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Copeptin Associates with Cause-Specific Mortality in Patients with Impaired Renal Function: Results from the LURIC
Vera Krane1,2, Bernd Genser3,4, Marcus E Kleber5
1Department of Medicine 1, Division of Nephrology, and krane_v@ukw.de.
Insights
Elevated copeptin levels, a marker for arginine vasopressin (AVP), are linked to increased mortality risk in chronic kidney disease (CKD) patients. This association was not observed in individuals with normal kidney function.
Area of Science:
- Nephrology
- Cardiovascular Medicine
- Endocrinology
Background:
- In chronic kidney disease (CKD), arginine vasopressin (AVP) dysfunction may contribute to cardiovascular and infectious complications.
- AVP dysregulation leads to increased V1a and V1b receptor activation, potentially exacerbating CKD-related health issues.
Purpose of the Study:
- To investigate the association between copeptin, a surrogate marker for AVP, and cause-specific mortality across the spectrum of renal function.
- To determine if copeptin levels predict mortality in patients with varying degrees of kidney impairment.
Main Methods:
- Copeptin levels were measured in two cohorts: LURIC (n=3131) and 4D-Study (n=1241).
- Patients were stratified by estimated glomerular filtration rate (eGFR): ≥90, 60-89, <60 mL/min/1.73 m², and hemodialysis.
- Cox proportional hazards regression was used to assess the association between copeptin and mortality during follow-up periods of 9.9 and 4 years, respectively.
Main Results:
- Median copeptin levels significantly increased with decreasing eGFR, rising from 5.6 pmol/L (eGFR ≥90) to 80.8 pmol/L (hemodialysis).
- In patients with eGFR 60-89 mL/min/1.73 m², each SD increase in copeptin was associated with a 25% higher risk of coronary mortality, 30% for infectious mortality, and 15% for all-cause mortality.
- Similar associations were observed in patients with more advanced renal disease, but no significant link to mortality was found in those with normal renal function.
Conclusions:
- Copeptin concentrations are independently associated with increased coronary, infectious, and all-cause mortality in patients with renal impairment.
- The study highlights the prognostic value of copeptin in CKD patients, particularly concerning cardiovascular and infectious risks.
- No significant association between copeptin and mortality was found in individuals with normal kidney function.
Background:
In chronic kidney disease (CKD) arginine vasopressin (AVP) cannot efficiently act via renal V2-receptors. AVP is upregulated leading to augmented activation of V1a- and V1b-receptors, which might contribute to the increase in cardiovascular and infectious complications in CKD. Here, we evaluate copeptin, a surrogate of AVP, and its association with cause specific mortality among patients within the whole spectrum of renal function.
Methods:
Copeptin was measured in baseline samples from the LURIC (n = 3131 patients with coronary angiograms) and the 4D-Study (n = 1241 type 2 diabetic hemodialysis patients). Patients were stratified into 4 groups: estimated glomerular filtration rate (eGFR) ≥90 mL/min/1.73 m2, 60-89 mL/min/1.73 m2, <60 mL/min/1.73 m2, and hemodialysis. The association of copeptin with mortality was assessed by Cox proportional hazards regression during 9.9 years of median follow-up in the Ludwigshafen Risk and Cardiovascular Health (LURIC) study and 4 years of median follow-up in the German Diabetes Dialysis Study (4D-Study).
Results:
Median copeptin increased with decreasing eGFR: 5.6 [interquartile range (IQR), 3.1-8.1] pmol/L (eGFR ≥90 mL/min/1.73 m2), 6.7 (2.9-10.5) pmol/L (eGFR 60-89 mL/min/1.73 m2), 15.3 (6.7-23.9) pmol/L (eGFR <60 mL/min/1.73 m2), and 80.8 (51.2-122) pmol/L (hemodialysis), respectively. Per SD increase in copeptin, the risk of coronary, infectious, and all-cause mortality increased by 25, 30, and 15% [hazard ratios (HR), 1.25; 95% CI, 1.13-1.39; HR, 1.30; 95% CI, 0.98-1.71; and HR, 1.15; 95% CI, 1.05-1.25], respectively, in patients with eGFR 60-89 mL/min/1.73 m2. Except for coronary death, results were similar among patients with more advanced renal disease. No significant association was found in patients with normal renal function.
Conclusions:
Copeptin concentrations were independently associated with coronary, infectious, and all-cause mortality in patients with renal impairment. In patients with normal renal function no significant association was found.
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