High Activation of the AKT Pathway in Human Multicystic Renal Dysplasia

Pathobiology ◽  
2020 ◽  
Vol 87 (5) ◽  
pp. 302-310
Author(s):  
Alexia Apostolou ◽  
Brice Poreau ◽  
Loris Delrieu ◽  
Julien Thévenon ◽  
Pierre-Simon Jouk ◽  
...  
Keyword(s):  
Mesangial Cells ◽  
Renal Dysplasia ◽  
Mtor Pathway ◽  
Multicystic Dysplastic Kidney ◽  
Renal Development ◽  
Glomerular Mesangial Cells ◽  
Dysplastic Kidney ◽  
Cell Proliferation And Differentiation ◽  
Identical Manner ◽  
Multicystic Renal Dysplasia

Multicystic renal dysplasia is a congenital cystic anomaly of the kidney caused by abnormal metanephric differentiation with immature tubules. It is surrounded by mesenchymal collars and islands of immature mesenchyma present between the cysts. The PI3K-AKT-mTOR signaling pathway is a key regulator involved in cell growth, proliferation, motility, survival, and apoptosis. Activation of the PI3K-AKT-mTOR pathway results in the survival and proliferation of tumor cells in many cancers. The aim of this study is to analyze the topographic expression of phospho-AKT, phospho-mTOR, and phospho-70S6K in renal development and in the multicystic dysplastic kidney (MCDK). A total of 17 fetal kidneys of development age from the first to the third trimester and 13 cases of pathological kidneys with MCDK were analyzed by immunohistochemistry in order to evaluate the expression of phospho-AKT (S473), phospho-mTOR, and phospho-70S6K. Phospho-AKT and phospho-mTOR were expressed early in renal development and in an identical manner for every structure derived from the ureteric bud, such as collecting ducts and urothelium. Phospho-p70S6K was expressed early in the urothelium and in glomerular mesangial cells. Later, their expressions differed according to the needs of cell proliferation and differentiation over time by becoming more selective. In MCDK, phospho-AKT, phospho-mTOR, and phospho-70S6K have the same profile: a high cytoplasmic expression in cystic epithelium, loose mesenchyma, and primitive tubes. This study demonstrates the essential and specific role of the PI3K-AKT-mTOR pathway in the formation of cysts in multicystic renal dysplasia.

scholarly journals Insulin-like growth factor (IGF) and IGF binding protein gene expression in multicystic renal dysplasia.

1997 ◽  
Vol 8 (1) ◽  
pp. 85-94
Author(s):  
D G Matsell ◽  
T Bennett ◽  
R A Armstrong ◽  
P Goodyer ◽  
C Goodyer ◽  
...  
Keyword(s):  
Gene Expression ◽  
Renal Dysplasia ◽  
Multicystic Dysplastic Kidney ◽  
Fetal Life ◽  
Histopathological Changes ◽  
Mesenchymal Tissue ◽  
Multicystic Renal Dysplasia ◽  
Igf Binding ◽  
Metanephric Blastema ◽  
Igfbp 3

Multicystic dysplastic kidney disease is the most common form of renal dysplasia that leads to ESRD in children. This study describes the histopathological changes of multicystic dysplasia that occur from early fetal life to the postnatal period. At 14 wk gestation, early cystic enlargement of various segments of the nephron have been identified, in addition to a displaced metanephric blastema adjacent to zones of normal nephrogenesis. At later stages, the predominant features include cyst enlargement with marked fibromuscular collars, architectural disorganization, and replacement of the interstitium with a disarray of mesenchymal tissue. This study investigated the expression of the mRNA encoding the insulin-like growth factors (IGF) and IGF binding proteins (IGFBP) and have demonstrated IGF-II, IGFBP-2, and IGFBP-3 to be altered. Apart from their expression in the displaced metanephric blastema, both IGF-II and IGFBP-2 were overexpressed in abnormal tissue elements in all kidneys from fetal to postnatal life. IGF-II gene expression was localized to mesenchymal tissue, specifically in the periductal fibromuscular collars. IGFBP-2 mRNA was found to be expressed exclusively in the cyst epithelia of all cysts at all ages studied, whereas IGFBP-3 mRNA was absent from these epithelia. This study details the failure of normal IGF expression in the development of multicystic renal dysplasia and suggests a role for the IGF system in the progressive histopathological changes of this disorder.

Distal ureteral atresia – an embryological dilemma

2022 ◽  
pp. 205141582110481
Author(s):  
Subramanya Kattepura ◽  
Attibele Mahadevaiah Shubha ◽  
Kanishka Das
Keyword(s):  
Preoperative Diagnosis ◽  
Renal Dysplasia ◽  
Urogenital Sinus ◽  
Multicystic Dysplastic Kidney ◽  
Level Of Evidence ◽  
Case Presentation ◽  
Contralateral Kidney ◽  
Urinary Tract Anomaly ◽  
Dysplastic Kidney ◽  
Associated Malformations

Introduction: Distal ureteral atresia is a rare urinary tract anomaly generally associated with ipsilateral renal dysplasia and abnormalities such as multicystic dysplastic kidney, hydronephrosis and megaureter in the contralateral kidney. Despite burgeoning investigation modalities, definitive preoperative diagnosis of this condition is rarely feasible, also the embryological disarray of events that result in the development of this anomaly and the associated malformations is not clearly understood. Case presentation: We hereby report two cases of distal ureteral atresia and discuss the diversity in their presentations, diagnosis, atypical associations and management and review the possible embryological mal-development. Conclusion: Distal ureteral atresia with urogenital sinus as in Case 1 has not been documented so far and a plausible embryological explanation is deduced regarding its occurrence. The course of the affected kidney following timely and adequate relief of obstruction in Case 2 is depicted, highlighting the eventual management. Level of evidence: Not applicable

Platelet-activating factor and the kidney

1986 ◽  
Vol 251 (1) ◽  
pp. F1-F11 ◽  
Author(s):  
D. Schlondorff ◽  
R. Neuwirth
Keyword(s):  
De Novo ◽  
Mesangial Cells ◽  
Biological Activities ◽  
Platelet Activating Factor ◽  
Calcium Ionophore ◽  
Initial Step ◽  
Renal Physiology ◽  
Dependent Manner ◽  
Glomerular Mesangial Cells ◽  
Isolated Kidney

Platelet-activating factor (PAF) represents a group of phospholipids with the basic structure of 1-alkyl-2-acetyl-sn-glycero-3-phosphocholine. A number of different cells are capable of producing PAF in response to various stimuli. The initial step of PAF formation is activation of phospholipase A2 in a calcium-dependent manner, yielding lyso-PAF. During this step arachidonic acid is also released and can be converted to its respective cyclooxygenase and lipoxygenase products. The lyso-PAF generated is then acetylated in position 2 of the glycerol backbone by a coenzyme A (CoA)-dependent acetyltransferase. An additional pathway may exist whereby PAF is generated de novo from 1-alkyl-2-acetyl-sn-glycerol by phosphocholine transferase. PAF inactivation in cells and blood is by specific acetylhydrolases. PAF exhibits a variety of biological activities including platelet and leukocyte aggregation and activation, increased vascular permeability, respiratory distress, decreased cardiac output, and hypotension. In the kidney PAF can produce decreases in blood flow, glomerular filtration, and fluid and electrolyte excretion. Intrarenal artery injection of PAF may also result in glomerular accumulation of platelets and leukocytes and mild proteinuria. PAF increases prostaglandin formation in the isolated kidney and in cultured glomerular mesangial cells. PAF also causes contraction of mesangial cells. Upon stimulation with calcium ionophore the isolated kidney, isolated glomeruli and medullary cells, and cultured mesangial cells are capable of producing PAF. The potential role for PAF in renal physiology and pathophysiology requires further investigation that may be complicated by 1) the multiple interactions of PAF, prostaglandins, and leukotrienes and 2) the autocoid nature of PAF, which may restrict its action to its site of generation.

Cytogenomic aberrations in isolated multicystic dysplastic kidney in children

2021 ◽  
Author(s):  
Tian-Jian Chen ◽  
Renfang Song ◽  
Adam Janssen ◽  
Ihor V. Yosypiv
Keyword(s):  
Multicystic Dysplastic Kidney ◽  
Dysplastic Kidney

scholarly journals Laparoscopic transposition for crossing vessels (vascular hitch) in pure extrinsic pelvic-ureteric junction obstruction: a successful case report of a 2-year-old infant with horseshoe kidney

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Satoshi Ieiri ◽  
Kouji Nagata
Keyword(s):  
Laparoscopic Surgery ◽  
Left Kidney ◽  
Horseshoe Kidney ◽  
Renal Scintigraphy ◽  
Multicystic Dysplastic Kidney ◽  
Extrinsic Compression ◽  
Dysplastic Kidney ◽  
Renal Vessels ◽  
The Right ◽  
Crossing Vessels

Abstract Background Pediatric hydronephrosis induced by pelvic-ureteric junction obstruction (PUJO) is treated by dismembered pyeloplasty (DP) via open and laparoscopic surgery. The etiology of PUJO involves both intrinsic stenosis and extrinsic compression of crossing vessels (CVs). PUJO owing to CVs is also treated by DP, as there is no consensus concerning this vascular condition. We encountered a 2-year-old infant with pure extrinsic PUJO combined with horseshoe kidney who successfully underwent laparoscopic transposition for CVs (vascular hitch). Case presentation A 2-year-old boy was prenatally diagnosed with left multicystic dysplastic kidney (MDCK) and right hydronephrosis and received a definitive diagnosis after birth. At 6 months old, renal scintigraphy revealed a non-functioning pattern in the left kidney and an obstructive pattern in the right, showing no response to furosemide loading. The patient also had recurrent urinary tract infection, and his right hydronephrosis gradually worsened. We decided to perform surgery for the right PUJO. Preoperative enhanced computed tomography detected three right renal vessels independently branching from the abdominal aorta. The middle renal vessels were located at the ventral side of the pelvis and coincident with the site of PUJO. These vessels were suspected of being CVs. The patient underwent laparoscopic surgery electively. A 5-mm trocar was inserted at the umbilicus for a 5-mm, 30° rigid scope. Two additional ports were then inserted under laparoscope inspection. The dilated right pelvis and CVs were detected after ascending colon mobilization. To confirm the pathogenesis of PUJO, the CVs were dissected and taped. After taping the CVs, an intraoperative diuretic test was performed using furosemide loading. Peristalsis of the right ureter was recognized, and the extrinsic PUJO owing to the CVs was definitively confirmed. We therefore performed transposition for the CVs (vascular hitch procedure). The CVs were mobilized in the cranial direction and those were wrapped by dilated pelvis. The post-operative course was uneventful. The renal scintigraphy findings improved and showed a favorable response of furosemide loading. Conclusions The laparoscopic vascular hitch procedure is minimally invasive and effective for extrinsic PUJO due to CVs. Anastomotic stricture after Anderson and Hynes DP can be prevented by appropriate patient selection.

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