Combined liver-kidney transplantation with delayed kidney implantation: A case report.

INTRODUCTION: In rare cases, patients require a combined liver-kidney transplant. However, the peri- and postoperative care of liver transplant recipients differs from kidney transplant recipients, which can lead to conflicts of interest. In the case of poor coagulation status and/or instable hemodynamics of the patient, liver transplantation, followed by delayed kidney transplantation can lead to better postoperative recovery. PRESENTATION OF CASE: In our case report, we present a 48-year old man with Alagille syndrome and IgA nephropathy with bilirubin-associated acute kidney injury, causing him to develop both end-stage liver and kidney disease. He underwent a combined liver-kidney transplant as the first patient in the Netherlands, in which the donor kidney was transplanted one day after the liver transplantation. One-year post-transplant patient is in good clinical condition, with normal liver function and an eGFR of 57 ml/min. CONCLUSION: Combined liver-kidney transplantation with delayed kidney implantation in a medical center with no previous experience with this technique is feasible and safe. This could be better for both the patient and the kidney graft.

Renal outcome and plasma methylmalonic acid levels after isolated or combined liver or kidney transplantation in patients with methylmalonic acidemia: A multicenter analysis.

BACKGROUND: Methylmalonic acidemia (MMAemia) is characterized by accumulation of methylmalonic acid (MMA) in all body tissues. To minimize disease-related complications, isolated kidney (KTx), liver (LTx) or combined liver-kidney transplantation (LKTx) have been suggested. However, the impact of these different transplant strategies on outcome are unclear. METHODS: In this multicenter retrospective observational study, we compared plasma MMA levels and estimated glomerular filtration rate (eGFR) data of 83 patients. Sixty-eight patients (82%) had a mut0-type MMAemia, one patient had a mut--type MMAemia, and seven (7.3%) had an inherited defect in cobalamin metabolism (cblA- or cblB-type MMAemia). Median observation period was 3.7 years (0-15.1 years). RESULTS: Twenty-six (31%) patients underwent KTx, 24 (29%) LTx and 33 (40%) LKTx. Posttransplant, mean plasma MMA concentration significantly decreased in all three cohorts; but at month 12, plasma MMA in KTx (1372 ± 1101 µmol/L) was 7.8-fold higher than in LTx (176 ± 103 µmol/L; P < 0.001) and 6.4-fold higher than in LKTx (215 ± 110 µmol/L; P < 0.001). Comparable data were observed at month 24. At time of transplantation, mean eGFR in KTx was 18.1 ± 24.3 mL/min/1.73 m2, in LTx 99.8 ± 29.9 mL/min/1.73 m2, and in LKTx 31.5 ± 21.2 mL/min/1.73 m2. At month 12 posttransplant, mean eGFR in KTx (62.3 ± 30.3 mL/min/1.73 m2) was 33.4% lower than in LTx (93.5 ± 18.3 mL/min/1.73 m2; P = 0.0053) and 25.4% lower than in LKTx (83.5 ± 26.9 mL/min/1.73 m2; P = 0.0403). CONCLUSIONS: In patients with isolated MMAemia, LTx and LKTx lead to markedly lower plasma MMA levels during the first 2 years posttransplant than KTx and are associated with a better preservation of kidney function. LTx should therefore be part of the transplant strategy in MMAemia.

Update on hepatorenal Syndrome: Definition, Pathogenesis, and management.

Hepatorenal syndrome (HRS) is acute kidney injury (AKI) that occurs without evidence of structural abnormalities in the kidneys in patients with liver disease. It is thought to be due to splanchnic vasculature dilatation that is associated with intense increase of renal arteries' tone, leading to renal cortex ischemia and AKI. Nitric oxide, endotoxins, neurohormonal changes, bacterial infection, high serum bilirubin and bile acids are examples for factors contributing to HRS development. Nevertheless, other unknown factors may have role in HRS pathophysiology. Hence, further discussion and research are needed to clearly understand HRS. Plasma volume restoration and vasoconstrictors are the cornerstone of HRS treatment. Others such as octreotide, noradrenaline, infection control, systemic inflammatory response prevention, shunting, and renal replacement therapy are currently used to manage HRS. Liver or combined liver and kidney transplantation is currently the ultimate cure for HRS. This review was written to help in better understanding the pathogenesis, diagnosis, and treatment options for HRS.

Long-Term Transplantation Outcomes in Patients With Primary Hyperoxaluria Type 1 Included in the European Hyperoxaluria Consortium (OxalEurope) Registry.

INTRODUCTION: In primary hyperoxaluria type 1 (PH1), oxalate overproduction frequently causes kidney stones, nephrocalcinosis, and kidney failure. As PH1 is caused by a congenital liver enzyme defect, combined liver-kidney transplantation (CLKT) has been recommended in patients with kidney failure. Nevertheless, systematic analyses on long-term transplantation outcomes are scarce. The merits of a sequential over combined procedure regarding kidney graft survival remain unclear as is the place of isolated kidney transplantation (KT) for patients with vitamin B6-responsive genotypes. METHODS: We used the OxalEurope registry for retrospective analyses of patients with PH1 who underwent transplantation. Analyses of crude Kaplan-Meier survival curves and adjusted relative hazards from the Cox proportional hazards model were performed. RESULTS: A total of 267 patients with PH1 underwent transplantation between 1978 and 2019. Data of 244 patients (159 CLKTs, 48 isolated KTs, 37 sequential liver-KTs [SLKTs]) were eligible for comparative analyses. Comparing CLKTs with isolated KTs, adjusted mortality was similar in patients with B6-unresponsive genotypes but lower after isolated KT in patients with B6-responsive genotypes (adjusted hazard ratio 0.07, 95% CI: 0.01-0.75, P = 0.028). CLKT yielded higher adjusted event-free survival and death-censored kidney graft survival in patients with B6-unresponsive genotypes (P = 0.025, P < 0.001) but not in patients with B6-responsive genotypes (P = 0.145, P = 0.421). Outcomes for 159 combined procedures versus 37 sequential procedures were comparable. There were 12 patients who underwent pre-emptive liver transplantation (PLT) with poor outcomes. CONCLUSION: The CLKT or SLKT remains the preferred transplantation modality in patients with PH1 with B6-unresponsive genotypes, but isolated KT could be an alternative approach in patients with B6-responsive genotypes.

Summary of clinical characteristics, diagnosis and treatment of primary hyperoxaluria type 1 in mainland China / 器官移植

Objective To investigate the clinical manifestations, treatment and prognosis of primary hyperoxaluria type 1 (PH1). Methods Relevant literature review was conducted from Chongqing VIP, CNKI, Wanfang Data, PubMed, Web of Science, Embase and Cochrane databases. Clinical data of 57 patients with PH1 were collected, and the clinical manifestations, diagnosis and treatment and prognosis were analyzed. Results A total of 35 eligible studies were searched, including 57 patients with PH1, 39 male and 18 female, aged 0.2-57.0 years old, and the age of onset was from date of birth to 42 years old. The specificity of clinical symptoms of 57 patients with PH1 was relatively low, including 41 cases of renal stones, 21 cases of renal calcification and/or calcium deposition, 12 cases of oxalic acid deposition outside the urinary system, 12 cases of lumbago, backache and abdominal pain, and 8 cases of ureteral stones. Besides, alternative symptoms, such as decreased urine output, metabolic acidosis, disorder of water and electrolyte, anemia and gross hematuria were also reported. Thirty-three patients were diagnosed with end-stage renal disease (ESRD) upon admission. Twenty-six patients received transplantation. Among them, 17 cases underwent kidney transplantation (2 cases repeatedly received combined liver-kidney transplantation due to recurrence of stones and resumption of dialysis, and 1 case repeatedly received liver transplantation due to resumption of dialysis), 7 cases received combined liver-kidney transplantation, 2 cases underwent liver transplantation, and 3 cases received sequential liver-kidney transplantation, respectively. Thirty-one patients did not undergo transplantation. Significant differences were observed in the survival rate between patients treated with and without transplantation (85% vs. 58%, P < 0.05). Conclusions Clinical manifestations of PH1 are diverse and lack of specificity. A majority of PH1 patients are diagnosed with ESRD upon admission. Clinical prognosis of patients undergoing transplantation is better than that of those counterparts without transplantation. Prior liver transplantation or combined liver-kidney transplantation is recommended.

Case Report: Combined Liver-Kidney Transplantation to Correct a Mutation in Complement Factor B in an Atypical Hemolytic Uremic Syndrome Patient.

Pathogenic gain-of-function variants in complement Factor B were identified as causative of atypical Hemolytic Uremic syndrome (aHUS) in 2007. These mutations generate a reduction on the plasma levels of complement C3. A four-month-old boy was diagnosed with hypocomplementemic aHUS in May 2000, and he suffered seven recurrences during the following three years. He developed a severe hypertension which required 6 anti-hypertensive drugs and presented acrocyanosis and several confusional episodes. Plasma infusion or exchange, and immunosuppressive treatments did not improve the clinical evolution, and the patient developed end-stage renal disease at the age of 3 years. Hypertension and vascular symptoms persisted while he was on peritoneal dialysis or hemodialysis, as well as after bilateral nephrectomy. C3 levels remained low, while C4 levels were normal. In 2005, a heterozygous gain-of-function mutation in Factor B (K323E) was found. A combined liver and kidney transplantation (CLKT) was performed in March 2009, since there was not any therapy for complement inhibition in these patients. Kidney and liver functions normalized in the first two weeks, and the C3/C4 ratio immediately after transplantation, indicating that the C3 activation has been corrected. After remaining stable for 4 years, the patient suffered a B-cell non-Hodgkin lymphoma that was cured by chemotherapy and reduction of immunosuppressive drugs. Signs of liver rejection with cholangitis were observed a few months later, and a second liver graft was done 11 years after the CLKT. One year later, the patient maintains normal kidney and liver functions, also C3 and C4 levels are within the normal range. The 12-year follow-up of the patient reveals that, in spite of severe complications, CLKT was an acceptable therapeutic option for this aHUS patient.

A comparison between combined liver kidney transplants to liver transplants alone: A systematic review and meta-analysis.

BACKGROUND: Since the introduction of the Model for End-stage Liver disease criteria in 2002, more combined liver kidney transplants are performed. Until 2017, no standard allocation policy for combined liver kidney transplant (CLKT) was available and each transplant center decided eligibility for CLKT or liver transplant alone (LTA) on a case-by-case basis. The aim of this systematic review was to compare the clinical outcomes of CLKT compared to LTA in patients with renal dysfunction. METHODS: Databases were systematically searched for studies published between January 2010 and March 2021. Outcomes were expressed as risk ratios and pooled with a random-effects model. The primary outcome was patient survival. RESULTS: Four studies were included. No differences were observed for mortality risk at 1 year (risk ratio (RR) 1.03 [confidence interval (CI) 0.97-1.09], 3 years (RR 1.06 [CI 0.99-1.13]) and 5 years (RR 1.08 [CI 0.98-1.19]). The risk of graft loss was similar in the first year (RR 1.10 [CI 0.93-1.30], while 3-year risk of graft loss was significantly lower in CLKT patients (RR 1.15 [CI 1.08-1.24]). CONCLUSIONS: CLKT has similar short-term graft and patient survival as LTA in patients with renal dysfunction. More data is needed to decide from which KDIGO stage patients benefit the most from CLKT.

Combined Liver-Kidney Transplantation With Preformed Anti-human Leukocyte Antigen Donor-Specific Antibodies.

INTRODUCTION: The impact of preformed donor-specific anti-human leukocyte antigen (HLA) antibodies (pDSAs) after combined liver-kidney transplantation (CLKT) is still uncertain. METHODS: We conducted a retrospective study in 8 European high-volume transplant centers and investigated the outcome of 166 consecutive CLKTs, including 46 patients with pDSAs. RESULTS: Patient survival was lower in those with pDSAs (5-year patient survival rate of 63% and 78% with or without pDSA, respectively; P = 0.04). The presence of pDSAs with a mean fluorescence intensity (MFI) ≥ 5000 (hazard ratio 4.96; 95% confidence interval: 2.3-10.9; P < 0.001) and the presence of 3 or more pDSAs (hazard ratio 6.5; 95% confidence interval: 2.5-18.8; P = 0.05) were independently associated with death. The death-censored liver graft survival was similar in patients with or without pDSAs. Kidney graft survival was comparable in both groups. (The 1- and 5-year death-censored graft survival rates were 91.6% and 79.5%, respectively, in patients with pDSAs and 93% and 88%, respectively, in the donor-specific antibody [DSA]-negative group, P = not significant). Despite a higher rate of kidney graft rejection in patients with pDSAs (5-year kidney graft survival rate without rejection of 87% and 97% with or without pDSAs, respectively; P = 0.04), kidney function did not statistically differ between both groups at 5 years post-transplantation (estimated glomerular filtration rate 45 ± 17 vs. 57 ± 29 ml/min per 1.73 m2, respectively, in patients with and without pDSAs). Five recipients with pDSAs (11.0%) experienced an antibody-mediated kidney rejection that led to graft loss in 1 patient. CONCLUSION: Our results suggest that CLKT with pDSAs is associated with a lower patients' survival despite good recipients', liver and kidney grafts' outcome.

Combined liver-kidney transplantation for rare diseases.

Combined liver and kidney transplantation (CLKT) is indicated in patients with failure of both organs, or for the treatment of end-stage chronic kidney disease (ESKD) caused by a genetic defect in the liver. The aim of the present review is to provide the most up-to-date overview of the rare conditions as indications for CLKT. They are major indications for CLKT in children. However, in some of them (e.g., atypical hemolytic uremic syndrome or primary hyperoxaluria), CLKT may be required in adults as well. Primary hyperoxaluria is divided into three types, of which type 1 and 2 lead to ESKD. CLKT has been proven effective in renal function replacement, at the same time preventing recurrence of the disease. Nephronophthisis is associated with liver fibrosis in 5% of cases and these patients are candidates for CLKT. In alpha 1-antitrypsin deficiency, hereditary C3 deficiency, lecithin cholesterol acyltransferase deficiency and glycogen storage diseases, glomerular or tubulointerstitial disease can lead to chronic kidney disease. Liver transplantation as a part of CLKT corrects underlying genetic and consequent metabolic abnormality. In atypical hemolytic uremic syndrome caused by mutations in the genes for factor H, successful CLKT has been reported in a small number of patients. However, for this indication, CLKT has been largely replaced by eculizumab, an anti-C5 antibody. CLKT has been well established to provide immune protection of the transplanted kidney against donor-specific antibodies against class I HLA, facilitating transplantation in a highly sensitized recipient.

Combined liver and kidney transplantation in children and long-term outcome.

Combined liver-kidney transplantation (CLKT) is a rarely performed complex surgical procedure in children and involves transplantation of kidney and either whole or part of liver donated by the same individual (usually a cadaver) to the same recipient during a single surgical procedure. Most common indications for CLKT in children are autosomal recessive polycystic kidney disease and primary hyperoxaluria type 1. Atypical haemolytic uremic syndrome, methylmalonic academia, and conditions where liver and renal failure co-exists may be indications for CLKT. CLKT is often preferred over sequential liver-kidney transplantation due to immunoprotective effects of transplanted liver on renal allograft; however, liver survival has no significant impact. Since CLKT is a major surgical procedure which involves multiple and complex anastomosis surgeries, acute complications are not uncommon. Bleeding, thrombosis, haemodynamic instability, infections, acute cellular rejections, renal and liver dysfunction are acute complications. The long-term outlook is promising with over 80% 5-year survival rates among those children who survive the initial six-month postoperative period.

Combined liver-kidney transplant in a 21-month-old child with type 1 primary hyperoxaluria-The perioperative challenges.

Primary hyperoxaluria type 1(PH 1) is the most common indication for a paediatric combined liver-kidney transplant. It is a technically challenging procedure. We describe the challenges in managing a 21-month-old female child weighing 7 kg for a combined liver-kidney transplant from two related living donors.

Living donor liver transplantation for congenital hepatic fibrosis in children.

Congenital hepatic fibrosis (CHF) often accompanies autosomal recessive polycystic kidney disease (ARPKD), which stems from a PKHD1 gene mutation. The aim of this study was to clarify the prognosis of children with CHF who received living donor liver transplantation (LDLT) from donors who might be heterozygous carriers of a hepatorenal fibrocystic disease. Fourteen children with CHF who underwent LDLT at our center were enrolled. Eight and two patients had ARPKD and nephronophthisis, respectively. Eight of the donors were the recipients' fathers, and six donors were their mothers. We examined the histological and radiological findings of the donor livers and complications in the recipients following the liver transplantation. Seven of the donor livers presented morphological abnormalities of the bile ducts. Abdominal computed tomography revealed liver cysts in eight donors. One recipient underwent re-LT for graft failure due to rejection. Three patients presented with rejection, and one presented with sepsis. The overall survival rate was 100% and the original graft survival rate was 93%. In conclusion, the prognosis of recipients who received a LDLT from their parents for CHF was excellent. However, the morphology of half the donor livers was abnormal. Careful follow-up is needed to ensure long-term graft survival.

Long-term outcome of methylmalonic aciduria after kidney, liver, or combined liver-kidney transplantation: The French experience.

Organ transplantation is discussed in methylmalonic aciduria (MMA) for renal failure, and poor quality of life and neurological outcome. We retrospectively evaluated 23 French MMA patients after kidney (KT), liver-kidney (LKT), and liver transplantation (LT). Two patients died, one after LKT, one of hepatoblastoma after KT. One graft was lost early after KT. Of 18 evaluable patients, 12 previously on dialysis, 8 underwent KT (mean 12.5 years), 8 LKT (mean 7 years), and 2 LT (7 and 2.5 years). At a median follow-up of 7.3 (KT), 2.3 (LKT), and 1.0 years (LT), no metabolic decompensation occurred except in 1 KT. Plasma and urine MMA levels dramatically decreased, more after LKT. Protein intake was increased more significantly after LKT than KT. Enteral nutrition was stopped in 7/8 LKT, 1/8 KT. Early complications were frequent after LKT. Neurological disorders occurred in four LKT, reversible in one. Five years after KT, four patients had renal failure. The metabolic outcomes were much better after LKT than KT. LKT in MMA is difficult but improves the quality of life. KT will be rarely indicated. We need more long-term data to indicate early LT, in the hope to delay renal failure and prevent neurodevelopmental complications.

Impact on the hepatic flow velocity after pediatric combined liver-kidney transplantation compared to isolated pediatric liver transplantation-A matched-pair analysis.

BACKGROUND: Combined liver-kidney transplantation (CLKT) in children is still a rarely performed procedure. Our aim was to analyze the effect of the simultaneous transplantation of the kidney in pediatric CLKT on the liver graft flow velocity, and vascular complications compared to singular liver transplantation (LTX) in children. METHODS: All pediatric CLKT performed at our institution from 1998 to 2016 were matched with singular LTX and retrospectively analyzed. RESULTS: Overall 30 CLKT were performed in 28 children (median age 8 years, range 1-16) and matched with 30 children undergoing singular LTX (median age 7.9 years, range 1-16). No significant differences were found concerning the systolic peak flow velocity of the hepatic artery (HA) or the resistance index (RI). Vascular complications of the hepatic vessels occurred in 16.7% (CLKT) and 6.7% (LTX). The 1-/5- and 10-year patient survival was 93.3%/93.3% and 93.3% (CLKT) and 100%/100% and 92.9% (LTX). 1-/5-and 10-year liver graft survival was 76.7%/73.2% and 73.2% (CLKT) and 84.4%/75.9% and 69.6% (LTX). CONCLUSION: The simultaneous transplantation of the kidney in CLKT had no negative impact on hepatic flow velocity or vascular complications. Frequent Doppler ultrasound examinations, accurate volume management, and avoidance of abdominal pressure might be an explanation for the results and an excellent graft- and patient survival.

Renal function after combined liver-kidney transplantation: A longitudinal study of pediatric and adult patients.

It has been proposed that the liver protects the kidney in CLKT. However, few studies have examined long-term renal function after CLKT and contrasted renal function of CLKT patients to KT patients beyond one year after transplantation. We studied long-term renal function of CLKT patients and compared renal function of CLKT patients to KT patients between one and five years after transplantation. Patients who underwent CLKT between 1993 and 2011 were included (n = 34; 11 children and 23 adults). Ninety-six (27 children and 69 adults) KT patients were selected as controls. GFR was estimated (eGFR) and measured (mGFR) with 51 Cr-EDTA clearance. Mean mGFR was 63 at one and 70 at ten years after pediatric CLKT. Mean eGFR was 75 at one and 50 at ten years after adult CLKT. Difference in mean mGFR between pediatric CLKT and KT patients was 8 (95% CI -7 to 23) and 11 (95% CI -4 to 26) at one and five years after transplantation, respectively. Difference in mean eGFR between adult CLKT and KT patients was 8 (95% CI -5 to 20) and 1 (95% CI -10 to 12) at one and five years after transplantation, respectively. Longitudinal changes in GFRs were somewhat similar in CLKT and KT patients in both age-groups but pediatric CLKT patients had on average higher GFRs than pediatric KT patients. In long-term follow-up, renal function remains stable in pediatric CLKT patients but declines in adult CLKT patients.

Combined liver-kidney transplantation versus liver transplant alone based on KDIGO stratification of estimated glomerular filtration rate: data from the United Kingdom Transplant registry - a retrospective cohort study.

Patient selection for combined liver-kidney transplantation (CLKT) is a current issue on the background of organ shortage. This study aimed to compare outcomes and post-transplant renal function for patients receiving CLKT and liver transplantation alone (LTA) based on native renal function using estimated glomerular filtration rate (eGFR) stratification. Using the UK National transplant database (NHSBT) 6035 patients receiving a LTA (N = 5912; 98%) or CLKT (N = 123; 2%) [2001-2013] were analysed, and stratified by KDIGO stages of eGFR at transplant (eGFR group-strata). There was no difference in patient/graft survival between LTA and CLKT in eGFR group-strata (P > 0.05). Of 377 patients undergoing renal replacement therapy (RRT) at time of transplantation, 305 (81%) and 72 (19%) patients received LTA and CLKT respectively. A significantly greater proportion of CLKT patients had severe end-stage renal disease (eGFR < 30 ml/min/1.73 m2 ) at 1 year post-transplant compared to LTA (9.5% vs. 5.7%, P = 0.001). Patient and graft survival benefit for patients on RRT at transplantation was favouring CLKT versus LTA (P = 0.038 and P = 0.018, respectively) but the renal function of the long-term survivors was not superior following CLKT. The data does not support CLKT approach based on eGFR alone, and the advantage of CLKT appear to benefit only those who are on established RRT at the time of transplant.

Combined liver-kidney transplantation for primary hyperoxaluria type I in children: Single Center Experience.

Primary hyperoxalurias are rare inborn errors of metabolism with deficiency of hepatic enzymes that lead to excessive urinary oxalate excretion and overproduction of oxalate which is deposited in various organs. Hyperoxaluria results in serious morbid-ity, end stage kidney disease (ESKD), and mortality if left untreated. Combined liver kidney transplantation (CLKT) is recognized as a management of ESKD for children with hyperoxaluria type 1 (PH1). This study aimed to report outcome of CLKT in a pediatric cohort of PH1 patients, through retrospective analysis of data of 8 children (2 girls and 6 boys) who presented by PH1 to Wadi El Nil Pediatric Living Related Liver Transplant Unit during 2001-2017. Mean age at transplant was 8.2 ± 4 years. Only three of the children underwent confirmatory genotyping. Three patients died prior to surgery on waiting list. The first attempt at CLKT was consecutive, and despite initial successful liver transplant, the girl died of biliary peritonitis prior to scheduled renal transplant. Of the four who underwent simultaneous CLKT, only two survived and are well, one with insignificant complications, and other suffered from abdominal Burkitt lymphoma managed by excision and resection anastomosis, four cycles of rituximab, cyclophosphamide, vincristine, and prednisone. The other two died, one due to uncontrollable bleeding within 36 hours of procedure, while the other died awaiting renal transplant after loss of renal graft to recurrent renal oxalosis 6 months post-transplant. PH1 with ESKD is a rare disease; simultaneous CLKT offers good quality of life for afflicted children. Graft shortage and renal graft loss to oxalosis challenge the outcome.

Transplantation for infantile nephronophthisis with loss-of-function mutation in NPHP3: Lesson from a case.

The choice of KT only or CLKT for infantile NPHP with mild liver fibrosis is understudied. A 5-year-old girl was transferred to our center for KT due to ESRD. Her primary disease was infantile NPHP with compound heterozygous NPHP3 mutations: c.458A>C(p.Q153P)/missense mutation and c.2032A>T(p. K678X)/nonsense mutation. The patient had elevated liver enzymes and biopsy-proven liver fibrosis. As liver synthesis was acceptable, only KT was performed. However, liver fibrosis progressed at 1.5 years after transplantation, manifested with portal hypertension and hypersplenism. Common causes for portal hypertension were excluded, and the progression was attributed to NPHP. AMR attacked allograft at about 2 years post-transplant. To solve both the liver and the kidney problems, CLKT was performed. Her liver and kidney function recovered initially, but she unfortunately died of pneumonia and subsequent intracranial hemorrhage two weeks later. Nonsense mutation in NPHP3 gene may be correlated with rapid progression of liver disease in infantile NPHP. More studies are required to determine the role of CLKT in these cases; however, combined transplantation may improve long-term graft and patient survival.

Health-related quality of life after combined liver and kidney transplantation in children.

While reduced HRQOL following isolated organ transplantation has been previously reported, there are no data in the context of children following CLKT. Twenty-three children who underwent CLKT at our institution were included in the study. The indication for CLKT was PH1 in 13 patients and ARPKD in 10 patients. Quantification of HRQOL was facilitated through the use of the PedsQL 4.0 Generic Core Scale. The results of the study were compared to healthy children and published data of children who had undergone LTx or KTx. The CLKT samples' child self-report showed good HRQOL. No statistically significant difference was found between the patients with PH1 and patients with ARPKD (P=.4). Compared to healthy children, a significant difference in the total scale score, the physical health score, and the school functioning was reported. HRQOL did not differ significantly when compared to patients following isolated LTx or KTx. To improve HRQOL after CLKT, a focus on patients' physical health, educational performances, and overall quality of life is crucial. Thus, coordinated medical care across disciplines and psychological and social support is essential to achieve this goal.