Volume 34, Issue 2

Acute kidney injury (AKI) is a frequent complication for hospitalized patients and is associated with significantly increased morbidity and mortality. Probably, the delay in diagnosis of AKI resulting from currently available renal function markers such as serum creatinine contributes to the fact that to date, no simple, safe, and effective intervention to prevent or successfully treat AKI in the general patient population has been found. At the time of diagnosis of established AKI, irreversible organ damage might already have occurred. Neutrophil gelatinase-associated lipocalin (NGAL) is a protease-resistant polypeptide, which is released from the distal nephron in response to ischemic, toxic, or inflammatory insult to the kidney. Available data suggest NGAL to be an early and predictive biomarker for AKI. Novel renal biomarkers indicating cellular/tissue damage might guide patient-tailored earlier initiation of nephroprotection or withdrawal of nephrotoxins directed at improvement of outcomes in patients developing AKI.

Acute kidney injury (AKI) is a frequent complication of hospitalized patients and associated with significantly increased morbidity and mortality. Probably, the delay in the diagnosis of AKI resulting from currently available renal function markers, such as serum creatinine contributes to the fact that to date, no simple, safe, and effective intervention to prevent or successfully treat AKI in the general patient population has been found. At the time of diagnosis of established AKI, irreversible organ damage might already have occurred. Neutrophil gelatinase-associated lipocalin (NGAL) is a protease-resistant polypeptide, which is released from the distal nephron in response to ischemic, toxic, or inflammatory insult to the kidney. Available data suggest NGAL to be an early and predictive biomarker for AKI. Novel renal biomarkers indicating cellular/tissue damage might guide patient-tailored earlier initiation of nephroprotection or withdrawal of nephrotoxins directed at improvement of outcomes in patients developing AKI.

This article outlines the role of bladder cancer tumor markers in diagnosis and therapy with a particular focus on the most important biomarkers. A MEDLINE based literature search was performed to examine the field of bladder cancer markers. Further determination of recurrence and progression markers will contribute to establish better treatments for the individual patient. Molecular staging of urological tumors will allow selecting cases that will require systemic treatment. Therapeutically, knowledge of cancer progression pathways allows for drug therapies against specific tumor targets. It is necessary and important to integrate under the same objectives basic translational and clinical research.

This article outlines the role of bladder cancer tumor markers in diagnosis and therapy with a particular focus on the most important biomarkers. A MEDLINE based literature search was performed to examine the field of bladder cancer markers. Further determination of recurrence and progression markers will contribute to establish better treatments for the individual patient. Molecular staging of urological tumors will allow selecting cases that will require systemic treatment. Therapeutically, knowledge of cancer progression pathways allow for drug therapies against specific tumor targets. It is necessary and important to integrate under the same objectives basic translational and clinical research.

Thrombocytopenia is commonly found in patients with apparent bleeding tendency, and in the laboratory evaluation of patients with other disorders or in clinically healthy individuals. Identification of the underlying cause is therefore crucial. There are several different laboratory tests available for this purpose. Flow cytometry employs very small sample volumes, which is of particular interest in patients with severe thrombocytopenia or in pediatric samples. Thus, the immunological determination of platelet numbers by flow cytometry is recommended as the reference method to achieve an exact quantification of very low platelet numbers, which could influence therapeutic decisions. In addition, flow cytometric analysis of immature platelets plays a role in the differentiation of increased platelet destruction and decreased platelet synthesis. As this parameter can be measured by current hematology analyzers, it will become more important in routine use. Another field for flow cytometry is the investigation of immunologically mediated thrombocytopenias. These can be caused by antibodies against platelet-specific glycoproteins such as autoimmune thrombocytopenia or by antibodies against heparin-PF4 (platelet factor 4) complexes such as heparin-induced thrombocytopenia (HIT). Moreover, flow cytometric assays are used for the diagnosis of rare congenital thrombocytopenias, where they are either able to confirm a certain diagnosis, e.g., Bernard-Soulier syndrome, or at least establish a basis for further analyses. The contribution of flow cytometry to the investigation of lymphoma and leukemia, which regularly cause thrombocytopenia by bone marrow infiltration, is not discussed in this article.

Thrombocytopenia is commonly found in patients with apparent bleeding tendency, and in the laboratory evaluation of patients with other disorders or in clinically healthy individuals. Identification of the underlying cause is therefore crucial. There are several different laboratory tests available for this purpose. Flow cytometry employs very small sample volumes, which is of particular interest in patients with severe thrombocytopenia or in pediatric samples. Thus, the immunological determination of platelet numbers by flow cytometry is recommended as the reference method to achieve an exact quantification of very low platelet numbers, which could influence therapeutic decisions. In addition, flow cytometric analysis of immature platelets plays a role in the differentiation of increased platelet destruction and decreased platelet synthesis. As this parameter can be measured by current hematology analyzers, it will become more important in routine use. Another field for flow cytometry is the investigation of immunologically mediated thrombocytopenias. These can be caused by antibodies against platelet-specific glycoproteins such as autoimmune thrombocytopenia or by antibodies against heparin-platelet factor 4 complexes such as heparin-induced thrombocytopenia. Moreover, flow cytometric assays are used for the diagnosis of rare congenital thrombocytopenias, where they are either able to confirm a certain diagnosis, e.g., Bernard-Soulier syndrome, or at least establish a basis for further analyses. The contribution of flow cytometry to the investigation of lymphoma and leukemia, which regularly cause thrombocytopenia by bone marrow infiltration, is not discussed in this article.

The comparability of quantitative results determined in different laboratories is still unsatisfactory despite enormous standardization efforts of scientific societies. To improve this situation, the working group “Richtwerte” (guide values) of the DGKL has expanded former proposals on z-transformation by combining it with a scale shift, and with a rescaled biological standard deviation according to the model of the intelligence quotient. Quotient reporting should be combined with conventional result reporting as demonstrated by several examples using a colour coding.

Low responsiveness to clopidogrel is an important cause of adverse events after coronary stenting. Multiple electrode platelet aggregometry (MEA) measured by the Multiplate ® system seems to be suitable for monitoring clopidogrel treatment. We validated this method by analyzing hirudin blood samples from 150 healthy volunteers to establish reference ranges of the MEA tests, from 75 hematologic patients with anemia or thrombopenia to determine the dependence of MEA values on hematocrit (HCT) and platelet count, and from 1005 patients after percutaneous coronary intervention (PCI) and 600 mg clopidogrel loading-dose to test the reproducibility of the results under clinical conditions. It was found that MEA results are not affected by the different methods of blood withdrawal and sample transport, if the blood is kept at rest for 30 min before measuring. Measuring must be performed within 3 h after blood withdrawal. It was found that MEA results are not valid in patients with HCT ≤0.30 L/L or platelets ≤100/nL. Because clopidogrel loading also causes a decrease of thrombin receptor activating peptide (TRAP) values, clopidogrel responsiveness, defined by ADP values under the lower reference level (men: 32 U, women: 46 U), can only reliably be classified if the TRAP value is >20 U and the TRAP/ADP ratio >3. Clopidogrel monitoring should be performed within 24 h after PCI, despite the risk of unclear results in approximately 12%. In summary, by concentrating on preanalytical conditions and blood count, MEA is suitable to detect clopidogrel response. The TRAP test should be performed simultaneously to allow a valid assessment.

Low responsiveness to clopidogrel is an important cause of adverse events after coronary stenting. Multiple electrode platelet aggregometry (MEA) measured by the Multiplate ® system seems to be suitable for monitoring clopidogrel treatment. We validated this method by analyzing hirudin blood samples from 150 healthy volunteers to establish reference ranges of the MEA tests, from 75 hematologic patients with anemia or thrombopenia to determine the dependence of MEA values on hematocrit (HCT) and platelet count, and from 1005 patients after percutaneous coronary intervention (PCI) and 600 mg clopidogrel loading dose to test the reproducibility of the results under clinical conditions. It was found that MEA results are not affected by the different methods of blood withdrawal and sample transport, if the blood is kept at rest for 30 min before measuring. Measuring must be performed within 3 h after blood withdrawal. It was found that MEA results are not valid in patients with HCT ≤0.30 L/L or platelets ≤100/nL. Because clopidogrel loading also causes a decrease of thrombin receptor-activating peptide (TRAP) values, clopidogrel responsiveness, defined by ADP values under the lower reference level (men: 32 U, women: 46 U), can only reliably be classified if the TRAP value is >20 U and the TRAP/ADP ratio <3. Clopidogrel monitoring should be performed within 24 h after PCI, despite the risk of unclear results in ∼12%. In summary, by concentrating on preanalytical conditions and blood count, MEA is suitable to detect clopidogrel response. The TRAP test should be performed simultaneously to allow a valid assessment.