A special issue on from bench to bedside: An integrated and multidisciplinary approach to tackling diabetic kidney disease DOI Open Access
Janaka Karalliedde, Claire E. Hills

Diabetic Medicine, Год журнала: 2024, Номер unknown

Опубликована: Дек. 15, 2024

More than 800 million people have chronic kidney disease (CKD) globally and type 2 diabetes accounts for between 30% 50% of cases CKD.1 Diabetic Kidney (DKD) is associated with increased cardiovascular (CVD) morbidity mortality in many countries also the leading cause end stage needing replacement therapy (dialysis or transplantation).2 DKD impacts on length quality life significantly contributes to global healthcare expenditure these human economic costs are likely rise further future.2, 3 Prognosis progression can differ from one individual another, which often a consequence interactions traditional emerging risk factors as well social-demographic factors, such ethnicity socio-economic factors.4 The recent Research UK health inequalities report demonstrated that South Asian Black backgrounds three five times more require dialysis white background.5 This observation may be part linked increasing prevalence currently unknown determinants progression. management requires multifactorial multidisciplinary approach key focus early identification CKD screening then prompt intervention focussing important lifestyle modifications, using evidence-based medical treatments holistic care.3, 6 With advances pillars treatment includes renin angiotensin system inhibition, sodium glucose co-transporter inhibition (SGLT2-inh), non-steroidal mineralocorticoid receptor antagonists glucagon like peptide 1 agonists (GLP-1 RA) parallel CVD factor modification, there an opportunity intervene change risk.7, 8 For DKD, gaps care options limited contrast diabetes, indeed, high burden this cohort underappreciated.9 natural history has evolved over last 40 years, remains significant residual ESKD premature CVD.9, 10 Despite 30 not optimal present late when modifiability progression/risk less feasible. There thus urgent need better methods biomarkers aid stratification ensure those at highest recognized guideline directed therapies initiated promptly morbidity/mortality.8, 11 glycaemic control challenging setting individualized approach. pathophysiology multifaceted encompasses metabolic haemodynamic perturbations lead structural functional disturbances including glomerular hyper-filtration, mesangial expansion interstitial fibrosis, convergence fundamental mechanisms, 'sterile' inflammation age changes, example cell senescence.12, 13 Although precise role development unclear, studies suggest accelerated ageing phenotype, coupled maladaptive immune response, underlies Furthermore, coexistence disease, so called 'cardiorenal syndrome', occurs face multi-organ crosstalk, evidence suggesting systemic vascular robust predictor poor dyslipidaemia. As obesity, syndrome continue rise, major worldwide. A understanding interrelationships crosstalk different organs/systems contributing complications will enhance scientific could facilitate new interventions prevent treat diabetes-related co-morbidities. mechanisms underpin clinical benefits existing therapies, GLPRA SGLT2i, inform how why drug works both within inter-organ cardiovascular-kidney-metabolic other secondary diabetes. special issue diabetic medicine focussed basic translational research, potential therapeutic targets,12-15 changing diabetes,10 scenarios,11 guidelines their implementation day-to-day patient practice.16 We hope readers enjoy reading collection articles apply related learning drive future research help improve outcomes DKD. None. authors declare no conflicts interest.

Язык: Английский

The PKM2 activator TEPP‐46 suppresses cellular senescence in hydrogen peroxide‐induced proximal tubular cells and kidney fibrosis in CD‐1db/db mice DOI Creative Commons

S. Ishihara,

M. Kayes, Hirofumi Makino

и другие.

Journal of Diabetes Investigation, Год журнала: 2025, Номер unknown

Опубликована: Янв. 22, 2025

ABSTRACT Aim/Introduction Senescence is a key driver of age‐related kidney dysfunction, including diabetic disease. Oxidative stress activates cellular senescence, induces abnormal glycolysis, and associated with pyruvate kinase muscle isoform 2 (PKM2) dysfunction; however, the mechanisms linking PK activation to senescence have not been elucidated. We hypothesized that PKM2 by TEPP‐46 could suppress oxidative stress‐induced renal tubular cell injury senescence. Materials Methods To investigate effects on we conducted β‐galactosidase staining western blot analysis human primary cells (pRPTECs) treated hydrogen peroxide or without TEPP‐46. IL‐6 levels glycolytic flux were measured. Cell viability apoptosis assessed via MTS assay caspase 3 cleavage. For in vivo experiments, utilized CD‐1 db/db mice, fibrotic type diabetes model, which exhibit fibrosis. After 4 weeks intervention, fibrosis expression markers analyzed. Results In pRPTECs, increased number β‐galactosidase‐positive cells, (p16, p21, p53), p38 phosphorylation; co‐incubation suppressed these alterations. Hydrogen reduced viability, induced apoptosis, mesenchymal alterations, lactate production secretion; inhibitor mitigated effects. intervention fibrosis, tended reduce senescence‐associated molecules kidney. Conclusions be molecular target for protection against organ damage,

Язык: Английский

Процитировано

0
The role of kidney biopsy in deciphering diabetic versus non-diabetic origin of kidney disease among patients with type 2 diabetes mellitus and nephrotic range proteinuria: A retrospective study DOI Creative Commons

Efstratios Kardalas,

Aggeliki Paikopoulou,

Dimitra A. Vassiliadi

и другие.

Metabolism Open, Год журнала: 2024, Номер 23, С. 100313 - 100313

Опубликована: Авг. 28, 2024

Diabetes mellitus (DM) is tightly associated with the increased prevalence of diabetic kidney disease (DKD). Nonetheless, severe renal function impairment and/or nephrotic range-proteinuria could also result from non-diabetic (non-DRD) among patients DM. The 'Gold standard' for differential diagnosis between DKD and non-DRD biopsy, although no real consensus exists. Thus, this study intends to associate clinical biochemical profile DM histopathological data biopsy.In addition, we aimed evaluate role especially when other causes, than DM, are highly suspected disease.

Язык: Английский

Процитировано

0
A special issue on from bench to bedside: An integrated and multidisciplinary approach to tackling diabetic kidney disease DOI Open Access
Janaka Karalliedde, Claire E. Hills

Diabetic Medicine, Год журнала: 2024, Номер unknown

Опубликована: Дек. 15, 2024

More than 800 million people have chronic kidney disease (CKD) globally and type 2 diabetes accounts for between 30% 50% of cases CKD.1 Diabetic Kidney (DKD) is associated with increased cardiovascular (CVD) morbidity mortality in many countries also the leading cause end stage needing replacement therapy (dialysis or transplantation).2 DKD impacts on length quality life significantly contributes to global healthcare expenditure these human economic costs are likely rise further future.2, 3 Prognosis progression can differ from one individual another, which often a consequence interactions traditional emerging risk factors as well social-demographic factors, such ethnicity socio-economic factors.4 The recent Research UK health inequalities report demonstrated that South Asian Black backgrounds three five times more require dialysis white background.5 This observation may be part linked increasing prevalence currently unknown determinants progression. management requires multifactorial multidisciplinary approach key focus early identification CKD screening then prompt intervention focussing important lifestyle modifications, using evidence-based medical treatments holistic care.3, 6 With advances pillars treatment includes renin angiotensin system inhibition, sodium glucose co-transporter inhibition (SGLT2-inh), non-steroidal mineralocorticoid receptor antagonists glucagon like peptide 1 agonists (GLP-1 RA) parallel CVD factor modification, there an opportunity intervene change risk.7, 8 For DKD, gaps care options limited contrast diabetes, indeed, high burden this cohort underappreciated.9 natural history has evolved over last 40 years, remains significant residual ESKD premature CVD.9, 10 Despite 30 not optimal present late when modifiability progression/risk less feasible. There thus urgent need better methods biomarkers aid stratification ensure those at highest recognized guideline directed therapies initiated promptly morbidity/mortality.8, 11 glycaemic control challenging setting individualized approach. pathophysiology multifaceted encompasses metabolic haemodynamic perturbations lead structural functional disturbances including glomerular hyper-filtration, mesangial expansion interstitial fibrosis, convergence fundamental mechanisms, 'sterile' inflammation age changes, example cell senescence.12, 13 Although precise role development unclear, studies suggest accelerated ageing phenotype, coupled maladaptive immune response, underlies Furthermore, coexistence disease, so called 'cardiorenal syndrome', occurs face multi-organ crosstalk, evidence suggesting systemic vascular robust predictor poor dyslipidaemia. As obesity, syndrome continue rise, major worldwide. A understanding interrelationships crosstalk different organs/systems contributing complications will enhance scientific could facilitate new interventions prevent treat diabetes-related co-morbidities. mechanisms underpin clinical benefits existing therapies, GLPRA SGLT2i, inform how why drug works both within inter-organ cardiovascular-kidney-metabolic other secondary diabetes. special issue diabetic medicine focussed basic translational research, potential therapeutic targets,12-15 changing diabetes,10 scenarios,11 guidelines their implementation day-to-day patient practice.16 We hope readers enjoy reading collection articles apply related learning drive future research help improve outcomes DKD. None. authors declare no conflicts interest.

Язык: Английский

Процитировано

0