A new era in the science and care of kidney diseases

Zoccali, Carmine; Mallamaci, Francesca; Lightstone, Liz; Jha, Vivek; Pollock, Carol; Tuttle, Katherine; Kotanko, Peter; Wiecek, Andrzej; Anders, Hans Joachim; Remuzzi, Giuseppe; Kalantar-Zadeh, Kamyar; Levin, Adeera; Vanholder, Raymond

doi:10.1038/s41581-024-00828-y

Cited by 4 publications

(1 citation statement)

References 132 publications

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“…CKM syndrome is characterized by early dysfunctional adiposity that can progress to hyperglycemia and insulin resistance ( 10 ). This predisposes patients to systemic inflammatory and oxidative stresses, which, when combined with genetic and environmental factors, cascades into cardiorenal dysfunction ( 11 , 12 ). At this point, the cardiovascular system, kidney, and systemic metabolic network cascade through a series of communications that ultimately lead to coronary artery disease, peripheral artery disease, stroke, heart failure, or renal failure ( 9 ).…”

Section: Ckm Syndrome and Lymphaticsmentioning

confidence: 99%

Targeting lymphatic function in cardiovascular-kidney-metabolic syndrome: preclinical methods to analyze lymphatic function and therapeutic opportunities

Fowler,

Song,

Tam

et al. 2024

Front. Cardiovasc. Med.

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The lymphatic vascular system spans nearly every organ in the body and serves as an important network that maintains fluid, metabolite, and immune cell homeostasis. Recently, there has been a growing interest in the role of lymphatic biology in chronic disorders outside the realm of lymphatic abnormalities, lymphedema, or oncology, such as cardiovascular-kidney-metabolic syndrome (CKM). We propose that enhancing lymphatic function pharmacologically may be a novel and effective way to improve quality of life in patients with CKM syndrome by engaging multiple pathologies at once throughout the body. Several promising therapeutic targets that enhance lymphatic function have already been reported and may have clinical benefit. However, much remains unclear of the discreet ways the lymphatic vasculature interacts with CKM pathogenesis, and translation of these therapeutic targets to clinical development is challenging. Thus, the field must improve characterization of lymphatic function in preclinical mouse models of CKM syndrome to better understand molecular mechanisms of disease and uncover effective therapies.

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Section: Ckm Syndrome and Lymphaticsmentioning

confidence: 99%

Targeting lymphatic function in cardiovascular-kidney-metabolic syndrome: preclinical methods to analyze lymphatic function and therapeutic opportunities

Fowler,

Song,

Tam

et al. 2024

Front. Cardiovasc. Med.

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Apigenin’s Health Benefits in Kidney Disease: Pharmacological Insights and Future Perspectives

Wu,

Dai,

et al. 2024

Food Reviews International

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Sustained Reduction of Elevated Intact Parathyroid Hormone Concentrations with Extended-Release Calcifediol Slows Chronic Kidney Disease Progression in Secondary Hyperparathyroidism Patients

Bishop,

Ashfaq,

Strugnell

et al. 2024

Am J Nephrol

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Introduction. Chronic kidney disease (CKD) drives onerous human and healthcare costs, underscoring an urgent need to avert disease progression. Secondary hyperparathyroidism (SHPT) develops as CKD advances, and persistently elevated parathyroid hormone (PTH) may be nephrotoxic and associated with earlier dialysis onset. This study examines, for the first time, the hypothesis that sustained reduction of elevated intact PTH (iPTH) with extended-release calcifediol (ERC) reduces the nephrotoxic impact of SHPT and forestalls renal decline. Methods. Changes in estimated glomerular filtration rate (eGFR) were analyzed post-hoc in 126 adults with SHPT, stage 3-4 CKD and low serum 25-hydroxyvitamin D (25D) treated for one year with ERC in pivotal trials. ERC was administered at 30 μg/day increasing, as needed, to 60 μg/day to achieve ≥30% reductions in iPTH. Calcium, phosphorus, 25D, 1,25-dihydroxyvitamin D (1,25D), iPTH, eGFR, fibroblast growth factor 23 (FGF23), bone turnover markers (BTM), and urine albumin-to-creatinine ratio (uACR) were measured at baseline (BL) and regular intervals. Participants were categorized by achievement (or not) of sustained ≥30% iPTH reductions over the last 2 quarters of treatment to evaluate differences in eGFR decline. Results. For all participants, 25D increased 58.5±2.3 (SE) ng/mL (p<0.001) by the end of treatment (EOT), 1,25D increased 10.1±1.8 pg/mL (p<0.001), iPTH decreased from 143.8±5.8 pg/mL to 108.8±7.2 (p<0.001), BTMs improved (p<0.01) and eGFR declined 2.2±0.5 mL/min/1.73m2 (p<0.001). The rate of eGFR decline was >5-fold higher (p=0.014) in participants who did not achieve sustained iPTH reductions of ≥30% (3.2±0.7; 12.7±2.2%) than in those who did (0.6±0.8; 2.9±2.4%). It was highest in the 30 participants who did not exhibit an iPTH lowering response in both of the last 2 quarters of treatment (5.4±0.9; 20.9±3.4%). Duration of iPTH reduction had no impact on safety parameters. Degree of iPTH reduction at EOT was also associated with slower CKD progression. Conclusion. Sustained reduction of elevated iPTH with ERC treatment was associated with slower rates of eGFR decline in patients with SHPT and stage 3-4 CKD without raising safety concerns. A prospective trial is warranted to confirm this finding.

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A new era in the science and care of kidney diseases

Cited by 4 publications

References 132 publications

Targeting lymphatic function in cardiovascular-kidney-metabolic syndrome: preclinical methods to analyze lymphatic function and therapeutic opportunities

Targeting lymphatic function in cardiovascular-kidney-metabolic syndrome: preclinical methods to analyze lymphatic function and therapeutic opportunities

Apigenin’s Health Benefits in Kidney Disease: Pharmacological Insights and Future Perspectives

Sustained Reduction of Elevated Intact Parathyroid Hormone Concentrations with Extended-Release Calcifediol Slows Chronic Kidney Disease Progression in Secondary Hyperparathyroidism Patients

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