Morphometric Studies of Cystic and Tubulointerstitial Kidney Diseases with Hepatic Fibrosis in Children

Portal tract fibrosis with biliary ductular enlargement or proliferation occurs in a number of genetic diseases that have cystic or tubulointerstitial renal lesions. These include some with renal cystic disease such as autosomal recessive diseases (e.g., infantile polycystic disease, juvenile polycystic disease, and Meckel's syndrome), autosomal dominant diseases (e.g., adult polycystic disease), and, rarely, tuberose sclerosis and dominant glomerulocystic disease. Portal tract fibrosis with biliary enlargement and proliferation occurs also with tubulointerstitial kidney diseases. These probably include at least three disorders in the category nephronophthisis-congenital hepatic fibrosis (one autosomal recessive disease and two either autosomal or X-linked recessive diseases) plus Jeune's syndrome (the tubulointerstitial diseases Fanconi's familial nephronophthisis and anti-tubular membrane antibody disease do not regularly cause hepatic fibrosis). Morphometric data on ratios of bile ductules to connective tissue in hepatic portal tracts show high values for infantile polycystic disease (mean, 0.616) compared to lower values for juvenile polycystic disease (mean, 0.286). That the cystic renal lesions of the first two diseases differ in type and time course is known. Similar data on ratios of glomeruli plus tubules to connective tissue in renal cortices and of tubules to connective tissue in outer medullary zones of kidneys, respectively, are as follows: for Fanconi's nephronophthisis, 0.445 and 0.197; for anti-tubular basement membrane antibody disease, 0.585 and 0.164; and for the three types of nephronophthisis-congenital hepatic fibrosis studied, 0.668 and 0.446, 1.39 and 0.921, and 1.18 and 0.12. These data support clinical impressions that the category nephrophthisis-congenital hepatic fibrosis includes more than one disease entity.     

Morphometric studies of cystic and tubulointerstitial kidney diseases with hepatic fibrosis in children

Portal tract fibrosis with biliary ductular enlargement or proliferation occurs in a number of genetic diseases that have cystic or tubulointerstitial renal lesions. These include some with renal cystic disease such as autosomal recessive diseases (e.g., infantile polycystic disease, juvenile polycystic disease, and Meckel's syndrome), autosomal dominant diseases (e.g., adult polycystic disease) and, rarely, tuberose sclerosis and dominant glomerulocystic disease. Portal tract fibrosis with biliary enlargement and proliferation occurs also with tubulointerstitial kidney diseases. These probably include at least three disorders in the category nephronophthisis-congenital hepatic fibrosis (one autosomal recessive disease and two either autosomal or X-linked recessive diseases) plus Jeune's syndrome (the tubulointerstitial diseases Fanconi's familial nephronophthisis and anti-tubular membrane antibody disease do not regularly cause hepatic fibrosis). Morphometric data on ratios of bile ductules to connective tissue in hepatic portal tracts show high values for infantile polycystic disease (mean, 0.616) compared to lower values for juvenile polycystic disease (mean, 0.286). That the cystic renal lesions of the first two diseases differ in type and time course is known. Similar data on ratios of glomeruli plus tubules to connective tissue in renal cortices and of tubules to connective tissue in outer medullary zones of kidneys, respectively, are as follows: for Fanconi's nephronophthisis, 0.445 and 0.197; for anti-tubular basement membrane antibody disease, 0.585 and 0.164; and for the three types of nephronophthisis-congenital hepatic fibrosis studied, 0.668 and 0.446, 1.39 and 0.921, and 1.18 and 0.12. These data support clinical impressions that the category nephrophthisis-congenital hepatic fibrosis includes more than one disease entity.     

Familial Juvenile Nephronophthisis in Two Siblings — Histological Findings at an Early Stage —

We present two female siblings with familial juvenile nephronophthisis (FJN) which was diagnosed at the early stage of renal failure. Diagnosis was made during the investigation of anemia in case 1 and by a subsequent family survey in case 2. Most patients with FJN are not identified until the terminal stage of renal failure and such cases have rarely been reported in Japan. Case 2 had a reduction in the maximum urinary concentration ability but no azotemia, and among the FJN patients reported in Japan so far she has the least advanced renal disease. Histological examination of the renal biopsy in case 1 showed typical findings of FJN, such as thickening and lamination of the tubular basement membrane (TBM), interstitial fibrosis, and round cell infiltration of the interstitium. In case 2, renal biopsy revealed an irregular marked thickening of the TBM with trivial interstitial changes and a normal glomerular appearance. The histology of these two cases suggests that the TBM may be the primary site affected in FJN.     

小儿囊肿性肾病47例

目的探讨小儿囊肿性肾病的常见病因及其临床特点。方法本院1995年1月～2006年12月共收治47例囊肿性肾病患儿。男31例,女16例;诊断时年龄1h～14岁;回顾分析其病因和临床特点。结果遗传性21例（44.68%）。包括常染色体隐性遗传多囊肾病（ARPKD）16例（34.04%）,肾单位肾痨（NPH）5例（10.64%）;发育异常24例（51.07%）。包括髓质海绵肾（MSK）13例（27.66%）,囊肿性肾发育不良（CRD）10例（21.28%）及孤立多房性肾囊肿（SMC）1例（2.13%）;获得性2例（4.25%）,均为单纯性肾囊肿（SRC）。16例ARPKD囊肿分布于皮质和髓质,肾衰竭12例（75%）,肾脏外损害9例（56.25%）。5例NPH囊肿分布于皮髓质交界处,肾衰竭5例（100%）,缺血性视网膜炎致盲1例（20%）。13例MSK囊肿局限于肾锥体,各有3例（23.08%）表现为继发性肾结石、泌尿系感染（UTI）和远端肾小管酸中毒,另2例（15.38%）表现为继发性肾积水,肾衰竭2例（15.38%）与病程长、结石并反复感染有关。10例CRD均为单肾囊性变,表现为腹部包块7例（70%）,宫内诊断5例（50%）。SRC2例和SMC1例均为局灶性肾囊肿,仅表现为腹部包块,手术切除后痊愈。结论小儿囊肿性肾病以遗传性及发育异常性疾病为主,常见病因有ARPKD、NPH、MSK和CRD;ARPKD和NPH为进行性肾衰竭或肾外病变,预后差;MSK和CRD属肾脏发育异常,尽早诊断和治疗,预后好。     

肾间质中单个核细胞浸润与肾脏疾病临床转归的关系

目的：肾小管间质病变程度是肾脏疾病预后的决定因素。该实验研究肾间质中单个核细胞的浸润、肾小管间质病变的程度与肾脏疾病临床转归三者关系,探讨肾间质单个核细胞的浸润在肾脏疾病临床转归中的作用。方法：选择1998年2月至2000年9月因各种原发和继发性肾脏疾病而入院行肾穿刺活检术的患儿共42例,肾组织用CD4+,CD8+,CD68+3种单克隆抗体标记淋巴细胞和单核-巨噬细胞,计算CD4+,CD8+,CD68+在肾间质中浸润的密度,用等级相关分析其与肾小管间质病变程度以及与临床转归的关系。结果：肾间质中CD4+,CD8+,CD68+细胞浸润密度与肾小管间质病变程度呈正相关(rs=0.570, P=0.029;rs=0.368,P=0.009,rs=0.468,P=0.003)。肾小管间质病变程度与临床转归之间呈正相关(rs=0.467, P=0. 001 )。肾间质CD8+,CD68+细胞的浸润密度与临床转归之间也呈正相关(rs=0.398,P=0.004;rs=0.328,P=0. 036)。肾间质中单个核细胞浸润的种类数与临床转归正相关(rs=0.453, P=0. 003)。结论：肾间质单个核细胞浸润的密度和种类数与肾脏疾病预后密切相关。肾小管间质单个核细胞浸润可能促进了肾小管间质的病变,使肾脏疾病预后不良。     

The Renal Lesion of Congenital Hepatic Fibrosis: Pathologic and Morphometry Analysis, with Comparison to the Renal Lesion of Infantile Polycystic Disease

The renal lesion of congenital hepatic fibrosis (CHF = Blyth and Ockenden's juvenile polycystic disease of liver and kidneys) was analyzed from 6 specimens from patients aged 3 3/12 to 19 3/12 years and compared with that of 5 patients with infantile polycystic disease (IPCD) aged 6 months to 14 4/12 years. Pathologic, microdissection, injection, and morphometric studies show that the predominantly medullary cystic lesion of CHF shows different distribution in medullary, cortico-medullary, and cortical zones of kidney from the lesion of IPCD, and shows a different time course, from early life to renal insufficiency, from that of IPCD. The renal cysts in CHF affect deep or central collecting tubules, in contrast to the involvement of more peripheral orders of collecting tubules in IPCD. Papillary pore counts, performed for 1 patient, gave significantly low values, in contrast to normal values reported for IPCD. The findings support the previously published conclusion, based on differences in the hepatic lesions of the two conditions, that CHF and IPCD are difference diseases, rather than different permissible manifestations of a single disease.     

疑难病研究——幼儿Castleman’s病

Castleman's病是一种局限性或系统性血管淋巴滤泡增生性淋巴结病,儿童罕见,其病因和发病机制不明。临床表现为淋巴系病变,伴或不伴有全身症状。临床分为单中心型(UCD)和多中心型(MCD)。病理改变包括透明血管型、浆细胞型和混合型。本病确诊需依据淋巴结病理活检。MCD目前无有效治疗,激素和α-干扰素可能对部分病人有效。UCD进行手术切除或加放疗可获完全缓解。     

Combined True Thymic Hyperplasia and Lymphoid Hyperplasia in Grave's Disease

True thymic hyperplasia (enlarged gland composed of histologically unremarkable cortical and medullary parenchyma) and lymphoid hyperplasia (medullary lymphoid follicles in the clinical setting of autoimmunity) usually develop as independent pathologic processes. We reviewed the clinical features and gross and microscopic pathology of 2 hyperthyroid patients with features of both thymic hyperplasia and lymphoid hyperplasia. The diagnosis of thymic hyperplasia was supported by thymic weights greater than two standard deviations above the mean weight for age and histologic evidence of expanded cortical and medullary parenchyma. The diagnosis of lymphoid hyperplasia was supported by the increased number and size of medullary lymphoid follicles and the association with Grave's disease. This unusual combination results from two separate pathogenic mechanisms operating simultaneously in hyperthyroid patients. Elevated thyroid hormones directly stimulate the proliferation of thymic epithelium, producing thymic hyperplasia. The immune abnormalities underlying Grave's disease can also result in lymphoid hyperplasia of the thymus.     

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.     

激素耐药型和激素依赖型肾病患儿肾脏病理计量分析

目的 探讨病理计量分析评价激素耐药型（SR）和激素依赖型（SD）肾病综合征患儿的肾脏病理损害及其临床应用意义。方法 采用自行研制的评分法,对73例SR型和SD型肾病患儿的肾脏病理从病理类型、肾小球病变、小管间质病变、肾脏总的病理损害4个方面计量分析,并以血尿素氮为应变量,临床表现和肾脏病理计分为自变量进行逐步回归分析。结果 （1）病理类型评分结果：微小病变、局灶节段肾小球硬化、膜性肾病、系膜毛细血管性肾小球肾炎和系膜增生性肾小球肾炎五组间的年龄、病程、复发次数、血尿素氮、胆固醇、白蛋白、尿蛋白定量、肾脏总的病理损害的差异均无显著意义,而五组患儿的肾小球病变计分分别为1,5,5,6,5,微小病变组与其他各组比较差异有显著意义（H＝19．278,P＜0．01）。（2）73例患儿肾小球病变计分结果：正常2例（3％）,轻度53例（73％）,中度17例（23％）,重度1例（1％）。且正常、轻度、中度三组间血尿素氮、小管间质病变的差异有显著意义（H＝8．40,P,0．01;H＝11．56,P＜0．05）。（3）肾小管间质病变计分结果：轻度23例（34％）,中度37例（18％）,且轻、中、重三组间病程、复发次数、血尿素氮、肾小球病变计分的差异均有显著意义。（H值分别为25．016,38．775,14．944,10．625,P值均＜0．01）。（4）肾脏损害的总分结果：轻度33例（45％）,中度34例（7％）,重度6例（8％）,轻、中、重三组间病程、复发次数、血尿素氮的差异有显著意义（H值分别为19．42,14．335,18．923,P值均＜0．01）。（5）以血尿素氮为应变量行逐步回归分析,小管间质及肾小球损害对血尿素氮均有显著影响,小管间质病变的回归系数为0．862（P＜0．01）;肾小球病变的回归系数为0．212（P＜0．05）。结论 采用评分法对肾脏病理进行主分评价其病变程度,具有临床实用性,尤其对小管间质病变的计分评价对判断肾功能受损更有价值。     

Bile Acid Synthetic Defects and Liver Disease: A Comprehensive Review

Bile acid synthetic defects (BASD), uncommon genetic disorders that are responsible for approximately 2% of persistent cholestasis in infants, are reviewed with emphasis on morphology of associated liver disease. The associated liver diseases may be life threatening, and are treatable, usually by replacement of deficient primary bile acids. Specific diagnosis is made by analysis of body fluids (bile, blood, and urine) using fast atom bombardment-mass spectroscopy (FAB-MS) and gas chromatography-mass spectroscopy (GC-MS). Inborn errors have been demonstrated for four single enzymes involved in modification of the sterol nucleus and in five steps in modification of the side-chain to form cholic and chenodeoxycholic acids, the primary bile acids. With few exceptions, BASD cause liver diseases that vary from severe to mild depending on the defect. In three of four known defects of sterol nucleus modification, liver disease is progressive. Progression of liver disease is most rapid when the defect results in accumulation of toxic monohydroxy and unsaturated oxo-bile acids. Liver disease may be transient, delayed in onset and mild. Reduced bile flow caused by atypical bile acids contributes to cholestasis and may be the dominant factor in defects of side-chain synthesis, peroxisomal abiogenesis and S-L-O syndrome. Pathological findings may include intralobular cholestasis with giant cell transformation, prevalence of necrotic hepatocytes including giant cell forms, and hepatitic injury confined to the portal limiting plate where the smallest bile ductules may be injured and where fibrosis typically develops. Interlobular bile ducts are usually spared. Ultrastructure of liver reveals nonspecific changes with the possible exception of unusual canalicular morphology in some defects. The course of BASD may be modified by replacement of deficient primary bile acids, which produces beneficial feedback inhibition of abnormal bile acid production and enhances choluresis. Giant cell transformation is present in all symptomatic infants with BASD and seems to have a more consistent association with BASD than with the many other liver diseases in infants where it occurs. We hypothesize that immature hepatocytes of infants may fuse to form multinucleate hepatocytes whenever atypical or toxic bile acids are present and the pool of normal bile acids is critically reduced. This review was supported by NCRR, NIH grant RR-08084.     

Medullary Cystic Disease and Juvenile Nephronophthisis in Separate Members of the Same Family

The clinical and pathological findings in three sibs dying in renal failure at 9, 15, and 21 years of age respectively are presented. The three sibs showed a similar clinical presentation with an insidious onset of azotaemia without hypertension in association with obligatory dilute urine virtually free of albumin and formed elements. There was renal osteodystrophy in all cases with tertiary hyperparathyroidism in one case.Necropsies were performed on the boy dying at 9 years of age and the girl dying at 21 years of age. In the former the renal histology most closely corresponded to that described in juvenile nephronophthisis while in the latter the appearances were those of medullary cystic disease.We hence affirm that familial juvenile nephronophthisis and medullary cystic disease are basically the same disease and suggest that the development of cysts may be a secondary process, possibly consequent upon interstitial fibrosis and basement membrane thickening, becoming more pronounced with length of survival.The diagnosis in life may be suggested by the familial incidence and characteristic clinical presentation supported by renal biopsy.     

Serum Gliadin Antibodies for Detection and Control of Childhood Coeliac Disease

Serum gliadin antibodies of the IgA and IgG isotypes were determined by means of the diffusion-in-gel enzyme-linked immunosorbent assay (DIG-ELISA) in children during different phases of coeliac disease. Fourteen children were studied before onset of dietary treatment, 16 during a period of gluten-free diet and 16 during gluten challenge. The control groups consisted of 44 children with other gastrointestinal diseases and 14 children without gastrointestinal disorders. All of the children studied had been subjected to small-intestinal biopsy. On the basis of the results obtained in this study the diagnostic sensitivity with regard to untreated coeliac disease was found to be 100 % and the diagnostic specificity 97 %. In 10 coeliac children followed during the phases of diagnostic evaluation antibody levels decreased in all during dietary treatment and increased in 8 during a subsequent gluten challenge. It is suggested that determination of IgA and IgG gliadin antibodies by means of DIG-ELISA may be used as a diagnostic test for coeliac disease in children and that this test may be useful in monitoring the dietary treatment in children with known coeliac disease. Moreover, the DIG-ELISA is an inexpensive and technically simple method     

Outcomes of kidney transplantation in children with nephronophthisis: An analysis of the North American Pediatric Renal Trials and Collaborative Studies (NAPRTCS) Registry

Abstract: NPHP is an autosomal recessive chronic tubulointerstitial nephropathy that progresses to ESRD. In the 2006 NAPRTCS report, NPHP was the primary diagnosis in 2.8% of all renal transplant patients. At our pediatric center, that covers a population in which the NPHP1 gene is prevalent, 24% of transplant recipients had a primary diagnosis of NPHP. Since no previous literature reports have documented kidney transplant outcomes in patients with NPHP, a review of the 2006 NAPRTCS database was performed. The results of this review illustrate that patients with NPHP as their underlying kidney disease have a significantly better overall graft survival when compared with all other patients registered in the NAPRTCS database. Sub‐analysis demonstrated that this benefit is statistically significant only for LD kidney transplant recipients. CrCl was better in NPHP at all time points from transplant up to five‐yr follow‐up. Moreover, in NPHP LD transplant recipients the decline of CrCl over five yr was slower compared with non‐NPHP LD transplant recipients. Rates of thrombosis, acute, and chronic rejection as well as causes of graft failure were similar in NPHP patients and all other patients. This review demonstrates that NPHP transplant recipients have excellent outcomes that are shown to be better compared with the general pediatric transplant population.     

Renal histopathology in Alagille's syndrome

Various renal abnormalities have been reported in Alagille's syndrome (arteriohepatic dysplasia), usually as single case reports. The renal findings at autopsy of four patients with Alagille's syndrome, ranging in age from 4 1/2 months to 7 years, 2 of whom had evidence of renal dysfunction, are described and are compared with kidneys from patients with other cholestatic liver diseases of childhood. Two of the Alagille's patients had histologic findings suggestive of membranous nephropathy and special stains revealed accumulation of lipid in the glomerular and tubular basement membranes. Immunofluorescence of 1 revealed extensive accumulation of IgG and IgM. One patient had medullary cysts and mild interstitial fibrosis, and the fourth had a large subcapsular cyst and mild tubulointerstitial nephritis. All 4 cases, when examined with the electron microscope, revealed varying degrees of basement membrane thickening, splitting, and vacuolation with dense osmiophilic particles, most prominent in the patients with membranous nephropathy. These ultrastructural findings did not correlate with the degree of hyperlipidemia, but rather with the patient's age, and were also observed in other cholestatic diseases. The findings suggest that Alagille's syndrome is frequently associated with renal abnormalities, including lipid deposition, which may in some instances, lead to clinically significant renal impairment.     

Microdissection Study of the Myentric Plexus in Acardia, Ataxia-telangiectasia, Cystic Fibrosis, Extrahepatic Biliary Atresia, Pediatric Aids and Werdnig-Hoffmann Disease

Microdissection-point count morphometric study of the myenteric (Auerbach) plexus or esophagus, small intestine, and colon was done for infants and children with acardia (2), ataxia-telangiectasia (5), cystic fibrosis of the pancreas (CFP) (25), extrahepatic biliary atresia (EBA) (17), pediatric AIDS (10), and Werdnig-Hoffmann disease (WHD) (8). Values for fractional area of neural tissue in the plane of the plexus were compared to those of control patients in same age range as those in each disease category by t-test. Statistically abnormal values included low values for small intestine and colon in Werdnig-Hoffmann disease, high values for small intestine and colon in biliary atresia, and high value for colon but a low value for small intestine in cystic fibrosis. Values for all three loci were within the normal range for ataxia telangiectasia and pediatric AIDS. The mechanisms of the low value for small and large intestines in WHD, which causes chronic constipation as a result of skeletal muscle weakness, and of the high values for colon in CFP and EBA, both causing malabsorption with bulky stools, are unclear. The value for small intestine in acardia was normal for term but lower than expected for fetal bowel of the same size, possibly because of reduced neural crest inflow to the fetal bowel.     

Mortality from group C meningococcal disease: a case for a conjugate vaccine?

This 17-year retrospective review of children with meningococcal disease (MCD) has determined the mortality due to serogroup C, in order to assess the potential impact of a group C conjugate vaccine. Four hundred and forty-nine cases of MCD were admitted to our hospitals during 1977–1993; 78 due to group C, 11 of whom died. There was a significant increase in the proportion of cases due to group C from 1986 onwards (10% vs 21%), and an increase in the total number of cases of MCD (151 vs 298). The currently available group C polysaccharide vaccine has low efficacy below 2 years of age and could not have prevented 54 cases of group C disease. A conjugate group C vaccine administered between 2 and 4 months of age could have prevented 68 cases, including all fatal cases. The recent increase in MCD is partly due to an increase in group C disease. A meningococcal group C conjugate vaccine could prevent most cases of infection due to group C, and decrease the mortality from MCD by up to 30%.     

The pathological spectrum of pediatric kidney disease: 18-Year experience from a single tertiary care center in northern Taiwan

BackgroundGlomerular disease is one of the leading causes of chronic kidney disease in children worldwide. Recent studies outlined the changing spectrum of glomerular disease in certain countries. Therefore, our study aimed to evaluate the histopathological patterns and changes in pediatric kidney disease over the past 18 years in northern Taiwan.MethodsThis was a retrospective chart review study of pediatric patients (≤18 years of age) undergoing percutaneous renal biopsies (PRBs) of native kidneys between January 2002 and July 2020 from a Pediatric Care Center at Chang Gung Memorial Hospital, Taoyuan, Taiwan.ResultsThis study analyzed a total of 339 pediatric native PRBs. The mean age of the subjects was 13.7 ± 7.0 years (184 girls and 155 boys). The most common indications of PRBs included acute nephritic syndrome (55.7%), idiopathic nephrotic syndrome (22.7%), persistent asymptomatic hematuria (13.9%), and unexplained renal failure (7.7%). Our study revealed that proliferative lupus nephritis (LN), minimal change disease (MCD)-related nephrotic syndrome, and IgA nephropathy (IgAN) were the most frequent biopsy-proven pediatric glomerular diseases. In addition, we showed that severe acute post-streptococcal glomerulonephritis (APSGN) was infrequent and has not even been diagnosed since 2010.ConclusionOur result revealed that the spectrum of biopsy-proven pediatric kidney disease has not changed significantly over the past two decades. Furthermore, proliferative LN, MCD, and primary IgAN continue to be the most common histopathological diagnoses among Taiwanese children.     

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.     

Juvenile nephronophthisis associated with new skeletal abnormalities, tapetoretinal degeneration and liver fibrosis

This report concerns a boy presenting renal disease with tubulointerstitial nephropathy which suggests familial juvenile nephronophthisis, hepatosplenomegaly due to congenital hepatic fibrosis, tapetoretinal degeneration, probable endocrine involvement and congenital skeletal abnormalities. The associations presented in this paper have not previously been reported.