Hyperkalemia-Related Discontinuation of Renin-Angiotensin-Aldosterone System Inhibitors and Clinical Outcomes in CKD: A Population-Based Cohort Study

Leon, Silvia J.; Whitlock, Reid; Rigatto, Claudio; Komenda, Paul; Bohm, Clara; Sucha, Ewa; Bota, Sarah E.; Tuna, Meltem; Collister, David; Sood, Manish M.; Tangri, Navdeep

doi:10.1053/j.ajkd.2022.01.002

Cited by 69 publications

(61 citation statements)

References 28 publications

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“…Also 31.5 % patients with advanced CKD presented with severely increased proteinuria; advanced CKD was 3.5 times higher if a patient had severe proteinuria, as also reported in other studies (3, 13, 37, 49). Furthermore, few (18.8 %) patients with advanced CKD and 21.4 % of those with early CKD were using ACEIs or ARBs; similar findings have been reported from other studies on the underutilization of ACEIs/ARBs when they were clinically indicated or discontinuation of RAAS inhibitors by clinicians during the course of CKD possibly due to their associated side effects (50-52). Angiotensin converting enzyme inhibitors (ACEIs) or angiotensin receptors blockers (ARBs) had no significant association with advanced CKD, possibly due to the small numbers on these agents, unlike findings from other studies that did demonstrate that the use of ACEIs/ARBs had beneficial effects for kidney events and cardiovascular outcomes compared to other antihypertensive medications in patients with CKD (52-54).…”

Section: Discussionsupporting

confidence: 82%

Demographic and clinical profile of black patients with chronic kidney disease attending Charlotte Maxeke Johannesburg Academic Hospital (CMJAH) in Johannesburg, South Africa

Meremo

Paget

Duarte

et al. 2022

Preprint

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Background The prevalence of chronic kidney disease (CKD) is increasing worldwide; black patients have an increased risk of developing CKD and end stage kidney disease (ESKD) at significantly higher rates than other races. Methods A cross sectional study was carried out on black patients with CKD attending the kidney outpatient clinic at Charlotte Maxeke Johannesburg Academic Hospital (CMJAH) in South Africa, between September 2019 to March 2020. Demographic and clinical data were extracted from the ongoing kidney outpatient clinic records and interviews, and were filled in a questionnaire. Patients provided blood and urine for laboratory investigations as standard of care, data were descriptively and inferentially analysed using STATA version 17. Multivariable logistic regression analysis was used to identify demographic and clinical data associated with advanced CKD. Results A total of 312 black patients with CKD were enrolled during the study period; 58% patients had advanced CKD, of whom 31.5% had grossly increased proteinuria, 96.7% had hypertension, 38.7% had diabetes mellitus and 38.1% had both hypertension and diabetes mellitus. For patients with advanced CKD, the median age was 61 (IQR 51-69) years, eGFR 33 (30 -39) mL/min/1.73 m2, serum bicarbonate 22 (IQR 20 – 24), hemoglobin 12.9 (IQR 11.5 – 14.0) g/dl, serum transferrin 2.44 (IQR 2.23 – 2.73) g/L, serum uric acid 0.43 (IQR 0.37 – 0.53) and serum potassium 4.4 (IQR 3.9 – 4.8) mmol/L. The prevalence of metabolic acidosis was 62.4%, anemia 46.4%, gout 30.9%, low transferrin levels 16.6% and hyperkalemia 8.8% among those with advanced CKD, while the prevalence of metabolic acidosis and anemia was 46.6% and 25.9% respectively in those with early CKD. Variables with higher odds for advanced CKD after multivariable logistic regression analysis were hypertension (OR 3.3, 95% CI 1.2 - 9.2, P = 0.020), diabetes mellitus (OR 1.8, 95% CI 1.1 - 3.3, P = 0.024), severe proteinuria (OR 3.5, 95% CI 1.9 - 6.5, P = 0.001), angina (OR 2.5, 95% CI 1.2 - 5.1, P = 0.008), anaemia (OR 2.9, 95% CI 1.7 - 4.9, P= 0.001), hyperuricemia (OR 2.4, 95% CI 1.4 - 4.1, P = 0.001), and metabolic acidosis (OR 2.0, 95% CI 1.2 - 3.1, P= 0.005). Other associations with advanced CKD were widow/widower (OR 3.2, 95% CI 1.4 - 7.4, P = 0.006), low transferrin (OR 2.4, 95% CI 1.1 - 5.1, P= 0.028), hyperkalemia (OR 5.4, 95% CI 1.2 - 24.1, P= 0.029), allopurinol (OR 2.4, 95% CI 1.4 - 4.3, P = 0.005) and doxazosin (OR 1.9, 95% CI 1.2 - 3.1, P = 0.006). Conclusion Hypertension and diabetes mellitus were strongly associated with advanced CKD, suggesting a need for primary and secondary population-based prevention measures. Metabolic acidosis, anaemia with low transferrin levels, hyperuricemia and hyperkalemia were highly prevalent in our patients, including those with early CKD, and they were strongly associated with advanced CKD, calling for the proactive role of clinicians and dietitians in supporting the needs of CKD patients in meeting their daily dietary requirements towards preventing and slowing the progression of CKD.

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Section: Discussionsupporting

confidence: 82%

Demographic and clinical profile of black patients with chronic kidney disease attending Charlotte Maxeke Johannesburg Academic Hospital (CMJAH) in Johannesburg, South Africa

Meremo

Paget

Duarte

et al. 2022

Preprint

View full text Add to dashboard Cite

show abstract

“…Also 31.5% patients with advanced CKD presented with severely increased proteinuria; advanced CKD was 3.5 times higher if a patient had severe proteinuria, as also reported in other studies [ 39 , 59 , 60 ]. Furthermore, few (18.8%) patients with advanced CKD and 21.4% of those with early CKD were using ACEIs or ARBs; similar findings have been reported from other studies on the underutilization of ACEIs/ARBs when they were clinically indicated or discontinuation of RAAS inhibitors by clinicians during the course of CKD possibly due to their associated side effects [ 61 – 63 ]. Angiotensin converting enzyme inhibitors (ACEIs) or angiotensin receptors blockers (ARBs) had no significant association with advanced CKD, possibly due to the small numbers on these agents, unlike findings from other studies that did demonstrate that the use of ACEIs/ARBs had beneficial effects for kidney events and cardiovascular outcomes compared to other antihypertensive medications in patients with CKD [ 63 – 65 ].…”

Section: Discussionsupporting

confidence: 78%

Demographic and clinical profile of black patients with chronic kidney disease attending a tertiary hospital in Johannesburg, South Africa

et al. 2022

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Background The prevalence of chronic kidney disease (CKD) is increasing worldwide; black patients have an increased risk of developing CKD and end stage kidney disease (ESKD) at significantly higher rates than other races. Methods A cross sectional study was carried out on black patients with CKD attending the kidney outpatient clinic at Charlotte Maxeke Johannesburg Academic Hospital (CMJAH) in South Africa, between September 2019 to March 2020. Demographic and clinical data were extracted from the ongoing kidney outpatient clinic records and interviews, and were filled in a questionnaire. Patients provided blood and urine for laboratory investigations as standard of care, and data were descriptively and inferentially entered into REDcap and analysed using STATA version 17. Multivariable logistic regression analysis was used to identify demographic and clinical variables associated with advanced CKD. Results A total of 312 black patients with CKD were enrolled in the study with a median age of 58 (IQR 46–67) years; 58% patients had advanced CKD, 31.5% of whom had grossly increased proteinuria, 96.7% had hypertension, 38.7% had diabetes mellitus and 38.1% had both hypertension and diabetes mellitus. In patients with advanced CKD, the median age was 61 (IQR 51–69) years, eGFR 33 (30–39) mL/min/1.73 m2, serum bicarbonate 22 (IQR 20–24), haemoglobin 12.9 (IQR 11.5–14.0) g/dl and serum uric acid 0.43 (IQR 0.37–0.53). The prevalence of metabolic acidosis was 62.4%, anemia 46.4% and gout 30.9% among those with advanced CKD, while the prevalence of metabolic acidosis and anaemia was 46.6% and 25.9% respectively in those with early CKD. Variables with higher odds for advanced CKD after multivariable logistic regression analysis were hypertension (OR 3.3, 95% CI 1.2–9.2, P = 0.020), diabetes mellitus (OR 1.8, 95% CI 1.1–3.3, P = 0.024), severe proteinuria (OR 3.5, 95% CI 1.9–6.5, P = 0.001), angina (OR 2.5, 95% CI 1.2–5.1, P = 0.008), anaemia (OR 2.9, 95% CI 1.7–4.9, P = 0.001), hyperuricemia (OR 2.4, 95% CI 1.4–4.1, P = 0.001), and metabolic acidosis (OR 2.0, 95% CI 1.2–3.1, P = 0.005). Other associations with advanced CKD were loss of spouse (widow/widower) (OR 3.2, 95% CI 1.4–7.4, P = 0.006), low transferrin (OR 2.4, 95% CI 1.1–5.1, P = 0.028), hyperkalemia (OR 5.4, 95% CI 1.2–24.1, P = 0.029), use of allopurinol (OR 2.4, 95% CI 1.4–4.3, P = 0.005) and doxazosin (OR 1.9, 95% CI 1.2–3.1, P = 0.006). Conclusion Hypertension and diabetes mellitus were strongly associated with advanced CKD, suggesting a need for primary and secondary population-based prevention measures. Metabolic acidosis, anemia with low transferrin levels, hyperuricemia and hyperkalemia were highly prevalent in our patients, including those with early CKD, and they were strongly associated with advanced CKD, requiring clinicians and dietitians to be proactive in supporting the needs of CKD patients in meeting their daily dietary requirements towards preventing and slowing the progression of CKD.

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“…Nonetheless, the risk of hyperkalaemia in patients with CKD leads physicians to down-titrate or withdraw RASI [ 31 , 32 , 33 , 34 ], thus depriving CKD patients of the well-recognized protective effects of these drugs [ 35 , 36 ]. Indeed, several studies reported that RASI was underutilized in CKD patients, and that their rate of prescription was even lower for those in severe CKD stages.…”

Section: Hyperkalaemia In General Population and In Chronic Kidney Di...mentioning

confidence: 99%

“…Indeed, several studies reported that RASI was underutilized in CKD patients, and that their rate of prescription was even lower for those in severe CKD stages. Notably, CKD patients who discontinued RASI experienced higher CV events in CKD patients [ 31 , 32 , 33 , 34 ].…”

Section: Hyperkalaemia In General Population and In Chronic Kidney Di...mentioning

confidence: 99%

Chronic Hyperkaliemia in Chronic Kidney Disease: An Old Concern with New Answers

Borrelli

Matarazzo

Lembo

et al. 2022

IJMS

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Increasing potassium intake ameliorates blood pressure (BP) and cardiovascular (CV) prognoses in the general population; therefore the World Health Organization recommends a high-potassium diet (90–120 mEq/day). Hyperkalaemia is a rare condition in healthy individuals due to the ability of the kidneys to effectively excrete dietary potassium load in urine, while an increase in serum K+ is prevalent in patients with chronic kidney disease (CKD). Hyperkalaemia prevalence increases in more advanced CKD stages, and is associated with a poor prognosis. This scenario generates controversy on the correct nutritional approach to hyperkalaemia in CKD patients, considering the unproven link between potassium intake and serum K+ levels. Another concern is that drug-induced hyperkalaemia leads to the down-titration or withdrawal of renin-angiotensin system inhibitors (RASI) and mineralocorticoids receptors antagonists (MRA) in patients with CKD, depriving these patients of central therapeutic interventions aimed at delaying CKD progression and decreasing CV mortality. The new K+-binder drugs (Patiromer and Sodium-Zirconium Cyclosilicate) have proven to be adequate and safe therapeutic options to control serum K+ in CKD patients, enabling RASI and MRA therapy, and possibly, a more liberal intake of fruit and vegetables.

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Hyperkalemia-Related Discontinuation of Renin-Angiotensin-Aldosterone System Inhibitors and Clinical Outcomes in CKD: A Population-Based Cohort Study

Cited by 69 publications

References 28 publications

Demographic and clinical profile of black patients with chronic kidney disease attending Charlotte Maxeke Johannesburg Academic Hospital (CMJAH) in Johannesburg, South Africa

Demographic and clinical profile of black patients with chronic kidney disease attending Charlotte Maxeke Johannesburg Academic Hospital (CMJAH) in Johannesburg, South Africa

Demographic and clinical profile of black patients with chronic kidney disease attending a tertiary hospital in Johannesburg, South Africa

Chronic Hyperkaliemia in Chronic Kidney Disease: An Old Concern with New Answers

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