Nithin Karakala

Urinary Angiotensinogen and Risk of Severe AKI

BACKGROUND Biomarkers of AKI that can predict which patients will develop severe renal disease at the time of diagnosis will facilitate timely intervention in populations at risk of adverse outcomes. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Liquid chromatography/tandem mass spectrometry was used to identify 30 potential prognostic urinary biomarkers of severe AKI in a group of patients that developed AKI after cardiac surgery. Angiotensinogen had the best discriminative characteristics. Urinary angiotensinogen was subsequently measured by ELISA and its prognostic predictive power was verified in 97 patients who underwent cardiac surgery between August 1, 2008 and October 6, 2011. RESULTS The urine angiotensinogen/creatinine ratio (uAnCR) predicted worsening of AKI, Acute Kidney Injury Network (AKIN) stage 3, need for renal replacement therapy, discharge >7 days from sample collection, and composite outcomes of AKIN stage 2 or 3, AKIN stage 3 or death, and renal replacement therapy or death. The prognostic predictive power of uAnCR was improved when only patients classified as AKIN stage 1 at the time of urine sample collection (n=79) were used in the analysis, among whom it predicted development of stage 3 AKI or death with an area under the curve of 0.81. Finally, category free net reclassification improvement showed that the addition of uAnCR to a clinical model to predict worsening of AKI improved the predictive power. CONCLUSIONS Elevated uAnCR is associated with adverse outcomes in patients with AKI. These data are the first to demonstrate the utility of angiotensinogen as a prognostic biomarker of AKI after cardiac surgery.

Association of elevated urinary concentration of renin-angiotensin system components and severe AKI.

BACKGROUND Prognostic biomarkers that predict the severity of AKI at an early time point are needed. Urinary angiotensinogen was recently identified as a prognostic AKI biomarker. The study hypothesis is that urinary renin could also predict AKI severity and that in combination angiotensinogen and renin would be a strong predictor of prognosis at the time of AKI diagnosis. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS In this multicenter, retrospective cohort study, urine was obtained from 204 patients who developed AKI after cardiac surgery from August 2008 to June 1, 2012. All patients were classified as having Acute Kidney Injury Network (AKIN) stage 1 disease by serum creatinine criteria at the time of sample collection. Urine output was not used for staging. Urinary angiotensinogen and renin were measured, and the area under the receiver-operating characteristic curve (AUC) was used to test for prediction of progression to AKIN stage 3 or in-hospital 30-day mortality. These biomarkers were added stepwise to a clinical model, and improvement in prognostic predictive performance was evaluated by category free net reclassification improvement (cfNRI) and chi-squared automatic interaction detection (CHAID). RESULTS Both the urinary angiotensinogen-to-creatinine ratio (uAnCR; AUC, 0.75; 95% confidence interval [CI], 0.65 to 0.85) and the urinary renin-to-creatinine ratio (uRenCR; AUC, 0.70; 95% CI, 0.57 to 0.83) predicted AKIN stage 3 or death. Addition of uAnCR to a clinical model substantially improved prediction of the outcome (AUC, 0.85; cfNRI, 0.673), augmenting sensitivity and specificity. Further addition of uRenCR increased the sensitivity of the model (cfNRI(events), 0.44). CHAID produced a highly accurate model (AUC, 0.91) and identified the combination of uAnCR >337.89 ng/mg and uRenCR >893.41 pg/mg as the strongest predictors (positive predictive value, 80.4%; negative predictive value, 90.7%; accuracy, 90.2%). CONCLUSION The combination of urinary angiotensinogen and renin predicts progression to very severe disease in patients with early AKI after cardiac surgery.

Urinary angiotensinogen predicts adverse outcomes among acute kidney injury patients in the intensive care unit

IntroductionAcute kidney injury (AKI) is commonly observed in the intensive care unit (ICU), where it can be caused by a variety of factors. The objective of this study was to evaluate the prognostic value of urinary angiotensinogen, a candidate prognostic AKI biomarker identified in post-cardiac surgery patients, in this heterogeneous population.MethodsUrinary angiotensinogen was measured by ELISA and corrected for urine creatinine in 45 patients who developed AKI in the ICU. Patients were grouped by AKI etiology, and the angiotensinogen-to-creatinine ratio (uAnCR) was compared among the groups using the Kruskal-Wallis test. The ability of uAnCR to predict the following endpoints was tested using the area under the ROC curve (AUC): the need for renal replacement therapy (RRT) or death, increased length of stay (defined as hospital discharge > 7 days or death ≤ 7 days from sample collection), and worsening AKI (defined as an increase in serum creatinine > 0.3 mg/dL after sample collection or RRT).ResultsuAnCR was significantly elevated in patients who met the composite outcome RRT or death (89.4 vs 25.4 ng/mg; P = 0.01), and it was a strong predictor of this outcome (AUC = 0.73). Patients with uAnCR values above the median for the cohort (55.21 ng/mg) had increased length of stay compared to patients with uAnCR ≤ 55.21 ng/mg (22 days vs 7 days after sample collection; P = 0.01). uAnCR was predictive of the outcome increased length of stay (AUC = 0.77). uAnCR was also a strong predictor of worsening of AKI (AUC = 0.77). The uAnCR of patients with pre-renal AKI was lower compared to patients with AKI of other causes (median uAnCR 11.3 vs 80.2 ng/mg; P = 0.02).ConclusionsElevated urinary angiotensinogen is associated with adverse events in AKI patients in the ICU. It could be used to identify high risk patients who would benefit from timely intervention that could improve their outcomes.

Intravenous fluids in sepsis: what to use and what to avoid.

Purpose of reviewSeptic shock is one of the most common and life-threatening conditions afflicting critically ill patients. Intravenous volume resuscitation is considered an initial and very important step in management. The most suitable fluid for volume expansion during septic shock remains unclear. In this review, we focus on the benefits and adverse effects of the most commonly used intravenous fluids in critically ill septic patients. Recent findingsThe debate about the benefits of colloids over crystalloids has been ongoing for the last few decades. With recent literature showing apparent harm from the use of hydroxyethyl starches (HESs), and given the growing concerns of adverse renal and acid–base abnormalities associated with 0.9% saline compared with balanced crystalloid solutions, it may be time to change the nature of the ‘fluid debate’. SummaryCrystalloids should still be considered as the first-choice drug for volume resuscitation in patients with septic shock. Colloids such as albumin can be considered in some clinical settings. HES should be avoided. Balanced crystalloids might have an important role to play in the management of septic shock.

Peritonitis from Mycobacterium wolinskyi in a chronic peritoneal dialysis patient.

We report the case of acute peritonitis caused by a rapidly growing mycobacterium in a chronic peritoneal dialysis patient, whose renal failure had been caused by diabetic glomerulosclerosis. The organism cultured from the peritoneal dialysis fluid was Mycobacterium wolinskyi. Peritonitis caused by M. wolinskyi in a chronic peritoneal dialysis patient has never been reported before.

Continuous Renal Replacement Therapy: Reviewing Current Best Practice to Provide High-Quality Extracorporeal Therapy to Critically Ill Patients

Continuous renal replacement therapy (CRRT) use continues to expand globally. Despite improving technology, CRRT remains a complex intervention. Delivery of high-quality CRRT requires close collaboration of a multidisciplinary team including members of the critical care medicine, nephrology, nursing, pharmacy, and nutrition support teams. While significant gaps in medical evidence regarding CRRT persist, the growing evidence base supports evolving best practice and consensus to define high-quality CRRT. Unfortunately, there is wide variability in CRRT operating characteristics and limited uptake of these best practices. This article will briefly review the current best practice on important aspects of CRRT delivery including CRRT dose, anticoagulation, dialysis vascular access, fluid management, and drug dosing in CRRT.

We Use Heparin as the Anticoagulant for CRRT.

Continuous Renal Replacement Therapy (CRRT) usually requires anticoagulation to prevent clotting of the extracorporeal circuit. Interruptions due to filter clotting significantly reduce total therapy time and CRRT efficacy. Although heparin has traditionally been the most common anticoagulant used for CRRT, increasing evidence suggests that heparin is less effective than regional citrate in prolonging circuit life and considerably increases patient bleeding risk. Advantages of regional citrate anticoagulation (RCA) include less bleeding, increased circuit life, and less blood transfusion requirement. RCA should be the anticoagulant of choice for CRRT.

Hepatorenal Acute Kidney Injury and the Importance of Raising Mean Arterial Pressure.

Background: The efficacy of vasoconstrictors in hepatorenal syndrome (HRS) is variable. We hypothesized that the effectiveness of vasoconstrictor therapy in improving kidney function ultimately relates to the magnitude of the achieved mean arterial pressure (MAP) increase. Methods: A retrospective study was conducted to identify cirrhotic individuals treated with vasoconstrictors for acute kidney injury (AKI) presumably caused by HRS to examine the relationship between change in MAP and change in serum creatinine (sCr) using multivariate mixed linear regression. Results: Among 73 patients treated with midodrine/octreotide, change in MAP inversely correlated with change in sCr (p = 0.0005). The quartile with the greatest increase in MAP (+15.9 to +29.4 mm Hg) was associated with a subsequent absolute decrease in sCr. The strength of the correlation increased when the analysis was restricted to those who met the HRS criteria (n = 27, p = 0.002), where the third (+5.3 to +15.6 mm Hg) and fourth (+15.9 to +20.9 mm Hg) quartiles of MAP change were associated with a decrease in sCr. A similar but stronger correlation was found among 14 patients treated with norepinephrine either after failing midodrine/octreotide (n = 10) or de novo (n = 4; p = 0.002), where a rise in MAP of +19.2 to 25 mm Hg was associated with a larger reduction in sCr. Associations remained significant after adjustment for baseline parameters. Conclusions: The magnitude of MAP rise during HRS therapy with midodrine/octreotide or norepinephrine correlated with a reduction in sCr concentration. Our results suggest that achieving a pre-specified target of MAP increase might improve renal outcomes in hepatorenal AKI.

Proteomic Analysis for Identification of Biomarkers that Predict Severe Acute Kidney Injury

The search for acute kidney injury (AKI) biomarkers has identified a number of urine proteins that can be used to predict the presence of AKI but has struggled to identify proteins that are prognostic for severe AKI. In this review, we discuss 2 currently available biomarkers and the designs of the studies in which they were identified and relate this to the AKI characteristics they predict clinically. We discuss recent advances in mass spectrometry and sample preparation, which have improved the ability to identify low abundance proteins as well as the ability to characterize more of the protein by mass spectrometry. We show how these changes can lead to a deeper and more thorough analysis of the urine proteome. Finally, we highlight 2 important issues that can help in the identification of these biomarkers, appropriate study design and adequate technical characteristics in the analysis.

Timing of Renal Replacement Therapy for Acute Kidney Injury

Acute kidney injury (AKI) is common in critically ill patients and associated with increased morbidity and mortality. With the increased use of renal replacement therapy (RRT) for severe AKI, the optimal time for initiation of RRT has become one of the most probed and debated topic in the field of nephrology and critical care. There appears to be an increased trend toward earlier initiation of RRT to avoid life-threatening complications associated with AKI. Despite the presence of a plethora of studies in this field, the lack of uniformity in study design, patient population types, definition of early and late initiation, modality of RRT, and results, the optimal time for starting RRT in AKI still remains unknown. The beneficial effects reported in observational studies have not been supported by clinical trials. Recently, 2 of the largest randomized control trials evaluating the timing of RRT in critically ill patients with AKI showed differing results. We provide an in-depth review of the available data on the timing of dialysis in patients with AKI.