Osteoporosis § If eGFR > 30 mL/min/1.73m2 § measuring BMD in first 3 months if §Receive corticosteroids §Risk factors for osteoporosis as in general population. (2D) KDIGO Guideline for the Care of Kidney Transplant Recipients American Journal of Transplantation 2009; 9 (Suppl 3): S42–S43
  • 75. §In first 12 mo after KT , eGFR > 30 mL/min/1.73 m2 and low BMD, §We suggest §Vitamin D (calcitriol/alfacalcidiol) OR §Bisphosphonates be considered. (2D) §Consider bone biopsy to guide treatment , before bisphosphonates use due to the high incidence of adynamic bone disease. (Not Graded) §Insufficient data to guide treatment after the first 12 months. (Not Graded) Post KT- Osteoporosis KDIGO Guideline for the Care of Kidney Transplant Recipients American Journal of Transplantation 2009; 9 (Suppl 3): S42–S43
  • 76. §CKD stages 4–5T § BMD testing not be performed routinely § BMD does not predict fracture risk as it does in the general population Post KT- Osteoporosis KDIGO Guideline for the Care of Kidney Transplant Recipients American Journal of Transplantation 2009; 9 (Suppl 3): S42–S43
  • 77. §Treatment with a bisphosphonate, vitamin D sterol or calcitonin after kidney transplantation may protect against immunosuppression-induced reductions in BMD and prevent fracture.
  • 78. Hyperuricemia and gout § Suggest treating hyperuricemia in KTRs when there are complications, such as gout, tophi, or uric acid stones. (2D) §colchicine for treating acute gout, with appropriate dose reduction for reduced kidney function and concomitant CNI use. (2D) § Avoiding allopurinol in patients receiving azathioprine. (1B) KDIGO Guideline for the Care of Kidney Transplant Recipients American Journal of Transplantation 2009; 9 (Suppl 3): S42–S43
  • 79. Outline §Outcome of kidney transplantation §Complication & medical Management of KTRs § Post transplant diabetes mellitus § Hypertension § Dyslipidemia § Electrolyte disturbance § Bone disease § Recurrent diseases § Malignancy § Failing kidney & allograft nephrectomy
  • 80. Recurrent primary disease §The risk of recurrence by prevalence §FSGS §IgA §MPGN §HUS §Primary oxalosis §Fabry’s disease §Lupus nephritis §AntiGBM disease KDIGO Guideline for the Care of Kidney Transplant Recipients American Journal of Transplantation 2009; 9 (Suppl 3): S42–S43
  • 81. Screening for recurrent diseases KDIGO Guideline for the Care of Kidney Transplant Recipients American Journal of Transplantation 2009; 9 (Suppl 3): S42–S43
  • 82. Recurrent disease : FSGS § Sporadic recurrence is approximately 30% § Risk factors for recurrence §Recurrent FSGS in a previous KT (strongest risk) §white recipient §younger recipient (6-15 yr) §rapidly progressive FSGS in native kidneys §diffuse mesangial proliferation on histology §Treatment options: plasmapheresis or, high-dose CyclosporinA ,ACEIs, KDIGO Guideline for the Care of Kidney Transplant Recipients American Journal of Transplantation 2009; 9 (Suppl 3): S42–S43
  • 83. § Incidence of recurrence varies from 13% to 53% § Single-nucleotide polymorphisms in IL-10 and TNF-alpha genes shown to predict recurrence risk §ACEI/ARBs reduce proteinuria and preserve kidney function in recurrent IgAN §Use of ATG as induction therapy was associated with a reduction in recurrence risk from 41% to 9% when compared to IL2 receptor antagonists KDIGO Guideline for the Care of Kidney Transplant Recipients American Journal of Transplantation 2009; 9 (Suppl 3): S42–S43 Recurrent disease : IgAN
  • 84. Survival without recurrence and induction therapy in IgAN recipients Berthoux F, et al.. Transplantation 2008; 85: 1505–1507.
  • 85. Outline §Outcome of kidney transplantation §Complication & medical Management of KTRs § Post transplant diabetes mellitus § Hypertension § Dyslipidemia § Electrolyte disturbance § Bone disease § Recurrent diseases § Malignancy § Failing kidney & allograft nephrectomy
  • 86. Vaccination § Approved, inactivated vaccines, by general schedules ,except HBV vaccination. (1D) § ideally prior to KT and HBsAb titers 6–12 weeks after course (2D) § annual HBsAb titers. (2D) § revaccination if Ab titer falls below 10 mIU/ mL. (2D) § Avoiding vaccinations, in first 6 months after KT (except influenza vaccination, ) (2C) §Additional vaccine : epidemiological risk § Rabies, (2D) § Tick-borne meningoencephalitis, (2D) • § Japanese B encephalitis—inactivated, (2D) § Meningococcus, (2D) § Pneumococcus, (2D) KDIGO Guideline for the Care of Kidney Transplant Recipients American Journal of Transplantation 2009; 9 (Suppl 3): S42–S43
  • 87. Contraindicated vaccinations after KT Varicella zoster BCG Smallpox Intranasal influenza Live oral typhoidTy21a and other newer vaccines Measles (except during an outbreak) /Mumps/Rubella Oral polio Live Japanese B encephalitis vaccine Yellow fever KDIGO Guideline for the Care of Kidney Transplant Recipients American Journal of Transplantation 2009; 9 (Suppl 3): S42–S43
  • 88. Cancer after Kidney Transplantation § Overall incidence of cancer in KTRs recipients is greater than in dialysis patients and general population § Mechanism §1) inhibits normal tumor surveillance mechanisms, allowing unchecked proliferation of “spontaneously occurring” neoplastic cells §2) immunosuppression allows uncontrolled proliferation of oncogenic viruses §3) factors related to primary kidney disease or the ESRD milieu (acquired renal cystic disease) might promote neoplasia. Brenner and Rector's The Kidney, 10th edition
  • 89. § Routine use of CNIs increased risk of skin cancers § Sirolimus has antineoplastic effects § Everolimus effective in treatment of RCC Cancer after Kidney Transplantation Brenner and Rector's The Kidney, 10th edition
  • 90. Cancers categorized by SIR for kidney transplant patients and cancer incidence KDIGO Guideline for the Care of Kidney Transplant Recipients American Journal of Transplantation 2009; 9 (Suppl 3): S42–S43
  • 91. Viral-associated cancers KDIGO Guideline for the Care of Kidney Transplant Recipients American Journal of Transplantation 2009; 9 (Suppl 3): S42–S43
  • 92. Posttransplant Lymphoproliferative Disorder (PTLD) § Can occur early after KT and high morbidity and mortality § 90% are non-Hodgkin’s lymphomas § Extranodal, GI tract, and CNS lymphoma is more common § Most cases occur in first 24 months after transplant §Risk factors include §(1) EBV- positive donor and EBV-negative recipient §(2) CMV-positive donor and CMV-negative recipient §(3) pediatric recipient §(4) aggressive immunosuppression, esp with antilymphocyte antibody or tacrolimus. KDIGO Guideline for the Care of Kidney Transplant Recipients American Journal of Transplantation 2009; 9 (Suppl 3): S42–S43
  • 93. Clinical and Pathologic Spectrum PTLD Brenner and Rector's The Kidney, 10th edition
  • 94. EBV and PTLD §Monitoring high-risk (donor EBV +/recipient-) NAT PCR(2C): §once in 1st week after KT(2D); §then at least monthly for 3–6 months then q 3 months until the end of the first post-transplant year (2D) §after treatment for ac rejection. (2D) §EBV-seronegative pts with increasing EBV load à immunosuppressive medication reduced. (2D) § We recommend that patients with EBV disease, including PTLD, have a reduction or cessation of immunosuppressive medication. (1C) KDIGO Guideline for the Care of Kidney Transplant Recipients American Journal of Transplantation 2009; 9 (Suppl 3): S42–S43
  • 95. Smoking § General populationà strong evidence smoking causes CVD, cancer, chronic lung disease and premature death §In KTRs, cigarette smoking is associated with CVD and cancer. KDIGO Guideline for the Care of Kidney Transplant Recipients American Journal of Transplantation 2009; 9 (Suppl 3): S42–S43
  • 96. Pharmacological therapies for smoking cessation in KTRs Class Drug Consideration Nicotine replacement Nicotine gum, inhaler, nasal spray, lozenge and patch combinations with other nicotine and non- nicotine replacement agents Antidepressant Bupropion SR Monitor CsA blood levels and increase CsA dose as needed a4b2 nicotinic receptor partial agonist Varenicline Caution : including depression and suicidal ideationa KDIGO Guideline for the Care of Kidney Transplant Recipients American Journal of Transplantation 2009; 9 (Suppl 3): S42–S43
  • 97. Outline §Outcome of kidney transplantation §Complication & medical Management of KTRs § Post transplant diabetes mellitus § Hypertension § Dyslipidemia § Electrolyte disturbance § Bone disease § Recurrent diseases § Malignancy § Failing kidney & allograft nephrectomy
  • 98. Allograft nephrectomy §Indication § Allograft failure with symptomatic rejection fever, malaise, hematuria, and graft pain § Infarction due to thrombosis § Severe infection e.g. emphysematous pyelonephritis § Allograft rupture Brenner and Rector's The Kidney, 10th edition
  • 99. Failing kidney § Preparation for dialysis § Immunosuppression weaned gradually §prevent acute rejection, resulting in transplanted nephrectomy § Listed again for another transplant if no contraindication Brenner and Rector's The Kidney, 10th edition
  • 100. Thank you for your attention