Kidney

  • Article
    | Open Access

    Necroptosis, a form of cell death, occurs in acute renal injury. Here, the authors show that ferroptosis—a form of cell death dependent on iron - also occurs during acute kidney injury, and show that an inhibitor of ferroptosis can improve survival in a mouse model of acute kidney damage.

    • Wulf Tonnus
    • , Claudia Meyer
    •  & Andreas Linkermann
  • Article
    | Open Access

    Kidney intercalated cells are involved in acid-base homeostasis in the kidneys. Here, the authors use single cell transcriptomics and find that interalated cells exhibit a transcriptional response conducive to defense and can engulf and acidify internalized bacteria, similarly to professional phagocytes.

    • Vijay Saxena
    • , Hongyu Gao
    •  & Andrew L. Schwaderer
  • Review Article
    | Open Access

    Hypertension is one of the most important risk factors for cardiovascular disease. The kidneys, which have a very high metabolic rate, play a fundamental role in blood pressure regulation. In this review, the authors discuss recent studies on the role of renal metabolism in the development of hypertension.

    • Zhongmin Tian
    •  & Mingyu Liang
  • Article
    | Open Access

    DsbA-L upregulation prevents lipid-induced renal injury in diabetic nephropathy. Here, the authors show that DsbA-L knockout attenuates tubulointerstitial fibrosis in mice, and show that this occurs via activation of Smad3 and p53, which result in modulation of CTGF, a regulator of kidney fibrosis.

    • Xiaozhou Li
    • , Jian Pan
    •  & Dongshan Zhang
  • Article
    | Open Access

    Salt levels in culture affect the polarisation of Th17 cells, which normally protect the host from fungal and bacterial infections. Here, the authors study patients with salt-losing tubulopathies (SLT) to find that, while Th17 immunity is dampened in SLT patients, their Th17-inducing signaling pathways are intact and can be reinvigorated by exogenous salt.

    • Rhys D. R. Evans
    • , Marilina Antonelou
    •  & Alan D. Salama
  • Article
    | Open Access

    Ketamine is a general anesthetic that is used also as an anti-depressant, but its use is associated with cystitis. Here, the authors show that ketamine is an antagonist of the Cav1.2 channel in bladder smooth muscle cells, that ablation of this channel in mice mimics the cystitis induced by ketamine, and show that this effect can be abrogated by an agonist of this ion channel.

    • Huan Chen
    • , David H. Vandorpe
    •  & Weiqun Yu
  • Article
    | Open Access

    The kidney is vascularized with highly specialized and zonated endothelial cells that are essential for its filtration function. Here, Barry et al. provide a single-cell RNA sequencing analysis of the kidney vasculature that highlights its transcriptional heterogeneity and uncovers pathways important for its development and function.

    • David M. Barry
    • , Elizabeth A. McMillan
    •  & Shahin Rafii
  • Article
    | Open Access

    How reproducible human kidney organoids derived from different iPSC lines are, and how faithful they are to human kidney tissue remain unclear. Here, the authors use four human iPSC lines to derive kidney organoids and show how organoid composition is reproducible, comparable to human tissue and of improved quality after transplantation.

    • Ayshwarya Subramanian
    • , Eriene-Heidi Sidhom
    •  & Anna Greka
  • Article
    | Open Access

    Persistently low levels of estimated glomerular filtration rate (eGFR) are a biomarker of chronic kidney disease. Here, the authors reinterpret the genetic architecture of kidney function across ancestries, to identify not only genes, but the tissue and anatomical contexts of renal homeostasis.

    • Jacklyn N. Hellwege
    • , Digna R. Velez Edwards
    •  & Adriana M. Hung
  • Article
    | Open Access

    Levels of sodium and potassium in urine are associated with cardiovascular traits. Here, Pazoki et al. perform genome-wide association studies for urinary sodium and potassium secretion and identify 50 and 13 novel loci, respectively, some of which show a potential causal relationship with blood pressure based on MR analysis.

    • Raha Pazoki
    • , Evangelos Evangelou
    •  & Abbas Dehghan
  • Article
    | Open Access

    The glomerular filtration barrier is a complex structure in charge of renal ultrafiltration. Here the authors present a glomerulus-on-a-chip for disease modelling and high-throughput drug screening where human podocytes and human glomerular endothelial cells are separated by an extracellular matrix resembling the in vivo basement membrane.

    • Astgik Petrosyan
    • , Paolo Cravedi
    •  & Stefano Da Sacco
  • Article
    | Open Access

    Single-cell studies in solid tissues remain challenging and have benefited from the development of single-nuclei RNA sequencing strategies. Here Lake et al. apply single-nucleus RNA sequencing to human kidney tissues to provide a comprehensive molecular and cellular atlas of the human kidney, with potential implications for the understanding of kidney physiology and disease.

    • Blue B. Lake
    • , Song Chen
    •  & Sanjay Jain
  • Article
    | Open Access

    In vivo decorporation of U(VI) from bones is an unsolved challenge because of the formation of stable uranium phosphate complexes. Here, the authors develop a hydroxypyridonone-based ligand with strong uranium complexation and low cytotoxicity. They find this ligand effectively removes uranium from kidney and bones in mice, and is suitable for oral administration.

    • Xiaomei Wang
    • , Xing Dai
    •  & Shuao Wang
  • Article
    | Open Access

    Sphingomyelin phosphodiesterase acid-like 3b (SMPDL3b) is a lipid raft enzyme known to affect membrane lipid composition. Here, Mitrofanova et al. show that increased expression of SMPDL3b in diabetes impairs insulin signaling and ceramide-1-phosphate (C1P) availability in podocytes, and that C1P supplementation protects mice from diabetic kidney disease.

    • A. Mitrofanova
    • , S. K. Mallela
    •  & A. Fornoni
  • Article
    | Open Access

    Kinase inhibitors used in chemotherapy are known for their adverse effects on kidney physiology. Here, Calizo et al. show that dasatinib is associated with a higher risk of glomerular toxicity compared to other kinase inhibitors, due to deleterious effects on cytoskeletal biomechanics in podocytes.

    • Rhodora C. Calizo
    • , Smiti Bhattacharya
    •  & Evren U. Azeloglu
  • Article
    | Open Access

    The use of pluripotent-stem cell derived organs for transplantation would be promising, if organs can be grown in a suitable host. Here, the authors use interspecific blastocyst complementation to generate a mouse pluripotent stem cell-derived kidney in anephric Sall1 mutant rats.

    • Teppei Goto
    • , Hiromasa Hara
    •  & Masumi Hirabayashi
  • Article
    | Open Access

    Nephrogenesis ceases after postnatal day 2 in the mouse or after the 36th week of gestation in humans, but how this is regulated is unclear. Here, the authors identify a role for the RNA-binding protein Lin28 and suppression of let-7 microRNA in regulating the duration of nephrogenesis.

    • Alena V. Yermalovich
    • , Jihan K. Osborne
    •  & George Q. Daley
  • Article
    | Open Access

    Cubilin and the transmembrane protein amnionless (AMN) form the endocytic receptor cubam that is essential for intestinal vitamin B12 uptake. Here the authors present the 2.3 Å crystal structure of AMN in complex with the amino-terminal region of cubilin and discuss cubam architecture and disease causing mutations.

    • Casper Larsen
    • , Anders Etzerodt
    •  & Christian Brix Folsted Andersen
  • Article
    | Open Access

    The molecular mechanisms that underlie associations in GWAS, incl. chronic kidney disease (CKD), are largely unknown. Here, the authors perform an integrative analysis of genetic, transcriptomic and epigenomic data from human kidney to pinpoint plausible molecular pathways of CKD genetic associations.

    • Xiaoguang Xu
    • , James M. Eales
    •  & Maciej Tomaszewski
  • Article
    | Open Access

    Elevated serum urate levels are a risk factor for gout. Here, Tin et al. perform whole-exome sequencing in 19,517 individuals and detect low-frequency genetic variants in urate transporter genes, SLC22A12 and SLC2A9, associated with serum urate levels and confirm their damaging nature in vitro and in silico.

    • Adrienne Tin
    • , Yong Li
    •  & Anna Köttgen
  • Article
    | Open Access

    Injuries in the embryonal kidney can be repaired by a cell migratory response but how this is regulated at a molecular level is unclear. Here, the authors show in mice that deletion of Cxcl12 and Myc delays pronephros injury repair by changing mitochondrial metabolism and glycolysis.

    • Toma A. Yakulov
    • , Abhijeet P. Todkar
    •  & Gerd Walz
  • Article
    | Open Access

    Patients with diabetic nephropathy suffer from impaired albumin reabsorption by proximal tubular epithelial cells. Here authors use diabetic and transgenic mouse models and in vitro models to show the cause for this lies in the down regulation and internalization of the ion channels, ORAI1-3.

    • Bo Zeng
    • , Gui-Lan Chen
    •  & Shang-Zhong Xu
  • Article
    | Open Access

    Nrf2 regulates oxidative and electrophilic stress responses by modulating the expression of enzymes involved in detoxification pathways. Here Suzukiet al. show that Nrf2 activation in early tubular development promotes nephrogenic diabetes insipidus by regulating aquaporin 2 expression and trafficking and water permeability.

    • Takafumi Suzuki
    • , Shiori Seki
    •  & Masayuki Yamamoto
  • Article
    | Open Access

    The polyol pathway, which converts glucose into sorbitol and fructose, is active in chronic conditions like hepatic steatosis and chronic kidney disease. Here, Andres-Hernandoet al. show that fructose production promotes renal injury and fructokinase inhibition protects against kidney damage during ischaemic acute kidney disease.

    • Ana Andres-Hernando
    • , Nanxing Li
    •  & Miguel A. Lanaspa
  • Article
    | Open Access

    T cells contribute to development of high blood pressure but their role in salt-sensitive hypertension is less clear. Liuet al. show that CD8+ T cells upregulate and activate Na-Cl co-transporter NCC in distal convoluted tubules via direct cell-cell contact and ROS-Src activation, leading to Na+retention and salt-sensitive hypertension.

    • Yunmeng Liu
    • , Tonya M. Rafferty
    •  & Shengyu Mu
  • Article
    | Open Access

    The water channel AQP2 mediates the concentration of urine in the kidney. Here Ando et al. show that Wnt5 promotes collecting duct permeability by regulating AQP2 expression and localization through activation of the calmodulin/calcineurin signalling pathway.

    • Fumiaki Ando
    • , Eisei Sohara
    •  & Shinichi Uchida
  • Article
    | Open Access

    Iron overload can be either hereditary or acquired via transfusions, and current treatments include the use of iron chelators that have adverse effects in some patients. Here the authors modify siderocalin to enhance iron excretion in urine, and demonstrate therapeutic efficacy in iron overload mouse models.

    • Jonathan Barasch
    • , Maria Hollmen
    •  & Andong Qiu
  • Article
    | Open Access

    Branching morphogenesis is essential for the formation of most epithelial organs. Here, the authors show that Neurofibromatosis 2 (NF2), the Hippo pathway kinases LATS1 and LATS2, and the transcriptional co-activators YAP and TAZ control tip identity, RET signalling and branching morphogenesis in the mouse kidney.

    • Antoine Reginensi
    • , Leonie Enderle
    •  & Helen McNeill
  • Article
    | Open Access

    Diabetic kidney disease is associated with ER stress in podocytes. Here the authors use various genetically modified mouse models to study ER-stress-related signalling pathways and propose a mechanistic framework that links insulin signalling with ER stress in podocytes of diabetic mice.

    • Thati Madhusudhan
    • , Hongjie Wang
    •  & Berend Isermann
  • Article |

    The transcription factor Wilms’ tumour 1 (WT1) regulates kidney development, and Wt1 mutations are associated with renal cancer. Here the authors identify WT1 target genes in renal progenitors during early kidney development in mouse embryos and show that loss of Wt1suppresses FGF and induces BMP signalling.

    • Fariba Jian Motamedi
    • , Danielle A. Badro
    •  & Andreas Schedl
  • Article |

    Loss-of-function mutations in PKD1, the gene encoding the plasma membrane receptor Polycystin-1, lead to renal cyst formation in polycystic kidney disease. Here, Castelli et al. show that Polycystin-1 interacts with the Par3 polarity complex and has a role in the morphogenesis of kidney tubules during mouse development.

    • Maddalena Castelli
    • , Manila Boca
    •  & Alessandra Boletta
  • Article
    | Open Access

    Poor maternal nutrition is known to affect fetal kidney development. This study shows that the sodium potassium ATPase ligand, ouabain, protects kidneys from cell death induced by serum starvationin vitro and from abnormal kidney development due to a low-protein diet in vivo.

    • Juan Li
    • , Georgiy R. Khodus
    •  & Anita Aperia