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.

The level and distribution of selected organochlorine pesticides in water of River Satluj Pakistan.

The study was aimed to identify different environmental factors (selected organochlorine pesticides) affecting the river water of Satluj. River Sutlej is about 1400 kilometers long and its water is extensively used for irrigation in Punjab, located both in India and Pakistan, which was also a reason of dispute between both countries for its water share. The study area was divided into four zones, Sulemanki Zone, Islam Zone, Mailsi Syphone Zone and Panjnad Zone. Liquid Liquid Extraction (LLE) technique was used for the collected water samples followed by high performance liquid chromatography (HPLC) UV-Visible detector The current finding revealed that aldrin was not detected during summer period in water samples of SZ-1 (Sulemanki Barrage), SZ-2 and SZ-3 (Maisli Siphon) of the study area. Lindane and DDE were found more in the samples of sediments from the study area at SZ-4 ranging from 2.238-8.226 ppb and 4.234-6.876 ppb, respectively. Heaptachlor (in sediments) was found to be0.032-234 ppb only at SZ-4.Endosulfan concentrations in water (winter) at SZ-3 was 0.06 ppb and at SZ-4,it was 0.05 ppb; dieldrin in water (winter) at SZ-4 was 0.0314 ppb and heptachlor was detected at SZ-1 (0.0315 ppb) and SZ-2 (0.0310 ppb) in water during winter season, were reaching to the Maximum Concentrations Limits (MCL), while all other residues investigated were found below the MCLin all the compartments of the study area set by various agencies like WHO/FAO- Codex Alimenterious. Present findings revealed that although the organochlorine pesticides are banned for agricultural use in many countries, including Pakistan, their presence in various samples might be due to illegal use of these pesticides in the study area and its neighboring regions. The overall study area comprises of mainly urban, suburban and agricultural land being the largest cotton growing area of the country. There is a need to take serious steps to minimize water pollution caused by pesticides to achieve a healthy lifestyle.

Presence of selected organochlorine pesticides (OCPs) in sediments and biota of River Satluj, Pakistan: first report.

In the developed countries, the use of OCPs (organochlorine pesticides) has been banned. However, in South Asia several of them are still in use. In Pakistan and India a constant addition of OCPs into the atmosphere has been indicated by various researchers. In this study levels of selected organochlorine pesticide residues were assessed in sediment and biota collected from four (4) water reservoirs (3 Barrages & 1 Siphon) on the River Satluj Pakistan, along 231 miles (372 km) of River stretch which was further divided into 12 sampling sites. It was aimed to find out the levels of organochlorine pesticide (OCPs) residues in sediments and from selected fish species (Labeo rohita, Wallagu attu, Cyprinus carpio) of the River Satluj Pakistan. The Organochlorine residues (seven pesticides) present in samples of sediments and biota were investigated through multi residue method, using Gas Chromatograph (GC-ECD).In the current study, the concentration of DDT, was investigated in Wallago attu (0.786-3.987 ppb), Labeo rohita (0.779-4.355 ppb) and Cyprinus carpio (1.234-5.654 ppb). DDE was also found in Cyprinus carpio (1.244-6.322 ppb), Wallag attu (0.877-4.221 ppb) and Labeo rohita (2.112-5.897 ppb). Aldrin was not observed in Labeo rohita and Wallago attu. Currently, lindane and DDE was found predominately high in the sediments of study area at SZ-4 (Panjnad Barrage) ranging (2.238-8.226 ppb) and (4.234-6.876 ppb), respectively. Heaptachlor was found only at SZ-4 (Panjnad Barrage) from the sediments with concentration ranging (0.032-234 ppb). In short all other residues investigated were found below the MCL (maximum concentration level) in all the compartments of the study area set by various agencies like WHO/FAO- Codex Alimenterious.

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.

Human organ and tissue transplantation in Pakistan: when a regulation makes a difference.

Organ transplantation must be viewed in relation to the prevailing cultural, religious and economic conditions of a nation. Over the past two decades, Pakistan has emerged as one of the largest centres for commercial renal transplantation. Government efforts, supported by professional associations, civil society organizations and the media, along with World Health Organization technical assistance, have led to the development of legislation regulating this practice and curbing organ trade in conformity with international guidelines. Although only two years have passed since the enactment of the law, there is evidence that conditions have significantly improved, raising hopes for ethical and safe organ transplantation in Pakistan. This study reviews the salient features of the legislation and lists the foreseeable evolving challenges and opportunities.

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.

Anthropometric indices of middle socio-economic class school children in Karachi compared with NCHS standards--a pilot study.

OBJECTIVE: To measure height and weight of school going children (2-18 years of age) in Karachi. By means of these parameters we were able to document where the Pakistani paediatric population plot on NCHS growth centile charts. METHODS: A population based cross-sectional study (in government and private schools, Karachi), in which height and weight were taken using standardized techniques. Two thousand two hundred forty five healthy school-going children 2 to 16 years of age (calculated from date of birth); sex, height and weight were documented. After the survey was completed, height and weight of the children were plotted on NCHS centiles curves. RESULTS: P5, P25 and P50 centiles for height and weight of the Pakistani girls and boys was much below that of NCHS. However, P95 for boys and girls weight and height did not differ markedly in the Pakistani and NCHS centiles. CONCLUSION: Height and weight of these children is below the NCHS centile for height and weight. Children plotting near the P95 NCHS, indicates that obesity may be a serious concern in our population. However, further studies are required for support. This pilot study indicates the need for development of centile charts for Pakistani paediatric population.

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.

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.

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.

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.

Human organ and tissue transplantation in Pakistan; when a regulation makes a difference

Organ transplantation must be viewed in relation to the prevailing cultural, religious and socio-economic conditions of a nation. Over the past two decades, Pakistan has emerged as one of the largest centres for commercial renal transplantation. Government efforts, supported by professional associations, civil society organizations and the media, along with World Health Organization technical assistance, have led to the development of legislation regulating this practice and curbing organ trade in conformity with international guidelines. Although only two years have passed since the enactment of the law, there is evidence that conditions have significantly improved, raising hopes for ethical and safe organ transplantation in Pakistan. This study reviews the salient features of the legislation and lists the foreseeable evolving challenges and opportunities