TY - JOUR
A1 - Klammert, Uwe
A1 - Müller, Thomas D.
A1 - Hellmann, Tina V.
A1 - Wuerzler, Kristian K.
A1 - Kotzsch, Alexander
A1 - Schliermann, Anna
A1 - Schmitz, Werner
A1 - Kuebler, Alexander C.
A1 - Sebald, Walter
A1 - Nickel, Joachim
T1 - GDF-5 can act as a context-dependent BMP-2 antagonist
JF - BMC Biology
N2 - Background
Bone morphogenetic protein (BMP)-2 and growth and differentiation factor (GDF)-5 are two related transforming growth factor (TGF)-β family members with important functions in embryonic development and tissue homeostasis. BMP-2 is best known for its osteoinductive properties whereas GDF-5—as evident from its alternative name, cartilage derived morphogenetic protein 1—plays an important role in the formation of cartilage. In spite of these differences both factors signal by binding to the same subset of BMP receptors, raising the question how these different functionalities are generated. The largest difference in receptor binding is observed in the interaction with the type I receptor BMPR-IA. GDF-5, in contrast to BMP-2, shows preferential binding to the isoform BMPR-IB, which is abrogated by a single amino acid (A57R) substitution. The resulting variant, GDF-5 R57A, represents a “BMP-2 mimic” with respect to BMP receptor binding. In this study we thus wanted to analyze whether the two growth factors can induce distinct signals via an identically composed receptor.
Results
Unexpectedly and dependent on the cellular context, GDF-5 R57A showed clear differences in its activity compared to BMP-2. In ATDC-5 cells, both ligands induced alkaline phosphatase (ALP) expression with similar potency. But in C2C12 cells, the BMP-2 mimic GDF-5 R57A (and also wild-type GDF-5) clearly antagonized BMP-2-mediated ALP expression, despite signaling in both cell lines occurring solely via BMPR-IA. The BMP-2- antagonizing properties of GDF-5 and GDF-5 R57A could also be observed in vivo when implanting BMP-2 and either one of the two GDF-5 ligands simultaneously at heterotopic sites.
Conclusions
Although comparison of the crystal structures of the GDF-5 R57A:BMPR-IAEC- and BMP-2:BMPR-IAEC complex revealed small ligand-specific differences, these cannot account for the different signaling characteristics because the complexes seem identical in both differently reacting cell lines. We thus predict an additional component, most likely a not yet identified GDF-5-specific co-receptor, which alters the output of the signaling complexes. Hence the presence or absence of this component then switches GDF-5′s signaling capabilities to act either similar to BMP-2 or as a BMP-2 antagonist. These findings might shed new light on the role of GDF-5, e.g., in cartilage maintenance and/or limb development in that it might act as an inhibitor of signaling events initiated by other BMPs.
KW - growth and differentiation factor 5
KW - ligand-receptor complex
KW - crystal structure
KW - antagonist
Y1 - 2015
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-125550
VL - 13
IS - 77
ER -
TY - JOUR
A1 - Weich, Alexander
A1 - Werner, Rudolf A.
A1 - Buck, Andreas K.
A1 - Hartrampf, Philipp E.
A1 - Serfling, Sebastian E.
A1 - Scheurlen, Michael
A1 - Wester, Hans-Jürgen
A1 - Meining, Alexander
A1 - Kircher, Stefan
A1 - Higuchi, Takahiro
A1 - Pomper, Martin G.
A1 - Rowe, Steven P.
A1 - Lapa, Constantin
A1 - Kircher, Malte
T1 - CXCR4-Directed PET/CT in Patients with Newly Diagnosed Neuroendocrine Carcinomas
JF - Diagnostics
N2 - We aimed to elucidate the diagnostic potential of the C-X-C motif chemokine receptor 4 (CXCR4)-directed positron emission tomography (PET) tracer \(^{68}\)Ga-Pentixafor in patients with poorly differentiated neuroendocrine carcinomas (NEC), relative to the established reference standard \(^{18}\)F-FDG PET/computed tomography (CT). In our database, we retrospectively identified 11 treatment-naïve patients with histologically proven NEC, who underwent \(^{18}\)F-FDG and CXCR4-directed PET/CT for staging and therapy planning. The images were analyzed on a per-patient and per-lesion basis and compared to immunohistochemical staining (IHC) of CXCR4 from PET-guided biopsies. \(^{68}\)Ga-Pentixafor visualized tumor lesions in 10/11 subjects, while \(^{18}\)F-FDG revealed sites of disease in all 11 patients. Although weak to moderate CXCR4 expression could be corroborated by IHC in 10/11 cases, \(^{18}\)F-FDG PET/CT detected significantly more tumor lesions (102 vs. 42; total lesions, n = 107; p < 0.001). Semi-quantitative analysis revealed markedly higher 18F-FDG uptake as compared to \(^{68}\)Ga-Pentixafor (maximum and mean standardized uptake values (SUV) and tumor-to-background ratios (TBR) of cancerous lesions, SUVmax: 12.8 ± 9.8 vs. 5.2 ± 3.7; SUVmean: 7.4 ± 5.4 vs. 3.1 ± 3.2, p < 0.001; and, TBR 7.2 ± 7.9 vs. 3.4 ± 3.0, p < 0.001). Non-invasive imaging of CXCR4 expression in NEC is inferior to the reference standard \(^{18}\)F-FDG PET/CT.
KW - CXCR4
KW - NET
KW - NEC
KW - 68Ga-Pentixafor
KW - 18F-FDG
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-234231
SN - 2075-4418
VL - 11
IS - 4
ER -
TY - JOUR
A1 - Harter, Philipp
A1 - Hauke, Jan
A1 - Heitz, Florian
A1 - Reuss, Alexander
A1 - Kommoss, Stefan
A1 - Marmé, Frederik
A1 - Heimbach, André
A1 - Prieske, Katharina
A1 - Richters, Lisa
A1 - Burges, Alexander
A1 - Neidhardt, Guido
A1 - de Gregorio, Nikolaus
A1 - El-Balat, Ahmed
A1 - Hilpert, Felix
A1 - Meier, Werner
A1 - Kimmig, Rainer
A1 - Kast, Karin
A1 - Sehouli, Jalid
A1 - Baumann, Klaus
A1 - Jackisch, Christian
A1 - Park-Simon, Tjoung-Won
A1 - Hanker, Lars
A1 - Kröber, Sandra
A1 - Pfisterer, Jacobus
A1 - Gevensleben, Heidrun
A1 - Schnelzer, Andreas
A1 - Dietrich, Dimo
A1 - Neunhöffer, Tanja
A1 - Krockenberger, Mathias
A1 - Brucker, Sara Y.
A1 - Nürnberg, Peter
A1 - Thiele, Holger
A1 - Altmüller, Janine
A1 - Lamla, Josefin
A1 - Elser, Gabriele
A1 - du Bois, Andreas
A1 - Hahnen, Eric
A1 - Schmutzler, Rita
T1 - Prevalence of deleterious germline variants in risk genes including \(BRCA1/2\) in consecutive ovarian cancer patients (AGO-TR-1)
JF - PLoS ONE
N2 - Background
Identification of families at risk for ovarian cancer offers the opportunity to consider prophylactic surgery thus reducing ovarian cancer mortality. So far, identification of potentially affected families in Germany was solely performed via family history and numbers of affected family members with breast or ovarian cancer. However, neither the prevalence of deleterious variants in \(BRCA1/2\) in ovarian cancer in Germany nor the reliability of family history as trigger for genetic counselling has ever been evaluated.
Methods
Prospective counseling and germline testing of consecutive patients with primary diagnosis or with platinum-sensitive relapse of an invasive epithelial ovarian cancer. Testing included 25 candidate and established risk genes. Among these 25 genes, 16 genes (\(ATM\), \(BRCA1\), \(BRCA2\), \(CDH1\), \(CHEK2\), \(MLH1\), \(MSH2\), \(MSH6\), \(NBN\), \(PMS2\), \(PTEN\), \(PALB2\), \(RAD51C\), \(RAD51D\), \(STK11\), \(TP53\)) were defined as established cancer risk genes. A positive family history was defined as at least one relative with breast cancer or ovarian cancer or breast cancer in personal history.
Results
In total, we analyzed 523 patients: 281 patients with primary diagnosis of ovarian cancer and 242 patients with relapsed disease. Median age at primary diagnosis was 58 years (range 16–93) and 406 patients (77.6%) had a high-grade serous ovarian cancer. In total, 27.9% of the patients showed at least one deleterious variant in all 25 investigated genes and 26.4% in the defined 16 risk genes. Deleterious variants were most prevalent in the \(BRCA1\) (15.5%), \(BRCA2\) (5.5%), \(RAD51C\) (2.5%) and \(PALB2\) (1.1%) genes. The prevalence of deleterious variants did not differ significantly between patients at primary diagnosis and relapse. The prevalence of deleterious variants in \(BRCA1/2\) (and in all 16 risk genes) in patients <60 years was 30.2% (33.2%) versus 10.6% (18.9%) in patients \(\geq\)60 years. Family history was positive in 43% of all patients. Patients with a positive family history had a prevalence of deleterious variants of 31.6% (36.0%) versus 11.4% (17.6%) and histologic subtype of high grade serous ovarian cancer versus other showed a prevalence of deleterious variants of 23.2% (29.1%) and 10.2% (14.8%), respectively. Testing only for \(BRCA1/2\) would miss in our series more than 5% of the patients with a deleterious variant in established risk genes.
Conclusions
26.4% of all patients harbor at least one deleterious variant in established risk genes. The threshold of 10% mutation rate which is accepted for reimbursement by health care providers in Germany was observed in all subgroups analyzed and neither age at primary diagnosis nor histo-type or family history sufficiently enough could identify a subgroup not eligible for genetic counselling and testing. Genetic testing should therefore be offered to every patient with invasive epithelial ovarian cancer and limiting testing to \(BRCA1/2\) seems to be
not sufficient.
KW - medicine
KW - Genetic causes of cancer
KW - ovarian cancer
KW - cancer risk factors
KW - histology
KW - cancer detection and diagnosis
KW - breast cancer
KW - genetic testing
KW - human genetics
Y1 - 2017
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-173553
VL - 12
IS - 10
ER -
TY - JOUR
A1 - Schmidt, Uwe
A1 - Werner, Luis
A1 - Arrowsmith, Merle
A1 - Deissenberger, Andrea
A1 - Hermann, Alexander
A1 - Hofmann, Alexander
A1 - Ullrich, Stefan
A1 - Mattock, James D.
A1 - Vargas, Alfredo
A1 - Braunschweig, Holger
T1 - Trans‐selektive Dihydroborierung eines cis‐Diborens durch Insertion: Synthese eines linearen sp\(^3\)‐sp\(^2\)‐sp\(^3\)‐Triborans und anschließende Kationisierung
JF - Angewandte Chemie
N2 - Die Reaktion zwischen Aryl‐ und Amino(dihydro)boranen und Dibora[2]ferrocenophan 1 führt zur Bildung von 1,3‐trans‐Dihydrotriboranen durch formale Hydrierung und Insertion eines Borylens in die B=B Doppelbindung. Die Aryltriboran‐Derivate unterliegen einer reversiblen Photoisomerisierung zugunsten eines cis‐1,2‐μ‐H‐3‐Hydrotriborans, während eine Hydridabstraktion zu kationischen Triboranen führt, welche die ersten doppelt basenstabilisierten B\(_3\)H\(_4\)\(^+\)‐Analoga darstellen.
KW - Diboren
KW - Hydroborierung
KW - Kation
KW - Photoisomerisierung
KW - Triboran
Y1 - 2020
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-219713
VL - 132
IS - 1
ER -
TY - JOUR
A1 - Schmidt, Uwe
A1 - Werner, Luis
A1 - Arrowsmith, Merle
A1 - Deissenberger, Andrea
A1 - Hermann, Alexander
A1 - Hofmann, Alexander
A1 - Ullrich, Stefan
A1 - Mattock, James D.
A1 - Vargas, Alfredo
A1 - Braunschweig, Holger
T1 - trans-Selective Insertional Dihydroboration of a cis-Diborene: Synthesis of Linear sp\(^3\)-sp\(^2\)-sp\(^3\)-Triboranes and Subsequent Cationization
JF - Angewandte Chemie International Edition
N2 - The reaction of aryl‐ and amino(dihydro)boranes with dibora[2]ferrocenophane 1 leads to the formation 1,3‐trans ‐dihydrotriboranes by formal hydrogenation and insertion of a borylene unit into the B=B bond. The aryltriborane derivatives undergo reversible photoisomerization to the cis ‐1,2‐μ‐H‐3‐hydrotriboranes, while hydride abstraction affords cationic triboranes, which represent the first doubly base‐stabilized B3H4\(^+\) analogues.
KW - cations
KW - hydroboration
KW - photoisomerization
KW - triboranes
KW - diborenes
Y1 - 2020
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-208090
VL - 59
IS - 1
ER -
TY - JOUR
A1 - Werner, Rudolf
A1 - Solnes, Lilja
A1 - Javadi, Mehrbod
A1 - Weich, Alexander
A1 - Gorin, Michael
A1 - Pienta, Kenneth
A1 - Higuchi, Takahiro
A1 - Buck, Andreas
A1 - Pomper, Martin
A1 - Rowe, Steven
A1 - Lapa, Constantin
T1 - SSTR-RADS Version 1.0 as a Reporting System for SSTR-PET Imaging and Selection of Potential PRRT Candidates: A Proposed Standardization Framework
JF - Journal of Nuclear Medicine
N2 - Reliable standards and criteria for somatostatin receptor (SSTR) positron emission tomography (PET) are still lacking. We herein propose a structured reporting system on a 5-point scale for SSTR-PET imaging, titled SSTR-RADS version 1.0, which might serve as a standardized assessment for both diagnosis and treatment planning in neuroendocrine tumors (NET). SSTR-RADS could guide the imaging specialist in interpreting SSTR-PET scans, facilitate communication with the referring clinician so that appropriate work-up for equivocal findings is pursued, and serve as a reliable tool for patient selection for planned Peptide Receptor Radionuclide Therapy.
KW - Radionuclide Therapy
KW - Standardisierung
KW - Positronen-Emissions-Tomografie
KW - 68Ga-DOTATATE/-TOC
KW - Gastrointestinal
KW - Neuroendocrine
KW - Neuroendocrine Tumor
KW - Oncology
KW - GI
KW - PET
KW - PET/CT
KW - PRRT
KW - RADS
KW - SSTR
Y1 - 2018
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-161298
SN - 0161-5505
N1 - This research was originally published in JNM. Rudolf A. Werner, Lilja B. Solnes, Mehrbod Som Javadi, Alexander Weich, Michael A. Gorin, Kenneth J. Pienta, Takahiro Higuchi, Andreas K. Buck, Martin G. Pomper, Steven P. Rowe, Constantin Lapa. SSTR-RADS Version 1.0 as a Reporting System for SSTR-PET Imaging and Selection of Potential PRRT Candidates: A Proposed Standardization Framework. J. Nucl. Med. July 1, 2018, vol. 59, no. 7, 1085-1091. © SNMMI
ER -
TY - JOUR
A1 - Werner, Rudolf A.
A1 - Weich, Alexander
A1 - Higuchi, Takahiro
A1 - Schmid, Jan S.
A1 - Schirbel, Andreas
A1 - Lassmann, Michael
A1 - Wild, Vanessa
A1 - Rudelius, Martina
A1 - Kudlich, Theodor
A1 - Herrmann, Ken
A1 - Scheurlen, Michael
A1 - Buck, Andreas K.
A1 - Kropf, Saskia
A1 - Wester, Hans-Jürgen
A1 - Lapa, Constantin
T1 - Imaging of Chemokine Receptor 4 Expression in Neuroendocrine Tumors - a Triple Tracer Comparative Approach
JF - Theranostics
N2 - C-X-C motif chemokine receptor 4 (CXCR4) and somatostatin receptors (SSTR) are overexpressed in gastro-entero-pancreatic neuroendocrine tumors (GEP-NET). In this study, we aimed to elucidate the feasibility of non-invasive CXCR4 positron emission tomography/computed tomography (PET/CT) imaging in GEP-NET patients using [\(^{68}\)Ga]Pentixafor in comparison to \(^{68}\)Ga-DOTA-D-Phe-Tyr3-octreotide ([\(^{68}\)Ga]DOTATOC) and \(^{18}\)F-fluorodeoxyglucose ([\(^{18}\)F]FDG). Twelve patients with histologically proven GEP-NET (3xG1, 4xG2, 5xG3) underwent [\(^{68}\)Ga]DOTATOC, [\(^{18}\)F]FDG, and [\(^{68}\)Ga]Pentixafor PET/CT for staging and planning of the therapeutic management. Scans were analyzed on a patient as well as on a lesion basis and compared to immunohistochemical staining patterns of CXCR4 and somatostatin receptors SSTR2a and SSTR5. [\(^{68}\)Ga]Pentixafor visualized tumor lesions in 6/12 subjects, whereas [\(^{18}\)F]FDG revealed sites of disease in 10/12 and [\(^{68}\)Ga]DOTATOC in 11/12 patients, respectively. Regarding sensitivity, SSTR-directed PET was the superior imaging modality in all G1 and G2 NET. CXCR4-directed PET was negative in all G1 NET. In contrast, 50% of G2 and 80% of G3 patients exhibited [\(^{68}\)Ga]Pentixafor-positive tumor lesions. Whereas CXCR4 seems to play only a limited role in detecting well-differentiated NET, increasing receptor expression could be non-invasively observed with increasing tumor grade. Thus, [\(^{68}\)Ga]Pentixafor PET/CT might serve as non-invasive read-out for evaluating the possibility of CXCR4-directed endoradiotherapy in advanced dedifferentiated SSTR-negative tumors.
KW - SSTR
KW - peptide receptor radionuclide therapy
KW - neuroendocrine tumor
KW - [\(^{68}\)Ga]Pentixafor
KW - CXCR4
KW - chemokine receptor
KW - PET/CT
KW - DOTATOC
KW - PRRT
KW - Positronen-Emissions-Tomografie
Y1 - 2017
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-158008
VL - 7
IS - 6
ER -
TY - JOUR
A1 - Werner, Rudolf A.
A1 - Beykan, Seval
A1 - Higuchi, Takahiro
A1 - Lückerath, Katharina
A1 - Weich, Alexander
A1 - Scheurlen, Michael
A1 - Bluemel, Christina
A1 - Herrmann, Ken
A1 - Buck, Andreas K.
A1 - Lassmann, Michael
A1 - Lapa, Constantin
A1 - Hänscheid, Heribert
T1 - The impact of \(^{177}\)Lu-octreotide therapy on \(^{99m}\)Tc-MAG3 clearance is not predictive for late nephropathy
JF - Oncotarget
N2 - Peptide Receptor Radionuclide Therapy (PRRT) for the treatment of neuroendocrine tumors may lead to kidney deterioration. This study aimed to evaluate the suitability of \(^{99m}\)Tc-mercaptoacetyltriglycine (\(^{99m}\)Tc-MAG3) clearance for the early detection of PRRT-induced changes on tubular extraction (TE). TE rate (TER) was measured prior to 128 PRRT cycles (7.6±0.4 GBq \(^{177}\)Lu-octreotate/octreotide each) in 32 patients. TER reduction during PRRT was corrected for age-related decrease and analyzed for the potential to predict loss of glomerular filtration (GF). The GF rate (GFR) as measure for renal function was derived from serum creatinine. The mean TER was 234 ± 53 ml/min/1.73 m² before PRRT (baseline) and 221 ± 45 ml/min/1.73 m² after a median follow-up of 370 days. The age-corrected decrease (mean: -3%, range: -27% to +19%) did not reach significance (p=0.09) but significantly correlated with the baseline TER (Spearman p=-0.62, p<0.001). Patients with low baseline TER showed an improved TER after PRRT, high decreases were only observed in individuals with high baseline TER. Pre-therapeutic TER data were inferior to plasma creatinine-derived GFR estimates in predicting late nephropathy. TER assessed by \(^{99m}\)Tc-MAG3clearance prior to and during PRRT is not suitable as early predictor of renal injury and an increased risk for late nephropathy.
KW - renal scintigraphy
KW - neuroendocrine tumor
KW - 177Lu
KW - MAG3
KW - PRRT
Y1 - 2016
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-177318
VL - 7
IS - 27
ER -
TY - INPR
A1 - Löffler, Mona C.
A1 - Mayer, Alexander E.
A1 - Trujillo Viera, Jonathan
A1 - Loza Valdes, Angel
A1 - El-Merahib, Rabih
A1 - Ade, Carsten P.
A1 - Karwen, Till
A1 - Schmitz, Werner
A1 - Slotta, Anja
A1 - Erk, Manuela
A1 - Janaki-Raman, Sudha
A1 - Matesanz, Nuria
A1 - Torres, Jorge L.
A1 - Marcos, Miguel
A1 - Sabio, Guadalupe
A1 - Eilers, Martin
A1 - Schulze, Almut
A1 - Sumara, Grzegorz
T1 - Protein kinase D1 deletion in adipocytes enhances energy dissipation and protects against adiposity
T2 - The EMBO Journal
N2 - Nutrient overload in combination with decreased energy dissipation promotes obesity and diabetes. Obesity results in a hormonal imbalance, which among others, activates G-protein coupled receptors utilizing diacylglycerol (DAG) as secondary messenger. Protein kinase D1 (PKD1) is a DAG effector which integrates multiple nutritional and hormonal inputs, but its physiological role in adipocytes is unknown. Here, we show that PKD1 promotes lipogenesis and suppresses mitochondrial fragmentation, biogenesis, respiration, and energy dissipation in an AMP-activated protein kinase (AMPK)-dependent manner. Moreover, mice lacking PKD1 in adipocytes are resistant to diet-induced obesity due to elevated energy expenditure. Beiging of adipocytes promotes energy expenditure and counteracts obesity. Consistently, deletion of PKD1 promotes expression of the β3-adrenergic receptor (ADRB3) in a CCAAT/enhancerbinding protein (C/EBP)-α and δ-dependent manner, which leads to the elevated expression of beige markers in adipocytes and subcutaneous adipose tissue. Finally, deletion of PKD1 in adipocytes improves insulin sensitivity and ameliorates liver steatosis. Thus, loss of PKD1 in adipocytes increases energy dissipation by several complementary mechanisms and might represent an attractive strategy to treat obesity and its related complications.
KW - AMP-activated protein kinase (AMPK)
KW - Beige adipocytes
KW - β3 adrenergic receptor (ADRB3)
KW - C/EBP
KW - Protein kinase D1 (PKD1)
Y1 - 2018
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-176093
ER -
TY - JOUR
A1 - Lapa, Constantin
A1 - Werner, Rudolf A.
A1 - Bluemel, Christina
A1 - Lueckerath, Katharina
A1 - Muegge, Dirk O.
A1 - Strate, Alexander
A1 - Haenscheid, Heribert
A1 - Schirbel, Andreas
A1 - Allen-Auerbach, Martin S.
A1 - Bundschuh, Ralph A.
A1 - Buck, Andreas K.
A1 - Herrmann, Ken
T1 - Prediction of clinically relevant hyperkalemia in patients treated with peptide receptor radionuclide therapy
JF - EJNMMI Research
N2 - Background
Peptide receptor radionuclide therapy (PRRT) is applied in patients with advanced neuroendocrine tumors. Co-infused amino acids (AA) should prevent nephrotoxicity. The aims of this study were to correlate the incidence of AA-induced hyperkalemia (HK) (≥5.0 mmol/l) and to identify predictors of AA-induced severe HK (>6.0).
Methods
In 38 patients, standard activity of \(^{177}Lu\)-labelled somatostatin analogs was administered. Pre-therapeutic kidney function was assessed by renal scintigraphy and laboratory tests. For kidney protection, AA was co-infused. Biochemical parameters (potassium, glomerular filtration rate, creatinine, blood urea nitrogen (BUN), sodium, phosphate, chloride, and lactate dehydrogenase (LDH)) were obtained prior to 4 and 24 h after the AA infusion. Incidence of HK (≥5.0) was correlated with pre-therapeutic kidney function and serum parameters. Formulas for the prediction of severe hyperkalemia (>6.0) were computed and prospectively validated.
Results
At 4 h, HK (≥5.0) was present in 94.7% with severe HK (>6.0) in 36.1%. Values normalized after 24 h in 84.2%. Pre-therapeutic kidney function did not correlate with the incidence of severe HK.
Increases in K+ were significantly correlated with decreases in phosphate (r = −0.444, p < 0.005) and increases in BUN (r = 0.313, p = 0.056). A baseline BUN of >28 mg/dl had a sensitivity of 84.6% and a specificity of 60.0% (AUC = 0.75) in predicting severe HK of >6.0 (phosphate, AUC = 0.37).
Computing of five standard serum parameters (potassium, BUN, sodium, phosphate, LDH) resulted in a sensitivity of 88.9% and a specificity of 79.3% for the prediction of severe HK >6.0 (accuracy = 81.6%).
Conclusions
A combination of serum parameters predicted prospectively the occurrence of relevant HK with an accuracy of 81.6% underlining its potential utility for identifying ‘high-risk’ patients prone to PRRT.
KW - amino acids
KW - kidney function
KW - hyperkalemia
KW - PRRT
KW - NET
KW - MAG3
Y1 - 2014
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-124963
VL - 4
IS - 74
ER -