Rituximab in glomerular diseases: a case series and narrative review / Rituximab em doenças glomerulares: uma série de casos e revisão narrativa

Abstract Introduction: The use of Rituximab (RTX) in glomerular diseases (GD) has increased in the past years, although it is still only used in a small fraction of patients. Methods: A single center retrospective study of adult patients with membranous nephropathy (MN), focal segmental glomerulosclerosis (FSGS), lupus nephritis (LN), and vasculitis treated with RTX as first or second-line therapy was conducted at our center from 2010 to 2020. Results: We identified 19 patients; 36.8% had MN and 25.0% each had FSGS, LN, and vasculitis. RTX was first-line therapy in 26.3% of patients and in 73.7% it was second-line therapy. Mean follow-up time was 7.7 ± 7.2 years. In MN, 2 patients (28.6%) had complete remission (CR), 2 patients (28.6%) had partial remission (PR), and 3 patients (42.9%) had no response (NR). In FSGS, 2 patients (50.0%) presented CR, 1 patient (25.0%) had no response, and 1 patient had renal deterioration. Two patients (50.0%) had a LN class IV with a CR after RTX, 1 patient with LN class IIIC/V had no response, and 1 patient with LN class II had renal deterioration. In vasculitis, 3 patients (75.0%) presented CR and 1 patient had PR. Infusion reactions were present in 2 patients (10.5%) and one patient had multiple infectious complications. Conclusions: The efficacy of RTX in treating different types of immune-mediated GD has been demonstrated with different response rates, but an overall safe profile. In our case series, the results are also encouraging. Longitudinal studies are needed to better understand the effect of RTX in GD.

Resumo Introdução: O uso de Rituximab (RTX) em doenças glomerulares (DG) aumentou nos últimos anos, embora ainda utilizado apenas em uma pequena fração de pacientes. Métodos: Conduzimos em nosso centro, de 2010-2020, um estudo retrospectivo de único centro de pacientes adultos com nefropatia membranosa (NM), glomeruloesclerose segmentar focal (GESF), nefrite lúpica (NL) e vasculite tratada com RTX como terapia de primeira ou segunda linha. Resultados: Identificamos 19 pacientes; 36,8% tinham NM; 25,0% cada apresentava GESF, NL e vasculite. RTX foi terapia de primeira linha em 26,3% dos pacientes e em 73,7% foi terapia de segunda linha. O tempo médio de acompanhamento foi 7,7 ± 7,2 anos. Em NM, 2 pacientes (28,6%) tiveram remissão completa (RC), 2 pacientes (28,6%) remissão parcial (RP), e 3 pacientes (42,9%) não tiveram resposta (NR). Na GESF, 2 pacientes (50,0%) apresentaram RC, 1 paciente (25,0%) não teve resposta e, 1 paciente, deterioração renal. Dois pacientes (50,0%) apresentaram NL classe IV com RC após RTX, 1 paciente com NL classe IIIC/V não teve resposta, e 1 paciente com NL classe II apresentou deterioração renal. Na vasculite, 3 pacientes (75,0%) apresentaram RC e 1 paciente RP. Reações à infusão ocorreram em 2 pacientes (10,5%) e um paciente apresentou múltiplas complicações infecciosas. Conclusões: A eficácia do RTX em tratar diferentes tipos de DG imunomediada tem sido demonstrada com diferentes taxas de resposta, mas com perfil geral seguro. Em nossa série de casos, os resultados também são encorajadores. Estudos longitudinais são necessários para compreender melhor o efeito do RTX na DG.

Fetal Tuberous Sclerosis: Sirolimus for the Treatment of Fetal rhabdomyoma.

BACKGROUND: Sirolimus constitutes a safe and effective treatment for cardiac manifestations of tuberous sclerosis complex (TSC) in children but only four cases describing prenatal treatment of rhabdomyomas with mTOR inhibitors have been published. CASE: In this case, sirolimus was initiated at 26 weeks´ gestation in a pregnant woman with TSC with a fetus with a large rabdomyoma conditioning severe arrythmia. There was a significant reduction in the tumor size with ongoing treatment and a partial reversion of the arrythmia. CONCLUSION: m-TOR inhibitors can be considered for severe cases of fetal rhabdomyomas with poor prognosis given its potencial benefits.

High-Dose Cyclophosphamide and Tacrolimus as Graft-versus-Host Disease Prophylaxis for Matched and Mismatched Unrelated Donor Transplantation.

The optimal prophylaxis regimen for graft-versus-host disease (GVHD) in the setting of single-locus mismatched unrelated donor (MMUD) allogeneic hematopoietic stem cell transplantation (alloHSCT) is unclear. The use of high-dose post-transplant cyclophosphamide (PTCy) after haploidentical transplantation is effective at overcoming the negative impact of HLA disparity on survival. Limited information is available regarding the efficacy of this strategy in alloHSCT from MMUDs. Most of the published studies have used the triple immunosuppressant model of haploidentical transplant combining PTCy with calcineurin inhibitors and mycophenolate mofetil or methotrexate. In our study, we propose the use of a simpler GVHD prophylaxis protocol comprising PTCy in combination with tacrolimus for MMUD and matched unrelated donor (MUD) alloHSCT. We performed a retrospective analysis of 109 consecutive recipients of alloHSCT from unrelated donors (MMUD, n = 55; MUD, n = 54) in a single center. Graft source was primarily peripheral blood (98%). No differences were observed between the MMUD and MUD groups with respect to 100-day cumulative incidence of grade II to IV acute GVHD (aGVHD; 31% versus 32%, respectively, P = .9), grade III to IV aGVHD (9% versus 7%, P = .7), and moderate/severe chronic GVHD (cGVHD) at 2 years (18% versus 14%, P = .6). Both groups showed similar cumulative incidence of 1 year nonrelapse mortality (13% versus 9%; P = .5) and 3-year relapse rates (24% versus 25%, P = .7). Progression-free survival and overall survival at 3 years for MMUD and MUD were 56% and 57% (P = .9) and 64% and 65% (P = .6), respectively. The 3-year probability of survival free of moderate/severe cGVHD and relapse was 56% and 55%, respectively. GVHD prophylaxis with PTCy and tacrolimus achieves low rates of severe aGVHD and cGVHD, as well as good survival outcomes, in recipients of both MMUD and MUD peripheral blood alloHSCT. This strategy overcomes the negative impact of single-locus HLA disparity.

Transient and Persistent AKI and Outcomes in Patients Undergoing Major Abdominal Surgery.

INTRODUCTION: Acute kidney injury (AKI) is a frequent diagnosis in surgical patients which has a detrimental effect on short-term and long-term outcomes. The purpose of this study was to evaluate the incidence and predictive factors of transient and persistent postoperative AKI in patients submitted to major abdominal surgery and to characterize the impact of AKI on in-hospital mortality. METHODS: This study was a cross-examination of a retrospective analysis of clinical data of 450 patients who underwent major abdominal surgery from January 2010 to February 2011. Only AKI developing in the first 48 h after surgery was considered. AKI was diagnosed using the Kidney Disease: Improving Global Outcome (KDIGO) classification based on both serum creatinine (SCr) and urine output criteria. Persistent and transient AKI were defined according to the Acute Disease Quality Initiative (ADQI) workgroup definitions. RESULTS: In our study, 22.4% of patients developed AKI in the first 48 h post-surgery (n = 101), and 48% of patients had persistent AKI (n = 49), defined as postoperative AKI, with a duration of more than 48 h. Older age (adjusted odds ratio [OR] 1.06 [1.00-1.11], p = 0.039), hypertension (adjusted OR 4.60 [1.17-18.11], p = 0.029), and higher preoperative SCr (adjusted OR 22.67 [4.00-128.46], p < 0.001) were independent predictors of persistent AKI. The overall in-hospital mortality was 6.4% (n = 29). Persistent AKI was associated with higher mortality than transient AKI (51.9 vs. 20.7%; unadjusted OR 13.03 [5.78-29.36], p < 0.001; adjusted OR 4.20 [1.02-17.27], p = 0.047). CONCLUSION: In this cohort of patients submitted to major abdominal surgery, persistent AKI was an independent predictor of in-hospital mortality in contrast to transient AKI.

Quantitative PCR Is Faster, More Objective, and More Reliable Than Immunohistochemistry for the Diagnosis of Cytomegalovirus Gastrointestinal Disease in Allogeneic Stem Cell Transplantation.

Diagnosis of gastrointestinal (GI) cytomegalovirus (CMV) disease relies on the presence of GI symptoms and detection of CMV, mainly by immunohistochemistry (IHC), in GI biopsy specimens. Thus, in a symptomatic patient, a positive CMV-IHC result is accepted as a diagnosis of CMV disease. However, a positive CMV-PCR in GI tissue is considered "possible" CMV disease. Therefore, it would be very useful if, in practice, both techniques showed equal sensitivity and reliability. This is because PCR has many practical advantages over IHC for detecting CMV. The aim of this study was to compare quantitative PCR with IHC for the diagnosis of GI CMV disease. A total of 186 endoscopic GI biopsy specimens from 123 patients with GI symptoms after an allogeneic stem cell transplantation (allo-SCT; 2004-2017) were analyzed by IHC and PCR on 113 paraffin-embedded and 73 fresh samples. The results were then compared. Of the patients with macroscopic lesions in the mucosa and CMV-IHC-positive biopsy specimens (eg, "proven" CMV disease, n = 28), all but 1 were CMV-PCR positive. Of the patients without macroscopic lesions in the mucosa and CMV-IHC-positive biopsy specimens (eg, probable CMV disease, n = 4), only 1 was CMV-PCR positive. Eight patients had CMV-IHC-negative/CMV-PCR-positive gut biopsy specimens. These cases fall within the current definition of possible CMV disease. In 6 of these 8 cases (75%), the viral load in GI tissue was very high (>10,000 copies/µg). Taken together, the results from the proven and probable cases revealed that CMV-PCR shows the same sensitivity (100%), specificity (98%), and positive (93%) and negative predictive value (100%) as CMV-IHC. Detection of CMV in fresh GI mucosa by quantitative PCR is as useful as IHC for the diagnosis of GI CMV disease. The results show that quantitative PCR has the same sensitivity, specificity, and positive/negative predictive value as IHC.

Neutrophil, lymphocyte and platelet ratio as a predictor of postoperative acute kidney injury in major abdominal surgery.

BACKGROUND: Surgery is one of the leading causes of acute kidney injury (AKI) in hospitalized patients. Major abdominal surgery has the second higher incidences of AKI, after cardiac surgery. AKI results from a complex interaction between hemodynamic, toxic and inflammatory factors. The pathogenesis of AKI following major abdominal surgery is distinct from cardiac and vascular surgery. The neutrophil, lymphocytes and platelets (N/LP) ratio has been demonstrated as an inflammatory marker and an independent predictor for AKI and mortality after cardiovascular surgery. The aim of this study was to evaluate the prognostic ability of the post-operative N/LP ratio after major abdominal surgery. METHODS: We cross-examined data of a retrospective analysis of 450 patients who underwent elective or urgent major nonvascular abdominal surgery at the Department of Surgery II of Centro Hospitalar Lisboa Norte from January 2010 to February 2011. N/LP ratio was determined using maximal neutrophil counts and minimal lymphocyte and platelet counts in the first 12 h after surgery. AKI was considered when developed within 48 h after surgery. RESULTS: One-hundred and one patients (22.4%) developed AKI. Patients with higher N/LP ratio had an increased risk of developing postoperative AKI (6.36 ± 7.34 vs 4.33 ± 3.36, p < 0.001; unadjusted OR 1.1 (95% CI 1.04-1.16), p = 0.001; adjusted OR 1.05 (95% CI 1.00-1.10), p = 0.048). Twenty-nine patients died (6.44%). AKI was an independent predictor of mortality (20.8 vs 2.3%, p < 0.0001; unadjusted OR 11.2, 95% CI 4. 8-26.2, p < 0.0001; adjusted OR 3.56, 95% CI 1.0 2-12.43, p = 0.046). In a multivariate analysis higher N/LP ratio was not associated with increased in-hospital mortality. CONCLUSION: Postoperative N/LP ratio was independently associated with AKI after major abdominal surgery, although there was no association with in-hospital mortality.

Innovative strategies minimize engraftment syndrome in multiple myeloma patients with novel induction therapy following autologous hematopoietic stem cell transplantation.

Autologous stem cell transplantation (PBSCT) is standard for young patients in MM and its TRM has decreased after the 2000s. Bortezomib and immunomodulatory agents (IMiDs) in MM have improved the outcome. However, they seem to boost pro-inflammatory stage increasing the incidence of engraftment syndrome (ES). Favorable factors in PBSCT such as G-CSF could increase inflammatory stage during transplant. Corticosteroids have shown an excellent response of ES and some authors propose them as prophylaxis for ES. The aim was to analyze the impact of G-CSF avoidance and corticosteroids' prophylaxis in 170 patients diagnosed of MM treated with bortezomib/IMiDs that underwent PBSCT. We established three groups: Group-I [(G-CSF_administration), 60 patients (35%)], group-II [(nonG-CSF), 60 patients (35%)] and group-III [(nonG-CSF plus corticosteroid's prophylaxis), 50 patients (30%)]. A decreased ES incidence among groups was observed: 62, 42, and 22% (P < 0.0001). The incidence of symptoms mimicking a capillary leak syndrome associated with ES dropped: 43, 32, and 0% (P = 0.03). The G-CSF avoidance and corticosteroids had impact over admission 24, 21, and 20 days (P = 0.001). The most important variables related to ES were HCT-CI >2 (p < 0.0001; HR 8.5) and risk groups (p < 0.0001; HR 7.2). Hence, G-CSF avoidance and corticosteroid's prophylaxis decrease morbidity in patients undergoing PBSCT with MM treated with bortezomib/IMiDs.

Acute kidney injury in major abdominal surgery: incidence, risk factors, pathogenesis and outcomes.

Acute kidney injury (AKI) is a common complication in patients undergoing major abdominal surgery. Various recent studies using modern standardized classifications for AKI reported a variable incidence of AKI after major abdominal surgery ranging from 3 to 35%. Several patient-related, procedure-related factors and postoperative complications were identified as risk factors for AKI in this setting. AKI following major abdominal surgery has been shown to be associated with poor short- and long-term outcomes. Herein, we provide a contemporary and critical review of AKI after major abdominal surgery focusing on its incidence, risk factors, pathogeny and outcomes.

Membranoproliferative glomerulonephritis and interstitial nephritis in the setting of Epstein-Barr virus-related hemophagocytic syndrome
.

BACKGROUND: Hemophagocytic syndrome (HPS) is a rare, aggressive disorder characterized by dysregulation of lymphocyte and macrophage activity, which culminates in tissue infiltration with hemophagocytosis and ultimately organ failure. Renal involvement frequently ensues and usually results in acute tubular necrosis with associated interstitial inflammation. Less frequently, glomerulopathy can also be found. CASE: We report a case of a 24-year-old Caucasian woman with previous asymptomatic hematuria, mild proteinuria, and normal renal function who presented to us with fever. Laboratory findings revealed pancytopenia, elevated lactate dehydrogenase, and ferritin as well as liver and kidney failure. Renal biopsy showed a tubulointerstitial nephritis superimposed in a membranoproliferative glomerulonephritis with crescents. Extensive etiologic investigation was negative except for Epstein-Barr virus (EBV) viral load. EBV-DNA was then identified by in situ hybridization in the renal biopsy. HPS could be diagnosed with the presence of six criteria: fever, splenomegaly, bicytopenia, high ferritin, hypertriglyceridemia, and high levels of soluble CD25. Steroid therapy was initiated with resolution of HPS as well as complete recovery of renal and liver function. CONCLUSION: In this case, we believe that EBV triggered both HPS and tubulointerstitial nephritis. Steroid therapy successfully treated the inflammatory syndrome, allowing renal function recovery without compromising EBV infection resolution.
.

Multiple brown tumors - a rare presentation in the modern era
.

Chronic kidney disease (CKD) commonly evolves with disturbances in mineral and bone metabolism, currently defined as CKD-MBD. Management strategies have progressed over the years, but our knowledge regarding evaluation and treatment is still sparse. Herein, we describe a rare case of a hemodialysis patient with apparently fairly controlled hyperparathyroidism (HPTH), who developed multiple symptomatic brown tumors involving the scull, mandible, vertebrae, pelvis, and metacarpus. Parathyroidectomy allowed complete resolution of the bone lesions preventing disastrous consequences.
.

Diabetes, deafness and renal disease.

Deafness, kidney disease and diabetes are not a usual association, neither is a family history of these diseases. We present the case of a 47-year-old woman with non-nephrotic proteinuria, no haematuria, normal renal function, sensorineural hearing loss, recently diagnosed diabetes and maculopathy. There was a maternal family history of deafness, diabetes and renal disease. Renal biopsy revealed focal and segmental glomerulosclerosis (FSGS), leading to the pursuit of an m.3243A > G mitochondrial mutation and diagnosis of maternally inherited diabetes and deafness. The association of FSGS with mitochondrial diseases is not well known among nephrologists. Its timely diagnosis is important to avoid exposure to ineffective and unnecessary immunosuppression.

Life-saving vascular access in vascular capital exhaustion: single center experience in intra-atrial catheters for hemodialysis / Acesso vascular life-saving na exaustão do capital vascular: experiência de um centro com cateteres intra-auriculares para hemodiálise

Abstract Introduction: Intra-atrial catheter (IAC) placement through an open surgical approach has emerged as a life-saving technique in hemodialysis (HD) patients with vascular access exhaustion. Objective: To assess the complications of IAC placement, as well as patient and vascular access survival after this procedure. Methods: The authors retrospectively analyzed all seven patients with vascular capital exhaustion, without immediate alternative renal replacement therapy (RRT), who underwent IAC placement between January 2004 and December 2015 at a single center. Results: Seven patients were submitted to twelve IAC placements. Bleeding (6/7) and infections (3/7) were the main complications in the early postoperative period. Two (2/7, 29%) patients died from early complications and 5/7 were discharged with a properly functioning IAC. The most frequent late complication was catheter accidental dislodgement in all remaining five patients, followed by catheter thrombosis and catheter-related infections in the same proportion (2/5). During follow-up, two of five patients died from vascular accesses complications. After IAC failure, one patient was transferred to peritoneal dialysis and a kidney transplant was performed in the other. Only one patient remains on HD after the third IAC, with a survival of 50 months. The mean patient survival after IAC placement was 19 ± 25 (0-60) months and the mean IAC patency was 8 ± 11 (0-34) months. Conclusion: Placing an IAC to perform HD is associated to significant risks and high mortality. However, when alternative RRT are exhausted, or as a bridge to others modalities, this option should be considered.

Resumo Introdução: A colocação de cateteres intra-auriculares (IAC) tem surgido como uma técnica life-saving nos doentes em hemodiálise (HD) com exaustão de acessos vasculares. Objetivo: Analisar as complicações decorrentes da colocação de IAC, assim como a sobrevivência dos doentes e do acessos vascular após este procedimento. Métodos: Os autores analisaram retrospetivamente sete doentes com exaustão de acessos vasculares para HD, sem alternativa imediata de terapêutica substitutiva renal, submetidos a colocação de IAC entre Janeiro de 2004 e Dezembro de 2015. Resultados: Os sete doentes foram submetidos à colocação de doze IAC. A hemorragia (6/7) e as infeções (3/7) foram as principais complicações no pós-operatório imediato. Dois (2/7, 29%) doentes faleceram por complicações precoces e 5/7 tiveram alta com cateter funcionante. A complicação tardia mais frequente foi a exteriorização acidental do cateter em todos os doentes, seguida da trombose e infeção relacionada com o cateter, na mesma proporção (2/5). Durante o seguimento, dois dos cinco doentes faleceram por complicações associadas com o acesso vascular. Após a falência do IAC, um doente foi transferido para diálise peritoneal e outro foi submetido a transplantação renal. Apenas um doente permanece em HD após o terceiro IAC, com uma sobrevivência de 50 meses. A sobrevivência média dos doentes após colocação de IAC foi de 19 ± 25 (0-60) meses e a patência média do IAC foi de 8 ± 11 (0-34) meses. Conclusão: A colocação de um IAC para HD esteve associado a riscos significativos e mortalidade elevada. Contudo, quando as terapêuticas de substituição renal alternativas estão esgotadas, ou como uma ponte para outras modalidades, esta opção deve ser considerada.

Acute kidney injury, long-term renal function and mortality in patients undergoing major abdominal surgery: a cohort analysis.

BACKGROUND: Acute kidney injury (AKI) is frequent during hospitalization and may contribute to adverse consequences. We aimed to evaluate long-term adverse renal function and mortality after postoperative AKI in a cohort of patients undergoing major abdominal surgery. METHODS: We performed a retrospective analysis of adult patients who underwent major non-vascular abdominal surgery between January 2010 and February 2011 at the Department of Surgery II of Hospital de Santa Maria-Centro Hospitalar Lisboa Norte, Portugal. Exclusion criteria were as follows: chronic kidney disease on renal replacement therapy, undergoing renal replacement therapy the week before surgery, death before discharge and loss to follow-up through January 2014. Patients were categorized according to the development of postoperative AKI in the first 48 h after surgery using the Kidney Disease: Improving Global Outcomes classification. AKI was defined by an increase in absolute serum creatinine (SCr) ≥0.3 mg/dL or by a percentage increase in SCr ≥50% and/or by a decrease in urine output to <0.5 mL/kg/h for >6 h. Adverse renal outcomes (need for long-term dialysis and/or a 25% decrease in estimated glomerular filtration rate after hospital discharge) and mortality after discharge were evaluated. Cumulative mortality was analysed with the Kaplan-Meier method and log-rank test and outcome predictive factors with the Cox regression. Significance was set at P < 0.05. RESULTS: Of 390 selected patients, 72 (18.5%) developed postoperative AKI. The median follow-up was 38 months. Adverse renal outcomes and death after hospital discharge were more frequent among AKI patients (47.2 versus 22.0%, P < 0.0001; and 47.2 versus 20.5%, P < 0.0001, respectively). The 4 year cumulative probability of death was 44.4% for AKI patients, while it was 19.8% for patients with no AKI (log-rank test, P < 0.0001). In multivariate analysis, AKI was a risk factor for adverse renal outcomes (adjusted hazard ratio 1.6, P = 0.046) and mortality (adjusted hazard ratio 1.4, P = 0.043). CONCLUSIONS: AKI after major abdominal surgery was independently associated with the risk of long-term need for dialysis and/or renal function decline and with the risk of death after hospital discharge.

Long-term risk of mortality after acute kidney injury in patients with sepsis: a contemporary analysis.

BACKGROUND: Acute kidney injury (AKI) is associated with increased short-term mortality of septic patients; however, the exact influence of AKI on long-term mortality in such patients has not yet been determined. METHODS: We retrospectively evaluated the impact of AKI, defined by the "Risk, Injury, Failure, Loss of kidney function, End-stage kidney disease" (RIFLE) classification based on creatinine criteria, on 2-year mortality in a cohort of 234 hospital surviving septic patients who had been hospitalized at the Infectious Disease Intensive Care Unit of our Hospital. RESULTS: Mean-follow-up was 21 +/- 6.4 months. During this period, 32 patients (13.7%) died. At 6 months, 1 and 2 years of follow-up, the cumulative probability of death of patients with previous AKI was 8.3, 16.9 and 34.2%, respectively, as compared with 2.2, 6 and 8.9% in patients without previous AKI (log-rank, P < 0.0001). In the univariate analysis, age (hazard ratio 1.4, 95% CI 1.2-1.7, P < 0.0001), as well as pre-existing cardiovascular disease (hazard ratio 3.6, 95% CI 1.4-9.4, P = 0.009), illness severity as evaluated by nonrenal APACHE II (hazard ratio 1.3, 95% CI 1.1-1.6, P = 0.002), and previous AKI (hazard ratio 4.2, 95% CI 2.1-8.5, P < 0.0001) were associated with increased 2-year mortality, while gender, race, pre-existing hypertension, cirrhosis, HIV infection, neoplasm, and baseline glomerular filtration rate did not. In the multivariate analysis, however, only previous AKI (hazard ratio 3.2, 95% CI 1.6-6.5, P = 0.001) and age (hazard ratio 1.4, 95% CI 1.2-1.6, P < 0.0001) emerged as independent predictors of 2-year mortality. CONCLUSIONS: Acute kidney injury had a negative impact on long-term mortality of patients with sepsis.

Acute kidney injury requiring dialysis: a very unusual presentation of non-Hodgkin's lymphoma.

Acute kidney injury due to lymphomatous infiltration of the kidneys is uncommon, and it is rarely the initial manifestation of the lymphoma. Here, we present a case of lymphomatous infiltration of the kidneys resulting in acute kidney injury requiring dialysis, as the initial presentation of non-Hodgkin's lymphoma. Renal biopsy established the diagnosis, and renal function completely recovered after chemotherapy.