85 application/pdf German Publikationsserver der Universitätsbibliothek Marburg Universitätsbibliothek Marburg the antenatal Bartter´s Syndrom Querschnittstudie zu Nierenfunktion und Knochenstoffwechsel bei Patienten mit hereditärer Salzverlusttubulopathie monograph 2015 The antenatal Bartter´s syndrome, also known as the Hyperprostaglandin E syndrome (HPS), is a congenital, autosomal recessively inherited salt loosing tubulopathy, evoked by mutations in the genes of the proteins NKCC2, ROMK, Barttin, or ClC-Kb. Clinically, a massive electrolyte loss with hypokalemia, hypochloremic acidosis, and hypercalciuria can be seen (depending on type). In addition, there is a highly increased renin activity, and increased PGE2 secretion. If not treated, this disease is fatal and can lead to the death of the affected child. Based on this fact, an early treatment (normally from birth) with a COX inhibitor (indomethacin) and sufficient salt and water intake is very important in order to suppress the symptoms. The aBS / HPS patients usually have normotensive values due to their continuous salt loss. However a study from 2006 contradicts this statement. This study states, that despite renal salt loss, elevated blood pressure were found among patiens in respected study. The aim of this study was primarily to follow-up the renal function in patients with aBS / HPS in young adulthood. In addition, the secondary criteria, such as the frequency of arterial hypertension, body water, degradation, and bone metabolism disorder, are reviewed as well. In this study, a total of 13 patients in young adulthood with antenatal Bartter´s syndrome were studied and observed. There were 6 male and 7 female patients with the average age of 21.3 years. The genetic defect distribution showed 6 patients with NKCC2, 3 patients with ROMK and 4 patients with ClC-Kb. The various renal function parameters, blood pressure measurement with 24-hour ABPM, a bioelectrical impedance analysis, and various metabolic bone parameters were examined and the results were evaluated. The 24-hour ABPM is a well accepted and frequently used method for diagnosis and therapy control in the presence of arterial hypertension. The evaluation of the results from the 24-hour ABPM was performed by calculating the associated standard deviation scores on body size (SDS height), as these are normally distributed in contrast to the blood pressure readings. With this method, the value of the patients can be compared with ease. The same method of calculation was also performed for the evaluation of bone metabolism. For the evaluation of bioelectrical impedance, analysis was performed by means of calculating the z-score, only with a different formula. The results of renal function parameters showed a decreased glomerular filtration rate in 9 of 13 patients. The incidence of proteinuria in aBS / HPS patients was quite high, at least in this study with 10 of 13 patients. 5 of these 10 patients showed renal tubular involvement. The glomerular filtration rate (GFR) is negatively correlated with proteinuria (r = -0.4 p [0.01). NGAL was raised as a specific tubular injury marker in 4 patients. Due to the low number of patients, no strong statement could be made regarding NGAL as a suitable parameter for an early detection of kidney function reduction in aBS/HPS patient. Increased systolic blood pressure values during the day were observed only in 2 patients. However, there is a significant correlation between FeNa with SDS-systolic-day values. In addition, based on z-score, a reduced body water aBS / HPS were confirmed in this study. The body water was strongly correlated with lean mass. Most of the patients with aBS/HPS have small body height, at least this fact is observed in this study. It was also confirmed by a significant difference between age and height of age. The decreased glomerular filtration rate leads to increased cFGF-23 expression, and beside that there was a significant negative correlation between cFGF-23 with GFR. A metabolic disorder appears to be possible due to increased cFGF-23 and PTH. In the other hand, the other biomarkers of bone metabolism are in the normal range. At the end of this study, the following statements can be summarized: • A slowly progressive renal damage in aBS/HPS patient seems possible • Arterial hypertension in aBS/HPS patient was not confirmed • A proportional reduction of body water and lean body mass in aBS/HPS patients has been confirmed, possibly due to continuous loss of electrolyte • Due to chronic electrolyte loss, this disease could lead to a change in metabolic bone defect specially in cFGF-23 and PTH opus:6593 https://doi.org/10.17192/z2016.0199 ths Prof. Dr. med. Klaus Günter Klaus, Günter (Prof. Dr. med.) Medical sciences Medicine Medizin Ix JH, Shlipak MG, Brandenburg VM, Ali S, Ketteler M, Whooley MA. (2006) Association between human fetuin-A and the metabolic syndrome: data from the Heart and Soul Study. Circulation 113: 1760-1767 Lipton A, Ali SM, Leitzel K, Chinchilli V, Witters L, Engle L, Holloway D, Bekker P, Dunstan CR. (2002) Serum Osteoprotegerin Levels in Healthy Controls and Cancer Patients. 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J Biol Chem 280: 19883-19887 antenatales Bartter Syndrom https://archiv.ub.uni-marburg.de/diss/z2016/0199/cover.png doctoralThesis Philipps-Universität Marburg 2016-03-31 Medizin hyperprostaglandin E syndrom Zentrum für Kinder- und Jugendmedizin Misdhayini, Myra Maysarwasila Misdhayini Myra Maysarwasila Cross-sectional study on renal function and bone metabolism in patients with hereditary salt loosing tubulopathy urn:nbn:de:hebis:04-z2016-01993 Niere Das antenatale Bartter-Syndrom, auch Hyperprostaglandin E-Syndrom genannt, ist eine angeborene, autosomal-rezessiv vererbte Salzverlusttubulopathie, die durch Mutationen in den Genen für die Proteine NKCC2, ROMK, Barttin oder ClC-Kb hervorgerufen werden kann. Klinisch ist ein massiver Elektrolytverlust mit Hypokaliämie, hypochlorämischer Alkalose und Hyperkalziurie (je nach Typ) zu beobachten. Außerdem kommt es zu einer stark gesteigerten Reninaktivität und erhöhten PGE2-Ausscheidung. Unbehandelt verläuft diese Erkrankung tödlich, deshalb ist eine frühzeitige Therapie (meistens seit Geburt) mit COX-Inhibitoren (Indomethacin) und ausreichender Flüssigkeitszufuhr notwendig, um die Symptomatik zu unterdrücken. Die aBS/HPS-Patienten haben normalerweise aufgrund ihres kontinuierlichen Salzverlusts normotensive Blutdruckwerte. Eine Studie aus dem Jahr 2006 widerspricht dieser Aussage, da es bei Patienten dieser Studie trotz renalem Salzverlust zu erhöhtem Blutdruck kam. Das Ziel der vorliegenden Arbeit war in erster Linie die Nachuntersuchung der Nierenfunktion bei Patienten mit aBS/HPS im jungen Erwachsenenalter. Außerdem sollten die Nebenkriterien, wie die Häufigkeit einer arteriellen Hypertonie, Körperwasserverminderung und Knochenstoffwechselstörungen, überprüft werden. In dieser Studie wurden insgesamt 13 Patienten im jungen Erwachsenenalter mit antenatalem Bartter-Syndrom untersucht. Es waren 6 männliche und 7 weibliche Patienten mit einem Altersmittelwert von 21,31 Jahren beteiligt. Die Gendefektsverteilung ergab für 6 Patienten NKCC2, 3 Patienten ROMK und 4 Patienten ClC-Kb. Es wurden die verschiedenen Nierenfunktionsparameter, eine Blutdruckmessung mittels 24-Stunden-ABPM, eine bioelektrische Impedanzanalyse und verschiedene Knochenstoffwechselparameter untersucht und die Ergebnisse ausgewertet. Die 24-Stunden-ABPM ist eine gut akzeptierte und häufig eingesetzte Methode zur Diagnosesicherung und Therapiekontrolle bei Vorliegen einer arteriellen Hypertonie. Die Auswertung der Ergebnisse aus der 24-Stunden-ABPM erfolgte mittels Berechnung der zugehörigen Standard-Deviation-Score nach Körpergröße (SDSheight), da diese im Gegensatz zu den Blutdruckmesswerten normalverteilt sind und einen Vergleich der Werte untereinander ermöglichen. Die gleiche Berechnungsmethode wurde auch für die Auswertung der Knochenstoffwechselparameter angewendet. Die Auswertung der Bioelektrischen Impedanz Analyse erfolgte auch mittels der Berechnung des z-Scores, allerdings mit anderen Formeln. Die Ergebnisse der Nierenfunktionsparameter zeigten eine verminderte glomeruläre Filtrationsrate bei 9 von 13 Patienten. Die Häufigkeit einer Proteinurie bei aBS/HPS-Patienten war mit 10 von 13 Patienten zumindest in dieser Studie relativ hoch. Die Hälfte, also 5 von 10 Patienten, zeigten eine tubuläre Beteiligung. Die glomeruläre Filtrationsrate (GFR) korreliert negativ mit der Proteinurie (r= -0,4 p[0,01). NGAL als spezifische tubuläre Schädigung war bei 4 Patienten erhöht. Aufgrund der geringen Anzahl der Probanden konnte keine sichere Aussage bezüglich NGAL als geeignetem Parameter zur Früherkennung einer Nierenfunktionseinschränkung bei aBS/HPS-Patienten getroffen werden. Erhöhte systolische Blutdruckwerte tagsüber wiesen nur 2 Patienten auf. Es gibt eine signifikante Korrelation zwischen FeNa mit SDS-systolischen-tagsüber-Werten. Außerdem wurde anhand der z-Scores ein vermindertes Körperwasser bei aBS/HPS-Patienten bestätigt. Das Körperwasser korrelierte stark signifikant mit der Magermasse. Die aBS/HPS-Patienten wiesen eine unterdurchschnittliche Körpergröße auf, zumindest trat diese Beobachtung in der dieser Arbeit zugrunde liegenden Studie auf. Bestätigt wurde dies durch den signifikanten Unterschied zwischen Alter und Height of Alter. Die verminderte glomeruläre Filtrationsrate führt zur erhöhten cFGF-23-Expression, es gab hier eine negative signifikante Korrelation zwischen cFGF-23 mit der GFR. Eine Knochenstoffwechselstörung erscheint aufgrund erhöhtem cFGF-23 und PTH möglich. Allerdings blieben die anderen Biomarker des Knochenstoffwechsels im Normbereich. Zusammenfassend lässt sich sagen, dass die vorliegende Arbeit die folgende Aussagen zulässt: • Eine langsam progrediente Nierenschädigung bei aBS/HPS-Patienten erscheint möglich. • Eine arterielle Hypertonie bei aBS/HPS-Patienten konnte nicht bestätigt werden. • Eine proportionale Reduktion des Körperwasser als auch der Magermasse konnte bei aBS/HPS-Patienten aufgrund des kontinuierlichen Elektrolytverlusts nachgewiesen werden. • Der chronische Elektrolytverlust könnte zu einem veränderten Knochenstoffwechsel in Bezug auf cFGF-23 und PTH führen. Hyperprostaglandin E Syndrom renal function 2016-03-07