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Journal of Family Medicine and Primary... May 2024Historically, it takes an average of 17 years to move new treatments from clinical evidence to daily practice. Given the highly effective treatments now available to...
Historically, it takes an average of 17 years to move new treatments from clinical evidence to daily practice. Given the highly effective treatments now available to prevent or delay kidney disease onset and progression, this is far too long. The time is now to narrow the gap between what we know and what we do. Clear guidelines exist for the prevention and management of common risk factors for kidney disease, such as hypertension and diabetes, but only a fraction of people with these conditions worldwide are diagnosed, and even fewer are treated to target. Similarly, the vast majority of people living with kidney disease are unaware of their condition because in the early stages, it is often silent. Even among patients who have been diagnosed, many do not receive appropriate treatment for kidney disease. Considering the serious consequences of kidney disease progression, kidney failure, or death, it is imperative that treatments are initiated early and appropriately. Opportunities to diagnose and treat kidney disease early must be maximized beginning at the primary care level. Many systematic barriers exist, ranging from patient to clinician to health systems to societal factors. To preserve and improve kidney health for everyone everywhere, each of these barriers must be acknowledged so that sustainable solutions are developed and implemented without further delay.
PubMed: 38948565
DOI: 10.4103/jfmpc.jfmpc_518_24 -
Frontiers in Pharmacology 2024Diabetic nephropathy (DN) constitutes a major microvascular complication of diabetes and is a primary cause of mortality in diabetic individuals. With the global rise in... (Review)
Review
Diabetic nephropathy (DN) constitutes a major microvascular complication of diabetes and is a primary cause of mortality in diabetic individuals. With the global rise in diabetes, DN has become an urgent health issue. Currently, there is no definitive cure for DN. , a Chinese herbal medicine traditionally used, exhibits a wide range of pharmacological effects and is frequently used in the prevention and management of DN. This paper offers an extensive review of the biological mechanisms by which delivers therapeutic advantages in DN management. These mechanisms include activating podocyte autophagy, regulating non-coding RNA, modulating gut microbiota, alleviating lipotoxicity, counteracting oxidative stress, and diminishing inflammatory responses, underscoring the therapeutic potential of in DN treatment.
PubMed: 38948461
DOI: 10.3389/fphar.2024.1390672 -
Cureus May 2024Introduction Diabetes mellitus (DM) remains a primary cause of morbidity and mortality, leading to complications such as blindness, kidney failure, and lower limb...
Introduction Diabetes mellitus (DM) remains a primary cause of morbidity and mortality, leading to complications such as blindness, kidney failure, and lower limb amputations. Early detection of kidney damage, indicated by microalbuminuria (MA), is crucial for managing DM. Given the impact of these conditions, evaluating the prevalence of chronic kidney disease (CKD) in diabetic populations within primary healthcare is essential. Methodology This was a cross-sectional and observational study. Adults diagnosed with DM type 1 or 2 from five primary care units (PCUs) located in the North of Portugal, were included in this study. Descriptive and correlational statistics were performed using IBM SPSS Statistics for Windows, Version 28.0 (IBM Corp., Armonk, NY). Statistical significance was set to < 0,05. Logistic regression models were created to identify the factors associated with CKD and DM Results A sample of 357 diabetic patients was obtained, with 166 (46.5%) females. Of the sample, 250 (70.1%) were aged 65 or older, and the median known duration of DM was 9.36 years. Excess weight or obesity accounted for 79.8%, with a median body mass index of 28.73 kg/m and hypertension in 284 (79.6%). An estimated glomerular filtration rate (eGFR) less than 60 mL/min was present in 89 (24.9%) and an MA of 30 mg/dL or higher was present in 68 (19.0%). In total, 130 (36.4%) individuals exhibited eGFR and MA consistent with CKD. Among these, 25 (78.1%) had other identifiable causes of CKD besides DM, hypertension, overweight, or obesity. Binary logistic regression models were constructed to find a relationship between CKD with eGFR < 60 mL/min and MA. A statistically significant association was found between CKD with eGFR < 60 mL/minute and age (odds ratio [OR] = 1.150; < 0.001), kidney stones (OR = 5.112; = 0.003), absence of excess weight or obesity (OR = 0.267; < 0.001). The use of GLP1 agonists showed statistical significance as a predictor (OR = 4.653; = 0.042) of the presence of MA. Discussion The study investigates the impact of DM and its complications in the surveyed population. While most patients had controlled DM (284, 76.2%), prolonged disease duration correlated with poorer glycemic control, underscoring the need for more effective management strategies in advanced disease stages. Notably, a third of individuals with DM had CKD, with significant implications for therapeutic interventions and heightened risks of renal failure and cardiovascular morbidity. MA was a crucial marker for endothelial injury, with prevalence influenced by DM duration and medication type. However, in many cases, correct identification of CKD was lacking, suggesting under-recognition of renal deterioration in DM. While the study offers valuable insights, its limited sample size and geographic scope warrant cautious interpretation, emphasizing the need for broader, context-specific research to inform comprehensive healthcare strategies. Conclusions In conclusion, this study highlights the significant burden of CKD among diabetic patients, emphasizing the need for proactive screening, personalized management, and accurate diagnosis. Despite limitations, it underscores the importance of early detection and tailored interventions, advocating for improved diabetes care to mitigate renal complications on a broader scale.
PubMed: 38947587
DOI: 10.7759/cureus.61417 -
Heliyon Jun 2024Diabetic nephropathy (DN) has emerged as the foremost cause of end-stage renal disease (ESRD) globally. Endoplasmic reticulum (ER) stress plays a critical role in DN...
Diabetic nephropathy (DN) has emerged as the foremost cause of end-stage renal disease (ESRD) globally. Endoplasmic reticulum (ER) stress plays a critical role in DN progression. Triterpenoid saponin from Aralia taibaiensis (sAT) has been reported to possess anti-diabetic and anti-oxidant effects. The aim of this study was to examine the influence of sAT on DN treatment and elucidate potential underlying mechanisms. A high-fat diet (HFD) and Streptozotocin (STZ) were employed to induce DN in male Sprague Dawley (SD) rats which were subsequently treated with varying concentrations of sAT for 8 weeks. Our findings reveal that different doses of sAT significantly mitigated hyperglycemia, reduced urinary albumin excretion, and decreased plasma creatinine and blood urea nitrogen levels in DN rats. Moreover, sAT administration improved body weight, alleviated renal fibrosis and histopathological changes in the diabetic kidneys. Notably, sAT treatment partially restored increased Bax expression and decreased Bcl-2 expression. Additionally, sAT inhibited ER stress-related proteins, including GRP78, p-PERK, ATF4 and CHOP in kidneys of DN rats. These results suggest that sAT ameliorated experimental diabetic nephropathy, at least in part, through ER stress pathway. These findings provide a scientific basis for the potential development of sAT as a therapeutic agent for DN treatment.
PubMed: 38947426
DOI: 10.1016/j.heliyon.2024.e31775 -
Cell Biology International Jun 2024Diabetic nephropathy (DN) is the predominant secondary nephropathy resulting in global end-stage renal disease. It is attracting significant attention in both domestic... (Review)
Review
Diabetic nephropathy (DN) is the predominant secondary nephropathy resulting in global end-stage renal disease. It is attracting significant attention in both domestic and international research due to its widespread occurrence, fast advancement, and limited choices for prevention and treatment. The pathophysiology of this condition is intricate and involves multiple molecular and cellular pathways at various levels. This article provides a concise overview of the molecular processes involved in the development of DN. It discusses various factors, such as signaling pathways, cytokines, inflammatory responses, oxidative stress, cellular damage, autophagy, and epigenetics. The aim is to offer clinicians a valuable reference for DN's diagnosis, treatment, and intervention.
PubMed: 38946126
DOI: 10.1002/cbin.12212 -
Journal of Medical Case Reports Jul 2024Necrotizing myopathies and muscle necrosis can be caused by immune-mediated mechanisms, drugs, ischemia, and infections, and differential diagnosis may be challenging.
BACKGROUND
Necrotizing myopathies and muscle necrosis can be caused by immune-mediated mechanisms, drugs, ischemia, and infections, and differential diagnosis may be challenging.
CASE PRESENTATION
We describe a case of diabetic myonecrosis complicated by pyomyositis and abscess caused by Escherichia coli. A white woman in her late forties was admitted to the hospital with a 1.5 week history of bilateral swelling, weakness, and mild pain of the lower extremities and inability to walk. She had a history of type 1 diabetes complicated by diabetic retinopathy, neuropathy, nephropathy, and end-stage renal disease. C-reactive protein was 203 mg/l, while creatinine kinase was only mildly elevated to 700 IU/l. Magnetic resonance imaging of her lower limb muscles showed extensive edema, and muscle biopsy was suggestive of necrotizing myopathy with mild inflammation. No myositis-associated or myositis-specific antibodies were detected. Initially, she was suspected to have seronegative immune-mediated necrotizing myopathy, but later her condition was considered to be explained better by diabetic myonecrosis with multifocal involvement. Her symptoms alleviated without any immunosuppressive treatment. After a month, she developed new-onset and more severe symptoms in her right posterior thigh. She was diagnosed with emphysematous urinary tract infection and emphysematous myositis and abscess of the right hamstring muscle. Bacterial cultures of drained pus from abscess and urine were positive for Escherichia coli. In addition to abscess drainage, she received two 3-4-week courses of intravenous antibiotics. In the discussion, we compare the symptoms and findings typically found in pyomyositis, immune-mediated necrotizing myopathy, and diabetic myonecrosis (spontaneous ischemic necrosis of skeletal muscle among people with diabetes). All of these diseases may cause muscle weakness and pain, muscle edema in imaging, and muscle necrosis. However, many differences exist in their clinical presentation, imaging, histology, and extramuscular symptoms, which can be useful in determining diagnosis. As pyomyositis often occurs in muscles with pre-existing pathologies, the ischemic muscle has likely served as a favorable breeding ground for the E. coli in our case.
CONCLUSIONS
Identifying the etiology of necrotizing myopathy is a diagnostic challenge and often requires a multidisciplinary assessment of internists, pathologists, and radiologists. Moreover, the presence of two rare conditions concomitantly is possible in cases with atypical features.
Topics: Humans; Pyomyositis; Female; Abscess; Escherichia coli Infections; Necrosis; Magnetic Resonance Imaging; Anti-Bacterial Agents; Escherichia coli; Diabetes Mellitus, Type 1; Urinary Tract Infections
PubMed: 38946001
DOI: 10.1186/s13256-024-04614-z -
Diabetes & Metabolism Journal Jul 2024Although the prevalence of diabetic kidney disease (DKD) is increasing, reliable biomarkers for its early detection are scarce. This study aimed to evaluate the...
BACKGROUND
Although the prevalence of diabetic kidney disease (DKD) is increasing, reliable biomarkers for its early detection are scarce. This study aimed to evaluate the association of adenosine and succinate levels and their related pathways, including hyaluronic acid (HA) synthesis, with DKD.
METHODS
We examined 235 participants and categorized them into three groups: healthy controls; those with diabetes but without DKD; and those with DKD, which was defined as estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2. We compared the concentrations of urinary adenosine, succinate, and HA and the serum levels of cluster of differentiation 39 (CD39) and CD73, which are involved in adenosine generation, among the groups with DKD or albuminuria. In addition, we performed multiple logistic regression analysis to evaluate the independent association of DKD or albuminuria with the metabolites after adjusting for risk factors. We also showed the association of these metabolites with eGFR measured several years before enrollment. This study was registered with the Clinical Research Information Service (https://cris.nih.go.kr; Registration number: KCT0003573).
RESULTS
Urinary succinate and serum CD39 levels were higher in the DKD group than in the control and non-DKD groups. Correlation analysis consistently linked urinary succinate and serum CD39 concentrations with eGFR, albuminuria, and ΔeGFR, which was calculated retrospectively. However, among the various metabolites studied, only urinary succinate was identified as an independent indicator of DKD and albuminuria.
CONCLUSION
Among several potential metabolites, only urinary succinate was independently associated with DKD. These findings hold promise for clinical application in the management of DKD.
PubMed: 38945526
DOI: 10.4093/dmj.2023.0377 -
Spectrochimica Acta. Part A, Molecular... Jun 2024Serum creatinine (CR) is regarded as one of the most sought out prognostic biomarkers in medical evaluation of chronic kidney disease (CKD). In light of the diagnostic...
Serum creatinine (CR) is regarded as one of the most sought out prognostic biomarkers in medical evaluation of chronic kidney disease (CKD). In light of the diagnostic significance of CR, the utility of a fluorescence biosensor for its detection in human urine specimens has been explored based on Förster resonance energy transfer (FRET) across nitrogen-doped carbon dots (N-CDs) and gold nanoparticles (GNPs). A straightforward microwave-assisted synthesis procedure has been adopted to prepare N-CDs (λ = 400 nm, λ = 540 ± 5 nm) with bright green emissions. On addition of pre-synthesized GNPs, the radiative emanation of the N-CDs is completely suppressed on account of FRET across the N-CDs and the GNPs. About 77 % of their fluorescence intensity is recovered after adding CR to GNPs@N-CDs nanocomposite. The limit of detection for CR sensing is estimated as 0.02 µg•mL. This biosensor is selective enough to recognize CR in the existence of potential interfering substances (e.g., ascorbic acid, glucose, glutathione, urea, and electrolytes). Its practical utility for CR detection has been validated further on the basis of satisfactory correlation with the benchmark Jaffe method, as observed in artificial/human urine specimens. Consequently, this manuscript marks a pioneering report on employing CDs and GNPs-based FRET for identifying CR in urine specimens of CKD patients.
PubMed: 38945007
DOI: 10.1016/j.saa.2024.124752 -
The American Journal of the Medical... Jun 2024Diabetic Nephropathy is one of the most severe complications of Diabetes Mellitus and the main cause of end-stage kidney disease worldwide. Despite the therapies...
BACKGROUND
Diabetic Nephropathy is one of the most severe complications of Diabetes Mellitus and the main cause of end-stage kidney disease worldwide. Despite the therapies available to control blood glucose and blood pressure, many patients continue to suffer from progressive kidney damage. Chronic hyperglycemia is the main driver of changes observed in diabetes; however, it was recently discovered that inflammation and oxidative stress contribute to the development and progression of kidney damage. Therefore, it is important to search for new pharmacological therapies that stop the progression of DN. Sodium tungstate (NaW) is an effective short and long-term antidiabetic agent in both type 1 and type 2 diabetes models.
METHODS
In this study, the effect of NaW on proinflammatory signalling pathways, proinflammatory proteins and fibrosis in the streptozotocin (STZ)-induced type 1 diabetic rat model was analysed using histological analysis, western blotting and immunohistochemistry.
RESULTS
NaW treatment in diabetic rats normalize parameters such as glycemia, glucosuria, albuminuria/creatinuria, glomerular damage, and tubulointerstitial damage. NaW decreased the proinflammatory signaling pathway NF-κB, inflammatory markers (ICAM-1, MCP-1 and OPN), profibrotic pathways (TGFβ1/Smad2/3), reduced epithelial-mesenchymal transition (α -SMA), and decreased renal fibrosis (type IV collagen).
CONCLUSION
NaW could be an effective drug therapy for treating human diabetic nephropathy.
PubMed: 38944202
DOI: 10.1016/j.amjms.2024.06.001 -
Biomedicine & Pharmacotherapy =... Jun 2024Diabetes mellitus (DM) is a metabolic disorder characterized by hyperglycemia, with its prevalence linked to both genetic predisposition and environmental factors.... (Review)
Review
Diabetes mellitus (DM) is a metabolic disorder characterized by hyperglycemia, with its prevalence linked to both genetic predisposition and environmental factors. Epigenetic modifications, particularly through histone deacetylases (HDACs), have been recognized for their significant influence on DM pathogenesis. This review focuses on the classification of HDACs, their role in DM and its complications, and the potential therapeutic applications of HDAC inhibitors. HDACs, which modulate gene expression without altering DNA sequences, are categorized into four classes with distinct functions and tissue specificity. HDAC inhibitors (HDACi) have shown efficacy in various diseases, including DM, by targeting these enzymes. The review highlights how HDACs regulate β-cell function, insulin sensitivity, and hepatic gluconeogenesis in DM, as well as their impact on diabetic cardiomyopathy, nephropathy, and retinopathy. Finally, we suggest that targeted histone modification is expected to become a key method for the treatment of diabetes and its complications. The study of HDACi offers insights into new treatment strategies for DM and its associated complications.
PubMed: 38941890
DOI: 10.1016/j.biopha.2024.117010