Kidney360最新文献

Background: Immunoglobulin A nephropathy (IgAN) is the leading cause of primary glomerulonephritis and carries a high risk of progression to end-stage kidney disease. Endothelin-1 (ET-1) type A (ETA) receptor activation may be a key driver of proteinuria, inflammation, and fibrosis in patients with kidney diseases. Atrasentan, a highly potent and highly selective antagonist of the ETA receptor demonstrated a statistically significant and clinically-meaningful proteinuria reduction of 36.1% (95% CI: 26.4%, 44.6%; p<0.001) relative to placebo, at Week 36 in the ongoing ALIGN phase 3 trial. Based on these data, atrasentan is indicated to reduce proteinuria in adults with primary IgAN at risk of rapid disease progression.

Methods: We explored the biological effects and changes in gene transcription with atrasentan in cultured human renal mesangial cells, grouped ddY (gddY) mouse model of IgAN, and Wistar rats injected with anti-Thy1.1 (CD90) antibody to induce mesangial injury and mesangioproliferative glomerulonephritis (MPGN). The effect of atrasentan on proteinuria and kidney gene transcriptome were evaluated in both animal models, and histological and morphometric assessments of rat kidneys were conducted.

Results: In separate transcriptomics analyses of all 3 models, atrasentan reversed gene expression changes related to cell proliferation, pro-inflammatory, and pro-fibrotic signatures. In human renal mesangial cells stimulated with ET-1, atrasentan reduced mesangial cell proliferation and matrix expansion. After 7 days, atrasentan treatment in the MPGN rat model diminished renal mesangial hypercellularity and matrix expansion, decreased glomerular and tubulointerstitial structural alterations, and significantly reduced proteinuria. In gddY mice, atrasentan treatment for 4 days significantly reduced mean albuminuria by >60%.

Conclusions: The acute mechanistic effects of atrasentan demonstrated in vitro and in vivo support the therapeutic potential of atrasentan in IgAN. The ongoing AFFINITY and ASSIST phase 2 trials, and the ALIGN phase 3 trial in patients with IgAN will further evaluate the translation of these mechanistic effects to the clinical efficacy and safety of atrasentan.

Background: Many patients with kidney failure experience deteriorating financial situations that affect their everyday lives. 'Financial toxicity (FT)' provides a person-centered perspective of this phenomenon. However, little is known about this concept in the nephrology context. This study aimed to explore the impact of FT in patients receiving dialysis.

Methods: This exploratory qualitative study purposively recruited patients on long-term dialysis based on their treatment modalities and socioeconomic levels from three centres in Hong Kong. Individual semi-structured interviews were conducted using an interview guide. Recordings were transcribed verbatim and transcripts were analysed using a thematic analysis approach.

Results: Twenty-five patients were interviewed. Three themes emerged, namely: contributors, experiences, and mitigators of FT. FT was commonly triggered by decreased employment/income and increased healthcare expenditures. While experiencing FT, patients often reduced their spending, avoided social activities, perceived negative thoughts and emotions, and reconsidered their treatment options. To mitigate these impacts, patients utilised personal resources and various assistance/subsidy schemes. FT was more marked if the patient was unable to obtain public financial assistance. Of note, patients who were given information about the financial aspect of dialysis were better able to cope with FT.

Conclusions: Deteriorating financial situations have multidimensional impacts on the material, psychological, and behavioural aspects of patients' lives. While efforts are warranted to make healthcare systems more equitable, interventions to alleviate these impacts are not limited to monetary assistance. They can include practical support for coping with life changes and planning personal finances.

Background: Nephrologists do not routinely discuss conservative kidney management (CKM) with their patients, hindering informed decision-making about kidney failure treatments. Nudges are interventions that facilitate behavior change and may assist nephrologists with discussing CKM.

Methods: We designed a behavioral nudge, called CKM Jumpstart, to assist nephrologists with discussing CKM with their patients. CKM Jumpstart was developed using human-centered design principles in 3 phases: 1) Discovery (March-June 2022): literature review and deliberation about the challenges to discussing CKM with an advisory panel; 2) Design (June-December 2022): multiple cycles of prototyping of CKM Jumpstart with input from the advisory panel and 10 nephrologists across the US; and, 3) Implementation (April 2023-July 2025): testing a final version of CKM Jumpstart in 36 clinic visits with 19 nephrologists recruited from the greater Seattle area and conducting qualitative interviews with nephrologists about their experiences using CKM Jumpstart.

Results: In the Discovery phase, we identified 4 major challenges to discussing CKM: 1) attitudes favoring dialysis as the norm; 2) lack of clarity about patients' healthcare values; 3) difficulty describing CKM; and, 4) fear of upsetting patients. The Design phase produced a prototype of CKM Jumpstart that addressed these challenges by providing a communication framework and example language that nephrologists could try to discuss patients' healthcare values and CKM. During the Implementation phase, all the nephrologists tried CKM Jumpstart at least once and were nudged to have conversations about values, CKM and/or kidney failure treatment options more broadly. Nephrologists selectively used parts of CKM Jumpstart that suited their communication style. Some felt conversations occurred too early in patients' disease course and were uncertain about how to address conflicting values and treatment preferences.

Conclusions: Behavioral nudging assists nephrologists with discussing healthcare values and CKM with patients. It can also reveal persistent challenges with having these discussions among nephrologists.