Cyst Enlargement Research Articles

Monocyte/macrophage pyroptosis and C5b-9-induced cyst enlargement in Pkd1-/- mice.

The levels of C5b-9, terminal products of complement activation, were significantly elevated in autosomal dominant polycystic kidney disease (ADPKD). However, the precise mechanisms by which C5b-9 facilitates cyst growth remain incompletely elucidated. Three groups of chronic-onset Pkd1-/- mice were established: one group received intravenous injections of 0.5 mg/kg C5b-9, another was administered 1.0 mg/kg monoclonal anti-C9 antibodies, and a control group received 1 mg/kg IgG isotype control (IC). All treatments were administered biweekly for two months (postnatal day [PD] 180-240). Renal macrophages from distinct subsets were sorted using fluorescence-activated cell sorting (FACS). To deplete macrophages, liposome clodronate (LC) was injected intraperitoneally. Sublethal irradiation followed by bone marrow (BM) reconstruction was performed in Pkd1-/- mice to evaluate the role of BM-derived macrophages (BMDMs) in ADPKD progression. (1) In vitro, sublytic C5b-9 did not affect the viability of renal tubular epithelial cells (RTECs), but significantly induced M1-like polarization and pyroptosis of BMDMs. (2) In vivo, C5b-9 notably triggered pyroptosis of Ly6C+ monocytes and a reduction in circulating monocyte numbers as cysts enlarged. (3) Residual Ly6C+ monocytes infiltrated renal tissues and differentiated into Ly6C+ macrophages, which exhibited a greater susceptibility to pyroptosis compared to Ly6C- macrophages. (4) Although limited evidence has recently suggested that Ly6C- monocytes may also be affected by C5b-9, upregulation of CCR2 in Ly6C- macrophages was observed in C5b-9-treated Pkd1-/- mice, implying that Ly6C- monocytes could represent a significant source of M2 macrophages. C5b-9 infusion promoted RTEC proliferation by inducing pyroptosis of Ly6C+ monocytes/macrophages, contributing to progressive cyst enlargement in chronic-onset PKD mice.

Adamts1 and Cyst Expansion in Polycystic Kidney Disease.

Autosomal dominant polycystic kidney disease (ADPKD) is characterized by mutations in either the Pkd1 or Pkd2 genes leading to progressive cyst growth and often kidney failure. We have previously demonstrated that tubules can enlarge following loss of Pkd1 without an increase in tubular cell numbers, suggesting that tubular basement membrane remodeling is important for cystic dilation. RNA sequencing of Pkd1 null kidneys revealed increased expression of 17 metalloproteinases, of which A Disintegrin and Metalloproteinase with Thrombospondin Motif 1 (Adamts1) is the most highly expressed and upregulated. Mice were generated with inducible tubule-specific knockout of Adamts1 alone (AtsTKO), Pkd1 alone (PkdTKO), or both (P/ATKO) following doxycycline induction from 4-6 weeks age. Uninduced mice were used as controls. AtsTKO mice had no detectable phenotype through 12 weeks age. Upregulation of Adamts1 in PkdTKO kidneys correlated with a significant increase in the 70 kDa cleavage product of the V1 isoform of versican, which localized to the tubular basement membrane and adjacent interstitial mononuclear cells. Simultaneous deletion of both Adamts1 and Pkd1 (P/ATKO) reduced Adamts1 expression levels by >90%, prevented V1 versican cleavage, and reduced interstitial macrophage accumulation and activation. P/ATKO mice demonstrated reduced cystic enlargement, improved BUN and creatinine and better survival than did PkdTKO mice. Preventing Adamts1 upregulation following loss of tubular Pkd1 effectively reduced cyst growth and preserved kidney function.

Tubercular dactylitis/Spina ventosa-A rare skeletal form of extrapulmonary tuberculosis.

A 9-year-old girl presented with progressive, painful swelling over the left index finger, associated with local signs of inflammation and restriction of finger movements. After the swelling was punctured using a needle, chronic discharging sinus formed. Examination revealed firm swelling over the right parotid area, bilateral cervical and left axillary lymphadenopathy, and firm swelling over the left index finger with a chronic discharging sinus over the lateral aspect of proximal phalanx. Mantoux intradermal injection was reactive (22x24 mm induration). Blood and pus cultures were sterile. Hand radiograph revealed dactylitis (Figure 1A-C). Fine aspiration and cytology of the cervical lymph node showed degenerated inflammatory cells, epithelioid granuloma and acid-fast bacilli. She was initiated on 4-drug antitubercular therapy (ATT). At 2-months follow-up, she was asymptomatic and had the pain and swelling over the left finger have reduced with significant radiological improvement. Tubercular dactylitis or 'spina ventosa' (wind-filled sail) refers to cystic expansion of short, tubular bones. It is commonly seen in younger children (between 1 and 6 years of age) and adults (between 20 and 50 years of age). A common presentation in endemic areas is presence of a painless, fusiform swelling over a single digit, most commonly the proximal phalanx of index or middle finger as in the index case, or over the metacarpals of middle and ring fingers. Earliest radiological clues include periosteitis followed by gradual destruction of bone and cyst formation in the cavity giving a ballooned-out appearance.

Hepatocyte differentiation requires anisotropic expansion of bile canaliculi.

During liver development, bipotential progenitor cells called hepatoblasts differentiate into hepatocytes or cholangiocytes. Hepatocyte differentiation is uniquely associated with multi-axial polarity, enabling the anisotropic expansion of apical lumina between adjacent cells and formation of a three-dimensional network of bile canaliculi (BC). Cholangiocytes, the cells forming the bile ducts, exhibit the vectorial polarity characteristic of epithelial cells. Whether cell polarization feeds back on the gene regulatory pathways governing hepatoblast differentiation is unknown. Here, we used primary hepatoblasts to investigate the contribution of anisotropic apical expansion to hepatocyte differentiation. Silencing of the small GTPase Rab35 caused isotropic lumen expansion and formation of multicellular cysts with the vectorial polarity of cholangiocytes. Gene expression profiling revealed that these cells express reduced levels of hepatocyte markers and upregulate genes associated with cholangiocyte identity. Time-course RNA sequencing demonstrated that loss of lumen anisotropy precedes these transcriptional changes. Independent alterations in apical lumen morphology induced either by modulation of the subapical actomyosin cortex or increased intraluminal pressure caused similar transcriptional changes. These findings suggest that cell polarity and lumen morphogenesis feedback to hepatoblast-to-hepatocyte differentiation.

8110 Lymphocytic Hypophysitis secondary to a ruptured Rathke’s Cleft Cyst complicated by post surgical recurrence: A rare phenomenon

Abstract Disclosure: M.S. Maharaul: None. F. Thelmo: None. I. Ahmed: None. Introduction: Lymphocytic hypophysitis secondary to ruptured Rathke’s cleft cyst (RCC) is a rare entity. Rathke’s cleft cysts are benign fluid-filled intra-sellar cysts that originate from the remnants of Rathke’s pouch and contain mucoid material. Most are asymptomatic; some may get symptomatic during cyst expansion and rupture releasing liquid content and trigger local inflammation. Surgical resection followed by glucocorticoids is usually curative. Case: A 42-year-old female presented to the hospital with one week history of right sided frontal headache associated with blurred vision in right eye. MRI Brain showed a 15 mm complex cystic lesion in the sella with suprasellar extension associated with peripheral calcifications. On admission, endocrine laboratory investigations including pregnancy test were normal. Ophthalmic testing did not reveal any acute abnormalities. Transsphenoidal surgery was performed for tumor resection. Pathology examination revealed infiltration of massive lymphocytes, macrophages, plasma cells, and eosinophils that were diagnostic of lymphocytic hypophysitis in the anterior pituitary lobe. She was started on glucocorticoids and discharged home. Rheumatology and Infectious diseases workup were unrevealing. On follow up 3 weeks later, she had self-discontinued steroids. The following week, she presented to the emergency room again with a right sided headache and blurred vision. MRI Brain revealed a 16 mm recurrent inflammatory mass lesion in the sella. Endocrine panel demonstrated an 8 am serum cortisol level of 7.4 mcg/dl, ACTH 20 pg/ml, FSH 6.2 mIU/ml, LH 4.9 mIU/ml, free T4 1.1 ng/dl and prolactin 8 ng/ml. She underwent transsphenoidal resection of the mass again and was restarted on glucocorticoids. This time pathology examination revealed an epithelial lined cyst most compatible with Rathke’s cleft cyst. She continued to remain on a glucocorticoid taper during the follow up period. On re-evaluation, her endocrinology laboratory investigations continued to show a deficiency of gonadotropins for which she is following up with OBGYN, but the remaining pituitary hormones were all within normal limits. Conclusion: Rathke’s Cleft Cysts (RCCs) should be in the differential diagnoses for evaluation of hypophysitis. There have only been a handful of cases in the literature of hypophysitis associated with a ruptured RCC, and only one case of recurrence after surgical debulking. This case provides an insight into the clinical behavior, diagnosis, and timely management of lymphocytic hypophysitis due to a ruptured Rathke’s cleft cyst and management post-recurrence. Presentation: 6/3/2024

Tubule-Specific Deletion of Adamts1 Slows Cyst Expansion in Polycystic Kidney Disease

Tubule-Specific Deletion of Adamts1 Slows Cyst Expansion in Polycystic Kidney Disease

Role of Surgery in Vestibular Schwannoma following prior Stereotactic Radiosurgery.

Stereotactic radiosurgery (SRS) is widely used for treating vestibular schwannoma (VS), offering high tumour control rates, especially in small to medium-sized tumours. However, a subset of patients experiences SRS failure, requiring subsequent salvage microsurgery (MS). The primary reason for salvage surgery is continued tumour growth, but other causes include symptom progression and cystic enlargement. Salvage surgery is more challenging due to increased tumour adhesion to critical structures, resulting in higher complication rates, particularly for facial nerve preservation. Studies suggest subtotal resection may offer better outcomes than gross total resection in terms of facial nerve function, though treatment remains complex and outcomes vary.

The impact of blastocyst grade on singleton birth weight in fresh IVF‒ET cycles in ART: a retrospective study

BackgroundThe positive correlation between embryo quality and pregnancy outcomes has been confirmed in many studies, but there are few on the impact of embryo quality on neonatal weight, especially among neonates from fresh IVF‒ET cycles in ART. Therefore, this study aimed to compare the birth weights of infants from different blastocyst grades in fresh IVF-ET cycles and explore related factors affecting birth weight.MethodsThe main outcome measure was singleton birth weight. A total of 1301 fresh cycles of single blastocyst transplantation and single live birth profiles were retrospectively analyzed and divided into four groups according to blastocyst quality: the excellent group (grade AA), which included 170 cycles; the good group (grade AB/BA), which included 312 cycles; the average group (grade BB/CA/AC), which included 559 cycles; and the poor group (grade BC/CB), which included 260 cycles. The relationships among cystic cavity expansion, endocytic cell mass, ectodermal trophoblast cell grade, and birth weight were studied. Multiple linear regression analysis was performed to investigate the relationship between blastocyst quality and neonatal birth weight and logistic regression for the risk factors for low birth weight newborns.ResultsWith decreases in the blastocyst quality, including ICM, TE quality, and embryo expansion stage, birth weight declined, and Z scores correspondingly decreased. After adjusting for confounders, the average and poor groups (P = 0.01 and P = 0.001, respectively) and blastocysts with TE grade C (P = 0.022) resulted in singletons with lower birth weight. Additionally, the poor group and blastocysts with Grade C TEs had a greater chance of leading to low birth weight infants compared with the other groups.ConclusionOur findings indicated that excellent and good-grade blastocyst transplantation could achieve better pregnancy outcomes and that average and poor-grade blastocyst transplantation, especially with grade C TEs, were associated with single birth weight loss. No association was found between the embryo expansion stage or ICM quality and neonatal birth weight.

Risk factors for long-term urination and sexual function impairment following laparoscopic resection of presacral lesions

BACKGROUNDPresacral cysts are rare congenital lesions predominantly affecting females. Surgery is often recommended after diagnosis due to the risk of malignant transformation and complications associated with cyst enlargement. Laparoscopic excision is increasingly favored due to its enhanced visualization and precision.AIMTo assess long-term urinary, sexual function outcomes and quality of life in female patients undergoing laparoscopic resection of presacral cysts.METHODSWe conducted a retrospective review of female patients who underwent laparoscopic resection of presacral cysts between August 2012 and May 2020. Patient demographics, surgical outcomes, and postoperative complications were analyzed. The urinary function was assessed using the International Consultation on Incontinence Questionnaire Female Lower Urinary Tract Symptoms Module (ICIQ-FLUTS), the sexual function was evaluated using the Female Sexual Function Index (FSFI), and quality of life was assessed using the 36-item Short-Form Health Survey (SF-36).RESULTSAmong the 32 female patients included, 10 experienced postoperative urinary incontinence, predominantly of the mixed type. The risk factors for urinary incontinence included abdominal distension and the proximity of the cyst to the rectum. Notably, urinary incontinence significantly impacted the overall lower urinary tract symptoms and quality of life. Additionally, seven patients reported postoperative sexual dysfunction, with previous abdominal or pelvic surgery and cyst location under S3 identified as risk factors, affecting the mental health aspects of their quality of life.CONCLUSIONLaparoscopic cyst resection in females poses risks of urinary and sexual dysfunction, potentially impacting quality of life. Thus, tailored management approaches are crucial.

Ketogenic Interventions in Autosomal Dominant Polycystic Kidney Disease: A Comprehensive Review of Current Evidence.

Autosomal Dominant Polycystic Kidney Disease (ADPKD) is a genetic disorder characterized by the development and enlargement of multiple kidney cysts, leading to progressive kidney function decline. To date, Tolvaptan, the only approved treatment for this condition, is able to slow down the loss of annual kidney function without stopping the progression of the disease. Furthermore, this therapy is approved only for patients with rapid disease progression and its compliance is problematic because of the drug's impact on quality of life. The recent literature suggests that cystic cells are subject to several metabolic dysregulations, particularly in the glucose pathway, and mitochondrial abnormalities, leading to decreased oxidative phosphorylation and impaired fatty acid oxidation. This finding paved the way for new lines of research targeting potential therapeutic interventions for ADPKD. In particular, this review highlights the latest studies on the use of ketosis, through ketogenic dietary interventions (daily calorie restriction, intermittent fasting, time-restricted feeding, ketogenic diets, and exogenous ketosis), as a potential strategy for patients with ADPKD, and the possible involvement of microbiota in the ketogenic interventions' effect.

Urethral duplication with a large cystic dorsal penile mass in a newborn: a case report

BackgroundUrethral duplication is a rare urogenital anomaly with varying anatomical orientations leading to diverse clinical presentations. We present a case of urethral duplication in a neonate featuring a large dorsal cystic mass on the penis, an unusual presentation.Case presentationA term male neonate with a prenatally diagnosed 10 × 10 cm genitourinary cystic mass was delivered via caesarean section. Examination revealed a large cystic mass extending dorsally from the pubic symphysis over a flattened, elongated penile shaft with a single urethral opening in the glans and undescended testes. A size 6-French feeding tube inserted into the urethra drained the bladder.Urethral communication with the cystic mass was confirmed via voiding cystourethrogram and cyst enlargement noted during voiding. Cyst fluid analysis indicated a urinary origin. Computed tomography and ultrasound were not diagnostic. Initial imaging revealed a dorsal cystic mass projecting from the pubic symphysis without bladder connection.Surgical intervention at 3 weeks revealed a Type IIA-2 urethral duplication, with a dorsal hypoplastic urethra communicating with the posterior urethra. Correction included resection of the dorsal urethra, cyst excision, and reconstruction of the penis with the orthotopic ventral urethra and bilateral orchidopexies.Satisfactory functional and cosmetic outcomes were observed at 2 and 8 months after surgery.ConclusionThis case highlights the significance of identifying unique urethral duplication presentations. The novel occurrence of Type IIA-2 urethral duplication terminating in a dorsal cystic mass underscores diagnostic complexity, surgical intricacies, and aesthetic considerations associated with such cases.

Enlarging neurenteric cyst at the craniocervical junction with a fluid-fluid level on magnetic resonance imaging: illustrative case.

Neurenteric cysts are relatively rare benign congenital intracranial cystic lesions that enlarge rarely and very slowly. The authors present a case of an enlarging neurenteric cyst at the craniocervical junction with a fluid-fluid level on magnetic resonance imaging (MRI). A 34-year-old man with no significant medical history underwent head MRI to investigate mild headaches. An incidental cystic lesion, approximately 8 mm in diameter, was revealed at the craniocervical junction. Serial follow-up MRI showed cyst enlargement with a fluid-fluid level. Four years later, the cyst reached a size of 15 mm and was surgically removed. The cyst contained cloudy fluid with a high protein concentration, without any bleeding or tissue fragments. Pathological examination confirmed the diagnosis of a neurenteric cyst. The patient recovered well, was discharged home, and has remained recurrence free for 2 years. The growth dynamics of the relatively rapidly expanding neurenteric cyst at the craniocervical junction were monitored over time using MRI. This cyst exhibited the distinctive feature of a fluid-fluid level as it enlarged. Investigating the mechanisms underlying fluid-fluid level formation may offer novel insights into the pathogenesis of cyst enlargement. https://thejns.org/doi/10.3171/CASE24180.

P2Y2R and Cyst Growth in Polycystic Kidney Disease.

Key Points Polycystic kidney disease (PKD) is characterized by continuous cyst growth, which results in a decline in kidney function.Deletion of P2Y2R and pharmacological antagonism of purinergic signaling significantly reduced cyst growth in an orthologous PKD mouse model.P2Y2R was expressed in cysts of human PKD nephrectomies, which makes P2Y2R a reasonable target for treatment of PKD. Background Autosomal dominant polycystic kidney disease (ADPKD) is characterized by multiple bilateral kidney cysts that gradually enlarge, resulting in a decline in kidney function. Cyst growth is significantly driven by ATP-dependent chloride secretion mediated by the ion channel TMEM16A. This pathway is further augmented in advanced stages of the disease by hypoxia and activation of hypoxia-inducible factor (HIF)-1α. The mechanisms by which ATP leads to activation of TMEM16A and how HIF-1α contributes to cyst growth in vivo have remained elusive. Methods Mice with an inducible tubule-specific deletion of Pkd1 were compared with mice with an additional codeletion of the purinergic receptor P2y2r. Furthermore, animals were challenged by pharmacological activation of HIF-1α and Pkd1-deficient mice were treated with suramin, an antagonist of purinergic signaling. In addition, expression of P2Y2R, TMEM16A, and HIF-1α was analyzed in nephrectomy samples from 27 patients with ADPKD. Results Genetic deletion of P2y2r significantly inhibited cyst growth in vivo. In addition, aggravation of the polycystic phenotype mediated by pharmacological activation of HIF-1α was reduced by deletion of P2y2r. Application of suramin to pharmacologically inhibit purinergic signaling also suppressed cyst enlargement in vivo. Analysis of kidney samples from 27 patients with ADPKD revealed significant expression of P2Y2R at the luminal site of the cyst-lining epithelium. Conclusions P2Y2R was significantly expressed in human and mouse polycystic kidneys. Deletion and antagonism of P2Y2R reduced cyst enlargement in an ADPKD mouse model.

#1936 Investigating genetic and environmental modifiers of autosomal dominant polycystic kidney disease through a distinct PKD2-founder variant (p.Arg803*)

Abstract Background and Aims Autosomal dominant polycystic kidney disease (ADPKD) is among the most common hereditary diseases that lead to kidney failure [1]. Apart from progressive, cystic enlargement of the kidneys, classic ADPKD is inevitably associated with polycystic liver disease (PLD) and arterial hypertension [2] due to mutated PKD1 (78%) or PKD2 (15%) [3]. Despite knowledge of the diagnostic PKD1 or PKD2 variant, there is great intrafamilial variability in terms of disease progression and organ involvement. Therefore, there is an unmet medical need to establish better genotype-phenotype correlations. In 2022, Taiwanese colleagues identified a PKD2 founder variant (NM_000297.4 (PKD2): c.2407C>T (p.Arg803*)) which accounts for 17.8% of all ADPKD cases in Taiwan [4]. As we also detected patients with PKD2-Arg803* in our European center, we hypothesize that p.Arg803* constitutes a recurrent mutation. The established Taiwanese cohort provides the unique opportunity to build up a sister cohort of patients with this specific mutation. This novel approach can aid in identifying genetic and environmental modifiers of ADPKD, which in turn is essential in elucidating the pathogenesis, as well as the adequate classification, prognosis and treatment of ADPKD patients. Method For patient recruitment, the search was carried out simultaneously in a multi-pronged approach. First, the European Rare Kidney Disease Network (ERKNet), relevant registries and biobanks were searched to identify patients. In addition, authors of ClinVar entries and published literature with specific mentions of the variant were contacted. Lastly, clinical and genetic ADPKD specialists were reached out to directly. Deep phenotyping was performed by a specific clinical questionnaire that was sent to the respective treating physicians via Microsoft Forms. This included baseline information about patients as well as clinical parameters. Specifically, a detailed analysis of kidney, liver, CNS and further manifestations of ADPKD was performed. In addition to the main mutation, additional findings in relevant ADPKD genes were documented. Environmental factors such as smoking, estrogen use, diets and exercise were also been explicitly recorded. Results Through systematic search, 545 institutions or clinicians were contacted in 47 countries. Thus far, about 170 patients with PKD2-p.Arg803* have been identified in 25 centers from 15 countries outside of Taiwan. The process of deep phenotyping is ongoing (completed on 20 patients as of 01/2024). A preliminary analysis of this smaller cohort showed a mean age of 62 (range: 38–90) years and a sex distribution (F:M) of 11: 9. The median total kidney volume was 1437 ml (IQR 2525.5) mL and three patients had reached kidney failure at age 70, 72 and 69. Eighteen out of the 20 patients had three or more liver cysts with a median total liver volume of 1849 (IQR 822.5) mL. Conclusion We are continuing to expand the cohort, aiming to reach full datasets in about 80 international patients for joint analysis with the Taiwanese founder cohort. Detailed statistical analysis of the joint cohort will allow us to better characterize modifiers on the genetic and environmental level. We hope our project can contribute to further understanding disease variability in ADPKD.

#2498 PKD2 recurrent haplotype in ADPKD patients

Abstract Background and Aims Autosomal Dominant Polycystic Kidney Disease (ADPKD) is a systemic renal ciliopathy characterized by progressive renal cyst expansion and extrarenal manifestations following loss-of-function mutations. ADPKD is primarily caused by PKD1 (72-75%) and PKD2 (15-18%), with a high level of allelic heterogeneity: it is rare to identify the same germ-line mutation in different families since mutations are “private”. In recent years the identification of several new genes has underlined the genetic heterogeneity of ADPKD. The Aim of this study is to describe a cohort of PKD2 gene-linked families with the same germ-line mutation. Method Patients (pts) with ADPKD referral to the Genetic Kidney Diseases clinic of the UOC of Nephrology of ULSS8 Berica (San Bortolo Hospital in Vicenza) were enrolled and followed prospectively. Diagnosis of ADPKD was made upon the revised Ravine's criteria. Complete clinical details were recorded, including family history and pedigree. We performed NGS with Sophia Genetic “Nephropathies Solution” Panel or Sanger sequencing to identify disease-causing mutations in the cohort. Furthermore, microsatellite analysis was performed in PKD2 gene pts with same germ-line nonsense mutation c.2533C>T (p.Arg845Ter), to identify disease haplotype. Results We identified a cohort of 30 ADPKD pts belonging to 13 families with same PKD2 germ-line nonsense mutation c.2533C>T (p.Arg845Ter). Regarding pedigree analysis, 8 families had their origin from the same geographical area and the remaining 5 were from an area 100 km away. In 4 families, we found a common individual. Concerning the microsatellite analysis, all 30 pts shared the same haplotype Chromosome 4 CEN – VG2 (TG)20, VG3 (TA + GA)32, VG4 (CA)13, D4S2929 (AC)26, D4S1563 (TG)20 – TEL indicating that those families may originate from a common ancestor. Conclusion We found the same PKD2 germline mutation in 30 ADPKD pts belonging to 13 families that share the same haplotype. Since, ADPKD mutations are “private” and Vicenza province counts almost 860000 inhabitants, our findings provide an evidence that a founder effect exists, maybe due to a founder effect in our region.

Cross-Species Insights into Autosomal Dominant Polycystic Kidney Disease: Provide an Alternative View on Research Advancement.

Autosomal Dominant Polycystic Kidney Disease (ADPKD) is a prevalent hereditary disorder that affects the kidneys, characterized by the development of an excessive number of fluid-filled cysts of varying sizes in both kidneys. Along with the progression of ADPKD, these enlarged cysts displace normal kidney tissue, often accompanied by interstitial fibrosis and inflammation, and significantly impair renal function, leading to end-stage renal disease. Currently, the precise mechanisms underlying ADPKD remain elusive, and a definitive cure has yet to be discovered. This review delineates the epidemiology, pathological features, and clinical diagnostics of ADPKD or ADPKD-like disease across human populations, as well as companion animals and other domesticated species. A light has been shed on pivotal genes and biological pathways essential for preventing and managing ADPKD, which underscores the importance of cross-species research in addressing this complex condition. Treatment options are currently limited to Tolvaptan, dialysis, or surgical excision of large cysts. However, comparative studies of ADPKD across different species hold promise for unveiling novel insights and therapeutic strategies to combat this disease.

Kidney Measurement and Glomerular Filtration Rate Evolution in Children with Polycystic Kidney Disease.

Autosomal dominant polycystic kidney disease (ADPKD) is an inherited disorder characterized by renal tubular cystic dilatations. The cysts can develop anywhere along the nephron, and over time the cystic dilatation leads to kidney enlargement. On the other hand, the cysts begin to reduce the number of functional nephrons as a consequence of cystic expansion that further contributes to the decline in renal function over the years. The pressure exerted by the dilated cysts leads to compensatory mechanisms that further contribute to the decline in renal function. These structural changes are responsible of glomerular hyperfiltration states, albuminuria, proteinuria, and hematuria. However, the presentation of ADPKD varies in children, from a completely asymptomatic child with incidental ultrasound detection of cysts to a rapidly progressive disease. There have been reports of early onset ADPKD in children younger than 2 years that showed a more rapid decline in renal function. ADPKD is caused by a mutation in PKD1 and PKD2 genes. Today, the PKD1 gene mutation seems to account for up to 85% of the cases worldwide, and it is associated with worse renal outcomes. Individuals with PKD2 gene mutation seem to present a milder form of the disease, with a more delayed onset of end-stage kidney disease. The cardinal sign of ADPKD is the presence of renal cysts during renal ultrasound. The current guidelines provide clinicians the recommendations for genetic testing in children with a positive family history. Given that the vast majority of children with ADPKD present with normal or supra-normal kidney function, we explored the glomerular filtration rates dynamics and the renal ultrasound-adjusted percentiles. In total, 14 out of 16 patients had kidney percentiles over 90%. The gene mutations were equally distributed among our cohort. In addition, we compared the modified Schwartz formula to the quadratic equation after adjusting the serum creatinine measurements. It seems that even though children with ADPKD have enlarged kidneys, the renal function is more likely normal or near normal when the quadratic estimation of glomerular filtration rate is used (qGFR tended to be lower, 111.95 ± 12.43 mL/min/1.73 m2 when compared to Schwartz eGFR 126.28 ± 33.07 mL/min/1.73 m2, p = 0.14). Also, when the quadratic equation was employed, not even a single patient reached the glomerular hyperfiltration threshold. The quadratic formula showed that glomerular filtration rates are linear or slightly decreasing after 1 year of follow-up (quadratic ΔeGFR = -0.32 ± 5.78 mL/min/1.73 m2), as opposed to the Schwartz formula that can falsely classify children in a hyperfiltration state (ΔeGFR = 7.51 ± 19.46 mL/min/1.73 m2), p = 0.019.

Post-partum thyroiditis with concurrent enlargement of thyroglossal duct cyst due to presumed thyroiditis within the cyst wall- a pathophysiological link or a coincidence?

Post-partum thyroiditis with concurrent enlargement of thyroglossal duct cyst due to presumed thyroiditis within the cyst wall- a pathophysiological link or a coincidence?

High-Resolution Spatial Lipidomic Profiling of the Kidney During Periods of Cyst Expansion in a Mouse Model of ADPKD

Introduction: The progression of renal pathology in autosomal dominant polycystic kidney disease (ADPKD) involves a complex series of changes including renal cyst formation, interstitial cyst expansion, tubular atrophy, and fibrosis. Changes to in tissue metabolism and cyst fluid metabolite composition have been shown in ADPKD models, however it has been diffcult to discretely localize these compounds to specific regions of the kidney. Further, very little is known about lipid profiles within the kidney during ADPKD. We hypothesized that spatial lipidomic analysis during periods of cyst expansion would reveal new understanding of changes in lipid metabolism during this critical window of pathology. In this study we focused on changes in the mcwPkd1nl/nl mouse, a hypomorphic ADPKD model that rapidly develops a cystic phenotype. Methods: Kidneys were collected from female cystic mcwPkd1nl/nl mice at postnatal days 7, 14 and 28, representing periods preceding, during and at maximal cyst expansion, respectively. Control kidneys were collected from female wild-type littermates at postnatal day 7 and 28. Tissues were rapidly cryoembedded for 10 mm sectioning onto Intellislides (BrukerDaltonik). Slides were scanned on a Reflecta MF-5000 scanner and sprayed with 7 mg/mL CHCA in 70% Acetonitrile, 30% water and 0.1% TFA using a TM Sprayer Model M3 (HTX Technologies, LLC). Mass spec imaging data was acquired with a Bruker timsTOF Flex system (BrukerDaltonik) with a Smartbeam 3D laser at 10kHz and 10 μm resolution. Imaging data analysis was performed in SCiLS Lab software (version 2023b, Bruker). Calculations were performed on data normalized to total ion count (TIC). Spatial segmentation analysis of data was performed using an unsupervised bisecting k-means algorithm and resulting clusters were investigated by ROC. Lipid annotation was performed the Lipid Species annotation tool with MSDial VS68 spectral library in Metaboscape (version 2022b, Bruker). Results: There were vast global differences between lipid composition of wild-type and cystic kidneys at postnatal day 28. When comparing cystic to wild-type kidneys phosphoinositol and ceremide lipid species were decreased and other metabolites, such as thiophene-3-carboxylate and benzothiazine-2-carbonitrile, were increased at both PN7 and PN28. Further numerous lipid compounds were identified only within cystic fluid that have not been previously annotated. Conclusions: The results of this study, for the first time, reveals alterations in lipid molecule profiles throughout the cystic kidney in tandem with morphological changes. This is a major step forward in understanding how lipid metabolism changes in response to cyst expansion during the progression of ADPKD, as well as revealing molecular changes that precede cellular pathology. This work has been supported by Children’s Wisconsin Foundation and Children’s Research Institute. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Analysis of the prenatal ultrasound diagnostic value and prognostic factors of fetal mediastinal cysts.

A prenatal fetal mediastinal cyst is a benign disease. However, if a cyst enlargement grows, it may compress the adjacent organs and affect the fetal cardiopulmonary function. This study aimed to compare and analyze the prenatal ultrasound characteristics of different mediastinal cysts, and to evaluate the pregnancy outcome of the fetus and the factors affecting the prognostic of the fetus. To compare and analyze the prenatal ultrasound characteristics of different types of mediastinal cysts, and to evaluate the fetal pregnancy outcome and the influencing factors of fetal prognosis. A retrospective analysis of patients with prenatal diagnoses of mediastinal cysts was conducted to evaluate the ultrasound characteristics and to monitor the pregnancy outcomes to identify prognostic influences and provide a reliable basis for patient prognosis. In total, 30 patients were diagnosed with mediastinal cysts [including bronchogenic cysts (n=12), esophageal cysts (n=9), pericardial cysts (n=5), and thymic cysts (n=4)] on prenatal ultrasonography. The diagnostic accuracy rate was 93.33%; two cases of esophageal cysts were misdiagnosed as bronchial cysts. In total, 4 (44.44%) of 9 esophageal cysts and 4 thymic cysts were located in the anterior mediastinum, 10 (83.33%) of 12 bronchogenic cysts and 5 pericardial cysts were located in the middle mediastinum, and 2 (16.67%) of 12 bronchogenic cysts and 5 (55.56%) of 9 esophageal cysts were located in the posterior mediastinum. There were significant differences in the distribution of the cyst location, morphology, and cyst wall thickness (P<0.05). After delivery, 17 patients had clinical symptoms. There was a significant difference in the clinical symptoms between patients with a maximum diameter of postpartum cysts <5 and ≥5 cm (P<0.05), and children with a low gestational age and birth weight were more likely to have clinical symptoms. The prenatal ultrasound features of fetal mediastinal cysts were similar. However, the ultrasound characteristics related to the cyst location, morphology, and cyst wall thickness were helpful in providing an accurate diagnosis. In addition, the postpartum cyst size, location, adjacent relationship with the surrounding tissues, volume, gestational age, and weight were related to patient prognosis.