Tubulointerstitial nephritis (TIN) and uveitis (TINU) syndrome is a rare disease. The renal prognosis is generally thought to be better in children with TINU syndrome than in adults. However, data ...are scarce. We aimed to investigate the long-term renal prognosis in a French cohort of children with TINU syndrome.
We performed a national retrospective study including 23 French pediatric nephrology centers enrolling patients with TINU syndrome diagnosed between January 2000 and December 2018.
A total of 46 patients were included (52% female, median age 13.8 years). At diagnosis of TIN, the median estimated glomerular filtration rate (eGFR) was 30.6 ml/min per 1.73 m2 (4.9–62.8). The median time between diagnosis of uveitis and TIN was 0.4 months (−4.1; +17.1). All patients had anterior uveitis, but 12 (29%) were asymptomatic. Nearly all patients (44 of 46) received steroid treatment, and 12 patients (26%) received a second-line therapy. At last follow-up (median 2.8 years), the median eGFR was 87.5 ml/min per 1.73 m2 (60.3–152.7) and <90 ml/min per 1.73 m2 in 20 patients.
In our study, nearly half of the patients had renal sequelae at last follow-up. Given the possible progression to chronic kidney disease, long-term monitoring of children with TINU syndrome is mandatory. Approximately a quarter of the children had asymptomatic uveitis suggesting all children presenting with TIN should undergo systematic ophthalmologic screening even in the absence of ocular signs.
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The hepatocyte nuclear factor-1beta encoded by the TCF2 gene plays a role for the specific regulation of gene expression in various tissues such as liver, kidney, intestine, and pancreatic islets and ...is involved in the embryonic development of these organs. TCF2 mutations are known to be responsible for the maturity-onset diabetes of the young type 5 associated with renal manifestations. Several observations have suggested that TCF2 mutations may be involved in restricted renal phenotypes. Eighty children (median age at diagnosis 0.2 yr) with renal cysts, hyperechogenicity, hypoplasia, or single kidneys were studied. Quantitative multiplex PCR amplification of short fluorescence fragments for the search of large genomic rearrangements and sequencing for the detection of point mutations were performed. TCF2 anomalies were detected in one third of patients (25 of 80). The main alteration was the complete deletion of the TCF2 gene detected in 16 patients. Family screening revealed de novo TCF2 anomalies in nine of 17 probands with a high prevalence of deletions (seven of nine). TCF2 anomalies were associated with bilateral renal anomalies (P < 0.001) and bilateral cortical cysts (P < 0.001). However, abnormal renal function, detected in 40% of patients, was independent of the TCF2 genotype. No difference in renal function or severity of renal morphologic lesions was observed between patients with a TCF2 deletion and those with point mutations. In conclusion, TCF2 molecular anomalies are involved in restricted renal phenotype in childhood without alteration of glucose metabolism. These findings have important implications in the diagnosis of patients with renal dysplasia with cysts and their follow-up.
Non-invasive prognosis of the clinical progression of disease is of high interest, especially in newborn and children. Neonatal ureteropelvic (UPJ) junction obstruction needs close and invasive ...surveillance to determine the necessity of pyeloplasty. A number of groups have initiated research with the aim to find non-invasive biomarkers for UPJ obstruction. Two different strategies have been followed. One strategy, based on the knowledge obtained in animal models of UPJ obstruction, has identified a number of individual urinary markers of severe UPJ obstruction. Combining these markers might allow prediction of which patients will require surgery and in which patients UPJ obstruction will spontaneously resolve. The other strategy is based on urinary proteomics. In this strategy the entire urinary proteome is probed for a set of biomarkers that correlates with the degree of UPJ obstruction. In subsequent steps, these sets of urinary biomarkers are used for prediction of the clinical evolution of UPJ obstruction patients. This proteomic-based strategy allowed prediction, several months in advance, of the clinical evolution of neonates with UPJ-obstruction. Both strategies will be complementary and will hopefully replace in the near future the invasive follow-up of newborns with UPJ obstruction.
An important issue in congenital unilateral ureteropelvic junction (UPJ) obstruction, a frequent pathology in newborns, is whether infants should undergo surgery. Non-invasive biomarkers to reduce or ...replace the current invasive clinical exploration are not available. The objective of this study was to identify urinary markers of UPJ obstruction. We compared a number of proteome technologies to study the urinary proteome in UPJ obstruction and selected online capillary electrophoresis coupled to mass-spectrometry for the selection of non-invasive prognostic biomarkers. We selected 53 urinary biomarkers that were able to distinguish between different levels of UPJ obstruction. In a prospective study using these 53 biomarkers, we predicted with 97% accuracy, and several months in advance, the clinical outcome of 36 UPJ-obstruction patients. Some of the discriminating biomarkers were identified. A newly identified marker, proSAAS (proprotein convertase subtilisin/kexin type 1 inhibitor), generated a new hypothesis in the physiopathology of UPJ obstruction. These results show that analysis of urinary polypeptides in newborns with UPJ obstruction can predict their clinical outcome.
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