Rare inherited kidney diseases: an evolving field in Nephrology / Doenças renais hereditárias raras: um campo em evolução na Nefrologia

Abstract There are more than 150 different rare genetic kidney diseases. They can be classified according to diagnostic findings as (i) disorders of growth and structure, (ii) glomerular diseases, (iii) tubular, and (iv) metabolic diseases. In recent years, there has been a shift of paradigm in this field. Molecular testing has become more accessible, our understanding of the underlying pathophysiologic mechanisms of these diseases has evolved, and new therapeutic strategies have become more available. Therefore, the role of nephrologists has progressively shifted from a mere spectator to an active player, part of a multidisciplinary team in the diagnosis and treatment of these disorders. This article provides an overview of the recent advances in rare hereditary kidney disorders by discussing the genetic aspects, clinical manifestations, diagnostic, and therapeutic approaches of some of these disorders, named familial focal and segmental glomerulosclerosis, tuberous sclerosis complex, Fabry nephropathy, and MYH-9 related disorder.

Resumo As doenças renais genéticas raras compreendem mais de 150 desordens. Elas podem ser classificadas segundo achados diagnósticos como (i) distúrbios do crescimento e estrutura, (ii) doenças glomerulares, (iii) tubulares e (iv) metabólicas. Nos últimos anos, houve uma mudança de paradigma nesse campo. Os testes moleculares tornaram-se mais acessíveis, nossa compreensão sobre os mecanismos fisiopatológicos subjacentes a essas doenças evoluiu e novas estratégias terapêuticas foram propostas. Portanto, o papel do nefrologista mudou progressivamente de mero espectador a participante ativo, parte de uma equipe multidisciplinar, no diagnóstico e tratamento desses distúrbios. O presente artigo oferece um panorama geral dos recentes avanços a respeito dos distúrbios renais hereditários raros, discutindo aspectos genéticos, manifestações clínicas e abordagens diagnósticas e terapêuticas de alguns desses distúrbios, mais especificamente a glomeruloesclerose segmentar e focal familiar, complexo da esclerose tuberosa, nefropatia de Fabry e doença relacionada ao MYH9.

An unusual presentation of urethral duplication presenting with chronic bladder retention, left scrotal transposition and left renal agenesis

ABSTRACT Introduction and objective Urethral duplication is a rare congenital anomaly, with roughly 200 cases reported in the literature (1). It is more frequent in males, with few cases reported in females. The clinical presentation differs according to the anatomical variant present. The duplication most commonly occurs in the sagittal plane with one urethra located ventrally and the other dorsally (2). Usually the ventral urethra is the more functional of both. Duplications occurring in the coronal plane are quite rare and they are usually associated with bladder duplication (3). The purpose of this paper was to present a video of a boy with an unusual urethral duplication form. Materials and Methods Patient was born premature due to oligohydramnios at 7 months-gestational age and he has initial diagnosis of hypospadia. Since then, he presented at least 7 febrile UTI and mother complained of difficult micturition and a presence of a mass at lower abdomen. Patient was referred to our institution and we identified urethral duplication with a glandar and scrotal meatus, palpable bladder and left penile-hemiscrotum transposition. US and CT-scan showed left kidney agenesis and overdistended bladder. VCUG and retrograde urethrography showed duplication, presence of contrast in the seminal vesicles and complete catheterizing of both urethras was not possible. Results The topic urethra was dysplastic and not patent to a 4Fr plastic tube so we were unable to access it endoscopically. We performed initially a Mitrofanoff procedure to allow CIC and treat chronic retention. Six months later, we assessed both urethras surgically and concluded that dorsal urethra was dysplastic after 3cm still in the penile area and scrotal urethra was not possible to be catheterized. We excised the ventral urethra because of dribbling complaints up to bulbar area and reconstructed the scrotal transposition, keeping the topic urethra for cosmetic issues. Patient had excellent outcome, performs CIC every 4 hours and has not presented further UTI episodes. Discussion and conclusion The urethral duplication is an anomaly that has multiple anatomical presentations. There are several theories about the etiology, but none can explain all types of presentations. There is also more than one rating available, and the Effmann classification is the most detailed. The case exemplifies this varied spectrum of anatomic urethral duplication. It resembles the urethral duplication type IIa-Y, however, ventral urethra meatus was located in penoscrotal area and both urethras were at least partially hypoplastic/dysplastic associated with obstruction and bladder retention. In determining how to best manage a patient with Y-type urethral duplication, the caliber and quality of the orthotopic urethra must first be assessed. Published reports suggest that best outcomes are those using the ventral duplicated urethra for the reconstruction (4). In this case, none of urethras were functional and a supravesical outlet channel had to be provided. The treatment of this condition requires an individualized planning and a vast technical knowledge of reconstructive surgery.

Tumor fibroso solitario y síndrome Doege-Potter / Solitary fibrous tumor and Doege-Potter syndrome

El tumor fibroso solitario es raro. Si bien su localización más frecuente es la pleura, han sido informados algunos casos de ubicación retroperitoneal. Es difícil diferenciarlo imagenológicamente de otras neoplasias, por lo que casi siempre el diagnóstico es histológico. Dado que los tumores fibrosos solitarios tienen presentaciones clínicas muy diversas, una mejor compresión de la ubicación y sus características imagenológicas ayudaría a abreviar la lista de diagnósticos diferenciales. Comunicamos un tumor fibroso solitario de localización retroperitoneal cuyo diagnóstico fue confirmado por examen histológico.

The solitary fibrous tumor is uncommon. Even though it frequently locates in the pleura, a few cases have been reported in the retroperitoneum. Differentiation from other neoplasms is difficult, and therefore the diagnosis is always attained through histological examination. Although solitary fibrous tumors have variable clinical behaviors, a better comprehension of the location and its imaging characteristics would help to decrease the list of differential diagnoses. We report a solitary fibrous tumor located in the retroperitoneum whose diagnosis was confirmed by histological examination.

Retrocaval ureter and contra lateral renal agenesis – a case report and review of literature

ABSTRACT Associated congenital anomalies are seen in 21% of retrocaval ureter patients; among them, associated contralateral renal agenesis is a very rare entity. We report one such case of right circumcaval ureter with left renal agenesis, diagnosed after febrile UTI. Surgical correction with uretero-ureterostomy was successful. In literature very few such cases are reported and only one case with renal failure was reported. Unilateral renal agenesis cases complicated by associated such anomalies need definitive management and lifelong clinical monitoring to diagnose and prevent chronic kidney disease.

Mayer-Rokitansky-Kuster-Hauser syndrome type II: A rare case.

Mayer-Rokitansky-Kuster-Hauser (MRKH) is a malformation complex comprising absent vagina and absent or rudimentary uterus. MRKH syndrome may be attributed to an initial affection of the intermediate mesoderm consequently leading (by the end of the 4th week of fetal life) to an alteration of the blastema of the cervicothoracicsomites and the pronephricducts. These latter subsequently induce the differentiation of the mesonephric and then the Wolffian and Mullerian ducts. There are very sparse such cases reported. We present a case of type II MRKH or Mullerian renal cervical somite association (i.e., Mullerian duct aplasia, renal dysplasia, and cervical somite anomalies).

Anomalías nefrourológicas congénitas en niños hospitalizados / Nephrourological congenital anomalies in children hospitalized

Introducción : las anomalías congénitas nefrourológicas se encuentran en segundo lugar en frecuencia entre las malformaciones detectadas por ecografía prenatal. La importancia del diagnóstico precoz radica en la posibilidad de prevenir infecciones urinarias, corregir la obstrucción urinaria y evitar o enlentecer el deterioro de la función renal. En nuestro país, el 30,4% de los menores de 15 años en diálisis crónica tiene una insuficiencia renal por nefrouropatía malformativa. Los objetivos fueron conocer la tasa de hospitalización, describir las características clínicas y evolutivas de los niños hospitalizados con diagnóstico ecográfico pre y postnatal de malformación nefrourológica. Material y métodos: estudio descriptivo, prospectivo. Se incluyeron los niños con ecografía del aparatourinario patológica hospitalizados en el sector de cuidados moderados del HP-CHPR entre 01/07/2012 y el 30/6/2013, se excluyeron aquellos con disfunción vesical o glomerulopatía crónica. Se valoró: edad, sexo, hallazgo ecográfico, diagnóstico nosológico, manifestaciones clínicas, evolución y tratamiento. Resultados: se incluyeron 44 niños, la tasa de hospitalización fue 3.9‰, relación masculino/femenino 1,9/1; la mediana de edad 23 meses (percentil 75: 91 meses). Se realizó ecografía prenatal en 36/44, de las cuales 18 fueron patológicas. Se controlaron ecográficamente luego del nacimiento 11/18. En los 26 pacientes restantes, el diagnóstico ecográfico se realizó en la etapa postnatal previo a la internación en 15 y durante la hospitalización en 11. El número de malformaciones halladas fue 66; 22 fueron bilaterales. Predominaron el reflujo vésicoureteral(n=19), las obstrucciones (n=15), y la agenesia/displasia renal (n=18). Requirieron tratamiento quirúrgico 21, endoscópico seis.(...)

Introduction: congenital abnormalities of urinary tract andkidneys rank second in frequency of structuralabnormalities on antenatal ultrasound. Early diagnosisallows to prevent urinary tract infections, to treat urinarytract obstruction and to avoid or slow the decline in renalfunction. In our country 30,4% of patients younger than 15years old on chronic dialysis have a kidney failurebecause of a congenital abnormality.The aims of this study were to know the hospitalizationrate and to describe clinic and evolutionary characteristicsof hospitalized children with a congenital abnormality ofurinary tract and kidneys diagnosed by antenatal/postnatal ultrasound.Patients and methods: a descriptive and prospectivestudy was performed. Hospitalized children in HP-CHPR,between 01/07/2012 and 30/06/2013, with pathologicultrasound of kidneys or urinary tract, were included.Children with bladder dysfunction or glomerulopathy wereexcluded. We considered age, gender, ultrasoundfindings, definitive diagnosis, clinic manifestations,treatment and outcome.Results: we included 44 children. Hospitalization rate was3.9 0/00, the relation male/female was 1.9/1 and themedian age 23 months (75th percentile: 91 months).Antenatal ultrasound was performed in 36/44 patients; 18of them were pathologic; among these last ones, 11/18underwent postnatal ultrasound to control findings. In theother 26 patients, the diagnosis of pathologic ultrasoundwas made after birth: in 15 of them before thehospitalization and in 11 during the hospitalization. Wefound 66 affected kidneys; 22 were bilateral. The mostfrequent diagnosis were: vesicoureteric reflux (n=19),obstruction (n=15) and renal dysplasia/ agenesis (n=18).Twenty one patients underwent surgical treatment and 6underwent endoscopic treatment; 8 patients receivedmore than one invasive treatment...

MDCT Findings of Right Circumaortic Renal Vein with Ectopic Kidney

Anomalies of renal vasculature combined with ectopic kidneys were found on a multi-detector CT scan. Knowledge of renal vascular variation is very important for surgical exploration, radiologic intervention and staging for urologic cancer. We present an extremely rare case of a right circumaortic renal vein combined with a right ectopic kidney. The right kidney was located at the level between the third and fifth lumbar vertebra. The right circumaortic renal vein crossed the aorta and returned to the inferior vena cava behind the aorta.

Uterus didelphys with obstructed right hemivagina, ipsilateral renal agenesis and right pyocolpos: a case report

Uterus didelphys with obstructed hemivagina and ipsilateral renal agenesis [OHVIRA Syndrome] is a rare congenital anomaly of the female genital tract. Uterus didelphys occurs when the midline fusion of the mullerian ducts is arrested, either completely or incompletely. Women with didelphic uterus may be asymptomatic and unaware of having a double uterus. They may present with complaints of dysmenorrhoea and dyspareunia. A 25 year old woman attending the infertility clinic at Nizwa regional referral hospital presented with history of dysmenorrhoea and foul vaginal discharge with right cystic pelvic mass. She was diagnosed as a case of double uterus with obstructed right hemivagina and right pyocolpos with ipsilateral renal agenesis after routine ultrasonography in the clinic followed by MRI. Excision of the right vaginal septum with drainage of 200 ml of purulent discharge was performed. She was relieved of her symptoms and conceived promptly after the surgical excision of the partial vaginal septum

blind-ending ureter with infection due to vesicoureteric reflux with associated renal agenesis: a rare cause of pain abdomen

We report a 12-year-old male child with an unusual cause of abdominal pain, i.e. a blind-ending ureter with vesicoureteral reflux. The pain improved with antibiotic therapy, implying infection as the cause of pain. This entity is difficult to diagnose clinically, thereby affecting management. Usually, a blind-ending ureter is not filled on intravenous urography [IVU] and the diagnosis is confirmed by retrograde pyelography, which is an invasive procedure. We illustrate the contribution of IVU and computerized tomographic cystography, which has not been reported earlier, in the evaluation of such cases

Joubert syndrome: large clinical variability and a unique neuroimaging aspect / Síndrome de Joubert: grande variabilidade clínica e uma neuroimagem característica

Joubert syndrome (JS) is an autosomal recessive inherited disorder characterized by hypotonia, cerebellar vermis hypoplasia, ocular abnormalities (e.g, pigmentary retinopathy, oculomotor apraxia and nystagmus), renal cysts and hepatic fibrosis. Respiratory abnormalities, as apnea and hyperpnea, may be present, as well as mental retardation. At least seven JS loci have been determined and five genes identified. Herein, we report five children, belonging to independent families, with JS: they shared the same typical MRI abnormality, known as molar tooth sign, but had an otherwise quite variable phenotype, regarding mostly their cognitive performance, visual abilities and extra-neurological compromise.

A síndrome de Joubert (SJ) é uma doença hereditária, autossômica recessiva, caracterizada por hipotonia, hipoplasia do vermis cerebelar, anormalidades oculares (p.ex., retinite pigmentar, apraxia oculomotora e nistagmo), cistos renais e fibrose hepática. Anormalidades respiratórias tais como apnéia e hiperpnéia podem estar presentes, assim como deficiência mental. Pelo menos sete loci e cinco genes diferentes associados à SJ já foram identificados. Este artigo relata cinco crianças com SJ, pertencentes a diferentes famílias. Todos os pacientes compartilham a mesma anormalidade típica da RM, conhecida como sinal do dente molar, e apresentam ampla variabilidade clínica em relação ao desempenho cognitivo, comprometimento visual e alterações extra-neurológicas.

Diagnóstico y evolución de las malformaciones congénitas del riñón y vías urinarias: 1999-2005: Holguín 2007 / Diagnosis and evolution of congenital malformations of the kidney and urinary tract

Con el objetivo de evaluar la experiencia clínica en los Servicios de Nefrología y Urología del Hospital Pediátrico Provincial Docente Octavio de Concepción y de la Pedraja de Holguín se realizó un estudio descriptivo de 351 pacientes atendidos entre enero 1999 y diciembre 2005. En esta serie de 351 pacientes fueron diagnosticadas 535 malformaciones congénitas del riñón y vías urinarias de 19 tipos. El reflujo vesico ureteral primario, la estenosis de la unión ureteropiélica y el doble sistema excretor fueron en ese orden, las malformaciones más frecuentes, siendo la edad más común de diagnóstico durante el primer año de vida. La mayoría de los pacientes se presentaron con infección del tracto urinario y un número importante fueron asintomáticos. La ultrasonografía y la uretrocistografía miccional convencional resultaron una combinación efectiva para el diagnóstico de estas. La mayoría de los pacientes a los que se les realizó diagnóstico prenatal tenían una Hidronefrosis Congénita. La valva de uretra posterior fue la principal causa de insuficiencia renal crónica. Los grados I, II y III de reflujo vesico ureteral primario casi siempre desaparecen espontáneamente, siendo el tratamiento médico o conservador la piedra angular en el manejo de estos pacientes. Apreciamos una relación directa entre la nefropatía de reflujo y el grado de esta entidad.

accuracy of ultrasound in the diagnosis of congenital abnormalities

To determine the accuracy of ultrasound in the diagnosis of congenital abnormalities at the Aga Khan University Hospital, Karachi. The data of congenital abnormalities was obtained from the obstetrical database and medical records of all cases complicated by congenital abnormalities, delivering from January 2001 to December 2003 and was reviewed. Antenatal ultrasounds had been performed by operators with different level of experience. In addition this data was retrieved from the termination and Congenital anomaly register. A structured data collection form was used to collect information of different variables of interest. Congenital abnormalities, complicated 2.8%[n=170], of all deliveries, including all cases of termination of pregnancy, stillbirth and live births. Out of the total, 11.6% occurred in women above the age of 35 years. Consanguinity was found in 18.2% cases. Prenatal diagnosis was made in just under half of the cases [48.8%]. Central nervous system and renal abnormalities were commonly diagnosed. However, facial defects, heart defects or skeletal defects were more commonly missed. Antenatal ultrasound successfully diagnosed foetal abnormalities in 48.8% of cases, and more than 90% Central Nervous system defects and renal abnormalities. In contrast about a quarter of Cardiac defects and none of the facial defects were detected. Based on these findings we recommend that the Sonologist should incorporate four chamber view of the heart and also look at the face carefully

Low birth weight and its implication in renal disease.

It has been demonstrated that intrauterine growth retardation, defined as birth weight below the 10th percentile, gives rise to a reduction in nephron number. Oligonephropathy has been suggested to increase the risk for systemic and glomerular hypertension in adult life as well as enhance risk for expression of renal disease after exposure to potentially injurious renal stimuli. Diseases, such as diabetes, that damage the kidney, may enhance this risk. In addition, it has been hypothesized that the same factors affecting kidneys in utero also impact on pancreatic tissue development, thus predisposing infants of low birth weight to an increased risk for the subsequent development of diabetes and diabetic nephropathy, consistent with the so-called "thrifty phenotype" hypothesis. Impact of low birth weight on nondiabetic renal disease has also been shown in some studies. In the current scenario, chronic kidney disease is increasing all over the world and the major two causes are diabetes and hypertension. Once the issues are shifting from management of end-stage renal disease to prevention of chronic kidney disease, prevention of low birth weight is likely to be an issue for the nephrologists in future.

Quiste renal simple y polidactilia: a propósito de 1 caso / Single renal cyst and polydactyly: apropos of 1 case

Se presentó el caso de una paciente de 23 años de edad a quien se le detectó asociación infrecuente de 2 anomalías congénitas: quiste renal único y polidactilia del pie derecho. Se reseñaron los aspectos clínicos y se mostraron los resultados de los estudios imagenológicos. Se revisó el tema

Growth and developmental status in chronic renal insufficiency in infancy and early childhood

This study was carried out to evaluate growth and developmental status of 60 infants with chronic renal insufficiency that occurred before the age of one year as a result of congenital renal disorder. All patients received standard treatment of CRF and patients on corticosteroids were excluded. Ten patients with ESRD underwent peritoneal dialysis. An adequate caloric intake was supplied to ensure proper weight for all patients. Clinical, skeletal, anthropometric, nutritional and developmental assessments were done for all patients. It was concluded that chronic renal insufficiency in infancy may have serious impacts on growth and development that may not be prevented by adequate nutrition

Riñón en herradura: sintomático / Horseshoe kidney: symptomatic

Presentamos un estudio retrospectivo de pacientes portadores de Riñon en Herradura (R:H:), en un período de 10 años. Encontramos 12 casos, todos estudiados con Ecografía, Pielografía, Uretrocistografía y DMSA. Cinco de 12 pacientes presentaron Reflujo Vesico-ureteral, 2 Obstrucción Pielo-ureteral. La sintomatología más frecuente fue Infección Urinaria. El manejo de las patologías asociadas a R.H., fue el mismo utilizado cuando éstas se presentan aisladas. La incidencia de R.H. en nuestra área geográfica es muy inferior a la descrita en la literatura

Fístula renal congénita: informe de un caso y revisión de la literatura / Congenital renal fistula: report of a case and literature review

Las fístulas renales congénitas son trastornos raros. Su característica clínica mas importante es la hematuria macroscópica. La arteriografía renal es el mejor estudio para su diagnóstico. La embolización arterial es un buen procedimiento para tratar definitivamente estas lesiones en forma conservadora. Se presenta un caso de fístula arteriovenosa renal congénita tratada con buenos resultados mediante embolización supraselectiva, y se revisa la literatura