Acute tubulointerstitial nephritis in children- a retrospective case series in a UK tertiary paediatric centre.

BACKGROUND: Acute tubulointerstitial nephritis (AIN) is an uncommon cause of acute kidney injury in children, accounting for less than 10% of cases. There is limited information regarding the range of underlying diagnoses and how these may differ geographically. We undertook a retrospective case note review of consecutive cases of biopsy-proven AIN, presenting to a single UK tertiary paediatric centre, to describe the range of AIN in our caseload, define key characteristics and response to treatment, with the aim of informing paediatric nephrology practice. METHODS: Cases were identified retrospectively from departmental records. Data extracted included demographics, presenting clinical and biochemical features, renal biopsy histology, treatment and follow-up. RESULTS: Ten cases were identified over 8 years (2007-2014). Age range 6-16 years. Male:Female ratio 1:9. Final diagnoses included 6 tubulointerstitial nephritis and uveitis syndrome (TINU), 2 idiopathic, 1 sarcoidosis, 1 child with Streptococcal disease. Of the TINU cases, timing of eye symptoms varied in relation to AIN presentation. Cases had a varied investigative work-up. Median presenting plasma creatinine was 303 µmol/l (range 152-932 µmol/l). Renal function improved spontaneously in 1 idiopathic case and improved with antimicrobial treatment in a child with Streptococcal disease. Eight cases received immunosuppressive treatment with intravenous methylprednisolone (approximately 10 mg/kg for 3-5 days) and / or oral prednisolone (1-2 mg/kg initially, reducing over 7-28 days). At 1 month, median creatinine had fallen to 91 µmol/l (range 41-120 µmol/l) with median eGFR 61 ml/min/1.73m2 (range 51-103 ml/min/1.73m2). At last follow-up (median 18.5 months, range 2-70 months), median creatinine was 71 µmol/l (range 47-90 µmol/l) with median eGFR 80 ml/min/1.73m2, range 63 to 101 ml/min/1.73m2). Two patients received antihypertensives at diagnosis and 1 further patient at 1 month follow-up. Eight patients received electrolyte supplementation. Median time to discontinuing electrolyte supplementation was 3.5 months (range 1-12 months). CONCLUSION: To our knowledge, this is the only contemporary UK case series of biopsy-proven AIN in children. Our population has a high proportion of TINU. Treatment was accompanied by improvement of renal function, however 7/10 patients had an eGFR < 90 ml/min/1.73m2 at last follow-up. We suggest a standardised investigative work-up and recommend long-term follow-up.

Increased serum concentration of sphingosine-1-phosphate in juvenile-onset systemic lupus erythematosus.

PURPOSE: Sphingosine-1-phosphate (S1P) is an active sphingolipid with chemotactic abilities and has been linked to inflammatory mediators and autoimmune disease. The aim of this study was to assess whether children with juvenile-onset systemic lupus erythematosus (JSLE) express increased systemic and/or urinary concentrations of S1P. METHODS: A subgroup of patients participating in the UK JSLE Cohort Study, were invited to participate. Cross sectional serum and urine samples were prospectively collected along with demographic and standard clinical data. Results were compared to a cohort of disease controls (Henoch Schonlein Purpura; HSP) and healthy controls (HC). RESULTS: The median age of JSLE patients (n = 15) was 13.6 years (7.2-16.9 years). The serum concentrations of S1P in JSLE patients (7.4 uM, IQR 6.3-12.3 uM) were statistically significantly increased when compared to patients with HSP (n = 10; 5.2 uM, IQR 4.0-7.9 uM; p = 0.016) and HCs (n = 10; 3.8 uM, IQR 2.1-5.8 uM; p = 0.003). There was a trend towards increased serum S1P concentrations between patients with active lupus nephritis (n = 8; 8.7 uM, IQR 6.2-15.3 uM) compared to lupus non-nephritis (n = 7; 6.6 uM, IQR 6.3-10.6 uM; p = 0.355). No relationship was found between disease activity markers and S1P. Urine S1P concentrations were no different between JSLE patients (56.0 nM, IQR 40.3-96.6 nM) and HCs (58.7 nM, IQR 0-241.9 nM; p = 0.889). CONCLUSIONS: We have demonstrated, for the first time, an increased serum concentration of S1P in a cohort of JSLE patients. These findings highlight a role of S1P in the pathophysiology of JSLE that warrants further investigation.

Steroid-sensitive nephrotic syndrome and vascular endothelial growth factor gene polymorphisms.

Genetic polymorphisms have been recognized as important determinants of gene expression. Three common single nucleotide polymorphisms have been identified in the promoter and 5' untranslated region of the vascular endothelial growth factor (VEGF) gene: -460 C --> T, -141 A --> C and +405 G --> C. As VEGF has been postulated to play a role in the pathogenesis of childhood steroid-sensitive nephrotic syndrome (SSNS), this study tested the hypothesis that VEGF genotype may be associated with susceptibility to SSNS. We examined the genotype frequencies of these polymorphisms in a total of 116 children with SSNS and 150 control subjects, using polymerase chain reaction-restriction fragment length polymorphism analysis (PCR-RFLP). There were no statistically significant differences in any of the genotype frequencies between SSNS patients and controls. We conclude that VEGF -460, -141 and +405 genotypes are not associated with susceptibility to childhood SSNS.