Biomarkers and laboratory parameters

Emergency diagnostics services, vital parameters

Prompt laboratory diagnostics plays an essential role in the assessment of a patient’s medical status, in particular in emergency hospital admissions and critical illnesses. This is why the IKC provides diagnostic services for approximately 60 vital or urgent diagnostic parameters 24 hours a day, seven days a week, including biomarkers of the cardiovascular system, inflammation, renal function and neurological diseases as well as tests for drugs-of-abuse. Given its status as an interdisciplinary emergency laboratory, the Institute of Clinical Chemistry performs time-sensitive viral and auto-antibody tests (hepatitis, HIV, EBV, CMV, Influenza, SARS-COV2) outside normal working hours on behalf of the Department of Immunology or the Institute of Medical Virology. More than 90% of results on emergency analyses are forwarded to the attending physicians within less than one hour.

Cardiovascular disease

Cardiovascular disease is the most common cause of death and reason for hospitalization. Typical symptoms – chest pain or shortness of breath – may have various causes that can be ruled out or confirmed via laboratory diagnostics. In addition to ECG testing, the highly sensitive measurement of troponin T plays a critical role in the diagnosis of acute myocardial infarction. The measurement of natriuretic peptides (NT-proBNP) facilitates the diagnosis of congestive heart failure. D-dimer is a valuable marker in the exclusion of pulmonary embolism or aortic dissection.

Coronary heart disease, i.e. atherosclerosis of the coronary arteries, is often the reason behind a heart attack and heart failure. Many risk factors relating to atherosclerosis (www.agla.ch) are identified and monitored in the laboratory, including diabetes (glucose, HbA1c) and dyslipidemia (elevated blood levels of total and LDL cholesterol or triglycerides and low HDL cholesterol). More recent risk factors, such as C-reactive protein (CRP), apolipoproteins, lipoprotein(a) and homocysteine, are also measured in the Institute of Clinical Chemistry.

In addition to these diagnostic efforts, the identification of risk factors and biomarkers of cardiovascular disease constitutes the research priorities of the IKC.

Renal and urinary tract diseases

The kidneys play an essential role in the homeostasis of water, electrolyte and acid-base balance, and are responsible for the excretion of many potentially toxic metabolites and drugs. The kidneys also have several endocrine functions, such as the synthesis of erythropoietin and the activation of vitamin D. The kidneys are affected by many diseases and treatments, and a diseased kidney often impairs the function of other organs. Therefore, renal function and urine tests in the laboratory are frequently investigated by many different tests in the laboratory.

One of the most common laboratory tests is the measurement of creatinine to determine the glomerular filtration rate (GFR), which indicates the plasma volume filtered per minute in the kidney. Albumin in urine is an important screening test (e.g. for diabetes patients), as it enables even slight structural damage of the kidneys to be detected in the urine. These two tests form the basis for classification of the severity of renal damage.

Urinalysis is an important screening and diagnostic tool to help detect kidney and urinary tract disorders. Thereby, the urine sample is analyzed using semi-quantitative test strips or microscopy. These examinations enable the detection of, for example, bacterial urinary tract infections or inflammatory kidney diseases. Structural damage to the kidneys can also be detected and differentiated by the measurement of protein markers in the urine.
In addition to these relatively frequently performed laboratory tests, many special tests are performed at the Institute of Clinical Chemistry in order to differentiate renal diseases from urinary tract diseases (see, for example, calculi and to detect consequential damage (electrolytes and minerals, some hormones).
As blood plasma is filtered through the kidneys many times a day, the resulting urine serves as an important sample material for the diagnosis of many metabolic disorders, hormonal disorders and systemic diseases.

Calculi

It is important to identify the composition of kidney stones in order to guide prevention and treatment. We use X-ray diffraction and infrared spectroscopy to determine the qualitative and quantitative composition of various calculi: primarily, kidney stones, but also gallstones and other calculi are  examined. Drug-induced calculi can be identified using LC-MS.

Further tests in patients with kidney stones include, amongst others, the determination of certain blood and/or urine parameters (e.g. calcium, oxalate, citrate, uric acid) by means of clinical-chemistry methods.

Liver disease

The liver is the central organ for all metabolic process and is responsible for the production of vital proteins (e.g. coagulation factors and albumin) as well as the degradation and excretion of metabolic end products, drugs and toxic substances.

The many different forms of liver disease involve four pathobiochemical reactions that can be detected using clinical laboratory methods, partly before they are clinically manifest:

• Dying liver cells (necrosis) release enzymes into the blood, alanine aminotransferase (ALT, GPT) aspartate aminotransferase (AST, GOT) and glutamate dehydrogenase (GLDH).
• Impairments in bile formation and excretion (cholestasis) are characterized by increased plasma concentrations of bilirubin and bile acids, as well as increased activities of gamma-glutamyl transferase (GGT) and alkaline phosphatase.
• The functional capacity of the liver can be estimated by measuring the plasma concentration of albumin and ammonia as well as the activity of cholinesterase and the activated partial thromboplastin time (Coagulation laboratory of the Department of Hematology).
• The replacement of functioning liver tissue by fibrous connective tissue (fibrosis, late stage cirrhosis) cannot be detected directly by specific laboratory tests. Several of the parameters mentioned above and also other laboratory parameters (e.g. blood platelet count) are combined in algorithms as an indirect method for liver fibrosis assessment.

In addition to these general liver function parameters, the Institute of Clinical Chemistry provides a wide range of laboratory tests for the diagnosis and monitoring of specific liver diseases; e.g. toxicological analyses, trace element analysis, metabolic disorders, markers of alcohol abstinence (CDT, ethyl glucuronide). Laboratory diagnosis of viral or autoimmune hepatitis is performed in the Department of Immunology.

Pancreatic and gastrointestinal diseases

The Institute of Clinical Chemistry offers the 14C-urea breath test to diagnose peptic ulcer disease (gastric ulcer).

Acute inflammation of the pancreas (pancreatitis) can be diagnosed by increased enzyme activity of pancreatic amylase or lipase in plasma or urine. CRP helps to define the degree of severity. Pancreatic elastase in stool is an important parameter in the follow-up of chronic pancreatitis.

Many disorders of the small intestine are characterized by impaired absorption of minerals, vitamins or trace elements and as well as a lack of proteins. Tests to confirm this are performed at the Institute of Clinical Chemistry. The relatively common carbohydrate malabsorbtion disorder lactose intolerance is genetically tested. The Institute of Clinical Chemistry offers the measurement of calprotectin in stool samples to diagnose and monitor inflammatory bowel diseases (ulcerative colitis and Crohn’s disease). Finally, the Institute also offers various tumor marker tests in the follow-up of gastrointestinal cancers.

Neurological disorders

Cerebrospinal fluid (CSF) analysis is an important tool for the diagnosis of diseases of the central nervous system (CNS). The IKC offers rapid diagnostic services for this. An impairment of the blood-cerebrospinal fluid barrier (e.g. due to inflammation) is associated with increased protein levels in the CSF. In clinical CSF diagnostics, the CSF/serum albumin ratio is used to estimate the blood-brain integrity. Glucose and lactate are key diagnostic parameters when an infectious CNS disease is suspected. In addition to these main emergency analyses for CSF, the IKC also offers the measurement of CSF levels of various electrolytes, metabolites, enzymes and hormones; e.g. orexin for the diagnosis of narcolepsy.

Other CSF tests are performed in other laboratories, namely in the Department of Hematology (emergency cell counts or Gram stains), the CSF laboratory of the Department of Neurology (quantitative determination of CSF/serum ratios for albumin and immunoglobulins, qualitative detection of oligoclonal bands, cell counts and differentiation, and the spectrometric detection of hemoglobin and degradation products), the Institute of Neuropathology (protein 14-3-3 in patients with suspected Creutzfeldt-Jakob disease), the Institute of Medical Microbiology and the Institute of Medical Virology for the detection of pathogens.

Inflammation

Inflammation is a local or systemic immune reaction of an organism to an endogenous stimulus (e.g. uric acid crystals and tissue destruction) or exogenous stimulus (e.g. viruses, bacteria, allergens and cold/heat). The five cardinal signs of inflammation – redness, swelling, pain, heat and loss of function of tissue or organs – and the general reaction of the body (fever, night sweats and a general feeling of being unwell) are often unspecific and often emerge only late. Biomarkers in the blood (e.g. CRP, interleukin 6, procalcitonin) assist in an earlier and more specific detection of inflammation, and may help distinguish between bacterial infection, viral infection and non-infectious inflammation. Early detection of inflammation enables prompt treatment that may prevent long-term damage or even death. Exclusion of bacterial inflammation at an early stage may obviate the use of antibiotics.

To identify the origin of inflammation and to make a differential diagnosis of inflammatory diseases numerous laboratory tests are required that are only partially performed at the Institute of Clinical Chemistry. Causative agents of an infectious disease are identified at the Institute of Medical Microbiology or Medical Virology, while the diagnosis of inflammatory or malignant systemic disease is performed in the clinical laboratories of the Department of Immunology.

Cancer

Tumor markers are proteins that are either directly formed by malignant tumor cells or formed by non-tumor cells as a physical reaction to the tumor. These proteins can be measured in the blood or other body fluids. The primary indication for the determination of a tumor marker is the treatment and monitoring of a known cancer; i.e. the early detection of relapses or metastases. Tumor markers are often able to show progression, relapse or metastasis at an earlier stage than other diagnostic procedures.

With a few exceptions (e.g. PSA), tumor markers are not organ-specific. Neither do normal test results rule out the presence of a tumor, nor does an increased concentration of tumor markers prove malignant disease. Therefore, tumor markers are generally not suitable for the screening of cancers in asymptomatic patients.

Anemia

Anemia is defined as a hemoglobin concentration below 130 g/L in men and 120 g/L in women. Possible causes include bleeding, impairment of red blood cell formation (erythropoiesis) and the reduced lifespan of red blood cells (hemolytic anemia).

A series of laboratory tests are performed at the Institute of Clinical Chemistry that help to identify possible causes of anemia; e.g. iron deficiency, a lack of vitamin B12, folic acid or vitamin B6, or hemolysis (see also Department of Hematology).

Hormone diagnostics

The IKC offers a broad range of tests to determine hormone levels by immunoassays or mass-spectrometry:

• Thyroid hormones (TSH, freeT3 and T4, thyroglobulin and calcitonin)
• Sex and pregnancy hormones (estradiol, progesterone, free and total testosterone, sex hormone-binding globulin, DHEAS, 17-OH progesterone, androstenedione, dihydrotestosterone, LH, FSH, anti-Müllerian hormone
• Adrenal cortex function (ACTH, cortisol)
• Regulation of blood pressure (aldosterone, renin, catecholamines, metanephrines)
• Insulin and growth hormones (insulin, C-peptide, HGH, IGF1)
• Calcium- and bone metabolism (parathyroid hormone, 25-OH vitamin D, 1,25(OH)2 vitamin D, bone-specific alkaline phosphatase, beta-CrossLaps)
• Hormones produced by neuroendocrine tumors (chromogranin A, gastrin, glucagon, vasoactive intestinal peptide, pancreatic polypeptide, catecholamines, metanephrines, 5-hydroxyindoleacetic acid)

The IKC works in close collaboration with specialists from the following USZ clinics to select and interpret these laboratory parameters: Internal Medicine, Diabetology and Endocrinology, Reproductive Medicine and Endocrinology, Nuclear Medicine and Gastroenterology.

Metabolic disorders

Diabetes mellitus and lipid metabolism disorders are the most common metabolic disorders and significant risk factors for cardiovascular and renal disease. In addition to the concentration of glucose in plasma, for some years, also HbA1c levels have been used to diagnose diabetes mellitus. Moreover, HbA1c is important in therapeutic monitoring of diabetes mellitus. As an additional parameter for the diagnosis and monitoring of diabetes and its complications, the Institute of Clinical Chemistry offers the measurement of fructosamine, insulin and C-peptide or hydroxybutyrate.

In addition to routine lipid profile analysis (total, LDL- and HDL-cholesterol and triglycerides), the Institute of Clinical Chemistry also measures apolipoproteins, free fatty acids and bile acids, and offers lipoprotein electrophoresis.
Besides other classic metabolic parameters, such as uric acid, urea and homocysteine, the IKC also provides laboratory parameters for the diagnosis of rare metabolic disorders; e.g. free fatty acids, bile acids, citrate, pyruvate, homocysteine and methylmalonic acid. Mass spectrometry opens up new possibilities and indications in metabolic profiling, which will be used initially for scientific studies (metabolomics and lipidomics).

Vitamins and trace elements

Although vitamins perform essential functions, they are produced in the human body either at all or in sufficient amounts. Given today’s nutritional status, severe vitamin deficiency (avitaminosis), such as rickets due to vitamin D deficiency or scurvy due to vitamin C deficiency, is extremely rare. However, even a slight deficiency can produce symptoms. In Switzerland, vitamin D and folic acid deficiencies, as well as vitamin B12 deficiency in vegetarians, are common. These and many other vitamins are measured in the IKC. Additionally, the IKC identifies various functional/metabolic markers that are better indicators of vitamin deficiency as compared to blood concentrations of the respective vitamin (e.g. methylmalonic acid for vitamin B12 deficiency).
Trace elements, such as iron, copper, zinc and selenium, are found at only relatively small quantities in body fluids and tissue. The concentration of trace elements in blood, urine or liver tissue is measured in order to diagnose a deficiency (e.g. selenium or zinc) or excess (e.g. iron and copper storage diseases). Iron deficiency is diagnosed based on the measurement of reduced ferritin levels (anemia). At the IKC, hemochromatosis (a hereditary disorder characterized by excessive iron accumulation) can also be diagnosed using genetic testing.

Laboratory diagnostics during pregnancy

Therapeutic drug monitoring

Therapeutic drug monitoring refers to the optimization of dosage based on drug concentration in serum, plasma or whole blood. This is primarily important for drugs with a narrow therapeutic range. It is also performed when a particular drug therapy despite an adequate dosage either has no clinical effect or results in adverse side-effects. Monitoring of blood levels at an early stage and corresponding adjustment of drug dosages as part of therapeutic drug monitoring enable optimal therapy from the beginning.
Pharmacokinetic interactions between drugs can also be identified by therapeutic drug monitoring. Furthermore, many drugs are metabolized by enzymes, which often display genetic polymorphisms (pharmacogenetics). Also, in these cases therapeutic drug monitoring is useful to optimize drug therapy.

We analyze a broad range of drug classes, 365 days per year, primarily using mass spectrometry methods (LC-MS, GC-MS).

Pharmacogenetics

In addition to factors such as age, gender, height, weight, lifestyle and nutritional habits, concomitant medication and co-morbidities, the genetic variability of patients also affects drug efficacy and tolerability.
The aim of pharmacogenetic diagnostics is to determine genetic differences that influence drug metabolism (pharmacokinetics) and drug effects (pharmacodynamics). The pharmacogenetic information allows to select the right drug and dose for an individual patient. In turn, this helps to optimize the efficacy of the drug and to avoid side-effects.

Toxicology

For clinical advice in the context of (suspected) poisoning, please contact Tox Info Suisse.
Different techniques can be applied to identify a suspected toxic agent in a blood or urine sample. Unfortunately, it is not possible to cover all possible toxins using a single analytical method. Therefore, contact us at an early stage in case of suspected poisoning, so that we can advise you to order the best available analytical detection method and provide the best suitable sample.
In the case of a suspected intoxication with a drug or medicine, we can implement various screening procedures based on immunological methods, LC-MS and/or GC-MS. Our methods – which are normally used for therapeutic drug monitoring – can be applied to quantify identified or already known toxins. If solvent posioning (e.g. methanol) or antifreeze poisoning (e.g. ethylene glycol) is suspected, we use methods based on GC-MS.
Heavy metal poisoning (e.g. lead) can be detected by atomic absorption spectrometry.

In the event of an emergency, a toxicological analysis can be performed at any time (service available 365 days of the year). Please contact us immediately for any suspected poisoning:
Tel +41 44 255 22 67 (Mon-Fri, 8 am-5 pm)
Tel. +41 44 255 22 68 (emergency number)

Metabolomics and lipidomics

As part of our research activities, we have established various mass spectrometry methods for the measurement of about 100 different metabolic products (metabolomics), especially lipids (lipidomics). In particular, we focus on the measurement of atypical sphingolipids, some of which play a role in the pathogenesis of hereditary sensory and autonomic neuropathy (HSAN1) and are associated with diabetes or the risk of myocardial infarction (sphingolipids research). Other methods for the analysis of amino acids and metabolites of the central carbon metabolism are currently being developed. As clinical relevance of most of the metabolites still needs to established, the majority of analyses are not listed in the diagnostic tests provided by the IKC. They are carried out exclusively as part of research projects and only after consultation may be conducted within the framework of collaborations.