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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]

Autosomal recessive disorders are prevalent in Pakistan, a developing South Asian country where consanguineous marriages are common. This study seeks to determine the prevalence of monogenic causes in children presenting with nephrocalcinosis and nephrolithiasis at a dialysis and transplant center in Karachi, Pakistan. A retrospective analysis was conducted in children aged 1-18 years presenting with nephrocalcinosis, between 2010 and 2019. Demographic information, clinical profile, laboratory parameters and stone analysis were collected, on a pre-designed questionnaire. One hundred and twenty-six children were included, with 11 and 3 diagnosed with renal tubular acidosis and Bartter's syndrome respectively. Next-generation sequencing and Sanger sequencing was performed on 112 children. Eighty-seven patients were diagnosed with primary hyperoxaluria, with mutations in alanine-glyoxylate-aminotransferase gene found in 73, followed by glyoxylate reductase/hydroxy-pyruvate reductase in 13, and 4-hydroxy-2-oxaloglutarate aldolase in 1. Twenty-five patients reported negative for mutations. Sixty-four percent were males, with a statistically significant difference (p < 0.05). History of parental consanguineous marriage was found in 98% of the cohort. Fifty-four and 40 patients presented to the clinic with Chronic Kidney Disease Stage 1 and Stage 5, respectively, with a statistically significant difference p = 0.007. Mutations noted in our cohort are different and more severe than those reported in the developed world. The disease poses a major disease burden in developing world context with the only treatment option of combined liver-kidney transplantation not available in Pakistan., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Lung cancer (LC) is the number one cancer killer of women both in the USA and around the world. Besides cigarette smoking, an important feature in the etiology of LC is its strong association with exposure of toxic metals. The primary objective of the present investigation was to assess the concentrations of toxic/essential elements (Ni, Ca, Se, Zn, Co, K, Cr, As, Cu, Na, Fe, Hg, Cd, Mg, Mn, and Pb) in the serum samples of LC female patients with female controls by atomic absorption spectrometry after wet-acid digestion procedure. Carcinoembryonic antigen (CEA) was also measured in the serum of the patients using immunoradiometric method. Comparative appraisal of the data revealed that concentrations of Cr, Mg, Cd, Pb, Hg, As, and Ni were noted to be high significantly in serum of LC female patients, while the average Fe, Co, Mn, Na, K, Zn, Ca, and Se were observed at higher levels in female controls (p < 0.05). The correlation study revealed significantly different mutual associations among the elements in the both donor groups. Markedly, variations in the elemental levels were also noted for different types (non-small cell lung cancer and small cell lung cancer) and stages (I, II, III, & IV) of LC patients. Multivariate analyses showed substantially diverse apportionment of the metals in the female patients and female controls. Hence, present findings suggest that the toxic and essential metals accumulated in the body may pose a high risk for LC progression in Pakistani females.

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.

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.

Background: Long-term effects of uninephrectomy for kidney donation are of particular interest in the currently increasing practice of living-donor transplantation. We have retrospectively analyzed the general health status and renal and cardiovascular consequences of living-related kidney donation., Methods: Data of living-related kidney donors who were regularly followed up in a dedicated clinic at the Sindh Institute of Urology and Transplantation between July 2000 and January 2004 was retrieved. They had donated their kidneys from 1986 onward. Data on weight, blood pressure, creatinine clearance, level of proteinuria, and new onset diabetes mellitus were analyzed., Results: Seven hundred and thirty-six donors with a mean age of 36+/-10.9 years (M:F 1.1:1) were evaluated. With a mean postnephrectomy duration of 3+/-3.2 years (range 6 months-18 years), the creatinine clearance fell to 87% of prenephrectomy values, and 49 (6.7%) had a creatinine clearance of less than 60 mL/ min. Hypertension developed in 76 (10.3%) donors, and 179 (24.3%) had proteinuria exceeding 150 mg/24 hr. Overweight (27.8%) and obese subjects (11.5%) had a higher prevalence of hypertension and new onset diabetes mellitus. One donor developed end-stage renal failure., Conclusion: Donor nephrectomy has minimal adverse effects on overall health status. Regular donor follow-up identifies at-risk populations and potentially modifiable factors.

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.

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.

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.

Most laboratories in Pakistan use expensive imported clinical chemistry reagent kits resulting in high cost/test to the patients. To reduce these costs, reagents were prepared from basic chemicals, substrates and enzymes imported from Sigma Chemical Company U.K. This reduced the cost/test by up to 500% in some reagents. The quality of these reagents was tested by Wellcome External, Q.C. Locally prepared reagents were comparable to or better than commercial reagents systems in terms of accuracy and precision. This paper describes the preparations according to I.F.C.C., costs and quality control of some of the reagents i.e., glucose, calcium, bilirubin, albumin, total protein, urea, ALT, AST and LDH and their comparisons with equivalent commercial kits.