Vitamin D, a modulator of musculoskeletal health in chronic kidney disease

The spectrum of activity of vitamin D goes beyond calcium and bone homeostasis, and growing evidence suggests that vitamin D contributes to maintain musculoskeletal health in healthy subjects as well as in patients with chronic kidney disease (CKD), who display the combination of bone metabolism disorder, muscle wasting, and weakness. Here, we review how vitamin D represents a pathway in which bone and muscle may interact. In vitro studies have confirmed that the vitamin D receptor is present on muscle, describing the mechanisms whereby vitamin D directly affects skeletal muscle. These include genomic and non‐genomic (rapid) effects, regulating cellular differentiation and proliferation. Observational studies have shown that circulating 25‐hydroxyvitamin D levels correlate with the clinical symptoms and muscle morphological changes observed in CKD patients. Vitamin D deficiency has been linked to low bone formation rate and bone mineral density, with an increased risk of skeletal fractures. The impact of low vitamin D status on skeletal muscle may also affect muscle metabolic pathways, including its sensitivity to insulin. Although some interventional studies have shown that vitamin D may improve physical performance and protect against the development of histological and radiological signs of hyperparathyroidism, evidence is still insufficient to draw definitive conclusions

Primary Versus Secondary Prevention of Chronic Kidney Disease: The Case of Dietary Protein

The proclamation that “the greatest medicine of all is to teach people how not to need it” (Hippocrates. 460-370 BC, Greece) is the basic principle of primary disease prevention, which aims to prevent disease before it ever occurs. Preventing exposures to hazards that cause disease, such as altering unhealthy behaviors, is one example of primary disease prevention. Secondary or tertiary disease prevention, however, refers to reducing the impact of a disease that has already occurred, or limiting the impact of an ongoing illness that has lasting effects, respectively. Salutary diets or lifestyles for primary versus secondary/tertiary disease prevention may not necessarily align.Full Tex

Evaluation of machine learning algorithms and relevant biomarkers for the diagnosis of multiple sclerosis based on optical coherence tomography

Multiple sclerosis (MS) is a prevalent neurodegener- ative disease with significant visual pathway-related symptoms. Optical coherence tomography (OCT) has emerged as a valuable tool, and machine learning (ML) techniques hold promise for MS diagnosis. However, ex- isting studies often lack comprehensive feature exploita- tion and require interpretable model analysis to improve clinical insights and diagnostic criteria. This study evaluates machine learning models for classification of healthy controls and MS patients using a comprehensive set of macular and optic-disc parameters from OCT imaging. The study included a dataset of 77 MS eyes and 54 control eyes, obtained by ophthalmic examination and OCT measurements from Optic Disc and Macular Cube scan protocols of a Cirrus HD-OCT 5000 (Carl Zeiss, Meditec, Dublin, CA, USA). Our results identi- fied 19 features, validated by p-values (p < 0.001), as effective discriminators between MS patients and healthy controls. Patient-wise cross-validation is used to eval- uate the performance of five ML algorithms. Gaussian Naive Bayes achieved the best AUC (87.9% ± 7.7%), while SHAP analysis reinforced the alignment with clin- ical observations of MS-related visual pathway changes and ganglion cell layer degeneration, with minimum ganglion cell thickness being the feature with the highest impact on classification. These findings underscore the potential of OCT-ML for early diagnosis and personal- ized treatment of MS.This research is part of the grant TED2021-131951B-I00 funded by MCIN/AEI/10.13039/501100011033 and by the the “European Union NextGenerationEU/PRTR” and the grant ”Primeros Proyetos” funded by the ETSI Telecomunicaci´on (Universidad Polit´ecnica de Madrid)

Evaluation of machine learning algorithms and relevant biomarkers for the diagnosis of multiple sclerosis based on optical coherence tomography

Multiple sclerosis (MS) is a prevalent neurodegener- ative disease with significant visual pathway-related symptoms. Optical coherence tomography (OCT) has emerged as a valuable tool, and machine learning (ML) techniques hold promise for MS diagnosis. However, ex- isting studies often lack comprehensive feature exploita- tion and require interpretable model analysis to improve clinical insights and diagnostic criteria. This study evaluates machine learning models for classification of healthy controls and MS patients using a comprehensive set of macular and optic-disc parameters from OCT imaging. The study included a dataset of 77 MS eyes and 54 control eyes, obtained by ophthalmic examination and OCT measurements from Optic Disc and Macular Cube scan protocols of a Cirrus HD-OCT 5000 (Carl Zeiss, Meditec, Dublin, CA, USA). Our results identi- fied 19 features, validated by p-values (p < 0.001), as effective discriminators between MS patients and healthy controls. Patient-wise cross-validation is used to eval- uate the performance of five ML algorithms. Gaussian Naive Bayes achieved the best AUC (87.9% ± 7.7%), while SHAP analysis reinforced the alignment with clin- ical observations of MS-related visual pathway changes and ganglion cell layer degeneration, with minimum ganglion cell thickness being the feature with the highest impact on classification. These findings underscore the potential of OCT-ML for early diagnosis and personal- ized treatment of MS.This research is part of the grant TED2021-131951B-I00 funded by MCIN/AEI/10.13039/501100011033 and by the the “European Union NextGenerationEU/PRTR” and the grant ”Primeros Proyetos” funded by the ETSI Telecomunicaci´on (Universidad Polit´ecnica de Madrid)

Vitamin D, a modulator of musculoskeletal health in chronic kidney disease

The spectrum of activity of vitamin D goes beyond calcium and bone homeostasis, and growing evidence suggests that vitamin D contributes to maintain musculoskeletal health in healthy subjects as well as in patients with chronic kidney disease (CKD), who display the combination of bone metabolism disorder, muscle wasting, and weakness. Here, we review how vitamin D represents a pathway in which bone and muscle may interact. In vitro studies have confirmed that the vitamin D receptor is present on muscle, describing the mechanisms whereby vitamin D directly affects skeletal muscle. These include genomic and non-genomic (rapid) effects, regulating cellular differentiation and proliferation. Observational studies have shown that circulating 25-hydroxyvitamin D levels correlate with the clinical symptoms and muscle morphological changes observed in CKD patients. Vitamin D deficiency has been linked to low bone formation rate and bone mineral density, with an increased risk of skeletal fractures. The impact of low vitamin D status on skeletal muscle may also affect muscle metabolic pathways, including its sensitivity to insulin. Although some interventional studies have shown that vitamin D may improve physical performance and protect against the development of histological and radiological signs of hyperparathyroidism, evidence is still insufficient to draw definitive conclusions

A commentary from the European Renal Best Practice (ERBP) on the Kidney Disease Improving Global Outcomes (KDIGO) 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease in children and adults

The Kidney Disease: Improving Global Outcomes (KDIGO) 2024 Guidelines for identification and management of chronic kidney disease (CKD) are a welcome development coming 12 years after the paradigm changing 2012 guidelines. We are living in an unprecedented era in nephrology with novel therapies, including sodium-glucose cotransporter-2 inhibitors, glucagon-like peptide-1 receptor agonists and non-steroidal mineralocorticoid receptor antagonists now being proven in multiple randomised controlled clinical trials to reduce both the progression of CKD and cardiovascular morbidity and mortality. The KDIGO 2024 CKD guideline is aimed at a broad audience looking after children and adults with CKD and provide practical and actionable steps to improve care. This commentary reviews the guideline sections pertaining to the evaluation and risk assessment of individuals with CKD from a European perspective. We feel that despite the last guideline being published 12 years ago, and that the assessment of CKD has been emphasized by many other national/international nephrology, cardiology and diabetology guidelines and societies, the diagnosis and treatment of CKD remains poor across Europe. As such the KDIGO 2024 CKD Guidelines should be seen as an urgent call to action to improve diagnosis and care of children and adults with CKD across Europe. We know what we need to do. We now need to get on and do it

Chronic kidney disease and arrhythmias: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference.

Patients with chronic kidney disease (CKD) are predisposed to heart rhythm disorders, including atrial fibrillation (AF)/atrial flutter, supraventricular tachycardias, ventricular arrhythmias, and sudden cardiac death (SCD). While treatment options, including drug, device, and procedural therapies, are available, their use in the setting of CKD is complex and limited. Patients with CKD and end-stage kidney disease (ESKD) have historically been under-represented or excluded from randomized trials of arrhythmia treatment strategies,1 although this situation is changing.2 Cardiovascular society consensus documents have recently identified evidence gaps for treating patients with CKD and heart rhythm disorders [...

Global, regional, and national burden of chronic kidney disease, 1990–2017 : a systematic analysis for the Global Burden of Disease Study 2017

Background Health system planning requires careful assessment of chronic kidney disease (CKD) epidemiology, but data for morbidity and mortality of this disease are scarce or non-existent in many countries. We estimated the global, regional, and national burden of CKD, as well as the burden of cardiovascular disease and gout attributable to impaired kidney function, for the Global Burden of Diseases, Injuries, and Risk Factors Study 2017. We use the term CKD to refer to the morbidity and mortality that can be directly attributed to all stages of CKD, and we use the term impaired kidney function to refer to the additional risk of CKD from cardiovascular disease and gout. Methods The main data sources we used were published literature, vital registration systems, end-stage kidney disease registries, and household surveys. Estimates of CKD burden were produced using a Cause of Death Ensemble model and a Bayesian meta-regression analytical tool, and included incidence, prevalence, years lived with disability, mortality, years of life lost, and disability-adjusted life-years (DALYs). A comparative risk assessment approach was used to estimate the proportion of cardiovascular diseases and gout burden attributable to impaired kidney function. Findings Globally, in 2017, 1·2 million (95% uncertainty interval [UI] 1·2 to 1·3) people died from CKD. The global all-age mortality rate from CKD increased 41·5% (95% UI 35·2 to 46·5) between 1990 and 2017, although there was no significant change in the age-standardised mortality rate (2·8%, −1·5 to 6·3). In 2017, 697·5 million (95% UI 649·2 to 752·0) cases of all-stage CKD were recorded, for a global prevalence of 9·1% (8·5 to 9·8). The global all-age prevalence of CKD increased 29·3% (95% UI 26·4 to 32·6) since 1990, whereas the age-standardised prevalence remained stable (1·2%, −1·1 to 3·5). CKD resulted in 35·8 million (95% UI 33·7 to 38·0) DALYs in 2017, with diabetic nephropathy accounting for almost a third of DALYs. Most of the burden of CKD was concentrated in the three lowest quintiles of Socio-demographic Index (SDI). In several regions, particularly Oceania, sub-Saharan Africa, and Latin America, the burden of CKD was much higher than expected for the level of development, whereas the disease burden in western, eastern, and central sub-Saharan Africa, east Asia, south Asia, central and eastern Europe, Australasia, and western Europe was lower than expected. 1·4 million (95% UI 1·2 to 1·6) cardiovascular disease-related deaths and 25·3 million (22·2 to 28·9) cardiovascular disease DALYs were attributable to impaired kidney function. Interpretation Kidney disease has a major effect on global health, both as a direct cause of global morbidity and mortality and as an important risk factor for cardiovascular disease. CKD is largely preventable and treatable and deserves greater attention in global health policy decision making, particularly in locations with low and middle SDI