Clinical outcome in cardiac transplant recipients with chronic kidney disease under high dose and low dose everolimus therapy

2011 ◽  
Vol 59 (S 01) ◽  
Author(s):  
U Fuchs ◽  
A Zittermann ◽  
B Schulze ◽  
W Deyerling ◽  
K Hakim-Meibodi ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Clinical Outcome ◽  
Low Dose ◽  
High Dose ◽  
Cardiac Transplant ◽  
Transplant Recipients

scholarly journals Efficacy and Safety of Low-Dose Everolimus as Maintenance Immunosuppression in Cardiac Transplant Recipients

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Uwe Fuchs ◽  
Armin Zittermann ◽  
Uwe Schulz ◽  
Jan F. Gummert
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Primary Endpoint ◽  
Low Dose ◽  
Blood Levels ◽  
Cardiac Transplant ◽  
Transplant Recipients ◽  
Maintenance Immunosuppression ◽  
Trough Blood ◽  
Safety Parameters

For cardiac transplant (CTx) recipients, the recommended everolimus (EVL) dose is 0.75 mg bid or 1.5 mg bid and the target trough blood level is 3–8μg/L. We studied a cohort of 56 CTx patients with chronic kidney disease receiving 0.75 mg bid EVL to maintain blood levels of 5–8 ug/L (designated RD group) and a cohort of 51 CTx patients with chronic kidney disease receiving 0.5 mg bid to maintain blood levels of 3–5 ug/L (designated LD group). The primary endpoint was a composite of death, rejection and premature EVL discontinuation up to 1 year after introduction of EVL. The primary endpoint was reached by 32% of patients in the LD group and by 41.1% of patients in the RD group (). Biochemical safety parameters were comparable in both groups. Our results indicate that low-dose EVL may be as effective and safe as regular dose EVL.

scholarly journals Cyclophilin D Promotes Acute, but Not Chronic, Kidney Injury in a Mouse Model of Aristolochic Acid Toxicity

Toxins ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 700
Author(s):  
Khai Gene Leong ◽  
Elyce Ozols ◽  
John Kanellis ◽  
Frank Y. Ma ◽  
David J. Nikolic-Paterson
Keyword(s):  
Chronic Kidney Disease ◽  
Acute Kidney Injury ◽  
Cell Death ◽  
Kidney Disease ◽  
Low Dose ◽  
Aristolochic Acid ◽  
Chinese Herb ◽  
Kidney Injury ◽  
High Dose ◽  
Cyclophilin D

The plant-derived toxin, aristolochic acid (AA), is the cause of Chinese Herb Nephropathy and Balkan Nephropathy. Ingestion of high dose AA induces acute kidney injury, while chronic low dose ingestion leads to progressive kidney disease. Ingested AA is taken up by tubular epithelial cells of the kidney, leading to DNA damage and cell death. Cyclophilin D (CypD) participates in mitochondrial-dependent cell death, but whether this mechanism operates in acute or chronic AA-induced kidney injury is unknown. We addressed this question by exposing CypD-/- and wild type (WT) mice to acute high dose, or chronic low dose, AA. Administration of 5 mg/kg AA to WT mice induced acute kidney injury 3 days later, characterised by loss of kidney function, tubular cell damage and death, and neutrophil infiltration. All of these parameters were significantly reduced in CypD-/- mice. Chronic low dose (2 mg/kg AA) administration in WT mice resulted in chronic kidney disease with impaired renal function and renal fibrosis by day 28. However, CypD-/- mice were not protected from AA-induced chronic kidney disease. In conclusion, CypD facilitates AA-induced acute kidney damage, but CypD does not contribute to the transition of acute kidney injury to chronic kidney disease during ongoing AA exposure.

Transcriptomic Signatures of Exacerbated Progression in Leptospirosis Subclinical Chronic Kidney Disease with Secondary Nephrotoxic Injury

2021 ◽  
Author(s):  
Li-Fang Chou ◽  
TingWen Chen ◽  
Huan-Yu Yang ◽  
Ya-Chung Tian ◽  
Ming-Yang Chang ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Topoisomerase Ii ◽  
Low Dose ◽  
Expression Patterns ◽  
Kidney Injury ◽  
Differentially Expressed ◽  
High Dose ◽  
Integrin Linked Kinase ◽  
Topoisomerase Ii Α

High-incidence regions of Leptospirosis caused by Leptospira spp., coincide with chronic kidney disease. This study investigates whether asymptomatic leptospirosis is an emerging culprit that predispose to progressive chronic kidney disease when superimposed on secondary nephrotoxic injury. Kidney histology/function and whole-transcriptomic profiles were evaluated for leptospira-infected C57/BL6 mice with adenine-induced kidney injury. The extent of tubulointerstitial kidney lesions and the expression of inflammation/fibrosis genes in infected mice with low-dose (0.1%) adenine, particularly in high-dose (0.2%) adenine-fed superimposed on leptospira-infected mice, were significantly increased compared with mice following infection or adenine diet alone and the findings are consistent with renal transcriptome analysis. Pathway enrichment findings showed integrin β- and fibronectin-encoding genes had distinct expression within the integrin-linked kinase signaling pathway which were up-regulated in 0.2% adenine-fed leptospira-infected mice but not in 0.2% adenine-fed mice, indicating background subclinical leptospiral infection indeed enhanced subsequent secondary nephrotoxic kidney injury and potential pathogenic molecules associated with secondary nephrotoxic leptospirosis. Comparative analysis of gene-expression patterns with UUO-induced mouse renal fibrosis and patients with chronic kidney disease showed that differentially expressed orthologous genes such as hemoglobin α, PDZ binding kinase and DNA topoisomerase II α were identified in infected mice fed with low-dose and high-dose adenine, respectively, revealing differentially expressed signatures identical to those found in the datasets and may serve as markers of aggravated kidney progression. This study indicates that background subclinical leptospirosis, when subjected to various degrees of subsequent secondary nephrotoxic injury, may predispose to exacerbated fibrosis, mimicking the pathophysiological process of progressive chronic kidney disease.

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