Edema and Outcome in Patients with Nephrotic-Range Albuminuria and Hypoalbuminemia: A Danish Multicenter cohort study

Nephrotic syndrome is characterized by proteinuria, hypoalbuminemia, and edema, though not all patients present with edema. This study investigates edema prevalence and its association with venous thromboembolism, kidney failure, and mortality in patients with nephrotic-range albuminuria and hypoalbuminemia. We conducted a Danish multicenter cohort study, including patients with plasma albumin <30 g/L and nephrotic-range albuminuria in the Central Denmark Region (2012-2022). Patients were identified using the laboratory information system and followed until death, lost to follow-up, or end of study. Data on demographics, comorbidities, biochemical markers, medical treatment, renal pathology, edema, venous thromboembolism, bleeding, kidney failure, and death were collected. Among 1,219 patients, 758 (62%) had edema at diagnosis. Patients with edema had a higher urine albumin creatinine ratio (4245 mg/g [3046-6079] vs. 3546 mg/g [2691-5125]) or a higher 24-hour urine albumin excretion rate (4559 mg/day [3146-6591] vs. 3546 mg/day [2828-5578]) and lower plasma albumin (26 g/l [22-28] vs. 28 g/l [26-29]) than those without edema. Venous thromboembolism occurred in 54 (4%) patients, with an incidence rate of 15 (95% CI, 11-21) per 1000 person-years in patients with edema vs. 10 (95% CI, 10-17) in patients without. Edema was also associated with faster kidney failure progression (edema: 188 days (IQR, 28-581); non-edema: 364 days (IQR, 116-920)) and higher one-year all-cause mortality (edema: 19%; non-edema: 16%). Edema affects approximately 60% of patients with nephrotic-range albuminuria and hypoalbuminemia, associated with increased risk of venous thromboembolism, faster kidney failure progression, and higher one-year all-cause mortality, highlighting its prognostic information in nephrotic syndrome.