Surgeons bring RRT to patients in Guyana

The needs and expectations of developing countries have grown in an increasingly globalized world, particularly the demand for specialized health services in addition to primary care. Exactly how to pay for such health care—via private insurers, government subsidies, or a mixture of both—is a subject of great debate.1

One form of acute/chronic care for which the need is significant is renal replacement therapy (RRT). In fact, this type of care is nonexistent in developing countries, and the unfortunate reality is that a diagnosis of end-stage renal disease (ESRD) is tantamount to a death sentence.2 This situation was most certainly the case in Guyana, South America, when we began our efforts there in 2008 to deliver RRT. This article describes the 14 medical missions the authors made to Guyana, with an emphasis on the logistics and outcomes of the team’s public-private partnership. This model is now being extended to the CARICOM (Caribbean community), a grouping of 15 countries in the Caribbean basin.3

Contrasts in kidney failure treatment

The incidence of kidney failure in developed countries has been well-documented. In the U.S., 13 percent of the population reportedly were afflicted with chronic kidney disease (CKD) between 1999 and 2004.4 It is estimated that some 10 percent of the adult population in the U.S. and Europe is affected by kidney disease, with nearly 1 million requiring some form of RRT.5 Typically, these patients are treated with some form of dialysis after the establishment of either vascular or peritoneal access. However, kidney transplantation is the most cost-effective form of RRT, leading to improved quality of life with clear survival advantage over dialysis to the point that physicians encourage preemptive transplantations in lieu of initiating dialysis.6

Patients in developing countries face more dire circumstances. Due to socioeconomic and logistical factors, these patients rarely have access to any form of RRT. In India, for instance, even conservative calculations point to 100,000 new cases of ESRD per year requiring RRT. Because most dialysis centers are located in inaccessible metropolitan settings, many rural Indian patients are not treated and succumb.7 In many other Asian countries as well, the incidence of ESRD is rising rapidly due to the rise of other risk factors, such as diabetes and hypertension.8 By the end of 2002, more than 300,000 patients in Asia were reportedly on dialysis.9

In Guyana, which has a population of nearly 750,000, as many as 8,000 to 10,000 new hypertension and diabetes cases are reported annually. When this team began its intervention there in 2008, 200 Guyanese patients required dialysis.10,11 However, it is important to note that all of these numbers pertaining to developing countries are most likely underestimated due to the absence of national registries that collect such information.

Costs of RRT

In the U.S., the overall cost of managing a patient with CKD and hemodialysis (HD) specifically has been estimated to be from $22,000 to $88,000 per patient per year.12 The cost of a kidney transplant in the U.S. can exceed $250,000.13

The cost of HD in developing countries, such as Brazil, China, India, and Indonesia, ranges from $5,000 to $7,500 per patient per year.14 The leaders of this mission, Rahul M. Jindal, MD, PhD, FACS (senior author of this article) and George Subraj (a philanthropist of Guyanese origin who funded the trips), made two preliminary fact-finding visits to Guyana in early 2008 and found only three dialysis chairs in the entire country. The cost of HD per session in Guyana was approximately $200 per dialysis session. Assuming a thrice-weekly regimen, the yearly cost for HD per patient in Guyana would be $31,200. In a nation where the gross income per capita was $2,900 in 2010, with little state support and no viable insurance system, patients have few options and often die from kidney disease.15

Networks

Our efforts in Guyana began with the establishment of a key network composed of the following: (1) philanthropic Guyanese-Americans; (2) U.S. transplant physicians; (3) the Guyanese government; and (4) Guyanese physicians. The Guyanese-American community was instrumental in helping the team understand the socioeconomic conditions of their native country. Mr. Subraj provided most of the funding (transport and local stay for the five-member team). The transplant team, led by Dr. Jindal, consisted of transplant surgeons, a nephrologist, an operating room nurse, a dialysis nurse, and an anesthesiologist.

The Guyanese government played a significant role in facilitating this nascent RRT program in their country. They provided the use of Balwant Singh Hospital (Georgetown, Guyana), dialysis fluid, and anti-rejection medications at no charge to the patient. The local staff identified patients, performed the necessary workup, scrubbed for operations, and provided postoperative and follow-up care. It was through this network that the team was able to provide quality, lifesaving health care to Guyanese patients with CKD and ESRD.

Results of the first peritoneal dialysis program

We introduced peritoneal dialysis (PD) to the country carefully selecting appropriate patients and performing 17 catheter placements in the first phase over the course of one year. This was accompanied by teaching and follow up via Skype clinics. Table 1 displays the demographics, cause of kidney failure, complications, and outcomes.16 The mean age of the 17 patients was 43.6, with the youngest being eight years old and the eldest 76 years old. Five patients died, including the eight-year-old and a 15-year-old, both approximately two weeks after PD catheter placement due to acute kidney and multi-organ failure. The other deaths were attributed to co-morbidities or unknown causes. Other complications included two conversions to HD that became necessary due to inadequate clearance, one instance of PD catheter malfunction that was successfully corrected, and one instance of PD catheter exit site infection that failed initial treatment with antibiotics but was surgically corrected. Aside from these negative outcomes, most patients did well with their self-administered PD regimen. Of note, in four cases, the PD regimen served as a successful bridge to kidney transplantation. These patients likely would have died before obtaining the transplant if not for this bridge. We continue to perform PD during our visits and to follow these patients in conjunction with our colleagues in Guyana.16

Table 1. Peritoneal dialysis patients in Guyana

Name Age Gender Cause of kidney failure Complication Outcome
EG 34 F Hypertension None Patient doing well with PD
JA 08 F Acute kidney failure None Died of multi-organ failure
DD 48 F Diabetes, hypertension Exit site abscess Incision and drainage of abscess
GW 48 M Hypertension, polycystic kidneys None Living kidney transplant from daughter
DW 25 F Hypertension Single episode peritonitis Living kidney transplant from sister
AG 49 F Diabetes, hypertension PD blocked Required temporary HD, otherwise doing well with PD
AS 51 M Diabetes, hypertension None Patient doing well with PD
DB 48 F Hypertension None Died of myocardial infarction
FR 65 M Diabetes Blocked, tube replaced Patient doing well with PD
KL 44 M Hypertension None Died at home, unknown reason
TS 15 M Acute kidney failure None Died of liver failure
KK 43 F Hypertension Single episode peritonitis Died at home, unknown reason
GE 34 F Diabetes Inadequate clearance Switched to HD
RA 76 M Polycystic kidneys Inadequate clearance Switched to HD
ST 68 M Obstructive uropathy None Patient doing well with PD
PM 48 F Diabetes Single episode peritonitis Living kidney transplant from sister-in-law
KS 38 M Hypertension None Living kidney transplant from brother

First vascular access program

We introduced the concept of vascular access for dialysis to Guyana. Table 2 shows the demographics, causes of kidney failure, and outcomes for this population. Of note, a significant number of patients failed to attend their follow-up appointments or died of unknown causes. Patients were given the option of PD or HD. Those who were unsuited for PD due to logistics, lack of training, or medical issues (such as previous abdominal surgery) were placed on HD via vascular access. The HD option follows as a corollary that patients who underwent vascular access procedures were sicker with a more advanced disease. The high cost of HD may have deterred patients from being compliant, thus leading to inadequate dialysis and early death. Despite relatively poor outcomes, we hope that with the reduction of costs associated with HD and with more teaching, results will improve in the next few years.

Table 2. Vascular access patients in Guyana

Name Age Gender Cause of kidney failure Complication Outcome
LL 69 M Hypertension Superficialization Currently on HD
BZ 36 F DM and PCKD None Unknown (lost to follow-up)
AM 60 M Hypertension None Died of unknown cause
BF 56 F DM None Unknown (lost to follow-up)
SS 56 M Unknown None Currently on HD
EB 45 F Hypertension Thrombosis, new native AVF Currently on HD
KH 45 F Hypertension None Currently on HD
JS 45 F PCKD None Died of unknown cause
UJ 60 M Hypertension None Died of unknown cause
PF 34 F DM and hypertension None Died of unknown cause
DP 46 M Hypertension None Unknown (lost to follow-up)
SB 43 M Hypertension None Currently on HD
RK 52 M Unknown None Unknown (lost to follow-up)
ON 53 M Hypertension None Died of unknown cause
WG 19 F Unknown None Died of unknown cause

Tissue typing and cross-matching

Tissue typing and cross-matching were done gratis at the Immunology Department of Walter Reed National Military Medical Center (WRNMMC), Bethesda, MD, to ensure standard quality as required by various regulatory bodies in the U.S. See Table 3 for the results of the tissue typing and cross-matching. In total, 13 transplants were performed following this laboratory work. It is also interesting to note the instances in which patients did not receive a transplant or the more viable of two potential donors was selected. Patient KH, for instance, did not receive a kidney because of the presence of unacceptable antigens, whereas KS did not receive one from either of two donors because of a positive cross-match. In two cases (DW and HG), tissue typing allowed us to select the better match.

Table 3. Tissue typing and cross-matching results for potential donors and recipients

Recipient Potential donor(s) HLA mismatch results CDC XM results Presence of unacceptable antigens Transplant performed
MM LM 1B / 1DR / 1DQ Negative Negative Yes
GW MG 1A / 1B / 1DR / 1DQ Negative Negative Yes
MS CC 1A / 2B / 2C / 1DR / 2DQ Negative Negative Yes
JS BS 1A / 1B / 1DR Negative Negative Yes
GR KR 1A / 1B / unk C / 1DR / 1DQ Negative Negative Yes
AR VR 1B / 1DR Negative Negative Yes
RH RH 1A / 1B / 2C / 1DR Negative Negative Yes
MD RB 1A / 2B / 1C / 1DR Negative Negative Yes
DW PW1 1A / 1B Negative (HI) Negative Yes
PW2 1A / 1B / 1DR / 1DQ Negative (DTT) Negative No
PG OJ 2A / 2B / 1C / 2DR / 2DQ Negative Negative Yes
SC 2A / 2B / 2C / 2DR / 2DQ Negative DR04 No
AB UB 1A / 1C Negative Negative Yes
KS MS 1B / 1C Negative Negative Yes
RM 2A / 2B / 2C / 1DR / 1DQ Negative (HI) Negative Yes
HG JP 1A / 2B / 1C Negative Negative Yes
NG 1A / 1B / 1C / 1DR / 1DQ Negative Negative No
JG SG 1A / 1B / 1C Negative Negative No
KH DP 2A / 2B / 2C / 2DR / 2DQ Negative DR04 / DQ09 / DR53 No
KS BI 2A / 2B / 2C / 2DR / 2DQ Positive (T- and B-lymphocytes) A01, 11 / B57 / DR07,11 / DR52 No
DJ 1A / 1B / 1C / 2DR / 2DQ Positive (T- and B-lymphocytes) A24 / DR07,14 / DR52 / DQ02 No

HLA mismatch=human leukocyte antigen mismatch.

CDC XM is the cross-matching study done to ascertain recipient’s response to donor’s T- and B-cell lymphocytes.

A negative response following the addition of HI (heat inactivation) or DTT (dithiothreitol) is also deemed favorable; these additions demonstrate an acute (IgM-mediated) response to donor lymphocytes that usually does not pose a barrier to transplantation.

A positive CDC XM (involving either T- or B-cells) even after testing with HI/DTT served as an absolute contraindication for surgery, as did the presence of any unacceptable antigens (shown in the second-to-last column).

Results of the first kidney transplant program

The list of 13 patients who received transplanted kidneys between 2008 and 2012 are presented in Table 4. Of these recipients, three died from kidney failure or other co-morbidities. The unfortunate case of kidney failure was a result of poor compliance with the necessary anti-rejection medication, a problem all too common in the transplant population. This case demonstrated that when offered a viable treatment option, some patients, regardless of need, will refuse to comply. The case also highlighted the need for more patient education.17

Table 4. Transplant patients

Recipient Date of Transplant Donor (initials, relation, age, gender, and post-op complications) Cause of kidney failure Current serum creatinine (mg/dL) Current medications Recipient outcome and complications
MM, 18-year-old male 07/12/2008 LM, mother, 43-year-old female, wound infection that resolved, otherwise well HTN 1.0 at last visit 1 year before death, 7.0 death None Died of kidney failure 3 years post-op due to non-compliance with anti-rejection meds
GW, 43-year-old male 01/31/2009 MG, daughter, 24-year-old female, otherwise well DM and PCKD 2.1 CC / PG Developed 6-cm brain lesion cleared with reduction of immune-suppressants, otherwise well
MS, 59-year-old male 05/23/2009 CC, wife, 31-year-old female, otherwise well HTN 1.9 CC / PG / PD Wound infection that resolved with treatment, otherwise well
JS, 58-year-old male 05/24/2009 BS, son, 34-year-old male, pain near surgical incision, otherwise well DM and prostatic obstruction 1.2 None Died of myocardial infarction 2 months after surgery
GR, 36-year-old male 03/18/2011 KR, brother, 32-year-old male, otherwise well Unknown 1.2 CC / PG / PD Otherwise well
AR, 55-year-old male 05/25/2011 VR, wife, 40-year-old female, otherwise well HTN 1.3 CC / PG / PD Otherwise well
RH, 56-year-old male 05/27/2011 RH, daughter, 19-year-old female, otherwise well HTN 1.2 CC / PG / PD Otherwise well
MD, 38-year-old male 08/31/2011 RB, brother, 43-year-old male, otherwise well PCKD 1.0 CC / PG / PD Otherwise well
DW, 23-year-old female 12/13/2011 PW1, sister, 25-year-old female, otherwise well HTN 1.0 CC / PG / PD Otherwise well
PG, 48-year-old male 03/08/2012 OJ, sister-in-law, 45-year-old female, otherwise well DM and HTN 1.0 CC / PG / PD Post-transplant DM, otherwise well
AB, 54-year-old male 03/07/2012 UB, daughter, 19-year-old female, otherwise well HTN 1.2 None Died of cerebrovascular event 2 months after surgery
KS, 31-year-old male 07/14/2012 MS, father, 60-year-old male, otherwise well HTN 1.4 CC / PG / PD Otherwise well
HG, 20-year-old male 10/23/2012 JP, altruistic living donor, 27-year-old female, otherwise well Unknown 1.0 CC / PG / PD Otherwise well

CC = CellCept, PG = tacrolimus, PD = prednisone, DM = diabetes mellitus, HTN = hypertension, PCKD = polycystic kidney disease

All transplants were from living donors because Guyana, like most other developing countries, has no deceased donor program. The donors were related except in one case of an unrelated altruistic donor. We are working to establish a deceased donor program similar to the one started by the United Network for Organ Sharing.18

Ethical dilemmas

Our efforts in Guyana were not without ethical dilemmas. In one case, patient JG (in Table 3) was not transplanted despite having a living donor and a negative cross-match. Our predicament with him centered on the fact that he needed a transplant but had bacterial endocarditis and was noncompliant with his antibiotics regimen. The team questioned how well he would comply with anti-rejection medications after transplantation and elected not to proceed. The patient died a few months later from septic endocarditis.

In the case of recipient HG, the dilemma was that she was not a Guyanese native but instead from neighboring Antigua. The ethical question was, should a non-Guyanese citizen receive health care services provided by the Guyanese government? After much discussion and legal counseling, and because Guyana has an open immigration policy with Antigua, we chose to proceed, and she received a kidney. Other ethical issues involving potential medical tourism, commoditization of organs, and donations involving minors also came up. These cases clearly demonstrated to us that the same ethical issues that plague larger Western programs may also affect a small, nascent transplant service in a developing country.19-21

Immunosuppression

Though induction therapy is often useful in solid organ transplantation, it was not employed here to avoid the associated steep cost.22 Also to save costs, we used generic medications: maintenance immunosuppression consisted of tacrolimus, mycophenolate, and low-dose prednisone, which was tapered off after six months. Random samples to check tacrolimus levels were conducted at our laboratories in WRNMMC. Usual prophylactic medications, such as trimethorprim-sulfamethoxazole, valganciclovir, and anti-fungals, were prescribed. All patients also received a ureteric stent that a local surgeon removed using flexible cystoscopy two weeks after the operation.

Skype clinics

In conducting our renal transplant therapy in Guyana over the last four years, the team faced a key challenge with respect to keeping in touch with our patients, the local physicians, and nurses. Although we found e-mail sufficient for staying in contact with the staff, we felt it might not be adequate for communicating with the patients, as most of them did not have personal computers. Instead, we elected to use Skype via the local hospital.23

For a typical clinical encounter, the patients would go to the Balwant Singh Hospital, where staff would set them up with a computer and help connect them with the transplant surgeon via Skype. Team members would interview each patient and provide information on proper care. During each encounter, the local Guyanese health care professionals would perform a physical exam and conduct any needed laboratory tests. Our patients conveyed to us that they enjoyed these Skype clinics; though not the same as a real physical encounter, they liked having at least some remote contact with the U.S. team in conjunction with the local physicians. More than 450 patients with CKD were examined with direct contact and approximately 100 patients via these Skype clinics.

Teaching local staff and sustainability

We had to teach the local staff and their patients how to maintain their dialysis regimens and how to properly monitor their immunosuppressive therapy post-transplantation. The procurement of dialysis fluid and its proper usage was one challenge. For the sake of simplicity, we encouraged the use of one solution (Dianeal 2.5 percent) for dialysis exchanges. Both staff and patients were instructed in how to properly carry out PD and how to monitor their fluid status. Patients were instructed in the use of a blood pressure cuff and a kilogram scale, and to watch for signs of edema at home. We showed them how to keep a log and emphasized good fluid-restriction practices.

Strict adherence to immunosuppressive therapy after transplant was crucial, and we strived to impress on both local staff and patients the importance of compliance. We noted to them that if the challenge of compliance is met with less than due diligence, the invaluable donated kidney will be rejected. We encouraged patients to keep a log of their medication use, to adhere to a schedule, and to have their medications accessible at all times. We encouraged the involvement of family members to ensure patient compliance. We created a handbook for the staff detailing the work-up and postoperative management with emphasis on compliance. This educational process is crucial to the sustainability of the RRT program in Guyana.

Public-private partnership

We would like to emphasize that our efforts in Guyana came to fruition because of an intricate partnership between the private and public sector. The initial idea and funding for our trip came from Mr. Subraj, who saw a dire need in his home country and sought to help those in despair. The Guyana government provided access to hospitals and key materials, such as dialysis fluids, and generic medications for the patients.24 The team believes we have demonstrated that such a model of public-private partnership can lead to the establishment of a program that provides a sophisticated surgical procedure at no cost to the patient in a developing country.25-27

Public health program

We initiated a pilot program that trained high school students from remote villages in clinical skills, such as monitoring/recording of blood pressure, blood sugar, peripheral edema, and dietary practices. In this way, these students serve as health advocates in their communities. The initial phase will encompass seven villages of approximately 1,000 people each. The information will be collected and analyzed to inform the government of Guyana about the incidence and prevalence of diabetes, hypertension, kidney failure, and poor sanitation. We anticipate that the government of Guyana eventually will allocate resources for treating and preventing these diseases. We also hope that other communities in Guyana will emulate this model.28 This volunteerism and method of surveillance is the only form of health care that is accessible to some of these villagers.29,30

Ongoing efforts in Guyana

The team recently completed its 15th medical mission to Guyana, April 5 to 10. We carried out two additional living kidney transplants, six vascular and peritoneal access procedures, as well as kidney biopsies for diagnostic purposes. The team examined more than 100 patients in various stages of CKD. We continued our efforts in training high school students in carrying out the unique public health program mentioned earlier in this article. We are currently reaching seven villages, each numbering an estimated 1,000 individuals. The team also conducted a press conference to reach out to the locals, and a work-up of an additional three patients who at press time were scheduled to receive living kidney transplants in July has been completed.

The future

Our team has created a comprehensive RRT in Guyana where none existed by a network of U.S. transplant heath care professionals, U.S. philanthropists, Guyanese health care professionals, and the government of Guyana. This work included medical, surgical, education, advocacy, and a strong public health component. A number of publications in peer-reviewed journals have also resulted from the work of this team.14,16,21

We plan to continue our efforts in Guyana until the local physicians are trained in the art and science of kidney transplantation. We are currently working with the Guyana Ministry of Health to establish a deceased donor kidney program.31 This model will also be tested in select CARICOM countries this year. In fact, during our most recent trip to Guyana, some patients were from CARICOM countries. In all, we hope that our efforts will serve as a template for philanthropic efforts in other developing countries.

guyanaoverlay

Dr. Jindal’s book detailing the first kidney transplant in Guyana.

guyana1

The surgical team, including Dr. Falta (fourth from the left), Dr. Womble (third from right), and Dr. Jindal (second from right), with other hospital staff.

guyana4

Inset: A mother makes a plea to save her dying son, which started the team’s efforts in Guyana. Main photo: Their house.

guyana6

Dr. Jindal (left) examines a patient in the ICU, with Mr. Subraj.

guyana2

Some of the high school students and teachers that the authors trained for surveillance of hypertension and diabetes, with Dr. Jindal (back row, second from left) and Mr. Subraj (far right).

guyana3

Dr. Jindal conducting a Skype clinic from Mr. Subraj’s offices in Queens, NY.

guyana5

Then-President of Guyana, the honorable Mr. Bharrat Jagdeo (left), greets Dr. Jindal at a reception to honor the transplant team.

guyana9

Dr. Jindal addressing a high school assembly on prevention and early diagnosis of diabetes and hypertension. To his left are Mr. Subraj and nephrologist Thakor G. Patel, MD, while to his right is the school principal.

guyana7

Guyanese patient GR (left), 36, waits to receive a kidney from his 32-year-old brother, KR (right).

guyana8

Dr. Jindal addressing a press conference with the Minister of Health, Dr. Leslie Ramsammy (second to left).


Acknowledgements

The authors would like to acknowledge the following contributors who provided RRT to the people of Guyana: Mr. Subraj, philanthropist and president of Zara Realty, Queens, NY, who funded the entire program; the government of Guyana for providing the use of facilities and medications; the staff of Balwant Singh Hospital, where the transplants and related surgeries were performed; the departments of pathology and nephrology at Drexel University, Philadelphia, PA; the department of nephrology at the Walter Reed National Military Medical Center and their supporting staff for tissue-typing and cross-matching analysis; and Arthur Womble, MD, of the Southeastern Pain Management Institute, Gadsden, AL, who provided anesthesia support and pain management.

Disclaimer

The views expressed in this paper are those of the authors and do not reflect the official policy of the U.S. Army, the U.S. Department of Defense, or the U.S. government. No financial conflict of interest exists.


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