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Biomedicine & Pharmacotherapy =... Jun 2024Astragaloside IV (AS-IV) exhibits diverse biological activities. Despite this, the detailed molecular mechanisms by which AS-IV ameliorates diabetic nephropathy (DN) and...
Phenylsulfate-induced oxidative stress and mitochondrial dysfunction in podocytes are ameliorated by Astragaloside IV activation of the SIRT1/PGC1α /Nrf1 signaling pathway.
Astragaloside IV (AS-IV) exhibits diverse biological activities. Despite this, the detailed molecular mechanisms by which AS-IV ameliorates diabetic nephropathy (DN) and shields podocytes from oxidative stress (OS) and mitochondrial dysfunction remain poorly understood. In this study, we used biochemical assays, histopathological analysis, Doppler ultrasound, transmission electron microscopy,flow cytometry, fluorescence staining, and Western blotting and other methods. AS-IV was administered to db/db mice for in vivo experimentation. Our findings indicated that AS-IV treatment significantly reduced diabetes-associated markers, proteinuria, and kidney damage. It also diminished ROS levels in the kidney, enhanced the expression of endogenous antioxidant enzymes, and improved mitochondrial health. Phenyl sulfate (PS), a protein-bound uremic solute of enteric origin, has been closely linked with DN and represents a promising avenue for further research. In vitro, PS exposure induced OS and mitochondrial dysfunction in podocytes, increasing ROS levels while decreasing antioxidant enzyme activity (Catalase, Heme Oxygenase-1, Superoxide Dismutase, and Glutathione Peroxidase). ROS inhibitors (N-acetyl-L-cysteine, NAC) as the positive control group can significantly reduce the levels of ROS and restore antioxidant enzymes protein levels. Additionally, PS reduced markers associated with mitochondrial biosynthesis and function (SIRT1, PGC1α, Nrf1, and TFAM). These adverse effects were partially reversed by AS-IV treatment. However, co-treatment with AS-IV and the SIRT1 inhibitor EX527 failed to restore these indicators. Overall, our study demonstrates that AS-IV effectively attenuates DN and mitigates PS-induced OS and mitochondrial dysfunction in podocytes via the SIRT1/PGC1α/Nrf1 pathway.
PubMed: 38901196
DOI: 10.1016/j.biopha.2024.117008 -
World Journal of Urology Jun 2024Preoperative proteinuria is a prognostic factor of chronic kidney disease (CKD). We assessed the association between preoperative proteinuria and postoperative renal...
PURPOSE
Preoperative proteinuria is a prognostic factor of chronic kidney disease (CKD). We assessed the association between preoperative proteinuria and postoperative renal function after partial nephrectomy (PN).
METHODS
We retrospectively reviewed our records of patients with a single malignant renal mass who underwent PN between 2000 and 2021. Patients with data on preoperative proteinuria were included. Baseline characteristics and eGFR differences over time between patients with and without proteinuria were evaluated. Univariate and multivariable logistic regression models (LRM) tested for presence of CKDIII or higher at 12-month and at last follow-up.
RESULTS
Two hundred ninety-five patients were included. Twenty-two of them had preoperative proteinuria. No differences of age, smoking status, hypertension or diabetes, tumor size and use of ischemia were observed. Patients with proteinuria had a higher rate of CKD-III at baseline. At a median follow-up of 46.5 months (IQR 19-82), 117 patients developed de novo CKD-III, without differences in the two groups. No differences in decline in eGFR were observed. At univariate LRM, predictors of CKD-III at 12 months after PN were preoperative proteinuria (OR 3.2, 95%CI 1.4-7.8, p = 0.005), age and baseline eGFR, while predictors of CKD-III at last follow-up were age and baseline eGFR. At multivariable LRM, only baseline eGFR predicted CKD-III at 12-month and at last-follow-up.
CONCLUSIONS
Preoperative eGFR is the only independent predictor of long-term renal function after PN. Preoperative proteinuria correlates with renal function at 12 months. Proteinuria should be assessed before PN to identify patients at higher risk of renal functional deterioration in the 12 months following PN.
Topics: Humans; Nephrectomy; Kidney Neoplasms; Male; Proteinuria; Female; Middle Aged; Retrospective Studies; Carcinoma, Renal Cell; Preoperative Period; Aged; Glomerular Filtration Rate; Renal Insufficiency, Chronic; Correlation of Data; Kidney
PubMed: 38900287
DOI: 10.1007/s00345-024-05042-w -
Indian Journal of Dermatology,... Jun 2024Background Several studies have reported that psoriasis has a positive correlation with type 2 diabetes mellitus (DM). Understanding the risk of psoriasis in diabetic...
Background Several studies have reported that psoriasis has a positive correlation with type 2 diabetes mellitus (DM). Understanding the risk of psoriasis in diabetic patients is significant because it allows for early intervention and potential insights into the common pathways between the two conditions. Objectives We analysed the risk of psoriasis according to the estimated glomerular filtration rate (eGFR) and proteinuria level in DM patients using Korean population-based data. Methods This study was a retrospective cohort study using data collected from the country in the form of exploratory data analysis. A total of 927,234 participants diagnosed with DM were enrolled. Patients under the age of 20 with existing psoriasis or psoriasis developed within 1 year and missing data were excluded. The development of psoriasis was the primary outcome within a follow-up period of 7.83 ± 1.68 years. Results Of the 840,395 final participants, 28,010 (3.33%) patients developed psoriasis. In multivariate-adjusted Cox proportional hazards regression models, the DM patients with eGFR < 30 had a higher risk of psoriasis after adjustment (eGFR 60-90, hazard ratio [HR] 1 (Ref.); eGFR < 30, HR 1.173, 95% CI 1.089-1.264). In addition, there was an increased psoriatic risk of patients with DM and proteinuria after adjustment (negative, HR 1 (Ref.); 2+, HR 1.164, 95% CI 1.080-1.254; 3+, HR 1.433, 95% CI 1.273-1.613; 4+, HR 1.508, 95% CI 1.177-1.931). Limitations The severity of psoriasis was not measured since the occurrence of psoriasis was the outcome. Details of oral hypoglycaemic agents such as type and dose were not investigated. Conclusion This study showed that a decrease in eGFR and aggravation of proteinuria increase the risk of psoriasis in diabetic patients. Therefore, by using eGFR and proteinuria as predictive risk factors of psoriasis in DM patients, early and proactive treatment may play a vital role in managing diabetic patients.
PubMed: 38899413
DOI: 10.25259/IJDVL_669_2023 -
Kidney International Reports Jun 2024
PubMed: 38899179
DOI: 10.1016/j.ekir.2024.03.005 -
World Journal of Clinical Cases Jun 2024Glomerulopathy with fibrillary deposits is not uncommon in routine nephropathology practice, with amyloidosis and fibrillary glomerulonephritis being the two most...
BACKGROUND
Glomerulopathy with fibrillary deposits is not uncommon in routine nephropathology practice, with amyloidosis and fibrillary glomerulonephritis being the two most frequently encountered entities. Renal amyloid heavy and light chain (AHL) is relatively uncommon and its biopsy diagnosis is usually limited to cases that show strong equivalent staining for a single immunoglobulin (Ig) heavy chain and a single light chain, further supported by mass spectrometry (MS) and serum studies for monoclonal protein. But polyclonal light chain staining can pose a challenge.
CASE SUMMARY
Herein we present a challenging case of renal AHL with polyclonal and polytypic Ig gamma (IgG) staining pattern by immunofluorescence. The patient is a 62-year-old Caucasian male who presented to an outside institution with a serum creatinine of up to 8.1 mg/dL and nephrotic range proteinuria. Despite the finding of a polyclonal and polytypic staining pattern on immunofluorescence, ultrastructural study of the renal biopsy demonstrated the presence of fibrils with a mean diameter of 10 nm. Congo red was positive while DNAJB9 was negative. MS suggested a diagnosis of amyloid AHL type with IgG and lambda, but kappa light chains were also present supporting the immunofluorescence staining results. Serum immunofixation studies demonstrated IgG lambda monoclonal spike. The patient was started on chemotherapy. The chronic renal injury however was quite advanced and he ended up needing dialysis shortly after.
CONCLUSION
Tissue diagnosis of AHL amyloid can be tricky. Thorough confirmation using other available diagnostic techniques is recommended in such cases.
PubMed: 38898862
DOI: 10.12998/wjcc.v12.i17.3200 -
World Journal of Clinical Cases Jun 2024Many guidelines have recommended renin-angiotensin system inhibitors (RASI) as the first-line treatment for patients with chronic kidney disease (CKD). We studied RASI...
BACKGROUND
Many guidelines have recommended renin-angiotensin system inhibitors (RASI) as the first-line treatment for patients with chronic kidney disease (CKD). We studied RASI prescription trends from 2010 to 2019, and analyzed the characteristics associated with RASI prescription in Chinese hospitalized CKD patients.
AIM
To study the prescription of renin angiotensin system inhibitors in hospitalized patients with CKD in China.
METHODS
It was retrospectively, cross-sectional reviewed RASI prescriptions in hospitalized CKD patients in China from 2010 to 2019. RASI prescribing trends were analyzed from 2010 to 2019, and bivariate and multivariate logistic regression analyses were conducted to identify characteristics associated with RASI prescription.
RESULTS
A total of 35090 CKD patients were included, with 10043 (28.6%) RASI prescriptions. Among these patients, 18919 (53.9%) met the criteria for RASI treatments based on the 2012 kidney disease: Improving global outcomes guidelines. Of these, 7246 (38.3%) patients received RASI prescriptions. RASI prescriptions showed an initial rapid increase from 2011 to 2012, reached its peak around 2015 and 2016, and then exhibited a subsequent slight decreasing trend. Both bivariate and multivariate analyses showed that several characteristics, including the male gender, age less than 60-year-old, nephrology department admission, lower CKD stage, history of hypertension or diabetes, proteinuria, glomerulonephritis as the CKD etiology, and non-acute kidney injury were associated with RASI prescriptions.
CONCLUSION
The frequency of RASI prescriptions showed an initial increase but a slight decreasing trend in more recent years. CKD patients with certain characteristics such as elderly age, advanced disease stage, surgery department admission, or acute kidney injury were less likely to receive RASI prescriptions. In the application of RASI in hospitalized CKD patients is insufficient. The actual clinical practice needs to be improved. The development of related research is helpful to guide the correct choice of clinical treatment strategy.
PubMed: 38898860
DOI: 10.12998/wjcc.v12.i17.3061 -
Frontiers in Pediatrics 2024To evaluate glomerular and tubular renal functions and analyze blood pressure in a cohort of pediatric patients with juvenile idiopathic arthritis (JIA).
OBJECTIVES
To evaluate glomerular and tubular renal functions and analyze blood pressure in a cohort of pediatric patients with juvenile idiopathic arthritis (JIA).
METHODS
A total of 40 pediatric patients, 20 (50%) with JIA and 20 (50%) healthy control subjects, were studied, and performed the renal function on 24-h collection and the 24-h ambulatory blood pressure monitoring (ABPM). Moreover, we compared renal function and blood pressure trends between the groups of JIA patients with different disease activities.
RESULTS
No statistically significant differences were observed between patients with JIA and healthy children in terms of glomerular filtration rate (GFR), fractional excretion of sodium (FENa), tubular reabsorption of phosphate (TRP), and calcium-creatinine urine ratio (CaU/CrU). In contrast, we observed significantly higher values in JIA patients than in controls for the presence of hematuria ( < 0.0001) and proteinuria ( < 0.0001). Compared to the control group there were significantly higher values of hematuria and proteinuria/day in both groups of JIA patients with low disease activity (respectively, = 0.0001 and = 0.0002) and moderate disease activity (respectively = 0.0001 and = 0.0012). Systolic and diastolic dipping were significantly reduced in patients with JIA compared with healthy controls ( < 0.0001 and < 0.0001, respectively).
CONCLUSIONS
Our study showed that children with JIA, already in the early stages of the disease, have higher values of hematuria and proteinuria, which are early warning signs of nephropathy. Therefore, detailed screening of renal function and pressure monitoring in patients are necessary to monitor their evolution over time.
PubMed: 38895193
DOI: 10.3389/fped.2024.1395961 -
Nutrients May 2024Low protein diet (LPD) seems beneficial in ameliorating the complications of chronic kidney disease (CKD), in reducing proteinuria and the decline in kidney function,...
Low protein diet (LPD) seems beneficial in ameliorating the complications of chronic kidney disease (CKD), in reducing proteinuria and the decline in kidney function, thus postponing the need for kidney replacement therapy (KRT). However, this type of intervention was less investigated in diabetic kidney disease (DKD). This is a single-center, prospective, interventional study that aims to assess the efficacy of reducing proteinuria and the rate of decline in the estimated glomerular filtration rate (eGFR). Patients with advanced DKD (stable proteinuria > 3 g/g and eGFR < 30 mL/min) with a good nutritional status and accepting a LPD were evaluated for inclusion. Ninety-two of the 452 screened patients (66% males, median age 61 years, proteinuria 4.8 g/g creatininuria, eGFR 11.7 mL/min/1.73 m) completed the study. Intervention consisted of LPD supplemented with ketoanalogues of essential amino acids (KA) along with conventional nephroprotective therapy. Efficacy parameters were the variation in proteinuria and in eGFR from baseline to the end of the study. Proteinuria decreased 3-fold, and the rate of decline in eGFR decreased 5-fold in the intervention phase. No patient initiated KRT or died. LPD supplemented with KA seems effective in safely postponing KRT by reducing proteinuria and the decline in kidney function in advanced DKD.
Topics: Humans; Male; Proteinuria; Glomerular Filtration Rate; Middle Aged; Diet, Protein-Restricted; Diabetic Nephropathies; Female; Prospective Studies; Aged; Amino Acids, Essential; Treatment Outcome
PubMed: 38892620
DOI: 10.3390/nu16111687 -
International Journal of Molecular... May 2024Pathogenic variants in the gene lead to a systemic disease with karyomegalic interstitial nephritis (KIN) at the forefront clinically. The phenotypic-genotypic features...
Pathogenic variants in the gene lead to a systemic disease with karyomegalic interstitial nephritis (KIN) at the forefront clinically. The phenotypic-genotypic features of a mutation-related disease involving five members of a Hungarian Caucasian family are presented. Each had adult-onset chronic kidney disease of unknown cause treated with renal replacement therapy and elevated liver enzymes. Short stature, emaciation, latte-colored skin, freckles, and a hawk-like nose in four patients, a limited intellect in two patients, and chronic restrictive lung disease in one patient completed the phenotype. Severe infections occurred in four patients. All five patients had ceased. Four patients underwent autopsy. KIN and extrarenal karyomegaly were observed histologically; the livers showed no specific abnormality. The genotyping using formalin-fixed tissue samples detected a hitherto undescribed homozygous mutation (c.1673_1674insT/p.Met558lfs*4; exon 5) in three of these patients and a heterozygous mutation in one patient. The reason for the heterozygosity is discussed. In addition, 56 family members consented to the screening for mutation from which 17 individuals proved to be heterozygous carriers; a blood chemistry evaluation of their kidney and liver function did not find any abnormality. The clinical presentation of FAN1-related disease was multifaceted, and not yet described manifestations were observed besides kidney and liver disease. Mutation in this gene should be suspected in adults with small kidneys of unknown cause, elevated liver enzymes, and recurrent infections, even without a family history.
Topics: Humans; Male; Female; Hungary; Mutation; Adult; Phenotype; Pedigree; Middle Aged; Exodeoxyribonucleases; Multifunctional Enzymes; Endodeoxyribonucleases; Genotype; Renal Insufficiency, Chronic
PubMed: 38892095
DOI: 10.3390/ijms25115907 -
International Journal of Molecular... May 2024Type 1 Diabetes Mellitus (T1DM) can generate severe complications, such as Diabetic Kidney Disease (DKD) or Diabetic Nephropathy (DN), with it emerging as the leading...
Type 1 Diabetes Mellitus (T1DM) can generate severe complications, such as Diabetic Kidney Disease (DKD) or Diabetic Nephropathy (DN), with it emerging as the leading cause of terminal (end-stage) renal disease all over the world. For T1DM, the clinical evaluation of DKD uses markers like the Glomerular Filtration Rate (GFR) and the Urinary Albumin Excretion (UAE). However, early diagnosis of DKD is still a challenge. For this reason, investigating molecular markers, such as microRNAs (miRNAs), offers a promising perspective to an early diagnosis, highlighting the stability and the ability to reflect incipient molecular manifestations. Thus, here we investigated four miRNAs (hsa-let-7i-5p, hsa-miR-143-3p, hsa-miR-501-3p, and hsa-miR-100-5p) regarding nephropathy in patients with T1DM, considering the albuminuria (micro and macro) as a standard to evaluate the groups. As a result, we found a reduced expression of miR-100-5p in patients with MIC, indicating a protective role in nephropathy. Beyond that, expression levels between the groups (Non vs. UAE) were not significant when comparing the miRNAs miR-501-3p and miR-143-3p. Finally, miR-143-3p and miR-100-5p were linked to some target genes such as AKT1, MMP13, and IGF1R, that are connected to signal pathways and cellular metabolism.
Topics: MicroRNAs; Humans; Diabetic Nephropathies; Diabetes Mellitus, Type 1; Male; Female; Adult; Middle Aged; Down-Regulation; Biomarkers; Albuminuria; Receptor, IGF Type 1; Glomerular Filtration Rate
PubMed: 38891851
DOI: 10.3390/ijms25115663