High Incidence of CPLANE1-Related Joubert Syndrome in the Products of Conceptions from Early Pregnancy Losses

Background: The fetal monogenic causes of early pregnancy losses (EPLs) are mainly unknown, with only a few articles on the subject published. In our previous study of EPLs using whole-exome sequencing analysis, we confirmed a genetic diagnosis of CPLANE1-related Joubert syndrome (JS) in three EPLs from two couples and identified a relatively common CPLANE1 allele among our population (NM_001384732.1:c.1819delT;c.7817T>A, further after referred as "complex allele"). Pathogenic variants in the CPLANE1 (C5orf42) gene are reported to cause JS type 17, a primary ciliopathy with various system defects. Aims: To examine the hypothesis that the CPLANE1 "complex allele," whether homozygous or compound heterozygous, is a common cause of EPLs in our population. Study Design: Cohort study/case-control study.ontrol study. Methods: In this study, we used polymerase chain reaction-based methods to screen for CPLANE1 "complex allele" presence among 246 euploid EPLs (< 12 gestational weeks) from families in North Macedonia. We also investigated the impact of this allele in 650 women with EPLs versus 646 women with no history of pregnancy loss and at least one livebirth, matched by ethnic origin. Results: We found a high incidence of JS in the total study group of EPLs (2.03%), with a considerably higher incidence among Albanian families (6.25%). Although not statistically significant, women with EPLs had a higher allele frequency of the CPLANE1 "complex allele" (AF = 1.38%) than the controls (AF = 0.85%; p = 0.2). Albanian women had significantly higher frequency of the "complex allele" than the Macedonians (AF = 1.65% and 0.39%, respectively; p = 0.003). Conclusion: To the best of our knowledge, this is the highest reported incidence of fetal monogenic disease that might cause EPLs. Targeted screening for the CPLANE1 "complex allele" would be warranted in Albanian ethnic couples because it would detect one JS in every 16 euploid EPLs. Our findings have a larger impact on the pathogenesis of pregnancy loss and contribute to a better understanding of the pathogenicity of the variants in the CPLANE1 gene.

Multiple and large simple renal cysts are associated with glomerular filtration rate decline: a cross-sectional study of Chinese population.

BACKGROUND: Although simple renal cyst (SRC) is a kind of structural alterations of kidney with age, the relationship between SRC and renal function is still obscure. We investigated the relationship between SRC and renal function in Chinese population. METHODS: The medical records of 41,842 individuals who underwent physical examinations at the Health Check-up Center at our institution in 2018 were reviewed. According to whether with SRC, they were divided into no-SRC and SRC groups. SRCs were classified into subgroups based on number (< 2 vs. ≥ 2) and size (< 2 cm vs. ≥ 2 cm). Logistic regression was used to examine the relationship between SRC and estimated glomerular filtration rate (eGFR). RESULTS: Multinomial logistic regression analysis showed that the adjusted odds ratio (OR) for eGFR slight decline in subjects with SRC was 1.26(95% confidence interval (95% CI):1.17-1.35, p < 0.001), and the OR for eGFR severe decline was 1.35(95% CI: 1.16-1.56, p < 0.001) compared with no-SRC. The adjusted OR of SRC number ≥ 2 and ≥ 2 cm on the risk of eGFR severe decline was the highest (OR:1.68, 95% CI:1.25-2.23, p < 0.01) of four SRC subgroups. CONCLUSIONS: SRC is related to eGFR decline, especially when the person with one more SRCs and the size of SRC is more than 2 cm. SRC could be a warning sign for clinicians to judge the decline of renal function.

Acquired cystic kidney disease in patients on maintenance hemodialysis, prevalence and associated factors: a cross-sectional study.

Introduction: Acquired Cystic Kidney Disease (ACKD) is a known complication in patients on maintenance hemodialysis, and it is associated with a high risk of malignant transformation. There is a paucity of data on ACKD in sub-Saharan Africa. Objectives: To determine the prevalence and factors associated with acquired cystic kidney disease in patients on maintenance hemodialysis. Methods: patients on maintenance hemodialysis were screened for ACKD. Patients with hereditary cystic kidney disease were excluded. Renal ultrasounds were performed by two radiologists. ACKD was defined as 3 or more bilateral renal cysts in a small or normal size kidney. Associated factors were determined using logistic regression. A p-value <0.05 was significant. Results: a total of 158 participants were enrolled and 61.4% (97) were male. Their mean (SD) age was 45.8 (14.9) years. The median dialysis vintage was 33.5 [10.7-63.2] months. The mean (SD) length of the kidneys was 85.1 (17.5) mm on the left and 81.2 (17.1) mm on the right. The prevalence of ACKD was 31.6% (n=50). Septated cysts (4), calcification of the wall of the cysts (2), irregular thick calcified wall (1), septated cysts with calcification (1) and hemorrhagic cyst (1) cysts were also observed. Dialysis vintage > 36 months (OR 7.1, 95% CI: 3.3 - 15.5) and male sex (OR 2.6, 95% CI: 1.2-5.6) were independently associated with ACKD. Conclusion: the prevalence of ACKD is high in a population of Cameroonians on maintenance. This result calls for the implementation of strategies to screen for the condition and its complications.

Relationship Between Pancreatic Cysts and Cysts in Other Organs in Patients Undergoing Medical Checkup.

OBJECTIVE: We investigated the association between pancreatic cysts and cystic diseases of other organs using abdominal ultrasonography in patients undergoing medical checkup. METHODS: Between April 2021 and March 2022, 4496 patients had a comprehensive medical checkup at our hospital, which included abdominal ultrasonography. RESULTS: Among 4496 patients, 172 (3.8%), 1592 (35.4%), and 1425 (31.7%) had pancreatic, liver, and renal cysts, respectively. Multivariate analysis revealed that the significant factors were female sex and the presence of renal cysts. CONCLUSION: Pancreatic cysts were more common in females. Renal cysts are relatively commonly detected on abdominal ultrasonography. If renal cysts are detected, comorbidities with pancreatic cysts should be considered.

Proportion of malignancy in Bosniak classification of cystic renal masses version 2019 (v2019) classes: systematic review and meta-analysis.

OBJECTIVES: Determine the proportion of malignancy within Bosniak v2019 classes. METHODS: MEDLINE and EMBASE were searched. Eligible studies contained patients with cystic renal masses undergoing CT or MRI renal protocol examinations with pathology confirmation, applying Bosniak v2019. Proportion of malignancy was estimated within Bosniak v2019 class. Risk of bias was assessed using QUADAS-2. RESULTS: We included 471 patients with 480 cystic renal masses. No class I malignant masses were observed. Pooled proportion of malignancy were class II, 12% (6/51, 95% CI 5-24%); class IIF, 46% (37/85, 95% CI 28-66%); class III, 79% (138/173, 95% CI 68-88%); and class IV, 84% (114/135, 95% CI 77-90%). Proportion of malignancy differed between Bosniak v2019 II-IV classes (p = 0.004). Four studies reported the proportion of malignancy by wall/septa feature. The pooled proportion of malignancy with 95% CI were class III thick smooth wall/septa, 77% (41/56, 95% CI 53-91%); class III obtuse protrusion ≤ 3 mm (irregularity), 83% (97/117, 95% CI 75-89%); and class IV nodule with acute angulation, 86% (50/58, 95% CI 75-93%) or obtuse angulation ≥ 4 mm, 83%, (64/77, 95% CI 73-90%). Subgroup analysis by wall/septa feature was limited by sample size; however, no differences were found comparing class III masses with irregularity to class IV masses (p = 0.74) or between class IV masses by acute versus obtuse angles (p = 0.62). CONCLUSION: Preliminary data suggest Bosniak v2019 class IIF masses have higher proportion of malignancy compared to the original classification, controlling for pathologic reference standard. There are no differences in proportion of malignancy comparing class III masses with irregularities to class IV masses with acute or obtuse nodules. KEY POINTS: • The proportion of malignancy in Bosniak v2019 class IIF cystic masses is 46% (37 malignant/85 total IIF masses, 95% confidence intervals (CI) 28-66%). • The proportion of malignancy in Bosniak v2019 class III cystic masses is 79% (138/173, 95% CI 68-88%) and in Bosniak v2019 class IV cystic masses is 84% (114/135, 95% CI 77-90%). • Class III cystic masses with irregularities had similar proportion of malignancy (83%, 97/117, 95% CI 75-89%) compared to Bosniak class IV masses (84%, 114/135, 95% CI 77-90%) overall (p = 0.74) with no difference within class IV masses by acute versus obtuse angulation (p = 0.62).

Evolution of Bosniak IIF Renal Cysts and Impact of the 2019 Bosniak Classification.

PURPOSE: The follow-up of Bosniak IIF renal cysts is associated with significant costs, radiation, and anxiety. Recent studies have suggested a risk of malignancy and upgrading lower than previously reported. We aimed to determine their clinical outcomes and to evaluate the impact of the 2019 Bosniak classification on the diagnosis of such lesions. MATERIALS AND METHODS: We identified all radiology reports with the diagnosis of a Bosniak IIF cyst at our institution between January 2000 and December 2018. Imaging was reviewed to confirm the diagnosis and determine progression based on the 2005 Bosniak classification. Radiological and clinical characteristics were established, and the 2019 Bosniak criteria were retrospectively applied. RESULTS: Out of 252 cysts reviewed, 55 (22%) were reclassified as Bosniak II upon revision using the 2005 Bosniak classification. A total of 181 Bosniak IIF cysts were included for final analysis. The median imaging follow-up was 50 months. Four (2.2%) cysts progressed to Bosniak III or IV. Five (2.8%) patients underwent surgical interventions, with only 1 malignant pathology being reported. No malignant progression was observed after 36 months. When applied to our cohort, the 2019 Bosniak classification would have led to a 76% decrease in Bosniak IIF diagnoses, with no increase in Bosniak III or IV diagnoses, and identical classification of the confirmed malignant pathology. CONCLUSIONS: Upgrading and malignancy rates among Bosniak IIF cysts was markedly lower than traditionally reported. No patient had a significant progression beyond 36 months. More than 20% of Bosniak IIF cysts were initially overdiagnosed. The 2019 Bosniak classification may help to reduce the overdiagnosis of Bosniak IIF lesions requiring follow-up.

Simple renal cyst as an independent risk factor for hypertension.

A simple renal cyst (SRC) may increase the risk for hypertension. The authors examined the relationship between a SRC and hypertension in participants receiving physical examinations at Hebei Medical University. This study enrolled 66 883 participants who received physical examinations at our center from January 2012 to December 2017. Demographic data, medical history related to hypertension, hematological indexes, hypertension, and SRC subtype based on ultrasound examinations were examined. The relationship between SRC and hypertension was analyzed using univariate and multivariate logistic regression analysis in different models. Subgroup analysis and propensity score (PS) matching were also performed. Based on SRC subtype (unitary vs. multiple, small vs. large, unilateral vs. bilateral), a comprehensive scoring system was established to determine the effect of SRC load on hypertension. The results of univariate and multivariate analysis indicated that SRC was a risk factor for hypertension (P < .01). Subgroup and interaction analysis showed the homogeneity that SRC was an independent risk factor for hypertension in multiple subgroups (P > .05). A SRC remained an independent risk factor for hypertension after PS matching (P < .01). Based on a scoring system that considered different SRC subtypes, the risk for hypertension increased with renal cyst load (P < .01). In conclusions, a SRC was an independent risk factor for hypertension, and there was a positive correlation between SRC load and hypertension. The risk of hypertension increased gradually with the size, number, and location of a SRC. Careful follow-up or excision should be considered for patients with SRCs.

Assessment of the workload and financial burden of Bosniak IIF renal cyst surveillance in a tertiary referral hospital.

BACKGROUND: The Bosniak classification is a CT classification which stratifies renal cysts based on imaging appearances and therefore associated risk of malignancy. Bosniak IIf cysts are renal which have complex features and therefore require surveillance. AIMS: The aim of this study is to assess the economic and workload burden of diagnosing and following up Bosniak IIf cysts on the urology service in a tertiary hospital in the West of Ireland. METHODS: All patients with a diagnosis of Bosniak IIf renal cysts attending our urology service between 1st of January 2012 and 31st December 2020 were analysed. The following data were collected: number and modality of follow up scans, number of MDT discussions, number and type of outpatient appointments, surgical intervention, and length of follow up. Financial data were provided by the hospital finance department. RESULTS: One hundred and sixty-two patients were included. Total cost of follow up was €164,056, costing €1,012.7 per patient. Cost of outpatient visits was €77,850. Follow-up length ranged from 1 to 109 months, median follow up time 17.5 months. Overall cost of imaging was €74,518. There were a total of 80 MDT discussions at an overall cost of €11,688. CONCLUSIONS: This study demonstrates that surveillance of patients with Bosniak IIf renal cysts represents a significant burden upon both radiology and urology services. Surveillance for these patients could be streamlined in the future through a number of initiatives such as virtual OPDs and dedicated MDTs.

Prevalence, risk factors and clinical characteristics of renal dysfunction in Chinese outpatients with growth simple renal cysts.

BACKGROUND: Researchers have proved that simple renal cysts (SRCs) might be correlated with renal dysfunction, but it is still controversial. Thus, we conducted clinical research study with large sample size and long-term follow-up to clarify the relationship between SRCs and renal dysfunction. METHODS: A total of 571 SRCs patients in outpatients of nephrology department were included, we investigated the clinical characteristics of growth SRCs compared with non-growth SRCs, evaluated the incidence of renal dysfunction in SRCs and explored the risk factors of renal dysfunction in growth SRCs. RESULTS: The mean baseline age was 51.31 ± 14.37 years in the whole cohort, ranging from 19 to 79 years, and 57.6% of them were male. The median follow-up duration was 3 years, ranging from 1 to 10 years. In addition, the final maximum diameter increased 1 mm (2.74%) per year. Patients in growth SRCs group tented to have higher percentage of hypertension, hematuria, large cyst and multiple cysts compared with non-growth SRCs group. The prevalence of renal dysfunction was 15.6% after the follow-up, and the prevalence of renal dysfunction was about 10 times higher in growth SRCs group than non-growth SRCs group (23.3% vs. 2.4%). Renal dysfunction was significantly associated with age, female, total cholesterol, diastolic blood pressure, final maximum diameter and yearly change in maximum diameter in growth SRCs. CONCLUSIONS: SRCs were closely related to the decline of renal function, we recommend close follow-up for growth SRCs.

[Joubert syndrome: incidence and clinicoradiological description of a genotyped series of seven cases]. / Síndrome de Joubert: incidencia y descripción clinicorradiológica de una serie genotipada de siete casos.

INTRODUCTION: Joubert syndrome is produced by an alteration of the ciliary proteins essential for the structure and function of neurons and organs such as the kidneys, liver, sight, and hearing. Some 34 mutations are currently known. OBJECTIVE: Calculate the incidence / prevalence, describe the phenotype / genotype and radiological alterations of this ciliopathy in our health area. PATIENTS AND METHODS: We reviewed the medical records with a diagnosis of Joubert Syndrome in the last 10 years to collect phenotype, radiological characteristics, and extra-neurological manifestations in relation to the genetic alteration detected. RESULTS: 7 cases were included: 5 children (6 -17 years). They had 6 different mutations. Hypotonia, thin / long fingers and delayed psychomotor development were constant. They presented dysmorphic features, mental retardation, ocular apraxia, and nystagmus indistinctly in 3/7; Neonatal apnea/hyperpnea 2/7; hypoplasia of vermis 7/7; Molar syndrome was evident in 6/7 and in 2/7 there was elongation-thinning of cerebellar peduncles. Pontomesencephalic junction tightness 6/7; fastigium of the IV ventricle high in 4/7. Among the somatic complications, retinopathy 2/7, retinal coloboma 1/7, liver fibrosis 1/7, nephronoptysis 1/7 and renal cyst 1/7. CONCLUSIONS: The incidence of Joubert syndrome was at least 1 / 20,000 newborns / year. The pontomesencephalic and peduncular radiological alterations were constant. Hypotonia, psychomotor retardation, and thin / long fingers affected all cases.

TITLE: Síndrome de Joubert: incidencia y descripción clinicorradiológica de una serie genotipada de siete casos.Introducción. El síndrome de Joubert se produce por una alteración de las proteínas ciliares esenciales para la estructura y la función de neuronas y órganos como los riñones, el hígado, la retina y el oído. Se conocen unas 34 mutaciones en la actualidad. Objetivo. Calcular la incidencia/prevalencia y describir el fenotipo/genotipo y las alteraciones clinicorradiológicas de esta ciliopatía en nuestra área de salud. Pacientes y métodos. Revisamos las historias clínicas con diagnóstico de síndrome de Joubert en los últimos 10 años para recoger el fenotipo, las características radiológicas y las manifestaciones extraneurológicas en relación con la alteración genética detectada. Resultados. Se incluyeron siete casos, de los cuales cinco eran varones (6-17 años). Presentaban seis mutaciones diferentes. Fue constante la hipotonía, los dedos finos/largos y el retraso en el desarrollo psicomotor. Presentaban rasgos dismórficos, retraso mental, apraxia ocular y nistagmo indistintamente, 3/7; apnea/hiperpnea neonatal, 2/7; hipoplasia de vermis, 7/7; síndrome del molar, 6/7; elongación-adelgazamiento de los pedúnculos cerebelosos, 2/7; estrechez en la unión pontomesencefálica, 6/7, y fastigio del IV ventrículo alto, 4/7. Entre las complicaciones somáticas había: retinopatía, 2/7; coloboma retiniano, 1/7; fibrosis hepática, 1/7; nefronoptisis, 1/7, y quiste renal 1/7. Conclusiones. La incidencia del síndrome de Joubert fue de al menos 1/20.000 recién nacidos/año. Las alteraciones radiológicas pontomesencefálicas y pedunculares fueron constantes. La hipotonía, el retraso psicomotor y los dedos finos/largos afectaron a todos los casos.

Postnatal outcome of prenatally-detected "simple" renal cysts: Are they really simple?

BACKGROUND: The majority of simple renal cysts diagnosed postnatally are asymptomatic and rarely require treatment unless they become symptomatic or complex. We hypothesised that prenatally-detected simple renal cysts would have a similar harmless outcome. AIMS: To establish the natural history and postnatal outcome of prenatally-diagnosed simple renal cysts. STUDY DESIGN: Single-centre retrospective case-series review (12-year period). SUBJECTS: All patients with prenatally-diagnosed simple renal cysts (defined as a solitary, non-septated, non-communicating cyst in an otherwise normal kidney). OUTCOME MEASURES: Prenatal and postnatal changes to cyst size, persistence, resolution or modification of diagnosis. Data is presented as the proportion of patients or median (range). RESULTS: 30 cysts were detected (2 bilateral, 26 unilateral) in 28 fetuses (median gestational age of 23 [20-36] weeks). Median maximum diameter was 15 (4-35) mm at initial diagnosis and 17.5 (4-100) mm across all prenatal scans. On follow-up scans diagnosis was modified in 16 (53%) to: multicystic dysplastic kidney (MCDK), dilated duplex kidney, hydronephrosis, urinoma, renal agenesis and adrenal mass. 12 (40%) cysts resolved. 2 (7%) asymptomatic cysts persisted at one year postnatally. Cyst maximum diameter in the modified diagnosis group (21.5 [10-100] mm) was significantly larger than the simple cyst group (12 [4-20] mm) (P = 0.03). CONCLUSIONS: Our study revealed the challenges of prenatal ultrasound imaging, with modified diagnoses in over half the cases. Kidneys with solitary cysts could evolve into multicystic kidneys or involute completely, which suggests a true alteration in morphology rather than sonographic error. Persistent simple cysts in an otherwise normal kidney, however, resolved spontaneously or remained asymptomatic. Prenatally-detected simple cysts should be monitored with serial imaging.

Association of Abdominal Aortic Aneurysm and Simple Renal Cysts: A Systematic Review and Meta-Analysis.

BACKGROUND-OBJECTIVE: Prior studies have suggested a higher prevalence of simple renal cysts (SRC) among patients with aortic disease, including abdominal aortic aneurysms (AAA). Thus, the aim of this study was to systematically review all currently available literature and investigate whether patients with AAA are more likely to have SRC. METHODS: This study was performed according to the PRISMA guidelines. A meta-analysis was conducted with the use of random effects modeling and the I-square was used to assess heterogeneity. Odds ratios (OR) and the corresponding 95% confidence intervals (CI) were synthesized to compare the prevalence of several patients' characteristics between AAA vs. no-AAA cases. RESULTS: Eleven retrospective studies, 9 comparative (AAA vs. no-AAA groups) and 3 single-arm (AAA group), were included in this meta-analysis, enrolling patients (AAA: N = 2,297 vs. no-AAA: N = 35,873) who underwent computed tomography angiography as part of screening or preoperative evaluation for reasons other than AAA. The cumulative incidence of SRC among patients with AAA and no-AAA was 55% (95% CI: 49%-61%) and 32% (95% CI: 22%-42%) respectively, with a statistically higher odds of SRC among patients with AAA (OR: 3.02; 95% CI: 2.01-4.56; P< 0.001). The difference in SRC prevalence remained statistically significant in a sensitivity analysis, after excluding the study with the largest sample size (OR: 2.71; 95% CI: 1.91-3.84; P< 0.001). CONCLUSIONS: Our meta-analysis demonstrated a 3-fold increased prevalence of SRC in patients with AAA compared to no-AAA cases, indicating that the pathogenic processes underlying SRC and AAA could share a common pathophysiologic mechanism. Thus, patients with SRC could be considered at high risk for AAA formation, potentially warranting an earlier AAA screening.

Complex renal cysts (Bosniak ≥IIF): interobserver agreement, progression and malignancy rates.

OBJECTIVE: The objective was to assess the interobserver agreement rate, progression rates and malignancy rates in the assessment of complex renal cysts (≥ Bosniak IIF) using a population-based database. METHODS: A regional database identified 452 complex renal cysts in 415 patients between 2009 and 2019. Each patient was tracked and followed up using a unique identifier and deterministic linkage methodology. The interobserver agreement rate between radiologists was calculated using a weighted kappa statistic. Progression and malignancy rates of cysts (Bosniak ≥IIF) over the 11-year period were calculated. RESULTS: The linear-weighted kappa value was 0.69 for all complex cysts. The rate of progression and regression of Bosniak IIF cysts was 4.6% (7/151) and 3.3% (5/151), respectively. All malignant IIF cysts progressed within 16 months of diagnosis. The malignancy rate of surgically resected Bosniak III and IV cysts was 79.3% (23/29) and 84.5% (39/46), respectively. Of all malignant tumours, 73.8% and 93.7% were of low ISUP grade and low stage, respectively. CONCLUSIONS: This study further confirms that there is a good degree of agreement between radiologists in classifying complex renal masses using the Bosniak classification. The progression rate of Bosniak IIF cysts is low, but the malignancy rates of surgically resected Bosniak IIF, III and IV cysts are high. Benign cysts are frequently resected, and a very high proportion of histopathologically confirmed cancers in complex renal cysts are of low grade and stage. KEY POINTS: • There is a good degree of agreement between radiologists in classifying complex renal masses using the Bosniak classification. • The rate of progression of Bosniak IIF cysts is low, and malignant cysts progress early during surveillance. Although the malignancy rates of resected Bosniak IIF, III and IV cysts are high, the rate of benign cyst resection is significant.

Intrauterine Growth Restriction and Risk of Diverse Forms of Kidney Disease during the First 50 Years of Life.

BACKGROUND AND OBJECTIVES: Previous studies have shown that individuals with low birth weight (LBW) or small for gestational age (SGA) have higher risk of kidney failure. This study investigates birth-related exposures and risk of CKD and other kidney diagnoses. DESIGN, SETTING, PARTICIPANT, & MEASUREMENTS: The Medical Birth Registry of Norway has registered extensive medical data on all births in Norway since 1967. The Norwegian Patient Registry has registered diagnostic codes for all admissions and outpatient visits to Norwegian hospitals since 2008. Data from these registries were linked, and risk of CKD and other groups of kidney disease were analyzed using logistic regression statistics. LBW (below the tenth percentile), SGA (birth weight below the tenth percentile for gestational age), and preterm birth (<37 weeks) were analyzed as exposures. RESULTS: A total of 2,663,010 individuals were included. After a mean follow-up of 26 years (maximum 50 years), 4495 had been diagnosed with CKD and 12,818 had been diagnosed with other groups of kidney disease. LBW was associated with an odds ratio (OR) for CKD of 1.72 (95% confidence interval [95% CI], 1.60 to 1.90), SGA with an OR of 1.79 (95% CI, 1.65 to 1.94), and preterm birth with an OR of 1.48 (95% CI, 1.33 to 1.66). Analyses using diagnosis of CKD at stages 3-5 as end point showed similar results. Results were similar for men and women. We analyzed adjusted ORs for other groups of kidney disease and found that LBW was associated with an adjusted OR of 1.44 (95% CI, 1.33 to 1.56) for acute kidney disease, 1.24 (95% CI, 1.14 to 1.36) for GN, 1.35 (95% CI, 1.17 to 1.56) for cystic kidney disease, and 1.15 (95% CI, 1.06 to 1.25) for kidney disease resulting from kidney or urinary tract malformations. CONCLUSIONS: LBW, SGA, and preterm birth are associated with higher risk of CKD in the first 50 years of life. Risk of other groups of kidney disease was less pronounced. PODCAST: This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2020_08_17_CJN04080320.mp3.

Age and sex prevalence estimate of Joubert syndrome in Italy.

OBJECTIVE: To estimate the prevalence of Joubert syndrome (JS) in Italy applying standards of descriptive epidemiology and to provide a molecular characterization of the described patient cohort. METHODS: We enrolled all patients with a neuroradiologically confirmed diagnosis of JS who resided in Italy in 2018 and calculated age and sex prevalence, assuming a Poisson distribution. We also investigated the correlation between proband chronological age and age at diagnosis and performed next-generation sequencing (NGS) analysis on probands' DNA when available. RESULTS: We identified 284 patients with JS: the overall, female- and male-specific population-based prevalence rates were 0.47 (95% confidence interval [CI] 0.41-0.53), 0.41 (95% CI 0.32-0.49), and 0.53 (95% CI 0.45-0.61) per 100,000 population, respectively. When we considered only patients in the age range from 0 to 19 years, the corresponding population-based prevalence rates rose to 1.7 (95% CI 1.49-1.97), 1.62 (95% CI 1.31-1.99), and 1.80 (95% CI 1.49-2.18) per 100,000 population. NGS analysis allowed identifying the genetic cause in 131 of 219 screened probands. Age at diagnosis was available for 223 probands, with a mean of 6.67 ± 8.10 years, and showed a statistically significant linear relationship with chronological age (r 2 = 0.79; p < 0.001). CONCLUSIONS: We estimated for the first time the age and sex prevalence of JS in Italy and investigated the patients' genetic profile. The obtained population-based prevalence rate was ≈10 times higher than that available in literature for children population.

Presence of Renal Simple Cysts Is Associated With Increased Risk of Abdominal Aortic Aneurysms.

We compared the incidence of renal simple cysts in 271 patients with abdominal aortic aneurysm (AAA) and 1387 patients without AAA (controls) using computed tomography (CT) angiography and abdominal CT, as a health screening program. The AAA group had significantly higher prevalence of renal simple cysts (55% vs 19%, P = .001) and chronic obstructive pulmonary disease (COPD; 12% vs 1%, P = .011) than the controls. After propensity score matching (n = 164), the prevalence of renal simple cysts was still significantly higher in the AAA group. In multivariate analysis, independent predictors of AAA were age, male gender, smoking history, hypertension, high-sensitivity C-reactive protein, creatinine, COPD, and renal simple cysts. The structural weakness predisposing for renal simple cysts may be associated with the initiation of AAA formation. More studies are needed to determine whether the presence of renal simple cysts can be considered as a risk factor for AAA.

Nephronophthisis due to a novel DCDC2 variant in a patient from African-Caribbean descent: A case report.

Nephronophthisis-19 (NPHP19) due to truncating mutations in the DCDC2 gene has only been described previously in two patients. We describe a new case in a patient from the island country of Saint Vincent and the Grenadines, in the West Indies. This condition is a renal-hepatic ciliopathy with phenotypic characteristics that include hepatosplenomegaly, hepatic fibrosis with bile cholestasis, increased kidney echogenicity, and end-stage renal disease.Here, we report a 13-year-old African-Caribbean female with areas of absence of heterozygosity suggesting parental consanguinity or identity by decent due to the founder effect, harboring a novel homozygous pathogenic variant (c.383C>G, p.S128*) in exon 3 of DCDC2. Her phenotype is consistent with the other two known cases of NPHP19, however, this patient also presents psychiatric symptoms. These psychiatric findings were not present in the first two documented cases, and we discuss possible etiologies of these symptoms. Our study presents the first patient from the West Indies with NPHP19, and also highlights the need to investigate the frequency of pathogenic variants within at-risk populations.

A cross-sectional study of patients referred for HNF1B-MODY genetic testing due to cystic kidneys and diabetes.

BACKGROUND/OBJECTIVES: Patients referred for HNF1B testing present very heterogeneous phenotypes. Despite suggestive characteristics, many do not harbor mutations in HNF1B. Our objective was to evaluate the clinical characteristics of probands referred for HNF1B genetic testing through a nationwide monogenic diabetes screening program. METHODS: Probands tested for HNF1B mutations in the 2005-2018 period (N = 50) were identified in the Polish Monogenic Diabetes Registry, which prospectively recruits primarily pediatric patients and their families on a nationwide scale. Variants that had been reported pathogenic were reassessed using criteria of the American College of Medical Genetics and Genomics (ACMG). A structured medical interview was performed with all available individuals, their parents, and/or their physicians. For each patient, HNF1B score was calculated based on available clinical information. RESULTS: The study group numbered 36 unrelated probands (28% lost to follow-up): 14 with pathogenic or likely-pathogenic variants in HNF1B, one with a variant of uncertain significance, and 21 negative for HNF1B mutations. Presence of cystic kidneys (OR = 9.17, 95% CI:1.87-44.92), pancreatic abnormalities (OR = 15, 95% CI:1.55-145.23), elevated liver enzymes (OR = 15, 95% CI:1.55-145.23) best discriminated HNF1B-positive cases from the negative ones. Presence of impaired glucose tolerance coupled with kidney disease in the proband and one parent was also highly predictive for HNF1B mutations (OR = 11.11, 95% CI:1.13-109.36). HNF1B-score with recommended cutoff distinguished patients with and without HNF1B findings with 100% sensitivity and 47.6% specificity. Addition of four clinical variables to select patients based on HNF1B score improved specificity to 71.4% (95% CI:47.8%-88.7%) while retaining 100% sensitivity. CONCLUSIONS: Detailed medical interview may enable more accurate patient selection for targeted genetic testing.

Healthcare recommendations for Joubert syndrome.

Joubert syndrome (JS) is a recessive neurodevelopmental disorder defined by a characteristic cerebellar and brainstem malformation recognizable on axial brain magnetic resonance imaging as the "Molar Tooth Sign". Although defined by the neurological features, JS is associated with clinical features affecting many other organ systems, particularly progressive involvement of the retina, kidney, and liver. JS is a rare condition; therefore, many affected individuals may not have easy access to subspecialty providers familiar with JS (e.g., geneticists, neurologists, developmental pediatricians, ophthalmologists, nephrologists, hepatologists, psychiatrists, therapists, and educators). Expert recommendations can enable practitioners of all types to provide quality care to individuals with JS and know when to refer for subspecialty care. This need will only increase as precision treatments targeting specific genetic causes of JS emerge. The goal of these recommendations is to provide a resource for general practitioners, subspecialists, and families to maximize the health of individuals with JS throughout the lifespan.