Drug Safety

, Volume 37, Issue 5, pp 369–377 | Cite as

Adherence to Renal Function Monitoring Guidelines in Patients Starting Antihypertensive Therapy with Diuretics and RAAS Inhibitors: A Retrospective Cohort Study

  • Jan C. van Blijderveen
  • Sabine M. Straus
  • Maria A. de Ridder
  • Bruno H. Stricker
  • Miriam C. Sturkenboom
  • Katia M. Verhamme
Original Research Article



Acute kidney injury (AKI) might complicate antihypertensive therapy. In The Netherlands, general practitioner clinical practice guidelines provide clear recommendations on monitoring of renal function to minimize this risk. Our objective was to investigate how day-to-day clinical practice corresponds to the guidelines.


We conducted a retrospective cohort study in a dynamic population, using data on >9,000 adults that was retrieved from the Integrated Primary Care Information database. We investigated whether serum creatinine (SCR) was measured within 30 and 365 days after the start of (combined) use of a diuretic, an angiotensin-converting enzyme inhibitor, and/or angiotensin receptor blocker. We also investigated the association between calendar year, sex, type of therapy, risk factors for AKI and practice and SCR measurement.


Of 6,593 subjects who met the study criteria for single drug therapy, SCR was measured in 1,233 subjects within 30 days and in 3,896 subjects within 365 days. For combined drug therapy recipients (n = 2,497), these were 545 and 1,687, respectively. Associated cumulative probabilities were 19 % and 66 % with single drug therapy, and 22 % and 74 % with combined drug therapy. Significant differences were observed between practices. SCR measurement was associated with other characteristics, except for sex. Within 365 days, SCR increased >30 % of baseline in 103 subjects (1.6 %) after the start of single drug therapy, and in 85 (3.4 %) subjects who initiated combined drug therapy. In the majority (>70 %) of these subjects, this did not result in subsequent monitoring or adjustment of antihypertensive treatment.


Results from this study suggest that, on average, renal function is not monitored as strictly as recommended by relevant clinical practice guidelines.



We thank Marcel de Wilde, Kris Sieradzan and Mees Mosseveld for the collection of data and maintenance of the IPCI database.

Conflicts of interest

No sources of funding were used to assist in the preparation of this study. Miriam C. Sturkenboom is heading a research group that occasionally conducts research for pharmaceutical companies, including Novartis, Boehringer Ingelheim, Pfizer and Eli Lilly. None of these are related to the subject of this manuscript. Katia M. Verhamme has received unconditional grants from Yamanouchi, Boehringer Ingelheim, Pfizer and Novartis. None of these are related to the subject of this manuscript. Jan C. van Blijderveen, Sabine M. Straus, Maria A. de Ridder and Bruno H. Stricker have no conflicts of interest that are directly relevant to the content of this study.


  1. 1.
    Jafar TH, et al. Angiotensin-converting enzyme inhibitors and progression of nondiabetic renal disease: a meta-analysis of patient-level data. Ann Intern Med. 2001;135(2):73–87.PubMedCrossRefGoogle Scholar
  2. 2.
    Gelfand ML, Garren MG, Rowan RL. Acute anuria associated with chlorothiazide and hydrochlorothiazide therapy: recovery. N Y State J Med. 1964;64:1865–70.PubMedGoogle Scholar
  3. 3.
    Pfeffer MA, et al. Effects of candesartan on mortality and morbidity in patients with chronic heart failure: the CHARM-Overall programme. Lancet. 2003;362(9386):759–66.PubMedCrossRefGoogle Scholar
  4. 4.
    Yusuf S, et al. Telmisartan, ramipril, or both in patients at high risk for vascular events. N Engl J Med. 2008;358(15):1547–59.PubMedCrossRefGoogle Scholar
  5. 5.
    Lapi F, et al. Concurrent use of diuretics, angiotensin converting enzyme inhibitors, and angiotensin receptor blockers with non-steroidal anti-inflammatory drugs and risk of acute kidney injury: nested case-control study. BMJ. 2013;346:e8525.PubMedCentralPubMedCrossRefGoogle Scholar
  6. 6.
    The National Collaborating Centre for Chronic Conditions. Chronic kidney disease: national clinical guideline for early identification and management in adults in primary and secondary care; 2011. http://www.nice.org.uk/nicemedia/live/12069/42116/42116.pdf.
  7. 7.
    The Dutch College of General Practitioners. Cardiovascular risk management. 1st revision [Cardiovasculair risicomanagement (eerste herziening)]; 2012. https://www.nhg.org/standaarden/volledig/cardiovasculair-risicomanagement#Begrippen.
  8. 8.
    Kalra PA, et al. Questionnaire study and audit of use of angiotensin converting enzyme inhibitor and monitoring in general practice: the need for guidelines to prevent renal failure. BMJ. 1999;318(7178):234–7.PubMedCentralPubMedCrossRefGoogle Scholar
  9. 9.
    Hurley JS, et al. Laboratory safety monitoring of chronic medications in ambulatory care settings. J Gen Intern Med. 2005;20(4):331–3.PubMedCentralPubMedCrossRefGoogle Scholar
  10. 10.
    Raebel MA, et al. Laboratory monitoring of potassium and creatinine in ambulatory patients receiving angiotensin converting enzyme inhibitors and angiotensin receptor blockers. Pharmacoepidemiol Drug Saf. 2007;16(1):55–64.PubMedCrossRefGoogle Scholar
  11. 11.
    Gerardin-Marais M, et al. Diuretic drug therapy monitoring in the elderly: a cohort study. Eur J Clin Pharmacol. 2008;64(4):433–7.PubMedCrossRefGoogle Scholar
  12. 12.
    Coleman JJ, et al. Oversight: a retrospective study of biochemical monitoring in patients beginning antihypertensive drug treatment in primary care. Br J Clin Pharmacol. 2010;70(1):109–17.PubMedCentralPubMedCrossRefGoogle Scholar
  13. 13.
    Bootsma JE, et al. Adherence to biochemical monitoring recommendations in patients starting with renin angiotensin system inhibitors: a retrospective cohort study in the Netherlands. Drug Saf. 2011;34(7):605–14.PubMedCrossRefGoogle Scholar
  14. 14.
    Fournier JP, et al. Laboratory monitoring of patients treated with antihypertensive drugs and newly exposed to non steroidal anti-inflammatory drugs: a cohort study. PLoS ONE. 2012;7(3):e34187.PubMedCentralPubMedCrossRefGoogle Scholar
  15. 15.
    Geerts AF, et al. A pharmacy medication alert system based on renal function in older patients. Br J Gen Pract. 2012;62(601):e525–9.PubMedCentralPubMedGoogle Scholar
  16. 16.
    Mathieson L, Severn A, Guthrie B. Monitoring and adverse events in relation to ACE inhibitor/angiotensin receptor blocker initiation in people with diabetes in general practice: a population database study. Scott Med J. 2013;58(2):69–76.PubMedCrossRefGoogle Scholar
  17. 17.
    McDowell SE, et al. Laboratory monitoring and adverse patient outcomes with antihypertensive therapy in primary care. Pharmacoepidemiol Drug Saf. 2010;19(5):482–9.PubMedGoogle Scholar
  18. 18.
    Vlug AE, et al. Postmarketing surveillance based on electronic patient records: the IPCI project. Methods Inf Med. 1999;38(4–5):339–44.PubMedGoogle Scholar
  19. 19.
    van der Lei J, et al. The introduction of computer-based patient records in The Netherlands. Ann Intern Med. 1993;119(10):1036–41.PubMedCrossRefGoogle Scholar
  20. 20.
    Hvidberg E, Andersen AH. New classification of drugs. The Medical list and the Drug catalogue are introduced in Anatomical–Therapeutic–Chemical classification code (ACT-code) in 1981. Ugeskr Laeger. 1980;142(6):396–7.PubMedGoogle Scholar
  21. 21.
    Knight EL, et al. Predictors of decreased renal function in patients with heart failure during angiotensin-converting enzyme inhibitor therapy: results from the studies of left ventricular dysfunction (SOLVD). Am Heart J. 1999;138(5 Pt 1):849–55.PubMedCrossRefGoogle Scholar
  22. 22.
    Levey AS, et al. A new equation to estimate glomerular filtration rate. Ann Intern Med. 2009;150(9):604–12.PubMedCentralPubMedCrossRefGoogle Scholar
  23. 23.
    KDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney Int. 2013;3(1):19–62.Google Scholar
  24. 24.
    Thomas MC. Diuretics, ACE inhibitors and NSAIDs—the triple whammy. Med J Aust. 2000;172(4):184–5.PubMedGoogle Scholar
  25. 25.
    Verduijn M, Folmer H. Pharmacotherapeutic guideline pain management [Farmacotherapeutische richtlijn pijnbestrijding]; 2007. http://download.nhg.org/FTP_NHG/standaarden/FTR/Pijnbestrijding_text.html#noot18.
  26. 26.
    Platts-Mills TF, et al. Life-threatening hyperkalemia after 2 days of ibuprofen. Am J Emerg Med. 2013;31(2):465 e1–2.PubMedCrossRefGoogle Scholar
  27. 27.
    Hsu CY, et al. Community-based incidence of acute renal failure. Kidney Int. 2007;72(2):208–12.PubMedCentralPubMedCrossRefGoogle Scholar
  28. 28.
    Onuigbo MA. Can ACE inhibitors and angiotensin receptor blockers be detrimental in CKD patients? Nephron Clin Pract. 2011;118(4):c407–19.PubMedCrossRefGoogle Scholar
  29. 29.
    Fried LF, et al. Combined angiotensin inhibition for the treatment of diabetic nephropathy. N Engl J Med. 2013;369(20):1892–903.PubMedCrossRefGoogle Scholar
  30. 30.
    Makani H, et al. Efficacy and safety of dual blockade of the renin–angiotensin system: meta-analysis of randomised trials. BMJ. 2013;346:f360.PubMedCentralPubMedCrossRefGoogle Scholar
  31. 31.
    McDowell SE, Ferner RE. Biochemical monitoring of patients treated with antihypertensive therapy for adverse drug reactions: a systematic review. Drug Saf. 2011;34:1049–59.PubMedCrossRefGoogle Scholar
  32. 32.
    Bardach NS, et al. Effect of pay-for-performance incentives on quality of care in small practices with electronic health records: a randomized trial. JAMA. 2013;310(10):1051–9.PubMedCrossRefGoogle Scholar
  33. 33.
    Scott A, et al. The effect of financial incentives on the quality of health care provided by primary care physicians. Cochrane Database Syst Rev. 2011;9:CD008451.PubMedGoogle Scholar
  34. 34.
    Roksnoer LC, et al. Urinary markers of intrarenal renin–angiotensin system activity in vivo. Curr Hypertens Rep. 2013;15(2):81–8.PubMedCrossRefGoogle Scholar
  35. 35.
    Wong J. Is there benefit in dual renin–angiotensin–aldosterone system blockade? No, yes and maybe: a guide for the perplexed. Diab Vasc Dis Res. 2013;10(3):193–201.PubMedCrossRefGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2014

Authors and Affiliations

  • Jan C. van Blijderveen
    • 1
  • Sabine M. Straus
    • 1
  • Maria A. de Ridder
    • 1
  • Bruno H. Stricker
    • 2
    • 3
  • Miriam C. Sturkenboom
    • 1
  • Katia M. Verhamme
    • 1
  1. 1.Department of Medical InformaticsErasmus Medical CenterRotterdamThe Netherlands
  2. 2.Department of EpidemiologyErasmus Medical CenterRotterdamThe Netherlands
  3. 3.Drug Safety UnitInspectorate of HealthcareThe HagueThe Netherlands

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