Renal Pathology Tutorial

The entire power point slides on renal pathology is now available in myvasc.blogspot.com and slideshare.net/edwinchowyw/slideshows

Immunisation in renal transplant patients

Warm and Cold Ischemic Time

There are in fact 2 warm ischemic times. We usu mean the donor warm ischemic time (ie Ischemia during organ retrieval, from the time of cross clamping (or of asystole in non-heart-beating donors), until cold perfusion is commenced.

Cold Ischemic Time: Ischemia when the organ is cooled with a cold perfusion solution after ORGAN PROCUREMENT surgery, and ends after the tissue reaches physiological temperature during implantation procedures.


The following article addresses the issue of warm ischemic time:

Warm ischemia in transplantation : Search for a consensus definition
Auteur(s) / Author(s)
HALAZUN K. J. (1) ; AL-MUKHTAR A. (1) ; ALDOURI A. (1) ; WILLIS S. (1) ; AHMAD N. (1) ;
Affiliation(s) du ou des auteurs / Author(s) Affiliation(s)
(1) Department of Organ Transplantation, St. James University Hospital, Leeds, ROYAUME-UNI
Résumé / Abstract
"Warm ischemia" is a term used to describe ischemia of cells and tissues under normothermic conditions. In the transplant setting, this term is used to describe two physiologically distinct periods of ischaemia: (1) Ischemia during implantation, from removal of the organ from ice until reperfusion, and (2) Ischemia during organ retrieval, from the time of cross clamping (or of asystole in non-heart-beating donors), until cold perfusion is commenced. These periods of warm ischemia differ in their nature and the magnitude of their pathophysiologic consequences. In much transplant literature, however, the term "warm ischaemia" is used to describe both of these periods indiscriminately. This paper attempts to produce a definition to distinguish between the two periods of warm ischemia. Methods. We conducted a questionnaire survey of all UK transplant surgeons. The definitions proposed in the survey were: (a) warm ischemia and re-warm ischemia; (b) first warm ischemia and second warm ischemia; (c) in-situ warm ischemia and ex-vivo warm ischemia; (d) warm ischemia in donor and warm ischemia in recipient; (e) no opinion or other opinion. Results. There was a 64% response rate among 134 consultants with no consensus definition being reached. The majority of consultants (31.4%) preferred the terms "warm ischemia in donor", and "warm ischemia in recipient" to distinguish the two periods. Conclusions. This paper highlights the need to adopt uniform terms to avoid confusion between different types of warm ischemia in transplantation.
Revue / Journal Title
Transplantation proceedings ISSN 0041-1345 CODEN TRPPA8
Source / Source
2007, vol. 39, no5, pp. 1329-1331 [3 page(s) (article)] (15 ref.)

Interpreting Hepatitis C results

Hepatitis C detection

What are the diagnostic tests for hepatitis C virus and how are they used to diagnose hepatitis C virus infection?

A number of diagnostic tests are currently available for hepatitis C virus. They are categorized below according to the function of the specific tests.

What about screening tests?

Screening tests are done to determine the presence of antibodies to hepatitis C virus in the blood. The enzyme immunosorbent assay (EIA) is the conventional, initial screening test to diagnose hepatitis C infection. The EIA measures specific antibodies to small pieces of the hepatitis C virus proteins (antigens). This test, therefore, is referred to as the anti-hepatitis C virus antibody test. Patients who have elevated liver enzymes (ALT/AST) and/or any of the risk factors for hepatitis C virus can be diagnosed to have hepatitis C virus with a greater than 95% certainty when the EIA is positive.

On the other hand, certain patients whose immune systems are impaired (suppressed) may not have detectable anti-hepatitis C virus antibodies even if they are actually infected with hepatitis C virus. Such immunosuppressed patients include those who are on renal dialysis, suffer from cancer and are receiving chemotherapy (drugs to kill cancer cells), or have active HIV infection. These patients cannot produce enough anti-hepatitis C virus antibodies necessary to generate a positive EIA test.

When there is a low likelihood (risk) of hepatitis C infection, individuals who test positive for hepatitis C by EIA should undergo confirmatory testing using a specialized assay that likewise tests for antibodies against the hepatitis C virus proteins. This assay is called the Recombinant Immunoblot Assay (RIBA).

Both the EIA and RIBA tests, however, do not distinguish among acute, chronic, and resolved hepatitis C virus infections because the anti-hepatitis C virus antibodies are in the blood in all three of these situations. Although EIA and RIBA are tests that measure antibodies against hepatitis C virus, these antibodies do not confer protection to the patient against acquiring hepatitis C virus. Rather, they only indicate exposure of the patient to the virus.

What are molecular tests for hepatitis C virus?

As previously described, hepatitis C virus is an RNA virus. The code of the genetic material, hepatitis C virus RNA, is unique to this virus. Several types of tests (assays) are available to measure the hepatitis C virus RNA in a person's blood. These tests are referred to as molecular tests because they examine the virus at the molecular level. The two most common systems for measuring hepatitis C virus RNA are the reverse transcription polymerase chain reaction (RT-PCR) assay and the branched chain DNA (bDNA) assay. Recently, a third type of assay, called transcription-mediated amplification (TMA), has been released.

First of all, it is important to put in perspective the relative amount of virus in an individual infected with hepatitis C virus as compared to some other types of chronic viral infection. The average number of virus particles/milliliter of blood in an individual with chronic hepatitis C virus is hundreds of thousands to several million. In contrast, someone with active hepatitis B infection has several hundred million to billions of copies (virus particles) per milliliter of blood. The relatively low concentration of the hepatitis C virus in the blood is one of the reasons it took so long for scientists to characterize the hepatitis C virus.

RT-PCR is a very powerful tool for detecting relatively low amounts of genetic material (RNA or DNA). The basis of this technique is the amplification of a target piece of nucleic acid several million times so that this target becomes measurable. Due to the extreme sensitivity of this technique, however, the slightest contamination can lead to a false positive result. On the other hand, RNA is relatively unstable (degrades easily), so that blood and tissue samples need to be handled with special precautions. If not, this instability would lead to a false negative result, that is, a negative result in someone who has hepatitis C virus.

In the early 1990's, each laboratory had its own in-house technique for the RT-PCR assay and the reliability of these assays was quite variable. Even as of now, the FDA has not approved any of the RT-PCR assays. However, most laboratories currently use one of the several available diagnostic kits that are automated and designed to reduce the likelihood of contamination. There are two types of RT-PCR, qualitative and quantitative. Qualitative hepatitis C virus RT-PCR provides the greatest sensitivity, meaning that it can measure as few as 100 copies (viral particles) of hepatitis C virus/ml of serum. As the name implies, however, qualitative RT-PCR provides only a positive (presence of hepatitis C virus) or negative (absence of hepatitis C virus) result.

By contrast, quantitative RT-PCR measures the amount of virus. These tests, however, are only accurate within a certain range of viremia (circulating virus in the blood). This means that quantitative assays are not as sensitive as qualitative assays and can only detect as few as 500 copies/ml. Moreover, these assays are less accurate at extremely high viral levels (over 2 million copies/ml). In the past year, there has been an attempt to standardize these various quantitative assays so that the levels of virus that are measured by different assays can be compared. As a matter of fact, results of quantitative RT-PCR are now reported in standard International Units/ml (IU/ml).

Branched chain DNA (bDNA) is the other quantitative technique. It is based on the amplification of the detection signal rather than of the nucleic acid itself. As a result, this test is less prone to contamination and is more accurate when measuring higher levels of the virus as compared to RT-PCR. However, the bDNA assay is not as sensitive as the RT-PCR and is unable to measure levels of virus below 200,000 copies/ml.

Finally, transcription mediated amplification (TMA) is a qualitative technique that is distinct from PCR. This test can measure as few as 2 to 5 copies of virus/ml.

What is the role of the qualitative molecular tests?

Qualitative RT-PCR is a useful test in determining whether or not a patient has circulating virus in the blood (viremia). Hence, it can be used to confirm that a reactive (positive) anti-hepatitis C virus result reflects active hepatitis C virus infection. However, confirmatory testing is usually not necessary in someone who tested reactive (positive) for anti-hepatitis C virus and also has risk factors and abnormal liver tests. In this situation, the RT-PCR most certainly would be positive. On the other hand, an individual who is anti-hepatitis C virus reactive and has risk factors but normal liver tests should undergo confirmatory testing with RT-PCR. This person may have cleared the viral infection some time ago, leaving the anti-hepatitis C virus as a marker of past exposure.

Qualitative hepatitis C virus RNA testing should also be done in individuals who may have been recently exposed to hepatitis C. Hepatitis C virus RNA is more sensitive (that is, will detect more cases) than the conventional anti-hepatitis C virus (EIA) testing in this setting. The reason for this greater sensitivity is that it may take a person as many as six to eight weeks after exposure to hepatitis C virus to develop the antibodies, whereas hepatitis C virus RNA becomes detectable five to ten days after exposure. Finally, qualitative hepatitis C virus RNA testing may be helpful to assess the patient's virologic response at certain time points during antiviral therapy (see treatment of hepatitis C virus below).

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)


References
1. Foley R, Parfrey P, Sarnak M. NKF: Controlling the epidemic of CV disease in CRD: V. Part I. Clinical epidemiology of cardiovascular disease in chronic renal disease. UpToDate 2000; Vol 8 No 2
2. Stewart G, Jardine A, Briggs J. Ischaemic heart disease following renal transplantation. Nephrol Dial Transplant 2000; 15 (2) : 269 – 277
3. Kasiske B, Harini A, Chekkera, Roel J. Explained and unexplained ischemic heart disease risk after renal transplantation. J Am Soc Nephrol 2000; 11 : 1735 – 1743.
4. Wheeler D. Ischaemic heart disease after renal transplantation: how to assess and minimize the risk. Nephrol Dial Transplant 1999; 14 : 1075 – 1077.
5. Vella J, Sayegh M. Risk factors for cardiovascular disease in the renal transplant recipient. UpToDate 2000; Vol 8 No 2
6. Silkensen J. Long-term complications in renal transplantation. JASN 2000; 11 : 582 – 588.
7. Roodnat J, Mulder P, Zietse R et al. Cholesterol as an independent predictor of outcome after renal transplantation. Transplantation 2000; 69 : 1704 – 1710
8. Levey A. NKF: Controlling the epidemic of CV disease in CRD: II. Executive summary. UpToDate 2000; Vol 8 No 2
9. Kasiske B. NKF: Controlling the epidemic of CV disease in CRD: V. Part III. Hyperlipidemia in patients with chronic renal disease. UpToDate 2000; Vol 8 No 2.
10. Meyer K, Levey A. Controlling the epidemic of cardiovascular disease in chronic renal disease: report from the National Kidney Foundation task force on cardiovascular disease. J Am Soc Nephrol 1998; 9 : S31 – S42.
11. I.V. Recommendations for the management of cardiovascular risk factors. Nephrol Dial Transplant 2000; 15 (Suppl 5) : S58 – S154.
12. Foley R, Parfrey P, Sarnak M. Epidemiology of cardiac disease in chronic renal disease. J Am Soc Nephrol 1998; 9 : S16 – S23
13. Mailloux L, Levey A. NKF: Controlling the epidemic of CV disease in CRD: V. Part II. Hypertension in patients with chronic renal disease. UpToDate 2000; Vol 8 No 2.
14. Kasiske B, Vazquez M, Harmon W et al. Recommendations for the outpatient surveillance of renal transplant recipients. J Am Soc Nephrol 2000; 11 : S1 – S86
15. Murphy S, Foley R, Parfrey P. NKF: Controlling the epidemic of CV disease in CRD: V. Part VI. Screening and treatment for cardiovascular disease in patients with CRD. UpToDate 2000; Vol 8 No 2.
16. Beto J, Bansal V. NKF: Controlling the epidemic of CV disease in CRD: V. Part V. Tobacco use; physical activity; menopause; and homocysteine. UpToDate 2000; Vol 8 No 2.
17. Sunder-Plassmann G, Floth A, Fodinger M. Hyperhomocysteinemia in organ transplantation. Current Opinion in Urology 2000; 10 : 87 – 94.
18. Rosenkrantz A, Mayer G. Mechanisms of hypertension after renal transplantation. Current Opinion in Urol 2000; 10 (2) : 81 – 86.
19. Olyaei A, deMattos A, Bennett W. A practical guide to the management of hypertension in renal transplant recipients. Drugs 1999; 58 (6) : 1011 – 1027.
20. Sayegh M, Vella J. Hypertension after renal transplantation. UpToDate 2000; Vol 8 No 2.
21. Zeier M, Mandelbaum A, Ritz E. Hypertension in the transplanted patient. Nephron 1998; 80 (3) : 257 – 268
22. Sheperd J, Cobbe S, Ford I et al. Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia. N Eng J Med 1995; 333 (20) : 1301 – 1307.
23. Sacks F, Pfeffer M, Moye L et al. The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels. N Eng J Med 1996; 335 (14) : 1001 – 1009
24. Scandinavian simvastatin survival study group. Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival study (4S). Lancet 1994; 344 : 1383 – 1389.
25. The long-term intervention with pravastatin in ischaemic disease (LIPID) study group. Prevention of cardiovascular events and death with pravastatin in patients with coronary heart disease and a broad range of initial cholesterol levels. N Eng J Med 1998; 339 (19) : 1349 – 1357.
26. Downs J, Clearfield M, Weis S. Primary prevention of acute coronary events with lovastatin in men and women with average cholesterol levels: results of AFCAPS / TexCAPS. JAMA 1998; 279 (2) : 1615 – 1622.
27. Law M, Wald N, Thompson S. By how much and how quickly does reduction in serum cholesterol concentration lower risk of ischaemic heart disease. Br Med J 1994; 308 : 367 – 372
28. Ansell B, Watson K, Fogelman A. An evidence-based assessment of the NCEP adult treatment panel II guidelines. JAMA 1999; 282 (21) : 2051 – 2057.
29. Ministry of Health Malaysia, Academy of Medicine Malaysia. Second consensus statement on management of hyperlipidemia. 1998.
30. Holdaas H, Fellstrom B, Jardine AG, Holme I et al. Effect of fluvaswtatin on cardiac outcomes in renal transplant recipients: a multicentre, randomised, placebo-controlled trial. Lancet 2003; 361 :2024 – 2031
31. Wanner C, Quaschning T, Weingartner K. Impact of dyslipidaemia in renal transplant recipients. Current Opinion in Urology 2000; 10 : 77 – 80.
32. Wheeler D. Statins and the kidney. Current Opinion in Nephrology & Hypertension 1998; 7 (5) : 579 – 584
33. Jardine H, Holdaas H. Fluvastatin in combination with cyclosporin in renal transplant recipients: a review of clinical and safety experience. Journal of Clinical Pharmacy & Therapeutics 1999; 24 (6) : 397 – 408.
34. Arnadottir M, Berg A. Treatment of hyperlipidemia in renal transplant recipients. Transplantation 1997; 63 : 339 – 345.
35. Castro R, Queiros I, Fonseca J et al. Therapy of post-transplant hyperlipidaemia: comparative study with simvastatin and fish oil. Nephrol Dials Transplant 1997; 12 : 2140 – 2143
36. Hulley S, Grady D, Bush T et al. Randomized trial of estrogen plus progestin for secondary prevention of coronary heart disease in postmenopausal women. JAMA 1998; 280 (7) : 605 - 613.
37. Rodino M, Shane E. Osteoporosis after organ transplantation. Am J Med 1998; 104 (5) : 459 – 469.
38. Rosen H, Rosenblatt M. Osteoporosis after transplantation. UpToDate 2000; Vol 8 No 2.
39. Fan S, Almond M, Ball E et al. Pamidronate therapy as prevention of bone loss following renal transplantation. Kid Int 2000; 57 : 684 – 690.
40. Butterly D, Quarles L. Parathyroid and mineral metabolism after renal transplantation. UpToDate 2000; Vol 8 No 2.
41. Adachi J, Bensen W, Brown J et al. Intermittent etidronate therapy to prevent corticosteroid-induced osteoporosis. N Eng J Med 1997; 337 : 382 – 387.
42. Saag K, Emkey R, Gruber B et al. Alendronate for the management of glucocorticoid-induced osteoporosis: results of the multicenter US study. (Abstract). Arthritis & Rheumatism 1997; 40 : S136.
43. Cueto-Manzano A, Konel S, Freemont A, et al. Effect of 1,25-dihydroxyvitamin D3 and calcium carbonate on bone loss associated with long-term renal transplantation. J Am Soc Nephrol 2000; 35 (20):227-236
44. Amin S, Simms W, Felson D. A meta-analysis evaluating the efficacy of calcium and vitamin D for corticosteroid-induced osteoporosis. (Abstract). Arthritis & Rheumatism 1997; 40 : S136.
45. Sambrook P, Birmingham J, Kelly P et al. Prevention of corticosteroid osteoporosis – a comparison of calcium, calcitriol and calcitonin. N Eng J Med 1993; 328 : 1747 – 1752.
46. Diamond T, McGuigan L, Barbagallo S et al. Cyclical etidronate plus ergocalciferol prevents glucocorticoid-induced bone loss in post-menopausal women. Am J Medicine 1995; 98 (5) : 459 - 463.
47. Niaudet P. Complications of renal transplantation in children. UpToDate 2000; Vol 8 No 2.
48. Kotanko P, Pusey C, Levy J. Recurrent glomerulonephritis following renal transplantation. Transplantation 1997; 63 (8) : 1045 – 1052.
49. The EBPG Expert Group on Renal Transplantation. European best practice guidelines for renal transplantation (part 1). Nephrol Dial Transplant 2000; 15 Suppl 7.
50. Sayegh M, Kaplan A. Focal glomerulosclerosis: recurrence after transplantation. UpToDate 2000; Vol 8 No 2.
51. Cosyns J, Couchoud C, Pouteil-Noble C et al. Recurrence of membranous nephropathy after renal transplantation: probability, outcome and risk factors. Clin Nephrol 1998; 50 (3) : 144 – 153.
52. Sayegh M. Membranous nephropathy and renal transplantation. UpToDate 2000; Vol 8 No 2.
53. Hariharan S. Recurrent and de novo diseases after renal transplantation. Seminars in Dialysis 2000; 13 (3) : 195 – 199
54. Sayegh M. Membranoproliferative glomerulonephritis: recurrence after transplantation. UpToDate 2000; Vol 8 No 2.
55. Sayegh M. IgA nephropathy: recurrence after transplantation. UpToDate 2000; Vol 8 No 2.
56. Sayegh M. AntiGBM antibody disease: recurrence after transplantation. UpToDate 2000; Vol. 8 No.2.
57. Sayegh M.TTP-HUS: recurrence after transplantation. UpToDate 2000; Vol 8 No 2.
58. Sayegh M. Development of malignancy following solid organ transplantation. UpToDate 2000; Vol 8 No 2.
59. Jamil B, Nicholls K, Becker G, Walker R. Impact of acute rejection therapy on infections and malignancies in renal transplant recipients. Transplantation 1999; 68 (10) : 1597 – 1619.
60. Sheil R. Patterns of malignancies following renal transplantation. Transplant Proc 1999; 31 (12) : 1263 – 1265

Renal Tranplantation and Nutrition-CPG

44. RENAL TRANSPLANTATION AND NUTRITION

44.1 Dietary modification
The first 21 days after successful transplantation should focus on a diet of optimal protein and energy intake as well as restrictions of total fat, saturated fat, cholesterol and simple sugars to restore nitrogen balance and minimise clinical symptoms of post-transplant diabetes and hyperlipidaemia.1 (Level C)
44.1.1 Calorie intake
Adequate calorie intake of at least 35kcal/kg/day (range of 35 to 50 kcal/kg/day)
a. 40%-50%: Carbohydrate
b. <> 25 kg/m2 is overweight and >30kg/m2 is obese.
c. Increased caloric intake may occur after transplantation primarily because of enhanced appetite associated with steroid use.3
d. May have adverse effect on coronary vascular disease.
44.2.2 Malnutrition
Incidence: 10% of patients exhibit low serum albumin levels at 1 year and 20% at 10 year after transplantation.4
Suspect malnutrition in the presence of low serum albumin (although factors other than calorie intake may contribute to hypoalbuminaemia).
Diagnosed by the presence of low serum albumin levels.
Corticosteroid accelerates the protein catabolic rate and frequently creates a negative nitrogen balance.
Malnutrition is associated with increased risk of infection, delayed wound healing and general debility.

44.2.3 Post transplantation hyperlipidaemia
Incidence: 60% of patients exhibit total cholestrol levels > 240mg/dl (high risk).5
Reported changes in serum lipid levels are:
↑ triglyceride
↑ total cholestrol
↑LDL cholesterol
↑apolipoprotein B
a. Pathogenesis of hyperlipidaemia in renal transplant patients: (multifactorial)6,7,8
• Age
• Body weight
• Sex
• Pretransplantation lipid levels
• Renal dysfunction
• Proteinuria
• Drugs eg. Sirolimus, β Blockers, Diuretics, Prednisolone, Cyclosporin etc
b. Consequences of hyperlipidaemia
• Correlation with chronic allograft nephropathy
• Development of cardiovascular and peripheral vascular disease
c. Treatment
• Weight reduction
• Increase exercise
• Dietary modification as recommended for non transplant population (National Cholesterol Education Programme)

Step 1
Intake of saturated fat 8% to 10% of total calories
Fat intake of 30 % of total calories
Saturated fat intake < 300mg/day

If Step 1 fails, then proceed to Step 2

Step 2
Intake of saturated fat to 7% of total calories
Saturated fat intake < 200mg/day

• Drug therapy
Drug therapy is indicated if dietary modification fails (Refer to chapter 45)

44.2.4 Post transplantation diabetes mellitus (PTDM)
Incidence : Peak incidence in the first year post-transplant affecting 3% to 4% of patients.10
a. Predisposing factors:
• Tacrolimus
• Family history of diabetes mellitus
• Prednisolone
• Cyclosporin
b. Management
• Diet modification
• Exercise
• Weight loss
• Cessation of smoking
• Metformin
• Sulfonylureas
• Insulin - half of patients with PTDM may require insulin. Treatment with insulin is also required during periods of stress and intercurrent illness.11



References
1. Edwards MS, Doster S. Renal transplantation diet recommendations: results of a survey or renal dietitians in the United States J Am Diet Assoc 1990; (6): 843-6
2. Modlin CS Flechner SM Goormastic M. Should obese patients lose weight before receiving a kidney transplant? Transplantation 1997; 64: 597-604
3. Johnson CP Gallagher-Lepak S, Zhu YR et al. Factors influencing weight gain after renal transplantation. Transplantation 1993; 56: 822-27
4. Guijarro C, Massy ZA, Ma JZ et al. Serum albumin and mortality after renal transplantation Am J Kid Dis 1996; 27: 117-123
5. Aakhus S, Dahl K, Wideroe TE Hyperlipidaemia in renal transplant patients. J Int Med 1996; 239: 407-415
6. Cattran DC, Steiner G, Wilson D et al. Hyperlipidaemia after renal transplantation: natural history and pathophysiolology. Ann Inter Med 1991; 79: 554
7. Vathsala A, Weinberg RB, Schoenberg L et al. Lipid abnormalities in cyclcosporin prednisolone treated renal transplant recipients. Transplantation 1989; 48: 37
8. Massy ZA, Kasiske BL: Post transplantation hyperlipidaemia: Mechanisms and management, J Am Soc Nephrol 1996; 7: 971
9. Summary of the second report of the National Cholestrol Education Program (NCEP) Expert Panel on Detection, Evaluation and treatment of high blood cholesterol in adults(Adult Panel 11). JAMA 1993; 269: 3015
10. Roth D, Milgrom M, Esquenazi V et al. Posttransplantation hyperglycaemia: Increased incidence in cyclosporin treated renal allograft recipients Transplantation 1989; 47:278-281
11. Sumrani N, Delaney V, Ding Z et al. Diabetes mellitus after renal transplantation in the cyclosporin era : analysis of risk factors. Transplantation 1991; 51: 343-47