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Kidney development requires the coordinated growth and differentiation of multiple cells. Despite recent single cell profiles in nephrogenesis research, tools for data analysis are rapidly developing, and offer an opportunity to gain additional insight into kidney development. In this study, single-cell RNA sequencing data obtained from embryonic mouse kidney were re-analyzed. Manifold learning based on partition-based graph-abstraction coordinated cells, reflecting their expected lineage relationships. Consequently, the coordination in combination with ForceAtlas2 enabled the inference of parietal epithelial cells of Bowman’s capsule and the inference of cells involved in the developmental process from the S-shaped body to each nephron segment. RNA velocity suggested developmental sequences of proximal tubules and podocytes. In combination with a Markov chain algorithm, RNA velocity suggested the self-renewal processes of nephron progenitors. NicheNet analyses suggested that not only cells belonging to ureteric bud and stroma, but also endothelial cells, macrophages, and pericytes may contribute to the differentiation of cells from nephron progenitors. Organ culture of embryonic mouse kidney demonstrated that nerve growth factor, one of the nephrogenesis-related factors inferred by NicheNet, contributed to mitochondrial biogenesis in developing distal tubules. These approaches suggested previously unrecognized aspects of the underlying mechanisms for kidney development.

analyses of foot processes, mitochondria, and basement membranes by structured illumination microscopy using elastica Massonand periodic-acid-Schiff-stained kidney sections, Kidney International Reports (2021), doi:

Dietary phosphate intake is closely correlated with protein intake. However, the effects of the latter on phosphate-induced organ injuries remain uncertain. Herein, we investigated the effects of low (10.8%), moderate (23.0%), and high (35.2%) dietary casein and egg albumin administration on phosphate-induced organ injuries in rats. The moderate and high casein levels suppressed renal tubulointerstitial fibrosis and maintained mitochondrial integrity in the kidney. The serum creatinine levels were suppressed only in the high casein group. Phosphate-induced muscle weakness was also ameliorated by high dietary casein. The urinary and fecal phosphate levels in the early experiment stage showed that dietary casein did not affect phosphate absorption from the intestine. High dietary egg albumin showed similar kidney protective effects, while the egg albumin effects on muscle weakness were only marginally significant. As the plasma branched-chain amino acid levels were elevated in casein- and egg albumin-fed rats, we analyzed their effects. Dietary supplementation of 10% branched-chain amino acids suppressed phosphate-induced kidney injury and muscle weakness. Although dietary protein restriction is recommended in cases of chronic kidney disease, our findings indicate that the dietary casein, egg albumin, and branched-chain amino acid effects might be reconsidered in the era of a phosphate-enriched diet.

Background Phospholipase A2 receptor 1 (PLA2R1) and thrombospondin type-1 domain-containing 7A (THSD7A) are the two major pathogenic antigens for membranous nephropathy (MN). It has been reported that THSD7A-associated MN has a higher prevalence of comorbid malignancy than PLA2R1-associated MN. Here we present a case of MN whose etiology might change from idiopathic to malignancy-associated MN during the patient’s clinical course. Case presentation A 68-year-old man with nephrotic syndrome was diagnosed with MN by renal biopsy. Immunohistochemistry showed that the kidney specimen was negative for THSD7A. The first course of corticosteroid therapy achieved partial remission; however, nephrotic syndrome recurred 1 year later. Two years later, his abdominal echography revealed a urinary bladder tumor, but he did not wish to undergo additional diagnostic examinations. Because his proteinuria increased consecutively, corticosteroid therapy was resumed, but it failed to achieve remission. Another kidney biopsy was performed and revealed MN with positive staining for THSD7A. PLA2R1 staining levels were negative for both first and second biopsies. Because his bladder tumor had gradually enlarged, he agreed to undergo bladder tumor resection. Pathological examination indicated that the tumor was THDS7A-positive bladder cancer. Subsequently, his proteinuria decreased and remained in remission. Conclusions This case suggests that the etiology of MN might be altered during the therapeutic course. Intensive screening for malignancy may be preferable in patients with unexpected recurrence of proteinuria and/or change in therapy response.