Plasma C-terminal agrin fragment and rapid kidney function decline in chronic kidney disease patients

Lorenz, Georg; Hettwer, Stefan; McCallum, Wendy; Angermann, Susanne; Wen, Ming; Schmaderer, Christoph; Heemann, Uwe; Roos, Marcel; Renders, Lutz; Steubl, Dominik

doi:10.1097/md.0000000000015597

Cited by 4 publications

(5 citation statements)

References 18 publications

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“…Supporting this concept, several studies reported strong positive correlation between CAF concentration and creatinine (a well‐established marker of kidney functionality) and negative correlation between CAF and estimated GFR in patients with chronic kidney disease 96 and undergoing kidney transplantation 53,94 . In a 57‐week study, CAF was reported to have a high predictive power in determining rapid kidney function decline in patients affected by chronic kidney disease, independently from estimated GFR 97 . Hence, although the authors acknowledged that NMJ‐derived CAF may play a partial role also in the elevated concentrations observed among kidney‐dysfunctional patients, the presence of kidney‐related diseases seems an independent predictor of elevated CAF.…”

Section: Methodological Considerationsmentioning

confidence: 91%

“… 53 , 94 In a 57‐week study, CAF was reported to have a high predictive power in determining rapid kidney function decline in patients affected by chronic kidney disease, independently from estimated GFR. 97 Hence, although the authors acknowledged that NMJ‐derived CAF may play a partial role also in the elevated concentrations observed among kidney‐dysfunctional patients, the presence of kidney‐related diseases seems an independent predictor of elevated CAF. In this context, particular attention should be paid when investigating CAF in diabetic patients, as this pathology is the leading cause of chronic kidney disease.…”

Section: Methodological Considerationsmentioning

confidence: 99%

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C‐terminal agrin fragment as a biomarker of muscle wasting and weakness: a narrative review

Monti

Sarto

Sartori

et al. 2023

J cachexia sarcopenia muscle

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Ageing is accompanied by an inexorable loss of muscle mass and functionality and represents a major risk factor for numerous diseases such as cancer, diabetes and cardiovascular and pulmonary diseases. This progressive loss of muscle mass and function may also result in the insurgence of a clinical syndrome termed sarcopenia, exacerbated by inactivity and disease. Sarcopenia and muscle weakness yield the risk of falls and injuries, heavily impacting on health and social costs. Thus, screening, monitoring and prevention of conditions inducing muscle wasting and weakness are essential to improve life quality in the ageing modern society. To this aim, the reliability of easily accessible and non-invasive bloodderived biomarkers is being evaluated. C-terminal agrin fragment (CAF) has been widely investigated as a neuromuscular junction (NMJ)-related biomarker of muscle dysfunction. This narrative review summarizes and critically discusses, for the first time, the studies measuring CAF concentration in young and older, healthy and diseased individuals, cross-sectionally and in response to inactivity and physical exercise, providing possible explanations behind the discrepancies observed in the literature. To identify the studies investigating CAF in the above-mentioned conditions, all the publications found in PubMed, written in English and measuring this biomarker in blood from 2013 (when CAF was firstly measured in human serum) to 2022 were included in this review. CAF increases with age and in sarcopenic individuals when compared with age-matched, non-sarcopenic peers. In addition, CAF was found to be higher than controls in other muscle wasting conditions, such as diabetes, COPD, chronic heart failure and stroke, and in pancreatic and colorectal cancer cachectic patients. As agrin is also expressed in kidney glomeruli, chronic kidney disease and transplantation were shown to have a profound impact on CAF independently from muscle wasting. CAF concentration raises following inactivity and seems to be lowered or maintained by exercise training. Finally, CAF was reported to be cross-sectionally correlated to appendicular lean mass, handgrip and gait speed; whether longitudinal changes in CAF are associated with those in muscle mass or performance following physical exercise is still controversial. CAF seems a reliable marker to assess muscle wasting in ageing and disease, also correlating with measurements of appendicular lean mass and muscle function. Future research should aim at enlarging sample size and accurately reporting the medical history of each patient, to normalize for any condition, including chronic kidney disease, that may influence the circulating concentration of this biomarker.

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Section: Methodological Considerationsmentioning

confidence: 91%

Section: Methodological Considerationsmentioning

confidence: 99%

C‐terminal agrin fragment as a biomarker of muscle wasting and weakness: a narrative review

Monti

Sarto

Sartori

et al. 2023

J cachexia sarcopenia muscle

View full text Add to dashboard Cite

show abstract

“…53,94 In a 57-week study, CAF was reported to have a high predictive power in determining rapid kidney function decline in patients affected by chronic kidney disease, independently from estimated GFR. 97 Hence, although the authors acknowledged that NMJ-derived CAF may play a partial role also in the elevated concentrations observed among kidney-dysfunctional patients, the presence of kidneyrelated diseases seems an independent predictor of elevated CAF. In this context, particular attention should be paid when investigating CAF in diabetic patients, as this pathology is the leading cause of chronic kidney disease.…”

Section: Methodological Considerationsmentioning

confidence: 99%

Effects of a 2‐year exercise training on neuromuscular system health in older individuals with low muscle function

Monti

Tagliaferri

Zampieri

et al. 2023

J cachexia sarcopenia muscle

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Background Ageing is accompanied by a progressive loss of skeletal muscle mass and strength, potentially determining the insurgence of sarcopenia. Evidence suggests that motoneuron and neuromuscular junction (NMJ) degeneration contribute to sarcopenia pathogenesis. Seeking for strategies able to slow down sarcopenia insurgence and progression, we investigated whether a 2-year mixed-model training involving aerobic, strength and balance exercises would be effective for improving or preserving motoneuronal health and NMJ stability, together with muscle mass, strength and functionality in an old, sarcopenic population. Methods Forty-five sarcopenic elderly (34 females; 11 males) with low dual-energy X-ray absorptiometry (DXA) lean mass and Short Physical Performance Battery (SPPB) score <9 were randomly assigned to either a control group [Healthy Aging Lifestyle Education (HALE), n = 21] or an intervention group [MultiComponent Intervention (MCI), n = 24]. MCI trained three times per week for 2 years with a mix of aerobic, strength and balance exercises matched with nutritional advice. Before and after the intervention, ultrasound scans of the vastus lateralis (VL), SPPB and a blood sample were obtained. VL architecture [pennation angle (PA) and fascicle length (Lf)] and cross-sectional area (CSA) were measured. As biomarkers of neuronal health and NMJ stability status, neurofilament light chain (NfL) and C-terminal agrin fragment (CAF) concentrations were measured in serum. Differences in ultrasound parameters, NfL and CAF concentration and physical performance between baseline and follow-up were tested with mixed ANOVA or Wilcoxon test. The relationship between changes in physical performance and NfL or CAF concentration was assessed through correlation analyses. Results At follow-up, MCI showed preserved VL architecture (PA, Lf) despite a reduced CSA (À8.4%, P < 0.001), accompanied by maintained CAF concentration and ameliorated overall SPPB performance (P = 0.007). Conversely, HALE showed 12.7% decrease in muscle CSA (P < 0.001), together with 5.1% and 5.5% reduction in PA and Lf (P < 0.001 and P = 0.001, respectively), and a 6.2% increase in CAF (P = 0.009) but improved SPPB balance score (P = 0.007). NfL concentration did not change in either group. In the population, negative correlations between changes in CAF concentration and SPPB total score were found (P = 0.047), whereas no correlation between NfL and SPPB variations was observed. Conclusions The present findings suggest that our 2-year mixed aerobic, strength and balance training seemed effective for preventing the age and sarcopenia-related increases in CAF concentration, preserving NMJ stability as well as muscle structure (PA and Lf) and improving physical performance in sarcopenic older individuals.

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“…Interestingly, also renal function has been linked to raised levels of circulating CAF since this biomarker has been reported to be higher in patients developing acute kidney injury and undergoing kidney transplantation [55]. Reports showed CAF to have a high predictive power in determining rapid kidney function decline in patients affected by CKD, and – above that – CAF was cross-sectionally correlated to appendicular lean mass, handgrip, and gait speed from estimated glomerular filtration rate (GFR) [56].…”

Section: “The Good”: Assess and Monitor Muscle Mass Nutrition And Phy...mentioning

confidence: 99%

“…C-terminal agrin fragment (CAF) has been investigated as a neuromuscular junctiona related biomarker of muscle dysfunction [55][56][57][58]. Interestingly, also renal function has been linked to raised levels of circulating CAF since this biomarker has been reported to be higher in patients developing acute kidney injury and undergoing kidney transplantation [55].…”

Section: Biomarkersmentioning

confidence: 99%

The Good, the Bad, and the Serum Creatinine: Exploring the Effect of Muscle Mass and Nutrition

De Rosa,

Greco,

Rauseo

et al. 2023

Blood Purif

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Muscle wasting (sarcopenia) is one of the hallmarks of critical illness. Patients admitted to intensive care unit develop sarcopenia through increased protein catabolism, a decrease in protein syntheses, or both. Among the factors known to promote wasting are chronic inflammation and cytokine imbalance, insulin resistance, hypermetabolism, and malnutrition. Moreover, muscle wasting, known to develop in chronic kidney disease patients, is a harmful consequence of numerous complications associated with deteriorated renal function. Plenty of published data suggest that serum creatinine (SCr) reflects increased kidney damage and is also related to body weight. Based on the concept that urea and creatinine are nitrogenous end products of metabolism, the urea:creatinine ratio (UCR) could be applied but with limited clinical usability in case of kidney damage, hypovolemia, excessive, or protein intake, where UCR can be high and independent of catabolism. Recent data suggest that the sarcopenia index should be considered an alternative to serum creatinine. It is more reliable in estimating muscle mass than SCr. However, the optimal biomarker of catabolism is still an unresolved issue. The SCr is not a promising biomarker for renal function and muscle mass based on the influence of several factors. The present review highlights recent findings on the limits of SCr as a surrogate marker of renal function and the assessment modalities of nutritional status and muscle mass measurements.

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Plasma C-terminal agrin fragment and rapid kidney function decline in chronic kidney disease patients

Abstract: Supplemental Digital Content is available in the text

Cited by 4 publications

References 18 publications

C‐terminal agrin fragment as a biomarker of muscle wasting and weakness: a narrative review

C‐terminal agrin fragment as a biomarker of muscle wasting and weakness: a narrative review

Effects of a 2‐year exercise training on neuromuscular system health in older individuals with low muscle function

The Good, the Bad, and the Serum Creatinine: Exploring the Effect of Muscle Mass and Nutrition

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