Need For Kidney Transplantation Research Articles

Effective and new technologies in kidney tissue engineering.

Kidney disease encompasses a wide spectrum of conditions, ranging from simple infections to chronic kidney disease. When the kidneys are unable to filter blood and remove waste products, these abnormalities can lead to kidney failure. In severe cases of kidney failure, kidney transplantation is considered the only definitive treatment. Worldwide, the World Health Organization (WHO) repeatedly emphasizes the importance of organ donation and increasing transplantation rates. Many countries implement national programs to promote the culture of organ donation and improve patient access to kidney transplantation. The extent to which this procedure is performed varies across countries and is influenced by several factors, including the volume of organ donation, medical infrastructure, access to technology and health policies. However, a kidney transplant comes with challenges and problems that impact its success. Kidney tissue engineering is a new approach that shows promise for repairing and replacing damaged kidney tissue. This article reviews recent advances in kidney tissue engineering, focusing on engineered structures such as hydrogels, electrospinning, 3D bioprinting, and microfluidic systems. By mimicking the extracellular environment of the kidney, these structures provide suitable conditions for the growth and development of kidney cells. The role of these structures in the formation of blood vessels, the mimicry of kidney functions and the challenges in this field were also discussed. The results of this study show that kidney tissue engineering has high potential for treating kidney diseases and reducing the need for kidney transplantation. However, to achieve clinical application of this technology, further research is required to improve the biocompatibility, vascularization and long-term performance of engineered tissues.

On the diagnosis of chronic kidney disease using a machine learning-based interface with explainable artificial intelligence

Chronic Kidney Disease (CKD) is increasingly recognised as a major health concern due to its rising prevalence. The average survival period without functioning kidneys is typically limited to approximately 18 days, creating a significant need for kidney transplants and dialysis. Early detection of CKD is crucial, and machine learning methods have proven effective in diagnosing the condition, despite their often opaque decision-making processes. This study utilised explainable machine learning to predict CKD, thereby overcoming the 'black box' nature of traditional machine learning predictions. Of the six machine learning algorithms evaluated, the extreme gradient boost (XGB) demonstrated the highest accuracy. For interpretability, the study employed Shapley Additive Explanations (SHAP) and Partial Dependency Plots (PDP), which elucidate the rationale behind the predictions and support the decision-making process. Moreover, for the first time, a graphical user interface with explanations was developed to diagnose the likelihood of CKD. Given the critical nature and high stakes of CKD, the use of explainable machine learning can aid healthcare professionals in making accurate diagnoses and identifying root causes.

Subsequent kidney transplant after pediatric heart transplant: Prevalence and risk factors

Pediatric heart failure and transplantation carry associated risks for kidney failure and potential need for kidney transplant following pediatric heart transplantation (KT/pHT). This retrospective, United Network of Organ Sharing study of 10,030 pediatric heart transplants (pHTs) from 1987 to 2020 aimed to determine the incidence of waitlisting for and completion of KT/pHT, risk factors for KT/pHT, and risk factors for nonreceipt of a KT/pHT. Among pHT recipients, 3.4% were waitlisted for KT/pHT (median time of 14 years after pHT). Among those waitlisted, 70% received a KT/pHT, and 18% died on the waitlist at a median time of 0.8 years from KT/pHT waitlisting (median age of 20 years). Moderate-high sensitization at KT/pHT waitlisting (calculated panel reactive antibody, ≥ 20%) was associated with a lower likelihood of KT/pHT (adjusted hazard ratio, 0.67; 95% confidence interval, 0.47-0.95). Waitlisting for heart transplantation simultaneously with kidney transplant (adjusted hazard ratio, 3.73; 95% confidence interval, 2.01-6.92) was associated with increased risk of death on the KT/pHT waitlist. While the prevalence of KT/pHT is low, there is substantial mortality among those waitlisted for KT/pHT. These findings suggest a need to consider novel risk factors for nonreceipt of KT/pHT and death on the waitlist in prioritizing criteria/guidelines for simultaneous heart-kidney transplantation.

15. STUDY ON THE NEED FOR KIDNEY TRANSPLANTATION AND PATIENTS ON KIDNEY TRANSPLAT WAITING LIST IN LAO CAI PROVINE 2023

Objectives: This study aims to determine the need for kidney transplantation and patients on kidney transplant waiting list in Lao Cai provine 2023. 
 Methods: A cross-sectional descriptive study was conducted on all patients undergoing hemodialysis at 4 hospitals in Lao Cai province from October 2022 to March 2023. 
 Results: Lao Cai province has 4 hemodialysis units with a need for kidney transplants in the province of 214 people, mainly at the provincial general hospital, with an average age of 50, men making up the majority with more than 60% and the majority of patients have been on dialysis for less than 5 years. 74% of patients in need of a kidney transplant were on the waitlist. Initially, it was determined that Lao Cai has 159 patients waiting for a kidney transplant with an average age of 43 and 61.6% have been on dialysis for less than 5 years. Among these patients, the majority of patients with blood type O account for more than 40%, and the rates of hepatitis B and C are 13.7% and 17.8%, respectively. Chronic glomerulonephritis is the main cause, accounting for more than 80% of patients requiring hemodialysis. 
 Conclusions: In 2023, Lao Cai has 214 patients in need of kidney transplant. 159 patients waiting for a kidney transplant are concentrated mainly at the provincial general hospital with an average age of 43, most of whom have been on dialysis for less than 5 years. The main cause of dialysis is chronic glomerulonephritis.

Sikh and Muslim perspectives on kidney transplantation: phase 1 of the DiGiT project – a qualitative descriptive study

ObjectivesKidney transplantation offers patients better quality of life and survival compared with dialysis. The risk of end stage renal disease is higher among ethnic minorities and they experience longer wait...

From designing minimum data set to developing kidney transplantation registry in Iran.

Currently, population growth and increasing life expectancy are becoming one of the biggest public health challenges in the world, which has increased the prevalence of chronic diseases such as end-stage renal disease and the need for kidney transplantation. The use of a variety of registries has the potential to determine the effectiveness of clinical care and costs and improve the quality of patient care. The aim of this study is to design minimum data set to develop a kidney transplantation registry in Iran to improve the quality of care for people with end-stage renal disease. The present research is descriptive-applied. The minimum data set was reviewed and evaluated in expert panel meetings. The various elements of the minimum data set were discussed, and specialists in urology, nephrology, health information management, and medical informatics presented their views. The characteristics of the kidney transplantation registry in the form of eight axes of purpose, structure, data sources, minimum data set, classification systems, data processing and reporting, distribution and access to information, and data quality were extracted and finally these characteristics were approved by experts. The relevant tables were validated and were within the acceptable range from the point of view of experts. In developing a kidney transplantation registry in Iran, the necessary requirements and features for designing a web-based registry have been considered. The prototype of this registry in the country will help to collect higher quality data. It is hoped that by developing this registry, a step will be taken to better manage the information on people with end-stage renal disease, provide better services to these patients, and facilitate related research.

Management of Hyperkalemia in Patients with Chronic Kidney Disease Using Renin Angiotensin Aldosterone System Inhibitors.

Use of renin-angiotensin-aldosterone system (RAAS) inhibiting medications is critical in the prevention of cardiovascular disease and kidney function decline in patients with chronic kidney disease (CKD); however, these agents can lead to hyperkalemia, an electrolyte disorder associated with risk of arrythmia, conduction disorders, and increased overall mortality. Discontinuation, or reduction of dose, of RAAS inhibitor therapy in hyperkalemic patients with CKD can lead to loss of kidney and cardiovascular protection afforded by these medications. Given the high prevalence of hyperkalemia among patients with CKD utilizing RAAS inhibitors, clear management principles are critical to minimize risk and maximize benefit when facing this clinical dilemma. Strategies to mitigate hyperkalemia that do not interfere with optimal RAAS inhibitor therapy should be prioritized when managing potassium elevation in patients with CKD. These strategies include discontinuing non-RAAS inhibitor medications known to cause hyperkalemia, correction of metabolic acidosis, and maximization of medication therapies that lower serum potassium, including diuretics and sodium-glucose cotransporter-2 (SGLT-2) inhibitors. Initiation of potassium exchange resins should also be considered to allow for sustained RAAS inhibitor utilization. An approach which employs multiple strategies concurrently is important to mitigate hyperkalemia and maintain long-term use of RAAS-inhibitors. Persistence of RAAS inhibitor use in patients with CKD is important to slow kidney function decline, delay onset of dialysis or the need for kidney transplant, and prevent adverse cardiovascular outcomes. When hyperkalemia develops among patients with CKD utilizing a RAAS inhibitor, a deliberate effort to reduce serum potassium levels using an approach that allows for continuation of maximally dosed RAAS inhibitor therapy is important. Patient education and engagement in the potassium management process is important for sustained success.

#5309 MODELLING LONG-TERM OUTCOMES FOR PATIENTS WITH IMMUNOGLOBULIN A NEPHROPATHY (IGAN) FROM SHORT-TERM PROTEINURIA DATA

Abstract Background and Aims Immunoglobulin A nephropathy (IgAN) is rare kidney disease that leads to glomerular injury, progressive loss of kidney function and progression to kidney failure. Pre-specified interim proteinuria data from ongoing clinical trials is being used as the basis of regulatory approval of new therapies but little is known about the translation of these results to long-term patient outcomes; a topic of particular interest to heath technology assessment (HTA) groups looking to inform decisions on reimbursement before final renal outcome data are available. The objective of this study was to model long-term outcomes for patients with IgAN based on short-term proteinuria data. Method We developed a de novo model including a short-term (36-week) decision tree and a long-term Markov model to capture expected lifetime outcomes associated with treatment for IgAN. We used achievement of proteinuria <1 g/day as a clinically relevant treatment target. The short-term model included data on proteinuria level and distribution of chronic kidney disease (CKD) health states (CKD 1/2, 3, 4, and 5). At the end of 36 weeks of treatment, patients were categorized into groups based on their proteinuria level (<1g/day and ≥1 g/day) and CKD stage before transitioning to the long-term Markov model. In the long-term model, proteinuria level-based, CKD health state transition matrices derived from analysis of UK National Registry of Rare Kidney Disease (RaDaR) data, and transition matrices to dialysis and transplant derived from the US Renal Data System (USRDS) were used. Other included clinical inputs of complications and mortality were derived from extension of US Optum data analyses and literature. Health-related quality of life (HRQoL) was assessed as health state utilities and disutility associated with complications. Hypothetic scenarios of improvement in short-term proteinuria and impact on long term outcomes were tested. Model outputs included life years (LYs) and quality-adjusted life years (QALYs). Effectiveness was discounted at 3% annually. Deterministic sensitivity analysis was conducted. Results Over a lifetime, patients receiving treatment that increased the probability of achieving proteinuria <1 g/day by 10% in the short-term, were modelled to have gained an additional 0.388 LYs from reduced CKD/transplant/dialysis-related mortality and 0.633 QALYs from delaying CKD progression to kidney failure. As expected, results improved when the probability of achieving proteinuria <1 g/day increased; with a 30% increase in the probability of achieving proteinuria <1 g/day, LYs gained were 0.562 (Figure 1) and QALYs 0.968 (Figure 2). Results were most sensitive to time horizon and long-term extrapolation of CKD health state transition matrices. Conclusion Despite challenges inherent in the translation of surrogate endpoints to long-term outcomes, combining short-term proteinuria from clinical trials and long-term CKD data from real-world registry and claims-based data provides a solution. Based on modelling, treatments that increase the probability of achieving <1 g/day in the short-term, are expected to provide benefits to patients with IgAN in the long-term including less time with advanced kidney disease, less time on dialysis and avoiding the need for kidney transplant resulting in improved survival, and better quality of life. Refinement and customization of country-specific model inputs will help ensure outputs are relevant for different jurisdictions and as representative of anticipated real-world outcomes as possible.

Electrolytes Play a Role in Detecting Cisplatin-Induced Kidney Complications and May Even Prevent Them-Retrospective Analysis.

Background and Objective: Cisplatin is a chemotherapy drug used to treat several types of malignancies. It is a platinum-based compound that interferes with cell division and DNA replication. Cisplatin has been associated with renal damage. This study evaluates the early detection of nephrotoxicity through routine laboratory tests. Materials and Methods: This is a retrospective chart review based on the Saudi Ministry of National Guard Hospital (MNGHA). We evaluated deferential laboratory tests for cancer patients treated with cisplatin between April 2015 and July 2019. The evaluation included age, sex, WBC, platelets, electrolytes, co-morbidities and interaction with radiology. Results: The review qualified 254 patients for evaluation. Around 29 patients (11.5%) had developed kidney function abnormality. These patients presented with abnormally low magnesium 9 (31%), potassium 6 (20.7%), sodium 19 (65.5%) and calcium 20 (69%). Interestingly, the whole sample size had abnormal electrolytes presenting magnesium 78 (30.8%), potassium 30 (11.9%), sodium 147 (58.1%) and calcium 106 (41.9%). Some pathological features were detected, such as hypomagnesemia, hypocalcemia and hypokalemia. In addition, infections that needed antibiotics were dominant in patients treated with cisplatin alone, representing 50% of this group. Conclusions: We report that an average of 15% of patients with electrolyte abnormalities develop renal toxicity and reduced function. Moreover, electrolytes may serve as an early indicator for renal damage as part of chemotherapy complication. This indication represents 15% of renal toxicity cases. Changes in electrolyte levels have been reported with cisplatin. Specifically, it has been linked to hypomagnesemia, hypocalcemia and hypokalemia. This study will help reduce the risk of dialysis or the need for kidney transplant. It is also important to manage any underlying conditions and control patients' intake of electrolytes.

Treatment for secondary hyperparathyroidism focusing on parathyroidectomy.

Secondary hyperparathyroidism (SHPT) is a major problem for patients with chronic kidney disease and can cause many complications, including osteodystrophy, fractures, and cardiovascular diseases. Treatment for SHPT has changed radically with the advent of calcimimetics; however, parathyroidectomy (PTx) remains one of the most important treatments. For successful PTx, removing all parathyroid glands (PTGs) without complications is essential to prevent persistent or recurrent SHPT. Preoperative imaging studies for the localization of PTGs, such as ultrasonography, computed tomography, and 99mTc-Sestamibi scintigraphy, and intraoperative evaluation methods to confirm the removal of all PTGs, including, intraoperative intact parathyroid hormone monitoring and frozen section diagnosis, are useful. Functional and anatomical preservation of the recurrent laryngeal nerves can be confirmed via intraoperative nerve monitoring. Total or subtotal PTx with or without transcervical thymectomy and autotransplantation can also be performed. Appropriate operative methods for PTx should be selected according to the patients' need for kidney transplantation. In the case of persistent or recurrent SHPT after the initial PTx, localization of the causative PTGs with autotransplantation is challenging as causative PTGs can exist in the neck, mediastinum, or autotransplanted areas. Additionally, the efficacy and cost-effectiveness of calcimimetics and PTx are increasingly being discussed. In this review, medical and surgical treatments for SHPT are described.

Variations in the branching pattern of renal artery

Background: In terms of living kidney transplantation programs worldwide, India is only second to the United States of America. Every year, over 7500 renal transplants are done in India, with 90% of the transplants coming from living donors and the rest from deceased donors. Aims and Objectives: The aim of the study is to examine and describe differences in human renal arteries, compare past studies with the present study, and report the occurrence of major categories of variation. Materials and Methods: This observational study was carried out on 25 well-embalmed adult cadavers in the Department of Anatomy, Rajah Muthiah Medical College, Annamalai Nagar, Chidambaram from December 2016 to October 2018. In all the 25 specimens, the renal artery took its origin from the lateral side of the abdominal aorta. Results: We observed that there is a 92% correlation between L1 and L2, 8% between L3 and L1, and zero between L1 and L2. Accessory renal artery (ARA) was discovered in 18 specimens (36%), with 10 on the right side and eight on the left. Superior polar arteries – 4 (8%), inferior polar arteries – 1 (2%), and hilar arteries – 5% on the right side (10%). Superior polar arteries – 6%, inferior polar arteries – 0%, and hilar arteries – 5% on the left side (10%). Conclusion: Living donor grafts have become a primary source for preserving the donor pool as the need for kidney transplantation rises, and a successful allograft with numerous arteries has become a must. All major vascular channels have not entirely regressed if there are polar or numerous renal arteries to a regularly positioned kidney.

Clinical characteristics and outcomes of a patient population with atypical hemolytic uremic syndrome and malignant hypertension: analysis from the Global aHUS registry

IntroductionAtypical hemolytic uremic syndrome (aHUS) is a rare form of thrombotic microangiopathy (TMA) often caused by alternative complement dysregulation. Patients with aHUS can present with malignant hypertension (MHT), which may also cause TMA.MethodsThis analysis of the Global aHUS Registry (NCT01522183) assessed demographics and clinical characteristics in eculizumab-treated and not-treated patients with aHUS, with (n = 71) and without (n = 1026) malignant hypertension, to further elucidate the potential relationship between aHUS and malignant hypertension.ResultsWhile demographics were similar, patients with aHUS + malignant hypertension had an increased need for renal replacement therapy, including kidney transplantation (47% vs 32%), and more pathogenic variants/anti-complement factor H antibodies (56% vs 37%) than those without malignant hypertension. Not-treated patients with malignant hypertension had the highest incidence of variants/antibodies (65%) and a greater need for kidney transplantation than treated patients with malignant hypertension (65% vs none). In a multivariate analysis, the risk of end-stage kidney disease or death was similar between not-treated patients irrespective of malignant hypertension and was significantly reduced in treated vs not-treated patients with aHUS + malignant hypertension (adjusted HR (95% CI), 0.11 [0.01–0.87], P = 0.036).ConclusionsThese results confirm the high severity and poor prognosis of untreated aHUS and suggest that eculizumab is effective in patients with aHUS ± malignant hypertension. Furthermore, these data highlight the importance of accurate, timely diagnosis and treatment in these populations and support consideration of aHUS in patients with malignant hypertension and TMA.Trial registration detailsAtypical Hemolytic-Uremic Syndrome (aHUS) Registry.Registry number: NCT01522183 (first listed 31st January, 2012; start date 30th April, 2012).Graphical abstract

Renal outcome in patients with complex anorectal malformations

Introduction: Anorectal malformations (ARMs) are one of the most frequent congenital malformations in pediatric surgery. Its estimated incidence ranges between 1 in 2000 and 1 in 5000 live newborns approximately. The aim of the work is to present the associated urinary anomalies and functional renal outcomes in patients with worse prognosis anorectal malformations treated in our department Material and methods: A retrospective review of the patients operated at our center with complex anorectal malformations was performed, including urological abnormalities and long-term renal follow-up. Collected data included the type of urinary abnormality, classified as high or low, renal function (glomerular filtration rate and blood creatinine level), the presence of chronic kidney failure (CKD), the need for surgery to correct the urinary abnormality, the need for kidney transplantation and complications and long-term results. Results: A total of 55 patients were included, 32 girls and 23 boys. Mean age at the time of corrective surgery for the anorectal malformation was 9 months (SD 2.18). The mean follow-up of the patients was 13 years (SD 7.01). Sixty-nine per cent of the patients presented some urological anomaly, being more frequent in the cloacal group. Renal structural abnormalities were found in 22 (40%) of 55 patients. They were identified in 11 (47%) cloacal patients, being the most frequent renal dysplasia (n=7; 32%), followed by position abnormalities in 3. Regarding the lower urinary tract anomalies, it was described in 32 (58%) patients. In the cloacal group, the incidence was 65%, being the most frequent vesicoureteral reflux (n = 14, 60%) as well as in the group of patients with a fistula to the prostatic urethra and in the group with exstrophies of the cloaca (n = 3, 42%). Regarding the rest of the lower urinary tract anomalies, the general incidence of anatomic bladder anomalies (bladder diverticulum, patent urachus) was 15%. As a pathology related to the upper urinary tract: primary obstructive megaureter 5%, ureterocele 1% and posterior urethral valves 1%. Conclusions: Patients with complex anorectal malformations have a significant risk for renal impairment. Adequate screening, high level of suspicion, treatment and long term follow up of any associated urinary anomaly in patients with complex anorectal malformations is essential to preserve renal function and prevent CKD. Care by a multidisciplinary team and adequate transition to adulthood is essential to optimize the medical management of patients and long-term outcomes.

Risk factors for end stage renal disease in children with anorectal malformation and outcome comparison to children with isolated urological anomalies

End stage renal disease (ESRD) requiring kidney transplant (KT) remains an important cause of morbidity in anorectal malformations (ARM) patients. Current literature is scarce on defining the risk factors for ESRD and the outcomes of KT in ARM patients. This study aimed to identify predisposing factors to ESRD in ARM patients and verify if the long term outcome of KT in these patients differs from pure urological anomalies (UA). Databases of ARM and KT patients treated at our center between 2000 and 2016 were used for comparing characteristics of ARM cases which developed ESRD and those who did not, and the outcome features of MAR-KT vs UA-KT. Out of 117 ARM patients, 9 developed ESRD. All of them had a complex ARM. Association with UA were significantly higher in ARM-KT compared to other ARM patients (100% vs. 52%, p=0.001). The most common UA associated to KT in ARM patients was renal dysplasia. During the same period 23 patients underwent KT as a sequelae of pure urological anomalies (UA-KT group). The most represented UA were primary vesico-ureteral reflux (65.2%) and posterior urethral valves (14%) in UA-KT (table 2). ARM-KT patients required more often hemodialysis before KT (50% vs. 8.7%, p=0.05) and an aorto-caval anastomosis at the transplant (75% vs. 30%, p=0.04) compared to UA-KT. Moreover ARM-KT patients experienced more often graft failure and and the need for a second KT (50% vs. 8.6%, p=0.02). To our knowledge, this is the first study describing the differences in terms of risk factors and outcomes of KT in ARM patients. We observed a need for KT in 7% of ARM, which is at the higher end of the range reported in the literature. Bilateral dysplasia and cloaca malformation seem the leading cause to ESRD for ARM patients compared to vesico-ureteral reflux and posterior urethral valve in UA-KT. Our experience showed that KT has worst outcome in ARM vs pure UA patients. Patients with complex ARM are more frequently associated to renal dysplasia which lead to KT. Graft in ARM patients seems to be the more vulnerable and prone to failure.

MO1005: Analysis of Expression of Immune System Genes that are Responsible for Activation and Inhibition of T-Cell Immune Response in Renal Transplant Recipients after Extracorporeal Photochemotherapy

Abstract BACKGROUND AND AIMS Due to the increasing need for kidney transplantation, there is a demand for new methods of preventing rejection of the transplant based on the mechanisms of natural regulation of the immune response. Extracorporeal photopheresis (ECP) is one of these technologies whose clinical efficacy in the prevention and treatment of acute renal transplant rejection has been confirmed by many studies, but the mechanism of its effect has not been fully understood. Characterization of the genes responsible for the activation and inhibition of the immune response during ECP is an important step towards the modification of immunosuppressive therapy. The aim of this study was to analyze the changes in the expression level of the genes responsible for the activation and inhibition of the T-cell response in the recipients of the renal graft after ECP. METHOD An open cohort randomized trial was conducted with 20 patients who underwent a single group cadaver kidney transplantation from an unrelated donor. The recipients of the compared groups received standard immunosuppressive therapy and the same therapy in combination with ECP procedures, according to the study protocol. Each recipient of the main group received 15 sessions of ECP within 6 months. The level of gene expression was analyzed by real-time RT-PCR. Comparison of the study groups was carried out at point 1 (1st–4th day) and 2 (30th day). RESULTS The analysis of clinical data did not show statistically significant clinical differences, but in the specific consideration of each pair of cases, the tendency to some improvement in the transplant organ engraftment rate in the early terms after the transplant, and better survival of the graft and the recipient was revealed. For instance, patients of the main group revealed no transplant rejection by clinical laboratory signs as well as the results of histological examination of biopsy specimens. In the comparison group, acute graft rejection was clinically diagnosed and was confirmed by histological examination as humoral type rejection. The level of expression of genes involved in immune response regulation (CD28, CTLA4, PDL1 and FOXP3) and cytokine genes (TNFA, IL1, IL2, IL10 and IFNG) in the studied groups was determined. A decrease in the level of expression of the genes for the proinflammatory cytokines IL1, IL2 and IFNG was noted by the 30th day after transplantation. At the same time, the expression of the genes PDL1 and FOXP3, which regulate the development of the regulatory response, significantly increased by the 30th day after transplantation. Correlations of the level of gene expression with the presence/absence of rejection episodes have not been established. To assess the effect of the ECP on these gene expression, a comparison was made of the level sof transcript representation of patients receiving standard immunotherapy and immunotherapy in combination with ECP, and a significant increase in the expression of PDL1 and FOXP3 genes (Fig. 1A and B) was found in the group of patients who underwent ECP procedures (P = .0009 and .0013, respectively). CONCLUSION According to the results of comparative analysis, the level of expression of pro-inflammatory cytokines' genes IL1, IL2 and IFNG decreased to the 30th day after transplantation. A 30-day comparison between groups shows an increase in the expression level of the PDL1 and FOXP3 genes. Increased expression of these genes may be associated with the activation of regulatory T-cells and the development of peripheral tolerance and can become a criterion for the modification of immunosuppressive therapy.

Kidney Transplantation in Single Ventricle Palliated Patients: A Pediatric Cardiac Care Consortium Study

<h3>Purpose</h3> Development of chronic kidney disease is well described in patients with complex congenital heart disease such as palliated single ventricle patients. It is also well known that presence of kidney disease contributes to morbidity and mortality in these patients. However, there is no study if the progression of kidney disease in these patients necessitates kidney transplantation and risk factors associated with need for kidney transplantation (KTX). <h3>Methods</h3> A retrospective cohort study of patients undergoing single ventricle palliation in the Pediatric Cardiac Care Consortium (PCCC), a large US-based registry. Outcomes and transplants were captured in the PCCC and by linkage with the Organ Procurement Transplant Network (OPTN) through 2019. <h3>Results</h3> Between 1982 -2019, 7751 patients with SV palliation were seen at US centers and 6385 patients had identifiers allowing appropriate linkage with OPTN database. Of these, 14 patients (0.22%) underwent KTX. Patients undergoing KTX were predominantly male (71%), white race (64.3%) and underwent KTX at a mean age of 21 (±9) years, mean time to KTX from last cardiac surgery 15.2 (±8.7) years. Cardiac diagnostic group was systemic right ventricle in 8/14 (57%). At follow-up, 11/14 (78%) were alive while 3/14 (22%) died at a mean age of 29 (±10.6) years. There were no differences in the demographic and diagnosis between those who received KTX versus those who did not. However, at follow up only 50.4% of patients without KTX were alive compared to 78.6% in the KTX group (p=0.03) while the mean age at death was 1 (0, 14) years in non-KTX group compared to 33.0 (17.0, 37.0) years in the KTX group (p= 0.011). Two patients needed kidney transplantation after heart transplantation. <h3>Conclusion</h3> First of its kind study shows that kidney transplantation is rarely performed in patients with single ventricle palliation although kidney disease is well documented in this population. This study findings potentially reflect selection bias and survival bias. We plan to elucidate the same further. Need for KTX appears to be higher in males with systemic right ventricle anatomy in the second or early third decade. Given that there is high mortality in the overall cohort, and given improved survival of patients undergoing combined heart kidney transplantation, further studies should focus on patient selection and early intervention.

Multi-Target Drugs for Kidney Diseases.

Kidney diseases such as AKI, CKD, and GN can lead to dialysis and the need for kidney transplantation. The pathologies for kidney diseases are extremely complex, progress at different rates, and involve several cell types and cell signaling pathways. Complex kidney diseases require therapeutics that can act on multiple targets. In the past 10 years, in silico design of drugs has allowed for multi-target drugs to progress quickly from concept to reality. Several multi-target drugs have been made successfully to target AA pathways and transcription factors for the treatment of inflammatory, fibrotic, and metabolic diseases. Multi-target drugs have also demonstrated great potential to treat diabetic nephropathy and fibrotic kidney disease. These drugs act by decreasing renal TGF-β signaling, inflammation, mitochondrial dysfunction, and oxidative stress. There are several other recently developed multi-target drugs that have yet to be tested for their ability to combat kidney diseases. Overall, there is excellent potential for multi-target drugs that act on several cell types and signaling pathways to treat kidney diseases.

Liver transplantation for congenital hepatic fibrosis.

Congenital hepatic fibrosis (CHF) is a hereditary fibrocystic disease that can progress to portal hypertension and recurrent cholangitis requiring liver transplantation (LT). It can be associated with renal pathology and need for kidney transplantation (KT). We describe the clinical characteristics and outcomes of patients undergoing liver transplantation alone (LTA) and simultaneous liver-kidney transplantation (SLKT) for CHF using the Unites States Scientific Registry of Transplant Recipients. A total of 197 patients who received LT for CHF between 2002 and 2018 were identified - 87 (44.2%) received SLKT, 110 (55.8%) received LTA. The 1-, 3- and 5-year patient survival were 99.0%, 96.2% and 94.6%. The 1-, 3- and 5-year liver graft survival were 94.9%, 91.1% and 89.6%. No significant differences in patient or liver graft survival were observed between the SLKT and LTA groups, or between paediatric and adult recipients. 53.3% of patients with CHF necessitating LT also have significant renal disease requiring KT. Kidney graft survival for isolated KT prior to LT were poorer compared with KT performed simultaneously or after LT. Both LTA and SLKT for CHF are associated with excellent long-term outcomes in paediatric and adult patients.

MO1028EFFECTIVENESS AND KIDNEY PROGNOSIS IN THE TREATMENT OF CORTICORRESISTANT NEPHROTIC SYNDROME IN PEDIATRICS

Abstract Background and Aims To report the response to different treatments and the renal prognosis in a cohort of patients with corticosteroid-resistant nephrotic syndrome (CRNS). Method Retrospective observational study in patients with CRNS. For this, the results of the histology, the different treatment guidelines used in each case and the evolution of renal function were collected, determining the results in terms of remission and renal survival in the different groups. Results Of the initial cohort of 37 patients, 33 were included, excluding 4 patients with Finnish-type genetic CRNS. The mean age at diagnosis was 6.1 years. 54.5% were women. Regarding the initial biopsy, 45.5% corresponded to minimal changes (15 patients), 27.3% (9) focal and segmental glomerulosclerosis, 15.1% (5) diffuse mesangial proliferation and 12.1% (4) others. The mean follow-up was 53 months (3-115 months). 27 patients (84.4%) received cyclosporine (CyA), 66.7% (18) of them presented complete remission and 22.2% (6) partial response. Of the patients in complete remission, 33% had at least one relapse after 17 months of treatment (7–27 months). Rituximab was administered in 12 patients (37.5%), of which 7 had not previously responded to immunosuppressants. 100% of frequent relapsers presented complete remission after administration of Rituximab, although 3 had subsequent relapses (60%) after 21 months of treatment (12-34 months). 57% of the patients who did not respond to immunosuppressants did not respond to Rituximab either, with Ofatumumab allowing complete remission in one of them. When relating the results with the histology, we saw how the remission in minimal changes and diffuse mesangial proliferation was 100% and 80%, respectively, although it was 33.3% in focal and segmental glomerulosclerosis. Similarly, renal failure was more frequent in patients with focal segmental glomerulosclerosis (77.7%). Of the remissions (24; 72.7%), 3 were partial (9.1%) and 6 (18.2%) did not respond to any immunosuppressive treatment, with the need for kidney transplantation in 2 of them (6%) and with 1 deceased due to an infectious cause (3%). Conclusion Histology and, especially, focal and segmental glomerulosclerosis, play a prognostic role in the CRNS with a lower remission rate and a greater deterioration in renal function and the need for associated kidney transplantation.

MO465PROGNOSTIC IMPLICATION OF URINARY POTASSIUM EXCRETION IN PATIENTS WITH CHRONIC KIDNEY DISEASE

Abstract Background and Aims Plasma potassium levels are impacted by decreased kidney function and are known to be associated with increased mortality, adverse cardiovascular events and adverse kidney events. However, the prognostic implication of urinary potassium is unclear. Method We conducted an observational study of 1102 patients with chronic kidney disease (CKD) who were hospitalized between 2010 and 2018. The expected primary outcomes were all-cause mortality, adverse cardiovascular events and CKD progression. CKD progression was defined as a 30% increase in serum creatinine, the initiation of maintenance dialysis or the need for kidney transplantation. The Cox proportional hazards model was used to analyse the association between urinary potassium excretion and adverse clinical outcomes after adjustment for potential confounders. Results At baseline, 66% of the patients were men, with a median age of 72 years (interquartile range or IQR, 64–79 years); 61% of the patients were diabetic, and 54% of them were hypertensive. The median values for estimated glomerular filtration rate (eGFR) was 12 mL/min/1.73m2 (IQR, 8–18), serum potassium 4.5 mmol/L (IQR, 4.1–5.1) and urinary potassium/creatinine ratio (UK/Cr) 27 mmol/gCr (IQR, 20–38). Over a median follow-up period of 2.6 years (IQR 0.2–4.5), the number of all-cause deaths was 87. There were 171 cases of cardiovascular events and 860 cases of CKD progression. After adjusting for the eGFR, serum potassium level, proteinuria, renin–angiotensin system inhibitors, diuretics and other potential confounders, UK/Cr was found to be neither significantly associated with all-cause mortality nor with adverse cardiovascular events. However, a low UK/Cr was associated with an increased risk of CKD progression (adjusted hazard ratio [95% confidence interval] for the first, second and third quartiles, compared with the fourth quartile, were as follows: 2.09 [1.43-3.06], 1.33 [0.96-1.86] and 1.05 [0.75-1.46]) Conclusion A low UK/Cr might be an independent risk factor for poor renal outcome.