Long Term Complications after Renal Transplantation- CPG

-45. LONG-TERM COMPLICATIONS AFTER RENAL TRANSPLANTATION

45.1 Cardiovascular disease
17% of deaths in renal transplant are due to cardiovascular disease.1 The death rate from cardiovascular disease is 10 – 20 times increased in the younger age groups.

Table 45.1: Risk factors for IHD post renal transplant2,3,4,5,6,7,8,9
age family history of IHD left ventricular hypertrophy
male sex hypertension acute rejection
smoking high LDL levels
diabetes mellitus low HDL levels

Elevated body mass index, hyperhomocysteinaemia, increased lipoprotein A and increased circulating inflammatory factors (CRP, fibrinogen) are associations.5,10,11 It is recommended to aggressively modify identifiable risk factors to lower cardiovascular risk. (Level B)
All renal transplant patients are considered at high risk of IHD.1,9,11,12 If they had an old myocardial infarction (MI) they are considered very high risk.8
45.1.1 The following steps may be taken to lower the IHD risk in patients (Level B):
a. Decrease LDL cholesterol (refer to 44.1.3 on lipid lowering therapy)
b. Blood pressure <> 1 g/day and <> 55%14
• Folic acid supplement (5 mg/day) to reduce homocysteine levels8,14,16,17
* caution in patients at risk of bleeding



45.1.2 Hypertension
The incidence of hypertension post renal transplant is 60 – 80% with the use of cyclosporine and tacrolimus.13,18 Treatment is to protect from cardiovascular complications and injury to the allograft.13
It is assumed the patient has no acute rejection, is on the lowest steroid and cyclosporine dose, has decreased salt intake and is limiting weight gain. The management is similar to other cases of hypertension. Comorbid factors e.g. cardiovascular disease, left ventricular hypertrophy, diabetes mellitus, hypercholesterolaemia, obesity are taken into account.

Table 45.2: The following anti-hypertensives may be used in renal transplant recipients19
Agent Notes
Calcium channel blockers Headache, oedema common. Diltiazem, verapamil and amlodipine elevate cyclosporine levels. Nifedipine causes gum hypertrophy.13
Beta blockers Lipid side effects. Worsens peripheral vascular disease, asthma, heart block. Useful in IHD.
Vasodilators Postural hypotension, palpitations. Alpha blockers useful in benign prostatic hypertrophy.
Methyl dopa Sedation, liver damage.
Minoxidil Hirsutism and fluid retention. Useful in uncontrolled hypertension.

Table 45.3: The following anti-hypertensives are used with caution
Agent Notes
ACE inhibitors and AII receptor antagonists13,20 Decreased GFR, hyperkalaemia, anaemia, cough.
Contraindicated in renal artery stenosis.
Renal function should be closely monitored.
Useful in HT with proteinuria or post-transplant erythrocytosis.
Diuretics Metabolic side effects, dehydration.
Useful in fluid overload

a. Suspect a secondary cause of HT if:
• Hypertension is poorly controlled despite good compliance and maximum anti-HT drugs
• Malignant hypertension
• Recent onset hypertension
• Hypertension with progressive graft dysfunction
b. Secondary causes include20,21:
• Graft renal artery stenosis
• Chronic allograft nephropathy
• Recurrent or de novo glomerulonephritis (active urine sediment with CRF)
• Chronic cyclosporine toxicity

45.1.3 Lipid lowering therapy
Lowering LDL cholesterol in patients with IHD or in high risk patients for primary prevention leads to clinical benefit beyond a doubt.2,22,23,24,25,26,27,28 (Level A)
a. Patients should be screened at least once during the first 6 months and again at 1 year after renal transplant with fasting total cholesterol, LDL, HDL and TG. Thereafter annual screening with fasting lipid profile. Changes in immunosuppressive therapy, graft function or IHD risk may warrant additional screening.14 (Level A)
b. Cholesterol lowering in renal transplant recipients: (Level A)
For primary prevention start with HMG CoA reductase inhibitor (statin) if total cholesterol is 7 or LDL > 5 mmol/l.22,26 With IHD, start if total cholesterol is 4 or LDL > 3 mmol/l.23,25
• Primary prevention: target LDL <>1.55 mmol/l is protective)
*(Conversion from mg/dl to mmol/l cholesterol: x 0.02586)
(Conversion from mmol/l to mg/dl cholesterol: x 38.67)

Cholesterol usually will not change with diet modification. Statins are the drugs of first choice for decreasing LDL.2,9 Statins reduced the incidence of cardiac deaths and non fatal myocardial infarction in renal transplant recipients.30,31,32

There are 2 classes of statins: hydrophilic (pravastatin and fluvastatin) which do not cause myopathy and lipophilic (lovastatin, simvastatin and atorvastatin) which cause myopathy.2,33,34,35 In the former class maximum dose can be used; in the latter reduce the dose to half, e.g. 5 – 10 mg/day simvastatin and 20mg/day lovastatin. Caution as statins may interact with cyclosporin.
Fibrates may be used for hypertriglyceridaemia and decreased HDL: target TG <> 2.5 SD below the young adult mean value; t score) may be diagnosed with dual energy X’ray absorptiometry (DEXA) at the time of renal transplant, after 6 months and then every 12 months if results are abnormal.14 (Level B)
Intravenous pamidronate 0.5 mg/kg given at the time of renal transplant and one month later reduces bone loss.6,37,38,39,40 (level B) This drug prevents bone resorption and may cause transient hypocalcaemia and hypophosphataemia. Oral alendronate and etidronate are alternatives.6,41,42 Calcium supplements (500 –1000 mg/day elemental calcium) and calcitriol 0.25 ug/day may reduce long term bone loss.6,37,43,44,45,46 (Level D) The side effect is hypercalcaemia.
Hormone replacement therapy is recommended for post-menopausal women.6,37

45.3 Recurrence of primary disease
All reports are from observational studies. (Level D)

Table 45.4: Recurrence of primary disease post renal transplant
Type of GN Recurrence rate
Graft loss De novo rate
Focal glomerulosclerosis 8/16 children, 3/27 adults 47; renal transplant (Tx) within 3 years of nephrotic syndrome and rapid progression to ESRF are associated with recurrence

20 – 30%;
50% in children <> 5 years post renal transplant49,53,55 <> 18 years old.14 (Level A)

45.5 Post transplant lymphoproliferative disorder (Level C)
The incidence of post transplant lymphoproliferative disorder (PTLD) is more common in transplanted children compared to adults (10.1% versus 1.2%) especially in presence of vigorous immunosuppression. 80% of PTLD are in transplants with EBV +ve donor to EBV –ve recipients. In 30%, acute rejection are observed before diagnosis of PTLD.
45.5.1 Treatment
The treatment of PTLD consists of:
a. marked decrease or cessation of immunosuppression
b. a small percentage (~ 2%) may require chemotherapy
In children the outcome of PTLD is more favourable than adult in terms of patient and graft survival.

45.6 Other cancers
There is no increased incidence of lung, prostate, colon and uterine cancer6. The incidence of breast cancer is decreased 25 – 30%. However colon and breast cancers are common.
45.6.1 Screening include:

a. Breast: Mammography every 1 – 2 years at age 50 – 69 years.14 (Level A)
b. Colon: Faecal occult blood yearly and flexible sigmoidoscopy every 5 years in patients > 50 years old.14 (Level A)


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