More than tubular dysfunction: cystinosis and kidney outcomes

Atmış, Bahriye; Bayazıt, Aysun Karabay; Cevizli, Derya; Kör, Deniz; Fidan, Hatice; Bişgin, Atıl; Kılavuz, Sebile; Erdoğan, Kıvılcım Eren; Melek, Engin; Gönlüşen, Gülfiliz; Anarat, Ali; Mungan, Neslihan Önenli

doi:10.1007/s40620-021-01078-y

Cited by 4 publications

(10 citation statements)

References 27 publications

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“…In autosomal recessive hereditary diseases, consanguineous marriages increase the risk of being affected, and in our study, consanguineous marriage was found in 77.8% of cases, while family history was present in 22.2%. Similar rates have been reported in other studies conducted in our country, where the rate of consanguineous marriages is generally high in the general population 4,9,11,12 . In contrast to our population, Greco et al reported the rate of consanguineous marriages as 8.6% 13 .…”

Section: Discussionsupporting

confidence: 91%

“…Likewise, a recent extensive cohort study conducted in Turkey revealed that the prevailing mutations were c.681G>A p.Glu227Glu and c.18-21del p.Thr7Phefs*7, both linked to early-onset disease and a more severe clinical progression. 4 In the study by Atmış et al 9 , it was reported that patients with the c.451A>G mutation had older ages at diagnosis and longer follow-up periods compared to patients with other mutations. In our study, similar to the previously reported findings from the same region in our country, the homozygous c.451A>G p.Arg151Gly mutation was also found to be prevalent 9,15 .…”

Section: Discussionmentioning

confidence: 99%

“…4 In the study by Atmış et al 9 , it was reported that patients with the c.451A>G mutation had older ages at diagnosis and longer follow-up periods compared to patients with other mutations. In our study, similar to the previously reported findings from the same region in our country, the homozygous c.451A>G p.Arg151Gly mutation was also found to be prevalent 9,15 . The higher proportion of patients with the homozygous c.451A>G p.Arg151Gly mutation, which was the initial description was provided by Topaloglu et al in Turkey 16 , in our study might have contributed to the higher average age at diagnosis compared to previous studies.…”

Section: Discussionmentioning

confidence: 99%

“…Cukurova Anestezi ve Cerrahi Bilimler Dergisi factor affecting kidney survival 9 . This study aims to assess cystinosis, a rare condition with significant multisystem impact and potential complications, particularly kidney failure.…”

Section: Original Articlementioning

confidence: 99%

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Evaluation of Cystinosis Patients and Factors Associated with Chronic Kidney Disease

AVCI,

PARMAKSIZ

2023

J Cukurova Anesth Surg

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Introduction: Cystinosis is a rare genetic, lysosomal storage disorder, leading to kidney involvement and other organs. The most critical factor determining the prognosis is its impact on the kidneys especially nephropatic cystinosis. This study aimed to evaluate cystinosis patients and identify factors associated with chronic kidney disease (CKD). Methods: The medical records of 18 nephropatic cystinosis patients were retrospectively reviewed. Demographic and clinical features, prognosis were evaluated. Patients were classified according to their estimated glomerular filtration rate (eGFR) at last visit as eGFR60 ml/min/1.73 m2, and were compared for CKD related factors. Results: The mean age at diagnosis was 46.61±50.42 months. The most common allel was c. 451A>G. Polyuria, polydipsia, vomiting, growth retardation, and renal osteodystrophy were typical presenting symptoms. At diagnosis, the mean eGFR was 72.94±21.69 ml/min/1.73 m². After an average follow-up of 68.28±60.18 months, the mean eGFR was 63.97±23.59 ml/min/1.73 m², and CKD was observed in 44.4% of patients, and 5 (27.8%) underwent kidney replacement theraphy (KRT). In patients with GFR

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Original Articlementioning

confidence: 99%

See 2 more Smart Citations

Evaluation of Cystinosis Patients and Factors Associated with Chronic Kidney Disease

AVCI,

PARMAKSIZ

2023

J Cukurova Anesth Surg

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“…The importance of lysosomes in renal physiology is also highlighted by the evidence that diseases involving abnormal lysosomal functionality, such as lysosomal storage disorders (LSD), often manifest severe renal phenotypes [ 4 ]. For instance, Fabry’s disease [ 5 , 6 ] and cystinosis [ 7 , 8 ] involve the accumulation of catabolites within kidney lysosomes and are usually characterized by inflammation and tubulointerstitial fibrosis, which are common features of end-stage renal diseases [ 4 ]. In addition, it has been recently shown that abnormal expression of specific lysosomal proteins might result in defective water reabsorption.…”

Section: Introductionmentioning

confidence: 99%

TRPML1-Induced Lysosomal Ca2+ Signals Activate AQP2 Translocation and Water Flux in Renal Collecting Duct Cells

Scorza

Milano

Saponara

et al. 2023

IJMS

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Lysosomes are acidic Ca2+ storage organelles that actively generate local Ca2+ signaling events to regulate a plethora of cell functions. Here, we characterized lysosomal Ca2+ signals in mouse renal collecting duct (CD) cells and we assessed their putative role in aquaporin 2 (AQP2)-dependent water reabsorption. Bafilomycin A1 and ML-SA1 triggered similar Ca2+ oscillations, in the absence of extracellular Ca2+, by alkalizing the acidic lysosomal pH or activating the lysosomal cation channel mucolipin 1 (TRPML1), respectively. TRPML1-dependent Ca2+ signals were blocked either pharmacologically or by lysosomes’ osmotic permeabilization, thus indicating these organelles as primary sources of Ca2+ release. Lysosome-induced Ca2+ oscillations were sustained by endoplasmic reticulum (ER) Ca2+ content, while bafilomycin A1 and ML-SA1 did not directly interfere with ER Ca2+ homeostasis per se. TRPML1 activation strongly increased AQP2 apical expression and depolymerized the actin cytoskeleton, thereby boosting water flux in response to an hypoosmotic stimulus. These effects were strictly dependent on the activation of the Ca2+/calcineurin pathway. Conversely, bafilomycin A1 led to perinuclear accumulation of AQP2 vesicles without affecting water permeability. Overall, lysosomal Ca2+ signaling events can be differently decoded to modulate Ca2+-dependent cellular functions related to the dock/fusion of AQP2-transporting vesicles in principal cells of the CD.

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Unveiling cystinosis in India

Heroor,

Verma,

Achanta

et al. 2024

J Rare Dis

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Background Cystinosis, a rare autosomal recessive disease, stems from genetic alterations in the CTNS gene, leading to a malfunction of lysosomal ‘cystinosin’ protein. This dysfunction causes intracellular cystine accumulation, resulting in nephropathic and ocular abnormalities. Cystinosis is relatively rare in Asian countries, partly due to underreporting and lack of awareness, and cases often lack sufficient genetic evidence to support their diagnosis. This study presents a descriptive case series involving four Indian patients with cystinosis, elucidating clinical and genetic aspects. Methods All four patients underwent comprehensive ophthalmic evaluations. The corneal cystine crystal (CCC) score was determined using anterior segment optical coherence tomography (AS-OCT) and in vivo confocal microscopy (IVCM). Genetic testing was performed using whole exome sequencing (WES). Results Corneal crystal deposition, a hallmark of cystinosis, was evident in all cases. Systemic analysis revealed manifestations such as polyuria, bony abnormalities, growth retardation, hypothyroidism, and developmental delay. Genetic testing in two patients identified a homozygous pathogenic variant c.18_21delGACT (p.Thr7PhefsX7) in the CTNS gene, previously reported to cause cystinosis in different ethnic populations. Conclusions Our case series sheds light on underrepresented cases of cystinosis in the Indian population. The rarity of this condition poses diagnostic challenges, leading to delayed or inaccurate diagnoses. AS-OCT can serve as a viable alternative to IVCM for assessing corneal crystal density status in cystinosis. Timely recognition and management are crucial in preventing complications, and the inclusion of genetic testing can expedite cystinosis diagnosis.

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More than tubular dysfunction: cystinosis and kidney outcomes

Cited by 4 publications

References 27 publications

Evaluation of Cystinosis Patients and Factors Associated with Chronic Kidney Disease

Evaluation of Cystinosis Patients and Factors Associated with Chronic Kidney Disease

TRPML1-Induced Lysosomal Ca2+ Signals Activate AQP2 Translocation and Water Flux in Renal Collecting Duct Cells

Unveiling cystinosis in India

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