Chronic kidney disease in children following lung and heart–lung transplantation

Abstract:  CKD is a major co-morbidity in pediatric lung transplant recipients. We report the prevalence of renal impairment post-lung transplant at a single center, using a modified, age-adjusted eGFR for the best approximation of true GFR, and investigated associations and possible predictors of decline in renal function post-transplant. Renal function was assessed by eGFR pre-transplant, three and 12 months post-transplant, and at last follow-up. Decline in renal function was analyzed as percentage fall in eGFR in two phases (0–3 and 3–12). Furthermore, we investigated impact of gender, age, pre-transplant diagnosis and renal function, transplant type, early post-transplant dialysis, and tacrolimus trough levels on decline in eGFR using multivariate analysis. Over a five-yr period, 30 transplants were performed. Mean eGFR pretransplant was 117 mL/min/1.73 m² (s.d. 35) with mean decline in eGFR during the first three months post-transplant of 33% (s.d. 31, p < 0.001). Thereafter, mean decline in eGFR was 8% (s.d. 18, p = 0.02). None of the factors assessed were significantly associated with decline in eGFR post-transplant. In conclusion, many children have decline in renal function following lung transplantation, particularly early post-transplant. Unlike in adults, we were unable to detect any predictors of renal impairment in pediatric lung transplant recipients.     

Causes and outcome of late referral of children who develop end-stage kidney disease

Aims: This study aims to characterise the timing of referral to a paediatric nephrology unit of children who develop end‐stage kidney disease (ESKD). This study also aims to determine whether late referral (LR) influences outcomes and to explore factors that may lead to LR. Methods: A retrospective case review of all incident patients with ESKD who received renal replacement therapy (RRT) at a single paediatric centre. Time between referral to a paediatric nephrologist and commencement of RRT, demographic and clinical data were collated. Estimated glomerular filtration rate (eGFR) at referral was calculated using height and creatinine. LR was defined as having an eGFR ≤30 mL/min/1.73 m² when first seen by a paediatric nephrologist. Results: RRT was initiated for 74 patients <18 years of age between 1988 and 2010. The median age at referral was 2.0 years (birth–15.9 years) and age at RRT was 10.0 years (6 days–17.4 years). Children referred before age 1 year (41%) had a more prolonged course before ESKD. Median (interquartile range) eGFR at referral of children >1 year was 27.2 (9.0–52.0) mL/min/1.73 m². Twenty‐two (55%) of these children were referred late (LR) with an eGFR ≤30 mL/min/1.73 m². LR patients were more likely to have glomerulonephritis or haemolytic uraemic syndrome and to live in a remote or outer regional area. LR patients had higher urea, lower haemoglobin and were more likely to receive haemodialysis via a vascular catheter. Conclusions: A significant proportion of children who develop ESKD are referred late to nephrology units with potentially preventable complications. Aetiology of renal disease and geographic isolation contribute to LR.     

肾损伤因子在肾脏疾病中的应用

中性粒细胞明胶酶相关脂质运载蛋白(neutrophil gelatinase-assocliated lipocalin,NGAL)是脂质运载蛋白家族的新成员,存在于人类的一些正常组织中.近年来研究表明NGAL与肾脏疾病有一定的关系.NGAL是急性肾损伤的早期标志物,与传统的急性肾功能不全(ARF)实验室指标血肌酐相比,NGAL可以更早且准确地诊断ARF;NGAL在慢性肾脏疾病中也发挥着一定的功能,可体现慢性肾脏疾病的进展程度及治疗效果;在终末肾病中,NGAL可以作为血液透析以及疗效的指标.     

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.     

Cardiac magnetic resonance imaging in children with chronic kidney disease and renal transplantation

CV disease is the major cause of death in patients with CKD. Recently, CMR imaging emerges as a complementary method providing advantages in cardiac assessment; however, data on CMR in pediatric CKD are scarce. We performed CMR in 15 children: two with CKD, six on peritoneal dialysis, seven on hemodialysis, and in 18 children 5.1 (0.4-15.4) yr after kidney Tx. Eight children underwent CMR six months before and after Tx. Results are presented as mean z score ± SD. LV EF was higher and in the normal range in Tx patients compared with CKD (-0.3 ± 1 vs. -2.1 ± 1.6, respectively, p < 0.05), whereas RV EF was similar (-0.9 ± 1.4 vs. -0.9 ± 1.8, p = n.s.). End-diastolic and end-systolic LV volume index (0 ± 1.7 vs. 2.1 ± 3.1; 0.2 ± 1.2 vs. 3.1 ± 3.7, both p < 0.05) and LV mass index (1.4 ± 1.5 vs. 3.4 ± 2.9, p < 0.05) were lower in Tx children. All parameters improved in the eight children after Tx. In conclusion, our CMR analysis suggests marked improvement of cardiac function and morphology in children after kidney Tx. CMR might be an appropriate complementary method for measuring detailed cardiac status in children with CKD.     

Body growth in children with polycystic kidney disease

We analysed the body growth of 121 prepubertal children with polycystic kidney disease participating in a longitudinal multicentre study. The patients were followed from an age of 1 to 9 years in girls and 1 to 10 years in boys over a mean period of 3.6 years. Children with end-stage renal disease were excluded. Fifty-four patients had the autosomal dominant form of the disease and 67 the autosomal recessive form. At last observation, 2% of patients with the dominant form and 28% of those with the recessive form had an estimated glomerular filtration rate of < 60 ml/(min 1.73 m²). At first observation, the mean height SD score (SDS) in patients with the dominant form was almost the same as in controls, whilst in those with the recessive form it was significantly decreased (girls –0.82 SDS, boys -0.68 SDS, p < 0.001). During the follow-up the height SDS decreased slightly in both groups (NS). In patients with autosomal recessive kidney disease the degree of growth retardation appeared to be related to renal function: at last observation the height of girls with an estimated glomerular filtration rate of < 60ml/(min 1.73 m²) was more retarded than that of boys (mean -2.1 SDS versus -1.5 SDS, NS). The height SDS and renal function at last observation correlated in girls ( r = 0.83, p < 0.001) but not in boys ( r = 0.55) with the recessive form. No correlation was found between the height SDS and hypertension. The weight-for-height SDS at onset was significantly reduced in patients with the recessive form with decreased renal function. Our data suggest that the autosomal recessive, but not the dominant, form of polycystic kidney disease is associated with early growth retardation, which seems to be more severe in girls, probably due to the more rapid deterioration of renal function.     

Comparison of parameters of chronic kidney disease following paediatric preemptive versus non‐preemptive renal transplantation

Sinha R, Marks SD. Comparison of parameters of chronic kidney disease following paediatric preemptive versus non‐preemptive renal transplantation.
Pediatr Transplantation 2010: 14:583–588. © 2010 John Wiley & Sons A/S. Abstract: PRT is the preferred modality for renal replacement therapy in children. Despite this, there are no studies CKD parameters as per K/DOQI criteria between PRT and NPRT in children. This was a single‐centre cross‐sectional study of RTR with at least one yr of post‐transplant follow‐up. CKD parameters as per K/DOQI were compared between PRT and NPRT. Thirty percent (39/129) of our study population was PRT. Despite similar baseline characteristics at the time of transplantation and similar post‐transplantation follow‐up period, a significantly lower proportion of PRT (1, 2%) were in Stage 4 CKD in contrast to NPRT (14, 16%); p = 0.03. This was also reflected in better CKD parameters among PRT with significantly lower incidences of hypertension and acidosis (p = 0.02). CKD medications were also more commonly prescribed in NPRT (p = 0.002). We demonstrated improved CKD parameters and lower use of CKD medications among PRT when compared with NPRT. This finding should act as an added impetus for PRT programmes.     

新生儿急性肾损伤与慢性肾脏病

由于新生儿处于从宫内环境向宫外环境的过渡期,内环境变化大,且肾脏的结构、功能发育不成熟,与成人相比,肾脏储备能力低下。在正常情况下,新生儿肾脏的成熟能与生长发育相适应,维持内环境于一个相对平衡状态,但在各病理因素影响下,却极易出现急性肾损伤,不仅会造成水电解质紊乱和酸碱失衡,增加短期的不良预后,还会影响生后肾脏结构功能的进一步成熟,甚而增加远期慢性肾脏病的风险。     

Complications of chronic kidney disease in children post-renal transplantation – A single center experience

Abstract:  Similar to adults, CKD may persist after pediatric RTx. Clinical and laboratory parameters were analyzed retrospectively in 23 RTx recipients (13 males, age 11.9 ± 5.2 yr), initially treated with prednisone, calcineurin inhibitor (TAC = 18, cyclosporine neoral = 5), and MMF at four months post-RTx (T1) and at 3.4 ± 2.8 yr post-RTx (T2). Mean (±s.d.) cystatin C GFR (mL/min/1.73 m²) was 72 ± 19 at T1 and 70 ± 22 at T2 (NS). At T2, CKD stage I was present in five patients (22%), stage II in eight patients (35%), and stage III in 10 patients (43%). At T2, calcineurin inhibitors were utilized in 19, MMF in 13, and SIR in 13 patients. The prevalence of hypertension was 69% at T1 and 87% at T2 (p = NS). Anemia was diagnosed in 61% at T1 and 69% at T2 with average therapeutic MMF (2.78 ± 1.3 mg/mL) and SIR (7.62 ± 2.3 mg/mL) trough levels. Hypercholesterolemia was detected in 44.0% at T1 and 47% at T2. Bone disease was diagnosed in 26.0% at T1 and 21.7% at T2. Mean height Z-scores were −1.0 ± 1.2 (T1) and −1.0 ± 1.59 (T2, NS), with 21% at T1 and 30% at T2 below two SDS. We observed suboptimal growth, hypertension, hypercholesterolemia, bone disease, and anemia in a significant proportion of transplanted children.     

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。     

PAX2与急慢性肾脏疾病研究进展

配对盒基因2(paired box2,PAX2)是一种核转录因子,表达在发育期肾脏。研究表明PAX2通过与PTIP的相互作用使染色质处于可转录状态,与Grg4的相互作用削弱了其与PTIP结合而抑制转录。 PAX2在急性肾损伤时再表达,参与促进细胞增殖修复。先天PAX2基因突变与先天性肾脏输尿管异常密切相关。在慢性肾脏疾病,PAX2起到促进增殖及囊肿形成的作用。该文就PAX2的功能及其在急性肾损伤和慢性肾脏疾病中作用的相关研究进行综述。     

Survival of childhood polycystic kidney disease following renal transplantation: the impact of advanced hepatobiliary disease

Childhood PKD encompasses the diagnoses of AR and ADPKD, glomerulocystic disease, and syndromes such as tuberous sclerosis or Jeune's syndrome. Given the fact that a majority of PKD children with ESRD carry the diagnosis of ARPKD, natural history studies assessing the long-term prognosis of PKD patients following renal transplantation must focus on morbidity and mortality issues related to complications from congenital hepatic fibrosis. Using the NAPRTCS registry, we analyzed the patient and graft survival rates of 203 PKD patients and 7044 non-PKD patients undergoing renal transplantation between 1987 and 2001. Deceased PKD patients, all with a diagnosis of ARPKD, were further identified and characterized using a special questionnaire submitted to the principal investigators. Overall graft and patient survival rates were not significantly different between PKD and non-PKD patients. No differences in rates of acute rejection or time to first rejection were noted between PKD and non-PKD patients. The relative risk of living longer than 3 yr in the PKD patients was not significantly different from non-PKD patients (RR = 0.70, p = 0.28). Sepsis was identified as a likely factor in the cause of death in nine (64%) ARPKD patients and was comfirmed with a positive blood culture in four patients. Despite similar graft and patient survival rates among PKD and non-PKD children following renal transplantation, our results suggest that ARPKD transplant recipients appear to be at increased risk for sepsis that may be related to hepatic fibrosis and ascending cholangitis. The utility of early liver transplantation in ARPKD patients with significant hepatobiliary disease is discussed.     

Multicystic kidney dysplasia: a prospective study on the natural history of the affected and the contralateral kidney

In a 6-year period, 41 young infants with multicystic kidney dysplasia were seen in our department. In 30 cases, the diagnosis had already been suspected by prenatal ultrasonography. A prospective protocol was proposed to the parents which comprised ultrasound evaluation every 3 months until the age of 24 months and renal function assessment at the age of 18 months. In 33 patients, the study was completed as scheduled. At the start of the study, the maximal diameter of the multicystic kidney was above the mean length of normal kidneys in all cases where precise measurement was possible. Within 24 months, 7 of the dysplastic kidneys disappeared, 20 regressed in size, 1 remained unchanged and only 5 increased in size. Between the age of 0 to 3 months, renal length of the contralateral kidney was within the normal range in 19 infants and above +2SD in 14 cases. At the age of 18 to 24 months, renal length was, with few exceptions, between 0 and +4SD. Inulin clearance was normal in all 33 individuals with a median value of 112 ml/min per 1.73 m². Conclusion As a rule, multicystic kidneys shrink in the first 2 years of life. In most cases the contralateral kidney maintains a normal renal function as a consequence of progressive compensatory hypertrophy. Received: 19 November 1997 / Accepted in revised form: 31 January 1998     

儿童肾囊性疾病的诊治

Potter分型将儿童肾囊性疾病分为4型:常染色体隐性遗传性多囊性肾病、多囊性肾发育不良、常染色体显性遗传性多囊性肾病、梗阻性囊性发育不良肾.此外,单纯性肾囊肿、发生在肾肿瘤及其他伴囊性肾病的综合征也可引起肾脏呈囊性改变.这类病由于其发病机制和病理基础不同,临床诊断及治疗方案选择亦不同,要正确诊断这类疾病,需要仔细分类并查明病因.该文就儿童常见的肾囊性疾病进行综述.     

Pediatric kidney transplantation

Since first performed in 1954, kidney transplantation has evolved as the preferred long-term treatment of children with end stage renal disease (ESRD). The etiology of chronic kidney disease (CKD) and ESRD in children is broad and can be quite complicated, necessitating a multidisciplinary team to adequately care for these patients and their myriad needs. Precise surgical techniques and modern protocols for immunosuppression provide excellent long-term patient and graft survival. This article reviews the many etiologies of renal failure in the pediatric population focusing on those most commonly leading to the need for kidney transplantation. The processes of evaluation, kidney transplantation, short-term and long-term complications, as well as long-term outcomes are also reviewed.