Querschnittstudie zu Nierenfunktion und Knochenstoffwechsel bei Patienten mit hereditärer Salzverlusttubulopathie

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 Elektrolytverl...

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Bibliographic Details
Main Author: Misdhayini, Myra Maysarwasila
Contributors: Klaus, Günter (Prof. Dr. med.) (Thesis advisor)
Format: Dissertation
Language:German
Published: Philipps-Universität Marburg 2015
Zentrum für Kinder- und Jugendmedizin
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Table of Contents: 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