July/August 2018: Abstract Roundup


Renal Resistive Index as Early Biomarker of AKI

Journal of Cardiothoracic and Vascular Anesthesia. doi.org/10.1053/j.jvca.2018.04.014

Renal resistive index (RRI), determined by intraoperative Doppler, seems to be a promising early biomarker of acute kidney injury (AKI). As RRI is studied, the ease, efficiency, and precision with which it can be interpreted will be linked to its clinical usefulness and robustness. Benjamin Y. Andrew, MHS, RD, and colleagues conducted a study to examine the usefulness of computer vision technology in developing an automated algorithm to estimate RRI, with equivalent reliability and reproducibility to human experts.

The retrospective study was conducted at a single-center university hospital and included adult cardiac surgery patients from July 1, 2013, to July 10, 2014, with intraoperative transesophageal echocardiography-determined renal blood flow measurement.

Renal Doppler waveforms were retrospectively obtained and assessed by blinded human expert raters. A total of 430 images were divided into development and validation cohorts. Using computer vision techniques, an algorithm for automated RRI analysis was built and tuned for alignment with experts using bootstrap resampling in the development cohort. The algorithm was then applied to the validation cohort.

Waveform analysis time per image averaged 0.144 seconds. By interclass correlation coefficient and in Bland-Altman analysis, agreement was excellent (0.939; 95% confidence interval [CI], 0.921-0.953; and –0.0015; 95% CI, –0.0054 to 0.0024, respectively).

The analysis “confirmed the value of computer vision technology to develop an algorithm for RRI estimation from automatically processed intraoperative renal Doppler waveforms. This simple-to-use and efficient tool further adds to the clinical and research value of RRI, already the ‘earliest’ among several early AKI biomarkers being assessed,” the authors said.


Trends in Outcomes of D-AKI among Heart Failure Hospitalizations

Journal of Cardiac Failure. doi.org/10.1016/j.cardfail.2018.05.001

Patients hospitalized with heart failure often develop dialysis-requiring acute kidney injury (D-AKI); however, according to Ashish Correa, MD, there are no data on national trends after 2002. Dr. Correa and colleagues utilized the Nationwide Inpatient Sample (2002-2013) to identify hospitalizations for heart failure with and without D-AKI, and analyzed trends in incidence, in-hospital mortality, length of stay, and associated costs.

The analysis included 11,205,743 hospitalizations for heart failure. During the period 2002-2013, the incidence of D-AKI doubled (0.51% to 1.09%). Independent predictors of D-AKI in heart failure hospitalizations were male sex, younger age, African-American and Hispanic race, and comorbidities and procedures such as sepsis and the need for mechanical ventilation.

There was an association between D-AKI and higher odds of both in-hospital mortality (adjusted odds ratio [aOR], 2.49; 95% confidence interval [CI], 2.36-2.63; P<.01) and adverse discharge (discharge to skilled nursing facility or nursing home) (aOR, 2.04; 95% CI, 1.95-2.13; P<.01). During the study period, in-hospital mortality and risk of mortality due to D-AKI decreased, as did length of stay and costs.

“The incidence of D-AKI in heart failure hospitalizations doubled across 2003-2013. Despite declining in-hospital mortality, length of stay, and cost, D-AKI was associated with worse outcomes,” the researchers concluded.



Risk Factors for CKD Progression Modeled with Time-Centered Approach

Clinical Journal of the American Society of Nephrology. 2018;13(5):693-701

In modeling risk of progression of chronic kidney disease (CKD), traditional methods do not include estimates of the time it takes for progression to occur. Elaine Ku, MD, and colleagues conducted an analysis to estimate median time spent in each of CKD stages 3a to 5 and ways the time differs according to risk factors associated with CKD progression. The study included 3682 participants in the Chronic Renal Insufficiency cohort in mixed models to estimate person-specific trajectories of function. The trajectories were then used to estimate time spent in each CKD stage.

Median follow-up was 9.5 years. During follow-up, participants spend longer in earlier CKD stages, ranging from a median of 7.9 years in stage 3a to 0.8 years in stage 5. In earlier stages of disease, there was an association between known risk factors for CKD progression and larger differences in time until progression to the next stage: compared with those with proteinuria <1 g/g, proteinuria ≥1 g/g was associated with 8 years shorter time spent in stage 3a, 5.6 years shorter time in stage 3b, but only 6 months shorter time in stage 5.

“There are marked variations in the time spent in the different stages of CKD, according to risk factors and stage of disease,” the researchers concluded.



Risks of Significant Kidney Events with Add-On Hypertensive Medications

Clinical Journal of the American Society of Nephrology. 2018;13(5):727-734

There are few data regarding the comparative effectiveness of add-on hypertensive medications added to an angiotensin-converting enzyme (ACE) inhibitor or angiotensin II receptor blocker (ARB) in individuals with diabetes on the risk of significant kidney events.

Emily B. Schroeder, MD, and colleagues conducted an observational multicenter study of 21,897 individuals with diabetes to compare those who added beta-blockers, dihydropyridine calcium channel blockers, loop diuretics, or thiazide diuretics to a regimen that included ACE inhibitors or ARBs. Using Cox proportional hazard models with propensity score weighting, the study examined the hazard of significant kidney events, cardiovascular events, and death.

The composite significant kidney event was the first occurrence of a ≥30% decline in estimated glomerular filtration rate (eGFR) to an eGFR <60 mL/min/1.73 m2, dialysis initiation, or kidney transplant.

Over a maximum of 5 years, there were 4707 significant kidney events, 1498 deaths, and 818 cardiovascular events. Compared with thiazide diuretics, hazard ratios for significant kidney events for beta blockers, calcium channel blockers, and loop diuretics were 0.81 (95% confidence interval [CI], 0.74-0.89), 0.67 (95% CI, 0.58-0.78), and 1.19 (95% CI, 1.00-1.41), respectively. Hazard ratios for mortality were 1.19 (95% CI, 0.97-1.44), 0.73 (95% CI, 0.52-1.03), and 1.67 (95% CI, 1.31-2.13), respectively, compared with thiazide diuretics. Also compared with thiazide diuretics, hazard ratios for cardiovascular events were 1.65 (95% CI, 1.39-1.96), 1.05 (95% CI, 0.80-1.39), and 1.55 (95% CI, 1.05-2.27), respectively.

In conclusion, the researchers said, “Compared with thiazide diuretics, calcium channel blockers were associated with a lower risk of significant kidney events and a similar risk of cardiovascular events.”



Risks Associated with Opioid Use in Patients on Hemodialysis

Clinical Journal of the American Society of Nephrology. 2018;13(5):746-753

Despite frequent pain experienced by patients on hemodialysis, and the resulting risk of opioid-related complications, there are limited data on assessments of the risks of opioid use among that patient population. Utilizing data form the US Renal Data System, Julie H. Ishida, MD, and colleagues conducted a cohort study to determine the association between opioid use and time to first visit to the emergency department or hospitalization for altered mental status, fall, and fracture. The cohort included 140,899 Medicare beneficiary adults on maintenance hemodialysis in 2011. Risk was evaluated according to average daily total opioid use (>60 mg, ≤60 mg, and per 60-mg dose increment), and specific agents (per 60-mg dose increment).

Median age of the cohort was 61 years, 52% were men, and 50% were white. Overall, 64% received opioids, and 17% had an episode of altered mental status (15,568 events), fall (7646 events), or fracture (4151 events) in 2011. There was an association between opioid use for all outcomes in a dose-dependent manner. There was an association between all agents and a significantly higher hazard of altered mental status; there was also an association between several agents and a significantly higher hazard of fall and fracture.

“Opioids were associated with adverse outcomes in patients on hemodialysis, and this risk was present even at lower dosing and for agents that guidelines have recommended for use,” the researchers said



Biomarkers Predict AKI Progression in Children

Journal of the American Society of Nephrology. 2018;29(5):1549-1556

The risk for adverse outcomes in children with acute kidney injury (AKI) increases dramatically with progression to higher stages of AKI. Currently, there are no reliable methods to aid in prediction of progression of AKI among hospitalized children. Jason H. Greenberg, MD, and colleagues conducted a prospective cohort study designed to determine whether biomarkers of inflammation and kidney injury predict AKI progression. The study was conducted at three centers among children undergoing cardiopulmonary bypass.

Urine biomarkers were measured on the first day of AKI as defined by serum creatinine. AKI progression was defined as a worsening of AKI stage or stage 3 AKI for ≥2 consecutive days.

Of the 408 children in the study cohort, 43% (n=176) developed postoperative AKI. Of those patients, 145 had stage 1 AKI, 25 had stage 2 AKI, and six had stage 3 AKI on the first day of AKI diagnosis. A total of 28 (7%) had AKI progression.

On the first day of AKI, in patients with AKI progression, nine of the 17 biomarkers of interest were significantly higher than in patients without AKI progression. Of the injury biomarkers, urine liver fatty acid binding protein had the highest discrimination for AKI progression (optimism-corrected area under the curve [AUC], 0.70; 95% confidence interval [CI], 0.58-0.81); of the inflammatory biomarkers, plasma IL-8 had the highest discrimination (optimism-corrected AUC, 0.80; 95% CI, 0.69-0.91).

In conclusion, the researchers said, “If validated in additional cohorts, plasma IL-8 could be used to improve clinical care and guide enrollment in therapeutic trials of AKI.”


Predictors of Risk of Dialysis in First Year of Life in ARPKD Patients

Journal of Pediatrics. doi.org.10.1016/j.jpeds.2018.03.052

To identify a basis for parental counseling following prenatal and perinatal diagnosis of autosomal recessive polycystic kidney disease (ARPKD), Kathrin Burgmaier, MD, and colleagues conducted an analysis to examine the prenatal, perinatal, and postnatal risk factors for dialysis within the first year of life in children with ARPKD. The analysis utilized a dataset of 385 patients from the ARegPKD international registry.

Of the 385 children, 9.4% (n=36) began dialysis in the first year of life. Results of multivariable Cox regression analysis showed an independent association between the presence of oligohydramnios or anhydramnios, prenatal kidney enlargement, low Apgar score, and the need for postnatal breathing support and an increased hazard ratio for the need for dialysis within the first year of life. The association with the Apgar score and with perinatal assisted breathing was time-dependent and was not present after 5 and 8 months of life, respectively.

“This study, which identified risk factors associated with onset of dialysis in ARPKD in the first year of life may be helpful in prenatal parental counseling in cases of suspected ARPKD,” the researchers concluded.


AKI in the Pediatric ICU and Subsequent Use of Health Services

Clinical Journal of the American Society of Nephrology. 2018;13(5):685-692

There are few data available on the long-term burden of acute kidney injury (AKI) in the pediatric intensive care unit. Erin Hessey, MSc, and colleagues conducted a retrospective cohort study designed to determine whether there is an association between pediatric AKI and higher use of health services following hospital discharge.

Children ≤18 years of age admitted to two tertiary centers in Montreal, Canada, were included in the study; only data from the first admission per patient was analyzed. AKI was defined using (1) serum creatinine alone or (2) serum creatinine and/or urine output. Outcomes of interest were 30-day, 1-year, and 5-year hospitalizations, emergency department visits, and physician visits per person-time using provincial administrative data.

The study included a total of 2041 children; 56% were male and mean age at admission was 6.5 years. Using the AKI definition of serum creatinine alone, 299 of 1575 (19%) developed AKI. When urine output was included in the definition of AKI, 355 of 1622 (22%) children developed AKI. There was an association between both AKI defined using serum creatinine alone and serum creatinine and urine output and higher 1- and 5-year hospitalization risk and higher 5-year physician visits. Following adjustments, there was no association between AKI and emergency department use.

In conclusion, the researchers said, “AKI is independently associated with higher hospitalizations and physician visits postdischarge.”



Infection-Related Mortality Following Kidney Transplantation

Clinical Journal of the American Society of Nephrology. 2018;13(5):755-762

Following kidney transplantation, the most common noncardiovascular causes of death are infections. Susanna Kinnunen, MD, and colleagues conducted a study to analyze the current infection-related mortality rate in kidney transplant recipients in a nationwide cohort in Finland.

The cohort included 3249 adults who underwent first kidney transplant from 1990 to 2012. The researchers analyzed infectious causes of death, and compared mortality rates for infection between 1990-1999 and 2000-2012. Cox regression and competing risk analyses were utilized to examine risk factors for infection-related deaths.

During follow-up, 953 patients (29%) died, with 204 infection-related deaths. In the more recent cohort, the mortality rate per 1000 patient-years due to infections was lower compared with the 1990-1999 cohort (4.6; 95% confidence interval [CI], 3.5-6.1 vs 9.1, 95% CI, 7.6-10.7). The incidence rate ratio of infectious death was 0.51 (95% CI, 0.30-0.68).

Bacterial infections were the main causes of infectious deaths: septicemia in 38% and pulmonary infections in 45%. Two percent of infectious deaths were caused by viral infections and 3% by fungal infections. In multivariable analyses, there was an association between older recipient age, higher plasma creatinine concentration at the end of the first year post-transplant, diabetes as a cause of end-stage kidney disease, longer duration of pre-transplant dialysis, acute rejection, low albumin level, and earlier era of transplantation and increased risk of infection-related mortality.

The researchers said, “The risk of death due to infectious causes after kidney transplantation in Finland dropped by one half since the 1990s. Common bacterial infections remained the most frequent cause of infection-related mortality, whereas opportunistic viral, fungal, or unconventional bacterial infections rarely caused deaths after kidney transplantation.”