Pediatric kidney transplantation in the developing world: challenges and solutions.

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.

A renal transplantation model for developing countries.

The estimated incidence of end-stage renal disease (ESRD) in Pakistan is 100 per million population. Paucity and high costs of renal replacement therapy allows only 10% to get dialysis and 4-5% transplants. Our center, a government organization, started a dialysis and transplant program in 1980s where all services were provided free of charge to all patients. It was based on the concept of community government partnership funded by both partners. The guiding principles were equity, transparency, accountability and development of all facilities under one roof. This partnership has sustained itself for 30 years with an annual budget of $25 million in 2009. Daily 600 patients are dialyzed and weekly 10-12 receive transplants. One- and 5-year graft survival of 3000 transplants is 92% and 85%, respectively. The institute became a focus of transplantation in Pakistan and played a vital role in the campaign against transplant tourism and in promulgation of transplant law of 2007, and also helped to increase altruistic transplants in the country. This model emphasizes that in developing countries specialized centers in government sector are necessary for transplantation to progress and community support can make it available to the common man.

Living related renal transplants with lifelong follow-up. A model for the developing world.

AIMS: To describe the dynamic of a model of public government partnership for dialysis and transplantation in developing countries. MATERIALS: A model was established on the philosophy of public-government partnership to provide an integrated dialysis and transplant service "Free with dignity" with lifelong follow-up care and medications. The government provided 50% of funds and the public was motivated to donate the rest. This included affluent individuals, corporations, business houses and the general public. RESULTS: This model has been sustained for the last two decades. In 2008, 655,000 patients were treated at SIUT. Over 600 patients are dialyzed each day with a total of 165,411 dialysis sessions/year. Thus far 2,249 transplants have been performed, 431 in 2008. One- and 5-year graft survival rates were 92% and 85%, respectively. The laboratory performed 4.1 million tests and radiological investigations numbered 164,217. Over $ 6 million were spent on medications. Free services offered by the model have motivated the government to increase its funding from $ 2.1 million in 1998 to $ 10 million in 2008 and the public has matched these figures with total donations exceeding $ 20 million. CONCLUSIONS: For transplantation to be successful in developing countries, it has to be made available to the common people who constitute 90% of the population. Our model of public-government partnership has made dialysis and transplantation available to the disenfranchised with lifelong follow-up and medications. Transplantation has become relevant to them, resulting in societal acceptance of transplantation as a preferred mode of therapy. This has motivated society to support both living related and deceased donor programs.

Health status and renal function evaluation of kidney vendors: a report from Pakistan.

Unrelated kidney transplants have lead to commerce and kidney vending in Pakistan. This study on 104 vendors reports demographics, history, physical and systemic examination, ultrasound findings, renal and liver function and GFR by Cockcroft-Gault. Results were compared with 184 age, sex and nephrectomy duration matched living-related donors controls. Comparison of vendors versus controls showed mean age of 30.55 +/- 8.1 versus 30.65 +/- 7.85 (p = 0.91) years, M:F of 4.5:1 versus 4.2:1 and nephrectomy period of 33.89 +/- 30 versus 32.01 +/- 29.71 (p = 0.60) months respectively. Of the vendors 67% were bonded laborers earning <50 $/month as compared to controls where 68% were skilled laborers and self-employed earning >100 $/month. History of vendors revealed jaundice in 8%, stone disease in 2% and urinary tract symptoms in 4.8%. Postnephrectomy findings between vendors versus donors showed BMI of 21.02 +/- 2.8 versus 23.02 +/- 4.2 (p = 0.0001), hypertension in 17% versus 9.2% (p = 0.04), serum creatinine (mg/dL) of 1.17+/-0.21 versus 1.02 +/- 0.27 (p = 0.0001), GFR (mL/min) of 70.94 +/- 14.2 versus 95.4 +/- 20.44 (p = 0.0001), urine protein/creatinine of 0.150 +/- 0.109 versus 0.10 +/- 0.10 (p = 0.0001), hepatitis C positivity in 27% versus 1.0% (p = 0.0001) and hepatitis B positive 5.7% versus 0.5% (p = 0.04), respectively. In conclusion, vendors had compromised renal function suggesting inferior selection and high risk for developing chronic kidney disease in long term.

Non-HLA antibodies after rejection of HLA identical kidney transplants.

1. Non-HLA antibodies reactive against CLL and lymphoblast lines were detected by cytotoxicity in sera from 22 patients who had been transplanted with kidneys from HLA identical donors. 2. Whether these antibodies had been responsible for the rejection of the HLA identical grafts remain to be determined. 3. Among 71 patients who received HLA mismatched transplants, and had rejected their grafts, 65 (93%), formed antibodies to HLA or MICA antigens. The 5 patients who did not develop antibodies were shown to have antibodies against CLL and lymphoblast lines, suggesting that these grafts may have been rejected by non-HLA antibodies.

Improving kidney and live donation rates in Asia: living donation.

Organ transplantation started with organs donated by living subjects. Increasing demands brought cadaveric organ donation. The brain-death law, mandatory for this procedure, is prevalent in all countries involved in organ transplantation except Pakistan. Spain is the leading country in cadaveric organ donation (32.5 pmp). Despite the sources of living and cadaveric organs, both heart-beating and non-heart-beating, the gap between the demand and supply has widened. An example is the United States, where the numbers of patients on the waiting list for kidney transplantation have risen from 30,000 in 1988 to more than 116,000 in 2001. This has caused a resurgence in living donors all over the world. These can be related, unrelated, spousal, marginal, or ABO-incompatible donors. Family apprehensions, medical care costs, and nonexistent social security can be barriers to this form of organ donation. Unrelated organ donation can open the doors to commercialism. To make this process more successful, transplantation should be made reachable by all sectors of the population. This is possible when transplantation is taken to the public sector institutions and financed jointly by the government and community. To increase living organ donation especially in Asian countries, which face barriers of low literacy rates, ignorance, and cultural and religious beliefs, more efforts are needed. Public awareness and education play an important role. Appreciation and supporting the donors is necessary and justified. It is a noble act and should be recognized by offering job security, health insurance, and free education for the donor's children.

Management of pediatric urolithiasis in Pakistan: experience with 1,440 children.

PURPOSE: We evaluated the efficacy and safety of different modalities for pediatric urolithiasis in a developing country in 2 eras, namely before and after the advent of minimally invasive surgery. MATERIALS AND METHODS: We retrospectively reviewed the records of 1,440 children younger than 14 years treated with various modalities during a 14-year period. From 1987 to 1995, 486 and 50 patients were treated with open surgery, and extracorporeal shock wave lithotripsy (ESWL, Dornier Medical Systems, Inc., Marietta, Georgia) and minimally invasive methods, respectively. Between 1996 and 2000, 518 and 386 children were treated with surgery and minimally invasive methods, respectively. RESULTS: Of the 1,440 children 795 (55.2%) had renal, 198 (13.8%) had ureteral and 447 (31%) had bladder calculi. Of the renal stones 556 (70%), 177 (22%) and 62 (7.8%) were treated with open surgery, ESWL and percutaneous nephrolithotomy, respectively. Of the ureteral calculi 85 (43%), 37 (18.6%) and 76 (38%) were managed by ESWL, ureterorenoscopy and open surgery, respectively. Of the bladder calculi 307 (68%), 77 (17.2%) and 63 (14%) were treated with open vesicolithotomy, transurethral pneumatic cystolithotripsy and ESWL, respectively. The renal stone clearance rate was 98% after open surgery, 84% after ESWL and 68% after percutaneous nephrolithotomy monotherapy at 3 months of followup. Similarly the ureteral stone-free rate was 54% after ESWL and 86.9% after ureterorenoscopy. Of the patients with bladder calculi 48% and 93% become stone-free after ESWL and transurethral pneumatic cystolithotripsy, respectively. CONCLUSIONS: The use of ESWL, percutaneous nephrolithotomy and ureterorenoscopy has resulted in treating a large number of children with a short hospital stay and early return to school. Open surgery is reserved only for complex stones.

Pediatric urolithiasis: developing nation perspectives.

PURPOSE: We evaluated epidemiology, etiology, dietary and urinary risk factors, and the composition of calculi in pediatric stone formers in Pakistan. MATERIALS AND METHODS: This retrospective study includes 1,440 children treated between 1987 and 2000. Case records were reviewed for demographics, etiology and clinical symptoms. Dietary and urinary risk factors were analyzed prospectively in idiopathic stone formers. Stone composition was analyzed by infrared spectroscopy. RESULTS: There were 1,075 males and 365 females for a male-to-female ratio of 3:1. The peak age for renal and bladder stones was 6 to 10 and 1 to 5 years, respectively. Overall 795 stones (55%) were renal, 198 (14%) were ureteral and 447 (31%) were vesical. Bladder stones were present in 60% of cases in the mid 1980s but decreased to 15% in the mid 1990s. The clinical symptoms were abdominal pain in 511 patients (51%) and fever in 193 (19.5%). There were anatomical abnormalities in 96 patients (12%), metabolic abnormalities in 206 (25%), infection stones in 60 (7%) and idiopathic stones in 444 (55%). Urinary analysis in idiopathic stone formers revealed hypercalciuria in 17 (11%), hyperoxaluria in 62 (40%), hyperuricosuria in 41 (27%) and hypocitruria in 97 (63%). Diet involved a low intake of protein in 60 cases (44%), calcium in 45 (33%), potassium in 105 (77%) and high oxalate in 75 (55%). The composition was calcium oxalate in 362 stones (47%), ammonium hydrogen urate in 210 (27%) and struvite in 49 (6.4%). Stones recurred in 30 patients (2%). CONCLUSIONS: The pattern of calculous disease changed from a predominantly lower tract site in the mid 1980s to the upper tract in the mid 1990s. Stone composition, urinary risk factors and dietary analysis suggest that diet, dehydration and poor nutrition are the main causative factors of stone disease.

Living-related pediatric renal transplants: a single-center experience from a developing country.

We retrospectively analyzed the results of 75 living-related pediatric renal transplants performed at our center between January 1986 and December 1999. The major causes of end-stage renal disease (ESRD) were glomerulonephritis (26%) and nephrolithiasis (16%), while the etiology was unknown in 50%. The mean age of the recipients was 12 yr (range 6-17 yr) and that of the donors was 39 yr (range 20-65 yr). The majority (73%) of donors were parents. Eighty five per cent of donors were one-haplotype matched and the rest identical. Immunosuppression was based on a triple drug regimen. Thirty per cent of recipients were rapid metabolizers of cyclosporin A (CsA) (area under the curve [AUC]: < 6,000 ng/mL/h), while 16% were slow metabolizers (AUC: > 8,000 ng/mL/h). Forty three (57%) children encountered 59 rejection episodes, the majority of which (59%) were recorded in the first month post-transplant. Seventy-four per cent of the rejection episodes were steroid sensitive and the rest, except two, were resolved by therapy with antithymocyte globulin (ATG) or orthoclone thymocyte 3 (OKT3). After a mean follow-up of 37 months, 17 (22%) grafts had chronic rejection and 76% of these recipients had previously experienced acute rejection episodes. The overall infection rate was high, necessitating two hospital admissions/patient/year. The majority (53%) of the infections were bacterial. Urinary tract infections (UTIs) were seen in 17 (23%) recipients. Twelve of these had ESRD as a result of stone disease and eight grafts were lost because of UTIs. Eight per cent of recipients developed tuberculosis (TB), and extra-pulmonary lesions were seen in 50%. Surgical complications were encountered in eight patients. Free medication to all recipients and parental support ensured a compliance rate of 93%. Baseline growth deficit was seen in children of the two groups studied (the 6-12 yr and 13-17 yr age-groups), with Z-scores of - 2.39 and - 2.12, respectively. No growth catch-up was observed at 12 and 24 months in either group. Post-donation complications were seen most commonly in donors > 50 yr of age and included: proteinuria (> 300 mg/24 h, four patients), hypertension (three patients), and diabetes (one patient). Twenty-four grafts were lost, 54% as a result of immunological and the rest as a result of non-immunological causes, and 17 recipients died during the follow-up period. Infections were the main cause of patient and graft loss. Overall 1- and 5-yr graft and patient survival rates were 88% and 65%, and 90% and 75%, respectively.

Renal transplantation in Pakistan.

The economic indicators of Pakistan show that the GNP is dollar 70 billion and foreign exchange reserves stand at dollar 8.0 billion and foreign debt at more than dollar 36 billion. Against this backdrop, the government is unlikely to provide state-of-the-art facilities for management of end-stage organ failure. The unequal distribution of wealth leaves more than 40% below the poverty line. Economic solutions are based on temporary fixes where foreign aid and loans keeps the government machinery operational. Many of the basic health measures such as immunization are also foreign funded. Under such a scenario, local philanthropy has come to play a vital role. SIUT developed a model based on self-help--a model based on a community-government partnership, where the doctor plays the pivotal role and the beneficiary is the patient. SIUT acquired funds by developing a community-government partnership. The government fulfills about 40% of the total budget and the rest comes from the community as donations. The scheme has been extremely successful in providing free medical care and renal support to thousands of patients. It has been sustained over the past 15 years through complete transparency, public audit and accountability. These confidence-building means stimulate the community to come forward and donate money, equipment and medicines. The goal of transplantation is to provide organs to all with long-term survival of the graft. The emerging challenges to achieve this goal and efforts that can be made to increase and sustain transplant activity in Pakistan require a concerted effort on the part of the government, society and the medical profession.