September 2019 Abstract Roundup

Outpatient AKI More Prevalent than Inpatient AKI

Nephrology Dialysis Transplantation. 2019;34(3):493-501

There have been numerous studies of acute kidney injury (AKI) in the hospital setting; however, there are limited data on outcomes for patients with outpatient AKI. Maxwell D. Leither, MD, and colleagues conducted a retrospective study to examine whether outpatient AKI is associated with increased mortality and renal events. The study defined AKI as a 50% increase in creatinine.

Adult patients receiving primary care at a health system during an 18-month exposure period were stratified by outpatient serum creatinine values into one of five groups: no outpatient AKI; outpatient AKI with recovery; outpatient AKI without recovery; outpatient AKI without repeat creatinine measurement; and no creatinine measurement available. Cox proportional models were used to assess the principal outcomes of all-cause mortality and renal events (50% decline in estimated glomerular filtration rate to <30 mL/min/1.73 m2).

A total of 384,869 patients were eligible for inclusion in the study. Of those, 51% had at least one creatinine level measured during the exposure period. Outpatient AKI occurred in 1.4% of patients compared with occurrence of hospital AKI in only 0.3% of patients.

Average follow-up was 5.3 years. There was an association between outpatient AKI and an increased risk of all-cause mortality (adjusted hazard ratio [aHR], 1.90; 95% confidence interval [CI], 1.76-2.06). Results were consistent across all AKI groups. There was also an association between outpatient AKI and an increased risk of renal events (aHR, 1.33; 95% CI, 1.11-1.59). The risk remained in patients who recovered renal function.

In conclusion, the researchers said, “Outpatient AKI is more prevalent than inpatient AKI and is a risk factor for all-cause mortality and renal events, even among those who recovered kidney function. Further research is necessary to determine risk factors and identify strategies for preventing outpatient AKI.”

Higher Net Ultrafiltration Rate Associated with Lower Survival in Critically Ill Patients

JAMA Network Open. doi:10.1001/jamanetworkopen.2019.5418

More than two-thirds of critically ill patients with acute kidney injury (AKI) experience fluid overload, a complication that is independently associated with mortality. International practice guidelines recommend net ultrafiltration (NUF) in patients with fluid overload that is resistant to treatment with diuretics. Results from previous studies have suggested that NUF could reduce the number of deaths in that patient population. However, according to Raghavan Murugan, MD, MD, FRCP, and colleagues, there are few data available regarding the optimal rate of NUF in critically ill patients.

The RENAL (Randomized Evaluation of Normal vs Augmented Level) of Renal Replacement Therapy trial included 1434 patients with AKI being treated with continuous venovenous hemodiafiltration. Patients were stratified into three groups based on net ultrafiltration rates: high (NUF rate >1.75 mL/kg/h); middle (NUF rate from 1.01 to 1.75 mL/kg/h); and low (NUF rate <1.01 mL/kg/h).

There was no association with death from day 0 to day 6 in the high-tertile group compared with the low-tertile group. However, from day 7 to day 12, death occurred in 51 patients in the high-tertile group versus 30 patients in the low-tertile group. From day 13 to day 26, there were 45 deaths in the high-tertile group versus 25 in the low-tertile group; from day 27 to 90, there were 48 deaths in the high-tertile group versus 29 in the low-tertile group.

“Among critically ill patients, NUF rates >1.75 mL/kg/h compared with NUF rates <1.01 mL/kg/h were associated with lower survival. Residual confounding may be present from unmeasured risk factors, and randomized clinical trials are required to confirm these findings,” the researchers said.

Hepatitis A and Acute Kidney Injury

Advances in Chronic Kidney Disease. 2019;26(3):171-178

Due to targeted vaccination of children at risk for hepatitis A in the past decade, the disease is considered rare in the United States. According to Maria Andrievskaya, MD, and colleagues, evolving epidemiology has resulted in decreasing immunity and increased hepatitis A infections among adults who are more likely to experience severe disease. In the past 2 years, there has been a surge in cases of hepatitis A, associated with a high volume of hospitalizations related to hepatitis A and complications in otherwise healthy adults. The resurgence of hepatitis A is challenging the traditional understanding that acute kidney injury (AKI) is a rare extrahepatic manifestation among vulnerable patients. The researchers present a review of the epidemiologic factors that contributed to the current public health concern regarding prevalence of hepatitis A as well as the association between hepatitis A and AKI.


Advances in Management of ADPKD

Lancet. 2019;393(10184):919-935

The most common hereditary kidney disease is autosomal dominant polycystic kidney disease (ADPKD), a leading cause of end-stage renal disease. As evidenced by various clinical manifestations, including enlarged kidneys filled with growing cysts, hypertension, and multiple extrarenal complications such as liver cysts, intracranial aneurysms, and cardiac valvular disease, ADPKD is a systemic disorder. Emilie Cornec-Le Gall, MD, and colleagues provided a review of advances in the treatment of ADPKD.

Clinical research using molecular genetics and advanced imaging techniques has revealed new data and provided enhanced tools for diagnosis and prognosis for individual patients and their families.

Phase 3 randomized, placebo-controlled trials have examined management of ADPKD, resulting in the availability of a disease-modifying therapeutic drug for patients at high risk of disease progression. These trials have provided a basis for recommendations regarding disease management.

“Implementation of these advances has the potential to delay kidney failure, reduce the symptom burden, lessen the risk of cardiovascular complications, and prolong life,” the authors said.

Growth Patterns in Kidney Cyst Number and Volume in Patients with ADPKD

Clinical Journal of the American Society of Nephrology. 2019;14(60:823-833

Researchers, led by Kyongtae T. Bae, PhD, MD, conducted a study designed to evaluate the growth pattern of kidney cyst number and cyst volume in association with kidney size, demographics, and genotypes in autosomal dominant polycystic kidney disease (ADPKD). Serial magnetic resonance images were used to measure kidney cyst number and cyst volume in 236 patients with ADPKD. The patients were 15 to 46 years of age at baseline; maximum follow-up was 14.23 years. The growth pattern was analyzed in association with sex, age, height-adjusted kidney volumes, and genotype using linear mixed models of repeated measurements and tests of interactions with age as a time-dependent covariate to assess rates of change over time.

The mean height-adjusted total cyst number increased exponentially over time from a baseline value of 762 to 1715 at the last clinic visit. The mean height-adjusted total cyst volume increased exponentially from 305 to 770 mL. Over time, height-adjusted kidney volume, height-adjusted total cyst number, and height-adjusted total cyst volume were highly correlated. Female participants and participants with larger height-adjusted total kidney volume at baseline showed smaller rates of change in the log of height-adjusted total cyst number and cyst volume. Genotype did not significantly affect the rate of growth.

“Both height-adjusted total cyst number and height-adjusted total cyst volume increased exponentially and more than doubled over 14.23 years of follow-up. Compared with PKD2 plus no mutation detected, PKD1 was associated with a greater cyst number and volume at a given age, but no significant difference in the rate of growth,” the researchers said.


Efficacy of Therapies for Depression Among Patients on Maintenance Hemodialysis

Annals of Internal Medicine. doi:10.7326/M18-2229

Depression is often seen in patients receiving maintenance hemodialysis. Rajnish Mehrotra, MD, MS, and colleagues conducted a multicenter, parallel-group, open-label, randomized controlled trial designed to examine the effect of an engagement interview on acceptance of treatment for depression (phase 1) and to compare the efficacy of cognitive behavioral therapy (CBT) versus sertraline (phase 2) for the treatment of depression in that patient population.

The study was conducted at 41 dialysis facilities in three US metropolitan areas. Eligible patients had been receiving hemodialysis for a minimum of 3 months and had a Beck Depression Inventory-II score of ≥15.  A total of 184 patients participated in phase 1, and 120 subsequently participated in phase 2.

In phase 1, participants were randomized to the engagement interview group or the control group; in phase 2, participants received either 12 weeks of CBT delivered in the dialysis facility or treatment with sertraline. The primary outcome of interest for phase 1 was the proportion of patients who initiated depression treatment within 28 days; for phase 2, the primary outcome was depressive symptoms measured by the Quick Inventory of Depressive Symptoms–Clinician-Rated (QIDS-C) at 12 weeks.

There was no difference between the two groups in the proportion of patients who began treatment for depression following the engagement interview or the control visit (66% vs 64%, respectively; P=.77; estimated risk difference, 2.1 (95% confidence interval [CI], –12.1 to 16.4). In phase 2, compared with CBT, sertraline treatment resulted in lower QIDS-C depression scores at 12 weeks (effect estimate, –1.84; 95% CI, –3.54 to –0.13; P=.035). There were more adverse events in the sertraline group than in the CBT group.

In conclusion, the researchers said, “An engagement interview with patients receiving maintenance hemodialysis had no effect on their acceptance of treatment for depression. After 12 weeks of treatment, depression scores were modestly better with sertraline treatment than with CBT.”


Noninvasive Assessment of Kidney Function via AI-GFR Estimation

 Nature Partner Journals/Digital Medicine. [npj Digital Medicine, volume 2, Article number: 29 (2019)]

Ultrasound imaging of the kidney is considered optimal in clinical practice due to its safety, convenience, and affordability. However, according to Chin-Chi Kuo, MD, PhD, and colleagues in Taiwan, the high subjective variability in image acquisition and interpretation makes incorporating  experience-based prediction into standardized practice diffcult.

Previous studies have reported conflicting results regarding whether kidney function should be screened in all asymptomatic adults. There are limited data on whether testing the urine for protein or testing the blood for serum creatinine is more appropriate in the context of routine screening. Development of a noninvasive and accessible tool for the diagnosis of chronic kidney disease (CKD) would be a valuable aid in clinical practice. Dr. Kuo et al. developed a deep algorithm based on kidney ultrasound and clinical data to examine the possibility of such a tool.

The researchers tested the algorithm in a large registry-based cohort of patients with CKD. Results were reported online.

The cohort included 1299 patients; median age was 65 years and 45% (n=582) were men; 45% had diabetes and 74.7% had hypertension. Median serum creatinine level was 2.07 mg/dL and median estimated glomerular filtration rate (eGFR) was 30.12 mL/min/1.73 m2.

For classification of eGFR with a threshold of 60 mL/min/1.73 m2, the model achieved an overall accuracy of 85.6%, which was higher than that of experienced nephrologists. The area under the receiving operating characteristic curve was 0.904. Attained specificity was up to 92.1%, indicating the effectiveness of the deep learning algorithm for assessing CKD using ultrasound images. However, the sensitivity was only moderate (~60.7%).

The relationship between artificial intelligence (AI) and estimates of eGFR based on serum creatinine was strong, indicated by a Pearson correlation coefficient of 0.741.

In summary, the researchers said, “Our model is the first fundamental step toward realizing the potential of transforming kidney ultrasound imaging into an effective, real-time, distant screening tool. AI-GFR estimation offers the possibility of noninvasive assessment of kidney function, a key goal of AI-powered functional automation in clinical practice.”


Vitamin B6 in Pediatric Kidney Transplant Recipients

Journal of Renal Nutrition. 2019;29(3):205-208

Patients who have undergone renal transplantation are at risk for altered vitamin B6 status and metabolism due to changes in diet, medication regimens, and continuing renal dysfunction. Given its role in the body’s inflammatory and immune response, vitamin B6 may be of particular interest post-transplantation. In pediatric patients with chronic kidney disease, there is an association between dialysis and inadequate dietary intake of vitamin B6. Matthew Harmer, BSc (Hons), BM, MRCPCH, and colleagues conducted a study to examine the vitamin B6 intake and status of a cohort of children who have received a renal transplant graft.

Of the 10 pediatric patients in the cohort, median age was 11.9 years and median serum vitamin B6 concentration was 62.45 nmol/L. Two children had values above the reference range and none had values below the reference range. Mean vitamin B6 intake was 138.7% of reference nutrient intake and none of the patients were receiving vitamin B6 supplementation.

“In this sample, no children appeared biochemically deficient, but 20% had elevated concentrations. Dietary intakes were not excessive, and no children reported oral vitamin B6 supplementation. Exploration of vitamin B6 metabolism in this population is required,” the researchers said.