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Keywords:

  • Country;
  • developing;
  • pediatric;
  • renal transplant

Abstract

  1. Top of page
  2. Abstract
  3. Introduction
  4. Human Development Parameters in the Developing World
  5. The Burden of End Stage Kidney Disease in Children
  6. Access to Renal Replacement Therapy
  7. Kidney Transplantation
  8. Overcoming the Challenges in Developing Countries
  9. Conclusions
  10. Disclosure
  11. References

The prevalence of pediatric RRT and transplantation are low in developing countries, 6–12 and <1 to 5 per million child population (pmcp), respectively. This is due to low GDP/capita of <$10 000, government expenditure on health of <2.6–9% of GDP and paucity of facilities. The reported incidence of pediatric CKD and ESRD is <1.0–8 and 3.4–35 pmcp, respectively. RRT and transplantation are offered mostly in private centers in cities where HD costs $20–100/session and transplants $10 000–20 000. High costs and long distance to centers results in treatment refusal in up to 35% of the cases. In this backdrop 75–85% of children with ESRD are disfranchised from RRT and transplantation. Our center initiated an integrated dialysis–transplant program funded by a community-government partnership where RRT and transplantation was provided “free of cost” with life long follow-up and medication. Access to free RRT at doorsteps and transplantation lead to societal acceptance of transplantation as the therapy of choice for ESRD. This enabled us to perform 475 pediatric transplants in 25 years with 1- and 5-year graft survival of 96% and 81%, respectively. Our model shows that pediatric transplantation is possible in developing countries when freely available and accessible to all who need it in the public sector.


Abbreviations
ATG

antithymocyte globulin

AUC

area under the curve

AZA

azathioprine

CKD

chronic kidney disease

CyA

cyclosporine

ESRD

end stage renal disease

GDP

gross domestic product

HD

hemodialysis

IFTA

interstitial fibrosis and tubular atrophy

PD

peritoneal dialysis

PMCP

per million children population

PMP

per million population

RRT

renal replacement therapy.

Introduction

  1. Top of page
  2. Abstract
  3. Introduction
  4. Human Development Parameters in the Developing World
  5. The Burden of End Stage Kidney Disease in Children
  6. Access to Renal Replacement Therapy
  7. Kidney Transplantation
  8. Overcoming the Challenges in Developing Countries
  9. Conclusions
  10. Disclosure
  11. References

In developed countries pediatric kidney transplantation has become a routinely successful procedure where 1- and 5-year graft survival rates are 93% and 77% from deceased donors and 95% and 85% from living donors [1]. These outcomes are a cumulative effect of two decades of improvements in dialysis procedures, surgical techniques, immunosuppression, diagnosis and treatment of rejection and finally, effective control of infections [1]. In contrast, developing countries have poorly developed pediatric programs where transplant rates are <5 pmp [2]. The main reasons are poor economic indications, low government expenditure on health and underdeveloped renal replacement therapy (RRT) for children [2-5]. In this report we present an overview of human development, pediatric end stage renal disease (ESRD), RRT and transplantation in developing countries. It highlights the challenges encountered and their solutions for establishing a successful and viable pediatric transplant program in low resource.

Human Development Parameters in the Developing World

  1. Top of page
  2. Abstract
  3. Introduction
  4. Human Development Parameters in the Developing World
  5. The Burden of End Stage Kidney Disease in Children
  6. Access to Renal Replacement Therapy
  7. Kidney Transplantation
  8. Overcoming the Challenges in Developing Countries
  9. Conclusions
  10. Disclosure
  11. References

Majority of the countries are ranked low in the Human Development Index [4]. The major population of the Earth resides in developing countries where ⋍50% are rural dwellers [4]. The human development parameters of 13 developing countries are given in Table 1 [4]. The majority of the countries have a gross domestic product (GDP) per capita of <$10 000 and a quarter of the people live below the poverty line. The government expenditure on health is between 2.6% and 9% of the GDP. Child population (<15 years) constitutes between 23% and 40% of the population and 5–31% are malnourished. Poor health facilities and lack of resources result in infant mortality rates of 7.8–59%. In this backdrop of economic deprivation children are generally deprived of basic health facilities. Therefore for health providers, care for children with chronic kidney diseases (CKD), RRT and transplantation are the least of the priorities, resulting in low RRT and transplant rates [2-5].

Table 1. Overview of pediatric end stage kidney disease and transplantation in developing countries
CountryLatin AmericaAfricaMiddle EastAsiaUSA
BrazilChileSudanEgyptS. AfricaIranTurkeyJordanS. ArabiaKuwaitIndiaMalaysiaPakistan
Demographics
Population (millions)196.717.344.682.656.577.9746.627.92.8124128.9176.9313
Urban population %86%89%41%43%62%71%70%78%82%98%30%73%36%83%
Child population < 1525%23%40%31%36%33%26%37%31%26%33%30%36%16.0%
GDP per capita10 36714 3112210567310 27811 55813 668817223 480 329614 012260945 989
Population below poverty line %21.415.1 2223 18.113.3  27.53.822.3 
Govt expenditure on health % GDP9.08.27.35.08.55.56.79.35.03.39.24.82.616.2
Infant mortality42%7.8%59%23%48%45%23%23%18%9%50%8%64%8%
Malnutrition children %2.1%0.5%30%5.4%8.7%  1.6% 1.5%43%12.7%30.9%0%
End-stage renal disease (ESRD)
Renal care registaryYesYesYesNoNoYesYesNoYesYesNoYesYesYes
Nephrologists/pmp 9.60.76.51.1 2.5 4.7 1.50.61.2 
Pediatric CKD prevalence/incidence (pmcp) 43/5.7  8.8%/1–2 15.6/9.2 –/<140/8  
% presenting in ESRD 4263 753624373054   
Pediatric ESRD prevalence/incidence (pmcp)23.4/––/8.4    –/3.414.5/10.7 328/35 –/12 80/15
RRT prevalence (pmp; all patients)49011254.5680130565810 810 70815701800
Etiology of ESRD
Primary glomerulopathies22.4%19.6%25.4%21.6%34.9%12%22.4%31%14.1%8.7%27.5%18.6%26%24.5%
Congenital urologic/cystic diseases71.0%52.4%23.9%68.9%41.7%61.4%50.0%50%81.2%80.7%61.6%18.6%8%46.2%
Nephrocalcinosis/nephrolithiasis9.3%3.4%1.2%14.5%4.3%19%4.7%5.2%3.6%16%2.6%
Unknown3.7%39.1%6.1%8.4%11.3%1.2%5.7%35.8%50%6.2%
RRT modality in children
HD42%35%35%92% >80%64%62%18%24%89%31%100%29%
PD45%57%56%8% 10–15%30%9%46%50%11%51%39%
Preemptive transplant13%12.1%39%23% 27%6%24%25%26%2%18%24%
Kidney Transplantation
Total Transplant Rate pmp (all patients)20.4512.261.7315.635.127.223.231.115.5726.214.7224.6454.35
% Children Transplanted13.5 3.9  341520 75 17 2.5 pmcp
Total Transplant / Number of years300 / 25178 / 138 / 5216 / 28282 / 19922 / 2283 / 2934 / 684 / 1586 / 1345 / 1377 / 575 / 136291 / 15
Mean Age of Recipients11.5 ± 4.510.9 ± 3.7 12.9 ± 3.112 yrs13.1 ± 3.514.9 ± 2.24yr - 19yr12.2 ± 4.613.2 yrs13.3 ± 4.0 12 yr (6-17) 
Kidney Donor Living78%39%100%100%21%95%79%100%44%58%95%58%100%51%
Kidney Donor Deceased32%61%0%0%79%5%21%0%56%42%5%32%49%
Immunosuppression
CyA v/s TAC %70 / 3096 / -55 / 4560 / 4050 / 50100/0100/00/10093/-100/051/4855/37100/-42/47
AZA v/s MMF %70/3080/20 60/40−/50−/100−/100−/100 100/049/5118/6685/1522/63
Induction (IL-2/ATG) %1009 100 201000473224058
% Graft Survival 1 and 5 year90, 7287, 78 93, 7382, 4489, 7291, 6797, (3-yr) 9198, 9288, (10-yr) 8491, 8091, 7988, 6596, 86
% Patient Survival 1 and 5 year95, 9398, 98 98, 8897, 8497, 9598, 92100, (3-yr) 10099, 9699, (10-yr) 9895.3, 87.997, 9790, 7598, 95
Causes of Graft Loss
% Acute Rejection1111  61510 41  2815
% Chronic Rejection/Recurrence49/1321/- 67/862544533/3323/−47/−33/−46/-46/-36/7
% Death with function1520  6 45     89
% Non-compliance 25 236    188.4 7 
Causes of Patient Los
% Cardiovascular   33    86 66411212
% InfectionMajor Cause88 4083Major Cause85  10033188232
References[20, 34][12, 17, 37][6, 27, 40][18, 40][40, 43, 44][7, 32][3, 10, 19, 45][13, 46][14, 35, 47][15, 36][8, 48, 49][21, 48][11, 48, 50][9]

The Burden of End Stage Kidney Disease in Children

  1. Top of page
  2. Abstract
  3. Introduction
  4. Human Development Parameters in the Developing World
  5. The Burden of End Stage Kidney Disease in Children
  6. Access to Renal Replacement Therapy
  7. Kidney Transplantation
  8. Overcoming the Challenges in Developing Countries
  9. Conclusions
  10. Disclosure
  11. References

The incidence of CKD in children remains largely unknown in the developing world (Table 1). Brazil, Chile, Malaysia, Saudi Arabia and Kuwait have well-established registries while in others they have been recently established. The number of nephrologists pmp are low and vary from <1 to 9.5 pmp. CKD prevalence rates based on referral to tertiary centers are probably underestimates and vary from 15.6 per million child population (pmcp) in Saudi Arabia to 40 pmcp in Malaysia. Generally children are referred late where 24–63% present in ESRD with associated co-morbids. The reasons for late referrals are neglect, alternate therapies, long distances from the tertiary centers and finally economic constraints [6-8]. Incidence of ESRD when reported ranges from 3.4 pmcp in Turkey to a high of 35 pmcp in Kuwait. These figures reported from tertiary centers are also likely to be biased and underreported. Children present with small shrunken kidneys where etiology remains unknown in up to or >50% of the cases (Table 1) [2]. These findings contrast from the developed world, for example. The United States, with rates of 6% [9]. The etiology of ESRD shows wide variations, glomerulonephritis in 8–40% and congenital urologic/cystic diseases in 8–80% of the cases. In some countries neglected and misdiagnosed stone disease lead to ESRD where rates vary from 2.6% in Turkey, 9% in Sudan, to 16% in Pakistan [6, 10, 11].

Establishment of dedicated pediatric nephrology services in some high income countries, for example, Chile, Jordan, Saudi Arabia and Kuwait [12-15], allow children to present early and histological diagnosis shows glomerulonephritis in 8–31% and congenital urologic/cystic diseases in 50–80% with low number of unknowns (Table 1). Our data of 801 biopsies in children showed primary GN in 87% and secondary GN in 6% of the patients [16] as compared to our earlier findings of 26% [11]. Establishment of pediatric nephrology services in Turkey, Saudi Arabia and Kuwait have improved the care of children with CKD and ESRD [13-15].

Access to Renal Replacement Therapy

  1. Top of page
  2. Abstract
  3. Introduction
  4. Human Development Parameters in the Developing World
  5. The Burden of End Stage Kidney Disease in Children
  6. Access to Renal Replacement Therapy
  7. Kidney Transplantation
  8. Overcoming the Challenges in Developing Countries
  9. Conclusions
  10. Disclosure
  11. References

RRT prevalence rates are generally low in developing countries and range from 4.5 pmp in Sudan to 1125 pmp in Chile, in contrast to the United States of 1800 pmp (Table 1). These wide variations depend on economics, nephrologists, availability of dialysis services and sociocultural factors [6, 7, 17-19]. RRT data on children in pmcp are only available from Brazil 6.5, Turkey 11.9, Kuwait 17 and Malaysia 8 pmcp, respectively [10, 15, 20, 21]. RRT therapy is mainly available in urban centers, often long distances from rural settings, and therefore inaccessible to the majority. Exceptions are Chile and Brazil with rural dialysis centers [17, 20]. RRT is government supported and universally available in some high income countries such as Chile, Jordan, Kuwait and Saudi Arabia, while in the rest it is mainly in private centers on out of pocket expenses. Other sources are nongovernmental organizations and insurance in countries such as Iran, Malaysia, Pakistan and Turkey [2, 7, 10, 21]. The cost ranges from $20 to $100 for a dialysis session, and the annual cost of continuous ambulatory peritoneal dialysis is $7000–9000 [2, 22-24]. These charges are beyond the means of most of the population considering the per capita GDP of <$10 000 (Table 1). Paucity of facilities in the public sector, high costs in the private and inaccessibility of centers render 75–85% of the children disfranchised from RRT [20, 21, 25]. In fact 35% refuse RRT in India due to high costs [8] and 8% in Iran [26]. In Sudan, although RRT is freely available in government sector, 22% refuse RRT due to travel cost [6, 27]. In Turkey half of the dialysis population demands transport facilities by the dialysis centers [28]. Hemodialysis (HD) is the main modality of RRT in most of the countries (Table 1) while peritoneal dialysis (PD) is offered in high-income countries, Brazil, Chile, Kuwait and Malaysia (Table 1). HD is the therapy of choice firstly due to high costs of PD as most consumables are imported [24, 29] and secondly PD lines are more prone to infections due to poor hygiene and living conditions especially in rural areas [29]. Furthermore HD is preferred as many children present with co-morbids and are malnourished often requiring emergency dialysis [6, 8, 10, 20]. In our experience almost 50% of the children were malnourished requiring dietary supplements and 10% needed urgent emergency dialysis. In these cases establishment of permanent angioaccess was essential as the majority of the patients lived in far off places in village setups where temporary lines were more prone to infection often leading to mortality. To avoid complications of HD and PD and high costs of these procedures many centers opt for pre-emptive transplants with a range of 6–39% (Table 1). These rates are comparable to those in the United States [9].

Kidney Transplantation

  1. Top of page
  2. Abstract
  3. Introduction
  4. Human Development Parameters in the Developing World
  5. The Burden of End Stage Kidney Disease in Children
  6. Access to Renal Replacement Therapy
  7. Kidney Transplantation
  8. Overcoming the Challenges in Developing Countries
  9. Conclusions
  10. Disclosure
  11. References

Overall kidney transplantation rates are low in developing countries mainly due to economic and paucity of facilities [30, 31] (Table 1). In children rates are largely unknown and where reported are low, <0.1 pmcp in Pakistan and 4–5 pmcp in Kuwait (Table 1). Most reports are single center experiences except multicenter reports from Chile with 178 and Iran 922 transplants, respectively (Table 1) [17, 32]. Similar to RRT there are social, economic and logistic issues related to access and availability of kidney transplantation.

Social issues

A challenge in many countries is to convince the parents that transplantation is a successful mode of therapy, as there are apprehensions on long-term graft and patient survival [11]. In a low socioeconomic backdrop kidney donors have fears of postdonation medical problems and compromised ability to earn a livelihood [33]. There is a shortage of donors due to the absence of deceased donor program and as a result the majority of organs come from living donors (Table 1). However, in countries with established deceased donor programs, for example, Brazil, Chile, Saudi Arabia and Kuwait, the percentage of children getting transplants is higher (Table 1) [17, 34-36].

Economic issues

Poor economic conditions in developing countries, growing child population and high infant mortality rates take the focus of government and health planners toward the unmet problems of family welfare, immunization and perinatal care. The growing burden of CKD in children where the majority presents in ESRD has motivated some low income countries to initiate a renal care program, for example, Sudan [27]. Although the health spending is low, <10% in most of the countries, transplantation is state funded in some countries with higher GDPs, for example, Malaysia, Kuwait, Chile and Saudi Arabia [21, 35-37]. The percentage of children getting transplant thus varies from 3.9% in Sudan to 75% in Kuwait and the overall transplant rates in children are <15/year in a majority of the countries (Table 1). Transplantation is mainly performed in private centers where the costs range from $10 000–20 000 [38] together with a yearly immunosuppression cost of $3000–4000/year [39]. High costs of drugs often lead to noncompliance, for example, 25% in Chile and 23% in Egypt [2, 18, 37]. Cyclosporin (CyA) and azathioprine (Aza) are the mainstay of immunosuppression in majority of the countries. Many centers now use induction protocols either with antithymocyte globulin (ATG) or interlukin-2 antagonists (IL-2) (Table 1). Graft loss due to acute rejection range from 2% to 41% depending on immunosuppression protocols and donor type with high numbers in countries with deceased donor, for example Saudi Arabia (Table 1) [35]. Interstitial fibrosis tubular atrophy (IFTA) is a major cause of graft loss while other causes were infections and noncompliance due to discontinuation of drugs (Table 1) [19]. Infections remain a major challenge in developing countries due to poor social-economic and environmental conditions. Therefore the major cause of death is infections up to 100% in Kuwait (Table 1) [36]. The graft survival rates at 1 and 5 years range from 98% to 92% in Saudi Arabia to 88% and 65% in Pakistan (Table 1).

Logistic issues

Transplant centers are situated in large cities while 50% of the population resides in rural areas. The logistic issues vis-a-vis cost of travel, reallocation and lodging in the pre- and posttransplant period creates financial and logistic problems where many families shy away from transplantation [26, 29, 39, 40]. In general poor access, nonavailability and high costs render transplantation beyond the means of the majority. The population being disfranchised—transplantation becomes irrelevant [39, 40].

Overcoming the Challenges in Developing Countries

  1. Top of page
  2. Abstract
  3. Introduction
  4. Human Development Parameters in the Developing World
  5. The Burden of End Stage Kidney Disease in Children
  6. Access to Renal Replacement Therapy
  7. Kidney Transplantation
  8. Overcoming the Challenges in Developing Countries
  9. Conclusions
  10. Disclosure
  11. References

A model for funding RRT and transplantation

Economic constraints, paucity of RRT facilities in the government and high costs in the private sector in Pakistan necessitated a system where RRT and transplantation could be funded and offered “free of charge” to the patients with lifelong follow-up and medications. Our institute, a government sector organization, initiated an integrated dialysis and transplant program in the 1980s where the community was asked to help fund dialysis and transplantation. The guiding principle of this partnership has been equity, transparency and accountability to both partners. All services are provided “free” without consideration of caste, color, creed or religious affiliation. The aim is to provide comprehensive services; therefore all facilities have been developed under one roof to include radiology, laboratory, nuclear medicine and rehabilitation and teaching facilities [41].

This model of community-government partnership has sustained itself for 25 years with the funding by the two partners having increased to over $30 million [38]. Annually, over 1000 patients receive 200 000 dialysis sessions and 350–550 receive transplants, 10–15% being children. About 40% of the patients come from other provinces of the country as far as 2000 km [38, 41]. To maintain this large number of patients a number of economizing strategies were introduced to reduce cost without compromising quality. Basic hemodialysis machines were used which costs 30% less than more sophisticated units, plus in-house preparation of dialysis fluid by selfimporting bulk reagents, dialysis reuse on automated systems except Hepatitis B positive patients and the use of generic immunosuppressants which are 30% cheaper than patents [42].

RRT at the doorstep of patients

The two important factors that hindered access to RRT and transplantation were costs and long distance to travel for dialysis or transplantation. Having overcome the economic issues the institute focus was on logistics and accessibility. This was achieved by establishing satellite dialysis centers in the outskirts of the city, as well as at 500 and 2000 km from the center where patients could be dialyzed and referred for transplantation [41, 42]. Presently of the 700 patients dialyzed daily some 300 are treated at six satellite centers of the institute. To facilitate transplanted children and ensure 100% follow-up, the medical social department provides travel costs and free accommodation to about 5–19% of the patients each year. Posttransplant immunosuppressive drugs are provided free for life and for 3 months at a time for patients living in far off places [38, 41].

Societal acceptance of RRT and transplantation

Free treatment and access to RRT and transplant for children are not the only hurdles in the developing world. Apprehensions on long-term transplant outcome and donor well being are important issues. Good outcomes and rehabilitation of children posttransplant on one hand was a driver for others to have their children transplanted [11] and donor well being on the other. Donor well being and the donor follow-up clinic [38] provided proof to prospective donors that one can live a normal life postdonation. Indeed many of the apprehensions are removed when kidney donors propagate donation. We observed a fall of donation refusal rates in our earlier period of 60% compared to 15% in the present [38]. This is also reflected in the increase of renal transplants performed at our center from about 100 per year in 1990s to >400 in 2009 [38].

Pediatric kidney transplantation at the Institute

In a period of 25 years, 3448 live related transplants were performed at our center and of these 475 (13.7%) were children up to the age of 18 years. The experience to cater to children developed under the umbrella of adult program. Pediatric services developed gradually with the training of nurses, pediatric nephrologists and pediatric transplant surgeons. Expertise for angioaccess, anesthesia and intensive care had to be acquired to successfully transplant children. The developmental stages of histocompatibility techniques, procedures to evaluate graft dysfunction, infection diagnostics and availability of immunosuppression drugs in three eras of our transplant program are given in Table 2. The demographics, immunosuppression protocol, infection rates, causes of graft dysfunction, graft and patient survival of 475 transplants are given in Table 3. Initially recipients were all >6 years of age; however, with the development of expertise we were able to transplant children <6 years in era 3. Development of pediatric nephrology services allowed early presentation of CKD cases where etiology could be determined. In the present era the cause of ESRD is thus known in 60% of the cases (Table 3).

Table 2. Diagnostic services and availability of immunosuppression drugs in three eras of transplant program
 Era 1 (1986–1995)Era 2 (1996–2005)Era 3 (2006–2011)
Histocompatibility testingMicrolymphocytotoxicityHLA-A, B by PCR—1996Enzyme linked immunoassay (ELIZA) beads technology—2010
 HLA A and B—1988Flow cross match forClass I antibodies
 Complement dependent cross match (CDC)—1988T and B lymphocytes—1997Class II antibodies
 PRA-lymphocytotoxicity—1990HLA-DQ by PCR 2000MICA Antibodies
 HLA-DR—Microlymphocytotoxicity—1992Monocyte CDC—2002Flow monocyte cross match 2008
 T and B cell cross match—1994  
 HLA-DR by PCR—1994  
 Clinical/biochemistryColor Doppler (resistive index >0.7)Graft immunochemistry—2006
Dysfunction monitoringUrine outputCD3 (<100/cm) for ATG therapy—1997C4d—2006
 Ultrasound kidneyTacrolimus level—2002Sirolimus level 0.5–1 mg; BD—2007
 Graft biopsy——1991 Everolimus level 1–2 mg; OD—2009
 Cyclosporine level—1992  
  CyA (8 mg/kg)/Aza/steroidCyA/Aza/steroid
ImmunosuppressionCyclosporine (10 mg/kg)Tacrolimus generic (0.15—3 mg/kg)/steroid (0.5 mg/kg)/Aza or MMF (150–200 mg/day)Tacrolimus/steroid/MMF
 Steroid (1 mg/kg)Anti rejectionSirolimus—2007
 Azathioprin (1.5 mg/kg)Anti-thymocyte globulin (ATG) (3–4 mg/kg—10 days)Evirolimus—2009
 Anti rejectionOKT3 (5 mg/day—10 days)Induction
 Methylprednisolone (250 mg—5 days)InductionATG
 Anti-lymphocyte globulin (ALG; 3–4 mg/kg—10 days)ATG (3–4 mg/kg—5 days)IL-2 (20 mg—Days 0 & 4)—2007
   Plasmapheresis—2009
   Anti-CD-20—2009
 Routine cultureCMV rapid antigen—1994Polyoma BK—viral loads—2008
Infection monitoringTB culture sensitivity—1990Polyoma BK PCR qualitative—2003HCV, RNA viral loads—2008
 Serology CMV—1990TB PCR—1996CMV viral loads—2009
 Serology HCV—1994CMV PCR—2004 
 Serology HBV—1990Fungal cultures—2000 
 Serology HIV—1992HCV PCR—1996 
  HCV genoytpe—1997 
Table 3. Outcomes of 475 pediatric transplants in the three eras
 Era 1 (1986–1995), n = 31Era 2 (1996–2005), n = 150Era 3 (2006–2011), n = 294p-Value
Demographics
Recipient age15.2 ± 1.715.3 ± 2.514.5 ± 3.10.021
Donor age39.2 ± 9.536.3 ± 9.637.4 ± 8.80.216
HLA match3.58 ± 0.993.79 ± 1.23.88 ± 1.20.370
ESRD Cause Unknowns27 (87%)92 (61%)120 (40%)0.001
Immunosuppression
Induction
ATG0%7 (4.7%)6 (2.0%)0.173
IL-20%3 (2.0%)84 (29%)0.001
CyA/Steroid/Aza (initial)31 (100%)150 (100%)225 (76.5%)0.001
CYA/Steroid/MMF (conversion)0%16 (11%)32 (11%)0.155
TAC/Steroid/MMF (conversion)0%15 (10%)66 (22%)0.001
TAC/Steroid/MMF (Initial)0%9 (6%)32 (10.9%)0.046
Acute rejection15 (48.4%)53 (35%)50 (17%)0.001
Infection
UTI12 (38.7%)45 (30%)59 (20.1%)0.011
TB6 (19%)15 (10%)4 (1.4%)0.001
HCV RNA4 (13%)26 (17.3%)29 (10%)0.006
CMV10 (6.6%)15 (5.1%)0.312
Graft survival
1- and 5-year83%, 54%90%, 73%96%, 81%0.001
Causes of graft loss
Death with function6 (19%)2 (1.3%)2 (0.7%)0.001
Pyelonephritis3 (9.6%)11 (7%)8 (2.7%)0.035
Patient survival
1- and 5-year87%, 58%96%, 84%97%, 94%0.001
Causes of death
Sepsis14 (45%)25 (16.7%)7 (2.4%)0.001

Immunosuppressive protocols depended largely on the availability of drugs in the country. Generics being 30% cheaper with acceptable bioequivalence and good outcomes become the mainstay of treatment [42]. We introduced pharmacokinetic profiling of cyclosporine on 4th or 5th day of transplant by an abbreviated area under the curve (AUC) to determine the adequacy of the drug exposure [42]. AUC undertaken in 386 children on 8 mg/kg/body weight showed adequate levels (range 6000–8000 ng/ml/h) in 155 (40%), high in 34 (9%) and low in 197 (51%) of the children. AUCs thus enabled to readjust the doses in the early transplant period to achieve adequate levels. Induction with ATG and IL-2 was given only to poorly matched (≤2 antigen match) patients and children <12 years of age. Use of induction agents and tailoring of immunosuppression was not only cost effective but also reduced rejection rates from 48% in era 1–17% in era 3 (Table 3).

Infections

Infections remain a major challenge in our center where patients die with functioning grafts (Table 3). Investment in technology for timely diagnosis and strict surveillance for urinary tract infections, cytomegalovirus, BK virus and tuberculosis has played a significant role in diagnosis and reducing infections. Graft loss due to infection reduced from 10% to 3%, death with functioning graft from 19% to <1% and death due to sepsis from 45% to 2% in Era 3, respectively (Table 3).

Our patient and graft outcomes have improved from Era 1 to Era 3 and are comparable to the United States where 1 and 5 years graft survival is 95.5% and 85.7% and patient survival 98% and 96%, respectively (Table 3) [9].

Conclusions

  1. Top of page
  2. Abstract
  3. Introduction
  4. Human Development Parameters in the Developing World
  5. The Burden of End Stage Kidney Disease in Children
  6. Access to Renal Replacement Therapy
  7. Kidney Transplantation
  8. Overcoming the Challenges in Developing Countries
  9. Conclusions
  10. Disclosure
  11. References

The major challenge in developing countries is to provide optimal treatment to children with ESRD. Poor economics, paucity of RRT and transplantation facilities in the government sector and high costs in private sector render majority of children disfranchised from RRT and transplantation. The prevalence rates of RRT and transplantation are therefore low 6–12 and <1 to 5 pmcp, respectively. Our model of community-government partnership has shown that pediatric RRT and transplantation can be successfully established in a developing country. Society can be motivated to accept transplantation as the therapy of choice for ESRD provided the outcomes are good and it is available “free of cost” to all who need it. Transparency and equity ensure community support and sustainability. In a country with economic constraints and shrinking healthcare facilities we were able to expand our services exponentially both for dialysis and transplantation. Community funds ensure sustainability and also motivate the government to come forward with capital investments. In developing countries the focus should be on community screening and measures to minimize progression of CKD to ESRD. Unfortunately, paucity of primary healthcare facilities and ineffective preventive programs render many children in ESRD. Inaccessibility and high costs of RRT make transplantation as the best, cost effective and life saving option. Our community-government model has shown that it is a sustainable option and can be duplicated and developed in other developing countries.

References

  1. Top of page
  2. Abstract
  3. Introduction
  4. Human Development Parameters in the Developing World
  5. The Burden of End Stage Kidney Disease in Children
  6. Access to Renal Replacement Therapy
  7. Kidney Transplantation
  8. Overcoming the Challenges in Developing Countries
  9. Conclusions
  10. Disclosure
  11. References