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ABSTRACT Hemophagocytic syndrome or hemophagocytic lymphohistiocytosis (HLH) is an infrequent and underdiagnosed condition caused by an overactive immune response, resulting in blood cells phagocytosis. After kidney transplantation (KTx), HLH is usually secondary (or reactive) to infectious and neoplastic processes and has a high mortality rate. No effective treatment is available for this condition. Usual procedures include detecting and treating the pathology triggering the immune system dysregulation, other than administration of intravenous human immunoglobulin (IVIG) and high doses of steroids, and plasmapheresis. The best protocol for maintenance immunosuppressive therapy is also unknown. This article presents two cases of post-KTx reactive HLH that underwent adjuvant IVIG treatment and obtained good clinical results. Despite the high morbidity and mortality associated with reactive HLH after KTx, the early and precise diagnosis and the administration of IVIG therapy along with the treatment of the triggering disease, was an effective strategy to control HLH.

RESUMO A síndrome hemofagocítica (SHF) ou linfo-histiocitose hemofagocítica é uma condição infrequente e subdiagnosticada que tem por base a ativação excessiva da resposta imune, resultando em fagocitose das células do sangue. Após o transplante renal (TxR), a SHF é habitualmente secundária (ou reativa) a processos infecciosos e neoplásicos, culminando em elevadas taxas de mortalidade. Não há evidências quanto ao tratamento ideal dessa condição. Além de investigação e tratamento da patologia desencadeante do processo de desregulação do sistema imune, há descrições do uso de imunoglobulina humana (IVIG), esteroides em altas doses e plasmaférese. Não há evidências quanto à melhor forma de delinear a imunossupressão de manutenção. Este artigo apresenta dois casos de SHF reativa pós-TxR que realizaram tratamento adjuvante com IVIG, obtendo bons resultados clínicos. Apesar da elevada morbimortalidade associada à SHF reativa após o TxR, o diagnóstico ágil e preciso, associado à instituição de terapia com IVIG adjuvante ao tratamento da doença desencadeante, foi uma estratégia eficaz em conter o processo.

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RESUMO

Hemophagocytic syndrome or hemophagocytic lymphohistiocytosis (HLH) is an infrequent and underdiagnosed condition caused by an overactive immune response, resulting in blood cells phagocytosis. After kidney transplantation (KTx), HLH is usually secondary (or reactive) to infectious and neoplastic processes and has a high mortality rate. No effective treatment is available for this condition. Usual procedures include detecting and treating the pathology triggering the immune system dysregulation, other than administration of intravenous human immunoglobulin (IVIG) and high doses of steroids, and plasmapheresis. The best protocol for maintenance immunosuppressive therapy is also unknown. This article presents two cases of post-KTx reactive HLH that underwent adjuvant IVIG treatment and obtained good clinical results. Despite the high morbidity and mortality associated with reactive HLH after KTx, the early and precise diagnosis and the administration of IVIG therapy along with the treatment of the triggering disease, was an effective strategy to control HLH.

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There is no evidence of whether everolimus (EVR) reduces cytomegalovirus (CMV) events in patients receiving steroid-free regimens. Besides, studies evaluating a tacrolimus (TAC) and EVR regimen are limited to 1-year follow-up. In this single-center prospective randomized trial, the incidence of CMV and 3-year efficacy and safety outcomes of EVR were compared to those of mycophenolate sodium (MPS) in a steroid-free regimen based on low-exposure TAC. Both groups received rabbit anti-thymocyte globulin (r-ATG) induction (6 mg/kg) and the steroids were withdrawn at day 7. Maintenance immunosuppression consisted of TAC (4-7 ng/ml until month 3 and 2-4 ng/ml thereafter) plus EVR (3-8 ng/ml) in the EVR group (n = 59); and TAC (4-7 ng/ml during all follow-up) plus MPS (1440 mg) in the MPS group (n = 56). The EVR group presented with a lower incidence of CMV events (18.6% vs. 50%, P = 0.001). No differences were observed in biopsy-proven acute rejection (6.8% vs. 3.6%, P = 0.680),graft loss (0.0% vs. 1.8%, P = 0.487),death (6.8% vs. 1.8%, P = 0.365), or estimated glomerular filtration rate at 36 months (61.1 ± 25.4 vs. 66.3 ± 24 ml/min/1.73 m2 , P = 0.369). A higher proportion of patients discontinued MPS treatment (8.5% vs. 26.8%, P = 0.013) for safety issues. In conclusion, EVR was associated with lower rates of CMV events in patients induced with standard dose r-ATG and a maintenance steroid-free regimen based on TAC. This regimen effectively prevented acute rejection and demonstrated a more favorable safety profile. (ClinicalTrials.gov:NCT02084446).

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BACKGROUND: This study aimed to evaluate renal function before, during, and after the course of tuberculosis (TB) disease in kidney transplant recipients, and assess the risk factors for non-recovery of baseline renal function. METHODS: We performed a retrospective, single-center cohort study, including all patients with confirmed or presumed TB diagnosis after kidney transplant (n=34, 2.1%). Renal function was assessed by serum creatinine (Cr) and glomerular filtration rate (GFR) adjusted for deaths and graft losses. RESULTS: A significant increase was seen in serum Cr during TB disease and treatment: 1.5 mg/dL at baseline (Crbase ), 1.7 mg/dL at diagnosis (P<.001 vs. Crbase ), and 2.4 mg/dL during the peak (P<.001 vs. Crbase ). According to acute kidney injury (AKI) Kidney Disease: Improving Global Outcomes (KDIGO) classification, 29 (85%) patients had AKI: 16 stage 1, 2 stage 2, and 11 stage 3. Three months after the end of the TB treatment, five patients (14.7%) had lost their graft and two others (5.9%) had died. The GFR was lower than the baseline (42.4 mL/min vs 51.6 mL/min, P=.007). In the univariate analysis, peak Cr (odds ratio [OR] 1.276, 95% confidence interval [CI] 0.955-1.705, P=.100), AKI KDIGO stages 2 or 3 (OR 4.958, 95% CI 1.062-23.157, P=.042), severe disease (OR 5.700, 95% CI 1.147-28.330, P=.033), and acute rejection (AR) episodes after TB diagnosis (OR 3.937, 95% CI 0.551-28.116, P=.172) were associated with non-recovery of baseline renal function. No variable was identified in the multivariable model. CONCLUSION: Post-transplantation TB was associated with a high incidence of AKI, and complete recovery of baseline renal function was not achieved after treatment. The severity of TB disease, AKI, and AR episodes that occurred after TB diagnosis are potential causes for this outcome.

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