May/June 2017: Abstract Roundup

Acute Kidney Injury

Prepregnancy AKI Associated with Adverse Outcomes in Pregnancy
Journal of the American Society of Nephrology. 2017;28(5):1566-1574

There are few data available on the effect of clinically recovered acute kidney injury (AKI) on future pregnancy outcomes. Jessica Sheehan Tangren, MD, and colleagues retrospectively studied all women who delivered infants between 1998 and 2007 at Massachusetts General Hospital. The outcome of interest was whether there was an association of a previous episode of recovered AKI with subsequent adverse maternal and fetal outcomes.

The women with recovered AKI had increased rates of preeclampsia compared with the control group (women without kidney disease) (23% vs 4%; P<.001). Infants of women in the recovered AKI group were born earlier than infants of women in the control group (37.6 vs 392 weeks; P<.001), with increased rates of small for gestational age births (15% vs 8%; P=.03).

Following adjustment for multiple variables, recovered AKI remained associated with increased risk for preeclampsia and adverse fetal outcomes. The association also remained following matching 1:2 by age, race, body mass index, diastolic blood pressure, parity, and diabetes status.

In summary, the researchers said, “A past episode of AKI, despite return to normal renal function before pregnancy, associated with adverse outcomes in pregnancy.”

Dipyrone in the ICU Associated with Adverse Renal Side Effects
European Journal of Anaesthesiology. DOI:10.1097/EJA.0000000000000627

Dipyrone (metamizole) is used in perioperative and intensive care unit (ICU) pain therapy, but there are few data on its potential renal side effects, particularly in the critical care environment. Researchers, led by Thomas Stueber, MD, recently conducted a retrospective cohort study to examine the perioperative nephrotoxic potential of dipyrone in patients prone to acute kidney injury (AKI). The single-center study was conducted in a tertiary referral hospital from January 2013 until June 2013, and included 500 consecutive patients ≥18 years of age who were referred to the anesthesia ICU.

Analysis found an association between the use of dipyrone and an increased incidence of AKI in dose-dependent manner with a 1.6-fold increase in the incidence of AKI with each additional gram of intravenous dipyrone per day. In addition, patients who received dipyrone in the ICU presented with a prolonged duration of vasopressor therapy.

“Increasing dipyrone dosage is a potential independent risk factor for AKI in adult ICU patients and may prolong vasopressor therapy. Clinical evidence for a benefit of dipyrone therapy in the ICU is insufficient and needs further critical evaluation,” the researchers said.

Chronic Kidney Disease

A Review of Anemia Management in Patients with Kidney Disease
Current Opinion in Nephrology and Hypertension. Doi:10.1097/MNH.0000000000000317

David Collister, MD, and colleagues provided a review of the state of anemia management with erythropoietin (EPO)-stimulating agents and iron supplementation in patients with chronic kidney disease and in patients with end-stage renal disease on dialysis. The review focused on novel therapies.

The review includes data on health-related quality of life as well as the uncertainties concerning the optimal iron utilization in patients with kidney disease. Novel therapies for iron supplementation discussed were iron-based phosphate binders and dialysate iron delivery, as well as alternatives to EPO-stimulating agents such as hypoxia-inducible factor prolyl hydroxylase inhibitors.

In summary, the researchers said, “Individualization of hemoglobin targets using EPO-stimulating agents and iron supplementation may be considered in younger, healthier patients with kidney disease to improve health-related quality of life. Optimal iron utilization in kidney disease patients in unclear, but novel iron base phosphate binders and dialysate iron delivery may play a role in intravenous iron avoidance and its potential complications. Phase 3 randomized controlled trials of hypoxia-inducible factor prolyl hydroxylase inhibitors are ongoing and are promising new alternatives to EPO-stimulating agents and their known adverse effects.”

Continuous Renal Replacement Therapy 

Timing of Initiation of CRRT in the ICU
Journal of Critical Care. dx/doi.org/10.1016/j.jcrc.2016.12.014

Optimal timing for initiation of early continuous renal replacement therapy (CRRT) is uncertain. Seung Don Baek, MD, and colleagues recently conducted an investigation to examine the clinical impacts of three time-interval parameters on morbidity and mortality in a cohort of 177 patients with septic shock-induced acute kidney injury. The intervals studies were: (1) time from vasopressor initiation to CRRT initiation (Tvaso-CRRT); (2) time from intensive care unit (ICU) admission to CRRT initiation (TICU-CRRT); and (3) time from endotracheal intubation to CRRT initiation (Tendo-CRRT).

The proportion of patients with Tvaso-CRRT less than 24 hours was significantly higher compared with those in the non-survival group (84.3% vs 58.5%, P<.001). Tvaso-CRRT less than 24 hours and Sequential Organ Failure Assessment score were independent factors associated with 28-day mortality and 90-day mortality. Length of stay in the ICU and duration of mechanical ventilation were significantly correlated with TICU-CRRT and Tendo-CRRT, but not with mortality (P<.001 for both associations).

The researchers said, “Considering the possible therapeutic measurement by physicians on the basis of the results in this study, early CRRT could be defined by a Tvaso-CRRT less than 24 hours.”

AVF/AVG Access Safe in ICU Patients on CRRT
Hemodialysis International. doi: 10.1111/hdi.12550

In critically ill patients with end-stage renal disease (ESRD), insertion of hemodialysis catheters carries the risk of complications; however, the use of arteriovenous fistula of graft (AVF/AVG) is considered contraindicated in this patient population. Anas al Rifai, MD, and colleagues conducted a single-center analysis of 48 consecutive hospitalized patients with ESRD on maintenance hemodialysis who underwent continuous renal replacement therapy (CRRT) using AVF/AVG from 2012 to 2013. The primary outcome of interest was complications related to access.

Mean age of the cohort was 60 years, 48% were male, and 88% required vasopressor support. Median duration of AVF/AVG use for CRRT was 4 days. Ten of the 48 patients had complications related to the access and five required catheter placement. Sixty-five percent of the overall cohort survived to hospital discharge and 94% (n=29) had functional AVF/AVG access at time of discharge.

In their conclusion, the researchers said, “In our experience, use of AVF/AVG for CRRT can be performed with a low serious complication rate and low risk of access loss, potentially avoiding catheter-related complications.”

Diabetes

Dipeptidyl Peptidase-4 Inhibitors in Patients with Type 2 Diabetes and CKD
Journal of Diabetes. Doi:10.1111/1753-0407.12546

A recent study was designed to perform a meta-analysis of data from randomized controlled trials on the effects of dipeptidyl peptidase-4 (DPP-4) inhibitors in patients with type 2 diabetes with moderate-to-severe chronic kidney disease (CKD).

The meta-analysis, conducted by Man Yang, MD, and colleagues, included 12 studies representing ten trials. Compared with placebo or no treatment, there was significant improvement in hemoglobin A1c (HbA1c) level at week 12 with DPP-4 inhibitor treatment. The improvement was seen only in patients on dialysis at 24 weeks. Mean change in HbA1c level with DPP-4 inhibitor treatment was equivalent to treatment with sulfonylureas at 52 or 54 weeks.

There were no significant differences in severe or any hypoglycemic events between DPP-4 inhibitors and controls at weeks 12, 24, 52, or 54. However, DPP-4 inhibitors were associated with fewer symptomatic hypoglycemic events compared with sulfonylureas at 52 or 54 weeks.

“DPP-4 inhibitors were effective and comparable with sulfonylureas in type 2 diabetes patients with moderate-to-severe CKD,” the researchers said.

Fabray Disease

Men with Classical Fabray Disease Likely to Experience Renal Events
Journal of the American Society of Nephrology. 2017;28(5):1631-1641

Patients with Fabray disease often experience comorbidities with renal, cardiac, and cerebrovascular manifestations. It is known that there are phenotypic differences between classically and nonclassically affected patients, but there are few data on the natural course of classical and nonclassical disease in men and women. Maarten Arends, MD, and colleagues recently conducted a retrospective analysis to examine event-free survival from birth to the first clinical visit, stratified by sex and phenotype.

Patients were classified by phenotype on the basis of characteristic symptoms and enzyme activity. Men and women with classical Fabray disease had higher event rate compared with those with nonclassical disease (hazard ratio [HR] for men, 5.63; 95% confidence interval [CI], 3.17 to 10.00; P<.001; HR for women, 2.88; 95% CI, 1.54-5.40; P<.001). Men with classical Fabry disease had lower estimated glomerular filtration rate (eGFR), higher left ventricular mass, and higher plasma globotriaosylsphingosine concentrations compared with men with nonclassical disease or women with either phenotype (P<.001).

In conclusion, the researchers said, “Before treatment with enzyme replacement therapy, men with classical Fabray disease had a history of more events than men with nonclassical disease or women with either phenotype; women with classical Fabray disease were more likely to develop complications than women with nonclassical disease. These data may support the development of new guidelines for the monitoring and treatment of Fabray disease and studies on the effects of interventions in subgroups of patients.”

Geriatric Nephrology

Incidence of Gout Associated with eGFR Level
Clinical Journal of the American Society of Nephrology. 2017;12(4):577-584

There are few data on the risk of gout across stages of chronic kidney disease. Researchers, led by Vivian S. Tan, MD, performed a retrospective cohort study using linked healthcare databases from Ontario, Canada, from 2002 to 2010. The primary outcome of interest was the 3-year cumulative incidence of gout.

The cohort included 282,925 adults ≥66 years of age. Mean age was 75 years and 57.9% were women. Results were stratified by level of kidney function: eGFR ≥90 mL/min/1.73 m2, 60-89, 45-59, 30-44, 15-29, and chronic dialysis.

The 3-year cumulative incidence of gout was higher in older adults with lower levels of estimated glomerular filtration rate. In women, the incidence of gout ranged from 0.6% to 3.4%; in men, the incidence ranged from 0.8% to 4.6%, depending on eGFR. Among patients on chronic dialysis, the 3-year cumulative incidence of gout was lower than in those with more moderate reductions in kidney function. Following adjustment for clinical characteristics, the association between a greater loss of kidney function and a higher risk of diagnosed gout remained.

“Patients with a lower level of eGFR had a higher 3-year cumulative incidence of gout, with the exception of patients receiving dialysis. Results can be used for risk stratification,” the researchers said.

Risk of Dementia among Older Kidney Transplant Recipients
Journal of the American Society of Nephrology. 2017;28(5):1575-1583

Kidney transplant recipients ≥55 years of age may develop post-transplant dementia and Alzheimer’s disease (AD) associated with their long-standing kidney disease and/or neurotoxic immunosuppressive agents. Mara A. McAdams-DeMarco, MD, and colleagues studied 40,918 kidney transplant recipients ≥55 years of age (January 1, 1999, to December 31, 2011) linked to Medicare claims through the US Renal Data System.

Older adults had a 10-year dementia risk that ranged from 5.1% for patients 55 to 60 years of age to 17.0% for transplant recipients ≥75 years of age. The 10-year risk for AD ranged from 1.0% to 6.7%, respectively. Older recipient age and pretransplant diabetes were the strongest predictors for dementia and AD.

Among those who developed dementia, the 10-year graft loss risk was 43.1%, compared with 28.8% among those who did not develop dementia. The corresponding mortality risks were 89.9% and 55.7%, respectively. Results were similar for AD.

“We conclude that older kidney transplant recipients have a high risk of post-kidney transplant dementia and AD, and these sequelae associate with a profound effect on patient and graft survival,” the researchers said.

Integrated Treatment Approach Helps Older Patients Self-Manage CKD
Clinical Journal of the American Society of Nephrology. 2017;12(4):635-634

Self-management is an important component of a treatment regimen for patients with chronic kidney disease (CKD). Older patients with CKD may find the self-management component challenging, due to the effect of aging on functional capacity. C. Barrett Bowling, MD, and colleagues conducted an exploratory qualitative study designed to examine the relationship among factors facilitating or impeding CKD management in the older patient population. The researchers held six focus groups at the Veterans Affairs Medical Center in Atlanta, Georgia. The participants were veterans ≥70 years of age with moderate-to-severe CKD.

Mean age was 75.1 years, 60% were black, and 96.7% were men. The main organizing concept that developed was managing complexity. Participants often had other chronic conditions in addition to CKD, and recommendations for self-management of CKD fell within a complex regimen of recommendations for management of other conditions. One effective strategy suggested was prioritization for managing the complexity, such as focusing on blood pressure control.

In conclusion, the researchers said, “Among older veterans with moderate-to-severe CKD, multimorbidity presents a major challenge for CKD self-management. Because virtually all older adults have multimorbidity, an integrated treatment approach that supports self-management across commonly occurring conditions may be necessary to meet the needs of these patients.”