Kidney360最新文献

Background: The primary aim compared kidney endpoints between patients with type 2 diabetes (T2D) 36 months after initiation on a sodium-glucose cotransporter-2 inhibitor (SGLT2i) or a GLP-1 receptor agonist (GLP-1RA). Secondary aims compared estimated glomerular filtration rate (eGFR), hemoglobin A1c (HbA1c), weight, and urine albumin-to-creatinine ratio (UACR) changes.

Methods: We conducted a retrospective cohort study of propensity score matched veterans with T2D, baseline eGFR>20mL/min/1.73m2, and initiated on a SGLT2i vs GLP-1RA between 4/1/2009-9/1/2020. Cox proportional hazard models were constructed to evaluate effectiveness between both groups on composite endpoint (decline of >=40% in eGFR from baseline, ESRD event, and all-cause mortality) and its components adjusting for baseline characteristics. Spline models were constructed to evaluate eGFR change and linear mixed effects models were constructed to evaluate changes in HbA1c, weight, and UACR. We used an intent-to-treat (ITT) approach as our main analysis followed by a per-protocol (PP) approach excluding veterans who discontinued or switched therapy during the study period.

Results: A total of 29,146 propensity score matched veterans were included in SGLT2i and GLP-1RA groups (14,573 per group). In the ITT and PP analyses, veterans initiated on SGLT2i had a 35% (HR=0.65; 95% CI: 0.62, 0.68) and 34% (HR=0.66; 95% CI: 0.62, 0.69) reduction in the hazard of experiencing the composite endpoint compared to veterans initiated on GLP-1RA adjusting for baseline characteristics, respectively. Between 6-36 months, we found an improved chronic eGFR slope with SGLT2i compared to GLP-1RA in both ITT and PP analyses; +1.19 mL/min/1.73 m2 (95% CI: 0.93, 1.45) and +1.29 mL/min/1.73m2 (95% CI: 1.01, 1.57), respectively. The annual difference in chronic eGFR slope in both ITT and PP analyses were +0.97 mL/min/1.73m2/year (95% CI: 0.82, 1.11) and +1.08 mL/min/1.73m2/year (95% CI: 0.92, 1.25). Improved HbA1c, weight loss and UACR were reported for both groups.

Conclusion: In this real-world study, veterans with T2D initiated on SGLT2i were associated with reduced hazard of experiencing mortality, worsening eGFR, or developing ESRD and improved glycemic, metabolic, and renal endpoints compared to GLP-1RA use.

Systemic amyloidoses are a group of disorders that can be hereditary or acquired and have various renal manifestations and outcomes. Light chain amyloid has been considered the most common renal amyloid and thus been the focus of substantial research and therapeutic interest but with improvement in diagnostic techniques. However, there has been growing interest in rarer forms of renal amyloid, including amyloid serum A protein, leukocyte chemotactic factor 2 amyloid, and transthyretin amyloid. In this review, we provide an update on diagnostics, renal outcomes, and therapeutic landscape in these specific types of amyloid.

Background: We investigated whether psychosocial determinants self-efficacy and social support are associated with Health-Related Quality of Life in hemodialysis patients enrolled in the CONVINCE trial.

Methods: We used baseline data from the cohort of patients involved in the CONVINCE randomized trial of hemodiafiltration versus hemodialysis. Measures included age, gender, relationship status, children, housing, education, employment, comorbidities, dialysis schedules, time of first dialysis, residual kidney function, general self-efficacy and social support scores, and PROMIS measurements for health-related quality of life. Associations were analyzed using hierarchical regression.

Results: One thousand three hundred and sixty patients from CONVINCE were the cohort of interest. Mean age was 62±13.5 years (range 20-92), and 66.9% were men. Self-efficacy was a significant predictor for all health-related quality of life domains: depression (β = -0.36, p < 0.001), anxiety (β = -0.35, p < 0.001), social participation (β = 0.32, p < 0.001), cognition (β = 0.29, p < 0.001), fatigue (β = -0.29, p < 0.001), physical function (β = 0.27, p < 0.001), sleep disturbance (β = -0.23, p < 0.001), pain interference (β = 0.21, p < 0.001), pain intensity (β = -0.17, p < 0.001), interdialytic symptoms (β = -0.14, p = 0.002) and intradialytic symptoms (β = -0.14, p = 0.002). Social support was a significant predictor for cognition (β = 0.21, p < 0.001), sleep disturbance (β = -0.11, p = 0.017) and intradialytic symptoms (β =- 0.11, p = 0.02).

Conclusions: Higher general self-efficacy scale scores are associated with improvements in cognition, depression, anxiety, social participation, fatigue, physical function, sleep disturbance, pain interference, interdialytic symptoms, pain intensity and intradialytic symptoms. Associations for self-efficacy are larger than those for social support and stronger than previously reported. It is plausible that targeted psychosocial interventions may improve health outcomes in people on hemodialysis.

Background: The disruption of calcium signaling associated with polycystin deficiency is a key factor in abnormal epithelial growth in Autosomal Dominant Polycystic Kidney Disease (ADPKD). Calcium homeostasis can be influenced by mechanotransduction. The mechanosensitive cation channel PIEZO1 has been implicated in sensing intrarenal pressure and regulating urinary osmoregulation, but its role in kidney cystogenesis is unclear.

Methods: We hypothesized that altered mechanotransduction contributes to cystogenesis in ADPKD, and that activation of mechanosensitive cation channels could be a therapeutic strategy.

Results: We demonstrate that Yoda1, a PIEZO1 activator, increases intracellular calcium and reduces forskolin-induced cAMP levels in mouse inner medullary collecting duct (mIMCD3) cells. Notably, knockout of polycystin-2 attenuated the efficacy of Yoda1 in reducing cAMP levels in mIMCD3 cells. Yoda1 also reduced forskolin-induced mIMCD3 cyst surface area in vitro and cystic index in mouse metanephros ex vivo in a dose-dependent manner. However, collecting duct-specific Piezo1 knockout neither induced cystogenesis in wild-type mice nor altered cystogenesis in the Pkd1RC/RC mouse model.

Conclusions: These findings support the potential role of PIEZO1 agonists in mitigating cystogenesis by increasing intracellular calcium and reducing cAMP levels, but the unaltered in vivo cystic phenotype following Piezo1 knockout in the collecting duct suggests possible redundancy in mechanotransductive pathways.

Background: Balkan endemic nephropathy (BEN) is characterized with later onset and milder forms of hypertension, and with lower pulse wave velocity (PWV) than other end-stage kidney disease (ESKD). Longer telomeres are associated with better cardiovascular (CV) prognosis. Therefore, we hypothesized that telomere length (TL) could be longer in BEN patients compared to other ESKD patients.

Methods: A total of 124 patients undergoing hemodialysis (HD) (68 BEN, 56 non-BEN) were enrolled and followed-up for 72 months. TL was measured in leukocytes by Southern blot at inclusion.

Results: Age and sex-adjusted TL was significantly longer in the BEN group (p<0.001). TL was negatively associated with carotid-femoral PWV in BEN patients. BEN patients had significantly lower CV mortality than non-BEN ESKD patients (p<0.001). In the BEN group shorter TL (1kb change) was the only determinant of shorter survival (HR 0.11). Using the TL threshold defined by ROC analysis (TL < 6.21 kb), we showed in both groups significantly higher CV mortality in the presence of short telomeres (Log-rank (Mantel-p<0.001).

Conclusions: Longer telomeres are associated with less CV mortality in patients undergoing chronic HD. BEN patients had longer TL and longer survival than other ESKD patients. In BEN patients, TL was negatively associated with arterial stiffness and positively associated with survival. This study confirmed our hypothesis that BEN is associated with slower vascular aging and that longer TL may partially explain this phenomenon.

Background: Chronic kidney disease (CKD) affects more women than men worldwide, however, men comprise the majority of patients who receive kidney replacement therapy. We aimed to describe the perspectives of patients and their caregivers regarding gender disparities in CKD.

Methods: Semi-structured interviews were conducted with 45 patients with CKD (20 women) and 14 caregivers (12 women) from seven clinics in Austria. The interviews were analyzed thematically.

Results: Five themes were identified in this study. Participants perceived that women were "disadvantaged and vulnerable" (silent and intimidated, single mother predicament, impeded access to care and support due to socioeconomic disadvantage, had to fend for themselves); "fulfilling gender roles and norms" (primarily responsible for childcare, pressure to perform well as homemakers, put others' needs before their own, encouraging husband's treatment adherence), and "protecting their own health" (self-disciplined, vigilant, confronted health challenges, advocated for their needs). Men were seen to "place the onus of care on others" (expected help from family, relied on others for decisions). Both men and women experienced a "disease-related identity crisis and distress" (women: impaired body image, mental distress; men: denial and self-destruction, emasculated by sickness).

Conclusions: Women with CKD felt vulnerable and were inclined to fulfill gender norms and responsibilities as caregivers but were also vigilant about protecting their own health. Men tended to be reluctant to accept CKD and appeared to depend on others for disease management. Better awareness and addressing these concerns can inform strategies to minimize gender disparities in access to care and outcomes in CKD.