Copeptin: an indicator and predictor of kidney damage in patients with type 2 diabetes

This study investigated the relationship between protein levels in the blood and their relationship with kidney failure.

Arginine vasopressin (AVP) is a protein found in most mammals that is responsible for controlling the level of liquid in the body. AVP is released into the blood when dehydration occurs, stimulating the kidneys to take in water that would otherwise be expelled as urine. Although it has an essential role in the body, high levels of AVP are thought to result in kidney damage by causing hypertension (high blood pressure), albuminuria (too much protein in the urine), and glomerulosclerosis (scarring of the kidney blood vessels).

Importantly it has been shown that diabetic mammals have higher levels of AVP in their blood than non-diabetics. Copeptin is a protein specific to humans that performs the same function and can be measured in the place of AVP. It is thought to have a similar relationship with diabetes and kidney damage.

This study aimed to investigate the relationship between copeptin levels and kidney damage in patients with type 2 diabetes mellitus (T2DM). T2DM is a disease that results in hyperglycemia (high blood sugar) due to a lack of insulin (protein that controls blood sugar levels) or due to insulin resistance (body does not respond to the insulin produced).

1,328 patients with T2DM were included in this study with an average follow-up of 6.5 years. Patients were divided into two groups; those who received drugs that caused renin–angiotensin–aldosterone system inhibition (RAASi) (349 patients) and those who did not (979 patients).

RAASi drugs target proteins that control blood pressure and water balance in the blood, for example Captopril and Takturna. These drugs can affect the kidneys and may cause kidney damage. The study was divided this way so that the natural decline in kidney function throughout diabetes (i.e. seen in those not taking RAASi drugs) could be compared to the decline in those who were taking drugs that may affect the kidneys (i.e. those taking the RAASi drugs).  At the beginning of the study, kidney function was found to be better in those not taking RAASi drugs compared to those taking RAASi drugs. 

In those not taking RAASi drugs, when copeptin levels were high, kidney function was found to be low and vice versa. This remained true even when typical kidney decline risk factors were taken into account. When copeptin levels were high at the start of the study, this was associated with significantly decreased kidney function by the end of the study compared to those who had low levels at the start of the study. In essence, higher initial copeptin levels predicted a greater decline in kidney function over time. 

In those taking RAASi drugs, high copeptin levels at the beginning of the study were associated with decreased kidney function. However, high levels at the start of the study were not predictive of a significantly decreased kidney function by the end of the study compared to those with lower levels at the beginning of the study.

The authors concluded that measuring copeptin could be a potential method of early diagnosis and intervention for kidney damage in patients with type 2 diabetes who have not received RAASi drugs. 

Natural copeptin levels may have been skewed in patients as they had not fasted prior to blood being drawn. This means copeptin may have been released to combat high blood sugar/salt levels therefore producing a false high level result.