ArticleNephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association2013
Glomerular cell death and inflammation with high-protein diet and diabetes.
Article in Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 1 of them a synthesis that pooled it.
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Who cites it
27 citing papers in PubMed, 1 synthesis or guideline pooled it, 44 citations in OpenAlex.
- Association between dietary inflammatory index and risk of chronic kidney disease and low glomerular filtration rate; a systematic review and meta-analysis of observational studies.Journal of health, population, and nutrition · 2025Pooled it
- Probiotic Soy Milk Consumption and Renal Function Among Type 2 Diabetic Patients with Nephropathy: a Randomized Controlled Clinical Trial.Probiotics and antimicrobial proteins · 2019Trial
- A Simplified and Robust Model for the Study of Diabetic Nephropathy: Streptozotocin-Induced Diabetic Mice Fed a High-Protein Diet.International journal of molecular sciences · 2025Article
- Renal microcirculation and mechanisms in diabetic kidney disease.Frontiers in endocrinology · 2025Review
- Mannan-Binding Lectin Is Associated with Inflammation and Kidney Damage in a Mouse Model of Type 2 Diabetes.International journal of molecular sciences · 2024Article
- Proximal tubular RAGE mediated the renal fibrosis in UUO model mice via upregulation of autophagy.Cell death & disease · 2022Article
- Serum Amyloid A3 Promoter-Driven Luciferase Activity Enables Visualization of Diabetic Kidney Disease.International journal of molecular sciences · 2022Article
- Effect ofAnalytical cellular pathology (Amsterdam) · 2022Article
- How important is dietary management in chronic kidney disease progression? A role for low protein diets.The Korean journal of internal medicine · 2021Review
- Microbiota, epidemiological and nutritional factors related to ketoacidosis at the onset of type 1 diabetes.Acta diabetologica · 2020Observational
- An enigma: does a high-protein diet accelerate renal damage in humans? Lessons from diabetic animal models.American journal of physiology. Renal physiology · 2020Article
- Diet and Chronic Kidney Disease.Advances in nutrition (Bethesda, Md.) · 2019Review
- Review
- Article
- The Benefit of Anti-Inflammatory and Renal-Protective Dietary Ingredients on the Biological Processes of Aging in the Kidney.Biology · 2018Review
- Article
- Immunity and inflammation in diabetic kidney disease: translating mechanisms to biomarkers and treatment targets.American journal of physiology. Renal physiology · 2017Review
- Association of Serum Amyloid A with Kidney Outcomes and All-Cause Mortality in American Indians with Type 2 Diabetes.American journal of nephrology · 2017Article
- Inhibition of autophagy increased AGE/ROS-mediated apoptosis in mesangial cells.Cell death & disease · 2016Article
- Involvement of Endoplasmic Reticulum Stress, Autophagy, and Apoptosis in Advanced Glycation End Products-Induced Glomerular Mesangial Cell Injury.Scientific reports · 2016Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundOverfeeding amino acids (AAs) increases cellular exposure to advanced glycation end-products (AGEs), a mechanism for protein intake to worsen diabetic kidney disease (DKD). This study assessed receptor for AGE (RAGE)-mediated apoptosis and inflammation in glomerular cells exposed to metabolic stressors characteristic of high-protein diets and/or diabetes in vitro with proof-of-concept appraisal in vivo.
methodsMouse podocytes and mesangial cells were cultured under control and metabolic stressor conditions: (i) no addition; (ii) increased AAs (4-6-fold>control); (iii) high glucose (HG, 30.5 mM); (iv) AA/HG combination; (v) AGE-bovine serum albumin (AGE-BSA, 300 µg/mL); (vi) BSA (300 µg/mL). RAGE was inhibited by blocking antibody. Diabetic (streptozotocin) and nondiabetic mice (C57BL/6J) consumed diets with protein calories of 20 or 40% (high) for 20 weeks. People with DKD and controls provided 24-h urine samples.
resultsIn podocytes and mesangial cells, apoptosis (caspase 3/7 activity and TUNEL) increased in all metabolic stressor conditions. Both inflammatory mediator expression (real-time reverse transcriptase-polymerase chain reaction: serum amyloid A, caspase-4, inducible nitric oxide synthase, and monocyte chemotactic protein-1) and RAGE (immunostaining) also increased. RAGE inhibition prevented apoptosis and inflammation in podocytes. Among mice fed high protein, podocyte number (WT-1 immunostaining) decreased in the diabetic group, and only these diabetic mice developed albuminuria. Protein intake (urea nitrogen) correlated with AGE excretion (carboxymethyllysine) in people with DKD and controls.
conclusionsHigh-protein diet and/or diabetes-like conditions increased glomerular cell death and inflammation, responses mediated by RAGEs in podocytes. The concept that high-protein diets exacerbate early indicators of DKD is supported by data from mice and people.
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