Journal of The American Society of Nephrology最新文献

Background: Cardiac surgery-associated acute kidney injury is a common serious complication after cardiac surgery. Currently, there are no specific pharmacological therapies. Our understanding of its pathophysiology remains preliminary.

Methods: A total of 2504 patients with and without acute kidney injury (AKI) following cardiac surgery were enrolled. High-performance liquid chromatography coupled with mass spectrometry was used for untargeted analysis of metabolites in plasma, identifying significant differential metabolites. Subsequently, a tandem liquid chromatography-mass spectrometry-based approach using isotope-labeled standard addition was performed for targeted analysis of the metabolic marker N-acetyl-tryptophan. The function of N-acetyl-tryptophan was determined using different kidney injury mouse models and epithelial cellular models. Transcriptome sequencing, surface plasmon resonance and protein mutation were employed to explore the mechanism of N-acetyl-tryptophan on the kidney.

Results: We identified a total of 32 differential metabolites related to AKI occurrence based on a cohort of 1042 patients. Among them, N-acetyl-tryptophan was elevated in plasma of patients with cardiac surgery-associated acute kidney injury compared with those who do not develop AKI after cardiac surgery. The higher level of N-acetyl-tryptophan in plasma was confirmed by accurate targeted quantification. N-acetyl-tryptophan exhibited kidney protective effects in ischemia/reperfusion-, cisplatin-, and unilateral ureteral obstruction-induced kidney injury mouse models. Mechanistically, N-acetyl-tryptophan exerted kidney protective effects by interacting with KEAP1 at 483 and 508 sites, resulting in Nrf2 nuclear translocation and the transcription of proteasome genes.

Conclusions: N-acetyl-tryptophan plays a key role in kidney protection.

Background: People with chronic kidney disease (CKD) have a higher risk for progression to tuberculosis disease following infection with Mycobacterium tuberculosis. We produced a nationwide incidence estimate and description of tuberculosis among people with kidney failure.

Methods: We completed a cross-sectional descriptive analysis of people with a reported case of tuberculosis in the United States between 2010 and 2021. We stratified all people with tuberculosis by reported kidney failure status. The primary outcome was tuberculosis incidence among people with kidney failure. We also compared characteristics of people with tuberculosis by reported kidney failure status.

Results: Approximately 3% of people (2,892 of 111,155) diagnosed with tuberculosis between 2010 and 2021 also had kidney failure. Annual tuberculosis incidence ranged from 26.1 to 45.4 per 100,000 people with kidney failure and 2.1 to 3.5 per 100,000 people without kidney failure. Among people with kidney failure, 924 (32%) had extrapulmonary tuberculosis only, and nearly 40% died: 286 were diagnosed with tuberculosis after death, and 792 died during treatment. People with tuberculosis and kidney failure had approximately twice the prevalence of a false-negative tuberculin skin test result (39%) compared to people with tuberculosis alone (20%).

Conclusions: Tuberculosis incidence among people with kidney failure between 2010 and 2021 in the United States was 10-fold that among people without kidney failure.

Background: The parathyroid calcium-sensing receptor (CASR) controls the release of parathyroid hormone (PTH) in response to changes in serum calcium levels. Activation of the renal CASR increases urinary calcium excretion and is particularly important when CASR-dependent reductions in PTH fail to lower serum calcium. However, the role of the renal CASR in protecting against hypercalcemia and the direct effects of chronic CASR activation on tubular calcium handling remains to be fully elucidated.

Methods: Experimental hypercalcemia was induced using the Vitamin D analog (Dihydrotachysterol, DHT) in mice with Ksp-Cre dependent deletion of the Casr (Ksp-Casr) in kidney with Cre negative littermates (WT) serving as controls. Urinary and fecal electrolyte determinations, dual-energy x-ray absorptiometry, molecular and biochemical evaluation, and in vitro tubule microperfusion were performed in both sexes.

Results: Ksp-Cre-driven Casr deletion strongly reduced CASR abundance in the thick ascending limb (TAL). At baseline, no marked differences were detected in electrolyte handling and tubular permeability characteristics across the TAL. 3 days of DHT administration induced hypercalcemia in both WT and Ksp-Casr mice. However, while WT mice developed hypercalciuria, this response was absent in Ksp-Casr mice. Urinary excretion of magnesium and other electrolytes did not differ between hypercalcemic WT and Ksp-Casr mice. Intestinal electrolyte absorption was comparable between the two groups. Microperfusion of isolated cortical TALs revealed no baseline differences in the transepithelial voltage, resistance, or ion permeabilities. Following hypercalcemia, transepithelial resistance increased and calcium permeability markedly decreased in WT mice, but not in Ksp-Casr mice, with only minor alterations in magnesium permeability and no changes in transepithelial voltage.

Conclusions: In hypercalcemic mice, absence of the CASR in TAL prevented the increase in urinary calcium excretion. The CASR specifically regulated the paracellular permeability of the TAL, especially for calcium.