Pediatric Tubulointerstitial nephritis and uveitis syndrome -pathogenesis and long-term prognosis

Thesis event information

Date and time of the thesis defence

Topic of the dissertation

Pediatric Tubulointerstitial nephritis and uveitis syndrome -pathogenesis and long-term prognosis

Doctoral candidate

Licentiate of Medicine Sari Rytkönen

Faculty and unit

University of Oulu Graduate School, Faculty of Medicine, Research Unit of Clinical Medicine, University of Oulu

Subject of study

Medicine

Opponent

professor Risto Tertti, University of Turku

Custos

professor h.c. Matti Nuutinen, OYS paediatric and Youth polyclinic

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Tubulointerstitial nephritis and uveitis syndrome -pathogenesis and long-term prognosis.

Tubulointerstitial nephritis (TIN) and uveitis (TINU) syndrome are rare inflammatory conditions affecting the kidneys and eyes with uveitis in 30–80% of TIN patients. TIN, characterized by kidney tubulointerstitial inflammation and mostly sparing glomeruli, presents with systemic symptoms like fever, fatigue and malaise along with elevated inflammatory markers and abnormal kidney function as well as low molecular weight proteinuria. TIN may result from various factors, including infections, systemic diseases and medications, and there is some indication about genetic susceptibility to it. Usually, no predisposing factors are identified in children and TIN is considered to be idiopathic and probably of autoimmune origin.
This study focused on the role of inflammatory cytokines and regulatory cells in TIN/TINU syndrome. We identified FOXP3+ regulatory T-cells in kidney biopsies from TIN patients, noting a significant reduction in those TINU patients who had chronic uveitis. This suggests that altered regulatory T-cell dynamics might influence the disease progression. Additionally, our investigation into IL-10 single nucleotide polymorphisms (SNP) revealed an association with increased susceptibility to TINU syndrome, indicating a genetic predisposition.
In our relatively large pediatric cohort, 25% of the TIN/TINU patients exhibited reduced glomerular filtration rate (< 90 mL/min/1.73 m2) at the latest follow-up visit after a median follow-up of 5.7 years, with 24% experiencing relapses during glucocorticoid tapering. Uveitis was diagnosed in 63% of patients and uveitis was chronic in around 40% and persisted in 21% of cases at the latest follow-up visit. Based on our results, we suggest evidence-based follow-up protocols in TIN and TINU syndromes.
In conclusion, our findings suggest that TIN and TINU syndromes involve complex immune mechanisms, with genetic factors like IL-10 polymorphisms playing a role. Despite treatment, the long-term outcomes for pediatric TIN/TINU patients show variability, underlining the need for vigilant monitoring and tailored management strategies. Future research should focus on elucidating the pathomechanisms and on exploring new therapeutic targets.
Last updated: 28.3.2025