Muscle mass, muscle strength and mortality in kidney transplant recipients: results of the TransplantLines Biobank and Cohort Study

Vliet, Iris M Y van; Post, Adrian; Boslooper-Meulenbelt, Karin; Veen, Yvonne van der; Jong, Margriet F C de; Dijkstra, Gerard; Meijer, Vincent E de; Leuvenink, Henri; Gan, C. Tji-Joong; Sanders, Jan-Stephan; Verschuuren, Erik; Damman, Kevin; Lexmond, Willem S.; Blokzijl, J.; Borst, Martin H. de; Erasmus, Michiel E.; Porte, Robert J.; Boer, Marieke T. de; Pol, Robert A.; Berger, Stefan P.; Eisenga, Michele F.; Neto, Antonio W. Gomes; Kremer, Daan; Londen, Marco van; Jong, J.H. Annema‐de; Siebelink, Marion J.; Pelt, L Joost van; Niesters, Hubert G. M.; Bodewes, Frank; Hepkema, Bouke; Ranchor, Adelita V.; Douwes, Rianne M.; Jager‐Wittenaar, Harriët; Navis, Gerjan; Bakker, Stephan J. L.

doi:10.1002/jcsm.13070

Cited by 11 publications

(10 citation statements)

References 43 publications

(97 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Similarly, our prior meta-analysis observed a consistent inverse relationship between higher upper extremity muscle strength and all-cause mortality [ 8 ]. A recent cohort study evaluating the association between handgrip strength index and mortality in kidney transplant recipients yielded similar results [ 40 ]. Despite the availability of handgrip strength reference values for different populations, there are few reports on the optimal handgrip strength for preventing all-cause mortality in CKD.…”

Section: Discussionmentioning

confidence: 66%

Thresholds of handgrip strength for all-cause mortality in patients with chronic kidney disease: a secondary systematic review with dose-response meta-analysis

Chen,

Zhang,

Huang

et al. 2024

Renal Failure

View full text Add to dashboard Cite

Background Although handgrip strength is associated with all-cause mortality in patients with chronic kidney disease (CKD), whether this relationship is dose-related is unknown. Therefore, we examined dose-response relationships between handgrip strength and all-cause mortality in CKD patients based on previous studies by meta-analysis. Methods Data sources included three electronic databases (PubMed, Web of Science, and Embase) from inception through October 2023. The included cohort was a CKD population not limited to disease stage, and their handgrip strength was objectively measured. Two researchers independently screened studies, extracted data, and assessed the risk of bias. We utilized estimates of handgrip strength categories using robust-error meta-regression (REMR), pooled study-specific estimates, and established dose-response relationships. Outcomes of interest included only all-cause mortality. Results A total of 18 studies with 4810 participants (aged 47–71 years) were included. REMR modeling showed a U-shaped trend of association between handgrip strength and all-cause mortality in patients with CKD. Higher handgrip strength values, from 10 kg to approximately 28 kg, were associated with lower mortality risk. After that, the risk of death increased slightly. Conclusion A U-shaped association exists between handgrip strength and all-cause mortality risk in CKD patients. Future studies with quantitative measurements for each CKD stage will help to determine precise relative risk estimates between handgrip strength and mortality risk in patients with different stages of CKD.

show abstract

Section: Discussionmentioning

confidence: 66%

Thresholds of handgrip strength for all-cause mortality in patients with chronic kidney disease: a secondary systematic review with dose-response meta-analysis

Chen,

Zhang,

Huang

et al. 2024

Renal Failure

View full text Add to dashboard Cite

show abstract

“…In model 3, we additionally adjusted for plasma haemoglobin (Hb). In sensitivity analyses, we substituted CER for length‐indexed CER 17 and length^2‐indexed CER, 18 given that muscle mass depends on body size. Furthermore, we repeated the analyses after exclusion of the 5% most extreme ferritin or TSAT values by calculating absolute differences from the median.…”

Section: Methodsmentioning

confidence: 99%

Iron deficiency is related to lower muscle mass in community‐dwelling individuals and impairs myoblast proliferation

Vinke

Gorter

Eisenga

et al. 2023

J cachexia sarcopenia muscle

Self Cite

View full text Add to dashboard Cite

Background Loss of muscle mass is linked with impaired quality of life and an increased risk of morbidity and premature mortality. Iron is essential for cellular processes such as energy metabolism, nucleotide synthesis and numerous enzymatic reactions. As the effects of iron deficiency (ID) on muscle mass and function are largely unknown, we aimed to assess the relation between ID and muscle mass in a large population‐based cohort, and subsequently studied effects of ID on cultured skeletal myoblasts and differentiated myocytes. Methods In a population‐based cohort of 8592 adults, iron status was assessed by plasma ferritin and transferrin saturation, and muscle mass was estimated using 24‐h urinary creatinine excretion rate (CER). The relationships of ferritin and transferrin saturation with CER were assessed by multivariable logistic regression. Furthermore, mouse C2C12 skeletal myoblasts and differentiated myocytes were subjected to deferoxamine with or without ferric citrate. Myoblast proliferation was measured with a colorimetric 5‐bromo‐2′‐deoxy‐uridine ELISA assay. Myocyte differentiation was assessed using Myh7‐stainings. Myocyte energy metabolism, oxygen consumption rate and extracellular acidification rate were assessed using Seahorse mitochondrial flux analysis, and apoptosis rate with fluorescence‐activated cell sorting. RNA sequencing (RNAseq) was used to identify ID‐related gene and pathway enrichment in myoblasts and myocytes. Results Participants in the lowest age‐ and sex‐specific quintile of plasma ferritin (OR vs middle quintile 1.62, 95% CI 1.25–2.10, P < 0.001) or transferrin saturation (OR 1.34, 95% CI 1.03–1.75, P = 0.03) had a significantly higher risk of being in the lowest age‐ and sex‐specific quintile of CER, independent of body mass index, estimated GFR, haemoglobin, hs‐CRP, urinary urea excretion, alcohol consumption and smoking status. In C2C12 myoblasts, deferoxamine‐induced ID reduced myoblast proliferation rate (P‐trend <0.001) but did not affect differentiation. In myocytes, deferoxamine reduced myoglobin protein expression (−52%, P < 0.001) and tended to reduce mitochondrial oxygen consumption capacity (−28%, P = 0.10). Deferoxamine induced gene expression of cellular atrophy markers Trim63 (+20%, P = 0.002) and Fbxo32 (+27%, P = 0.048), which was reversed by ferric citrate (−31%, P = 0.04 and −26%, P = 0.004, respectively). RNAseq indicated that both in myoblasts and myocytes, ID predominantly affected genes involved in glycolytic energy metabolism, cell cycle regulation and apoptosis; co‐treatment with ferric citrate reversed these effects. Conclusions In population‐dwelling individuals, ID is related to lower muscle mass, independent of haemoglobin levels and potential confounders. ID impaired myoblast proliferation and aerobic glycolytic capacity, and induced markers of myocyte atrophy and apoptosis. These findings suggest that ID contributes to loss of muscle mass.

show abstract

“…However, some studies have reported beneficial effects of dialysis on skeletal muscle, such as the reduction of skeletal muscle fibrosis, the restoration of satellite cell populations, and an overall increase in muscle strength and endurance [135]. Clearly, transplantation is the treatment of choice for ESRD patients, as it improves survival and quality of life, including increases in physical performance and muscle strength [434][435][436]. Surprisingly, to date, only a few studies have analyzed skeletal muscle tissue in transplanted CKD patients to determine changes on histological, cellular, and molecular levels.…”

Section: The Effects Of Dialysis and Kidney Transplantation On Ckd-as...mentioning

confidence: 99%

Skeletal Muscle Injury in Chronic Kidney Disease—From Histologic Changes to Molecular Mechanisms and to Novel Therapies

Heitman,

Alexander,

Faul

2024

IJMS

View full text Add to dashboard Cite

Chronic kidney disease (CKD) is associated with significant reductions in lean body mass and in the mass of various tissues, including skeletal muscle, which causes fatigue and contributes to high mortality rates. In CKD, the cellular protein turnover is imbalanced, with protein degradation outweighing protein synthesis, leading to a loss of protein and cell mass, which impairs tissue function. As CKD itself, skeletal muscle wasting, or sarcopenia, can have various origins and causes, and both CKD and sarcopenia share common risk factors, such as diabetes, obesity, and age. While these pathologies together with reduced physical performance and malnutrition contribute to muscle loss, they cannot explain all features of CKD-associated sarcopenia. Metabolic acidosis, systemic inflammation, insulin resistance and the accumulation of uremic toxins have been identified as additional factors that occur in CKD and that can contribute to sarcopenia. Here, we discuss the elevation of systemic phosphate levels, also called hyperphosphatemia, and the imbalance in the endocrine regulators of phosphate metabolism as another CKD-associated pathology that can directly and indirectly harm skeletal muscle tissue. To identify causes, affected cell types, and the mechanisms of sarcopenia and thereby novel targets for therapeutic interventions, it is important to first characterize the precise pathologic changes on molecular, cellular, and histologic levels, and to do so in CKD patients as well as in animal models of CKD, which we describe here in detail. We also discuss the currently known pathomechanisms and therapeutic approaches of CKD-associated sarcopenia, as well as the effects of hyperphosphatemia and the novel drug targets it could provide to protect skeletal muscle in CKD.

show abstract

Muscle mass, muscle strength and mortality in kidney transplant recipients: results of the TransplantLines Biobank and Cohort Study

Cited by 11 publications

References 43 publications

Thresholds of handgrip strength for all-cause mortality in patients with chronic kidney disease: a secondary systematic review with dose-response meta-analysis

Thresholds of handgrip strength for all-cause mortality in patients with chronic kidney disease: a secondary systematic review with dose-response meta-analysis

Iron deficiency is related to lower muscle mass in community‐dwelling individuals and impairs myoblast proliferation

Skeletal Muscle Injury in Chronic Kidney Disease—From Histologic Changes to Molecular Mechanisms and to Novel Therapies

Contact Info

Product

Resources

About