Diabetic kidney disease (DKD) is a long-term and serious complication of diabetes that affects millions of people worldwide. It is characterized by proteinuria, glomerular damage, and renal fibrosis, leading to end-stage renal disease, and the pathogenesis is complex and involves multiple cellular and molecular mechanisms. Among three kinds of intraglomerular cells including podocytes, glomerular endothelial cells (GECs) and mesangial cells (MCs), the alterations in one cell type can produce changes in the others. The cell-to-cell crosstalk plays a crucial role in maintaining the glomerular filtration barrier (GFB) and homeostasis. In this review, we summarized the recent advances in understanding the pathological changes and interactions of these three types of cells in DKD and then focused on the signaling pathways and factors that mediate the crosstalk, such as angiopoietins, vascular endothelial growth factors, transforming growth factor-β, Krüppel-like factors, retinoic acid receptor response protein 1 and exosomes, etc. Furthermore, we also simply introduce the application of the latest technologies in studying cell interactions within glomerular cells and new promising mediators for cell crosstalk in DKD. In conclusion, this review provides a comprehensive and updated overview of the glomerular crosstalk in DKD and highlights its importance for the development of novel intervention approaches.

Systemic lupus erythematosus (SLE) is a systemic autoimmune disorder caused by the loss of tolerance to endogenous nuclear antigens such as double‑stranded DNA, leading to the proliferation of T cells and subsequent activation of B cells, which results in serious organ damage and life‑threatening complications such as lupus nephritis. Lupus nephritis (LN) develops as a frequent complication of SLE, accounting for >60% of SLE cases, and is characterized by proteinuria and heterogeneous histopathological findings. Glomerular injury serves a role in proteinuria as podocyte damage is the leading contributor. Numerous studies have reported that podocytes are involved in the immune response that promotes LN progression. In LN, immune complex deposition stimulates dendritic cells to secrete inflammatory cytokines that activate T cells and B cells. B cells secrete autoantibodies that attack and damage the renal podocytes, leading to renal podocyte injury. The injured podocytes trigger inflammatory cells through the expression of toll‑like receptors and trigger T cells through major histocompatibility complexes and CD86, thereby participating in the local immune response and the exacerbation of podocyte injury. Based on the existing literature, the present review summarizes the research progress of podocytes in LN under the local immune microenvironment of the kidney, explores the mechanism of podocyte injury under the immune microenvironment, and evaluates podocytes as a potential therapeutic target for LN.

Glomerular diseases are major components of kidney disease, mainly manifested as podocyte disease, immune complex-associated glomerulonephritis, and renal autoimmune disease. They are the third leading cause of end-stage renal disease, especially in younger populations. Podocyte death or shedding is a key factor in the progression of glomerular diseases, and autophagy plays an important role in maintaining podocyte homeostasis. Dysfunction of autophagy has been associated with the progression of various glomerular diseases. Modulation of autophagy has been shown to play a protective role in experimental models of glomerular diseases, suggesting that autophagy is a potential therapeutic target for glomerular diseases. Traditional Chinese medicine (TCM) has unique advantages in the treatment of kidney disease. In vivo and in vitro studies have shown that TCM compounds can reduce podocyte apoptosis, inhibit inflammation, improve endoplasmic reticulum stress and oxidative stress responses, and play an active role via autophagy. This review summarizes the roles of autophagy in glomerular diseases and provides evidence that TCM compounds can regulate autophagy through different signaling pathways to ameliorate glomerular diseases.

Focal segmental glomerulosclerosis (FSGS) is a histological lesion with a variety of potential causes, including rare variants of podocyte-related genes. Recently, it has been found that variants in the TBC1D8B gene on the X chromosome can lead to early-onset focal segmental glomerulosclerosis and steroid-resistant nephrotic syndrome by affecting endocytosis and recycling of nephrin. Here, we report a 19-year-old Chinese patient with nephrotic syndrome and normal kidney function. He had a complete remission of nephrotic syndrome after full-dose prednisone and cyclosporine treatment. Unfortunately, a relapse of nephrotic syndrome occurred during prednisone tapering. Focal segmental glomerulosclerosis was proven by a kidney biopsy, and a hemizygous pathogenic variant located in the TBC (Tre-2-Bub2-Cdc16) domain of TBC1D8B was detected by whole-exome sequencing. By comparing our case with reports of other patients with TBC1D8B variants, we suggest possible genotype-phenotype correlations. To our knowledge, this is the first report identifying a pathogenetic variant in the TBC domain of TBC1D8B in an adult-onset focal segmental glomerulosclerosis patient with steroid-dependent NS. With this report, we broaden the clinical and genetic spectrum of X-linked genetic FSGS.

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Collapsing glomerulopathy (CG) is a clinicopathologic entity characterized by segmentar or global collapse of the glomerulus and hypertrophy and hyperplasia of podocytes. The Columbia classification of 2004 classified CG as a histological subtype of focal segmental glomerulosclerosis (FSGS). A growing number of studies have demonstrated a high prevalence of CG in many countries, especially among populations with a higher proportion of people with African descent. The present study is a narrative review of articles extracted from PubMed, Medline, and Scielo databases from September 1, 2020 to December 31, 2021. We have focused on populational studies (specially cross-sectional and cohort articles). CG is defined as a podocytopathy with a distinct pathogenesis characterized by strong podocyte proliferative activity. The most significant risk factors for CG include APOL1 gene mutations and infections with human immunodeficiency virus and severe acute respiratory syndrome coronavirus 2. CG typically presents with more severe symptoms and greater renal damage. The prognosis is notably worse than that of other FSGS subtypes.

Traditionally collapsing glomerulopathy (CG) is associated with medications, autoimmune disease, viral infection and the APOL1 gene variant seen in blacks/African Americans. Most reported cases of acute kidney injury (AKI) in COVID-19 infected individuals have been in individuals without prior CKD. In this report, we present a 49-year-old African American female with a past medical history of chronic kidney disease (CKD) stage 4, hypertension, type 2 diabetes mellitus, recent COVID-19 infection, and a repeat positive blood test for COVID-19 more than 21 days after the initial result, who presented with an AKI on CKD. Renal biopsy revealed a collapsing glomerulopathy. She was started on hemodialysis and did not receive immunosuppressive therapy due to the advanced scaring seen on the renal biopsy. Concerning the pathophysiology of COVID-19-associated CG, researchers have postulated different mechanisms such as a direct cytopathic effect of the virus on podocytes, immune dysregulation, and fluid imbalance. This is one of a few cases of AKI on CKD due to CG related to COVID-19. The mechanism of CG was, however, unclear. Currently, there is no specific interventions to prevent the development of CG in patients with COVID-19 infection. Further studies should investigate measures to prevent the development of CG.

Steroid-resistant nephrotic syndrome (SRNS) constitutes the second most frequent cause of chronic kidney disease in childhood. The etiology of SRNS remains largely unknown and no standardized treatment exists. Recent advances in genomics have helped to build understanding of the molecular mechanisms and pathogenesis of the disease. The genetic polymorphisms in genes encoding proteins which are involved in the pharmacokinetics and pharmacodynamics of glucocorticoids (GCs) partially account for the different responses between patients with nephrotic syndrome. More importantly, single-gene causation in podocytes-associated proteins was found in approximately 30% of SRNS patients. Some potential biomarkers have been tested for their abilities to discriminate against pediatric patients who are sensitive to GCs treatment and patients who are resistant to the same therapy. This article reviews the recent findings on genetic mechanisms, predictive biomarkers and current therapies for SRNS with the goal to improve the management of children with this syndrome.

Psoriasis is a chronic inflammatory dermatosis with complex genetic basis supported by family investigation. Renal involvement in psoriasis is sparsely studied and its pathogenesis is still unclear.
We describe the case of a 7-year-old boy presented new onset of nephropathy two weeks after a flare-up of psoriasis. His mother had a long history of psoriasis without abnormal urinalysis records. The case showed non-nephrotic range proteinuria, microscopic hematuria without any other abnormal results including renal function, complement cascade, and ultrasound. Renal pathological demonstrated the diagnosis of C3 glomerulonephritis (C3GN) showing mesangial proliferative glomerulonephritis with C3 staining only, effacement of podocyte process and intramembranous electron dense deposit by electric microscopy. Parent-child trio WES performed to screening the common variants of psoriasis susceptibility locus and also the rare variants associated with C3GN. We identified a missense single nucleotide polymorphism of CARD14 (*607211, rs34367357, p.Val585Ile) carried by the proband and his mother. Meta-analysis proved the association of rs34367357 and psoriasis (p = 0.006, OR = 1.23). A hemizygouse mutation of CLCN5 (*300008, c.1904A＞G,p.Asn635Ser) was identified for diagnosis of Dent disease (*300009).
The case highlights the genetic study is necessary to facilitate disease differentiation in new onset of nephropathy with psoriasis in children.

Idiopathic membranous nephropathy (IMN) is one of the main types of chronic kidney disease in adults and one of the most common causes of end‑stage renal disease. In recent years, the morbidity of IMN among primary glomerular diseases has markedly increased, while the pathogenesis of the disease remains unclear. To address this, a number of experimental models, including Heymann nephritis, anti‑thrombospondin type‑1 domain‑containing 7A antibody‑induced IMN, cationic bovine serum albumin, anti‑human podocyte antibodies and zymosan‑activated serum‑induced C5b‑9, have been established. This review comprehensively summarized the available animal and cell models for IMN. The limitations and advantages of the current models were discussed and two improved models were introduced to facilitate the selection of an appropriate model for further studies on IMN.