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Introduction: Diabetic Kidney Disease (DKD) is a major complication of Diabetes Mellitus (DM). Renal biopsy is the gold standard for the diagnosis and management of many renal diseases. Renal Interstitial Fibrosis and Tubular Atrophy (IFTA), as well as the number of obsolescent glomeruli, are prognostic factors associated with Diabetic Nephropathy (DN). Aim: To describe the renal biopsy profile of patients with DM presenting with renal disease and to determine the significance of IFTA scoring and the number of obsolescent glomeruli in predicting DKD and its severity. Materials and Methods: This cross-sectional study was conducted over a period of three years, from 2019 to 2022, involving a total of 189 patients selected through purposive sampling. Patients with DM who presented with renal disease and required renal biopsy to confirm the diagnosis were admitted to the Department of General Medicine and Nephrology at Kempegowda Institute of Medical Sciences Hospital and Research Centre, Bengaluru, Karnataka, India. The biopsy reports were obtained and analysed. Data were analysed using Statistical Package for the Social Sciences (SPSS) version 20.0 and results were expressed using descriptive and inferential statistics. A p-value of <0.05 was considered statistically significant. Results: The mean age of the participants was 53.02±11.00 years, with an age range from 21 to 81 years. Among the subjects, 78.3% were males and 21.7 were females. Based on the renal biopsy findings, DN was the most common condition, found in 127 subjects (67.6%). Nearly 50.0% of those with DN had Class IV chronic DN, followed by Class III (42.5%). Chronic interstitial nephritis was the most common Non Diabetic Kidney Disease (NDKD), accounting for 24.6% of cases. IFTA scoring was significantly associated with DKD and there was a significant positive correlation between the severity of IFTA scores and the number of obsolescent glomeruli with the class of DKD. A unit rise in the IFTA score and the number of obsolescent glomeruli increased the risk of having severe DKD (Class III and Class IV) by 4.32 times and 1.24 times, respectively, compared to those with less severe forms (Class I and II) (p<0.05). Conclusion: The IFTA scoring and the number of obsolescent glomeruli were found to be significant independent predictors of the severity of DKD. [ABSTRACT FROM AUTHOR]

Objective Pathogenesis of antiphospholipid syndrome (APS) remains poorly elucidated. We aimed to evaluate for the first time kidney transcriptome profiles in primary APS vs systemic lupus erythematosus (SLE) and control subjects. Methods We performed RNA sequencing on archival formalin-fixed paraffin-embedded kidney biopsies from APS (n  = 4), SLE (n  = 5) and control (n  = 3) individuals, differential gene expression analysis (DGEA) and enrichment analysis using gene ontology (GO) and CORUM, KEGG and Reactome pathway databases. Results Two-dimensional projection showed a distinct gene profile in primary APS vs control kidneys samples, but similar to SLE. DGEA in APS vs controls returned 276 upregulated and 217 downregulated genes, while the comparison between APS and SLE identified 75 upregulated and 111 downregulated genes. In 276 upregulated genes, enriched GO terms were (innate) immune response, inflammatory response, leucocyte and lymphocyte activation, cytokine production and T cell activation. CORUM and KEGG revealed complement-related genes (C3, C4A, C4B). Expression levels showed logFC values of 2.25 (P  = 1.58e-05) for C3, 2.17 (P  = 2.69e-06) for C4A and 2.135 (P  = 3.7e-06) for C4B in APS vs controls, without differences between APS and SLE. Interferon (IFN) alpha/beta signalling was revealed by Reactome. Expression levels of nine IFN-regulated genes found upregulated in APS vs control kidneys (P -values ≤ 0.001 for all). Examining neutrophil-extracellular traps (NETs)-related gene expression, 13 of 15 upregulated NETs-related genes exhibited higher expression in APS vs controls but not vs SLE. Conclusion Complement, interferon and NETs-related genes are highly expressed in APS kidney tissues, similarly to SLE, pointing out the role of innate immunity in APS nephropathy pathogenesis and potential treatment targets. [ABSTRACT FROM AUTHOR]

The role of aldosterone has yet to be well appreciated in chronic kidney disease (CKD). Two variables define CKD: an estimated glomerular filtration rate of <60 ml/min/1.73 m2 and a spot urine albumin‐creatinine ratio of >30 mg/g. Both are needed for an accurate diagnosis. The presence of CKD at this level is associated with an elevated risk of cardiovascular death and a greater risk of CKD progression to kidney failure and subsequent dialysis. This paper presents an overview of aldosterone's importance in CKD and its contribution to the inflammatory processes involved in CKD development. Data on outcomes, both surrogate and hard, related to outcomes on CKD progression will also be discussed in the context of mineralocorticoid blockade. Based on recent epidemiological data as well as data examining markers of diabetic kidney disease progression, it is clear that use of both renin‐angiotensin system inhibitors and aldosterone receptor antagonists have a significant role in altering the natural history of kidney disease progression itself, as well as reducing the risk of cardiovascular events that generally accompany long‐standing kidney disease. This paper will discuss these issues and the management of consequent hyperkalaemia when both steroidal and non‐steroidal mineralocorticoid receptor antagonists are used in detail. [ABSTRACT FROM AUTHOR]

Prolonged hyperglycemic conditions in type 2 diabetes mellitus (T2DM) cause pathological and functional damage to many organs and tissues, including the kidneys, retina, skin, and neuronal tissues, resulting in the development of microvascular diabetic complications. The altered renin angiotensin aldosterone system (RAAS) pathway has been reported to play an important role in the development of insulin resistance in T2DM and associated complications. The current study was carried out to evaluate the association of risk factors and altered expression of RAAS genes in T2DM patients without complications and T2DM patients with complications (retinopathy, nephropathy, and neuropathy). Four hundred and twenty subjects including 140 healthy controls, 140 T2DM patients with diabetic complications, and 140 T2DM patients without diabetic complications were included in the study. Risk factors associated with the development of T2DM and diabetic complications were evaluated. Further, expression analysis of RAAS genes (AGT, ACE, ACE2, and AGT1R) was carried out using qRTPCR in healthy controls, T2DM patients with complications, and T2DM patients without complications. Various risk factors like urban background, higher BMI, alcoholism, smoking, and family history of diabetes among others were found to be associated with the development of T2DM as well as diabetic complications. The expression level of AGT, ACE, and AGT1R was found to be upregulated whereas ACE2 was found to be downregulated in T2DM patients with complications and T2DM patients without complications as compared to controls. Altered expression of the studied genes of RAAS pathway is associated with the development of microvascular diabetic complications. [ABSTRACT FROM AUTHOR]

Aim Methods Results Conclusion Although South Asians have an increased risk to develop diabetes, data on the difference in development and progression of diabetic nephropathy between ethnic groups are not consistent. The aim of this study was to evaluate possible differences in the development and progression of albuminuria in South Asians and Western Europeans (WE) with type 2 diabetes in a large closed cohort of South Asians with type 2 diabetes.Data on 1269 South Asians and 2272 Dutch adults with type 2 diabetes who were treated in our diabetes clinic in 2006 or referred thereafter were extracted from electronic medical records. Microalbuminuria and macroalbuminuria were defined separately for men and women based on albumin/creatinine ratios in early morning urine samples. We defined 3 outcomes: (1) no albuminuria, (2) persistent microalbuminuria and (3) macroalbuminuria at the end of follow‐up. Cox proportional hazard models were used to discriminate differences in time from diabetes diagnosis until development and progression of albuminuria between the two ethnic groups, adjusted for retinopathy, hypertension, smoking and age at diabetes diagnosis.South Asians have a higher adjusted risk for developing microalbuminuria: HR 1.4, (95% CI 1.2, 1.6) and macroalbuminuria: HR: 1.2 (1.0, 1.4) compared to Western Europeans. However, mean time to progress from micro‐ to macroalbuminuria was not different between the ethnic groups (3.9 ± 4.0 yrs vs. 3.4 ± 3.9 yrs respectively).South Asians have a higher adjusted risk to develop micro‐ and macroalbuminuria compared with Western Europeans. When microalbuminuria is present, time to progression from micro‐ to macroalbuminuria is not different between the two groups. [ABSTRACT FROM AUTHOR]

Background and Aim Materials and Methods Results Conclusion Vitamin K deficiency is common in persons with kidney disease, which is a known complication of diabetes. We aimed to assess the association of vitamin K status as reflected by plasma dephosphorylated‐uncarboxylated matrix Gla protein (dp‐ucMGP) with mortality, cardiovascular disease (CVD) and progression to end‐stage kidney disease (ESKD) in persons with type 1 diabetes.We analysed plasma dp‐ucMGP in stored baseline samples from a cohort of 667 persons with type 1 diabetes (baseline visit: 2009–2011). Information on mortality and CVD was obtained through linkage to registers. Cox‐proportional hazards models were applied to estimate hazard ratios (HRs) of mortality, CVD and ESKD per one doubling of dp‐ucMGP.A total of 53 deaths were recorded during follow‐up. Persons with higher dp‐ucMGP (reflecting lower vitamin K status) had higher mortality in the unadjusted model (HR: 2.06 [95% confidence interval—CI: 1.22–3.45]), but not in the fully adjusted model (HR: 0.88 [95% CI: 0.44–1.73]). Particularly, adjustment for glomerular filtration rate and urinary albumin excretion rate attenuated the HR. A similar pattern was observed in unadjusted models for incidence of CVD (HR: 1.58 [95% CI: 1.03–2.42]) and risk of ESKD (HR: 7.62 [95% CI: 4.25–13.68]). In the fully adjusted models, the HRs became statistically insignificant.In persons with type 1 diabetes, lower vitamin K status was associated with higher mortality, CVD and progression to ESKD, however, not after adjustment for other risk factors. Interventional studies are needed to elucidate the role of vitamin K in persons with type 1 diabetes. [ABSTRACT FROM AUTHOR]

Diabetes mellitus (DM) is a chronic malady that is measured to be life-threatening. Diabetes Mellitus type 2 is accounts for the majority of increased risk of Neuropathy and Nephropathy. Utilizing machine learning (ML) predictive model algorithms can aid in the management of diabetes mellitus type 2 (T2DM) by lowering the risk of neuropathy and nephropathy problems in early stages. The increased screening can be avoided the loss of life our study creates predictive model to forecast the diabetes through Gradient Boosting, SVM and Random forest algorithms. The development and work by comparing the performance accomplished using various parameters and algorithms, it originates that by using a selected number of features, we can still build sufficient results. [ABSTRACT FROM AUTHOR]

Diabetic nephropathy (DN) can be prevented with early therapeutic intervention in diabetic patients. Recent investigations suggest that β-amyrin, a pentacyclic triterpenoid, could offer significant benefits with its potential antihyperglycemic and nephroprotective effects. We investigated the protective effects of β-amyrin alone and combined it with metformin, the cornerstone therapy for diabetes, using a hyperglycemic adult Zebrafish (ZF) model. The ZF were subjected to hyperglycemia by immersing them in 111 mM glucose solutions. Treatment efficacy was assessed by measuring serum glucose and insulin levels and antioxidant, ER stress, apoptosis, and proinflammatory markers. ZF kidneys were also studied for immunohistochemistry and histopathology. Results revealed that the combined treatment of β-amyrin and metformin resulted in a significant decrease (p ≤ 0.05) in blood glucose levels to 104.54 ± 1.63 mg/dL, in comparison to 388.75 ± 4.32 mg/dL in the untreated diseased control group. The reduction in hyperglycemia was more pronounced than treatment with either compound alone. Moreover, treatment with the combination restored renal function in diseased ZF, leading to significantly lower (p ≤ 0.05) serum urea (SU: 19.57 ± 1.61 mg/dL) and serum creatinine (SC: 0.56 ± 0.02 mg/dL) values compared to treatment with β-amyrin (SU:27.02 ± 0.96 mg/dL; SC: 0.7 ± 0.01 mg/dL) or metformin (SU: 24.53 ± 1.29 mg/dL; SC: 0.6 ± 0.02 mg/dL) alone. The treatment also reduced oxidative stress markers, apoptosis and ER stress markers, and proinflammatory cytokines. Histopathological analysis showed improved renal architecture with significantly lower (p ≤ 0.05) renal tubular injury scores with the combination than with individual treatment. This study provides novel insights into the combined therapeutic effects of β-amyrin and metformin in mitigating hyperglycemia-induced renal damage through key molecular pathways, highlighting a potentially effective therapeutic strategy for diabetic nephropathy. The findings hold promising translational relevance for developing combination therapies aimed at improving clinical outcomes in diabetic nephropathy patients. [ABSTRACT FROM AUTHOR]

Anti-tubular basement membrane (anti-TBM) antibody nephritis is a rare type of tubulointerstitial nephritis associated with progressive decline in kidney function. It is characterized histopathologically by tubular atrophy and dilation, interstitial fibrosis, lymphocyte and macrophage-predominant cellular infiltration, and linear deposition of IgG and complement along the tubular basement membrane. We herein present a case of a 69-year-old male who was recently diagnosed with chronic lymphocytic leukemia (CLL) and was referred for evaluation of kidney failure, ultimately diagnosed as anti-TBM antibody nephritis progressing into end-stage kidney disease (ESKD). This case report highlights the management challenges of anti-TBM antibody nephritis as a rare kidney disorder. [ABSTRACT FROM AUTHOR]

Nail-patella syndrome (NPS) is an autosomal dominant disease caused mostly by mutations in the LMX1B gene and is characterized by hypoplastic nails, hypoplastic patella, elbow deformities, glaucoma, and nephropathy, sometimes leading to kidney failure. The combination and the severity of symptoms vary greatly from patient to patient. Because a kidney biopsy may show nonspecific findings, patients with nephropathy alone may not be diagnosed without undergoing genetic testing. We examined the case of a 6-year-old girl with persistent high proteinuria who was not diagnosed by kidney biopsy but had a diagnosis of a de novo mutation in the LMX1B gene following genetic testing. Retrospectively, only the thumbs showed triangular lunulae, while the third and fourth fingers lacked skin creases over the distal interphalangeal joints, which is subtle but characteristic of NPS. Notifying pediatric nephrologists of these findings can help avoid unnecessary kidney biopsies and lead to early detection of the disease. [ABSTRACT FROM AUTHOR]

Objective: Diabetic nephropathy is a prevalent cause of chronic kidney disease worldwide. Magnesium plays a critical role in insulin resistance, and insulin, in turn, regulates magnesium levels. We aimed to investigate the association between hypomagnesemia and albuminuria in patients with type 2 diabetes mellitus (T2DM). Design, Patients and Measurements: This retrospective single‐centre study encompassed 1178 patients aged 18 and above with T2DM, who attended our outpatient clinic between January 2019 and August 2020. Albuminuria levels were categorised according to Kidney Disease Outcomes Quality Initiative guidelines. In the literature, when examining cut‐off values for hypomagnesemia, it is observed that studies typically use hospital normal level as a reference point. Hypomagnesemia, defined as magnesium levels below 1.6 mg/dL, was compared to normomagnesemia (magnesium between 1.6 and 2.4 mg/dL). The primary objective was to explore the impact of magnesium levels on albuminuria, while the secondary objective was to determine the prevalence of hypomagnesemia. The multivariate logistic regression analyses were performed according to age, gender (male), HbA1c, and presence of hypomagnesemia. Results: The mean age of the participants was 58.7 ± 12.2 years, with 44% being male. Hypomagnesemia was identified in 5.3% of the patients. Advanced age and female gender were more common among patients with hypomagnesemia (p =.001). Magnesium levels exhibited a negative correlation with HbA1c and fasting blood glucose, and a positive correlation with creatinine levels (r = −.117, r = −.131, r =.117, p <.001 for all three variables). Hypomagnesemia was significantly more prevalent in patients with albuminuria (15.9% vs. 4.7%, p <.001). Moreover, participants with the presence of hypomagnesemia were independently associated with a higher risk of albuminuria (odds ratio 3,64 1.76–7.52, p =.001). Conclusion: Albuminuria is more frequently observed in patients with hypomagnesemia. [ABSTRACT FROM AUTHOR]

Diabetes is a metabolic disorder whose prevalence has become a worrying condition in recent decades. Chronic diabetes can result in serious health conditions such as impaired kidney function, stroke, blindness, and myocardial infarction. Despite a variety of currently available treatments, cases of diabetes and its complications are on the rise. This review article provides a comprehensive account of the ameliorative effect of prebiotics and probiotics individually or in combination i.e. synbiotics on health complications induced by Type 2 Diabetes Mellitus (T2DM). Recent advances in the field underscore encouraging outcomes suggesting the consumption of synbiotics leads to favorable changes in the gut microbiota. These changes result in the production of bioactive metabolites such as short-chain fatty acids (crucial for lowering blood sugar levels), reducing inflammation, preventing insulin resistance, and encouraging the release of glucagon-like peptide-1 in the host. Notably, novel strategies supplementing synbiotics to support gut microbiota are gaining attraction as pivotal interventions in mitigating T2DM-induced health complications. Thus, by nurturing a symbiotic relationship between prebiotics and probiotics i.e. synbiotics, these interventions hold promise in reshaping the microbial landscape of the gut thereby offering a multifaceted approach to managing T2DM and its associated morbidities. Supporting the potential of synbiotics underscores a paradigm shift toward holistic and targeted interventions in diabetes management, offering prospects for improved outcomes and enhanced quality of life for affected individuals. Nevertheless, more research needs to be done to better understand the single and multispecies pre/pro and synbiotics in the prevention and management of T2DM-induced health complications. [ABSTRACT FROM AUTHOR]

Objective: To examine the renoprotective effects of metabolic surgery in patients with established chronic kidney disease (CKD). Background: The impact of metabolic surgery compared with glucagon-like peptide-1 receptor agonists (GLP-1RA) in patients with established CKD has not been fully characterized. Methods: Patients with obesity (body mass index =30 kg/m²), type 2 diabetes, and baseline estimated glomerular filtration rate (eGFR) 20-60 mL/min/1.73 m² who underwent metabolic bariatric surgery at a large US health system (2010-2017) were compared with nonsurgical patients who continuously received GLP-1RA. The primary end point was CKD progression, defined as a decline of eGFR by =50% or to <15 mL/min/1.73 m2, initiation of dialysis, or kidney transplant. The secondary end point was the incident kidney failure (eGFR <15 mL/min/1.73 m2, dialysis, or kidney transplant) or all-cause mortality. Results: 425 patients, including 183 patients in the metabolic surgery group and 242 patients in the GLP-1RA group, with a median follow-up of 5.8 years (IQR, 4.4-7.6), were analyzed. The cumulative incidence of the primary end point at 8 years was 21.7% (95% CI: 12.2-30.6) in the surgical group and 45.1% (95% CI: 27.7 to 58.4) in the nonsurgical group, with an adjusted hazard ratio of 0.40 (95% CI: 0.21 to 0.76), P=0.006. The cumulative incidence of the secondary composite end point at 8 years was 24.0% (95% CI: 14.1 to 33.2) in the surgical group and 43.8% (95% CI: 28.1 to 56.1) in the nonsurgical group, with an adjusted HR of 0.56 (95% CI: 0.31 to 0.99), P= 0.048. Conclusions: Among patients with type 2 diabetes, obesity, and established CKD, metabolic surgery, compared with GLP-1RA, was significantly associated with a 60% lower risk of progression of kidney impairment and a 44% lower risk of kidney failure or death. Metabolic surgery should be considered as a therapeutic option for patients with CKD and obesity. [ABSTRACT FROM AUTHOR]

Introduction: Diabetic Kidney Disease (DKD) is a major complication of Diabetes Mellitus (DM). Renal biopsy is the gold standard for the diagnosis and management of many renal diseases. Renal Interstitial Fibrosis and Tubular Atrophy (IFTA), as well as the number of obsolescent glomeruli, are prognostic factors associated with Diabetic Nephropathy (DN). Aim: To describe the renal biopsy profile of patients with DM presenting with renal disease and to determine the significance of IFTA scoring and the number of obsolescent glomeruli in predicting DKD and its severity. Materials and Methods: This cross-sectional study was conducted over a period of three years, from 2019 to 2022, involving a total of 189 patients selected through purposive sampling. Patients with DM who presented with renal disease and required renal biopsy to confirm the diagnosis were admitted to the Department of General Medicine and Nephrology at Kempegowda Institute of Medical Sciences Hospital and Research Centre, Bengaluru, Karnataka, India. The biopsy reports were obtained and analysed. Data were analysed using Statistical Package for the Social Sciences (SPSS) version 20.0 and results were expressed using descriptive and inferential statistics. A p-value of

Chronic kidney disease is globally recognized as a highly impactful non-communicable disease. The inability of early identification contributes to its high mortality rate and financial burden on affected individuals. Chronic kidney disease of uncertain etiology (CKDu) constitutes a significant global public health concern. This condition does not arise from traditional risk factors such as diabetes, hypertension, or glomerulonephritis. More than 150 articles were analysed to understand risk factors of CKDu. This study aimed to investigate the potential association between dissolved organic compounds, such as Polycyclic Aromatic Hydrocarbons and Humic Acid, and the incidence of CKDu. Through a comprehensive literature review, we identified CKDu clusters worldwide, including notable nephropathies, and explored their potential links with organic compounds. Our analysis revealed that organic compounds can leach from sediments and low-rank lignite deposits into groundwater, subsequently contaminating water supplies and food. These compounds have been implicated in the development of diabetes and increased heavy metal mobility, both of which are risk factors for kidney disease. Our findings suggest that exposure to organic compounds may contribute to the etiology of CKDu, underscoring the need for regular monitoring and establishment of baseline and threshold values in water and soil. We also emphasize the importance of analyzing organic compounds in groundwater in CKDu hotspots and establishing distinct registries for CKD and CKDu implementation. [ABSTRACT FROM AUTHOR]

This research presents novel insights into the temporal dynamics of clinical and instrumental parameters pertaining to the emergence of cardiorenal syndrome in feline patients afflicted with hypertrophic cardiomyopathy. It elucidates that within pedigreed felines, the progression of congestive heart failure syndrome may precipitate the subsequent evolution and exacerbation of secondary renal damage, thus significantly complicating the trajectory of the primary pathological process. This study establishes, for the first time, theprevalence of cardiorenal syndrome, affecting 51.0% of the population within the broader cohort of cats afflicted with hypertrophic cardiomyopathy (n= 49). Moreover, it substantiates the role of the cardiorenal continuum in felines as apredictor of amore severe course of hypertrophic cardiomyopathy. Manifesting as concentric myocardial hypertrophy in domestic felines, cardiorenal syndrome is characterized by dyspnea, hypothermia, and circulatory insufficiency. Statistically significant findings include an elevated median nocturnal respiratory rate of 34.0 breaths/min (p0.001) compared to clinically healthy counterparts (18.0 breaths/min) in affected felines. Additionally, felines afflicted with hypertrophic cardiomyopathy and cardiorenal syndrome exhibit astatistically significant (p 0.001) elevation in median mean arterial blood pressure to 140.0 mmHg compared to clinically healthy counterparts (104.0 mmHg), sinus tachycardia at 199.0 beats/min (171.5 beats/min in healthy felines), resulting in astatistically significant (p 0.001) reduction in PQ intervals by 67.0 ms (75.5 ms in healthy felines), and an increase in QT interval by 204.0 ms (165.5 ms in healthy felines). Electrocardiographic assessments reveal indications of compromised intra-atrial and intraventricular conduction in hypertrophic cardiomyopathy-afflicted felines with cardiorenal syndrome, along with an augmented amplitude of the ventricular complex. Echocardiographic evaluations confirm alterations such as pulmonary vein dilation, pronounced left atrial anteroposterior enlargement, interventricular septal and left ventricular free wall hypertrophy, decreased longitudinal contractility of the left and right ventricles, and clinically significant diastolic dysfunction.

Abstract Background Previous studies examined the association of Helicobacter pylori infection (H. pylori) with complications of diabetes, but the results have been inconsistent. The aim of this study of patients with type-2 diabetes (T2D) was to determine the association of H. pylori infection with the major complications of diabetes. Methods This single-center retrospective study examined patients with T2D who received H. pylori testing between January 2016 and December 2021. Logistic regression analyses were used to evaluate the association of H. pylori infection with four major complications of diabetes. Results We examined 960 patients with T2D, and 481 of them (50.1%) were positive for H. pylori. H. pylori infection was significantly associated with diabetic nephropathy (odds ratio [OR] = 1.462; 95% confidence interval [CI]: 1.006,2.126; P = 0.046). In addition, the co-occurrence of H. pylori positivity with hypertension (OR = 4.451; 95% CI: 2.351,8.427; P

Abstract Diabetic nephropathy, characterized by inflammation and oxidative stress, poses a management challenge. This study investigates the effect of Polygonum hyrcanicum extract on diabetic nephropathy in alloxan-induced diabetic mice. In this experimental animal study, the P. hyrcanicum extract was prepared using continuous macerations. Thirty male Albino mice, divided into five groups, were induced with alloxan-induced diabetes. They received intraperitoneal injections of the plant extract (100 and 200 mg/kg) and metformin (300 mg/kg) for four weeks. Kidney and blood samples were collected to assess protein carbonyl, glutathione, lipid peroxidation, TNF-α and IL-6 levels. The amount of total flavonoid and phenolic content in the hydroalcoholic extract of P. hyrcanicum were 7.5 ± 0.3 mg of quercetin and 88.2 ± 1.3 mg gallic acid per gram of extract respectively. The antioxidant activity level of the hydroalcoholic extract was determined to be 1.78 ± 0.51 mM equivalent per gram of extract. Alloxan administration resulted in a significant reduction in glutathione levels and a significant increase in protein carbonyl, lipid peroxidation, TNF-α, and IL-6 levels. Hydroalcoholic extract of P. hyrcanicum effectively reduced oxidative stress markers and inflammatory cytokines (TNF-α, IL-6), indicating its potential in mitigating diabetic nephropathy. However, no significant difference in efficacy was observed between the 100 mg/kg and 200 mg/kg doses in terms of reducing these toxicities.

Resumen: Antecedentes y objetivo: Las vesículas extracelulares (VEs) reflejan el estado fisiopatológico de sus células de origen y constituyen un reservorio de información renal accesible en la orina. Cuando la biopsia no es una opción, las VEs se presentan como un centinela de funcionalidad y daño, constituyendo una aproximación no invasiva. Sin embargo, el análisis de las VEs de la orina requiere de un aislamiento previo que ralentiza y dificulta su traslación a la práctica clínica. El objetivo de este trabajo es mostrar la aplicabilidad de la tecnología «sensor de imágenes de reflectancia interferométrica de una sola partícula» (SP-IRIS) mediante la plataforma ExoView® para el análisis directo de las VEs de la orina y de proteínas implicadas en funcionalidad renal. Materiales y métodos: La tecnología ExoView® permite la cuantificación y el fenotipado de las VEs presentes en la orina y la cuantificación de sus proteínas, de membrana e internas. En este trabajo se aplica esta tecnología a la cuantificación de las VEs de la orina y de sus proteínas con expresión renal tubular, amnionless (AMN) y secreted frizzled-related protein 1 (SFRP1), empleando únicamente 5 μl de orina. La expresión tubular se confirmó por inmunohistoquímica. Resultados: El tamaño medio de las VEs analizadas fue de 59 ± 16 nm para las capturadas por la tetraspanina CD63, 61 ± 16 nm para las capturadas por la tetraspanina CD81 y 59 ± 10 nm para la tetraspanina CD9, siendo CD63 la subpoblación de VEs mayoritaria en la orina (48,92%). La distribución de AMN y SFRP1 en las 3 tetraspaninas de captura resultó ser similar para ambas proteínas, expresándose mayoritariamente en CD63 (48,23% para AMN y 52,1% para SFRP1). Conclusiones: Este trabajo evidencia la aplicabilidad y las ventajas de la técnica ExoView® para el análisis directo de las VEs de la orina, y su cargo proteico en relación con el túbulo renal. El empleo de volúmenes mínimos, 5 μl, y el tiempo total de análisis no superior a 3 h facilita la traslación a la práctica clínica diaria de las VEs como fuente de información diagnóstica. Abstract: Background and objective: Extracellular vesicles (EVs) reflect the pathophysiological state of their cells of origin and are a reservoir of renal information accessible in urine. When biopsy is not an option, EVs present themselves as sentinels of function and damage, providing a non-invasive approach. However, the analysis of EVs in urine requires prior isolation, which slows down and hinders translation to clinical practice. The aim of this study is to show the applicability of the “single particle interferometric reflectance imaging sensor” (SP-IRIS) technology through the ExoView® platform for the direct analysis of urine EVs and proteins involved in renal function. Materials and methods: The ExoView® technology enables the quantification and phenotyping of EVs present in urine and the quantification of their membrane and internal proteins. We have applied this technology to the quantification of urinary EVs and their proteins with renal tubular expression, amnionless (AMN) and secreted frizzled-related protein 1 (SFRP1), using only 5 μl of urine. Tubular expression was confirmed by immunohistochemistry. Results: The mean size of the EVs analysed was 59 ± 16 nm for those captured by tetraspanin CD63, 61 ± 16 nm for those captured by tetraspanin CD81, and 59 ± 10 nm for tetraspanin CD9, with CD63 being the majority EVs subpopulation in urine (48.92%). The distribution of AMN and SFRP1 in the three capture tetraspanins turned out to be similar for both proteins, being expressed mainly in CD63 (48.23% for AMN and 52.1% for SFRP1). Conclusions: This work demonstrates the applicability and advantages of the ExoView® technique for the direct analysis of urine EVs and their protein content in relation to the renal tubule. The use of minimum volumes, 5 μl, and the total analysis time not exceeding three hours facilitate the translation of EVs to daily clinical practice as source of diagnostic information.

Abstract The contribution of chronic kidney disease (CKD) towards the risk of developing cardiovascular disease (CVD) is magnified with co-existing type 1 or type 2 diabetes. Lipids are a modifiable risk factor and good lipid management offers improved outcomes for people with diabetic kidney disease (DKD). The primary purpose of this guideline, written by the Association of British Clinical Diabetologists (ABCD) and UK Kidney Association (UKKA) working group, is to provide practical recommendations on lipid management for members of the multidisciplinary team involved in the care of adults with DKD.

Diabetes is a multifactorial disorder that involves several molecular mechanisms and is still one of the key global health challenges with increasing prevalence and incidence. Gut microbiome dysbiosis could activate and recognize receptors that trigger the inflammation response and modulation of insulin sensitivity. In addition, the intricate role of gut microbiota dysbiosis in the onset and development of T2D (Type 2 diabetes mellitus) and associated microvascular complications was identified. These complications include diabetic nephropathy (DN) and diabetic retinopathy (DR), diabetic neuropathy, cerebrovascular disorders, and coronary heart disease. A recent interesting strategy to improve these complications is probiotics administration. The safety and health effects of probiotics against various diseases have been validated by various in vitro, in vivo and clinical studies. In this review, the related mechanisms between the gut microbiome, initiation, and progression of T2D and its common microvascular complications (DN and DR) have been discussed.

Hypophosphatemic osteomalacia in an adult often gives clinical diagnostic challenges. Usually, they are caused by either tumor-induced osteomalacia or due to genetically mediated hypophosphatemia, particularly X-linked hypophosphatemia. However, heavy metal toxicity, leading to global proximal renal tubular dysfunction, is a rare cause, and in particular, cadmium toxicity is rarely encountered in clinical practice. The presence of bony pain and neurological deficit, along with a classical exposure history, provides the diagnostic clue. In this background, here we present a middle-aged man who had severe bony pains all over his body and lower back stiffness for five years. He underwent an initial workup as a suspected spondyloarthropathy but was later on, found to have hypophosphatemic osteomalacia and severe proximal renal tubular dysfunction. Further, the workup revealed elevated FGF-23. His occupational history revealed prolonged exposure to cadmium fumes in the silverware industry. He improved moderately with treatment; however, significant renal damage is still present. This case highlights the importance of considering cadmium toxicity in proper clinical and occupational contexts in the evaluation of hypophosphatemic osteomalacia in an adult.

Immunoglobulin A (IgA) vasculitis, or Henoch‐Schonlein purpura, is the most common systemic vasculitis in children, clinically presenting as palpable purpura in combination with arthritis, gastrointestinal involvement, or kidney injury. Subcutaneous edema is reported in patients with IgA vasculitis, and it commonly affects the lower extremities, especially around joints. Here, we report a case of IgA vasculitis with a rare presentation of edema isolated to the periorbital area in a 7‐year‐old boy, who subsequently developed crescentic glomerulonephritis with nephrotic range proteinuria. Isolated periorbital edema is an uncommon cutaneous feature of IgA vasculitis. [ABSTRACT FROM AUTHOR]

Background: Previous studies examined the association of Helicobacter pylori infection (H. pylori) with complications of diabetes, but the results have been inconsistent. The aim of this study of patients with type-2 diabetes (T2D) was to determine the association of H. pylori infection with the major complications of diabetes. Methods: This single-center retrospective study examined patients with T2D who received H. pylori testing between January 2016 and December 2021. Logistic regression analyses were used to evaluate the association of H. pylori infection with four major complications of diabetes. Results: We examined 960 patients with T2D, and 481 of them (50.1%) were positive for H. pylori. H. pylori infection was significantly associated with diabetic nephropathy (odds ratio [OR] = 1.462; 95% confidence interval [CI]: 1.006,2.126; P = 0.046). In addition, the co-occurrence of H. pylori positivity with hypertension (OR = 4.451; 95% CI: 2.351,8.427; P < 0.001), with glycated hemoglobin A1c (HbA1c) of at least 8% (OR = 2.925; 95% CI: 1.544,5.541; P = 0.001), and with diabetes duration of at least 9 years (OR = 3.305; 95% CI:1.823,5.993; P < 0.001) further increased the risk of diabetic nephropathy. There was no evidence of an association of H. pylori infection with retinopathy, neuropathy, or peripheral vascular disease. Conclusions: Our study of T2D patients indicated that those with H. pylori infections had an increased risk of nephropathy, and this risk was greater in patients who also had hypertension, an HbA1c level of 8% or more, and diabetes duration of 9 years or more. [ABSTRACT FROM AUTHOR]

The aim of this study was to assess the effect of triterpenoids on the development of diabetic nephropathy in an experimental model of diabetes mellitus. For this purpose, a destoned and dehydrated olive oil (DDOO) was used, comparing its effects to a destoned olive oil (DOO). DDOO had a higher triterpenoid content than DOO but an equal content of alcoholic polyphenols. Four study groups (n = 10 animals/group) were formed: healthy rats, diabetic control rats (DRs), and DRs treated orally with 0.5 mL/kg/day of DOO or DDOO for two months. DRs showed impaired renal function (proteinuria, increased serum creatinine, decreased renal creatinine clearance) and morphology (glomerular volume and glomerulosclerosis). These alterations correlated with increased systemic and renal tissue oxidative stress and decreased prostacyclin production. DDOO administration significantly reduced all variables of renal damage, as well as systemic and renal oxidative stress, to a greater extent than the effect produced by DOO. In conclusion, triterpenoid-rich olive oil may prevent kidney damage in experimental diabetes mellitus. [ABSTRACT FROM AUTHOR]

Diabetic nephropathy, characterized by inflammation and oxidative stress, poses a management challenge. This study investigates the effect of Polygonum hyrcanicum extract on diabetic nephropathy in alloxan-induced diabetic mice. In this experimental animal study, the P. hyrcanicum extract was prepared using continuous macerations. Thirty male Albino mice, divided into five groups, were induced with alloxan-induced diabetes. They received intraperitoneal injections of the plant extract (100 and 200 mg/kg) and metformin (300 mg/kg) for four weeks. Kidney and blood samples were collected to assess protein carbonyl, glutathione, lipid peroxidation, TNF-α and IL-6 levels. The amount of total flavonoid and phenolic content in the hydroalcoholic extract of P. hyrcanicum were 7.5 ± 0.3 mg of quercetin and 88.2 ± 1.3 mg gallic acid per gram of extract respectively. The antioxidant activity level of the hydroalcoholic extract was determined to be 1.78 ± 0.51 mM equivalent per gram of extract. Alloxan administration resulted in a significant reduction in glutathione levels and a significant increase in protein carbonyl, lipid peroxidation, TNF-α, and IL-6 levels. Hydroalcoholic extract of P. hyrcanicum effectively reduced oxidative stress markers and inflammatory cytokines (TNF-α, IL-6), indicating its potential in mitigating diabetic nephropathy. However, no significant difference in efficacy was observed between the 100 mg/kg and 200 mg/kg doses in terms of reducing these toxicities. [ABSTRACT FROM AUTHOR]

The dynamics of nephropathy development in rats with type 2 diabetes mellitus, caused by a high-fat diet and the streptozotocin administration (25 mg/kg), and metabolic syndrome, caused by addition of 20% fructose solution to the diet, was evaluated during the experiment. Models with moderate severity of metabolic changes without significant changes in body weight were obtained after 24 weeks. To study neuropathy severity, the method of electroneuromyography was used; the velocities of motor and sensory excitation propagation along the caudal nerve fibers were measured. In modeled diabetes mellitus against the background of hyperglycemia, a marked decrease in motor and sensory propagation rates was observed, and an increase in the response durations was noted from week 12 to week 24, indicating pronounced neuropathy. In the fructose model, the motor response duration increased from week 12, which possibly indicates the development of peripheral neuropathy. [ABSTRACT FROM AUTHOR]

Background The initiation of type-2 diabetes mellitus (T2DM) is frequently asymptomatic and gradual. One reason newly diagnosed type-2 diabetes mellitus patients have a higher risk of microvascular problems is untreated long-standing hyperglycemia. The objective of our study was to evaluate the frequency of microvascular problems in recently diagnosed patients with type 2 diabetes mellitus at a tertiary care hospital in India. Material and Methods: A cross-sectional study was undertaken in the medicine department of a tertiary care hospital. The study included a cohort of 100 patients who were recently diagnosed with type 2 diabetes mellitus. Microvascular complications were diagnosed after a thorough study of the patient's medical history, clinical assessment, and pertinent diagnostic tests. Results: Subjects who had an IDRS score of 60 or higher showed a higher occurrence of peripheral neuropathy (86.5% vs 13.5%, p=0.371), retinopathy (91.7% vs 8.3%, p=0.157), and nephropathy (77.8% vs 22.2%, p=0.410) compared to subjects with an IDRS score below 60. However, there was no statistically significant difference in the occurrence of microvascular problems between the two IDRS subgroups. Those diagnosed with nephropathy exhibit a statistically significant higher average IDRS score compared to those without nephropathy (65.00±17.32 vs 62.66±12.50, p-value = 0.037). However, no statistically significant difference was detected in the mean values of the IDRS scores of the other two microvascular complications. Conclusion: IDRS is a valuable tool for predicting newly diagnosed type 2 diabetes mellitus. However, further large, multi-centric studies will be required to detect its usefulness in microvascular complications. [ABSTRACT FROM AUTHOR]

Background: Diabetic nephropathy is the leading cause of end-stage renal disease (ESRD) worldwide, and it is estimated that ∼20% of type 2 diabetic patients reach ESRD during their lifetime. Diabetic nephropathy is the leading cause of chronic kidney disease in patients starting renal replacement therapy and is associated with increased cardiovascular mortality. Diabetic nephropathy has been classically defined by the presence of proteinuria >0.5 g/24 h. This stage has been referred to as overt nephropathy, clinical nephropathy, proteinuria, or macroalbuminuria. Aims and Objectives: To Assess the prevalence of diabetic nephropathy in type 2 DM patients. Materials and Methods: In this prospective study, 52 patients diagnosed diabetics were studied. Group A had 26 patients with at least one risk factor are hypertension, hypercholesterolemia and obesity. Group B had 26 patients without any of the risk factors. Patients who were selected for presence of Diabetic nephropathy with abnormal serum Creatinine, creatinine clearance and urinary albumin levels. Results and Observations: As many as 8 out of 52 patients were found to have Diabetic nephropathy. The number was significantly higher in group A compared to group B. Incidence of nephropathy was higher with higher number of associated risk factors. Urinary microalbuminuria was the commonest abnormality, Serum creatinine was found in only 25.84% of total positive cases. Conclusion: The large differences observed in the prevalence of nephropathy among different studies could be attributed to the differences in study design and methodologies adopted for defining the disease. Hypertension, obesity and hypercholesterolemia can contribute to development of nephropathy, and also, urinary microalbuminuria appears to be much more sensitive than serum creatinine. [ABSTRACT FROM AUTHOR]

Diabetic nephropathy (DN) is one of the most common kidney diseases, but its exact pathophysiology remains unknown. Toll-like receptors (TLRs) are innate immune receptors that recognize pathogen- and danger-associated molecular patterns, which can result in an inflammatory response. TLR4, TLR2, TLR5, TLR7, TLR8, TLR9, and TLR11 are essential in the pathogenesis of DN, according to recent evidence collected from both in vivo and in vitro studies. Studies have shown that TLR2 and TLR4 expression is higher in patients with renal failure and nephrotic diabetes. They also play critical roles in podocyte injury and inflammation caused by high glucose. TLR2 and TLR4 may be helpful therapeutic targets to prevent or delay DN in patients with type 2 diabetes mellitus. Additionally, TLR7 may contribute to kidney damage in type 1 diabetes mellitus, whereas downregulation of TLR9 expression inhibits inflammation and apoptosis pathways associated with DN. [ABSTRACT FROM AUTHOR]

Context: Sweat glands (SGs) play a vital role in thermal regulation. The function and structure are altered during the different pathological conditions. Objective: These alterations are studied through three techniques: biopsy, sweat analytes and electrical activity of SG. Methods: The morphological study of SG through biopsy and various techniques involved in quantifying sweat analytes is focussed on here. Electrical activities of SG in diabetes, neuropathy and nephropathy cases are also discussed, highlighting their limitations and future scope. Results and Conclusion: The result of this review identified three areas of the knowledge gap. The first is wearable sensors to correlate pathological conditions. Secondly, there is no device to look for its structure and quantify its associated function. Finally, therapeutic applications of SG are explored, especially for renal failure. With these aspects, this paper provides information collection and correlates SG with pathologies related to diabetes. Hence this could help researchers develop suitable technologies for the gaps identified. [ABSTRACT FROM AUTHOR]

Nonalcoholic fatty liver disease is the most prevalent chronic liver disease globally and is linked to augmented susceptibility to type 2 diabetes mellitus (DM), cardiovascular disease, and microvascular complications inherent to DM, such as nephropathy, neuropathy, and retinopathy. The fibrosis-4 (FIB-4) scoring system, a noninvasive tool, is useful for predicting the extent of liver fibrosis across diverse pathologies. This study aimed to assess the potential predictive role of FIB-4 scores in microvascular complications associated with diabetes. The medical records of patients with type 2 DM admitted to our endocrinology clinic between February 2019 and December 2020 were retrospectively evaluated. Parameters including demographic attributes, fasting blood glucose, glycated hemoglobin, aspartate aminotransferase, alanine aminotransferase, thrombocyte levels, and microvascular complications were recorded. The FIB-4 score was computed, and patients were categorized based on these scores (<1.3 and ≥ 1.3). The analysis included 312 patients with a median age of 60 (50–68 years); 39.7 % were men. The median duration of diabetes was 10 years (5–20 years), and the median FIB-4 score was 0.93 (0.63–1.34). Neuropathy, nephropathy, and retinopathy were observed in 50.6 %, 31.4 %, and 34 % of the patients, respectively. Although the FIB-4 score did not differ significantly between patients with and without neuropathy or retinopathy, patients with nephropathy exhibited higher FIB-4 scores. Notably, patients with FIB-4 scores ≥ 1.3 demonstrated a significantly higher prevalence of nephropathy. Logistic regression analysis demonstrated that higher FIB-4 scores were significantly associated with an increased risk of nephropathy. The FIB-4 score is a cost-effective and straightforward tool with potential applicability in predicting nephropathy in individuals with type 2 DM. [ABSTRACT FROM AUTHOR]

Introduction: Diabetic nephropathy is a growing public health challenge with implications on health. Renal function decline impacts the functional ability and overall health and well-being of individuals with diabetic nephropathy due to development of several renal manifestations. The objective of the study was to determine the effect of an exercise-based rehabilitation program on functional capacity and renal function among individuals with type 2 diabetic nephropathy. Methods: A total of 283 individuals were screened and 60 eligible participants aged 45–70 years with diabetic nephropathy were randomly allocated (n = 30 each) to the intervention group (IG) and control group (CG), respectively. The study outcome measures comprised of functional capacity (6-min walk test) and renal function assessed at baseline, 12th week and 24th week. Participants allocated to IG received 12 weeks of exercise based rehabilitation (comprising of supervised + home-based exercises) along with standard care and followed-up till 24th week. Results: The repeated measures ANOVA with Greenhouse–Geisser correction indicated significant timepoint*group interaction effect for 6-min walk distance F (1.71, 90.59) = 619, p < 0.001, serum creatinine F (1.23, 65.14) = 174.8, p < 0.001, estimated glomerular filtration rate F(1.15, 60.88) = 105.2, p < 0.001, serum urea F(1.48, 78.45) = 261.4, p < 0.001 and urine protein F (1.13, 59.82) = 4.58, p < 0.328. Conclusion: The study found that exercise based rehabilitation improved both functional capacity and renal function among individuals with type 2 diabetic nephropathy. [ABSTRACT FROM AUTHOR]

Multicentric carpotarsal osteolysis syndrome (MCTO) is a rare skeletal disorder characterized by progressive osteolysis involving the carpal and tarsal bones, and often associated with nephropathy. It is caused by heterozygous mutation in the MAF bZIP transcription factor B (MAFB) gene. Heterogeneous clinical manifestation and wide spectrum of disease severity have been observed in patients with MCTO. Here, we report a case of a male patient who presented with kidney failure in childhood with progressive disabling skeletal deformity. He was diagnosed with MCTO at 31‐years‐old, where a de novo pathogenic heterozygous variant in NM_005461.5:c.212C>A: p.(Pro71His) of the MAFB gene was identified. While there has been little data on the long‐term prognosis and life expectancy of this disease, this case report sheds light on the debilitating disease course with multiple significant morbidities of a patient with MCTO throughout his lifetime of 33 years. [ABSTRACT FROM AUTHOR]

The utilization of contrast media (CM) in clinical diagnostic imaging and interventional procedures has escalated, leading to a gradual increase in the incidence of contrast-induced acute kidney injury (CI-AKI). Presently, the scarcity of effective pharmacological treatments for CI-AKI poses significant challenges to clinical management. Firstly, we explore the pathogenesis of CI-AKI in this review. Beyond renal medullary ischemia and hypoxia, oxidative stress, cellular apoptosis, and inflammation, emerging mechanisms such as ferroptosis, release of neutrophil extracellular traps (NETs), and nitrosative stress, which offer promising avenues for the management of CI-AKI, are identified. Secondly, a comprehensive strategy for the early prevention of CI-AKI is introduced. Investigating the risk factors associated with CI-AKI is essential for the timely identification of high-risk groups. Additionally, exploring early sensitive biomarkers is crucial for early diagnosis. A synergistic approach that combines these sensitive biomarkers, CI-AKI risk factors, and disease risk prediction models enhances both the accuracy and efficiency of early diagnostic processes. Finally, we explore recent pharmacological and non-pharmacological interventions for the management of Cl-AKI. Beyond the traditional focus on the antioxidant N-acetylcysteine (NAC), we look at active compounds from traditional Chinese medicine, including tetramethylpyrazine (TMP), salvianolic acid B (Sal B), as well as emerging preventive medications like N-acetylcysteine amide (NACA), alprostadil, and others, which all showed potential benefits in animal and clinical studies for CI-AKI prevention. Furthermore, innovative strategies such as calorie restriction (CR), enhanced external counterpulsation (EECP), and mesenchymal stem cell therapy are highlighted as providing fresh insights into Cl-AKI prevention and management. [ABSTRACT FROM AUTHOR]

Fabry disease (FD) leads to significant morbidity and mortality, which may indicate accelerated ageing. However, it is still unclear whether there is a relationship between telomere length (TL), a marker of biological ageing, and disease outcome. We aimed to examine the relationship between leukocyte TL (LTL) dynamics and the presence of advanced disease stages and/or late complications of FD, including hypertrophic cardiomyopathy, nephropathy and stroke, both cross-sectionally and longitudinally. DNA was extracted from peripheral blood leukocytes and quantitative PCR was utilized to determine relative LTL in 99 Fabry patients. In the longitudinal analysis, we included 50 patients in whom at least three measurements were performed over a period of 5–10 years. The results showed a significant inverse correlation between LTL and age (ρ = −0.20, p = 0.05). No significant differences in LTL were found between females and males (p = 0.79) or between patients receiving disease-specific therapy and those without (p = 0.34). In a cross-sectional analysis, no association was found between the presence (p = 0.15) or number (p = 0.28) of advanced stages of the disease and/or late complications and LTL. Similarly, in a longitudinal analysis, no difference in LTL dynamics was found regarding the presence (p = 0.16) of advanced stage organ involvement and/or late complications or their number. These findings indicate that LTL dynamics in adulthood may not be a reliable indicator of disease outcomes in Fabry patients. Therefore, LTL may more accurately reflect the disease burden in early life, when TL is primarily determined. [ABSTRACT FROM AUTHOR]

The present study aimed to assess metal/heavy metal intake by the population via food environment of the Uddanam region, a hotspot for chronic kidney disease of uncertain aetiology (CKDu) in India. The food samples included rice/paddy, marine/freshwater fish, green gram/black gram (whole), and green leafy vegetables (GLVs, i.e. amaranth/spinach). These were analysed for metal/heavy metal (chromium, nickel, copper, arsenic, lead, magnesium, calcium, aluminium, manganese, iron, zinc, barium, cadmium, mercury, and uranium) content using standard procedures. The total heavy metal intake was calculated as a sum of the intake from each food source. The daily dietary intake was compared to safe intake levels (from the Institute of Medicine of the National Academies and National Institute of Nutrition). The intake was higher than safe levels for lead, chromium, and manganese. It is advisable to reduce heavy metal exposure by adopting agricultural practices and public health interventions in terms of diet. [ABSTRACT FROM AUTHOR]

The contribution of chronic kidney disease (CKD) towards the risk of developing cardiovascular disease (CVD) is magnified with co-existing type 1 or type 2 diabetes. Lipids are a modifiable risk factor and good lipid management offers improved outcomes for people with diabetic kidney disease (DKD). The primary purpose of this guideline, written by the Association of British Clinical Diabetologists (ABCD) and UK Kidney Association (UKKA) working group, is to provide practical recommendations on lipid management for members of the multidisciplinary team involved in the care of adults with DKD. [ABSTRACT FROM AUTHOR]

A 14‐year‐old male tiger developed anorexia with elevated blood urea nitrogen and creatinine levels. The patient had a palpable abdominal mass and demonstrated neutrophilic leukocytosis and anaemia. Leukocytes, yeast and bacteria were present in the urine. The animal was non‐responsive to therapy and was subsequently euthanised. Extensive acute renal papillary necrosis (RPN) with pyelonephritis, chronic nephritis and polycystic renal disease were evident during gross and microscopic pathology examinations. The histologic occurrence of fungal spores and pseudohyphae morphologically consistent with Candida species were observed within the necrotic papillary regions of the kidney and within multiple foci of mild parakeratotic hyperkeratosis present in the gingiva and tongue. Candida albicans along with a slight growth of Escherichia coli were recovered from kidney cultures. Possible contributory factors for the renal candidiasis and associated RPN include predisposing oral candidiasis, polycystic renal disease, ischaemic nephrosclerosis, age‐associated or other forms of immunodeficiency and therapy with meloxicam, a non‐steroidal anti‐inflammatory drug. The absence of apparent lower urinary tract involvement coupled with the presence of intravascular renal 'Candida emboli' suggest that chronic oral candidiasis was the probable source of the kidney infection. [ABSTRACT FROM AUTHOR]

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Background: Gowing number of studies have demonstrated the association between gut microbiome and T2DM microvascular complications, however the causal relationship remains unclear. Therefore, we using the Mendelian randomization (MR) approach to investigate this causal relation. Methods: Using gut microbiome data from the International MiBioGen Consortium genome-wide association study (GWAS) and T2DM microvascular complications data from the FinnGen Consortium GWAS to perform MR analyses. Single nucleotide polymorphisms (SNPs) were selected as instrumental variables (IVs), the inverse variance weighting (IVW) method was used as the primary analysis method, and the results were tested for heterogeneity and horizontal pleiotropy. Results: Our research identified that there are 5 known microbial species and 2 unknown microbial species in the gut microbiome that were causally related to T2DM retinopathy. Besides, three and seven known microbial species causal relationships between the gut microbiome and T2DM neuropathy and T2DM nephropathy, respectively. Conclusions: Using MR methods, we demonstrated the causal relationship between gut microbiome and microvascular complications in T2DM, providing a new strategy for the prevention and treatment of it. [ABSTRACT FROM AUTHOR]

Diabetes mellitus is associated with secondary complications such as diabetic retinopathy (DR), nephropathy (DN), and cardiomyopathy (DCM), all of which significantly impact patient health. Intercellular adhesion molecule‐1 (ICAM‐1) has been implicated in inflammatory responses and endothelial dysfunction, both crucial in the pathogenesis of these complications. The goal of this review is to investigate at potential therapy methods that target ICAM‐1 pathways and to better understand the multifaceted role of ICAM‐1 in secondary diabetic problems. A meticulous analysis of scholarly literature published globally was conducted to examine ICAM‐1involvement in inflammatory processes, endothelial dysfunction, and oxidative stress related to diabetes and its complications. Elevated ICAM‐1 levels are strongly associated with augmented leukocyte adhesion, compromised microvascular function, and heightened oxidative stress in diabetes. These pathways contribute significantly to DR, DN, and DCM pathogenesis, highlighting ICAM‐1 as a key player in their progression. Understanding ICAM‐1 role in secondary diabetic complications offers insights into novel therapeutic strategies. Targeting ICAM‐1 pathways may mitigate inflammation, improve endothelial function, and ultimately attenuate diabetic complications, thereby enhancing patient health outcomes. Continued research in this area is crucial for developing effective targeted therapies. Significance statement: This review centers its attention on the function of intercellular adhesion molecule‐1 (ICAM‐1) in the development and progression of diabetic retinopathy, nephropathy, and cardiomyopathy.The role of ICAM‐1 in the pathophysiology of various disorders is investigated.The article emphasizes the significance of ICAM‐1 as a critical target for therapeutic interventions and the molecular mechanisms behind the contribution of ICAM‐1 are explored. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to determine the frequency of albuminuria in urine among Type 2 diabetic patients attending primary healthcare and to assess the factors influencing albuminuria. Methods: The research was conducted as a cross-sectional descriptive study between June 1, 2020, and August 31, 2020, at Kanyon Family Health Center in the Vezirköprü district of Samsun province. The study included 211 individuals. After obtaining informed consent from the participants, a face-to-face study form was administered to gather sociodemographic characteristics, smoking habits, comorbidities, and medication information. Albuminuria was detected using test strips, and the color change in the strip was evaluated by the same researcher in daylight each time, and the albumin/creatinine ratio in instantaneous spot urine was approximately calculated. Data analysis was performed with SPSS 24.0 (SPSS 24.0 for Windows, SPSS Inc., Chicago, IL, USA). Results: Of the participants, 52.1% (n=110) were female. The average age was 59.8±13.3 years (min:25-max:80). Hypertension was diagnosed in 47.4%, atherosclerotic heart disease in 27%, hyperlipidemia in 23.7%, obesity in 22.7%, and cerebrovascular disease in 2.4%. When the duration of diabetes diagnosis was evaluated, 27.5% had been diagnosed with diabetes for 0-5 years, 26.6% for 6-10 years, 15.6% for 11-15 years, 14.2% for 16-20 years, and 16.1% for more than 20 years. In addition, 39.3% had been regular smokers for the last 6 months and 37% had never smoked in their lives. 78.7% (n=166) of the patients were normoalbuminuric, 19% (n=40) were microalbuminuria, and 2.4% (n=5) were macroalbuminuria when albumin/creatinine ratio in spot urine was evaluated. The incidence of microalbuminuria and severe albuminuria was significantly higher in older patients, those with longer durations of diabetes, and former smokers (all; p<0.001). A positive correlation was found between age, duration of diabetes, hypertension, obesity, and albuminuria (r: 0.48, r: 0.68, r: 0.47, r: 0.55; p≤0.05, respectively). Microalbuminuria levels were higher in patients who had smoked throughout their lives compared to smokers and never smokers (p≤0.05). Furthermore, patients diagnosed with Type 2 diabetes for 16-20 years and over 20 years had higher microalbuminuria levels than those newly diagnosed (p<0.001). Conclusion: In our study, age, duration of diabetes diagnosis, hypertension, obesity, and smoking history were associated with albuminuria. By integrating practical screening protocols and adopting a holistic approach to patient care, family physicians can play an important role in reducing the burden of diabetic nephropathy in primary health care and improving patient outcomes. [ABSTRACT FROM AUTHOR]

Hypophosphatemic osteomalacia in an adult often gives clinical diagnostic challenges. Usually, they are caused by either tumor‑induced osteomalacia or due to genetically mediated hypophosphatemia, particularly X‑linked hypophosphatemia. However, heavy metal toxicity, leading to global proximal renal tubular dysfunction, is a rare cause, and in particular, cadmium toxicity is rarely encountered in clinical practice. The presence of bony pain and neurological deficit, along with a classical exposure history, provides the diagnostic clue. In this background, here we present a middle‑aged man who had severe bony pains all over his body and lower back stiffness for five years. He underwent an initial workup as a suspected spondyloarthropathy but was later on, found to have hypophosphatemic osteomalacia and severe proximal renal tubular dysfunction. Further, the workup revealed elevated FGF‑23. His occupational history revealed prolonged exposure to cadmium fumes in the silverware industry. He improved moderately with treatment; however, significant renal damage is still present. This case highlights the importance of considering cadmium toxicity in proper clinical and occupational contexts in the evaluation of hypophosphatemic osteomalacia in an adult. [ABSTRACT FROM AUTHOR]

Human inborn errors of immunity (IEIs), previously referred to as primary immunodeficiency disorders (PIDs), are a heterogeneous spectrum of inherited abnormalities of the immune system with different organ involvement. The number of identified IEIs is rapidly increasing, highlighting the non-negligible role of an interdisciplinary approach in clinical diagnosis. Kidney disorders are one of the important comorbidities in some of the affected patients and play a significant role in the diagnosis and course of disease. According to recent studies, 22 types of human IEI with renal manifestations have been identified so far, including immunodeficiency with congenital thrombocytopenia, thymic defects with additional congenital anomalies, complement deficiencies, type 1 interferonopathies, immunity related to non-hematopoietic tissues, congenital neutropenia's, common variable immunodeficiency disorder (CVID) phenotype and immuno-osseous dysplasia. Based on this classification, we herein review IEIs with renal features and explain the genetic defect, inheritance, and type of renal manifestations. [ABSTRACT FROM AUTHOR]

Diabetes is a multifactorial disorder that involves several molecular mechanisms and is still one of the key global health challenges with increasing prevalence and incidence. Gut microbiome dysbiosis could activate and recognize receptors that trigger the inflammation response and modulation of insulin sensitivity. In addition, the intricate role of gut microbiota dysbiosis in the onset and development of T2D (Type 2 diabetes mellitus) and associated microvascular complications was identified. These complications include diabetic nephropathy (DN) and diabetic retinopathy (DR), diabetic neuropathy, cerebrovascular disorders, and coronary heart disease. A recent interesting strategy to improve these complications is probiotics administration. The safety and health effects of probiotics against various diseases have been validated by various in vitro, in vivo and clinical studies. In this review, the related mechanisms between the gut microbiome, initiation, and progression of T2D and its common microvascular complications (DN and DR) have been discussed. [ABSTRACT FROM AUTHOR]

The residue from roselle beverage production is rich in polyphenols and dietary fiber. We investigated its potential as a preventive and therapeutic agent for type 2 diabetes mellitus (T2DM). Male Wistar rats were fed a high-fat high-fructose diet (HFFD) for 17 weeks, reaching insulin resistance by week 9, and induced to T2DM with streptozotocin (STZ) at week 13. Roselle beverage residue (RBR) was administered ad libitum mixed at 6% with the HFFD. Rats received HFFD+RBR as a preventive strategy starting at week 1 (healthy) and week 9 (insulin resistant), whereas the treatment strategy in T2DM rats started at week 14 alone or in combination with metformin (200 mg/kg/day), with a control metformin-treated group. All RBR-supplemented groups showed reduced serum glucose levels (1.4-fold to 1.8-fold) compared with the HFFD+STZ control group. Preventive RBR administration enhanced pancreatic function, leading to improved insulin sensitivity (6.5-fold to 7.9-fold). Gene expression analysis identified slight alterations in hepatic and skeletal muscle glucose metabolism. Additionally, RBR supplementation demonstrated a preventive role in mitigating hyperuricemia (2.1-fold to 2.2-fold), with no effect on glomerular hyperfiltration. While the exact mechanisms underlying RBR effects remain to be fully elucidated, our findings highlight its promising potential as a dietary supplement for preventing and treating T2DM. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to evaluate the relationship between monocyte/high-density lipoprotein (HDL) ratio (MHR), an inflammatory marker, and diabetic nephropathy (DN), a microvascular complication of diabetes in diabetic patients and to investigate the effect of sodium-glucose co-transporter 2 inhibitors (SGLT2i) on MHR. Material and methods: The study included 119 diabetic patients. Hemogram, glucose, HbA1c, urea, creatinine, albumin, HDL cholesterol, LDL cholesterol, triglycerides, total cholesterol, MHR, NLR (neutrophil-lymphocyte ratio), and CRP parameters were evaluated in blood parameters taken after 8–10 h of fasting before and 6 months after SGLT2 inhibitor use, and albumin, creatinine, and albumin/creatinine parameters were evaluated in urine samples. Parameters were compared according to nephropathy status and SGLT2i type used. Results: The MHR in diabetic nephropathy (DN (+)) patients was significantly higher than in DN (−) patients (p = 0.005). There was no significant difference in NLR value in both groups. The MHR value decreased significantly after the use of SGLT2i in all patients participating in the study (p = 0.01). NLR value decreased in DN (−) patients after SGLT2i use. No difference was observed in DN (+) patients. Conclusion: In this study, results supporting the relationship between DN and MHR and the effect of SGLT2i drugs on MHR were found. The use of MHR value as a marker in clinical course monitoring and shaping the treatment according to these markers may be useful in terms of prediction and treatment of complications. [ABSTRACT FROM AUTHOR]

Nephropathy is the decline in kidney function. A promising treatment for numerous types of illness is using natural materials as natural chemical compounds. The inquiry was conducted to investigate cannabidiol (CBD) potential for renal syndrome protection. The five equal groups of fifty male Sprague-Dawley rats weighing 150 ± 25 g each were designed; group I received distilled water orally, while group II got an intraperitoneal injection of doxorubicin (18 mg/kg bwt). Group III received CBD (26 mg/kg bwt) orally, while group IV received 1 ml of CBD (26 mg/kg bwt) and group V received trimetazidine (10 mg/kg bwt), in addition to a single intraperitoneal dose of doxorubicin (18 mg/kg bwt) on the 11th day for both groups (IV, V). The administration of CBD (26 mg/kg bwt) led to a noticeable improvement in oxidative stress parameters (SOD and GSH) in rats by significantly lowering enzyme activity (ALT and AST), as well as serum creatinine and urea, IL-6, and MDA, confirming the anti-inflammatory accuracy of CBD linked to significant lowering to IL6R DNA frequency concentration in line with histopathology results. As a result of its anti-inflammatory and antioxidant capabilities, cannabidiol may have protective quality, and CBD medication could be related to controlling renal problems. [ABSTRACT FROM AUTHOR]

Background: Flavonoids like chyrsin, which are abundant in plant extracts, honey, and bee propolis, have antiviral, anti-cancer, anti-bacterial, anti-inflammatory, anti-allergic, anti-mutagenic, anti-anxiolytic, and other therapeutic uses. However, no research has been published on how chrysin protects rats against HFD/STZ- induced changes to the glycoprotein moiety via controlling the metabolism of glucose. Methods: For two weeks, albino male wistar rats were fed a high-fat diet in order to develop diabetes. Upon two weeks, a low dosage of streptozotocin (35 mg/kg, diluted in 0.1 M sodium citrate buffer, pH 4.5) was administered into the animals after they had been fasted for the whole night. Blood glucose, insulin, hepatic, and renal indicators were analyzed using commercially available diagnostic kits, and other parameters were ascertained biochemically. Results: For 30 days, high-fat diet- and streptozotocin-induced diabetic rats were given 40 mg/kg b.w./day of chrysin, which significantly reduced blood glucose, homeostatic model assessment of insulin resistance, glycogen phospharylase, hepatic and renal markers, and increased insulin, glycogen content, and glycogen synthase levels. Conclusion: However, the altered activity of the glycoprotein components and the carbohydrate metabolic enzymes was restored upon chrysin administration. On several criteria, the chrysin's effect was similar to that of metformin. Chrysin is therefore a potential antidiabetic agent.