Diagnosis and management of primary hyperoxalurias: best practices.

The primary hyperoxalurias (PH 1, 2, and 3) are rare autosomal recessive disorders of glyoxylate metabolism resulting in hepatic overproduction of oxalate. Clinical presentations that should prompt consideration of PH include kidney stones, nephrocalcinosis, and kidney failure of unknown etiology, especially with echogenic kidneys on ultrasound. PH1 is the most common and severe of the primary hyperoxalurias with a high incidence of kidney failure as early as infancy. Until the recent availability of a novel RNA interference (RNAi) agent, PH care was largely supportive of eventual need for kidney/liver transplantation in PH1 and PH2. Together with the Oxalosis and Hyperoxaluria Foundation, the authors developed a diagnostic algorithm for PH1 and in this report outline best clinical practices related to its early diagnosis, supportive treatment, and long-term management, including the use of the novel RNAi. PH1-focused approaches to dialysis and kidney/liver transplantation for PH patients with progression to chronic kidney disease/kidney failure and systemic oxalosis are suggested. Therapeutic advances for this devastating disease heighten the importance of early diagnosis and informed treatment.

Acute kidney injury: prediction, prognostication and optimisation for liver transplant.

The definition and diagnostic criteria of renal dysfunction in cirrhosis have undergone significant recent changes. Acute kidney injury (AKI) is defined by a change in serum creatinine of ≥ 26.4 µmol/L (0.3 mg/dL) in < 48 h. Its severity is defined by stages. Chronic kidney disease (CKD) is defined by a reduction in the estimated glomerular filtration rate (GFR) to < 60 mL/min for more than 3 months. Both AKI and CKD can be related to reduced renal perfusion, the so-called functional renal failure; or due to structural damage to the renal parenchyma. Hemodynamic changes and excess inflammation are the pathophysiological processes that predispose the cirrhotic patient to the development of functional AKI. Events that cause further perturbation of hemodynamics or promote further inflammation such as bacterial infection will precipitate AKI. Management starts by removing potential precipitating factors and replenish the intravascular volume. Albumin is the preferred volume expander as it has multiple properties that can significantly reduce the extent of inflammation as well as improving the intravascular volume. Non-responders to albumin infusion should receive vasoconstrictor therapy such as terlipressin, titrated to patient's blood pressure response, and is effective in approximately 50% of patients. All patients with renal and liver dysfunction should be evaluated for liver transplantation, with renal replacement therapy as a bridge. Guidelines are in place for combined liver and kidney transplants. Future studies on AKI should evaluate the effects of vasoconstrictors on renal function as defined by recent criteria, and to develop biomarkers to identify susceptible patients so to institute treatment early.

Disseminated Trichosporon asahii infection in a combined liver-kidney transplant recipient successfully treated with voriconazole.

INTRODUCTION: Trichosporon asahii is an emerging cause of systemic fungal infection in an immunocompromised host. Several life threatening disseminated T. asahii infection in single solid organ (liver or kidney) transplant recipients, in neutropenic and hematological malignancy patients have been reported. CASE PRESENTATION (METHODS AND RESULTS): A 49-year old gentleman who underwent simultaneous living-donor liver transplantation (donor sister) and kidney transplant (donor wife) developed fever and subsegmental patchy consolidation with right sided pleural effusion on fourth postoperative day. Central line blood stream infection was suspected. Blood culture grew creamy white colonies of T. asahii on blood agar with characteristic dirty-green colonies on CHROMagar. Laboratory analysis of pleural fluid also revealed budding yeast cells identified as T. asahii. Microscopy of the isolates showed hyphae, arthroconidia, and blastospores. The isolates were identified as T. asahii by VITEK MS which uses matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) technology. Initially liposomal amphotericin B and micafungin was initiated, but due to lack of clinical and microbiological response, patient was switched to voriconazole. Simultaneously, tacrolimus doses were reduced to one-third in view of interaction with voriconazole. Subsequently, patient improved with resolution of fever and microbiological cure. CONCLUSION: This is the first case report of disseminated T. asahii infection in a combined liver-kidney transplant recipient successfully treated with voriconazole. Azole antifungal are the promising drug of choice for systemic T. asahii infection. Drug interactions should be considered while using these antifungal agents.

Trasplante combinado hígado-riñón en la fundación valle del Lili, Cali, Colombia - Experiencia de un centro / The experience of the Fundacion Valle Del Lili in Cali, Colombia with Combined Liver and Kidney Transplantation

Introducción: el trasplante combinado de hígado y riñón (CLK) ha mostrado ser una buena alternativa para pacientes con diagnóstico concomitante de enfermedad renal crónica (ERC) y enfermedad hepática terminal. Algunos estudios han mostrado además un beneficio inmunológico del trasplante combinado, con disminución de la tasa de rechazo del injerto renal. Objetivo: describir las indicaciones y los resultados clínicos en receptores de trasplante CLK en un hospital de alta complejidad. Materiales y métodos: se seleccionaron los pacientes con trasplante CLK del registro institucional de trasplante (TRENAL) entre 2000 y 2011. Se describieron las características demográficas y clínicas y se estimó la sobrevida de los pacientes y de los injertos con el método Kaplan Meier. Resultados: en un período de 11 años, se realizaron 16 trasplantes CLK. Esto corresponde al 1.51% de los trasplantes de riñón y al 3.48% de los trasplantes de hígado hechos en la institución durante el mismo periodo de tiempo. La mayoría de los receptores fueron de sexo masculino (10/16). La mediana de la edad fue 56.5 años. La mediana del MELD fue de 17 (RIQ: 12.5-20.5, Rango 8-24). El diagnóstico hepático más frecuente fue cirrosis por NASH (4/16). Todos los pacientes tenían diagnóstico de ERC, en 4 casos secundaria a diabetes mellitus. Las indicaciones más comunes del trasplante fueron ascitis de difícil manejo, encefalopatía recurrente y desnutrición. El tiempo promedio de isquemia en frío del hígado fue de 7,3 horas, y del riñón 9,6 horas. La sobrevida de los pacientes y de los injertos hepático y renal fue de 87,5% al año y 67,3% a los 5 años. Cuatro pacientes murieron, 2 casos como consecuencia de sepsis y otros 2 por malignidad. Conclusión: el trasplante CLK en la Fundación Valle del Lili tiene resultados clínicos satisfactorios y comparables a los reportados en otros centros.

Introduction: Combined liver and kidney transplantation (CLK) has been shown to be a good alternative for patients with concomitant diagnosis of chronic kidney disease (CKD) and end-stage liver disease. Some studies have also shown immunological benefits from combined transplantation with decreased rates of kidney graft rejection. Objective: The objective of this study was to describe the indications and clinical outcomes of CLK transplant recipients in a highly complex hospital. Materials and Methods: CLK transplant patients were selected from the institutional transplant registry (Trenal) from 2000 to 2011. Demographic and clinical characteristics were described and survival of patients and grafts were estimated with the Kaplan-Meier method. Results: Over a period of 11 years, 16 CLK transplants were performed. This was 1.51% of kidney transplants and 3.48% of liver transplants done in the institution during this period. Most recipients were male (10/16). The median age was 56.5 years. The median MELD was 17 (IQR: 12.5 to 20.5, range: 8 to 24). The most frequent diagnosis was liver cirrhosis due to NASH (4/16). All patients had been diagnosed with CKD: four cases were secondary to diabetes mellitus. The most common indications for transplants were difficult to manage ascites, recurrent encephalopathy and malnutrition. The average liver cold ischemia time was 7.3 hours, and the average kidney cold ischemia time 9.6 hours. The five-year liver graft survival rate was 87.5%, and the five-year kidney graft survival rate was 67.3%. Four patients died: two as the result of sepsis and two as the result of malignancy. Conclusion: CLK transplantation results at the Fundación Valle del Lili have been satisfactory and comparable to those reported by other transplant centers.

Combined liver-kidney transplantation for polycystic liver and kidney disease: analysis from the United Network for Organ Sharing dataset.

BACKGROUND & AIMS: The purpose of this study was to evaluate predictors of outcomes in combined liver-kidney transplants for polycystic liver and kidney disease. METHODS: We queried the United Network for Organ Sharing dataset for combined liver-kidney transplants performed from 1988 to 2013. RESULTS: Out of 107 patients who had combined liver-kidney transplants for polycystic liver and kidney disease, 84 were women (78.5%) with a mean age of 54.9 ±7.2 years. Kaplan-Meier analysis demonstrated that patients undergoing liver-kidney transplantation for polycystic liver and kidney disease had better survival than patients with polycystic liver disease undergoing liver transplant alone and those undergoing liver-kidney transplantation for other indications. This group had a 1-, 3- and 5-year survival of 91%, 90% and 90%, respectively. Multivariable analysis demonstrated that an indication of polycystic liver and kidney disease for combined liver-kidney transplant (hazard ratio, 0.29; 95% confidence interval, 0.129-0.526; P < 0.001) and Model for End-Stage Liver Disease score (hazard ratio, 1.271; 95% confidence interval, 1.093-1.477; P = 0.002) are independently associated with patient survival. In a propensity score analysis adjusting for age, gender, cold ischaemia time and total bilirubin and excluding hepatitis C, we found that patients transplanted with combined liver-kidney for other indications have similar survival compared with our study group. CONCLUSIONS: Combined liver-kidney transplantation for polycystic liver and kidney disease can achieve good outcomes in selected patients. On Cox regression analysis, patients with polycystic liver and kidney disease undergoing liver-kidney transplantation had better survival compared with patients with combined liver-kidney for other indications. After excluding hepatitis C patients, those transplanted for polycystic liver and kidney disease vs other indications had similar survival after combined liver-kidney transplantation. Interestingly, patients in the combined polycystic liver and kidney disease group have significantly better outcomes than patients with polycystic liver disease undergoing liver transplant alone.

Simultaneous Liver-Kidney Transplantation.

In 2014, simultaneous liver kidney transplants (SLK) accounted for 8.2 % of all liver transplants performed in the USA. Prior to introduction of the model of end stage liver disease (MELD) system, SLK accounted for 2.5 % in 2001 and only 1.7 % in 1990. Transplant centers have struggled to balance the moral and ethical aspects of SLK in the setting of organ scarcity with an algorithm that best qualifies patients for such treatment options. Few centers have even ventured into DCD territory for SLK. Advancement in immunosuppression protocols and treatment of HCV and HIV have impacted SLK over the years. Simulation modeling has allowed us to analyze the future impact of our decisions that are made today. All of these advancements have given, and will continue to give new perspectives to SLK. The purpose of this review article is to highlight these advances and bring to light the studies that have made this transplant option successful.

Outcomes after combined liver-kidney transplant vs. kidney transplant followed by liver transplant.

INTRODUCTION: The decision for isolated kidney transplant (KT) vs. combined liver-kidney transplant (CLKT) in patients with end-stage renal disease (ESRD) with compensated cirrhosis remains controversial. We sought to determine outcomes of patients requiring listing for a liver transplant (LT) following either a cadaveric or living donor KT and compare these outcomes to similar patients receiving a CLKT. METHODS: Our dataset included the United Network for Organ Sharing (UNOS)/Standard Transplant and Analysis and Research (STAR) kidney files from 1987 to 2012 after being joined with the liver files from 2002 to 2012. Outcomes of patients who received a CLKT with an international normalized ratio (INR) ≤1 and total bilirubin ≤1 were compared to patients who received a primary KT and subsequently required listing for LT between zero and five yr or after five yr. RESULTS: For the three groups, 244 patients had a CLKT, 216 were wait-listed for LT between zero and five yr after KT (0-5 WL), and 320 were wait-listed five yr after KT (+5 WL). From the time of KT, the 0-5 WL group had significantly worse survival than the CLKT group and the +5 WL group. The +5 WL had the best survival of all groups. For the 0-5 WL group, 45% underwent LT and 40% died while waiting compared to the +5 WL group with 53% having LT and 26% died while waiting. At the time of LT, the 0-5 WL group had a higher model for end-stage liver disease (MELD) score, higher incidence of being in the ICU at the time of transplant, and higher incidence of requiring life support. From the time of LT, the CLKT trended toward better survival (p = 0.0549) than both the 0-5 WL and +5 WL groups, which had equivalent survival. CONCLUSION: The 0-5 WL group is a higher risk group with poorer survival due to a higher incidence of dying on the waitlist. Better identification of patients with a high risk for hepatic decompensation following KT and agreement for regional exception for LT in the event of decompensation may improve utilization of organs and better survival for those patients.