Urinary Potassium Excretion and Renal and Cardiovascular Complications in Patients with Type 2 Diabetes and Normal Renal Function

Abstract

Background and objectives We investigated the association of urinary potassium and sodium excretion with the incidence of renal failure and cardiovascular disease in patients with type 2 diabetes.Design, setting, participants, & measurements A total of 623 Japanese type 2 diabetic patients with eGFR$60 ml/min per 1.73 m 2 were enrolled in this observational follow-up study between 1996 and 2003 and followed-up until 2013. At baseline, a 24-hour urine sample was collected to estimate urinary potassium and sodium excretion. The primary end point was renal and cardiovascular events (RRT, myocardial infarction, angina pectoris, stroke, and peripheral vascular disease). The secondary renal end points were the incidence of a 50% decline in eGFR, progression to CKD stage 4 (eGFR,30 ml/min per 1.73 m 2 ), and the annual decline rate in eGFR.Results During the 11-year median follow-up period, 134 primary end points occurred. Higher urinary potassium excretion was associated with lower risk of the primary end point, whereas urinary sodium excretion was not. The adjusted hazard ratios for the primary end point in Cox proportional hazards analysis were 0.56 (95% confidence interval [95% CI], 0.33 to 0.95) in the third quartile of urinary potassium excretion (2.33-2.90 g/d) and 0.33 (95% CI, 0.18 to 0.62) in the fourth quartile (.2.90 g/d) compared with the lowest quartile (,1.72 g/d). Similar associations were observed for the secondary renal end points. The annual decline rate in eGFR in the fourth quartile of urinary potassium excretion (-1.3 ml/min per 1.73 m 2 /y; 95% CI, -1.5 to -1.0) was significantly slower than those in the first quartile (-2.2; 95% CI, -2.4 to -1.8).Conclusions Higher urinary potassium excretion was associated with the slower decline of renal function and the lower incidence of cardiovascular complications in type 2 diabetic patients with normal renal function. Interventional trials are necessary to determine whether increasing dietary potassium is beneficial.

Risk for acute kidney injury in primary health care

“…Physiologically, the elderly are more susceptible to AKI, and it is important to understand the association of this pathology with a more or less severe consequence for this population (25) . The strict control of hypertension and diabetes is a strategy that should reduce the risk of renal complications (26) . In addition, a study showed hypertension and diabetes are risk factors for AKI (27) .…”

Rationale and Design of a Randomized Placebo-Controlled Clinical Trial Assessing the Renoprotective Effects of Potassium Supplementation in Chronic Kidney Disease

“…This hypothesis has recently been addressed in 6 large CKD cohorts (Table 1) [11][12][13][14][15][16]. Smyth et al [13] performed their analysis in the ONTARGET and TRANSCEND cohorts.…”

“…This suggests that dietary intake is not the primary determinant of serum K + in CKD and adds to the safety of our proposed K + supplementation trial. Araki et al [11] analyzed the association between 24-h urinary K + excretion, renal outcomes, and CV events in Japanese patients with type 2 diabetes. During a median follow-up of 11 years, patients in the highest quartile of urinary K + excretion (>2.9 g/day) had significantly fewer CV events, 50% reduction in eGFR, or start of renal replacement therapy than patients in the lowest quartile (< 1.72 g/day).…”

“…The recommendations by the World Health Organization, European Food Safety Authority, and U.S. Department of Health and Human Services to define dietary reference values for dietary K + intake (90-120 mmol/day) are echoing this awareness [8][9][10]. Of interest, recent studies also suggest an effect of dietary K + on renal outcomes in patients with chronic kidney disease (CKD) [11][12][13][14][15]. That is, urinary K + excretion (as proxy for intake) was associated with slower progression of CKD in the majority of these studies (Table 1) [16].…”

“…Besides renoprotective effects, higher K + intake has also been associated with a lower risk of CV events [2,11,18]. For example, the PURE-study (including > 100,000 subjects worldwide) showed inverse relationships between urinary K + excretion, blood pressure, and CV outcomes [6,7].…”