Diabetic nephropathy: is it always there? Assumptions, weaknesses and pitfalls in the diagnosis

Ioannou, Kyriakos

doi:10.14310/horm.2002.1755

Cited by 33 publications

(13 citation statements)

References 92 publications

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“…According to the World Health Organization, an estimated 422 million people were living with diabetes worldwide in 2014, a figure that is projected to rise to about 642 million people by 2040 accompanied by a paralleled increase in its associated complications (2,3). One of the associated complications of diabetes is diabetic nephropathy (DN)a microvascular complication characterized by albuminuria and progressive loss of kidney function (4) and is also considered to be the leading cause of end-stage renal disease (ESRD) in the United States (5) and across the globe (6,7).…”

Section: Introductionmentioning

confidence: 99%

Anthropometric Measures and Incident Diabetic Nephropathy in Participants With Type 2 Diabetes Mellitus

Hukportie

Zhou

et al. 2021

Front. Endocrinol.

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BackgroundThe prevalence of diabetes is on the rise globally coupled with its associated complications, such as diabetic nephropathy (DN). Obesity has been identified as a risk factor for the development of DN but it is still unclear which obesity index is the best predictor of incident DN.MethodsData from the participants with type 2 diabetes mellitus (T2DM) in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study were used to examine the sex-specific association between waist circumference (WC), waist-to-height ratio (WHtR), and body mass index (BMI) with incident DN risk.ResultsAmong the 8,887 participants with T2DM (5,489 men and 3,398 women), 5,296 participants (3,345 men and 1,951 women) developed the DN composite outcome during a follow-up period of 24302 person-years. Among men, null associations were observed between all anthropometric measures with incident DN in the multivariate analysis although the 3rd quartile of WHtR showed marginally significant results (P = 0.052). However, among women, both central and general obesity measures were associated with increased risks of incident DN. Compared with participants in the WC <88 cm category, the fully adjusted HR and 95% CI for those in the ≥88 cm of WC was 1.35 (95% CI 1.15-1.57). Compared with the lowest quartile, the fully adjusted HRs and 95% CIs for the 2nd to the 4th quartile of WHtR were 1.09 (95% CI 0.96-1.25), 1.12 (95% CI 0.98-1.28), and 1.14 (95% CI 1.00-1.30) respectively; also, compared with the normal BMI category, the fully adjusted HRs and 95% CIs for class I – class III obese were 1.36 (95% CI 1.10 – 1.67), 1.43 (95% CI 1.16 – 1.78) and 1.32 (95% CI 1.05 – 1.66) respectively.ConclusionsAmong participants with T2DM, higher levels of both central and general obesity indexes were associated with DN risk among women but not in men. Women with T2DM should maintain a healthy weight targeted at reducing both central and general obesity to enhance nephroprotection. Trial registration: ClinicalTrials.gov., no. NCT00000620.

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Section: Introductionmentioning

confidence: 99%

Anthropometric Measures and Incident Diabetic Nephropathy in Participants With Type 2 Diabetes Mellitus

Hukportie

Zhou

et al. 2021

Front. Endocrinol.

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“…Diabetic nephropathy (DN) is a common complication of type 2 diabetes. If left untreated, it can lead to glomerulosclerosis, which can seriously increase the disability and mortality rates in patients with type 2 diabetes [ 1 ]. In addition, DN is considered to contribute to the occurrence of end-stage renal disease.…”

Section: Introductionmentioning

confidence: 99%

The Efficacy of Hydroxychloroquine Combined with Huangqi Tablets in the Treatment of Diabetic Nephropathy

Chen

Sheng

Kong

2021

Journal of Healthcare Engineering

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Objective. This study aimed to analyze the effect of hydroxychloroquine combined with Huangqi tablets in the treatment of diabetic nephropathy (DN). Methods. Eighty patients with DN were enrolled and divided into two groups by a random number table. 27 patients received routine treatment + hydroxychloroquine (group A), while 27 patients received routine treatment + hydroxychloroquine + Huangqi tablets (group B) and 26 patients received routine treatment (group C). Results. FPG, 2h PG, and HbA1c levels as well as TC and TG levels were lower in group B than in groups A and C at the end of 3 months of treatment and were lower in group A than in group C ( P < 0.05). SCR, BUN, and 24-hour urine protein were reduced in group B after therapy, whereas eGFR was increased and the difference between groups A and C was significant ( P = 0.05 ). After treatment, VEGF, IGF-1, and TGF-1 levels were lower in group B than in groups A and C and in group A than in group C ( P = 0.05 ). Total symptom scores at 2, 4, and 6 months after treatment was lower in group B than in groups A and C, and they were lower in group A than in group C at all time points ( P < 0.05). The total effective rates of treatment in groups A, B, and C were 66.67%, 88.89%, and 38.46% ( P < 0.05). The incidence of adverse reactions in groups A, B, and C was 37.04%, 25.93%, and 11.54% ( P > 0.05). Conclusion. Hydroxychloroquine combined with Huangqi tablets in the treatment of DN showed the best efficacy, with better control of blood glucose and lipids, which can more effectively delay the progression of renal lesions and effectively inhibit the expression of VEGF, IGF, and TGF-β1 in tethered cells with high safety.

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“…The incidence of DN is increasing in developing countries, including China (3). DN is characterized by albuminuria and progressive loss of kidney function (4), and risk factors include hyperglycemia and genetic polymorphisms (5). Moreover, the dysfunction of podocytes contributes to the development of DN (6), and DN progression can be slowed by reducing podocyte injury (7).…”

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confidence: 99%

Adipose mesenchymal stem cell-derived extracellular vesicles containing microRNA-26a-5p target TLR4 and protect against diabetic nephropathy

Duan

Luo

Wang

et al. 2020

Journal of Biological Chemistry

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Diabetic nephropathy (DN) is a complication of diabetes that is increasing in prevalence in China. Extracellular vesicles (EVs) carrying microRNAs (miRs) may represent a useful tool in the development of therapies for DN. Here, we report that EVs released by adipose-derived mesenchymal stem cells (ADSCs) during DN contain a microRNA (miR), miR-26a-5p, that suppresses DN. Using bioinformatic analyses, we identified differentially expressed miRs in EVs from ADSCs and in DN and predicted downstream regulatory target genes. We isolated mesenchymal stem cells (MSCs) from adipose tissues, and collected EVs from the ADSCs. We exposed mouse glomerular podocytes and MP5 cells to high glucose (HG), ADSCs-derived EVs, miR-26a-5p inhibitor/antagomir, Toll-like receptors 4 (TLR4) plasmids, or the NF-κB pathway activator (phorbol-12-myristate-13-acetate, PMA). We used the CCK-8 assay and flow cytometry to investigate the impact of miR-26a-5p on cell viability and apoptosis and validated the results of these assays with in vivo experiments in nude mice. We found that in DN, miR-26a-5p is expressed at very low levels, whereas TLR4 is highly expressed. Of note, EVs from ADSCs ameliorated the pathological symptoms of DN in diabetic mice, and transferred miR-26a-5p to HG-induced MP5 cells, improving viability while suppressing apoptosis of MP5 cells. We also found that miR-26a-5p protects HG-induced MP5 cells from injury by targeting TLR4, inactivating the NF-κB pathway and down-regulating vascular endothelial growth factor A (VEGFA). Moreover, ADSCs-derived EVs transferred miR-26a-5p to mouse glomerular podocytes, which ameliorated DN pathology. These findings suggest that miR-26a-5p from ADSC-derived EVs protects against DN.

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Diabetic nephropathy: is it always there? Assumptions, weaknesses and pitfalls in the diagnosis

Cited by 33 publications

References 92 publications

Anthropometric Measures and Incident Diabetic Nephropathy in Participants With Type 2 Diabetes Mellitus

Anthropometric Measures and Incident Diabetic Nephropathy in Participants With Type 2 Diabetes Mellitus

The Efficacy of Hydroxychloroquine Combined with Huangqi Tablets in the Treatment of Diabetic Nephropathy

Adipose mesenchymal stem cell-derived extracellular vesicles containing microRNA-26a-5p target TLR4 and protect against diabetic nephropathy

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