Andrew S. Allegretti

Continuous renal replacement therapy outcomes in acute kidney injury and end-stage renal disease: a cohort study

IntroductionContinuous renal replacement therapy (CRRT) is a widely used but resource-intensive treatment. Despite its broad adoption in intensive care units (ICUs), it remains challenging to identify patients who would be most likely to achieve positive outcomes with this therapy and to provide realistic prognostic information to patients and families.MethodsWe analyzed a prospective cohort of all 863 ICU patients initiated on CRRT at an academic medical center from 2008 to 2011 with either new-onset acute kidney injury (AKI) or pre-admission end-stage renal disease (ESRD). We examined in-hospital and post-discharge mortality (for all patients), as well as renal recovery (for AKI patients). We identified prognostic factors for both in-hospital and post-discharge mortality separately in patients with AKI or ESRD.ResultsIn-hospital mortality was 61% for AKI and 54% for ESRD. In patients with AKI (n = 725), independent risk factors for mortality included age over 60 (OR 1.9, 95% CI 1.3, 2.7), serum lactate over 4 mmol/L (OR 2.2, 95% CI 1.5, 3.1), serum creatinine over 3 mg/dL at time of CRRT initiation (OR 0.63, 95% CI 0.43, 0.92) and comorbid liver disease (OR 1.75, 95% CI 1.1, 2.9). Among patients with ESRD (n = 138), liver disease was associated with increased mortality (OR 3.4, 95% CI 1.1, 11.1) as was admission to a medical (vs surgical) ICU (OR 2.2, 95% CI 1.1, 4.7). Following discharge, advanced age became a predictor of mortality in both groups (AKI: HR 1.9, 95% CI 1.2, 3.0; ESRD: HR 4.1, 95% CI 1.5, 10.9). At the end of the study period, only 25% (n = 183) of patients with AKI achieved dialysis-free survival.ConclusionsAmong patients initiating CRRT, risk factors for mortality differ between patients with underlying ESRD or newly acquired AKI. Long-term dialysis-free survival in AKI is low. Providers should consider these factors when assessing prognosis or appropriateness of CRRT.

Prognosis of acute kidney injury and hepatorenal syndrome in patients with cirrhosis: A prospective cohort study

Background/Aims. Acute kidney injury is a common problem for patients with cirrhosis and is associated with poor survival. We aimed to examine the association between type of acute kidney injury and 90-day mortality. Methods. Prospective cohort study at a major US liver transplant center. A nephrologists review of the urinary sediment was used in conjunction with the 2007 Ascites Club Criteria to stratify acute kidney injury into four groups: prerenal azotemia, hepatorenal syndrome, acute tubular necrosis, or other. Results. 120 participants with cirrhosis and acute kidney injury were analyzed. Ninety-day mortality was 14/40 (35%) with prerenal azotemia, 20/35 (57%) with hepatorenal syndrome, 21/36 (58%) with acute tubular necrosis, and 1/9 (11%) with other (p = 0.04 overall). Mortality was the same in hepatorenal syndrome compared to acute tubular necrosis (p = 0.99). Mortality was lower in prerenal azotemia compared to hepatorenal syndrome (p = 0.05) and acute tubular necrosis (p = 0.04). Ten participants (22%) were reclassified from hepatorenal syndrome to acute tubular necrosis because of granular casts on urinary sediment. Conclusions. Hepatorenal syndrome and acute tubular necrosis result in similar 90-day mortality. Review of urinary sediment may add important diagnostic information to this population. Multicenter studies are needed to validate these findings and better guide management.

Calciphylaxis: A Rare But Fatal Delayed Complication of Roux-en-Y Gastric Bypass Surgery

Gastric bypass is a commonly used surgical procedure that has shown impressive health benefits for patients with morbid obesity. However, mineral bone abnormalities (hypocalcemia, hypovitaminosis D, and secondary hyperparathyroidism) and micronutrient (e.g., iron) deficiencies are common complications after gastric bypass surgery due to alterations in the digestive anatomy. These abnormalities, their treatments, and a number of other factors associated with obesity can set up a perfect storm to induce calciphylaxis, a rare but highly fatal condition with severe comorbid conditions. We present a fatal case of nonuremic calciphylaxis coincident with symptomatic hypocalcemia in a morbidly obese man with a history of Roux-en-Y gastric bypass surgery.

Counseling potential donors to the risk of ESRD after kidney donation: glass half-full or half-empty?

Living kidney donation accounts for about 6000 kidney transplants in the United States annually (1). While it is important to quantify risks to potential donors, studies examining donor outcomes are limited and the appropriate control group is debatable. In 2009, Ibrahim et al (2) reported, in a single center study, 11 cases of end-stage renal disease (ESRD) out of 3698 donors between 1963 and 2007 (rate of 0.3%). Though not matched directly to a healthy cohort, they reported similar rates of ESRD compared to the general population. Nephrologists have long craved a large-scale comparison study to help counsel potential donors about the risk of ESRD.

Prognosis of Patients with Cirrhosis and AKI Who Initiate RRT

BACKGROUND AND OBJECTIVES Literature on the prognosis of patients with cirrhosis who require RRT for AKI is sparse and is confounded by liver transplant eligibility. An update on outcomes in the nonlisted subgroup is needed. Our objective was to compare outcomes in this group between those diagnosed with hepatorenal syndrome and acute tubular necrosis, stratifying by liver transplant listing status. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Retrospective cohort study of patients with cirrhosis acutely initiated on hemodialysis or continuous RRT at five hospitals, including one liver transplant center. Multivariable regression and survival analysis were performed. RESULTS Four hundred seventy-two subjects were analyzed (341 not listed and 131 listed for liver transplant). Among nonlisted subjects, 15% (51 of 341) were alive at 6 months after initiating RRT. Median survival was 21 (interquartile range [IQR], 8, 70) days for those diagnosed with hepatorenal syndrome and 12 (IQR, 3, 43) days for those diagnosed with acute tubular necrosis (P=0.25). Among listed subjects, 48% (63 of 131) received a liver transplant. Median transplant-free survival was 15 (IQR, 5, 37) days for those diagnosed with hepatorenal syndrome and 14 (IQR, 4, 31) days for those diagnosed with acute tubular necrosis (P=0.60). When stratified by transplant listing, with adjusted Cox models we did not detect a difference in the risk of death between hepatorenal syndrome and acute tubular necrosis (hazard ratio [HR], 0.81; 95% confidence interval [95% CI], 0.59 to 1.11, among those not listed; HR, 0.73; 95% CI, 0.44 to 1.19, among those listed). CONCLUSIONS Cause of AKI was not significantly associated with mortality in patients with cirrhosis who required RRT. Among those not listed for liver transplant, mortality rates were extremely high in patients both with hepatorenal syndrome and acute tubular necrosis. PODCAST This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2017_11_09_CJASNPodcast_18_1_A.mp3.

The Effect of Bicarbonate Administration via Continuous Venovenous Hemofiltration on Acid-Base Parameters in Ventilated Patients

Background. Acute kidney injury (AKI) and metabolic acidosis are common in the intensive care unit. The effect of bicarbonate administration on acid-base parameters is unclear in those receiving continuous venovenous hemofiltration (CVVH) and mechanical ventilatory support. Methods. Metabolic and ventilatory parameters were prospectively examined in 19 ventilated subjects for up to 96 hours following CVVH initiation for AKI at an academic tertiary care center. Mixed linear regression modeling was performed to measure changes in pH, partial pressure of carbon dioxide (pCO2), serum bicarbonate, and base excess over time. Results. During the 96-hour study period, pCO2 levels remained stable overall (initial pCO2 42.0 ± 14.6 versus end-study pCO2 43.8 ± 16.1 mmHg; P = 0.13 for interaction with time), for those with initial pCO2 ≤40 mmHg (31.3 ± 5.7 versus 35.0 ± 4.8; P = 0.06) and for those with initial pCO2 >40 mmHg (52.7 ± 12.8 versus 53.4 ± 19.2; P = 0.57). pCO2 decreased during the immediate hours following CVVH initiation (42.0 ± 14.6 versus 37.3 ± 12.6 mmHg), though this change was nonsignificant (P = 0.052). Conclusions. We did not detect a significant increase in pCO2 in response to the administration of bicarbonate via CVVH in a ventilated population. Additional studies of larger populations are needed to confirm this finding.

Classifying Fecal Microbiota Transplantation Failure: An Observational Study Examining Timing and Characteristics of Fecal Microbiota Transplantation Failures

&NA; Fecal microbiota transplantation (FMT) is an effective treatment for recurrent Clostridium difficile infection (rCDI), with cure rates higher than 80%.1–3 FMT failure is defined as diarrhea and a positive stool laboratory test for C difficile at any point during the 8‐week follow‐up period after FMT.4

Epidemiology: Chronic disease, cancer, and exercise — a common link

Advances in precision medicine have greatly improved outcomes for patients with cancer. New findings that demonstrate a substantial contribution of major chronic diseases and disease markers to the risk of cancer incidence and mortality highlight the impact of chronic disease on cancer risk and suggest that chronic diseases should be targeted in cancer prevention strategies.

Serum Angiopoietin‐2 Predicts Mortality and Kidney Outcomes in Decompensated Cirrhosis

Acute kidney injury in decompensated cirrhosis has limited therapeutic options, and novel mechanistic targets are urgently needed. Angiopoietin‐2 is a context‐specific antagonist of Tie2, a receptor that signals vascular quiescence. Considering the prominence of vascular destabilization in decompensated cirrhosis, we evaluated Angiopoietin‐2 to predict clinical outcomes. Serum Angiopoietin‐2 was measured serially in a prospective cohort of hospitalized patients with decompensated cirrhosis and acute kidney injury. Clinical characteristics and outcomes were examined over a 90‐day period and analyzed according to Angiopoietin‐2 levels. Primary outcome was 90‐day mortality. Our study included 191 inpatients (median Angiopoietin‐2 level 18.2 [interquartile range 11.8, 26.5] ng/mL). Median Model for End‐Stage Liver Disease (MELD) score was 23 [17, 30] and 90‐day mortality was 41%. Increased Angiopoietin‐2 levels were associated with increased mortality (died 21.9 [13.9, 30.3] ng/mL vs. alive 15.2 [9.8, 23.0] ng/mL; P < 0.001), higher Acute Kidney Injury Network stage (stage I 13.4 [9.8, 20.1] ng/mL vs. stage II 20.0 [14.1, 26.2] ng/mL vs. stage III 21.9 [13.0, 29.5] ng/mL; P = 0.002), and need for renal replacement therapy (16.5 [11.3, 23.6] ng/mL vs. 25.1 [13.3, 30.3] ng/mL; P = 0.005). The association between Angiopoietin‐2 and mortality was significant in unadjusted and adjusted Cox regression models (P ≤ 0.001 for all models), and improved discrimination for mortality when added to MELD score (integrated discrimination increment 0.067; P = 0.001). Conclusion: Angiopoietin‐2 was associated with mortality and other clinically relevant outcomes in a cohort of patients with decompensated cirrhosis with acute kidney injury. Further experimental study of Angiopoietin/Tie2 signaling is warranted to explore its potential mechanistic and therapeutic role in this population.

Case 12-2017 — A 34-Year-Old Man with Nephropathy

A 34-year-old man presented with worsening renal function. Eleven weeks earlier, fever, fatigue, and decreased appetite had developed. A urinalysis showed proteinuria, and imaging studies revealed nephromegaly. An additional diagnostic procedure was performed.