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INTRODUCTION: Hyperparathyroidism (HPT) can contribute to metabolic bone disease following kidney transplantation. We evaluated post-transplant trends in intact parathyroid hormone (iPTH) and determined predictors of HPT in pediatric kidney transplant (KTx) recipients. METHODS: In this single-center study, retrospective data were collected on 88 children from 2013 to 2019. Data collected included dialysis vintage, biochemical parameters, post-transplant trends in iPTH, 25(OH)Vitamin D levels and estimated glomerular filtration rate (eGFR ml/min/1.73 m2 ). Pre-transplant treatment for HPT was quantified with a Treatment Burden score (TB, score range: 0-100). After log-transforming skewed variables (iPTH and eGFR), multivariable linear regression was performed to determine predictors of log {iPTH} at 6 and 36 months (mo) post-transplant. RESULTS: Median age was 12.8 (range: 1.9-20.5) years, and dialysis vintage was 11.2 (range: 0.0-112.9) months. The majority were of Hispanic and African Ancestry (77.3%). Median post-transplant iPTH was 69.5 (range: 1.8-306.8) pg/ml at 6 mo with a gradual downward trend to 59.0 (range: 28.0-445.0) pg/ml at 36 mo. Significant multivariable predictors of higher log {iPTH} post-transplant included longer dialysis vintage, higher TB, and lower log{eGFR} at 6 mo, and higher TB, lower log{eGFR}, and deceased donor transplant at 36 mo. CONCLUSIONS: Recognition of risk factors for HPT and monitoring iPTH post-transplant may facilitate timely interventions to mitigate cardiovascular and bone disease in pediatric KTx recipients. KEY MESSAGE: Describe serial trends in intact PTH after kidney transplantation. Pre- and post-transplant factors that contribute to persistence or re-occurrence of hyperparathyroidism after kidney transplantation in children include longer dialysis vintage, high pre-transplant treatment burden and decreased post-transplant GFR. Recognition of these factors, and monitoring intact PTH after kidney transplantation, could facilitate timely interventions to mitigate cardiovascular and bone disease in children.
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Doenças Ósseas Metabólicas , Hiperparatireoidismo , Transplante de Rim , Criança , Humanos , Hispânico ou Latino , Hiperparatireoidismo/etiologia , Transplante de Rim/efeitos adversos , Hormônio Paratireóideo , Estudos Retrospectivos , Lactente , Pré-Escolar , Adolescente , Adulto Jovem , População NegraRESUMO
BACKGROUND: Mycophenolate Mofetil (MMF) is an effective immunosuppressant used in kidney transplant recipients to prevent acute rejection. Complications such as diarrhea, leukopenia, and infections may necessitate the reduction or discontinuation of MMF. The objective of the study was to investigate the prevalence, timing, and reasons for MMF discontinuation and its association with outcomes in pediatric kidney transplant recipients. METHODS: Seven Pediatric Nephrology Research Consortium (PNRC) centers participated in a retrospective analysis of kidney transplant recipients <21 years of age. Characteristics and outcomes of patients in whom MMF was discontinued were compared to those who continued taking MMF throughout the first 2 years post-transplant. RESULTS: The study population included 288 participants (mean age 11.2 years) from 7 North American transplant centers. MMF was discontinued in 93/288 (32%) of participants. Common reasons for discontinuation included infections (35%), diarrhea (32%), leukopenia (15%), and others (18%). Increased cumulative alloimmunity (55% vs. 42%, p = .02), increased number of hospitalizations (82% vs. 67%, p = .01), and viral replications (79% vs. 47%, p < .0001) were observed in the MMF discontinuation group compared to the continuation group. Greater eGFR decline also occurred in the MMF discontinuation group over 2 years of follow-up (-7 vs. -1 mL/min/1.73 m2 , p = .05). CONCLUSIONS: Almost a third of pediatric kidney transplant recipients who begin MMF for maintenance immunosuppression have it discontinued within the first 2 years post-transplant, and this subset of patients is more likely to experience adverse outcomes. New strategies are needed to manage MMF therapy and improve post-transplant outcomes.
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Transplante de Rim , Leucopenia , Nefrologia , Humanos , Criança , Ácido Micofenólico , Estudos Retrospectivos , Prevalência , Rejeição de Enxerto/prevenção & controle , Rejeição de Enxerto/epidemiologia , Imunossupressores/efeitos adversos , Diarreia/epidemiologia , Diarreia/etiologia , Leucopenia/etiologia , Leucopenia/induzido quimicamenteRESUMO
BACKGROUND: Primary FSGS manifests with nephrotic syndrome and may recur following KT. Failure to respond to conventional therapy after recurrence results in poor outcomes. Evaluation of podocyte B7-1 expression and treatment with abatacept (a B7-1 antagonist) has shown promise but remains controversial. METHODS: From 2012 to 2020, twelve patients developed post-KT FSGS with nephrotic range proteinuria, failed conventional therapy, and were treated with abatacept. Nine/twelve (< 21 years old) experienced recurrent FSGS; three adults developed de novo FSGS, occurring from immediately, up to 8 years after KT. KT biopsies were stained for B7-1. RESULTS: Nine KTRs (75%) responded to abatacept. Seven of nine KTRs were B7-1 positive and responded with improvement/resolution of proteinuria. Two patients with rFSGS without biopsies resolved proteinuria after abatacept. Pre-treatment UPCR was 27.0 ± 20.4 (median 13, range 8-56); follow-up UPCR was 0.8 ± 1.3 (median 0.2, range 0.07-3.9, p < 0.004). Two patients who were B7-1 negative on multiple KT biopsies did not respond to abatacept and lost graft function. One patient developed proteinuria while receiving belatacept, stained B7-1 positive, but did not respond to abatacept. CONCLUSIONS: Podocyte B7-1 staining in biopsies of KTRs with post-transplant FSGS identifies a subset of patients who may benefit from abatacept. A higher resolution version of the Graphical abstract is available as Supplementary information.
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Glomerulosclerose Segmentar e Focal , Podócitos , Adulto , Criança , Humanos , Adulto Jovem , Glomerulosclerose Segmentar e Focal/tratamento farmacológico , Glomerulosclerose Segmentar e Focal/patologia , Abatacepte/uso terapêutico , Proteinúria/tratamento farmacológico , Proteinúria/etiologia , Podócitos/patologia , Coloração e Rotulagem , RecidivaRESUMO
Renal imaging is widely used in the assessment of surrogate markers of nephron mass correlated to renal function. Autopsy studies have tested the validity of various imaging modalities in accurately estimating "true" nephron mass. However, in vivo assessment of nephron mass has been largely limited to kidney volume determination by ultrasonography (US) in pediatric populations. Practical limitations and risks create challenges in incorporating more precise 3D volumetric imaging, like magnetic resonance imaging (MRI), and computed tomography (CT) technologies, compared to US for routine kidney volume assessment in children. Additionally, accounting for structural anomalies such as hydronephrosis when estimating renal parenchymal area in congenital anomalies of the kidney and urinary tract (CAKUT) is important, as it correlates with chronic kidney disease (CKD) progression. 3D imaging using CT and MRI has been shown to be superior to US, which has traditionally relied on 2D measurements to estimate kidney volume using the ellipsoid calculation. Recent innovations using 3D and contrast-enhanced US (CEUS) provide improved accuracy with low risk. Indexing kidney volume to body surface area in children is an important standard that may allow early detection of CKD progression in high-risk populations. This review highlights current understanding of various imaging modalities in assessing nephron mass, discusses applications and limitations, and describes recent advances in the field of imaging and kidney disease. Although renal imaging has been a long-standing, essential tool in assessing kidney disease, innovation and new applications of established technologies provide important tools in the study and management of kidney disease in children.
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Hidronefrose , Néfrons , Criança , Humanos , Rim/diagnóstico por imagem , Imageamento por Ressonância Magnética , Néfrons/diagnóstico por imagem , Insuficiência Renal Crônica , UltrassonografiaRESUMO
BACKGROUND AND OBJECTIVES: Arteriovenous fistulae (AVF) and grafts (AVG) are preferred permanent vascular access (PVA) for chronic hemodialysis (HD) patients. Our objective was to examine the change in markers of HD efficacy after successful establishment of a PVA among children who started HD with a tunneled cuffed catheter (TCC). MATERIALS AND METHODS: Retrospective chart reviews were completed on patients from 20 pediatric dialysis centers. All patients used TCC prior to AVF/AVG, and each patient acted as his/her own control. Data on markers of HD efficacy (single-pool Kt/V, urea reduction ratio (URR), serum albumin and hematocrit (Hct)) were collected at the creation of AVF/AVG and for 2 years thereafter. Statistical methods included hypothesis testing and statistical modeling after adjusting for relevant demographic variables. RESULTS: First PVA was created in 98 individual children: 87 (89%) were AVF and 11 (11%) were AVG. The mean TCC vintage prior to AVF/AVG was 10.4 ± 17.3 months. At 1-year follow-up, Kt/V improved by 0.15 ± 0.06 (p = 0.02) and URR improved by 4.54 ± 1.17% (p < 0.0001). Furthermore, PVA was associated with improved serum albumin by 0.31 ± 0.07 g/dL (p < 0.0001) and Hct by 2.80 ± 0.65% (p < 0.0001) at 1 year. These HD efficacy markers remained statistically significant at 2nd-year follow-up. These observations were further supported by the adjusted models. Conversion to AVF was associated with statistically significant improvement in all four markers of HD efficacy at 1-year follow-up. This trend was not demonstrated for subjects who were converted to AVG. CONCLUSION: Switching to PVA was associated with improved markers of HD efficacy, single-pool Kt/V, URR, serum albumin, and Hct. This improvement was mostly demonstrated at 1 year and maintained for the 2nd year. The potential differential impact of the type of PVA on the trajectory of markers of HD efficacy should be further investigated.
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Derivação Arteriovenosa Cirúrgica , Falência Renal Crônica , Nefrologia , Derivação Arteriovenosa Cirúrgica/efeitos adversos , Criança , Feminino , Humanos , Falência Renal Crônica/diagnóstico , Falência Renal Crônica/terapia , Masculino , Diálise Renal , Estudos RetrospectivosRESUMO
Congenital lower urinary tract obstruction is associated with oligohydramnios and significant perinatal mortality and long-term chronic kidney disease. The counseling of families facing this diagnosis, especially when prenatal intervention is proposed, is fraught with ambiguity. This review aims to equip the provider with the current evidence behind the conventional and novel biomarkers predictive of chronic kidney disease. The relevant clinical predictors are categorized by when they are identified, antenatally or postnatally, and as either anatomic or chemical. They are considered for their prognostic value and the challenges in obtaining them, specifically the risk to the fetus in the case of prenatal biomarkers. Serum creatinine in infancy is the traditional chemical biomarker of kidney function and continues to be a consistent predictor of future serum creatinine. ß-2 microglobulin may provide earlier information regarding fetal glomerular and tubular function and is also predictive of long-term serum creatinine. Renal parenchymal area is an anatomic surrogate of nephron mass that is used in both prenatal and postnatal settings. Understanding the anatomic and chemical biomarkers is essential for future refinement of the staging algorithm used to distinguish which patients may benefit from early in utero intervention.
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Obstrução do Colo da Bexiga Urinária/patologia , Biomarcadores/sangue , Biomarcadores/urina , Creatinina/sangue , Fetoscopia , Humanos , Insuficiência Renal Crônica/etiologia , Ultrassonografia Pré-Natal , Obstrução do Colo da Bexiga Urinária/diagnóstico por imagem , Obstrução do Colo da Bexiga Urinária/embriologia , Sistema Urinário/anormalidadesRESUMO
BACKGROUND: Permanent vascular access (PVA) is preferred for long-term hemodialysis. Arteriovenous fistulae (AVF) have the best patency and the lowest complication rates compared to arteriovenous grafts (AVG) and tunneled cuffed catheters (TCC). However, AVF need time to mature. This study aimed to investigate predictors of time to first cannulation for AVF in pediatric hemodialysis patients. METHODS: Data on first AVF and AVG of patients at 20 pediatric dialysis centers were collected retrospectively, including demographics, clinical information, dialysis markers, and surgical data. Statistical modeling was used to investigate predictors of outcome. RESULTS: First PVA was created in 117 children: 103 (88%) AVF and 14 (12%) AVG. Mean age at AVF creation was 15.0 ± 3.3 years. AVF successfully matured in 89 children (86.4%), and mean time to first cannulation was 3.6 ± 2.5 months. In a multivariable regression model, study center, age, duration of non-permanent vascular access (NPVA), and Kt/V at AVF creation predicted time to first cannulation, with study center as the strongest predictor (p < 0.01). Time to first cannulation decreased with increasing age (p = 0.03) and with increasing Kt/V (p = 0.01), and increased with duration of NPVA (p = 0.03). Secondary failure occurred in 10 AVF (11.8%). Time to first cannulation did not predict secondary failure (p = 0.29), but longer time to first cannulation tended towards longer secondary patency (p = 0.06). CONCLUSIONS: Study center is the strongest predictor of time to first cannulation for AVF and deserves further investigation. Time to first cannulation is significantly shorter in older children, with more efficient dialysis treatments, and increases with longer NPVA duration.
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Derivação Arteriovenosa Cirúrgica , Terapia de Substituição Renal Contínua , Falência Renal Crônica/terapia , Tempo para o Tratamento , Adolescente , Criança , Feminino , Humanos , Masculino , Estudos RetrospectivosRESUMO
BACKGROUND: Studies in the use of the calcimimetic, cinacalcet, in pediatric chronic kidney disease (CKD) are few and limited to older children with secondary hyperparathyroidism (sHPT), a major morbid complication contributing to poor growth, bone deformities, and cardiovascular disease. Our objectives were to determine a safe and effective dosing regimen of cinacalcet in the treatment of infants and young children with sHPT that was refractory to standard care and to examine their growth during treatment. METHODS: Ten young pediatric patients with advanced CKD were studied retrospectively during 11 courses of treatment with cinacalcet. All had severe sHPT with intact parathyroid hormone (iPTH) levels ≥ 500 pg/ml and were refractory to standard therapy with phosphate binders and active vitamin D analogs at high doses for > 30 days. The cinacalcet dose was advanced by 50% every 2-4 weeks to achieve a decline in the iPTH to a goal of 150-300 pg/ml. Linear growth was assessed at 6-month intervals by change in z-scores (â³SDS) for length before and during cinacalcet therapy. RESULTS: Median age at initiation of cinacalcet was 18 months (IQR 6, 36) with an average starting dose of 0.7 ± 0.2 mg/kg/day. Median effective dose required to reach iPTH goal of 150-300 pg/ml was 2.8 mg/kg/day (IQR 2.0, 3.1), and time to goal was 112 days (IQR 56, 259) with a median overall decline in iPTH of 82% from baseline by 6 months (p < 0.0001). No subject experienced a clinical adverse event, although 4 had biochemical asymptomatic hypocalcemia. Linear growth improved significantly during cinacalcet therapy (â³SDS - 0.62 ± 1.2 versus + 0.91 ± 1.4; p < 0.005). By multiple regression analysis, the primary determinants of growth were concurrent treatment with growth hormone and age < 2 years (R2 = 89.6%; p < 0.001). A shorter treatment time required to achieve iPTH goals also was associated with improved growth (r = - 0.75; p < 0.01). CONCLUSIONS: Cinacalcet may be used effectively and safely in infants and small children with refractory sHPT in advanced CKD using a cautious dosing regimen. Cinacalcet successfully brings iPTH to target level and supports growth when other treatments have been ineffective.
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Calcimiméticos/administração & dosagem , Cinacalcete/administração & dosagem , Hiperparatireoidismo Secundário/tratamento farmacológico , Falência Renal Crônica/complicações , Calcimiméticos/efeitos adversos , Criança , Pré-Escolar , Cinacalcete/efeitos adversos , Relação Dose-Resposta a Droga , Esquema de Medicação , Resistência a Medicamentos , Feminino , Humanos , Hiperparatireoidismo Secundário/diagnóstico , Hiperparatireoidismo Secundário/etiologia , Lactente , Masculino , Hormônio Paratireóideo/sangue , Estudos Retrospectivos , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
BACKGROUND: Nephrotic syndrome (NS) results in hypercoagulability and increased risk of infection. Furthermore, infection increases the risk of venous thromboembolism (VTE). Our objective was to determine the prevalence of infection, VTE, and the associated outcomes among a cohort of hospitalized children with NS. METHODS: All children with NS admitted to 17 pediatric hospitals across North America from 2010 to 2012 were included. Prevalence of infection and VTE was determined. Wilcoxon rank-sum and logistic regression were performed. RESULTS: Seven-hundred thirty hospitalizations occurred among 370 children with NS. One-hundred forty-eight children (40%) had ≥ 1 infection (211 episodes) and 11 (3%) had VTE. Those with VTE had infection more frequently (p = 0.046) and were younger at NS diagnosis (3.0 vs. 4.0 years; p = 0.008). The most common infectious pathogen identified was Streptococcus pneumoniae. The median hospital length of stay for those with infection [10 vs 5 days (p < 0.0001)] or VTE [22 vs 6 days (p < 0.0001)] was longer than those without either complication. Of those with infection, 13% had an intensive care unit (ICU) stay compared with 3.3% of those without infection. Median ICU stay was 4 days in those with VTE compared to 0 days in those without (p < 0.001). By logistic regression, only the number of ICU days was associated with VTE (OR 1.074, 95% CI 1.013-1.138). CONCLUSIONS: Hospitalized children with NS have high rates of infection. Presence of VTE was associated with infection. Both were associated with longer hospitalizations and ICU stays.
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Síndrome Nefrótica/complicações , Infecções Pneumocócicas/epidemiologia , Streptococcus pneumoniae/isolamento & purificação , Tromboembolia Venosa/epidemiologia , Criança , Pré-Escolar , Feminino , Humanos , Unidades de Terapia Intensiva/estatística & dados numéricos , Tempo de Internação/estatística & dados numéricos , Modelos Logísticos , Masculino , América do Norte/epidemiologia , Infecções Pneumocócicas/etiologia , Prevalência , Estudos Retrospectivos , Fatores de Risco , Tromboembolia Venosa/etiologiaRESUMO
The original version of this article unfortunately contained a mistake. The name of Vimal Chadha was presented incorrectly. The corrected author list is given above.
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BACKGROUND: Hemodialysis (HD) guidelines recommend permanent vascular access (PVA) in children unlikely to receive kidney transplant within 1 year of starting HD. We aimed to determine predictors of primary and secondary patency of PVA in pediatric HD patients. METHODS: Retrospective chart reviews were performed for first PVAs in 20 participating centers. Variables collected included patient demographics, complications, interventions, and final outcome. RESULTS: There were 103 arterio-venous fistulae (AVF) and 14 AV grafts (AVG). AVF demonstrated superior primary (p = 0.0391) and secondary patency (p = 0.0227) compared to AVG. Primary failure occurred in 16 PVA (13.6%) and secondary failure in 14 PVA (12.2%). AVF were more likely to have primary failure (odds ratio (OR) = 2.10) and AVG had more secondary failure (OR = 3.33). No demographic, clinical, or laboratory variable predicted primary failure of PVA. Anatomical location of PVA was predictive of secondary failure, with radial having the lowest risk compared to brachial (OR = 12.425) or femoral PVA (OR = 118.618). Intervention-free survival was predictive of secondary patency for all PVA (p = 0.0252) and directly correlated with overall survival of AVF (p = 0.0197) but not AVG. Study center demonstrated statistically significant effect only on intervention-free AVF survival (p = 0.0082), but not number of complications or interventions, or outcomes. CONCLUSIONS: In this multi-center pediatric HD cohort, AVF demonstrated primary and secondary patency advantages over AVG. Radial PVA was least likely to develop secondary failure. Intervention-free survival was the only predictor of secondary patency for AVF and directly correlated with overall access survival. The study center effect on intervention-free survival of AVF deserves further investigation.
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Derivação Arteriovenosa Cirúrgica/efeitos adversos , Falência Renal Crônica/terapia , Diálise Renal/métodos , Enxerto Vascular/efeitos adversos , Grau de Desobstrução Vascular , Adolescente , Canadá , Criança , Feminino , Humanos , Masculino , Diálise Renal/efeitos adversos , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Falha de Tratamento , Estados UnidosRESUMO
BACKGROUND: Urinary biomarkers may be indicators of acute kidney injury (AKI), although little is known of their developmental characteristics in healthy neonates across a full range of gestational age (GA). The purpose of this study was to examine patterns of urinary biomarkers across GA groups from birth to 3 months of age. METHODS: Fifty-two infants ranging from 24 to 41 weeks' GA had urine assayed from birth through 3 months of age for 7 biomarkers including albumin (ALB), beta-2-microglobulin (B2M), cystatin-C (CysC), epidermal growth factor (EGF), neutrophil-gelatinase-associated lipocalin (NGAL), osteopontin (OPN), and uromodulin (UMOD). RESULTS: Of the seven urinary biomarkers, EGF and UMOD increased while others decreased with advancing GA. By 3 months of age, EGF and UMOD had increased in preterm infants to levels similar to those of term infants. UMOD/ml and EGF/ml appeared to be predominantly developmental biomarkers distinguishing estimated glomerular filtration rate (GFR) <30 ml/min/1.73 m(2) with receiver operator characteristic area under the curve (ROC-AUC) of 0.82; p = 0.002. When factored by urine creatinine CysC/cr + ALB/cr were the most significant functional markers with AUC = 0.79; p = 0.004; sensitivity 96 %; specificity 58 %. CONCLUSIONS: Among healthy neonates, urinary biomarkers vary with GA. These data support the use of urinary biomarkers in the assessment of normal kidney development in the absence of injury.
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Injúria Renal Aguda/urina , Biomarcadores/urina , Lactente Extremamente Prematuro/urina , Recém-Nascido/urina , Recém-Nascido Prematuro/urina , Idade Gestacional , Humanos , Estudos Longitudinais , Valores de ReferênciaRESUMO
OBJECTIVES: To distinguish between cystatin C (CysC) and creatinine (Cr) as markers of estimated glomerular filtration rate (eGFR) in preterm infants and to correlate eGFR with total kidney volume (TKV) as a surrogate of nephron mass. STUDY DESIGN: Sixty preterm (<37 weeks' gestational age [GA]) and 40 term infants were enrolled at birth. Serum Cr and CysC levels were assessed during the first week of life. Renal ultrasounds were performed to assess kidney dimensions with calculation of the TKV as a surrogate of nephron mass. Six equations derived from reference inulin, iohexol, and iothalamate clearance studies were used to calculate eGFR. Multiple regression analysis was applied to assess the relative impact of neonatal measures on eGFR, including TKV, GA, and mean arterial pressure (MAP). RESULTS: Renal lengths correlated with GA and were within the reference values for intrauterine measurements. Estimation equations for glomerular filtration rate (GFR) based on Cr, CysC, and combined CysC + Cr demonstrated that Cr-based equations consistently underestimated GFR, whereas CysC and combined equations were more consistent with referenced inulin clearance studies. Term infants demonstrated significantly better eGFR than preterm infants. TKV, GA, and MAP correlated positively with eGFR, although only MAP and GA remained significant when adjusted for other covariates. CONCLUSIONS: Primary determinants of eGFR in preterm infants are GA and MAP. The CysC level is a superior biomarker to serum Cr in the assessment of GFR in premature infants.
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Creatinina/sangue , Cistatina C/sangue , Taxa de Filtração Glomerular , Recém-Nascido Prematuro/fisiologia , Rim/anatomia & histologia , Injúria Renal Aguda/sangue , Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/fisiopatologia , Biomarcadores/sangue , Estudos Transversais , Feminino , Idade Gestacional , Humanos , Recém-Nascido , Recém-Nascido Prematuro/sangue , Rim/diagnóstico por imagem , Rim/fisiopatologia , Modelos Lineares , Masculino , Análise Multivariada , Tamanho do Órgão , Valores de Referência , UltrassonografiaRESUMO
BACKGROUND: The mechanisms responsible for the hyperphosphatemia in patients with sickle cell disease (SCD) and preserved glomerular filtration rate (GFR) are not fully understood. The role of fibroblast growth factor 23 (FGF23), a phosphaturic hormone has not been investigated in SCD. Hence, we evaluated parameters of renal tubular phosphorus handling and their relation to prevailing FGF23 levels in a cohort of young SCD patients. METHODS: Renal tubular phosphate handling and circulating levels of various analytes including FGF23 and parathyroid hormone (PTH) were measured in 24 children with SCD and normal estimated GFR in a cross sectional study. Correlation and regression analysis were employed to derive relationships between serum phosphorus and several variables. RESULTS: Most children showed elevated age- adjusted serum phosphorus (5.1 ± 0.7 mg/dl) levels. Tubular re-absorption of phosphorus(TRP) (96.3 ± 2.1%) and tubular maximum re-absorption of phosphorus per unit volume of GFR (TMP/GFR) (4.9 ± 0.6 mg/dl) were both elevated. Plasma intact FGF23 concentrations were elevated (81 ± 38 pg/ml) while the average PTH values were normal in most patients (50 ± 27 pg/ml). Univariate analysis showed significant correlations of serum phosphorus with TMP/GFR, alkaline phosphatase, age, lactate dehydrogenase (LDH), and log intact FGF23. TMP/GFR correlated with log intact FGF23 (r = 0.5, P< or = 0.01) but not with PTH. Multiple regression analysis yielded an independent relationship of serum phosphorus with TMP/GFR. CONCLUSION: The elevated serum phosphorus concentrations with simultaneously increased TMP/GFR and elevated FGF23 levels collectively suggest that patients with SCD display proximal tubular resistance to the action of FGF23 before any decline in GFR.
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Anemia Falciforme/complicações , Fatores de Crescimento de Fibroblastos/sangue , Hiperfosfatemia/patologia , Túbulos Renais/patologia , Fosfatos/sangue , Adolescente , Anemia Falciforme/fisiopatologia , Cálcio/metabolismo , Estudos de Coortes , Estudos Transversais , Feminino , Fator de Crescimento de Fibroblastos 23 , Seguimentos , Taxa de Filtração Glomerular , Humanos , Hiperfosfatemia/sangue , Hiperfosfatemia/etiologia , Túbulos Renais/metabolismo , Masculino , Hormônio Paratireóideo/sangue , PrognósticoRESUMO
Study-specific data quality testing is an essential part of minimizing analytic errors, particularly for studies making secondary use of clinical data. We applied a systematic and reproducible approach for study-specific data quality testing to the analysis plan for PRESERVE, a 15-site, EHR-based observational study of chronic kidney disease in children. This approach integrated widely adopted data quality concepts with healthcare-specific evaluation methods. We implemented two rounds of data quality assessment. The first produced high-level evaluation using aggregate results from a distributed query, focused on cohort identification and main analytic requirements. The second focused on extended testing of row-level data centralized for analysis. We systematized reporting and cataloguing of data quality issues, providing institutional teams with prioritized issues for resolution. We tracked improvements and documented anomalous data for consideration during analyses. The checks we developed identified 115 and 157 data quality issues in the two rounds, involving completeness, data model conformance, cross-variable concordance, consistency, and plausibility, extending traditional data quality approaches to address more complex stratification and temporal patterns. Resolution efforts focused on higher priority issues, given finite study resources. In many cases, institutional teams were able to correct data extraction errors or obtain additional data, avoiding exclusion of 2 institutions entirely and resolving 123 other gaps. Other results identified complexities in measures of kidney function, bearing on the study's outcome definition. Where limitations such as these are intrinsic to clinical data, the study team must account for them in conducting analyses. This study rigorously evaluated fitness of data for intended use. The framework is reusable and built on a strong theoretical underpinning. Significant data quality issues that would have otherwise delayed analyses or made data unusable were addressed. This study highlights the need for teams combining subject-matter and informatics expertise to address data quality when working with real world data.
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BACKGROUND: Exertional heat stroke (EHS) results in a constellation of systemic inflammatory responses resulting in multiorgan failure and an extremely high mortality. CASE DIAGNOSIS AND TREATMENTS: We present the case of an 11-year-old obese male who suffered EHS with rhabdomyolysis and concurrent renal, pulmonary, and hepatic failure. Conventional therapies including continuous veno-venous hemodiafiltration (CVVHDF) were ineffective in preventing ongoing deterioration in clinical status. Liver biopsy was reported as "extensive hepatocyte ballooning" and liver-kidney transplantation was tentatively planned. CONCLUSIONS: The addition of therapeutic plasma exchange using the Prismaflex® system (Gambro, Lakewood, CO, USA) resulted in a reversal of the inflammatory process and recovery from multiorgan failure. Liver biopsy was not a reliable indicator of irreversible hepatic injury.
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Golpe de Calor/terapia , Insuficiência de Múltiplos Órgãos/terapia , Troca Plasmática , Criança , Hemodiafiltração , Humanos , MasculinoRESUMO
Rationale & Objective: PRESERVE seeks to provide new knowledge to inform shared decision-making regarding blood pressure (BP) management for pediatric chronic kidney disease (CKD). PRESERVE will compare the effectiveness of alternative strategies for monitoring and treating hypertension on preserving kidney function; expand the National Patient-Centered Clinical Research Network (PCORnet) common data model by adding pediatric- and kidney-specific variables and linking electronic health record data to other kidney disease databases; and assess the lived experiences of patients related to BP management. Study Design: Multicenter retrospective cohort study (clinical outcomes) and cross-sectional study (patient-reported outcomes [PROs]). Setting & Participants: PRESERVE will include approximately 20,000 children between January 2009-December 2022 with mild-moderate CKD from 15 health care institutions that participate in 6 PCORnet Clinical Research Networks (PEDSnet, STAR, GPC, PaTH, CAPRiCORN, and OneFlorida+). The inclusion criteria were ≥1 nephrologist visit and ≥2 estimated glomerular filtration rate (eGFR) values in the range of 30 to <90 mL/min/1.73 m2 separated by ≥90 days without an intervening value ≥90 mL/min/1.73 m2 and no prior dialysis or kidney transplant. Exposures: BP measurements (clinic-based and 24-hour ambulatory BP); urine protein; and antihypertensive treatment by therapeutic class. Outcomes: The primary outcome is a composite event of a 50% reduction in eGFR, eGFR of <15 mL/min/1.73 m2, long-term dialysis or kidney transplant. Secondary outcomes include change in eGFR, adverse events, and PROs. Analytical Approach: Longitudinal models for dichotomous (proportional hazards or accelerated failure time) and continuous (generalized linear mixed models) clinical outcomes; multivariable linear regression for PROs. We will evaluate heterogeneity of treatment effect by CKD etiology and degree of proteinuria and will examine variation in hypertension management and outcomes based on socio-demographics. Limitations: Causal inference limited by observational analyses. Conclusions: PRESERVE will leverage the PCORnet infrastructure to conduct large-scale observational studies that address BP management knowledge gaps for pediatric CKD, focusing on outcomes that are meaningful to patients. Plain-Language Summary: Hypertension is a major modifiable contributor to loss of kidney function in chronic kidney disease (CKD). The purpose of PRESERVE is to provide evidence to inform shared decision-making regarding blood pressure management for children with CKD. PRESERVE is a consortium of 16 health care institutions in PCORnet, the National Patient-Centered Clinical Research Network, and includes electronic health record data for >19,000 children with CKD. PRESERVE will (1) expand the PCORnet infrastructure for research in pediatric CKD by adding kidney-specific variables and linking electronic health record data to other kidney disease databases; (2) compare the effectiveness of alternative strategies for monitoring and treating hypertension on preserving kidney function; and (3) assess the lived experiences of patients and caregivers related to blood pressure management.
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OBJECTIVE: Pica is the compulsive consumption of non-nutritive substances, and this disorder may occur more frequently in dialysis patients. The purpose of our study was to determine the prevalence of pica and the associated demographic and metabolic characteristics. DESIGN: Retrospective, cross-sectional analysis. SETTING: Hospital-based, outpatient, pediatric hemodialysis unit. SUBJECTS: Eighty-seven pediatric patients on chronic dialysis therapy were interviewed. Sixty-seven patients were receiving hemodialysis, whereas the remaining 20 were maintained on peritoneal dialysis. The predominantly nonwhite (93%) patient population had a mean age of 17.2 ± 7.2 years. Dialysis efficiency, estimated by urea clearance per patient volume (Kt/V), averaged 1.5 ± 0.5. INTERVENTION: Standard patient interview and documentation of laboratory and dialytic parameters. MAIN OUTCOME MEASURE: Prevalence of pica and associated comorbid conditions. RESULTS: The survey indicated that 46% of patients experienced pica, further divided into simple "ice" pica (34.5%) versus "hard" pica (12.6%). Hard pica included the consumption of chalk, starch, sugar, soap, sand, clay, Ajax cleanser, sponge, wood, and potting soil. Patients on hemodialysis were 8.3 times more likely to have hard pica compared with those on peritoneal dialysis. Greater than 5 years on dialysis was associated with a 3.2 odds ratio of having pica (P = .02). Anemia was the most significant morbid association, occurring at an odds ratio of 4.4 (P = .001) for all pica and 10.6 (P = .004) for hard pica. CONCLUSION: Pica, therefore, is prevalent and potentially harmful, requiring further attention in the nutritional management of pediatric dialysis patients.
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Diálise Peritoneal/efeitos adversos , Pica/epidemiologia , Diálise Renal/efeitos adversos , Adolescente , Anemia/epidemiologia , Criança , Doença Crônica , Estudos Transversais , Feminino , Humanos , Masculino , Avaliação Nutricional , Razão de Chances , Prevalência , Estudos Retrospectivos , Ureia/metabolismo , Adulto JovemRESUMO
Background: Severe congenital lower urinary tract obstruction (cLUTO) is associated with poor postnatal outcomes, including chronic and end stage kidney disease, and high mortality. Studies of the impact of fetal intervention through vesicoamniotic shunting are marred by a device malfunction rate of up to 60%. In this study, we delineate the postnatal course and infant kidney function following definitive urinary diversion in utero. Materials and Methods: This is a retrospective, single-center cohort study of 16 male infants who survived the fetal intervention to birth, from 2010 to 2014 at a single center. All had patent shunts in place at birth. Perinatal and biochemical characteristics were collected with patients followed for one year, or until demise, with serial measures of serum creatinine (SCr) and serum cystatin C (CysC). Results: Of the 16 males, 81% were non-white (38% black, 43% Hispanic). Shunts were placed at a median of 20 weeks (IQR 19,23) gestation, with median fetal bladder volume of 39 cm3 (IQR 9.9,65). All neonates were born preterm [median 34 weeks (IQR 31,35)] and the majority with low birth weight [median 2340 grams (1,895, 2,600)]. 63% required positive pressure ventilation. Advanced chronic kidney disease stage 4-5 at 1 year of age was predicted by neonatal characteristics: peak SCr ≥2â mg/dl, time to peak SCr > 6 days, discharge SCr ≥1.0â mg/dl, CysC ≥2.5â mg/l, urine protein:creatinine ≥4.8â mg/mg, urine microalbumin:creatinine ≥2.2â mg/mg. In infancy, a nadir SCr ≥0.5â mg/dl occurring before 160 days (5.3 months) of age was also predictive of advanced chronic kidney disease stage 4-5 at 1 year. Three patients died in the neonatal period, with 1 receiving kidney replacement therapy (KRT). Three additional patients required KRT before 12 months of age. Conclusions: Even with definitive vesicoamniotic shunting for cLUTO, postnatal morbidity and mortality remain high, emphasizing the role of renal dysplasia, in spite of urinary diversion, in postnatal kidney dysfunction. Neonatal and infant biochemical parameters exhibit distinct trends that offer families and physicians a better understanding of the prognosis of childhood kidney function.
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Oxidative stress occurs when there is an imbalance between reactive oxygen species/reactive nitrogen species and antioxidant systems. The interplay between these complex processes is crucial for normal pregnancy and fetal development; however, when oxidative stress predominates, pregnancy related complications and adverse fetal programming such as preterm birth ensues. Understanding how oxidative stress negatively impacts outcomes for the maternal-fetal dyad has allowed for the exploration of antioxidant therapies to prevent and/or mitigate disease progression. In the developing kidney, the negative impact of oxidative stress has also been noted as it relates to the development of hypertension and kidney injury mostly in animal models. Clinical research addressing the implications of oxidative stress in the developing kidney is less developed than that of the neurodevelopmental and respiratory conditions of preterm infants and other vulnerable neonatal groups. Efforts to study the oxidative stress pathway along the continuum of the perinatal period using a team science approach can help to understand the multi-organ dysfunction that the maternal-fetal dyad sustains and guide the investigation of antioxidant therapies to ameliorate the global toxicity. This educational review will provide a comprehensive and multidisciplinary perspective on the impact of oxidative stress during the perinatal period in the development of maternal and fetal/neonatal complications, and implications on developmental programming of accelerated aging and cardiovascular and renal disease for a lifetime.