Spleen-Restricted Posttransplant Lymphoproliferative Disorder in the First Year After Kidney Transplant - A Case Report.

Posttransplant lymphoproliferative disorders (PTLDs) are a feared complication after transplant. They are mostly of B cell origin and are frequently Epstein-Barr virus (EBV)-positive, particularly in early onset PTLD. Later on, non-B and EBV-negative PTLD are increasingly reported. EBV seronegative receptors (particularly when paired with an EBV seropositive donor) together with the net degree of immunosuppression-a concept often difficult to quantify-are the most consistently described risk factors for the development of PTLD. Conversely, its association with a particular immunosuppressive agent or other virus, namely cytomegalovirus (CMV) infection or disease, has been inconsistently reported. We present a challenging case where an EBV negative monomorphic peripheric T-cell lymphoma was diagnosed in the first year after kidney transplant in a patient with a recent history of CMV disease from a resistant strain.

Viral Clearance and Serological Response to SARS-CoV-2 in Kidney Transplant Recipients.

OBJECTIVES: Knowledge about the impact of coronavirus disease 2019 (COVID-19) on kidney transplant recipients (KTRs) concerning viral shedding and humoral immune response against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is limited. The aim of this study is to analyze viral dynamics and the antibody response to SARS-CoV-2 in KTRs with COVID-19 and study their association with clinical data. MATERIALS AND METHODS: Consecutive KTRs diagnosed with COVID-19 at our center were evaluated for clinical presentation and outcome; duration of viral shedding and viral burden by reverse transcription-polymerase chain reaction assay cycle threshold; and magnitude of seroconversion to SARS-CoV-2. RESULTS: Six KTRs identified with COVID-19 were hospitalized. Presenting symptoms were similar to those in the general population. Four patients had severe disease and, of these, 2 required mechanical ventilation, 4 had acute kidney injury, and 3 had secondary bacterial infections. Immunosuppression was reduced in all patients. Five patients were treated with hydroxychloroquine. No patient required dialysis or died. Patients with severe disease had a longer duration of viral shedding, which lasted more than 40 days, and had IgG antibodies against SARS-CoV-2, which were detected from 3 weeks to as long as 10 weeks after symptom onset. In patients with less severe disease no IgG antibodies where detected between 9 and 14 weeks after symptom onset. CONCLUSIONS: In our series, KTRs with severe COVID-19 had prolonged viral shedding and a stronger humoral immune response to SARS-CoV-2. These preliminary data need to be confirmed with further studies and over a longer period of time.

Visceral Dissemination of Mucocutaneous Leishmaniasis in a Kidney Transplant Recipient.

Intracellular protozoan of the genus Leishmania, endemic in the Mediterranean basin, are the cause of cutaneous (CL), mucocutaneous (MCL), and visceral leishmaniasis (VL). A 75-year-old woman was admitted nine years after a second kidney transplant (KT), due to persistent pancytopenia and fever. She presented edema and erythema of the nose in the last two years and an exophytic nodular lesion located on the left arm, with areas of peripheral necrosis and central ulceration in the last 18 months. A bone marrow biopsy revealed features compatible with Leishmania amastigotes, and polymerase chain reaction test (PCR) for Leishmania infantum was positive. Moreover, biopsy and PCR for L. infantum of the cutaneous lesion on the patient's left arm and nose and PCR from peripheral blood were positive. Thus, a diagnosis of CL, MCL, and VL was made, and liposomal amphotericin B was initiated, but the patient had an unfavorable outcome and died. This is the first report of a KT recipient presenting with the entire spectrum of leishmaniasis. In Portugal, this infection is rare-so a high degree of clinical suspicion is required for its diagnosis, especially in endemic regions, as visceral leishmaniasis is a potentially life-threatening infection.

Reactivation of Hepatitis B virus in kidney transplant recipients with previous clinically resolved infection: A single-center experience / Reactivación del virus de la hepatitis B en receptores de trasplante renal con infección previa resuelta clínicamente: una experiencia de un solo centro

BACKGROUND: Hepatitis B virus (HBV) reactivation in kidney transplant recipients (KTR) involves important morbidity and mortality. Despite being more common in patients who are HBsAg-positive, it may occur in patients with clinically resolved infection (HBsAg-negative and anti-HBc-positive), in whom the presence of the protective anti-HB antibody is thought to decrease the risk of reactivation. Data regarding reactivation rates in this population are scarce. OBJECTIVE: To retrospectively evaluate the risk of HBV reactivation in KTR with previously resolved infection. MATERIAL AND METHODS: Retrospective cohort study including patients who underwent a kidney transplant between January 1994 and December 2014 with resolved HBV infection at the time of transplantation (anti-HBc seropositivity without detectable HBsAg, with or without anti-HB-positive antibodies and normal liver enzymes). RESULTS: Out of 966 patients, 95 patients with evidence of resolved HBV infection were analyzed, of which 86 had a titer of anti-HBs >10 mIU/ml. Mean follow-up time was 93 months; 12 patients had lost anti-HBs. Two patients showed evidence of reactivation. Risk factors associated with loss of anti-HBs were elderly age (>60) and occurrence of acute graft rejection (p < 0.05). CONCLUSION: The risk of HBV reactivation in KTR with previously resolved infection is not negligible at 2%. Elderly age and acute rejection were associated with loss of anti-HBs, and these patients may benefit from closer monitoring of HBV DNA levels. Routine serology and/or HBV viral load monitoring in HBsAg-negative, anti-HBc-positive patients is recommended and should be emphasized in these patients

INTRODUCCIÓN: La reactivación del virus de la hepatitis B (VHB) en receptores de trasplante renal (RTR) supone una importante morbilidad y mortalidad. A pesar de ser más frecuente en pacientes con HBsAg positivo, puede suceder en pacientes con infección clínicamente resuelta (HBsAg-negativo y anti-HBc-positivo). En estos casos, la presencia del anticuerpo protector anti-HBs parece disminuir el riesgo de reactivación. Existen escasos datos relativos a las tasas de reactivación en esta población. OBJETIVOS: Evaluación retrospectiva del riesgo de reactivación del VHB en RTR con infección previa resuelta. MATERIAL Y MÉTODOS: Estudio de cohorte retrospectivo, incluyendo RTR entre enero de 1994 y diciembre de 2014, con infección VHB resuelta en el momento del trasplante (anti-HBc seropositivo, HBsAg indetectable, con o sin anticuerpo anti-HBs e enzimas hepáticas normales). RESULTADOS: De un total de 966, 95 pacientes con evidencia de infección VHB resuelta fueron analizados; 86 tenían un título de anti-HBs > 10 mIU/ml. El tiempo medio de seguimiento fue de 93 meses, 12 pacientes habían perdido anti-HBs. Dos pacientes tuvieron evidencia de reactivación. Los factores de riesgo asociados a la pérdida de anti-HBs fueron la edad avanzada (> 60) y la evidencia de rechazo agudo del injerto (p < 0,05). CONCLUSIÓN: El riesgo de reactivación del VHB en RTR con infección previamente resuelta (2%) no es despreciable. La edad avanzada y el rechazo agudo están asociados a la pérdida de anti-HBs, y estos pacientes podrían beneficiarse de una vigilancia de los niveles de DNA del VHB. Las serologías de rutina y/o la monitorización de la carga viral en pacientes HBsAg-negativo, anti-HBc-positivo está recomendado y debería ser enfatizado en estos pacientes

Reactivation of Hepatitis B virus in kidney transplant recipients with previous clinically resolved infection: A single-center experience.

BACKGROUND: Hepatitis B virus (HBV) reactivation in kidney transplant recipients (KTR) involves important morbidity and mortality. Despite being more common in patients who are HBsAg-positive, it may occur in patients with clinically resolved infection (HBsAg-negative and anti-HBc-positive), in whom the presence of the protective anti-HB antibody is thought to decrease the risk of reactivation. Data regarding reactivation rates in this population are scarce. OBJECTIVE: To retrospectively evaluate the risk of HBV reactivation in KTR with previously resolved infection. MATERIAL AND METHODS: Retrospective cohort study including patients who underwent a kidney transplant between January 1994 and December 2014 with resolved HBV infection at the time of transplantation (anti-HBc seropositivity without detectable HBsAg, with or without anti-HB-positive antibodies and normal liver enzymes). RESULTS: Out of 966 patients, 95 patients with evidence of resolved HBV infection were analyzed, of which 86 had a titer of anti-HBs >10mIU/ml. Mean follow-up time was 93 months; 12 patients had lost anti-HBs. Two patients showed evidence of reactivation. Risk factors associated with loss of anti-HBs were elderly age (>60) and occurrence of acute graft rejection (p<0.05). CONCLUSION: The risk of HBV reactivation in KTR with previously resolved infection is not negligible at 2%. Elderly age and acute rejection were associated with loss of anti-HBs, and these patients may benefit from closer monitoring of HBV DNA levels. Routine serology and/or HBV viral load monitoring in HBsAg-negative, anti-HBc-positive patients is recommended and should be emphasized in these patients.

Normalization of glomerular filtration rate in obese children.

BACKGROUND: Glomerular filtration rate (GFR) is conventionally indexed to body surface area (BSA), but this may lead to biased results when applied to subjects of abnormal body size. The aim of our study was to examine the impact of normalization to the BSA and alternative body size descriptors on measured and estimated GFR in overweight and obese children. METHODS: This was a cross-sectional study of 313 children aged 8-9 years old. GFR was measured by 24-h creatinine clearance (CrCl) and additionally estimated from serum creatinine and cystatin C (CysC) using the combined Zappitelli formula, both as absolute values and adjusted to various body size descriptors. The results were compared between 163 normal-weight, 89 overweight and 61 obese children. RESULTS: Compared to the normal-weight children, mean absolute GFR (both measured and estimated) was higher in the overweight and obese children, whereas BSA-adjusted GFR was lower. Linear regression models fitted in normal-weight children revealed equally close associations between absolute GFR and squared height, ideal body weight (IBW) and BSA derived from IBW. Normalization of GFR to the IBW-derived BSA completely eliminated the discrepancy between absolute and BSA-indexed GFR in overweight and obese children. CONCLUSIONS: Indexing of GFR to BSA calculated from the ideal-rather than actual-body weight is a promising approach to avoid overcorrection when studying obese children. Further studies should assess the accuracy of this approach across the full range of age and BMI distribution.

Decreased renal function in overweight and obese prepubertal children.

BACKGROUND: Obesity is a potentially modifiable risk factor for the development and progression of kidney disease, both in adults and children. We aim to study the association of obesity and renal function in children, by comparing estimated glomerular filtration rate (eGFR) in nonoverweight and overweight/obese children. Secondarily, we aim to evaluate the accuracy of equations on eGFR estimation when compared to 24-h urinary creatinine clearance (CrCl). METHODS: Cross-sectional study of 313 children aged 8-9 y, followed in the birth cohort Generation XXI (Portugal). Creatinine and cystatin C, GFR estimated by several formulas and CrCl were compared in 163 nonoverweight and 150 overweight/obese, according to World Health Organization growth reference. RESULTS: Overweight/obese children had significantly lower eGFR, estimated by all methods, except for CrCl and revised Schwartz formula. Despite all children having renal function in the normal range, eGFR decreased significantly with BMI z-score (differences ranging from -4.3 to -1.1 ml/min/1.73 m(2) per standard deviation of BMI). The Zappitelli combined formula presented the closest performance to CrCl, with higher correlation coefficients and higher accuracy values. CONCLUSION: Young prepubertal children with overweight/obesity already present significantly lower GFR estimations that likely represent some degree of renal impairment associated with the complex deleterious effects of adiposity.

Conversion from sirolimus to everolimus in kidney transplant recipients receiving a calcineurin-free regimen.

BACKGROUND: Everolimus (EVL) and sirolimus (SRL) were introduced into immunosuppressive regimens, in an attempt to replace or reduce the dose of the nephrotoxic calcineurin inhibitors (CNI). In our institution, due to an administrative decision, conversion from SRL to EVL, was carried out, providing us the opportunity to investigate the effectiveness and safety profile of both drugs and to review the practical conversion dose between them. METHODS: We retrospectively analyzed the medical records of 51 maintenance kidney transplant recipients receiving an SRL-based CNI-free regimen, who were switched to EVL. SRL dose was concentration controlled to a through level of 4-8 ng/mL. Patients were converted to a variable dose of EVL that was adjusted to achieve a trough concentration of 3-8 ng/mL. RESULTS: SRL mean dose at time of conversion was 2.0 ± 0.9 mg/d. Initial EVL mean dose was 1.3 ± 0.5 mg/d. Six months after conversion, mean EVL trough level was 6.2 ± 2.8 ng/mL. EVL dose at this point was 2.0 ± 0.9 mg/d, which was not statistically different from SRL dose at the time of conversion (p = 0.575), suggesting a conversion factor of 1:1. During this six month period post conversion, no significant changes were observed in serum creatinine, hematocrit level, platelet count, proteinuria or lipid levels. No patient experienced an acute rejection episode. CONCLUSIONS: Conversion from SRL to EVL in renal transplant recipients receiving a CNI-free immunosuppressive regimen can be performed safely with a low trough level range of EVL. We report for the first time a conversion factor between SRL and EVL.

Lung and renal transplantation.

UNLABELLED: Renal transplantation is the most common type of solid organ transplantation and kidney transplant recipients are susceptible to pulmonary complications of immunosuppressive therapy, which are a diagnostic and therapeutic challenge. AIM: To evaluate patients admitted to the Renal Transplant Unit (RTU) of Hospital de S. João with respiratory disease. SUBJECT AND METHODS: We performed a retrospective study of all patients admitted to RTU with respiratory disease during a period of 12 months. RESULTS: Thirty-six patients were included. Mean age 55.2 (+/-13.4) years; 61.1% male. Immunosuppressive agents most frequently used were prednisolone and mycophenolate mofetil associated with ciclosporin (38.9%) or tacrolimus (22.2%) or rapamycin (13.9%). Thirty-one patients (86.1%) presented infectious respiratory disease. In this group the main diagnoses were 23 (74.2%) pneumonias, 5 (16.1%) opportunistic infections, 2 (6.5%) tracheobronchitis, and 1 case (3.2%) of lung abscesses. Microbiological agent was identified in 7 cases (22.6%). Five patients (13.9%) presented rapamycin-induced lung disease. Fibreoptic bronchoscopy was performed in 15 patients (41.7%), diagnostic in 10 cases (66.7%). Mean hospital stay was 17.1 (+/-18.5) days and no related death was observed. CONCLUSION: Respiratory infections were the main complications in these patients. Drug-induced lung disease implies recognition of its features and a rigorous monitoring of drug serum levels. A more invasive diagnostic approach was determinant in the choice of an early and more specific therapy.

Kidney biopsy findings in heterozygous Fabry disease females with early nephropathy.

Fabry disease is an X-linked glycosphingolipidosis caused by deficiency of alpha-galactosidase. Progressive chronic kidney disease (CKD) is a major cause of morbidity and mortality in males. Although 40% of heterozygous females may develop renal involvement, pathologic data on Fabry nephropathy in heterozygotes are scarce. We reviewed the kidney biopsies of four affected females who had normal to slightly sub-normal renal function, two of them with overt proteinuria. Chronic non-specific degenerative lesions and glycosphingolipid accumulation per cell type were semi-quantitatively assessed by light and electron microscopy. Cellular distribution of glycosphingolipid deposits was best assessed on semithin sections. Podocyte effacement was seen only in proteinuric patients. Combined analysis of our data with those of two earlier series showed that glomerular sclerosis and tubulointerstitial fibrosis are predictors of proteinuria and CKD stage. There was no histopathological evidence supporting a major role of vascular damage in the early pathogenesis of Fabry nephropathy in females.