Plasma leucine-rich α-2-glycoprotein 1 - a novel marker of diabetic kidney disease in children and adolescents with type 1 diabetes mellitus?

BACKGROUND: Glomerular endothelial dysfunction and neoangiogenesis play a significant role in the pathogenesis of diabetic kidney disease (DKD). Leucine-rich α-2 glycoprotein 1 (LRG1) is a recently discovered protein that participates in the molecular pathway of inflammation and angiogenesis. We aimed to investigate efficacy of LRG1 to predict estimated glomerular filtration rate (eGFR) decrease in children and adolescents with type 1 diabetes mellitus (T1DM). METHODS: The study comprised 72 participants with diabetes duration for ≥ 2 years. At study initiation, LRG1, urine albumin, eGFR (cystatin C-based, and Schwartz), HbA1c, and lipid values were evaluated and diabetes-related clinical features and anthropometric measurements were collected. These results were compared with final control values after ≥ 1 year. Patients were divided into subgroups according to presence of albuminuria progression, eGFR decrease, and metabolic control parameters. RESULTS: There was positive correlation between LRG1 level and Schwartz and cystatin C-based eGFR decline (r = 0.360, p = 0.003; r = 0.447, p = 0.001, respectively), and negative correlation between final cystatin C-based eGFR and LRG1 (p = 0.01, r = -0.345). Patients with cystatin C-based eGFR decrease > 10% had significantly higher LRG1 levels (p = 0.03), however, LRG1 was not different between albuminuria progression subgroups. A 0.282 µg/ml increase in LRG1 correlated with a 1% decrease in eGFR in simple linear regression analysis (ß = 0.282, %CI 0.11-0.45, p = 0.001) and LRG1 was an independent predictor of GFR decline even in the presence of covariates. CONCLUSIONS: Our study supports the relationship between plasma LRG1 and eGFR decline and suggests LRG1 may be an early marker of DKD progression in children with T1DM. A higher resolution version of the Graphical abstract is available as Supplementary information.

Catch-up Growth and Discontinuation of Fludrocortisone Treatment in Aldosterone Synthase Deficiency.

BACKGROUND: Aldosterone synthase deficiency (ASD) caused by mutations in the CYP11B2 gene is characterized by isolated mineralocorticoid deficiency. Data are scarce regarding clinical and biochemical outcomes of the disease in the follow-up. OBJECTIVE: Assessment of the growth and steroid profiles of patients with ASD at the time of diagnosis and after discontinuation of treatment. DESIGN AND METHOD: Children with clinical diagnosis of ASD were included in a multicenter study. Growth and treatment characteristics were recorded. Plasma adrenal steroids were measured using liquid chromatography-mass spectrometry. Genetic diagnosis was confirmed by CYP11B2 gene sequencing and in silico analyses. RESULTS: Sixteen patients from 12 families were included (8 females; median age at presentation: 3.1 months, range: 0.4 to 8.1). The most common symptom was poor weight gain (56.3%). Median age of onset of fludrocortisone treatment was 3.6 months (range: 0.9 to 8.3). Catch-up growth was achieved at median 2 months (range: 0.5 to 14.5) after treatment. Fludrocortisone could be stopped in 5 patients at a median age of 6.0 years (range: 2.2 to 7.6). Plasma steroid profiles revealed reduced aldosterone synthase activity both at diagnosis and after discontinuation of treatment compared to age-matched controls. We identified 6 novel (p.Y195H, c.1200 + 1G > A, p.F130L, p.E198del, c.1122-18G > A, p.I339_E343del) and 4 previously described CYP11B2 variants. The most common variant (40%) was p.T185I. CONCLUSIONS: Fludrocortisone treatment is associated with a rapid catch-up growth and control of electrolyte imbalances in ASD. Decreased mineralocorticoid requirement over time can be explained by the development of physiological adaptation mechanisms rather than improved aldosterone synthase activity. As complete biochemical remission cannot be achieved, a long-term surveillance of these patients is required.

Does fludrocortisone treatment cause hypomagnesemia in children with primary adrenal insufficiency?

Background/aim: Aldosterone is a mineralocorticoid that secreted from adrenal glands and a known factor to increase magnesium excretion by direct and indirect effects on renal tubular cells. Although the frequency of hypomagnesemia was found to be approximately 5% in adult studies, there is no study in the literature investigating the frequency of hypomagnesemia in children by using fludrocortisone, which has a mineralocorticoid activity. Materials and methods: A multi-center retrospective study was conducted, including children who were under fludrocortisone treatment for primary adrenal insufficiency and applied to participant pediatric endocrinology outpatient clinics. Results: Forty-three patients (58.1% male, 41.9% prepubertal) included in the study, whose median age was 9.18 (0.61-19) years, and the most common diagnosis among the patients was a salt-wasting form of congenital adrenal hyperplasia (67.4%). Mean serum magnesium level was 2.05 (±0.13) mg/dL, and hypomagnesemia was not observed in any of the patients treated with fludrocortisone. None of the patients had increased urinary excretion of magnesium. Conclusion: Unlike the studies performed in adults, we could not find any evidence of magnesium wasting effect of fludrocortisone treatment with normal or even high doses in children and adolescents.

Inner retinal thickness and optic disc measurements in obese children and adolescents.

PURPOSE: This study aimed to evaluate optic nerve head parameters and inner retinal layer thicknesses in obese children and adolescents. METHODS: Forty-one eyes of 41 pediatric obese participants and 41 eyes of 41 age- and sex-matched healthy controls were included in this study. Body mass index was calculated, based on sex and age, using body weight and height measurements. Blood lipid values (i.e., cholesterol, low-density lipoprotein, high-density lipoprotein, and triglyceride) were measured in obese participants. Optical coherence tomography was used to examine optic nerve head parameters, including rim area, disc area, cup-to-disc ratio, and cup volume, as well as the thicknesses of retinal nerve fiber layers and macular ganglion cell-inner plexiform layers. RESULTS: Optic disc parameters were similar in obese and healthy children (p>0.05). The percentage of binocular retinal nerve fiber layer thickness symmetry was significantly different between obese and control groups (p=0.003). Compared to the control group, participants in the obese group exhibited thinner retinal nerve fiber layers in the superior quadrants (p=0.04) and thinner ganglion cell-inner plexiform layers in the superior-temporal sectors (p=0.04). There were no statistically significant correlations between the ocular parameters and lipid blood test values assessed in this study (p>0.05). Body mass index was significantly negatively correlated with the mean retinal nerve fiber layer thickness (r=-0.33, p=0.03) in the obese group. There was no significant correlation between intraocular pressure and body mass index (r=0.05, p=0.74). CONCLUSION: Compared to healthy children, obese children had greater binocular retinal nerve fiber layer thickness asymmetry and thinner retinal nerve fiber and ganglion cell-inner plexiform layers in several sectors. Blood lipid levels were not associated with retinal thickness or optic disc parameters in obese children.

Evaluation of optic disc, retinal nerve fiber and macular ganglion cell layers in pediatric diabetes.

PURPOSE: Our aim was to compare optic disc parameters, retinal nerve fiber (RNFL) and macular ganglion cell layers between children and adolescents with diabetes mellitus (type 1) and healthy controls. METHODS: Sixty-three eyes of 63 pediatric diabetic patients without diabetic retinopathy and 44 eyes of 44 healthy controls were included in this cross-sectional and comparative study. Diabetic and control groups were similar in the aspect of age, gender and refractive error. Measurements of optic disc parameters (i.e., rim area, disc area, cup-to-disc ratio, cup volume), thickness of RNFL and macular ganglion cell-inner plexiform layers (GCL + IPL) were taken with the spectral domain optical coherence tomography. RESULTS: There were not statistically significant differences between the diabetic patients and healthy controls in terms of intraocular pressure (p = 0.14), retinal nerve fiber layer thickness (p = 0.61), rim area (p = 0.92), disc area (p = 0.10), vertical cup-to-disc ratio (p = 0.16), cup volume (p = 0.13), and average macular GCL + IPL thickness (p = 0.43). On the other hand, binocular RNFL thickness symmetry percentage was statistically significantly different in the diabetic and control groups (p = 0.01). CONCLUSION: Diabetic children and adolescents without diabetic retinopathy have more binocular RNFL thickness asymmetry compared to healthy controls.