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Pakistan is a low-middle income country where incidence of End Stage Kidney Disease (ESKD) is 100-150 per million population (pmp). Paucity and high costs of renal replacement therapy (RRT) renders the majority disfranchised, since the dialysis rate is 15 pmp and the transplant rate is 4-5 pmp. In view of this, our center started an integrated dialysis and transplant program where all treatment is provided "Free of Cost" to all patients, with lifelong follow-up and medications. The model is based on the concept of community-government partnership funded by both partners. The annual contribution in 2021 was $37.4 million. >1,500 patients were dialyzed daily, and 6-8 received transplants weekly. Of the 6,553 transplants performed between 1985-2021, 988 (15%) were children. Overall, the 1 and 5-year graft survival rate was 97% and 88%. The donor clinic has 3,786 donors in regular yearly follow-up for up to 30-35 years where ESKD prevalence is 0.29%. Access to dialysis was increased by establishing six satellite centers reducing patient time and travel costs. Cost reductions by dialyzer reuse and generic drugs resulted in an annual saving of $5.8 m. This sustainable model has overcome the inherent socio-economic, logistic, cultural, and gender biases in RRT in LMICs. It has provided RRT with equity to the disfranchised in Pakistan and can be replicated in other LMICs with community-government support., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zafar and Rizvi.)

Introduction/aim: The Luminex assay, where beads are coated with a single HLA antigen, has been shown to detect HLA antibodies with more sensitivity and specificity as compared to microlymphocytotoxicity (CDC) assay and flow cross match (FCXM). We report the impact of low Mean Flourescence intensity (MFI) pre-transplant DSA by Luminex with negative CDC and FCXM on acute rejection, graft function, and survival., Methods: In this retrospective study between January 2015 to December 2021, 45 recipients had pre-transplant anti-HLA donor-specific antibodies (DSAs) detected by Luminex. Two control groups of 45 patients each matched for age and gender, first with non-DSA HLA antibodies and second with no antibodies by Luminex were selected to compare outcomes with DSA group., Results: In the DSA group of 45, 22 (48.8%) had class I (MFI mean 4043 ± 1909, range: 1096-7111), 20 (44.4%) class II (MFI mean 3601 ± 2310, range: 1031-9259), and 3 (6.6%) both class I (MFI mean 4746 ± 1922) and class II (MFI mean 3940 ± 2312) antibodies. Acute rejection episodes were reported in 15.6%, DSA group, 17.8% in non-DSA, and 24.4% in no antibody group (p = .538). Death censored graft survival at 1 and 5 years was 98% and 93% in DSA group, 100% and 95% in non-DSA and 93% and 85% in the no antibody group (p = .254)., Conclusions: Patients with low MFI DSA pre-transplant, with a negative CDC and FCXM under ATG induction, have similar graft outcomes at 1 and 5 years when compared to non-DSA and no antibody groups., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Recurrent urinary tract infections (UTIs) after kidney transplantation are a common problem adversely affecting graft outcomes. This retrospective study aimed to report the frequency and risk factors of recurrent UTI and their impact on graft and patient outcomes in kidney transplant recipients at the Sindh Institute of Urology and Transplantation, Karachi, Pakistan, in January-December 2015. Five-year graft and patient survival rates were compared among different groups using Kaplan-Meier analysis. Of the 251 recipients, 67 developed one episode of UTI. Of these 67, 29 had 76 episodes of recurrent UTI. Out of the 76 episodes of recurrent UTI, Escherichia coli was the most common pathogen in 32 cases. Organisms causing recurrent UTI showed resistance to carbapenem in 19 cases versus 2 in the non-recurrent UTI group (P = 0.006). The estimated glomerular filtration rate at 1 year was 57.8 ± 16.23 mL/min/1.73 m2 in the recurrent UTI group vs. 61.9 ± 15.7 mL/min/1.73 m2 in the non-recurrent UTI group (P = 0.001). Graft survival in the recurrent UTI group at 5 years was significantly lower (76%) than in the non-recurrent UTI (95%) and no UTI groups (93%) (log-rank P = 0.006), with no significant effect on patient survival in these groups (P = 0.429). The presence of double-J stent (P = 0.036) and cytomegalovirus infections (P = 0.013) independently predicted recurrent UTI. Recurrent UTIs are common in low-resource settings and adversely affect graft outcomes. Appropriate prophylaxis and treatment are important to reduce recurrent UTI to improve graft outcomes., (Copyright © 2022 Copyright: © 2022 Saudi Journal of Kidney Diseases and Transplantation.)

This study was carried out to determine the impact of one-year posttransplant serum creatinine (SCr) levels on the long-term outcomes of living-related donor kidney transplants. A retrospective cohort study included 773 adult living-related renal transplant recipients from 2010 to 2012, with a minimum follow-up period of five years. Demographics and posttransplantation follow-up data including immunosuppression regimens, rejection episodes, and survival rates were evaluated. Patients were divided into four cohorts (G1, G2, G3, and G4 based on SCr at the end of the 1 st year: G1, SCr <88.4 μ mol/L; G2, 88.5≤ SCr ≤ 132.6 μmol/L; G3, 132.7≤ SCr ≤176.8 mol/L; and G4, SCr ≥176.9 μ mol/L). Comparisons between the groups used the Chi-square test for qualitative parameters and analysis of variance for continuous variables. Five-year graft survival for G1 was 98% as compared to 76% in G4 (P <0.001). Recipients of G4 encountered more acute rejection episodes in 21% of the cases as compared to 7.3% in G1 (P = 0.001). Donors were older in G4 (42.07 ± 10.4 years) as compared to G1 (30.1 ± 8.5 years) (P = 0.001). A third of the donors in G1 were HLA identical as compared to 7% in G4. Prediction of long-term graft survival is possible by the SCr level at one year post transplant. This can be of great importance, especially to identify those patients who require close monitoring in follow-up. Donor age, HLA, and acute rejection impact SCr at one year and hence graft outcome.

Objectives: Plasma cell-rich acute rejection is an aggressive form of acute rejection that occurs late after transplant and is usually resistant to standard antirejection therapy. This study reports the safety, efficacy, and outcomes of plasma cell-rich acute rejection after treatment with bortezomib, a proteasome inhibitor, in 10 patients after a first living-related renal transplant., Materials and Methods: Plasma cell-rich acute rejection was diagnosed using the 2007 Banff classification. The treatment protocol for plasma cell-rich acute rejection included methylprednisolone (500 mg/kg), 7 sessions of plasmapheresis, antithymocyte globulin (3-5 mg/kg/day for 10 days), rituximab (2 doses at 375 mg/m2), and bortezomib (1 cycle at 1.3 mg/m2)., Results: The mean age of recipients and donors was 23.70 ± 11.39 and 37.30 ± 12.82 years, respectively. The mean time to plasma cell-rich acute rejection was 3.1 ± 2.5 years. The mean serum creatinine level at rejection was 4.8 ± 2.7 mg/dL. After treatment, serum creatinine decreased to 3.3 ± 1.8 mg/dL. Serum creatinine levels at 1-year and 2-year follow-up were 3.0 ± 2.3 and 3.3 ± 0.9 mg/dL, respectively. There was 1 graft failure due to recurrence of glomerulonephritis/de novo glomerulonephritis. No significant adverse effects were noted in the patients. Bortezomib successfully reverted plasma cell-rich acute rejection and stabilized graft function, with patients showing 2-year graft survival after rejection of 90%., Conclusion: Bortezomib-based treatment was successful in reverting plasma cell-rich acute rejection and stabilizing graft function, with graft survival of 90% at 2 years. Further studies with large cohorts and randomized trials with or without bortezomib will help in better evaluation of its efficacy, safety, and outcomes.

Aim: Living donor kidney is the main source of donor organs in low to middle income countries. We aimed to develop a living donor risk model that predicts graft and patient survival in an emerging economy., Methods: We used data from the Sindh Institute of Urology and Transplantation (SIUT) database (n = 2283 recipients and n = 2283 living kidney donors, transplanted between 1993 and 2009) and conducted Cox proportional hazard analyses to develop a composite score that predicts graft and patient survivals., Results: Donor factors age, creatinine clearance, nephron dose (estimated by donor/recipient body weight ratio) and human leukocyte antigen (HLA) match were included in the living donor risk model. The adjusted hazard ratios (HRs) for graft failures among those who received a kidney with living donor scores (reference to donor score of zero) of 1, 2, 3 and 4 were 1.14 (95%CI: 0.94-1.39), 1.24 (95%CI:1.03-1.49), 1.25 (95%CI:1.03-1.51) and 1.36 (95%CI:1.08-1.72) (P-value for trend =0.05). Similar findings were observed for patient survival., Conclusions: Similar to findings in high income countries, our study suggests that donor characteristics such as age, nephron dose, creatinine clearance and HLA match are important factors that determine the long-term patient and graft survival in low income countries. However, other crucial but undefined factors may play a role in determining the overall risk of graft failure and mortality in living kidney donor transplant recipients., (© 2016 Asian Pacific Society of Nephrology.)

Objectives: Our aim was to analyze the immunohistopathologic features of plasma cell-rich acute rejection in a living-related renal transplant setting., Materials and Methods: Renal allograft biopsies of 50 cases of plasma cell-rich acute rejection were reviewed, and the main immunohistopathologic features were analyzed. The biopsies were studied using light microscopy, immunofluorescence, and immunohistochemistry and reported according to Banff classification. Biopsy findings were correlated with graft function and outcome., Results: From February 2012 to December 2013, 50/1630 (3%) dysfunctional renal allograft biopsies showed plasma cell-rich acute rejection. Among acute changes, interstitial inflammation was of moderate degree in 8 cases (16%) and severe in 42 cases (84%). Mild tubulitis was found in 4 cases (8%), moderate tubulitis in 8 cases (16%), and severe tubulitis in 38 cases (76%). Glomerulitis was found in 2 cases (4%). No presence of arteritis was found. All plasma cell-rich acute rejection cases were of tubulointerstitial type, and most were of type IB. The mean percent of plasma cells on light microscopy in all cases was 28.8 ± 11.7%, and the range was 10% to 60%, with 46 cases (92%) showing plasma cell percent of ≥ 20%. The mean plasma cell percent on immunohistochemistry for CD138 was 29.0 ± 12.4%. Microvascular inflammation was found in 34 cases (68%). C4d testing was done by immunofluorescence in 22 cases (44%) and was positive in 8 cases (36%). Interstitial fibrosis/tubular atrophy was mild in 18 (36%), moderate in 28 (56%), and severe in 4 cases (8%). Plasma cell enrichment did not correlate with a variety of clinical and pathologic features (all P > .05)., Conclusions: Plasma cell enrichment is not an independent prognostic morphologic feature and may represent either T-cell-mediated or antibody-mediated rejection or a mixture of these processes. Further investigations regarding its pathogenesis, accurate categorization, and treatment are needed.

Objectives: Our aim was to determine the clinical significance of borderline lymphocytic infiltrates on indicated renal allograft biopsies in a living related renal transplant setting., Materials and Methods: The study was conducted at the histopathology department of Sindh Institute of Urology and Transplantation. A retrospective review of 421 renal transplant patients was conducted from October 2007 to September 2008 to identify patients in whom a histologic diagnosis of borderline changes was made on dysfunctional renal allograft biopsies. Demographic, clinical, and laboratory data; biopsy findings; treatments given; and responses to treatment were collected and analyzed. Standard biopsy indications determined the need for graft biopsies. Biopsies were reported according to Banff criteria., Results: Mean age was 26.92 ± 9.14 years (range, 10-45) for recipients and 38.46 ± 9.16 years (range, 19-50) for donors. Males were predominant among recipients (84.6% vs 15.4%), and females were predominant among donors (57.7% vs 42.3%). The best serum creatinine levels were 1.79 ± 1.15 mg/dL (range, 0.83-6.12). These were achieved after a median of 3 days (interquartile range, 2-7.25). Dysfunctional biopsies exhibiting borderline infiltrates were performed at a median duration of 5.5 days (interquartile range, 3-14.25). Mean serum creatinine at the time of biopsy was 2.34 ± 1.43 mg/dL (range, 1.25-8.25). The biopsies showed borderline cellular infiltrates (interstitial inflammation 1 [i1] and tubulitis 1 and [t1] lesions). All recipients except one received antirejection treatment (antithymocyte globulin, n = 5; escalation of mycophenolate mofetil dosage, n = 1; pulse steroids, n = 19); all recipients responded with a decline in serum creatinine toward baseline, with a mean serum creatinine of 1.31 ± 0.42 mg/dL (range, 0.40-2.71). This response was achieved at a median duration of 9.73 ± 5.32 days (range, 1-23) after starting treatment., Conclusions: The borderline cellular infiltrates on dysfunctional renal allograft biopsies signify evolving phases of acute cellular rejection. These infiltrates responded favorably to antirejection treatment in our setting.

Kidney paired exchange is an established method of overcoming incompatibility in donor-recipient pairs and expanding the living-donor pool. It is infrequently performed in developing countries. We report the first kidney paired exchange in Pakistan, successfully performed at our center. One donor-recipient pair consisted of a 38-year-old female recipient (blood type, B positive) and her 40-year-old husband (A positive) as the potential donor. The second pair consisted of a 30-year-old male recipient (A positive) and his 30-year-old wife (B positive) as the potential donor. The donors were exchanged with the recipients, and both pairs were antigen matched for human leukocyte antigen A and human leukocyte antigen DR. Luminex antibody screening was negative, as were the crossmatches for T and B cells and for IgG and IgM. The transplant procedures and recoveries proceeded uneventfully. The recipients are maintaining serum creatinine levels around 0.78 mg/dL and 0.90 mg/dL, 1 year after transplant. Kidney paired exchange is a relatively low-cost option for overcoming the barrier of incompatibility in a resource-constrained setting.

Background: Long-term follow-up and management of donors was undertaken in a specialist kidney transplant unit in Pakistan to identify risk and prevent adverse outcomes in living related kidney donors., Methods: In an observation cohort study between 1985 and 2012, 3748 donors were offered free medical follow-up and treatment 6 to 12 months after donation and annually thereafter. Each visit included history, physical examination, blood tests for renal, lipid, glucose profiles, and 24-hour urine for proteinuria and creatinine clearance. Preventive intervention was undertaken for new onset clinical conditions. Donor outcomes were compared with 90 nondonor healthy siblings matched for age, sex, and body mass index., Results: Of the 3748 donors, 2696 (72%) were in regular yearly follow-up for up to 27 years (median, 5.6; interquartile range, 7.9). Eleven (0.4%) died 4 to 22 years after donation with all-cause mortality of 4.0/10 000 person years. Six (0.2%) developed end-stage renal disease 5 to 17 years after donation, (2.7/10 000 person years). Proteinuria greater than 1000 mg/24 hours developed in 28 patients (1%), hypertension in 371 patients (13.7%), and diabetes in 95 patients (3.6%). Therapeutic intervention-controlled protein was less than 1000 mg/24 hours, blood pressure was below 140/90 mm Hg, and glycemic control in 85% up to 15 years after onset. Creatinine clearance fell from 109.8 ± 22.3 mL/min per 1.73 m predonation to 78 ± 17 at 1 year, 84 ± 19 at 5 years, and 70 ± 20 at 25 years. Comparison of 90 nondonor sibling and donor pairs showed significantly higher fasting glucose and hypertension in nondonors., Conclusions: Long-term follow-up of donors has demonstrated end-stage renal disease in 0.6% at 25 years. Regular follow-up identified new onset of disease and allowed interventions that may have prevented adverse outcomes.

Background: Acute rejections (ARs) with plasma cell-rich infiltrates (PCARs) are associated with poor outcomes., Patients and Methods: Between February 2012 and December 2013, 1630 dysfunctional renal graft biopsies were performed. Of these, 50 (3%) showed PCAR. ARs with >10% plasma cells were defined as PCAR. Human leukocyte antigen (HLA) antibodies were tested in historic sera and at the time of PCAR. Treatment for PCAR comprised methylprednisolone, antithymocyte globulin, plasmapheresis, and anti-CD20 antibody., Results: Of the 1630 dysfunctional biopsies, 50 (3%) had PCAR which occurred 3.1 ± 2.55 yr after transplant. The percentage of plasma cells was 28.8 ± 11.7, and CD138, 29.0 ± 12.4. Donor-specific antibodies (DSAs) were found in 32 (64%) overall, Class I in 15% and Class II in 65%. Post-treatment serum creatinine improved from 3.80 ± 2.59 to 2.66 ± 1.59 mg/dL in DSA positive (p < 0.003) and from 2.59 ± 1.09 to 2.08 ± 0.86 mg/dL in DSA negative (p < 0.008). One- and two-yr graft survival after PCAR was 72%, 42% in the DSA-positive vs. 89%, 82% in the DSA-negative group, respectively (p = 0.071)., Conclusions: Our results show that PCAR occurs late after transplant and in many cases is associated with DSAs. Graft outcome was poor when PCAR was associated with DSAs., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: To determine Serum Cystatin C (S.CysC) levels in healthy potential kidney donors and its correlation with Serum Creatinine (S.Cr), Glomerular filtration rate (GFR) by 24 hour urinary Creatinine clearance (CCL) and GFR by formulae of Cockcroft Gault (CCG) and Modification of diet in Renal Disease (MDRD)., Methods: A Cross sectional study was conducted at Sindh Institute of Urology and Transplantation (SIUT), Karachi, between June and December 2012. One hundred and three potential healthy kidney donors were enrolled in the study to measure their S.CysC and correlate it with S.Cr, CCL and GFR by CCG and MDRD. Statistical analysis was done by SPSS 17., Results: The mean age of the healthy kidney donors was 32.19 + 8.27 years with a M:F ratio of 1.86:1. The mean Serum Creatinine (S.Cr) was 0.86 + 0.18 mg/dl and mean S.CysC was 0.88 + 0.12 mg/dl. S.CysC showed significant correlation with S.Cr (r = 0.78, p < 0.001), CCL (r = 0.67, p < 0.001), GFR CCG (r = 0.54, p < 0.001) and GFR MDRD (r = 0.67, p < 0.001). Correlation of S.CysC was better than S.Cr for CCL, S.Cr (0.60) vs S.CysC (0.67) and GFR CCG, S.Cr (0.41) vs S.CysC (0.54). Correlation was comparable for MDRD, S.Cr (0.67) vs S.Cys (0.67)., Conclusion: S.CysC is better marker of kidney function in potential healthy kidney donors. It is a reliable, convenient and economical marker that can be used especially in routine clinical practice.

Objectives: We evaluated cystatin C concentration as a marker of glomerular filtration rate in renal transplant recipients, and its correlation with creatinine-based glomerular filtration rate by urinary creatinine clearance, and the Cockroft-Gault and Modification of Diet in Renal Disease formulas., Materials and Methods: In this cross-sectional study, we measured serum cystatin C levels and its correlation with serum creatinine, creatinine clearance, and glomerular filtration rate using the Cockroft-Gault formula and Modification of Diet in Renal Disease formulas., Results: One hundred two recipients between June and December 2012, were examined. The mean subject age was 31.87 ± 8.37 years; the male:female ratio was 4.3:1. Mean serum creatinine concentration was 141.44 ± 43.31 mol/L (1.60 ± 0.49 mg/dL) and serum cystatin C 122.09 ± 38.95 nmol/L (1.63 ± 0.52 mg/L). Serum cystatin C was significantly correlated with serum creatinine (r=0.90; P<.001), creatinine clearance (r=0.77; P<.001), and the Cockroft-Gault (r=0.73; P<.001) and the Modification of Diet in Renal Disease formulas (r=0.82; P<.001). We assessed the correlation among serum cystatin C with serum creatinine, creatinine clearance, the Cockroft-Gault and Modification of Diet in Renal Disease at 1, 2-3, 4-5, and more than 5 years after transplant. The correlation between serum cystatin C and serum creatinine ranged from 0.8 to 1.0; cystatin C and creatinine clearance ranged from 0.8 to 0.85; serum cystatin C and the Cockroft-Gault Formula ranged from 0.7 to 0.8; and serum cystatin C and the Modification of Diet in Renal Disease formulas ranged from 0.8 to 0.84., Conclusions: Our results show that serum cystatin C is a reliable marker for estimating glomerular filtration rate among renal transplant recipients. This test can determine the glomerular filtration rate of renal transplant recipients on follow-up. Further studies are required to establish serum cystatin C as a standard test for monitoring glomerular filtration rate in transplanted patients.

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., (© Copyright 2013 The American Society of Transplantation and the American Society of Transplant Surgeons.)

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., (©2011 The Authors Journal compilation © 2011 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Objective: To asses the prevalence of post-transplant renal tubular acidosis (RTA) and its associated risk factors., Methods: A cross-sectional study was conducted on 100 live related renal transplant recipients, with a transplant duration of more than one year and an estimated GFR > 40 ml/min/1.73m2. Patients with acute graft rejection within last 6 months, unstable graft function, acute urinary tract infection and diarrhoea were excluded. Renal Tubular Acidosis (RTA) was diagnosed on the basis of plasma bicarbonate, venous pH, urine and serum anion gap measurements., Results: Out of 100 patients (74 male, 26 female) RTA was observed in 40 (29 male, 11 female). Patients with RTA had a lower GFR (65.87 +/- 12.35 versus 74.23 +/- 14.8 ml/min/1.73m2, P = 0.004) and higher number of previous acute rejections. Lower bicarbonate was associated with higher serum chloride (108.2 +/- 3.19 versus 105.72 +/- 3.9 mEq/L, P = 0.001) and higher potassium concentration (3.95 +/- 0.53 vs 3.61 +/- 0.46 mg/dl, P = 0.001). Higher phosphorous level (3.46 +/- 0.71 in RTA vs 3.19 +/- 0.59 mg/dl in non-RTA, P = 0.045) but lower total serum calcium concentrations were found in patients with RTA. Intake of angiotensin converting enzyme inhibitors (ACE 1) was associated with the development of RTA. Calcineurin inhibitor (CNI) therapy was not associated with an increased likelihood of RTA. While no difference was noted in sex, age, pre-transplant dialysis duration, post transplant period, body mass index and serum albumin levels., Conclusion: There is a high prevalence of RTA in renal transplant recipients. In most of the patients, this is subclinical and does not require treatment.

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.

Purpose of Study: The present review summarizes the findings of most important reports on pediatric transplants from the developing world and highlights the challenges and results of the activity., Recent Findings: In the past 3 years, 10 reports appeared in the literature on pediatric renal transplantation and further six more in the past 5 years. The experience ranges from 1 to 28 years for 11-300 transplants. Recipients were older than 6 years and donors were living relatives in more than 94% of the series. Cyclosporine, azathioprin and steroids are the mainstay of immunosuppression and in many centres the high costs of drugs resulted in noncompliance and discontinuation of immunosuppression. Therefore, acute rejection rates were high, more than 40% in half of the series. One-year and 5-year survival rates for grafts were 89-98% and 67-84% and for patients 88-98% and 65-90%, respectively. Major causes of graft loss were chronic rejection, acute rejection and infection and for the patients, it was infection. Growth analysis is not generally reported but when reported the deficit remains or gets worse., Summary: Pediatric transplantation activity in the developing world is limited to older children using mostly living related parental donors. High rejection and infection rates result in poor patient and graft survival.

Donor shortage and absence of transplant law lead to unrelated commercial transplants in Pakistan. We report the socio-economic and outcome parameters of 126 local recipients of unrelated kidney vendor transplants presenting to our institute between 1997 and 2007. Their outcome was compared with 180 recipients of living-related donor transplants matched for age, gender and transplant duration as controls. Age of commercial recipients was 35.63 +/- 11.57 years with an M:F ratio of 2.4:1. Majority (92%) were transplanted in northern Pakistan paying US$7271 +/- 2198. All were educated with 50% being graduates or above and rich earning a monthly salary of US$517 +/- 518 with 44% earning >US$500. Comparison of commercial recipients with controls showed high comorbidities 35 (28%) vs. 14 (8%) (P = 0.0001) with diabetes, hepatitis-C and cardiovascular diseases. Donor age was 29.97 +/- 6.16 vs. 32.63 +/- 9.3 years (P = 0.035). Biologic agents induction in 101 (80%) vs. 14 (8%) (P = 0.0001), acute rejections in 42 (33%) vs. 31 (17%) (P = 0.005), 1-year creatinine 1.84 +/- 1.28 vs. 1.27 +/- 0.4 mg/dl (P = 0.0001), surgical complications 28 (22%) vs. 14 (8%) (P = 0.001), tuberculosis 14 (11%) vs. 6 (6%) (P = 0.007), acute hepatitis 20 (16%) vs. 3 (2%) (P = 0.0001), cytomegalovirus 33 (26%) vs. 21 (11%) (P = 0.001) and recurrent urinary tract infection 35 (28%) vs. 30 (16%) (P = 0.034). Overall 1- and 5-year graft survival was 86% and 45% vs. 94% and 80%, respectively (P = 0.00001). Total deaths were 34 (27%) vs. 12 (6.0%) (P = 0.001). In conclusion, recipients of the vended kidneys are poor candidates, educated, rich and often self-selecting. Their outcome is poor, which will leave them poorer still and back to dialysis if not death.

Objective: To evaluate the utility of serum CD30 (sCD30) levels as predictor of early acute graft rejection in live related renal transplant programme., Methods: This prospective study included 50 consecutive renal transplant recipients who received their first live related renal allograft at the Sindh Institute of Urology and Transplantation (SIUT) between October 2006 and March 2007. Blood samples were obtained one day before transplantation and on the third and fourteenth posttransplant days. Blood samples were also obtained from 50, age and sex matched healthy control individuals. Levels of serum sCD30 were measured by Enzyme Linked Immunosorbent Assay (ELISA)., Result: Donor-recipient blood group matching was identical in all patients. Pre-transplant lymphocyte crossmatch for T and B cells was negative, and panel reactive antibodies (PRA) were 0% for all recipients. The mean age of recipients was 31.6 +/- 10.23 years (range 5 to 55 years), while mean donor age was 32.74 +/- 8.48 years (range 21-50 years). Eleven (22%) recipients and donors were HLA identical while remaining (78%) were one haplotype match. Average serum sCD30 pre-transplant levels (37.8 +/- 4.97U/ml) were significantly higher than those of healthy individual's mean value of 8.48 +/- 4.97 U/ml, (P = 0.001). Eight (16%) patients developed acute rejection episode during this follow up period. Rejections were described and classified according to BANFF 97 classification., Conclusion: In this small single center study the serum levels of sCD30 did not show any significant difference between rejection and non rejection group in our transplant population.

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.

In recent years, Pakistan has emerged as one of the largest centres for commerce and tourism in renal transplantation. Kidney vendors belong to Punjab in eastern Pakistan, the agricultural heartland, where 34% people live below poverty line. We report results of a socioeconomic and health survey of 239 kidney vendors. The mean age was 33.6 +/- 7.2 years (M:F 3.5:1). Mean nephrectomy period was 4.8 +/- 2.3 years. Ninety per cent of the vendors were illiterate. Sixty-nine per cent were bonded labourers who were virtual slaves to landlords, labourers 12%, housewives 8.5% and unemployed 11%. Monthly income was $US15.4 +/- 8.9 with 2-11 dependents per family. Majority (93%), vended for debt repayment with mean debt of $1311.4 +/- 819. The mean agreed sale price was $1737 +/- 262. However, they received $1377 +/- 196 after deduction for hospital and travel expenses. Postvending 88% had no economic improvement in their lives and 98% reported deterioration in general health status. Future vending was encouraged by 35% to pay off debts and freedom from bondage. This study gives a snapshot of kidney vendors from Pakistan. These impoverished people, many in bondage, are examples of modern day slavery. They will remain exploited until law against bondage is implemented and new laws are introduced to ban commerce and transplant tourism in Pakistan.

Background: Post-transplantation lymphoproliferative disorder (PTLD) after heart transplantation is a fatal complication, and standard treatment is either ineffective or too toxic. We have studied the incidence, clinical course, prognostic factors, and different treatment regimens pertaining to PTLD in 110 heart and 80 kidney transplant recipients., Methods: Information was abstracted from chart review of 110 heart transplant recipients and 80 kidney transplant recipients between January 1989 and October 2002. We report 15 patients with PTLD, 6 patients received a heart transplant and 9 patients received a renal transplant., Results: The overall incidence of PTLD was 8.9% (5.4% in heart and 13.7% in kidney transplant recipients). The average interval between transplantation and the diagnosis of PTLD in heart transplantation patients was 5.5 years, and their overall mean age was 44 years. The indications for transplantation were ischemic cardiomyopathy in 5 patients (1 patient received both heart and kidney transplants), glomerulonephritis in 6 patients, diabetes nephropathy in 2 patients, and polycystic disease in 2 patients. Six patients were diagnosed with early disease (<12 months), 7 with late onset (1 to 10 years), and 2 with very late onset (>10 years). Five patients had PTLD grade 2 (2 heart and 3 kidney transplants) and 10 patients had PTLD grade 3 (4 heart and 6 kidney transplants). Immunosuppressive treatment for PTLD patients consisted of cyclosporine, 73% (11/15); tacrolimus, 6.6% (1/15); prednisone, 100% (15/15); azathioprine, 80% (12/15); mycophenolate mofetil, 20% (3/15); murine monoclonal anti-human CD3 (OKT3), 7% (1/15); and anti-thymocyte globulin, 13% (2/15). PTLD developed in 11.5% of patients with primary Epstein-Barr virus infection and in 28.9% of patients with primary cytomegalovirus infection. Five patients received rituximab therapy, 5 had conventional chemotherapy, 3 had radiotherapy, 3 had reduction in immunosuppression, 2 had ganciclovir, 1 underwent surgery, and 1 patient died before receiving treatment. The mortality rate was 26.6%. The average interval between transplantation and the diagnosis of PTLD in heart transplant recipients was 5.5 years. The mortality rate was significantly higher in the control group than in the rituximab group., Conclusions: Caucasian race and male gender were independent risk factors for developing PTLD. Pretransplant cytomegalovirus seropositive status is a strong predictor of developing PTLD. Management of PTLD requires randomized controlled trials of various chemotherapeutic and antiviral drugs regimens. Treatment of PTLD with rituximab is a beneficial alternative with a favorable outcome. Patients in whom primary Epstein-Barr virus, cytomegalovirus, or hepatitis C infection develop after transplantation should be managed with heightened surveillance for the development of PTLD. Further randomized trials are needed to evaluate the efficacy of antiviral drugs, intravenous immunoglobulin, interferon, and prophylactic Epstein-Barr virus immunization strategies.

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.

Objective: Evaluation of fractional excretion of Sodium, Potassium and Magnesium as indicators of cyclosporine (CsA) toxicity in de-novo renal transplant recipients., Methods: A prospective study was conducted on 59 live related renal allograft recipients. Fractional excretion(FE) of sodium (Na+), potassium (K+) and magnesium (Mg2+) were calculated on day 1, 3, 5 and 10 post transplant. Graft dysfunctions were evaluated by colour-Doppler, CsA levels and renal biopsy. Normal ranges were determined on 30 healthy subjects., Results: The mean creatinine on day 1 was 3.1 +/- 1.3 mg/dl and declined to 1.6 +/- 1.2 on day 10. FE of Na+, K+ and Mg2+ were 12 +/- 9%, 34 +/- 20% and 13 +/- 10% respectively on day 1 and reduced to 2.2 +/- 2%, 11 +/- 14% and 11 +/- 14% on day 10. Of the 59 recipients, 38 (64%) had uneventful recovery (group A), 21(36%) had graft dysfunction [6 acute rejection (group B) and 15 either acute tubular necrosis or high CsA(group C)]. In group A, on day 1, FENa+, FEK+ and FEMg2+ were 5 +/- 4%, 24 +/- 12% and 6.6 +/- 3% respectively and these declined to 1.2 +/- 0.6%, 4.6 +/- 0.7% and 6 +/- 3% respectively on day 10. Compared to group A, group C had significantly high values on day 1, FENa+ 15 +/- 8%, FEK+ 36 +/- 24% and FEMg2+ 21 +/- 10% (p < 0.0001) and on day 10, FENa+ 3.7 +/- 2.7%, FEK+ 20 +/- 15% and FEMg2+ 15 +/- 8% (p < 0.05). In the group B, day 1 and day 10 levels were FENa+ 6 +/- 3%, FEK+ 26 +/- 13% and FEMg2+ 7 +/- 2.8% and FENa+ 1.2 +/- 0.7%, FEK+ 4.2 +/- 0.5%, FEMg2+ 7 +/- 4% respectively. CsA levels and AUC did not correlate with CsA toxicity., Conclusion: FE of magnesium is a useful marker of CsA toxicity independent of CsA blood levels. FE studies can supplement renal biopsy findings.

Objective: To evaluate the effect of cyclosporine (CSA) on serum magnesium and its fractional excretion in renal transplant recipients., Methods: A cross sectional comparative study on 50 live related renal transplant recipients on CSA therapy with serum creatinine < 2.0 mg/dl and 30 healthy controls. Serum creatinine, magnesium and its fractional excretion and CSA levels were monitored. Patients were followed at 6 months., Results: The mean serum creatinine in patients was 1.41 +/- 0.42 mg/dl, cyclosporine 210 +/- 66 ng/ml at a dose of 4.8 +/- 1.4 mg/kg/day. The serum magnesium was 1.77 +/- 0.32 mg/dl vs 1.98 +/- 0.17 mg/dl in healthy controls (p < 0.05). Fractional excretion was 5.05 +/- 2.53% in patients vs 2.8 +/- 1.05% in controls (p < 0.05). No correlation was found between CSA levels (100-400 ng/ml) and serum magnesium (r = 0.053) or FEMg% (r = 0.215). Of the 50 recipients 27 (54%) had FEMg% in the control range. At 6 months follow up no difference in CSA levels was found between recipients with FEMg% in the normal range vs those with FEMg > 5%. However, serum creatinine increased from 1.42 +/- 0.30 mg/dl to 1.68 +/- 0.82 mg/dl (p < 0.05)., Conclusion: CSA therapy lowers serum magnesium as compared to healthy controls and there is marked increase in FEMg% in 50% of the patients. Patients with FEMg > 5% developed renal function deterioration. FEMg percent can thus be a good follow up marker of CSA chronic toxicity in stable transplant recipients.

DNA methods have resulted in improved renal allograft survival rates in cadaveric renal transplantation. This paper describes the impact of DNA typing by PCRSSP on a living related renal transplant (LRRT) programme. It evaluates error rates in serology, acute rejections, graft function and survival rates between the two typing methods. Serological typing was done on CTS 120 antisera Class 1 and 60 antisera Class 2 and 72 antisera Terasaki Class1 and 72 antisera Class2 Antigens. Low resolution PCR-SSP typing was done by 24 primers for HLA A , 48 for HLA B and 24 for HLA DR. Of the 585 transplants, 159 (Group I) were serology based, 172 serology and PCR-SSP for HLA DR (Group II) and 254 on serology and PCR-SSP for HLA A and B and only PCR-SSP for HLA DR (Group III). Error rates in serology as compared to PCR-SSP were 24% for HLA A, 16% for HLA B and 35% for HLA DR. Acute rejection in Group I were 39% Group II 30% and Group III 26% (p 0.02). Graft function of serum creatinine<1.5 mg/dl at 1 year was found in 26% of Group I patients as compared to 48% of Group III (p<0.0001). One and three year graft survival was 93% and 87% for Group II as compared to 81% and 69% for Group I respectively (p 0.0001). Matching by this combination of serology and PCR-SSP is not only economical for a developing country but also improves graft survival by 12% at 1 and 18% at 3 years.

Healthcare in developing countries less funded than developed nations (0.8 to 4% vs. 10 to 15%, respectively), and must contend against approximately 1/3 of the population living below the poverty line ($1US/day), poor literacy (58% males/29% females), and less access to potable water and basic sanitation. Cultural and societal constraints combine with these economic obstacles to translate into poor transplantation activity. Donor shortage is a universal problem. Paid donation comprises 50% of all transplants in Pakistan. Post-transplant infections are a major problem in developing countries, with 15% developing tuberculosis, 30% cytomegalovirus, and nearly 50% bacterial infections. The solutions to these problems may seem simplistic: alleviate poverty, educate the general population, and expand the transplant programs in public sector hospitals where commerce is less likely to play a major role. The SIUT model of funding in a community-government partnership has increased the number of transplantations and patient and organ survival substantially. Over the last 15 years, it has operated by complete financial transparency, public audit and accountability. The scheme has proven effective and currently 110 transplants/year are performed, with free after care and immunosuppressive drugs. Confidence has been built in the community, with strong donations of money, equipment and medicines. We believe this model could be sustained in other developing nations.

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.

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.

DNA methods have resulted in improved renal allograft survival rates in cadaveric renal transplantation. This paper describes the impact of DNA typing by PCR-SSP on a living-related renal transplant (LRRT) programme. It evaluates error rates in serology, acute rejections, graft function and survival rates between the two typing methods. Serological typing was carried out on CTS 120 antisera Class 1, 60 antisera Class 2, 72 antisera Terasaki Class 1 and 72 antisera Class 2 antigens. Low-resolution PCR-SSP typing was carried out by 24 primers for HLA-A, 48 for HLA-B and 24 for HLA-DR. Of the 585 transplants: 159 (Group I) were serology based; 172 were serology and PCR-SSP based for HLA-DR (Group II); and 254 were serology and PCR-SSP based for HLA-A and -B, and only PCR-SSP based for HLA-DR (Group III). Error rates in serology compared with PCR-SSP were 24% for HLA-A, 16% for HLA-B and 35% for HLA-DR. Acute rejections were 39%, 30% 26% in Groups I, II and III, respectively (P= 0.02). Graft function of serum creatinine <1.5 mg/dl at 1 year was found in 26% of the Group I patients compared with 48% of those in Group III ( P <0.0001). One- and 3-year graft survival was 93% and 87% for Group II compared with 81% and 69% for Group I, respectively ( P= 0.0001). Matching by this combination of serology and PCR-SSP is not only economical for a developing country but also improves graft survival by 12% and 18% at 1 and 3 years, respectively. [ABSTRACT FROM AUTHOR]

Class 1 HLA-A and -B and Class 2 HLA-DR allele frequencies were determined in Pakistani ethnic linguistic population groups. A total of 942 potential kidney donors for living-related transplants were tested by Collaborative Transplant Study (CTS) 120 antisera trays for HLA-A and -B. All subjects homozygous for an allele, showing weak reactions or with crossreactions were retested by PCR-SSP using CTS primers, 24 for HLA-A and 48 for HLA-B. Class 2 HLA-DR were determined only by PCR–SSP with 24 primers from the CTS. The common antigen frequencies for HLA-A were A1=0.312, A2=0.402, A11=0.312, A24=0.221, A26=0.178 and A19, and splits=0.296. At HLA-B the common alleles were B8=0.234, B 35=0.213, B44=0.145, B51=0.197 and B60=0.177. Common HLA-DR alleles were DR 2=0.382, DR3(17)=0.424, DR5(11)=0.185, DR 6(13)=0.180 and DR 7=0.240. These results provide baseline data for ethnic Pakistani population groups based on DNA methods. This will help in studies relating to disease associations and cadaveric organ allocation programmes. [ABSTRACT FROM AUTHOR]