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Sichuan Da Xue Xue Bao. Yi Xue Ban =... Nov 2023Diabetic kidney disease (DKD) is a common complication of diabetes mellitus and approximately 1/3 of diabetic patients may progress to DKD. A typical early clinical... (Review)
Review
Diabetic kidney disease (DKD) is a common complication of diabetes mellitus and approximately 1/3 of diabetic patients may progress to DKD. A typical early clinical manifestation of DKD is microalbuminuria and patients may present with macroproteinuria accompanied by a decrease in renal function condition as the disease progresses. It is generally believed that the likelihood of a reversal of the disease is reduced after the development of macroproteinuria in patients with DKD, and that eventually some patients' condition may develop into end-stage renal disease (ESRD). Moreover, the thickening of the glomerular basement membrane, mesangial matrix expansion, Kimmelstiel-Wilson (K-W) nodules, and glomerulosclerosis in end-stage diabetes mellitus are typical pathologic changes of DKD. However, some DKD patients, especially those with type 2 diabetes mellitus (T2DM) combined with DKD, may have diverse clinical manifestations, showing variations in disease progression and regression, and manifesting as non-classical types of DKD, such as normoalbuminuric DKD, proteinuria-reduced DKD, and DKD with rapid decline in renal function. In addition, the formation of crescents, a special pathological change, is observed in renal biopsy. However, this issue is currently under-recognized by clinicians and therefore deserves more attention. In order to improve clinicians' understanding of the presentations and pathological changes of non-classical DKD and the level of DKD prevention and treatment in China, we present a preliminary introduction to the clinical phenotypes and pathological changes of non-classical types of DKD in this paper by summarizing the findings of our prior studies as well as domestic and international literature.
Topics: Humans; Diabetic Nephropathies; Diabetes Mellitus, Type 2; Albuminuria; Kidney Failure, Chronic; China; Kidney
PubMed: 38162079
DOI: 10.12182/20231160102 -
International Journal of Molecular... Dec 2023Zinc (Zn) and copper (Cu) have been shown to have the potential to improve glucose metabolism through interactions with cytokines and signaling events with multiple...
Zinc (Zn) and copper (Cu) have been shown to have the potential to improve glucose metabolism through interactions with cytokines and signaling events with multiple genes. miRNA-375 and the Calpin-10 gene are potential genetic biomarkers for the early prediction of diabetic nephropathy (DN). 128 healthy controls and 129 type 2 diabetic (T2DM) participants were matched for age and sex. Three subgroups were identified from the T2DM group: 39 patients had microalbuminuria, 41 had macroalbuminuria, and 49 patients had renal problems. Circulating miR-375 expression levels were measured via qPCR. Calpain-10 SNP 19 (rs3842570) genotyping was assessed with allele-specific PCR in all the included participants. Spectrophotometry was used to measure the concentrations of serum copper, zinc, and magnesium, while ELISA was used to measure the levels of TGF-β and IL-17. There was significant up-regulation in the expression of miR-375 and serum levels of TGF-β, IL-17, Cu, and the Cu/Zn ratio, whereas, in contrast to the control group, the Zn and Mg levels were lower in the T2DM group. The DN groups had significantly lower miR-375, TGF-β, IL-17, Mg, and Zn levels compared with the T2DM without nephropathy group. Furthermore, between TGF-β, IL-17, and miRNA-375, there were notable correlations. Calpain-10 SNP 19 genotype 22 and allele 2 were linked to a higher incidence of T2DM and DN. Significant TGF-β, Cu, Cu/Zn ratio, HbAc1, and creatinine levels, but insignificant miRNA-375 levels, were associated with genotype 22 of Calpain-10 SNP 19. interactions between the Calpain-10 SNP 19 genotype 22 and IL-17, TGF-β, mineral levels, and miRNA-375 might contribute to the aetiology of DN and T2DM and may have clinical implications for diagnosis and management.
Topics: Humans; Calpain; Copper; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Interleukin-17; MicroRNAs; Transforming Growth Factor beta; Zinc
PubMed: 38139275
DOI: 10.3390/ijms242417446 -
Frontiers in Endocrinology 2023The objective of this study was to investigate changes in serum tumor markers in type 2 diabetes mellitus (T2DM) with microalbuminuria and analyze the relationship...
OBJECTIVES
The objective of this study was to investigate changes in serum tumor markers in type 2 diabetes mellitus (T2DM) with microalbuminuria and analyze the relationship between tumor markers and microalbuminuria.
METHODS
A total of 956 T2DM patients aged 40-70 years hospitalized in the Department of Endocrinology, Xinhua Hospital, China, affiliated with Shanghai Jiaotong University School of Medicine, were enrolled from January 2018 to December 2020. The sample comprised 313 T2DM patients with microalbuminuria and 643 T2DM patients with normal urinary microalbumin levels. After assessing the changes in serum tumor markers in T2DM with microalbuminuria, we analyzed the risk of microalbuminuria by the serum tumor marker category using multiple logistic regression analysis.
RESULTS
Serum CEA, CA199, CA125, CA153, CA211, SCC, CA242, and CA50 levels were significantly higher in T2DM patients with microalbuminuria than in those without microalbuminuria, while serum AFP levels were lower in the microalbuminuria group ( < 0.05). Following adjustment of confounders, serum CEA, CA211, and SCC were independently associated with microalbuminuria in T2DM. An ROC curve was used to estimate the cutoff point of tumor markers for microalbuminuria. Taking the values under the cutoff points as a reference, values for CEA, CA211, and SCC above the cutoff points indicated a significantly high risk of microalbuminuria. The OR of increased CEA for microalbuminuria was 2.006 (95%CI 1.456-2.765), the OR of increased CA211 for microalbuminuria was 1.505 (95%CI 1.092-2.074), and the OR of increased SCC for microalbuminuria was 1.958 (95%CI 1.407-2.724).
CONCLUSION
Several serum tumor markers were related to microalbuminuria in T2DM. Serum tumor markers such as CEA, SCC, and CA211 may indicate early diabetic nephropathy, particularly when elevated in combination.
Topics: Humans; Biomarkers, Tumor; Diabetes Mellitus, Type 2; China; Neoplasms; Diabetic Nephropathies
PubMed: 38130399
DOI: 10.3389/fendo.2023.1247099 -
Nephron 2024Arteriolar hyalinosis (AH) has been shown to be associated with albuminuria and GFR. In this study, we investigated whether or not index of AH (IAH) is a predictor of...
INTRODUCTION
Arteriolar hyalinosis (AH) has been shown to be associated with albuminuria and GFR. In this study, we investigated whether or not index of AH (IAH) is a predictor of the onset of macroalbuminuria and impaired renal function (eGFR <60 mL/min/1.73 m2 [eGFR <60]) in type 2 diabetic patients with early diabetic nephropathy.
METHODS
The study population consisted of 35 patients with type 2 diabetes (25 men; age: 47 ± 9 years; eGFR: 92.7 ± 18.0 mL/min/1.73 m2) with normo- or microalbuminuria who underwent percutaneous renal biopsy. These patients were followed for at least 5 (18 ± 6, range: 6-28) years. The study endpoint was the onset of macroalbuminuria or eGFR <60. Light and electron microscopy-based morphometric analyses were performed to quantitatively evaluate glomerular and interstitial structural changes.
RESULTS
During the observation period, 9 out of the 35 patients progressed to macroalbuminuria, and 15 out of the 35 patients developed eGFR <60. The annual rate of eGFR decline was significantly correlated with IAH (r = -0.40, p = 0.016). Kaplan-Meier analysis demonstrated that AH was associated with a significantly higher risk of onset of macroalbuminuria and eGFR <60, and microalbuminuria is associated with the onset of macroalbuminuria but not the onset of eGFR <60.
CONCLUSIONS
Aggravated AH is a histological risk factor which predicts the onset of macroalbuminuria and eGFR <60 in patients with type 2 diabetes. These findings provide novel insights into the mechanism of progression of diabetic nephropathy.
Topics: Humans; Diabetes Mellitus, Type 2; Middle Aged; Male; Female; Albuminuria; Diabetic Nephropathies; Glomerular Filtration Rate; Adult; Arterioles; Disease Progression; Hyalin; Kidney
PubMed: 38118427
DOI: 10.1159/000535875 -
BMC Nephrology Dec 2023Advanced glycation end products (AGEs) deposited in the lens are correlated with those in the kidneys, indicating a possible value in evaluating diabetic kidney disease...
BACKGROUND
Advanced glycation end products (AGEs) deposited in the lens are correlated with those in the kidneys, indicating a possible value in evaluating diabetic kidney disease (DKD). This study explored the value of noninvasively measuring lens AGEs to diagnose and evaluate the severity of diabetic nephropathy in patients with type 2 diabetes mellitus (T2DM).
METHODOLOGY
A total of 134 T2DM patients admitted to the Fifth People's Hospital of Shanghai from March 2020 to May 2021 were selected randomly. Patients were divided into low-, medium-and high-risk groups according to the risk assessment criteria for DKD progression and into DKD and non-DKD (non-DKD) groups according to the Guidelines for the Prevention and Treatment of Diabetic Nephropathy in China. The concentrations of noninvasive AGEs in the lens in all the groups were retrospectively analyzed.
RESULTS
The concentration of noninvasive lens AGEs in the high-risk patients, according to the 2012 guidelines of the Global Organization for Improving the Prognosis of Kidney Diseases, was significantly higher than that in the remaining groups. Regression analysis suggested the value of lens AGEs in diagnosing DKD and evaluating DKD severity. Cox regression analysis indicated that the noninvasive lens AGE concentration was positive correlated with the course of disease.
CONCLUSION
The receiver operating characteristic (ROC) curve suggested that using noninvasive lens AGE measurements has clinical value in the diagnosis of DKD (area under the curve 62.4%,95% confidence interval (CI) 52.4%-73.9%, p = 0.014) and in assessing the severity of DKD (area under the curve 83.2%, 95% CI 74.1%-92.3%, P < 0.001). Noninvasive lens AGE testing helps screen T2DM patients for DKD and evaluate the severity of DKD.
Topics: Humans; Diabetic Nephropathies; Diabetes Mellitus, Type 2; Retrospective Studies; China; Glycation End Products, Advanced
PubMed: 38115082
DOI: 10.1186/s12882-023-03428-3 -
BMC Medicine Dec 2023Solute carrier family 13 member 5 (SLC13A5) is a Na-coupled citrate co-transporter that mediates entry of extracellular citrate into the cytosol. SLC13A5 inhibition has...
BACKGROUND
Solute carrier family 13 member 5 (SLC13A5) is a Na-coupled citrate co-transporter that mediates entry of extracellular citrate into the cytosol. SLC13A5 inhibition has been proposed as a target for reducing progression of kidney disease. The aim of this study was to leverage the Mendelian randomization paradigm to gain insight into the effects of SLC13A5 inhibition in humans, towards prioritizing and informing clinical development efforts.
METHODS
The primary Mendelian randomization analyses investigated the effect of SLC13A5 inhibition on measures of kidney function, including creatinine and cystatin C-based measures of estimated glomerular filtration rate (creatinine-eGFR and cystatin C-eGFR), blood urea nitrogen (BUN), urine albumin-creatinine ratio (uACR), and risk of chronic kidney disease and microalbuminuria. Secondary analyses included a paired plasma and urine metabolome-wide association study, investigation of secondary traits related to SLC13A5 biology, a phenome-wide association study (PheWAS), and a proteome-wide association study. All analyses were compared to the effect of genetically predicted plasma citrate levels using variants selected from across the genome, and statistical sensitivity analyses robust to the inclusion of pleiotropic variants were also performed. Data were obtained from large-scale genetic consortia and biobanks, with sample sizes ranging from 5023 to 1,320,016 individuals.
RESULTS
We found evidence of associations between genetically proxied SLC13A5 inhibition and higher creatinine-eGFR (p = 0.002), cystatin C-eGFR (p = 0.005), and lower BUN (p = 3 × 10). Statistical sensitivity analyses robust to the inclusion of pleiotropic variants suggested that these effects may be a consequence of higher plasma citrate levels. There was no strong evidence of associations of genetically proxied SLC13A5 inhibition with uACR or risk of CKD or microalbuminuria. Secondary analyses identified evidence of associations with higher plasma calcium levels (p = 6 × 10) and lower fasting glucose (p = 0.02). PheWAS did not identify any safety concerns.
CONCLUSIONS
This Mendelian randomization analysis provides human-centric insight to guide clinical development of an SLC13A5 inhibitor. We identify plasma calcium and citrate as biologically plausible biomarkers of target engagement, and plasma citrate as a potential biomarker of mechanism of action. Our human genetic evidence corroborates evidence from various animal models to support effects of SLC13A5 inhibition on improving kidney function.
Topics: Humans; Biomarkers; Calcium; Citrates; Creatinine; Cystatin C; Drug Development; Genome-Wide Association Study; Kidney; Mendelian Randomization Analysis; Renal Insufficiency, Chronic; Symporters
PubMed: 38110950
DOI: 10.1186/s12916-023-03227-5 -
Therapeutic Advances in Chronic Disease 2023Magnesium (Mg) deficiency is closely linked with proteinuria.
BACKGROUND
Magnesium (Mg) deficiency is closely linked with proteinuria.
OBJECTIVES
To assess the impact of oral Mg citrate supplementation on the clinical outcome of diabetic nephropathy (DN) patients.
DESIGN
This was a prospective, randomized, controlled, open-label study.
METHODS
Sixty DN patients were recruited from Nephrology and Endocrinology departments, Ain Shams University Hospitals, Cairo, Egypt. Patients were assigned by stratified randomization based on their Mg status, to either Mg citrate group, ( = 30), who received the standard regimen + oral Mg citrate 2.25 g/day or Control group, ( = 30), who received the standard regimen only. The primary endpoint was a change in urinary albumin to creatinine ratio (UACR) after 12 weeks. Secondary outcomes were insulin resistance, glycemic control, lipid profile, serum osteocalcin, quality of life (QoL) and Mg tolerability.
RESULTS
Out of a total of 60 patients enrolled, only 54 patients (26 in Mg citrate group and 28 in the control group) completed the study. Groups were comparable at baseline. The UACR median percent reduction was significantly higher in the Mg citrate group (-6.87%) (-0.9%) in the Control group, = 0.001. After 12 weeks, the estimated glomerular filtration rate significantly improved in the Mg citrate group Control group ( = 0.001). Comparable change was observed in glycemic indices. Lipid profile significantly improved in the Mg citrate group Control group ( = 0.001). Serum osteocalcin levels significantly declined in the Mg citrate group ( = 0.001) control group. Regarding QoL, the total score and all domains significantly improved in the Mg citrate group compared to control. The Mg supplement was tolerable with only mild reported side effects that required no intervention.
CONCLUSION
Oral Mg citrate supplementation improved microalbuminuria in DN patients. It also had favorable effects on serum osteocalcin, lipid profile and QoL with no reported major side effects.
TRIAL REGISTRATION
ClinicalTrials.gov identifier: NCT03824379.
PubMed: 38107482
DOI: 10.1177/20406223231214641 -
Frontiers in Endocrinology 2023Abnormal gut microbiota and blood trimethylamine-N-oxide (TMAO) metabolome have been reported in patients with type 2 diabetes mellitus (T2DM) and advanced diabetic...
BACKGROUND
Abnormal gut microbiota and blood trimethylamine-N-oxide (TMAO) metabolome have been reported in patients with type 2 diabetes mellitus (T2DM) and advanced diabetic nephropathy. This study aimed to investigate the gut microbiota profiles and a group of targeted urine metabolic characteristics in T2DM patients with or without microalbuminuria, to determine the correlation between the gut microbiota composition, trimethylamine (TMA) metabolism, and the clinical features during progression of diabetic kidney disease (DKD).
METHODS
This study included 26 T2DM patients with microalbuminuria (Micro), 26 T2DM patients with normoalbuminuria (Normo), and 15 healthy controls (HC). Urine and Fecal samples were detected using ultra performance liquid chromatography tandem mass spectrometry and 16S ribosomal DNA gene sequencing, respectively.
RESULTS
The TMAO/TMA ratio decreased gradually during the HC-Normo-Micro transition. The levels of TMA, choline and betaine were significantly different between the HC group and the T2DM patients belonging to both Normo and Micro groups. At the operational taxonomic unit (OTU) level, the gut microflora diversity was significantly reduced in the Micro groups compared to the HC groups and the Normo groups. Taxonomic analyses revealed significant consumption in the relative abundances of eight bacterial genera and significant enrichment of two bacterial genera during the HC-Normo-Micro transition. Furthermore, the relative abundances of six bacterial genera, namely, Ruminococcus_1, [Eubacterium]_ruminantium_group, Roseburia, Faecalibacterium, Fusicatenibacter and Coprococcus_3 exhibited significant differences, and were associated with elevated urinary albumin creatinine ratio (UACR), TMAO/TMA, TMA and its precursors in the Micro group compared with the other groups.
CONCLUSION
The imbalance of gut microbiota has occurred in patients with early-stage DKD, and the consumption of short-chain fatty acid-producing bacteria were associated with the accumulation of TMA and UACR.
Topics: Humans; Bacteria; Diabetes Mellitus, Type 2; Dysbiosis; Methylamines; Gastrointestinal Microbiome
PubMed: 38075058
DOI: 10.3389/fendo.2023.1257457 -
American Journal of Translational... 2023This retrospective study aims to analyze the effect of telmisartan (TEL) combined with calcitriol (CTL) on therapeutic efficacy, inflammatory status, and renal...
PURPOSE
This retrospective study aims to analyze the effect of telmisartan (TEL) combined with calcitriol (CTL) on therapeutic efficacy, inflammatory status, and renal interstitial fibrosis (RIF) in patients with diabetic nephropathy (DN).
METHODS
First, 126 DN patients admitted between September 2019 and September 2022 were selected, of which 66 cases (research group) were treated with TEL + CTL, and 60 cases (control group) were given TEL alone. The therapeutic efficacy, complications (fever, dizziness, headache, nausea and vomiting, and gastrointestinal reactions), inflammatory status (interleukin (IL)-1β, high-sensitivity C-reactive protein (hs-CRP), and tumor necrosis factor (TNF)-α), RIF (transforming growth factor (TGF)-β1, vascular endothelial growth factor (VEGF), and homocysteine (Hcy)), and renal function (blood urea (BUN), serum creatinine (Cr), and microalbuminuria (mAlb)) were compared between the two groups. Finally, a univariate analysis was performed to identify factors leading to poor prognosis (ineffective treatment) in patients.
RESULTS
A statistically higher overall response rate was determined in the research group as compared to the control group (P<0.05). The two groups exhibited equivalent complication rates (P>0.05). Markedly lower post-treatment IL-1β, hs-CRP, TNF-α, TGF-β1, VEGF, Hcy, BUN, Scr, and mAlb were identified in the research group than those in the control group (P<0.05). Moreover, hs-CRP, TNF-α, BUN, and treatment modality were found to be closely associated with poor prognosis in DN patients (P<0.05).
CONCLUSIONS
TEL + CTL has a good effect on DN and a comparable safety profile to TEL monotherapy. This combination can significantly inhibit inflammation and RIF and improve renal function in DN patients.
PubMed: 38074815
DOI: No ID Found -
BMC Nephrology Dec 2023This study aimed to identify the factors relating to moderately increased albuminuria among middle-aged and older individuals in Japan.
BACKGROUND
This study aimed to identify the factors relating to moderately increased albuminuria among middle-aged and older individuals in Japan.
METHODS
We conducted specific health examinations in which we measured albuminuria levels, and administered a questionnaire survey to record participants' lifestyles in western Tokushima Prefecture, Japan. A total of 1,660 people whose albuminuria was less than 300 mg/g creatinine (Cr) were analyzed. We divided participants into two groups-those with normal albuminuria (< 30 mg/gCr) and those with moderately increased albuminuria (≥ 30 mg/gCr, > 300 mg/gCr)-and compared their characteristics. To investigate all relevant factors, we conducted a multivariate logistic regression analysis.
RESULTS
The moderately increased albuminuria group were significantly older and had, among them, significantly higher percentages of a body mass index (BMI) ≥ 25 kg/m, diabetes, hypertension, and mild liver disorder (aspartate transaminase ≥ 31 U/L or alanine aminotransferase ≥ 31 U/L or gamma-glutamyl transferase ≥ 51 U/L). (p < 0.01) In a multivariate logistic regression analysis that used microalbuminuria as an independent variable, we found the adjusted odds ratio (AOR) and 95% confidence interval (CI) to be significantly higher among individuals with diabetes (AOR: 2.04, 95% CI: 1.40-2.99); hypertension (AOR: 1.90, 95% CI: 1.36-2.65); BMI ≥ 25 kg/m (AOR: 1.76, 95% CI: 1.27-2.44); and mild liver disorder (AOR: 1.54, 95% CI: 1.10-2.18).
CONCLUSIONS
In addition to diabetes, hypertension, and BMI ≥ 25 kg/m, this study found that among the middle-aged and older general population living in western Tokushima Prefecture, there were cases of mild liver disorder (elevated serum transaminase), which independently associated with moderately increased albuminuria. Therefore, in health checkups targeting the general population, there is a need to consider measuring albuminuria, even in those who have only mild liver dysfunction (health guidance level).
TRIAL REGISTRATION
N/A.
Topics: Middle Aged; Humans; Aged; Cross-Sectional Studies; Albuminuria; Japan; Diabetes Mellitus; Hypertension; Liver Diseases; Alanine Transaminase; Risk Factors
PubMed: 38053047
DOI: 10.1186/s12882-023-03411-y