Combined liver and kidney transplantation in a patient with sickle cell disease

Sickle cell intrahepatic cholestasis is a potentially fatal end-organ complication of sickle cell anemia. Renal involvement in sickle cell anemia is common, and in some cases, can present as acute renal failure. Although renal transplants have been performed in patients with sickle cell anemia since the late 1960s and a number of liver transplants have been recently performed for these complications, there has not been experience with dual organ transplantation for sickle cell anemia-related complications. We describe the case of a patient with sickle cell anemia who underwent successful combined liver and kidney transplantation after the development of acute sickle cell intrahepatic cholestasis and renal failure requiring continuous venovenous hemodialysis. The patient underwent a successful combined liver and kidney transplant with limited perioperative complications and preserved allograft function. At 22 months posttransplant, the patient expired as a result of an acute pulmonary embolus in the setting of bilateral hip fractures. Autopsy revealed no evidence of liver or kidney allograft rejection and evidence of chronic sickle cell nephropathy in the native kidney. Combined liver and kidney transplantation is a viable therapeutic option in patients with severe end-organ effects of sickle cell anemia.     

Liver transplantation in a patient with acute liver failure due to sickle cell intrahepatic cholestasis

BACKGROUND: Sickle cell intrahepatic cholestasis is a potentially catastrophic complication of sickle cell anemia Once acute liver failure develops, transplantation is the only option. We describe a patient with sickle cell intrahepatic cholestasis who underwent liver transplantation. METHODS: Data were obtained from the chart. Serial hemoglobin S levels were monitored, and measures were taken to maintain hemoglobin S <20% to prevent sickle cell crisis. RESULTS: Although the allograft functioned well initially, the patient developed veno-occlusive disease and required repeat transplantation at 5 months after transplant. Histologic examination of the explant revealed occlusion of the terminal hepatic venules due to fibrosis and packed red cells. Repeat transplant was complicated by thrombosis of the intrahepatic portion of the hepatic artery, and sepsis. The patient died of sepsis after a third transplant. CONCLUSION: Liver transplantation for sickle cell disease involving the liver may carry a high risk of graft loss due to vascular problems. Repeat transplantation may not be feasible if disease recurs.     

Iron Overload After Pediatric Liver Transplantation: A Case Report

Iron is an essential nutrient for living cells; however, an excessive accumulation of iron leads to organ damage and directly affects systemic immunity. Iron overload is clinically classified as hereditary or secondary. Most of secondary iron overload is caused by frequent blood transfusions because there is no active mechanism to excrete iron from the body. As recommended in various guidelines, chelation therapy is effective for reducing iron burden and improving organ function. There have been few reports on iron overload through blood transfusion during the perioperative period of liver transplantation. This report presents a case of iron overload due to repeated transfusions after pediatric liver transplantation managed by chelation therapy. The patient, an 11-month-old female with biliary atresia, underwent living donor liver transplantation. She revealed refractory anemia and required frequent blood transfusion. Both serum ferritin and transferrin saturation tended to increase after repeated transfusions, leading to secondary iron overload. Iron chelation therapy was started to prevent progression to organ failure and infection due to iron overload, and yielded a favorable outcome. It is crucial to consider the possibility of secondary iron overload and to achieve early detection and treatment to avoid progression to irreversible organ damage.     

Long-term follow-up after liver transplantation in patients with hepatic iron overload.

Patients with hepatic iron overload who undergo orthotopic liver transplantation (OLT) have a worse 1-year survival than those who undergo transplantation for other indications; the long-term outcome in this population is unknown. The purpose of this study is to report long-term follow-up after OLT in a cohort of patients with hepatic iron overload. Five liver transplant centers in the United States reported follow-up data on 37 patients receiving a first liver transplant who had severe hepatic iron overload in their native livers. Kaplan-Meier 5-year survival among these patients was compared with survival data from all age-matched liver transplantations reported to the United Network for Organ Sharing (UNOS) over the same time period (1987 to 1993). The 5-year survival rate after OLT was 40% in the hepatic iron overload group compared with an overall survival rate of 62% for all patient groups from the UNOS registry (P =.0009). Although sepsis was the cause of 53% of all deaths occurring within the first year after OLT, cardiac complications accounted for 50% of the late mortality in patients with hepatic iron overload. In conclusion, long-term survival after OLT is significantly decreased in patients with hepatic iron overload. Infectious and cardiac complications are the most common causes of death in these patients. Further studies are needed to define the relationship between hepatic iron overload and mortality and to examine the effect of iron depletion on outcome after OLT in this patient population.     

Intravenous iron therapy in renal failure: friend and foe?

Anemia is a common feature of chronic renal dysfunction and is associated with significant morbidity and mortality. Although acquired insufficiency of erythropoietin is virtually universal, iron deficiency is also a common contributor to the development of anemia. Iron replacement, in particular via the intravenous route, has become commonplace and results in improved hematocrits either on its own or in association with an erythropoiesis stimulating agent. However, intravenous iron is not without its potential complications. These include acute allergic reactions, iron overload, potentially accelerated cardiovascular disease and risk of infection. It is the purpose of this review to critically evaluate the available clinical and experimental evidence linking iron supplementation therapy with these complications.     

Altered metabolism of tacrolimus in hepatic veno-occlusive disease

Tacrolimus is widely used for the prophylaxis and treatment of graft-versus-host disease after allogeneic hematopoietic stem cell transplantation (HSCT) and graft rejection in solid organ transplantation. The metabolism of tacrolimus has been reported to be impaired in association with liver dysfunction, mostly as documented in liver transplant recipients. Hepatic veno-occlusive disease (VOD) is one of the serious complications after allogeneic HSCT. It is characterized by jaundice, fluid retention, and painful hepatomegaly, caused by endothelial cell injury resulting from the toxicity of the conditioning regimen. The impaired metabolism of tacrolimus in hepatic VOD has not previously been reported in the literature. Here, we report the notable alteration in the metabolism of tacrolimus in two patients with hepatic VOD, in whom the half-lives of tacrolimus were markedly prolonged (288 and 146 h).     

Low dose desferrioxamine can improve erythropoiesis in iron-overload hemodialysis patients without side effects

OBJECTIVE: Multiple blood transfusions were often required to treat anemia in uremia patients before the era of recombinant human erythropoietin (r-HuEPO). Iron overload thus frequently occurred in chronic hemodialysis patients. Desferrioxamine (DFO) is an effective chelating agent, which can remove excessive iron and can enhance erythropoiesis. Large dose DFO treatment is a therapy associated with the development of severe complications. In this study, a low dose DFO regime was used to treat iron overloaded hemodialysis patients. The efficacy and side effects of this regiment were evaluated. MATERIALS AND METHODS: Eight iron overloaded chronic hemodialysis patients were enrolled in this study. All patients received DFO 500 mg intravenously twice-a-week for eight months. Serum aluminum, transferrin saturation (TFS) and r-HuEPO requirement were recorded before and after DFO treatment. Serum ferritin and hematocrit (Hct) were measured before, during, and after the DFO withdrawal period. All patients were evaluated and followed closely during treatment. RESULTS: Changes in aluminum, TFS and r-HuEPO dosage were unremarkable (p > 0.05). Hct increased significantly after eight months of DFO treatment (from 25.3% to 27.0%, p < 0.05). Ferritin level was reduced by 43.2% at the end of treatment and an evident decline of ferritin was achieved after four months of treatment (2102 ng/mL to 1166 ng/mL, p < 0.05). All patients tolerated the treatment well and no complications were found. CONCLUSION: Low dose DFO can chelate iron effectively in chronic hemodialysis patients. This treatment can enhance erythropoiesis without adverse effects.     

Pumping iron: revisiting risks, benefits and strategies in treatment of iron deficiency in end-stage renal disease

Iron deficiency is a common cause of anemia in patients with end stage renal disease (ESRD). Intravenous iron administration, especially in those requiring treatment with erythropoiesis stimulating agents (ESA) is an essential component of the management of anemia in ESRD patients. Iron improves hemoglobin, reduces ESA dose requirement and also has nonerythropoietic effects including improvement in physical performance, cognition and amelioration of restless leg syndrome. However, iron can promote oxidative stress, cause endothelial dysfunction, inflammation and tissue injury, and has a potential to cause progression of both CKD and cardiovascular disease. In this review, we discuss the benefits and risks associated with i.v. iron and the practical aspects of iron administration that can minimize the complications related to iron therapy in ESRD.     

Iron metabolism in transplantation

Recipient's iron status is an important determinant of clinical outcome in transplantation medicine. This review addresses iron metabolism in solid organ transplantation, where the role of iron as a mediator of ischemia–reperfusion injury, as an immune‐modulatory element, and as a determinant of organ and graft function is discussed. Although iron chelators reduce ischemia–reperfusion injury in cell and animal models, these benefits have not yet been implemented into clinical practice. Iron deficiency and iron overload are associated with reduced immune activation, whose molecular mechanisms are reviewed in detail. Furthermore, iron overload and hyperferritinemia are associated with poor prognosis in end‐stage organ failure in patients awaiting kidney, or liver transplantation. This negative prognostic impact of iron overload appears to persist after transplantation, which highlights the need for optimizing iron management before and after solid organ transplantation. In contrast, iron deficiency and anemia are also associated with poor prognosis in patients with end‐stage heart failure. Intravenous iron supplementation should be managed carefully because parenterally induced iron overload could persist after successful transplantation. In conclusion, current evidence shows that iron overload and iron deficiency are important risk factors before and after solid organ transplantation. Iron status should therefore be actively managed in patients on the waiting list and after transplantation.     

Liver transplantation in a patient with S(beta)o-thalassemia

BACKGROUND: Patients presenting sickle cell disease may develop different types of hepatic complications. Intrahepatic cholestasis is a potentially fatal complication of the disease, and sometimes the only possible solution is transplantation. Postoperative transfusion management has not yet been well established. In this report, we describe the transfusional program of a patient presenting sickle cell disease and intrahepatic cholestasis who underwent liver transplantation 2 years ago. METHODS: Data were obtained from the chart and the blood bank records. RESULTS: The liver transplantation was performed successfully. Despite mild allograft dysfunction 3 months after surgery, secondary to intrahepatic sickling, the patient has been doing well with the transfusional management adopted (sickle-cell hemoglobin <20%). CONCLUSION: Sickle cell disease should not be a criterion for exclusion from liver transplantation. Regular transfusion with monitoring of sickle-cell hemoglobin is a very important measure to minimize the risk of intrahepatic sickling and possible rejection.     

Kidney Transplant from the Same Donor without Maintenance Immunosuppression after Previous Hematopoietic Stem Cell Transplant

In January 2005, an 18‐year‐old male patient with acute myeloid leukemia (AML) received a haploidentical hematopoietic stem cell transplantation (HSCT) from his father. He developed hemolytic uremic syndrome and end‐stage renal disease (ESRD) requiring hemodialysis on day 357 after HSCT. On day 1020 after HSCT, a living kidney donation from the stem cell donor was carried out. The creatinine before kidney transplantation (KT) was ≈450 μmol/L, 268 μmol/L on day 2 after KT, 88 μM on day 38 and 89 μmol/L on day 960 (day 1980 after HSCT). Immunosuppression was gradually discontinued: cortisone on day 28, tacrolimus on day 32 and MMF on day 100 after KT (day 1120 after HSCT). As of June 2010, 66 months after HSCT and 32 months after KT, the patient has had neither rejection episodes nor clinical manifestations of transplantation‐related complications. The patient reached 100% hematopoietic donor chimerism prekidney transplant and retained this state postkidney transplant. This unique case is the first report of a successful kidney transplant without immunosuppression after HSCT from the same haploidentical donor.     

Multiple intracranial aneurysms in sickle cell anemia. Report of two cases

Neurological complications of sickle cell anemia occur in 18% to 29% of patients with homozygous hemoglobin S disease. A review of the literature yielded reports of two cases, both treated conservatively, of multiple intracranial aneurysms occurring in patients with sickle cell anemia. The authors report two cases of subarachnoid hemorrhage secondary to multiple intracranial aneurysms in patients with sickle cell anemia. One of the two patients underwent three craniotomies for ablation of six intracranial aneurysms. The techniques used in the treatment of these patients are presented.     

Successful Kidney and Hematopoietic Stem Cell Transplantation for Malignant Lymphoma from Different Donors: A Case Report and Literature Review

There are particularly few reports on kidney transplantation after hematopoietic stem cell transplantation (HSCT) for malignant lymphoma, and none of the cases reported a favorable outcome in patients who received kidney transplantation from a different donor to HSCT. In this report, we describe the first case of kidney transplantation from a different donor to HSCT with a successful outcome. Furthermore, we reviewed the previously reported cases. A 59-year-old female patient received an HSCT from her younger brother after chemotherapy for malignant lymphoma. After HSCT, she did not have graft-versus-host disease (GVHD) requiring maintenance treatment. The patient developed chronic kidney disease requiring kidney replacement therapy, probably due to drug toxicity or cardio-renal syndrome. At age 65, she underwent an ABO-compatible, HLA-A, -B, -DR 5/6 mismatched kidney transplantation from her husband. Immunosuppressive therapy with tacrolimus, mycophenolate mofetil, methylprednisolone, and basiliximab was administered. The patient had urinary tract infections at 7 days, 9 weeks, and 4 months after kidney transplantation, and cytomegalovirus antigenemia at 9 weeks after kidney transplantation, which improved with antibiotic and valganciclovir, respectively. When each infection occurred, we weakened immunosuppressive therapy. Four years after kidney transplantation, the patient is in good clinical condition with a serum creatinine of 1.2 mg/dL, without critical infection or malignancy. In this case, we believe that it was important to optimize the immunosuppressive therapy. In addition, from a review of previous cases, it seemed important that there was no GVHD requiring maintenance therapy in order to prevent excessive immunosuppression.     

Liver transplantation and hepatitis C

End-stage liver disease caused by chronic hepatitis C viral infection is one of the major indications for liver transplantation. However, evidence for ongoing viral replication can already be found days after surgery and may lead sequentially to lobular hepatitis, chronic active hepatitis, fibrosis and liver cirrhosis. In some patients, this evolution is remarkably fast, most probably enhanced by the immunosuppressive therapy. A minority of patients develop a clinical picture of progressive cholestatic liver disease with histological signs of chronic rejection, which may necessitate retransplantation. While the 1- and 5-year survival rates for all patients transplanted because of hepatitis C virus (HCV)-induced liver cirrhosis are satisfactory, severe complications of disease recurrence are nonetheless expected during the first and second decade after liver transplantation. Larger and preferably randomized studies are needed to investigate whether combination therapy with interferon and ribavirin, preferably initiated as soon as possible after liver transplantation, prevents the fast evolution to cirrhosis without the appearance of chronic rejection and the expected complications of recurrent end-stage HCV-induced liver disease. The final goal should be the inhibition of viral replication even before liver transplantation, but other antiviral strategies should probably be used to attain this goal in patients with decompensated cirrhosis. Although the recurrence of a hepatitis C infection and concomitant disease in the liver graft may cause substantial morbidity, end-stage liver disease and liver failure caused by a chronic hepatitis C infection remain good indications for liver transplantation.     

Liver transplantation in sickle cell anemia: a case of acute sickle cell intrahepatic cholestasis and a case of sclerosing cholangitis

Very few cases of liver transplantation in patients with sickle cell disease have been reported in peer-reviewed literature. We reviewed the medical records of two patients with sickle cell disease that received liver transplantation at our institution. The first patient was a 27-year-old female who presented with encephalopathy and cholestatic jaundice with a Hemoglobin S (HbS) level of 69.6%. She was diagnosed with acute sickle cell intrahepatic cholestasis. The second patient was a 26-year-old female with sclerosing cholangitis who presented with encephalopathy, bleeding, and cholestatic jaundice. Her HbS level was normal. Both patients underwent liver transplantation successfully but died in the postoperative period from multiorgan failure. We report a rare case of liver transplantation for acute sickle cell intrahepatic cholestasis and a novel case of transplantation in a patient with sickle cell disease and sclerosing cholangitis. Liver transplantation did not lead to a successful outcome in either case.     

Spur cell anemia in alcoholic cirrhosis: cure by orthotopic liver transplantation and recurrence after liver graft failure

Spur cell anemia is an acquired form of hemolytic anemia caused by a structural abnormality of red cell membranes that results in spiculated erythrocytes. These peculiarly shaped red blood cells, called acanthocytes, have a shortened survival and undergo splenic sequestration and destruction. Spur cell anemia has been known to occur in several conditions, including chronic liver disease, and more specifically in alcoholic cirrhosis. Treatment of this disorder has been disappointing and usually indicates end-stage liver disease. Liver transplantation has been reported as the most effective treatment. We herein present a case of severe spur cell hemolytic anemia that successfully reverted after orthotopic liver transplantation and recurred secondary to resumption of alcohol intake and consequent liver graft failure. This case conclusively demonstrates the association among alcoholic cirrhosis, end-stage liver disease, and spur cell hemolytic anemia.     

Antineutrophil cytoplasmic antibody-associated glomerulonephritis in chronic graft-versus-host disease after allogenic hematopoietic stem cell transplantation

Graft-versus-host disease (GVHD) is one of the most frequent complications that occur after hematopoietic stem cell transplantation (HSCT). Recently, renal involvement, including membranous nephropathy, focal segmental glomerulosclerosis, and minimal change disease, has been described as a manifestation of chronic GVHD. This case report describes a patient who developed antineutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis after HSCT. Following preparation with chemotherapy, a 29-year-old man with chronic myeloid leukemia underwent allogenic peripheral blood stem cell (PBSC) transplantation, after which first acute and then chronic GVHD developed. Treatment with prednisone resulted in improvement in the patient's GVHD. After the termination of steroid therapy and about 10 months after PBSC transplantation, nephritic syndrome appeared and the patient's serum creatinine value increased to 1.7 mg/dL. Laboratory evaluation revealed perinuclear antineutrophilic cytoplasmic antibody (p-ANCA) in the serum. Histological examination of renal biopsy tissue showed focal segmental proliferative glomerulonephritis with glomerulosclerosis in 20% of available glomeruli, large cellular crescents in 6% of glomeruli, and no staining of immunoglobulins or complement along the capillary walls. Electron microscopy revealed no immune deposits. After treatment with prednisone 60 mg/d, diltiazem 120 mg/d, and enalapril 10 mg/d, the proteinuria gradually decreased, and p-ANCA was undetectable. These findings suggest that in this patient the ANCA-associated glomerulonephritis was associated with renal involvement that occurred during the course of chronic GVHD.     

Hematopoietic stem cell transplantation in patients with active fungal infection: not a contraindication for transplantation

Increasing use of more aggressive treatment approaches in patients with hematologic malignancies leads to an increased frequency of invasive fungal infections, which is a major cause of transplant-related mortality in hematopoietic stem cell recipients. In this respect, the presence of an active fungal infection prior to transplantation may hinder subsequent hematopoietic stem cell transplantation (HSCT); which sometimes is the only curative treatment. We report here the results of 13 consecutive patients transplanted with active fungal infection. Thirteen patients (7 males and 6 females) with a median age of 34 years (range, 16-53 years) underwent 15 HSCT between September 2003 and April 2007. In this group of 15 patients, consisting of hematologic malignancies with high risk of relapse or severe aplastic anemia, 11 (73%) transplants performed in subjects with active invasive fungal infection (IFI) patients survived 30 days after transplantation. Three patients (1 patient with primary disease relapse, 1 patient with graft versus host disease [GVHD] complicated with fungal pneumonia, and 1 patient with severe sinusoidal obstruction syndrome and GVHD complicated with aspiration pneumonia) died on days +66, +74, and +62 posttransplantation, respectively, within the first 100 days of HSCT. After a median follow-up time of 306 days (range, 145-680 days), four of 13 (31%) patients with active IFI were alive and disease free. Among a population of HSCT recipients with a dismal prognosis without transplantation, performing the procedure despite active IFI saved a considerable proportion of the patients. The presence of active IFI did not seem to be an absolute contraindication for HSCT, particularly among high-risk patients in whom a treatment delay could be fatal.     

Anaesthesia for renal transplantation in sickle cell disease

Sickle cell disease (SCD) is associated with many pathological and functional abnormalities affecting all organ systems. Renal manifestations of SCD may result in end-stage renal disease (ESRD), which can be treated by chronic haemodialysis or renal transplantation. Renal transplantation was successfully performed in a 25-yr-old male with sickle cell beta-thalassaemia and nephrotic syndrome. We present a case report of this patient, a discussion of the renal complications associated with SCD and the perioperative management of a patient with SCD undergoing renal transplantation.     

Successful Salvage Therapy by Second Haploidentical Allogeneic Hematopoietic Stem Cell Transplantation in a Severe Aplastic Anemia Patient Presenting Donor-Specific Anti-HLA Antibodies After Graft Failure From Matched Sibling Donor HSCT: A Case Report and Review

BackgroundHematopoietic stem cell transplantation (HSCT) is potentially curative for severe aplastic anemia (SAA). Graft failure (GF) remains a life-threatening complication after HSCT. Preexisting anti-HLA antibodies, especially HLA-specific antibodies (DSA), have been demonstrated as a risk of GF.Case presentationThis report describes a woman with acquired SAA who presented with anti-HLA antibodies and GF. After the treatment of anti-HLA antibodies, engraftment was achieved through a second alternative donor HSCT. This work complied with the Declaration of Helsinki and the Declaration of Istanbul.ConclusionsBased on our experience in treating this case, we hold that the presence of preoperative anti-HLA antibodies could discount the efficacy of HSCT and anti-HLA antibody screening should be performed before HSCT. Additionally, a second HSCT is feasible to prolong survival.