The Role of the Kidneys and Liver in the Elimination of Glucagon (MCR_EndCir)

University Hospital, Gentofte, Copenhagen

Status: Completed

Conditions: Chronic Kidney Diseases; Liver Cirrhosis; Hyperglucagonemia

Treatments: Biological: Primed tracer infusion; Biological: Glucagon infusion

Study type: Interventional

Funder types: Other

Identifiers

NCT05056584

H-16043802

Details and patient eligibility

About

The study aims to evaluate the kinetics and effect of glucagon in patients with chronic kidney disease and liver cirrhosis and matched healthy subjects, respectively.

Full description

In the present project the investigators wish to identify whether the effect, elimination and degradation of glucagon differ between healthy control subjects and patients with Chronic Kidney Disease (CKD) and liver cirrhosis, respectively. By performing glucagon infusions on healthy control subjects and matched subjects with either limited renal and hepatic function, the contribution of both organs to the metabolic clearance rate (MCR) of glucagon can be tested. A primed infusion of stable isotopic labelled tracers will allow the researchers to investigate the effects of the glucagon infusion on the glucose, lipid and amino acid metabolism.

The quantification of the MCR of glucagon will be accompanied by a range of pharmacodynamic measures in order to substantiate whether a potentially altered glucagon MCR inflicts pharmacodynamic changes of glucagon, which could contribute to the pathophysiology of CKD and liver cirrhosis.

Enrollment: 48 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

The CKD group

• Men/women between 18 and 75 years of age
• CKD stage 4 or 5
• Normal liver function (alanine aminotransferase (ALAT), aspartate aminotransferase (ASAT), albumin and coagulation factor II, VII and X (INR) within normal range,
• Informed consent

The cirrhosis group

• Men/women between 18 and 75 years of age
• Verified diagnosis of cirrhosis - Child-Pugh Score of 5-12
• Normal kidney function (estimated glomerular filtration rate (eGFR) above 60 ml/min/1.73m2 and absence of proteinuria)
• Informed consent

The control group

• Men/women between 18 and 75 years of age
• Normal kidney function (estimated glomerular filtration rate (eGFR) above 60 ml/min/1.73m2 and absence of proteinuria)(plasma creatinine ≤105 micromol/L (µM) for men and ≤90 µM for women)
• Normal liver function (alanine aminotransferase (ALAT), aspartate aminotransferase (ASAT), albumin and coagulation factor II, VII and X (INR) within normal range
• Informed consent

Exclusion criteria

All groups

• Diagnosis of diabetes and/or HbA1c ≥43 mmol/mol and/or fasting plasma glucose ≥6 mmol/l.
• Previous kidney transplantation with remaining kidney graft
• Present treatment with oral glucocorticoids
• Polycystic kidney disease
• Pregnancy or breastfeeding
• Inflammatory bowel disease
• Surgical procedure within the last 3 months
• Haemoglobin < 6 mmol/l (women) or < 7 mmol/l (men)
• First-degree relatives with diabetes
• Any condition that the investigators feel would interfere with trial participation

Trial design

Primary purpose: Basic Science

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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48 participants in 3 patient groups

Healthy control subjects

Experimental group

Description:

Healthy control subjects, matched for age, sex and BMI

Treatment:

Biological: Glucagon infusion

Biological: Primed tracer infusion

Patients with End-stage Renal Disease

Experimental group

Description:

Patients with hemodialysis-treated ESRD.

Treatment:

Biological: Glucagon infusion

Biological: Primed tracer infusion

Patients with liver cirrhosis

Experimental group

Description:

Patients with Child-Pugh A or B Cirrhosis

Treatment:

Biological: Glucagon infusion

Biological: Primed tracer infusion