PMID- 37405775
OWN - NLM
STAT- MEDLINE
DCOM- 20230707
LR  - 20240210
IS  - 2574-3805 (Electronic)
IS  - 2574-3805 (Linking)
VI  - 6
IP  - 7
DP  - 2023 Jul 3
TI  - Medication-Related Adverse Events and Discordancies in Cystatin C-Based vs Serum 
      Creatinine-Based Estimated Glomerular Filtration Rate in Patients With Cancer.
PG  - e2321715
LID - 10.1001/jamanetworkopen.2023.21715 [doi]
LID - e2321715
AB  - IMPORTANCE: Serum creatinine-based estimated glomerular filtration rate (eGFRcr) 
      may overestimate the glomerular filtration rate (GFR) in patients with cancer. 
      Cystatin C-based eGFR (eGFRcys) is an alternative marker of GFR. OBJECTIVE: To 
      determine whether the therapeutic drug levels and adverse events (AEs) associated 
      with renally cleared medications were higher in patients with cancer whose 
      eGFRcys was more than 30% lower than their eGFRcr. DESIGN, SETTING, AND 
      PARTICIPANTS: This cohort study analyzed adult patients with cancer at 2 major 
      academic cancer centers in Boston, Massachusetts. These patients had their 
      creatinine and cystatin C measured on the same day between May 2010 and January 
      2022. The date of the first simultaneous eGFRcr and eGFRcys measurement was 
      considered to be the baseline date. EXPOSURE: The primary exposure was eGFR 
      discordance, defined as an eGFRcys that was more than 30% lower than the eGFRcr. 
      MAIN OUTCOMES AND MEASURES: The primary outcome was risk of the following 
      medication-related AEs within 90 days of the baseline date: (1) supratherapeutic 
      vancomycin trough level greater than 30 mug/mL, (2) 
      trimethoprim-sulfamethoxazole-related hyperkalemia (>5.5 mEq/L), (3) baclofen 
      toxic effect, and (4) supratherapeutic digoxin level (>2.0 ng/mL). For the 
      secondary outcome, a multivariable Cox proportional hazards regression model was 
      used to compare 30-day survival of those with vs without eGFR discordance. 
      RESULTS: A total of 1869 adult patients with cancer (mean [SD] age, 66 [14] 
      years; 948 males [51%]) had simultaneous eGFRcys and eGFRcr measurement. There 
      were 543 patients (29%) with an eGFRcys that was more than 30% lower than their 
      eGFRcr. Patients with an eGFRcys that was more than 30% lower than their eGFRcr 
      were more likely to experience medication-related AEs compared with patients with 
      concordant eGFRs (defined as eGFRcys within 30% of eGFRcr), including vancomycin 
      levels greater than 30 mug/mL (43 of 179 [24%] vs 7 of 77 [9%]; P = .01), 
      trimethoprim-sulfamethoxazole-related hyperkalemia (29 of 129 [22%] vs 11 of 92 
      [12%]; P = .07), baclofen toxic effects (5 of 19 [26%] vs 0 of 11; P = .19), and 
      supratherapeutic digoxin levels (7 of 24 [29%] vs 0 of 10; P = .08). The adjusted 
      odds ratio for vancomycin levels more than 30 mug/mL was 2.59 (95% CI, 1.08-7.03; 
      P = .04). Patients with an eGFRcys more than 30% lower than their eGFRcr had an 
      increased 30-day mortality (adjusted hazard ratio, 1.98; 95% CI, 1.26-3.11; 
      P = .003). CONCLUSIONS AND RELEVANCE: Results of this study suggest that among 
      patients with cancer with simultaneous assessment of eGFRcys and eGFRcr, 
      supratherapeutic drug levels and medication-related AEs occurred more commonly in 
      those with an eGFRcys more than 30% lower than their eGFRcr. Future prospective 
      studies are needed to improve and personalize GFR estimation and medication 
      dosing in patients with cancer.
FAU - Hanna, Paul E
AU  - Hanna PE
AD  - Division of Nephrology, Department of Medicine, Massachusetts General Hospital, 
      Boston.
FAU - Wang, Qiyu
AU  - Wang Q
AD  - Division of Nephrology, Department of Medicine, Massachusetts General Hospital, 
      Boston.
FAU - Strohbehn, Ian A
AU  - Strohbehn IA
AD  - Division of Nephrology, Department of Medicine, Massachusetts General Hospital, 
      Boston.
FAU - Moreno, Daiana
AU  - Moreno D
AD  - Division of Nephrology, Department of Medicine, Massachusetts General Hospital, 
      Boston.
FAU - Harden, Destiny
AU  - Harden D
AD  - Division of Nephrology, Department of Medicine, Massachusetts General Hospital, 
      Boston.
FAU - Ouyang, Tianqi
AU  - Ouyang T
AD  - Division of Nephrology, Department of Medicine, Massachusetts General Hospital, 
      Boston.
FAU - Katz-Agranov, Nurit
AU  - Katz-Agranov N
AD  - Division of Nephrology, Department of Medicine, Massachusetts General Hospital, 
      Boston.
FAU - Seethapathy, Harish
AU  - Seethapathy H
AD  - Division of Nephrology, Department of Medicine, Massachusetts General Hospital, 
      Boston.
FAU - Reynolds, Kerry L
AU  - Reynolds KL
AD  - Division of Hematology and Oncology, Department of Medicine, Massachusetts 
      General Hospital, Boston.
FAU - Gupta, Shruti
AU  - Gupta S
AD  - Division of Renal Medicine, Brigham and Women's Hospital, Boston, Massachusetts.
AD  - Adult Survivorship Program, Dana-Farber Cancer Institute, Boston, Massachusetts.
FAU - Leaf, David E
AU  - Leaf DE
AD  - Division of Renal Medicine, Brigham and Women's Hospital, Boston, Massachusetts.
FAU - Sise, Meghan E
AU  - Sise ME
AD  - Division of Nephrology, Department of Medicine, Massachusetts General Hospital, 
      Boston.
LA  - eng
GR  - K23 DK117014/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20230703
PL  - United States
TA  - JAMA Netw Open
JT  - JAMA network open
JID - 101729235
RN  - AYI8EX34EU (Creatinine)
RN  - 0 (Cystatin C)
RN  - H789N3FKE8 (Baclofen)
RN  - 8064-90-2 (Trimethoprim, Sulfamethoxazole Drug Combination)
RN  - 6Q205EH1VU (Vancomycin)
RN  - 73K4184T59 (Digoxin)
SB  - IM
MH  - Male
MH  - Adult
MH  - Humans
MH  - Aged
MH  - Glomerular Filtration Rate
MH  - Creatinine
MH  - Cohort Studies
MH  - Cystatin C
MH  - Baclofen
MH  - *Hyperkalemia
MH  - Trimethoprim, Sulfamethoxazole Drug Combination
MH  - Vancomycin
MH  - Digoxin/adverse effects
MH  - *Neoplasms/drug therapy
PMC - PMC10323710
COIS- Conflict of Interest Disclosures: Dr Reynolds reported receiving clinical trial 
      funding for Massachusetts General Hospital from Bristol-Myers Squibb during the 
      conduct of the study and being an employee at Teladoc, receiving research funding 
      from Project Datasphere, and receiving personal fees from CME Outfitters and 
      MedScape outside the submitted work. Dr Gupta reported receiving a grant from the 
      National Institute of Diabetes and Digestive and Kidney Diseases of the National 
      Institutes of Health (NIDDK/NIH) during the conduct of the study as well as 
      personal fees from GlaxoSmithKline, Secretome, and Proletariat Therapeutics and 
      grants from GE Healthcare and BTG International outside the submitted work. Dr 
      Leaf reported receiving grants from the NIH during the conduct of the study. Dr 
      Sise reported receiving a grant from the NIH during the conduct of the study; 
      personal fees from Novartis, Travere, and Mallinckrodt outside the submitted 
      work; and grants from Gilead, Merck, Angion, EMD Serono, and Otsuka outside the 
      submitted work. No other disclosures were reported.
EDAT- 2023/07/05 13:05
MHDA- 2023/07/07 06:42
PMCR- 2023/07/05
CRDT- 2023/07/05 11:35
PHST- 2023/07/07 06:42 [medline]
PHST- 2023/07/05 13:05 [pubmed]
PHST- 2023/07/05 11:35 [entrez]
PHST- 2023/07/05 00:00 [pmc-release]
AID - 2806843 [pii]
AID - zoi230639 [pii]
AID - 10.1001/jamanetworkopen.2023.21715 [doi]
PST - epublish
SO  - JAMA Netw Open. 2023 Jul 3;6(7):e2321715. doi: 
      10.1001/jamanetworkopen.2023.21715.