Nephrotic Syndrome Linked With End-Stage Kidney Disease, Cardiovascular Issues

Patients with nephrotic syndrome were far more likely than healthy controls to suffer end-stage kidney disease, particularly if they had focal segmental glomerulosclerosis or membranous nephropathy.

People with nephrotic syndrome face significantly higher risk of end-stage kidney disease, cardiovascular problems, and death, according to new research.

The study, published in the Journal of the American Society of Nephrology, highlights the need to better understand how nephrotic conditions can lead to declines in health overall.

Corresponding author Alan S. Go, MD, of Kaiser Permanente Northern California, and colleagues, explained that the term nephrotic syndrome describes symptoms associated with rare kidney diseases, such as focal segmental glomerulosclerosis (FSGS), membranous nephropathy, and minimal change disease. Those clinical manifestations include peripheral edema, heavy proteinuria, hypoalbuminemia, and hypercholesterolemia.

Nephrotic syndrome has already been linked with a number of conditions, including cardiovascular and thromboembolic events, but the investigators said such research has never been based on a robust data set to provide an accurate estimate of risk.

In hopes of changing that, Go and colleagues used electronic health records to evaluate the cases of 907 adult patients with primary nephrotic syndrome who received care at Kaiser Permanente Northern California between 1996 and 2012. Those patients were then matched on a 1:100 basis with healthy controls, none of whom had diabetes, nephrotic syndrome, or proteinuria.

Among the patients with definite (655) or presumed (252) nephrotic syndrome, 40% had FSGS, 40% had membranous nephropathy, and 20% had minimal change disease. The patients had a median age of 49, and 43% were women.

The investigators found that those with nephrotic syndrome had significantly higher rates of end-stage kidney disease, with an adjusted hazard ratio (aHR) of 19.63 (95% confidence interval). Acute coronary syndrome, heart failure, and ischemic stroke risks were also elevated (aHR, 2.58, 3.01, and 1.80, respectively. Venous thromboembolism risk was also higher (aHR, 2.56), as was risk of death (aHR, 1.34).

Go and colleagues said among the three etiologies of primary nephrotic syndrome, risk levels were generally similar, with the exception of end-stage kidney disease, which was more common in patients with FSGS and membranous nephropathy compared to those with minimal change disease.

“Our study findings support and materially extend results from previous studies that investigated outcomes in adults with [nephrotic syndrome],” Go and colleagues said, noting that previous research has shown, for instance, that FSGS is a leading cause of end-stage kidney disease.

While cardiovascular outcomes have been less well-studied in the group, investigators said their study confirmed that cardiovascular impacts are an area of concern.

Go and his coauthors said one of the major strengths of their study was the diversity of its population and the comprehensiveness of the data set available through Kaiser Permanente’s fully integrated healthcare system.

“This allowed for the assessment of laboratory data across all practice settings to systematically screen for adults with documented evidence of nephrotic range proteinuria, and the determination of baseline demographic and clinical characteristics,” they wrote.

There are also some limitations to their study. The long-term nature of the data meant the data for certain variables were not available, and it was also possible that some etiologies were misclassified, they said.

Go and colleagues concluded that patients with nephrotic syndrome ought to be surveilled carefully to control risk factors for kidney disease progression and to identify and manage cardiovascular risk factors.


Go AS, Tan TC, Chertow GM, et al. Primary nephrotic syndrome and risks of ESKD, cardiovascular events, and death: The Kaiser Permanente nephrotic syndrome study [published online ahead of print, 2021 Jun 18]. J Am Soc Nephrol. 2021;ASN.2020111583. doi:10.1681/ASN.2020111583

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