Glomerulocystic Disease Research Articles

Hepatocyte Nuclear Factor 1 Beta Mutation-associated Newborn Onset of Glomerulocystic Kidney Disease: A Case Presentation.

Mutations in hepatocyte nuclear factor-1 beta (HNF1B) are the most commonly identified genetic cause of renal malformations. Heterozygous mutations are associated with renal cysts and diabetes syndrome. Various renal developmental abnormalities and maturity-onset diabetes of the young could be the presenting factors of these mutations. A 10-year-old boy who was evaluated for bilateral cystic kidneys and chronic kidney disease from the newborn period was diagnosed with HNF1B-related glomerulocystic disease by DNA sequencing. The differential diagnosis of autosomal dominant polycystic kidney disease was a diagnostic pitfall. The genetic screening of the family revealed his mother, sister, and brother to have the same mutation. Therefore, genetic diagnosis and counseling are important for cystic kidney diseases not only for formulating the diagnosis and early management plan but also for the diagnosis of potential asymptomatic cases in the family.

GATA3 Is a Useful Immunohistochemical Marker to Differentiate Variants of Renal Tubular Lesions from Different Segments of Renal Tubules

Abstract Introduction/Objective GATA3 is found in glomerular mesangial cells, and the distal tubules & collecting ducts in metanephros and eventual kidneys, but not associated with the proximal tubules and loops of Henle. We hypothesize that GATA3 can be used as a marker to identify the origin of tubular differentiation in most renal tumors. Methods/Case Report Ten negative controls and 43 renal mass lesions (RCC, papillary, clear cell papillary, and chromophobe carcinomas, oncocytoma, and polycystic kidney disease). GATA3 nuclear stain was graded as negative (absent stain), equivocal and positive (< 5 and > 5% cells, respectively). Details of their GATA3 nuclear expression was analyzed for identifying their tubular segmental origins. Results (if a Case Study enter NA) In 10 normal renal parenchyma, GATA3 was positive in mesangial cells, distal tubules, and collecting ducts, but was negative in the proximal tubules and loop of Henle. The cystic lining of glomerulocystic renal disease was stained negatively for GATA3 (proximal tubular origin), whereas pediatric and adult variants of polycystic kidney diseases was positive for GATA3 staining (distal tubular origin). 1/10 ten clear cell RCC and papillary RCC showed focal positive GATA3 stain. GATA3 showed weakly positive staining in some oncocytomas (4/11) and some chromophobe RCC (4/11), indicating that they might be derived from the junctional segment between the loop of Henle and the distal tubules. By contrast, all clear cell papillary RCC (distal tubule origin) were diffusely positive. Conclusion Our results indicate that GATA3 is a useful immunohistochemical marker to determine the developmental origin in the specific renal tubular segment for the majority of renal mass lesions. Thus, it may be useful for routine differential diagnosis of these lesions.

Developmental Renal Glomerular Defects at the Origin of Glomerulocystic Disease

The architecture of renal glomeruli is acquired through intricate and still poorly understood developmental steps. In our study we identify a crucial glomerular morphogenetic event in nephrogenesis that drives the remodeling/separation of the prospective vascular pole (the future entrance of the glomerular arterioles) and the urinary pole (the tubular outflow). We demonstrate that this remodeling is genetically programmed. In fact, in mouse and human, the absence of HNF1B impairs the remodeling/separation of the two poles, leading to trapping and constriction of the tubular outflow inside the glomerulus. This aberration gives rise to obstructive glomerular dilations upon the initiation of primary urine production. In this context, we show that pharmacological decrease of glomerular filtration significantly contains cystic expansion. From a developmental point of view, our study discloses a crucial event on glomerular patterning affecting the "inside-outside" fate of the epithelia in the renal glomerulus.

Loss of Zeb2 in mesenchyme-derived nephrons causes primary glomerulocystic disease

Primary glomerulocystic kidney disease is a special form ofrenal cystic disorder characterized by Bowman's space dilatation in the absence of tubular cysts. ZEB2 is a SMAD-interacting transcription factor involved in Mowat-Wilson syndrome, a congenital disorder with an increased risk for kidney anomalies. Here we show that deletion of Zeb2 in mesenchyme-derived nephrons with either Pax2-cre or Six2-cre causes primary glomerulocystic kidney disease without tubular cysts in mice. Glomerulotubular junction analysis revealed many atubular glomeruli in the kidneys ofZeb2 knockout mice, which explains the presence of glomerular cysts in the absence of tubular dilatation. Gene expression analysis showed decreased expression of early proximal tubular markers in the kidneys of Zeb2 knockout mice preceding glomerular cyst formation, suggesting thatdefects in proximal tubule development during early nephrogenesis contribute to the formation of congenital atubular glomeruli. At the molecular level, Zeb2 deletion caused aberrant expression of Pkd1, Hnf1β, and Glis3, threegenes causing glomerular cysts. Thus, Zeb2 regulates the morphogenesis of mesenchyme-derived nephrons andis required for proximal tubule development and glomerulotubular junction formation. Our findings also suggest that ZEB2 might be a novel disease gene in patients with primary glomerular cystic disease.

Renal Lesions in Cetaceans from Brazil

This study reports the occurrence of renal lesions in cetaceans from the coast of Brazil subjected to necropsy examination between 1996 and 2011. The animals (n=192) were by-caught in fishing nets, were found dead on beaches or died despite attempted rehabilitation. Kidney samples were evaluated grossly and microscopically and, depending on the histopathological findings, immunohistochemical and ultrastructural analyses were conducted. Due to autolysis, a diagnosis was reached in only 128 animals, of which 82 (64.1%) had kidney lesions. Cystic renal disease was the most common lesion observed in 34 cases (26.6%) and these were classified as simple cysts in eight cases (6.3%), polycystic kidney disease in one rough-toothed dolphin (Steno bredanensis), secondary glomerulocystic disease in 16 cases (12.5%) and primary glomerulocystic disease in nine cases (7%). Other lesions included membranous glomerulonephritis (28 cases; 21.9%), membranoproliferative glomerulonephritis (20 cases; 15.6%), lymphoplasmacytic interstitial nephritis (21 cases; 16.4%), lipidosis (19 cases; 14.8%), glomerulosclerosis (8 cases; 6.3%) and pyogranulomatous nephritis(five cases; 3.9%); two of the later were associated with the migration of nematode larvae. Additionally, tubular adenoma was identified in a Franciscana (Pontoporia blainvillei). The pathological implications of these lesions are discussed according the cause of death, age or sex of the animals. Furthermore, the lesions were compared with those of other marine and terrestrial mammals, including man.

Selective dicer suppression in the kidney alters GSK3β/β-catenin pathways promoting a glomerulocystic disease.

Dicer is a crucial enzyme for the maturation of miRNAs. Mutations in the Dicer gene are highly associated with Pleuro Pulmonary Blastoma-Family Dysplasia Syndrome (PPB-FDS, OMIM 601200), recently proposed to be renamed Dicer syndrome. Aside from the pulmonary phenotype (blastoma), renal nephroma and thyroid goiter are frequently part of Dicer syndrome. To investigate the renal phenotype, conditional knockout (cKO) mice for Dicer in Pax8 expressing cells were generated. Dicer cKO mice progressively develop a glomerulocystic phenotype coupled with urinary concentration impairment, proteinuria and severe renal failure. Higher cellular turnover of the parietal cells of Bowman’s capsule precedes the development of the cysts and the primary cilium progressively disappears with cyst-enlargement. Upregulation of GSK3β precedes the development of the glomerulocystic phenotype. Downregulation of β-catenin in the renal cortex and its cytosolic removal in the cells lining the cysts may be associated with observed accumulation of GSK3β. Alterations of β-catenin regulating pathways could promote cystic degeneration as in other models. Thus, miRNAs are fundamental in preserving renal morphology and function. Alteration of the GSK3β/β-catenin pathway could be a crucial mechanism linking miRNA dysregulation and the development of a glomerulocystic disease.

Glomerulocystic disease.

Glomerulocystic disease is a rare cause of cystic kidney diseases and can occur at any age. It is characterized by cystic dilatation of the Bowman’s capsule and normal tubules, and needs to be differentiated from other cystic renal diseases. It commonly presents as renal failure. We present a case of a 52-year-old female, with renal failure who was subsequently found to have glomerulocystic disease on renal biopsy.

Glomerulocystic kidney disease

Glomerulocystic disease is a rare renal cystic disease with a long descriptive history. Findings from recent studies have significantly advanced the pathophysiological understanding of the disease processes leading to this peculiar phenotype. Many genetic syndromes associated with glomerulocystic disease have had their respective proteins localized to primary cilia or centrosomes. Transcriptional control of renal developmental pathways is dysregulated in obstructive diseases that also lead to glomerulocystic disease, emphasizing the importance of transcriptional choreography between renal development and renal cystic disease.

Glomerulocystic disease: a severe form in a monozygous twin

One of monozygous twins presented with anuria from birth and was diagnosed on renal biopsy with glomerulocystic kidney disease. There was no associated congenital or hereditary disorder. The other twin was normal and ultrasonography of the renal tracts of both infants was normal. He was managed by peritoneal dialysis. As renal transplantation was not available, the parents discharged him without further treatment.

Quistes renales, manifestación de diversas patologías

Many diseases can be associated with kidney cysts and they may be classified as hereditary and non-hereditary renal cystic disease. The first group can be sub-classified as autosomal recessive cystic disease, such as autosomal recessive polycystic kidney disease and nephronophthisis, as autosomal dominant kidney disease such as autosomal dominant polycystic kidney disease, glomerulocystic disease and tuberous sclerosis, and as cysts associated with syndromes. Cystic dysplasia, multicystic dysplastic kidney, simple cyst, multilocular cysts, Wilm's tumor and acquired cystic kidney disease are classified in the second group. The genetic study of renal cysts is becoming increasingly important, due to the possible therapeutic interventions that could be devised in the future. The aim of this review is to provide a fast and easy clinical approach to renal cysts.

Glomerulocystic Kidney Disease and its rare associations: an autopsy report of two unrelated cases

BackgroundGlomerulocystic kidney disease is an uncommon type of cystic renal disease. It is characterized by cortical microsysts, which are represented by cystic dilatation of Bowman's spaces.Case presentationWe describe a case of glomerulocystic disease in a neonate and another in an abortus associated with tracheo-oesophageal fistula and megacystic-megaureter syndrome. The kidney on autopsy was sponge-like and revealed presence of cysts corresponding to dilatations of Bowman's space microscopically. In these two cases, the Glomerulocystic Kidney Disease in one case corresponded to a sporadic form and, in the other, to a syndromic, non-heritable form of glomerulocystic kidney disease.ConclusionThe associated anomalies in Glomerulocystic Kidney disease are well described in the literature. Two more new unrelated associations are described in this article.

Congenital Anomalies in the Fetus: Approaches to Examination and Diagnosis

Ongoing developments in prenatal diagnosis, coupled with methods of pregnancy intervention and termination, have brought the demands of fetal medicine to the doorstep of general pathology. The requirements for comprehensive fetal examinations are remarkably diverse, ranging from gross to microscopic to molecular evaluation. Pathologists, as essential members of a diagnostic team that includes ultrasonographers, obstetricians, perinatologists, medical geneticists, nurses, and others, must obtain data and tissue that facilitates diagnosis, either at the time of examination or at a later date, as indications for testing become apparent. To do this, pathologists must understand a wide variety of artifacts, changes unique to the fetus, and congenital disorders, and they should be familiar with the medical-legal and ethical demands of practice. This review introduces practical techniques of dissection; acquisition and preservation of data; and tissue collection, storage, and testing. It also includes recommendations for the operation of a fetal pathology service. Approaches to the study of macerated, disrupted, or hydropic fetuses are given, and the work-up of certain representative conditions (velocardiofacial syndrome, Fanconi anemia, glomerulocystic disease, and trisomy 21) is presented.

High-resolution ultrasonography in the differential diagnosis of cystic diseases of the kidney in infancy and childhood: preliminary experience.

Autosomal recessive polycystic kidney disease, autosomal dominant polycystic disease, and glomerulocystic disease may all appear in the perinatal period as bilaterally enlarged echogenic kidneys. Current ultrasonographic equipment can better demonstrate the underlying pathologic state and assist in the differentiation of these conditions. The primary abnormality in autosomal recessive polycystic kidney disease is at the level of the collecting ducts, which are dilated and saccular. The nephrons remain normal. These dilated ectatic tubules are seen in their usual distribution as a radial array, with major ducts being perpendicular to the renal capsule, in both the renal cortex and the medulla. The peripheral renal cortex does not normally contain collecting ducts and remains unaffected in patients with mild disease. Autosomal dominant polycystic disease is characterized by cystic changes involving both the nephron and the collecting ducts. The nephron may become cystic at any point. Multiple discrete cysts of varying sizes are seen in both the renal cortex and the medulla in the severely affected infant. Subcapsular cysts are seen regularly. Glomerulocystic disease is an unusual sporadic condition characterized by the cystic dilation of the space of Bowman and the proximal convoluted tubule. On ultrasonographic examination tiny, isolated cysts, usually smaller than those occurring in autosomal dominant polycystic kidney disease, are seen in the echogenic renal cortex and may extend to the periphery of the kidney. No cysts are seen in the renal medulla. Correlation between pathologic findings and sonographic images is of value in correctly diagnosing these conditions.

Sonographic findings in dominantly inherited Glomerulocystic Disease (GCD): A new entity?: Michelle L. Robbin, M.D., Suzanne M. Bergman, M.D., Cindy K. Sharp, M.D., Lisa M. Guay-Woodford, M.D. University of Alabama at Birmingham, Birmingham, AL

Sonographic findings in dominantly inherited Glomerulocystic Disease (GCD): A new entity?: Michelle L. Robbin, M.D., Suzanne M. Bergman, M.D., Cindy K. Sharp, M.D., Lisa M. Guay-Woodford, M.D. University of Alabama at Birmingham, Birmingham, AL

Prenatally Diagnosed Bilateral Hyperechoic Kidneys With Normal Amniotic Fluid: Postnatal Outcome

We evaluated a subset of infants with bilateral markedly hyperechoic "bright" kidneys noted prenatally in association with normal amniotic fluid volume during gestation. Prenatal ultrasound showed increased renal parenchymal echogenicity bilaterally with preservation of the medullary pyramid architecture. These children were followed for up to 3 years to determine potential changes in the sonographic appearance of the echogenic renal parenchyma and to assess renal function. In 3 years 8 cases of bilateral hyperechoic fetal kidneys were identified. During postnatal followup renal echogenicity resolved in 4 cases, diminished in 1 and remained the same in 3. The serum creatinine and electrolytes were normal in all cases followed for more than 3 months. Other renal findings included vesicoureteral reflux in 2 of 7 cases, mild pelvic ectasia in 1 and tiny medullary calcifications in 1. The specific etiology of increased echogenicity is unknown, although 1 infant appeared to have a form of autosomal recessive disease with liver hyperechogenicity as well. We conclude that fetuses with bilateral hyperechoic kidneys associated with normal amniotic fluid volume have a favorable outcome. Ultrasonographic finding of marked parenchymal hyperechogenicity appears to improve with time; in our experience renal function is normal and the infants thrive. Continued followup is necessary to determine the long-term natural history of this phenomenon, as is subsequent prenatal and postnatal evaluation of future siblings to assess genetic risk.

New mouse model for polycystic kidney disease with both recessive and dominant gene effects

In the course of studying the genetics of chlorambucil mutagenesis, we have uncovered a new model for autosomal polycystic kidney disease (PKD). In the homozygous condition, the gene, jcpk, causes a very severe disease characterized by cysts in all segments of the nephron. Death usually occurs before 10 days of age. Extrarenal involvement was also noted; enlarged bile ducts, pancreatic ducts, and gall bladder often accompanied the PKD. In addition, approximately 25% of the aged +/jcpk heterozygotes show evidence of glomerulocystic disease. This gene maps to Chromosome 10 between two DNA markers, D10Mit20 and D10Mit42. Because this gene causes extrarenal abnormalities and because it has a heterozygote effect, it may be an informative animal model for the commonly occurring human adult dominant PKD.

Glomerulocystic Kidney Disease: A Single Entity?

A case of glomerulocystic disease in a young adult with no family history or presence of other extrarenal malformations is described. Histological study revealed the presence of numerous cortical cysts corresponding to dilatations of Bowman's space. The patient had mild stable chronic renal failure for 5 years. In our patient, the disease corresponded to a sporadic adult form of glomerulocystic disease.

Diffuse Bilateral Glomerulocystic Disease of the Kidneys and Multiple Cardiac Rhabdomyomas in a Newborn: Relationship with Tuberous Sclerosis and Review of the Literature

A case of glomerulocystic disease of the kidneys in a newborn is described. The kidneys were very large and diffusely cystic. Histologically, all portions of the nephron were involved and some of the cysts were lined by a prominent hyperplastic eosinophilic epithelium. This, together with the presence of numerous cardiac rhabdomyomas, a nodular haemangiomatous harmartoma and histiocytoid cell nests in the spleen were strongly suggestive of tuberous sclerosis. The relation between glomerulocystic kidney disease and tuberous sclerosis is discussed.

Hepatoblastoma with Glomerulocystic Disease – a Mere Coincidence or an Association?

We report here a coexistence of hepatoblastoma and GCK in a 3-month-old child and discuss the possibility of an addition to the already known associations between liver lesions and GCK

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.