The Involvement of Renal Capsule Is Associated With Acute Kidney Injury in Patients With Acute Pancreatitis

Background: Acute pancreatitis (AP) is characterized by pancreatic/peripancreatic inflammation. Involvement of renal capsule refers to peripancreatic inflammation extending beyond the Gerota fascia and disappearance of renal rim sign (+) on CT images. However, its association with acute kidney injury (AKI), an important complication of AP, was rarely studied.Aim: This study aimed to assess the relationship between the involvement of renal capsule and AKI in a cohort of patients with AP.Methods: We retrospectively screened all the patients admitted for AP from January 2018 to December 2019. The involvement of renal capsule was judged by experienced radiologists according to the CT imaging. Propensity score matching (PSM) was used to control for biases in group sizes and baseline characteristics. The primary outcome was the development of AKI during the index admission. We also categorized the pararenal inflammation with the renal rim grade (RRG) and compared the incidence of AKI among different grades.Results: Involvement of renal capsule was identified in 71 of 503 patients (14.1%). The incidence of AKI was significantly higher in these patients when compared with the matched controls (43/71, 60.6% vs. 12/71, 16.9%, p < 0.001). Moreover, mortality also differed between groups (12.7% vs. 1.4%, p = 0.017). Multivariable logistic regression showed that renal capsule involvement is an independent risk factor of AKI (odds ratio, 4.355; 95% confidence interval, 1.434, 13.230, p = 0.009). Patients with RRG grade III had a significantly higher incidence of AKI than the other two grades (60.6% for Grade III, 17.1% for Grade II, and 3.8% for Grade I, p < 0.001).Conclusion: Involvement of renal capsule is associated with higher AKI incidence and mortality.

Deubiquitinating Enzyme USP8 Is Essential for Skeletogenesis by Regulating Wnt Signaling

Disturbance in a differentiation program of skeletal stem cells leads to indecorous skeletogenesis. Growing evidence suggests that a fine-tuning of ubiquitin-mediated protein degradation is crucial for skeletal stem cells to maintain their stemness and osteogenic potential. Here, we demonstrate that the deubiquitinating enzyme (DUB) ubiquitin-specific protease 8 (USP8) stabilizes the Wnt receptor frizzled 5 (FZD5) by preventing its lysosomal degradation. This pathway is essential for Wnt/β-catenin signaling and the differentiation of osteoprogenitors to mature osteoblasts. Accordingly, deletion of USP8 in osteoprogenitors (Usp8Osx) resulted in a near-complete blockade in skeletal mineralization, similar to that seen in mice with defective Wnt/β-catenin signaling. Likewise, transplanting USP8-deficient osteoprogenitors under the renal capsule in wild-type secondary hosts did not to induce bone formation. Collectively, this study unveils an essential role for the DUB USP8 in Wnt/β-catenin signaling in osteoprogenitors and osteogenesis during skeletal development.

Local application of Usag-1 siRNA can promote tooth regeneration in Runx2-deficient mice

Runt-related transcription factor 2 (Runx2)-deficient mice can be used to model congenital tooth agenesis in humans. Conversely, uterine sensitization-associated gene-1 (Usag-1)-deficient mice exhibit supernumerary tooth formation. Arrested tooth formation can be restored by crossing both knockout-mouse strains; however, it remains unclear whether topical inhibition of Usag-1 expression can enable the recovery of tooth formation in Runx2-deficient mice. Here, we tested whether inhibiting the topical expression of Usag-1 can reverse arrested tooth formation after Runx2 abrogation. The results showed that local application of Usag-1 Stealth small interfering RNA (siRNA) promoted tooth development following Runx2 siRNA-induced agenesis. Additionally, renal capsule transplantation of siRNA-loaded cationized, gelatin-treated mouse mandibles confirmed that cationized gelatin can serve as an effective drug-delivery system. We then performed renal capsule transplantation of wild-type and Runx2-knockout (KO) mouse mandibles, treated with Usag-1 siRNA, revealing that hindered tooth formation was rescued by Usag-1 knockdown. Furthermore, topically applied Usag-1 siRNA partially rescued arrested tooth development in Runx2-KO mice, demonstrating its potential for regenerating teeth in Runx2-deficient mice. Our findings have implications for developing topical treatments for congenital tooth agenesis.

Acute abdominal pain induced by renal leiomyoma in a young patient: a case report

Renal leiomyoma is a rare benign mesenchymal tumor of the kidney that predominantly originates from the renal capsule or pelvis. However, because of its nonspecific clinical and imaging features, renal leiomyoma remains poorly characterized and may even lead to radical or partial nephrectomy on the basis of preoperative suspicion of renal carcinoma. We herein present a case involving a 12-year-old boy with acute abdominal pain who was diagnosed with renal leiomyoma based on both clinical imaging and histopathological examination. One year after radical nephrectomy, the patient recovered to good condition. This case demonstrates that the comprehensive application of imaging and histology are essential for early clinical diagnosis and effective treatment of renal leiomyoma.

What is it necessary to know about kidney stones?

Everyone who at least once in his/her life has suffered from a kidney stone, which, at a moment far from perfect, tried to go beyond the kidney and blocked the lumen of the ureter, subsequently recalls this situation as unbearable pain, the repetition of which is feared like the plague. This pain is explained by the stretching of the renal capsule with urine due to its inability to enter the bladder. The preferred localization of stones is the right kidney due to the peculiarities of its anatomical location; this pathology is noted more often in men. Kidney stones can occur at any age, and almost always bring a lot of suffering to patients. The general practitioner should have a general idea of the clinical picture of the manifestations of urolithiasis and the structure of stones, since recommendations in terms of adherence to a diet and an appropriate lifestyle depend on this knowledge.

Intrarenal injection of mesenchymal stem cell for treatment of lupus nephritis in mice – a pilot study

The current project is to explore feasibility of direct intra-renal injection of human bone marrow derived mesenchymal stem cells (hMSC) for treatment of lupus nephritis in mice. The treatment protocol involved aged male BXSB (20 weeks) injected with 1 × 106 hMSC unilaterally under the renal capsule. Mice were harvested after 10 weeks follow-up for postmortem exam. Controls included untreated age matched male BXSB and healthy C57Bl/6. At the end of follow-up period, the survival of treated BXSB was 10 folds higher at 62.5% compared to survival of untreated control at 6.3%. The survival of C57Bl/6 remained at 100% with or without similar treatment. The renal pathology review was most significant for decreased tissue inflammation in treated BXSB compared to untreated controls. Renal tissue expression of IL-1b, IL17 were decreased and CTLA-4 was increased by RT PCR among treated compared to untreated BXSB. Thus, direct delivery of hMSC by intrarenal injection is a promising route for treatment of lupus nephritis as shown in this xenogeneic model. Further studies -using expanded numbers of mice to include other lupus strains- are warranted to investigate the mechanisms involved and to optimize treatment protocol for safety and efficacy.