Matrix metalloproteinase-7 (MMP-7) is a secreted zinc- and calcium-dependent endopeptidase that degrades a broad range of extracellular matrix substrates and additional substrates. MMP-7 playsa crucial role in a diverse array of cellular processes and appears to be a key regulator of fibrosis in several diseases, including pulmonary fibrosis, liver fibrosis, and cystic fibrosis. In particular, the relationship between MMP-7 and kidney fibrosis has attracted significant attention in recent years. Growing evidence indicates that MMP-7 plays an important role in the pathogenesis of kidney fibrosis. Here, we summarize the recent progress in the understanding of the role of MMP-7 in kidney fibrosis. In particular, we discuss how MMP-7 contributes to kidney fibrotic lesions via the following three pathways: epithelial-mesenchymal transition (EMT), transforming growth factor-beta (TGF-β) signaling, and extracellular matrix (ECM) deposition. Further dissection of the crosstalk among and regulation of these pathways will help clinicians and researchers develop effective therapeutic approaches for treating chronic kidney disease.

Dickkopf-related protein 3 (DKK3) is a secreted glycoprotein that has been implicated in the pathogenesis of a variety of diseases. Recent evidence suggests that urinary DKK3 may serve as a potential biomarker for monitoring kidney disease progression and assessing the effects of interventions. We review the biological role of DKK3 as an agonist in chronic kidney disease (CKD) and autosomal dominant polycystic kidney disease (ADPKD) and as an antagonist in idiopathic membranous nephropathy (IMN). In addition, we present the clinical applications of DKK3 in acute kidney disease and tubulointerstitial fibrosis, suggesting that urine DKK3 may be a potential biomarker for acute kidney disease and CKD. Further research into the mechanism of DKK3 and its use as a diagnostic tool, alone or in combination with other biomarkers, could prove clinically useful for better understanding the pathology of kidney diseases and improving early detection and treatment.

Over the past decade, the prevalence of obesity has increased, accompanied by a parallel increase in the prevalence of chronic kidney disease (CKD). Mounting evidence suggests that high body mass index (BMI) and obesity are important risk factors for CKD, but little is known about the mechanisms of obesity‐related kidney disease (ORKD). The NLRP3 inflammasome is a polyprotein complex that plays a crucial role in the inflammatory process, and numerous recent studies suggest that the NLRP3 inflammasome is involved in ORKD development and may serve as a key modulator of ORKD. Moreover, inhibiting activation of the NLRP3 inflammasome has been shown to attenuate ORKD. In this review, we summarize recent progress in understanding the link between the NLRP3 inflammasome and ORKD and discuss targeting the NLRP3 inflammasome as a novel therapeutic approach for ORKD.

Histone deacetylase 6 (HDAC6), a cytoplasmic enzyme that plays important roles in many biological processes, is one isoform of a family of HDAC enzymes that catalyse the removal of functional acetyl groups from proteins. HDAC6 stands out from the other members of this family because it almost exclusively deacetylates cytoplasmic proteins and exerts deacetylation-independent effects, which has led to the successful development of relatively isoform-specific inhibitors of its enzymatic action. Numerous studies have recently demonstrated that HDAC6 expression and activity are increased in kidney disease, such as autosomal dominant polycystic kidney disease (ADPKD), renal fibrosis, and acute kidney injury (AKI), among others. Moreover, HDAC6 inhibitors have been investigated for use in treating these diseases. In fact, HDAC6 inhibitors effectively limit the progression of kidney diseases, suggesting that targeting HDAC6 may provide a novel treatment approach. However, the primary challenge in developing HDAC6-targeted therapies is understanding how the renoprotective effect of NDAC6 inhibitors can be selectively harnessed. Here, we discuss the unique function of HDAC6 and recapitulate the alluring potential of its inhibitors in kidney diseases.

Normocytic normochromic anemia is a common complication of chronic kidney disease (CKD) and is associated with numerous adverse consequences. Certain symptoms previously attributed to CKD are now known to be a consequence of anemia. Anemia contributes to an increased cardiac output, and the development of left ventricular hypertrophy, angina and congestive heart failure, leading to high morbidity and mortality in patients with CKD. The multifunctional α-klotho (KL) protein, which is predominantly expressed in the kidneys, is associated with the occurrence of anemia in patients with CKD. The present review presents current evidence on the potential role of α-KL in renal anemia. Low expression of α-KL appears to improve anemia in patients with CKD, and has been hypothesized to be a compensatory mechanism to attenuate the effects of anemia in patients with CKD. Further understanding of the role of α-KL in renal anemia may offer novel insights into the treatment of patients with CKD complicated with anemia.