Organ Donation in Syria.

The first living donor kidney transplant in Syria was performed 44 years ago; by the end of 2022, 6265 renal transplants had been performed in Syria. Kidney, bone marrow, cornea, and stem cells are the only organs or tissues that can be transplanted in Syria. Although 3 heart transplants from deceased donors were performed in the late 1980s, cardiac transplant activities have since discontinued. In 2003, national Syrian legislation was enacted authorizing the use of organs from living unrelated and deceased donors. This important law was preceded by another big stride: the acceptance by the higher Islamic religious authorities in Syria in 2001 of the principle of procurement of organs from deceased donors, provided that consent is given by a first- or second-degree relative. After the law was enacted, kidney transplant rates increased from 7 per million population in 2002 to 17 per million population in 2007. Kidney transplants performed abroad for Syrian patients declined from 25% in 2002 to <2% in 2007. Rates plateaued through 2010, before the political crisis started in 2011. Forty-four years after the first successful kidney transplant in Syria, patients needing an organ transplant rely on living donors only. Moreover, 20 years after the law authorizing use of organs from deceased donors, a program is still not in place in Syria. The war, limited resources, and lack of public awareness about the importance of organ donation and transplant appear to be factors inhibiting initiation of a deceased donor program in Syria. A concerted and ongoing education campaign is needed to increase awareness of organ donation, change negative public attitudes, and gain societal acceptance. Every effort must be made to initiate a deceased donor program to lessen the burden on living donors and to enable national self-sufficiency in organs for transplant.

Capacity for the management of kidney failure in the International Society of Nephrology Middle East region: report from the 2023 ISN Global Kidney Health Atlas (ISN-GKHA).

The highest financial and symptom burdens and the lowest health-related quality-of-life scores are seen in people with kidney failure. A total of 11 countries in the International Society of Nephrology (ISN) Middle East region responded to the ISN-Global Kidney Health Atlas. The prevalence of chronic kidney disease (CKD) in the region ranged from 4.9% in Yemen to 12.2% in Lebanon, whereas prevalence of kidney failure treated with dialysis or transplantation ranged from 152 per million population (pmp) in the United Arab Emirates to 869 pmp in Kuwait. Overall, the incidence of kidney transplantation was highest in Saudi Arabia (20.2 pmp) and was lowest in Oman (2.2 pmp). Chronic hemodialysis (HD) and peritoneal dialysis (PD) services were available in all countries, whereas kidney transplantation was available in most countries of the region. Public government funding that makes acute dialysis, chronic HD, chronic PD, and kidney transplantation medications free at the point of delivery was available in 54.5%, 72.7%, 54.5%, and 54.5% of countries, respectively. Conservative kidney management was available in 45% of countries. Only Oman had a CKD registry; 7 countries (64%) had dialysis registries, and 8 (73%) had kidney transplantation registries. The ISN Middle East region has a high burden of kidney disease and multiple challenges to overcome. Prevention and detection of kidney disease can be improved by the design of tailored guidelines, allocation of additional resources, improvement of early detection at all levels of care, and implementation of sustainable health information systems.

Kidney Retransplantation in Children.

Pediatric kidney transplant recipients will likely require a retransplant in their lifetime. Although the significant advances in clinical management and newer immunosuppressive agents have had a significant effect to improve short-term allograft function, it is apparent that long-term allograft function remains suboptimal. Therefore, it is likely that most pediatric renal allograft recipients will require 1 or more retransplants during their lifetime. In the West, an increasing number of patients on the deceased donor wait list are awaiting a retransplant; in the US, 15% of current annual transplants are retransplants. Unfortunately, the use of a second or subsequent grafts in pediatric recipients has inferior long-term graft survival rates compared with initial grafts, with decreasing rates with each subsequent graft. Multiple issues influence the outcome of retransplant, with the most significant being the cause of the prior transplant failure. Nonadherenceassociated graft loss poses unresolved ethical issues that may affect a patient's access to retransplant. Graft nephrectomy prior to retransplant may benefit selected patients, but the effect of an in situ failed graft on the development of panel reactive antibodies remains to be definitively determined. It is important that these and other factors discussed in this presentation be taken into consideration during the counseling of families on the optimal approach for their child who requires a retransplant.

Outcomes of steroid-resistant nephrotic syndrome in children not treated with intensified immunosuppression.

BACKGROUND: The aim of the current PodoNet registry analysis was to evaluate the outcome of steroid-resistant nephrotic syndrome (SRNS) in children who were not treated with intensified immunosuppression (IIS), focusing on the potential for spontaneous remission and the role of angiotensin blockade on proteinuria reduction. METHODS: Ninety-five pediatric patients who did not receive any IIS were identified in the PodoNet Registry. Competing risk analyses were performed on 67 patients with nephrotic-range proteinuria at disease onset to explore the cumulative rates of complete or partial remission or progression to kidney failure, stratified by underlying etiology (genetic vs. non-genetic SRNS). In addition, Cox proportional hazard analysis was performed to identify factors predicting proteinuria remission. RESULTS: Eighteen of 31 (58.1%) patients with non-genetic SRNS achieved complete remission without IIS, with a cumulative likelihood of 46.2% at 1 year and 57.7% at 2 years. Remission was sustained in 11 children, and only two progressed to kidney failure. In the genetic subgroup (n = 27), complete resolution of proteinuria occurred very rarely and was never sustained; 6 (21.7%) children progressed to kidney failure at 3 years. Almost all children (96.8%) received proteinuria-lowering renin-angiotensin-aldosterone system (RAAS) antagonist treatment. On antiproteinuric treatment, partial remission was achieved in 7 of 31 (22.6%) children with non-genetic SRNS and 9 of 27 children (33.3%) with genetic SRNS. CONCLUSION: Our results demonstrate that spontaneous complete remission can occur in a substantial fraction of children with non-genetic SRNS and milder clinical phenotype. RAAS blockade increases the likelihood of partial remission of proteinuria in all forms of SRNS. A higher resolution version of the Graphical abstract is available as Supplementary information.

Cancer and Infection Screening in Potential Living Donors.

Living donor transplant is a safe practice but is not completely risk free. Although both infection and malignancy transmissions have occurred through living organ donation, in the global view, the number of these events is negligible in contrast to the successful lifesaving transplants performed each year; however, an event can be devastating for the recipient, donor, and treatment team if it occurs. Each living donor is unique, and the donor evaluation is multifactorial, taking into the account the medical, social, and family history of individual donors, needs of the recipient, and determination of the anatomic and functional suitability of the donor organ. These considerations can be further complicated by geographical and temporal components. Although the balancing of all practical considerations can be complex, a thorough medical assessment for infection and malignancy of a potential living donor is central in protecting the donor and the intended transplant recipient. Good medical practice requires consistent donor evaluation and reasonable followup.

Pediatric Kidney Transplantation in the Middle East: Challenges and Solutions.

OBJECTIVES: Pediatric kidney transplant is the best option for treating children with end-stage renal disease. Poor economics and paucity of renal replacement therapy and transplant facilities are the most important challenges of pediatric kidney transplantation in the Middle East. The aim of the study was to collect data on the rates of pediatric kidney transplant during a recent year from the Middle East countries. MATERIALS AND METHODS: All well-known kidney transplant centers from the Middle East were contacted to answer specified questions related to adult and pediatric kidney transplant volume from both living and deceased donors that was performed in each country during a recent year (preferably 2021, or, if not available, 2020 or 2019). RESULTS: In the single recent year, 8772 kidney transplants were performed for adult and pediatric patients in Middle East countries, making a total kidney transplant rate per million populations per year of 10.9 (ranging from 1.2 in Yemen and Pakistan to 39.7 in Turkey). Of these, 1399 transplants were from deceased donors (rate of deceased donor kidney transplants of 15.9%, ranging from 0% in 10 countries to 64.2% in Iran). Of 8772 total kidney transplants, 746 were pediatric recipients (<18 years old), with 166 pediatric kidney transplants from deceased donors (percent of deceased donor pediatric kidney transplant of 22.2%, ranging from 0% in 11 countries to 100% in Tunisia). Average pediatric kidney transplant rate per million populations per year was 0.93 (ranging from <0.1 in Pakistan to 3.2 in Syria). Average pediatric kidney transplant share was about 8.5% of total kidney transplants (ranging from 3.2 in Iraq to 20% in Algeria). The deceased kidney transplant program is currently available in only 8 of the 18 Middle Eastern countries included in this study. However, a deceased program is active in some Middle East countries (ie, Iran, Turkey, Kingdom of Saudi Arabia, Kuwait, and United Arab Emirates). Of note, Turkey had the highest kidney transplant rate per million populations per year (39.7), Syria had the highest pediatric kidney transplant rate per million populations per year (3.2), and Iran had the highest deceased donor kidney transplant percent of the total kidney transplants (64.2%). In the Middle East, Iran alone performed 63.5% (888/1399) of all deceased donor kidney transplants and 63.9% (106/166) of all deceased donor pediatric kidney transplants. Algeria had the highest pediatric kidney transplant share of the total transplants (20%). Low health spending, poorly developed infrastructures, delayed referral of children with chronic kidney disease, comorbidities, lack of technical expertise, inadequate pediatric dialysis programs, extended dialysis time, organ shortage, commercial transplantation, and posttransplant infections are the main pre- and posttransplant challenges. The community-government partnership model from the Sindh Institute of Urology and Transplantation in Karachi Pakistan showed that pediatric renal replacement therapy and transplant can be successfully established in a developing country. CONCLUSIONS: Although pediatric kidney transplant is active in many parts of the Middle East, it is still inactive in others, mostly relying on living donors. The lack of deceased donor programs in most Middle Eastern countries is a main issue to be addressed to adequately responding to the increasing demand for organs.

Pediatric Versus Adult Kidney Transplant Activity in Arab Countries.

OBJECTIVES: This study aimed to evaluate current activities of pediatric versus adult kidney transplant in the Arab world. MATERIALS AND METHODS: A questionnaire was mailed to all kidney transplant centers in Arab countries to collect the most recent data on kidney transplant activity. RESULTS AND CONCLUSIONS: There were 3309 kidney transplants performed over a single year, with a transplant rate of 9.5 per million population; 298 of these were pediatric kidney transplant procedures, with a rate of 0.87 per million population, which is much lower than that shown in developed countries where it ranges from 5 to 10 per million population. Of all kidney transplants, the pediatric share is 9%, a rate that is twice as high as that shown among European children. Kidney transplant programs in most Arab countries rely exclusively on living donors, as there is a severe shortage of deceased donors. Of all transplants (that is, combined adult and pediatric), 93.5% were from living donors. Deceased donor pediatric kidney transplant is only available in the Kingdom of Saudi Arabia, Tunisia, and Kuwait. In these 3 Arab countries, which have stable deceased donor transplant programs, deceased donor transplant procedures ranged from 14% to 31% of all transplants. Of the 212 adult and pediatric transplant procedures that were performed from deceased donors in the 8 countries that perform deceased donor transplant, only 29 were for pediatric recipients. Surprisingly, the share of pediatric kidney transplant procedures was not better in the countries with higher overall kidney transplant rate or in those where deceased donor transplant was available. In general, pediatric kidney transplant procedures are still inactive in most Arab countries and mostly relies on living donors. The lack of well-developed deceased donor programs is the main issue to be addressed.

Impact of COVID-19 Pandemic on Management of Pediatric Kidney Transplant Recipients.

Children appear to be less commonly and less severely affected by COVID-19 than adults, accounting for 1% to 5% of all COVID-19 cases. The COVID-19 pande mic has challenged pediatric kidney transplant programs to provide safe and consistent care during this difficult and unprecedented time. So far during this pandemic, best practices being delivered to pediatric kidney transplant patients are based on available information from published literature and expert opinions. The key areas of pediatric kidney transplant care that may be affected by the COVID-19 pandemic include transplant activity, outpatient clinic activity, monitoring, multidisciplinary care, medications (immunosuppression and others), patient/family education/support, school and employment, and care of pediatric kidney transplant patients who are COVID-19 positive. It has been presumed that children with chronic kidney disease and/or those who take immunosuppressants may be at increased risk for complications from COVID-19 infection; however, available evidence has now suggested that immunosuppressed children with kidney transplant are not at increased risk of severe COVID-19 disease. Clinicians should remain aware that transplant recipients may present with atypical symptoms. In addition, because evidence-based reports to support specific adjustments to immunosuppressive medications in relation to COVID-19 are not yet available, decisions on reduction or discontinuation of immunosuppression should be on a case-by-case basis for kidney transplant recipients who are COVID-19 positive. Reports to support evidence-based management of pediatric kidney transplant patients during the COVID-19 pandemic are lacking; therefore, expert opinion and available knowledge and experience remain subject to biases.

Deceased Organ Donation in Syria: Challenges and Solutions.

The first living-donor kidney transplant in Syria was performed 41 years ago; by 2019, 5407 renal transplants had been performed there. Three heart transplants from deceased donors were performed in the late 1980s; cardiac transplant activities have since discontinued. In 2003, a new, national Syrian legislation was enacted authorizing the use of organs from living unrelated donors and from deceased donors. This important law was preceded by another big stride in this regard: the acceptance by the higher Islamic religious authorities in Syria in 2001 of the principle of procurement of organs from deceased donors, provided that consent is given by a first- or second-degree relative. After the enactment of this law, kidney transplant rates increased from 7 per million population in 2002 to 17 per million population in 2007. Kidney transplants performed abroad for Syrian patients declined from 25% in 2002 to < 2% in 2007. Kidney transplants continued at comparable rates until 2010, before the beginning of the political crisis in 2011. Four decades after the first successful kidney transplant in Syria, however, patients needing an organ transplant must rely on living donors only. Moreover, 17 years after the law authorizing use of organs from deceased donors, a program is still not in place in Syria, and additional improvement of the legal framework is needed. The war, limited resources, and lack of public awareness about the importance of organ donation and transplant appear to be major factors inhibiting initiation of a deceased-donor program in Syria. A concerted and ongoing education campaign is needed to increase awareness of organ donation, change negative public attitudes, and gain societal acceptance. Every effort must be made to initiate a deceased-donor program to lessen the burden on living donors and to enable national self-sufficiency in organs for transplant.

How Did the War Affect Organ Transplantation in Syria?

Since 2011, the Syrian conflict has destroyed much of the country's infrastructure. The deteriorating humanitarian situation has involved health workers and facilities. In 2010, before the war, 385 kidney transplants were performed in Syria. This number declined to 154 in 2013 (60% less) before increasing to 251 transplants in 2018, which is still 35% less than the number of transplants performed before the war. In addition, the number of operational kidney transplant centers has decreased from 8 in 2010, distributed over 3 cities, to only 4 in 2013, all located in Damascus, which increased to 6 centers in 2019. Interestingly, with regard to type of living donor, the percentage of unrelated kidney donors has decreased by 20% for unclear reasons. Another alarming statistic is that more than 50% of kidney transplant physicians and surgeons are no longer practicing transplant medicine in their centers, either because they have left the country or because their centers had become nonoperational. Since the war, free and timely provision of immunosuppressive drugs for all patients in all provinces has been a leading challenge for health authorities and transplant patients. This difficulty has led to adverse medical consequences for patients. A project to initiate liver transplant came to a halt because of complex reasons but mainly because foreign trainers could not visit Syria. Although the autologous bone marrow transplant program had slowed until recently, it has become more active, involving both autologous and allogeneic transplants. The deceased-donor program is still not available in Syria; the war has just reinforced the many reasons that prevented the start of this program before the conflict. The commitment of transplant teams despite these large challenges continues to be extraordinary. The Syrian conflict has affected all aspects of organ transplant, paralyzing new projects and negatively affecting existing programs.

Genetic screening in children with challenging nephrotic syndrome.

Genetic screening paradigms for the nephrotic syndrome (NS) in the developed world are well established; however, screening in developing countries has received only minor attention. We retrospectively analyzed a cohort of all children who underwent genetic testing for challenging NS from our registry in the 10-year interval from 2000 to 2010 and based on 58 patients aged 0-12 years with at least one of the following clinical diagnosis: Nonsyndromic steroid-resistant nephrotic syndrome (SRNS), familial NS, and congenital NS. Of these, 23 patients (~40%) had a history of familial disease occurrence. All cases were screened for NPHS2 and WT1 mutations by direct sequencing of all exons of the genes. In addition, all patients who were diagnosed during the first three months of life were screened for NPHS1 mutations too. A genetic disease cause was identified in 12 patients (20.7%); of these, five novel mutations, all in NPHS2 accounting for 42% of all mutations and 9% of the cohort. Nine patients were found to have NPHS2 mutations. Only one case with SRNS had a mutation in WT1. Of the five congenital NS, two cases were found to have NPHS1 mutations and one case with NPHS2 mutation. Therefore, mutations in NPHS2 were the most commonly identified and explained in 15.5% of the screened patients and WT1 mutation in 1.7% of cases, whereas NPHS1 mutations were found in 40% of congenital NS cases. A genetic disease cause was identified in 20.7% of the screened patients. Among 12 identified mutations, abnormalities in NPHS2 (n = 9) were most commonly identified.

Worldwide view of nephropathic cystinosis: results from a survey from 30 countries.

BACKGROUND: Nephropathic cystinosis is a rare inherited metabolic disorder leading to progressive renal failure and extra-renal comorbidity. The prognosis relies on early adherence to cysteamine treatment and symptomatic therapies. Developing nations [DiN] experience many challenges for management of cystinosis. The aim of this study was to assess the management characteristics in DiN compared with developed nations [DeN]. METHODS: A questionnaire was sent between April 2010 and May 2011 to 87 members of the International Pediatric Nephrology Association, in 50 countries. RESULTS: A total of 213 patients were included from 41 centres in 30 nations (109 from 17 DiN and 104 from 13 DeN). 7% of DiN patients died at a median age of 5 years whereas no death was observed in DeN. DiN patients were older at the time of diagnosis. In DiN, leukocyte cystine measurement was only available in selected cases for diagnosis but never for continuous monitoring. More patients had reached end-stage renal disease in DiN (53.2 vs. 37.9%, p = 0.03), within a shorter time of evolution (8 vs. 10 yrs., p = 0.0008). The earlier the cysteamine treatment, the better the renal outcome, since the median renal survival increased up to 16.1 [12.5-/] yrs. in patients from DeN treated before the age of 2.5 years of age (p = 0.0001). However, the renal survival was not statistically different between DeN and DiN when patients initiated cysteamine after 2.5 years of age. The number of transplantations and the time from onset of ESRD to transplantation were not different in DeN and DiN. More patients were kept under maintenance dialysis in DiN (26% vs.19%, p = 0.02); 79% of patients from DiN vs. 45% in DeN underwent peritoneal dialysis. CONCLUSIONS: Major discrepancies between DiN and DeN in the management of nephropathic cystinosis remain a current concern for many patients living in countries with limited financial resources.

Long-Term Outcome of Steroid-Resistant Nephrotic Syndrome in Children.

We investigated the value of genetic, histopathologic, and early treatment response information in prognosing long-term renal outcome in children with primary steroid-resistant nephrotic syndrome. From the PodoNet Registry, we obtained longitudinal clinical information for 1354 patients (disease onset at >3 months and <20 years of age): 612 had documented responsiveness to intensified immunosuppression (IIS), 1155 had kidney biopsy results, and 212 had an established genetic diagnosis. We assessed risk factors for ESRD using multivariate Cox regression models. Complete and partial remission of proteinuria within 12 months of disease onset occurred in 24.5% and 16.5% of children, respectively, with the highest remission rates achieved with calcineurin inhibitor-based protocols. Ten-year ESRD-free survival rates were 43%, 94%, and 72% in children with IIS resistance, complete remission, and partial remission, respectively; 27% in children with a genetic diagnosis; and 79% and 52% in children with histopathologic findings of minimal change glomerulopathy and FSGS, respectively. Five-year ESRD-free survival rate was 21% for diffuse mesangial sclerosis. IIS responsiveness, presence of a genetic diagnosis, and FSGS or diffuse mesangial sclerosis on initial biopsy as well as age, serum albumin concentration, and CKD stage at onset affected ESRD risk. Our findings suggest that responsiveness to initial IIS and detection of a hereditary podocytopathy are prognostic indicators of favorable and poor long-term outcome, respectively, in children with steroid-resistant nephrotic syndrome. Children with multidrug-resistant sporadic disease show better renal survival than those with genetic disease. Furthermore, histopathologic findings may retain prognostic relevance when a genetic diagnosis is established.

Rabies Acquired Through Kidney Transplantation in a Child: A Case Report.

Rabies is usually transmitted to humans through bites of infected animals; however, it can rarely be transmitted through deceased donor organs or tissues when not suspected. Here, we report a case of rabies transmission in a child. The child was a 5-year-old girl who was admitted to the pediatric intensive care unit with encephalitis of unexplained cause 3.5 months after she received a kidney transplant from a deceased donor. The laboratory and imaging studies did not reveal any explanation for her rapidly declining clinical and neurologic condition, which ended with death 4 days after admission. Death of another recipient from the same donor led to an investigation that revealed rabies as the cause. Both corneas were explanted from other recipients to prevent further death. Polymerase chain reaction sequence analysis of the corneas was consistent with a rabies virus from the same donor's state of residence. Rabies transmission, although rare, should be suspected when a donor comes from or has visited endemic countries. Donors with unclear causes of death should be rejected.

Recurrent Nephrotic Syndrome After Renal Transplant in Children.

OBJECTIVES: Recurrent disease occurs in around 30% of children transplanted for steroid-resistant nephrotic syndrome. Its precipitating risk factors have rarely been studied in the Middle East. The aim of our study was to determine what characterizes posttransplant recurrence of nephrotic syndrome in Syrian children. MATERIALS AND METHODS: We performed a retrospective analysis of 12 nephrotic children who received 1 renal allograft at the Kidney Hospital in Damascus from 2002 to 2013. RESULTS: Native kidney biopsy results showed focal segmental glomerulosclerosis in 9 of 10 patients. Four patients had 1 or more sibling affected with nephrotic syndrome, and the remaining patients were labeled as having sporadic disease. Genetic screening for NPHS2, NPHS1, and Wilms tumor gene (WT1) mutations were done for 6 patients, and 1 novel homozygous NPHS2 mutation was identified in 1 patient. All patients received transplants from living donors. Four patients had recurrence of initial disease after transplant (overall recurrence rate of 33%). However, 1 patient showed complete and spontaneous remission 20 months after transplant; As expected, the patient with NPSH2 mutation had no recurrence. Patients with sporadic disease showed risk of recurrence 5 times higher than patients with familial disease (P = .24). Interestingly, all recurrent cases had received a kidney from a related donor and were initially classified as having sporadic disease. Although not statistically significant, the risk of recurrence from related donor grafts was 6.75 times higher than from unrelated donors (P = .16). To the best of our knowledge, this observation, the first of its kind, has never been investigated or pointed out in the literature. CONCLUSIONS: Further research is needed to confidently determine whether living related donor grafts are associated with increased incidence of recurrence of nephrotic syndrome.

The effect of the Syrian crisis on organ transplantation in Syria.

The war in Syria that started in March 2011 has destroyed much of the country's infrastructure including many hospitals. The total number of kidney transplants performed in Syria in 2010 was 385 transplants before the number gradually declined to 154 transplants in 2013, a decrease of 60%. In addition, the number of operational kidney transplant centers has decreased from 8 to 4 centers. Unrelated-donor kidney transplant decreased from 70% during the years that preceded the crisis to 47% in 2013. More than 50% of physicians and surgeons involved in kidney transplant are not practicing transplant currently in their centers. Difficulties in the provision of immunosuppressive drugs for all patients in all provinces constitute a major challenge for the health authorities and transplant patients, especially patients who cannot arrange an alternate source. The project to initiate liver transplant came to a halt because foreign trainers could not visit Syria. The autologous bone marrow transplant program continued to function, but in a smaller and irregular manner. The commitment of transplant teams despite the large challenges was, and still is, extraordinary. In conclusion, all aspects of organ transplant have been affected, paralyzing new projects and negatively affecting existing programs.

The impact of living-unrelated transplant on establishing deceased-donor liver program in Syria.

Liver transplant is the criterion standard for patients with end-stage liver disease. Yet there is no liver transplant in Syria. Traveling abroad for a liver transplant is a luxury few Syrians can afford. There is currently an on-going debate whether to start a liver transplant program using living or deceased donors. In 2003, a new law was enacted, authorizing the use of organs from volunteer strangers and deceased donors. Despite the positive aspects of this law (allowing unrelated donors to increase the number of transplants in the country); the negative aspects also were obvious. The poor used the law to sell their organs to the rich, and this model is in violation of the Istanbul Declaration. To better document transplant communities' perceptions on organ donation, an e-mail survey was sent to a nationally representative sample of physicians (n = 115) that showed that 58% of respondents did not support the start of liver transplant from live donors, as they fear a considerable risk for the donor and the recipient. Seventy-one percent of respondents believe that unrelated kidney donation has contributed to tarnishing the reputation of transplant, and 56% believe that a deceased-donor program can run in parallel with unrelated organ donations. The interest in deceased-donor program has been affected negatively by the systematic approach of using poor persons as the source of the organ. This lack of interest has affected starting a liver program that relies on deceased donors; especially the need for kidneys is more than livers. Health authorities in Syria were inclined to initiate a liver transplant program from live donors, despite the risks of serious morbidities and mortality. In conclusion then, paid kidney donation in actual effect is actually a hindrance to establishing a deceased-donor liver program.

Genotype-phenotype associations in WT1 glomerulopathy.

WT1 mutations cause a wide spectrum of renal and extrarenal manifestations. Here we evaluated disease prevalence, phenotype spectrum, and genotype-phenotype correlations of 61 patients with WT1-related steroid-resistant nephrotic syndrome relative to 700 WT1-negative patients, all with steroid-resistant nephrotic syndrome. WT1 patients more frequently presented with chronic kidney disease and hypertension at diagnosis and exhibited more rapid disease progression. Focal segmental glomerulosclerosis was equally prevalent in both cohorts, but diffuse mesangial sclerosis was largely specific for WT1 disease and was present in 34% of cases. Sex reversal and/or urogenital abnormalities (52%), Wilms tumor (38%), and gonadoblastoma (5%) were almost exclusive to WT1 disease. Missense substitutions affecting DNA-binding residues were associated with diffuse mesangial sclerosis (74%), early steroid-resistant nephrotic syndrome onset, and rapid progression to ESRD. Truncating mutations conferred the highest Wilms tumor risk (78%) but typically late-onset steroid-resistant nephrotic syndrome. Intronic (KTS) mutations were most likely to present as isolated steroid-resistant nephrotic syndrome (37%) with a median onset at an age of 4.5 years, focal segmental glomerulosclerosis on biopsy, and slow progression (median ESRD age 13.6 years). Thus, there is a wide range of expressivity, solid genotype-phenotype associations, and a high risk and significance of extrarenal complications in WT1-associated nephropathy. We suggest that all children with steroid-resistant nephrotic syndrome undergo WT1 gene screening.