Genetic and radiological aspects of pediatric renal cystic disease: A case series / Aspectos genéticos e imagenológicos de la enfermedad quística renal en pediatría: serie de casos

Renal cystic diseases are common conditions whose etiology can be highly heterogeneous. They require a correct approach for adequate diagnosis and management. We aimed to illustrate part of the spectrum of renal cystic diseases through some clinical cases managed in our service. We describe 11 clinical cases including clinical entities such as renal multicystic dysplasia, and autosomal dominant and autosomal recessive polycystic renal disease, among other pathologies. Renal cystic diseases are heterogeneous in their clinical presentation, natural history, radiological findings, and genetic and pathophysiological basis. An integral clinical approach is needed to get a clear etiological diagnosis and offer adequate individualized care and follow-up for patients.

Las enfermedades quísticas renales son condiciones frecuentes cuya etiología puede ser muy heterogénea, por lo que se requiere un adecuado abordaje para su diagnóstico y manejo. El objetivo de este trabajo fue ilustrar parte del espectro de la enfermedad renal quística por medio de casos clínicos manejados en la Fundación Valle del Lili. Se describen 11 casos clínicos que incluyen enfermedades como displasia multiquística renal, enfermedad poliquística renal autosómica dominante y autosómica recesiva, entre otras. Las enfermedades quísticas renales varían en su presentación clínica, historia natural, hallazgos imagenológicos, bases genéticas y fisiopatológicas, por consiguiente, el enfoque diagnóstico y el manejo integral se debe realizar de forma individualizada y con un abordaje multidisciplinario.

Autosomal dominant polycystic kidney disease with ectopic unilateral multicystic kidney: a case report.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary renal disorder and the fourth cause of death of end-stage renal disease. The disease has a prevalence of 1:400-1:1000 accounting for 10% of patients on dialysis. In most ADPKD patients, bilateral kidneys are similarly affected, with numerous fluid-filled cysts arising from different nephron segments. Only a few cases of ADPKD with ectopic unilateral multicystic kidney have been reported. It has been observed that the deterioration of their kidney function seemed to be quicker than their age- and sex-matched controls and siblings especially when the ectopic kidney is dysplastic. CASE PRESENTATION: We report a case of a 46-year-old Ghanaian male patient who presented with left flank pain and hematuria with high BP and deranged renal function. Abdominal ultrasonography showed both kidneys to be larger than normal and had multiple cysts of varying sizes with the right kidney located in the right iliac fossa. Follow up Abdominopelvic computer tomographic scan (CT-Scan) without contrast showed enlarged kidneys with the renal parenchyma replaced by innumerable cyst of varying sizes. The right kidney was ectopically located in the right aspect of the pelvis. A diagnosis of ADPKD with right pelvic ectopic multicystic kidney was made. He was put on antihypertensives, analgesia for the left flank pain and to have follow up at the urology and nephrology departments. CONCLUSION: In most ADPKD patients, bilateral kidneys are similarly affected. Only a few cases of ADPKD with ectopic unilateral multicystic kidney have been reported. It has been observed that the deterioration of their kidney function seemed to be quicker than their age- and sex-matched controls and siblings especially when the ectopic kidney is dysplastic.

Unilateral Multicystic Dysplastic Kidney Management: A National Survey.

Risks of contralateral kidney abnormalities and chronic kidney disease necessitate follow-up for unilateral multicystic dysplastic kidneys (MCDK). A nationwide survey of senior UK pediatricians was conducted. Of the 60 responses obtained, 62% routinely perform a dimercaptosuccinic acid scan to confirm diagnosis. Eight percent routinely perform a cystogram to investigate contralateral vesicoureteric reflux. Sixty-two percent would routinely measure renal function (frequency ranging from once only to "every 2 years"). Twenty-five percent recalled MCDK nephrectomy being performed within the previous 5 years. Respondents voiced concerns that national guidance may result in an overcautious approach but could balance consensus and safe variation, and offer families choice and reassurance. The mean estimated cost of follow-up from birth to 18 years ranged from £258 to £3854. Results demonstrate significant variation in management, highlighting the need for a clear pathway to decrease unwanted variability and to ensure those at high risk of renal sequelae are recognized early, without undue investigatory burden.

GFR measurements and ultrasound findings in 154 children with a congenital solitary functioning kidney.

BACKGROUND: Multicystic dysplastic kidney (MCDK) and unilateral renal agenesis (URA) are the most common reasons for a congenital solitary functioning kidney (SFK). We aimed to assess the presence of abnormalities in the congenital SFK and evaluate kidney function using chrome EDTA (CrEDTA) measurements. METHODS: We retrospectively reviewed the medical records of 154 children with MCDK and URA in the period from 2005 to 2022 to analyze results from ultrasound scans and CrEDTA glomerular filtration rate (GFR) examinations. RESULTS: Of 154 children with a solitary kidney due to MCDK (62%) or URA (38%), abnormalities on the congenital SFK were found in 13 children (8%). The abnormalities spontaneously resolved in 6 children (46%). The most common abnormality was hydronephrosis. Compensatory hypertrophy was found in 17% of the children within the first 6 months of life. 116 children (90%) had a standard GFR (sdGFR) above 75% of expected for the age. Out of those with a sdGFR below 75% of expected, 3 (23%) had abnormalities in the congenital SFK. There was no difference in sdGFR between children with MCDK and URA. CONCLUSIONS: Our study is the first using CrEDTA for GFR measurements and suggests that most children with a congenital SFK due to MCDK or URA have a kidney function within expected for the age. Compensatory hypertrophy of the SFK is found in a minority of children within the first six months of life, suggesting that this process is developing over time. The prevalence of abnormalities in the SFK seems low, however those with abnormalities (e.g. hydronephrosis) are at higher risk of reduced sdGFR.

Classifying and evaluating fetuses with multicystic dysplastic kidney in etiologic studies.

Multicystic dysplastic kidney (MCDK) is one of the most common fetal malformations, but its etiology remains unclear. Identification of the molecular etiology could provide a basis for prenatal diagnosis, consultation, and prognosis evaluation for MCDK fetuses. We used chromosome microarray analysis (CMA) and whole-exome sequencing (WES) to conduct genetic tests on MCDK fetuses and explore their genetic etiology. A total of 108 MCDK fetuses with or without other extrarenal abnormalities were selected. Karyotype analysis of 108 MCDK fetuses showed an abnormal karyotype in 4 (3.7%, 4/108) of the fetuses. However, CMA detected 15 abnormal copy number variations (CNVs) (14 pathogenic CNVs, and one variant of unknown significance [VUS] CNVs), in addition to four cases that were consistent with the results of karyotype analysis. Out of the 14 pathogenic CNVs cases, three were of 17q12 microdeletion, two of 22q11.21 microdeletion, 22q11.21 microduplication uniparental disomy (UPD), and one case of 4q31.3q32.2 microdeletion, 7q11.23 microduplication, 15q11.2 microdeletion, 16p11.2 microdeletion, and 17p12 microdeletion. Of the 89 MCDK fetuses with normal karyotype analysis and CMA, 15 were tested by WES. Two (13.3%, 2/15) fetuses were identified by WES as Bardet-Biedl syndrome (BBS) 1 and BBS2. Combined application of CMA-WES to detect MCDK fetuses can significantly improve the detection rate of genetic etiology, providing a basis for consultation, and prognosis evaluation.

Differentiating pediatric cystic nephroma from common renal multicystic lesions: A case report.

Pediatric cystic nephroma is a rare, clinically benign, renal tumor. Pediatric renal cystic lesions are complex. Imaging findings and tumor appearance are often nonspecific, and careful pathological examination is necessary. We discuss diagnosis of pediatric cystic nephroma and how to differentiate it from multicystic dysplastic kidney and cystic partially differentiated nephroblastoma.

Utility of renal scintigraphy in diagnosis of multicystic dysplastic kidney.

PURPOSE: To compare the prevalence of vesicoureteral reflux (VUR), febrile urinary tract infection (fUTI), and chronic kidney disease (CKD) among patients with multicystic dysplastic kidney (MCDK) diagnosed by renal scintigraphy (RS) versus follow-up renal ultrasound (RUS) alone. METHODS: This was a retrospective review of patients seen at a tertiary care center from 2010 to 2020 with MCDK diagnosed by RS or follow-up RUS. Differences in the prevalence of VUR, fUTI, and CKD by cohort were assessed using logistic regression analysis, Pearson X2 , and Fisher's Exact tests. Temporal trends in diagnostic methods used (RUS versus RUS + RS) were evaluated using the Cochran-Armitage trend test. RESULTS: One-hundred seventy-two patients were included: 50% (n = 86) underwent RUS + RS and 50% (n = 86) underwent RUS alone to diagnose MCDK. Prevalence of VUR, fUTI, and CKD did not significantly vary between groups. Among patients who had a VCUG, 4.4% had contralateral VUR (1.7% RUS + RS group; 7.4% RUS group; p = 0.19) and 14.5% had at least one fUTI (16.3% RUS + RS group; 12.8% RUS group; p = 0.52). Females were significantly more likely to have at least one fUTI (p = 0.04). Four patients (2.3%) developed CKD, all in the RUS + RS cohort (p = 0.12). Diagnosis of MCDK by RUS versus RUS + RS did not significantly vary over time (p = 0.17). CONCLUSION: Patients with unilateral MCDK confirmed by RS versus RUS alone do not significantly vary in the prevalence of VUR, fUTI, or CKD. Renal scintigraphy studies may not be necessary in unilateral MCDK diagnosis but continue to be used.

Reducing Unnecessary Imaging in Children With Multicystic Dysplastic Kidney or Solitary Kidney.

BACKGROUND AND OBJECTIVES: Children with isolated unilateral multicystic dysplastic kidney (MCDK) or congenital solitary kidney (CSK) undergo serial renal ultrasonography with variable frequency until they are transitioned to adult care. A growing body of literature suggests the value of frequent ultrasonography in this population is limited, providing no benefit to overall outcomes. Despite emerging evidence, ultrasound remains overused, resulting in avoidable health care expenditures and unnecessary use of resources. With our initiative, we aimed to improve quality of care by reducing avoidable ultrasounds in these children. METHODS: This was a single-center, prospective, interrupted time series of children <18 years with ultrasound-confirmed isolated unilateral MCDK or CSK in the outpatient nephrology clinic to evaluate the effect of a decision-making algorithm on the proportion of children receiving an avoidable ultrasound. An algorithm depicting a consensus, evidence-based protocol for managing pediatric MCDK or CSK was refined through content expert feedback and usability testing to standardize frequency of ultrasonography. Ultrasounds were deemed necessary after birth, at 6 months, and at 2, 5, 10, and 15 years. Differences pre- and postintervention were determined by using a U chart and t and F tests for significance. RESULTS: The algorithm resulted in a 47% reduction (P < .001) in the proportion of avoidable ultrasounds ordered in children with MCDK and CSK. This reduction was sustainable over a 6-month period and would result in at least $46 000 annual savings. CONCLUSIONS: Introduction of a clinical decision-making algorithm was associated with a reduction in avoidable ultrasound testing. Improving adherence across providers may allow for an even more pronounced reduction.

Posterior Urethral Valve and Prenataly Resolved Multicystic Dysplastic Kidney.

Multicystic dysplastic kidney is a rare congenital anomaly of the kidney and urinary tract. The association with the posterior urethral valve is also very rare. Here we present a patient with both entities and prenatal resolution of the cysts.A 10-week old baby was referred for nephrourological work up due to prenatal diagnosis of the left multicystic kidney. He had serial US scans during the pregnancy. Immediately before delivery the cysts were not seen (prenatal resolution). There were no extrarenal anomalies. The first postnatal ultrasound scan revealed normal sized right kidney without dilatation of the pelvicalyceal system. The bladder had normal thickness of the wall. Technetium-99m dimercaptosuccinic acid scan showed no activity on the left side, and the right kidney appeared normal. At two months of age, a poor urinary steam was observed and additional urologic work up was indicated on clinical suspicion of PUV. Voiding urethrocystography revealed posterior urethral valve and the baby underwent cytoscopic valve resection.Conclusion: We present a rare association of two congenital anomalies of the kidney and urinary tract with prenatal involution of the multicystic dysplastic kidney that is extremely rare event as seen in our case. Presence of posterior urethral valve must be suspected in a male baby with a poor urinary stream even when his ultrasound scan of urinary system appears normal.

A Newborn with Retrovesical Cysts and an Ipsilateral Multicystic Dysplastic Kidney.

We present a clinical imaging question focusing on a newborn with known prenatal history of a multicystic dysplastic kidney, and incidental ipsilateral retrovesical seminal vesical cysts, raising the diagnosis of Zinner syndrome. The diagnosis is challenging in this age group. Surgical management is generally proposed for symptomatic cases at an older age.

Retrospective evaluation of the pediatric multicystic dysplastic kidney patients: experience of two centers from southeastern Turkey

Background/aim: The objective of this study is to determine the clinical features of unilateral multicystic dysplastic kidney (MCDK) patients. Materials and methods: The demographic, clinical, laboratory, and radiologic features of MCDK patients at Diyarbakir Children's Hospital and Diyarbakir Gazi Yasargil Training and Research Hospital between January 2008-June 2019 were retrospectively evaluated. Results: A total of 111 [59 (53.2%) male and 52(46.8%) female] patients with MCDK were followed for a mean period of 41.89 ± 32.03 months. MCDK was located on the left and right sides in 46 (41.4%) and 65 (58.6%) of the children, respectively (p > 0.05). A total of 87 (78.4%) patients had antenatal diagnosis. The mean age at diagnosis was 13.7 ± 34.2 months. Of the 49 voiding cystourethrogram (VCUG)-performed patients, vesicoureteral reflux was detected in 11 patients (22.4%). Other associated urological anomalies in the patients were detected in 12 (10.8%) patients. On Tc-99m dimercaptosuccinic acid (DMSA) scintigraphy which was performed in all patients showed scarring in four children. Eight patients had history of UTI (7.2%). Renal failure, hypertension, and proteinuria were diagnosed in three children (2.7%). Sixty-nine (62%) patients developed compensatory hypertrophy. Conclusion: All cases should be followed up closely and VCUG should be reserved for patients with recurrent UTI and other urological problems indicated by ultrasonography and abnormal DMSA scan results.

Multicystic Dysplastic Kidney: Prenatal Compensatory Renal Growth Pattern.

OBJECTIVES: To assess the prenatal growth pattern of the normal kidney contralateral to a multicystic dysplastic kidney (MCDK). METHODS: A retrospective study was conducted in a single referral center over 4 years. Cases diagnosed prenatally as MCDK and confirmed postnatally constituted the study group. For creation of nomograms, only isolated cases of MCDK were included. RESULTS: Sixty-one fetuses had a diagnosis of an MCDK during the study period. After exclusion of cases with associated malformations, 47 fetuses remained, providing 94 measurements for creation of nomograms. The growth pattern of the normal kidney contralateral to an MCDK was linear throughout gestation (percentile = 20.01 + 1.5 gestational age; linear R2  = 0.753; r = 0.868) and was significantly higher during the third trimester (29-38 weeks' gestation) compared to the second trimester (22-28 weeks' gestation; P < .001). A comparison of the growth pattern of the normal kidney contralateral to the MCDK to the growth pattern of a solitary kidney revealed a significant higher compensatory trend during the third trimester (P < .0001). The mean kidney lengths at 22 and 38 weeks' gestation correlated with the 52nd and 88th and with the 84th and 90th percentiles for the normal kidney contralateral to the MCDK and a solitary kidney, respectively. CONCLUSIONS: According to our study, the normal kidney contralateral to an MCDK has a unique growth pattern during intrauterine life, with dominant growth during the third trimester. The exact mechanism for this pattern, in comparison to early renal hypertrophy shown in solitary kidneys, is currently not clear. These data provide relevant information for the multidisciplinary prenatal counseling of future parents regarding the future renal outcome.

Imaging of fetal cystic kidney disease: multicystic dysplastic kidney versus renal cystic dysplasia.

With the advent of routine prenatal imaging, the number of renal anomalies identified prenatally has significantly increased; however, the underlying etiologies of these anomalies and the clinical significance of these findings remains unclear. This confusion is especially true for the prenatal diagnosis of cystic renal changes. The terms "cystic kidney disease" and "renal cystic dysplasia" encompass myriad renal diseases. Although renal cystic dysplasia in infants shares many similarities with multicystic dysplastic kidney (MCDK), it is important to distinguish MCDK from other etiologies that would lead to renal cysts, to ensure proper patient diagnosis and appropriate counseling regarding risks and to guide clinical management. The purpose of this review is to highlight the multiple etiologies of cystic kidney disease, including genetic associations, associations with underlying syndromes, and associations with underlying anatomical abnormalities. Here we focus on prenatal imaging, associated pathological findings, and clinical significance, with an emphasis on the defining characteristics of MCDK as compared to other forms of cystic renal disease.

TP63-mutation as a cause of prenatal lethal multicystic dysplastic kidneys.

BACKGROUND: Ectrodactyly-ectodermal dysplasia-clefting syndrome 3 (EEC) is one of the six overlapping syndromes caused by mutations in the tumor protein p63 gene (TP63). EEC is suspected when patients have cleft hands or feet, polydactyly, and syndactyly, abnormal development of the ectodermally derived structures, and orofacial clefting. Genitourinary (GU) anomalies have been identified in patients with EEC, yet these are often under-recognized and under-reported. The available literature on sonographic prenatal findings is sparse, especially when considering GU anomalies. METHODS: We present the case of a male stillborn fetus, who was found antenatally to have multicystic dysplastic kidneys and anhydramnios. Following the termination of pregnancy, examination and autopsy further revealed unilateral polydactyly and bilateral syndactyly which had not been previously identified on antenatal ultrasound. RESULTS: Whole-exome sequencing (WES) revealed a de novo heterozygous pathogenic variant in exon 5 of the TP63 gene: p.His247Arg: c.740A>G (NM_003722.4) which has been reported in the literature. The His247Arg variant has been published as a pathogenic variant in association with EEC, both with and without orofacial clefting. CONCLUSION: Our prenatal case expands the phenotypic spectrum of TP63-related disorders in general. In addition, it adds to the phenotype associated with the His247Arg pathogenic variant responsible for EEC. Further, we highlight the importance of WES as a postnatal tool to help clarify unexpected findings, and as a way to add to the spectrum of existing phenotypes of known single-gene disorders.

Multicystic dysplastic kidney - treat each case on its merits.

OBJECTIVES: To assess outcomes of unilateral multicystic dysplastic kidney (MCDK) managed at an Australasian centre over a 15 year period. To assess if MCDK involution could be predicted based on change noted between first two postnatal ultrasound scans 6 months apart. SUBJECTS AND METHODS: A retrospective study was performed. RESULTS: One-hundred-and-six cases of unilateral MCDK were studied. Eighty-four of these presented antenatally. Twenty-two MCDK cases presented postnatally. Urological anomalies associated with MCDK included vesicoureteric reflux (VUR), ureterocele and contralateral pelviureteric junction obstruction (PUJO). Children undergoing surgical intervention for these anomalies were offered concurrent MCDK nephrectomy. Morbidity associated with MCDK under surveillance included febrile culture-positive urinary tract infection in 20 cases (20.7%), hypertension in four (3.7%) and Wilms' tumor in one (0.9%). Thirty-six cases (34%) underwent complete involution, 32 (30.2%) were in the process of involuting and 38 cases (35.8%) underwent nephrectomy because of failure of involution or associated morbidity. If the MCDK reduced in cranio-caudal interpolar length by 20% or more between the first postnatal USS and the next one 6 months later, then it was very likely to involute spontaneously. If the MCDK did not reduce in cranio-caudal interpolar length by 20% between the first postnatal scan and the next one 6 months later, then it was highly likely to fail to involute, and in our study, correlated with the outcome of nephrectomy. CONCLUSION: Although MCDK is a benign condition, it should be carefully investigated and followed-up, as involution may not occur in over a third. In some cases, morbidity may occur. Each case of MCDK should be managed on its own merits. LEVEL OF EVIDENCE: Level II - Prognosis study, Retrospective.

[Prenatal diagnosis of multicystic dysplastic kidney: about 18 cases]. / Diagnostic anténatal de la dysplasie rénale multikystique: à propos de 18 cas.

Multicystic dysplastic kidney (MCDK) is the most common Congenital Abnormalities of Kidney and Urinary Tract (CAKUT) in clinical practice. Its etiology and pathogenesis are still controversial and obstruction is a generally accepted causative assumption. Obstetric ultrasound is the gold standard for prenatal diagnosis and for the detection of other associated malformations. Prenatal management is based on ultrasound monitoring of pregnancy, of the disease, of the occurrence of other anomalies and of the amount of amniotic fluid. This study aims to report our experience in the Department of Gynecology-Obstetrics 2 at the University Hospital Hassan II-Fez in order to clarify the epidemiology of MCDK, highlight the role of obstetric ultrasound in positive and etiological diagnosis while describing the various sonographic appearances. It is essential to schedule for screening tests during pregnancy in order to assess the evolution of the disease diagnosed in the prenatal period, to implement a strategy in postpartum care and to establish a prognosis.

Antenatally detected ureterocele: Associated anomalies and postnatal prognosis.

OBJECTIVE: We purposed to review prenatal diagnoses of ureterocele, to determine the sonographic findings and additional abnormalities, and to illustrate the pregnancy outcomes of these patients. MATERIAL AND METHODS: We reviewed the records of 24 patients with the diagnosis of ureterocele in our referral center between January 2010-March 2017. Prenatal sonographic findings, antenatal course, and postnatal follow-up were obtained. RESULTS: The mean gestational age at first US diagnosis was 24.5 ± 2.9 weeks. 13 (54.1%) of fetuses were female, and 11 (45.9%) were male. Ureterocele was associated with the duplex kidney in 17 (70.8%), MCDK in 5 (20.8%) and hydronephrosis with a single system in 1 (4.2%) and pelvic kidney in 1 (4.2%) fetuses. Postnatal follow-up was achieved in 22 of 24 (91.6%) cases, and mean follow-up interval was 56 ± 14.2. Months. The diagnosis of ureterocele was confirmed in 22 (91.6%) cases postnatally. 15 of 22 (68%) cases were classified as extravesical ureterocele, and 7 (32%) cases were intravesical ureterocele. Postnatal confirmation of duplex kidney achieved in 16 of 17 (94.1%) patients. 17 (77.2%) patients were required surgical intervention, and 5 (22.8%) cases were managed conservatively. 15 of 16 (93.7%) cases who were diagnosed duplex kidney underwent surgery however 2 of 5 (40%) cases which were confirmed MCDK required an operation. Cystoscopic ureterocele incision was the initial approach for the surgical management and performed all of the cases which required surgery. It was curative in 10 of 17 (58.8%) patients and 7 (41.2%) cases needed to further operations. Ureteroselectomy and common-sheath ureteroneocystostomy was performed in 5 (29.1%) cases and. 2 (%11.7%) cases underwent partial nephrectomy. CONCLUSION: Ureterocele can be accurately diagnosed by prenatal sonography, and it is a significant clue for the diagnosis of a duplex kidney. Postnatal prognosis depends on associated anomaly and presence of reflux and upper pole function.