The renal protective effect of angiotensin receptor blockers depends on intra-individual response variation in multiple risk markers

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Standard

The renal protective effect of angiotensin receptor blockers depends on intra-individual response variation in multiple risk markers. / Schievink, Bauke; de Zeeuw, Dick; Parving, Hans-Henrik; Rossing, Peter; Lambers Heerspink, Hiddo Jan.

In: British Journal of Clinical Pharmacology, Vol. 80, No. 4, 10.2015, p. 678-86.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Schievink, B, de Zeeuw, D, Parving, H-H, Rossing, P & Lambers Heerspink, HJ 2015, 'The renal protective effect of angiotensin receptor blockers depends on intra-individual response variation in multiple risk markers', British Journal of Clinical Pharmacology, vol. 80, no. 4, pp. 678-86. https://doi.org/10.1111/bcp.12655

APA

Schievink, B., de Zeeuw, D., Parving, H-H., Rossing, P., & Lambers Heerspink, H. J. (2015). The renal protective effect of angiotensin receptor blockers depends on intra-individual response variation in multiple risk markers. British Journal of Clinical Pharmacology, 80(4), 678-86. https://doi.org/10.1111/bcp.12655

Vancouver

Schievink B, de Zeeuw D, Parving H-H, Rossing P, Lambers Heerspink HJ. The renal protective effect of angiotensin receptor blockers depends on intra-individual response variation in multiple risk markers. British Journal of Clinical Pharmacology. 2015 Oct;80(4):678-86. https://doi.org/10.1111/bcp.12655

Author

Schievink, Bauke ; de Zeeuw, Dick ; Parving, Hans-Henrik ; Rossing, Peter ; Lambers Heerspink, Hiddo Jan. / The renal protective effect of angiotensin receptor blockers depends on intra-individual response variation in multiple risk markers. In: British Journal of Clinical Pharmacology. 2015 ; Vol. 80, No. 4. pp. 678-86.

Bibtex

@article{7b077d6d1c9e4731ab2fb2258539a233,
title = "The renal protective effect of angiotensin receptor blockers depends on intra-individual response variation in multiple risk markers",
abstract = "AIMS: Angiotensin receptor blockers (ARBs) are renoprotective and targeted to blood pressure. However, ARBs have multiple other (off-target) effects which may affect renal outcome. It is unknown whether on-target and off-target effects are congruent within individuals. If not, this variation in short term effects may have important implications for the prediction of individual long term renal outcomes. Our aim was to assess intra-individual variability in multiple parameters in response to ARBs in type 2 diabetes.METHODS: Changes in systolic blood pressure (SBP), albuminuria, potassium, haemoglobin, cholesterol and uric acid after 6 months of losartan treatment were assessed in the RENAAL database. Improvement in predictive performance of renal outcomes (ESRD or doubling serum creatinine) for each individual using ARB-induced changes in all risk markers was assessed by the relative integrative discrimination index (RIDI).RESULTS: SBP response showed high variability (mean -5.7 mmHg, 5(th) to 95(th) percentile -36.5 to +24.0 mmHg) between individuals. Changes in off-target parameters also showed high variability between individuals. No congruency was observed between responses to losartan in multiple parameters within individuals. Using individual responses in all risk markers significantly improved renal risk prediction (RIDI 30.4%, P < 0.01) compared with using only SBP changes. Results were successfully replicated in two independent trials with irbesartan, IDNT and IRMA-2.CONCLUSIONS: In this post hoc analysis we showed that ARBs have multiple off-target effects which vary between and within individuals. Combining all ARB-induced responses beyond SBP provides a more accurate prediction of who will benefit from ARB therapy. Prospective trials are required to validate these findings.",
author = "Bauke Schievink and {de Zeeuw}, Dick and Hans-Henrik Parving and Peter Rossing and {Lambers Heerspink}, {Hiddo Jan}",
note = "{\textcopyright} 2015 The British Pharmacological Society.",
year = "2015",
month = oct,
doi = "10.1111/bcp.12655",
language = "English",
volume = "80",
pages = "678--86",
journal = "British Journal of Clinical Pharmacology, Supplement",
issn = "0264-3774",
publisher = "Wiley-Blackwell",
number = "4",

}

RIS

TY - JOUR

T1 - The renal protective effect of angiotensin receptor blockers depends on intra-individual response variation in multiple risk markers

AU - Schievink, Bauke

AU - de Zeeuw, Dick

AU - Parving, Hans-Henrik

AU - Rossing, Peter

AU - Lambers Heerspink, Hiddo Jan

N1 - © 2015 The British Pharmacological Society.

PY - 2015/10

Y1 - 2015/10

N2 - AIMS: Angiotensin receptor blockers (ARBs) are renoprotective and targeted to blood pressure. However, ARBs have multiple other (off-target) effects which may affect renal outcome. It is unknown whether on-target and off-target effects are congruent within individuals. If not, this variation in short term effects may have important implications for the prediction of individual long term renal outcomes. Our aim was to assess intra-individual variability in multiple parameters in response to ARBs in type 2 diabetes.METHODS: Changes in systolic blood pressure (SBP), albuminuria, potassium, haemoglobin, cholesterol and uric acid after 6 months of losartan treatment were assessed in the RENAAL database. Improvement in predictive performance of renal outcomes (ESRD or doubling serum creatinine) for each individual using ARB-induced changes in all risk markers was assessed by the relative integrative discrimination index (RIDI).RESULTS: SBP response showed high variability (mean -5.7 mmHg, 5(th) to 95(th) percentile -36.5 to +24.0 mmHg) between individuals. Changes in off-target parameters also showed high variability between individuals. No congruency was observed between responses to losartan in multiple parameters within individuals. Using individual responses in all risk markers significantly improved renal risk prediction (RIDI 30.4%, P < 0.01) compared with using only SBP changes. Results were successfully replicated in two independent trials with irbesartan, IDNT and IRMA-2.CONCLUSIONS: In this post hoc analysis we showed that ARBs have multiple off-target effects which vary between and within individuals. Combining all ARB-induced responses beyond SBP provides a more accurate prediction of who will benefit from ARB therapy. Prospective trials are required to validate these findings.

AB - AIMS: Angiotensin receptor blockers (ARBs) are renoprotective and targeted to blood pressure. However, ARBs have multiple other (off-target) effects which may affect renal outcome. It is unknown whether on-target and off-target effects are congruent within individuals. If not, this variation in short term effects may have important implications for the prediction of individual long term renal outcomes. Our aim was to assess intra-individual variability in multiple parameters in response to ARBs in type 2 diabetes.METHODS: Changes in systolic blood pressure (SBP), albuminuria, potassium, haemoglobin, cholesterol and uric acid after 6 months of losartan treatment were assessed in the RENAAL database. Improvement in predictive performance of renal outcomes (ESRD or doubling serum creatinine) for each individual using ARB-induced changes in all risk markers was assessed by the relative integrative discrimination index (RIDI).RESULTS: SBP response showed high variability (mean -5.7 mmHg, 5(th) to 95(th) percentile -36.5 to +24.0 mmHg) between individuals. Changes in off-target parameters also showed high variability between individuals. No congruency was observed between responses to losartan in multiple parameters within individuals. Using individual responses in all risk markers significantly improved renal risk prediction (RIDI 30.4%, P < 0.01) compared with using only SBP changes. Results were successfully replicated in two independent trials with irbesartan, IDNT and IRMA-2.CONCLUSIONS: In this post hoc analysis we showed that ARBs have multiple off-target effects which vary between and within individuals. Combining all ARB-induced responses beyond SBP provides a more accurate prediction of who will benefit from ARB therapy. Prospective trials are required to validate these findings.

U2 - 10.1111/bcp.12655

DO - 10.1111/bcp.12655

M3 - Journal article

C2 - 25872610

VL - 80

SP - 678

EP - 686

JO - British Journal of Clinical Pharmacology, Supplement

JF - British Journal of Clinical Pharmacology, Supplement

SN - 0264-3774

IS - 4

ER -

ID: 150711325