IL-10 polymorphisms +434T/C, +504G/T, and -2849C/T may predispose to tubulointersititial nephritis and uveitis in pediatric population

Rytkönen, Sari; Ritari, Jarmo; Peräsaari, Juha; Saarela, Ville; Nuutinen, Matti; Jahnukainen, Timo

doi:10.1371/journal.pone.0211915

Cited by 9 publications

(7 citation statements)

References 41 publications

(39 reference statements)

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“…A novel human glycoprotein, Krebs von den Lungen-6, was also observed to be significantly increased in sera and distal renal tubules of TINU patients [ 5 ]. Furthermore, certain interleukin-10 polymorphisms have been found to be more prevalent in TIN/TINU patients, broadening our understanding of the genetic basis of the disease [ 6 ].…”

Section: Discussionmentioning

confidence: 99%

Tubulointerstitial nephritis and uveitis syndrome in an adolescent female: a case report

2021

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Background Tubulointerstitial nephritis with uveitis syndrome is a rare disease affecting mainly children and young women. Tubulointerstitial nephritis with uveitis is a diagnosis of exclusion, requiring a high degree of clinical suspicion. Studies report recent infections or certain drugs as precipitating factors of a lymphocytic oculorenal immune response. The prognosis is usually favorable with topical and systemic corticosteroid therapy. Case presentation We report a literature review and the case of a 14-year-old white girl, who presented to the ophthalmology department with features of one-sided uveitis. Upon transfer of patient to nephrological care, diagnostic work-up revealed renal involvement. Renal biopsy showed a mixed-cell and granulomatous tubulointerstitial nephritis with some noncaseating granulomas, leading to a diagnosis of tubulointerstitial nephritis with uveitis syndrome. With topical ocular and systemic corticosteroid therapy, the patients’ condition improved over several weeks. Conclusions Our case highlights the importance of early recognition and treatment of this syndrome, where cross-specialty care typically leads to a favorable outcome.

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Section: Discussionmentioning

confidence: 99%

Tubulointerstitial nephritis and uveitis syndrome in an adolescent female: a case report

2021

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“…The pathomechanisms behind TIN have remained unclear. There are data suggesting that it is an autoimmune disorder with susceptibility to becoming chronic [ 14 , 15 ]. In previous studies, we and others have shown that there are associations between certain human leukocyte antigen types [ 13 , 28 , 29 ], genetic variations in the inflammatory mediators [ 15 ], and that regulatory T cell function is altered [ 14 ] in patients with TIN/TINU syndrome and chronic uveitis, which may suggest autoimmune origin.…”

Section: Discussionmentioning

confidence: 99%

“…There are data suggesting that it is an autoimmune disorder with susceptibility to becoming chronic [ 14 , 15 ]. In previous studies, we and others have shown that there are associations between certain human leukocyte antigen types [ 13 , 28 , 29 ], genetic variations in the inflammatory mediators [ 15 ], and that regulatory T cell function is altered [ 14 ] in patients with TIN/TINU syndrome and chronic uveitis, which may suggest autoimmune origin. This could, at least theoretically, increase the risk for chronic kidney dysfunction and kidney failure; however, there is some evidence that patients with the worst kidney outcome have had some other additional condition of autoimmune origin, such as sarcoidosis or inflammatory bowel disease [ 30 – 32 ].…”

Section: Discussionmentioning

confidence: 99%

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Long-term outcome of biopsy-proven idiopathic tubulointersitial nephritis with or without uveitis in children—a nationwide follow-up study

et al. 2021

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Background Only a few studies reporting the long-term outcome of children with idiopathic tubulointerstitial nephritis (TIN) and uveitis syndrome (TINU) are available. We studied the long-term kidney and ocular outcome in a nationwide cohort of children with TIN or TINU. Methods All patients followed up for a minimum of 1 year by a paediatrician and an ophthalmologist were enrolled. The data on plasma creatinine (P-Cr), estimated glomerular filtration rate (eGFR), proteinuria, hypertension and uveitis were collected retrospectively. Results Fifty-two patients were studied. Median age at time of diagnosis was 13.1 (1.8–16.9) years and median follow-up time was 5.7 (1.1–21.2) years. Forty-five (87%) patients were initially treated with glucocorticoids. The median of the maximum P-Cr was 162 μmol/l (47–1,016) and that of eGFR 47 ml/min/1.73m2 (8–124). Uveitis was diagnosed in 33 patients (63%) and 21 (40%) patients developed chronic uveitis. P-Cr normalised in a median of 2 months. Eleven (21%) patients had nephritis recurrence during or after discontinuation of glucocorticoids. At the latest follow-up, 13 (25%) patients had eGFR < 90 ml/min/1.73m2 (median 83; 61–89 ml/min/1.73m2). Six patients had tubular proteinuria; all presented with TIN without uveitis. Seven (13%) patients were hypertensive. Eleven (21%) patients had uveitis. One patient developed uraemia and was later transplanted. Conclusions Our study questions the previously reported good long-term kidney and ocular outcome of patients with TIN/TINU. Decreased kidney function and/or ocular co-morbidities may persist for several years; thus, both kidney and ocular follow-up for at least 1 year is warranted. Graphical abstract A higher resolution version of the Graphical abstract is available as Supplementary information

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“…Rytkönen et al studied IL-10 gene SNPs in a cohort of 30 pediatric cases of TINU or idiopathic TIN. They found a higher prevalence of the IL-10 SNP s3024490 in TINU/ATIN cases compared with its prevalence in a control group of 393 individuals from their own population [ 46 ]. IL-10 is an immunoregulatory cytokine that inhibits the synthesis of proinflammatory cytokines and chemokines.…”

Section: Genetic Biomarkersmentioning

confidence: 99%

New Biomarkers in Acute Tubulointerstitial Nephritis: A Novel Approach to a Classic Condition

Valenzuela

Draibe

Fulladosa

et al. 2020

IJMS

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Acute tubulointerstitial nephritis (ATIN) is an immunomediated cause of acute kidney injury. The prevalence of ATIN among the causes of acute kidney injury (AKI) is not negligible, especially those cases related to certain drugs. To date, there is a lack of reliable non-invasive diagnostic and follow-up markers. The gold standard for diagnosis is kidney biopsy, which shows a pattern of tubulointerstitial leukocyte infiltrate. The urinalysis findings can aid in the diagnosis but are no longer considered sensitive or specific. Atthe present time, there is a rising attentiveness tofinding trustworthy biomarkers of the disease, with special focus in urinary cytokines and chemokines that may reflect kidney local inflammation. Cell-based tests are of notable interest to identify the exact drug involved in hypersensitivity reactions to drugs, manifesting as ATIN. Certain single-nucleotide polymorphisms in HLA or cytokine genes may confer susceptibility to the disease according to pathophysiological basis. In this review, we aim to critically examine and summarize the available evidence on this topic.

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IL-10 polymorphisms +434T/C, +504G/T, and -2849C/T may predispose to tubulointersititial nephritis and uveitis in pediatric population

Cited by 9 publications

References 41 publications

Tubulointerstitial nephritis and uveitis syndrome in an adolescent female: a case report

Tubulointerstitial nephritis and uveitis syndrome in an adolescent female: a case report

Long-term outcome of biopsy-proven idiopathic tubulointersitial nephritis with or without uveitis in children—a nationwide follow-up study

New Biomarkers in Acute Tubulointerstitial Nephritis: A Novel Approach to a Classic Condition

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