PMID- 37657768
OWN - NLM
STAT- MEDLINE
DCOM- 20231121
LR  - 20231122
IS  - 1523-1755 (Electronic)
IS  - 0085-2538 (Linking)
VI  - 104
IP  - 6
DP  - 2023 Dec
TI  - Post hoc analysis of the SONAR trial indicates that the endothelin receptor 
      antagonist atrasentan is associated with less pain in patients with type 2 
      diabetes and chronic kidney disease.
PG  - 1219-1226
LID - S0085-2538(23)00610-5 [pii]
LID - 10.1016/j.kint.2023.08.014 [doi]
AB  - Pain is prevalent among patients with diabetes and chronic kidney disease (CKD). 
      The management of chronic pain in these patients is limited by nephrotoxicity of 
      commonly used drugs including non-steroidal anti-inflammatory drugs (NSAIDs) and 
      opioids. Since previous studies implicated endothelin-1 in pain nociception, our 
      post hoc analysis of the SONAR trial assessed the association between the 
      endothelin receptor antagonist atrasentan and pain and prescription of 
      analgesics. SONAR was a randomized, double-blind, placebo-controlled clinical 
      trial that recruited participants with type 2 diabetes and CKD (estimated 
      glomerular filtration rate 25-75 ml/min/1.73 m(2); urinary albumin-to-creatinine 
      ratio 300-5000 mg/g). Participants were randomized to receive atrasentan or 
      placebo (1834 each arm). The main outcome was pain-related adverse events (AEs) 
      reported by investigators. We applied Cox regression to assess the effect of 
      atrasentan compared to placebo on the risk of the first reported pain-related AE 
      and, secondly, first prescription of analgesics. We used the Anderson-Gill method 
      to assess effects on all (first and subsequent) pain-related AEs. During 2.2-year 
      median follow-up, 1183 pain-related AEs occurred. Rates for the first 
      pain-related event were 138.2 and 170.2 per 1000 person-years in the atrasentan 
      and placebo group respectively (hazard ratio 0.82 [95% confidence interval 
      0.72-0.93]). Atrasentan also reduced the rate of all (first and subsequent) 
      pain-related AEs (rate ratio 0.80 [0.70-0.91]). These findings were similar after 
      accounting for competing risk of death (sub-hazard ratio 0.81 [0.71-0.92]). 
      Patients treated with atrasentan initiated fewer analgesics including NSAIDs and 
      opioids compared to placebo during follow-up (hazard ratio = 0.72 [0.60-0.88]). 
      Thus, atrasentan was associated with reduced pain-related events and pain-related 
      use of analgesics in carefully selected patients with type 2 diabetes and CKD.
CI  - Copyright (c) 2023 International Society of Nephrology. Published by Elsevier Inc. 
      All rights reserved.
FAU - Chan, Kam Wa
AU  - Chan KW
AD  - Department of Clinical Pharmacy and Pharmacology, University Medical Center 
      Groningen, University of Groningen, Groningen, The Netherlands; Division of 
      Nephrology, Department of Medicine, The University of Hong Kong, Hong Kong SAR; 
      School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR.
FAU - Smeijer, J David
AU  - Smeijer JD
AD  - Department of Clinical Pharmacy and Pharmacology, University Medical Center 
      Groningen, University of Groningen, Groningen, The Netherlands.
FAU - Schechter, Meir
AU  - Schechter M
AD  - Department of Clinical Pharmacy and Pharmacology, University Medical Center 
      Groningen, University of Groningen, Groningen, The Netherlands; Diabetes Unit, 
      Department of Endocrinology and Metabolism, Hadassah Medical Center, Jerusalem, 
      Israel; Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel.
FAU - Jongs, Niels
AU  - Jongs N
AD  - Department of Clinical Pharmacy and Pharmacology, University Medical Center 
      Groningen, University of Groningen, Groningen, The Netherlands.
FAU - Vart, Priya
AU  - Vart P
AD  - Department of Clinical Pharmacy and Pharmacology, University Medical Center 
      Groningen, University of Groningen, Groningen, The Netherlands.
FAU - Kohan, Donald E
AU  - Kohan DE
AD  - Division of Nephrology, University of Utah Health, Salt Lake City, Utah, USA.
FAU - Gansevoort, Ron T
AU  - Gansevoort RT
AD  - Department of Clinical Pharmacy and Pharmacology, University Medical Center 
      Groningen, University of Groningen, Groningen, The Netherlands.
FAU - Liew, Adrian
AU  - Liew A
AD  - Mount Elizabeth Novena Hospital, Singapore.
FAU - Tang, Sydney C W
AU  - Tang SCW
AD  - Division of Nephrology, Department of Medicine, The University of Hong Kong, Hong 
      Kong SAR.
FAU - Wanner, Christoph
AU  - Wanner C
AD  - Department of Medicine, Division of Nephrology, Wurzburg University Clinic, 
      Wurzburg, Germany; Department of Clinical Research and Epidemiology, Renal 
      Research Unit, Comprehensive Heart Failure Center, Wurzburg University, Wurzburg, 
      Germany.
FAU - de Zeeuw, Dick
AU  - de Zeeuw D
AD  - Department of Clinical Pharmacy and Pharmacology, University Medical Center 
      Groningen, University of Groningen, Groningen, The Netherlands.
FAU - Heerspink, Hiddo J L
AU  - Heerspink HJL
AD  - Department of Clinical Pharmacy and Pharmacology, University Medical Center 
      Groningen, University of Groningen, Groningen, The Netherlands; The George 
      Institute for Global Health, Sydney, New South Wales, Australia. Electronic 
      address: h.j.lambers.heerspink@umcg.nl.
LA  - eng
SI  - ClinicalTrials.gov/NCT01858532
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20230831
PL  - United States
TA  - Kidney Int
JT  - Kidney international
JID - 0323470
RN  - 0 (Anti-Inflammatory Agents, Non-Steroidal)
RN  - V6D7VK2215 (Atrasentan)
RN  - 0 (Endothelin Receptor Antagonists)
SB  - IM
CIN - Kidney Int. 2023 Dec;104(6):1062-1064. PMID: 37981428
MH  - Humans
MH  - Anti-Inflammatory Agents, Non-Steroidal
MH  - Atrasentan/adverse effects
MH  - *Diabetes Mellitus, Type 2/complications/drug therapy
MH  - Endothelin Receptor Antagonists/adverse effects
MH  - Pain/drug therapy/etiology
MH  - *Renal Insufficiency, Chronic/complications/drug therapy
MH  - Double-Blind Method
OTO - NOTNLM
OT  - analgesics
OT  - atrasentan
OT  - chronic kidney disease
OT  - diabetes
OT  - nonsteroidal anti-inflammatory drug
OT  - opioids
OT  - pain
EDAT- 2023/09/02 05:42
MHDA- 2023/11/21 06:42
CRDT- 2023/09/01 19:27
PHST- 2023/05/17 00:00 [received]
PHST- 2023/08/05 00:00 [revised]
PHST- 2023/08/17 00:00 [accepted]
PHST- 2023/11/21 06:42 [medline]
PHST- 2023/09/02 05:42 [pubmed]
PHST- 2023/09/01 19:27 [entrez]
AID - S0085-2538(23)00610-5 [pii]
AID - 10.1016/j.kint.2023.08.014 [doi]
PST - ppublish
SO  - Kidney Int. 2023 Dec;104(6):1219-1226. doi: 10.1016/j.kint.2023.08.014. Epub 2023 
      Aug 31.