Introduction Renal biopsy performed in patients with type 2 diabetes mellitus (T2DM) for atypical or suspected diabetic kidney disease (DKD) reveals one of three possibilities: diabetic nephropathy (DN, pathological diagnosis of DKD), nondiabetic kidney disease (NDKD) and DN plus NDKD (mixed form). NDKD (including the mixed form) is increasingly being recognized worldwide. With the emerging concept of DKD and the complexity of routine application of renal biopsy, the identification of “clinical indicators” to differentiate DKD from NDKD has been an area of active research. Methods The PubMed database was searched for relevant articles mainly according to the keyword search method. We reviewed prevalence of the three types of DKD and different pathological lesions of NDKD. We also reviewed the clinical indicators used to identify DKD and NDKD. Results The literature search identified 40 studies (5304 data) worldwide between 1977 and 2019 that looked at global renal biopsy and pathological NDKD lesions. The overall prevalence rate of DN, NDKD and DN plus NDKD is reported to be 41.3, 40.6 and 18.1%, respectively. In Asia, Africa (specifically Morocco and Tunisia) and Europe, the most common isolated NDKD pathological type is membranous nephropathy, representing 24.1, 15.1 and 22.6% of cases, respectively. In contrast, focal segmental glomerulosclerosis is reported to be the primary pathological type in North America (specifically the USA) and Oceania (specifically New Zealand), representing 22% and 63.9% of cases, respectively. Tubulointerstitial disease accounts for a high rate in the mixed group (21.7%), with acute interstitial nephritis being the most prevalent (9.3%), followed by acute tubular necrosis (9.0%). Regarding clinical indicators to differentiate DKD from NDKD, a total of 14 indicators were identified included in 42 studies. Among these, the most commonly studied indicators included diabetic retinopathy, duration of diabetes, proteinuria and hematuria. Regrettably, indicators with high sensitivity and specificity have not yet been identified. Conclusion To date, renal biopsy is still the gold standard to diagnose diabetes complicated with renal disease, especially when T2DM patients present atypical DKD symptoms (e.g. absence of diabetic retinopathy, shorter duration of diabetes, microscopic hematuria, sub-nephrotic range proteinuria, lower glycated hemoglobin, lower fasting blood glucose). We conclude that renal biopsy as early as possible is of great significance to enable personalized treatment to T2DM patients.

Renal diseases are major global public health challenges due to their complex mechanisms and growing burden. PANoptosis, a unified programmed cell death pathway driven by the PANoptosome complex, involves the combined activation of pyroptotic, apoptotic, and necroptotic signaling, significantly contributing to renal tissue damage. This review systematically explores PANoptosis’s composition, regulatory mechanisms, and its role in kidney pathologies such as AKI, CKD, DKD, and renal tumors. It also examines the interplay between PANoptosis and key cellular processes like mitochondrial dysfunction, ER stress, non - coding RNAs, ferroptosis, and autophagy. Preclinical studies suggest that targeting PANoptosis - related molecules (e.g., Z-DNA Binding Protein 1(ZBP1), caspase − 8, NOD-like receptor thermal protein domain associated protein 3(NLRP3)) shows therapeutic potential for kidney diseases. However, clinical application is currently limited due to insufficient human data. Future research should focus on validating PANoptosis biomarkers in renal diseases, developing cell - death - context - specific inhibitors and agonists, and clarifying its advantages over single - mode cell death modulation. This review highlights PANoptosis as a promising therapeutic strategy while addressing unresolved issues in nephrology research.

With the increasing prevalence and mortality, chronic kidney disease (CKD) has become a world public health problem. As the primary pathological manifestation in CKD, renal fibrosis is often used as a critical target for the treatment of CKD and inhibits the progression of CKD to end-stage renal disease (ESRD). As a potential drug, natural products have been confirmed to have the potential as a routine or supplementary therapy for chronic kidney disease, which may target renal fibrosis and act through various pharmacological activities such as anti-inflammatory and anti-oxidation of natural products. This article briefly introduces the pathological mechanism of renal fibrosis and systematically summarizes the latest research on the treatment of renal fibrosis with natural products of Chinese herbal medicines.

Tripterygium wilfordii Hook. f. (TwHF) is a Chinese botanical drug containing a large number of metabolites. The discovered and recognized anti-inflammatory and immune-regulating effects have made it attract more and more attentions in trials and clinical researches. The extraction and processing of TwHF for pharmaceuticals is a manifestation of the role of traditional Chinese medicine. However, TwHF is toxic. Optimization of TwHF preparations has become a requirement for the development of TwHF pharmaceuticals. Our article introduces the main preparations of TwHF on the Chinese market and their characteristics. In particular, we summarize the clinical applications and influential mechanisms of TwHF and its preparations in kidney diseases. Considering that nephropathy is closely related to immune inflammation and TwHF is a botanical drug with a high number of metabolites, the application of TwHF in kidney diseases may be much more complicated. By revealing the role and mechanisms of TwHF in kidney diseases, this study aims to provide more insights to basic and clinical studies about nephropathy.

Type 2 diabetic kidney disease (T2DKD) is a common microvascular complication of type 2 diabetes mellitus (T2DM), and its incidence is significantly increasing. Microinflammation plays an important role in the development of T2DKD. Based on this, this study investigated the value of inflammatory markers including neutrophil–lymphocyte ratio (NLR), high-sensitivity C-reactive protein (hs-CRP), monocyte chemoattractant protein-1 (MCP-1) in the prediction of T2DKD. This was a cross-sectional survey study. A total of 90 patients with T2DM, who were hospitalized in the nephrology and endocrinology departments of the First Teaching Hospital of Tianjin University of Traditional Chinese Medicine from June 2021 to January 2022, were included and divided into three groups (A1, A2, A3) according to the urinary albumin-to-creatinine ratio (UACR). Observe and compare the basic information, clinical and laboratory data, and the inflammatory markers NLR, hs-CRP, MCP-1. Results revealed that high levels of NLR (OR = 6.562, 95% CI 2.060–20.902, P = 0.001) and MCP-1 (OR = 1.060, 95% CI 1.026–1.095, P < 0.001) were risk factors in the development of T2DKD. Receiver operating characteristic curve analysis showed that the area under curve of NLR and MCP-1 in diagnosing T2DKD were 0.760 (95% CI 0.6577–0.863, P < 0.001) and 0.862 (95% CI 0.7787–0.937, P < 0.001). Therefore, the inflammatory markers NLR and MCP-1 are risk factors affecting the development of T2DKD, which of clinical value may be used as novel markers of T2DKD.

Acute kidney injury (AKI) and chronic kidney disease (CKD) are closely interrelated renal disorders, where AKI frequently progresses to CKD, resulting in irreversible loss of renal function. In recent years, the roles of the NLRP3 inflammasome and mitophagy in the AKI-to-CKD transition have attracted significant attention. As a crucial component of the innate immune system, the NLRP3 inflammasome promotes AKI-to-CKD progression by mediating inflammatory responses and cellular pyroptosis during renal injury. Conversely, mitophagy exerts renoprotective effects through the selective removal of damaged mitochondria, maintenance of cellular homeostasis, and alleviation of inflammation and oxidative stress. Studies demonstrate that NLRP3 activation is closely associated with mitochondrial dysfunction, while mitophagy can suppress NLRP3 activation by clearing damaged mitochondria, establishing a negative feedback regulatory mechanism. During the AKI phase, mitochondrial damage and excessive NLRP3 activation exacerbate renal tubular epithelial cell injury and inflammatory responses. Concurrently, persistent NLRP3 activation and impaired mitophagy lead to chronic inflammation and fibrosis, accelerating the transition from AKI to CKD. Therefore, targeting the NLRP3 inflammasome and modulating mitophagy may emerge as novel therapeutic strategies for AKI-to-CKD transition. This review focuses on elucidating the molecular mechanisms between mitophagy and the NLRP3 inflammasome, along with related targeted therapies, to provide new insights for preventing AKI progression to CKD.