The effect of hyperkalemia and long inter-dialytic interval on morbidity and mortality in patients receiving hemodialysis: a systematic review

Figures & data

Table 1. Eligibility criteria for the identification of studies describing HK and LIDI in HD patients.

PICOS element	Inclusion criteria	Exclusion criteria
Population	Adults (aged ≥ 18 years) with acute renal failure or chronic/end-stage renal disease in receipt of hemodialysis	Patients not receiving hemodialysis Paediatric patients (aged < 18 years) Patients without acute renal failure or chronic/end-stage renal disease
Intervention and comparison	Hemodialysis	Interventions other than hemodialysis Other dialysis modalities (e.g., peritoneal dialysis, home dialysis)
Outcomes	Prevalence, incidence of HK All-cause mortality Cardiovascular mortality Cardiovascular events (including MI, stroke, heart failure, cardiac arrhythmias, TIA, angina)	Outcomes of interest not reported
Study design	Any relevant study design (including RCTs, non-RCTs, epidemiological studies, observational studies)	Case series, case reports Guidelines, letter, editorial, review, retracted Systematic reviews^a Non-human studies
Language restriction	English language only	Studies published in languages other than English
Publication date restriction	None	None

HK: hyperkalemia; MI: myocardial infraction; RCTs: randomized controlled trials; TIA: transient ischemic attack.

^aSuch study designs were used only to identify potentially relevant primary studies that had not been captured through database searches.

Figure 1. PRISMA flow diagram illustrating the study selection process. HK: hyperkalemia; LIDI: long inter-dialytic interval.

Table 2. Summary of patient characteristics and outcomes in studies reporting frequency of HK in HD patients stratified by population.

HD population (no. of studies)	Publication type	Study design	Cohort size (N)	Age (years)^a, % male	HD vintage (months)^a,b	Median prevalence (IQR)	Incidence rate
ESRD (n = 40) [9,17,20–23,25,26,29–31, 35–41,43,44,46,47, 50,54,55,59,63, 65–67,70,72,74–79, 82,84,85]	33 Full texts 7 Abstracts	22 Observational 3 non-RCT trials 12 RCTs 3 NR	10–55,183	60.6 (5.3), 59%	42.3 (27.9) 3x weekly schedule	19.0% (7.8–38.9%)	15.1–26.0 events per 100 patient-months
CKD (n = 21) [18,19,24,27,32–34, 42,45,48,49, 51,53,56–58,60,61, 64,69,71]	17 Full texts 4 Abstracts	14 Observational 2 non-RCT trials 3 RCTs 2 NR	5–74,219	56.3 (6.9), 58.8%	59.8 (20.1) 3x weekly schedule	24.0% (7.6–38.8%)	–
AKI (n = 4) [28,52,73,80]	2 Full texts 2 Abstracts	All observational	46–105	52.8 (14.7), 63.8%	Intermittent HD	27.3% (16.0–38.4%)	–
eHD (n = 5) [16,62,68,81,83]	3 Full text 2 Abstract	4 Observational 1 NR	37–489	53.8 (7.5), 60.2%	eHD	24.0% (21.1–37.6%)	–

AKI: acute kidney injury; CKD: chronic kidney disease; eHD: emergency hemodialysis; ESRD: end-stage renal disease; HD: hemodialysis; IQR: interquartile range; NR: not reported; RCTs: randomized controlled trials.

^aMean (SD).

^bReported in a limited number of studies only.

Figure 2. Median prevalence of HK (%) across the 70 included studies stratified by study-defined S-K⁺ thresholds. CKD: chronic kidney disease; ESRD: end-stage renal disease; HD: hemodialysis; HK: hyperkalemia; S-K⁺: serum potassium.

Table 3. Studies reporting mortality due to HK in patients receiving HD (n = 12).

Author, year, country	Population	Study period	Subgroup (N)	Age (years)^a, % male	S-K^+ levels (mmol/L)	Follow-up (months)	Death due to HK
Balle et al. 1990, Germany	ESRF due to analgesic-associated nephropathy	1970–1986	Total population (55)	61 (44–79), 34.5%	NR	57	7.3%
Chaaban et al. 2013, United Arab Emirates	CKD	NR	Control group (30)	48.9 (18.7), 52%	NR	3	0%
Charytan et al. 2017, USA	ESRD	NR	Placebo (51)	NR	> 6.0	8.3	0%
Jadoul et al. 2012, International	ESRD	1996–2008	Total population (37,765)	NR	> 5.0	19.1^a	1.3%
Li et al. 2012, China	ESRD	2006–2011	Total population (268)	NR	NR	60	4.5%
Li et al. 2020, China	CKD	2011–2015	Total population (210)	56.6 (16.6), 59.5%	NR	49.8^b	4.4%
Lomonte et al. 2004, Italy	ESRD/Leprosy	1980–2003	Total population (8)	61 (8.9), 75%	NR	NR	12.5%
Morduchowicz et al. 1992, Israel	ESRF	NR	Total population (84)	NR	NR	66	5%
Onuigbo et al. 2013, Italy	ESRD	2007–2010	Total population (466)	65.6 (19–97)^b, 49.1%	NR	28.9^a	3%
Poulikakos et al. 2015, UK	Renal failure	NR	Total population (75)	60 (14), 68%	NR	35.9^a	1.3%
Pun et al. 2012, USA	ESRD	2002–2005	Total population (363)	69 (59–78)^b, 55.4%	NR	NR	1.3%
Shibata et al. 1983, Japan	Renal failure	NR	Total population (62)	50 (26–78), 67.7%	NR	NR	3.2%

CKD: chronic kidney disease; ESRD: end-stage renal disease; ESRF: end-stage renal failure; HK: hyperkalemia; NR: not reported; S-K⁺: serum potassium.

^aMean (SD) or mean (range).

^bMedian (IQR).

Table 4. Studies reporting an association between HK and the inter-dialytic period.

Author, year, country (publication type)	Population	S-K^+ levels (mmol/L)	Subgroup (N)	Follow-up	HD schedule	HK prevalence
						Outcome measure	Value (95% CI)
Chevarria et al. 2010, Spain (Abstract)	ESRD on HD	>6.0	Total population (20)	12 months^a	3x weekly; MWF or TTS	OR	2.8 (1.47–5.33)
Singh et al. 2017, USA (Abstract)	ESRD on HD	>5.0	Dialysate K^+ <3.0 mmol/L (179)	12 days	Unclear; 6 HD within 12 days	Percentage	50.0
			Dialysate K^+ ≥3.0 mmol/L (33)	12 days			36.0
Yusuf et al. 2016, USA (Full text)	ESRD on maintenance HD	≥5.5	Day after LIDI 2007 cohort (28,774)	9 months^a (19,336^b)	3x weekly; MWF or TTS	Rate per 100 patient-months	58.7 (57.7–59.8)^c
			Day after LIDI 2008 cohort (34,788)	9 months^a (23,503^b)			62.2 (61.2–63.2)^c
			Day after LIDI 2009 cohort (34,571)	9 months^a (24,271^b)			62.9 (61.9–63.9)^c
			Day after LIDI 2010 cohort (36,888)	9 months^a (23,272^b)			61.6 (60.6–62.6)^c
			Day after SIDI 2007 cohort (28,774)	9 months^a (38,673^b)			28.8 (28.3–29.3)^c
			Day after SIDI 2008 cohort (34,788)	9 months^a (47,005^b)			27.6 (27.2–28.1)^c
			Day after SIDI 2009 cohort (34,571)	9 months^a (48,541^b)			26.3 (25.8–26.7)^c
			Day after SIDI 2010 cohort (36,888)	9 months^a (46,543^b)			26.2 (25.8–26.7)^c

CI: confidence interval; ESRD: end-stage renal disease; HD: hemodialysis; HK: hyperkalemia; LIDI: long inter-dialytic interval; MWF: Monday-Wednesday-Friday; OR: odds ratio; SIDI: short inter-dialytic interval; S-K⁺: serum potassium; TTS: Tuesday-Thursday-Saturday.

^aMean.

^bCumulative follow-up time in months.

^cRate of HK was computed as a ratio of total number of HK episodes and cumulative follow-up time; 95% CI for the rates of HK were calculated based on normal approximation.

Figure 3. Quality assessment of the 40 observational studies reporting on mortality. One additional study was an RCT but published as a conference proceeding making the quality assessment not informative.

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