Current Opinion in Nephrology and Hypertension最新文献

Purpose of review: Kidney intercalated cells play critical roles in regulating body acid-base balance. We recently discovered Foxp1 and two downstream transcriptional factors Dmrt2 and Hmx2 are essential for intercalated cell differentiation. This review incorporates these findings with previous reports to add insights to the molecular regulation of intercalated cell differentiation.

Recent findings: We reviewed the current understanding of intercalated cell differentiation and plasticity, and the contribution of single-cell sequencing to point to the existence of transitional cells during principal cell and intercalated cell differentiation or trans-differentiation. For molecular regulation of cell differentiation, we discuss how Notch and Foxi1 regulate principal cell/intercalated cell switch and intercalated cell differentiation, and the new finding of Foxp1 and downstream transcriptional factors in intercalated cell subtype specification.

Summary: The differentiation and balance of principal cell and intercalated cell subtypes are the foundation for maintaining acid-base balance. A clear understanding of the cellular and molecular controls of these processes provides the basis for designing intervention approaches for metabolism acidosis or alkalosis and other related diseases.

Purpose of review: The CKD-EPI equations were updated in 2021 to remove the race variable from eGFR estimation. In the same year, the creatinine-based EKFC equation was published, subsequently supplemented by the cystatin C-based EKFC equation. Recent findings suggest that the prevalence of chronic kidney disease (CKD) can vary depending on the equation, the biomarker, and the population studied.

Recent findings: Using the CKD-EPI 2021 equation instead of the CKD-EPI 2009 equation results in an increased prevalence of CKD among Black individuals in the U.S. and a decreased prevalence among non-Blacks. The CKD-EPI equations may underestimate the prevalence of CKD in India and in some sub-Saharan African populations. This is corrected by using the EKFC equation and dedicated Q-values. In general, the prevalence of CKD is slightly higher with EKFC than with the CKD-EPI equations. The CKD-EPI cys equation generally leads to a higher CKD prevalence than the CKD-EPIcrea equations. Few epidemiological data are available for EKFC cys .

Summary: The choice of biomarkers and equations has an impact on the prevalence of CKD, with implications that also depend on the characteristics of the population being studied.

Purpose of review: The purpose of this review is to: evaluate the clinical trial evidence base for the treatment of chronic kidney disease mineral and bone disorder (CKD-MBD) in patients with kidney failure as it relates to highly prioritized clinical outcomes; and discuss approaches and principles to develop needed trials in CKD-MBD.

Recent finding: Most clinical trials in CKD-MBD focus on biochemical outcomes, with few trials of surrogate outcomes (e.g., vascular calcification, left ventricular hypertrophy, bone mineral density), and even fewer of highly prioritized clinically important outcomes, such as mortality, cardiovascular disease events, or hospitalization. Within phosphate management, the recent LANDMARK trial did not detect a difference in a cardiovascular composite outcome between patients randomized to lanthanum carbonate vs. a calcium-based phosphate binder strategy over 3 years. The ongoing PHOSPHATE trial will provide needed evidence on phosphate treatment targets. There are no comparable, large trials of parathyroid hormone (PTH) targets. Observational approaches using clinical trial emulation suggest the potential for reduced cardiovascular disease and mortality with an 'emulated' low PTH target, but trials must be designed to confirm this. To ensure success, these trials must focus on practical treatment approaches, leveraging areas of practice variation and recognizing the dynamic nature of longitudinal CKD-MBD care.

Summary: More intensive treatment of CKD-MBD remains a promising approach to improve clinical outcomes in patients with kidney failure and should prompt ongoing efforts to obtain needed trials.

Purpose of review: Integrating sex-based analyses is becoming a key point in the new recommendations, particularly in nephrology.

Recent findings: Whereas single nephron glomerular filtration rate (GFR) is not different between men and women, male sex is associated, after multiple adjustments, with a higher number of nephrons. However, after indexation to body surface area, measured GFR (mGFR) in healthy potential kidney donors is not different between men and women between 20 and 50 years of age. After 50 years, mGFR decline seems faster in women than in men, which is concordant with the protective role of estrogens on renal function, as demonstrated in animal and some human studies. Conversely, testosterone has a detrimental effect on renal function. Of note, although testosterone has been shown to increase the kidney volume of the remnant kidney after a unilateral nephrectomy in animal models, this may generate deleterious hyperfiltration in the longer term.

Summary: Taken together, these data highlight the impact of sex on GFR, notably through sexual hormones whose receptors are expressed in glomerular cells.

Purpose of review: Hypertension is the most prevalent cardiovascular disease worldwide and the leading cause of mortality in both men and women. Despite well documented sex differences in prevalence, risk factors, and treatment responses, current guidelines still fail to take these specificities into account. A more tailored approach, accounting for sex-specific pathophysiological mechanisms and risk factors, is essential.

Recent findings: Studies show that hypertension is more prevalent in men than in women until menopause. After menopause, the prevalence increases in women, likely due to hormonal changes. Additionally, genetic, metabolic, and social risk factors differ between the sexes, as do cardiovascular risks and associated comorbidities. Pharmacokinetic and pharmacodynamic variations also impact antihypertensive treatment efficacy and side effects, highlighting the need for a more individualized therapeutic strategy. This review explores the pathophysiology of hypertension by sex, global risk factors with a focus on female-specific aspects, and sex-related cardiovascular risks. We also discuss antihypertensive treatments and their effectiveness based on gender-specific characteristics.

Summary: Incorporating sex differences into hypertension management could enhance treatment efficacy and reduce cardiovascular mortality. Further research is needed to refine guidelines and develop personalized therapeutic strategies, optimizing hypertension care and improving patient outcomes.

Purpose of review: Diabetes is a major global health concern, affecting millions and increasing morbidity and mortality. Recent research highlights fibroblast growth factor 23 (FGF23) as a potential contributor to type 2 diabetes and its cardiovascular complications. This review explores the role of FGF23 in metabolic and cardiovascular dysfunction and discusses possible therapeutic interventions.

Recent findings: Deregulated FGF23 is linked to insulin resistance, pancreatic β-cell dysfunction, and systemic inflammation. Studies suggest FGF23 influences glucose metabolism via insulin signaling, oxidative stress, and inflammation. Epidemiological data indicate that elevated FGF23 levels are associated with an increased risk of type 2 diabetes and posttransplant diabetes, independent of traditional risk factors. Higher FGF23 levels have also been linked with an increased cardiovascular risk in patients with diabetes, even without chronic kidney disease.

Summary: FGF23 is emerging as a key factor in the cardiovascular-kidney-metabolic syndrome, connecting diabetes and cardiovascular disease. While studies suggest consistent associations, causal mechanisms remain unclear. No therapies specifically target FGF23 to lower diabetes risk, but fibroblast growth factor receptor 4 (FGFR4) inhibitors show promise. Future research should examine the role of FGF23 in individuals with normal kidney function and explore whether modifying its levels could reduce diabetes and cardiovascular risk.

Purpose of review: Vascular calcification significantly contributes to cardiovascular morbidity and mortality, particularly in high-risk populations like chronic kidney disease (CKD) patients. Calprotectin, a heterodimeric protein with pro-inflammatory and pro-calcific properties, has emerged as a key molecule in vascular pathology. This review highlights the mechanisms linking calprotectin to vascular calcification, its clinical relevance, and its potential as a therapeutic target.

Recent findings: Vascular calcification is an active, cell-mediated process involving vascular smooth muscle cell (VSMC) dysfunction, inflammation, matrix remodeling, and cellular senescence. Calprotectin is strongly associated with cardiovascular disease and vascular calcification, particularly in CKD. Mechanistic studies reveal that calprotectin promotes calcification through the activation of RAGE and TLR4 signaling pathways, driving inflammatory cascades. Preclinical studies demonstrate that pharmacological inhibition of calprotectin attenuates vascular calcification in animal models, supporting its potential as a therapeutic target.

Summary: Calprotectin is emerging as a promising biomarker and therapeutic target in vascular calcification, particularly in CKD and aging-related vascular diseases. However, further studies are required to clarify its mechanisms and assess the long-term efficacy and safety of calprotectin-targeted therapies. A deeper understanding of calprotectin's multifaceted role could pave the way for innovative therapeutic strategies targeting both inflammation and mineralization in calcification-related vascular diseases.