459 research outputs found
The European dRTA registry: an initial data analysis
No full textCongress of the European-Renal-Association (ERA)-European-Dialysis-and-Transplant-Association (EDTA) ELECTR NETWORK (58th. 2021. Virtual)Detlef Bockenhauer, Francesco Emma, Amina Talhi, Svetlana Papizh, Bahriye Atmis, Nakisa Homan, Bagdagul Aksu, Fernando Santos, Olivia Boyer, Marc Fila, Umut Selda Bayrakci, Loai Akram Ouda Eid, Maria VanDyck, Carlos Moguel, Selçuk Yüksel, Nur Canpolat, Franz Schaefer, Jun Oh, Max Liebau, Maria Gema Ariceta Iraola, Rosa Vargas-Poussou, Elena Levtchenko, Sergio Camilo Lopez-Garcia, Tanja Wlodkowski, Rezan Topologl
Potassium leak channels and the KCNK family of two-P-domain subunits
No full textWith a bang, a new family of potassium channels has exploded into view. Although KCNK channels were discovered only five years ago, they already outnumber other channel types. KCNK channels are easy to identify because of their unique structure--they possess two preforming domains in each subunit. The new channels function in a most remarkable fashion: they are highly regulated, potassium-selective leak channels. Although leak currents are fundamental to the function of nerves and muscles, the molecular basis for this type of conductance had been a mystery. Here we review the discovery of KCNK channels, what has been learned about them and what lies ahead. Even though two-P-domain channels are widespread and essential, they were hidden from sight in plain view--our most basic questions remain to be answered
Syndrome of inappropriate secretion of anti-diuretic hormone due to hypothalamic hamartoma: use of tolvaptan
No full textObjectives: hypothalamic hamartoma (HH) typically presents with gonadotrophin-dependent precocious puberty and/or seizures. Other endocrine disturbances are rare. We describe an infant with syndrome of inappropriate secretion of anti-diuretic hormone (SIADH) and a HH.Case presentation: a 6-week-old infant presented with seizures and life-threatening hyponatremia. A HH was identified on magnetic resonance imaging. Clinical examination and biochemistry were consistent with SIADH, and serum copeptin was high during hyponatremia, further supporting this diagnosis. Tolvaptan was effective in normalizing plasma sodium and enabling liberalization of fluids to ensure sufficient nutritional intake and weight gain and manage hunger.Conclusions: hyponatremia due to SIADH is novel at presentation of a HH, and can be challenging to diagnose and manage. Successful management of hyponatremia in this case was achieved using tolvaptan.</p
Hyponatremia and cyst growth in neonatal polycystic kidney disease: a case for aquaretics?
No full textHyponatremia is a common complication in neonatal polycystic kidney disease and is thought to be due to water retention. Aquaretics are drugs that promote free water excretion by blocking the arginine vasopressine receptor type 2 (AVPR2) in the collecting duct and thus impair urinary concentration. AVPR2 is also a key stimulant for cyclic AMP production in the collecting duct and in this way promotes cyst proliferation and pathologic kidney growth in autosomal dominant polycystic kidney disease (ADPKD). Consequently, the aquaretic tolvaptan is now used to slow down progression of ADPKD in adult patients. Whether this beneficial effect on retarding cystic disease progression also extends to recessive forms of polycystic kidney disease (PKD) is currently not known. A case report in this edition of Pediatric Nephrology touches on the intersecting indications for tolvaptan for both hyponatremia and cyst retardation in neonatal PKD and suggests that use for one indication may have beneficial effects on the other
The Genetic Architecture of Structural Renal and Urinary Tract Malformations
No full textStructural renal and urinary tract malformations are the most common cause of kidney failure in children. These congenital anomalies of the kidneys and urinary tract (CAKUT) are a phenotypically diverse group of malformations that result from defects in embryonic kidney, ureter, and bladder development. A genetic basis for CAKUT has been proposed, with over 50 monogenic causes reported, however, a molecular diagnosis is detected in less than 20% of patients.
In this thesis, I used bioinformatics and statistical genetics methodology to investigate the genetic architecture of structural renal and urinary tract malformations using whole-genome sequencing (WGS) data from the 100,000 Genomes Project. Population-based rare and common variant association testing was performed in over 800 cases and 20,000 controls of diverse ancestry seeking enrichment of single-nucleotide/indel and structural variation on a genome-wide, per-gene, and cis-regulatory element basis.
Using a sequencing-based genome-wide association study (GWAS) I identified the first robust genetic associations of posterior urethral valves (PUV), the most common cause of kidney failure in boys. Bayesian fine-mapping and functional annotation mapped these two loci to the transcription factor TBX5 and planar cell polarity gene PTK7, with both signals replicated in an independent cohort. Significant enrichment of rare structural variation affecting cis-regulatory elements was also detected providing novel insights into the pathogenesis of this poorly understood disorder.
I also demonstrated that the contribution of known monogenic disease to CAKUT has been overestimated and that common and low-frequency variation plays an important role in phenotypic variability. These findings support an omnigenic rather than monogenic model of inheritance for CAKUT and are consistent with the extensive genotypic-phenotypic heterogeneity, variable expressivity, and incomplete penetrance observed in this condition. Finally, this work demonstrates the value of sequencing-based GWAS methodology in rare disease, beyond conventional monogenic gene discovery, and provides strong support for an inclusive diverse-ancestry approach
Where Architecture Meets Biology: An Interview with Detlef Mertins
No full textI began doing research on Mies van der Rohe in the early nineties, after Fritz Neumeyer had published his book The Artless World, (1994). Neumeyer foregrounds Mies\u27 library, the books that Mies read. He was also the first to collect all the things that Mies himself wrote. One of the things that I found very surprising was that Mies was a reader of science, and especially of biology in the 1920s. He had a collection of about 40 books by the botanist Raoul Francé, the author of Der Sanze als Erfinder ( The Plant as Inventor, 1920). This was surprising, for I had always thought of modernism as an architecture of technology rather than an architecture that was imbued with organic aspirations and ethos. One thought of organic architecture more in terms of biomorphic form; in the German context, one thought of Hugo Häring, but not the straight-up-and-down, orthogonal architecture that Mies developed, or his expression of structure
Potassium Metabolism
No full textPotassium levels in the blood are tightly regulated. Deviations from this normal range can be life-threatening, and treatment should be based on an understanding of the underlying physiology and pathophysiology of potassium metabolism. Here we discuss normal potassium metabolism, with specific emphasis on renal potassium handling. We further discuss the clinical assessment of abnormalities of blood potassium levels to guide rational treatment.</p
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