RESUMO
BACKGROUND & AIMS: The management of acute kidney injury (AKI) in cirrhosis is challenging. The EASL guidelines proposed an algorithm for the management of AKI, but this has never been validated. We aimed to prospectively evaluate this algorithm in clinical practice. METHODS: We performed a prospective cohort study in consecutive hospitalized patients with cirrhosis and AKI. The EASL management algorithm includes identification/treatment of precipitating factors, 2-day albumin infusion in patients with AKI ≥stage 1B, and treatment with terlipressin in patients with hepatorenal syndrome (HRS-AKI). The primary outcome was treatment response, which included both full and partial response. Secondary outcomes were survival and adverse events associated with terlipressin therapy. RESULTS: A total of 202 AKI episodes in 139 patients were included. Overall treatment response was 80%, while renal replacement therapy was required in only 8%. Response to albumin infusion was achieved in one-third of episodes. Of patients not responding to albumin, most (74%) did not meet the diagnostic criteria of HRS-AKI, with acute tubular necrosis (ATN) being the most common phenotype. The response rate in patients not meeting the criteria for HRS-AKI was 70%. Only 30 patients met the diagnostic criteria for HRS-AKI, and their response rate to terlipressin was 61%. Median time from AKI diagnosis to terlipressin initiation was only 2.5 days. While uNGAL (urinary neutrophil gelatinase-associated lipocalin) could differentiate ATN from other phenotypes (AUROC 0.78), it did not predict response to therapy in HRS-AKI. Ninety-day transplant-free survival was negatively associated with MELD-Na, ATN and HRS-AKI as well as uNGAL. Three patients treated with terlipressin developed pulmonary edema. CONCLUSIONS: The application of the EASL AKI algorithm is associated with very good response rates and does not significantly delay initiation of terlipressin therapy. IMPACT AND IMPLICATIONS: The occurrence of acute kidney injury (AKI) in patients with cirrhosis is associated with poor short-term mortality. Improving its rapid identification and prompt management was the focus of the recently proposed EASL AKI algorithm. This is the first prospective study demonstrating that high AKI response rates are achieved with the use of this algorithm, which includes identification of AKI, treatment of precipitating factors, a 2-day albumin challenge in patients with AKI ≥1B, and supportive therapy in patients with persistent AKI not meeting HRS-AKI criteria or terlipressin with albumin in those with HRS-AKI. These findings support the use of this algorithm in clinical practice.
Assuntos
Injúria Renal Aguda , Algoritmos , Cirrose Hepática , Terlipressina , Humanos , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/diagnóstico , Masculino , Feminino , Estudos Prospectivos , Pessoa de Meia-Idade , Cirrose Hepática/complicações , Terlipressina/administração & dosagem , Idoso , Albuminas/administração & dosagem , Vasoconstritores/administração & dosagem , Vasoconstritores/uso terapêutico , Lipressina/análogos & derivados , Lipressina/administração & dosagem , Lipressina/uso terapêutico , Resultado do Tratamento , Síndrome Hepatorrenal/etiologia , Síndrome Hepatorrenal/diagnóstico , Síndrome Hepatorrenal/tratamento farmacológico , Guias de Prática Clínica como AssuntoRESUMO
Simultaneous pancreas-kidney transplantation (SPKT) leads to increased survival and quality of life, and is an alternative treatment for insulin-dependent diabetes mellitus and end-stage kidney disease. Due to the particularities of this population (often with multiple comorbidities) and of the surgery (only performed in a few centers), a comprehensive analysis of patients' experience along the SPKT process is crucial to improve patient care and add value to this procedure. Therefore, we applied a systematic and iterative methodology with the participation of both patients and professional teams working together to explore and identify unmet needs and value-adding steps along the transplant patient journey at an established pancreas transplant program. Four main steps (to comprehend, to explore, to experiment and to assess) led to several interventions around three major areas: Administration and logistics, information and communication, and perceived quality of assistance. As a result, both displacements to the hospital for diagnostic purposes and the time delay involved in joining the patient waiting list for transplantation were reduced in parallel to the administrative procedures. In conclusion, the methodological implementation of key organizational changes has great impact on overall patient experience. Further quantitative analysis from the patient's perspective will consolidate our program and may add new prototype service design components.
Assuntos
Transplante de Rim , Transplante de Pâncreas , Humanos , Pâncreas , Avaliação de Resultados da Assistência ao Paciente , Qualidade de VidaRESUMO
Carfilzomib has been associated with the development of thrombotic microangiopathy (TMA) in relapsed/refractory multiple myeloma patients, a severe disease with no currently available aetiological treatment. We evaluated the potential role of terminal complement pathway in four patients with carfilzomib-induced TMA. Membrane attack complex (C5b-9) deposition on endothelial cells in culture exposed to plasma from patients during the acute phase of the disease suggests complement overactivation as a mechanism of potential endothelial damage in three out of four patients. If confirmed in larger cohorts, C5b-9 evaluation will allow early identification of patients who could benefit from complement blockade and treatment monitoring.
Assuntos
Proteínas do Sistema Complemento/efeitos dos fármacos , Mieloma Múltiplo/tratamento farmacológico , Oligopeptídeos/efeitos adversos , Microangiopatias Trombóticas/induzido quimicamente , Ubiquitina/antagonistas & inibidores , Adulto , Idoso , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/farmacologia , Anticorpos Monoclonais Humanizados/uso terapêutico , Complexo de Ataque à Membrana do Sistema Complemento/efeitos adversos , Complexo de Ataque à Membrana do Sistema Complemento/metabolismo , Proteínas do Sistema Complemento/metabolismo , Células Endoteliais/imunologia , Células Endoteliais/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/complicações , Oligopeptídeos/uso terapêutico , Estudos Prospectivos , Inibidores de Proteassoma/efeitos adversos , Inibidores de Proteassoma/uso terapêutico , Microangiopatias Trombóticas/tratamento farmacológico , Microangiopatias Trombóticas/etiologia , Microangiopatias Trombóticas/metabolismo , Ubiquitina/metabolismoRESUMO
BACKGROUND & AIMS: Acute kidney injury (AKI) is common in cirrhosis and is associated with poor prognosis. In patients who survive after AKI, it is not known whether the acute injury leads to chronic impairment of kidney function (chronic kidney disease [CKD]). The aim of the study was to determine the frequency of CKD at 3 months after an AKI episode and its effects on patient outcomes. METHODS: Patients admitted for complications of cirrhosis during a 6.5-year period were evaluated using the same protocol, with assessment of kidney function at regular intervals during and after hospitalization. CKD was defined as estimated glomerular filtration rate (eGFR) <60 ml/min/1.73m2 at 3 months after AKI. RESULTS: A total of 409 patients (168 with AKI and 241 without AKI) were included. After 3 months, 97 patients with AKI and 188 patients without AKI had survived. Of the 97 patients with AKI, 24 had developed CKD at 3 months compared to only 2 of the 188 patients without AKI (25% vs. 1%, odds ratio 31; p <0.0001). Risk factors independently associated with CKD were nosocomial AKI and severity of AKI (stage ≥1B). At diagnosis of CKD, all patients had stage 3A CKD and one-quarter of them progressed to stages 3B and 4 after 1 year. The transition from AKI to CKD was associated with an increased rate of 3-month hospital readmission, increased frequency of AKI, bacterial infections, ascites, and refractory ascites and a trend towards a higher need for liver transplantation. Transplant-free survival was not impaired. CONCLUSIONS: CKD frequently develops in patients with cirrhosis who survive AKI and has a negative impact on relevant clinical outcomes. The transition from AKI to CKD is common and should be considered a high-risk condition in patients with cirrhosis. LAY SUMMARY: Episodes of acute impairment of kidney function are common in patients with cirrhosis. This study shows that the development of chronic impairment of kidney function is frequent in patients surviving these acute episodes and that it is associated with a higher risk of developing other complications of cirrhosis and to a higher rate of 3-month hospital readmissions.
Assuntos
Injúria Renal Aguda/complicações , Cirrose Hepática/complicações , Readmissão do Paciente , Insuficiência Renal Crônica/etiologia , Índice de Gravidade de Doença , Injúria Renal Aguda/sangue , Injúria Renal Aguda/epidemiologia , Idoso , Creatinina/sangue , Feminino , Seguimentos , Taxa de Filtração Glomerular , Humanos , Cirrose Hepática/sangue , Cirrose Hepática/epidemiologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Insuficiência Renal Crônica/epidemiologia , Fatores de Risco , Espanha/epidemiologiaRESUMO
Kidney biomarkers appear to be useful in differential diagnosis between acute tubular necrosis (ATN) and other types of acute kidney injury (AKI) in cirrhosis, particularly hepatorenal syndrome (HRS-AKI). Distinction is important because treatment is different. However, kidney biomarkers are still not used in clinical practice. The aim of the current study was to investigate the accuracy of several biomarkers in differential diagnosis of AKI and in predicting kidney outcome and patient survival. This was a prospective study of 320 consecutive cases of AKI in patients hospitalized for decompensated cirrhosis. Evaluation of AKI was made with a diagnostic algorithm that included identification and removal/treatment of precipitating factors and albumin administration (1 g/kg for 2 days) to patients with AKI stage 1B or greater. Urinary neutrophil gelatinase-associated lipocalin (NGAL), monomeric NGAL (mNGAL), interleukin-18, and standard biomarkers were measured at diagnosis and on days 3, 7, and 14. Of the 320 cases, 153 were hypovolemia-induced AKI (48%), 93 were HRS-AKI (29%), 39 were ATN (12%), and 35 were due to miscellaneous causes (11%). Among all biomarkers, urinary NGAL measured at day 3 had the greatest accuracy for differential diagnosis between ATN and other types of AKI (area under the receiver operating characteristic curve, 0.87; 95% confidence interval, 0.78-0.95). The cutoff with the best predictive accuracy for ATN diagnosis was 220 µg/g creatinine. Progression of AKI during hospitalization was associated with persistently high NGAL levels, and NGAL was an independent predictive factor of AKI progression. Likewise, NGAL was also an independent predictive factor of 28-day mortality together with Model for End-Stage Liver Disease score. Conclusion: These results support the use of NGAL in clinical practice within the context of a diagnostic algorithm for differential diagnosis of AKI and outcome prediction in cirrhosis.
Assuntos
Injúria Renal Aguda/diagnóstico , Lipocalina-2/urina , Cirrose Hepática/complicações , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/mortalidade , Injúria Renal Aguda/urina , Idoso , Biomarcadores/urina , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Espanha/epidemiologiaRESUMO
BACKGROUND: Recurrence of immunoglobulin (Ig)A nephropathy (rIgAN) is a growing cause of kidney allograft dysfunction. This study was aimed at investigating factors associated with rIgAN and the subsequent progression to end-stage renal disease (ESRD). METHODS: Retrospective study including consecutive patients with IgA nephropathy (IgAN) who received a kidney transplant in our center between 1992 and 2016 and had a renal biopsy by clinical indication. The date of detection of chronic kidney disease (CKD) 5 was used as renal outcome. RESULTS: Eighty-six kidney transplants were performed in patients with IgAN, 38 (44%) were from living donors (related n = 26). rIgAN was diagnosed in 23 allografts (27%). Renal function and proteinuria at the end of the follow-up period were worst in the rIgAN patients compared to those without rIgAN (2.2 vs. 1.4 mg/dL, p = 0.014, and 1.16 vs. 0.49 g/day, p = 0.005, respectively). Risk of rIgAN and progression to CKD 5 decreased with patient's age (hazard ratio [HR] 0.95, 95% CI 0.92-0.98, p = 0.002, and HR 0.97, 95% CI 0.83-0.97, p = 0.008 per year, respectively). Patients with rIgAN had a higher risk of progression to CKD 5 (HR 6.7, 95% CI 1.3-35.7, p = 0.025). Full donor-recipient mismatch in the human leukocyte antigen (HLA)-B loci decreased the risk of rIgAN (HR 0.22, 95% CI 0.06-0.76, p = 0.017). CONCLUSIONS: rIgAN was an independent risk factor for ESRD after renal allograft. Younger age increased the risk of rIgAN and CKD 5. Conversely, HLA-B mismatching was a potential protective factor for rIgAN of this glomerular disease.
Assuntos
Glomerulonefrite por IGA/diagnóstico , Antígenos HLA-B/imunologia , Falência Renal Crônica/cirurgia , Transplante de Rim/efeitos adversos , Adulto , Fatores Etários , Aloenxertos/imunologia , Aloenxertos/patologia , Biópsia , Progressão da Doença , Feminino , Seguimentos , Glomerulonefrite por IGA/complicações , Glomerulonefrite por IGA/imunologia , Glomerulonefrite por IGA/cirurgia , Antígenos HLA-B/análise , Teste de Histocompatibilidade , Humanos , Rim/imunologia , Rim/patologia , Falência Renal Crônica/imunologia , Masculino , Pessoa de Meia-Idade , Fatores de Proteção , Recidiva , Estudos Retrospectivos , Fatores de Risco , Transplante HomólogoRESUMO
BACKGROUND: Monoclonal serum free light chains (sFLC) are a well-known cause of renal impairment (RI) in patients with multiple myeloma (MM). As an indicator of monoclonality, sFLC ratio has acquired a key role in the diagnosis and monitorization of the disease. However, its interpretation is altered in patients with chronic kidney disease (CKD). This study aims to evaluate the modification of the sFLC ratio reference range in patients with CKD, and propose an optimal range for patients with CKD. METHODS: Serum FLC κ/λ ratio and estimated glomerular filtration rate (eGFR) were retrospectively analyzed in 113 control patients (without hematologic disease), 63 patients with MM in complete remission and 347 patients with active MM. The three groups included patients with CKD (eGFR < 90). RESULTS: In the group of patients without active MM (n = 176), the sFLC ratio increased at different stages of CKD without pathological significance, with an increase in the number of false positives specially when eGFR is ≤55 ml/min. An optimal range was established for patients with eGFR ≤55 ml/min/1.73 m2: 0.82-3,6 with maximum sensitivity + specificity for that group with an improvement in the Area under the curve (AUC), 0.91 (0.84-0.97) compared with the current ranges proposed by Katzmann and Hutchinson. CONCLUSIONS: This study confirms the influence of eGFR on the interpretation of the sFLC ratio, showing a decreasing specificity in progressive CKD stages when using the reference sFLC range (Katzmann), especially in patients with eFGR ≤55. According to our results, we suggest a modified optimal range (0.82-3,6) for eGFR ≤55 ml/min/1.73 m2. It is necessary to validate this modified range in larger and prospective studies.
Assuntos
Taxa de Filtração Glomerular , Cadeias kappa de Imunoglobulina/sangue , Cadeias lambda de Imunoglobulina/sangue , Mieloma Múltiplo , Insuficiência Renal Crônica , Área Sob a Curva , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/sangue , Mieloma Múltiplo/complicações , Mieloma Múltiplo/diagnóstico , Valores de Referência , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/fisiopatologia , Sensibilidade e Especificidade , Índice de Gravidade de DoençaRESUMO
INTRODUCTION: Nonantigen-specific immunoadsorption (IA) has proven to be effective in acute antibody-mediated rejection (aAMR). However, there is a lack of solid studies evaluating the safety and efficacy of IA with antihuman Ig-columns in aAMR. For chronic-active AMR (cAMR), no studies have evaluated the efficacy of nonantingen-specific IA with antihuman Ig-columns. The purpose of this study was to evaluate the role of nonantigen-specific IA with antihuman Ig-columns in the treatment of both aAMR and cAMR in kidney transplantation. MATERIAL AND METHODS: In retrospective and observational study, kidney graft and recipient survival rates were assessed after treatment of aAMR and cAMR with nonantigen-specific IA with Ig-Flex columns (Therasorb) between January 2012 and May 2018. Protocols included nonantigen-specific IA, rituximab, intravenous immunoglobulin, and rescue plasma exchange, if necessary. RESULTS: The study included 14 patients with AMR (acute in 9, chronic active in 5). For aAMR, mean follow-up was 13 ± 6 months, and patient and graft survival were, respectively, of 100% and 83%, with a mean increase in estimated glomerular filtration rate (eGFR) of 7.98 ± 12.96, 10.18 ± 16.71, and 11.43 ± 13.85 mL/min/1.72 m2 (P > .05) at 3, 12 months after treatment, and at the end of follow-up, respectively. For cAMR, mean follow-up was 14 ± 8 months, and patient and graft survival were, respectively, of 100% and 60%, with an average increase in eGFR of 4.30 ± 7.86, 5.64 ± 10.47, and 14.5 ± 7.86 mL/min/m2 (P > .05) at 3, 12 months after IA treatment, and at the end of the follow-up, respectively, although 40% did not respond and required chronic hemodialysis. CONCLUSION: Nonantigen-specific IA with Ig-Flex columns was safe and effective for aAMR treatment in kidney transplantation. In cAMR, IA with Ig-Flex columns was associated with a satisfactory kidney graft survival, suggesting that IA could potentially offer some benefits supporting its indication in cAMR.
Assuntos
Rejeição de Enxerto , Sistema Imunitário/imunologia , Imunoglobulina G/imunologia , Transplante de Rim/métodos , Adulto , Idoso , Anticorpos , Feminino , Seguimentos , Taxa de Filtração Glomerular , Sobrevivência de Enxerto , Humanos , Imunoglobulinas Intravenosas , Masculino , Pessoa de Meia-Idade , Plasmaferese , Regeneração , Estudos RetrospectivosRESUMO
BACKGROUND: The possibility of clearing Cell-free Plasma Hemoglobin (CPH) from human plasma may appear attractive, especially when considering the noxious effects that CPH has on the immune function and the renal damage caused by its filtration. The existence of the so-called High Cut-Off (HCO) filters, possessing pores as big as 60 kDa, could potentially allow the clearance of the αß dimers (31.3 kDa), the form in which the α2ß2 hemoglobin tetramers (62.6 kDa) physiologically dissociate in plasma. We present herein the first reported case in which such an attempt was made. CASE PRESENTATION: The patient was a 51-year-old man with hemolytic crisis due to glucose-6-phosphate dehydrogenase deficiency, further complicated by pigment-induced nephropathy. He underwent a 48-h CVVHD session, in which a HCO filter was used. The Sieving Coefficient (SC) for CPH was initially 0.08 and decreased to 0.02 after 24 h. This unexpected low SC was due to the initial high concentration of CPH (4.24 g/L). At such concentrations, the α2ß2 tetramer poorly dissociates into the αß dimer; but increases exponentially at concentrations lower than 1 g/L. CONCLUSIONS: Clearance of CPH through a HCO filter is technically feasible but its performance markedly relies on the initial concentration of CPH. Critically ill patients with smoldering hemolysis, as it happens during septic shock or ECMO treatment, may benefit the most from the use of this membrane in order to clear CPH.
Assuntos
Injúria Renal Aguda/fisiopatologia , Injúria Renal Aguda/terapia , Deficiência de Glucosefosfato Desidrogenase/complicações , Hemólise , Diálise Renal/instrumentação , Diálise Renal/métodos , Hemofiltração/instrumentação , Hemofiltração/métodos , Hemoglobinas , Hepatite A/complicações , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Patients with Stage 5 chronic kidney disease who are on hemodialysis (HD) remain in a chronic inflammatory state, characterized by the accumulation of uremic toxins that induce endothelial damage and cardiovascular disease (CVD). Our aim was to examine microvesicles (MVs), monocyte subpopulations, and angiopoietins (Ang) to identify prognostic markers in HD patients with or without diabetes mellitus (DM). A total of 160 prevalent HD patients from 10 centers across Spain were obtained from the Biobank of the Nephrology Renal Network (Madrid, Spain): 80 patients with DM and 80 patients without DM who were matched for clinical and demographic criteria. MVs from plasma and several monocyte subpopulations (CD142+/CD16+, CD14+/CD162+) were analyzed by flow cytometry, and the plasma concentrations of Ang1 and Ang2 were quantified by ELISA. Data on CVD were gathered over the 5.5 yr after these samples were obtained. MV level, monocyte subpopulations (CD14+/CD162+ and CD142+/CD16+), and Ang2-to-Ang1 ratios increased in HD patients with DM compared with non-DM patients. Moreover, MV level above the median (264 MVs/µl) was associated independently with greater mortality. MVs, monocyte subpopulations, and Ang2-to-Ang1 ratio can be used as predictors for CVD. In addition, MV level has a potential predictive value in the prevention of CVD in HD patients. These parameters undergo more extensive changes in patients with DM.
Assuntos
Angiopoietina-1/sangue , Angiopoietina-2/sangue , Micropartículas Derivadas de Células/metabolismo , Nefropatias Diabéticas/sangue , Nefropatias Diabéticas/terapia , Células Endoteliais/metabolismo , Diálise Renal , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/terapia , Idoso , Biomarcadores/sangue , Estudos de Casos e Controles , Micropartículas Derivadas de Células/patologia , Nefropatias Diabéticas/diagnóstico , Nefropatias Diabéticas/mortalidade , Progressão da Doença , Células Endoteliais/patologia , Feminino , Humanos , Mediadores da Inflamação/sangue , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Monócitos/metabolismo , Valor Preditivo dos Testes , Prevalência , Diálise Renal/efeitos adversos , Diálise Renal/mortalidade , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/mortalidade , Espanha/epidemiologia , Fatores de Tempo , Resultado do TratamentoAssuntos
Estado Terminal , Soluções Isotônicas , Adulto , Soluções Cristaloides , Humanos , Cloreto de SódioRESUMO
BACKGROUND & AIMS: Non-steroidal anti-inflammatory drugs (NSAIDs) may cause impairment of kidney function in patients with cirrhosis. Investigational studies demonstrated reversibility of kidney dysfunction after drug withdrawal, but information based on clinical practice is lacking. The aim of the study was to investigate the characteristics and outcome of Acute Kidney Injury (AKI) developing in patients with cirrhosis treated with NSAIDs. METHODS: Prospective cohort study in a tertiary referral center of all patients with NSAIDs-associated AKI seen from 2002 to 2014. For comparison, three control groups of patients with hypovolemic-induced AKI, type-1 HRS and ATN, respectively, were also evaluated. Urinary excretion of neutrophil gelatinase-associated lipocalin (uNGAL) was measured in a subset of patients. RESULTS: Thirty patients with cirrhosis and NSAIDs-associated AKI were identified. In 19 patients (63%) AKI was transient and kidney function rapidly recovered (4±3 days) after NSAIDs withdrawal. In the remaining 11 patients (37%) AKI was more severe and persisted during hospitalization despite drug withdrawal. Patients with persistent AKI had remarkably higher uNGAL levels compared with those of patients with transient AKI (953±1,198 vs. 83±79 µg/g of creatinine, respectively, p=0.008). Moreover, seven of the 11 patients with persistent AKI (64%) died within three months compared with only one of the 19 (5%) patients with transient AKI (p=0.001). Mortality of persistent AKI was similar in NSAIDs patients compared to control groups. The only independent predictive factor of three-month mortality was persistent AKI. CONCLUSIONS: Patients with cirrhosis treated with NSAIDs may develop severe AKI which may be irreversible and associated with poor short-term outcome.
Assuntos
Injúria Renal Aguda/induzido quimicamente , Anti-Inflamatórios não Esteroides/efeitos adversos , Cirrose Hepática/tratamento farmacológico , Injúria Renal Aguda/mortalidade , Proteínas de Fase Aguda/urina , Adulto , Idoso , Estudos de Casos e Controles , Estudos de Coortes , Feminino , Humanos , Lipocalina-2 , Lipocalinas/urina , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Proteínas Proto-Oncogênicas/urinaRESUMO
In this study, we investigated if the therapeutic potential of peripheral blood mononuclear cell (PBMC) therapy in a murine model of ischemic AKI is related with the survival pattern of monocyte/macrophages in tissue. CD-1 mice were subjected to bilateral renal ischemia followed by reperfusion to induce AKI. M2-polarized PBMCs isolated from CD-1 mice were administered intravenously at different time points post-injury. Our results demonstrate that early administration of PBMC therapy attenuates renal tissue damage, reduces tissue cell death and prevents fibrosis development. Reduction of tissue pyroptosis was observed by reduction on NLRP3 inflammasome activation and decreasing IL-1beta and Caspase-1 expression in the kidney. Furthermore, the therapy was shown to mitigate ferroptosis by inducing GPX4 overexpression. Early administration of PBMCs increased the survival pattern of renal tissue-macrophages, promoting a "pro-survival phenotype" resulting in decreased pyroptotic marker NLRP3, IL-1beta and Caspase 1 and increased anti-ferroptotic gene GPX4. Conversely, delayed administration of PBMC therapy exhibits diminished efficacy in preventing cell death and fibrosis in tissue and provoked a decrease in the pro-survival phenotype of both monocyte /macrophages in tissue. Our findings highlight the therapeutic potential of PBMC therapy in mitigating AKI and preventing CKD progression by modulating tissue-resident macrophage survival and reducing their cell death pathways. The fact that the effectiveness of the therapy depends on the time of administration after the injury underscores the importance of early intervention in AKI management.
Assuntos
Injúria Renal Aguda , Fibrose , Leucócitos Mononucleares , Macrófagos , Monócitos , Animais , Injúria Renal Aguda/patologia , Injúria Renal Aguda/metabolismo , Macrófagos/metabolismo , Macrófagos/patologia , Macrófagos/efeitos dos fármacos , Camundongos , Monócitos/metabolismo , Monócitos/efeitos dos fármacos , Leucócitos Mononucleares/metabolismo , Masculino , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/metabolismo , Ferroptose/efeitos dos fármacos , Piroptose/efeitos dos fármacos , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Rim/patologia , Rim/efeitos dos fármacos , Rim/metabolismo , Modelos Animais de Doenças , Interleucina-1beta/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Morte Celular/efeitos dos fármacos , Inflamassomos/metabolismo , Caspase 1/metabolismoRESUMO
Macrophages must remove apoptotic cells to shield tissues from the deleterious components of dying cells. The development of chronic inflammation and autoimmune symptoms in systemic lupus is influenced by a deficiency in phagocytosis of apoptotic cells but the underlying mechanism is still unknown. Modifications in monocyte/macrophage phenotype brought on by an increase in their inflammatory phenotype would cause them to decrease the expression of CPT1a, which would reduce their ability to phagocytose, aggravating kidney damage in lupus nephritis. We aim to demonstrate that the deficiency of CPT1A in the immunological system determines lupus. For this purpose, we will monitor CPT1a expression in blood monocytes and phagocytosis and CPT1a expression of macrophages isolated from kidneys and the inflammatory state in kidneys in two experimental models of lupus nephritis such as lupus induced pristane model and in the OVA-IC in vivo model. Additionally, we will test if reestablishing CPT1a expression in tissue macrophages restores the lost phagocytic function. We evidenced that blood monocytes and macrophages isolated from kidneys in the two in vivo models have a reduced expression of CPT1a and a reduced phagocytosis. Phagocytosis could be restored only if macrophage administration leads to an increase in CPT1a expression in kidney macrophages. A new cell therapy to reduce kidney nephritis in lupus could be developed based on these results.
Assuntos
Lúpus Eritematoso Sistêmico , Nefrite Lúpica , Humanos , Monócitos , Nefrite Lúpica/metabolismo , Fagocitose , Macrófagos , Inflamação/metabolismo , Lúpus Eritematoso Sistêmico/metabolismoRESUMO
Contrast-induced encephalopathy is a neurological complication related to contrast used in endovascular procedures or computed tomography (CT). The main risk factors are arterial hypertension, diabetes mellitus, chronic kidney disease (CKD), hyperosmolar contrasts, the amount of infused contrast and its direct infusion in the posterior cerebral territory, or pathologies with blood-brain barrier damage. Symptomatology is non-specific and may present as altered level of consciousness, neurological focality or seizures. Diagnosis is done by exclusion after ischemic or hemorrhagic stroke has been ruled out; CT or MRI are useful for differentiation. Generally, it appears shortly after exposure and the symptoms lasts 48-72h with complete recovery, although cases with persistence of symptoms or longer duration have been described. Treatment consists of monitoring, supportive measures and kidney replacement therapy (KRT) with hemodialysis (HD) in patients in chronic KRT program. It is important for the nephrologist to be aware of this entity given the susceptibility of the patient on HD as well as its potential therapeutic role in these patients.
Assuntos
Encefalopatias , Meios de Contraste , Insuficiência Renal Crônica , Humanos , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/terapia , Meios de Contraste/efeitos adversos , Encefalopatias/induzido quimicamente , Nefrologia , Fatores de Risco , Diálise RenalRESUMO
Primary aldosteronism (PA) is the most frequent cause of secondary hypertension and is associated with a higher cardiometabolic risk than essential hypertension. The aim of this consensus is to provide practical clinical recommendations for its surgical and medical treatment, pathology study and biochemical and clinical follow-up, as well as for the approach in special situations like advanced age, pregnancy and chronic kidney disease, from a multidisciplinary perspective, in a nominal group consensus approach of experts from the Spanish Society of Endocrinology and Nutrition (SEEN), Spanish Society of Cardiology (SEC), Spanish Society of Nephrology (SEN), Spanish Society of Internal Medicine (SEMI), Spanish Radiology Society (SERAM), Spanish Society of Vascular and Interventional Radiology (SERVEI), Spanish Society of Laboratory Medicine (SEQC(ML)), Spanish Society of Anatomic-Pathology and Spanish Association of Surgeons (AEC).
Assuntos
Consenso , Hiperaldosteronismo , Hiperaldosteronismo/terapia , Hiperaldosteronismo/diagnóstico , Hiperaldosteronismo/complicações , Humanos , Hipertensão/terapia , Feminino , Adrenalectomia , Gravidez , Espanha/epidemiologiaRESUMO
Primary aldosteronism (PA) is the most frequent cause of secondary hypertension (HT), and is associated with a higher cardiometabolic risk than essential HT. However, PA remains underdiagnosed, probably due to several difficulties clinicians usually find in performing its diagnosis and subtype classification. The aim of this consensus is to provide practical recommendations focused on the prevalence and the diagnosis of PA and the clinical implications of aldosterone excess, from a multidisciplinary perspective, in a nominal group consensus approach by experts from the Spanish Society of Endocrinology and Nutrition (SEEN), Spanish Society of Cardiology (SEC), Spanish Society of Nephrology (SEN), Spanish Society of Internal Medicine (SEMI), Spanish Radiology Society (SERAM), Spanish Society of Vascular and Interventional Radiology (SERVEI), Spanish Society of Laboratory Medicine (SEQC(ML)), Spanish Society of Anatomic-Pathology, Spanish Association of Surgeons (AEC).
Assuntos
Hiperaldosteronismo , Humanos , Consenso , Hiperaldosteronismo/diagnóstico , Hiperaldosteronismo/terapia , Hipertensão/diagnóstico , Hipertensão/terapia , Hipertensão/etiologia , Programas de Rastreamento/normas , Programas de Rastreamento/métodos , Sociedades Médicas , Espanha/epidemiologiaRESUMO
C3 glomerulopathy is a rare disease caused by fluid phase dysregulation of the alternative complement pathway. Currently, treatment depends on clinical and histological severity and includes nephroprotection, unspecific immunosuppression, and terminal complement blockers (C5), without having an etiological treatment approved. C3 glomerulopathy has high recurrence rates after kidney transplantation with a high risk of graft loss. Fortunately, new molecules are being developed that specifically target the proximal alternative complement pathway, such as iptacopan, a factor B inhibitor that showed promising results in native kidneys and cases of transplant recurrence in a phase 2 clinical trial. We present 2 "real-world" cases of C3 glomerulopathy recurrence in kidney allografts treated with iptacopan, with initial excellent clinical response and safety profile, especially with early introduction. We also present follow-up biopsies that showed no C3 deposition during factor B inhibition. Our cases suggest that proximal blockade of the alternative complement pathway can be effective and safe in the treatment of C3 glomerulopathy recurrence in kidney transplantation, bringing other questions such as dual blockade (eg, in C3 and C5), the optimal patient profile to benefit from factor B inhibition or treatment duration and its potential use in other forms of membranoproliferative glomerulonephritis (eg, immune complex-mediated).
RESUMO
BACKGROUND & AIMS: The Acute Kidney Injury Network (AKIN) criteria are widely used in nephrology, but information on cirrhosis is limited. We aimed at evaluating the AKIN criteria and their relationship with the cause of kidney impairment and survival. METHODS: We performed a prospective study of 375 consecutive patients hospitalized for complications of cirrhosis. One-hundred and seventy-seven (47%) patients fulfilled the criteria of Acute Kidney Injury (AKI) during hospitalization, the causes being hypovolemia, infections, hepatorenal syndrome (HRS), nephrotoxicity, and miscellaneous (62, 54, 32, 8, and 21 cases, respectively). RESULTS: At diagnosis, most patients had AKI stage 1 (77%). Both the occurrence of AKI and its stage were associated with 3-month survival. However, survival difference between stages 2 and 3 was not statistically significant. Moreover, if stage 1 patients were categorized into 2 groups according to the level of serum creatinine used in the classical definition of kidney impairment (1.5mg/dl), the two groups had a significantly different outcome. Combining AKIN criteria and maximum serum creatinine, 3 risk groups were identified: (A) patients with AKI stage 1 with peak creatinine ≤ 1.5mg/dl; (B) patients with stage 1 with peak creatinine >1.5mg/dl; and (C) patients with stages 2-3 (survival 84%, 68%, and 36%, respectively; p<0.001). Survival was independently related to the cause of kidney impairment, patients with HRS or infection-related having the worst prognosis. CONCLUSIONS: A classification that combines the AKIN criteria and classical criteria of kidney failure in cirrhosis provides a better risk stratification than AKIN criteria alone. The cause of impairment in kidney function is key in assessing prognosis in cirrhosis.