Serum potassium and adverse outcomes across the range of kidney function: a CKD Prognosis Consortium meta-analysis

Kövesdy, Csaba P.; Matsushita, Kunihiro; Sang, Yingying; Brunskill, Nigel J.; Carrero, Juan Jesús; Chodick, Gabriel; Hasegawa, Takeshi; Heerspink, Hiddo Lambers; Hirayama, Atsushi; Landman, Gijs W. D.; Levin, Adeera; Nitsch, Dorothea; Wheeler, David C.; Coresh, Josef; Hallan, Stein; Shalev, Varda

doi:10.1093/eurheartj/ehy100

Cited by 231 publications

(221 citation statements)

References 59 publications

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“…Noteworthy, even moderate degrees of HK (sK ≥ 5.0 mEq/L) act as strong modifier of survival, as soundly demonstrated by a recent individual‐level data meta‐analysis of international cohorts including 1 217 986 participants followed up for a mean of 6.9 years . Indeed, even sK levels moderately high should not be underestimated because they still pose a higher risk for future increases to levels potentially triggering fatal arrhythmias.…”

Section: Introductionmentioning

confidence: 97%

“…a recent individual-level data meta-analysis of international cohorts including 1 217 986 participants followed up for a mean of 6.9 years. 4 Indeed, even sK levels moderately high should not be underestimated because they still pose a higher risk for future increases to levels potentially triggering fatal arrhythmias. Less evident is the role of HK on progression to end-stage renal disease (ESRD).…”

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confidence: 99%

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Cost‐analysis of persistent hyperkalaemia in non‐dialysis chronic kidney disease patients under nephrology care in Italy

Provenzano

Francesco²,

Iannazzo³

et al. 2020

Int J Clin Pract

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Aim In patients with chronic kidney disease (CKD), hyperkalaemia (HK) (potassium level ≥ 5.0 mEq/L) is associated with poor clinical outcomes. This study provides novel insights by comparing management costs of CKD patients with normokalaemia vs those with persistent HK regularly followed in renal clinics in Italy. Methods To this aim, a Markov model over life‐time horizon was developed. Time to end‐stage renal disease (ESRD) and time to death in CKD patients were derived from an observational multi‐centre database including 1665 patients with non‐dialysis CKD stage 1‐5 under nephrology care in Italy (15 years follow‐up). Resource use for CKD and HK management was obtained from the observational database, KDIGO international guidelines, and clinical expert opinion. Results Results showed that patients with normokalaemia vs persistent HK brought an average per patient lifetime cost‐saving of €16 059 besides delayed onset of ESRD by 2.29 years and increased survival by 1.79 years with increment in total survival and dialysis‐free survival in normokalaemia that decreased from early to advanced disease. Cost‐saving related to normokalaemia increased at more advanced CKD; however, it was already evident at early stage (3388.97€ at stage 1‐3a). OWSA confirmed cost‐saving associated with normokalaemia across all parameter variations. Discussion and conclusion This model is the first to simulate the impact of HK in non‐dialysis CKD patients on economic and clinical outcomes using real‐world data from nephrology clinics. In these patients, persistent HK results into higher lifetime costs, besides poorer clinical outcomes, that are evident since the early stages of CKD. Maintaining normokalaemia should therefore be of main concern in CKD treatment planning to improve long‐term economic and clinical outcomes.

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Section: Introductionmentioning

confidence: 97%

mentioning

confidence: 99%

Cost‐analysis of persistent hyperkalaemia in non‐dialysis chronic kidney disease patients under nephrology care in Italy

Provenzano

Francesco²,

Iannazzo³

et al. 2020

Int J Clin Pract

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“…In addition, the clinical relevance of MRAs, and, in particular, the third-generation MRA, finerenone, are being further investigated in patients with T2D in the ongoing Fidelio and Figaro trials, consisting of >11 000 patients with T2D and albuminuria, as an add-on to standard care with cardiovascular and renal endpoints. these two features are known to be associated with a risk of hyperkalaemia beyond T2D and the use of RAS inhibitors 39. Only a few episodes of hyperkalaemia were observed among patients with a long duration of T2D at high cardiovascular risk and, importantly, for most of the patients receiving RAS-inhibitor treatment.…”

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confidence: 99%

Effect of the mineralocorticoid receptor antagonist eplerenone on liver fat and metabolism in patients with type 2 diabetes: A randomized, double‐blind, placebo‐controlled trial (MIRAD trial)

Johansen

Schou

Rossignol

et al. 2019

Diabetes Obesity Metabolism

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Aim To investigate whether the mineralocorticoid receptor antagonist eplerenone has beneficial effects on liver fat and metabolism in patients with type 2 diabetes (T2D), the mineralocorticoid receptor antagonist in type 2 diabetes (MIRAD) trial. Material and methods In this 26‐week, double‐blind, randomized, placebo‐controlled trial, we enrolled 140 patients with T2D and high risk of cardiovascular disease. Patients were randomized 1:1 to either eplerenone with a target dose of 200 mg/day for patients with estimated glomerular filtration rate (eGFR) of 60 mL/min per 1.73 m2 or more and 100 mg/day for patients with eGFR between 41 and 59 mL/min per 1.73 m2 or placebo. The primary outcome measure was change in liver fat by proton magnetic resonance spectroscopy at week 26 from baseline; secondary outcomes were changes in metabolism, and safety by incident hyperkalaemia. Results No changes in liver fat in the eplerenone group 0.91% (95% CI −0.57 to 2.39) or the placebo group −1.01% (−2.23 to 0.21) were found. The estimated absolute treatment difference was 1.92% (−3.81 to 0.01; P = 0.049). There was no beneficial impact on supporting secondary outcome variables of metabolism as fat mass distribution, lipid metabolism or insulin resistance. Despite a high dosage of eplerenone 164 versus 175 mg in patients treated with placebo (P = 0.228), the number of patients with incident hyperkalaemia (≥5.5 mmol/L) was low, with six in the eplerenone versus two in the placebo group (P = 0.276). Conclusion The addition of high doses of eplerenone to background antidiabetic and antihypertensive therapy does not show beneficial effects on liver fat and metabolism in patients with T2D.

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Section: Introductionmentioning

confidence: 99%

“…Hyperkalemia poses a risk excess of mortality that becomes significant for even moderate increases of sK (≥5.0 mEq/L) [7][8][9][10][11][12][13]. Conversely, controversial data have been reported on the relationship between hyperkalemia and progression to end-stage kidney disease (ESKD) [1,4,10,[13][14][15]. Gaining insights into this latter association is critical because additional determinant of hyperkalemia is the prescription of inhibitors of renin-angiotensin-system (RASI) [16][17], that are the first-choice antihypertensive agents in CKD due to the nephroprotective efficacy - [20].…”

Section: Introductionmentioning

confidence: 99%

Competing-Risk Analysis of Death and ESKD by Hyperkalemia Status in Non-Dialysis CKD Patients Receiving Stable Nephrology Care

Provenzano¹,

Minutolo²,

Chiodini³

et al. 2018

Preprint

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Hyperkalemia burden in non-dialysis CKD under nephrology care is undefined. We prospectively followed 2443 patients with two visits (referral and control with 12-month interval) in 46 nephrology clinics. Patients were stratified in four categories of hyperkalemia (sK≥5.0 mEq/L) by sK at visit 1 and 2: Absent (no-no), Resolving (yes-no), New Onset (no-yes), Persistent (yes-yes). We assessed competing risks of ESKD and death after visit 2. Age was 65±15 y, eGFR 35±17 mL/min/1.73 m 2 , proteinuria 0.40 (0.14-1.21) g/24h. In the two visits sK was 4.8±0.6 and levels ≥6 mEq/L were observed in  4%. Hyperkalemia was absent in 46%, resolving 17%, new onset 15% and persistent 22%. Renin-angiotensin-system inhibitors (RASI) were prescribed in 79% patients. During 3.6-year follow-up, 567 patients reached ESKD and 349 died. Multivariable competing risk analysis [subhazard ratio-sHR, 95%Confidence Interval-CI] evidenced that new onset [sHR 1.34, 95%CI 1.05-1.72] and persistent [sHR 1.27, 95%CI 1.02-1.58] hyperkalemia predicted higher ESKD risk versus absent,independently from main determinants of outcome including eGFR change. Conversely, no effect on mortality was observed. Results were confirmed by testing sK as continuous variable. Therefore, in CKD under nephrology care, mild-to-moderate hyperkalemia status is common (37%) and predicts per se higher ESKD risk but not mortality.

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Serum potassium and adverse outcomes across the range of kidney function: a CKD Prognosis Consortium meta-analysis

Abstract: Outpatient potassium levels both above and below the normal range are consistently associated with adverse outcomes, with similar risk relationships across eGFR and albuminuria.

Cited by 231 publications

References 59 publications

Cost‐analysis of persistent hyperkalaemia in non‐dialysis chronic kidney disease patients under nephrology care in Italy

Cost‐analysis of persistent hyperkalaemia in non‐dialysis chronic kidney disease patients under nephrology care in Italy

Effect of the mineralocorticoid receptor antagonist eplerenone on liver fat and metabolism in patients with type 2 diabetes: A randomized, double‐blind, placebo‐controlled trial (MIRAD trial)

Competing-Risk Analysis of Death and ESKD by Hyperkalemia Status in Non-Dialysis CKD Patients Receiving Stable Nephrology Care

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