Renal function in the fetus and neonate – the creatinine enigma

The use of serum creatinine levels to estimate glomerular function in infants is admittedly fraught with inherent inaccuracies which are both physiological and methodological in nature. This characteristic can understandably reduce the neonatal clinician's confidence in the ability of serum creatinine levels to provide useful information relevant to their patients' medical care. The aim of this review is to provide further insight into the peculiarities of serum creatinine trends in both premature and term infants with special focus on the maturational and developmental changes occurring in the kidney during this crucial time-period. Though newer markers of glomerular function are gaining increasing traction in the clinical realm, the most prominent of which is currently cystatin C, creatinine nonetheless remains an important player in the scientific evolution of glomerular filtration rate (GFR) estimation. Not only do its limitations provide a level of distinction for newer markers of GFR, but its advantages persist in refining the precision of newer GFR formulae which incorporate multiple patient characteristics.     

儿童慢性肾脏病

儿童慢性肾脏病(chronic kidney disease,CKD)是严重影响儿童正常生长发育的慢性进展性疾病,该病起病隐匿,部分最终进展为终末期肾病(end-stage renal disease,ESRD),需肾脏替代治疗维持生命.该文就儿童慢性肾脏病的病因、发病机制、诊断及治疗作一综述,旨在使人们更早、更全面地了解CKD,并采取积极的措施,延缓CKD的进展,防止ESRD的发生.     

Clinical features of acute kidney injury in patients with Kawasaki disease

Although acute kidney injury (AKI) is a common complication in hospitalized children, AKI has rarely been reported in patients with Kawasaki disease (KD). Herein, we review the clinical trajectories of AKI in patients with KD. A total of 39 patients with KD who developed AKI have been reported in 28 publications as case reports. The causes of AKI include prerenal AKI associated with acute heart failure (AHF), intrinsic AKI caused by tubulointerstitial nephritis (TIN), acute nephritic syndrome (ANS), hemolytic uremic syndrome (HUS), immune complex-mediated nephropathy, rhabdomyolysis, and KD shock syndrome (KDSS). Six of the 39 patients (15.4%) underwent renal replacement therapy. While AHF and multiple organ dysfunction syndrome developed in 41% and 68% of KD patients with AKI, respectively, all patients recovered without any renal sequelae. Although the precise pathogenic mechanism underlying the development of AKI in patients with KD is unknown, several possible mechanisms have been proposed, including T-cell-mediated immunologic abnormalities for TIN, renal and glomerular endothelial injury resulting from vasculitis for HUS, immune complex-mediated kidney injury for immune complex-mediated nephropathy and ASN, and capillary leak and an increased release of cytokines with myocardial dysfunction for KDSS.     

Estimation of glomerular filtration rate in liver‐transplanted children:Comparison of simplified procedures using 51Cr‐EDTA and endogenous markers with Sapirstein’s method as a reference standard

Berding G, Geisler S, Melter M, Marquardt P, Lühr A, Scheller F, Knoop BO, Pfister E‐D, Pape L, Bischoff L, Knapp WH, Ehrich JHH. Estimation of glomerular filtration rate in liver‐transplanted children: Comparison of simplified procedures using ⁵¹Cr‐EDTA and endogenous markers with Sapirstein’s method as a reference standard.
Pediatr Transplantation 2010: 14:786–795. © 2010 John Wiley & Sons A/S. Abstract: This study evaluated simple procedures for GFR determination in 48 liver‐transplanted children. After injection of ⁵¹Cr‐EDTA, blood samples were obtained up to four h, and activity retention in the body was measured for 60 min with scintillation probes. As a reference, GFR was calculated according to Sapirstein. Simplified calculations were performed according to Brochner‐Mortensen, Russel, Devaux and Oberhausen. Additionally, GFR was determined using plasma creatinine and cystatin C according to Schwartz and Filler, respectively. The reference revealed mildly reduced GFR (62 ± 20 mL/min/1.73 m²). Russel’s method provided the highest degree of correlation (r² = 0.95), the smallest bias in GFR determination (−2%), and only one false exclusion plus one false diagnosis of chronic kidney disease. Oberhausen’s method with blood sampling at one h post‐injection performed slightly worse (r² = 0.67, bias: 3%). All other methods resulted in significantly different GFR estimates compared to the reference. Nevertheless, notably, the second narrowest 95% limits of agreement (−31% to 45%) was observed using cystatin C. In conclusion, this data implies to prefer Russel’s method as a simplified procedure, and if patients cannot be available long enough (four h) for measurements, Oberhausen’s method instead. If radiotracer methods are not available at all or for screening GFR, cystatin C appears to be the procedure of choice.     

Primary vesicoureteral reflux detected in neonates with a history of fetal renal pelvis dilatation: a prospective clinical and imaging study

OBJECTIVE: To assess the clinical outcome and imaging features of neonatal primary vesicoureteral reflux (VUR). STUDY DESIGN: We prospectively followed 43 infants with primary VUR identified from among a cohort of 497 infants with fetal renal pelvis dilatation. Postnatal renal ultrasound (US) examinations were performed at 5 days and 1, 3, 6, 12, and 24 months of life. Voiding cystourethrography was performed in the neonatal period and repeated at 12 and 24 months when VUR was persistent. Two radioisotopic examinations, including a 99mTc-MAG3 renogram and a plasma clearance of Cr-51 EDTA, were performed in all children with high-grade reflux. RESULTS: The incidence of primary VUR in our study group was 9%. Among the 43 patients followed, 11 (26%) had high-grade (IV-V) VUR and 32 (74%) had low-grade VUR. Resolution of reflux occurred in 2 of 11 (18%) patients with high-grade VUR and in 29 of 32 (90.6%) patients with low-grade VUR at age 2 years (P < .001). At age 2 years, 91% of the low-grade refluxing kidneys were normal on US, compared with only 35% of the high-grade refluxing kidneys. Split renal function was within normal range and single-kidney GFR was significantly increased in 13 of the 17 high-grade refluxing kidneys during follow-up. Furthermore, a strong association between dysplasia on US and poor renal function outcome was found. CONCLUSIONS: In most infants with VUR, the reflux is of low grade and resolves rapidly. In those children with high-grade VUR, spontaneous resolution is rare at age 2 years, but persistent reflux rarely impairs the maturation of renal function.     

Reduced nocturnal blood pressure dip and sustained nighttime hypertension are specific markers of secondary hypertension

OBJECTIVE: To investigate with the use of ambulatory blood pressure (BP) monitoring whether nocturnal BP dip and nighttime BP values are different in children with untreated primary and secondary hypertension. STUDY DESIGN: Ambulatory BP monitoring studies from 145 children with untreated hypertension were retrospectively analyzed. Forty-five children had primary hypertension and 100 children had secondary hypertension. RESULTS: Children with secondary hypertension had lower nocturnal BP dip for systolic and diastolic BP in comparison to children with primary hypertension (8% +/- 5% vs 14% +/- 4% for systolic and 14% +/- 7% vs 22% +/- 5% for diastolic BP, P < .0001 for both). Eleven percent of children with primary hypertension were classified as nondipper (BP dip <10%) for systolic BP and no child for diastolic BP; on the contrary, in children with secondary hypertension, 65% were nondippers for systolic and 21% for diastolic BP. Nocturnal systolic and diastolic BP loads were significantly greater in children with secondary hypertension than in those with primary hypertension. CONCLUSIONS: Reduced nocturnal BP dip and sustained nighttime BP elevation are specific markers of secondary hypertension in children with untreated hypertension. Children with blunted nocturnal BP dip or sustained nighttime hypertension should be thoroughly investigated searching for the underlying cause of hypertension.     

川崎休克综合征致急性肾损伤1例报告

目的探讨川崎休克综合征并发急性肾损伤的临床特征及治疗。方法回顾分析1例川崎休克综合征合并急性肾损伤患儿的临床资料。结果 12岁女性患儿,因发热、呕吐起病,诊断脓毒性休克,逐渐出现急性肾损伤;患儿于发热10天后热退,5次连续性肾脏替代治疗后尿量恢复,血压稳定,尿素氮和肌酐恢复正常。后期复查心脏彩超提示冠脉扩张,修正诊断为川崎休克综合征,加用阿司匹林口服出院。长期随访心脏彩超示冠脉扩张消失。结论川崎休克综合征早期诊断需与脓毒性休克鉴别,一旦并发急性肾损伤,积极采用血液净化治疗可有效改善预后。     

Practice recommendations for the monitoring of renal function in pediatric non‐renal organ transplant recipients

The management of non‐renal pediatric solid organ transplant recipients has become complex over the last decade with innovations in immunosuppression and surgical techniques. Post‐transplantation follow‐up is essential to ensure that children have functioning allografts for as long as possible. CKD is highly prevalent in these patients, often under recognized, and has a profound impact on patient survival. These practice recommendations focus on the early detection and management of hypertension, proteinuria, and renal dysfunction in non‐renal pediatric solid organ transplant recipients. We present seven practice recommendations. Renal function should be monitored regularly in organ transplant recipients, utilizing assessment of serum creatinine and cystatin C. GFR should be calculated using the new Schwartz formula. Transplant physicians should also monitor blood pressure using automated oscillometric devices and confirm repeated abnormal measures with manual blood pressure readings and ambulatory 24‐h blood pressure monitoring. Proteinuria and microalbuminuria should also be assessed regularly. Referrals to a pediatric nephrologist should be made for non‐renal organ transplant recipients with repeated blood pressures >95th percentile using the Fourth Task Force reference intervals, microalbumin/creatinine ratio >32.5 mg/g (3.7 mg/mmol) creatinine on repeated testing and/or GFR <90 mL/min/1.73 m².     

Sickle cell nephropathy: A review of novel biomarkers and their potential roles in early detection of renal involvement

Whether the underlying mutations are homozygous, heterozygous, or co-inherited with other hemoglobinopathies, sickle cell disease is known to afflict the kidneys, leading to the clinical entity known as sickle cell nephropathy (SCN). Although common, SCN remains diagnostically elusive. Conventional studies performed in the context of renal disorders often fail to detect early stage SCN. This makes the quest for early diagnosis and treatment more challenging, and it increases the burden of chronic kidney disease-related morbidity among patients. Novel diagnostic tools have been employed to overcome this limitation. In this study, we discuss various biomarkers of SCN, including those employed in clinical practice and others recently identified in experimental settings, such as markers of vascular injury, endothelial dysfunction, tubulo-glomerular damage, and oxidative stress. These include kidney injury molecule-1, monocyte chemoattractant protein-1, N-acetyl-B-D-glucosaminidase, ceruloplasmin, orosomucoid, nephrin, and cation channels, among others. Furthermore, we explore the potential of novel biomarkers for refining diagnostic and therapeutic approaches and describe some obstacles that still need to be overcome. We highlight the importance of a collaborative approach to standardize the use of promising new biomarkers. Finally, we outline the limitations of conventional markers of renal damage as extensions of the pathogenic process occurring at the level of the organ and its functional subunits, with a discussion of the expected pattern of clinical and biochemical progression among patients with SCN.