Neutrophil Gelatinase-Associated Lipocalin Measured on Clinical Laboratory Platforms for the Prediction of Acute Kidney Injury and the Associated Need for Dialysis Therapy: A Systematic Review and Meta-analysis.

RATIONALE & OBJECTIVE: The usefulness of measures of neutrophil gelatinase-associated lipocalin (NGAL) in urine or plasma obtained on clinical laboratory platforms for predicting acute kidney injury (AKI) and AKI requiring dialysis (AKI-D) has not been fully evaluated. We sought to quantitatively summarize published data to evaluate the value of urinary and plasma NGAL for kidney risk prediction. STUDY DESIGN: Literature-based meta-analysis and individual-study-data meta-analysis of diagnostic studies following PRISMA-IPD guidelines. SETTING & STUDY POPULATIONS: Studies of adults investigating AKI, severe AKI, and AKI-D in the setting of cardiac surgery, intensive care, or emergency department care using either urinary or plasma NGAL measured on clinical laboratory platforms. SELECTION CRITERIA FOR STUDIES: PubMed, Web of Science, Cochrane Library, Scopus, and congress abstracts ever published through February 2020 reporting diagnostic test studies of NGAL measured on clinical laboratory platforms to predict AKI. DATA EXTRACTION: Individual-study-data meta-analysis was accomplished by giving authors data specifications tailored to their studies and requesting standardized patient-level data analysis. ANALYTICAL APPROACH: Individual-study-data meta-analysis used a bivariate time-to-event model for interval-censored data from which discriminative ability (AUC) was characterized. NGAL cutoff concentrations at 95% sensitivity, 95% specificity, and optimal sensitivity and specificity were also estimated. Models incorporated as confounders the clinical setting and use versus nonuse of urine output as a criterion for AKI. A literature-based meta-analysis was also performed for all published studies including those for which the authors were unable to provide individual-study data analyses. RESULTS: We included 52 observational studies involving 13,040 patients. We analyzed 30 data sets for the individual-study-data meta-analysis. For AKI, severe AKI, and AKI-D, numbers of events were 837, 304, and 103 for analyses of urinary NGAL, respectively; these values were 705, 271, and 178 for analyses of plasma NGAL. Discriminative performance was similar in both meta-analyses. Individual-study-data meta-analysis AUCs for urinary NGAL were 0.75 (95% CI, 0.73-0.76) and 0.80 (95% CI, 0.79-0.81) for severe AKI and AKI-D, respectively; for plasma NGAL, the corresponding AUCs were 0.80 (95% CI, 0.79-0.81) and 0.86 (95% CI, 0.84-0.86). Cutoff concentrations at 95% specificity for urinary NGAL were>580ng/mL with 27% sensitivity for severe AKI and>589ng/mL with 24% sensitivity for AKI-D. Corresponding cutoffs for plasma NGAL were>364ng/mL with 44% sensitivity and>546ng/mL with 26% sensitivity, respectively. LIMITATIONS: Practice variability in initiation of dialysis. Imperfect harmonization of data across studies. CONCLUSIONS: Urinary and plasma NGAL concentrations may identify patients at high risk for AKI in clinical research and practice. The cutoff concentrations reported in this study require prospective evaluation.

The Use of Adsorption in Extracorporeal Liver Support: The Double Plasma Molecular Adsorption System (DPMAS).

Liver failure in the intensive care unit (ICU), whether acute or acute-on-chronic, remains a serious condition with reduced functions, various metabolite and toxin accumulation in the systemic circulation, and a high mortality rate. While transplantation remains the treatment of choice, the lack of organ transplants necessitates finding alternative solutions. Within the last years, several therapies aiming to support liver function have been developed in order to serve as a bridge to liver transplantation or as replacement therapy, allowing regeneration of the injured liver. In those therapies, nonbiological extracorporeal liver support devices are the most widely used, mainly based on detoxification by eliminating accumulated toxins notably by adsorption on specific membranes and/or with plasmapheresis. One of the most recent techniques is the double plasma molecular adsorption system combining plasma filtration and two specific adsorption membranes, which is largely described and studied in this chapter. This technique seems promising to remove deleterious toxins, cytokines and bilirubin in particular, is fairly simple to use, does not require a specific machine (it works on continuous renal replacement therapy machines), and has given encouraging results in the pilot studies published recently, in association with plasmapheresis or alone. However, further studies and evaluations are needed before this technique can be used routinely in ICU.

Characteristics of acute kidney injury in adult patients with severe COVID-19.

We conducted a retrospective cohort study to report the clinical characteristics, incidence and outcomes of patients with severe COVID-19 with acute kidney injury (AKI). One-hundred and sixtytwo intensive care unit (ICU) admitted patients in a tertiary level hospital in the city of Buenos Aires with COVID-19 diagnosis were included. We hypothesized that COVID-19 related AKI would develop in the period of more severe hypoxemia as an early event and late AKI would be more probably related to intensive care unit complications. For this purpose, we divided subjects into two groups: those with early AKI and late AKI, before and after day 14 from symptom onset, respectively. A stepwise multivariate analysis was conducted to find possible AKI predictors. AKI incidence was 43.2% (n = 70) of the total patients admitted into ICU with severe COVID-19, 11.1% (n = 18) required renal replacement therapy. In-hospital mortality was higher (58.6%) for the AKI group. AKI occurred on a median time of 10 (IQR 5.5-17.5) days from symptom onset. A history of hypertension or heart failure, age and invasive mechanical ventilation (IMV) requirement were identified as risk factors. Late AKI (n = 25, 35.7%) was associated with sepsis and nephrotoxic exposure, whereas early AKI occurred closer to the timing of IMV initiation and was more likely to have an unknown origin. In conclusion, AKI is frequent among critically ill patients with severe COVID-19 and it is associated with higher in-hospital mortality.

Llevamos a cabo un estudio retrospectivo con el objetivo de describir las características clínicas, incidencia y desenlaces de los pacientes con injuria renal aguda (IRA) asociada a la COVID-19. Se incluyeron 162 pacientes con diagnóstico de COVID-19 admitidos en una unidad de cuidados intensivos en un hospital de tercer nivel en la Ciudad de Buenos Aires. Nuestra hipótesis consistió en que la IRA asociada a COVID-19 sería un evento temprano asociado a la gravedad de la hipoxemia y la IRA tardía se relacionaría con complicaciones propias de la UCI. Por ello se clasificó la IRA en temprana y tardía, según sucediera antes o después de los 14 días desde el inicio de síntomas. Se realizó un análisis multivariado mediante regresión logística escalonada para evaluar posibles factores de riesgo. La incidencia de IRA fue de 43.2% (n = 70), 11.1% (n = 18) requirieron terapia de reemplazo renal. La mortalidad intrahospitalaria fue mayor (58.6%) en el grupo con IRA. El diagnóstico de IRA se realizó en una mediana de 10 (IQR = 5.5-17.5) días desde el inicio de los síntomas. El antecedente de hipertensión e insuficiencia cardíaca, la edad y el requerimiento de ventilación mecánica invasiva (VMI) fueron identificados como factores de riesgo para IRA. La IRA tardía (n = 25, 35.7%) estuvo asociada a sepsis y exposición a nefrotóxicos, mientras que la IRA temprana (n = 45, 64.2%) estuvo temporalmente asociada al inicio de la VMI y en muchos casos no se pudo filiar una etiología. En conclusión, la IRA es una complicación frecuente en pacientes con COVID-19 grave y está asociada a una alta mortalidad intrahospitalaria.

[Comparison between CKD-EPI and MDRD-equations to estimate glomerular filtration rate in chronic kidney disease patients]. / Comparación entre las ecuaciones CKD-EPI y MDRD para la estimación del filtrado glomerular en pacientes con enfermedad renal crónica.

The MDRD equation to estimate glomerular filtration rate (GFR) is the most widely used strategy to assess chronic kidney disease. Nonetheless, for the individual patient the true GFR can be underestimated with the risk of diagnosing a more elevated CKD stage. This novel CKD-EPI equation would improve accuracy and precision of estimations, and several authors recommend this new equation replace the former. In our country there is only a limited registration of these comparisons performed on a large number of patients. Therefore, our aim was to develop a comparison in a wide cohort of patients. The concordance between both equations to assign the GFR stages was determined by using the MDRD formula as a reference. The mean difference of GFR obtained with both equations as well as the Bland-Altman analysis were calculated. A cohort of 9319 individuals, of whom 67% were females, aged 58 ± 20 years, with serum creatinine values of 1.6 ± 1.03 mg/dl, was studied. In the whole group, CKD-EPI displayed an average GFR 0.61 ml/min/1.73 m2 larger than MDRD (p: NS). For CKD stages 2 and 3A the mean estimated GFR difference was 6.95 ± 4.76 and 3.21 ± 3.31, while the concordance was 81 and 74% respectively. The percentage of patients with GFR < 60 ml/min/1.73 m2, decreased from 76.3% with the former equation to 70.1% with the latter. The novel equation CKD-EPI reduces the number of patients with GFR values lower than 60 ml/min/1.73 m2 and consequently assigns a higher GFR stage to a considerable quantity of individuals.

International Society of Nephrology Global Kidney Health Atlas: structures, organization, and services for the management of kidney failure in Latin America.

Latin America is a region with a widely variable socioeconomic landscape, facing a surge in noncommunicable diseases, including chronic kidney disease and kidney failure, exposing significant limitations in the delivery of care. Despite region-wide efforts to explore and address these limitations, much uncertainty remains as to the capacity, accessibility, and quality of kidney failure care in Latin America. Through this second iteration of the International Society of Nephrology Global Kidney Health Atlas, we aimed to report on these indicators to provide a comprehensive map of kidney failure care in the region. Survey responses were received from 18 (64.2%) countries, representing 93.8% of the total population in Latin America. The median prevalence and incidence of treated kidney failure in Latin America were 715 and 157 per million population, respectively, the latter being higher than the global median (142 per million population), with Puerto Rico, Mexico, and El Salvador experiencing much of this growing burden. In most countries, public and private systems collectively funded most aspects of kidney replacement therapy (dialysis and transplantation) care, with patients incurring at least 1% to 25% of out-of-pocket costs. In most countries, >90% of dialysis patients able to access kidney replacement therapy received hemodialysis (n = 11; 5 high income and 6 upper-middle income), and only a small minority began with peritoneal dialysis (1%-10% in 67% of countries; n = 12). Few countries had chronic kidney disease registries or targeted detection programs. There is a large variability in the availability, accessibility, and quality of kidney failure care in Latin America, which appears to be subject to individual countries' funding structures, underreliance on cheap kidney replacement therapy, such as peritoneal dialysis, and limited chronic kidney disease surveillance and management initiatives.

Stent tunnel technique to save thrombosed native hemodialysis fistula with extensive venous aneurysm.

INTRODUCTION AND PURPOSE: The increasing number of patients undergoing hemodialysis and the limited number of access sites have resulted in an increasing number of techniques to maintain vascular access for hemodialysis. Thrombosed arteriovenous (AV) fistulas with large venous aneurysms have poor treatment results, with both endovascular and surgical techniques, leading to a high rate of definitive AV access loss. The purpose of this study was to review the feasibility and initial results of this novel endovascular treatment of thrombosed AV fistulas with large venous aneurysms. MATERIALS AND METHODS: A novel endovascular treatment technique of inserting nitinol auto-expandable uncovered stents stretching through the whole puncture site area, thus creating a tunnel inside the thrombus, was retrospectively analyzed and described. RESULTS: A total of 17 stents were placed in 10 hemodialysis fistulas, with a mean venous coverage length of 17.8 cm. In all the cases, 100% technical success was achieved, with complete restoration of blood flow in all patients. There were no procedure-related complications. The mean follow-up was 167 days (range 60-420 days), with a primary and assisted patency of 80% and 100%, respectively. No multiple trans-stent struts-related complications were observed. Three stent fractures were diagnosed with plain films at the site of puncture without consequence in the venous access permeability. CONCLUSION: The "stent tunnel technique" is a feasible, safe and effective alternative to salvage native hemodialysis access, thus extending the function of the venous access with no signs of stent-related complications and a respectable midterm patency.

Characteristics of acute kidney injury in adult patients with severe COVID-19 / Características de la injuria renal aguda en pacientes adultos con COVID-19 grave

Abstract We conducted a retrospective cohort study to report the clinical characteristics, incidence and out-comes of patients with severe COVID-19 with acute kidney injury (AKI). One-hundred and sixtytwo intensive care unit (ICU) admitted patients in a tertiary level hospital in the city of Buenos Aires with COVID-19 diagnosis were included. We hypothesized that COVID-19 related AKI would develop in the period of more severe hypoxemia as an early event and late AKI would be more probably related to intensive care unit complications. For this purpose, we divided subjects into two groups: those with early AKI and late AKI, before and after day 14 from symptom onset, respectively. A stepwise multivariate analysis was conducted to find possible AKI predictors. AKI incidence was 43.2% (n = 70) of the total patients admitted into ICU with severe COVID-19, 11.1% (n = 18) required renal replacement therapy. In-hospital mortality was higher (58.6%) for the AKI group. AKI occurred on a median time of 10 (IQR 5.5-17.5) days from symptom onset. A history of hypertension or heart failure, age and invasive mechanical ventilation (IMV) requirement were identified as risk factors. Late AKI (n = 25, 35.7%) was associated with sepsis and nephrotoxic exposure, whereas early AKI occurred closer to the timing of IMV initiation and was more likely to have an unknown origin. In conclusion, AKI is frequent among critically ill patients with severe COVID-19 and it is associated with higher in-hospital mortality.

Resumen Llevamos a cabo un estudio retrospectivo con el objetivo de describir las características clínicas, incidencia y desenlaces de los pacientes con injuria renal aguda (IRA) asociada a la COVID-19. Se incluyeron 162 pacientes con diagnóstico de COVID-19 admitidos en una unidad de cuidados intensivos en un hospital de tercer nivel en la Ciudad de Buenos Aires. Nuestra hipótesis consistió en que la IRA asociada a COVID-19 sería un evento temprano asociado a la gravedad de la hipoxemia y la IRA tardía se relacionaría con complicaciones propias de la UCI. Por ello se clasificó la IRA en temprana y tardía, según sucediera antes o después de los 14 días desde el inicio de síntomas. Se realizó un análisis multivariado mediante regresión logística escalonada para evaluar posibles factores de riesgo. La incidencia de IRA fue de 43.2% (n = 70), 11.1% (n = 18) requirieron terapia de reemplazo renal. La mortalidad intrahospitalaria fue mayor (58.6%) en el grupo con IRA. El diagnóstico de IRA se realizó en una mediana de 10 (IQR = 5.5-17.5) días desde el inicio de los síntomas. El antecedente de hipertensión e insuficiencia cardíaca, la edad y el requerimiento de ventilación mecánica invasiva (VMI) fueron identificados como factores de riesgo para IRA. La IRA tardía (n = 25, 35.7%) estuvo asociada a sepsis y expo sición a nefrotóxicos, mientras que la IRA temprana (n = 45, 64.2%) estuvo temporalmente asociada al inicio de la VMI y en muchos casos no se pudo filiar una etiología. En conclusión, la IRA es una complicación frecuente en pacientes con COVID-19 grave y está asociada a una alta mortalidad intrahospitalaria.

Cistatina C como predictor de síndrome cardiorrenal y mal pronóstico en pacientes internados por insuficiencia cardíaca aguda y función renal normal / Cystatin C as Marker of Cardiorenal Syndrome and Poor Prognosis in Patients Hospitalized with Acute Heart Failure and Normal Renal Function

Introducción: El desarrollo de disfunción renal en el contexto de una falla cardíaca aguda se conoce como síndrome cardiorrenal (SCR) tipo 1. El empeoramiento de la función renal (EFR) durante la internación es un predictor de mal pronóstico. La cistatina C ha surgido como un marcador de función renal alternativo a la creatinina. Objetivo: Demostrar la utilidad clínica de la cistatina C como predictor de EFR y factor pronóstico en pacientes con insuficiencia cardíaca aguda y sin disfunción renal evaluada por creatinina al ingreso. Material y métodos: Se llevó a cabo un estudio observacional, prospectivo, de pacientes consecutivos con diagnóstico de insuficiencia cardíaca aguda y sin disfunción renal, definida como un valor de creatinina < 1,3 mg/dl al ingreso. Se realizó un dosaje de cistatina C al ingreso. El punto final primario fue EFR y los secundarios fueron mortalidad hospitalaria, mortalidad total y reinternación por insuficiencia cardíaca. Resultados: Se incluyeron 166 pacientes con una mediana de edad de 85 años (IIC 77,7-89). La incidencia de EFR fue del 29,7%, con una mortalidad hospitalaria del 3,1% y una mortalidad total del 24,4%. La mediana de seguimiento fue de 193 días. El valor de cistatina C fue significativamente mayor en los pacientes que desarrollaron EFR (1,72 ± 0,58 mg/dl vs. 1,51 ± 0,41 mg/dl; p = 0,03) y en los pacientes que murieron en el seguimiento (1,76 ± 0,49 mg/dl vs. 1,51 ± 0,46 mg/dl; p = 0,004). La cistatina C resultó un predictor independiente de mortalidad (OR 3,03, IC 95% 1,22-7,47) y de EFR (OR 2,38, IC 95% 1,02-5,5) en el análisis multivariado. Se halló un punto de corte óptimo de 1,6 mg/dl de cistatina, con una sensibilidad del 61,22% y una especificidad del 60,34% para el desarrollo de EFR y del 61,54% y 61,98%, respectivamente, para mortalidad total. Conclusión: El valor de cistatina C al ingreso es predictor de desarrollo de EFR durante la internación y de mayor mortalidad en esta población con insuficiencia cardíaca aguda y función renal conservada al ingreso.

Comparación entre las ecuaciones CKD-EPI y MDRD para la estimación del filtrado glomerular en pacientes con enfermedad renal crónica / Comparison between CKD-EPI and MDRD-equations to estimate glomerular filtration rate in chronic kidney disease patients

La ecuación MDRD para la estimación del índice de filtrado glomerular (IFG), es la estrategia más utilizada para evaluar pacientes con enfermedad renal crónica (ERC). Sin embargo, puede subestimar el IFG con el riesgo de asignar al paciente a estadios más avanzados de ERC. La nueva ecuación CKD-EPI, mejoraría la exactitud y precisión de las estimaciones. Sus autores sugieren que reemplace a la anterior. No habiendo comparaciones de estas ecuaciones aplicadas en un gran número de pacientes en nuestro país, nuestro objetivo fue realizarla en una amplia cohorte de pacientes. Se evaluó la concordancia de asignación en estadios de ERC entre ambas ecuaciones, tomando como referencia los datos surgidos de MDRD. Se calculó la media de las diferencias de los IFG obtenidos empleando ambas ecuaciones y se aplicó el análisis estadístico de Bland-Altman. Se estudió una cohorte de 9 319 pacientes con una media de creatinina sérica de 1.60 ± 1.03 mg/dl, 67% de sexo femenino y edad media 58 ± 20 años. En el grupo total, CKD-EPI presentó una media de IFG 0.61 ml/min/1.73 m² mayor que MDRD (p: NS). En los estadios 2 y 3A las medias del IFG fueron respectivamente 6.95 ± 4.76 y 3.21 ± 3.31, y la concordancia de 81 y 74%. El porcentaje de pacientes con un IFG menor de 60 ml/min/1.73 m², se redujo de 76.3% (MDRD) a 70.1% (CKD-EPI). Por lo tanto, la nueva ecuación CKD-EPI disminuye el número de pacientes con IFG debajo de 60 ml/min/1.73 m² y asigna estadios de IFG más elevado a un número mayor de pacientes.

The MDRD equation to estimate glomerular filtration rate (GFR) is the most widely used strategy to assess chronic kidney disease. Nonetheless, for the individual patient the true GFR can be underestimated with the risk of diagnosing a more elevated CKD stage. This novel CKD-EPI equation would improve accuracy and precision of estimations, and several authors recommend this new equation replace the former. In our country there is only a limited registration of these comparisons performed on a large number of patients. Therefore, our aim was to develop a comparison in a wide cohort of patients. The concordance between both equations to assign the GFR stages was determined by using the MDRD formula as a reference. The mean difference of GFR obtained with both equations as well as the Bland-Altman analysis were calculated. A cohort of 9 319 individuals, of whom 67% were females, aged 58 ± 20 years, with serum creatinine values of 1.6 ± 1.03 mg/dl, was studied. In the whole group, CKD-EPI displayed an average GFR 0.61 ml/min/1.73 m² larger than MDRD (p: NS). For CKD stages 2 and 3A the mean estimated GFR difference was 6.95 ± 4.76 and 3.21 ± 3.31, while the concordance was 81 and 74% respectively. The percentage of patients with GFR < 60 ml/min/1.73 m², decreased from 76.3% with the former equation to 70.1% with the latter. The novel equation CKD-EPI reduces the number of patients with GFR values lower than 60 ml/min/1.73 m² and consequently assigns a higher GFR stage to a considerable quantity of individuals.

Elimination and clearance of pamidronate by haemodialysis.

Pamidronate (APD), a third-generation bisphosphonate, has proven to be useful in haemodialysis (HD) patients with ectopic calcifications and hypercalcaemia. Little is known about bisphosphonates clearance in patients undergoing HD. The authors' main objective was to study HD removal and clearance of APD. In total, 23 HD-requiring anuric end-stage renal disease (ESRD) adult individuals (12 men) aged 61.7 +/- 13 (mean +/- SD) years were admitted into the study. APD clearance and elimination were evaluated by (99m)Technetium APD (half-life 6 h). In total, 1 mg of labelled APD was injected via the arteriovenous graft prior to the start of HD. Blood samples were then drawn from the arterial (predialyser) and venous (postdialyser) lines of the extracorporeal circuit 2 h after the HD onset. In a subgroup of patients (n: 15) the dialysate was collected and quantified during the three initial HD hours. Venous APD concentrations (postdialyser) were 72 + 7% of arterial (predialyser) concentrations. Mean APD clearance was 69.3 + 16.6 mL/min, and mean APD extraction during dialysis session was 31.6 + 10.1%. In the present study involving HD-requiring anuric ESRD patients APD was successfully eliminated by HD. At the dose administered here none of the participants reported adverse events. APD is a potentially useful drug to be administered to HD-requiring ESRD patients, the understanding of its removal during HD as well as its dialytic clearance allows for a safer management of a drug that is usually eliminated by renal excretion.

Folic acid 5 or 15 mg/d similarly reduces plasma homocysteine in patients with moderate-advanced chronic renal failure.

BACKGROUND: Hyperhomocysteinaemia is an independent risk factor for cardiovascular disease with a remarkable prevalence in patients with chronic renal failure (CRF). Low doses of folic acid (FA) with or without vitamin B6 and B12 has been shown to effectively reduce plasma homocysteine (Hcy). The aim of this study was to compare the short-term effects of two different oral doses of FA (5 vs 15 mg/d) on plasma Hcy levels in subjects suffering from moderate-severe CRF. METHODS: A double-blind, double-dummy, comparative, two-stage randomised study was performed. Seventeen patients aged 45-71 years, with glomerular filtration rates between 15.4-50 mL/min 1.73/m2 were randomly assigned to receive FA 5 mg/d (FA-5, n: 8) or FA 15 mg/d (FA-15, n: 9) for 30 days. At the end of this 30-day double-blind period, all the participants were placed on FA 5 mg/d (open period), for 5 additional months. Both groups were also supplemented with vitamins B1, B6 and B12 throughout the trial. Blood samples were drawn at 0, 15, 30, 90 and 180 days to assess Hcy, complete blood count (CBC) and sequential multichannel analysis (SMA). Chest X-ray and a 12-lead electrocardiogram (ECG) were also performed. RESULTS: Plasma Hcy (mean +/- SEM) decreased from 27.9 +/- 1.4 (baseline) to 15.1 +/- 0.6, 13.3 +/- 0.9, 14.1 +/- 0.5 and 13.8 +/- 0.5 micromol/L (FA-5) and from 28.8 +/- 2.7 to 15.6 +/- 1.2, 14.4 +/- 1.3, 13.0 +/- 0.7 and 13.1 +/- 0.6 micromol/L (FA-15) at days 15, 30, 90 and 180, respectively. (P < 0.01 from day 15 to 180 vs baseline for both groups with no differences between them). Renal function remained stable throughout the entire period of the study in all but one patient in whom it deteriorated to pre-end stage disease. No adverse cardiovascular events developed during the trial. CONCLUSION: Both folic acid doses induced a significant and similar decrease in plasma Hcy in subjects with moderate-severe chronic renal failure. The possible dose-related effect of this approach in reducing the risk of accelerated sclerotic vascular disease and cardiovascular events in this especially vulnerable population should be a matter of further investigation.