Diabetic nephropathy (DN), as one of the chronic complications of diabetes, is the major cause of end-stage renal disease. However, the pathogenesis of this disease is not fully understood. In recent years, research on microRNAs (miRNAs) has become a hotspot because of their critical role in regulating posttranscriptional levels of protein-coding genes that may serve as key pathogenic factors in diseases. Several miRNAs were found to participate in the pathogenesis of DN, while others showed renal protective effects. Therefore, targeting miRNAs that are involved in DN may have a good prospect in the treatment of the disease. The aim of this review is to summarize DN-related miRNAs and provide potential targets for diagnostic strategies and therapeutic intervention.

Mitochondria are essential for eukaryotic cell activity and function, and their dysfunction is associated with the development and progression of renal diseases. In recent years, there has been a rapid development in mitochondria‐targeting pharmacological strategies as mitochondrial biogenesis, morphology, and function, as well as dynamic changes in mitochondria, have been studied in disease states. Mitochondria‐targeting drugs include nicotinamide mononucleotide, which supplements the NAD+ pool; mitochondria‐targeted protective compounds, such as MitoQ; the antioxidant coenzyme, Q10; and cyclosporin A, an inhibitor of the mitochondrial permeability transition pore. However, traditional drugs targeting mitochondria have limited clinical applications due to their inability to be effectively absorbed by mitochondria in vivo and their high toxicity. Recently, SS‐31, a mitochondria‐targeting antioxidant, has received significant research attention as it decreases mitochondrial reactive oxygen species production and prevents mitochondrial depolarization, mitochondrial permeability transition pore formation, and Ca²⁺‐induced mitochondrial swelling, and has no effects on normal mitochondria. At present, few studies have evaluated the effects of SS‐31 against renal diseases, and the mechanism underlying its action is unclear. In this review, we first discuss the pharmacokinetics of SS‐31 and the possible mechanisms underlying its protective effects against renal diseases. Then, we analyze its renal disease‐improving effects in various experimental models, including animal and cell models, and summarize the clinical evidence of its benefits in renal disease treatment. Finally, the potential mechanism underlying the action of SS‐31 against renal diseases is explored to lay a foundation for future preclinical studies and for the evaluation of its clinical applications.

Our previous study showed that proteasomal inhibitor MG132 can prevent diabetic nephropathy (DN) along with upregulation of nuclear factor (erythroid‐derived 2)‐like 2 (Nrf2). The present study was to investigate whether MG132 can prevent DN in wild‐type and Nrf2‐KO mice. Type 1 diabetes was induced in wild‐type and Nrf2‐KO mice by multiple low doses of streptozotocin. Two weeks after streptozotocin injection, both wild‐type and Nrf2‐KO mice were randomly divided into four groups: control, MG132, DM, and DM/MG132. MG132 (10 μg/kg/day) or vehicle was administered intraperitoneally for 4 months. Renal function, morphology, and biochemical changes were measured after 4‐month treatment with MG132. MG132 treatment suppressed proteasomal activity in the two genotypes. In wild‐type mice, MG132 attenuated diabetes‐induced renal dysfunction, fibrosis, inflammation, and oxidative damage along with increased Nrf2 and IκB expression. Deletion of Nrf2 gene resulted in a partial, but significant attenuation of MG132 renal protection in Nrf2‐KO mice compared with wild‐type mice. MG132‐increased IκB expression was not different between wild‐type and Nrf2‐KO mice. This work indicates that MG132 inhibits diabetes‐increased proteasomal activity, resulting in Nrf2 and IκB upregulation and renal protection, which could be used as a strategy to prevent diabetic nephropathy.

Purpose. To identify the epidemiology and pathological types of kidney diseases and their changes during the past decade, in a population from Northeast China.Methods. We retrospectively analysed clinical and renal pathological data from 4910 patients who received renal biopsies in the Second Hospital of Jilin University from 2008 to 2017.Results. Males received more renal biopsies than females (p< 0.001). The average age (p< 0.001) and percentage of elderly patients (p< 0.001) increased over time. The pathological types were primary glomerulonephritis (PGN, 73.2%), secondary glomerulonephritis (SGN, 23.7%), tubular-interstitial nephropathy (TIN, 2.8%), and hereditary nephropathy (HN, 0.3%). The most common forms of PGN were membranous nephropathy (MN, 37.2%) and IgA nephropathy (IgAN, 29.9%). Over time, the prevalence of IgAN decreased, but the prevalence of MN increased. MN was more common in middle-aged and elderly patients, but IgAN was most common in young adults. Analysis of SGN data indicated that lupus nephritis (LN, 34.0%), Henoch-Schönlein purpura glomerulonephritis (HSPN, 17.9%), and diabetic nephropathy (DN, 11.7%) were the most common forms. Over time, the prevalence of DN (p= 0.003), hypertension-associated renal damage (p= 0.005), and systemic vasculitis-associated nephritis (SVARD,p< 0.001) increased, but the prevalence of HSPN (p< 0.001) and hepatitis B virus-associated glomerulonephritis (HBV-GN,p= 0.001) decreased. Nephrotic syndrome was the main clinical manifestation of PGN.Conclusion. From 2008 to 2017, renal biopsies were increasingly performed in the elderly. There were notable changes in the epidemiology and pathological types of kidney disease among renal biopsy patients at our centre.

Obesity-related glomerulopathy, which is an obesity-triggered kidney damage, has become a significant threat to human health. Several studies have recently highlighted the critical role of inflammation in obesity-related glomerulopathy development. Additionally, excess adipose tissue and adipocytes in patients with obesity produce various inflammatory factors that cause systemic low-grade inflammation with consequent damage to vascular endothelial cells, exacerbating glomerular injury. Therefore, we conducted a comprehensive review of obesity-related glomerulopathy and addressed the critical role of obesity-induced chronic inflammation in obesity-related glomerulopathy pathogenesis and progression, which leads to tubular damage and proteinuria, ultimately impairing renal function. The relationship between obesity and obesity-related glomerulopathy is facilitated by a network of various inflammation-associated cells (including macrophages, lymphocytes, and mast cells) and a series of inflammatory mediators (such as tumor necrosis factor α, interleukin 6, leptin, adiponectin, resistin, chemokines, adhesion molecules, and plasminogen activator inhibitor 1) and their inflammatory pathways. Furthermore, we discuss a recently discovered relationship between micronutrients and obesity-related glomerulopathy inflammation and the important role of micronutrients in the body's anti-inflammatory response. Therefore, assessing these inflammatory molecules and pathways will provide a strong theoretical basis for developing therapeutic strategies based on anti-inflammatory effects to prevent or delay the onset of kidney injury.

Objective: To elucidate the potential causality of leukocyte telomere length (LTL) with immune-mediated inflammatory diseases (IMIDs), we conducted a Mendelian randomization (MR) study.Methods: The genetically predicted causation between LTL and IMIDs was evaluated using a two-sample MR method. We analyzed 16 major IMIDs, which included systemic lupus erythematosus (SLE), inflammatory bowel disease (IBD), ulcerative colitis (UC), Crohn’s disease (CD), ankylosing spondylitis (AS), sicca syndrome (SS), rheumatoid arthritis (RA), type 1 diabetes (T1D), primary sclerosing cholangitis (PSC), idiopathic pulmonary fibrosis (IPF), atopic dermatitis (AD), sarcoidosis, hypothyroidism, hyperthyroidism, psoriasis, and childhood asthma. The random-effects inverse-variance weighted (IVW) method was performed as the main analytical approach in MR. Various sensitivity analyses, including MR-Egger, MR robust adjusted profile score (MR-RAPS), weighted median, MR pleiotropy residual sum and outlier (MR-PRESSO) methods, weighted mode, radial plot, and radial regression, were used to guarantee the robustness of the results and detect horizontal pleiotropy. Cochran’s Q value was calculated to check for heterogeneity, and the MR Steiger approach was used to test the causal direction.Results: The MR results indicated significant inverse associations of LTL with risks of psoriasis (OR: 0.77, 95% CI: 0.66–0.89, and p = 3.66 × 10⁻⁴), SS (OR: 0.75, CI: 0.58–0.98, and p = 0.03), RA (OR: 0.77, 95% CI: 0.68–0.88, and p = 9.85 × 10⁻⁵), hypothyroidism (OR: 0.84, 95% CI: 0.78–0.91, and p = 7,08 × 10⁻⁶), hyperthyroidism (OR: 0.60, 95% CI: 0.44–0.83, and p = 1.90 × 10⁻³), sarcoidosis (OR: 0.67, 95% CI: 0.54–0.83, and p = 2.60 × 10⁻⁴), and IPF (OR: 0.41, 95% CI: 0.29–0.58, and p = 4.11 × 10⁻⁷) in the FinnGen study. We observed that longer LTL was associated with an increased risk of AS susceptibility (OR: 1.51, 95% CI: 1.18–1.94, and p = 9.66 × 10⁻⁴). The results of the IVW method showed no causal relationship between TL and SLE (OR: 0.92, 95% CI: 0.62–1.38, and p = 0.69) in the FinnGen study; however, a significantly positive correlation was shown between LTL and SLE in another larger GWAS (OR: 1.87, 95% CI: 1.37–2.54, and p = 8.01 × 10⁻⁵).Conclusion: Our findings reveal that abnormal LTL has the potential to increase the risk of IMIDs. Therefore, it could be treated as a predictor and may provide new potential treatment targets for IMIDs. However, the change of LTL may not be the direct cause of IMIDs. Further studies should aim at the pathogenic mechanism or potential protective effects of LTL in IMIDs.