Filippi syndrome: Three new families suggest that urinary system abnormalities may belong to clinical spectrum of the disease.

Filippi syndrome is a rare genetic disorder characterized by growth and neurodevelopmental delays, dysmorphism, and selective limb abnormalities. Although the syndrome was described approximately four decades ago, only a few families with molecularly confirmed diagnoses have been reported. In this article, we present three new patients of Filippi syndrome with unusual clinical and genetic aspects. These patients exhibited novel clinical features that have not previously been associated with Filippi syndrome, including renal hypoplasia/aplasia, renal cysts, renal cortical thinning, hypomelanotic, and hypermelanotic macules. All three patients had homozygous frameshift variants of the CKAP2L gene, specifically NM_152515.3: c.554_555del, c.981_982del, and c.1463_1467del, with the second being a novel variant. Given the limited number of reported Filippi syndrome patients to date and the ongoing discovery of new clinical aspects of the disease, exploring its potential connection with kidney and skin pigmentation abnormalities could be valuable for future research.

Urologic Considerations in Pediatric Chronic Kidney Disease.

Common causes of pediatric ESRD are distinct from those seen in the adult population. In the pediatric population, the most common are congenital anomalies of the kidney and urinary tract (CAKUT), affecting approximately 30% of children with CKD. These structural anomalies often require coordinated care with the pediatric urology team to address voiding issues, bladder involvement, and the potential need for surgical intervention. For pediatric nephrologists and urologists, common CAKUT that are encountered include antenatal hydronephrosis, obstructive uropathies (eg, posterior urethral valves), and vesicoureteral reflux. As more pediatric patients with CAKUT, CKD, and ESRD transition to adult care, it is important for receiving adult nephrologists to understand the clinical presentation, natural history, and prognosis for these diagnoses. This review outlines the diagnosis and potential interventions for these conditions, including strategies to address bladder dysfunction that is often seen in children with CAKUT. A discussion of these management decisions (including surgical intervention) for CAKUT, which are quite common to pediatric nephrology and urology practices, may provide unique learning opportunities for adult nephrologists who lack familiarity with these pediatric conditions.

New Report of a Different Clinical Presentation of CD151 Splicing Mutation (c.351+2T>C): Could TSPAN11 be Considered as a Potential Modifier Gene for CD151?

CD151, a member of the tetraspanin family, is essential for normal development of skin and kidney. To date, only 2 pathogenic variants of the CD151 gene have been identified in a related disorder with recessive inheritance. Here, in the third study of CD151 mutations, we report 3 affected siblings presenting variable degrees of renal and dermal symptoms. Whole exome sequencing (WES) was performed on the proband, followed by data analysis and in silico assessments. Confirmation of the mutation in the other patients were carried out using Sanger sequencing. The consequence of the CD151 mutation was investigated by RNA extraction and Sanger sequencing of PCR products from cDNA. Multiple computational tools were applied for protein alignment, homology modeling, and molecular interaction analysis. WES revealed the variant c.351+2T>C, NM_139029 (GRCh37) in CD151, and this was confirmed by Sanger sequencing in all patients. This variant is the result of a substitution of nucleotide T with C that changes the position +2 of the donor splice site in intron 5, leading to total loss of exon 5 from the transcript. The mentioned variant was not found in population allele frequency databases, and prediction tools concurred in its damaging effect on the protein. Based on the criteria from ACMG guidelines, this variant is pathogenic. Interestingly, in terms of clinical findings, symptoms and severity of the disease in the patients in this study were different compared to the previous report of the mutation and the disease. In addition, in silico analysis in this study appears to suggest a candidate protein, Tetraspanin-11 (TSPAN11), that could partially modify CD151 functions. This study supports the pathogenic effect of the CD151 variant c.351+2T>C, highlights the extensive variable expressivity amongst patients, reinforces the contribution of genomic content to clinical characteristics of CD151 mutations, and accentuates the importance of modifier genes.

Cardiorenal dysfunction and hypertrophy induced by renal artery occlusion are normalized by galangin treatment in rats.

Galangin is a polyphenolic compound found in Alpinia officinarum and propolis. This study investigated the effect of galangin on blood pressure, the renin angiotensin system (RAS), cardiac and kidney alterations and oxidative stress in two-kidney one-clipped (2K-1C) hypertensive rats. Hypertension was induced in male Sprague Dawley rats (180-220 g), and the rats were given galangin (30 and 60 mg/kg) and losartan (10 mg/kg) for 4 weeks (n = 8/group). Galangin decreased hypertension and cardiac dysfunction and hypertrophy, which was related to the reducing circulation angiotensin converting enzyme (ACE) activity and angiotensin II concentration (p < 0.05). These effects were consistent with the reduced overexpression of angiotensin II receptor type 1 (AT1R), transforming growth factor beta 1 (TGF-ß1) and collagen type I (Col I) protein in cardiac tissue (p < 0.05). Additionally, renal artery occlusion, procedure-induced kidney dysfunction and fibrosis were attenuated in the galangin-treated group. Galangin treatment normalized the overexpression of AT1R and NADPH oxidase 4 (Nox-4) protein and normalized the downregulation of nuclear factor-erythroid Factor 2-related Factor 2 (Nrf-2) and haem oxygenase 1 (HO-1) in 2K-1C rats (p < 0.05). Galangin exhibited antioxidative effects, as it reduced systemic and tissue oxidative stress markers and increased catalase activity in 2K-1C rats (p < 0.05). In conclusion, galangin attenuated hypertension, renin-angiotensin system activation, cardiorenal damage and oxidative stress induced by renal artery stenosis in rats. These effects might be associated with modulation of the expression of AT1R, TGF-ß1 and Col I protein in the heart as well as AT1R/Nox-4 and Nrf-2/HO-1 protein in renal tissue in hypertensive rats.

Bariatric surgery in a patient with cystinuria.

We recently encountered concern about the safety of bariatric surgery for a patient with cystinuria. Bariatric surgery procedures include those that cause malabsorption, like the Roux-en-Y gastric bypass procedure, and restrictive operations, such as the sleeve gastrectomy. These procedures produce beneficial effects on health and life expectancy, though whether kidney stones are prevented, as well as promoted, is not established. Although the importance of body weight to metabolic stone activity in patients with cystinuria is not established, the patient's physicians were concerned about whether any bariatric surgery procedure would affect her ability to drink sufficient quantities of water in order to reduce stone activity. Here we report the experience of a genetically defined patient with cystinuria who underwent a gastric sleeve procedure. In the months after the procedure, she lost 45 kg, though with time she regained 23 kg of that loss. She was able to maintain a urine volume of 4.0 L per day and has had no stone recurrence.

Is fetal isolated double renal collecting system an indication for chromosomal microarray?

Introduction: Duplication of the renal collecting system is one of the most common variants of urinary tract anatomy. The objective of our study was to examine the risk for chromosomal aberrations in this isolated prenatal sonographic finding.Methods: Data from all chromosomal microarray analyses (CMA) reported to the Ministry of Health between January 2013 and September 2017 were retrospectively obtained from a computerized database. All pregnancies with a sonographic diagnosis of the isolated duplex renal collecting system and documentation of CMA result were included. Rate of abnormal CMA findings was compared to the general population risk, based on a systematic review encompassing 9272 cases with normal ultrasound and a local data of 5541 pregnancies undergoing CMA due to maternal request.Results: Two pathogenic CMA finding was found amongst 143 pregnancies with double collecting system (1.4%), not significantly different from the risk for abnormal CMA results in the general population. In addition, five variants of unknown significance were demonstrated (3.5%).Conclusion: To our best knowledge, this analysis is the first report describing the rate of chromosomal anomalies in pregnancies with isolated duplex renal collecting system. Its results suggest that routine invasive prenatal testing with CMA analysis in such cases is no more useful than in the general population. Prospective well-adjusted studies are needed to guide the optimal management of these pregnancies.

Symptomatic abdominal aortic aneurysm in a patient with a horseshoe kidney.

Horseshoe kidney is the most common congenital renal anomaly, occurring in 0.15-0.25% of newborns. The association of a horseshoe kidney with an abdominal aortic aneurysm is rare. Only 0.12% of patients requiring abdominal aortic repair have a horseshoe kidney. This therapeutic challenge constitutes a patient presenting with a symptomatic abdominal aortic aneurysm and a horseshoe kidney. The horseshoe kidney was supplied by 4 renal arteries, 2 of which emerged from the aneurysmal sac. The patient underwent urgent open repair, with transperitoneal exposure, interposition of a bifurcated aorto-bi-iliac Dacron graft and re-implantation of the 2 anomalous renal arteries on the Dacron main body. Postoperatively, the patient was discharged from the intensive care unit on day 3, and discharged home on day 8, maintaining normal serum creatinine.

Aneurisma de aorta abdominal sintomático associado a rim em ferradura / Symptomatic abdominal aortic aneurysm in a patient with a horseshoe kidney

Resumo O rim em ferradura é a anomalia congênita renal mais comum, ocorrendo em 0,15 a 0,25% de nascidos vivos. A associação de rim em ferradura com aneurisma de aorta abdominal é rara, estando presente em apenas 0,12% dos pacientes submetidos a tratamento dos aneurismas de aorta abdominal. Este desafio terapêutico consiste em um caso de um paciente portador de um aneurisma de aorta abdominal sintomático associado a rim em ferradura. A irrigação do rim em ferradura dava-se por meio de quatro artérias, sendo que duas delas emergiam diretamente do saco aneurismático. O caso foi solucionado por meio de cirurgia aberta, em caráter de urgência, com acesso transperitoneal, interposição de enxerto de Dacron bifurcado aorto bi-ilíaco e reimplante das duas artérias renais anômalas no corpo principal do Dacron. O paciente teve boa evolução pós-operatória, recebendo alta da unidade de tratamento intensivo no 3º dia e alta hospitalar no 8º dia, mantendo níveis normais de creatinina sérica.

Abstract Horseshoe kidney is the most common congenital renal anomaly, occurring in 0.15-0.25% of newborns. The association of a horseshoe kidney with an abdominal aortic aneurysm is rare. Only 0.12% of patients requiring abdominal aortic repair have a horseshoe kidney. This therapeutic challenge constitutes a patient presenting with a symptomatic abdominal aortic aneurysm and a horseshoe kidney. The horseshoe kidney was supplied by 4 renal arteries, 2 of which emerged from the aneurysmal sac. The patient underwent urgent open repair, with transperitoneal exposure, interposition of a bifurcated aorto-bi-iliac Dacron graft and re-implantation of the 2 anomalous renal arteries on the Dacron main body. Postoperatively, the patient was discharged from the intensive care unit on day 3, and discharged home on day 8, maintaining normal serum creatinine.

Chromosomal microarray findings in pregnancies with an isolated pelvic kidney.

Objective To examine the risk for abnormal chromosomal microarray analysis (CMA) results among fetuses with an apparently isolated pelvic kidney. Methods Data from all CMA analyses performed due to an isolated pelvic kidney reported to the Israeli Ministry of Health between January 2013 and September 2016 were retrospectively obtained. Risk estimation was performed comparing the rate of abnormal observed CMA findings to the general population risk, based on a systematic review encompassing 9272 cases and on local data of 5541 cases. Results Of 120 pregnancies with an isolated pelvic kidney, two gain-of-copy number variants suggesting microduplication syndromes were demonstrated (1.67%). In addition, three variants of unknown significance were detected (2.5%). Conclusion The risk for clinically significant CMA findings among pregnancies with an isolated single pelvic kidney was not significantly different compared to both control populations. The results of our study question the practice of routine CMA analysis in fetuses with an isolated pelvic kidney.

Rim em Panqueca ­ Um Achado Incomum / Pancake Kidney ­ An Unusual Finding

Introdução: o rim em panqueca foi descrito pela primeira vez por Looney e Dodd (1926), mas apresenta outras nomenclaturas como "bolo", "disco", "rosca" e "rim em escudo", porque produz uma massa em forma de anel ou em forma de rosca. É uma ectopia renal congênita fundida muito rara. Objetivo: relatar um caso raro de rim em panqueca associado a apendicite. Materiais e Métodos: revisão do prontuário, registro fotográfico dos métodos diagnósticos e revisão da literatura. Resultados: jovem de 15 anos de idade, do sexo masculino, com dor em cólica no hipogástrio há dois dias com vômitos há um dia. A tomografia computadorizada demonstrou apendicite e uma massa lobulada fundida situada na cavidade pélvica que se estende de L2 a L4 com ureteres inserindo-se separadamente na bexiga urinária, caracterizando rim em panqueca. Conclusão: relatamos um caso de rim em panqueca, entidade muito rara e pouco relatada na literatura médica, muitas vezes insuspeitada na avaliação clínica inicial, porém que pode causar complicações, tais como a litíase renal e a hipertensão arterial.

Introduction: pancake kidney was first described by Looney and Dodd, but presents other nomenclatures such as "cake", "disk", "doughnut" and "shield kidney" because it produces a ring-shaped or doughnut-shaped mass. It is a very rare fused congenital renal ectopia. Objective: to report a rare case of pancake kidney associated with appendicitis. Materials and Methods: We carried out a review of medical records, photographic record of diagnostic methods and review from the literature. Results: 15 year old male patient with colic pain in the hypogastrium two days ago with vomiting a day ago. Computed tomography scan showed appendicitis and a fused lobulated mass located in the pelvic cavity extending from L2 to L4 with ureters inserting separately into the urinary bladder, characterizing pancake kidney. Conclusion: pancake kidney is an entity very rare and little reported in the medical literature, often unsuspected in the initial clinical evaluation, but that can lead to complications such as renal lithiasis and arterial hypertension.

Transplantation of a horseshoe kidney from a living donor: Case report, long term outcome and donor safety.

INTRODUCTION: The use of a horseshoe kidney in renal transplant remains controversial, when it is found in the evaluation of a living donor, anatomical, surgical and ethical issues are involved. PRESENTATION OF CASE: An uncomplicated horseshoe kidney was detected in a 51-year-old woman who was the only suitable donor for her 30-year-old son. Kidneys were fused in the inferior pole and no vascular or urinary abnormalities were detected during imaging evaluation. The surgical procedure was approved by the hospital transplant committee. A laparotomy was performed by means of a medial upper incision. The isthmus of the kidney was divided using a harmonic scalpel and the left segment was used; it had 2 arteries too distant to create a common one, thus anastomosed separately. The renal vein was side-to-side anastomosed to the right external iliac vein and a Lich-Gregoir ureteral implant was made. There were no intraoperative or postoperative complications in the donor who currently remains asymptomatic. Recipient developed a delayed graft function (DGF), and was discharged on the 12th day after surgery. After 24 months of surgery, renal function has remained stable with a serum creatinine of 128µmol/L (1.45mg/dL). DISCUSSION: There are 7 reports of a horseshoe kidney from living donors in 8 patients without morbidity and a good long term outcome of all recipients. CONCLUSION: If we anticipate a low operative risk and there is a suitable anatomy, we may consider the use of horseshoe kidneys from living donors a viable alternative.

Open Surgical Repair of Abdominal Aortic Aneurysm Coexisting with Horseshoe Kidney.

Horseshoe kidney (HSK) is the most common congenital abnormality of the urologic system encountered during abdominal aortic aneurysm (AAA) surgery. Here, the authors report a case of AAA coexisting with HSK that was successfully treated by open surgery. Two accessory renal arteries of 2.5 mm and 3.1 mm were reimplanted. One of the implanted arteries later occluded and infarct of the isthmus developed, but there was no impairment of renal function. The authors discuss the complexity of the surgical treatment of AAA coexisting with HSK, and place focus on which accessory renal arteries should be reconstructed.

Renal pyelic fusion anomaly.

Renal pyelic fusion anomalies are rare and detected incidentally on imaging. Most cases of pyelic fusion anomalies reported are in patients with horseshoe kidney. We report a rare case of pyelic fusion anomaly in normally located kidneys, which has not been reported so far.

Iliac artery aneurysm repair with preservation of a single ectopic pelvic kidney.

An ultrasonographic study in a 60-year-old man incidentally detected an iliac artery aneurysm that gave rise to the renal artery of a single ectopic pelvic kidney. Renal-preservation solution could not be used during surgery, because the unclamped renal vein would have enabled the solution to enter the systemic circulation. Therefore, cold saline solution was infused through the renal ostium, and the kidney was maintained under cold saline immersion. We performed aortoiliac bypass and then implanted the renal artery into the bypass graft. Postoperatively, the patient's serum creatinine level increased; after one year, his renal function was normal. We discuss our use of cold saline solution for renal preservation.

Congenital abnormalities and hepatoblastoma: a report from the Children's Oncology Group (COG) and the Utah Population Database (UPDB).

Beckwith-Wiedemann Syndrome (BWS) and familial adenomatous polyposis (FAP) are known to predispose to hepatoblastoma (HB). A case-control study was conducted through the Children's Oncology Group (COG) to study the association of HB with isolated congenital abnormalities. Cases (N = 383) were diagnosed between 2000 and 2008. Controls (N = 387) were recruited from state birth registries, frequency matched for sex, region, year of birth, and birth weight. Data on congenital abnormalities among subjects and covariates were obtained by maternal telephone interview. Odds ratios (OR) and 95% confidence intervals (CI) describing the association between congenital abnormalities with HB, adjusted for sex, birth weight, maternal age and maternal education, were calculated using unconditional logistic regression. There was a significant association of HB with kidney, bladder, or sex organ abnormalities (OR = 4.75; 95% CI: 1.74-13) which appeared to be specific to kidney/bladder defects (OR = 4.3; 95% CI: 1.2-15.3) but not those of sex organs (OR = 1.24; 95% CI: 0.37-4.1). Elevated but non-significant ORs were found for spina bifida or other spinal defects (OR = 2.12; 95% CI: 0.39-11.7), large or multiple birthmarks (OR = 1.33; 95% CI: 0.81-2.21). The results were validated through the Utah Population Database (UPDB), a statewide population-based registry linking birth certificates, medical records, and cancer diagnoses. In the UPDB, there were 29 cases and 290 population controls matched 10:1 on sex and birth year. Consistent with the COG findings, kidney/bladder defects were associated with hepatoblastoma. These results confirm the association of HB with kidney/bladder abnormalities.

Renal pyelic fusion with crossed solitary ureter: case report and review of literature.

Renal fusion anomalies are detected incidentally on imaging, with horseshoe kidney being the most common followed by crossed renal ectopia. We report a rare congenital anomaly of renal pyelic fusion with a solitary ureter. Both the renal units were in the normal position and location. This rare anomaly was associated with lumbar vertebral defects, neurogenic bladder, vesico-ureteric reflux, upper tract dilatation and recurrent urinary tract infections.