Single Cell RNA Sequencing Identifies a Unique Inflammatory Macrophage Subset as a Druggable Target for Alleviating Acute Kidney Injury.

Acute kidney injury (AKI) is a complex clinical disorder associated with poor outcomes. Targeted regulation of the degree of inflammation has been a potential strategy for AKI management. Macrophages are the main effector cells of kidney inflammation. However, macrophage heterogeneity in ischemia reperfusion injury induced AKI (IRI-AKI) remains unclear. Using single-cell RNA sequencing of the mononuclear phagocytic system in the murine IRI model, the authors demonstrate the complementary roles of kidney resident macrophages (KRMs) and monocyte-derived infiltrated macrophages (IMs) in modulating tissue inflammation and promoting tissue repair. A unique population of S100a9hi Ly6chi IMs is identified as an early responder to AKI, mediating the initiation and amplification of kidney inflammation. Kidney infiltration of S100A8/A9+ macrophages and the relevance of renal S100A8/A9 to tissue injury is confirmed in human AKI. Targeting the S100a8/a9 signaling with small-molecule inhibitors exhibits renal protective effects represented by improved renal function and reduced mortality in bilateral IRI model, and decreased inflammatory response, ameliorated kidney injury, and improved long-term outcome with decreased renal fibrosis in the unilateral IRI model. The findings support S100A8/A9 blockade as a feasible and clinically relevant therapy potentially waiting for translation in human AKI.

Perspectives on acute kidney injury strategy in China.

Acute kidney injury (AKI) has imposed a heavy disease burden in China, with substantial underdiagnosis and undertreatment. The incidence, cause and outcome of patients with AKI vary according to different geographic regions and economic development status; therefore, regional improvement strategies are needed. Defining the etiology of AKI is critical in making the proper therapeutic regimen, and a multidisciplinary cooperative AKI team is essential in order to establish the early diagnosis and proper management of patients with AKI.

Tubulointerstitial nephritis-induced hypophosphatemic osteomalacia in Sjögren's syndrome: a case report and review of the literature.

Sjögren's syndrome (SS) is a chronic autoimmune inflammatory disease that typically affects the salivary and lacrimal glands. Renal involvement is relatively uncommon and may precede other complaints. Tubulointestitial nephritis (TIN) is the most common renal involvement in SS. Osteomalacia occurring as the first manifestation of renal tubular disorder due to SS is very rare. We report a 39-year-old male who presented with polydipsia, polyuria, and multiple bone pain. Bone density test showed severe osteoporosis, and laboratory findings suggested hypokalemia, hypophosphatemia, and vitamin D deficiency, which supported the diagnosis of hypophosphatemic osteomalacia. He had nephrogenic loss of phosphate and potassium, tubular acidification, and concentration dysfunction. And, the diagnosis of chronic TIN was subsequently confirmed by renal biopsy. The patient reported dry mouth and physical examination showed multiple dental caries. Xerophthalmia, abnormal morphology, and function of the salivary glands by sonography and scintigraphy, together with positive anti-SSA and anti-SSB, confirmed the diagnosis of SS. The TIN indicated SS as the underlying cause of osteomalacia. After taking supplements of potassium, phosphate, vitamin D, and sodium bicarbonate for 1 month, bone pain was alleviated and serological potassium and phosphorus were also back to normal. In conclusion, renal involvement in SS may be latent and precede the typical sicca symptoms. Osteomalacia can be the first manifestation of renal disorder due to SS. Therefore, autoantibody investigations as well as the lacrimal and salivary gland examinations for SS should be considered and performed for suspected patients.