Impact of chronic kidney disease on the natural history of alkaptonuria

Faria, Bernardo; Vidinha, Joana; Pêgo, Cátia; Correia, Hildeberto; Sousa, Tânia

doi:10.1093/ckj/sfs079

Cited by 10 publications

(4 citation statements)

References 10 publications

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“…A progressive exacerbation of ochronotic manifestations in AKU leads to kidney stones and nephrolithiasis; thus, kidney disease gradually worsens and the patient sometimes starts renal replacement therapy [ 14 ]. Interestingly, despite the fact that AKU patients often suffer from kidney dysfunction, in 40 tested patients we did not observe increased CysC levels, while CatD is elevated compared to controls (Table 1 ).…”

Section: Utility and Discussionmentioning

confidence: 99%

ApreciseKUre: an approach of Precision Medicine in a Rare Disease

Spiga

Cicaloni

Bernini

et al. 2017

BMC Med Inform Decis Mak

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BackgroundAlkaptonuria (AKU; OMIM:203500) is a classic Mendelian genetic disorder described by Garrod already in 1902. It causes urine to turn black upon exposure to air and also leads to ochronosis as well as early osteoarthritis.Main body of the abstractOur objective is the implementation of a Precision Medicine (PM) approach to AKU. We present here a novel ApreciseKUre database facilitating the collection, integration and analysis of patient data in order to create an AKU-dedicated “PM Ecosystem” in which genetic, biochemical and clinical resources can be shared among registered researchers. In order to exploit the ApreciseKUre database, we developed an analytic method based on Pearson’s correlation coefficient and P value that generates as refreshable correlation matrix. A complete statistical analysis is obtained by associating every pair of parameters to examine the dependence between multiple variables at the same time.Short conclusionsEmploying this analytic approach, we showed that some clinically used biomarkers are not suitable as prognostic biomarkers in AKU for a more reliable patients’ clinical monitoring. We believe this database could be a good starting point for the creation of a new clinical management tool in AKU, which will lead to the development of a deeper knowledge network on the disease and will advance its treatment. Moreover, our approach can serve as a personalization model paradigm for other inborn errors of metabolism or rare diseases in general.Electronic supplementary materialThe online version of this article (doi:10.1186/s12911-017-0438-0) contains supplementary material, which is available to authorized users.

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Section: Utility and Discussionmentioning

confidence: 99%

ApreciseKUre: an approach of Precision Medicine in a Rare Disease

Spiga

Cicaloni

Bernini

et al. 2017

BMC Med Inform Decis Mak

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“…Levels of CatD, a protease capable of degrading proteins such as CysC ( Lenarčič et al, 1991 ), are particularly elevated in rheumatic diseases ( Khalkhali-Ellis and Hendrix Mary, 2014 ) such as AKU. Ochronotic manifestations in AKU gradually lead to kidney stones and nephrolithiasis ( Faria et al, 2012 ). Even though patients with AKU often suffer from renal dysfunction, a subset of AKU patients showed high values of CatD while CysC levels did not increase ( Braconi et al, 2018 ).…”

Section: Aprecisekure Digital Ecosystem Platformmentioning

confidence: 99%

Computational Approaches Integrated in a Digital Ecosystem Platform for a Rare Disease

et al. 2022

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Alkaptonuria (AKU) is an ultra-rare autosomal recessive disease caused by a mutation in the homogentisate 1,2-dioxygenase gene. One of the main obstacles in studying AKU and other ultra-rare diseases, is the lack of a standardized methodology to assess disease severity or response to treatment. Based on that, a multi-purpose digital platform, called ApreciseKUre, was implemented to facilitate data collection, integration and analysis for patients affected by AKU. It includes genetic, biochemical, histopathological, clinical, therapeutic resources and Quality of Life (QoL) scores that can be shared among registered researchers and clinicians to create a Precision Medicine Ecosystem. The combination of machine learning applications to analyse and re-interpret data available in the ApreciseKUre clearly indicated the potential direct benefits to achieve patients’ stratification and the consequent tailoring of care and treatments to a specific subgroup of patients. In order to generate a comprehensive patient profile, computational modeling and database construction support the identification of potential new biomarkers, paving the way for more personalized therapy to maximize the benefit-risk ratio. In this work, different Machine Learning implemented approaches were described:

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“…Furthermore, kidney involvement in AKU is rare, with reports owning the etiology to nephrolithiasis [ 5 ]. The pathophysiologic mechanism involved in chronic kidney disease (CKD) and quadriceps tendon (QT) rupture is attributed, in theory, to the decrease in renal function leading to calcium, phosphorus, vitamin D, and parathyroid hormone (PTH) imbalance.…”

Section: Introductionmentioning

confidence: 99%

Alkaptonuria in an Elderly Presenting with Asynchronous Rupture of both Quadriceps Tendons and Chronic Kidney Failure: Case Report and Literature Review

Issa,

Alsager

2023

jocr

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Introduction: Alkaptonuria (AKU) is a rare autosomal-recessive multisystemic disease. It is caused by a mutant homogentisate dioxygenase coding gene, leading to the acclamation of homogentisic acid (HGA), hence systemic manifestations. Renal manifestations and tendon rupture are rarely reported. Case Report: We report a 60-year-old male with chronic kidney disease for over a decade who was initially misdiagnosed with ankylosing spondylitis and rheumatoid arthritis. Later on, the patient presented to our institute with a non-synchronized (8 years) acute quadriceps tendon rupture. Conclusion: Physicians should be aware of the importance of prophylactic measures in the management of AKU, which is mainly medical management, to reduce the accumulation of HGA in the body. We further emphasize this point to reduce the incidence of subsequent tendon ruptures, as it significantly affects the quality of life. Keywords: Alkaptonuria, kidney failure, tendon, rupture, quadriceps tendon.

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Impact of chronic kidney disease on the natural history of alkaptonuria

Cited by 10 publications

References 10 publications

ApreciseKUre: an approach of Precision Medicine in a Rare Disease

ApreciseKUre: an approach of Precision Medicine in a Rare Disease

Computational Approaches Integrated in a Digital Ecosystem Platform for a Rare Disease

Alkaptonuria in an Elderly Presenting with Asynchronous Rupture of both Quadriceps Tendons and Chronic Kidney Failure: Case Report and Literature Review

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