Disclosures: Go reports being employed by Kaiser Permanente Northern California and receiving research funding from CSL Behring, Novartis, Amarin and Bristol Meyers-Squibb. Please see the study for all other authors’ relevant financial disclosures.
June 22, 2021
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Primary nephrotic syndrome tied to development of kidney failure, heart failure

Disclosures: Go reports being employed by Kaiser Permanente Northern California and receiving research funding from CSL Behring, Novartis, Amarin and Bristol Meyers-Squibb. Please see the study for all other authors’ relevant financial disclosures.
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Compared with a cohort free of kidney disease, patients with primary nephrotic syndrome were nearly 20-times more likely to develop kidney failure within 4.5 years of follow-up, research showed.

The findings, which were published in the Journal of the American Society of Nephrology, also demonstrated a greater likelihood of adverse cardiovascular events (including acute coronary syndrome and heart failure) with the condition.

Primary nephrotic syndrome
Data were derived from Go AS, et al. J Am Soc Nephrol. 2021;doi:10.1681/ASN.2020111583.

“Our study highlights the high risk of kidney failure and the underappreciated excess risks of different arterial and venous cardiovascular complications linked to primary nephrotic syndrome due to focal segmental glomerulosclerosis, membranous nephropathy, or minimal change disease,” Alan S. Go, MD, of Kaiser Permanente Northern California division of research, said in a related press release. “Additional information is needed on the most effective ways to lower the risks of both kidney and cardiovascular complications in patients.”

Utilizing electronic health record data from Kaiser Permanente Northern California, Go and colleagues identified 907 cases of primary nephrotic syndrome, which was defined as nephrotic-range proteinuria or diagnosed nephrotic syndrome (mean age was 49 years; 43% were women).

Outcomes were compared between these patients and 89,593 individuals without kidney disease during a median of 4.5 years.

End-stage kidney disease, cardiovascular outcomes

During this time, 369 patients developed end-stage kidney disease (defined as requiring maintenance dialysis or undergoing transplant), with researchers linking primary nephrotic syndrome to significantly higher adjusted rates (adjusted hazard ratio = 19.63).

Results also showed adults with primary nephrotic syndrome had higher adjusted rates of a variety of cardiovascular events, including acute coronary syndrome (aHR = 2.58), heart failure (aHR = 3.01), ischemic stroke (aHR = 1.80) and venous thromboembolism (aHR = 2.56).

Mortality

Higher mortality rates were observed for patients with primary nephrotic syndrome (aHR = 1.34), though researchers noted the rate of death with the condition was lower than that found in previous research.

“Our study findings support and materially extend results from previous studies that investigated outcomes in adults with [nephrotic syndrome] NS ...,” Go and colleagues wrote. “Of note, our cohort was considerably larger and only included patients with primary NS attributed to definite or presumed [focal segmental glomerulosclerosis] FSGS, [membranous nephropathy] MN or [minimal change disease] MCD in a more recent era (1996-2012). Our observed lower rate of death (2.37 per 100 person-year) compared with the earlier study can be explained, at least in part, by availability of more effective therapies for NS as well as cardiopreventive agents and approaches. Nonetheless, there remained an excess risk of death with primary NS that persisted even after accounting for differences in demographic characteristics, cardiovascular risk factors and other comorbidities.”

Further findings suggested that while excess ESKD risk differed based on nephrotic syndrome etiology (FSGS and membranous nephropathy led to greater risk than did minimal change disease), etiology showed no impact on cardiovascular outcomes or mortality.

“Our study ... points to the need for patients with primary nephrotic syndrome to be identified as early as possible so that they can begin to implement lifestyle changes — such as moving toward a healthy diet, stopping smoking, getting more exercise — and to be evaluated for preventive therapies that can reduce their risk for both cardiovascular disease and kidney failure,” Go said.