Shift from severe hypotension to salt-dependent hypertension in a child with autosomal recessive polycystic kidney disease after bilateral nephrectomies: a case report.

BACKGROUND: Autosomal recessive polycystic kidney disease (ARPKD) is a significant cause of morbidity and mortality in infants and children. In severe cases bilateral nephrectomies are considered but may be associated with significant neurological complications and life-threatening hypotension. CASE PRESENTATION: We describe a case of a 17 months old boy with genetically confirmed ARPKD who underwent sequential bilateral nephrectomies at the age of 4 and 10 months. Following the second nephrectomy the boy was started on continuous cycling peritoneal dialysis with blood pressure on the lower range. At the age of 12 months after a few days of poor feeding at home the boy experienced a severe episode of hypotension and coma of Glasgow Come Scale of three. Brain magnetic-resonance imaging (MRI) showed signs of hemorrhage, cytotoxic cerebral edema and diffuse cerebral atrophy. During the subsequent 72 h he developed seizures requiring anti-epileptic drug therapy, gradually regained consciousness but remained significantly hypotensive after discontinuation of vasopressors. Thus, he received high doses of sodium chloride orally and intraperitoneally as well as midodrine hydrochloride. His ultrafiltration (UF) was targeted to keep him in mild-to-moderate fluid overload. After two months of stable condition the patient started to develop hypertension requiring four antihypertensive medications. After optimizing peritoneal dialysis to avoid fluid overload and discontinuation of sodium chloride the antihypertensives were discontinued, but hyponatremia with hypotensive episodes reoccurred. Sodium chloride was reintroduced resulting in recurrent salt-dependent hypertension. CONCLUSIONS: Our case report illustrates an unusual course of blood pressure changes following bilateral nephrectomies in an infant with ARPKD and the particular importance of tight regulation of sodium chloride supplementation. The case adds to the scarce literature about clinical sequences of bilateral nephrectomies in infants, and as well highlights the challenge of managing blood pressure in these patients. Further research on the mechanisms and management of blood pressure control is clearly needed.

Kidney Transplant and Autosomal Recessive Polycystic Disease: A Case Report and Literature Review of 2 Brothers.

Autosomal recessive polycystic disease is a rare hepatorenal disorder. End-stage renal disease and liver fibrosis are serious presentations of this disease. Here, we report 2 brothers with autosomal recessive polycystic disease who presented with abnormal abdominal protrusion and hepatosplenomegaly during infancy and eventually underwent renal transplant. Congenital hepatic fibrosis and nephromegaly followed by renal failure developed, after which renal transplant was successfully performed. The remaining compli-cation after transplant was hematemesis and melena due to esophageal varices. Autosomal recessive polycystic disease has a broad spectrum of symptoms; similar pre-sentations with manifestations in siblings may explain some unknown genetic causes of this rare disease.

Early nephrectomy in neonates with symptomatic autosomal recessive polycystic kidney disease.

INTRODUCTION: Autosomal recessive polycystic kidney disease (ARPKD) is a rare cause of renal failure with a highly variable clinical course. Patients who are symptomatic early in life frequently require early nephrectomy and peritoneal dialysis. In these patients there are little data to guide clinicians on whether to select unilateral nephrectomy or bilateral nephrectomy at the initial operative intervention. We review our experience with this disease process. METHODS: A retrospective review was performed of 11 patients at our institution with ARPKD symptomatic within the first month of life. Charts were reviewed for relevant clinical data, and patients were divided into groups based on undergoing either unilateral or bilateral nephrectomy at their initial intervention. The decision for unilateral versus bilateral nephrectomy was decided by the clinical team without any available guidelines. RESULTS: Of the 11 patients reviewed, two patients died within the first two weeks from other complications. The remaining 9 all required nephrectomy, with 5 undergoing synchronous bilateral nephrectomy, and 4 undergoing initial unilateral nephrectomy. All four patients required removal of their contralateral kidney, a median of 25.5 days later. There was no difference in mortality, ventilator free days, or time to full feeds between the two groups, although the group undergoing initial unilateral nephrectomy had more TPN days than their counterparts (28 vs 17 days, p = 0.014). CONCLUSIONS: In our cohort, there were few significant differences between the groups based on choice of initial unilateral or bilateral nephrectomy, and all children ultimately required removal of both kidneys. These data suggest that anesthetic exposures and other clinical outcomes might be optimized by initial bilateral nephrectomy. LEVEL OF EVIDENCE: III.

Severe neurological outcomes after very early bilateral nephrectomies in patients with autosomal recessive polycystic kidney disease (ARPKD).

To test the association between bilateral nephrectomies in patients with autosomal recessive polycystic kidney disease (ARPKD) and long-term clinical outcome and to identify risk factors for severe outcomes, a dataset comprising 504 patients from the international registry study ARegPKD was analyzed for characteristics and complications of patients with very early (≤ 3 months; VEBNE) and early (4-15 months; EBNE) bilateral nephrectomies. Patients with very early dialysis (VED, onset ≤ 3 months) without bilateral nephrectomies and patients with total kidney volumes (TKV) comparable to VEBNE infants served as additional control groups. We identified 19 children with VEBNE, 9 with EBNE, 12 with VED and 11 in the TKV control group. VEBNE patients suffered more frequently from severe neurological complications in comparison to all control patients. Very early bilateral nephrectomies and documentation of severe hypotensive episodes were independent risk factors for severe neurological complications. Bilateral nephrectomies within the first 3 months of life are associated with a risk of severe neurological complications later in life. Our data support a very cautious indication of very early bilateral nephrectomies in ARPKD, especially in patients with residual kidney function, and emphasize the importance of avoiding severe hypotensive episodes in this at-risk cohort.

Individualized concept for the treatment of autosomal recessive polycystic kidney disease with end-stage renal disease.

Management of children with autosomal recessive polycystic kidney disease (ARPKD) who develop end-stage renal disease (ESRD) remains challenging because of concomitant liver disease. Patients with recurrent cholangitis are candidates for liver-kidney transplantation, while the treatment for patients with splenomegaly and pancytopenia due to portal hypertension is controversial. Herein, we report 7 children who were treated using an individualized treatment strategy stratified by liver disease. Two patients with recurrent cholangitis underwent sequential liver-kidney transplantation, while 4 patients with splenomegaly and pancytopenia but without recurrent cholangitis underwent splenectomy followed by isolated kidney transplantation. The remaining patient, who did not have cholangitis and pancytopenia, underwent isolated kidney transplantation. Blood cell counts were normalized after splenectomy was performed at the median age of 8.7 (range, 7.4-11.7) years. Kidney transplantation was performed at the median age of 8.8 (range, 1.9-14.7) years in all patients. Overwhelming post-splenectomy infections and cholangitis did not occur during the median follow-up period of 6.3 (range, 1.0-13.2) years. The estimated glomerular filtration rate at the last follow-up was 53 (range, 35-107) mL/min/1.73 m2 . No graft loss occurred. Our individualized treatment strategy stratified by recurrent cholangitis and pancytopenia can be a feasible strategy for children with ARPKD who develop ESRD and warrants further evaluation.

Management of delivery of a fetus with autosomal recessive polycystic kidney disease: a case report of abdominal dystocia and review of the literature.

BACKGROUND: Autosomal recessive renal polycystic kidney disease occurs in 1 in 20,000 live births. It is caused by mutations in both alleles of the PKHD1 gene. Management of delivery in cases of suspected autosomal recessive renal polycystic kidney disease is rarely discussed, and literature concerning abdominal dystocia is extremely scarce. We present a case of a patient with autosomal recessive renal polycystic kidney disease whose delivery was complicated by abdominal dystocia, and we discuss the factors that determined the route and timing of delivery. CASE PRESENTATION: A 23-year-old Caucasian woman, G2 P0, with a prior unremarkable pregnancy was referred to our tertiary center at 31 weeks of gestation because of severe oligoamnios (amniotic fluid index = 2) and hyperechogenic, dedifferentiated, and enlarged fetal kidneys. She had no other genitourinary anomaly. Fetal magnetic resonance imaging showed enlarged, hypersignal kidneys and severe pulmonary hypoplasia. We had a high suspicion of autosomal recessive renal polycystic kidney disease, and after discussion with our multidisciplinary team, the parents opted for conservative care. Ultrasound performed at 35 weeks of gestation showed a fetal estimated weight of 3550 g and an abdominal circumference of 377 mm, both above the 90th percentile. Because of the very rapid kidney growth and suspected risk of abdominal dystocia, we proposed induction of labor at 36 weeks of gestation after corticosteroid administration for fetal lung maturation. Vaginal delivery was complicated by abdominal dystocia, which resolved by continuing expulsive efforts and gentle fetal traction. A 3300-g (P50-90) male infant was born with Apgar scores of 1-7-7 at 1, 5, and 10 minutes, respectively, and arterial and venous umbilical cord pH values of 7.23-7.33. Continuous peritoneal dialysis was started at day 2 of life because of anuria. Currently, the infant is 1 year old and is waiting for kidney transplant that should be performed once he reaches 10 kg. Molecular analysis of PKHD1 performed on deoxyribonucleic acid (DNA) from the umbilical cord confirmed autosomal recessive renal polycystic kidney disease. CONCLUSIONS: Management of delivery in cases of suspected autosomal recessive renal polycystic kidney disease needs to be discussed because of the risk of abdominal dystocia. The route and timing of delivery depend on the size of the fetal abdominal circumference and the gestational age. The rate of kidney growth must also be taken into account.

Simultaneous laparoscopic left lateral sectionectomy and nephrectomy in the same living donor: The first case report.

With the presence of organ shortage, living donors remain important sources of grafts, especially for pediatric recipients. Laparoscopic nephrectomy has become the gold standard for living donors. Additionally, laparoscopic partial liver procurement in living donors has proven its safety and feasibility in the latest studies. We have combined both approaches to perform a simultaneous liver-kidney transplantation in a pediatric patient from the same living donor. Our experience of laparoscopic left lateral sectionectomy and laparoscopic nephrectomy in living donors was the basis for adapting to this procedure. A 29-year-old mother was an ABO-incompatible (ABOi) donor for the left lateral section (LLS) of the liver and left kidney for her 2-year-old son. The postoperative period was uneventful. Two sessions of plasmapheresis and rituximab induction were necessary to prepare for ABOi transplantation. The donor and recipient were discharged on postoperative days 5 and 28, respectively. Simultaneous laparoscopic left lateral sectionectomy and nephrectomy in the same living donor is feasible for transplantation from the parent to the child with advanced laparoscopic expertise.

Successful long-term outcome of pediatric liver-kidney transplantation: a single-center study.

INTRODUCTION: Liver-kidney transplantation is a rare procedure in children, with just ten to 30 cases performed annually worldwide. The main indications are autosomal recessive polycystic liver-kidney disease and primary hyperoxaluria. This study aimed to report outcomes of liver-kidney transplantation in a cohort of pediatric patients. METHODS: We retrospectively analyzed all pediatric liver-kidney transplantations performed in our center between September 2000 and August 2015. Patient data were obtained by reviewing inpatient and outpatient medical records and our transplant database. RESULTS: A total of 14 liver-kidney transplants were performed during the study period, with a median patient age and weight at transplant of 144.4 months (131.0-147.7) and 27.3 kg (12.0-45.1), respectively. The indications for liver-kidney transplants were autosomal recessive polycystic liver-kidney disease (8/14), primary hyperoxaluria -1 (5/14), and idiopathic portal hypertension with end-stage renal disease (1/14). Median time on waiting list was 8.5 months (5.7-17.3). All but two liver-kidney transplants were performed simultaneously. Patients with primary hyperoxaluria-1 tended to present a delayed recovery of renal function compared with patients transplanted for other indications (62.5 vs 6.5 days, respectively, P 0.076). Patients with liver-kidney transplants tended to present a lower risk of acute kidney rejection than patients transplanted with an isolated kidney transplant (7.2% vs 32.7%, respectively; P < 0.07). Patient and graft survival at 1, 3, and 5 years were 100%, 91.7%, 91.7%, and 91.7%, 83.3%, 83.3%, respectively. No other grafts were lost. CONCLUSION: Long-term results of liver-kidney transplants in children are encouraging, being comparable with those obtained in isolated liver transplantation.

[Early bilateral nephrectomy in neonatal autosomal recessive polycystic kidney disease : Improved prognosis or unnecessary effort?] / Frühe beidseitige Nephrektomie bei Säuglingen mit pränataler ARPKD : Prognoseverbesserung oder unnötiger Aufwand?

BACKGROUND: Neonatal autosomal recessive polycystic kidney disease (ARPKD) is associated with giant kidneys, lung hypoplasia, pulmonal hypertension, and end-stage renal failure. Depending on the study, mortality is reported to range between 20 and 80%. OBJECTIVES: Does bilateral nephrectomy improve survival? PATIENTS AND METHODS: Between 2010 and 2016, we treated 7 children with prenatally diagnosed ARPKD. All had a planned delivery by cesarean section. After birth, oscillated ventilation with nitrogen enrichment was initiated to achieve maximum oxygenation and to decrease pumonary hypertension. All children had bilateral massive kidney hyperplasia (length 13-16 cm). RESULTS: Nephrectomy on one side was performed within 72 h together with placement of a peritoneal dialysis catheter in the intensive care unit. Contralateral nephrectomy was performed after 1-2 weeks when the child was stabilized by dialysis. In 2 children, kidney transplantation has already been performed and they are doing fine. One child died after 10 months due to infection. The other children are stable on home peritoneal dialysis awaiting transplantation. CONCLUSIONS: Early bilateral nephrectomy in neonatal ARPKD is feasible, but requires distinctive care at a pediatric intensive care unit and a high amount of organizational efforts to treat these children adequately in the first few days. In our experience, the procedure is a promising approach to improve ventilation and enable dialysis. However, kidney transplantation, best from a living donor, is required within the first years of life.

Successful third renal transplantation in a child with an occluded inferior vena cava: A novel technique to use the venous interposition between the transplant renal vein and the infrahepatic inferior vena cava.

A girl aged 11 years and 3 months with occlusion of the inferior vena cava had experienced two renal transplant graft failures since birth. The third renal transplant from a live donor was carried out. Preoperative evaluation showed that the arteries from the right common to the right external iliac artery were absent, and the ilio-caval vein was occluded below the level of the renal vein. The donor's renal artery was anastomosed to the aorta. The donor's ovarian and large saphenous veins were used to extend the transplant renal vein to the recipient's patent inferior vena cava. The present report concludes that the extension of a short donor renal vein using other donor veins is a viable therapeutic option for pediatric patients with vascular occlusions.

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.

Longterm renal allograft survival after sequential liver-kidney transplantation from a single living donor.

Combined liver-kidney transplantation (CLKT) is well established as a definitive therapy with the potential to provide complete recovery for certain liver-kidney diseases, although the results might be contingent on the cause of transplantation. The purposes of the present study were to review the longterm outcome of renal allografts in CLKT patients from single living donors and to investigate the beneficial factors, compared with solitary renal transplantation. Thirteen patients underwent sequential liver transplantation (LT) and kidney transplantation (KT) from single living donors. The indications for KT were oxaluria (n = 7), autosomal recessive polycystic disease (n = 3), and others (n = 3). The same immunosuppressive regimen used after LT was also used after KT. KT was performed between 1.7 and 47.0 months after the LT. The overall patient survival rate was 92.3% at 10 years. In 12 of the 13 surviving patients, the renal allografts were found to be functioning in 11 patients after a mean follow-up period of 103.6 months. The death-censored renal allograft survival rate at 10 years was 100%, which was better than that of KT alone (84.9%) in Japan. Immunological protection conferred by the preceding liver allograft may have contributed to the longterm outcomes of the renal allografts. In addition, the donation of double organs from a single living and related donor may have a favorable impact on the graft survival rate. In the future, investigations of factors affecting the longterm outcome of renal allografts, including details of the involvement of de novo donor-specific antibody, will be needed. Liver Transplantation 23 315-323 2017 AASLD.

Intra-arterial nitroglycerin for intra-operative arterial vasospasm during pediatric renal transplantation.

Intra-operative arterial vasospasm during pediatric renal transplantation is an urgent clinical situation resulting in end-organ ischemia, associated changes in parenchymal turgor and color, diminished flow on ultrasound, and if left untreated, allograft loss. We hypothesized that intra-operative intra-arterial injection of nitroglycerin would reverse vasospasm and improve renal perfusion. A three-yr-old girl with end-stage renal disease due to autosomal recessive polycystic kidney disease on peritoneal dialysis underwent deceased donor renal transplantation. After optimal immediate reperfusion and hemodynamic parameters, the kidney lost turgor and became mottled in appearance despite adequate hilar arterial and venous Doppler waveforms. Two aliquots of 40 µg (0.4 mL of a 100 µg/mL) nitroglycerin solution were injected directly into the renal artery 10 min apart. Nitroglycerin resulted in dramatic change in the consistency and appearance of the allograft. An improvement in renal blood flow was demonstrated by ultrasound after the second intra-arterial nitroglycerin injection with only a transient decrease in systemic arterial blood pressure. The child experienced normal allograft perfusion on serial postoperative ultrasounds, with a prompt decrease in serum creatinine and excellent diuresis. Intra-arterial nitroglycerin is a promising option for intra-operative arterial vasospasm during pediatric renal transplantation with objective improvement in blood flow and perfusion.

Early bilateral nephrectomy in infantile autosomal recessive polycystic kidney disease.

The management of neonatal autosomal recessive polycystic kidney disease (ARPKD) complicated by severe pulmonary insufficiency presents complex clinical challenges. Where massive nephromegaly exists, early bilateral nephrectomy, supportive peritoneal dialysis and early aggressive nutrition can minimise infant mortality. Consensus, however, is lacking on the role and optimal timing of nephrectomy, with decision-making driven by the patient's clinical condition and the expertise of the centre. We report on our experience of an infant with ARPKD requiring neonatal renal replacement therapy and survival at 14 months following early bilateral nephrectomy.

Long-Term Follow-Up of Kidney Transplant Recipients With Polycystic Kidney Disease.

OBJECTIVES: Patients with polycystic kidney disease are candidates for kidney transplant. We report the results of our single center study of 250 first transplant recipients with polycystic kidney disease (autosomal dominant [64%], medullary cystic [16%], autosomal recessive [6%], and nonspecified [14%]). MATERIALS AND METHODS: Patient groups were divided and analyzed according to the origin of the graft (deceased donor or living donor). We also analyzed demographic data of donors and recipients, waiting time, duration of dialysis, transfusion, nephrectomy, hospitalization, morbidities, and graft and patient survival. The study was approved by the Ethical Review Committee of the Institute. All of the protocols conformed to the ethical guidelines of the 1975 Helsinki Declaration. RESULTS: The deceased-donor group comprised 79% and the living-donor group comprised 21% of the cases. Nephrectomy was performed on 21% of the recipients. The deceased-donor group showed significantly higher values than the living-donor group regarding rate of hemodialysis (82% vs 68%), duration of dialysis (1571 vs 1002 days), waiting time (1129 vs 33 days), and blood transfusions (45% vs 27%). In deceased-donor versus living-donor transplant recipients, surgical complications included arterial stenosis (1% vs 0%), venous thrombosis (1% vs 0%), urine leakage (0.5% vs 1.9%), ureteral stenosis (0.5% vs 0%), reflux (0% vs 1.9%), lymphocele (11.7% vs 8.1%), and hernia (5.2% vs 8.1%), with no statistically significant differences shown between the groups. The living-donor group had graft and patient survival rates as high as the deceased-donor group. CONCLUSIONS: The low rate of morbidity and excellent survival rates make kidney transplant an excellent option for patients with polycystic kidney disease. Although fear of future appearance of polycystic kidney disease may reduce the rate of related living donors, our study showed that graft and patient survival rates in the living-donor group were as high as in the deceased-donor group.

Laparoscopic-assisted retroperitoneal nephrectomy in autosomal recessive polycystic kidney disease.

OBJECTIVE: Autosomal recessive polycystic kidney disease (ARPKD) occurs in 1 in 20 000 live births. A mortality rate of 30-40% is reported, generally relating to pulmonary hypoplasia, and 60% require renal replacement therapy (RRT) by 10 years. In the neonatal period, the large kidneys can cause significant mass effect, with the need for prolonged respiratory support and difficulty in establishing feeds. Early postnatal peritoneal dialysis (PD) is required in up to 25%, and dialysis efficiency can similarly be compromised. In these situations, unilateral or bilateral nephrectomy may be recommended. All previous reports of nephrectomy in ARPKD have described an open approach, generally via a transperitoneal route, with the risk of compromising future PD. Here, we demonstrate laparoscopic-assisted retroperitoneal nephrectomy (LARN), which has been used successfully in two patients. PATIENTS AND RESULTS: Case 1: a 37/40, 3.2 kg female infant. She was extubated to CPAP d6 and commenced haemodialysis d7. Left LARN was performed d34 and CPAP was discontinued within 48 h. Right LARN was performed d49 as it was felt PD still would not be possible and PD was then successfully commenced d62. She unfortunately died aged 11/12. Case 2: a term 3.5 kg male infant. He was ventilator-dependent and required PD catheter insertion on d1. PD was discontinued for leakage d7, and haemodialysis commenced. Left LARN was performed d18. He remained ventilator-dependent and given this, and the PD leakage, right LARN was performed d20. He was extubated 48 h later, and PD successfully reintroduced after 1 week. He is currently aged 4/12. CONCLUSION: LARN is achievable in ARPKD. Although unilateral LARN may be sufficient, in these cases bilateral LARN was required. Relief of the mass effect allowed respiratory support to be discontinued and peritoneal dialysis to be established in both children.

Combined liver and kidney transplantation and kidney after liver transplantation in children: Indication, postoperative outcome, and long-term results.

CLKT and sequential KALT are decided on a case-by-case basis in children for special indications such as ARPKD or PH1. We report on 21 children who underwent CLKT or KALT at our hospital between 1998 and 2013. Eleven children were diagnosed with PH1 and six with ARPKD. Other diagnosis were Joubert syndrome (n = 1), nephronophthisis (n = 1), CF (n = 1), and hepatocellular carcinoma (n = 1). Children (12 males, nine females) were aged 7.8 ± 6.2 yr (range, 10 months to 18 yr) at time of transplantation. Average wait time was 1.9 ± 0.9 yr (range, four months to 2.3 yr). Fifteen patients received dialysis prior to transplantation. In PH1 patients, four children received CLKT, five received KALT, and two infants have received only an LTx, whereas all six patients with ARPKD received CLKT. In patients with other indications, CLKT was performed in three cases and KALT in one girl. Cumulative 10-yr survival of all 21 patients was 78.4%. At the time of transfer into adult care, 13 patients retained stable liver and kidney function. Regardless the underlying diagnosis, CLKT and KALT can be performed in children with good surgical outcomes and long-term survival.