Elevated levels of plasma copeptin, a measure of vasopressin (VP), independently predicts development of chronic kidney disease (CKD) as well as other kidney diseases, according to a new study.
Researchers from Skane University Hospital in Lund, Sweden, studied baseline copeptin in relationship to kidney disease diagnoses in 2 cohorts selected from the Swedish general population. According to national registry data, 89 of 5158 individuals in the Malmo Preventive Project (MPP) reinvestigation and 180 of 5162 participants in the Malmo Diet and Cancer Cardiovascular Cohort (MDC-CC), who initially had estimated glomerular filtration rates above 60 mL/min/1.73m2, developed CKD during 8.7 and 19.6 years of follow-up, respectively. In addition, 118 and 213 individuals in MPP and MDC-CC, respectively, received a diagnosis of another kidney disease, such as acute tubulointerstitial nephritis or chronic glomerulonephritis.
In multivariate analyses, each 1 standard deviation (SD) increment in Ln-transformed copeptin was associated with a significant 46% and 24% increased risk for CKD in the MPP and MDC-CC cohorts, respectively, after adjusting for traditional CKD risk factors and other variables, including diabetes, systolic blood pressure, antihypertensive treatment, estimated glomerular filtration rate, smoking, body mass index, and demographics.
In addition, each 1 SD increment in Ln-transformed copeptin was associated with a significant 31% greater risk for kidney diseases other than CKD in the MPP cohort and a non-significant 10% increased risk in the MDC-CC cohort. In a meta-analysis of data from both cohorts, each 1 SD increment in Ln-transformed copeptin was associated with a significant 18% greater risk.
“Our results point at copeptin, a measure of VP, as a marker for development of renal diseases,” Sofia Enhörning, MD, PhD, and her colleagues concluded in Nephrology Dialysis Transplantation. “In selected groups of patients, copeptin may in the future assist in detection of individuals that are at higher risk for developing renal diseases and its cardiovascular complications and who might benefit from preventive therapy such as hydration and pharmacological blockade of the VP system.”
How elevated VP might lead to CKD remains unclear, but it is hypothesized that VP-induced hyperfiltration is at least partially involved, the authors stated.
The primary CKD risk factors are metabolic diseases such as diabetes and hypertension, and previous studies have identified links between elevated copeptin and these diseases, Dr Enhörning’s team noted. Consequently, they suspected that part of the association between elevated copeptin and CKD during follow-up would be driven by new-onset metabolic disease. “However, this could not explain the observed association between copeptin and risk of developing other specified kidney diseases such as acute tubulointerstitial nephritis or hydronephrosis.”
Moreover, the investigators found no significant interaction between diabetes status and copeptin on the risk of CKD in either cohort. In subanalyses of individuals with and without diabetes, the association between copeptin and CKD remained only in the subgroup of individuals without diabetes in the MPP cohort. “Thus, it is likely that other pathophysiological mechanisms are involved.”
Enhorning S, Christensson A, and Melander O. Plasma copeptin as a predictor of kidney disease. Nephrol Dial Transplant 2018;1–9. doi: 10.1093/ndt/gfy017