A Practical Guide to Genetic Testing for Kidney Disorders of Unknown Etiology

Aron, Abraham W.; Besse, Whitney

doi:10.34067/kid.0007552021

Cited by 9 publications

(5 citation statements)

References 83 publications

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“…Complete molecular mechanisms encompassing the structure and function of protein are difficult to identify from a single panel of genetic testing. Therefore, structural and functional protein studies may provide better evidence when the genetic mutation is not identified in standard testing [89][90][91]. Genetic testing would help plan or anticipate the natural course of illness, as in the present study CEP 290 mutation would have guided the clinicians and families for early renal replacement therapy or enrolling in renal transplant lists.…”

Section: Genetic Testingmentioning

confidence: 86%

Single-Center Experience of Pediatric Cystic Kidney Disease and Literature Review

Grlić,

Gregurović,

Martinić

et al. 2024

Children

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Introduction: Pediatric cystic kidney disease (CyKD) includes conditions characterized by renal cysts. Despite extensive research in this field, there are no reliable genetics or other biomarkers to estimate the phenotypic consequences. Therefore, CyKD in children heavily relies on clinical and diagnostic testing to predict the long-term outcomes. Aim: A retrospective study aimed to provide a concise overview of this condition and analyze real-life data from a single-center pediatric CyKD cohort followed during a 12-year period. Methods and Materials: Medical records were reviewed for extensive clinical, laboratory, and radiological data, treatment approaches, and long-term outcomes. Results: During the study period, 112 patients received a diagnosis of pediatric CyKD. Male patients were more involved than female (1:0.93). Fifty-six patients had a multicystic dysplastic kidney; twenty-one of them had an autosomal dominant disorder; fifteen had an isolated renal cyst; ten had been diagnosed with autosomal recessive polycystic kidney disease; three had the tuberous sclerosis complex; two patients each had Bardet–Biedl, Joubert syndrome, and nephronophthisis; and one had been diagnosed with the trisomy 13 condition. Genetic testing was performed in 17.9% of the patients, revealing disease-causing mutations in three-quarters (75.0%) of the tested patients. The most commonly presenting symptoms were abdominal distension (21.4%), abdominal pain (15.2%), and oligohydramnios (12.5%). Recurrent urinary tract infections (UTI) were documented in one-quarter of the patients, while 20.5% of them developed hypertension during the long-term follow-up. Antibiotic prophylaxis and antihypertensive treatment were the most employed therapeutic modalities. Seventeen patients progressed to chronic kidney disease (CKD), with thirteen of them eventually reaching end-stage renal disease (ESRD). The time from the initial detection of cysts on an ultrasound (US) to the onset of CKD across the entire cohort was 59.0 (7.0–31124.0) months, whereas the duration from the detection of cysts on an US to the onset of ESRD across the whole cohort was 127.0 (33.0–141.0) months. The median follow-up duration in the cohort was 3.0 (1.0–7.0) years. The patients who progressed to ESRD had clinical symptoms at the time of initial clinical presentation. Conclusion: This study is the first large cohort of patients reported from Croatia. The most common CyKD was the multicystic dysplastic kidney disease. The most common clinical presentation was abdominal distention, abdominal pain, and oliguria. The most common long-term complications were recurrent UTIs, hypertension, CKD, and ESRD.

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Section: Genetic Testingmentioning

confidence: 86%

Single-Center Experience of Pediatric Cystic Kidney Disease and Literature Review

Grlić,

Gregurović,

Martinić

et al. 2024

Children

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“…Genome-wide association studies previously identi ed associations between SLC2A9 and serum urate concentrations 8 , including loss of function variants in SLC2A9 associated with elevated levels of serum urate 9 . Access to commercial genetic testing has consistently expanded, facilitating diagnosis of renal pathology in clinical settings 10 , including for SLC2A9 variants associated with hyperuricemia 11 . Accordingly, understanding iatrogenic hyperuricemia in the context of such polymorphisms in these transporters can enable health care providers to tailor treatment to individual patients and improve outcomes through precision medicine.…”

Section: Introductionmentioning

confidence: 99%

An Association of SLC2A9 variant rs7442295 with Uric Acid at Baseline and in Interaction with Iloperidone

Smieszek,

Chadwick,

Czeisler

et al. 2024

Preprint

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Uric acid concentrations are routinely measured during clinical laboratory evaluations, given serum urate levels correlate with blood pressure, metabolic syndrome, diabetes, gout, and cardiovascular disease. Circulating levels of uric acid are influenced by a complex mix of intrinsic and environmental factors, including genetics, diet, and drugs. We analyzed levels of uric acid in a recent phase 3 clinical trial of patients with bipolar mania treated with 24mg/day (12mg twice daily) of the antipsychotic iloperidone or placebo. Initial results revealed iloperidone treatment was associated with increases in uric acid from baseline, consistent with a similar, previous phase 3 study of iloperidone treatment of schizophrenia in adults. Pharmacogenetic analysis examining the urate transporter SLC2A9 revealed iloperidone associated increases were linked to a genetic variant (rs7442295), correlating with both urate levels at baseline and in interaction with iloperidone vs placebo. Further investigation suggested potentially clinically relevant sex differences associated with this variant, with male GG genotype patients exhibiting more frequent shifts from above the upper limit of normal for iloperidone-treated patients in comparison to female, AG/AA, and placebo groups. A pronounced increase of 35.91 µmol/L (0.674 mg/dL) was seen in iloperidone-treated patients homozygous for the for the rs7442295 (G) allele at the SLC2A9 gene, compared to a decrease of -16.5 µmol/L in the corresponding GG placebo group. Overall, the mechanism of this iloperidone-induced increase in serum urate levels is likely due to decrease in clearance of urate through interaction with the SLC2A9 urate transporter protein.

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“…The care for patients with kidney disease now often includes consideration of genetic testing. 1 , 2 , 3 As genetic testing becomes more commonplace in the nephrology specialty, there is an emerging need for partnership between the clinicians and genetics experts. 4 , 5 , 6 , 7 The clinician needs include help with the interpretation of genetic test results; resources to help facilitate patient discussions about the potential benefits, limitations, and risks of genetic testing; help in communicating test results to patients; and basic educational resources relating to the underlying genetic causes of chronic kidney disease (CKD).…”

Section: Introductionmentioning

confidence: 99%

“…Genetic testing can provide information on clinical management, prognosis, disease mitigation, transplant decision-making and reproductive planning. 1 , 6 , 7 , 8 , 9 However, there are associated complexities which arise from testing such as diagnostic versus predictive testing (testing at-risk individuals) and variant interpretation. This can lead to a lack of confidence about incorporating genomics into clinical practice.…”

Section: Introductionmentioning

confidence: 99%