Renal tubular acidosis associated with type III glycogenosis.

Two children who presented with severe failure to thrive were found to have Type III glycogen storage disease. They both also had defects of tubular acidification, an association not previously described. The nature of the tubular lesion is characterized and the explanation and therapeutic implications are discussed.     

外源性结缔组织生长因子对人肾小管上皮细胞胶原Ⅲ合成的影响

目的：结缔组织生长因子（CTGF）是一种重要的参与肾纤维化的细胞因子，为了进一步阐明外源性CTGF的作用机制，该文探讨了外源性CTGF对人肾小管上皮细胞胶原Ⅲ合成中的作用。方法：将体外培养的人肾小管上皮细胞HK2 分为3组：①对照组；②CTGF小剂量组（终浓度为2.5 ng/mL）；③CTGF大剂量组（终浓度为20 ng/mL）。用倒置显微镜观察细胞形态变化，RT-PCR检测HK2细胞胶原Ⅲα mRNA水平的变化，免疫组织化学方法观察HK2 细胞胶原Ⅲα的表达。结果：不同浓度的CTGF作用于HK2 细胞48 h后，均可使HK2 细胞由椭圆形变为梭形。大剂量CTGF刺激HK2 细胞48 h后胶原Ⅲα mRNA水平显著升高（P<0.05），大剂量CTGF组HK2 细胞胞浆表达胶原Ⅲα也显著增加（P<0.05）。结论：CTGF在体外能够诱导人肾小管上皮细胞发生形态改变，大剂量的CTGF刺激可以增加人肾小管上皮细胞胶原Ⅲ的合成。     

Clinical usefulness of cellulose acetate electrophoresis as a screening of proteinuria in childhood

Urine samples from 110 patients with different proteinuric diseases in childhood were analysed by Cellulose Acetate Electrophoresis (CAE) and several samples were also analysed by Sodium Dodecyl Sulphate Polyacrylamide Gel Electrophoresis (SDS-PAGE). CAE allowed the classification of proteinurias into 4 patterns; Tubular, Glomerular I, Glomerular II and Glomerular III, by albumin/globulin ratio, value of % gamma globulin fraction (% gamma) and alpha 1/alpha 2 globulin ratio. Proteinurias of the Tubular pattern included various diseases with tubular proteinuria, while proteinurias of the Glomerular I, II and III patterns included mainly postural proteinuria, proteinuria of nephrotic syndrome and proteinuria of various nephropathies, respectively. SDS-PAGE confirmed the tubular and the glomerular origins of the proteins. In the present study we described the clinical usefulness of CAE in the screening of proteinuric children for the following reasons. This method could be performed easily and immediately. This is one of the necessities for mass screening of proteinuric children. CAE can be helpful as one of indications of renal biopsy, since patients with the Glomerular III pattern often showed glomerular alterations and should be diagnosed histologically. Good correlation between % gamma and clinical data was found in follow-up study, so CAE is also helpful in understanding the disease course. Thus. CAE is recommended as a routine screening method of proteinuria as well as SDS-PAGE.     

Heterogeneity of osteogenesis imperfecta. Biochemical and morphological findings in a case of type III according to Sillence

A male infant with pale-blue sclerae, who died at the age of 6 weeks through the aspiration of food, presented multiple fractures and deformation of the long tubular bones. The clinical and radiological findings and the course indicated osteogenesis imperfecta, type III, according to Sillence's classification. The family history was unremarkable. Light and electron microscopic studies of iliac crest bone obtained postmortem, showed an abrupt interruption of endochondral ossification, with an active periosteal ossification. In the region of the fractures, a mixed desmochondral callus was seen. The endoplasic reticulum of the osteoblasts was markedly dilated, the mitochondria were swollen. The osteoid was reduced in quantity. A postmortem analysis of the collagen types I, II and III obtained from skin, cartilage and bone yielded chromatographically normal collagen constituents. An analysis of the amino acids of the collagen -chains showed an increased hydroxylysine content. The radiological findings and the clinical course both indicated type III osteogenesis imperfecta: identical biochemical findings have been described only for type II. The morphological and biochemical findings described here may be a manifestation of a variable expressivity of type III osteogenesis imperfecta. On the other hand, heterogeneity of type II osteogenesis imperfecta cannot be ruled out.Abbreviation OI osteogenesis imperfecta Supported by the Stiftung Volkswagenwerk, research project: Skeletal Dysplasia and by a grant of the Deutsche Forschungsgemeinschaft (Po 189/3-1)     

Experimental unilateral undescended testis: gubernaculectomy and anchoring or direct suture fixation?

This study was designed to evaluate whether creation of a unilateral undescended testis (U/L UDT) in rats by direct fixation of the testis can lead to changes in the contralateral (C/L) descended testis, and if so, whether this inherent problem of the model could be eliminated by anchoring the divided gubernaculum to indirectly fix the testis. Thirty male newborn rats were divided into three groups of 10 each and the procedure done on the 2nd day of life to create U/L UDT according to the group allocated: group I: sham-operated; group II: anchoring the gubernaculum after gubernaculectomy; group III: Direct suture fixation of the testis. Fertility, C/L testicular weight (TW), Johnsen score, seminiferous tubular diameter (STD), DNA flowcytometry, and serum anti-sperm antibodies (ASA) were studied. Fertility, C/L TW, Johnsen score, STD, and haploid cell population were significantly reduced in group III compared to group II, while significantly higher titers of ASA were found in group III. Gubernaculectomy and anchoring the gubernaculum to the anterior abdominal wall is a better technique of creation of experimental UDT, as direct fixation of the testis is potentially detrimental to the C/L normal, descended testis. Accepted: 13 October 1998     

The effect of zinc therapy on damaged testis in pre-pubertal rats

This experimental study was instituted to evaluate whether or not there is an effect of zinc aspartate administration on injured testes. Sixty prepubertal male Sprague-Dawley rats (weighing 180–240 g) were divided into six equal groups each containing ten rats. Group I was the control group. Rats in group II and group III which were blunt testicular trauma groups were subjected to right blunt testicular trauma to rupture the tunica albuginea. Just after this, animals in group III were given 30 mg/kg zinc aspartate intraperitoneally, and this treatment was continued for 30 days at a dose of 10 mg/kg per day. Animals in group IV and group V which were thermal injury groups were subjected to right thermal testicular injury with injection of boiling normal saline. After that, animals in group V were also treated with zinc aspartate as described in group III. Group VI was used as a sham group. After 30 days, both testes were removed and examined. Damage in ipsilateral testes was evaluated with histological scoring methods. Contralateral testes were evaluated with measurement of tubular diameter and percentage of spermatogenesis histologically. Ipsilateral testes from non-treated groups had much greater histological injury than treated groups (p>0.05). Additionally, contralateral testes had no evidence of injury. As a consequence, after acute testicular injury that takes form in a variety of ways, immediate administration of zinc aspartate and its continuation for some period may prevent the progression of the injury and improves the healing process.     

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??Objective??To analyze the clinical features and the results of genetic diagnosis in children with hypokalemic renal tubular diseases. Methods??The clinical data of 38 patients with hypokalemic renal tubular diseases were analyzed retrospectively??who were treated in Children’s Hospital Affiliated to Shanghai Jiao Tong University from Jan. 2010 to Jan. 2016. Results??Totally 38 patients with hypokalemic renal tubular diseases were enrolled in this study. There were 18 cases of renal tubular acidosis??RTA?? including 17 cases of type??RTA and 1 case of type?? RTA. There were 11 cases of Bartter syndrome??5 cases of Gitelman syndrome and 4 cases of Fanconi syndrome. The common clinical manifestations of hypokalemic renal tubular diseases included myasthenia??nausea??vomiting??polydipsia??polyurine and growth retardation. One case of Fanconi syndrome progressed to chronic Kidney disease??phase ????while the other
children had normal renal function. Glomerular proteinuria was found in 1??1 and 3 children with Bartter syndrome??Gitelman syndrome and Fanconi syndrome??respectively. Additionally??1 case with Fanconi syndrome has tubular proteinuria. However??urinary trace proteins associated with glomerular and tubular injury commonly elevated in these hypokalemic renal tubular diseases. Genetic analysis showed a new potential heterozygous mutations of ATPV0A4 in type??RTA and three heterozygous mutations of SLC12A3 in Gitelman syndrome. Conclusion??The clinical symptoms vary in patients and are featured mainly by myasthenia??nausea??vomiting??polydipsia??polyurine and growth retardation. Glomerular and tubular injuries are commonly found in hypokalemic renal tubular diseases. Moreover??genetic diagnosis may be helpful in diagnosis??treatment and genetic counseling.     

Effect of dietary treatment on the renal tubular function in a patient with hereditary tyrosinemia

In a 1 1/2-month-old girl with hereditary tyrosinemia, renal tubular function studies were done. The effect of a low tyrosine and phenylalanine formula on renal tubular functions was also studied. The tubular handling of phosphorus, uric acid, beta 2-microglobulin, and amino acids was disturbed. Low urinary osmolality was also seen. Creatinine clearance was increased during a period of the standard formula. Although treatment with the low tyrosine and phenylalanine diet produces dramatic improvement in plasma tyrosine and tyrosyluria, all tubular symptoms did not revert to normal. It is possible that tubular dysfunction of hereditary tyrosinemia may be irreversible changes.     

Renal tubular disorders

Renal tubular disorders in childhood are rare, but, when present, may produce profound electrolyte and volume disturbances. Children with hereditary tubular dysfunction commonly present in the first year of life with failure to thrive and other non-specific symptoms. Biochemical analysis of both serum and urine, together with clinical history and examination, remain fundamental for their diagnosis, whilst localization of the renal tubular defect to the proximal or distal nephron is necessary for understanding of the underlying pathophysiology and appropriate management. During recent years, important new information concerning diagnosis and treatment of selective tubular disorders has been acquired.     

Thalassemia B with distal renal tubular acidosis: a previously undescribed association

An infant with beta thalassemia major and distal renal tubular acidosis is described. Screening of forty patients with beta thalassemia major revealed no evidence of renal tubular acidosis. Although the possibility of coincidence cannot be completely excluded, we suggest that beta thalassemia major should be added to the list of conditions associated with distal renal tubular acidosis.     

Medullary sponge kidney associated with distal renal tubular acidosis in a 5-year-old girl

Introduction Medullary sponge kidney (MSK) is characterized by cystic dilatation of the inner medullary collecting ducts, which causes the kidneys to resemble a sponge.Case report Although distal renal tubular acidosis (dRTA) is commonly observed in patients with MSK, we report a 5-year-old girl with MSK who had features of both dRTA (nephrocalcinosis, hypercalciuria, hypocitraturia) and proximal tubular dysfunction (hyperuricosuria, impaired tubular phosphate reabsorption and proteinuria).Discussion Metabolic acidosis, hypercalciuria, hypocitraturia, tubular phosphate reabsorption and growth retardation in the patient improved with alkali therapy.     

Renal cell carcinoma in children: A single institution's experience

Seven patients with renal cell carcinomas (RCC) were treated at the Department of Pediatric Oncology in Prague over a period of 15 years. The average age at diagnosis was 8 years 9 months. Histology review showed five tumors to be of clear cell type with mixed tubular, papillary, and solid patterns; one tumor was purely papillary, eosinophilic type and one was composed of clear and eosinophilic cells. Five patients received chemotherapy and four of them also received radiotherapy. Four patients are without evidence of disease with a minimal follow-up period of 2 years. These four were all clinical stage I or II. Two stage III patients died of metastatic disease. One patient died of tumor emboli to the lungs at operation. Tumor diagnosis and treatment of the patients in the lower clinical stages seem to have a favorable prognostic impact in childhood RCC. Combined chemotherapy with vinblastine as one of the agents, and possibly additional immunotherapy, appears to have promising results, although the number of patients treated thus far is limited. © Wiley-Liss, Inc.     

Renal tubular acidosis and nerve deafness.

Two brothers are described with renal tubular acidosis and nerve deafness: the elder also had rickets and hypokalaemia. The parents were unaffected. Studies of urinary acidification and bicarbonate excretion were consistent with a distal tubular abnormality. This report strengthens the view previously proposed in similar cases that nerve deafness and renal tubular acidosis constitute a genetic entity. Examination for nerve deafness is indicated in any child with renal tubular acidosis.     

Renal Tubular Acidosis in a Case of Shwachman's Syndrome

ABSTRACT. We describe metabolic acidosis in a 15-month-old girl with clinical features of Shwachman's syndrome. Renal function tests indicated that the patient had type 1 renal tubular acidosis. Based on our findings and other reports of renal tubular dysfunction in patients with Shwachman's syndrome, we conclude that it is important to look for a possible renal tubular defect in this syndrome.     

毒胡萝卜素诱导肾小管上皮细胞内质网应激后中性粒细胞明胶酶相关脂质运载蛋白的变化

目的 观察毒胡萝卜素引起肾小管上皮细胞内质网应激后中性粒细胞明胶酶相关脂质运载蛋白(neutrophil gelatinase associated lipocalin,NGAL)的改变及意义.方法 使用毒胡萝卜素构建人肾小管上皮细胞内质网应激模型,免疫印迹法检测模型中内质网应激蛋白CHOP、GRP78表达水平,验证模型构建情况.Western-blot检测实验组(毒胡萝素组)与对照组(正常肾小管上皮细胞)中NGAL蛋白的表达情况.结果 毒胡萝卜素的最佳给药浓度分别为2.5 μmol/L和5rnol/L,分别作用4h和8h.与毒胡萝卜素作用4h比较,作用8h后细胞中内质网应激指标CHOP和GRP78蛋白的表达量显著增加(0.785±0.049比0.585±0.045),(0.728±0.064比0.523±0.030),差异有统计学意义(P＜0.05).与毒胡萝卜素作用4h细胞中NGAL蛋白的表达量比较,作用8h后表达量显著增加(0.826±0.057比0.567±0.024),并随着内质网应激的加重增加得更为明显(P＜0.05).结论 用毒胡萝卜素诱导正常人肾小管上皮细胞,能够出现内质网应激现象,可引起CHOP、GRP78和NGAL表达增加.随着内质网应激的加重,NGAL增加得更为明显.在内质网发生应激时NGAL表达增加,两者可能存在相关性.     

Renal tubular acidosis: diagnostic work-up,treatment and mechanisms of growth retardation

Astute clinical observations, careful evaluation of laboratory results, together with research aimed at understanding the mechanisms of growth failure in children with the various types of renal tubular acidosis, have led to a more cogent approach to the management of children with renal tubular acidosis. This review examines the different clinical presentations of renal tubular acidosis, the diagnostic workup, the recent advances in our understanding of the mechanisms of growth failure and current therapeutic modalities.     

Antioxidant defense mechanisms of endothelial cells and renal tubular epithelial cells in vitro: role of the glutathione redox cycle and catalase.

We recently demonstrated that endothelial cells are more susceptible than renal tubular epithelial cells to oxidant injury and that renal tubular epithelial cells with proximal tubular characteristics including porcine proximal tubular epithelial cells, opossum kidney proximal tubular epithelial cells, and normal human kidney cortical epithelial cells are more susceptible to oxidant injury than the distal nephron-derived Madin Darby canine kidney cell line. To determine the basis of this differential response, we evaluated several antioxidant defenses in the five cell lines. Glutathione levels were not significantly different among the five cell lines, but catalase and glutathione reductase levels were significantly (p less than 0.01) lower in endothelial cells compared to all renal tubular epithelial cells. Among renal tubular epithelial cells, Madin Darby canine kidney cells had significantly (p less than 0.05) higher glutathione peroxidase activity. To further evaluate the role of antioxidant defenses in limiting oxidant injury, we determined two responses to oxidant injury (ATP depletion and 51Cr release) when glutathione was depleted with buthionine sulfoxamine and when catalase was inhibited with aminotriazole. Oxidant-induced ATP depletion was accentuated when catalase was inhibited as well as when glutathione was depleted with buthionine sulfoxamine. In contrast, inhibition of catalase had little or no effect on 51Cr release, whereas glutathione depletion resulted in accentuated 51Cr release. We conclude that the increased susceptibility of endothelial cells to oxidant injury as compared with epithelial cells is associated with lower antioxidant defenses. Disruption of the glutathione redox cycle results in accentuated ATP depletion and lytic injury, whereas inhibition of catalase results in accentuated ATP depletion with little effect on lytic injury.(ABSTRACT TRUNCATED AT 250 WORDS)     

Renal tubular acidosis in a case of Shwachman's syndrome

We describe metabolic acidosis in a 15-month-old girl with clinical features of Shwachman's syndrome. Renal function tests indicated that the patient had type 1 renal tubular acidosis. Based on our findings and other reports of renal tubular dysfunction in patients with Shwachman's syndrome, we conclude that it is important to look for a possible renal tubular defect in this syndrome.     

PROXIMAL RENAL TUBULAR ACIDOSIS IN VITAMIN D DEFICIENCY RICKETS

An 8-month-old girl presented with classical vitamin D deficiency rickets, secondary hyper-parathyroidism and hyperchloraemic acidosis. Renal acidification and bicarbonate titration studies showed the patient to have a proximal renal tubular acidosis. Rickets, secondary hy-perparathyroidism and proximal tubular acidosis were corrected by administration of calcium and vitamin D. A causal relationship between hyperparathyroidism and renal proximal tubular acidosis is suggested.     

Renal tubular dysfunction in methylmalonic acidaemia

Renal tubular function was assessed in seven patients with methylmalonic acidaemia not responsive to vitamin B₁₂. Five patients failed to concentrate their urine normally and in these patients the glomerular filtration rate was also reduced. Fractional excretion of sodium was increased in four patients, fractional excretion of potassium in one patient and in three there was a decreased tubular reabsorption of phosphate. Although possibly representing primary tubular damage these findings were thought to be consistent with adaptive changes secondary to the reduced glomerular filtration rate. Two patients had evidence of a defect of urinary acidification and several had a degree of hyporeninaemic hypoaldosteronism suggesting type 4 renal tubular acidosis. In one patient with a mild variant no renal disease was detected. Decreased renal function and tubular abnormalities were common in patients with methylmalonic acidaemia. It is likely that they are linked and essentially secondary to the tubulo-interstitial nephritis that is histologically demonstrable on renal biopsy. The failure of urinary concentrating ability and the disturbed urine acidification will contribute to the metabolic derangement during episodes of decompensation.