Limitations of U25 CKiD and CKD-EPI eGFR formulae in patients 2-20 years of age with measured GFR > 60 mL/min/1.73 m2-a cross-sectional study.

BACKGROUND: When applying Pierce U25 formula for estimating glomerular filtration rate (eGFR), we observed a higher proportion of eGFR < 90 mL/min/1.73 m2 (chronic kidney disease (CKD) stage 2). We compared agreement and accuracy of the Pierce U25 (ages 2-25), Pottel (ages 2-100), and CKD-EPI (ages 18-100) formulae to GFR measurements. METHODS: Post hoc analysis of the three eGFRs compared to 367 99m technetium-diethylene-triamine penta-acetic acid (99Tc DTPA) GFR measurements (240 patients) using 3 sampling points and Brockner/Mørtensen correction (body surface area calculation based on ideal weight) on simultaneous serum creatinine and cystatin C measurements. RESULTS: Overall, the U25 formula performed well with a Spearman r of 0.8102 (95% confidence interval 0.7706 to 0.8435, p < 0.0001) while diagnostic accuracy was low in patients with normal mGFR. The U25 formula reclassified 29.5% of patients with normal mGFR as CKD stage 2; whereas the average of the modified Schwartz formula based on serum creatinine and the Filler formula based on cystatin C, only over-diagnosed CKD stage 2 in 8.5%, 24.5% within 10% and 62.7% within 30%. We therefore combined both. The average Schwartz/Filler eGFR had 36.5% of results within 10%, 84.7% within 30%, and normal mGFR accuracy was 26.8%, 63.9% for 10% and 30%, respectively, outperforming the CKD-EPI and Pottel formulae. CONCLUSIONS: The Pierce U25 formula results correlated well with mGFR < 75 mL/min/1.73 m2. Over the entire GFR range, accuracy was better for patients with a higher mGFR, when averaging the combined Schwartz/Filler formulae. More work is needed to prospectively confirm our findings in other centers.

Impact of the 2022 American Heart Association pediatric ambulatory blood pressure monitoring statement on the diagnosis of hypertension.

BACKGROUND: The diagnosis of hypertension and hypertension-induced target organ injury by the 2022 American Heart Association (AHA) ambulatory blood pressure threshold as compared with 2014 AHA and 2016 European Society of Hypertension (ESH) thresholds has not been evaluated. METHODS: In a cross-sectional study (n = 291, aged 5-18 years, at a tertiary care outpatient clinic), we compared 2022 AHA with 2014 AHA and ESH thresholds (revised with 2018 adult ESH thresholds where applicable) to diagnose ambulatory hypertension (AH), and detect ambulatory arterial stiffness index (AASI) and left ventricular target organ injury (LVTOI). RESULTS: The 2022 AHA threshold diagnosed significantly more AH (53%) than the 2014 AHA (42%, p < 0.01) and ESH (36%, p < 0.001) thresholds. The 2022 AHA threshold demonstrated only a moderate agreement with the 2014 AHA (kappa (k) = 0.77) and ESH (k = 0.66) thresholds to diagnose AH. Adjusted logistic regression analysis found that only the 2022 AHA threshold predicted elevated AASI significantly (odds ratio 2.40, 95% CI 1.09, 5.25, p = 0.02; AUC 0.61, p < 0.01). In those with elevated AASI, more participants had AH by the 2022 AHA threshold (72%) than the 2014 AHA (46%, p = 0.02) and ESH (48%, p = 0.03) thresholds. AH defined by the 2022 AHA threshold continued to maintain higher odds, larger AUC, and higher sensitivity to identify LVTOI than the 2014 AHA and ESH thresholds; however, the difference did not reach a statistically significant level. CONCLUSIONS: AH defined by the 2022 AHA threshold diagnoses more children with hypertension and identifies more children with hypertension-induced target organ injury than the 2014 AHA and ESH thresholds. A higher resolution version of the Graphical abstract is available as Supplementary information.

Ambulatory hypertension diagnosed by 24-h mean ambulatory versus day and night ambulatory blood pressure thresholds in children: a cross-sectional study.

BACKGROUND: The agreement between the commonly used ambulatory blood pressure (ABP) thresholds to diagnose ambulatory hypertension in children (patient's 24-h mean ABP classified by 24-h 95th ABP percentile threshold, American Heart Association [AHA] threshold, or patient's day and night mean ABP classified by day-night 95th ABP percentile thresholds) is not known. We evaluated the agreement among 24-h ABP threshold, AHA threshold, and day-night ABP thresholds to diagnose ambulatory hypertension, white coat hypertension (WCH) and masked hypertension (MH). METHODS: In a cross-sectional study design, we analyzed ABP recordings from 450 participants with suspected hypertension from a tertiary care outpatient hypertension clinic. The American Academy of Pediatrics thresholds were used to diagnose office hypertension. RESULTS: The 24-h ABP threshold and day-night ABP thresholds classified 19% ABP (95% confidence interval [CI], 0.15-0.23) differently into ambulatory normotension/hypertension (kappa [κ], 0.58; 95% CI, 0.51-0.66). Ambulatory hypertension diagnosed by 24-h ABP threshold in 27% participants (95% CI, 0.22-0.32) was significantly lower than that by day-night ABP thresholds in 44% participants (95% CI, 0.37-0.50; P < 0.001). The AHA threshold had a stronger agreement with 24-h ABP threshold than with day-night ABP thresholds for classifying ABP into ambulatory normotension/hypertension (k 0.94, 95% CI 0.91-0.98 vs. k 0.59, 95% CI 0.52-0.66). The diagnosis of ambulatory hypertension by the AHA threshold (26%; 95% CI, 0.21-0.31) was closer to that by 24-h ABP threshold (27%, P = 0.73) than by day-night ABP thresholds (44%, P < 0.001). Similar agreement pattern persisted among these ABP thresholds for diagnosing WCH and MH. CONCLUSIONS: The 24-h ABP threshold classifies a lower proportion of ABP as ambulatory hypertension than day-night ABP thresholds. The AHA threshold exhibits a stronger agreement with 24-h ABP than with day-night ABP thresholds for diagnosing ambulatory hypertension, WCH and MH. Our findings are relevant for a consistent interpretation of hypertension by these ABP thresholds in clinical practice.

Diagnosis of hypertension: Ambulatory pediatric American Heart Association/European Society of Hypertension versus blood pressure load thresholds.

The agreement between the traditionally-used ambulatory blood pressure (ABP)-load thresholds in children and recently-recommended pediatric American Heart Association (AHA)/European Society of Hypertension (ESH) ABP thresholds for diagnosing ambulatory hypertension (AH), white coat hypertension (WCH), and masked hypertension (MH) has not been evaluated. In this cross-sectional study on 450 outpatient participants, the authors evaluated the agreement between previously used ABP-load 25%, 30%, 40%, 50% thresholds and the AHA/ESH thresholds for diagnosing AH, WCH, and MH. The American Academy of Pediatrics thresholds were used to diagnose office hypertension. The AHA threshold diagnosed ambulatory normotension/hypertension closest to ABP load 50% in 88% (95% CI 0.79, 0.96) participants (k 0.67, 95% CI 0.59, 0.75) and the ESH threshold diagnosed ambulatory normotension/hypertension closest to ABP load 40% in 86% (95% CI 0.77, 0.94) participants (k 0.66, 95% CI 0.59, 0.74). In contrast, the AHA/ESH thresholds had a relatively weaker agreement with ABP load 25%/30%. Therefore, the diagnosis of AH was closest between the AHA threshold and ABP load 50% (difference 3%, 95% CI -2.6%, 8.6%, p = .29) and between the ESH threshold and ABP load 40% (difference 4%, 95% CI -2.1%, 10.1%, p = .19) than between the AHA/ESH and ABP load 25%/30% thresholds. A similar agreement pattern persisted between the AHA/ESH and various ABP load thresholds for diagnosing WCH and MH. The AHA and ESH thresholds diagnosed AH, WCH, and MH closest to ABP load 40%/50% than ABP load 25%/30%. Future outcome-based studies are needed to guide the optimal use of these ABP thresholds in clinical practice.

Diagnosis of Pediatric Hypertension: European Society of Hypertension-Recommended 24-Hour vs. 24-Hour-Day-Night Ambulatory Blood Pressure Thresholds.

BACKGROUND: The impact of diagnosing pediatric hypertension based on all three-24-hour, day and night ambulatory blood pressure (ABP) thresholds (combined ABP threshold) vs. conventionally used 24-hour ABP threshold is not known. METHODS: In this cross-sectional, retrospective study from a tertiary care outpatient clinic, we evaluated the diagnosis of hypertension based on the 24-hour European Society of Hypertension (ESH) and combined ESH ABP thresholds in untreated children with essential hypertension. The American Academy of Pediatrics (AAP) and Fourth Report thresholds were used to classify office blood pressure (OBP). RESULTS: In 159 children, aged 5-18 years, the 24-hour ESH and combined ESH thresholds classified 82% (95th confidence interval (CI) 0.68, 0.97) ABP similarly with the area under the curve (AUC) of 0.86 (95th CI 0.80, 0.91). However, the AUC of the 2 ABP thresholds was significantly higher in the participants with office hypertension than office normotension, with OBP classified by the AAP (AUC 0.93, 95th CI 0.84, 0.98 vs. 0.80, 95th CI 0.71, 0.88) or Fourth Report (AUC 0.93, 95th CI 0.83, 0.98 vs. 0.81, 95th CI 0.73, 0.88) threshold. With OBP classified by the either OBP threshold, the combined ESH threshold diagnosed significantly more masked hypertension (MH) (difference 15%, 95th CI 4.9, 24.7; P = 0.00); however, the diagnosis of white coat hypertension (WCH) by the 2 ABP thresholds did not differ significantly (difference 4%, 95th CI 1.8, 10; P = 0.16). CONCLUSIONS: In children with essential hypertension, the 24-hour and combined ESH thresholds have a stronger agreement for diagnosing WCH than MH.

Validity and utility of urinary CXCL10/Cr immune monitoring in pediatric kidney transplant recipients.

Individualized posttransplant immunosuppression is hampered by suboptimal monitoring strategies. To validate the utility of urinary CXCL10/Cr immune monitoring in children, we conducted a multicenter prospective observational study in children <21 years with serial and biopsy-associated urine samples (n = 97). Biopsies (n = 240) were categorized as normal (NOR), rejection (>i1t1; REJ), indeterminate (IND), BKV infection, and leukocyturia (LEU). An independent pediatric cohort of 180 urines was used for external validation. Ninety-seven patients aged 11.4 ± 5.5 years showed elevated urinary CXCL10/Cr in REJ (3.1, IQR 1.1, 16.4; P < .001) and BKV nephropathy (median = 5.6, IQR 1.3, 26.9; P < .001) vs. NOR (0.8, IQR 0.4, 1.5). The AUC for REJ vs. NOR was 0.76 (95% CI 0.66-0.86). Low (0.63) and high (4.08) CXCL10/Cr levels defined high sensitivity and specificity thresholds, respectively; validated against an independent sample set (AUC = 0.76, 95% CI 0.66-0.86). Serial urines anticipated REJ up to 4 weeks prior to biopsy and declined within 1 month following treatment. Elevated mean CXCL10/Cr was correlated with first-year eGFR decline (ρ = -0.37, P ≤ .001), particularly when persistently exceeding ≥4.08 (ratio = 0.81; P < .04). Useful thresholds for urinary CXCL10/Cr levels reproducibly define the risk of rejection, immune quiescence, and decline in allograft function for use in real-time clinical monitoring in children.

Current update and future directions on gut microbiome and nephrolithiasis.

The incidence of nephrolithiasis is increasing worldwide. Understanding how gut microbiome influences oxalate homeostasis has the potential to offer new strategies to prevent nephrolithiasis. The literature was reviewed to gather the evidence on the association between gut microbiome, hyperoxaluria and nephrolithiasis, and to identify the therapeutic interventions focused on the gut microbiome that could decrease hyperoxaluria and prevent nephrolithiasis. Gut microbiome is constituted by a plethora of microbiota including Oxalobacter formigenes (Oxf) and lactobacilli. Oxf can degrade dietary oxalate and induce enteral oxalate secretion. Animal studies suggested an association between oral Oxf supplementation and a decrease in hyperoxaluria. However, human studies have showed inconsistent results. Oral supplementation of lactobacilli did not show benefit in decreasing the hyperoxaluria. Antibiotic exposure, by affecting the gut microbiome, has been associated with an increase in nephrolithiasis. In vivo studies suggest fecal transplantation as a potential treatment option for reducing nephrolithiasis, but needs further evaluation in clinical studies. The current evidence suggests an association between gut microbiome and nephrolithiasis. However, the strategies focused on modulating gut microbiome for decreasing hyperoxaluria and preventing nephrolithiasis need further research. Judicious use of antibiotics in those predisposed to nephrolithiasis offers a preventative strategy for decreasing nephrolithiasis.

Comparative Analysis of American Heart Association and European Society of Hypertension Ambulatory Blood Pressure Thresholds for Diagnosing Hypertension in Children.

INTRODUCTION: The influence of using 24-hour ambulatory blood pressure (ABP) thresholds recommended by the American Heart Association (AHA) (24-hour mean ABP >95th percentile and ABP load >25%) or the European Society of Hypertension (ESH) (mean 24-hour ABP >95th percentile or >130/80 mm Hg if mean ABP 95th percentile exceeds 130/80 mm Hg) on the diagnosis of pediatric hypertension has been understudied. METHODS: In a cross-sectional, retrospective study of 159 children from a tertiary care outpatient clinic, we classified office blood pressure (OBP) as normotension or hypertension based on the OBP thresholds recommended by the American Academy of Pediatrics (AAP) and the fourth report on the diagnosis, evaluation, and treatment of high blood pressure in children and adolescents (herein referred to as the fourth report) by the National High Blood Pressure Educational Program Working Group on High Blood Pressure in Children and Adolescents separately. Thereafter, we evaluated the agreement between the ambulatory AHA and ESH thresholds for diagnosing normotension, white-coat hypertension (WCH), masked hypertension (MH), and hypertension based on the patient's ABP and OBP hypertension pattern. RESULTS: With office hypertension as per the AAP thresholds, the AHA and ESH thresholds classified 85% of subjects similarly into normotension, WCH, MH, and hypertension (κ = 0.78; 95% CI, 0.67-0.89). The agreement between the AHA and ESH thresholds did not change when OBP was reclassified by the fourth-report OBP thresholds (κ = 0.77; 95% CI, 0.65-0.88). With OBP classified by either AAP or fourth-report thresholds, the ESH thresholds diagnosed 6% to 7% more children as hypertensive, whereas the AHA threshold classified 11% more children as normotensive. CONCLUSION: The AHA and ESH thresholds have good agreement in classifying OBP. However, the ESH threshold classifies more OBP as hypertensive and the AHA threshold classifies more OBP as normotensive.

Kidney disease and organ transplantation in methylmalonic acidaemia.

OBJECTIVES: MMA is associated with chronic tubulointerstitial nephritis and a progressive decline in GFR. Optimal management of these children is uncertain. Our objectives were to document the pre-, peri-, and post-transplant course of all children with MMA who underwent liver or combined liver-kidney transplant in our centers. DESIGN AND METHODS: Retrospective chart review of all cases of MMA who underwent organ transplantation over the last 10 years. RESULTS: Five children with MMA underwent liver transplant (4/5) and combined liver-kidney transplant (1/5). Three were Mut0 and two had a cobalamin B disorder. Four of five were transplanted between ages 3 and 5 years. Renal dysfunction prior to transplant was seen in 2/5 patients. Post-transplant (one liver transplant and one combined transplant) renal function improved slightly when using creatinine-based GFR formula. We noticed in 2 patients a big discrepancy between creatinine- and cystatin C-based GFR calculations. One patient with no renal disease developed renal failure post-liver transplantation. Serum MMA levels have decreased in all to <300 µmol/L. Four patients remain on low protein diet, carnitine, coenzyme Q, and vitamin E post-transplant. CONCLUSIONS: MMA is a complex metabolic disorder. Renal disease can continue to progress post-liver transplant and close follow-up is warranted. More research is needed to clarify best screening GFR method in patients with MMA. Whether liver transplant alone, continued protein restriction, or the addition of antioxidants post-transplant can halt the progression of renal disease remains unclear.

Nephrotic state substantially enhances apparent mycophenolic acid clearance
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BACKGROUND: ; Several factors may decrease plasma protein binding of mycophenolic acid (MPA), the active compound of mycophenolate mofetil (MMF), and potentially enhance its clearance. It is unclear if MMF dose adjustments are required for the treatment of steroid-resistant nephrotic syndrome (SRNS). Therapeutic drug monitoring of MPA levels is not widely utilized in the treatment of steroid-resistant nephrotic syndrome (SRNS). MATERIALS AND METHODS: In this retrospective cohort study, the authors measured 182 MPA predose trough levels (1 - 45/patient, HPLC/MS/MS) in 10 patients aged 0.9 - 18 years with SRNS treated with MMF. Apparent MPA clearances (CL/F) were calculated from the dose/estimated AUC. Anthropomorphic data, blood parameters, and proteinuria levels were collected from electronic health records. We compared all parameters with apparent MPA clearance, including albumin level, microalbuminuria, proteinuria, triglycerides, cystatin C, and estimated glomerular filtration rate (eGFR), analyzed by nonlinear regression analysis. RESULTS: Median apparent clearance was 22.63 L/h (IQR 17.1, 32.47). Significant correlations were found between MPA Cl/F and serum albumin (r = -0.47), microalbuminuria (+0.54), triglycerides (+0.33), and cholesterol (+0.32). CL/F increased from a minimum of 2.4 L/h for the highest albumin levels to a maximum of 59.9 for albumin levels < 25 g/L. Similarly, the apparent MPA clearance increased significantly with higher triglycerides and lower hematocrit. CONCLUSION: This study confirms a significant increase of the apparent clearance of MPA with low serum albumin, microalbuminuria, proteinuria, high triglycerides, and low hematocrit. The 20-fold increase of the apparent clearance suggests that MMF unresponsiveness in the nephrotic state may be related to MPA underexposure.
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Discordant HIV DNA PCR results among infants diagnosed with HIV infection and initiated on ART: a case series.

This case series reports three infants diagnosed with HIV-1 infection using DNA polymerase chain reaction (PCR) testing. The three children were initiated on antiretroviral therapy (ART) at ten, four and six months of age. Their serological tests at 18 months of age were negative for HIV-1. The first child was discontinued from ART. The other two children were HIV-negative after 18 months, but were continued on ART. Such seroreversion may be either due to viral suppression or false-positive DNA PCR results. There is a need to develop guidelines to address such discordant cases.

Using simplified blood pressure tables to avoid underdiagnosing childhood hypertension.

BACKGROUND: Recent studies have revealed that hypertension remains underdiagnosed in a significant number of children despite their recorded office blood pressure (OBP) exceeding the recommended fourth report OBP thresholds. Simplified OBP thresholds have been proposed to reduce this underdiagnosis of hypertension in children. In clinical practice, OBP screened as elevated according to the fourth report OBP thresholds are referred for ambulatory blood pressure (ABP) monitoring to rule out 'white coat' hypertension. OBJECTIVES: The present study tested the usefulness of simplified OBP thresholds to screen abnormal OBP for ABP monitoring referral. METHODS: A total of 155 subjects were retrospectively analyzed with paired OBP and ABP recordings obtained from an outpatient referral clinic. OBP recordings were classified as abnormal according to the simplified and fourth report OBP thresholds. ABP measurements were classified as abnormal according to the ABP reference tables. RESULTS: Simplified blood pressure (BP) tables correctly identified all OBP classified as abnormal according to fourth report BP thresholds (kappa [κ] 0.72 [95% CI 0.61 to 0.83]) for systolic OBP; κ 0.92 [95% CI 0.86 to 0.99] for diastolic OBP). OBP classified as abnormal by the simplified BP thresholds and by the fourth report BP thresholds performed similarly for correctly identifying abnormal ABP measurements as per ABP references (overlapping 95% CIs of the sensitivity, specificity and predictive values and likelihood ratios). CONCLUSIONS: Simplified BP tables, proposed to reduce the underdiagnosis of hypertension in children, can serve as a useful screening tool to decide a referral for ABP monitoring. Future prospective studies are needed to establish these findings.

HISTORIQUE: De récentes études ont démontré que l'hypertension demeure sous-diagnostiquée chez de nombreux enfants, même si leur tension artérielle prise en cabinet (TAC) dépassait les seuils recommandés pour la quatrième TAC enregistrée. Certains ont proposé des seuils simplifiés de TAC pour réduire ce sous-diagnostic. En pratique clinique, les TAC considérées comme élevées selon les seuils pour la quatrième TAC enregistrée sont dirigées vers une surveillance de la tension artérielle en milieu ambulatoire (TAA), pour écarter le « syndrome de la blouse blanche ¼. OBJECTIFS: La présente étude portait sur l'utilité des seuils simplifiés de TAC pour dépister les TAC anormales en vue de les aiguiller vers la surveillance de la TAA. MÉTHODOLOGIE: Au total, 155 sujets ont fait l'objet d'une analyse rétrospective par rapport à des enregistrements appariés de TAC et de TAA obtenues dans une clinique de consultation ambulatoire. Les enregistrements de TAC étaient classés comme anormaux d'après le seuil simplifié et le seuil de la quatrième TAC enregistrée. Les mesures de TAA étaient classées comme anormales en fonction des tableaux de référence de la TAA. RÉSULTATS: Les tableaux simplifiés de la tension artérielle (TA) ont permis de dépister toutes les TAC classées comme anormales selon les seuils de quatrième TA enregistrée (kappa [κ] 0,72 [95 % IC 0,61 à 0,83] pour la TAC systolique; κ 0,92 [95 % IC 0,86 à 0,99] pour la TAC diastolique). La TAC classée comme anormale selon les seuils simplifiés de la TA et les seuils de la quatrième TAC enregistrée ont permis de déterminer les mesures anormales de TAA conformément aux références de TAA (chevauchement 95 % IC de la sensibilité, de la spécificité et des valeurs prédictives ainsi que des ratios de probabilité). CONCLUSIONS: Les tableaux simplifiés de la TA proposés pour réduire le sous-diagnostic d'hypertension chez les enfants peuvent être utiles pour orienter ou non les patients vers une surveillance de la TAA. D'autres études prospectives s'imposent pour confirmer ces observations.