Folic Acid and Homocysteine in Chronic Kidney Disease and Cardiovascular Disease Progression: Which Comes First

Cianciolo, Giuseppe; Pascalis, Antonio De; Lullo, Luca Di; Ronco, Claudio; Zannini, Chiara; Manna, Gaetano La

doi:10.1159/000471813

Cited by 71 publications

(73 citation statements)

References 68 publications

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“…Homocysteine is an intermediate in methionine metabolism, and its plasma level increases in ESKD patients. Hyperhomocysteinemia has been suggested to contribute to the increased risk of CVD in this population [73]. In an experimental study by Givvimani et al, cystathionine β-synthase heterozygous knockout mice, well-known models of hyperhomocysteinemia, showed decreased intestinal motility [74].…”

Section: Hyperhomocysteinemiamentioning

confidence: 99%

Constipation in chronic kidney disease: it is time to reconsider

Ikee

Yano

Tsuru³

2019

Ren Replace Ther

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Constipation is highly prevalent in patients with chronic kidney disease (CKD) and is primarily characterized by decreased intestinal motility. This chronic disorder affects the quality of life of patients. However, nephrologist and dialysis clinicians have long had a disproportionately limited understanding of constipation. Accumulating evidence has revealed a relationship between constipation and cardiovascular disease and CKD. The pathogenesis of constipation in CKD patients is multifactorial: decreased physical activity, comorbidities affecting bowel movement, such as diabetes mellitus, cerebrovascular disease, and hyperparathyroidism, a restricted dietary intake of plantbased fiber-rich foods, and multiple medications, including phosphate binders and potassium-binding resins, have all been implicated. CKD is associated with alterations in the composition and function of the gut microbiota, socalled gut dysbiosis. Recent studies showed that CKD-related gut dysbiosis decreased intestinal motility via intestinal inflammation or the increased generation of gut-derived uremic toxins, such as indoxyl sulfate and pcresyl sulfate. Furthermore, the gastrointestinal secretion of mucin was found to be decreased in CKD animal models, which may delay colonic transit by diminished lubrication in the alimentary tract. Thus, CKD-related gut dysbiosis may play a role in constipation, but limited information is currently available. Since constipation is often intractable, particularly in CKD patients, every available means needs to be employed in its treatment. The effects of probiotics, prebiotics, and synbiotics on the composition of the gut microbiota and gut-derived uremic toxins have been increasingly reported. However, their effects on stool consistency or frequency in CKD patients remain unclear. Some laxatives may be beneficial for improving not only bowel habits but also gut dysbiosis. Further studies are required to elucidate the CKD-specific pathogenesis of constipation and develop novel effective treatment options.

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Section: Hyperhomocysteinemiamentioning

confidence: 99%

Constipation in chronic kidney disease: it is time to reconsider

Ikee

Yano

Tsuru³

2019

Ren Replace Ther

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“…Hyperhomocysteinemia (HHcy) is associated with kidney damage [1]. Studies have shown that there are various degrees of Hcy metabolic abnormalities in various kidney diseases [2,3], such as nephrotic syndrome [4], lupus nephritis [5], and chronic nephritis [3,6,7], most of which are accompanied by HHcy. On the other hand, HHcy also shows an influence on the kidney, causing changes in kidney structure and function and exacerbating kidney damage.…”

Section: Introductionmentioning

confidence: 99%

Nitrative Stress-Related Autophagic Insufficiency Participates in Hyperhomocysteinemia-Induced Renal Aging

Zhang

et al. 2020

Oxidative Medicine and Cellular Longevity

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The kidneys are important organs that are susceptible to aging. Hyperhomocysteinemia (HHcy) is a risk factor for nephropathy and is associated with chronic nephritis, purpuric nephritis, and nephrotic syndrome. Numerous studies have shown that elevated serum homocysteine levels can damage the kidneys; however, the underlying mechanism of HHcy on kidney damage remains unclear. In this study, we make use of a diet-induced HHcy rat model and in vitro cell culture to explore the role of autophagy in HHcy-induced renal aging and further explored the underlying mechanism. We demonstrated that HHcy led to the development of renal aging. Promoted kidney aging and autophagic insufficiency were involved in HHcy-induced renal aging. HHcy decreased the expression of transcription factor EB (TFEB), the key transcription factor of autophagy-related genes in renal tissue. Further experiments showed that nitrative stress levels were increased in the kidney of HHcy rats. Interestingly, pretreatment with the peroxynitrite (ONOO-) scavenger FeTMPyP not only reduced the Hcy-induced nitrative stress in vitro but also partially attenuated the decrease in TFEB in both protein and mRNA levels. Moreover, our results indicated that HHcy reduced TFEB expression and inhibited TFEB-mediated autophagy activation by elevating nitrative stress. In conclusion, this study showed an important role of autophagic insufficiency in HHcy-induced renal aging, in which downregulation of TFEB plays a major role. Furthermore, downexpression of TFEB was associated with increased nitrative stress in HHcy. This study provides a novel insight into the mechanism and therapeutic strategy for renal aging.

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“…14 Although the reduction of Hcy levels through supplementation of folic acid and vitamins is possible, data from randomized trials revealed controversial results regarding CVD, mortality, and CKD progression. 13,15,16 In this issue of the Journal, Shi et al 17 Chronic kidney disease was present in 18.44% of the study population, while albuminuria was more frequent than reduced eGFR (12.8% vs 8.6%). In total, 30.6% and 10.3% of the participants were hypertensive or had HHcy, respectively, with a greater prevalence of hypertension or HHcy among patients with CKD.…”

mentioning

confidence: 98%

“…Homocysteine (Hcy), a sulfur‐containing aminoacid involved in cellular metabolism, is considered as an independent risk factor for cardiovascular disease (CVD) in end‐stage renal disease . Hyperhomocysteinemia (HHcy) is a common finding in CKD as it affects 85% of these patients . Hcy is excreted by the kidney, its metabolism is impaired in CKD and malnutrition leads to lack of folic acid and vitamin B 12 .…”

mentioning

confidence: 99%

“…12 Hyperhomocysteinemia (HHcy) is a common finding in CKD as it affects 85% of these patients. 13 Hcy is excreted by the kidney, its metabolism is impaired in CKD and malnutrition leads to lack of folic acid and vitamin B 12 . 14 Although the reduction of Hcy levels through supplementation of folic acid and vitamins is possible, data from randomized trials revealed controversial results regarding CVD, mortality, and CKD progression.…”

mentioning

confidence: 99%

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