Visceral leishmaniasis after kidney transplantation: Report of a new case and a review of the literature

Visceral leishmaniasis (VL) is a parasitic disease, caused by protozoa of the genus Leishmania, transmitted by the phlebotomies sand fly. In the last 20 years, the increasing frequency of organ transplantations and the improvement of associated immunosuppressive treatments have led to the recognition of several cases of VL complicating organ transplantation. Actually, less than 100 cases of VL after kidney transplantation are reported in the literature. In this context, VL is fatal without antileishmanial treatment which constitutes a difficult challenge.We report a case of VL in Tunisian renal transplant recipient treated successfully by liposomal amphotericin B (Ambisome®, Gilead Sciences Inc). Also, we review the epidemiological, clinical, biological and therapeutic aspects of VL associated with renal transplantation reported in the literature.Our report identifies that VL should be suspected in renal transplant recipients presenting unexplained fever, splenomegaly and pancytopeny. It also suggests a serological testing for leishmaniasis in the pre-operative check-up of transplant patients and donors living or traveling in endemic areas of leishmaniasis. Moreover, recipients should be tested regularly for leishmaniasis after transplantation. Liposomal amphotericin B may be considered the treatment of choice of VL, since it has a lower incidence of side effects.     

Visceral Leishmaniasis in a Kidney Transplant Recipient: Parasitic Interstitial Nephritis,a Cause of Renal Dysfunction

Visceral leishmaniasis (VL) due to Leishmania infantum is an endemic parasitic infection in the Mediterranean area. It most commonly affects immunosuppressed individuals, especially HIV patients and less frequently organ transplant recipients. Renal involvement seems to be frequent and is mostly associated with tubulointerstitial nephritis, as described in autopsy reports. In the 61 cases of renal transplant recipients with VL reported in the literature, renal dysfunction was noted at clinical presentation and was more frequently observed as a complication of antiparasitic therapy. However, no pathological analysis of the allograft lesions was reported. We present the case of a Swiss renal transplant recipient who developed VL after vacations in Spain and Tunisia, complicated by acute parasitic nephritis in the renal allograft 3 months after a well‐conducted treatment of liposomal amphotericin B.     

Leishmaniasis in solid organ and hematopoietic stem cell transplant recipients

Leishmaniasis occurs in <1% of solid organ and hematopoietic stem cell transplant recipients in endemic countries in which transplants are performed. Visceral leishmaniasis (VL) makes up the bulk of reported cases. The onset generally occurs months after transplantation and the mode of acquisition is often impossible to determine, but de novo vector‐borne infection and reactivation of inapparent infection are thought to be the principal means. The potential role of clinically inapparent donor infection is uncertain and screening is not currently recommended, nor is it recommended for recipients from endemic areas, some of whom may have detectable circulating protozoan nucleic acid. While transplant recipients with VL often present with the non‐specific findings of fever and cytopenia, the additional presence of hepatosplenomegaly in patients from endemic areas should lead to a directed diagnostic evaluation with bone marrow examination and PCR testing of marrow and peripheral blood having a high yield. Management may often be complicated by the presence of concomitant infections. A lipid formulation of amphotericin B is the preferred treatment, especially for VL, but the relapse rate in transplant recipients is approximately 25%. PCR monitoring of blood for either secondary prophylaxis or preemptive therapy requires further study.     

Management of chronic viral hepatitis before and after renal transplantation

Hepatitis C virus (HCV) infection is present in 2-50% of renal transplant recipients and patients receiving hemodialysis. Renal transplantation confers an overall survival benefit in HCV positive (HCV+) hemodialysis patients, with similar 5-year patient and graft survival to those without HCV infection. However, longer-term studies have reported increased liver-related mortality in HCV-infected recipients. Unfortunately, attempts to eradicate HCV infection before transplant have been disappointing. Interferon is poorly tolerated in-patients with end-stage renal disease and ribavirin is contraindicated because reduced renal clearance results in severe hemolysis. Antiviral therapy following renal transplantation is also poorly tolerated, because of interferon-induced rejection and graft loss. Although the prevalence of hepatitis B virus (HBV) infection has declined in hemodialysis patients and renal transplant recipients since the introduction of routine vaccination and other infection control measures, it remains high within countries with endemic HBV infection (especially Asia-Pacific and Africa). Renal transplantation is associated with reduced survival in HBsAg+ hemodialysis patients. Unlike interferon, lamivudine is a safe and effective antiviral HBV treatment both before and after renal transplantation. Lamivudine therapy commenced at transplantation should prevent early posttransplant reactivation and subsequent progression to cirrhosis and late liver failure. This preemptive therapy should also eradicate early liver failure from fibrosing cholestatic hepatitis. Because cessation of treatment may lead to severe lamivudine-withdrawal hepatitis, most patients require long-term therapy. The development of lamivudine-resistance will be accelerated by immunosuppression and may result in severe hepatitis flares with decompensation. Regular monitoring with liver function tests and HBV DNA measurements should enable early detection and rescue with adefovir. Chronic HCV and HBV infections are important causes of morbidity and mortality in renal transplant recipients. The best predictor for liver mortality is advanced liver disease at the time of transplant, and liver biopsy should be considered in all potential HBsAg+ or HCV+ renal transplant candidates without clinical or radiologic evidence of cirrhosis. Established cirrhosis with active viral infection should be considered a relative contraindication to isolated renal transplantation.     

A renal transplant recipient with pulmonary tuberculosis and visceral leishmaniasis: review of superimposed infections and therapy approaches

Visceral leishmaniasis (VL) is an acute or subacute disease that is almost invariably fatal if untreated. It is a rare disease in renal transplant recipients and frequently reported together with other infectious agents. A 39-year-old renal transplant patient was admitted to hospital for elective coronary surgery. In the post-operative period, he developed spiking fever and non-productive cough and his general condition deteriorated. While he was taking medication for non-specific pneumonia, a cavitary lesion occurred in his lung, and he had the diagnosis of pulmonary tuberculosis and antituberculous treatment was started. Despite treatment, his fever continued. As the patient developed pancytopenia and splenomegaly, a bone marrow aspiration was done. Evaluation of bone marrow aspirate indicated Leishmania parasites. He was successfully treated with a more intensive liposomal amphotericin (L-AmB). Complete cure was achieved during follow-up period of 10 months without clinical relapse. In the existence of fever and long-standing pancytopenia, VL should be suspected although the patient had another proved infection and did not live or visit an endemic area. L-AmB usage can be safely preferred for treatment of selected renal transplant recipients with VL as first-line therapy.     

Screening for transplant renal artery stenosis in hypertensive recipients using digital subtraction angiography

Digital subtraction angiography was used in 10 renal allograft recipients with sustained hypertension after transplantation to detect transplant renal artery stenosis. Recipients with end-to-end vascular anastomoses were visualized adequately in the anteroposterior projection. Two cases of transplant renal artery stenosis were identified by digital subtraction angiography and then verified by catheter angiography. Patients with end-to-side vascular anastomoses may require additional oblique projections. Digital subtraction angiography is a safe, noninvasive and cost-effective screening procedure to diagnose transplant renal artery stenosis in most recipients. Catheter angiography can be applied more selectively to those recipients with stenosis observed by digital subtraction angiography or when more detailed imaging is required.     

Neurocognitive Functions in Pediatric Renal Transplant Patients

Neurocognitive dysfunction is one of the major complications of chronic renal failure (CRF). Uremic state during CRF encompasses a wide spectrum of neurobehavioral and neurological disturbances. Recent studies showed that the pathophysiology of neurocognitive dysfunction in CRF is related to plasma levels of uremic solutes. Successful renal transplantation improves renal, metabolic, and endocrine functions and the quality of life. The aim of our study was to determine the state of neurocognitive function in pediatric renal transplant recipients. We prospectively performed a neurological examination and neuropsychological test battery (Bender-Gestalt Test, Cancellation Test, and Visual and Auditory Number Assay Test) in 20 pediatric renal transplant recipients between 6 and 16 years of age. Twenty healthy children and 20 children with CRF were included in the study as the control groups. Mean age of the renal transplant recipients was 13.50 ± 3.40 years old. Mean evaluation time after transplantation was 2.0 ± 0.5 years. Bender-Gestalt Test result was abnormal in 40% of patients. The results of the Cancellation Test and the Visual and Auditory Number Assay Test showed significant decline in pediatric renal transplant patients when compared with the control. We found that neurocognitive dysfunction was frequent in pediatric renal transplantation patients. Awareness of this potential problem may be helpful for early recognition and treatment. Our findings suggest that periodic neurocognitive assessments may be indicated in transplant recipients.     

Renal transplantation following previous heart, liver, and lung transplantation: an 8-year single-center experience

BACKGROUND: Long-term follow-up of heart, liver, and lung transplantation has led to an increased recognition of secondary end-stage renal failure (ESRF) in transplant recipients. This study examines our center's experience with renal transplantation following previous solid organ transplantation. METHODS: From January 1, 1992, to September 30, 1999, our center performed 18 renal transplants in previous solid organ recipients. During the same period, 815 total renal transplants were performed. One- and 3-year graft and patient survival, recipient demographics, donor type, and reason for transplantation were compared between these groups. RESULTS: Of the 18 recipients, 7 had prior heart transplants, 4 had prior liver transplants, and 7 had prior lung transplants. Cyclosporine toxicity contributed to renal failure in 17 (94.4%) of the patients-either as a sole factor (11 patients) or in combination with hypertension, renal artery stenosis, or tacrolimus toxicity (6 patients). Kaplan-Meier 1- and 3-year patient survival was 82.9% and 73.7%, compared with 95.5% and 90.7% in all renal transplant recipients. No surviving patient has suffered renal allograft loss. Mean current creatinine level is 1.4 mg/dL. CONCLUSIONS: Renal transplantation is an excellent therapy for ESRF following prior solid organ transplantation. One and 3-year patient and graft survival demonstrate the utility of renal transplantation in this patient population.     

Cancer incidence in patients on chronic dialysis and in renal transplant recipients

A markedly increased incidence of cancer in renal transplant recipients is now recognized; to determine if immunosuppression alone may be responsible for this increase in risk, cancer incidence was compared in 709 renal transplant recipients and 317 dialysis patients. Malignancy developed in 19 transplant recipients (2.7%) and in 33 patients on chronic dialysis (10.4%). In our report an excess of skin cancer was observed in the transplant series while tumors of the urinary tract were seen more frequently in patients on dialysis. Transplantation and consecutive immunosuppression does not appear to constitute an additional cancer risk for the uremic patient who is faced with the alternative to undergo chronic dialysis or renal transplantation.     

Pegylated interferon-α-based treatment for chronic hepatitis C in renal transplant recipients: an open pilot study

Treatment of hepatitis C in renal transplant recipients remains a controversial issue, as interferon therapy has been associated with a high risk of rejection and poor efficacy. We report here the use of pegylated interferon-α, alone or in combination with ribavirin, in renal transplant recipients with chronic hepatitis C. Eight renal transplant recipients with chronic hepatitis C were recruited. The mean delay between renal transplantation and antiviral therapy was 198.8 months. Sustained virological response was observed in four of out eight patients. Three patients with sustained virological response were genotype 2, one was genotype 1; fibrosis stages were F1 for one patient, F2 for 2, F3 for one. At baseline, renal dysfunction was moderate in seven patients and severe in one patient. No patient experienced rejection episodes during or after pegylated interferon-α therapy. One patient developed haemolytic uraemic syndrome, which eventually resulted in graft loss and return to dialysis. In conclusion, for renal transplant recipients treated with pegylated interferon-α-based therapy, we observed a low risk of renal dysfunction, acceptable tolerance and significant virological efficacy. This is therefore the first study to suggest that pegylated interferon-α could be proposed late after transplantation to renal transplant recipients.     

Clinical Utility of Cytomegalovirus Viral Load in Bronchoalveolar Lavage in Lung Transplant Recipients

The utility of cytomegalovirus (CMV) viral load (VL) by quantitative hybrid capture assay (Q-HCA) was investigated in bronchoalveolar lavage (BAL) from lung transplant recipients and compared with BAL cultures and blood VL. Forty-three consecutive BAL samples from 27 lung transplant recipients were analyzed. All samples had shell vial (SV) cultures in addition to Q-HCA. Histopathology was done on all lung tissues, and immunohistochemistry (IHC) in those with positive CMV cultures. Fifteen (56%) lung transplant recipients had both positive BAL SV cultures and BAL VL. Five of 15 had CMV pneumonitis with a VL in BAL >500 000 copies/mL (mean: 1638 450). Ten patients without CMV pneumonitis had VL in BAL <500 000 copies/mL (mean 81 820, p = 0.002). High VL in BAL and blood invariably meant CMV pneumonitis, but 2 patients with CMV pneumonitis had high BAL VL but relatively low blood VL. Initial CMV seronegativity was associated with pneumonitis (4/5 vs. 1/10; p = 0.004) and higher BAL CMV VL (p = 0.03). High CMV BAL or blood VL did not correlate with acute rejection or development of bronchiolitis obliterans syndrome (BOS). High CMV VL in BAL in lung transplant recipients is strongly associated with CMV pneumonitis, and may be more predictive than peripheral blood viral load.     

肾移植术后血脂的变化对移植肾功能的影响

目的:探讨肾移植患者血脂代谢情况及其对移植肾功能的影响。方法:检测89例肾移植患者肾移植前、后的血脂水平,并与移植后1年内发生急性排斥反应及移植后1年时发生慢性移植肾功能不全的患者进行血清肌酐水平相关性分析。结果:与正常对照组比较,肾移植前、后的血清总胆固醇、低密度脂蛋白胆固醇的水平显著升高(P<0.01),甘油三酯、高密度脂蛋白胆固醇、极低密度脂蛋白胆固醇水平无显著差异。血载脂蛋白A1水平显著低于正常对照组(P<0.01)。移植前、后上述血脂水平无显著差异。移植前高胆固醇血症与急性排斥反应的发生存在相关性,高胆固醇血症对慢性移植肾功能不全患者血清肌酐水平升高存在影响。结论:肾移植患者血脂代谢紊乱明显不同于正常人群,高脂血症对急性排斥反应及慢性移植肾功能不全的发生具有不良影响。     

Coronary Artery Calcification in Renal Transplant Recipients

Cardiovascular disease is the leading cause of mortality in renal transplant recipients. Although renal transplant recipients frequently undergo cardiac functional tests prior to surgery, coronary atherosclerosis can remain undetected. Coronary artery calcification (CAC), an early marker of atherosclerosis can be quantified using EBCT. The purpose of this study was to determine the extent and characteristics of CAC at the time of renal transplantation. We evaluated 79 consecutive incident asymptomatic renal transplant recipients. Patients were mostly White (62%), male (54%) and had a deceased donor renal transplant (61%). The mean age was 47 (12.1) years. Sixty-five percentage of subjects had CAC. The mean CAC score was 331.5 (562.4) with a median of 43.3. Older age, presence of diabetes, not having a preemptive transplant, deceased donor transplantation and hypercholesterolemia were significantly associated with presence of CAC univariately. Median CAC scores were significantly increased in subjects with diabetes (127.8 vs. 28.9, p=0.05), exposed to dialysis (102.9 vs. 3.7, p<0.001) and deceased donor recipients (169.7 vs. 7.5, p=0.02). Using multiple logistic regression, age and time on dialysis were significantly associated with the presence of CAC at the time of transplant. In summary, CAC is prevalent in patients undergoing kidney transplant. CAC may be a method to identify renal transplant recipients at increased risk for future cardiovascular events.     

Cardiac troponin levels in asymptomatic patients on the renal transplant waiting list

AIMS: Cardiac troponin levels predict mortality and cardiovascular events in asymptomatic patients receiving dialysis and may be a useful clinical tool to stratify high-risk asymptomatic individuals. METHODS: The present study examined levels of troponins I (cTnI) and T (cTnT) in patients with chronic renal impairment, patients receiving dialysis and renal transplant recipients. Patients receiving dialysis on the renal transplant waiting list were compared with those excluded from the list based on medical criteria. Median levels were compared using the Kruskal-Wallis test and proportions compared by chi-squared. RESULTS: Median troponin levels were higher in patients on dialysis than transplant recipients. Comparing patients receiving dialysis not listed compared with those listed for renal transplant, median cTnI levels were significantly higher (0.03 versus 0.02 microg/L, P < 0.01) whereas median cTnT levels were not. Patients listed for transplantation were younger, had less clinical cardiovascular disease and lower C-reactive protein than those awaiting renal transplantation. The proportion of patients with elevated cTnT was not substantially different between patients awaiting renal transplantation (38%) and those excluded (52%). Levels of cTnI and cTnT were inversely related to renal function in predialysis and transplant patients, but were not related to time on dialysis for those receiving dialysis therapy. CONCLUSION: As patients awaiting renal transplantation are clinically screened for cardiovascular disease but have frequently elevated cardiac troponin levels, troponin may be a useful clinical tool to identify high-risk asymptomatic patients on dialysis prior to renal transplantation. The influence of renal function on the interpretation of cardiac troponin and risk prediction requires further evaluation.     

Pregnancy under everolimus-based immunosuppression

The ability to give birth to a live child is one of the best success of kidney transplantation. While there are an increasing number of pregnancies reported in kidney transplant recipients treated with cyclosporine or tacrolimus, there is little evidence of pregnancy among kidney transplant recipients exposed to sirolimus or everolimus. We present the first successful delivery in an organ transplant recipient exposed to everolimus during the whole gestation. The absence of congenital anomalies in the child as well as the recipient's successful renal outcome are promising, although pregnancy in renal transplant recipients exposed to everolimus should be considered at higher risk.     

Maximising living donation with paediatric blood-group-incompatible renal transplantation

Long-term outcomes for paediatric renal transplant recipients have improved over the last 20 years, with better patient and renal allograft survival. As paediatric renal transplantation programmes have increased over this timeframe, living donation has become the favoured modality for renal replacement therapy and is advocated pre-emptively in as many cases as possible. However, one of the main barriers historically to living donation has been ABO blood-group incompatibility, with the result that patients were listed to be on call for a deceased donor renal transplant. The clinical scenario has now changed so that donors and recipients for renal transplantation can be worked up and listed for paired exchange and/or living-related ABO blood-group-incompatible renal transplantation (ABOi). There is extensive data in adult practice, and increasing evidence in paediatric practice that the short- and medium-term outcomes for both patient and renal allograft survival for ABOi is equivalent to that of blood-group-compatible renal transplantation.     

Anesthetic considerations for multivisceral transplantation

Multivisceral transplantation is defined as the en bloc transplantation of three or more abdominal organs. Although multivisceral transplant recipients do not yet enjoy the same survival rates as renal and liver transplant recipients, this procedure can be life saving and has shown improvements in survival rates over time. Advances in immunosuppression hold promise for the future of multivisceral transplantation.     

Urological evaluation prior to renal transplantation

Renal transplantation is the best available therapy for patients with end-stage renal failure. Urologists are often consulted regarding pretransplant evaluation and treatment of potential renal transplant recipients. Frequently the urologist is the primary surgeon in the transplant unit. This review highlights the importance of performing a comprehensive urological assessment before renal transplantation. A retrospective review of the urological and transplant literature using Medline was performed from 1976 to 2002, searching for renal transplantation and its association with urological cancers and urinary tract malformations. The pretransplant urological assessment aims to diagnose, treat, and optimize any preexisting urological disease. On occasion, certain urological diseases may not be obvious or may not have contributed to the progression to end-stage renal failure such as occult urinary tract neoplasms, urinary calculus disease, or benign prostatic hyperplasia. A thorough evaluation of the urinary tract prior to renal transplantation is mandatory to avoid unforeseen problems occurring posttransplant. If this assessment is consistently adhered to, only in very rare circumstances does a potential recipient have to be denied the opportunity of receiving an allograft based on a preexisting urological disease.     

Urological malignancy after renal transplantation

Immunosuppression in solid-organ recipients is associated with a greater risk of de novo malignancy after transplantation; herein we report the UK transplant registry (UKTR) database of urological cancer after renal transplantation in the UK transplant population. From September 1999 to January 2006 there were 10,847 kidney recipients with at least one period of follow-up reported after a kidney transplant (mean age at transplantation 42.4 years, sd 15.5; 6685 male, 61.6%, and 4162 female, 38.3%). The recipients represent a homogenous group who received different immunosuppression regimens. Skin cancer was excluded from the study. Unfortunately, the UKTR does not collect information about the presence or absence of cancer, either at registration onto the transplant waiting list or at transplantation. In all, 214 (1.9%) patients were reported to have a subsequent urological malignancy diagnosed among the 10,847 recipients. The UKTR was used to identify patients who developed urological malignancies after renal transplantation, which is a challenging event after solid-organ transplantation. Regular surveillance to diagnose early occurrence and adjustment of immunosuppression might be beneficial. In the presence of metastatic disease, chemotherapy treatment with adjustment or cessation of immunosuppressive therapy is required.     

Prostaglandin E2 in renal transplant recipients

The concentrations of prostaglandin E₂ (PGE₂), sodium, potassium and creatinine were determined in the blood and urine of 50 renal transplant recipients treated with cyclosporine A or azathioprine, as immunosuppressive agents, for at least one year post transplantation. Fourteen healthy subjects served as control group. The urinary PGE₂ excretion was significantly decreased in all treated renal transplant recipients and this reduction was associated with significant decrease in urinary excretion of sodium and potassium. On the other hand, a high elevation in blood PGE₂ concentration was observed while no significant changes were seen in sodium and potassium levels in the blood of these renal transplant recipients. The observations suggest an association between urinary PGE₂ reduction and immunosuppressive treatments in renal transplant recipients; also, PGE₂ may regulate intra-renal haemodynamics and influence the renal tubular electrolyte excretion. Moreover, urinary PGE₂ can be used as an indicator of successful renal transplantation.