Kidney Donation Guidelines in Sri Lanka

Donor protocol for kidney transplantation- reflection of our local setting

Introduction

Kidney donation is a very noble gesture and is looked upon worldwide as a selfless act. Kidney donation in sri lanka started in 1985 when the 1st transplant was conducted under the guidance of the pioneer of nephrology professor R. Sheriff and a surgical team led by professor.H. Sheriffdeen by the faculty of Medicine, University of Colombo. This was between a 38 year old gentleman who was a hospital staff worker and the a donor who was his father who was 63 years old .at the time HLA  and cross matching was not available locally which was sent to Royal free hospital London for donor patient compatibility.  Induction was with I.V Methyle prednisalone and maintenance therapy was with Azathioprine and oral prednisolone. (Sheriff R, 1987)

Since then our center has performed more than 1500 transplants. All transplants conducted are in accordance with the Human Tissue act of Sri Lanka, which was gazzeted in parliament as the Transplantation of Human tissues act (HTA) No 48 of 1987 (certified on 11th ,December 1987) under the Director General Health (DGHs)with circulars of Ministry of health on organ Transplantation which lay down procedures for the donation and removal of human bodies, organs and  tissues for therapeutic, scientific, educational and research purposes in Sri Lanka non related transplantation is allowed but has to be evaluated carefully before donation.

Let us go deeper in to the donor aspect of transplantation. And how we run our local donor transplant setup and compare them to international centers .and see how we can improve our donor recovery outcomes.

What needs to be assessed before being a donor.

  1. Types of donor
  2. Counseling before donation
  3. Consent for removal of organ
  4. Risks involved in donation
  5. Legal procedures
  6. Age eligibility for donation
  7. ABO Blood Grouping and Cross match Testing 
  8. Medical evaluation of donor and suitability to donate
  9. Renal function evaluation
  10. Suitability for donation
  11. Donor follow up evaluation

1.Types of donors

Related –

1st degree relatives ex: mother, father, brother

2nd degree relatives ex: maternal aunt, paternal aunt,grand parents etc.

Unrelated –

emotionally related- friend, colleague, neighbor etc.

Religious donor-

priest e.g. Buddhist priest seeking merit for this meritorious act (Buddhism is the major religion in Sri Lanka)

Paired exchange donation-

In paired exchange donation, two or more organ-recipient pairs trade donors so that each recipient gets an organ that is compatible with his or her blood type. As showed in figure 1. Ideally should be considered and is done in many leading transplant centers in the world. , paired kidney donation is an excellent way of increasing the donor pool and needs to be promoted to overcome the shortage of suitable kidney as shown in a study done in India. (P. K. Jha, 2015 ).

1
Figure 1: Paired exchange programme

Deceased donor-

once a patient is brain death and while he was alive has made the conscious decision to donate his organs after death. Or According to the Transplantation of Human Tissue Act of 1987, any person above the age of twenty one years may consent in writing to the donation, to take effect upon his death, of his body or any part thereof or any tissue. Such consent given during life should not have been revoked thereafter. In cases where the deceased has not given prior consent for a donation effective upon death, it shall be lawful for the next of kin of such deceased person, who is above the age of twenty-one years to give consent, if the deceased during life has not objected to donation.

2. Counselling before donation

It is a very important aspect of living donor kidney transplantation . as it has to be established that the donor is willing to donate from his own will and not forced by others (ex: family ,peer pressure) etc.

The treating clinician must explain all aspects of donation to the donor including that living donation is safe (Ibrahim HN, 2009) The donation is not a hindrance to daily living. He can get back to his normal life after the post-surgical recovery period. In some cases we do see surgical site infection ,hematomas and in very rare cases mortality, There is a 0.0031% mortality rate according to studies conducted is the USA from 1994-2009 which shows to be very minimal risk (Segev DL, 2010)

Obesity maybe a risk factor in donation as patients have longer surgical site healing time, higher risk of infection and as some studies show long term risk of heart failure. (Tavakol MM, 2009)

Pre-donation psychological evaluation is important by a trained psychologist in a professional capacity to asses and make sure that donor is of sound mind , and knows what they are committing to donation. which unfortunately needs to be done more in this part of the world. I am happy to say that in the last few months we have added that on to our protocol.

3. Consent

Written consent has to be taken from donors. In Sri Lankan law All donors have to be above 25 years of age if male and 30 years of age if female. In comparison , the UK guidelines for living donation where the age of donation is 18 years or above. (Anon., 2018)

seeking consent for the removal of organs from living donors, for the purposes of transplantation, is the responsibility of the treating physician. The donor should give valid consent without any external influence for donation.

There is a legal process to follow where the donor has to give a written affidavit with a signature of a lawyer where he states that the kidney he or she is giving is out of emotional humanitarianism and that there is no monitory gain involved. Also an affidavit is required from his next of kin for example donors wife has to give a written consent that she has knowledge of this donation and no objection for her husband’s donation.

Donors can refuse donation at any time even on the day of transplantation. It is completely up to that individual who donates.

4. Legal procedures

All donors have to have consent from the government of Sri Lanka and ministry of health for donation of a kidney.

There are many legal documents needed for ministry approval. they are as follows as shown in figure 2.

2
Figure 2 : legal documents needed for a donor authorization committee

Ethical review committee –

– In Sri Lanka we have a preliminary hospital body called the ethical review committee who interviews the donor and recipient before donation. They have to answer a series of cross questions that involve the recipient information. And for the recipient, information pertaining to the donor. If the committee is convinced this is a genuine case of donation then they approve the donation. Incase of some doubt then they will reject the donation or ask for additional paper work that can show their intention and relationship to be true. In this part of the world poverty is high and there are so many monitory transactions for donation. As clinicians we have to have a very watchful eye not to promote sale of organs. And be astute in our assessment and observations of the patient and donor.

Once the committee approval is obtained then we send the approval documents along with all the affidavits as mentioned earlier and the patients and donors birth certificate, certificate of residence and national Identity card information and police clearance certificate to the Ministry of Health. Here the Director General Health services will go through all documents and approve it or disapprove as they find fit.

Government approval letter –

Once we obtain the go ahead from the government and an approval letter for transplantation is in hand. Then we can proceed to transplantation. This takes 2 weeks in some cases one month to obtain.

5. Risks involved in donation

The risks associated with donor nephrectomy those associated with the surgery itself, and in some cases psychological aspects involved with donating an organ. Immediate, donor nephrectomy surgery-related risks include

  • pain,
  • surgical wound infection,
  • hernia,
  • bleeding,
  • blood clots,

most of these complications and risks are completely reversible after conservative intervention. Their total of 21.9% in this study is representative and comparable with series of other centers  (Matas AJ, 2001;) In other series  (Johnson EM, 1997),only severe or major complications are documented, so that the overall complication rate seems to be lower compared with that in this study in which all, including minor, complications are reported. Despite thorough pre-operative evaluation, not all possible problems can be avoided. Therefore it is important to give careful post-operative care. (Michael Siebels, 2003)

We anticipate urinary tract infections(UTI) from prolonged catheterization. We usually remove catheter on post op day 4. And give an antibiotic cover when removing the catheter. However in spite of this we have the occasional UTI which resolves with oral antibiotics and good hydration.

Some studied suggest pre prophylactic antibiotic pre donor nephrectomy and to be continued for 2 days post donor nephrectomy ,have showed a good outcome (Zomorrodi A1, 2008). But in our center we only start antibiotics on the day of donor nephrectomy. Maybe it is something to consider in the future to start prophylactic antibiotic.

In USA they found a higher incidence of complications mostly hypertension with increasing age at donation  (Lentine KL, 2016)

Pre eclamisia was found in some cases of donors in a single center study done on 490 pregnancies in which 239 were donors. And some of them showed to have developed pre eclamsia (Ibrahim HN, 2009) in Sri Lanka our female donor age is 30 hoping that there family would have been completed.

A more comprehensive study conducted in Canada from 1999 to 2009 of a retrospective cohort of living kidney donors of 85 women (131 pregnancies after cohort entry),they were matched in a 1:6 ratio with 510 healthy nondonors from the general population. Gestational hypertension or preeclampsia was more common among living kidney donors than among nondonors (occurring in 15 of 131 pregnancies [11%]. There were no significant differences between donors and nondonors with respect to rates of preterm birth or low birth weight. The study concluded that Gestational hypertension or preeclampsia was more likely to be seen in kidney donors than in matched nondonors. (Garg AX1, 2015 )

A study done by Oslo university assessed postoperative complication in living donor nephrectomies (LDN) from 1997-2008. There Postoperative complications were classified by the Clavien grading system. 1022 LDNs done during this period .Median age at donation was 47.7 years ranging from age 18.4-78.9. There was no peri- or postoperative mortality. There was a higher frequency of major complications in the laparoscopic group (4.1% vs. 2.6%), but it was not statistically significant. Infection in wound site developed in 3.7% of donors. Increased risk was associated with body mass index > 25 . in conclusion of their study they noted that the risk of major complications related to LDN is low. (Mjøen, 2009)

Specific long-term complications associated with living kidney donation include high blood pressure and elevated protein levels in urine (proteinuria) in a German single center study of 102 living kidney donors for 35 years showed that microalbuminuria was found in 22.6% of the donors  . (Schostak M, 2004 ). So long term follow up is very important in case of kidney donation.

To minimize the potential risks associated with donor nephrectomy, we will have to extensively test and evaluate these donors to ensure their eligibility to donate.

When looking at survival analysis In another study done by by Muzaale 217 patients who had donated  in USA from 1994 till 2011 were studied and compared to 9364 healthy matched controls. The risk was estimated at developing ESRD was 30.8 per 10 000 patients at 15 years post donation and 3.9 per 10 000 patients in control group. The risk was higher in black donors. The estimated lifetime risk per 10 000 individuals was 14 for healthy nondonors, 90 for donors and 326 for the general population. As showed in (figure 3) (Muzaale A, 2010)

3
Figure 3: Estimated lifetime risk for end-stage renal disease in a matched but unscreened general population, matched healthy general population and live kidney donors (from Muzaale)

6. Age Eligibility for donation

According to sri Lankan law male donors have to be 25 years or above and female donors have to be 30 years or above. . In comparison to the UK guidelines for living donation where the age of donation is 18 years or above. (Anon., 2018)

7. ABO Blood Grouping and Cross match Testing

Blood group-

Usually all recipients will be matched with a donor with a matching blood group.  As showed in figure 4. 

4
Figure .4. blood group compatibility

Cross-Match Testing –

Blood from the donor and recipient are tested together crossmatch involves placing recipient serum (potentially containing donor-specific anti-HLA antibodies) onto donor lymphocytes (containing HLA antigens). A cytotoxic reaction (deemed ‘positive’) suggests the presence of preformed DSAbs. This means the recipient has antibodies “against” the donor’s cells. If the crossmatch is negative, the pair is considered compatible. And can be considered for transplantation. In Sri Lanka we use CDC cross match -B cell T cell cross match. Using complement dependent micro cytotoxicity flurocence serology assay.

HLA Typing –

HLA typing is also called ‘tissue typing’. Antigens are present as proteins on cells found in the body. Out of over 100 different antigens that have been detected, there are a main six that have been shown to be the most important in organ transplantation. Of these six antigens, In interpreting crossmatches a basic understanding of HLA expression is required. The genes encoding HLA are found on chromosome 6 .HLA is divided into class I and class II. Class I molecules are HLA A, B and C while class II molecules are HLA DR, DP and DQ.

A person can make antibodies against another person’s HLA antigens. Antibodies can result from blood transfusions, pregnancy, infections or even a viral illness. Having one of these events does not mean a person will make antibodies but they could. If a recipient has strong antibodies against a donor’s HLA, the risk of rejection is high and a donor would not be suitable for that recipient. As studies have showed good HLA matching especially in the DR group show better outcomes in transplantation long term. graft survival rates have improved overall over time, the relative impact of HLA matching on the graft survival rate has remained strong and highly significant. Both the need for post transplant rejection treatment and the graft survival rates showed statistically highly significant associations with HLA matching. (Opelz G, 2007) in our center as it is not easy to find suitable donors we have a minimum of a 3 match policy  with  a DR match as a basic requirement.  

In other parts of the world they would consider ABO incompatible transplantation as to widen the donor pool. But in our country this has not been tried yet due to the large cost involved.

8. Medical evaluation of donor and suitability to donate

Suitability of a donor organ for transplantation is considered by a range of factors including age, size, medical history, lifestyle  and organ pathology.

Obtaining detailed information about the donor’s past medical and social history is necessary and very important to ask the following:

  • Diseases treated in the past
  • Surgeries done previously especially those that may affect organ function
  • history of renal dysfunction
  • history of recurrent renal calculi
  • Any history of proteinuria or hematuria 
  • Diabetes, hypertension and or other cardiovascular disease
  • Alcohol intake, smoking
  • History of recreational drug use – high incidence of drug use between the ages of 18-25 yrs is found therefore due to this factor male donation age is 25years and above. This is not a legal requirement but as every donor is evaluated by the ministry it is mandatory regulation.
  • Tumors or cancer—treatments done and current status
  •  Transmission of HIV, hepatitis B and hepatitis C, within the past 12 months.
  • Any prison time
  • High risk sexual behavior
  • Any present condition that could impact on the life of the donor at the time of surgery
  • Past history of : Tuberculosis or any family members with TB in close contact , malaria , hepatitis

Clinical/physical Examination of a Potential Kidney Donor

  • Body mass index(BMI) of donor usually should be a maximum of 35. More than that donors counselling has to be done as Obese donors carry more risk long term as showed in some studies. (Nogueira JM, 2010)
  •  Blood pressure less that >130/80 if higher we will do an 24 hr ambulatory bloody pressure (ABPM) monitoring and decide  
  • Blood sugar – screening for diabetes FBS of less than 100mg/dl and Hba1c < 6%
  •  Test for proteinuria
  • Examination abdominal masses / hernia Examination for scars or any surgical scars
  • Lymph node Examination
  • breasts  Examination in some cases if needed a Mammogram / testes  Examination
  • Cardiovascular system-Pulse rate. Any murmurs . pulse pressure- co relate with Echo and ECG if some cases stress test if needed
  • Respiratory systems –breath sounds/ bronchial asthma/ronchi, co-relate with chest Xray.
  • per vaginal examination- for prolapse in older donors. Any other infections
  • Mental health any signs of self-harm
  • In all our evaluations there are some donors that we may consider as an exception according to the clinical scenario. And need for the patient. We would call them marginal donors and except them for donation but with caution and a lot of counselling. (e.g.: slightly higher BP 140/80 with no end organ damage. Slightly higher FBS showing impaired glucose with a normal hba1c ,donor maybe obese with a BMI >35)

Screening tests for donors

In our center the following investigation form is followed out :

In some cases malaria thick and thin film although malaria was eradicated in our country since 2016.

In our center we check for

  • Hep B
  • Hep C
  • HIV
  • VDRL
  • CMV IgG/IgM
  • But according to the British transplant guidelines they check in addition :
    • Epstein-Barr virus (EBV or HHV4)
    • Herpes simplex virus (HSV or HHV1 and HHV2)
    • Varicella-zoster virus (VZV or HHV3)
    • Kaposi’s Sarcoma virus (KSKV or HHV8)

Which we may have to consider in the future in our donor evaluation.

9. Renal function evaluation

Renal profile- which includes

  • Sr.Creatinine ,
  • urea
  • sr.sodium
  • sr.potassium
  • sr.calcium
  • sr.Albumin
  • phosphorus.

Protein urea

  • 24 hr protein excretion
  • 24 hr creatinine clearance
  • UFR
  • Urine cultures + ABST

According to the British transplant society and other international centers they  do albumin creatinine ration (ACR) and Protein creatinine ratio (PCR) instead of 24 hour protein excretion this is now the preferred methods as with 24-hour urinary protein excretion you can overcome inaccuracies due to incomplete urine collection. But we admit all donors for evaluation so the incomplete collection is reduced.

Renal  function and imaging

  • Ultra sound scan abdomen
  • DTPA- to check for the blood supply, function and flow of urine and eGFR from the kidneys.
  • RENAL ANGIOGRAM- this is the imaging to see how the anatomy of both the kidneys are placed. Which kidney will be easier to take out and how many vessels there are on the kidneys. And check for any abnormalities.

In some centers they consider DMSA scans if clinically indicated. Which is not currently used in our center.

Cardiac assessment

  • ECG
  • ECHO
  • And in some cases Dobutamin STRESS TEST /exercise ECG with cardiology evaluation

Psychological assessment

All donors have to psychologically evaluated and given clearance for donation by a psychiatrist or a psychological counselor that the donor is of sound mind and is ready for donation. If the counselor suggests the patient is of high risk for drug abuse then we send out a drug panel.

10. Suitability for donation

After taking all aspects in to consideration.

  • legal
  • Ethical
  • HLA compatibility
  • medical fitness
  • psychological fitness

The donor has to be evaluated by the chief nephrologist, lead transplant surgeon and Lead anesthetist and all documents and medical reports have to be carefully presented and discussed thoroughly and cleared for transplantation. This is called an MDT multi-disciplinary team meeting. Where they will discuss the suitability for kidney donation by considering all that they have evaluated.  

If they agree for transplantation. After evaluating the clinical details of the recipient are also discussed and cleared for transplant, a date is set for the surgery after receiving the government go ahead for the transplant.

11. Follow up donor evaluation

this is done post transplantation for a maximum of 1 month. And regular follow up is needed . but we find the donors do not come back for further evaluation. This is a major problem which we face and needs to be addressed. As their well-being is our responsibility. We have written to the national science foundation to give us funding so that we can do a national donor evaluations free of charge. And we are awaiting a response. The cost factor is the biggest problem in this part of the world. But the donor’s life is much more important than that. And regular follow up is a must.

As many studied done over time in leading centers around the world show some good data on donor follow up outcomes.

Some studies show a 15-year experience of 162 living donors in Italy showed that the long-term incidence of hypertension in living donors was same as the general population. (Sansalone CV, 2006) also the analysis of 402 donor nephrectomies in Sweden showed ,hypertension was present in 38% of their donors, the age of prevalence of hypertension in these donors was not higher than in the general population (Fehrman-Ekholm I, . 2001)

Conclusion

From reflecting back at our own living donor evaluation protocol is it refreshing to note that we are not so backward in our approach when we compare leading centers around the world. But at the same time if looked at our own program with an eye on improvement there are many I can think of as changes. to give us and the donors a better chance and lift up our standard in our evaluation of them.

THESE INCLUDE

  • Adding the following to our virology screening
    • Include Epstein-Barr virus (EBV or HHV4)
    • Herpes simplex virus (HSV or HHV1 and HHV2)
    • Varicella-zoster virus (VZV or HHV3)
  • Change over from 24 hour Urine protein excretion to Albumin creatinine ratio (ACR)
  • Use better matches in HLA for a better outcome
  • Consider starting prophylactic antibiotics one day prior to surgery
  • Start a national database for kidney donors and evaluate them on the long run to see there outcomes after donation.

References

  1. Anon., 2018. UK guidelines for living donor kidney transplantation. In: s.l.:s.n.
  2. Fehrman-Ekholm I, D. F. B. B. T. G. E. C., . 2001. No evidence of accelerated loss of kidney function in living kidney donors: results from a cross-sectional follow-up.. Transplantation.
  3. Ibrahim HN, F. R. T. L., 2009. Long-term consequences of kidney donation. N Engl J Med.
  4. Johnson EM, R. M. G. K. D. R. N. J. M. A., 1997. Complications and risks of living donor nephrectomy.. Transplantation, p. 64: 1124–1128.
  5. Lentine KL, L. N. A. D. S. M. G. A. X. H., 2016. Perioperative Complications After Living Kidney Donation: A National Study. Am J Transplant, p. 1848–57. .
  6. Matas AJ, P. W. S. D., 2001;. 2500 living donor kidney transplants: a single-center experience.. Ann Surg , p. 234: 149–164.
  7. Michael Siebels, J. T. N. S. S. C. N. M.-B. G. H. D. F. O. R. W. L. A. H., 2003. Risks and complications in 160 living kidney donors who underwent nephroureterectomy. Nephrology Dialysis Transplantation, p. 2648–2654.
  8. Nogueira JM, W. M. J. S., 2010. A study of renal outcomes in obese living kidney donors.. Transplantation, pp. 993-9.
  9. Opelz G, D. B., 2007. Effect of human leukocyte antigen compatibility on kidney graft survival: comparative analysis of two decades.. Transplantation.
  10. P. K. Jha, S. S. S. B. B. M. J. R. S. M. K. P. R. D. R. A. a. V. K., 2015 . Paired kidney exchange transplantation: Maximizing the donor pool. Indian J Nephrol., p. 349–354. .
  11. Sansalone CV, M. G. A. P. R. O. M. I. S. S. D. R. A. M. M. P. M. C. G., 2006. Early and late residual renal function and surgical complications in living donors: a 15-year experience at a single institution.. Transplant.
  12. Schostak M, W. H. M. M. S. M. O. G. M. K., 2004 . Optimizing open live-donor nephrectomy – long-term donor outcome.. Clin Transplant, p. 301–305.
  13. Segev DL, M. A. C. B., 2010. Perioperative mortality and long-term survival following live kidney donation, ,. JAMA, pp. (pg. 959-966).
  14. Sheriff R, S. A. J. G. W. S. A. G. D. M. C. S. U. G. U. D. M. T. D. S. S., 1987. The first kidney transplantation in Sri Lanka.. ceylon med j.
  15. Tavakol MM, V. F. A. H., 2009. Long-term renal function and cardiovascular disease risk in obese kidney donors,. Clin J Am Soc Nephrol, pp. (pg. 1230-1238).
  16. Zomorrodi A1, B. A., 2008. Is antibiotic usage necessary after donor nephrectomy? A single center experience.. Saudi J Kidney Dis Transpl..
  17. Garg AX, Muirhead N, Knoll G, et al. Proteinuria and reduced kidney function in living kidney donors: a systematic review, meta-analysis, and meta-regression. Kidney Int 2006; 70: 1801-10.
  18. Ibrahim HN, Foley R, Tan L, et al. Long-term consequences of kidney donation. N Engl J Med 2009; 360: 459-69.
  19. Kasiske BL, Anderson-Haag T, Israni AK, et al. A prospective controlled study of living kidney donors: three-year follow-up. Am J Kidney Dis 2015; 66: 114-24.
  20. Krishnan N, Bradbury L, Lipkin GW. Comparison of baseline GFR levels by age bands with 1 year, 5 year and 10 year outcomes in live donors – UK cohort study
  21. Segev DL, Muzaale AD, Caffo BS, et al. Perioperative mortality and long-term survival following live kidney donation. JAMA 2010; 303: 959-66.
  22. Muzaale AD, Massie AB, Wang MC, et al. Risk of end-stage renal disease following live kidney donation. JAMA 2014; 311: 579-86.
  23. Matas AJ, Payne WD, Sutherland DER, et al. 2,500 living donor kidney transplants: a single-center experience. Ann Surg 2001; 234: 149-64.
  24. Kahematsu A, Tanabe K, Ishikawa N, et al. Impact of donor age on long-term graft survival in living donor kidney transplantation. Trans Proc 1998; 30: 31189.
  25. Fuggle SV, Allen JE, Johnson RJ, et al. Kidney Advisory Group of NHS Blood and Transplant. Factors affecting graft and patient survival after live donor kidney transplantation in the UK. Transplantation 2010; 89: 694-701. 14
  26. Ibrahim HN, Akkina SK, Leister E, Gillingham K, Cordner G, Guo H, Bailey R, Rogers T, Matas AJ. Pregnancy outcomes after kidney donation. Am J Transplant. 2009;9:825–834.
  27. Mjøen, H. H., 2009. Morbidity and Mortality in 1022 Consecutive Living Donor Nephrectomies: Benefits of a Living Donor Registry. Transplantation.
  28. Muzaale A, C. B. M. S. S. A., 2010. Perioperative mortality and long-term survival following live kidney donation. JAMA .
  29. Garg AX1, N. I. M. E. S. J. K. J. L. N., 2015 . Gestational hypertension and preeclampsia in living kidney donors.. N Engl J Med. .