Arterial Embolization of Polycystic Kidneys for Heterotopic Transplantation

Introduction: The purpose of this study was to evaluate the efficacy of polycystic kidney embolization, performed to reduce kidney volume before heterotopic kidney transplantation, as this technique could be an alternative to pretransplant nephrectomy. Materials and Methods: All patients who underwent pretransplant embolization of polycystic kidneys were included in a prospective register from June 2014 to February 2020. All patients underwent computed tomography (CT) scan with volumetric reconstruction (OsiriX, Bernex, Switzerland) before embolization and were then followed up at 3 and 6 months after embolization. Primary outcome was percentage of kidney volume reduction. Secondary outcomes were 30 day mortality and morbidity. Results: Thirty-one embolizations performed on 29 patients (medium age = 55.6; 62.1% male) were included between June 2014 and February 2020. All patients were under dialysis before embolization (9 peritoneal dialysis and 20 hemodialysis). Technical success was observed in 96.8% of cases. Mean procedural time was 65 minutes (range = 35–106 minutes) and mean length of in-hospital stay was 3.8 days (range = 3–6 days). A volume reduction allowing a kidney transplant was obtained for 28 patients (96.5%). The mean volume reduction was 39.9% (range = 6.01–68.2). The main observed complication was postembolization pain in 10 cases (32.2%). One patient needed complementary nephrectomy due to insufficient volume reduction. Twenty-three patients (79.3%) received renal transplant during follow-up with a mean delay of 19.5 month (range = 4–54). Conclusion: Polycystic kidney embolization is an effective and safe minimally invasive technique. It can be proposed as the first-choice technique for kidney transplant recipients as an alternative to pretransplantation nephrectomy.

SYNDROME DE MECKEL GRUBER: A PROPOS DUN CAS RARE

Meckel-Gruber syndrome is a monogenic congenital disorder characterized by occipital encephalocele, polydactyly, and polycystic kidneys. This syndrome is incompatible with life. We report a case diagnosed on fetal ultrasound at a gestational age of 22 SA and 6 days, presenting the clinical triad of Meckel-Gruber syndrome. A medical termination of the pregnancy was indicated. From this rare case, and through a review of the literature, we will discuss the different clinical, ultrasound and prognostic aspects of this rare pathology.

Sex-dependent Effects of Nephron Ift88 Disruption on Blood Pressure, Renal Function and Cystogenesis

Background: Primary cilia regulation of renal function and blood pressure (BP) in health and disease is incompletely understood. The current study investigated the effect of nephron ciliary loss on renal physiology, blood pressure and ensuing cystogenesis. Methods: Mice underwent doxycycline (DOX)-inducible nephron-specific knockout (KO) of the Ift88 gene at 2 months of age using a Cre-LoxP strategy. Blood pressure, kidney function, and renal pathology were studied 2 and 9 months after DOX (Ift88 KO) or vehicle (control). Results: At 2 months post DOX, male, but not female, Ift88 KO, compared to sex-matched control, mice had reduced BP, enhanced salt-induced natriuresis, increased urinary nitrite/nitrate (NOx) excretion, and increased kidney NOS3 levels which localized to the outer medulla; the reductions in BP in male mice were prevented by L-NAME. At 9 months post DOX, male, but not female, Ift88 KO mice had polycystic kidneys, elevated BP and reduced urinary NOx excretion. No differences were observed in plasma renin concentration, plasma aldosterone, urine vasopressin or urine PGE2 between Ift88 KO and control mice at 2 or 9 months post DOX. Conclusions: Nephron cilia disruption in male, but not female, mice: 1) reduces BP prior to cyst formation; 2) increases NOx production that may account for the lower BP prior to cyst formation; and 3) induces polycystic kidneys that are associated with hypertension and reduced renal NO production.

CEP55 promotes cilia disassembly through stabilizing Aurora A kinase

Primary cilia protrude from the cell surface and have diverse roles during development and disease, which depends on the precise timing and control of cilia assembly and disassembly. Inactivation of assembly often causes cilia defects and underlies ciliopathy, while diseases caused by dysfunction in disassembly remain largely unknown. Here, we demonstrate that CEP55 functions as a cilia disassembly regulator to participate in ciliopathy. Cep55−/− mice display clinical manifestations of Meckel–Gruber syndrome, including perinatal death, polycystic kidneys, and abnormalities in the CNS. Interestingly, Cep55−/− mice exhibit an abnormal elongation of cilia on these tissues. Mechanistically, CEP55 promotes cilia disassembly by interacting with and stabilizing Aurora A kinase, which is achieved through facilitating the chaperonin CCT complex to Aurora A. In addition, CEP55 mutation in Meckel–Gruber syndrome causes the failure of cilia disassembly. Thus, our study establishes a cilia disassembly role for CEP55 in vivo, coupling defects in cilia disassembly to ciliopathy and further suggesting that proper cilia dynamics are critical for mammalian development.