Selected highlights

The Translational PKD Center has published a number of high-impact publications since its inception. This is a selected list of publication highlights from the past 12 months.

Imaging classification of autosomal dominant polycystic kidney disease: A simple model for selecting patients for clinical trials

Journal of the American Society of Nephrology. 2014, in press.

Irazabal MV, Rangel LJ, Bergstralh EJ, Osborn SL, Harmon AJ, Sundsbak JL, Bae KT, Chapman, Grantham JJ, Mrug M, Hogan MC, El-Zoghby ZM, Harris PC, Erickson BJ, King BF, Torres VE, and the CRISP Investigators.

The disease spectrum in autosomal dominant polycystic kidney disease (ADPKD) is highly variable, so predictive information about disease severity can be helpful in selecting patients for studies and in the future for treatment. By examining a large population of patients with CT or MRI images, from which height-adjusted total kidney volume (HtTKV) was estimated and with more than three estimated glomerular filtration rate (eGFR) measurements, the team was able to create a model based on HtTKV and age to predict future eGFR decline. This model can be used as a simple way to prioritize patients for enrollment in clinical trials.

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Evidence of a third ADPKD locus is not supported by re-analysis of designated PKD3 families

Kidney International. 2014;85:383.

Paul BM, Consugar MB, M. Lee MR, Sundsbak JL, Heyer CM, Rossetti S, Kubly VJ, Hopp K, Torres VE, Coto E, Clementi M, Bogdanova N, de Almeida E, Bichet DG, Harris PC.

Previous studies identified five families found to be unlinked to the known ADPKD genes, PKD1 or PKD2, suggesting further genetic heterogeneity. This study performed mutation screening of PKD1 or PKD2 in these families and found a mutation to a known ADPKD gene in four of the five cases, with the other case having an atypical PKD presentation. A false-positive diagnosis by ultrasound was the major reason for misclassification. This study underscored the value of careful imaging and genetic testing to obtain the correct diagnosis in ADPKD and questioned whether there is further genetic heterogeneity.

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Phosphodiesterase 1A modulates cystogenesis in zebrafish

Journal of the American Society of Nephrology. 2014, in press.

Sussman CR, Ward CJ, Leightner AC, Smith JL, Agarwal R, Harris PC, Torres VE.

Elevated cyclic adenosine monophosphate (cAMP) has been implicated in PKD. Inhibition of cAMP by phosphodiesterases (PDEs) is thought to also play a role in cyst development in PKD. By using a zebrafish model to study PDE, the team determined that depletion of PDE1 results in the formation of cysts and that it plays an important role in regulating the level of cAMP. This work identifies PDE1 as a potential new drug target for PKD.

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Supervised segmentation of polycystic kidneys: A new application for stereology data

Journal of Digital Imaging. 2014;27:514.

Warner JD, Irazabal MV, Krishnamurthi G, King BF, Torres VE, Erickson BJ.

Kidney volume estimation using traditional imaging methods can be quite time-consuming. Using a volume-estimation method called stereology, the team developed a novel method to analyze polycystic kidneys. This method allows for true segmentation of PKD kidneys that opens the way for more elaborate analysis of these complex structures.

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Transition fibre protein FBF1 is required for the ciliary entry of assembled intraflagellar transport complexes

Nature Communications. 2014;4:2750.

Wei Q, Xu Q, Zhang Y, Li Y, Zhang Q, Hu Z, Harris PC, Torres VE, Ling K, Hu J.

Defects in the primary cilia or the surrounding region are the cause of PKD and syndromic ciliopathies. The machinery that helps to assemble cilia is called the intraflagellar transport (IFT) machinery, but how proteins are imported onto the cilia and interact with the IFT machinery is not well-understood. Using the model worm system C. elegans, the team determined that a transition fibre protein FBF1 is required for import of IFT particles into the cilia. This work provides a vital piece of the puzzle to unraveling how cilia defects cause disease in humans.

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Research publications

See a comprehensive list of publications on PubMed for these researchers in the Translational Polycystic Kidney Disease Center: