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Background: Chronic kidney disease (CKD) is a globally significant non-communicable disorder. CKD prevalence varies between countries and within a country. We compared the prevalence rates of CKD in South Africa with sub-Saharan Africa, Africa, and globally. Methods: We registered a systematic review with the International Prospective Register of Systematic Reviews for prevalence studies reporting CKD stages III-V from 2013 to 2021. The analysis sought to explain any significant differences in prevalence rates. The R statistical package was used for data analysis. Comparisons included measures of effect size due to the large sample sizes analysed. We also compared sex differences in prevalence rates, common aetiologies, and type of study methodologies employed. Results: Eight studies were analysed, with two from each region. The matched prevalence rates of CKD between the various regions and South Africa showed significant differences, except for one comparison between South Africa and an African study [p = 0.09 (95% CI − 0.04–0.01)]. Both sub-Saharan African studies had a higher prevalence than South Africa. One study in Africa had a higher prevalence, while the other had a lower prevalence, whilst one Global study had a higher prevalence, and the other had a lower prevalence compared to South Africa. The statistical differences analysed using the Cramer's V test were substantially less than 0.1. Thus, differences in comparisons were largely due to differences in sample sizes rather than actual differences. Conclusion: Variable prevalence rates between regions included disparities in sample size, definitions of CKD, lack of chronicity testing and heterogeneous laboratory estimations of eGFR. Improved consistency and enhanced methods for diagnosing and comparing CKD prevalence are essential. [ABSTRACT FROM AUTHOR]

The protein glycation due to high blood glucose mediate release of inflammatory intermediate contributes in the development of diabetic nephropathy. Ferulic acid (FA) is a phenolic compound distributed in different foods as whole grains. Inhibitors of DPP4 improve GLP-1-mediated insulin secretion and inhibit liver gluconeogenesis. This study investigated the impact of FA as anti-inflammatory, antioxidant and antiglycation against streptozotocin-induced diabetic nephropathy in rats. This study was carried out on total ninety male rats allocated into six (each 15 rats); group I (control). All other animals (groups II–VI) were receiving 65 mg/kg STZ for induction of diabetes. Rats in group II (untreated diabetic). Rats in groups III–V were treated with FA (10, 20, 30 mg/kg bw) respectively, i.p. for 8 weeks. Group VI received 10 units insulin daily, sc. Fasting blood samples were subjected for assay of glycated hemoglobin (HA1c), serum MDA, aldose reductase, total antioxidant, DPP4 while kidney tissue subjected for assay of malondialdehyde (MDA), reduced glutathione (GSH), catalase (CAT), superoxide dismutase (SOD), tumor necrosis factor-α (TNF-α), IL-1β and AGEs. Data obtained showed that, FA showed antioxidant activity by reducing MDA and enhancement antioxidant activity compared with untreated rats (p < 0.001) with dose dependence. In addition, FA reduced the activities of aldose reductase, DPP4 (p < 0.001), decreased IL-6, TNF-α and AGEs versus untreated rats (p < 0.001). Histological investigation revealed an improvement in the nephron structure in diabetic rat treated with FA versus untreated group. It was concluded that, FA possesses a potent antioxidant and anti-inflammatory and DPP4 inhibitor. For that, it was considered as a protective agent against the risk of diabetic nephropathy and can be used as alternative or complementary supplement. [ABSTRACT FROM AUTHOR]

Thioacetamide (TAA) exposure and hepatitis C virus infection are usually associated with renal dysfunction. Sofosbuvir (SFV) and daclatasvir (DAC) drugs combination has great value in the treatment of hepatitis C. The study aimed to identify the nephrotoxic effects of TAA and to evaluate the ameliorative role of SFV and DAC in this condition. Forty-eight adult male albino rats were divided into eight groups and received saline (control), SFV, DAC, SFV+DAC, TAA, TAA+SFV, TAA+DAC and TAA+SFV+DAC for eight weeks. Kidney and blood samples were retrieved and processed for histological (Hematoxylin and Eosin and Masson’s trichrome), immunohistochemical (α-smooth muscle actin), and biochemical analysis (urea, creatinine, total protein, albumin, malondialdehyde, reduced glutathione, superoxide dismutase, and tumor necrosis factor-α). Examination revealed marked destruction of renal tubules on exposure to TAA with either hypertrophy or atrophy of glomeruli, increase in collagen deposition, and wide expression of α-smooth muscle actin. Also, significant disturbance in kidney functions, oxidative stress markers, and tumor necrosis factor-α. Supplementation with either SFV or DAC produced mild improvement in the tissue and laboratory markers. Moreover, the combination of both drugs greatly refined the pathology induced by TAA at the cellular and laboratory levels. However, there are still significant differences when compared to the control. In conclusion, SFV and DAC combination partially but greatly ameliorated the renal damage induced by TAA which might be enhanced with further supplementations to give new hope for those with nephropathy associated with hepatitis. [ABSTRACT FROM AUTHOR]

The prognosis of hypertension leads to organ damage by causing nephropathy, stroke, retinopathy, and cardiomegaly. Retinopathy and blood pressure have been extensively discussed in relation to catecholamines of the autonomic nervous system (ANS) and angiotensin II of the renin–angiotensin aldosterone system (RAAS) but very little research has been conducted on the role of the ECS in the regulation of retinopathy and blood pressure. The endocannabinoid system (ECS) is a unique system in the body that can be considered as a master regulator of body functions. It encompasses the endogenous production of its cannabinoids, its degrading enzymes, and functional receptors which innervate and perform various functions in different organs of the body. Hypertensive retinopathy pathologies arise normally due to oxidative stress, ischemia, endothelium dysfunction, inflammation, and an activated renin–angiotensin system (RAS) and catecholamine which are vasoconstrictors in their biological nature. The question arises of which system or agent counterbalances the vasoconstrictors effect of noradrenaline and angiotensin II (Ang II) in normal individuals? In this review article, we discuss the role of the ECS and its contribution to the pathogenesis of hypertensive retinopathy. This review article will also examine the involvement of the RAS and the ANS in the pathogenesis of hypertensive retinopathy and the crosstalk between these three systems in hypertensive retinopathy. This review will also explain that the ECS, which is a vasodilator in its action, either independently counteracts the effect produced with the vasoconstriction of the ANS and Ang II or blocks some of the common pathways shared by the ECS, ANS, and Ang II in the regulation of eye functions and blood pressure. This article concludes that persistent control of blood pressure and normal functions of the eye are maintained either by decreasing systemic catecholamine, ang II, or by upregulation of the ECS which results in the regression of retinopathy induced by hypertension. [ABSTRACT FROM AUTHOR]

Background: Patients who undergo primary percutaneous coronary intervention (PCI), are at great risk of contrast-induced nephropathy (CIN). The PRECISE-DAPT score had been implemented nowadays to determine the best period of dual anti-platelet therapy after PCI. This Study aim To determine the predictive value of the admission PRECISE-DAPT score in the early diagnosis of CIN. Methods: A prospective cohort study carried out in the cardiology department at Zagazig university hospital and national heart institute, Cairo, during the period from January 2020 to August 2020. The study included 200 patients admitted with first acute ST segment elevation myocardial infarction (STEMI) and underwent primary percutaneous coronary intervention. All patients were subjected to complete history taking. General examination for all body systems and local cardiological examination were done. We also did full lab investigations as complete blood count (CBC), Creatine kinase-myocardial band (CK-MB), Troponin, creatinine (at admission and within 72h post PCI) and glomerular filtration rate (GFR). Patient's resting Electrocardiogram (ECG) and transthoracic echocardiography (TTE) were done. PRECISE-DAPT score was calculated for all cases. Coronary angiography and PCI were performed. Results: We detected a high statistically significant increase in precise DAPT score (23.6 ± 10.4) p <0.001 among CIN patients. CKMB, Platelet distribution width (PDW), contrast volume, left anterior descending (LAD) culprit vessel and PREISE-DAPT score are significant predictors for CIN among studied patients. Conclusion: The PRECISE-DAPT score can be a valuable tool to predict acute kidney injury in cases of STEMI undergoing PCI. [ABSTRACT FROM AUTHOR]

Objectives: Imaging appearances of immune checkpoint inhibitor-related nephritis have not yet been described. The primary objective of this study is to describe the appearances of immunotherapy-related nephritis on computerized tomography (CT) and positron emission tomography (PET). The secondary objectives are to investigate the association of radiologic features with clinical outcomes. Methods: CT and PET-CT scans before the initiation of immunotherapy (baseline), at nephritis, and after resolution of pathology-proven nephritis cases were reviewed. Total kidney volume, renal parenchymal SUVmax, renal pelvis SUVmax, and blood pool SUVmean were obtained. Results: Thirty-four patients were included. The total kidney volume was significantly higher at nephritis compared to baseline (464.7 ± 96.8 mL vs. 371.7 ± 187.7 mL; p < 0.001). Fifteen patients (44.1%) had > 30% increase in total kidney volume, which was associated with significantly higher renal toxicity grade (p = 0.007), higher peak creatinine level (p = 0.004), and more aggressive medical treatment (p = 0.011). New/increasing perinephric fat stranding was noted in 10 patients (29.4%) at nephritis. Among 8 patients with contrast-enhanced CT at nephritis, one (12.5%) developed bilateral wedge-shaped hypoenhancing cortical. On PET-CT, the renal parenchymal SUVmax-to-blood pool ratio was significantly higher at nephritis compared to baseline (2.13 vs. 1.68; p = 0.035). The renal pelvis SUVmax-to-blood pool SUVmean ratio was significantly lower at nephritis compared to baseline (3.47 vs. 8.22; p = 0.011). Conclusions: Bilateral increase in kidney size, new/increasing perinephric stranding, and bilateral wedge-shaped hypoenhancing cortical foci can occur in immunotherapy-related nephritis. On PET-CT, a diffuse increase in radiotracer uptake throughout the renal cortex and a decrease in radiotracer activity in the renal pelvis can be seen. Key Points: • CT features of immune checkpoint inhibitor-related nephritis include an increase in kidney volume, new/increasing perinephric stranding, and bilateral ill-defined wedge-shaped hypoenhancing cortical foci. • FDG-PET features of immune checkpoint inhibitor-related nephritis include an increase in FDG uptake throughout the renal cortex and a decrease in FDG activity/excretion in the collecting system. • > 30% increase in total kidney volume is associated with worse toxicity grade and more aggressive medical management. [ABSTRACT FROM AUTHOR]

Background: Studies assessing the concordance of albuminuria and retinal microvascular dysfunction (RMD) in type 2 diabetes (T2D) have yielded inconsistent results. Similar to ethnicity, hypertension may be a potential explanatory variable. We compared the association between albuminuria and RMD in West Africans with T2D with and without hypertension. Materials and methods: This was a cross-sectional study among 177 systematically sampled Ghanaians with T2D aged ≥ 35 years. Albuminuria was based on urinary albumin-creatinine ratio≥30 mg/g. Retinal images were analyzed and graded according to the Early Treatment Diabetic Retinopathy Study criteria. Logistic regression was used to examine the associations of albuminuria and RMD with adjustments for age, sex, socioeconomic status, diabetes duration, HbA1c, smoking, systolic blood pressure (BP), BMI, and total cholesterol. Results: RMD was more prevalent in individuals with albuminuria than in those without albuminuria (41.7% vs. 24.0%, p = 0.026). In the fully adjusted model, albuminuria remained significantly associated with RMD (odds ratio 2.41[95% CI:1.00–5.80], p = 0.049); the association between albuminuria and RMD was more pronounced in individuals with hypertension (3.10 [1.01–9.50], 0.048) than without hypertension (1.70[0.33–8.77],0.523). In analyses stratified by BP control, albuminuria was significantly associated with RMD in individuals with suboptimal BP (2.76[1.07–7.14], 0.037) but not in individuals with optimal BP (0.24[0.00–17.04],0.512) Conclusion: Our study shows positive associations between albuminuria and RMD among West Africans with T2D, with the strength of association, accentuated in individuals with hypertension/suboptimal BP. Future studies could further characterize the role of hypertension in the associations between albuminuria and RMD.

Idiopathic membranous nephropathy (IMN), a single-organ autoimmune disease, is recognized by autoantibodies to podocyte proteins and identified as the most frequent cause of nephrotic syndrome in adults. T cells are important contributors in autoimmunity since they promote B–cell development, antibody production, direct inflammation, and organ tissue cytotoxicity. This study investigated the inhibitory immune checkpoint (ICP) receptors expressed on T lymphocytes and other immune cells. Thus, PBMCs from IMN patients were obtained before treatment, and the levels of ICPs such as programmed cell death protein 1 (PD-1), cytotoxic T-lymphocyte-associated protein 4 (CTLA4), lymphocyte activation gene-3 (LAG-3), and T cell immunoglobulin-3 (TIM-3) were examined at both gene and protein expression using real time PCR and Western blot tests respectively. The results illustrated that gene expression levels of ICPs reduced significantly in comparison to the control which were verified by related fold changes of protein expression sequentially. Our study revealed that CTLA-4, PD-1, TIM-3, and LAG-3 expression is impaired in IMN patients before treatment which could be a potential target for therapy.

Objective: To find out the frequency of hypoglycemia in Type-2 Diabetics having nephropathy Methodology: This cross-sectional observational study was carried out in Medical Teaching Institute Khyber Teaching Hospital. Department of Medicine, from August 21, 2020, to January 21, 2021. Two-hundred and eighty-one (281) patients with Type 2 diabetic nephropathy were observed in due course and were subjected to detailed history and examination. A sample of 5 ml venous blood was obtained from the patients to measure blood glucose levels to detect hypoglycemia. Experienced pathologists analyzed all investigations. Results: The mean ± Standard deviation (SD) of age in this study was 60± 10.26 years. Female patients outnumbered males in this study. Hypoglycemia was reported in 21% of patients while 79% did not have hypoglycemia. Conclusion: Type-2 diabetics having nephropathy are prone to hypoglycemia. These patients should be carefully observed for clinical and biochemical features of hypoglycemia .

Diabetes mellitus (DM), one of the most serious non-communicable diseases, has long-term negative effects on the healthcare system due to its microvascular and macrovascular manifestations, which can be fatal if left untreated. Nutraceuticals, on the other hand, are alternative therapy choices of orally consumed natural food ingredients applicable in the management of several diseases, including diabetes mellitus. Through their antioxidant capabilities and bioactive components, nutraceuticals have been clinically demonstrated to be effective in preventing a number of ailments, including cancer, diabetes, heart disease, and kidney problems. Flavonoids, which are categorized as phytochemicals, are present in several of these nutraceuticals. Cocoa, one of the flavanols engaged in the treatment of diabetes mellitus, provides an additional non-pharmaceutical intervention in the management of diabetes mellitus, which, in part, is because of its high antioxidant capacity. Additionally, flavonoids improve insulin resistance and sensitivity, dyslipidemia, endothelial function, and blood pressure, as well as lower oxidative stress and inflammatory processes. As a result, they may be able to stop the progression of long-term vascular consequences of diabetes, such as cardiovascular disease, neuropathy, nephropathy, and retinopathy. Therefore, the effects of nutraceuticals (as an alternative treatment) on diabetic-related micro- and macrovascular problems are the main focus of this review.

Introduction: As the prevalence of kidney disease continues to rise worldwide, there is accumulating evidence that kidney injury and dysfunction, whether acute or chronic, is associated with major adverse outcomes, including mortality. Meanwhile, effective therapeutic options in the treatment of acute kidney injury (AKI) and chronic kidney disease (CKD) have been sparse. Many of the effective treatments that are routinely utilized for different pathologies in patients without kidney disease have failed to demonstrate efficacy in those with renal dysfunction. Hence, there is an urgent need for discovery of novel pathways that can be targeted for innovative and effective clinical therapies in renal disease states. Discussion: There is now accumulating evidence that the endocannabinoid (EC) system plays a prominent role in normal renal homeostasis and function. In addition, numerous recent studies have described mechanisms through which alteration in the EC system can contribute to kidney damage and disease. These include a potential role for cannabinoid receptors in tubulo-glomerular damage and fibrosis, which are common features of AKI, interstitial nephritis, glomerulopathy, and other conditions leading to AKI and CKD. Conclusion: These findings suggest that manipulating the EC system may be an effective therapeutic strategy for the treatment of kidney disease and injury. However, further mechanistic studies are needed to fully delineate the role of this system in various conditions affecting the kidneys. Furthermore, while most of the current literature is focused on the role of the EC system as a whole in renal pathophysiology, future studies will also need to clarify the contribution of each component of this system, including the EC mediators, in the pathogenesis of kidney disease and their potential role as part of a therapeutic strategy.

Objective: To analyze the pathological types, clinical characteristics and outcomes of human immunodeficiency virus (HIV)-infected patients with chronic kidney diseases (CKD). Methods: Thirty-two cases of HIV infection combined with CKD who underwent ultrasound guided renal biopsy in Shanghai Public Health Clinical Center from June 2016 to April 2021 were enrolled. Pathological types, clinical conditions and outcomes were all analyzed. Results: Among the 32 patients, there were 28 male and 4 female, with an average age of (43.5±12.3) years. The CD4+T lymphocyte count was (425.9±240.4) cells/μL. Twenty-six patients (81.3%) had been treated with antiretroviral therapy before renal puncture biopsy, and the median treatment time was 24 (1, 72) months. Among the pathological types, membranous nephropathy (8 cases, 25.0%) and IgA nephropathy (6 cases, 18.8%) accounted for the most types, followed by diabetic nephropathy (5 cases, 15.6%). No classical HIV-related nephropathy was found. During the follow-up period of 3 months to 5 years, the remission rate of renal disease reached 84.4% (13 complete remissions, 14 partial remissions), and the unresponsive rate was 9.4% (3 cases, including 1 case of lupus like immune complex mediated proliferative glomerulonephritis, 1 case of diabetes nephropathy, and 1 case of hypertensive nephropathy). The mortality rate was 6.3%(2 cases, all minor lesions). Conclusions: This study shows that the pathological types of HIV infected patients with CKD are various. Membranous nephropathy is predominant pathological type, and followed by IgA nephropathy and diabetes nephropathy, but classical HIV related nephropathy is not common. According to the pathological results of renal biopsy, renal disease related treatment based on antiretroviral therapy can alleviate renal disease or delay the progression of renal disease, but the prognosis of patients with minimal change nephropathy may be poor.

The article presents an historical analysis of publications devoted lead intoxication to kidney damage developing during contact with lead. It is shown that one of the manifestations of occupational intoxication with this metal can be toxic nephropathy.

Abstract Background Glycated albumin (GA) is known to reflect the current inflammatory burden in non-diabetes mellitus (DM) patients. In this study, we investigated whether GA at diagnosis could reflect the cross-sectional activity and predict poor outcomes during follow-up in non-DM patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). Methods The medical records of 118 immunosuppressive drug-naïve AAV patients were retrospectively reviewed, and 76 patients who had both GA and glycated haemoglobin (HbA1c) results but not DM were included in this study. Demographic, clinical, and laboratory data at diagnosis were assessed. Results The median age of AAV patients was 61 years, and 31 patients were male. GA was positively correlated with five-factor score (r = 0.282), Birmingham vasculitis activity score (BVAS) assigned to renal manifestation (r = 0.315), and blood urea nitrogen (r = 0.382), whereas negatively correlated with haemoglobin (r = -0.345). AAV patients with end-stage renal disease (ESRD) exhibited significantly higher GA than those without ESRD (15.8% vs. 13.6%). When the cut-off of GA at diagnosis for ESRD was set at GA ≥ 14.25%, AAV patients with GA ≥ 14.25% had a significantly higher risk for ESRD development than those without (relative risk 12.040). In addition, AAV patients with GA ≥ 14.25% exhibited significantly lower cumulative ESRD-free survival rates than those without (P = 0.020). Conclusion In conclusion, GA at diagnosis can reflect the cross-sectional BVAS assigned to renal manifestation of AAV and predict ESRD development during follow-up better than HbA1c or GA/HbA1c in AAV patients.

Wei-Hung Chan,1,2 Yu-Juei Hsu,3 Chiao-Pei Cheng,1 Kuan-Nien Chou,2,4 Chin-Li Chen,5 Shih-Ming Huang,6 Wei-Chih Kan,7,8,&ast; Yi-Lin Chiu6,&ast; 1Department of Anesthesiology, Tri-Service General Hospital, National Defense Medical Center, Taipei City, Taiwan, Republic of China; 2Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei City, Taiwan, Republic of China; 3Division of Nephrology, Department of Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei City, Taiwan, Republic of China; 4Department of Neurosurgery, Tri-Service General Hospital, National Defense Medical Center, Taipei City, Taiwan, Republic of China; 5Division of Urology, Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei City, Taiwan, Republic of China; 6Department of Biochemistry, National Defense Medical Center, Taipei City, Taiwan, Republic of China; 7Department of Nephrology, Department of Internal Medicine, Chi-Mei Medical Center, Tainan City, Taiwan, Republic of China; 8Department of Biological Science and Technology, Chung Hwa University of Medical Technology, Tainan City, Taiwan, Republic of China&ast;These authors contributed equally to this workCorrespondence: Yi-Lin Chiu, Department of Biochemistry, National Defense Medical Center, Rm. 7323, 7F, No. 161, Sec. 6, Minquan E. Road, Neihu Dist, Taipei City, 114201, Taiwan, Republic of China, Tel +886 02 87923100#18828, Fax +886 02 87910776, Email yilin1107@mail.ndmctsgh.edu.twPurpose: In this study, we use animal models combined with bioinformatics strategies to investigate the potential changes in overall renal transcriptional expression after traumatic brain injury.Methods: Microarray analysis was performed after kidney acquisition using unilateral controlled cortical impact as the primary mouse TBI model. Multi-oriented gene set enrichment analysis was performed for differentially expressed genes.Results: The results showed that TBI affected the gene set associated with mitochondria function in kidney cells, and a negative enrichment of gene sets associated with immune cell migration and epidermal development was also observed. Analysis of the disease phenotype gene set revealed that differential expression of mitochondria-related genes was associated with lactate metabolism. Alternatively, activation and adhesion of immune cells associated with the complement system may promote autoinflammation in kidney tissue. The simulated immune cell infiltration analysis showed an increase in the proportion of activated memory CD4 T cells and a decrease in the proportion of resting memory CD4 T cells, suggesting that activated memory CD4 T cell infiltration may be involved in the inflammation of renal tissue and cause damage to renal cells, such as principal cells, mesangial cells and loops of Henle cells.Conclusion: This study is the first to reveal the effects of brain trauma on the kidney. TBI may affect the expression of mitochondria function-related gene sets in renal cells by increasing lactate. It may also affect renal mesangial cells by inducing increased infiltration of immune cells through mechanisms related to complement system activation or autoimmune antibodies.Keywords: traumatic brain injury, nephropathy, complement system, lactate metabolism, immune cell infiltration

Nasrin S Saiyed,1 Umar Yagoub,1 Bandar Al Qahtani,2 Attiya Mohammed Al Zahrani,3 Ibrahim Al Hariri,4 Meerab Javed Syed,5 Mohammed Elmujtaba Elmardi,6 Muhammad Abdullah Tufail,7 Marwan Manajreh1 1Research Department, King Salman Armed Forces Hospital, Tabuk, Saudi Arabia; 2Academic Affairs Department, King Salman Armed Forces Hospital, Tabuk, Saudi Arabia; 3Surgery Department, King Salman Armed Forces Hospital, Tabuk, Saudi Arabia; 4Family Medicine Department, King Salman Armed Forces Hospital, Tabuk, Saudi Arabia; 5Internal Medicine Department, King Salman Armed Forces Hospital, Tabuk, Saudi Arabia; 6Cardiology Department, King Salman Armed Forces Hospital, Tabuk, Saudi Arabia; 7Ophthalmology Department, King Salman Armed Forces Hospital, Tabuk, Saudi ArabiaCorrespondence: Umar Yagoub, Director of Research Department, Research Department, King Salman Armed Forces Hospital, Tabuk, Saudi Arabia, Email mohammedumar2001@yahoo.comPurpose: The burden of type 2 diabetes (T2D) is high in Saudi Arabia, but data related to its complications are limited. This study aimed to determine the incidence of microvascular complications caused by T2D and evaluate the impact of the associated risk factors.Patients and Methods: This retrospective cohort study was conducted at two military hospitals in Tabuk, Saudi Arabia. Data on the socio-demographics, glycaemic profile, blood lipid indices, duration of T2D, and associated microvascular complications were collected from electronic health records and medical files. Descriptive statistics and Cox proportional hazards models were used for data analysis.Results: This study included 1563 T2D patients. The incidence of microvascular complications was 34.3% (95% confidence interval [CI], 32.0– 36.6). Retinopathy was the most common complication (incidence=20.0%; 95% CI, 18.0– 22.0%), while nephropathy was the least common complication (incidence=12.2%; 95% CI, 10.6– 13.8%). Advanced age (≥ 65 years) showed the highest risk of retinopathy (Hazard ratios [HR], 2.86; 95% CI, 2.56– 3.21), neuropathy (HR, 2.70; 95% CI, 2.40– 3.05), and nephropathy (HR, 2.37; 95% CI, 2.12– 2.64) compared with their counterparts. After adjusting for potential confounders, the study found that the significant risk factors for microvascular complications were longer duration (≥ 10 years) of T2D (HR, 5.3; 95% CI, 5.1– 5.6), uncontrolled hypertension (HR, 3.9; 95% CI, 3.3– 4.2), poor glycaemic control (HR, 4.6; 95% CI, 4.3– 5.1), obesity (HR, 2.3; 95% CI, 2.2– 2.6), and dyslipidaemia (HR, 1.6; 95% CI, 1.2– 2.0).Conclusion: Given the high burden of microvascular complications in military healthcare facilities in Tabuk, Saudi Arabia, a context-specific accessible public health program focusing on the promotion of a healthy lifestyle, physical activity, and consumption of a healthy diet, as well as the early diagnosis and management of diabetes, needs to be developed and implemented.Keywords: diabetes, microvascular complications, retinopathy, peripheral neuropathy, nephropathy, Saudi Arabia

Context: Tithonia diversifolia (Hemsl.) A. Grayhas been known for treatment of diabetes mellitus, yet its mechanism as anti-diabetic has not been defined. There are various therapeutic targets for diabetes and its complication such as diabetic nephropathy. Aims: To investigate the mechanism of phytoconstituents in Tithonia diversifolia to various targets of diabetic nephropathy and predict the pharmacokinetic profile such as absorption, distribution, metabolism, elimination, and toxicity (ADME-T). Methods: Eighteen phytoconstituents in Tithonia diversifolia were analyzed for drug-likeness. The molecular docking of molecules was performed to protein targets, then its molecular interaction was determined. ADME-T properties were predicted using three different web servers. Results: Drug-likeness analysis showed that all the phytoconstituents were within the range set by Lipinski’s rule of five. This study showed that Tithonia diversifolia have potential as a candidate for diabetic nephropathy therapy agent with various mechanisms by inhibiting α-glucosidase, ACE, ALR, DPP-4, LMW-PTP, RAGE, SGLT2, SUR1, and an analog of PPAR-γ. 5-Caffeoylquinic acid, catechin, diversifolin, hispidulin, tagitinin A, tagitinin C, tagitinin F, tithonine, and tirotundin were phytoconstituents with a high binding affinity to several proteins. β-gurjunene, tagitinin A,tagitinin C, tagitinin F, and tirotundin were predicted to have a better ADME-T properties than other compounds. In summary, tagitinin A, tagitinin C, tagitinin F, and tirotundin were showed the high binding affinity to various diabetes-related proteins and have a good ADME-T profile. Conclusions: This study suggests that Tithonia diversifolia constituents have potential properties as an anti-diabetic nephropathy agent, and further studies to analyze its potency are required.

Resumen: La patología glomerular más relacionada con enfermedad COVID-19 hasta la fecha parece ser la glomerulopatía colapsante, principalmente en pacientes de raza afroamericana y con alelos de riesgo para el gen APOL1. No obstante, en nuestra población, conformada por pacientes adultos mayores de raza caucásica, la patología más biopsiada desde el inicio de la pandemia ha sido la nefritis IgA o púrpura de Schönlein-Henoch.Desde la descripción del primer caso de esta entidad tras infección por SARS-CoV-2 por nuestro grupo de investigación hemos objetivado otros tres, los cuales se describen a continuación. En contraste con el resto de los casos publicados de vasculitis IgA, nuestros pacientes presentaban mayor deterioro de función renal y todos requirieron tratamiento inmunosupresor. Además, algunos presentaron recuperación incompleta de función renal. Esta serie de casos afianza la posibilidad de que la infección por SARS-CoV-2 sea un desencadenante más de esta patología. Abstract: COVID-19 most related glomerular disease to date seems to be collapsing glomerulopathy, mostly in young Afroamerican patients with APOL1 gene risk alleles. However, in our population, predominant in elderly Caucasian patients, most biopsied pathology since the beginning of the pandemic has been IgA nephritis or Schönlein-Henoch purpura.Since the description of the first case of this entity after SARS-CoV-2 infection by our research group, three more cases have arisen, which are described in the following article. In contrast to the rest of IgA vasculitis cases reported, our patients presented more renal function deterioration and all of them required immunosupresive therapy. Moreover, some showed incomplete recovery of renal function.This case series strengthens the hypothesis that SARS-CoV-2 infection may be another trigger of this pathology.

Background: Single gene mutations are important causes of glomerular disease in children. Of these genes, mutations in the FAT1 gene have been recently described in the literature as a cause of nephropathy in isolated form or multisystem involvement. The spectrum of renal disease associated with FAT1 gene mutations varies from asymptomatic proteinuria and hematuria to severe nephrotic syndrome and end-stage renal disease. Case Presentation: In this case report, we describe a 3-year-old child and two other family members with a novel frameshift homozygous mutation in the FAT1 gene consistent with the diagnosis of autosomal recessive colobomatous-microphthalmia, ptosis, nephropathy, and syndactyly syndrome with variable expression of the phenotype. Conclusion: This report adds to the genotype-phenotype correlation, highlighting the clinical importance of considering FAT1 gene defects as part of the differential diagnosis for congenital ptosis, syndactyly and nephropathy, especially with multiple affected family members. [JBCGenetics 2022; 5(1.000): 29-34]

Chronic hyperglycemia caused by diabetes results in systemic damage to the body, and the kidney ends up being the target of tissue damage. The use of antioxidants such as alpha-lipoic acid (ALA) has been shown to improve clinical and biochemical parameters in diabetic patients as they help in the prevention of oxidative stress. The present study aimed to undertake a comparative evaluation of the renal morphology of normal and diabetes-induced Wistar rats supplemented with ALA. The experiment had 4 experimental groups (n=7): a control group and a diabetic group that were fed commercial food; an alpha-lipoic group and an alpha-lipoic diabetic group that received the ALA supplement. Diabetes was induced with a single intraperitoneal injection of alloxane monohydrate administered after fasting. After 60 days of the experiment, the kidneys were excised to study the histomorphometric and stereological parameters of the glomeruli and renal tubules and the immunohistochemical parameters with a podocyte count. In the evaluation, the ALA promoted improvement in all of the relevant parameters of the glomerular areas and attenuation of tubular lesions of diabetic animals (p

The methodology for health risk assessment and hygienic standardization of chemicals often neglects such a vulnerable population group as people with chronic non-communicable diseases. According to the data provided by the WHO, the prevalence of such pathologies is high in many European countries; therefore, when a disease burden in a certain population is unaccounted for, this may result in lower accuracy of accomplished assessments. On the other hand, introduction of too conservative safe factors when hygienic standards are being developed for chemicals in various media leads to high uncertainty and excessive limitations. Our research goal was to provide scientific substantiation for a methodology for using experimental pathology models to improve reliability of hygienic standardization and accuracy of health risk assessments for sensitive population groups (people suffering from non-chronic communicable diseases) under exposure to naturally occurring chemicals. Another goal was to test this methodology by performing a case study on drinking water. The testing results indicate that a chronic 6-month exposure to model substances produced more apparent toxic effects on experimental animals with model pathologies (spontaneous hypertension and experimental histamine-induced nephropathy) in comparison with “healthy” animals. This allowed us to recommend using experimental models of congenital and induced animal pathology bearing in mind target organs for toxic effects produced by the analyzed chemicals to substantiate hygienic standards, health risks taken into account. This should be done at the stage when dose-dependent reactions are identified (determination of no-effect and / or threshold levels) in addition to studies performed on “healthy” animals. It is most appropriate to use this approach when the following conditions are met: 1) a research object is naturally occurring chemicals that are widely spread in the environment due to its natural formation; 2) pathologies of organs (systems) that are targets for biological effects produced by the tested chemicals are widely spread in a population (circulatory diseases, diseases of the excretory system, etc.).

ABSTRACT JC polyomavirus (JCPyV) is a ubiquitous, double-stranded DNA virus that causes the fatal demyelinating disease progressive multifocal leukoencephalopathy (PML) in immunocompromised patients. Current treatments for PML are limited to immune reconstitution, and no effective antivirals exist. In this report, we show that the oxindole GW-5074 (3-(3,5-dibromo-4-hydroxybenzylidene)-5-iodoindolin-2-one) reduces JCPyV infection in primary and immortalized cells. This compound potently inhibits virus spread, which suggests that it could control infection in PML patients. We demonstrate that GW-5074 inhibits endogenous ERK phosphorylation, and that JCPyV infection in GW-5074-treated cells cannot be rescued with ERK agonists, which indicates that the antiviral mechanism may involve its antagonistic effects on MAPK-ERK signaling. Importantly, GW-5074 exceeds thresholds of common pharmacological parameters that identify promising compounds for further development. This MAPK-ERK antagonist warrants further investigation as a potential treatment for PML. IMPORTANCE Human polyomaviruses, such as JCPyV and BKPyV, cause significant morbidity and mortality in immunocompromised or immunomodulated patients. There are no treatments for polyomavirus-induced diseases other than restoration of immune function. We discovered that the oxindole GW-5074 potently inhibits infection by both JCPyV and BKPyV. Further optimization of this compound could result in the development of antiviral therapies for polyomavirus-induced diseases.

Introduction: Medical renal diseases stand as one of the major health problems in pediatric age group considering its morbidity/mortality and the subsequent management plans. Objectives: In this manuscript, the spectrum of histopathological patterns of medical nephropathic lesions in Egyptian pediatric patients over duration of five years is reported with clinical indications. Patients and Methods: We conducted a retrospective study for analysis of our pathological reports of renal needle biopsies during the period from January 2014 until January 2019. One hundred and sixteen cases were included. Results: The most commonly encountered pediatric renal pathology was minimal change disease (27.59%), followed by congenital glomerular diseases (22.41%), focal segmental glomerulosclerosis (12.93%), and thrombotic microangiopathy (7.76%). The most common clinical indication for biopsy was nephrotic syndrome (37.07%) followed by impaired renal functions with elevated serum creatinine (21.55%). In addition, we report very rare histological findings in few cases including infantile nephropathic cystinosis, Barakat syndrome and C3 glomerulopathy. Conclusion: Minimal change disease and congenital glomerular diseases accounted for half of pediatric renal pathologies in the study population. The most common clinical indication for renal biopsy was nephrotic syndrome. Electron microscopic examination and genetic studies are mandatory for proper evaluation of pediatric nephropathies.

ObjectiveThis study assessed the efficacy of INV-202, a novel peripherally restricted cannabinoid type-1 receptor (CB1R) inverse agonist, in a streptozotocin-induced type-1 diabetes nephropathy mouse model.MethodsDiabetes was induced in 8-week-old C57BL6/J male mice via intraperitoneal injection of streptozotocin (45 mg/kg/day for 5 days); nondiabetic controls received citrate buffer. Diabetic mice were randomized to 3 groups based on blood glucose, polyuria, and albuminuria, and administered daily oral doses for 28-days of INV-202 at 0.3 or 3 mg/kg or vehicle.ResultsINV-202 did not affect body weight but decreased kidney weight compared with the vehicle group. While polyuria was unaffected by INV-202 treatment, urinary urea (control 30.77 ± 14.93; vehicle 189.81 ± 31.49; INV-202 (0.3 mg/kg) 127.76 ± 20; INV-202 (3 mg/kg) 93.70 ± 24.97 mg/24h) and albumin (control 3.06 ± 0.38; vehicle 850.08 ± 170.50; INV-202 (0.3 mg/kg) 290.65 ± 88.70; INV-202 (3 mg/kg) 111.29 ± 33.47 µg/24h) excretion both decreased compared with vehicle-treated diabetic mice. Compared with the vehicle group, there was a significant improvement in the urinary albumin to creatinine ratio across INV-202 groups. Regardless of the dose, INV-202 significantly reduced angiotensin II excretion in diabetic mice. The treatment also decreased Agtr1a renal expression in a dose-dependent manner. Compared with nondiabetic controls, the glomerular filtration rate was increased in the vehicle group and significantly decreased by INV-202 at 3 mg/kg. While the vehicle group showed a significant loss in the mean number of podocytes per glomerulus, INV-202 treatment limited podocyte loss in a dose-dependent manner. Moreover, in both INV-202 groups, expression of genes coding for podocyte structural proteins nephrin (Nphs1), podocin (Nphs2), and podocalyxin (Pdxl) were restored to levels similar to nondiabetic controls. INV-202 partially limited the proximal tubular epithelial cell (PTEC) hyperplasia and normalized genetic markers for PTEC lesions. INV-202 also reduced expression of genes contributing to oxidative stress (Nox2, Nox4, and P47phox) and inflammation (Tnf). In addition, diabetes-induced renal fibrosis was significantly reduced by INV-202.ConclusionsINV-202 reduced glomerular injury, preserved podocyte structure and function, reduced injury to PTECs, and ultimately reduced renal fibrosis in a streptozotocin-induced diabetic nephropathy mouse model. These results suggest that INV-202 may represent a new therapeutic option in the treatment of diabetic kidney disease.

IntroductionEarly initiation is essential for successful treatment of Fabry disease, but sensitive and noninvasive biomarkers of Fabry nephropathy are lacking. Urinary extracellular vesicles (uEVs) represent a promising source of biomarkers of kidney involvement. Among them, microRNAs (miRNAs) are important post-transcriptional regulators of gene expression that contribute to the development and progression of various kidney diseases. We aimed to identify uEV-derived miRNAs involved in the development and/or progression of Fabry nephropathy.MethodsPatients with genetically confirmed Fabry disease and matched control subjects were included. EVs were isolated from the second morning urine by size exclusion chromatography, from which miRNAs were extracted. miRNA urine exosome PCR panels were used to characterize the miRNA signature in a discovery cohort. Individual qPCRs were performed on a validation cohort that included chronological samples. We identified the target genes of dysregulated miRNAs and searched for potential hub genes. Enrichment analyses were performed to identify their potential function.ResultsThe expression of miR-21-5p and miR-222-3p was significantly higher in patients with stable renal function and those with progressive nephropathy compared with the corresponding controls. In addition, the expression of miR-30a-5p, miR-10b-5p, and miR-204-5p was significantly lower in patients with progressive nephropathy, however, in the chronological samples, this was only confirmed for miR-204-5p. Some of the identified hub genes controlled by the dysregulated miRNAs have been associated with kidney impairment in other kidney diseases.ConclusionThe miRNA cargo in uEVs changes with the development and progression of Fabry nephropathy and, therefore, represents a potential biomarker that may provide a new option to prevent or attenuate the progression of nephropathy. Furthermore, dysregulated miRNAs were shown to be potentially associated with pathophysiological pathways in the kidney.

BackgroundType 2 diabetes mellitus (T2DM) is a chronic, metabolic disorder in which concomitant insulin resistance and β-cell impairment lead to hyperglycemia, influenced by genetic and environmental factors. T2DM is associated with long-term complications that have contributed to the burden of morbidity and mortality worldwide. The objective of this manuscript is to conduct an Exome-Wide Association Study (EWAS) on T2DM Emirati individuals to improve our understanding on diabetes-related complications to improve early diagnostic methods and treatment strategies.MethodsThis cross-sectional study recruited 310 Emirati participants that were stratified according to their medically diagnosed diabetes-related complications: diabetic retinopathy, diabetic neuropathy, diabetic nephropathy, and cardiovascular complications. The Illumina’s Infinium Exome-24 array was used and 39,840 SNPs remained for analysis after quality control.FindingsThe analysis revealed the associations of various genes with each complication category: 1) diabetic retinopathy was associated to SHANK3 gene in locus 22q13.33 (SNP rs9616915; p=5.18 x10-4), ZSCAN5A gene in locus 19q13.43 (SNP rs7252603; p=7.55 x10-4), and DCP1B gene in locus 12p13.33 (SNPs rs715146, rs1044950, rs113147414, rs34730825; p=7.62 x10-4); 2) diabetic neuropathy was associated to ADH4 gene in locus 4q23 (SNP rs4148883; p=1.23 x10-4), SLC11A1 gene in locus 2q35 (SNP rs17235409; p=1.85 x10-4), and MATN4 gene in locus 20q13.12 (SNP rs2072788; p=2.68 x10-4); 3) diabetic nephropathy was associated to PPP1R3A gene in locus 7q31.1 (SNP rs1799999; p=1.91 x10-4), ZNF136 gene in locus 19p13.2 (SNP rs140861589; p=2.80 x10-4), and HSPA12B gene in locus 20p13 (SNP rs6076550; p=2.86 x10-4); and 4) cardiovascular complications was associated to PCNT gene in locus 21q22.3 (SNPs rs7279204, rs6518289, rs2839227, rs2839223; p=2.18 x10-4,3.04 x10-4,4.51 x10-4,5.22 x10-4 respectively), SEPT14 gene in locus 7p11.2 (SNP rs146350220; p=2.77 x10-4), and WDR73 gene in locus 15q25.2 (SNP rs72750868; p=4.47 x10-4).InterpretationWe have identified susceptibility loci associated with each category of T2DM-related complications in the Emirati population. Given that only 16% of the markers from the Illumina’s Infinium Exome chip passed quality control assessment, this demonstrates that multiple variants were, either, monomorphic in the Arab population or were not genotyped due to the use of a Euro-centric EWAS array that limits the possibility of including targeted ethnic-specific SNPs. Our results suggest the alarming possibility that lack of representation in reference panels could inhibit discovery of functionally important loci associated to T2DM complications. Further effort must be conducted to improve the representation of diverse populations in genotyping and sequencing studies.

Diabetic nephropathy (DN) represents the most common microvascular complication in patients with diabetes. This progressive kidney disease has been recognized as the major cause of end-stage renal disease with higher morbidity and mortality. However, its tangled pathophysiology is still not fully known. Due to the serious health burden of DN, novel potential biomarkers have been proposed to improve early identification of the disease. In this complex landscape, several lines of evidence supported a critical role of microRNAs (miRNAs) in regulating posttranscriptional levels of protein-coding genes involved in DN pathophysiology. Indeed, intriguing data showed that deregulation of certain miRNAs (e.g., miRNAs 21, -25, -92, -210, -126, -216, and -377) were pathogenically linked to the onset and the progression of DN, suggesting not only a role as early biomarkers but also as potential therapeutic targets. To date, these regulatory biomolecules represent the most promising diagnostic and therapeutic options for DN in adult patients, while similar pediatric evidence is still limited. More, findings from these elegant studies, although promising, need to be deeper investigated in larger validation studies. In an attempt to provide a comprehensive pediatric overview in the field, we aimed to summarize the most recent evidence on the emerging role of miRNAs in pediatric DN pathophysiology. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The incidence of microvascular complications such as diabetic retinopathy, diabetic nephropathy and diabetic neuropathy has increased in newly diagnosed diabetes patients. The aim of this study was to determine the factors affecting the incidence of microvascular complications in newly diagnosed patients with type 2 diabetes. PATIENTS AND METHODS: This study was conducted on 97 newly diagnosed type 2 DM patients who applied to Malatya Training and Research Hospital Endocrinology outpatient clinic between September 2021 and July 2022. The patient files were reviewed retrospectively and their age, height, weight, body mass index (BMI), fasting/postprandial blood glucose measurements, serum HDL cholesterol, LDL cholesterol, total cholesterol, triglyceride, HbA1c levels, glomerular filtration rate (GFR) and complications of retinopathy, nephropathy, and neuropathy were recorded. Mann-Whitney U, t-test, Kruskal-Wallis, Binary logistic regression analysis, and Chi-square analysis were used to analyze the data. RESULTS: The mean age of the patients included in the study was 47.40±7.78 (min: 23 - max: 62). Non-proliferative retinopathy was observed in 74.2% of patients, proliferative retinopathy in 25.8%, diffuse neuropathy in 49.5% and mononeuropathy was detected in 9.3% of them. Fasting blood glucose, postprandial blood glucose and HbA1c values were found to be higher in patients with proliferative retinopathy than in patients without retinopathy. Fasting blood glucose, postprandial blood glucose and HbA1c values were found to be higher in patients with neuropathy than in patients without neuropathy. In addition, patients with mononeuropathy had statistically significantly higher HbA1c values than patients with diffuse-type neuropathy. It was found that the urine protein values of patients with mononeuropathy were significantly higher than those without neuropathy and those with diffuse neuropathy. Each 0.677-unit increase in HbA1c increases the risk of proliferative retinopathy 1.98-fold, and every 1.018-unit increase increases the risk of neuropathy 2.76-fold. Proliferative retinopathy and mononeuropathy rates were discovered to be higher in patients with a family history. CONCLUSIONS: Microvascular complications are common in newly diagnosed T2DM patients and an increase in HbA1c is a significant risk factor. Every newly diagnosed T2DM patient should be screened for microvascular complications. [ABSTRACT FROM AUTHOR]

A long-term complication of obesity is the development of type 2 diabetes (T2D). Patients with T2D have been described as having epigenetic modifications. Epigenetics is the post-transcriptional modification of DNA or associated factors containing genetic information. These environmentally-influenced modifications, maintained during cell division, cause stable changes in gene expression. Epigenetic modifications of T2D are DNA methylation, acetylation, ubiquitylation, SUMOylation, and phosphorylation at the lysine residue at the amino terminus of histones, affecting DNA, histones, and non-coding RNA. DNA methylation has been shown in pancreatic islets, adipose tissue, skeletal muscle, and the liver. Furthermore, epigenetic changes have been observed in chronic complications of T2D, such as diabetic nephropathy, diabetic retinopathy, and diabetic neuropathy. Recently, a new drug has been developed which acts on bromodomains and extraterminal (BET) domain proteins, which operate like epigenetic readers and communicate with chromatin to make DNA accessible for transcription by inhibiting them. This drug (apabetalone) is being studied to prevent major adverse cardiovascular events in people with T2D, low HDL cholesterol, chronic kidney failure, and recent coronary events. This review aims to describe the relationship between obesity, long-term complications such as T2D, and epigenetic modifications and their possible treatments. [ABSTRACT FROM AUTHOR]

Puromycin treatment can cause glomerular injury to the kidney, leading to proteinuria. However, the pathogenesis of acute kidney injury and subsequent regeneration after puromycin administration in animal models remain unclear. In this work, we examined the characteristics of kidney injury and subsequent regeneration following puromycin treatment in adult zebrafish. We intraperitoneally injected 100 μg of puromycin into zebrafish; sacrificed them at 1, 3, 5, 7, or 14 days post-injection (dpi); and examined the morphological, functional, and molecular changes in the kidney. Puromycin-treated zebrafish presented more rapid clearance of rhodamine dextran than control animals. Morphological changes were observed immediately after the puromycin injection (1–7 dpi) and had recovered by 14 dpi. The mRNA production of lhx1a, a renal progenitor marker, increased during recovery from kidney injury. Levels of NFκB, TNFα, Nampt, and p-ERK increased significantly during nephron injury and regeneration, and Sirt1, FOXO1, pax2, and wt1b showed an increasing tendency. However, TGF-β1 and smad5 production did not show any changes after puromycin treatment. This study provides evidence that puromycin-induced injury in adult zebrafish kidneys is a potential tool for evaluating the mechanism of nephron injury and subsequent regeneration. [ABSTRACT FROM AUTHOR]

Background: Taxifolin (TXF) is a flavonoid found abundantly in citrus/onion. Encouraging results on its renoprotective effect have been reported in a limited number of drug-induced nephrotoxicity animal models. The present study aimed to evaluate for the first time the potential renoprotective effects of TXF in a paracetamol (PAR)-induced nephrotoxicity rat model. Methods: Rats were divided into three equal groups (n = 6 animals per group). Group 1 (PAR group, PARG) received PAR diluted in normal saline by gavage (1000 mg/kg). Group 2 (TXF group, TXFG) received TXF diluted in normal saline by gavage (50 mg/kg) one hour after PAR administration. Group 3 (control group, CG) received normal saline. Twenty-four hours after PAR administration, all animals were sacrificed using high-dose anesthesia. Blood samples were collected and kidneys were removed. Results: The serum blood urea nitrogen, creatinine levels and serum malondialdehyde levels were significantly increased in the PARG. The serum glutathione peroxidase, glutathione reductase and total glutathione levels were significantly higher in the TXFG. At the same time, the kidneys of the PARG animals demonstrated tubular epithelium swelling, distension and severe vacuolar degeneration. The kidneys of the TXFG animals showed mildly dilated/congested blood vessels. Conclusions: The TXF renoprotective effects are promising in preventing PAR-induced nephrotoxicity, mainly through antioxidant activity, and warrant further testing in future studies. [ABSTRACT FROM AUTHOR]

Protein turnover rate is finely regulated through intracellular mechanisms and signals that are still incompletely understood but that are essential for the correct function of cellular processes. Indeed, a dysfunctional proteostasis often impacts the cell's ability to remove unfolded, misfolded, degraded, non-functional, or damaged proteins. Thus, altered cellular mechanisms controlling protein turnover impinge on the pathophysiology of many diseases, making the study of protein synthesis and degradation rates an important step for a more comprehensive understanding of these pathologies. In this manuscript, we describe the application of a dynamic-SILAC approach to study the turnover rate and the abundance of proteins in a cellular model of diabetic nephropathy. We estimated protein half-lives and relative abundance for thousands of proteins, several of which are characterized by either an altered turnover rate or altered abundance between diabetic nephropathic subjects and diabetic controls. Many of these proteins were previously shown to be related to diabetic complications and represent therefore, possible biomarkers or therapeutic targets. Beside the aspects strictly related to the pathological condition, our data also represent a consistent compendium of protein half-lives in human fibroblasts and a rich source of important information related to basic cell biology. [ABSTRACT FROM AUTHOR]

Diabetic nephropathy (DN) is a common complication of diabetes. DN progresses to end-stage renal disease, which has a high mortality rate. Current research is focused on identifying non-invasive potential biomarkers in the early stage of DN. We previously indicated that pyruvate kinase M2 (PKM2) is excreted in the urine of rats after cisplatin-induced acute kidney injury (AKI). However, it has not been reported whether PKM2 can be used as a biomarker to diagnose DN. Therefore, we try to compare whether the protein PKM2 can be detected in the urine samples from diabetic patients as shown in the results of DN models. In this study, high-fat diet (HFD)-induced Zucker diabetic fatty (ZDF) rats were used for DN phenotyping. After 19 weeks of receiving a HFD, the DN model's blood glucose, blood urea nitrogen, and serum creatinine levels were significantly increased; severe tubular and glomerular damages were also noted. The following protein-based biomarkers were increased in the urine of these models: kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), and PKM2. PKM2 had the earliest detection rate. In the urine samples of patients, PKM2 protein was highly detected in the urine of diabetic patients but was not excreted in the urine of normal subjects. Therefore, PKM2 was selected as the new biomarker for the early diagnosis of DN. Our results reflect current knowledge on the role of PKM2 in DN. [ABSTRACT FROM AUTHOR]

[Objectives] This study was conducted to systematically present the research and development status of Wuling Powder over the years, and comprehensively analyze the hot spots and trends of Wuling Powder in the treatment of diseases, so as to provide reference for scholars in this field in the future. [Methods] China National Knowledge Network (CNKI) database was used as the literature retrieval source to search the literature related to Wuling Powder in the treatment of nephropathy, and then the data visualization analysis was carried out by using the software citespace. 5.7. R2. [Results] Through accurate retrieval, a total of 204 effective literatures were included. It was found that domestic research on the treatment of nephropathy by Wuling Powder was on the rise. From the analysis of knowledge graph, it was concluded that after long-term research and development, a relatively concentrated core research group had been formed in China, which mainly focused on "Wuling Powder", "chronic kidney disease,r and "diabetic nephropathy". [Conclusions] The research on the treatment of nephropathy by Wuling Powder shows a good development trend, and the research content is constantly enriched, and this research is still the current and future research hotspot. [ABSTRACT FROM AUTHOR]

Bioactive natural products are essential components for drug development. Protein glycation in diabetic subjects leads to diabetic complications as nephropathy and neuropathy. We investigated the impact of pomegranate hexane extract (PHE) as antioxidant, anti-inflammatory, and antiglycation in diabetic rats. Gas chromatography/mass spectrum (GC/MS) analysis of PHE revealed presence of resorcinol, catechol, tau-cadinol, metacetamol, scopoletin, phytol, and phenol, 3-pentadecyl as the most active ingredients that related to biological activity. Results obtained showed that, PHE increased serum aldose reductase and total antioxidant activity compared with untreated diabetic rats (p < 0.001). In addition, PHE exert antioxidant by enhancing, catalase and SOD (p < 0.001) and decreased MDA (p < 0.001), anti-inflammatory by inhibition production of 1 β (IL-1β), tumor necrosis factor (TNF-α) (p < 0.001), and AGEs (p < 0.001) against nephropathy in diabetic rats compared with untreated group. It was concluded that, pomegranate is promising in development a functional biomolecule in treatment and protection against diabetic complications as nephropathy. More study required to investigate the molecular action of these molecules. [ABSTRACT FROM AUTHOR]

Purpose: There is no clear information about the level of Apelin-13 in patients with diabetic nephropathy (DN). In this study, we investigated whether there is a relationship between Apelin-13 level and the severity of the disease in patients with DN. Methods: In our case–control study, we included patients who applied to the endocrinology outpatient clinic in 2019. Patients without a history of diabetes were determined as the healthy group (group 1). The patients were divided into 4 groups according to their microalbumin and creatinine levels. Venous blood samples were obtained from all patients for routine laboratory parameters and Apelin-13 levels. Homeostatic Model Assessment-Insulin Resistance (HOMA-IR) for insulin resistance was calculated using the formula: plasma glucose X insulin level/405. Results: Albumin was found to be significantly lower in group 5 (p = 0.032), hemoglobin A1c, microalbumin/creatinine and HOMA-IR values were found to be significantly lower in group 1 (p < 0.001 for each). Apelin-13 level was found to be significantly higher in group 4 and group 5 (p < 0.001). A negative correlation was found between Apelin-13 and GFR (r = − 0.286, p = 0.003). A positive correlation was found between Apelin-13 and HOMA-IR (r = 0.309, p = 0.009) and microalbumin/creatinine (r = 0.296, p < 0.001). Conclusion: In patients with DN, Apelin-13 level increases with the severity of the disease and can be used as a biomarker for staging of DN. [ABSTRACT FROM AUTHOR]

Background: Schimke immunoosseous dysplasia (SIOD) is an ultra-rare inherited disease affecting many organ systems. Spondyloepiphyseal dysplasia, T-cell immunodeficiency and steroid resistant nephrotic syndrome are the main symptoms of this disease. Case presentation: We aimed to characterize the clinical, pathological and genetic features of SIOD patients received at tertiary Pediatric Nephrology Center, University Hospital Motol, Prague, Czech Republic during the period 2001–2021. The mean age at diagnosis was 21 months (range 18–48 months). All patients presented with growth failure, nephropathy and immunodeficiency. Infections and neurologic complications were present in most of the affected children during the course of the disease. Conclusions: Although SIOD is a disease characterized by specific features, the individual phenotype may differ. Neurologic signs can severely affect the quality of life; the view on the management of SIOD is not uniform. Currently, new therapeutic methods are required. [ABSTRACT FROM AUTHOR]

The aim of this study was to analyze the possible nephroprotective effect of 3',4'-dihydroxyphenylglycol (DHPG), a polyphenolic compound of extra virgin olive oil (EVOO), on renal lesions in an experimental model of type 1 diabetes. Rats were distributed as follows: healthy normoglycemic rats (NDR), diabetic rats treated with saline (DR), and DR treated with 0.5 mg/kg/day or 1 mg/kg/day of DHPG. DR showed a significantly higher serum and renal oxidative and nitrosative stress profile than NDR, as well as reduced prostacyclin production and renal damage (defined as urinary protein excretion, reduced creatinine clearance, increased glomerular volume, and increased glomerulosclerosis index). DHPG reduced the oxidative and nitrosative stress and increased prostacyclin production (a 59.2% reduction in DR and 34.7–7.8% reduction in DHPG-treated rats), as well as 38–56% reduction in urinary protein excretion and 22–46% reduction in glomerular morphological parameters (after the treatment with 0.5 or 1 mg/kg/day, respectively). Conclusions: DHPG administration to type 1-like diabetic rats exerts a nephroprotective effect probably due to the sum of its antioxidant (Pearson's coefficient 0.68–0.74), antinitrosative (Pearson's coefficient 0.83), and prostacyclin production regulator (Pearson's coefficient 0.75) effects. [ABSTRACT FROM AUTHOR]

Chronic liver disorders are a serious global health issue due to their widespread incidence. Nephropathy described the deterioration of kidney function. Safe drug delivery by nanoparticles is a rapidly developing field with promising applications in the treatment of a wide variety of diseases. The current study aimed to evaluate the use of propolis nanoparticles for managing carbon tetrachloride (CCl4)-induced hepato-nephropathy on rats. Seventy adult males Spargue Dawley rats were allocated into 7 equal groups 10 rats of each. Control, CCl4, CCl4 +Silymarin, CCl4 + propolis, CCl4+Nanopropolis, CCl4 +Silymarin +Propolis, CCl4 +Silymarin +Nanopropolis. Hepato- nephropathy was induced with oral administration of CCl4 dissolved in olive oil at dose of (1gm/kg) for 4 weeks. Silymarin, propolis and nanopropolis were orally administrated at a dose of (200mg /kg), (100 mg/kg) and (30 mg /kg) respectively for 4 weeks post hepato-nephropathy onset. Biochemical, molecular analysis, histological assessment of liver and kidney and serum oxidative stress were done. CCl4 caused a marked deterioration in biochemical, oxidative stress markers (MDA, TAC, CAT), serum TNF-α, IgM, molecular markers (SMAD-2, SMAD-3, SMAD-7, MMP-9, Desmin, TGF-β1, and let-7b), and the histopathological pictures of both liver and kidney. The above-mentioned parameters were restored with administration of silymarim + Nano-propolis, silymarin + propolis, silymarin, Nano-propolis, and propolis in order. Based on the previous findings we could speculated that combined therapy of nano-propolis and silymarin could be implicated in managing hepato-nepheropathy since it improves both liver and kideny function by targeting let-7b/TGF-β/Smad Pathway. [ABSTRACT FROM AUTHOR]

Background: Micro vascular complications of T2DM are associated with severe morbidity, mortality and a huge economic burden. So, there is an important need to identify new biomarker able to identify disease onset and progression and can be used as a therapeutic target for management of these complications. The Aim of this study was to assessment the Serum progranulin level as a biomarker for the presence and severity of retinopathy in type 2 diabetic patients. Methods: The current case-control study was carried out conducted on (48 type 2 diabetic patients) at the Internal Medicine and ophthalmology out-patient clinic of Zagazig University Hospitals, during the period from May 2019 to October 2019. All patient referred to ophthalmic out-patient clinic for fundal examination by ophthalmologist in which diabetic retinopathy was diagnosed, a complete physical examination including the measurement of height, weight, body mass index, and blood pressure (BP) was performed for all patients. Results: The current study showed that there was a high statistically significant increase in serum PGRN level in diabetic patients with retinopathy, there was a statistically significant positive correlation between serum PGRN level with disease duration, urea, creatinine level and urinary ACR of studied retinopathy patients and also there was a high statistically significant increase in serum PGRN level in diabetic patients with proliferative retinopathy. Conclusions: According to our results serum PGRN level could be used as a biomarker for the presence of microvascular retinal complication and to anticipate the severity of diabetic retinopathy in T2DM patients. [ABSTRACT FROM AUTHOR]

Background: Cyanotic nephropathy (CN), was found in about 30%-50% of patients with congenital cyanotic heart disease (CCHD), causing significant proteinuria, decreasing the glomerular filtration rate (GFR) and azotemia. This study aimed to show the frequency of CN in children with CCHD and the associated risk factors. Methods: A cross sectional study was conducted in cardiology unit, pediatric department, Zagazig University Hospitals from March 2018 to June 2019. This study included 49 children of age ranged from 2 months to 11 years selected randomly from those admitted to the pediatric cardiology unit and diagnosed as having CCHD. They were subjected to full history taking, general examination and local examination of the heart, chest X-ray and echocardiography. Early morning urine and blood sample were taken for measuring urine albumin, protein, creatinine, urinary protein to creatinine ratio [UPCR], urinary albumin to creatinine ratio, serum creatinine level, complete blood count (CBC), prothrombin time (PT), partial thromboplastin time (PTT), and serum ferritin. Results: 65% of CCHD patients had renal impairment as regard to albuminuria also, 83.6% of them had CN depending on proteinuria. 37% of CCHD patients with significant albuminuria had renal insufficiency. Patients with CN had higher hematocrit (Hct)level, lower platelet count and longer time waiting for surgery. Conclusions: Children with CCHD are in high risk of renal insufficiency. Microalbuminuria, proteinuria, increased Hct level, decreased platelet count, longer time waiting for surgery, are risk factors of renal disease. [ABSTRACT FROM AUTHOR]

Objectives: To determine the chronic complications of diabetes mellitus (DM) in patients with prediabetes, and to compare prediabetics with normoglycemic group participants in terms of the presence of the complications of DM. Methods: An observational study was conducted between December 2018 to April 2019. The patients aged 18-65 years were recruited from an internal medicine outpatient clinic of a tertiary care hospital. A total of 106 prediabetic patients and 54 normoglycemic subjects were included to the study. OGTT-0th, OGTT-2nd and HbA1c levels, lipid parameters, blood pressure, the homeostasis model assessment of insulin resistan (HOMAIR), body mass index (BMI) were estimated. Nephropathy (urine protein/urine creatinine ratio, serum creatinine [sCre], Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] equation--creatinine clearance), retinopathy by dilated fundus examination and neuropathy (10-g monofilament testing and electroneuromyography [ENMG]) were assessed. Results: Age, gender, BMI, HOMA-IR, smoking status, lipid parameters, systolic blood pressure were similar in both groups. The values of oral glucose tolerance test (OGTT)-0th, OGTT-2nd and glycated hemoglobin (HbA1c) were higher in prediabetics. Although not statistically significant, proteinuria was slightly more occurred in the prediabetics than the controls. sCre was significantly higher, and CKD-EPI equation was significantly lower in prediabetics than in controls (p = 0.012, p = 0.001, respectively). We did not detected diabetic retinopathy in any participants. Neuropathy was slightly more occured in prediabetics, but it was not significantly different (p = 0.309). There were no correlation between sCre, CKD-EPI, proteinuria and age, BMI, HOMA-IR, OGTT-0th, OGTT-2nd, and HbA1c. Conclusions: Managing the prediabetes by early diagnosis is very meaningful in terms of prevention from DM and its complications. So, prediabetes may be a window of opportunity for diabetes associated morbidity. [ABSTRACT FROM AUTHOR]

Introduction: The number of human immunodeficiency virus (HIV)-infected individuals (HIIs) is increasing day by day and life expectancy is prolonged with the use of highly active antiretroviral therapy (HAART). With the advancing age, chronic diseases that may cause renal dysfunction will also begin to appear. In addition, HIV-associated nephropathy due to inflammation caused by HIV itself and renal dysfunction due to HAART use have been reported in the literature. Considering the social and medical problems caused by HIV, nephropathy as an additional disease makes patient management difficult. Therefore, it is important to detect nephropathy in the early period and take precautions. Creatinine is not always sufficient in the evaluation of nephropathy. New searches are needed in demonstrating nephropathy in HIIs compared to healthy individuals. It was aimed to evaluate cystatin C and NGAL levels in serum, and KIM1 and NGAL levels in urine to determine whether nephropathy developed in HIIs. Materials and Methods: Eighty-eight HIIs in whom renal dysfunction was not detected before and 81 healthy individuals were prospectively evaluated. Cystatin C and NGAL levels were studied in serum samples, while KIM1 and NGAL were studied in urine samples. Serum creatinine, spot urine protein and creatinine levels were recorded in these patients. Results: Of all participants, 114 (67.5%) were male and 55 (32.5%) were female. It was observed that the estimated-glomerular filtration rate (eGFR) was higher, cystatin C level in serum, and NGAL level in serum and urine were higher in the control group than the patient group. Serum creatinine, urinary protein and urinary creatinine levels were higher in the HIV-infected patient group compared to the healthy control group (p<0.05). The estimated-glomerular filtration rate was lower in patients using tenofovir disoproxil fumarate (TDF) than in patients not using TDF (p=0.017). When all participants were evaluated, urinary NGAL level was higher in women (p<0.001). Conclusion: In our study, HIIs had higher creatinine levels and lower eGFR compared to the control group. In the control group, cystatin C in serum and NGAL in urine and serum were higher. These parameters did not correlate with creatinine level and creatinine-based eGFR in serum, which were standardized to assess renal function. Our study was a cross-sectional study and only one measurement was made. In our study, the NGAL level was found to be higher in women, especially in the urine, and it was necessary to pay attention to the gender factor when using nephropathy markers. Low eGFR was noteworthy in patients using TDF. [ABSTRACT FROM AUTHOR]

MYH9-associated disorders represent rare group of autosomal dominant diseases and are caused by pathogenic mutations in the MYH9 gene. Clinically, they are represented by macro-platelet-thrombocytopenia, various degrees of renal dysfunction, hearing loss, and early onset cataracts. We describe the case of 14-year-old boy in medical follow-up from birth for thrombocytopenia. Systolic hypertension and nephrotic proteinuria were detected at preventive health check. Renal biopsy revealed sing of segmental glomerulosclerosis. Dialysis treatment was needed. Before transplantation due to the finding of chronic tonsillitis with positive bacterial capture in the culture examination, tonsillectomy was indicated. Postoperative period was complicated with arterial post-tonsillectomy hemorrhage. Six months after tonsillectomy, the patient underwent primary deceased-donor kidney transplantation without complication. Blood platelets showed fluctuating character in the zone of severe thrombocytopenia. However, no signs of bleeding were present. Three months after successful transplantation gene sequencing of whole exon was performed. The presence of the variant c.2105G>A [p.(Arg702HIS)] in exon 17 of the MYH9 gene has been detected. The variant c.2105G>A may be clinically manifested by progressive proteinuria with rapid deterioration of renal function. This case is an example of the delayed diagnosis of rare disease and highlights the usefulness of genetic testing. [ABSTRACT FROM AUTHOR]

Background: The causal association between IgA nephropathy (IgAN) and celiac disease (CeD) is based on their clinical coexistence. In this prospective study, we screened patients with IgAN for CeD and explored the utility of analysis of IgA anti-TG2 antibody deposits, for establishing a causal association. Methods: Biopsy-proven patients of IgAN were screened for serum IgA anti-tissue transglutaminase antibody (IgA anti-tTG Ab) titer and thereafter were invited to undergo endoscopic duodenal biopsy. Corresponding duodenal and kidney biopsies were subjected to IgA anti-TG2 antibody colocalization study using dual-color immunohistochemistry and immunofluorescence techniques. Additionally, kidney biopsies from 105 patients with IgAN who did not give consent for serology analysis, 30 non-IgA nephropathies, and 10 normal controls were also included. Dual-color-stained slides were interpreted based on stain distribution and intensity scores, and Pearson's index >0.3–1 on confocal imaging was considered significant. Results: Of a cohort of 151 patients with IgAN, 32 consented to undergo sero-screening and 5 of them had high serum anti-tTG Ab titer. Two out of the latter consented to endoscopic duodenal biopsies, in whom modified Marsh grade 3b changes were identified. Strong IgA anti-TG2 antibody deposits were noted in the kidney and duodenal biopsies of these patients. One patient out of non-consenting 105 patients with IgAN and 3 out of 30 patients with other non-IgA nephropathies also showed IgA anti-TG2 deposits. None of the healthy kidney tissues showed IgA anti-TG2 Ab deposits. Conclusions: Co-localized IgA anti-TG2 deposits in the kidney biopsies in patients with IgAN help to establish a pathogenic link with CeD. A small proportion of patients with IgAN have associated CeD. [ABSTRACT FROM AUTHOR]

Significance: Diabetes and its related complications are becoming an increasing public health problem that affects hundreds of millions of people globally. Increased disability and mortality rate of diabetic individuals are closely associated with various life-threatening complications, such as atherosclerosis, nephropathy, retinopathy, and cardiomyopathy. Recent Advances: Conventional treatments for diabetes are still limited because of undesirable side effects, including obesity, hypoglycemia, and hepatic and renal toxicity. Studies have shown that hydrogen sulfide (H2S) plays a critical role in the modulation of glycolipid metabolism, pancreatic β cell functions, and diabetic complications. Critical Issues: Preservation of endogenous H2S systems and supplementation of H2S donors are effective in attenuating diabetes-induced complications, thus representing a new avenue to treat diabetes and its associated complications. Future Directions: This review systematically recapitulates and discusses the most recent updates regarding the therapeutic effects of H2S on diabetes and its various complications, with an emphasis on the molecular mechanisms that underlie H2S-mediated protection against diabetic complications. Furthermore, current clinical trials of H2S in diabetic populations are highlighted, and the challenges and solutions to the clinical transformation of H2S-derived therapies in diabetes are proposed. Finally, future research directions of the pharmacological actions of H2S in diabetes and its related complications are summarized. Antioxid. Redox Signal. 38, 18–44. [ABSTRACT FROM AUTHOR]

Context: Blood oxygen saturation (SpO2) is lower in type 1 diabetes (T1D) compared with nondiabetic controls. Hypoxia (low tissue oxygenation) is thought to be a risk factor for progression of diabetic complications, but it is unknown whether hypoxemia (low SpO2) is associated with diabetic complications. Objective: To test if hypoxemia is associated with presence of diabetic complications in T1D. Design, Setting, and Methods: Cross-sectional study in persons with T1D divided by a previously suggested threshold in low (<96%) and high (≥96%) SpO2, measured in the supine position with pulse oximetry. Complications included albuminuria (2 of 3 consecutive measurements ≥30 mg/g), any diabetic retinopathy, neuropathy, and history of cardiovascular disease (CVD). Odds ratios were adjusted for age, diabetes duration, sex, smoking, physical activity, body mass index, systolic blood pressure, and blood hemoglobin. Results: We included 659 persons, 23 (3.5%) with low and 636 (96.5%) with high SpO2. In total, 151 (23%) had albuminuria, 233 (36%) had retinopathy, 231 (35%) had neuropathy, and 72 (11%) had CVD. The adjusted odds ratio (95% CI, P value) for low vs high SpO2 was 3.4 (1.3- 8.7, P=0.01) for albuminuria, 2.8 (1.0-7.5, P=0.04) for retinopathy, 5.8 (1.8-18.6, P<0.01) for neuropathy, and nonsignificant for CVD (0.6 [0.2-2.4, P=0.51]). Conclusions: SpO2 below 96% was associated with increased presence of albuminuria, retinopathy, and neuropathy in T1D, but not with CVD. Whether hypoxemia could be a target of intervention to prevent progression in microvascular disease in type 1 diabetes should be investigated. [ABSTRACT FROM AUTHOR]

Background/Aim: The prevalence of hypertension increases with age and one out of every three adults over the age of 40 has hypertension. Hypertensive end-organ damage is an important predictive factor for patient morbidity and mortality. This study aimed to investigate the role of the renal resistive index (RI) in predicting retinopathy and nephropathy in hypertensive patients. Methods: This study was cross-sectional in design. Sixty hypertensive patients who were followed in Samsun Research and Training Hospital Internal Medicine outpatient clinic were included in the study. In all patients, a routine ophthalmological examination, including visual acuity, anterior segment examination, and dilated ocular fundus examination, was performed. Urinary albumin to creatinine ratio (mg/g) was measured in spot urine samples, and a level ≥30 mg/g was accepted as the presence of proteinuria. Renal Doppler ultrasonography was performed using Esaote mylab x 9 model sonography device vovex probe (C1-8) 3.5 MHz. RI values were measured using Xflow Doppler at the level of interlobular or arcuate arteries of both kidneys. First, the patients were divided into two groups (with or without retinopathy). The patients who had retinopathy were then divided into two groups according to their retinopathy degree. Hypertensive retinopathy was graded according to the Scheie classification. The patients were also divided into two groups according to their proteinuria status (with or without proteinuria). Results: The mean of renal RI was 0.59 (0.04) in patients without retinopathy (n=15), 0.63 (0.05) in patients with grade 1 hypertensive retinopathy (n=29), and 0.66 (0.04) in patients with grade 2 hypertensive retinopathy (n=15). The difference between groups was statistically significant (overall P=0.001). It has been shown that proteinuria develops more frequently in cases in which the renal value is above 0.7, and these results were statistically significant (P=0.034). Conclusion: This study indicates that renal RI increase is a valuable tool for estimating retinopathy and proteinuria in hypertensive patients. [ABSTRACT FROM AUTHOR]