MAKE Risk Influenced by AKI Subphenotype

INVESTIGATORS have identified

2 distinct acute kidney injury (AKI) subphenotypes with different risks for major adverse kidney events (MAKE). The subphenotypes may improve risk stratification beyond using serum creatinine concentrations alone.

“Acute kidney injury (AKI) is a heterogeneous clinical syndrome with varying causes, pathophysiology, and outcomes,” Pavan K. Bhatraju, MD, MSc, of the University of Washington in Seattle, and colleagues explained. “We incorporated plasma and urine biomarker measurements to identify AKI subgroups (subphenotypes) more tightly linked to underlying pathophysiology and long-term clinical outcomes.”

In the ASSESS-AKI Study (Assessment, Serial Evaluation and Subsequent Sequelae), the investigators analyzed 29 clinical, plasma, and urine biomarkers associated with AKI development and identified 2 classes of patients. Class 1 patients had higher rates of preexisting congestive heart failure and lower concentrations of plasma inflammatory and urinary tubular injury biomarkers. Class 2 patients had higher rates of preexisting chronic kidney disease (CKD) and higher concentrations of biomarkers.

The investigators matched and compared 769 hospitalized adults with and 769 without AKI. The long-term risk for MAKE was 2.1- and 3.0-fold higher for patients with AKI class 1 and 2, respectively, compared with patients without AKI, Dr Bhatraju and colleagues reported in the American Journal of Kidney Diseases. The class 2 AKI group had a 1.4-fold increased risk for MAKE compared with the class 1 group, after adjustment for KDIGO AKI stage and other factors.

The higher risk of MAKE among class 2 patients was explained by a higher risk for CKD progression and dialysis, according to the investigators.

The risk for CKD progression was a significant 3.0-fold higher with class 2 compared with class 1 AKI. The risk for dialysis initiation was a significant 4.6-fold higher with class 2 vs 1. Patients with AKI class 1 or 2 had significantly increased risks for CKD development and early death compared patients without AKI.

“Key variables that differentiated the AKI subphenotypes included host response markers of inflammation, such as sTNFR-1, IL-6, IL-10, and urinary markers of tubular injury and inflammation, such as urinary NGAL and IL-18,” Dr Bhatraju’s team wrote. Serum creatinine ranked 20th out of the 29 variables for differentiating classes 1 and 2. Urine output data were not available, which is a study limitation.

Class 2 patients may benefit from closer follow-up for early signs of CKD progression, according to the researchers. ■

USE OF 5α-reductase inhibitors (5-ARIs) prior to a bladder cancer diagnosis may reduce patients’ risk for disease progression.

Using the Korean National Health Insurance Service database, investigators identified 22,845 men diagnosed with bladder cancer who had preexisting benign prostatic hyperplasia (BPH) treated with an α-blocker with or without a 5-ARI. To reduce biases, they propensity-score matched 5300 users of α-blockers only to 5300 users of 5-ARIs plus α-blockers. BPH medications were required to be taken 12 or more months before bladder cancer diagnosis.

The 5-ARI plus α-blocker group had a significant adjusted 16% and 26% lower risk of bladder instillation and radical cystectomy, respectively, compared with the α-blocker only group, indicating delayed grade and stage progression with 5-ARI use, Seok Ho Kang, MD, PhD, of Anam Hospital, Korea University College of Medicine, in Seoul, Korea, and colleagues reported in JAMA Network Open. The 5-ARI group also had a significant 17% reduced risk for allcause mortality.

The between-group differences in restricted mean survival time were 88.1 days for bladder instillation, 68.0 days for radical cystectomy, and 92.6 days for all-cause mortality.

The investigators also found that the 5-ARI plus α-blocker group had numerically lower incidence rates per 1000 person-years of bladder instillation (66.43 vs 85.59) and radical cystectomy (13.56 vs 19.57) compared with the α-blocker only group.

The investigators also found that only 5-ARI use of 2 years or more was significantly associated with reduced risk of radical cystectomy.

“This cohort study found that the prediagnostic prescription of a 5-ARI was associated with a reduced risk of [bladder cancer] progression,” Dr Kang’s team wrote. “However, the evidence was insufficient to inform the extension of 5-ARI indications.” ■

KT referrals

continued from page 1 nonadherence, based on their beliefs about its causes and implications. Their beliefs ultimately informed their decisions about referring patients for transplant evaluation.”

The investigators identified 3 themes from provider interviews. First, nonadherence to dialysis treatments, medical appointments, dietary advice, medications, weight loss regimens, wound care, or communication signaled to some providers that a patient was a “risky” rather than “good” candidate for transplant. Perceived reasons for patient nonadherence included socioeconomic factors, comorbidities, and lack of motivation. Second, providers considered the implications of nonadherence. They were concerned about wasting their limited time and resources, their emotional expenditure, a possible negative response from the transplant center, and the potential loss of a valuable and scarce kidney to a “risky” patient.

ED drugs cardioprotective

continued from page 1

Further, compared with sildenafil recipients, tadalafil-treated patients had significant 15%, 14%, and 15% lower 5-year risks for heart failure, myocardial infarction, and overall mortality, respectively.

“I think our study is the first to tease out specific differences among individual PDE5i in relation to cardiac outcomes, with our preliminary results suggesting that tadalafil may be superior to other PDE5i like sildenafil in relation to heart failure, myocardial infarction, and mortality,” Dr Ha told Renal & Urology News. “Since erectile dysfunction is a common harbinger for cardiac disease later in life, it is important for patients to understand what drugs may best address their medical issues, especially in a time when medical care may

Slow graft function

continued from page 1 within 7 days after transplantation, on long-term graft outcomes is well documented, it has been unclear whether SGF (poor kidney function not requiring dialysis) also leads to worse graft outcomes, Dr Venkataraman explained.

He and his colleagues studied 17,579 adult kidney-only transplant recipients from 2001 to 2021 in the Australia and New Zealand Dialysis

Third, providers’ beliefs about whether a patient would be invested in the transplant process affected their decision to delay, deny, or proceed with transplant referral. Providers’ responses were highly individual.

“Dialysis providers have varying understandings of their role in assessing patients,” McDonnell explained. “Where there is any gap between providers’ perceptions of the reasons and measures of nonadherence to transplant outcomes and sharing these measures with the dialysis and transplant provider communities for decision-making.

Addressing providers’ misperceptions and apprehension may also help, McDonnell added. She noted that previous studies on implicit bias in medical decision-making have shown that racial and ethnic minorities, lowincome patients, and other marginalized patients are less likely to receive preferred medical treatments.