Hereditary Hydronephrosis Research Articles

DEVELOPMENTAL RENAL PATHOLOGY: ITS PAST, PRESENT, AND FUTURE

Congenital anomalies of the kidney and urinary tract are responsible for approximately 40% of cases of childhood end-stage renal failure in the United States. This article describes the spectrum of developmental renal lesions in children (including renal agenesis, dysplasias, hereditary hydronephrosis, autosomal recessive and dominant polycystic kidneys, vesicoureteral reflux, diabetic embryopathy, some teratogenic drugs affecting renal development, and syndromes associated with renal dysplasias). The article quotes some historic references that established the foundation for further studies; reviews the embryology, pathology, postnatal renal development, and its possible consequences of renal function; as well as recent advances in fetal ultrasonography and molecular biology with some novel treatment and diagnostic modalities. Finally, an attempt is made to predict several future avenues in pharmacogenetics that are being built currently and that will allow a better prognosis for many children with congenital renal conditions.

Further evidence of genetic heterogeneity in hereditary hydronephrosis.

Hereditary hydronephrosis is a rare condition but several families are described in the literature. The inheritance pattern is autosomal dominant (McKusick number 143400) but the exact aetiology of the hydronephrosis is not clear. However, linkage with the HLA region on chromosome six has been shown previously. We report a family not showing linkage to this region, giving further evidence of genetic heterogeneity in this condition.

Structure, Sequence, and Chromosome 19 Localization of HumanUSF2and Its Rearrangement in a Patient with Multicystic Renal Dysplasia

The precise etiology of hydronephrosis caused by pelvi-ureteric junction obstruction is not yet known but there is convincing evidence for a genetic cause, with linkage analysis predicting a hereditary hydronephrosis locus on chromosome 6p. In previous studies, a patient was described with ade novoautosomal t(6;19)(p21;q13.1) translocation and suffering from bilateral multicystic renal dysplasia (MRD) caused by a bilateral complete pelvi-ureteric junction obstruction. In an effort to elucidate a possible correlation between this translocation and hereditary hydronephrosis, we have carried out an extensive molecular characterization of a chromosome 19 cosmid clone previously identified as spanning the translocation in this unique index case. DNA sequencing across a 9.2-kbBamHI fragment that straddles the translocation indicates the presence of DNA sequences with a high degree of similarity to theUSF2gene that encodes the transcription factor USF2 (upstream stimulator factor 2). The genomic structure ofUSF2consists of 10 exons distributed over a DNA region of about 11 kb. The putative promoter region is GC-rich and lacks TATA and CCAAT boxes, suggesting that expression of theUSF2gene may be controlled by a typical housekeeping gene promoter. The chromosome 19 breakpoint in the MRD patient appeared to have occurred in intron 7 of theUSF2gene. Northern blot analysis of a variety of human tissues revealed that theUSF2gene is ubiquitously expressed. Furthermore, Northern blot and 3′-RACE analysis of mRNA isolated from lung fibroblasts of the MRD patient failed to detect a fusion transcript involvingUSF2sequences, suggesting gene disruption rather than the generation of a fusion gene as a possible underlying mechanism.

Hereditary hydronephrosis and the short arm of chromosome 6

Hereditary hydronephrosis and the short arm of chromosome 6

Evidence for genetic heterogeneity in hereditary hydronephrosis caused by pelvi-ureteric junction obstruction, with one locus assigned to chromosome 6p.

Hereditary hydronephrosis (MIM 143400) is an autosomal dominant trait that causes unilateral or bilateral pelvi-ureteric junction (PUJ) obstruction. Linkage analysis was undertaken in 5 families with hereditary PUJ obstruction using the major histocompatibility complex locus as a test marker. The data as a whole supported a hereditary hydronephrosis locus on 6p. Maximal lod scores were 3.090 at a recombination fraction of 0.1 with full penetrance, and 2.486 at a recombination fraction of 0.1 with a penetrance of 90%. However, analysis of two point lod scores using the HOMOG program revealed significant evidence for genetic heterogeneity with one locus on 6p in 4 of the families, and a different locus in one family. After exclusion of this unlinked family, two point analysis gave a maximal lod score of 3.9 at a recombination fraction of 0.05 with full penetrance, and 4.2 at a recombination fraction of 0.0 with 90% penetrance. These data support the assignment of one of the loci for hereditary hydronephrosis to chromosome 6p.

Genuine Hereditary Hydronephrosis in a Three-Generation Family Clinicopathological and Genetic Implications with a Review of the Literature

The clinical features and management of genuine hereditary hydronephrosis (GHH) in 4 members of the same family are presented. Genealogical studies provide evidence of a dominant autosomal inheritance with complete penetrance. All affected members of the family had inherited the same HLA haplotype through the male line. This finding, added to those from previous association studies with histocompatibility typing (in 3 families), lends support to the localization of the GHH gene/s in the 6p human chromosome. Based on our findings from the present familial study and on a review of the literature, we suggest that all first-degree relatives of children or adults with genuine hydronephrosis should be screened by ultrasound. Such a prospective screening, including fetal echography, will lead to earlier diagnosis and treatment of asymptomatic cases and, moreover, will identify GHH cases for possible genetic counseling with regard to the empiric recurrence risk.

Male hypogonadism as a candidate of deficiency of postnatal testicular growth or differentiating factor(s): a new autosomal recessive mutation in the rat.

A new rat mutant showing severe male hypogonadism (hgn for the gene symbol) was found and isolated from the hereditary hydronephrosis rat strain originating from the Wistar-Imamichi rat. The affected rats have very tiny testes that weigh 26 mg in the adult, and contain small numbers of seminiferous tubules with degenerated Sertoli cells. It is difficult to identify the gonocyte in the seminiferous tubules in the mutant testis. Very small male accessory sex organs are all present in the mutant. The number of chromosomes is 42 (40A + XY). The structure of each chromosome is normal, showing that the mutant has male sex genes. Thus, it was considered that this status is not due to either lack of the H-Y antigen or Muellerian inhibiting factor or expression of the Tfm. By analyzing the pedigree of the matings producing the mutant, it was concluded that the status was expressed only in the male, but inherited with a single autosomal recessive trait with existence of the phenotypically normal fertile female recessive homozygote. A possible deficiency of certain known or unknown testicular growth or differentiating factor(s) in the mutant is suggested.

Influence of testosterone on hydronephrosis in the inbred mouse strain DDD.

Hereditary hydronephrosis was detected in all of the male mice of DDD inbred strain maintained at the National Institute of Animal Health Japan, but in only a few of the females. From the standpoint that male hormones are related to the development of hydronephrosis in this strain, the incidence and severity of the disease were investigated in gonadectomized mice treated with testosterone. In the males, the incidence of hydronephrosis was 50% (7/14) in the control (gonadectomized) group, and 73.3% (11/15), 100% (13/13) and 100% (12/12) in the 0.1 mg, 3.3 mg and 10 mg treatment groups respectively. The same tendency was observed in the female animals, though the incidence in each group was not so high. In both sexes the degree of severity increased in proportion to the dose of testosterone administrated. Blood testosterone levels were higher in intact DDD mice than in C57BL/6 mice, which had normal kidneys in both sexes. These results suggest that male hormones play a significant role in the development of hydronephrosis.

The Effect of Aspirin on Erythropoietin Formation in the Rat

SummaryThe effect of aspirin on Epo formation was studied in normal Wistar rats and rats with hereditary hydronephrosis in which, due to renomedullary damage, PGs synthesis by the kidney is supposedly diminished. The obtained results show that, in Wistar rats exposed to a hypoxic stimulus, aspirin effectively diminishes Epo formation, presumably by inhibiting PGs synthesis. Under the same conditions aspirin failed to abolish Epo production in rats with hereditary hydronephrosis. No difference in Epo formation was found between control Wistar and control hydronephrotic rats when exposed to a hypoxic stimulus. The presented results indicate that renal PGs are a contributory factor in the mechanism of hypoxia-induced Epo production, rather than the controlling one.

The mechanism of renomedullary antihypertensive action: haemodynamic studies in hydronephrotic rats with one-kidney renal-clip hypertension.

1. The protective action of the renal medulla was studied in one-kidney renal-clip hypertension in rats with unilateral hereditary hydronephrosis and almost complete atrophy of the medulla of the affected kidney. 2. Rats were unilaterally nephrectomized. The first group had a normal kidney remaining, and the animals from the second and third groups were left with a hydronephrotic kidney and received renomedullary and renocortical autotransplants respectively. Two weeks later all rats were made hypertensive by placing a silver clip (0.2 mm) on the renal artery. 3. From the fourth day after clipping until the end of the experiment blood pressure was found to be significantly (P less than 0.01) lower in rats with medullary transplants than in the other groups. No differences in renal excretory function, plasma volume and plasma renin activity were found between the groups either before or during development of hypertension (5 and 21 days after clipping). Early in the course of hypertension (5 days) cardiac output was significantly (P less than 0.05) lower in the rats with medullary transplants than in the other groups, although an increase in plasma volume was noted in all three groups. At that time no difference in total peripheral resistance was found between the groups. 4. The results are consistent with the hypothesis that the renomedullary antihypertensive substance(s) mitigates hypertension by preventing a hypertensive haemodynamic response to sodium/volume overload.

The renin-angiotensin system in rats with hereditary hydronephrosis

The renin-angotensin system was studied in rats suffering from hereditary hydronephrosis in which normal blood pressure, hyperkalemia, and damage to the renal medulla and distal tubules were found. An increased serum creatinine level, decreased creatinine clearance and increased 24 hrs urine volume were observed in rats with bilateral hydronephrosis. When compared to rats with normal kidneys, bilaterally hydronephrotic animals exhibited elevated plasma renin activity (9.9 +/- 1.3/S.E./ng AI/ml/hr vs. 2.4 +/- 0.4 in rats with normal kidneys), and decreased renal renin concentration (78 +/- 4 mug AII/g vs. 132 +/- 5). No correlation between the extent of kidney damage and renal renic concentration was found. After the hyperkalemia of the hydronephrotic rats was corrected, there were significant increases in both plasma renin activity and renal renin concentration, but the renal renin concentration remained significantly lower than that observed in animals with normal kidneys. The results suggest that renin production and/or storage capacity are diminished in hydronephrotic kidneys.

Genetic aspects of hydronephrosis associated with renal agenesis.

SummaryTwo families with hereditary hydronephrosis are reported and a further 4 families form the literature reviewed. In these families the condition may be unilateral or bilateral, and if unilateral, is more common on the left side.Hereditary pelvi‐ureteric obstruction is due to an autosomal dominant gene with variable penetrance. Evidence from animal studies relating to the pathogenesis of pelvi‐ureteric obstruction is discussed.It is suggested that the mild form of the condition may have more clinical significance than has been previously realised. The association of renal agenesis and hereditary hydronephrosis is also noted.

Unilateral Hereditary Hydronephrosis: A Report of Four Cases in Three Consecutive Generations

Unilateral Hereditary Hydronephrosis: A Report of Four Cases in Three Consecutive Generations

Hereditary unilateral hydronephrosis.

Case Reports1 November 1954HEREDITARY UNILATERAL HYDRONEPHROSISJ. FLOYD CANNON, M.D.J. FLOYD CANNON, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-41-5-1054 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptThe etiologic factors involved in cases of unilateral hydronephrosis are usually manifest from the results of a complete urologic study; however, there remains a group in which the etiology remains obscure. The two most common factors in the production of unilateral hydronephrosis, accounting for about 85 per cent of the cases, are calculi and ureteral constriction. Less common causes are stricture of the pelvis, ectopic kidney and aberrant vessels. Heredity has not previously been considered an etiologic factor. The hereditary factor present in the cases here reported indicates that this etiology should be considered when other causes are not discovered.... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Salt Lake City, Utah*Received for publication January 29, 1954. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byDominantly inherited ureteropelvic junction obstructionFamilial Pelviureteric Junction Hydronephrosis and its Association with a Duplex Pelvicaliceal System and Vesicoureteric Reflux. A Family StudyPrimary megaureter in a mother and daughterUreteropelvic Junction Obstruction: Its Occurrence in 3 Members of a Single FamilyUnique ureteropelvic junction obstruction in father and daughterGenetic Aspects of Hydronephrosis Associated with Renal AgenesisFamilial hydronephrosisÜber die (aseptische) HarnstauungsniereThe Hereditary Renal DiseasesUropoietic SystemThe spectrum of hereditary renal diseasesUnilateral Hereditary Hydronephrosis: A Report of Four Cases in Three Consecutive GenerationsDie Entleerungsstörungen der oberen HarnwegeCurrent pediatric references 1 November 1954Volume 41, Issue 5Page: 1054-1060KeywordsEtiologyHeredityKidneysPelvis ePublished: 1 December 2008 Issue Published: 1 November 1954 PDF downloadLoading ...