Insulin-like growth factor-1 expression in reflux nephropathy

Background Reflux nephropathy (RN) is recognised as a major cause of end-stage renal failure in children and young adults. Insulin-like growth factor-1 (IGF-1), a peptide growth factor produced by collecting ducts, and its receptor, insulin-like growth factor-1 receptor (IGF-1R), are present in the glomeruli and basolateral membrane of renal proximal tubular cells. Exogenous IGF-1 has been shown to enhance proliferation and reduce apoptosis of tubular cells following renal injury.Methods We designed this study to investigate the expression of IGF-1 in RN. The kidney specimens from 15 children with RN were obtained at the time of nephrectomy. Control material included normal kidney specimens obtained from adult patients during partial nephrectomy for an incidentaloma. Single-label immunofluorescence histochemistry was carried out using polyclonal antibodies to IGF-1 and IGF-1R employing laser scanning confocal microscopy. Double-label immunofluorescence histochemistry was carried out using monoclonal antibodies to vimentin and clusterin to assess tubulointerstitial fibrosis. IGF-1 and IGF-1R gene expression were evaluated by in situ hybridisation (ISH). The TUNEL method was utilised to assess tubular apoptosis.Results In the normal kidney there was strong IGF-1 and IGF-1R immunoreactivity in the proximal tubules, whereas IGF-1 and IGF-1R immunoreactivity was markedly reduced in RN specimens. Strong IGF-1 and IGF-1R mRNA expression was observed in the proximal tubules in normal kidneys, whereas IGF-1 and IGF-1R mRNA expression was undetectable in RN. Renal tubulointerstitial expression of vimentin and clusterin was markedly increased in RN kidneys. Decreased IGF-1 and IGF-1R expression in RN strongly correlated with severity of tubular apoptosis in RN compared with controls.Conclusion These data suggest that the downregulation of IGF-1 and IGF-1R may play an important role in the pathogenesis of RN, at least in part by increasing interstitial collagen deposition and tubular apoptosis.     

内毒素血症对新生鼠脑一氧化氮合酶表达的影响

目的　在脑的正常发育及一些病理条件下 ,一氧化氮合酶 (NOS)发挥一定作用 ,但不同亚型的NOS作用不同。该研究观察正常新生鼠脑以及内毒素血症时新生鼠脑 3种一氧化氮合酶 (NOS)亚型蛋白的表达 ,并探讨脂多糖 (LPS)和地塞米松 (DXM)对其表达的影响。方法　生后健康 7日龄Wistar大鼠 6 8只 ,随机分为对照组、内毒素血症组 (腹腔内注射E .coliLPS 5mg kg)及DXM组 (LPS 5mg kg +DXM 10mg kg) ,分别于用药后2 ,4 ,6 ,2 4h取脑进行NOS免疫组织化学染色。结果　正常对照组新生大鼠脑神经元型NOS(nNOS)明显表达 ,内皮型NOS(eNOS)微弱表达 ,诱导型NOS(iNOS)无表达。LPS腹腔注射后 4hnNOS表达开始增加 ;eNOS及iNOS表达于 6h开始增加 ,3者表达均于 2 4h时达高峰 ;3种NOS表达阳性细胞主要分布于脑皮质、海马、下丘脑、脑室旁核团、纹状体神经细胞。除此之外 ,nNOS在梨状皮质有较强表达 ,eNOS及iNOS在血管内皮细胞呈微弱表达。3种NOS亚型蛋白表达在DXM注射后 2～ 6h受到明显抑制 ,并持续至用药后 2 4h。结论　正常新生鼠脑表达nNOS及eNOS ,无iNOS表达 ;LPS诱导 3种NOS亚型的表达 ,其表达的部位及受诱导表达的程度亦不同 ,提示NOS在中枢神经系统的正常发育及LPS诱导的内毒素血症脑损伤发病中发挥一定作用 ,DXM具有神     

Nitric oxide synthase gene polymorphisms in children with minimal change nephrotic syndrome

Aims:  Nitric oxide (NO) attenuates many functions within the kidney, and all NO synthase (NOS) isoforms are constitutively expressed in the kidney. But the exact role of NO in renal diseases is still debatable. The aim of the present study was to investigate endothelial ( eNOS ), and neuronal ( nNOS ) NOS gene polymorphisms in children with minimal change nephrotic syndrome (MCNS).
Materials and methods:  Eighty-six Turkish children with clinical MCNS, ranging in age from 2 to 10 years, were compared with 114 healthy age- and sex-matched controls. The glu 298 Asp (G/T) polymorphism of the eNOS, and C276T (C/T) polymorphism of nNOS genes were genotyped using polymerase chain reaction.
Results:  The distribution of GG, TG, and TT genotypes for eNOS was 52%, 33% and 15% in MCNS compared with 61%, 26% and 13% in the controls ( P  > 0.05). The distribution of CC, TC, and TT genotypes for nNOS was 16%, 66% and 18% in MCNS compared with 10%, 43% and 47% in the controls. TT genotype distribution of nNOS was found to be lower in patients ( P  = 0.003). The eNOS and nNOS gene polymorphisms were not associated with gender, positive family history, frequency of relapses, or response to steroid.
Conclusions:  The present study is the first to investigate eNOS and nNOS gene polymorphisms in children with MCNS. The nNOS gene polymorphism may be associated with MCNS in children, but further studies in a larger population with different glomerular diseases are needed to confirm the results.     

内毒素诱导新生大鼠肾脏损害及地塞米松的干预作用

目的：探讨新生大鼠内毒素血症时肾脏损害的部分机制及地塞米松(Dex)的干预作用。方法：取7日 Wistar大鼠150只,随机分为A组(对照组)：等体积生理盐水腹腔注射;B组(LPS组)：内毒素(LPS)5 mg/kg腹腔注射制成内毒素血症模型;C组(治疗组)：LPS 5 mg/kg+Dex 5 mg/kg共同腹腔注射。各组于注射前(0 h)及注射后2,4,6,24 h分别断头处死留取肾脏。肾组织一氧化氮(NO)采用硝酸还原酶法测定,肾组织一氧化氮合酶(NOS)采用底物催化法测定,通过电镜观察肾脏超微结构变化。结果：①B组NO于2 h高于A组同时间点NO浓度(1.69±0.44 nmol/mg vs 1.20±0.36 nmol/mg),差异有显著性(P<0.05)。于24 h为同时间点A组的 2.3倍(3.12±0.41 nmol/mg vs 1.35±0.38 nmol/mg),差异有显著性(P<0.01);C组NO也于2 h明显高于A组同时间点NO浓度(1.63±0.27 nmol/mg vs 1.20±0.36 nmol/mg),(P<0.05),但于24 h升高程度低于B组(2.10±0.27 nmol/mg vs 3.12±0.41 nmol/mg) (P<0.05);②B组肾NOS于2 h明显高于A组同时间点NOS浓度(0.47±0.15 U/ml vs 0.38±0.12 U/ml) (P<0.05),于4 h短暂下降后于24 h明显高于同时间点A组NOS浓度(0.65±0.27 U/ml vs 0.38±0.15 U/ml) (P<0.05);C组NOS浓度自6 h逐渐升高,至24 h均明显低于B组 0.51±0.07 U/ml vs 0.65±0.27 U/ml) (P<0.05);③电镜下A组肾小球基底膜(GBM)完整,上皮细胞足突清晰,肾小管上皮细胞完整,可见刷状缘。B组6 h肾小球GBM完整,部分上皮细胞足突融合,肾小管上皮细胞线粒体空泡变性;24 h肾小球GBM断裂,上皮细胞足突明显融合,系膜细胞线粒体嵴断裂,空泡变性。肾小管上皮细胞线粒体扩张成大泡。C组24 h肾小球GBM基本正常,上皮细胞足突部分轻度融合,系膜细胞内少数线粒体空泡变性,肾小管可见刷状缘。 结论：新生鼠内毒素血症时肾脏NOS产生增加,诱导合成过量的NO参与肾损伤。Dex通过调节肾脏NOS而抑制NO的大量合成,具有肾脏保护作用。     

Microdissection demonstration of the lesion of the endocrine kidney in children

Microdissection of nephrons of kidneys of children showing advanced ischemic tubular atrophy, and removed for control of hypertension, demonstrates marked proximal convoluted tubular atrophy, with formation of multiple small proximal tubular diverticula. These diverticula presumably contribute to the microscopic appearance of large numbers of small tubules lined by low epithelial cells with pale or clear cytoplasm, adjacent to glomeruli in the cortices of kidneys showing ischemic tubular atrophy (endocrine kidney). Segmentation of such atrophic tubules leads to formation of blind segments (microcysts), as demonstrated in this study and by Oliver. The distinctive microscopic appearance of the endocrine kidney, a not infrequent finding in kidneys of children with chronic renal insufficiency who require nephrectomy for control of hypertension, has not hitherto been emphasized in the literature on pediatric renal disease.     

Microdissection Demonstration of the Lesion of the Endocrine Kidney in Children

Microdissection of nephrons of kidneys of children showing advanced ischemic tubular atrophy, and removed for control of hypertension, demonstrates marked proximal convoluted tubular atrophy, with formation of multiple small proximal tubular diverticula. These diverticula presumably contribute to the microscopic appearance of large numbers of small tubules lined by low epithelial cells with pale or clear cytoplasm, adjacent to glomeruli in the cortices of kidneys showing ischemic tubular atrophy (endocrine kidney). Segmentation of such atrophic tubules leads to formation of blind segments (microcysts), as demonstrated in this study and by Oliver.⁸ The distinctive microscopic appearance of the endocrine kidney, a not infrequent finding in kidneys of children with chronic renal insufficiency who require nephrectomy for control of hypertension, has not hitherto been emphasized in the literature on pediatric renal disease.     

Effects of maternal subtotal nephrectomy on the development of the fetal kidney: A morphometric study

The present study was designed to explore if maternal subtotal (5/6) nephrectomy affects the development of fetal rat kidneys using morphometric methods and examining whether there are any apoptotic changes in the fetal kidney. To generate 5/6 nephrectomized model rats, animals underwent 2/3 left nephrectomy on gestation day (GD) 5 and total right nephrectomy on GD 12. The fetal kidneys were examined on GDs 16 and 22. A significant decrease in fetal body weight resulting from maternal 5/6 nephrectomy was observed on GD 16, and a significant decrease in fetal renal weight and fetal body weight caused by maternal nephrectomy was observed on GD 22. Maternal 5/6 nephrectomy induced a significant increase in glomerular number, proximal tubular length, and total proximal tubular volume of fetuses on GD 22. Maternal 5/6 nephrectomy resulted in an increase in the number of apoptotic cells in the metanephric mesenchyme of the kidney on GD 16, and in the collecting tubules on GD 22. These findings suggest that maternal 5/6 nephrectomy stimulates the development of the fetal kidney while suppressing fetal growth.     

Posttranslational activation of endothelial nitric oxide synthase attenuates carbon tetrachloride-induced hepatotoxicity in newborn rats

Nitric Oxide (NO) can be cytotoxic or cytoprotective depending on amount and location of its generation. eNOS is important in modulating blood flow and is allosterically regulated. Inducible NOS (iNOS) tends to produce large quantities of NO leading to cell injury. We studied the role and regulation of NOS in carbon tetrachloride (CCl(4))-induced hepatotoxicity in newborn rats. eNOS was expressed before birth, significantly increased on day of life (DOL) 2 reaching a maximum at DOL-20. iNOS was absent at all ages. CCl(4) treatment resulted in hepatic injury in newborn rats and damage was intensified by co-administration of a general NOS inhibitor. CCl(4) treatment increased eNOS activity without change in mRNA or protein levels. Administration of CCl(4) resulted in an increase in phosphorylation of threonine protein kinase (Akt) and eNOS, associated with an increase in eNOS activity. Administration of wortmannin (phosphatidylinositol 3-kinase, PI3 K, inhibitor) attenuated the phosphorylation of Akt and eNOS and reduced eNOS activity. Co-administration of CCl(4) and wortmannin potentiated the degree of hepatic injury. iNOS was not detectable in CCl(4)-treated rats. This data indicates a protective role for eNOS in CCl(4)-induced hepatotoxicity in newborn rats with protection accomplished by activation of eNOS via posttranslational modification of the PI3 K/Akt signaling pathway.     

Extremely short small bowel induces focal tubulointerstitial fibrosis.

BACKGROUND: Arginine becomes an essential amino acid after massive resection of the small bowel as a result of decreased biosynthesis of citrulline in the remaining small bowel. It is also reported that nitric oxide (NO) is synthesized from l-arginine by NO synthase (NOS), and NO is involved in the regulation of blood flow in the kidney. The authors observed a patient with an extremely short small bowel, showing focal tubulointerstitial fibrosis. The experiment was designed to clarify whether massive small bowel resection (SBR) produces focal tubulointerstitial fibrosis in the kidney. METHODS: An experimental study was performed using 4-week-old rats with 90% proximal SBR either with or without arginine supplementation for 6 weeks after surgery. RESULTS: In rats without arginine supplementation, low plasma levels of citrulline and arginine increased urinary excretion of orotate, and focal tubulointerstitial fibrosis was observed 6 weeks after 90% SBR. The data from plasma amino acid chromatography and increased excretion of urinary orotate suggested the presence of arginine deficiency. The kidney pathology was similar to that of our patient. Rats with arginine supplementation after 90% SBR and pair-fed control rats without 90% SBR showed almost normal glomeruli and tubulointerstitium. CONCLUSIONS: Experimental study strongly suggests that arginine deficiency causes focal tubulointerstitial fibrosis in the kidney after massive SBR.     

Effects of maternal uninephrectomy on the development of fetal rat kidney with special reference to the proliferative activity and epidermal growth factor (EGF).

ABSTRACT Immunolocalization of proliferating cell nuclear antigen (PCNA), epidermal growth factor (EGF) and EGF receptor (EGFR) in the kidney of fetal rats from uninephrectomized mothers were examined. As the index of proliferative activity, PCNA positive cell ratios in glomeruli and proximal tubules were determined. In the fetuses from uninephrectomized mothers and sham-operated mothers, the PCNA positive cells were seen predominantly in the nephrogenic zone of the kidney. On fetal day 22, the PCNA positive cell ratio in the glomerulus of the fetus from uninephrectomized mothers (E fetus) was significantly lower than that in the glomerulus of the fetus from sham-operated ones (C fetus). The proximal tubular cells showed positive reaction to EGF and EGFR antibodies in both fetuses. On fetal day 22, the reactions of the proximal tubules to EGF and EGFR antibodies were stronger in E fetus than in C fetus.
These results indicate that maternal uninephrectomy causes decreased proliferative activity of the glomerulus and increased reactions of the proximal tubules to EGF and EGFR antibodies in fetal rat kidney, suggesting accelerated development of the kidney.     

Immunocytochemical Studies of the Distribution of Alpha and PI Isoforms of Glutathione S-Transferase in Cystic Renal Diseases

We describe immunohistochemical studies of the expression of alpha and pi class glutathione S-transferases (GSTs) in normal fetal kidneys. These define, in greater detail, changes in expression of alpha isoforms in the proximal tubule. At about 36 weeks of gestation expression of alpha isoforms was down-regulated in the distal tubules and collecting ducts while pi was expressed throughout the nephron. Tubular expression of alpha isoforms was restricted to the part adjacent to the glomerulus; cells farthest from the glomerulus were negative. After 40 weeks of gestation, alpha isoforms were expressed along the entire proximal tubule, while pi was restricted to the distal tubule and collecting ducts. GST expression was also studied in multicystic renal dysplasia, autosomal recessive polycystic kidney disease, and autosomal dominant polycystic kidney disease to determine whether the patterns of expression of alpha and pi isoforms allow identification of the origin of the cysts that characterize these diseases. Cysts were lined by epithelia that were strongly positive for alpha and pi isoforms. The epithelia of noncystic nephrons in renal cystic dysplasia demonstrated delayed maturity, suggesting that GST expression was dependent on the stage of development and not length of gestation.     

Developmentally increased cerebrovascular NO in newborn pigs curtails cerebral blood flow autoregulation.

We tested the hypothesis that a reduced ability of the newborn (1-2 d old) to autoregulate cerebral blood flow (CBF) during acute hypertension is contributed by an increased synthesis of nitric oxide (NO) from endothelial (e) and neuronal NO synthase (nNOS). As previously reported, CBF (measured by radiolabeled microsphere technique) in newborn pigs remained constant only between 50 and 90 mm Hg of mean arterial blood pressure. Treatment of newborn pigs with Nomega-monomethyl-L-arginine or specific nNOS inhibitors 7-nitroindazole monosodium, 3-bromo-7-nitroindazole, and 1-(2-trifluoromethylphenyl) imidazole extended the upper limit of CBF autoregulation as seen in saline-treated (control) juvenile (4-6-wk-old) animals. Cerebrovascular production of nitrite (stable NO oxidation product) in vivo was markedly increased during hypertension (mean arterial blood pressure > 90 mm Hg) in newborn but not in the juvenile pigs. Inhibition of NOS with Nomega-monomethyl-L-arginine, 7-nitroindazole monosodium, 3-bromo-7-nitroindazole, or 1-(2-trifluoromethylphenyl) imidazole prevented the hypertension-induced increase in nitrite levels. In addition, eNOS and nNOS protein expression and activity were 2- to 3-fold higher (p < 0.05) in the cerebral microvasculature of newborn than in the tissues of juvenile pigs. It is concluded that during acute hypertension, excess production of NO associated with increased activity of NOS curtails the upper limit of CBF autoregulation in the newborn subject; in addition, nNOS seems to serve a significant role in this important physiologic function.     

一氧化碳对热性惊厥大鼠海马一氧化氮合酶/一氧化氮体系的影响

目的：反复热性惊厥(FS)后血红素氧合酶(HO)/一氧化碳(CO)系统和一氧化氮合酶(nNOS)/一氧化氮(NO)系统上调,但二者相互关系不清。本研究观察HO抑制剂锌原卟啉Ⅸ(ZnPPⅨ)对FS大鼠海马神经元型NOS(nNOS)mRNA和蛋白表达及NO含量的影响,以探讨CO对NOS/NO体系的调节作用。方法：采用热水浴诱导大鼠FS,隔日诱导1次,共诱导10次。发育期大鼠随机分为3组:对照组,FS组,FS+ZnPPⅨ组(均n=16)。分光光度计间接测定血浆CO和NO含量;核酸原位杂交法检测海马nNOSmRNA表达;Westernblot方法检测海马nNOS蛋白含量。结果：反复FS后海马nNOSmRNA和蛋白表达增高。用ZnPPⅨ进行干预后,血浆CO含量下降,海马nNOSmRNA和蛋白表达及血浆NO含量呈现一致性的显著。结论：反复FS时,外源性给予HO抑制剂ZnPPⅨ可可抑制HO/CO系统,降低血浆CO,增加神经元NOS的基因表达及NO含量,提示CO可能下调NOS/NO系统活性。     

高浓度氧对早产鼠肺一氧化氮合酶表达的影响

目的：明确高浓度氧对早产大鼠肺一氧化氮(nitric oxide, NO)合成及一氧化氮合酶(nitric oxide synthase, NOS)表达的影响,以探讨内源性NO在新生儿高氧肺损伤中的作用。方法：3日龄早产鼠随机分为空气组和高氧组,检测实验3 d及7 d时两组肺湿重/干重比值(W/D),肺组织病理学改变,支气管肺泡灌洗液中NO含量及诱导型NOS(iNOS),内皮细胞型NOS(eNOS)在肺内的分布和表达(免疫组织化学方法)。结果：3 d时高氧组表现为急性肺损伤：充血、出血、炎性渗出;7 d时,W/D值高于空气组(5.54±0.41) vs (5.00±0.15),(P<0.05),病理改变依然明显。与空气组相比,暴露3 d及7 d时,高氧组灌洗液中的NO含量(17.06±5.86)和(23.75±4.07) μmol/L较空气组(5.59±2.03)和(7.93±2.33) μmol/L明显上升(P均<0.01)。高氧组肺气道和肺泡上皮细胞、炎症细胞iNOS表达强阳性,强度高于空气组(P<0.01),且高氧7 d组高于3 d组(P<0.01)。与空气组比较,7 d时高氧组气道上皮细胞eNOS表达增加(P<0.05)。结论：高氧可上调早产大鼠肺炎症细胞、上皮细胞NOS的表达,促进NO合成,提示内源性NO介导参与了高氧诱导的肺损伤。     

Abundance of endothelial nitric oxide synthase in newborn intrapulmonary arteries.

A monoclonal antibody to endothelial NOS (eNOS) was used to demonstrate the distribution and density of eNOS in the developing porcine lung. Lung tissue from large white pigs aged from less than 5 minutes to 3 months was immunostained and, using light microscopy, distribution of eNOS was assessed by a semiquantitative scoring system. At all ages eNOS was located on the endothelial cells of pulmonary and bronchial arteries and veins. Immunoreactivity for eNOS was greater in the larger, more proximal pulmonary arteries than at the periphery. In the lung of newborn pigs immunoreactivity for eNOS was present in arteries of all sizes but some showed no positive staining. At 2-3 days of age almost all arteries showed positive immunoreactivity. By 3 months of age the amount of eNOS had decreased and was less than that seen in the newborn. The highest level of eNOS was seen immediately after birth when the pulmonary arteries are dilating. eNOS may therefore play an important part in adaptation to extra-uterine life.     

硫化氢在单侧输尿管梗阻大鼠肾小管间质纤维化中的水平变化及其干预影响

目的：本研究通过构建单侧输尿管梗阻（UUO）诱导肾小管间质纤维化（TIF）大鼠模型,观察硫化氢（H2S）在血浆中的水平变化及两种关键合成酶胱硫醚β-合酶（CBS）、胱硫醚γ-裂解酶（CSE）在梗阻肾中的表达,并探讨H2S在TIF中的作用。方法：构建UUO致TIF大鼠模型,96只Sprague Dawley大鼠随机分为假手术组、模型组、NaHS低剂量治疗组（低剂量组）和NaHS高剂量治疗组（高剂量组）,每组24只。治疗组分别于术后立即腹腔注射NaHS 1.4 μmol/kg和7 μmol/kg,每日两次;假手术组和模型组同时腹腔注射等量生理盐水。各组分别于术后7 d、14 d及21 d随机处死8只大鼠,采用去蛋白法测定血浆H2S含量;梗阻肾组织行苏木精-伊红及Masson染色,观察肾脏病理学变化;免疫组化方法检测梗阻肾组织CBS、CSE蛋白表达;RT-PCR法检测梗阻肾组织CBS mRNA、CSE mRNA的表达。结果：UUO大鼠肾小管间质损伤程度与血浆H2S浓度呈负相关（r=-0.891,P0.05）。结论：H2S 参与UUO致肾小管间质纤维化的发展过程,而且CBS/H2S体系和CSE/H2S体系在TIF中发挥关键作用。外源性补充NaHS可以延缓TIF的进展。     

自发性高血压大鼠主动脉中一氧化氮/一氧化氮合酶体系的变化

目的 探讨自发性高血压大鼠主动脉中一氧化氮(NO)/一氧化氮合酶(NOS)体系的变化.方法 随机选取健康雄性4周龄Wistar大鼠7只和4周龄自发性高血压大鼠7只,分别作为正常对照组及高血压组.4周龄及12周龄时检测二组大鼠血压.8周龄时取2组大鼠主动脉组织,采用硝酸还原酶法测定其NO水平,Western blot法检查其内皮型NOS(eNOS)以及诱导型NOS(iNOS)蛋白水平.用SPSS 13.0软件对数据进行统计学分析.结果 12周龄时高血压组大鼠血压明显高于正常对照组[(24.1±0 5) kPa vs (15.9±0.3) kPa](P<0.05).12周龄时高血压组大鼠主动脉组织中NO水平较正常对照组主动脉中NO水平低[(7.2±1 7) μmol·(g prot)-1 vs (17.1±5.3) μmol·(g prot)-1](P<0.05).12周龄时高血压组大鼠主动脉中eNOS蛋白表达量与正常对照组大鼠比较差异无统计学意义[(0.5±0.2) vs (0.5±0.3)](P>0.05);12周龄时高血压组大鼠主动脉中iNOS蛋白表达量显著低于正常对照组大鼠[(0.9±0.3) vs (1.5±0.5)](P<0.05).结论 自发性高血压大鼠主动脉中NO/NOS体系下调参与高血压的形成过程.     

Labeled Lectin Studies of Renal Tubular Dysgenesis and Renal Tubular Atrophy of Postnatal Renal Ischemia and end-Stage Kidney Disease

Renal tubular dysgenesis (RTD), with hypoplasia especially of renal proximal convoluted tubules and clinical neonatal anuria or oliguria, has been reported as a congenital familial (autosomal recessive) disease, variably with features of oligohydramnios, Potter syndrome, or pulmonary hypoplasia. A similar tubular lesion due to antenatal tubular atrophy has been reported for conjoined twins with twin-twin transfusion syndrome or acardia and in infants of mothers given antihypertensive agents, including angiotensin-converting enzyme (ACE) inhibitors, during pregnancy, and it has been seen as a unilateral lesion in young infants with renal artery stenosis due to arteritis or medial arterial calcinosis. The renal tubular changes in RTD are very like those of the “endocrine kidney” in experimental animals and resemble those of the renal tubular atrophy of end-stage kidney diseases such as glomerulonephritis, tubulointerstitial kidney disease, obstructive uropathy/pyelonephritis, graft rejection of transplanted kidneys, or the renal parenchymal changes seen with protracted dialysis therapy. Labeled lectins that differentially mark proximal convoluted, distal convoluted and connecting, and collecting tubules showed no distinctive differences in stainingpatterns of the hypoplastic renal tubules of infants and children with RTD, postnatal renal artery obstruction, or the various types of end-stage renal disease with the lectins used (PNA, GSL1, UEA, and LTA). The findings suggest that the renal tubular changes in some if not all the conditions studied are the result of renal ischemia. The reported familial RTD with hypernephronic nephromegaly may be a specific disorder, but other forms could reflect renal ischemia acquired in utero or in early or later postnatal life.