Urinary neutrophil gelatinase-associated lipocalin as biomarker in the differential diagnosis of impairment of kidney function in cirrhosis.

BACKGROUND & AIMS: Impairment of kidney function is common in cirrhosis but differential diagnosis remains a challenge. We aimed at assessing the usefulness of neutrophil gelatinase-associated lipocalin (NGAL), a biomarker of tubular damage, in the differential diagnosis of impairment of kidney function in cirrhosis. METHODS: Two-hundred and forty-one patients with cirrhosis, 72 without ascites, 85 with ascites, and 84 with impaired kidney function, were studied. Urinary levels of NGAL were measured by ELISA. RESULTS: Patients with impaired kidney function had higher urinary NGAL levels compared to patients with and without ascites. Patients with urinary tract infection (n=25) had higher uNGAL values than non-infected patients. Patients with acute tubular necrosis (ATN) had uNGAL levels markedly higher (417µg/g creatinine (239-2242) median and IQ range) compared to those of patients with pre-renal azotemia due to volume depletion 30 (20-59), chronic kidney disease (CKD) 82 (34-152), and hepatorenal syndrome (HRS) 76 (43-263) µg/g creatinine (p<0.001 for all). Among HRS patients, the highest values were found in HRS-associated with infections, followed by classical (non-associated with active infections) type-1 and type-2 HRS (391 (72-523), 147 (83-263), and 43 (31-74) µg/g creatinine, respectively; p<0.001). Differences in uNGAL levels between classical type 1 HRS and ATN on the one hand and classical type 1 HRS and CKD and pre-renal azotemia on the other were statistically significant (p<0.05). CONCLUSIONS: uNGAL levels may be useful in the differential diagnosis of impairment of kidney function in cirrhosis. Urinary tract infections should be ruled out because they may increase uNGAL excretion.

Predictors of response to therapy with terlipressin and albumin in patients with cirrhosis and type 1 hepatorenal syndrome.

UNLABELLED: Terlipressin plus albumin is an effective treatment for type 1 hepatorenal syndrome (HRS), but approximately only half of the patients respond to this therapy. The aim of this study was to assess predictive factors of response to treatment with terlipressin and albumin in patients with type 1 HRS. Thirty-nine patients with cirrhosis and type 1 HRS were treated prospectively with terlipressin and albumin. Demographic, clinical, and laboratory variables obtained before the initiation of treatment as well as changes in arterial pressure during treatment were analyzed for their predictive value. Response to therapy (reduction in serum creatinine <1.5 mg/dL at the end of treatment) was observed in 18 patients (46%) and was associated with an improvement in circulatory function. Independent predictive factors of response to therapy were baseline serum bilirubin and an increase in mean arterial pressure of >or=5 mm Hg at day 3 of treatment. The cutoff level of serum bilirubin that best predicted response to treatment was 10 mg/dL (area under the receiver operating characteristic curve, 0.77; P < 0.0001; sensitivity, 89%; specificity, 61%). Response rates in patients with serum bilirubin <10 mg/dL or >or=10 mg/dL were 67% and 13%, respectively (P = 0.001). Corresponding values in patients with an increase in mean arterial pressure >or=5 mm Hg or <5 mm Hg at day 3 were 73% and 36%, respectively (P = 0.037). CONCLUSION: Serum bilirubin and an early increase in arterial pressure predict response to treatment with terlipressin and albumin in type 1 HRS. Alternative treatment strategies to terlipressin and albumin should be investigated for patients with type 1 HRS and low likelihood of response to vasoconstrictor therapy.

Peritoneal Dialysis After Liver Transplantation: A Systematic Review.

BACKGROUND: Chronic kidney disease following liver transplantation is a major long-term complication. Most liver transplant recipients with kidney failure will be treated with dialysis instead of kidney transplantation due to noneligibility and shortage in organ availability. In this population, the role of peritoneal dialysis (PD) as a modality of kidney replacement therapy (KRT) remains unclear. OBJECTIVE: To determine the feasibility regarding safety, technique survival, and dialysis efficiency of PD in liver transplant recipients requiring KRT for maintenance dialysis. DESIGN: Systematic review. SETTING: Interventional and observational studies reporting the use of PD after liver transplantation. PATIENTS: Adult liver transplant recipients with kidney failure treated with maintenance KRT. MEASUREMENTS: Extracted data included eligibility criteria, study design, demographics, and PD modality. The following outcomes of interest were extracted: rate of peritonitis and microorganisms involved, noninfectious peritoneal complications, technique survival, and kidney transplantation-censored technique survival. Non-PD complications included overall survival, liver graft dysfunction, and hospitalization rate. METHODS: The following databases were searched until July 2020: MedLine/PubMed, EMBASE, CINAHL, and Cochrane Library. Two reviewers independently screening all titles and abstracts of all identified articles. Due to the limited sample size, observational designs and study heterogeneity expected, no meta-analysis was pre-planned. Descriptive statistics were used to report all results. RESULTS: From the 5263 identified studies, 4 were included in the analysis as they reported at least 1 outcome of interest on a total of 21 liver transplant recipients, with an overall follow-up duration on PD of 19.0 (Interquartile range [IQR]: 9.5-29.5) months. Fifteen episodes of peritonitis occurred in a total cumulative PD follow-up of 514 patient-months, representing an incidence rate of 0.35 per year. These episodes did not result in PD technique failure, mortality, or impairment of liver graft function. LIMITATIONS: Limitations include the paucity of studies in the field and the small number of patients included in each report, a risk of publication bias and the impossibility to directly compare hemodialysis to PD in this population. These results, therefore, must be interpreted with caution. CONCLUSIONS: Based on limited data reporting the feasibility of PD in liver transplant recipients with kidney failure, no signal was associated with an increased risk of infectious complications. Long-term studies evaluating this modality need to be performed. REGISTRATION PROSPERO: CRD42020218374.

CONTEXTE: L'insuffisance rénale chronique est une complication majeure à long terme survenant après une transplantation hépatique. La plupart des transplantés du foie qui développent une insuffisance rénale seront traités par dialyze plutôt que par une greffe rénale; En raison de la pénurie d'organes et par non-éligibilité à la greffe rénale, la plupart des transplantés du foie qui developpent une insuffisance rénale avancée seront traités par dialyse. L'importance de la dialyse péritonéale (DP) comme modalité de remplacement rénal demeure toutefois inconnue dans cette population de patients. OBJECTIFS: Étudier la faisabilité de la DP en matière d'innocuité, d'efficacité et de survie de la technique chez les receveurs d'une greffe hépatique qui nécessitent une thérapie de remplacement rénal comme dialyse d'entretien. TYPE D'ÉTUDE: Revue systématique. CADRE: Les études interventionnelles et observationnelles signalant l'utilisation de la DP après une transplantation hépatique. SUJETS: Des adultes ayant subi une transplantation hépatique et dont l'insuffisance rénale secondaire est traitée par thérapie de remplacement rénal. MESURES: Les données extraites comprenaient les critères d'admissibilité, la méthodologie de l'étude, les caractéristiques démographiques des sujets et la modalité de DP. Les résultats d'intérêt suivants ont été extraits : le taux de péritonites et les microorganismes impliqués, les complications péritonéales non infectieuses, la survie de la technique et la survie de la technique censurée par la transplantation rénale. Les complications non liées à la DP comprenaient la survie globale, la défaillance du greffon hépatique et le taux d'hospitalisation. MÉTHODOLOGIE: Les bases de données Medline/PubMed, Embase, CINAHL et Cochrane Library ont été consultées jusqu'en juillet 2020. Deux réviseurs indépendants ont examiné les titres et résumés de tous les articles recensés. Aucune méta-analyse n'a été planifiée en raison de la nature observationnelle et de l'hétérogénéité attendue des études retenues, et de la faible taille de l'échantillon. Des statistiques descriptives ont été utilisées pour présenter les données. RÉSULTATS: Des 5263 études recensées, seules quatre ont été incluses dans l'analyse, rapportant un total de 21 transplantés hépatiques, dont la durée médiane sur DP s'établissait à 19.0 mois (IIQ: 95 à 29.5). Au cours d'un suivi cumulatif de 514 mois-patients sur DP, 15 épisodes de péritonite ont été observés, soit un taux d'incidence de 0,35 par année. Ces épisodes n'ont pas entraîné d'échec de la DP, ni de mortalité ou d'altération de la fonction du greffon hépatique. LIMITES: Les limites comprennent le manque d'études sur le sujet, le faible nombre de patients inclus dans chaque rapport, un risque de biais de publication et l'impossibilité de comparer directement l'hémodialyse à la DP dans cette population. Les résultats doivent ainsi être interprétés avec prudence. CONCLUSION: Selon les données limitées portant sur la faisabilité de la dialyse péritonéale chez les receveurs d'une greffe hépatique atteints d'insuffisance rénale, aucun signal notable n'est associé à un risque accru de complications infectieuses. Des études à long terme évaluant cette modalité sont nécessaires.

Acute Tubulointerstitial Nephritis in a Patient on Anti-Programmed Death-Ligand 1 Triggered by COVID-19: A Case Report.

RATIONALE: Immune checkpoint inhibitors are monoclonal antibodies used in the treatment of various types of cancers. The downside of using such molecules is the potential risk of developing immune-related adverse events. Factors that trigger these autoimmune side effects are yet to be elucidated. Although any organ can potentially be affected, kidney involvement is usually rare. In this case report, we describe the first known instance of a patient being treated with an inhibitor of programmed death-ligand 1 (anti-PD-L1, a checkpoint inhibitor) who develops acute tubulointerstitial nephritis after contracting the severe acute respiratory syndrome coronavirus 2. PRESENTING CONCERNS OF THE PATIENT: A 62-year-old patient, on immunotherapy treatment for stage 4 squamous cell carcinoma, presents to the emergency department with symptoms of lower respiratory tract infection. Severe acute kidney injury is discovered with electrolyte imbalances requiring urgent dialysis initiation. Further testing reveals that the patient has contracted the severe acute respiratory syndrome coronavirus 2. DIAGNOSIS: A kidney biopsy was performed and was compatible with acute tubulointerstitial nephritis. INTERVENTIONS: The patient was treated with high dose corticosteroid therapy followed by progressive tapering. OUTCOMES: Rapid and sustained normalization of kidney function was achieved after completion of the steroid course. NOVEL FINDINGS: We hypothesize that the viral infection along with checkpoint inhibitor use has created a proinflammatory environment which led to a loss of self-tolerance to renal parenchyma. Viruses may play a more important role in the pathogenesis of autoimmunity in this patient population than was previously thought.

Terlipressin and albumin vs albumin in patients with cirrhosis and hepatorenal syndrome: a randomized study.

BACKGROUND & AIMS: Hepatorenal syndrome is common in patients with advanced cirrhosis and constitutes a major problem in liver transplantation. There is no effective medical treatment for hepatorenal syndrome. METHODS: Forty-six patients with cirrhosis and hepatorenal syndrome, hospitalized in a tertiary care center, were randomly assigned to receive either terlipressin (1-2 mg/4 hour, intravenously), a vasopressin analogue, and albumin (1 g/kg followed by 20-40 g/day) (n = 23) or albumin alone (n = 23) for a maximum of 15 days. Primary outcomes were improvement of renal function and survival at 3 months. RESULTS: Improvement of renal function occurred in 10 patients (43.5%) treated with terlipressin and albumin compared with 2 patients (8.7%) treated with albumin alone (P = .017). Independent predictive factors of improvement of renal function were baseline urine volume, serum creatinine and leukocyte count, and treatment with terlipressin and albumin. Survival at 3 months was not significantly different between the 2 groups (terlipressin and albumin: 27% vs albumin 19%, P = .7). Independent predictive factors of 3-month survival were baseline model for end-stage liver disease score and improvement of renal function. Cardiovascular complications occurred in 4 patients treated with albumin alone and in 10 patients treated with terlipressin and albumin, yet permanent terlipressin withdrawal was required in only 3 cases. CONCLUSIONS: As compared with albumin, treatment with terlipressin and albumin is effective in improving renal function in patients with cirrhosis and hepatorenal syndrome. Further studies with large sample sizes should be performed to test whether the improvement of renal function translates into a survival benefit.

Acute Kidney Injury Due to Inferior Vena Cava Stenosis After Liver Transplantation: A Case Report About the Importance of Hepatic Vein Doppler Ultrasound and Clinical Assessment.

RATIONALE: Acute kidney injury (AKI) is a frequent complication after liver transplantation. In some patients, prompt intervention targeted at a specific etiology is of paramount importance. PRESENTING CONCERNS OF THE PATIENTS: A 25 years old man with advanced liver cirrhosis caused by sclerosing cholangitis and autoimmune hepatitis underwent orthotopic liver transplantation. One month after surgery, severe AKI developed in conjunction with recurrent ascites and lower extremity edema. Notable clinical findings included a persistently low urinary sodium excretion, a bland urinary sediment, and an abnormally monophasic hepatic vein waveform on Doppler ultrasound. DIAGNOSES: Inferior vena cava stenosis. INTERVENTIONS: Angioplasty with stent installation. OUTCOMES: Rapid improvement of renal function after stent installation. LESSONS LEARNED: The following case illustrates the importance of integrating clinical cues, ultrasound features, and laboratory findings. The combination of AKI associated with lower extremity edema, abnormal monophasic hepatic vein flow on Doppler ultrasound, and a low urinary sodium excretion after liver transplantation should evoke the possibility of inferior vena cava stenosis as the etiologic factor.

FONDEMENT: L'insuffisance rénale aiguë (IRA) est une complication survenant fréquemment à la suite d'une greffe hépatique. Pour certains patients, une intervention rapide et ciblée sur l'étiologie spécifique s'avère d'une importance capitale. PRÉSENTATION DU CAS: Un homme âgé de 25 ans atteint d'une cirrhose hépatique avancée causée par une cholangite sclérosante et une hépatite auto-immune a subi une greffe hépatique orthotopique. Un mois après l'intervention, le patient a développé une sévère IRA conjointement à des ascites récurrentes et un œdème des membres inférieurs. Parmi les principales manifestations cliniques figuraient la persistance d'une faible excrétion urinaire du sodium, la présence de sédiments urinaires neutres et une forme d'onde anormalement monophasique pour la veine hépatique à l'échographie Doppler. DIAGNOSTIC: Sténose de la veine cave inférieure. INTERVENTION: Angioplastie avec implantation d'une endoprothèse vasculaire. RÉSULTATS: Amélioration rapide de la fonction rénale à la suite de l'implantation de l'endoprothèse vasculaire. ENSEIGNEMENTS TIRÉS: Ce cas illustre l'importance d'intégrer les indicateurs cliniques, les informations obtenues à l'échographie et les résultats de laboratoire. L'IRA survenant à la suite d'une greffe hépatique, lorsqu'elle est associée à de l'œdème des membres inférieurs, à des ondes anormalement monophasiques de la veine hépatique à l'échographie Doppler, de même qu'à une faible excrétion urinaire de sodium, devrait évoquer la possibilité d'une sténose de la veine cave inférieure comme facteur étiologique.

Diagnostic performance of fractional excretion of urea and fractional excretion of sodium in the evaluations of patients with acute kidney injury with or without diuretic treatment.

BACKGROUND: The accuracy of fractional excretion of sodium (FENa) for the diagnosis of transient acute kidney injury (AKI) caused by decreased kidney perfusion is reported to be low in patients administered diuretics. STUDY DESIGN: This is a prospective study of diagnostic accuracy comparing the performance of fractional excretion of urea (FEur) with that of FENa to distinguish between transient and persistent AKI. SETTING & PARTICIPANTS: 99 patients hospitalized at a tertiary-care center who developed AKI (>or=30% increase in serum creatinine level from baseline within 1 week). INDEX TEST: FEur and FENa were calculated for each patient. REFERENCE TEST & MEASUREMENTS: Patients were classified as having transient or persistent AKI according to the clinical context and whether serum creatinine level returned to baseline within 7 days. Each group also was subdivided according to exposure to diuretics. FEur of 35% or less and FENa of 1% or less were used to define transient AKI. Sensitivity, specificity, and receiver operating characteristic curves were generated for each index test. RESULTS: Sensitivity and specificity of FEur were 48% and 75% in patients not administered diuretics and 79% and 33% in patients administered diuretics. Sensitivity and specificity of FENa were 78% and 75% in patients not administered diuretics and 58% and 81% in those administered diuretics. Receiver operating characteristic curves did not identify a better diagnostic cutoff value for FEur or FENa. LIMITATIONS: Small sample size, variable exposure to diuretics, and a high proportion of preexisting chronic kidney disease. CONCLUSIONS: In patients without diuretic use, FENa is better able to distinguish transient from persistent AKI. In patients administered diuretics, this distinction cannot be made accurately by means of FENa. FEur cannot be used as an alternative tool because it lacks specificity.