Urinary angiotensinogen and urinary sodium are associated with blood pressure in normoalbuminuric children with diabetes.

BACKGROUND: The aim of this study was to evaluate the association between blood pressure (BP) and urinary angiotensinogen excretion (uAGT) and renal sodium excretion (uNa) in children with type 1 diabetes mellitus (DM1). METHODS: The study group consisted of 52 children with DM1 (28 males and 24 females) with albumin/creatinine ratio (ACR) below 30 mg/g and glomerular filtration rate (eGFR) above 90 ml/min/1.73 m(2). BP was assessed by 24-h ambulatory blood pressure monitoring (ABPM). RESULTS: The patients showed significantly increased uAGT values with respect to controls (median 0.00 and range 1.76 vs. 0.00 and 0.00 ng/mg, respectively). The significant increase of uAGT was observed even in prehypertensive patients. uAGT concentrations showed positive correlation with systolic and diastolic 24-h BP and with mean arterial pressure (MAP) (r = 0.594). uNa values were negatively correlated with BP parameters, uAGT, ACR and eGFR. CONCLUSIONS: An increase in uAGT precedes hypertension (HTN) in normoalbuminuric children with DM1 and may be considered as a new marker of HTN. Decreased sodium excretion seems to be involved in the development of HTN and early renal injury. Both uAGT and uNa are associated with BP in normoalbuminuric diabetic children.

Hypertensive nephropathy in children - do we diagnose early enough?

BACKGROUND/AIMS: The aim was to evaluate the level of neutrophil gelatinase-associated lipocalin (NGAL), interleukin 18 (IL-18) and retinol binding protein (RBP) in children with primary hypertension and no features of hypertensive nephropathy. METHODS: The study group consisted of 19 children (15 males) aged 14.8 ± 2.18 years with primary hypertension. Estimated glomerular filtration rate (eGFR) and albumin/creatinine ratio (ACR) were within the normal range. Mean blood pressure (BP) was 141/79 mmHg (mean systolic BP percentile was 98, mean diastolic BP percentile was 80). Ambulatory BP measurement (ABPM), blood and urine biochemical measurements and features of end organ damage were assessed. The control group consisted of 20 healthy children. RESULTS: Hypertensive children showed significantly increased serum and urine NGAL concentration vs controls. Urine RBP was significantly higher in the study group vs controls. A positive correlation was found between urine NGAL and the index of mean systolic BP measured in ABPM, between urine IL-18 and the index of office diastolic BP, between serum NGAL and ACR, and between urine NGAL concentration and serum HDL. CONCLUSION: In children with primary hypertension, increased serum and urine NGAL may reflect kidney injury earlier than typical markers of hypertensive nephropathy.

Normal-range albuminuria does not exclude nephropathy in diabetic children.

Clinically detectable diabetic nephropathy (DN) begins with the development of microalbuminuria (MA). However, early renal dysfunction may be overlooked despite using that method. On the other hand, the gold standard in DN detection-that is, renal biopsy-is highly invasive. The aim of this study was to evaluate the level of neutrophil-gelatinase-associated lipocalin (NGAL) and interleukin (IL)-18 and their relations to albumin excretion rate (AER) in children with normal-range albuminuria, e.g. in those considered as not presenting diabetic nephropathy. The study group consisted of 22 children (age 12.7 +/- 3.5 years) with type 1 diabetes mellitus (T1DM). Long-term glycemic control was assessed on hemoglobin A1c (HbA1c) levels (8.52 +/- 1.78%). All patients presented normal estimated glomerular filtration rate (eGFR) (141 +/- 23 ml/min/1.73 m(2)) and normal urinary albumin excretion (13.09 +/- 7.63 mg/24 h). Fourteen healthy children served as a control group. Children with T1DM showed increased NGAL values with respect to controls-interestingly, both in serum (sNGAL) (867.43 +/- 341.98 vs. 655.29 +/- 196.17 ng/ml; p = 0.04) and in urine (uNGAL) (420.04 +/- 374.16 vs. 156.53 +/- 185.18 ng/ml, p = 0.04). IL-18 levels were not different in both groups both in serum (58.52 +/- 20.11 vs. 69.79 +/- 58.76 ng/ml; NS) and in urine (14.53 +/- 12.74 vs. 14.60 +/- 10.92 ng/ml; NS). Despite the relatively small study group, the positive correlation between sNGAL and AER was found [AER (mg/24 h) = 3.1893 + 0.01141 x sNGAL (ng/ml); r = 0.51; p = 0.014] as well as between uNGAL and AER [AER (mg/24 h) = 8.7538 + 0.01032 x uNGAL (ng/ml); r = 0.51; p = 0.016]. No relationship between sNGAL and uNGAL, and GFR and HbA1c were found. Normal-range albuminuria does not exclude diabetic nephropathy defined as increased sNGAL and uNGAL concentration. NGAL measurement can be more sensitive than MA and may become a useful tool for evaluating renal involvement in diabetic children.

Efficacy of plasma exchange in septic shock: a case report.

The mortality rate for severe sepsis and septic shock remains high. Additionally, this life-threatening state poses serious difficulties for the treatment of patients. Unfortunately, the mechanism of sepsis is complex and not well understood. In this paper, we present the case of a 2.5-year-old female with septic shock treated with plasma exchange (PE) as a nonstandard therapy. We analysed the medical history of disease, including patient data, physical examination, laboratory tests and treatment. Unexpectedly, we achieved clinical improvement after the first PE. During PE, the dose of catecholamine was reduced. In addition, the level of C-reactive protein seemed to be a better predictor of the efficacy of PE in septic shock compared to procalcitonin. We conclude that PE may improve the survival rate for patients with septic shock. These data could be useful in the search and introduction of new or alternative methods of treatment for critically ill children.

Efficacy and safety of rituximab treatment in children with primary glomerulonephritis.

BACKGROUND: The aim of our study was to analyze the efficacy and safety of rituximab, a chimeric monoclonal antibody against CD20 lymphocytes, as a nonstandard immunosuppressive therapy in children with different types of primary glomerulonephritis who were not eligible for routine treatment. METHODS: The study group was composed of 16 children with proteinuric glomerulopathies, not responding to standard immunosuppressive therapy. The indications included steroid-resistant nephrotic syndrome (n=14) and steroid-dependent nephrotic syndrome (n=2). The dose of rituximab was established as 375 mg/m2 of body surface area, administered by intravenous infusion once weekly for 1 to 4 weeks, depending on the CD19 lymphocyte count. We evaluated proteinuria and plasma concentration of CD19 lymphocytes at intervals of 1, 3 and 6 months, after which patients received a single repeat dose. RESULTS: Remission, defined as proteinuria less than 150 mg per 24 hours, was observed in 7 of the 16 children. There were no statistically significant differences in leukocyte counts between single and multiple rituximab doses. We also did not observe any clinical or biochemical side effects. CONCLUSIONS: In conclusion, we postulate that alternative rituximab therapy should be taken into consideration in nephrotic patients not responding to standard therapy.