Variations in the Density and Distribution of Cajal Like Cells Associated With the Pathogenesis of Ureteropelvic Junction Obstruction: A Systematic Review and Meta-Analysis

Abstract

Introduction: Cajal like cells (CLCs) in the upper urinary tract have an ability to generate coordinated spontaneous action potentials and are hypothesized to help propel urine from renal pelvis into the ureter. The objective of this review was to describe the variations in the density and distribution of CLCs associated with ureteropelvic junction obstruction (UPJO).Materials and Methods: Studies comparing the density and distribution of CLCs in the human upper urinary tract in patients with UPJO and healthy controls were included in this systematic review. We searched online electronic databases; Ovid MEDLINE, Scopus, PubMed and Cochrane reviews for the studies published before October 31, 2020. A meta-analysis was conducted to compare the density of CLCs at the ureteropelvic junction (UPJ) in patients with UPJO and matched controls.Results: We included 20 and seven studies in the qualitative and quantitative synthesis, respectively. In majority (55%) CLCs were located between the muscle layers of the upper urinary tract. The CLC density in the UPJ gradually increased with aging in both healthy subjects and patients with UPJO. The pooled analysis revealed that the density of CLCs at the UPJ was significantly low in patients with UPJO compared to the controls (SMD = −3.00, 95% CI = −3.89 to −2.11, p < 0.01).Conclusions: The reduction in CLC density at the UPJ in patients with UPJO suggests a contribution from CLCs in the pathogenesis of UPJO. Since age positively correlates with CLC density, it is imperative to carefully match age when conducting case control studies comparing the CLC density and distribution.Protocol Registration Number: CRD42020219882.

Morphometric variations of Cajal‐like cells are associated with pelviureteric junction obstruction in children

“…[2]). Based on a recent meta‐analysis, we inferred that a reduced CLC density could be linked to PUJO [2]. Nonetheless, we also showed that CLC density increases with age in healthy subjects, therefore, a lack of strict age matching of cases and controls may have confounded previous reports [2].…”

“…The density of CLCs has been presumed to be implicated in the pathogenesis of primary pelvi-ureteric junction obstruction (PUJO). Several observational studies have shown that a low density of CLCs is associated with primary PUJO, while other studies failed to demonstrate this (reviewed in Samaranayake et al [2]). Based on a recent meta-analysis, we inferred that a reduced CLC density could be linked to PUJO [2].…”

“…Several observational studies have shown that a low density of CLCs is associated with primary PUJO, while other studies failed to demonstrate this (reviewed in Samaranayake et al [2]). Based on a recent meta-analysis, we inferred that a reduced CLC density could be linked to PUJO [2]. Nonetheless, we also showed that CLC density increases with age in healthy subjects, therefore, a lack of strict age matching of cases and controls may have confounded previous reports [2].…”

Cajal‐like cell morphometry is not associated with pelvi‐ureteric junction obstruction in adults

“…We conducted an immunohistochemical analysis coupled with an advanced image segmentation approach to identify c-Kit expressing CLCs [2]. The results of the analysis are reported as mean (AE SD).…”

“…PUJO may arise due to intrinsic, extrinsic, or functional factors. Functional obstruction of PUJO could arise due to the impairment of pacemaker potentials of Cajal‐like cells (CLCs) located at the PUJ [1]. These specialised cells play a crucial role in regulating smooth muscle contractions, while contributing to mechanosensory functions.…”