CystAnalyser: A new software tool for the automatic detection and quantification of cysts in Polycystic Kidney and Liver Disease, and other cystic disorders.

The Polycystic Kidney Disease (PKD) is characterized by progressive renal cyst development and other extrarenal manifestation including Polycystic Liver Disease (PLD). Phenotypical characterization of animal models mimicking human diseases are commonly used, in order to, study new molecular mechanisms and identify new therapeutic approaches. The main biomarker of disease progression is total volume of kidney and liver in both human and mouse, which correlates with organ function. For this reason, the estimation of the number and area of the tissue occupied by cysts, is critical for the understanding of physiological mechanisms underlying the disease. In this regard, cystic index is a robust parameter commonly used to quantify the severity of the disease. To date, the vast majority of biomedical researchers use ImageJ as a software tool to estimate the cystic index by quantifying the cystic areas of histological images after thresholding. This tool has imitations of being inaccurate, largely due to incorrectly identifying non-cystic regions. We have developed a new software, named CystAnalyser (register by Universidade de Santiago de Compostela-USC, and Fundación Investigación Sanitaria de Santiago-FIDIS), that combines automatic image processing with a graphical user friendly interface that allows investigators to oversee and easily correct the image processing before quantification. CystAnalyser was able to generate a cystic profile including cystic index, number of cysts and cyst size. In order to test the CystAnalyser software, 795 cystic kidney, and liver histological images were analyzed. Using CystAnalyser there were no differences calculating cystic index automatically versus user input, except in specific circumstances where it was necessary for the user to distinguish between mildly cystic from non-cystic regions. The sensitivity and specificity of the number of cysts detected by the automatic quantification depends on the type of organ and cystic severity, with values 76.84-78.59% and 76.96-89.66% for the kidney and 87.29-93.80% and 63.42-86.07% for the liver. CystAnalyser, in addition, provides a new tool for estimating the number of cysts and a more specific measure of the cystic index than ImageJ. This study proposes CystAnalyser is a new robust and freely downloadable software tool for analyzing the severity of disease by quantifying histological images of cystic organs for routine biomedical research. CystAnalyser can be downloaded from https://citius.usc.es/transferencia/software/cystanalyser (for Windows and Linux) for research purposes.

Panorámica de la poliquistosis renal autosómica dominante en una región del sur de España / Overview of autosomal dominant polycystic kidney disease in the south of Spain

Introducción: La poliquistosis renal autosómica dominante es la enfermedad renal hereditaria más frecuente aunque los datos disponibles generalmente son tras el inicio del tratamiento renal sustitutivo. Objetivo: Conocer la situación global de la poliquistosis renal autosómica dominante en el ámbito sanitario de Granada. Material y métodos: Desde enero 2007 hasta diciembre 2016 hemos recogido información clínica, familiar y demográfica de todos los pacientes con poliquistosis renal autosómica dominante, estuvieran o no en tratamiento renal sustitutivo, atendidos en el área de Granada. Se han utilizado los programas informáticos SPSS 15.0 y GenoPro. Resultados: Mil ciento siete pacientes diagnosticados, el 50,6% son varones. Se han estudiado 4-6 generaciones/familia. El 99,1% de raza caucásica. Hay áreas geográficas con mayor concentración. No hay antecedentes familiares en el 2,43%. La edad media de diagnóstico es de 34±17,8 años y en el 57,7% de los casos, el diagnóstico se produce después de tener descendencia. El principal motivo de diagnóstico son los antecedentes familiares (46,4%). La edad media de entrada en técnica es de 54,2±11,05 años. El 96,3% de los fallecidos tenían algún grado de insuficiencia renal en el momento del exitus. La edad media del exitus es de 60,9±14,10 años, siendo desconocida la principal causa de muerte (33,5%) seguida de la cardiovascular (27,8%). Conclusiones: Casos y familias se concentran en algunas áreas geográficas, un número importante de individuos están sin diagnosticar, fallecen antes por causa cardiovascular y se diagnostican tarde respecto al momento reproductivo. Dado que no hay tratamiento curativo, la estrategia de prevención primaria mediante el diagnóstico genético preimplantacional adquiere protagonismo (AU)

Introduction: Although autosomal dominant polycystic kidney disease is the most common hereditary kidney disease, available data tend to be limited to after initiation of renal replacement therapy. Objective: To ascertain an overview of autosomal dominant polycystic kidney disease within the health area of Granada in southern Spain. Material and methods: From January 2007 to December 2016, we collected clinical, family and demographic information about all patients with autosomal dominant polycystic kidney disease, irrespective of whether or not they were treated with RRT, in the Granada health area. The computer software SPSS 15.0 and GenoPro were used. Results: 50.6% of the 1,107 diagnosed patients were men. 99.1% were Caucasian and 4-6 generations/family were studied. The geographical distribution was heterogeneous. There was no family history in 2.43%. The mean age of diagnosis was 34.0±17.80 years and the diagnosis was made after having offspring in 57.7% of cases. The main reason for diagnosis was family history (46.4%). The mean age of initiation of renal replacement therapy was 54.2±11.05 years. 96.3% of the deceased had some degree of renal failure at the time of death. The mean age of death was 60.9±14.10 years, the main cause of death being unknown in 33.5% of cases, followed by cardiovascular (27.8%). Conclusions: Cases and families were concentrated in certain geographical areas and a significant number of individuals were undiagnosed prior to cardiovascular death or diagnosed late after reproduction. Given that there is currently no curative treatment, the primary prevention strategy of preimplantation genetic diagnosis should play a leading role (AU)

Contrast-Enhanced Ultrasound (CEUS) of the Kidneys by Using the Bosniak Classification.

Ultrasound is the most used interdisciplinary non-ionizing imaging technique in clinical routine. Therefore, ultrasound has a special value in the diagnosis and monitoring of cystic renal lesions, which can be classified as non-complicated or complicated and by means of occurrence as solitary or multifocal lesions. The Bosniak classification (I-IV) classifies renal cysts in 5 different categories with the help of ultrasound and computed tomography image criteria and is used for decisions of further clinical treatment. Additionally to normal native B-mode sonography, several new methods are in clinical use to improve diagnostic accuracy of unclear cases. Contrast enhanced ultrasound and MRI/CT are able to find and characterize difficult pathologies. This review explains the most important pathologies of cystic lesions of the kidney and stresses the different imaging methods of native B-mode sonography and the new techniques of contrast enhanced ultrasound.

[Neuro-ophthalmological and ophthalmological findings in Joubert syndrome]. / Neuroophthalmologische und ophthalmologische Befunde beim Joubert-Syndrom.

BACKGROUND: Joubert syndrome (JS) belongs to the ciliopathies and is a mostly autosomal recessively inherited disease (in the case of OFD1 mutations, JS is an X-linked trait). It is characterised by midbrain-hindbrain malformations with developmental delay, hypotonia and ataxia and a broad spectrum of other facultative findings. The aim of our study was to examine the ophthalmological and neuro-ophthalmological features of JS in our patients and to compare our findings to those of other studies. METHODS: In a retrospective study we evaluated the ophthalmological and neuro-ophthalmological findings of 9 consecutive patients who met the diagnostic criteria of JS. RESULTS: All patients had abnormalities of ocular motility, 4/9 used head thrusts to shift gaze (oculomotor apraxia OMA). In 6/8 patients, the optokinetic reflex (OKN) was absent. Furthermore, 8/9 children showed nystagmus, mostly see-saw nystagmus. Manifest strabismus was found in 8/9 while 3/9 had a retinopathy with either abnormal ERG and/or fundus appearance with or without visual impairment. Chorioretinal colobomata were present in 5/9 cases. Two patients showed a unilateral congenital ptosis, one a facial nerve paresis. CONCLUSIONS: The early neuro-ophthalmological findings in JS are not pathognonomic, but may lead to the diagnosis of JS. The syndrome should be suspected in patients with nystagmus, especially see-saw nystagmus, and abnormal OKN and/or OMA, and/or colobomata of the fundus, and further paediatric examinations should be initiated.

[Cystic renal neoplasms. New entities and molecular findings]. / Zystische Nierentumoren. Neue Tumortypen und aktuelle molekulare Erkenntnisse.

Renal neoplasms with dominant cysts represent a broad spectrum of known as well as novel renal tumor entities. Established renal tumors with dominant cysts include cystic nephroma, mixed epithelial and stromal tumor, synovial sarcoma and multilocular cystic renal cancer (WHO classification 2004). Novel tumor types have recently been reported, which are also characterized by marked cyst formation. Examples are tubulocystic renal cancer and renal cancer in end-stage renal disease. These tumors are very likely to be included in a future WHO classification due to their characteristic phenotype and molecular features. Cysts and clear cell renal cell carcinoma frequently coexist in the kidneys of patients with von Hippel-Lindau disease. Cysts are also a component of many sporadic clear cell renal cell carcinomas. Multilocular cystic renal cell carcinoma is composed almost exclusively of cysts and is regarded as a specific subtype of clear cell renal cancer. Recent molecular findings suggest that clear cell renal cancer may develop via a cyst-dependent mechanism in von Hippel-Lindau syndrome as well as via cyst-independent molecular pathways in sporadic clear cell renal cancer.

[A clinical approach to renal cysts]. / 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.

Quistes renales, manifestación de diversas patologías / A clinical approach to renal cysts

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 cystc.

[Cystic kidney disease]. / Doença quística renal.

The kidney is one of the organs most frequently affected by cystic disease, which can be defined as the morbidity attributable to the presence of renal cysts. Renal cysts appear in a series of very diverse hereditary anomalies, acquired or developmental, occurring as an isolated form or in association with other renal or systemic alterations. Cysts are microscopic or macroscopic abnormal cavities, with saccular or fusiform shape, coated with epithelium and filled with liquid. They origin in the nephron or the collecting tubules, with which a connection can be maintained or not. They can occur at any point in life, from the prenatal period to adulthood, and one or both kidneys may be affected in a focal or diffuse form. Renal cyst pathogenesis is not completely understood, although there is evidence that it may be caused by hyperproliferative dysplasic secretion and matrix remodelling alterations, modulated by endocrine, paracrine, juxtacrine and autocrine stimuli, which induce obstructive alterations that are determinant in its genesis and evolution.

Complex renal cysts: findings on MR imaging.

OBJECTIVE: We retrospectively evaluated our experience with complex cystic renal masses on MR imaging, using T1-weighted, T2-weighted, and gadolinium-enhanced images, to determine whether imaging features could permit distinction between benign and malignant lesions. MATERIALS AND METHODS: Thirty-seven patients with complex cystic renal lesions were included in this retrospective study. The patients selected had undergone T1-weighted, T2-weighted, and gadolinium-enhanced MR imaging examinations using 1.5-T scanners, with at least one of the following findings: cyst fluid of heterogeneous signal intensity, mural irregularity, septa, mural masses or nodules, increased mural thickness, or intense mural enhancement. The diagnosis was established by histology in 19 patients and by follow-up studies in the remaining 18 patients. RESULTS: Fifty-five complex renal cystic lesions were present in the 37 patients. Among the 55 lesions, of 37 that contained fluid of a heterogeneous signal intensity, eight were malignant (22%); of 16 with irregular walls, 10 were malignant (63%); of four with septa, two were malignant (50%); of four with mural masses or nodules, three were malignant (75%); of 14 with a thick wall (>2 mm), 10 were malignant (71%); and of 32 with intense mural enhancement, 14 were malignant (44%). As independent variables, mural irregularity, mural masses or nodules, increased mural thickness, and intense mural enhancement each were highly associated with malignancy (p = .0003-.0022). The combination of mural irregularity and intense mural enhancement had the highest correlation with malignancy (p = .0002). CONCLUSION: The combination of mural irregularity and intense mural enhancement is a strong predictor of malignancy in renal cystic lesions. However, the appearance of benign and malignant lesions may overlap, suggesting that distinct separation of these entities is not currently possible in all cases with MR imaging.

[Current opinions on the etiology and pathogenesis of autosomal dominant polycystic kidney disease (ADPKD). II. Factors other than genetic factors which have an influence on disease course and selected clinical problems]. / Aktualne poglady na etiologie i patogeneze zwyrodnienia wielotorbielowatego nerek typu doroslych (ADPKD). Czesc II: inne niz genetyczne czynniki wplywajace na przebieg choroby i wybrane problemy kliniczne.

In the first part of this paper achievements in the genetic investigations of ADPKD and pathomechanism of cyst formation have been presented. Majority of authors acknowledge that first type of the disease (ADPKD1) in comparison with the second (ADPKD2) has more severe clinical course. On the basis of clinical analysis of selected affected families the larger and larger emphasis has been put on the influence of such factors like: presence of arterial hypertension, especially role of RAA system, sex, diet, hyperlipoproteinemia, environmental factors, toxic and infectious agents. It seems that genetic analysis of the RAA system and ADPKD will partially explain differences in the clinical course of the disease in different families. Persons with DD genotype in RAA system have statistically significant, more severe clinical course in comparison with their relatives with DI or II genotype. Decidedly worse course of the disease is observed in patients with positive family history of arterial hypertension and in persons with increased blood pressure. Patients sex play a major role. Men have more severe renal manifestations, when in women symptoms and complications associated with liver cysts are more frequent than in men. Frequency of intracranial aneurysms (ICA) in the population of patients with ADPKD have been presented. CT, MRA and classical angiography are in order screening tests for detection of ICA, especially in persons with family history of their prevalence. Prevalence of liver cysts and selected clinical symptoms and complications associated with extrarenal manifestations have been discussed. Problems associated with infections of the urinary tract and cysts, their etiology, pathomechanisms and treatment have been presented. Ultrasonography seems to be the best diagnostic tool because of it's accessibility, high sensitivity and low cost. It is accepted, that presence of 3 cysts in both kidneys in ADPKD kindreds in significant for diagnosis. Modified Ravine's criteria for diagnosis of ADPKD have also been presented. Employment of modern diagnostic methods in combination with genetic analysis (especially linkage analysis) enable early diagnosis in persons who are at risk of ADPKD.

Doença renal policística: atualizaçäo da patogenia / Policystic kidney diseases: update of pathogeny

Este artigo foi dividido em duas partes. A primeira consiste em breve revisäo da classificaçäo e características clínicas e diagnósticas das doenças renais policísticas (DRP), principalmente nas suas formas hereditárias. A segunda parte é composta por uma revisäo atualizada da patogenia das doenças císticas renais, onde säo comentados os possíveis mecanismos e hipóteses para a formaçäo e expansäo dos cistos, com alguns diagramas pessoais elucidativos, incluindo a cistogênese da doença renal císitica adquirida (DRCA), uma vez que parece haver um denominador comum ou mecanismo unificador na formaçäo dos cistos em todas as formas de doenças císticas.

[Cystic diseases of the kidney in adults]. / Cisticke bolesti bubrega kod odraslih osoba.

Contemporary review of polycystical renal disease at adults has been presented. Classification which would make the recognization and diagnosis of some cystic renal disease forms easier, is proposed. Considering the data an attempt to explain the pathogenetical mechanisms of these disease has been made. The short description of clinical features and diagnostical procedure, therapeutical approach, measures of prevention and the prognosis of some forms of cystic renal disease at adults are given.

[Multilocular cysts. An entity of difficult classification. Apropos of two cases]. / Quiste multilocular. Una entidad de difícil clasificación. A propósito de dos casos.

Renal multilocular cyst continues to be, up-to-date, an entity of unknown pathoetiology. In many occasions, particularly in children, it has been mistaken with a partially differentiated cystic nephroblastoma. Due to the absolute benignancy of the multilocular cyst and the likelihood of preserving the renal parenchyma, we consider of interest to contribute a brief review of the current pathoetiological theories and clinical development, as well as our experience in this disease.

Polycystic disease of the kidney. Evaluation and classification based on nephron segment and cell-type specific markers.

The usefulness of various segment and cell-type specific antibody, lectin and functional markers in the study of cystic renal lesions was evaluated. For this purpose, kidneys from recessive polycystic kidney disease (RPKD), thought to involve mainly the collecting ducts, and cystic kidneys of Meckel's syndrome (MS), which show dilation randomly along the nephron, were studied. The segment (and differentiation-stage)-specific anti-brush-border (specific for proximal tubules) antibodies stained morphologically normal proximal tubules, failed to react with cyst wall epithelium in RPKD, but readily stained some cysts in MS. Immunostaining for Tamm-Horsfall glycoprotein (distal tubules) similarly revealed normal tubular profiles, and also stained moderately dilated tubules, but not the large cysts in either disease type. Lectin markers of the distal tubules and collecting ducts (peanut agglutinin, Helix pomatia agglutinin and Dolichos biflorus agglutinin) reacted with both dilated tubules and with the cyst walls in RPKD and Meckel kidneys, suggesting that in RPKD, the dilations also occur in the distal nephron in addition to the collecting duct, and in MS in any part of the renal tubule. The cell type-specific functional marker of the collecting duct, anti-NaK-ATPase reactivity (found in principal cells) could be seen in RPKD but not in Meckel kidney cysts, suggesting a minor involvement of principal cells in MS. Consistent with this, only occasional carbonic anhydrase (found in intercalated cells) or band 3 (bicarbonate-chloride exchanger molecule of intercalated cells) of collecting ducts positive cells in the cysts could be seen, suggesting that intercalated cells are only sparsely seen in these lesions. The results show the usefulness of a panel of independent markers in studying the segment, cell-type and function-specific features of renal cystic lesions as a basis for their classification.