Background Novel urinary biomarkers are useful for the prediction of acute kidney injury (AKI). Most promising are the urine markers NGAL, IL-18, KIM-1, and LFABP. Each of these has shown considerable promise diagnosing AKI earlier than serum creatinine (Scr) using disease controls. We set out to determine reference levels of these markers in a healthy pediatric population. Methods Urine was collected from 368 healthy children and assayed for NGAL, IL-18, KIM-1, and LFABP using commercially available kits or assay materials. Analysis of biomarkers by linear regression and according to age groups (3–<5 years; 5–<10; 10–<15; 15–<18) was performed to determine if biomarker levels differed with age and gender. Results Median values were: NGAL (6.6 ng/ml; IQR 2.8–17), IL-18 (21.6 pg/ml; IQR 13.6–32.9), KIM-1 (410 pg/ml; IQR 226–703), LFABP (3.4 ng/ml; IQR 1.6–6.0). Significant gender differences were found with NGAL and IL-18 and significant age differences were found with all markers. 95th percentile values for each marker varied with age and gender greater than median values. Conclusions This is the largest pediatric reference range study for the urinary measurement of NGAL, IL-18, KIM-1, and LFABP and highlights age and gender differences in these markers. This information is essential for rational interpretation of studies and clinical trials utilizing these emerging AKI biomarkers.

A significant number of severely obese adolescents undergoing bariatric surgery have evidence of early kidney damage. To determine if kidney injury is reversible following bariatric surgery, we investigated renal outcomes in the Teen-Longitudinal Assessment of Bariatric Surgery cohort, a prospective multicenter study of 242 severely obese adolescents undergoing bariatric surgery. Primary outcomes of urine albumin-to-creatinine ratio and cystatin C-based estimated glomerular filtration rate (eGFR) were evaluated preoperatively and up to 3 years following bariatric surgery. At surgery, mean age of participants was 17 years and median body mass index (BMI) was 51 kg/m. In those with decreased kidney function at baseline (eGFR under 90 mL/min/1.73m), mean eGFR significantly improved from 76 to 102 mL/min/1.73m at three-year follow-up. Similarly, participants with albuminuria (albumin-to-creatinine ratio of 30 mg/g and more) at baseline demonstrated significant improvement following surgery: geometric mean of ACR was 74 mg/g at baseline and decreased to 17 mg/g at three years. Those with normal renal function and no albuminuria at baseline remained stable throughout the study period. Among individuals with a BMI of 40 kg/m and more at follow-up, increased BMI was associated with significantly lower eGFR, while no association was observed in those with a BMI under 40 kg/m. In adjusted analysis, eGFR increased by 3.9 mL/min/1.73m for each 10-unit loss of BMI. Early kidney abnormalities improved following bariatric surgery in adolescents with evidence of preoperative kidney disease. Thus, kidney disease should be considered as a selection criteria for bariatric surgery in severely obese adolescents who fail conventional weight management.

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Lower estimated insulin sensitivity was associated with risk for hyperfiltration over time, whereas increased albumin excretion was associated with hyperglycemia in youth-onset T2DM.

Background Hypertension is a common complication and is an important risk factor for graft loss and adverse cardiovascular outcomes in pediatric kidney transplantation. Ambulatory blood pressure monitoring (ABPM) is the preferred method to characterize blood pressure status. Methods and Materials We conducted a retrospective review of a large cohort of children and young adults with kidney transplant to estimate the prevalence of abnormal ambulatory blood pressure (ABP), assess factors associated with abnormal ABP, and examine whether ambulatory hypertension is associated with worse allograft function and left ventricular hypertrophy (LVH). Results Two hundred and twenty-one patients had ABPM and 142 patients had echocardiographic results available for analysis. One third of the patients had masked hypertension, 32% had LVH, and 38% had estimated GFR<60ml/min/1.73m2. African-American race/Hispanic ethnicity and requirement for more than one antihypertensive medication were independently associated with having masked hypertension. In a multivariate analysis, abnormal blood pressure (masked or sustained hypertension combined) was an independent predictor for LVH among patients not receiving antihypertensive treatment (p=0.025). In a separate analysis, the use of antihypertensive medications was independently associated with worse allograft function (p=0.002), although abnormal blood pressure was not a significant predictor. Conclusion In young kidney transplant recipients, elevated ABP is frequently unrecognized and undertreated. The high prevalence of abnormal ABP, including masked hypertension, and its association with LVH supports the case for routine ABPM and cardiac structure evaluation as the standard of care in these patients.

Background Recent meta-analyses support the utility of urinary biomarkers for the diagnosis and prognosis of acute kidney injury. It is critical to establish optimal sample handling conditions for short-term processing and long-term urinary storage, prior to widespread clinical deployment and meaningful use in prospective clinical trials. Study Design Prospective study. Setting & Participants Eighty children (median age, 1.1 [IQR, 0.5–4.2] years) undergoing cardiac surgery with cardiopulmonary bypass at our center. Fifty percent of the patients had acute kidney injury (defined as a 50% or greater increase in serum creatinine from baseline). Predictors We tested the effect on biomarker concentrations of short-term urine storage in ambient, refrigerator, and freezer conditions. We also tested the effects of multiple freeze-thaw cycles, as well as prolonged storage for five years. Outcomes Urine concentrations of neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule 1 (KIM-1), and interleukin 18 (IL-18). Measurements All biomarkers were measured using commercially available kits. Results All three biomarkers were stable in urine stored at 4°C for 24 hours, but showed significant degradation (5.6%-10.1% from baseline) when stored at 25°C. All three biomarkers showed only a small although significant decrease in concentration (0.77%-2.9% from baseline) after three freeze-thaw cycles. Similarly, all three biomarkers displayed only a small but significant decrease in concentration (0.84%-3.2%) after storage for 5 years. Limitations Only the three most widely studied biomarkers were tested. Protease inhibitors were not evaluated. Conclusions Short-term storage of urine samples for measurement of NGAL, KIM-1 and IL-18 may be performed at 4°C for up to 24 hours, but not at room temperature. These urinary biomarkers are stable at −80°C for up to five years of storage. Our results are reassuring for the deployment of these assays as biomarkers in clinical practice, as well as in prospective clinical studies requiring long term urine storage.

The injurious renal effects of obesity are present in childhood, although the natural history and clinical spectrum of obesity-related kidney disease in children are not known. In obese children with early kidney disease, identification of kidney injury, implementation of preventive strategies, and prompt treatment are essential to improving clinical outcomes.

An accurate assessment of kidney function prior to hematopoietic cell transplantation (HCT) can help to properly dose conditioning chemotherapy and follow patients for the development of chronic kidney disease. We cross-sectionally examined 94 children and young adults prior to HCT to compare formal nuclear GFR testing with estimated GFR using creatinine and cystatin C-based equations including the original Schwartz formula and the more recent formulas developed in the Chronic Kidney Disease in Children (CKiD) cohort. The median age of the cohort was 5.9 years (range 0.26–30.5 years). The mean cohort nuclear GFR was 107.4 ± 24.7 ml/min/1.73m2, with 18/94 (19.1%) subjects having abnormal kidney function (GFR <90 ml/min/1.73m2) prior to HCT. The creatinine-based original Schwartz and bedside CKiD formulas showed significant bias (95% confidence interval), overestimating the nuclear GFR by 57.4 (49.0–65.8) and 14.1 (7.1–21.1) ml/min/1.73m2, respectively. Cystatin C formulas had less mean bias and improved accuracy, but also had decreased sensitivity to detect abnormal kidney function prior to HCT. The Full CKiD equation showed the best performance, with a mean bias of −3.6 (−8.4–1.2) ml/min/1.73m2 that was not significantly different from the measured value and 87.7% of estimates within ±30% of the nuclear GFR. While the more recent bedside CKiD formula performed better than the original Schwartz formula, both formulas had poor sensitivity for detecting a low GFR. An abnormal pre-transplant nuclear GFR was not associated with post-HCT acute kidney injury, the need for dialysis, or death in the first 100 days. In conclusion, we observed cystatin C-based equations outperformed creatinine-based equations in estimating GFR in children prior to HCT. However, all formulas had decreased sensitivity to detect impaired GFR. Formal measurement of kidney function should be considered in children and young adults who need an accurate assessment of kidney function prior to HCT.