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Background: When applying Pierce U25 formula for estimating glomerular filtration rate (eGFR), we observed a higher proportion of eGFR < 90 mL/min/1.73 m 2 (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 99 m technetium-diethylene-triamine penta-acetic acid ( 99 Tc 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 m 2 . 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., (© 2023. The Author(s), under exclusive licence to International Pediatric Nephrology Association.)

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., (© 2023. The Author(s), under exclusive licence to International Pediatric Nephrology Association.)

Background: Nighttime blood pressure (BP) and systolic BP variability on ambulatory blood pressure monitoring (ABPM) have been strongly associated with target-organ damage in hypertensive adults. The clinical relevance of these variables in children with hypertension remains under-studied., Methods: The study group included children aged 5-18 years old referred to the outpatient nephrology clinic for an elevated casual BP who underwent an ABPM and echocardiography (ECHO) study and did not have secondary hypertension. The interpretation of ABPM parameters and left ventricular mass index (LVMI) was based on normative references., Results: Seventy-two children fulfilled the inclusion criteria. The association of various potential predictors including age, BMI z-score, casual BP z-score and ABPM parameters (BP z-score, BP load, nocturnal dipping and BP variability- within-subject standard deviation (SD) of BP) with LVMI was analyzed. On adjusted regression analysis, nighttime systolic BP load [standardized regression coefficient (β) 0.23; p < 0.05] and daytime systolic BP variability (β 0.37; p < 0.05) had significant association with LVMI., Conclusions: In children with primary hypertension, nighttime systolic BP load and daytime systolic BP variability had a stronger association with LVMI than casual BP and other ABPM parameters. Future longitudinal studies are needed to establish the causality among these variables.

Background: After parents raised concerns about potential lead (Pb) contamination of calcium carbonate for treatment of hyperphosphatemia in chronic kidney disease (CKD), we measured blood Pb using high-resolution sector field inductively coupled mass spectrometry in a quality-assurance investigation of ten pediatric dialysis patients (nine on hemodialysis) and six patients before dialysis., Methods: We assessed the kidney function as cystatin C estimated glomerular filtration rate (eGFR), blood Pb levels, calcium carbonate dose, and standard laboratory parameters, as well as Pb levels in the dialysis feed water., Results: Mean blood Pb concentration in the 16 pediatric CKD patients was 21.1 ± 15.8 µg/l with a maximum of 58 µg/l, which was significantly higher than that of 467 apparently healthy controls (median 6.35 µg/l, interquartile range 4.47, 8.71) and comparable to that of ten adult peritoneal dialysis (PD) patients. Lead levels correlated with red blood cell distribution width, eGFR, and calcium carbonate dose. Pb in dialysate feed water was always <0.00018 mg/l, which is below the accepted limit for water for dialysis of 0.005 mg/l., Conclusions: We found a high prevalence of elevated Pb levels in pediatric CKD patients that correlated with the calcium carbonate dose and GFR. Lead levels should be monitored in these patients.

The management of steroid-dependent nephrotic syndrome, especially in patients who have failed to respond to cytotoxic drugs, such as cyclophosphamide, remains challenging. Rituximab represents a new (off-label) therapeutic option. In a significant portion of patients, it has a short serum half-life following the recovery of CD20-positive cells. The addition of mycophenolate mofetil (MMF) as a maintenance therapy is also an attractive option, but one which requires testing in a prospective randomized clinical trial with therapeutic drug monitoring and mechanistic ancillary studies.

Beta-trace protein (BTP) is a novel marker of glomerular filtration rate (GFR). To date, no pediatric formula for calculating GFR based on BTP has been developed. We measured GFR, serum creatinine and BTP in 387 children who underwent 474 (99m)Tc-diethylene triamine pentaacetic acid renal scans. A BTP-based formula for estimating GFR was derived using stepwise linear regression analysis. A separate control group of 116 measurements in 99 children was used to validate the novel formula. A formula was also developed for each gender. The novel formula is: [formula: see text]. The Spearman rank correlation coefficient between the BTP-derived GFR estimate and the measured GFR was 0.80 [95% confidence interval (CI) 0.76-0.83], which is substantially better than that derived with the Schwartz formula (r = 0.70, 95% CI 0.65-0.74). The Bland-Altman analysis revealed a mean bias of 1.21% [standard deviation (SD) 28%] in the formula development dataset, which was virtually identical to the 1.03% mean bias (29.5% SD) in the validation group and no different from the Schwartz formula bias. The percentage of values within 10% (33.0 vs. 28.3%) and 30% deviation (76.8 vs. 72.6%) were better for BTP-based formula than for the Schwartz formula. Separate formulas according to gender did not perform better than that for the pediatric population. This BTP-based formula was found to estimate GFR with reasonable precision and provided improved accuracy over the Schwartz GFR formula.

Waiting times for specialist consultation have not been adequately studied, especially in the pediatric population. The aim of this study was to determine the extent to which pediatric nephrology subspecialty clinic referral waiting times are adhered to with regard to previously determined access targets. Referrals to the pediatric nephrology clinics at Children's Hospital, London, Ontario, Canada, received between October 2007 and November 2008 were retrospectively analyzed. Appointment schedule was allotted by a nephrologist based on the patient's presenting complaint, reported in the referral, in accordance with the previously determined access targets. Adherence to access targets was assessed by the actual clinic visit. There were a total of 250 referrals during the timeframe studied. The median waiting time was 73 (range 0-193) days. Overall, 64% (159/250) of patients met their access target. The median time that patients waited over their access target was 6 (range 0-78) days. Of the patients who did not meet their access targets, 31% (28/91) exceeded their target by 20% or more. Office handling was a component for patients with access target <1 week, whereas availability of clinic space was the main reason for nonadherence to access targets.

Incomplete distal renal tubular acidosis (idRTA) has recently been associated with osteoporosis and growth retardation, attributed to the mild persistent metabolic acidosis. We hypothesized a therapeutic benefit from bicarbonate therapy on growth parameters in children with idRTA. In a study group of 40 surgically treated patients with posterior urethral valve (PUV) and normal estimated glomerular filtration rate, we evaluated the change in height standard deviation scores (SDSs) while they were on bicarbonate therapy in the presence of idRTA and complete distal renal tubular acidosis (dRTA). Age- and gender-matched healthy subjects constituted the control group (n = 55). Incomplete dRTA was evaluated by ammonium chloride acidification. The baseline height SDS of -1.94 +/- 0.41 and -5.31 +/- 1.95 in the groups with idRTA and complete dRTA, respectively, were significantly lower than that of the controls. After a follow-up period of 24.7 +/- 8.3 months on sodium bicarbonate therapy, the idRTA patients had a 66% increase in height SDS compared with 26% and 3% increases in the patients with PUV with complete dRTA and without dRTA, respectively. At the end of follow-up, mean height SDS in the group with idRTA no longer remained significantly lower than that of the controls (P = 0.42). We concluded that bicarbonate therapy improves height SDS in idRTA. This issue needs further validation in larger studies.

Diarrhea-positive hemolytic uremic syndrome (HUS) is a common cause of acute renal failure in children. Diarrhea-negative (D-), or atypical HUS, is etiologically distinct. A Medline search identified seven previously reported D- cases of HUS secondary to cobalamin C (cblC) disease presenting in infancy. An infantile presentation is reported to be associated with a high mortality rate (6/7 cases). We describe the results of a 5-year longitudinal follow-up in a child diagnosed with D- HUS secondary to cblC disease in infancy. Mutation analysis in this patient identified homozygosity for the 271 dupA mutation (c.271 dupA) in the cblC MMACHC gene. We briefly review the published experience in cblC-associated HUS to highlight the clinical characteristics of this uncommon, but potentially treatable, condition.

Nephrotic syndrome in children is a clinical manifestation of different histopathological subtypes. There is a paucity of recent large studies dealing with the histopathological spectrum from developing countries. A prospective study was performed from January 1990 to December 2000 at our center, involving 600 children (with age of onset up to 16 years) with idiopathic nephrotic syndrome (INS). The objectives were: (1) to study the histopathological distribution of different subtypes of INS and (2) to compare the clinical and biochemical parameters at the time of diagnosis of minimal change disease (MCD) with non-MCD subtypes. For the purpose of this study we analyzed only those children with INS who underwent biopsies. The study group included 290 children in which adequate biopsy reports were available. There were 213 males and 77 females. Mean age at onset of INS was 7.9+5.1 years. Facial edema was found in 286 (98.6%), microhematuria in 120 (41.3%), gross hematuria in 7 (2.5%), and hypertension in 77(26.8%) patients. All patients of the study group were seronegative for HBsAg and HIV. Focal and segmental glomerulosclerosis (FSGS) was the most common histopathological subtype, occurring in 110 of 290 children (38%). Other subtypes included MCD in 95 children (32%), membranoproliferative glomerulonephritis (MPGN) in 44 children (15%), mesangioproliferative glomerulonephritis in 33 children (11%), membranous glomerulonephritis in 5 children (2%), and diffuse mesangial sclerosis in 3 children (1%). In children under 8 years of age, MCD was the most common entity, whereas FSGS predominated in children with age at onset greater than 8 years. The age at onset of nephrotic syndrome was significantly higher in the non-MCD group than the MCD group. The incidence of hypertension, microhematuria, and gross hematuria was significantly lower in the MCD group. MCD remains the most common histopathological subtype in Indian children with INS and onset under 8 years of age. The incidence of MPGN continues to be high. MCD can be differentiated from non-MCD subtype by younger age at onset, absence of hypertension, and absence of microscopic hematuria.

The current recommendations of kidney biopsy in childhood idiopathic nephrotic syndrome (CINS) were put forward to minimize unnecessary kidney biopsies in underlying minimal change disease (MCD). However, there remains a diversity of opinion about the criteria for biopsying children with idiopathic nephrotic syndrome. This study was conducted to prospectively study their usefulness in avoiding biopsies in MCD and to evaluate further modifications for minimizing biopsies in CINS. Of 400 consecutive CINS patients, 222 patients were subjected to kidney biopsy according to the current recommendations. The histopathology spectrum of these selectively biopsied children revealed focal segmental glomerulosclerosis (FSGS) in 39%, MCD in 34.2%, membranoproliferative glomerulonephritis (MPGN) in 16.2%, mesangioproliferative glomerulonephritis (MesPGN) in 7.6%, membranous nephropathy (MN) in 1.8%, and diffuse mesangial sclerosis (DMS) in 0.9%. We observed that despite the current recommendations and efforts to minimize biopsy, 34% of children had MCD on histopathology. Two or more clinical (hematuria and hypertension) or biochemical (renal insufficiency) parameters were present in all children with MPGN. Low C3 was present only in children with MPGN. All the steroid responders were found to have MCD, FSGS, or MesPGN on biopsy. Cyclophosphamide response correlated better with steroid responsiveness ( P=0.02) than with histo- pathology ( P=0.80) in MCD, FSGS, and MesPGN. Based on these observations, we suggest some modifications in current recommendations for kidney biopsy to minimize biopsying children with MCD. These are (1) biopsies in children (age 1-16 years) should be restricted (a) to a subgroup with two or more clinical and biochemical parameters and (b) in steroid non-responders, (2) the decision to administer cyclophosphamide should be based on steroid response pattern without requiring a prior routine biopsy.

The prognostic significance of distal renal tubular acidosis (DRTA) in the development of overt nephropathy (ON) in children with posterior urethral valves (PUV) is not clear. This condition was studied prospectively in 22 children with posterior urethral valve (PUV), with normal renal function. Prior to surgery, the children with ON had a higher incidence of bilateral reflux (P=0.006), but the difference was not significant for age at surgery (P=0.31), duration of voiding symptoms prior to surgery (P=0.30), presence of DRTA (P=0.35) and bladder abnormalities (P=0.27), with none of these factors being significant on logistic regression analysis. At the end of the follow-up, after surgery, age at surgery (P < or = 0.0001), duration of voiding symptoms prior to surgery (P < or = 0.0003), persistent DRTA (P=0.0001) and persistent bladder dysfunction (P=0.02) after surgery were significantly higher in children with ON. On univariate logistic regression analysis, age at surgery (P=0.009), duration of voiding symptoms prior to surgery (P=0.01), persistent DRTA (P=0.002) and persistent bladder abnormalities (P=0.03) after surgery were significant for ON after surgery, but on stepwise multivariate logistic regression analysis only persistent DRTA (P=0.002) turned out to be significant. We conclude that persistent DRTA after surgery can predict overt nephropathy in children with PUV after surgery.