Copeptin Predicts IgA Nephropathy Outcomes

Copeptin, a surrogate marker for arginine vasopressin (AVP), showed prognostic value of established risk markers.
Copeptin, a surrogate marker for arginine vasopressin (AVP), showed prognostic value of established risk markers.

Copeptin, a surrogate marker for arginine vasopressin (AVP), is associated with disease severity and prognosis in patients with IgA nephropathy (IgAN), new findings suggest.

In a prospective cohort of 59 patients with biopsy-proven IgAN, research collaborators at University Medical Center Groningen (UMCG) and Radboud University Medical Center Nijmegen (RUMC) found, during a 5-year follow-up, a positive association between the highest tertile of baseline copeptin and the incidence of a composite renal outcome of doubling of serum creatinine, end-stage renal disease (ESRD), or start of immunosuppressive therapy. In addition, copeptin showed prognostic value over the established risk markers mean arterial pressure (MAP), proteinuria, and estimated glomerular filtration rate (eGFR), according to the investigators.

In a multivariate model, adjusting for sex, eGFR, and MAP, the highest tertile of copeptin was associated with a 4.6-fold increased risk of the composite outcome compared with the 2 lower tertiles, lead investigators Ron T. Gansevoort, MD, PhD, of UMCG, and Jack F. Wetzels, MD, PhD, of RUMC, and colleagues reported in a paper published online ahead of print in Nephrology Dialysis Transplantation. In a model that adjusted only for 24-hour urine protein, the highest tertile was associated with a 4.8-fold increased risk.

During the 5-year follow-up, 19 patients (32%) experienced 1 or more of the study outcomes that define the composite renal outcome. Renal disease progressed in 13 patients (22%) as indicated by doubling of serum creatinine and ESRD developed in 5 patients (9%). Eight patients started immunosuppressive therapy.

The investigators noted that in water deprivation tests in IgAN patients performed by the same research group, an impaired urine concentrating capacity was found with elevated AVP and copeptin levels. “We hypothesize that in IgAN, when renal disease progresses, urine concentrating capacity declines,” the researchers wrote. “As a response, AVP secretion is stimulated to maintain water homeostasis. Because AVP levels rise and accelerate kidney damage, this may lead to a vicious circle causing progressive renal function loss.”

The researchers concluded that their results “suggest that measurement of copeptin could be of clinical value in this patient group because it may help to stratify patients according to risk and indication for treatment.”

The study is the first to investigate copeptin in IgAN, the researchers stated. Study strengths include a study population consisting of a well-defined group of patients with biopsy-proven disease, a 5-year follow-up and data collection and sample storage according to standardized protocols. Study limitations include a relatively small patient population and patient use of ACE inhibitors and angiotensin receptor blockers during the study, which “may have weakened the correlation between copeptin and proteinuria and possibly the correlation between copeptin and renal outcome during follow-up.”

Reference

1. Zittema D, van den Brand JA, Bakker SJ, et al. Copeptin, a surrogate marker for arginine vasopressin, is associated with disease severity and progression in IgA nephropathy patients. Nephrol Dial Transplant 2017; published online ahead of print.

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