肾小管功能受损的早期检测

近端肾小管受损时,小分子蛋白重吸收下降,尿中排泄相应增加。临床上通过检测尿中α1-微球蛋白、β2-微球蛋白、N-乙酰-β-D-氨基葡萄糖苷酶、视黄醇结合蛋白、胱蛋白酶抑制剂C和α-海藻糖酶可反映近端肾小管重吸收功能。     

1例肾单位肾痨12型的临床特点及TTC21B基因型研究

肾单位肾痨（NPHP）是一组常染色隐性遗传，主要累及肾小管间质的囊性肾病。该文报道1例TTC21B基因突变所致的NPHP 12型。患儿女，起病隐匿，3岁6个月首次就诊时即存在中量蛋白尿、肾功能损害、高血压2期，并伴有内脏反位、短指/趾，4岁前进展到终末期肾病。尿蛋白电泳以肾小球性蛋白尿为主。尿β2-微球蛋白、尿α1-微球蛋白等肾小管指标均明显增高。基因检测显示TTC21B基因存在c.1552T > C （p.C518R）、c.752T > G （p.M251R）复合杂合突变，前者来自父亲，后者来自母亲。c.752T > G为新发突变。TTC21B基因突变患儿的肾脏病理除了NPHP典型的肾小管改变外，多同时存在显著的肾小球损害。     

新生儿窒息对肾小管功能的影响:附30例分析

本文报道检测74例正常新生儿及30例窒息足月新生儿尿常规、尿肌酐及尿β_2微球蛋白,结果前二项两组无差异;但正常新生儿组β_2微球蛋白为1.28±1.16μg/ml,窒息组为5.79±3.21μg/ml,后者为前者的4.5倍(p值<0.001)。作者认为尿β_2微球蛋白的检测可作为诊断肾小管功能损伤的方法,并认为凡有围产期窒息的新生儿,常规检查尿β_2微球蛋白可作为监测肾小管功能方法之一,利于采取措施,降低死亡率。     

窒息新生儿的肾功能损害

观察了３６例窒息新生儿血肌酐、尿素氮及血、尿α１－微球蛋白和β２－微球蛋白浓度的变化，结果表明；窒息新生儿中普遍存在肾功能障碍，主要表现为肾小球滤过率降低和肾小管重吸收功能障碍，在及时反映肾小球滤过率改变方面，血α１－微球蛋白比β２－微球蛋白更为敏感，且肾小球滤过率的恢复要早于肾小管功能的恢复。     

三例新生儿马兜铃酸肾病临床特点及长期随访分析

目的 总结新生儿木通中毒所致马兜铃酸肾病的临床特点和转归.方法 回顾性分析3例新生儿因木通所致马兜铃酸肾病的临床表现、治疗和转归情况.结果 3例患儿均在服用含有木通的中药后出现呕吐、腹泻及尿量减少,出现急性肾功能衰竭、肾小球及肾小管损害.实验室检查表现为高血钾、低血钠,肌酐、尿素氮增高及代谢性酸中毒.轻度肾小球损害,表现为蛋白尿及血β2微球蛋白增高.肾小管功能损害表现为碱性尿,尿β2微球蛋白增高,尿糖、尿酮体及尿氨基酸阳性.经过对症治疗后肾功能在3～4周恢复正常,5～8个月尿蛋白转阴,3个月～1年尿氨基酸转阴,9个月～3年尿糖转阴,5.0～5.5年尿pH值降至7.0.5.5 ～6.0年后停止服用枸橼酸合剂.3例患儿随访12年,前11年内3例患儿的血清肌酐均在正常范围内,但近期随访显示2例患儿的血清肌酐升高,例3的血清肌酐正常.3例患儿估算肾小球滤过率(eGFR)均有所降低,其中例1、2的eGFR低于90 ml/(min·1.73 m2),近6年的eGFR每年降低1.1 ml/(min·1.73 m2)及0.6 ml/(min·1.73 m2),1例患儿的eGFR较前无明显降低.3例患儿血气正常,尿常规阴性,但血、尿β2微球蛋白仍较高.尿N-乙酰β葡萄糖苷酶(NAG)降至正常后又有所增高.结论 新生儿马兜铃酸肾病可引起急性肾功能衰竭和肾小管功能损害,经过对症治疗肾功能可在短期内恢复正常,但肾小球滤过率呈缓慢下降趋势且肾小管损害可持续多年,需要长期随访.     

气溶胶盐疗法对支气管哮喘患儿并肾脏损害的疗效

目的　观察气溶胶盐疗法 (盐疗 )对支气管哮喘 (哮喘 )患儿并肾功能损害的疗效。方法　对 5 0例哮喘患儿 (哮喘组 )盐疗前后留取清洁新鲜晨尿进行尿常规及尿肾功能系列检测 ,健康对照组 2 5例检测项目同上。观察盐疗前后患儿肾功能的改善情况。结果　哮喘组尿常规、尿微白蛋白 (Alb)均正常 ,而α1 微球蛋白 (α1 MG )、尿 β2 微球蛋白 (β2 MG )、N 乙酰 β 氨基葡萄糖苷酶 (NAG)在盐疗前后比较及盐疗前与对照组比较差异有显著性意义 (P <0 .0 1) ,而盐疗后与对照组比较差异无显著性意义 (P >0 .0 5 )。结论　哮喘患儿在尿常规尚未明显表现出肾脏受损时 ,肾近曲小管功能的损害已客观存在。而经盐疗后其肾脏损害的指标转为正常 ,说明其肾小管早期的损伤可能为可逆性、功能性损害     

52例肾脏疾病患儿的血、尿β_2微球蛋白测定(摘要)

β_2微球蛋白(β_2M)首先由Berggare于1968年分离提纯,1972年Pererson确定其氨基酸排列同HLA,由淋巴细胞产生。血β_2M上升,反映肾小球滤过率下降,尿β_2M上升,表明肾小管再吸收减少,可早期发现肾小管功能障碍。     

尿N-乙酰-β-D-氨基-葡萄糖苷酶及尿β2微球蛋白在过敏性紫癜肾损害早期诊断中的意义

目的探讨联合检测尿N-乙酰-β-D-氨基-葡萄糖苷酶(NAG)及尿β2微球蛋白(β2-MG)在过敏性紫癜(AP)肾损害早期诊断中的意义。方法以双夹心酶免疫法及放射免疫法检测94例AP患儿尿NAG、β2-MG水平。结果94例AP患儿中15例尿NAG异常,12例尿β2微球蛋白异常,5例尿NAG、β2微球蛋白均异常,尿NAG异常阳性率为15.96%(15/94),尿β2微球蛋白异常阳性率为12.78%(12/94);尿NAG及尿β2-MG异常的联合阳性率为28.72%(27/94),以上阳性率间两两比较:尿NAG与尿β2-MG阳性率无差异(X2=0.39P>0.05),而两者联合阳性率高于尿NAG(X2=4.41P<0.05),也高于尿β2-MG(X2=7.28P<0.05)。结论尿NAG及尿β2-MG均可作为早期诊断AP肾损害的尿标志性蛋白;应用两者联合指标,可提高其早期诊断阳性率。     

围产期窒息新生儿血清β_2-MG、尿NAG、Lys测定及尿氨基酸分析

围产期窒息是引起新生儿肾功能损害的重要原因,可致肾小球滤过率降低和肾小管重吸收障碍。本研究测定围产期窒息新生儿血清β_2-微球蛋白(β_2-Microglubin,β_2-MG)、尿N-乙酰-β-D-氨基葡萄糖苷     

β_2微球蛋白对肾病综合征肾功改变早期诊断的意义

应用放射免疫法对３７例小儿原发性肾病综合征（ＮＳ）在发病期进行血和尿β２微球蛋白（β２ＭＧ）检测。结果表明ＮＳ有肾小球和肾小管的功能改变，而血和尿β２ＭＧ检测为检查肾功能的敏感指标，对早期诊断本征肾功能有一定意义。     

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??Drug-induced kidney injury is one of the main causes of acute kidney injury in children. Certain drugs can lead to tubular epithelial injury??kidney immune inflammation??or alter the intraglomerular hemodynamics??or cause intrarenal obstruction??which contribute to clinical manifestations including acute kidney injury??acute tubular necrosis??acute or chronic interstitial nephritis??nephrolithiasis/crystal nephropathy??nephrotic syndrome??tubular dysfunction??et al. The setting of several biomarkers are used for prediction and detection of early drug-induced kidney injury. In clinical practice the risk factors of drug-induced kidney injury should be corrected in time and the related drugs be stopped and kidney function be monitored in order to achieve early diagnosis and early intervention??which can improve the prognosis.     

关注儿童用药后的肾损伤

药物性肾损伤是儿童急性肾损伤的主要原因之一。药物经由肾脏代谢排泄时导致肾小管上皮细胞损伤、肾脏免疫炎症,或导致肾内血流动力学改变,或形成结晶堵塞肾小管。临床主要表现为急性肾损伤、急性肾小管坏死、急慢性间质性肾炎、结晶性肾病、肾病综合征、肾小管功能障碍等。应用生物标志物可以早期监测药物性肾损伤。临床工作中应及时纠正药物性肾损伤的高危因素,及时停用相关药物和监测肾功能,力求早期诊断,早期干预,改善预后。     

Sulfasalazine and renal tubular function: lack of an effect

Sulfasalazine (SASP) is frequently used in the treatment of chronic inflammatory bowel disease (IBD), particularly colitis. Because the drug poses a theoretical risk for renal tubular damage, 26 patients, 8-18 years of age, with Crohn's ileocolitis were studied. Thirteen children were receiving SASP while 13 served as disease controls. Renal tubular function was assessed by measurement of urinary beta 2-microglobulin and n-acetylglucosaminidase activity. No abnormalities were found on routine measurement of renal function. Similarly, urinary beta 2-microglobulin and n-acetylglucosaminidase activities were within normal limits for patients receiving SASP, as well as for disease controls. Although there is a theoretical risk for renal tubular damage from the prolonged use of SASP, this study would suggest that IBD patients receiving the drug are at no greater risk for renal injury than their counterparts not receiving the medication.     

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.     

Long-term renal function in pediatric liver and heart recipients

Long-term survivors of pediatric liver and heart transplantation are at risk for progressive renal dysfunction as a result of chronic exposure to calcineuron inhibitors. This class of drugs causes alterations in renal perfusion that can result in irreversible renal injury including afferent arteriopathy, glomerulosclerosis, tubular atrophy and interstitial fibrosis. Approximately 3-6% of pediatric liver and heart recipients will develop end stage renal failure. A much larger percentage has chronic renal insufficiency and hypertension. Children with significant renal compromise in the pretransplant period and those with significantly elevated serum creatinine levels during the first post-transplant year may be at the highest risk to develop irreversible renal injury in long-term follow-up. Serum creatinine is a poor screening tool as it rises late in the course when the injury may no longer be reversible. Strategies to minimize long-term exposure to calcineuron inhibitors may reduce the prevalence of renal insufficiency in this vulnerable population.     

Kidneys of mice with hereditary tyrosinemia type I are extremely sensitive to cytotoxicity

Children with hereditary tyrosinemia type 1 (HT1) suffer from liver failure, renal tubular dysfunction, and rickets. The disease is caused by deficiency of fumarylacetoacetate hydrolase (FAH), the last enzyme of tyrosine catabolism, and leads to accumulation of the toxic substrate fumarylacetoacetate (FAA) in hepatocytes and renal proximal tubular cells. Patients are treated with 2-(2-nitro-4-trifluoro-methylbenzoyl)-1,3 cyclohexanedione (NTBC), which prevents accumulation of FAA by blocking an enzyme upstream of FAH. Liver transplantation is performed when patients do not respond to NTBC or develop hepatocellular carcinoma. This reduces the tyrosine load for the kidney but does not abolish renal exposure to locally produced FAA. To investigate the pathogenesis of liver and kidney damage induced by tyrosine metabolites, we challenged FAH-deficient mice with various doses of homogentisic acid (HGA), a precursor of FAA. Injecting NTBC-treated Fah-/- mice with low doses of HGA caused renal damage and death of renal tubular cells, as was shown by histologic analyses and deoxynucleotidyl transferase-mediated dUDP nick-end labeling (TUNEL) assay but did not lead to liver damage. In addition, kidney function, but not liver function, was affected after exposure to low doses of HGA. Administration of high doses of HGA led to massive cell death in both the liver and kidneys. Resistance to HGA-induced cell death was seen after withdrawing NTBC from Fah-/- mice. The finding that the kidneys of Fah-/- mice are especially sensitive to damage induced by low doses of HGA underscores the need to perform careful monitoring of the kidney function of tyrosinemia patients undergoing any form of treatment.     

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??Congenital abnormalies of the kidney and urinary tract??CAKUT?? are the main cause of chronic kidney disease ??CKD?? in childhood. Congenital hydronephrosis is a common type of CAKUT and is usually detected by prenatal renal ultrasonography. Severe congenital nephrosis can cause renal injury and end-stage renal disease??ESRD??. The etiology of congenital nephrosis is complicated and involves the abnormal expression of multiple genes. Studies on human tissue specimens and animal models show that oxidative stress?? chronic inflammation and apoptosis result in renal tubular atrophy and renal fibrosis. With advanced biological techniques such as proteomics?? new biological markers are emerging for early disease detection and the choice of the optimal treatment and monitoring.     

Serum and urinary neutrophil gelatinase‐associated lipocalin levels in children with chronic renal diseases

Background: Recent studies showed that serum and urinary neutrophil gelatinase‐associated lipocalin (NGAL) represents a novel, sensitive, specific biomarker for early detection of acute kidney injury. However, the clinical significance of measuring serum and urinary NGAL on chronic renal diseases remains unclear. Methods: In this study, we measured serum and urinary NGAL levels in patients with several common pediatric renal diseases such as renal dysfunction (estimated glomerular filtration rate < 90 mL/min/1.73 m²), proliferative glomerulonephritis, steroid‐resistant and steroid‐sensitive nephrotic syndrome, and tubular dysfunction. Results: Urinary NGAL level was significantly increased compared with the control in all of these disease groups except in patients with a remission stage of steroid‐sensitive nephrotic syndrome, although a significant increase in serum NGAL level was observed in the renal dysfunction group only. Both serum and urinary NGAL levels showed significant inverse correlations with an estimated glomerular filtration rate in the analysis with total subjects, and also in the analysis with the renal dysfunction group in urinary NGAL. In proteinuric patients, the extent of proteinuria significantly correlated with urinary NGAL level. In patients with tubular dysfunction, the increase of urinary NGAL level was remarkable compared with the other disease groups. Conclusion: These results indicated that urinary NGAL level is a better biomarker for chronic renal diseases in children than serum NGAL level, although multiple pathological mechanisms should be considered in evaluating these NGAL values.     

Value of SDS-polyacrylamide gel electrophoresis, small molecular weight proteins and alpha-1-acid glycoprotein for the diagnosis of tubular damage

The low molecular weight proteins alpha-1-microglobulin, beta-2-microglobulin, retinol binding protein, alpha-1-acid glycoprotein and the SDS-polyacrylamide gel electrophoresis (SDS-PAGE) were estimated in 31 healthy children and compared to 81 urine samples of children with tubular damage (TD). The tubular damage was diagnosed clinically and established by beta-2-microglobulin determination. Means for healthy children were: beta-2-microglobulin 109 +/- 77 micrograms/l, alpha-1-microglobulin 0.39 +/- 0.0 mg/dl, retinol binding protein 0.49 +/- 0.0 mg/dl, alpha-1-acid glycoprotein 0.69 +/- 0.0 mg/dl. Means for children with TD were: beta-2-microglobulin 8530 +/- 14693, alpha-1-microglobulin 2.98 +/- 2.28 mg/dl, retinol binding protein 1.68 +/- 2.44 mg/dl and alpha-1-acid glycoprotein 2.79 +/- 3.44 mg/dl. Comparing the panel of healthy children with sick children (TD) we found the following: b2m t = 3.2, p = less than 0.0005, a1m t = 6.5, p = less than 0.0005, rbp t = 2.65, p = less than 0.0005, a-1-agp t = 3.4, p = less than 0.005. a1m revealed tubular damage in 77 out of 81 tubular disorders, the rbp in 25 out of 81 and alpha-1-acid glycoprotein showed tissue damage or inflammation in 33 out of 81 patients. SDS-PAGE revealed tubular damage in 46 out of 81 patients with TD. We can assay that alpha-1-microglobulin is a useful marker for tubular damage. The determination of retinol binding protein and alpha-1-acid glycoprotein is useless for this purpose. The SDS-PAGE, though a potent tool for the differential diagnosis between glomerular or tubular damage, alone is not a reliable assay for the diagnosis of TD.