A Transcriptome-wide Translational Program Defined by LIN28B Expression Level.

LIN28 RNA binding proteins are dynamically expressed throughout mammalian development and during disease. However, it remains unclear how changes in LIN28 expression define patterns of post-transcriptional gene regulation. Here we show that LIN28 expression level is a key variable that sets the magnitude of protein translation. By systematically varying LIN28B protein levels in human cells, we discovered a dose-dependent divergence in transcriptome-wide ribosome occupancy that enabled the formation of two discrete translational subpopulations composed of nearly all expressed genes. This bifurcation in gene expression was mediated by a redistribution in Argonaute association, from let-7 to non-let-7 microRNA families, resulting in a global shift in cellular miRNA activity. Post-transcriptional effects were scaled across the physiological LIN28 expression range. Together, these data highlight the central importance of RBP expression level and its ability to encode regulation.

Gaps in Nephrology Referral Care Utilization in Patients at High-Risk of Progression to Kidney Failure.

Early nephrology specialty care slows progression of chronic kidney disease (CKD) to end-stage renal disease (ESRD). However, identifying which patients are expected to progress to end-stage disease has been historically challenging to predict. With a limited supply of nephrologists, optimizing nephrology referral is essential for improving patient outcomes. The Kidney Failure Risk Equation (KFRE) provides an accurate metric to identify patients who are at high risk of progression to kidney failure. In this study, we utilize the KFRE to perform a retrospective analysis in a local health network to identify rates of nephrology referral for CKD patients stratified by risk of kidney failure progression. We found a nephrology referral gap in CKD patients at higher risk of progression and an underutilization of albuminuria testing in CKD, suggesting opportunities to improve outcomes by 1) proactively targeting high-risk patients using EHR-based informatics strategies and 2) increasing albuminuria testing as a screening tool.

Analysis of Specialty Nephrology Care Among Patients With Chronic Kidney Disease and High Risk of Disease Progression.

Importance: Identification of patients with chronic kidney disease (CKD) with high risk of progression to kidney failure can help ensure they receive appropriate and effective nephrology care. Objective: To examine whether patients with CKD at various levels of kidney failure risk receive nephrology care within 1 year of established risk. Design, Setting, and Participants: This population-based, retrospective cohort study collected nationwide administrative health claims data from 156 733 adult patients who met the Kidney Disease: Improving Global Outcomes initiative CKD diagnostic criteria between January 1, 2012, and December 31, 2019, and had an available urine albumin to creatinine ratio within 90 days of a serum creatinine laboratory test. Patients with a history of dialysis or kidney transplant, a prior visit with a nephrologist in the past year, or palliative care billing codes or those who died or disenrolled within 1 year of the albumin to creatinine ratio measurement were excluded. Data analysis was performed from September 10, 2022, to February 14, 2022. Exposures: Kidney failure risk computed with the 5-year Kidney Failure Risk Equation. Main Outcomes and Measures: The main outcome was nephrology care rates across tiers of kidney failure risk, estimated as the proportion of individuals having a nephrologist visit within 1 year after index time. Results: The study population consisted of 156 733 patients with CKD (mean [SD] age, 74.6 [8.4] years; 91 906 [58.6%] female; 86 457 [55.2%] White). A total of 106 004 patients (67.6%) had a low (≤1%) 5-year risk of kidney failure. Nephrology visit rates increased with higher kidney failure risk. Among the 137 highest-risk patients, 79 (57.7%; 95% CI, 48.4%-64.7%) had a nephrology visit. Among 7730 patients with risk above a 10% threshold, 3208 (41.5%; 95% CI, 40.3%-42.4%) had a nephrology visit. Conclusions and Relevance: This study's findings suggest that nearly half of patients with CKD at high risk of progressing to kidney failure do not have a nephrologist visit within 1 year of established risk. These findings have implications in the design of risk-based guidelines for referral and in the practice of delivering nephrology care to patients with CKD.