Urinary biomarkers and progression of AKI in patients with cirrhosis.

BACKGROUND AND OBJECTIVES: AKI is a common and severe complication in patients with cirrhosis. AKI progression was previously shown to correlate with in-hospital mortality. Therefore, accurately predicting which patients are at highest risk for AKI progression may allow more rapid and targeted treatment. Urinary biomarkers of structural kidney injury associate with AKI progression and mortality in multiple settings of AKI but their prognostic performance in patients with liver cirrhosis is not well known. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A multicenter, prospective cohort study was conducted at four tertiary care United States medical centers between 2009 and 2011. The study comprised patients with cirrhosis and AKI defined by the AKI Network criteria evaluating structural (neutrophil gelatinase-associated lipocalin, IL-18, kidney injury molecule-1 [KIM-1], liver-type fatty acid-binding protein [L-FABP], and albuminuria) and functional (fractional excretion of sodium [FENa]) urinary biomarkers as predictors of AKI progression and in-hospital mortality. RESULTS: Of 188 patients in the study, 44 (23%) experienced AKI progression alone and 39 (21%) suffered both progression and death during their hospitalization. Neutrophil gelatinase-associated lipocalin, IL-18, KIM-1, L-FABP, and albuminuria were significantly higher in patients with AKI progression and death. These biomarkers were independently associated with this outcome after adjusting for key clinical variables including model of end stage liver disease score, IL-18 (relative risk [RR], 4.09; 95% confidence interval [95% CI], 1.56 to 10.70), KIM-1 (RR, 3.13; 95% CI, 1.20 to 8.17), L-FABP (RR, 3.43; 95% CI, 1.54 to 7.64), and albuminuria (RR, 2.07; 95% CI, 1.05-4.10) per log change. No biomarkers were independently associated with progression without mortality. FENa demonstrated no association with worsening of AKI. When added to a robust clinical model, only IL-18 independently improved risk stratification on a net reclassification index. CONCLUSIONS: Multiple structural biomarkers of kidney injury, but not FENa, are independently associated with progression of AKI and mortality in patients with cirrhosis. Injury marker levels were similar between those without progression and those with progression alone.

Early trends in cystatin C and outcomes in patients with cirrhosis and acute kidney injury.

Background. Acute kidney injury (AKI) is a common and severe complication in patients with cirrhosis. Progression of AKI to a higher stage associates with increased mortality. Intervening early in AKI when renal dysfunction is worsening may improve outcomes. However, serum creatinine correlates poorly with glomerular filtration in patients with cirrhosis and fluctuations may mask progression early in the course of AKI. Cystatin C, a low-molecular-weight cysteine proteinase inhibitor, is a potentially more accurate marker of glomerular filtration. Methods. We conducted a prospective multicenter study in patients with cirrhosis comparing changes in cystatin and creatinine immediately following onset of AKI as predictors of a composite endpoint of dialysis or mortality. Results. Of 106 patients, 37 (35%) met the endpoint. Cystatin demonstrated less variability between samples than creatinine. Patients were stratified into four groups reflecting changes in creatinine and cystatin: both unchanged or decreased 38 (36%) (Scr-/CysC-); only cystatin increased 25 (24%) (Scr-/CysC+); only creatinine increased 15 (14%) (Scr+/CysC-); and both increased 28 (26%) (Scr+/CysC+). With Scr-/CysC- as the reference, in both instances where cystatin rose, Scr-/CysC+ and Scr+/CysC+, the primary outcome was significantly more frequent in multivariate analysis, P = 0.02 and 0.03, respectively. However, when only creatinine rose, outcomes were similar to the reference group. Conclusions. Changes in cystatin levels early in AKI are more closely associated with eventual dialysis or mortality than creatinine and may allow more rapid identification of patients at risk for adverse outcomes.

Kidney biomarkers and differential diagnosis of patients with cirrhosis and acute kidney injury.

UNLABELLED: Acute kidney injury (AKI) is common in patients with cirrhosis and associated with significant mortality. The most common etiologies of AKI in this setting are prerenal azotemia (PRA), acute tubular necrosis (ATN), and hepatorenal syndrome (HRS). Accurately distinguishing the etiology of AKI is critical, as treatments differ markedly. However, establishing an accurate differential diagnosis is extremely challenging. Urinary biomarkers of kidney injury distinguish structural from functional causes of AKI and may facilitate more accurate and rapid diagnoses. We conducted a multicenter, prospective cohort study of patients with cirrhosis and AKI assessing multiple biomarkers for differential diagnosis of clinically adjudicated AKI. Patients (n = 36) whose creatinine returned to within 25% of their baseline within 48 hours were diagnosed with PRA. In addition, 76 patients with progressive AKI were diagnosed by way of blinded retrospective adjudication. Of these progressors, 39 (53%) patients were diagnosed with ATN, 19 (26%) with PRA, and 16 (22%) with HRS. Median values for neutrophil gelatinase-associated lipocalin (NGAL), interleukin-18 (IL-18), kidney injury molecule-1 (KIM-1), liver-type fatty acid binding protein (L-FABP), and albumin differed between etiologies and were significantly higher in patients adjudicated with ATN. The fractional excretion of sodium (FENa) was lowest in patients with HRS, 0.10%, but did not differ between those with PRA, 0.27%, or ATN, 0.31%, P = 0.54. The likelihood of being diagnosed with ATN increased step-wise with the number of biomarkers above optimal diagnostic cutoffs. CONCLUSION: Urinary biomarkers of kidney injury are elevated in patients with cirrhosis and AKI due to ATN. Incorporating biomarkers into clinical decision making has the potential to more accurately guide treatment by establishing which patients have structural injury underlying their AKI. Further research is required to document biomarkers specific to HRS.

Association of AKI with mortality and complications in hospitalized patients with cirrhosis.

UNLABELLED: Acute kidney injury (AKI) is a common and devastating complication in patients with cirrhosis. However, the definitions of AKI employed in studies involving patients with cirrhosis have not been standardized, lack sensitivity, and are often limited to narrow clinical settings. We conducted a multicenter, prospective observational cohort study of patients with cirrhosis and AKI, drawn from multiple hospital wards, utilizing the modern acute kidney injury network (AKIN) definition and assessed the association between AKI severity and progression with in-hospital mortality. Of the 192 patients who were enrolled and included in the study, 85 (44%) progressed to a higher AKIN stage after initially fulfilling AKI criteria. Patients achieved a peak severity of AKIN stage 1, 26%, stage 2, 24%, and stage 3, 49%. The incidence of mortality, general medical events (bacteremia, pneumonia, urinary tract infection), and cirrhosis-specific complications (ascites, encephalopathy, spontaneous bacterial peritonitis) increased with severity of AKI. Progression was significantly more common and peak AKI stage higher in nonsurvivors than survivors (P < 0.0001). After adjusting for baseline renal function, demographics, and critical hospital- and cirrhosis-associated variables, progression of AKI was independently associated with mortality (adjusted odds ratio = 3.8, 95% confidence interval 1.3-11.1). CONCLUSION: AKI, as defined by AKIN criteria, in patients with cirrhosis is frequently progressive and severe and is independently associated with mortality in a stage-dependent fashion. Methods for earlier diagnosis of AKI and its progression may result in improved outcomes by facilitating targeted and timely treatment of AKI.

Cerebrovascular accident secondary to paradoxical embolism following arteriovenous graft thrombectomy.

Thrombectomy is a common procedure performed to declot thrombosed dialysis arteriovenous fistula (AVF) or arteriovenous graft (AVG). Complications associated with access thrombectomy like pulmonary embolism have been reported, but paradoxical embolism is extremely rare. We report a case of a 74-year-old black man with past medical history significant for end-stage renal disease (ESRD), atrial fibrillation on anticoagulation with warfarin, who presented to our hospital with lethargy, aphasia, and right-sided hemiparesis following thrombectomy of a clotted AVG. Computed tomography (CT) scan of brain showed a hypodensity within the left posterior parietal lobe. INR was 2.0 on admission. Echocardiogram revealed a normal sized left atrium with no intracardiac thrombus, and bubble study showed the presence of right-to-left shunting. These findings suggest that the stroke occurred as a result of an embolus originating from the AVG. Paradoxical cerebral embolism is uncommon but can occur after thrombectomy of clotted vascular access in ESRD patients. Clinicians and patients should be aware of this serious and potentially fatal complication of vascular access procedure.

Cardiac Arrest Secondary to Bilateral Pulmonary Emboli following Arteriovenous Fistula Thrombectomy: A Case Report with Review of the Literature.

Number of patients with End Stage Renal Disease (ESRD) is growing worldwide. Hemodialysis remains the main modality of renal replacement therapy for ESRD patients. A patent hemodialysis access (arteriovenous fistula or arteriovenous graft) plays a key role in successful delivery of hemodialysis. Common vascular access issues encountered by patients and nephrologists are thrombosis and infection. The thrombosed access is declotted by various percutaneous techniques these days by multiple outpatient access centers in a timely fashion. Thrombolysis can give rise to various complications, a few of which can be life threatening. A young hemodialysis patient underwent percutaneous thrombolysis of his clotted arteriovenous fistula. Outpatient access thrombectomy was complicated immediately afterwards with cardiac arrest requiring cardiac resuscitation in the recovery room. The patient was admitted to intensive care unit after life sustaining care. Work up revealed multiple pulmonary emboli to both lung fields on CT scan of the chest. Patient was anticoagulated and discharged from the hospital. Thrombolysis of clotted hemodialysis access is associated commonly with occurrences of pulmonary embolic which are usually asymptomatic. Massive pulmonary embolization due to access thrombolysis is rare. Nephrologists and radiologists should be aware of this dangerous complication particularly in patients with preexisting cardiopulmonary disease.

Peritoneal dialysis in renal replacement therapy for patients with acute kidney injury.

Peritoneal dialysis (PD) was the first modality used for renal replacement therapy (RRT) of patients with acute kidney injury (AKI) because of its inherent advantages as compared to Hemodialysis. It provides the nephrologist with nonvascular alternative for renal replacement therapy. It is an inexpensive modality in developing countries and does not require highly trained staff or a complex apparatus. Systemic anticoagulation is not needed, and it can be easily initiated. It can be used as continuous or intermittent procedure and, due to slow fluid and solute removal, helps maintain hemodynamic stability especially in patients admitted to the intensive care unit. PD has been successfully used in AKI involving patients with hemodynamic instability, those at risk of bleeding, and infants and children with AKI or circulatory failure. Newer continuous renal replacement therapies (CRRTs) are being increasingly used in renal replacement therapy of AKI with less use of PD. Results of studies comparing newer modalities of CRRT versus acute peritoneal dialysis have been conflicting. PD is the modality of choice in renal replacement therapy in pediatric patients and in patients with AKI in developing countries.

Acute renal failure in an AIDS patient on tenofovir: a case report.

INTRODUCTION: Tenofovir is a potent nucleotide analogue reverse-transcriptase inhibitor used with other antiretroviral agents for the treatment of human immunodeficiency virus (HIV) infection. Despite the absence of renal toxicity observed in the major clinical trials of tenofovir, several case reports of acute renal failure (ARF) and proximal tubule dysfunction have been described. CASE PRESENTATION: We report a patient who developed ARF and Fanconi syndrome during treatment with tenofovir. Despite severe metabolic acidosis associated with a creatinine of 9.8 mg/dL (866 mumol/L), this patient's condition improved on discontinuation of tenofovir treatment without requiring renal replacement therapy. CONCLUSION: Vigilant screening of kidney function is required regularly after initiation of tenofovir due to possible appearance of renal failure.