{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T04:49:31Z","timestamp":1791348571255,"version":"4.3.1"},"reference-count":26,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2012,2,13]],"date-time":"2012-02-13T00:00:00Z","timestamp":1329091200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2012,3]]},"abstract":"<jats:p><jats:bold>WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT<\/jats:bold><\/jats:p><jats:p>\u2022\u2003Spironolactone has recently been shown to exert beneficial effects on the cardiovascular and renal systems. To date, its use in patients with chronic kidney disease has been limited due to potential risks of hyperkalaemia and declining renal dysfunction.<\/jats:p><jats:p><jats:bold>WHAT THIS STUDY ADDS<\/jats:bold><\/jats:p><jats:p>\u2022\u2003Non\u2010diabetic patients with early stage chronic kidney disease (CKD) on concomitant therapy with angiotensin converting enzyme (ACE) inhibition or angiotensin II receptor blockade with a serum potassium of &lt;5.5\u2003mmol\/L and no history of hyperkalaemia who were randomized in a trial to treatment with spironolactone for 40 weeks had low rates of serious hyperkalaemia (&lt;1%) and worsening renal function (&lt;3%). Frequent biochemical monitoring is required for the initial 4 weeks but only routine monitoring is needed thereafter.<\/jats:p><jats:p><jats:bold>AIM<\/jats:bold> Mineralocorticoid receptor blockade (MRBs) in combination with angiotensin converting enzyme (ACE) inhibitors and angiotensin\u2010II receptor blockade (ARBs) improve prognostic markers of cardiovascular and renal disease in early stage chronic kidney disease (CKD). Concerns relating to the safety and tolerability of MRBs in CKD may limit their use in a non clinical trial setting.<\/jats:p><jats:p><jats:bold>METHODS<\/jats:bold> In the Chronic Renal Impairment in Birmingham II study, 115 patients with non\u2010diabetic early stage CKD (eGFR 30\u201389\u2003ml\/min\/1.73m<jats:sup>2<\/jats:sup>) received 25\u2003mg daily of spironolactone for 4 weeks before randomization to continuing treatment or placebo for a further 36 weeks. All patients were on ACE inhibitors and\/or ARB therapy. Potassium and renal function were checked at weeks 1, 2, 4, 8, 16, 28 and 40. The incidence of hyperkalaemia, significant renal dysfunction (reduction eGFR \u226525%) and adverse effects was assessed.<\/jats:p><jats:p><jats:bold>RESULTS<\/jats:bold> After 40 weeks of treatment the incidence of serious hyperkalaemia (K<jats:sup>+<\/jats:sup>\u22656.0\u2003mmol\/L) was &lt;1%. A potassium 5.5\u20135.9\u2003mmol\/L occurred on \u22651 occasion over follow\u2010up in 11 patients (nine on spironolactone) and was predicted by baseline potassium \u22655.0\u2003mmol\/L and eGFR \u226445\u2003ml\/min\/1.73m<jats:sup>2<\/jats:sup>. Over follow\u2010up, three patients experienced significant renal dysfunction but no patients withdrew due to intolerance or side effects. Changes in potassium, eGFR and systolic blood pressure were most apparent in the first 4 eeks.<\/jats:p><jats:p><jats:bold>CONCLUSION<\/jats:bold> Spironolactone was well tolerated in selected patients with early stage CKD. Strict monitoring over the first month of treatment followed by standard surveillance as for ACE inhibitors and ARBs is suggested.<\/jats:p>","DOI":"10.1111\/j.1365-2125.2011.04102.x","type":"journal-article","created":{"date-parts":[[2011,9,28]],"date-time":"2011-09-28T07:48:46Z","timestamp":1317196126000},"page":"447-454","source":"Crossref","is-referenced-by-count":61,"title":["The safety and tolerability of spironolactone in patients with mild to moderate chronic kidney disease"],"prefix":"10.1111","volume":"73","author":[{"given":"Nicola C.","family":"Edwards","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard P.","family":"Steeds","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colin D.","family":"Chue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul M.","family":"Stewart","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles J.","family":"Ferro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan N.","family":"Townend","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2012,2,13]]},"reference":[{"key":"e_1_2_7_2_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199909023411001"},{"key":"e_1_2_7_3_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa030207"},{"key":"e_1_2_7_4_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000091405.00772.6E"},{"key":"e_1_2_7_5_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.328.7440.634"},{"key":"e_1_2_7_6_2","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/gfg295"},{"key":"e_1_2_7_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9343(01)00642-8"},{"key":"e_1_2_7_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncpneph0575"},{"key":"e_1_2_7_9_2","doi-asserted-by":"publisher","DOI":"10.1053\/j.ajkd.2007.10.040"},{"key":"e_1_2_7_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ki.5001854"},{"key":"e_1_2_7_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2009.03.066"},{"key":"e_1_2_7_12_2","doi-asserted-by":"publisher","DOI":"10.1210\/en.2002-220120"},{"key":"e_1_2_7_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncpneph1004"},{"key":"e_1_2_7_14_2","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-130-6-199903160-00002"},{"issue":"1","key":"e_1_2_7_15_2","first-page":"S1","article-title":"Guide to receptors and channels (GRAC)","volume":"158","author":"Alexander SPH","year":"2009","journal-title":"Br J Pharmacol"},{"key":"e_1_2_7_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ahj.2006.05.030"},{"key":"e_1_2_7_17_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000146378.65439.7A"},{"key":"e_1_2_7_18_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa040135"},{"key":"e_1_2_7_19_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.104.527549"},{"key":"e_1_2_7_20_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.c1768"},{"key":"e_1_2_7_21_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200109203451215"},{"key":"e_1_2_7_22_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.0000044937.95080.E9"},{"key":"e_1_2_7_23_2","doi-asserted-by":"publisher","DOI":"10.1053\/j.ajkd.2009.11.006"},{"key":"e_1_2_7_24_2","doi-asserted-by":"publisher","DOI":"10.1001\/archinte.160.5.685"},{"key":"e_1_2_7_25_2","doi-asserted-by":"publisher","DOI":"10.2215\/CJN.05850809"},{"key":"e_1_2_7_26_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrcardio.2009.175"},{"key":"e_1_2_7_27_2","doi-asserted-by":"publisher","DOI":"10.1159\/000237742"}],"container-title":["British Journal of Clinical Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fj.1365-2125.2011.04102.x","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/j.1365-2125.2011.04102.x","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,15]],"date-time":"2023-10-15T15:28:06Z","timestamp":1697383686000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1111\/j.1365-2125.2011.04102.x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,2,13]]},"references-count":26,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2012,3]]}},"alternative-id":["10.1111\/j.1365-2125.2011.04102.x"],"URL":"https:\/\/doi.org\/10.1111\/j.1365-2125.2011.04102.x","archive":["Portico"],"relation":{},"ISSN":["0306-5251","1365-2125"],"issn-type":[{"value":"0306-5251","type":"print"},{"value":"1365-2125","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,2,13]]}}}