Biomarkers and laboratory parameters

Emergency diagnostics, vital signs

Immediate laboratory diagnostics play an essential role in the assessment of patients, particularly in the case of emergency hospitalization and critical illness. For this reason, the IKC offers analysis of around 60 vital or diagnostically urgent parameters, such as cardiac markers, inflammation markers, renal function, cerebrospinal fluid markers and drugs of abuse, 24 hours a day, seven days a week. Outside of routine working hours, the Institute of Clinical Chemistry carries out time-critical virus and autoantibody diagnostics (hepatitis, HIV, EBV, CMV, rapid PCR tests for influenza or SARS-CoV2) for the Department of Immunology and the Institute of Medical Virology as an interdisciplinary emergency laboratory. More than 90% of emergency analyses are carried out at the IKC within one hour and the results are communicated to the attending physicians.

Cardiovascular diseases

Cardiovascular diseases are the most common causes of death and reasons for hospital admissions. The typical symptoms – chest pain or shortness of breath – can have various causes, which can be ruled out or confirmed by laboratory diagnostics: In addition to the ECG, the highly sensitive measurement of troponin T plays a key role in the diagnosis of acute myocardial infarction. The determination of natriuretic peptides (NT-proBNP) facilitates the diagnosis of “heart failure” (decompensated heart failure). D-dimer is a valuable marker for ruling out pulmonary embolism or aortic dissection.

Coronary heart disease, i.e. arteriosclerosis of the coronary arteries, is the underlying cause of heart attacks and often also heart failure. Many risk factors for arteriosclerosis are detected and monitored in the laboratory, namely diabetes (glucose, HbA1c) and lipid metabolism disorders (elevated blood levels of total and LDL cholesterol or triglycerides and low HDL cholesterol). Newer risk factors such as C-reactive protein (CRP), apolipoproteins, lipoprotein (a) and homocysteine are also measured at the Institute of Clinical Chemistry.

In addition to diagnostics, risk factors and biomarkers of cardiovascular diseases are the focus of research at the Institute of Clinical Chemistry.

Kidney and urinary tract diseases

The kidney plays a prominent role in the homeostasis of the water, electrolyte and acid-base balance and is responsible for the excretion of many potentially toxic metabolic products and drugs. The kidney also performs some endocrine functions, such as the synthesis of erythropoietin for blood formation and the activation of vitamin D. The kidney is affected by many diseases and therapies and the diseased kidney often impairs the function of other organs. This is why laboratory tests of kidney function and urine are frequent and varied.

The determination of creatinine to estimate the glomerular filtration rate (GFR), which indicates the volume of plasma filtered per minute in the kidney, is one of the most common laboratory tests. Albumin in urine is an important screening test, e.g. in diabetics, which can be detected in urine even in the case of slight structural damage to the kidney. Today, both tests together form the basis for the classification of kidney damage into degrees of severity.

The urine status is an important screening and diagnostic test for kidney and urinary tract diseases. The urine is examined using a semi-quantitative strip test and microscopically. For example, bacterial infections of the urinary tract or inflammatory kidney diseases can be detected. Structural damage to the kidney can also be detected and differentiated by determining the lead proteins in the urine.
In addition to these relatively common tests, the Institute of Clinical Chemistry carries out many (special) tests to differentiate between diseases of the kidneys and urinary tract (see also concrements, for example) and to detect secondary damage (electrolytes and minerals, some hormones).
As the plasma in the blood is filtered through the kidneys many times a day, the resulting urine serves as an important sample material for the diagnosis of many metabolic, hormonal and systemic diseases.

Concretions

In order to ensure suitable prevention or treatment for patients with urinary stones, it is important to know the composition of the urinary stone. We use X-ray diffraction and infrared spectroscopy to determine the qualitative and quantitative composition of various concretions, primarily urinary stones, but also gallstones and other concretions. Drug stones can be identified by LC-MS.

Clarifications in the context of a recurrent occurrence of kidney stones include the determination of certain parameters in the blood and/or urine (e.g. calcium, oxalate, citrate, uric acid), which we carry out using clinical-chemical methods.

Liver disease

The liver is the central organ of the entire metabolism and is responsible, among other things, for the production of vital proteins (e.g. coagulation factors or albumin) as well as the breakdown and excretion of metabolic end products, medicines and toxins.

The variety of liver diseases manifests itself in four pathobiochemical reactions that can be detected by laboratory methods, sometimes before they are clinically manifest:

• Dying liver cells (necrosis) release enzymes into the blood, which are measured at the Institute of Clinical Chemistry: Alanine aminotransferase (ALT, GPT), aspartate aminotransferase (AST, GOT) and glutamate dehydrogenase (GLDH)
• Disorders in the formation and excretion of bile (cholestasis) are manifested by increased plasma concentrations of bilirubin and bile acids as well as increased activities of gamma-glutamyl transferase (GT) and alkaline phosphatase
• The functional capacity of the liver can be estimated by measuring the plasma concentrations of albumin and ammonia as well as the activities of cholinesterase and thromboplastin time (coagulation laboratory of the Department of Hematology)
• The connective tissue transformation of the liver (fibrosis, late-stage cirrhosis) cannot be detected directly by specific laboratory tests. Some of the aforementioned and other laboratory parameters (e.g. platelet count) are combined in algorithms as indirect methods.

In addition to these general liver function parameters, the Institute of Clinical Chemistry offers a broad spectrum for the diagnosis and monitoring of specific liver diseases, e.g. toxicological detection methods, trace element analysis, metabolic diseases, alcohol abstinence markers (CDT, ethyl glucuronide). Laboratory diagnostics for viral or autoimmune hepatitis are carried out in the Department of Immunology.

Diseases of the pancreas and gastrointestinal tract

The Institute of Clinical Chemistry offers the 14C-urea breath test for the diagnosis of peptic ulcer disease.

Acute pancreatitis can be diagnosed by an increase in the enzyme activities of pancreatic amylase or lipase in the plasma or urine. CRP helps to differentiate the degree of severity. Pancreatic elastase in the stool is an important progression parameter for chronic pancreatitis.

Many diseases of the small intestine manifest themselves through the impaired absorption of minerals, vitamins or trace elements as well as a lack of proteins, which are examined at the Institute of Clinical Chemistry. As a relatively common specific assimilation disorder, lactose intolerance is genetically investigated. For the diagnosis and monitoring of inflammatory bowel diseases (ulcerative colitis and Crohn’s disease), the Institute of Clinical Chemistry offers the analysis of calprotectin in stool. Finally, the Institute offers various tumor markers for the follow-up care of carcinomas of the gastrointestinal tract.

Neurological diseases

A number of diseases of the central nervous system (CNS) are diagnosed with the help of laboratory tests of the cerebrospinal fluid (CSF). The IKC offers express diagnostics for this purpose. If the blood-cerebrospinal fluid barrier is impaired (e.g. in the case of inflammation), there is an increased amount of proteins in the cerebrospinal fluid. The albumin-cerebrospinal fluid/serum quotient is used in clinical CSF diagnostics to assess a barrier disorder. Glucose and lactate are important diagnostic parameters for suspected infectious CNS diseases. In addition to these most important emergency CSF analyses, the IKC offers CSF analyses of various electrolytes, metabolites, enzymes and hormones, e.g. orexin for the diagnosis of narcolepsy.

Further CSF examinations take place in other laboratories at the UZL, namely in the Department of Hematology (emergency cell counting or Gram staining), in the CSF laboratory of the Neurology Clinic (quantitative determination of CSF/serum quotients of albumin and immunoglobulins, qualitative detection of oligoclonal bands, cell counting and differentiation as well as spectrometric detection of haemoglobin and degradation products), in the Institute of Neuropathology (protein 14-3-3 for suspected Creutzfeld-Jakob disease), as well as in the Institutes of Medical Microbiology and Medical Virology for pathogen detection.

Inflammations

Inflammation is a local or systemic immune reaction of the organism to an endogenous (e.g. metabolic products such as uric acid crystals and tissue decay products) or exogenous (e.g. viruses/bacteria, allergens and cold/heat) stimulus. The five classic leading symptoms of inflammation – redness, swelling, pain, overheating and restricted function of the tissue or organ – and general reactions of the body, such as fever, night sweats and a general feeling of illness are often non-specific and often appear late. Biomarkers that can be determined in the blood (e.g. CRP, interleukin 6, procalcitonin) help to recognize inflammation earlier and more specifically and allow a rough distinction to be made between bacterial infections, viral inflammations and non-infectious inflammations. Early detection of inflammation enables early therapies that prevent long-term damage or even death. Early exclusion of bacterial inflammation can avoid the use of antibiotics.

The search for the cause and differential diagnosis of inflammation involves many laboratory tests, only some of which are carried out at the Institute of Clinical Chemistry. Germ testing for infections is carried out in the Institutes of Medical Microbiology or Medical Virology, while inflammatory or malignant systemic diseases are diagnosed in the laboratories of the Department of Immunology or the Department of Haematology.

Anemias

Anemia is defined as a reduction in the hemoglobin concentration below 130 g/L in men and below 120 g/L in women. Possible causes are bleeding, disorders of erythrocyte formation (erythropoiesis) or a shortened erythrocyte lifespan (hemolytic anemia).

The Institute of Clinical Chemistry carries out a range of laboratory tests that help to clarify possible causes of anemia, e.g. iron deficiency, vitamin B12, folic acid or vitamin B6 deficiency, or hemolysis.

Tumor diseases

Tumor markers are proteins that are either produced directly by malignant tumor cells or by cells foreign to the tumor as a reaction of the body to the tumor and can be measured in the blood or other body fluids. The main indication for a tumor marker test is to monitor the treatment and progress of a known cancer, i.e. the early detection of recurrences or metastases. Tumor markers can often indicate progression, recurrence or metastases earlier than other diagnostic methods.

With a few exceptions (e.g. PSA), tumor markers are not organ-specific. A normal measurement result does not rule out a tumor, nor does an elevated tumor marker concentration prove a malignant disease. For this reason, tumor markers are generally not suitable for screening cancer in asymptomatic patients.

Hormone diagnostics

The IKC offers a wide range of hormone tests:

• Thyroid hormones (TSH, free T3 and T4, thyroglobulin, 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 cortical function (ACTH, cortisol)
• Blood pressure regulation (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, b-Crosslabs)
• Hormones of neuroendocrine tumors (chromogranin A, gastrin, glucagon, vasoactive intestinal peptide, pancreatic polypeptide, catecholamines, metanephrines, hydroxyindoleacetic acid).

When selecting and interpreting these laboratory parameters, the IKC works closely with specialists from the USZ clinics for internal medicine, diabetology and endocrinology, reproductive endocrinology, nuclear medicine and gastroenterology.

Metabolic diseases

Diabetes mellitus and lipometabolic disorders are the most common metabolic diseases and significant risk factors for cardiovascular and kidney diseases. In addition to the glucose concentration in plasma, the HbA1c concentration has also been a diagnostic criterion for diabetes mellitus for some years. HbA1c is also important for the therapy monitoring of diabetes mellitus. The Institute of Clinical Chemistry also offers the determination of fructosamine, insulin and C-peptide or hydroxbutyrate as additional parameters for the diagnosis and monitoring of diabetes and its derailments.

In addition to the routine lipid status (total, LDL and HDL cholesterol and triglycerides), the Institute of Clinical Chemistry measures apolipoproteins, free fatty acids and bile acids and carries out lipoprotein electrophoresis.

In addition to other classic metabolic parameters such as uric acid, urea and homocysteine, the IKC also offers laboratory parameters for the diagnosis of rarer metabolic diseases, e.g. free fatty acids, bile acids, citrate, pyruvate, porphyrins, homocysteine and methylmalonic acid. Mass spectrometry opens up new possibilities and indications for metabolic analysis, which are initially used for scientific studies (metabolomics and lipidomics).

Vitamins and trace elements

Vitamins perform essential functions but cannot be produced by humans at all or not in sufficient quantities. Under today’s nutritional conditions, pronounced vitamin deficiencies (avitaminosis), such as rickets due to vitamin D deficiency or scurvy due to vitamin C deficiency, are very rare. However, even slight deficiencies can cause symptoms. In Switzerland, vitamin D or folic acid deficiency, as well as vitamin B12 deficiency in vegetarians, is the most common. These and many other vitamins are determined in the IKC. In addition, some functional metabolic markers are determined that detect a certain vitamin deficiency better than the blood concentration of the respective vitamin (e.g. methylmalonic acid for vitamin B12 deficiency).

Trace elements such as iron, copper, zinc and selenium are only found in relatively small quantities in body fluids and tissue. The concentration of trace elements in blood, urine or liver tissue is determined in order to diagnose a deficiency (e.g. selenium or zinc) or excess (e.g. iron and copper storage diseases). Iron deficiency is diagnosed by measuring a low ferritin level (anemia). Hereditary iron overload disease (hemochromatosis) is also diagnosed genetically at the IKC.

Laboratory diagnostics during pregnancy

Therapeutic drug monitoring

Therapeutic drug monitoring refers to the dose optimization of drugs based on their concentration in serum, plasma or whole blood. This is particularly important for drugs with a narrow therapeutic range if the clinical efficacy of a drug therapy does not occur despite appropriate dosing or if adverse drug reactions have already occurred. Early level determinations and corresponding dose adjustments as part of therapeutic drug monitoring enable optimal therapy from the outset.

Pharmacokinetic drug interactions can also be identified with the help of therapeutic drug monitoring. Many drugs are also metabolized by enzymes that exhibit genetic polymorphisms (pharmacogenetics). Here too, therapeutic drug monitoring can help to optimally adjust drug therapy.

We analyze a wide range of drug classes, mostly using mass spectrometric methods (LC-MS, GC-MS) 365 days a year.

Pharmacogenetics

In addition to factors such as age, gender, height, weight, lifestyle and dietary habits, comedications and concomitant diseases, the genetic variability of patients also influences the efficacy and tolerability of medication.

The aim of pharmacogenetic diagnostics is to identify genetic differences with an influence on drug metabolism (pharmacokinetics) or drug effect (pharmacodynamics). Pharmacogenetic information enables the choice and dosage of certain medications to be customized. This in turn helps to optimize the effectiveness of the medication and avoid side effects.

Toxicology

For clinical advice regarding In case of poisoning, please contact Tox Info Suisse.
Depending on the issue at hand, various techniques can be used to detect a suspected toxic agent in a blood or urine sample. Unfortunately, it is in principle impossible to cover all possible toxins with one analytical method. Therefore, please contact us at an early stage if you suspect a case so that we can inform you of the cause. the analytical detection method(s) to be selected.
In the case of suspected drug and medication intoxications, we can use various screening procedures based on immunological methods, LC-MS and/or GC-MS. Identified or already known toxins can be quantified with our methods, which are normally used for therapeutic drug monitoring. In cases of suspected solvent intoxication (e.g. methanol) or antifreeze intoxication (e.g. ethylene glycol), methods based on GC-MS are used.
Intoxication with heavy metals (e.g. lead) can be detected using atomic absorption spectrometry.

Metabolomics and lipidomics

As part of our research activities, we have established various mass spectrometric methods for the measurement of around 100 different metabolites (metabolomics), in particular lipids (lipidomics). A particular focus is on the measurement of atypical sphingolipids, some of which play a role in the pathogenesis of hereditary sensory neuropathy (HSAN1) and are associated with diabetes or heart attack risk(Research Sphingolipids). Further methods for analyzing amino acids and metabolites of the central carbon metabolism are being developed. The clinical relevance of most metabolites has yet to be established. For this reason, most of the analyses are not listed in the IKC’s diagnostic range. They are carried out exclusively within the framework of research projects, and after consultation also within the framework of collaborations.