Reversal of Roux-en-Y Gastric Bypass for Successful Salvage of Renal Allograft.

Enteric hyperoxaluria (EH) is a known complication of Roux-en-Y gastric bypass (RYGB) and can lead to nephrolithiasis, oxalate-induced nephropathy, and end-stage renal disease. Recurrent EH-induced renal impairment has been reported after kidney transplantation and may lead to allograft loss. EH occurs in up to one quarter of patients following malabsorption-based bariatric operations. We present a report of medically refractory EH in a renal transplant recipient with allograft dysfunction that was successfully managed with reversal of RYGB. The patient developed renal failure 7 years following gastric bypass requiring renal transplant. Following an uneventful living donor kidney transplant, the patient developed recurrent subacute allograft dysfunction. A diagnosis of oxalate nephropathy was made based on biopsy findings of renal tubular calcium oxalate deposition in conjunction with elevated serum oxalate levels and elevated 24-hr urinary oxalate excretion. Progressive renal failure ensued despite medical management. The patient underwent reversal of her RYGB, which resulted in recovery of allograft function. This report highlights an under-recognized, potentially treatable cause of renal allograft failure in patients with underlying gastrointestinal pathology or history of bariatric surgery and proposes a strategy for management of patients with persistent hyperoxaluria based on a review of the literature.

Anemia in patient with primary hyperoxaluria and bone marrow involvement by oxalate crystals.

We present a rare case of anaemia secondary to bone marrow infiltration by oxalate crystals and renal failure in a patient diagnosed with primary hyperoxaluria. In our case, the anaemia was recovered after the double liver and kidney transplantation, the latter was performed on two occasions after the failure of the first graft.

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.

Recurrence of Hyperoxaluria and Kidney Disease after Combined Intestine-Kidney Transplantation for Enteric Hyperoxaluria.

BACKGROUND: Enteric hyperoxaluria (EH) occurs with a rate of 5-24% in patients with inflammatory bowel disease, ileal resection and modern bariatric surgery. The excessive absorption of calcium oxalate causes chronic kidney disease (CKD) in patients with EH. In the literature, a single experience was reported in combined intestine-kidney transplantation (CIKTx) in patients with CKD due to EH. METHODS: After a report of 2 successful cases of CIKTx in patients with EH and CKD, one was performed at our center in a 59-year-old Caucasian female who developed intestinal failure with total parenteral nutrition (TPN) dependence after a complication post-bariatric surgery. Before CIKTx, she underwent kidney transplantation alone (KTA) twice, which failed due to oxalate nephropathy. RESULTS: In July 2014, the patient underwent CIKTx and bilateral allograft nephrectomy to avoid EH and oxalate stone burden. The postoperative course was complicated with acute tubular necrosis due to the use of high pressors related to perioperative bleeding. The patient was discharged 79 days after CIKTx with a serum creatinine (sCr) of 1.2 mg/dl and free of TPN. Her sCr increased at 7 months and a renal biopsy showed oxalate nephropathy. SLC26A6 (oxalate transporter) staining was significantly diminished in native duodenum/rectum as well as in intestinal allograft compared to control. CONCLUSIONS: KTA in patients with CKD secondary to EH should not be recommended due to high risk of recurrence. Although other centers showed good long-term outcomes in CIKTx, our patient experienced recurrence of EH due to oxalate transporter defect, early kidney allograft dysfunction and prolonged antibiotic use.

Long-term results of combined liver-kidney transplantation for primary hyperoxaluria type 1: the French experience.

Primary hyperoxaluria type 1 (PH1) is a hepatic metabolic defect leading to end-stage renal failure. The posttransplant recurrence of kidney disease can suggest a need for combined liver-kidney transplantation (LKT). However, the risk of LKT is theoretically far higher than the risk of kidney-alone transplantation (KAT). An unselected consecutive series of 54 patients with PH1 was analyzed according to the type of transplantation initially performed between May 1979 and June 2010 at 10 French centers. The duration of dialysis, extrarenal lesions, age, and follow-up were similar between the groups. Postoperative morbidity and mortality did not differ between the groups, and 10-year patient survival rates were similar for the LKT (n = 33) and KAT groups (n = 21; 78% versus 70%). Kidney graft survival at 10 years was better after LKT (87% versus 13%, P < .001) . Four patients (12.1%) lost their first kidney graft in the LKT group, whereas 19 (90%) did in the KAT group (P < .001). The recurrence of oxalosis occurred in 11 renal grafts (52%) in the KAT group but in none in the LKT group (P < .001). End-stage renal failure resulting from rejection was also higher in the KAT group (19% versus 9%, P < 0.0001). A second kidney transplant was performed for 15 patients (71%) in the KAT group versus 4 patients (12%) in the LKT group (P < 0.001). In conclusion, LKT for PH1 provides better kidney graft survival, less rejection, and similar long-term patient survival and is not associated with an increased short-term mortality risk. LKT must be the first-line treatment for PH1 patients with end-stage renal disease.

[Anal verruciform xanthoma in a transplant background for primary hyperoxaluria. Anal verruciform xanthoma after a combined hepato-renal transplantation]. / Xanthome verruciforme anal chez une patiente transplantée hépatique et rénale.

We report a case of anal verruciform xanthoma in a patient who underwent a combined liver and kidney transplantation for primary hyperoxaluria. Verruciform xanthoma is a rare and benign lesion arising in oral cavity and genital mucosa. It is characterized pathologically by papillary epithelial hyperplasia and aggregates of foamy macrophages in connective tissue papillae. This condition, whose pathogenesis remains unclear, has been reported in immunosuppressive background or associated with underlying dermatosis. We report here the second case of anal verruciform xanthoma. To our knowledge, this is the first report of verruciform xanthoma in association with primary hyperoxaluria.

Paediatric liver transplantation for metabolic disorders. Part 1: Liver-based metabolic disorders without liver lesions.

Liver-based metabolic disorders account for 10 to 15% of the indications for paediatric liver transplantation. In the last three decades, important progress has been made in the understanding of these diseases, and new therapies have emerged. Concomitantly, medical and surgical innovations have lead to improved results of paediatric liver transplantation, patient survival nowadays exceeding 80% 10-year after surgery with close to normal quality of life in most survivors. This review is a practical update on medical therapy, indications and results of liver transplantation, and potential future therapies, for the main liver-based metabolic disorders in which paediatric liver transplantation may be considered. Part 1 focuses on metabolic based liver disorders without liver lesions, and part 2 on metabolic liver diseases with liver lesions.

Liver and vascularized posterior rectus sheath fascia composite tissue allotransplantation.

Abdominal wall closure in pediatric solid organ recipients may be confounded by donor size discrepancy and structural insults from previous surgery. Here we describe the novel use of vascularized donor abdominal wall posterior rectus sheath fascia, as a composite tissue allotransplant (CTA), to achieve abdominal wall closure in a liver and double kidney pediatric recipient who could not be closed primarily due to donor/recipient size mismatch. The posterior rectus sheath fascia was procured in continuity with the liver and falciform ligament. Blood supply was achieved using the single hepatic artery anastomosis as part of the standard liver transplantation procedure. Specimens of posterior rectus sheath fascia taken on postoperative days 3 and 30 showed no signs of acute rejection. The patient succumbed to an overwhelming fungal infection on day 51, with no signs of intraabdominal involvement. The patient received no additional immunosuppression in conjunction with the posterior rectus sheath fascia allotransplant.

Living donor kidney transplantation in patients with hereditary nephropathies.

Patients with some hereditary nephropathies-including autosomal dominant polycystic kidney disease (ADPKD), Fabry disease and Alport syndrome-can progress to end-stage renal disease (ESRD) and are candidates for kidney transplantation. When considering whether a potential living donor is appropriate for a particular patient, clinicians should be aware of the increased risk of adverse outcomes for the donor and the recipient. Renal transplantation from a living related donor is not contraindicated in most nephropathies that have an autosomal recessive mode of inheritance (for example, autosomal recessive polycystic kidney disease and cystinosis). Renal transplant recipients with ADPKD, however, should only receive a kidney from a related donor if the disease has been excluded in the donor by imaging and/or genetic testing. Potential living related donors for patients with Alport syndrome should be evaluated carefully for the presence of microhematuria and microalbuminuria before a decision is made to perform transplantation, and mothers or heterozygous sisters of affected male recipients with X-linked Alport syndrome should be informed about the possible long-term increased risk of renal dysfunction associated with donation. Most patients with atypical hemolytic uremic syndrome should not receive a kidney transplant from a living donor because there is a high risk of disease recurrence and graft loss.

Amelioration of anemia after kidney transplantation in severe secondary oxalosis.

INTRODUCTION: In small bowel disease such as M. Crohn, the intestinal absorption of oxalate is increased. Severe calcium oxalate deposition in multiple organs as consequence of enteric hyperoxaluria may lead to severe organ dysfunction and chronic renal failure. The management of hemodialyzed patients with short bowel syndrome may be associated with vascular access problems and oxalate infiltration of the bone marrow leading to pancytopenia. Although the risk of recurrence of the disease is very high after renal transplantation, it may be the ultimate therapeutic alternative in secondary hyperoxaluria. CASE: Here, we report a patient with enteric oxalosis due to Crohn's disease. He developed end-stage renal disease, erythropoietin-resistant anemia, oxalate infiltration of the bone marrow and severe vascular access problems. Following high-urgency kidney transplantation, daily hemodiafiltration of 3 hours was performed for 2 weeks to increase oxalate clearance. Despite tubular and interstitial deposition of oxalate in the renal transplant, the patient did not require further hemodialysis and the hematocrit levels normalized. DISCUSSION: Early treatment of hyperoxaluria due to short bowel syndrome is essential to prevent renal impairment. Declining renal function leads to a further increase in oxalate accumulation and consecutive oxalate deposition in the bone marrow or in the vascular wall. If alternative treatments such as special diet or daily hemodialysis are insufficient, kidney transplantation may be a therapeutic alternative in severe cases of enteric oxalosis despite a possible recurrence of the disease.

[Kidney transplantation in children]. / Il trapianto di rene nel bambino.

Indications, procedures, complications, pharmacokinetics and outcomes of renal transplantation are different in children and in adults. Subjects <18 yrs old, are often included in a unique list as in Italy, benefiting from donors <15 yrs old, and the waiting time is reduced to <12 months in 71% of cases. The risk of thrombosis limits the use of donors <2 yrs and trans-plantation in infants <1 yr. The age at kidney transplantation is <5 yrs in 20-30% of children. In Italy living-related trans-plantation (LRT) is performed in 7% of cases, while in the USA it is more common (57%) and is often pre-emptive before entering dialysis (24%). Current therapy tends to reduce steroid treatment doses and, optimizing induction therapy with IL-2R inhibitors, using tacrolimus or mycophenolate or sirolimus. Transplanted patient survival is better in children than in adults (94-98% at 5 yrs). Infections, cardiovascular diseases and neoplasia induce 34, 15 and 12% of deaths, respectively, at 10 yrs; morbidity for infections and lymphoproliferative disease is increasing. Acute rejections declined from 70% in 1987 to 31% in 2002 in cadaveric transplantation (CT) and renal survival at 3 yrs increased from 50% in 1985 to 82% for CT and up to 92% in LRT. In adolescents (11-17 yrs old) renal survival is lower than in infants and in adults <65 yrs old. Renal losses are due to chronic transplant nephropathy (32%), vascular thrombosis (13%) and the recurrence of the original nephropathy (focal glomerulosclerosis up to 50%, membrano-proliferative glomerulonephritis up to 30%, and primary hyperoxaluria up to 90% if combined kidney-liver transplantation is not performed). Growth improves after transplantation particularly in children <5 yrs, while it is not completely satisfactory in adolescents. Overall, results indicate that kidney transplantation in children has very much improved and will offer in the near future even more favorable outcomes.

Domino hepatic transplantation using the liver from a patient with primary hyperoxaluria.

BACKGROUND: We report a case of domino liver transplantation using the liver harvested from a patient who underwent a combined liver and kidney transplantation for primary hyperoxaluria (PH). METHOD: A cadaveric liver transplantation was performed in a 19-year-old man with PH. In a second step, the PH liver harvested from the first patient was transplanted in a 69-year-old man with hepatitis C-related cirrhosis, not a candidate for a classic liver graft owing to multifocal hepatocellular carcinoma. RESULTS: At 8 months after transplantation, the domino recipient has normal hepatic function and no signs of tumoral recurrence, but he progressively developed hyperoxalemia, hyperoxaluria, and renal insufficiency. CONCLUSION: Regarding the favorable postoperative clinical evolution, domino liver transplantations using livers from PH patients may represent a new opportunity for marginal candidates for liver transplantation. However, the progressive renal insufficiency expected in such domino recipients should limit this procedure to selected cases.

[Allogenic liver transplantation: a form of "gene therapy" in metabolic diseases. Munich results and a review]. / Die allogene Lebertransplantation--eine Form der "Gentherapie" bei metabolischen Erkrankungen. Münchener Ergebnisse und Ubersicht.

INTRODUCTION: Liver transplantation is the method of choice for metabolic diseases and end-stage liver failure. METHODS: At the Klinikum Grosshadern we have performed liver transplantation for inborn errors of metabolism in 24 patients (5.3% of all transplantations, 16 adults, age 39 +/- 13 years; 8 children, age 9 +/- 3 years); 19 patients received a transplant for end-stage liver disease, and in 5 cases because of fulminant hepatic failure. RESULTS: Twenty-four patients received 27 transplants. In 3 cases, a split-liver transplantation was performed; one patient received a combined lung-liver graft. The 5-year survival rate for children is 100% and for adults 68%. CONCLUSIONS: Liver transplantation for inborn errors of metabolism not only replaces the diseased organ, but also leads to complete reversal of the metabolic defect.

A case of hyperoxaluria. Radiological aspects.

PURPOSE: Oxalosis is an unusual pathological condition with calcium oxalate deposits in soft tissue and bone, recognized as osteosclerosis on radiography. Osteosclerotic bone changes in patients treated with hemodialysis are in most cases due to secondary hyperparathyroidism, but several other diagnoses have to be considered. MATERIAL, METHODS AND RESULTS: We describe the case of a young woman with advanced renal failure treated with hemodialysis since her youth. She had skeletal pain and radiological examination showed: osteosclerosis with sclerotic vertebral bodies; irregular sclerosis and unsharp periostal outline in the tubular bones of the extremities; and acrolysis and calcifications of vascular and soft tissue in the hands. Histological examination showed changes typical of oxalosis. A liver biopsy excluded primary oxalosis type I, and she probably had a secondary oxalosis due to renal failure. This condition (as opposed to primary oxalosis) can be treated with renal transplantation. CONCLUSION: Oxalosis is a rare condition but it should be considered in patients with radiological skeletal changes and chronic renal failure and should not be misinterpreted as renal osteodystrophy. The classification of oxalosis as primary or secondary is important for further treatment.

Combined liver-kidney transplantation in primary hyperoxaluria type 1. Bone histopathology and oxalate body content.

In three patients with end-stage renal failure due to primary hyperoxaluria type 1, successful combined liver-kidney transplantation enabled us to assess the insoluble oxalate pool, which was compared with the histopathological changes observed in iliac crest biopsy specimens. Good correlation was observed between the histopathological grade of bone oxalosis and the estimated oxalate content of the body. In the end-stage of oxalate bone disease, hyperparathyroidism does not play a significant role in bone resorption, which appears to be the consequence of the granulomatous reaction induced by oxalate deposition. Combined liver-kidney transplantation should be performed long before this stage. Early hepatorenal grafting in uremia secondary to primary hyperoxaluria type 1 would avoid the deleterious clinical consequences of systemic oxalosis and shorten the duration of postransplant hyperoxaluria, which may compromise the course of kidney graft.

Endocytosis of calcium oxalate crystals and proliferation of renal tubular epithelial cells in a patient with type 1 primary hyperoxaluria.

A patient with primary hyperoxaluria who received a liver-kidney transplant is presented. A postoperative renal biopsy showed apparent tubular cell endocytosis of calcium oxalate crystals and cell proliferation, indicating that renal epithelial cells do not perceive urinary crystals as inert. Such cellular responses to crystals may have a role in nephrolithiasis.

Combined liver-kidney and isolated liver transplantations for primary hyperoxaluria type 1: the European experience. The European Study Group on Transplantation in Hyperoxaluria Type 1.

The data provided by 14 European centres concerning 22 combined liver-kidney and two isolated liver grafts performed in primary hyperoxaluria type 1 (PH1) were discussed at a workshop which drew the following main conclusions: 1. In end-stage renal failure due to PH1 1-year kidney graft survival rate is far better after combined liver-kidney transplantation than after kidney transplantation alone. This may be due to enhanced renal graft tolerance induced by the simultaneously grafted liver, in addition to the reduced risk of oxalate-induced damage to the kidney graft because the oxalate overproduction has been corrected. 2. Prolonged dialysis using conventional regimes gives rise to extensive systemic oxalosis, especially oxalate osteopathy, which leads to long-lasting excretion of large amounts of oxalate even after oxalate synthesis has been normalised by liver-kidney transplantation, with the risk of jeopardising the success of the kidney graft. In addition, oxalate arteriopathy may endanger the recipient's life. 3. Patients whose GFR is in the range of 25-60 ml/min per 1.73 m2 should be followed up closely, with sequential assessments based on the rate of loss of overall renal function and the plasma and urine oxalate values. An isolated liver transplantation should be considered once the disease has been shown to be following an aggressive course. If this strategy is not followed, planning for an elective liver-kidney graft should begin when GFR decreases to about 25 ml/min per 1.73 m2 and the operation should be as soon as possible. 4. As orthotopic liver transplantation involves the removal of the recipient's biochemically defective but otherwise normal liver, the diagnosis of PH1 should be unequivocally established in every case by the measurement of alanine: glyoxylate aminotransferase enzyme activity in a preoperative liver biopsy.

Bilateral renal autotransplantation with pyelovesicostomy: a surgical treatment of refractory enteric hyperoxaluria.

A 38-year-old man, with only 3 feet of small bowel remaining after multiple resections because of chronic inflammatory bowel disease, had severe symptomatic calcium oxalate nephroureterolithiasis. Because of the refractory symptoms, he was successfully treated with bilateral autotransplantation of the kidneys, totally bypassing the ureters. Anatomically effective urinary tract continuity was reestablished by means of bilateral pyelovesicostomies with concomitant rectus muscle vesicofixation to create direct stone-dumping channels into the urinary bladder. The patient is now completely without symptoms 18 months after surgery. A description and rationale for this surgical treatment is provided. Bilateral autotransplantation of the kidneys with direct drainage into the urinary bladder may be an attractive and viable therapeutic option in complicated patients with short-gut syndrome and severe refractory calcium oxalate nephroureterolithiasis.