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BMC Nephrol. 2019 Mar 25;20(1):104. doi: 10.1186/s12882-019-1292-3.

Urinary angiotensinogen level is associated with potassium homeostasis and clinical outcome in patients with polycystic kidney disease: a prospective cohort study.

Author information

1
Department of Internal Medicine, College of Medicine, Institute of Kidney Disease Research, Yonsei University, Seoul, 03722, Republic of Korea.
2
Division of Nephrology, Soonchunhyang University Hospital, Seoul, Republic of Korea.
3
Division of Nephrology and Hypertension, Department of Internal Medicine, Inha University College of Medicine, Incheon, Republic of Korea.
4
Medical Research Collaborating Center, Seoul National University Hospital and Seoul National University College of Medicine, Seoul, Republic of Korea.
5
Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Republic of Korea.
6
Department of Internal Medicine, Busan Paik Hospital, Inje University, Busan, Republic of Korea.
7
Department of Internal Medicine, Seoul National University College of Medicine, Boramae Medical Center, Seoul, Republic of Korea.
8
Department of Internal Medicine, College of Medicine, Institute of Kidney Disease Research, Yonsei University, Seoul, 03722, Republic of Korea. yoosy0316@yuhs.ac.

Abstract

BACKGROUND:

Guidelines for general hypertension treatment do not recommend the combined use of renin-angiotensin-aldosterone system (RAAS) inhibitors due to the risk of hyperkalemia. However, a recent clinical trial showed that polycystic kidney disease (PKD) patients had infrequent episodes of hyperkalemia despite receiving combined RAAS inhibitors. Because intrarenal RAAS is a main component for renal potassium handling, we further investigated the association between intrarenal RAAS activity and serum potassium level in patients with chronic kidney disease, particularly in PKD patients, and examined whether intrarenal RAAS activity has a prognostic role in patients with PKD.

METHODS:

A total of 1788 subjects from the KoreaN cohort study for Outcome in patients With Chronic Kidney Disease (KNOW-CKD) were enrolled in this study. Intrarenal RAAS activity was assessed by the measurement of urinary angiotensinogen (AGT). The primary outcome was the composite of all-cause mortality and renal function decline.

RESULTS:

Patients with PKD had a significantly lower serum potassium level in chronic kidney disease stages 1 to 3b than non-PKD patients. In logistic regression analysis, after adjusting for multiple confounders, PKD patients had a significantly lower risk of hyperkalemia than non-PKD patients. In multivariable linear regression analysis, the urinary AGT/creatinine (Cr) ratio was negatively correlated with the serum potassium level (β = - 0.058, P = 0.017) and positively correlated with the transtubular potassium gradient (TTKG, β = 0.087, P = 0.001). In propensity score matching analysis, after matching factors associated with serum potassium and TTKG, PKD patients had a significantly higher TTKG (P = 0.021) despite a lower serum potassium level (P = 0.004). Additionally, the urinary AGT/Cr ratio was significantly higher in PKD patients than in non-PKD patients (P = 0.011). In 293 patients with PKD, high urinary AGT/Cr ratio was associated with increased risk of the composite outcome (hazard ratio 1.29; 95% confidence interval, 1.07-1.55; P = 0.007).

CONCLUSIONS:

High activity of intrarenal RAAS is associated with increased urinary potassium excretion and low serum potassium level in patients with PKD. In addition, intrarenal RAAS activity can be a prognostic marker for mortality and renal function decline in these patients.

KEYWORDS:

Angiotensinogen; Polycystic kidney disease; Potassium

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