Acute Kidney Injury in Sepsis.

Sepsis-associated kidney injury is common in critically ill patients and significantly increases morbidity and mortality rates. Several complex pathophysiological factors contribute to its presentation and perpetuation, including macrocirculatory and microcirculatory changes, mitochondrial dysfunction, and metabolic reprogramming. Recovery from acute kidney injury (AKI) relies on the evolution towards adaptive mechanisms such as endothelial repair and tubular cell regeneration, while maladaptive repair increases the risk of progression to chronic kidney disease. Fundamental management strategies include early sepsis recognition and prompt treatment, through the administration of adequate antimicrobial agents, fluid resuscitation, and vasoactive agents as needed. In septic patients, organ-specific support is often required, particularly renal replacement therapy (RRT) in the setting of severe AKI, although ongoing debates persist regarding the ideal timing of initiation and dosing of RRT. A comprehensive approach integrating early recognition, targeted interventions, and close monitoring is essential to mitigate the burden of SA-AKI and improve patient outcomes in critical care settings.

Impact of Early Proteinuria Reduction in Glomerular Disease and Decline of Kidney Function: A Retrospective Cohort.

Background: In glomerular disease, the degree of proteinuria is closely related to the progression of chronic kidney disease, and its reduction is associated with a slower decline in the glomerular filtration rate (eGFR) and consequent improvement in the renal prognosis. The aim of this study was to evaluate the impact of proteinuria reduction on the decline of the eGFR in patients with glomerular disease, during the first year after the diagnosis. Methods: This was a retrospective analysis of patients with primary glomerular disease, followed at the Nephrology Department of Centro Hospitalar Universitário Lisboa Norte, during 2019. We analyzed demographic, clinical and laboratorial characteristics (creatinine, GFR, urine analysis and quantification of proteinuria determined by the proteinuria/creatinuria ratio, in the first morning urine or a 24 h urine sample). The outcome assessed was the decline in renal function, defined as a reduction in the GFR ≥ 25%, during the follow-up period. Results: We analyzed 197 patients with glomerular disease, with a mean age of 41.7 ± 19.7 years and follow-up time of 6.5 ± 5.3 years. At the time of the diagnosis, the eGFR was 81.5 ± 49.8 mL/min/1.73 m2 and proteinuria was 3.5 g/24 h (IQR 5.8). At one-year follow-up, median proteinuria was 0.9 g/24 h (IQR 2.4). At the end of the follow-up, mean eGFR was 72.1 ± 43.3 mL/min/1.73 m2. Proteinuria (p = 0.435) and the eGFR (p = 0.880) at the time of diagnosis did not correlate with long-term decline in the eGFR. Proteinuria < 1 g/24 h (HR 0.45 (95% CI 0.25−0.83) p = 0.011) after the first year was protective against long-term decline in the eGFR. It maintained this association with the long-term eGFR decline, independently of the duration of the follow-up (HR 0.30 (95% CI 0.17−0.52) p < 0.001). Conclusions: Proteinuria reduction to lower than 1 g/24 h, during the first year after diagnosis, was a protective factor for the long-term decline of kidney function, having a more important role than proteinuria or the GFR at the time of the diagnosis.

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.

Rituximab in glomerular diseases: a case series and narrative review.

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.

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.

ANCA Vasculitis Recurrence in Hemodialysis Patients: The Role of Rituximab.

Antineutrophil cytoplasmic antibodies-associated vasculitis (AAV) is characterized by systemic inflammation and is the most common cause of new-onset glomerulonephritis in adults older than 50 years. Renal disease secondary to AAV can lead to chronic kidney disease (CKD) requiring renal replacement therapy in approximately 20-25% of patients. Relapses are infrequent in the population on dialysis, and treatment guidelines do not specify these patients. Reports regarding the clinical course, survival, or relapse rate after beginning dialysis are scarce. The authors present 3 cases of CKD patients on hemodialysis who presented with AAV relapse, successfully treated with rituximab, and provide a literature review on relapse treatment.

Acute kidney disease and long-term outcomes in critically ill acute kidney injury patients with sepsis: a cohort analysis.

BACKGROUND: Acute kidney injury (AKI) is frequent during hospitalization and may contribute to adverse short- and long-term consequences. Acute kidney disease (AKD) reflects the continuing pathological processes and adverse events developing after AKI. We aimed to evaluate the association of AKD, long-term adverse renal function and mortality in a cohort of patients with sepsis. METHODS: We performed a retrospective analysis of adult patients with septic AKI admitted to the Division of Intensive Medicine of the Centro Hospitalar Lisboa Norte (Lisbon, Portugal) between January 2008 and December 2014. Patients were categorized according to the development of AKI using the Kidney Disease: Improving Global Outcomes (KDIGO) classification. AKI was defined as 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. AKD was defined as presenting at least KDIGO Stage 1 criteria for >7 days after an AKI initiating event. 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. RESULTS: From 256 selected patients with septic AKI, 53.9% developed AKD. The 30-day mortality rate was 24.5% (n = 55). The mean long-term follow-up was 45.9 ± 43.3 months. The majority of patients experience an adverse renal outcome [n = 158 (61.7%)] and 44.1% (n = 113) of patients died during follow-up. Adverse renal outcomes, 30-day mortality and long-term mortality after hospital discharge were more frequent among AKD patients [77.5 versus 43.2% (P < 0.001), 34.1 versus 6.8% (P < 0.001) and 64.8 versus 49.1% (P = 0.025), respectively]. The 5-year cumulative probability of survival was 23.2% for AKD patients, while it was 47.5% for patients with no AKD (log-rank test, P < 0.0001). In multivariate analysis, AKD was independently associated with adverse renal outcomes {adjusted hazard ratio [HR] 2.87 [95% confidence interval (CI) 2.0-4.1]; P < 0.001} and long-term mortality [adjusted HR 1.51 (95% CI 1.0-2.2); P = 0.040]. CONCLUSIONS: AKD after septic AKI 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.

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.

The neutrophil-to-lymphocyte ratio as a marker of vasculitis activity, severe infection and mortality in anca-associated vasculitis: A retrospective study.

INTRODUCTION: Anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) is a multisystemic disease. Despite the improvement in mortality rate since the introduction of immunosuppression, long-term prognosis is still uncertain not only because of the disease activity but also due to treatment associated adverse effects. The neutrophil-to-lymphocyte ratio (NLR) has been demonstrated as an inflammatory marker in multiple settings. In this study, we aimed to investigate the prognostic ability of the NLR in AAV patients. METHODS: We conducted a retrospective analysis of the clinical records of all adult patients with AVV admitted to the Nephrology and Renal Transplantation Department of Centro Hospitalar Universitário Lisboa Norte from January 2006 to December 2019. NLR was calculated at admission. The outcomes measured were severe infection at 3 months and one-year mortality. The prognostic ability of the NLR was determined using the receiver operating characteristic (ROC) curve. A cut-off value was defined as that with the highest validity. All variables underwent univariate analysis to determine statistically significant factors that may have outcomes. Only variables which significantly differed were used in the multivariate analysis using the logistic regression method. RESULTS: We registered 45 cases of AVV. The mean age at diagnosis was 67.5±12.1 years and 23 patients were male. The mean Birmingham Vasculitis Activity Score (BVAS) at presentation was 26.0±10.4. Twenty-nine patients were ANCA-MPO positive, 7 ANCA-PR3 positive and 9 were considered negative ANCA vasculitis. At admission, mean serum creatinine (SCr) was 4.9±2.5mg/dL, erythrocyte sedimentation rate (ESR) was 76.9±33.8mm/h, hemoglobin was 9.5±1.7g/dL, C-reactive protein was 13.2±5.8mg/dL and NLR was 8.5±6.8. Thirty-five patients were treated with cyclophosphamide, eight patients with rituximab for induction therapy. Twenty patients developed severe infection within the first three months after starting induction immunosuppression. In a multivariate analysis, older age (73.6±10.5 vs. 62.6±11.3, p=0.002, adjusted OR 1.08 [95% CI 1.01-1.16], p=0.035) and higher NLR (11.9±7.4 vs. 5.9±5.0, p=0.002, adjusted OR 1.14 [95% CI 1.01-1.29], p=0.035) were predictors of severe infection at 3 months. NLR ≥4.04 predicted severe infection at 3 months with a sensitivity of 95% and specificity of 52% and the AUROC curve was 0.0794 (95% CI 0.647-0.900). Nine patients died within the first year. Severe infection at 3 months was independently associated with mortality within the first year (OR 6.19 [95% CI 1.12-34.32], p=0.037). CONCLUSIONS: NLR at diagnosis was an independent predictor of severe infection within the first 3 months after immunosuppression start, and severe infection within the first three months was consequently correlated with one-year mortality. NLR is an easily calculated and low-cost laboratory inflammation biomarker and can prove useful in identifying AAV patients at risk of infection and poorer prognosis.

The neutrophil-to-lymphocyte ratio as a marker of vasculitis activity, severe infection and mortality in anca-associated vasculitis: A retrospective study.

INTRODUCTION: Anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) is a multisystemic disease. Despite the improvement in mortality rate since the introduction of immunosuppression, long-term prognosis is still uncertain not only because of the disease activity but also due to treatment associated adverse effects. The neutrophil-to-lymphocyte ratio (NLR) has been demonstrated as an inflammatory marker in multiple settings. In this study, we aimed to investigate the prognostic ability of the NLR in AAV patients. METHODS: We conducted a retrospective analysis of the clinical records of all adult patients with AVV admitted to the Nephrology and Renal Transplantation Department of Centro Hospitalar Universitário Lisboa Norte from January 2006 to December 2019. NLR was calculated at admission. The outcomes measured were severe infection at 3 months and one-year mortality. The prognostic ability of the NLR was determined using the receiver operating characteristic (ROC) curve. A cut-off value was defined as that with the highest validity. All variables underwent univariate analysis to determine statistically significant factors that may have outcomes. Only variables which significantly differed were used in the multivariate analysis using the logistic regression method. RESULTS: We registered 45 cases of AVV. The mean age at diagnosis was 67.5±12.1 years and 23 patients were male. The mean Birmingham Vasculitis Activity Score (BVAS) at presentation was 26.0±10.4. Twenty-nine patients were ANCA-MPO positive, 7 ANCA-PR3 positive and 9 were considered negative ANCA vasculitis. At admission, mean serum creatinine (SCr) was 4.9±2.5mg/dL, erythrocyte sedimentation rate (ESR) was 76.9±33.8mm/h, hemoglobin was 9.5±1.7g/dL, C-reactive protein was 13.2±5.8mg/dL and NLR was 8.5±6.8. Thirty-five patients were treated with cyclophosphamide, eight patients with rituximab for induction therapy. Twenty patients developed severe infection within the first three months after starting induction immunosuppression. In a multivariate analysis, older age (73.6±10.5 vs. 62.6±11.3, p=0.002, adjusted OR 1.08 [95% CI 1.01-1.16], p=0.035) and higher NLR (11.9±7.4 vs. 5.9±5.0, p=0.002, adjusted OR 1.14 [95% CI 1.01-1.29], p=0.035) were predictors of severe infection at 3 months. NLR ≥4.04 predicted severe infection at 3 months with a sensitivity of 95% and specificity of 52% and the AUROC curve was 0.0794 (95% CI 0.647-0.900). Nine patients died within the first year. Severe infection at 3 months was independently associated with mortality within the first year (OR 6.19 [95% CI 1.12-34.32], p=0.037). CONCLUSIONS: NLR at diagnosis was an independent predictor of severe infection within the first 3 months after immunosuppression start, and severe infection within the first three months was consequently correlated with one-year mortality. NLR is an easily calculated and low-cost laboratory inflammation biomarker and can prove useful in identifying AAV patients at risk of infection and poorer prognosis.

Genetic and Clinical Predictors of Age of ESKD in Individuals With Autosomal Dominant Tubulointerstitial Kidney Disease Due to UMOD Mutations.

INTRODUCTION: Autosomal dominant tubulo-interstitial kidney disease due to UMOD mutations (ADTKD-UMOD) is a rare condition associated with high variability in the age of end-stage kidney disease (ESKD). The minor allele of rs4293393, located in the promoter of the UMOD gene, is present in 19% of the population and downregulates uromodulin production by approximately 50% and might affect the age of ESKD. The goal of this study was to better understand the genetic and clinical characteristics of ADTKD-UMOD and to perform a Mendelian randomization study to determine if the minor allele of rs4293393 was associated with better kidney survival. METHODS: An international group of collaborators collected clinical and genetic data on 722 affected individuals from 249 families with 125 mutations, including 28 new mutations. The median age of ESKD was 47 years. Men were at a much higher risk of progression to ESKD (hazard ratio 1.78, P < 0.001). RESULTS: The allele frequency of the minor rs4293393 allele was only 11.6% versus the 19% expected (P < 0.01), resulting in Hardy-Weinberg disequilibrium and precluding a Mendelian randomization experiment. An in vitro score reflecting the severity of the trafficking defect of uromodulin mutants was found to be a promising predictor of the age of ESKD. CONCLUSION: We report the clinical characteristics associated with 125 UMOD mutations. Male gender and a new in vitro score predict age of ESKD.

Neutrophil, lymphocyte and platelet ratio as a predictor of mortality in septic-acute kidney injury patients / Relación entre neutrófilos, linfocitos y plaquetas como factor pronóstico de mortalidad en pacientes con lesión renal aguda por sepsis

BACKGROUND: AKI is frequent in critically ill patients, in whom the leading cause of AKI is sepsis. The role of intrarenal and systemic inflammation appears to be significant in the pathophysiology of septic-AKI. The neutrophils to lymphocytes and platelets (N/LP) ratio is an indirect marker of inflammation. The aim of this study was to evaluate the prognostic ability of N/LP ratio at admission in septic-AKI patients admitted to an intensive care unit (ICU). METHODS: This is a retrospective analysis of 399 septic-AKI patients admitted to the Division of Intensive Medicine of the Centro Hospitalar Universitário Lisboa Norte between January 2008 and December 2014. The Kidney Disease Improving Global Outcomes (KDIGO) classification was used to define AKI. N/LP ratio was calculated as: (Neutrophil count × 100)/(Lymphocyte count × Platelet count). RESULTS: Fifty-two percent of patients were KDIGO stage 3, 25.8% KDIGO stage 2 and 22.3% KDIGO stage 1. A higher N/LP ratio was an independent predictor of increased risk of in-hospital mortality in septic-AKI patients regardless of KDIGO stage (31.59 ± 126.8 vs 13.66 ± 22.64, p = 0.028; unadjusted OR 1.01 (95% CI 1.00-1.02), p = 0.027; adjusted OR 1.01 (95% CI 1.00-1.02), p = 0.015). The AUC for mortality prediction in septic-AKI was of 0.565 (95% CI (0.515-0.615), p = 0.034). CONCLUSIONS: The N/LP ratio at ICU admission was independently associated with in-hospital mortality in septic-AKI patients

ANTECEDENTES: La LRA es frecuente en pacientes críticos, en quienes la causa principal de LRA es la sepsis. El papel de la inflamación intrarrenal y sistémica parece ser significativo en la fisiopatología de la LRA por sepsis. La relación entre neutrófilos y linfocitos y plaquetas (N/LP) es un marcador indirecto de inflamación. El objetivo de este estudio fue evaluar la capacidad pronóstica de N/LP en el momento del ingreso en pacientes con LRA por sepsis ingresados en una unidad de cuidados intensivos. MÉTODOS: Se trata de un análisis retrospectivo de 399 pacientes con LRA por sepsis ingresados en la Unidad de Medicina Intensiva del Centro Hospitalario Universitario Lisboa Norte, entre enero de 2008 y diciembre de 2014. Se usó la clasificación del Kidney Disease Improving Global Outcomes (KDIGO) para definir la LRA. La relación N/LP se calculó como: (recuento de neutrófilos × 100)/(recuento de linfocitos × recuento de plaquetas). RESULTADOS: El 52% de los pacientes presentaba KDIGO estadio 3, el 25,8% KDIGO estadio 2 y el 22,3% KDIGO estadio 1. Un valor más elevado de N/LP fue un factor pronóstico independiente de mayor riesgo de mortalidad intrahospitalaria en pacientes con LRA por sepsis, independientemente del estadio KDIGO (31,59 ± 126,8 frente a 13,66 ± 22,64, p = 0,028); OR sin ajustar 1,01 (IC del 95%: 1,00-1,02, p = 0,027), OR ajustada 1,01 (IC del 95%: 1,00-1,02, p = 0,015). El AUC para la predicción de mortalidad en la LRA por sepsis fue de 0,565 (IC del 95%: 0,515-0,615, p = 0,034). CONCLUSIONES: La relación N/LP en el momento del ingreso en la unidad de cuidados intensivos se asoció de forma independiente con la mortalidad intrahospitalaria en pacientes con LRA por sepsis

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.

Neutrophil, lymphocyte and platelet ratio as a predictor of mortality in septic-acute kidney injury patients.

BACKGROUND: AKI is frequent in critically ill patients, in whom the leading cause of AKI is sepsis. The role of intrarenal and systemic inflammation appears to be significant in the pathophysiology of septic-AKI. The neutrophils to lymphocytes and platelets (N/LP) ratio is an indirect marker of inflammation. The aim of this study was to evaluate the prognostic ability of N/LP ratio at admission in septic-AKI patients admitted to an intensive care unit (ICU). METHODS: This is a retrospective analysis of 399 septic-AKI patients admitted to the Division of Intensive Medicine of the Centro Hospitalar Universitário Lisboa Norte between January 2008 and December 2014. The Kidney Disease Improving Global Outcomes (KDIGO) classification was used to define AKI. N/LP ratio was calculated as: (Neutrophil count×100)/(Lymphocyte count×Platelet count). RESULTS: Fifty-two percent of patients were KDIGO stage 3, 25.8% KDIGO stage 2 and 22.3% KDIGO stage 1. A higher N/LP ratio was an independent predictor of increased risk of in-hospital mortality in septic-AKI patients regardless of KDIGO stage (31.59±126.8 vs 13.66±22.64, p=0.028; unadjusted OR 1.01 (95% CI 1.00-1.02), p=0.027; adjusted OR 1.01 (95% CI 1.00-1.02), p=0.015). The AUC for mortality prediction in septic-AKI was of 0.565 (95% CI (0.515-0.615), p=0.034). CONCLUSIONS: The N/LP ratio at ICU admission was independently associated with in-hospital mortality in septic-AKI patients.

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.

Transient and persistent acute kidney injury in acute liver failure.

BACKGROUND: Acute Kidney Injury (AKI) is a very frequent complication in the Acute Liver Failure (ALF) population associated with negative outcomes. We aim to evaluate the impact of AKI duration on the outcomes of an ALF population. METHODS: A 20-year retrospective analysis of ALF patients admitted to an Intensive Care Unit (ICU) was performed. Chronic liver failure, chronic kidney disease on renal replacement therapy, dialysis requirement within the week prior or an ICU stay of less than 48 h after AKI diagnosis, were exclusion criteria. AKI was defined according to the KDIGO criteria and classified into transient (< 48 h duration) or persistent (48 h duration). RESULTS: A total of 51 patients were included in the analysis and most had AKI (66.7%). Persistent AKI patients (70.6%) presented more frequently with AKI at admission and a higher SOFA score than transient AKI and no AKI, p < 0.05. More severe AKI, sepsis, vasopressor support and mechanical ventilation were also more common (p < 0.05). Nineteen (55.9%) were classified as persistent AKI exclusively by serum creatinine and 15 (44.1%) by both serum creatinine and urine output criteria. Mean survival time at 30 days was 11.3 days for persistent AKI, 25.3 days for transient AKI and 27.0 days for no AKI, p = 0.01. Adjusted multivariate cox regression analysis showed that persistent AKI predicted in-hospital mortality but it lost significance when AKI severity was introduced in the model. CONCLUSION: Persistent AKI was common in ALF patients and associated with more severe AKI, worst systemic complications and a higher 30-day mortality, compared to transient and no AKI patients.

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.

Acute Kidney Injury Definition and Diagnosis: A Narrative Review.

Acute kidney injury (AKI) is a complex syndrome characterized by a decrease in renal function and associated with numerous etiologies and pathophysiological mechanisms. It is a common diagnosis in hospitalized patients, with increasing incidence in recent decades, and associated with poorer short- and long-term outcomes and increased health care costs. Considering its impact on patient prognosis, research has focused on methods to assess patients at risk of developing AKI and diagnose subclinical AKI, as well as prevention and treatment strategies, for which an understanding of the epidemiology of AKI is crucial. In this review, we discuss the evolving definition and classification of AKI, and novel diagnostic methods.