Neocapsular reconstruction for challenging partial nephrectomy: A feasibility study in a porcine model and recent clinical experience.

OBJECTIVES: Multifocal renal masses and large central-endophytic tumors can be challenging for partial nephrectomy (PN) due to the paucity of capsule remaining after tumor removal. Our objective was to develop a neocapsule to provide tamponade and test its feasibility/safety in a porcine model. METHODS: Eight live pigs (50-70 kg) underwent unclamped open right flank PN. Renal defects were 1 cm deep and had moderate ongoing venous bleeding. A 6 × 9 inch sheet of Nu-knit® was used for neocapsular reconstruction with Fibrillar™ packing to provide modest tamponade and preclude ongoing bleeding. Blood chemistry and hemoglobin (Hb) levels were drawn preoperatively and postoperative Days 3/5/8. On postoperative Day 8, euthanasia was performed, and both kidneys were inspected and analyzed for histologic changes. RESULTS: PN defects ranged from 1 × 1 × 1 cm to 4 × 2 × 1 cm; four pigs had PN performed in both poles and four in one pole. Neocapsular reconstruction was successful (n = 8), with no perioperative complications. Median baseline Hb was 10.4 g/dL, and median Hb postoperative Days 3/5/8 were 10.0/10.8/10.6 g/dL, respectively. Median baseline serum creatinine (SCr) was 1.9 mg/dL, and median SCr postoperative Days 3/5/8 were 1.5/1.4/1.5 mg/dL, respectively. At sacrifice, no significant hematomas were observed. Other than adjacent to the PN site, there were no significant histologic changes in the parenchyma for operative kidneys versus controls. Based on our experience, we recently performed neocapsular reconstruction safely/effectively after extensive PN for multifocal tumors and for an allograft with difficult-to-manage subcapsular hematoma. CONCLUSIONS: Neocapsular reconstruction after PN or capsular trauma appears feasible and safe and may be considered to reduce the risk of perioperative bleeding. However, further study will be needed to confirm the utility/efficacy of this approach.

Determining Bone-forming Ability and Frequency of Skeletal Stem Cells by Kidney Capsule Transplantation and Limiting Dilution Assay.

Adult stem cells not only maintain tissue homeostasis but are also critical for tissue regeneration during injury. Skeletal stem cells are multipotent stem cells that can even generate bones and cartilage upon transplantation to an ectopic site. This tissue generation process requires essential stem cell characteristics including self-renewal, engraftment, proliferation, and differentiation in the microenvironment. Our research team has successfully characterized and isolated skeletal stem cells (SSCs) from the cranial suture called suture stem cells (SuSCs), which are responsible for craniofacial bone development, homeostasis, and injury-induced repair. To assess their stemness features, we have demonstrated the use of kidney capsule transplantation for an in vivo clonal expansion study. The results show bone formation at a single-cell level, thus permitting a faithful assessment of stem cell numbers at the ectopic site. The sensitivity in assessing stem cell presence permits using kidney capsule transplantation to determine stem cell frequency by limiting dilution assay. Here, we described detailed protocols for kidney capsule transplantation and limiting dilution assay. These methods are extremely valuable both for the evaluation of skeletogenic ability and the determination of stem cell frequency.

Influencing Factors of Renal Blunt Impact Injury: A Finite Element Method Study / 医用生物力学

Objective To study influencing factors of renal blunt impact injury by using finite element (FE) method. Methods Based on CT images of the kidney, the kidney FE models for different age groups were constructed. The renal blunt impact test was reconstructed, and the influence of kidney material constitutive parameters, kidney tissue structure, kidney size, impact position and impact velocity on injury severity were analyzed. Results Under the same impact condition, the stress of renal cortex decreased with the kidney mass increasing, and increased with the impact velocity of the hammer increasing. The renal capsule had a certain energy absorption effect, so as to reduce the kidney stress. When the kidney was impacted, the stress of renal cortex under side impact was significantly higher than that under frontal impact. Conclusions Compared with viscoelastic constitutive model, Mooney Rivlin material constitutive model is more suitable for FE evaluation on renal injury severity. The renal injury decreases with the kidney mass increasing. The increase of impact velocity will intensify the renal injury severity. Renal capsule will reduce renal injury to a certain extent, so the existence of renal capsule structure must be considered in FE modeling of the kidney. Compared with frontal and rear impact, the renal injury severity is greater when the kidney is impacted from the lateral side.

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.

Development of a Novel Highly Spontaneous Metastatic Model of Esophageal Squamous Cell Carcinoma Using Renal Capsule Technology.

PURPOSE: Increasing evidence has demonstrated that animal models are imperative to investigate the potential molecular mechanism of metastasis and discover anti-metastasis drugs; however, efficient animal models to unveil the underlying mechanisms of metastasis in esophageal squamous cell carcinoma (ESCC) are limited. METHODS: ESCC cell EC9706 with high invasiveness was screened by repeated Transwell assays. Its biological characteristics were identified by flow cytometry as well as by the wound healing and CCK-8 assays. Besides, the levels of epithelial-mesenchymal transition-related markers were examined using Western blotting. Parental (EC9706-I0) and subpopulation (EC9706-I3) cells were employed to establish the renal capsule model. Next, the tumor growth was detected by a live animal imaging system, and hematoxylin and eosin staining was applied to evaluate the metastatic status in ESCC. RESULTS: EC9706-I3 cells showed rapid proliferation ability, S phase abundance, and high invasive ability; obvious upregulation in N-cadherin, Snail, Vimentin, and Bit1; and downregulation in E-cadherin. EC9706-I3 cells were less sensitive to the chemotherapy drug 5-fluorouracil than EC9706-I0 cells; however, both cell lines reached a tumorigenesis rate of 100% in the renal capsule model. The live animal imaging system revealed that the tumors derived from EC9706-I0 cells grew more slowly than those from EC9706-I3 cells at weeks 3-14. The EC9706-I3 xenograft model displayed a spontaneous metastatic site, including kidney, heart, liver, lung, pancreas, and spleen, with a distant metastatic rate of 80%. CONCLUSION: Our data suggested that the metastatic model was successfully established, providing a novel platform for further exploring the molecular mechanisms of metastasis in ESCC patients.

P63 Deficiency and CDX2 Overexpression Lead to Barrett's-Like Metaplasia in Mouse Esophageal Epithelium.

BACKGROUND: The cellular origin and molecular mechanisms of Barrett's esophagus (BE) are still controversial. Trans-differentiation is a mechanism characterized by activation of the intestinal differentiation program and inactivation of the squamous differentiation program. AIMS: Renal capsule grafting (RCG) was used to elucidate whether CDX2 overexpression on the basis of P63 deficiency in the esophageal epithelium may generate intestinal metaplasia. METHODS: P63-/-;Villin-Cdx2 embryos were generated by crossing P63+/- mice with Villin-Cdx2 mice. E18.5 esophagus was xenografted in a renal capsule grafting (RCG) model. At 1, 2, or 4 weeks after RCG, the mouse esophagus was immunostained for a proliferation marker (BrdU), squamous transcription factors (SOX2, PAX9), squamous differentiation markers (CK5, CK4, and CK1), intestinal transcription factors (CDX1, HNF1α, HNF4α, GATA4, and GATA6), intestinal columnar epithelial cell markers (A33, CK8), goblet cell marker (MUC2, TFF3), Paneth cell markers (LYZ and SOX9), enteroendocrine cell marker (CHA), and Tuft cell marker (DCAMKL1). RESULTS: The P63-/-;Villin-Cdx2 RCG esophagus was lined with proliferating PAS/AB+ cuboidal cells and formed an intestinal crypt-like structure. The goblet cell markers (TFF3 and MUC2) and intestinal transcription factors (CDX1, HNF1α, HNF4α, GATA4, and GATA6) were expressed although no typical morphology of goblet cells was observed. Other intestinal cell markers including enteroendocrine cell marker (CHA), Paneth cell markers (LYZ and Sox9), and intestinal secretory cell marker (UEA/WGA) were also expressed in the P63-/-;Villin-Cdx2 RCG esophagus. Squamous cell markers (PAX9 and SOX2) were also expressed, suggesting a transitional phenotype. CONCLUSION: CDX2 overexpression on the basis of P63 deficiency in esophageal epithelial cells induces Barrett's-like metaplasia in vivo. Additional factors may be needed to drive this transitional phenotype into full-blown BE.

Renal Capsule Transplantation to Assay Angiogenesis in Skeletal Development and Repair.

Renal capsule transplantation is a very helpful method to grow embryonic tissues or tumors in a vascular environment, allowing for long-term engraftment and biological analyses. This chapter describes the surgical procedure for the transplantation of embryonic skeletal elements in the renal capsule of adult mice and points out the manipulations that can be applied for assaying the role of angiogenesis during bone development and repair.

Preliminary study on the establishment of neonatal pig models of islet transplantation under the renal capsule / 器官移植

Objective To explore the feasibility and potential application value of establishing the neonatal pig models of islet transplantation under the renal capsule. Methods Nine wild-type neonatal Duroc pigs were selected, including 1 animal as the control (p6307), 6 as islet transplant donors and 2 as islet transplant recipients (p6210, p6207). After islet isolation and differentiation in vitro, islet transplantation under the renal capsule of the pig was performed. Immunosuppressive therapy of tacrolimus (Tac) combined with sirolimus was given after operation. Postoperative body weight, blood glucose and serum creatinine levels of the recipients were monitored. The p6210 recipient neonatal pig was sacrificed at postoperative 4 weeks, while the p6207 recipient and the control neonatal pig were sacrificed at postoperative 8 weeks. The islet grafts under the renal capsule were collected for pathological staining and insulin immunofluorescent staining. Results After islet transplantation under the renal capsule of the pigs, the growth rate of body weight of the recipients was significantly slower than that of the control neonatal pig, accompanied with intermittent symptoms, such as anorexia and diarrhea, etc. However, the blood glucose and serum creatinine levels of the recipients did not significantly differ from preoperative levels and those of the control neonatal pig. Evident islet mass was observed under the renal capsule of the p6210 recipient. Pathological staining and insulin immunofluorescent staining confirmed that the islet mass had the function of secreting insulin, whereas no obvious islet mass could be seen under the renal capsule of the p6207 recipient. Pathological staining detected no evident islet mass, suggesting the possibility of islet transplantation failure caused by rejection in the p6207 recipient. Conclusions The establishment of neonatal pig models of islet transplantation under the renal capsule is a feasible technique, which provides preliminary evidence for the establishment of composite islet-kidney donor graft in pig models for xenotransplantation in the treatment of end-stage diabetic nephropathy.

Proximal ureteral reconstruction using renal capsule flap: a canine experimental model.

INTRODUCTION: The aim of this article was to evaluate the effectiveness of using the renal capsule in ureteral reconstruction in a canine model. MATERIAL AND METHODS: Ten clinically healthy male adult dogs were used in this study. Dogs underwent ureteral reconstruction using a tube-shaped flap of the renal capsule. RESULTS: All but one animal (90%) survived till nephrectomy and thereafter. At 30 days after operation, the double-J stent was removed from the ureter, and at the 60th day, intravenous pyelography confirmed openness of the duct. The internal surface of the tunneled flap was coated with thick, folded urothelium. Maturing granulation tissue and angiogenesis as well as fiber producing fibroblasts were observed in the lamina propria. The presence of smooth muscle cells beneath the lamina propria indicated complete reconstitution of the damaged ureter. CONCLUSIONS: The results showed that the autologous renal capsular flap provided a practical option for treating ureteral defects in dogs with an acceptable outcome. So, using the selfsame renal capsular tissue is a feasible method for restoration of the injured proximal ureter.

Tolvaptan for Autosomal Dominant Polycystic Kidney Disease: Pharmacokinetics and Implications for Practice.

Autosomal dominant polycystic kidney disease (ADPKD) is incurable and occurs once in every 1,000 births. Confirmation of AKPKD is made through imaging and a positive family history. Symptoms typically appear in mid-life and include kidney, side, and/or back pain related to the rupture of kidney cysts, renal stones, infection, pressure of cysts against other organs, and stretching of the renal capsule. In addition to end stage renal disease, cerebral aneurysm may also be a threat to individuals with this diagnosis. Recent clinical trials have shown that tolvaptan, a vasopressin-2 receptor antagonist, produced a moderate to significant reduction in total kidney volume and improved function, leading to its recent approval by the U.S. Federal Drug Administration for treatment of patients with ADPKD. This article provides a comprehensive look at the pathophysiology of ADPKD, pharmacokinetics and pharmacodynamics of tolvaptan, and tolvaptan's clinical implications, effects, and contraindications. In addition, we present a case study discussing tolvaptan's clinical usefulness and address patient concerns in an adult presenting with rapidly progressing ADPKD.

Protective effect of dexamethasone implant on nephrotoxicity of adriamycin in rats / 中国临床药理学与治疗学

AIM: To study the establishment of adriamycin nephropathy rat model and the protective effects and mechanisms of dexamethasone implants (DEXI) through renal capsule implantation. METHODS: The adriamycin-induced nephropathy model was built by injecting Adriamycin (4 mg/kg) and Adriamycin (3.5 mg/kg) was injected again after week into tail-vein in SD rats. Renal capsule puncture was performed in model group. The excipient control group injected intra-renal capsule with drug-free excipient (1.4 mg/kg). The experimental group (2.8, 1.4, 0.7 mg/kg) was given by intrarenal capsule injection and positive drug group (0.1 mg/kg, qd × 8 w) was made by intragastric administration. The rat weight, kidney function and blood biochemical were observed and detected during the experiment. After the experiment, rat kidneys were stained with periodic acid-schiff to observe the morphological changes of mesangial and basement and sirius red to observe the renal tissue collagen fibers, expression of podocin and CD2AP were detected by immunohistochemistry. RESULTS: The blood protein content of adriamycin rats decreased, total blood cholesterol, uric acid, blood creatinine and urea nitrogen increased (P<0.05 or P<0.01), mesangium and fibers increased. The expression of Podocin protein in kidney tissue decreased and the expression of CD2AP protein increased (P<0.05 or P<0.01). DEXI increased the weight and blood protein levels of adriamycin rats, reduced blood lipids and blood uric acid levels (P<0.05 or P<0.01), improved renal function and tissue damage, and regulated the abnormal expression and distribution of Podocin and CD2AP proteins (P<0.05 or P<0.01). CONCLUSION: These results suggest that injecting adriamycin into the tail vein can establish a stable kidney disease model. DEXI renal capsule implantation can improve adriamycin nephropathy injury, and its mechanism may be related to restoration the expression and distribution of Podocin and CD2AP proteins on podocyte slit diaphragm.

Malignant fibrous histiocytoma arising from the renal capsule and gene mutation screening: A case report.

Malignant fibrous histiocytoma (MFH) is an aggressive soft tissue sarcoma. Renal MFH is rare and information about its molecular characterization is limited. We present here the case of a 77-year-old man who was incidentally found to have a huge right renal mass on computed tomography. Radical nephrectomy was performed. Pathological diagnosis was MFH arising from the renal capsule. We used Ion AmpliSeq Cancer Hotspot Panel version 2 primers to perform gene mutation screening. We detected 13 mutations in 11 hotspot oncogenes (CSF1R, FGFR3, KDR, APC, PDGFRA, TP53, FLT3, ERBB4, KIT, STK11, RET), but these were not matched to driver mutations.

A huge benign fibrous histiocytoma arising from the renal capsule: report of a case.

BACKGROUND: Neoplasms originating in the renal capsule are very rare. Benign fibrous histiocytoma(BFH) most commonly occurs in the dermis and subcutis, few cases of this tumor appear in the renal capsule. In particular, BFH larger than 20 cm are scarce. Here we report a rare huge one measuring 23 × 13 × 7 cm. CASE PRESENTATION: We report a 64-year-old man who presented with a few-months history of dull pain in the right groin. The tumor had its point of origin in the renal capsule which is a rare condition. Histologically, the tumor was composed of intersecting fascicles of fibroblastic cells forming a "storiform" pattern. Immunohistochemical studies were also performed, ultimately leading to the diagnosis of BFH. The patient was treated with radical nephrectomy. No recurrence was detected 4 months after surgery. CONCLUSIONS: BFH arising from the renal capsule was very rare. In particular, the case of more than twenty centimeters is extremely rare. The clinical presentation of renal BFH might be only a mass. However, differential diagnosis from renal cell carcinoma proved to be impossible before surgical intervention. It is difficult to diagnose only by means of histopathology, but the immunohistochemical method can provide a clear and definite diagnosis.

Key features of the nephrogenic zone in the fetal human kidney-hardly known but relevant for the detection of first traces impairing nephrogenesis.

In healthy newborn babies, nephrogenesis proceeds unnoticed until birth. With start of the perinatal period, morphogenetic activity in the renal outer cortex consisting of an inner maturation zone and an outer nephrogenic zone is downregulated by unknown signals. One of the results is that the entire nephrogenic zone as well as the contained progenitor cells and niches disintegrate. In contrast, a too early inactivation of the nephrogenic zone takes place in the kidneys of preterm and low birth weight babies. Although they are born in a period of active nephrogenesis, pathological findings show that they evolve to a high incidence oligonephropathy. However, very few data exist about cell biological changes that are evoked by harming, further most of causing molecules, exact cell targets, and related molecular pathways are not identified. Although impairment of nephrogenesis was the subject of research in animal species, there is only limited information available pertaining to the pathological traces in the nephrogenic zone of the human fetal kidney. In this situation, the lack of basic morphological data is particularly aggravating. Surprisingly, there are not even ultrastructural investigations available. Since concrete information is lacking also in relevant textbooks, the current contribution likes to present key features of the nephrogenic zone in the fetal human kidney. Simultaneously, it is a call to explore systematically a hardly known area.

Comparison of blood glucose-lowering function of transplant islets between subcutaneous adipose tissues of inguinal region and renal capsule in mice / 器官移植

Objective To compare the effect of transplant islets between the subcutaneous inguinal white adipose tissues and renal capsule in the treatment of type 1 diabetes mellitus in mouse models. Methods The mice with type 1 diabetes mellitus undergoing islet transplantation were divided into the white adipose group (n=10) and renal capsule group (n=10). The islets were isolated, purified and transplanted to the subcutaneous white adipose tissues of inguinal region and renal capsule. The random blood glucose level and glucose tolerance function of the recipient mice in two groups were continuously monitored after operation. Islet grafts of the surviving recipient mice were harvested at postoperative 100 d for histopathological examination. Results In the white adipose group, the blood glucose levels of 6 recipient mice were restored to normal at 1 month after transplantation, whereas the blood glucose levels of the other 4 recipient mice were high, which died before the end of monitoring. In the renal capsule group, the blood glucose levels of 10 recipient mice returned to normal within 10 d after transplantation. Islet grafts of the recipient mice in two groups could lower the blood glucose levels, whereas the islet grafts in the white adipose group required a longer time to exert the effect. The glucose tolerance function of the mice in the renal capsule group was significantly better than that of those in white adipose group (P < 0.05). Histopathological examination demonstrated that the insulin of the islet grafts was normally expressed in two groups. Conclusions The islets transplanted into the subcutaneous white adipose tissues of inguinal region can play an effective role in regulating the changes of blood glucose level. Although the blood glucose-lowering function is slightly weaker than that of the islets graft in the renal capsule, it has multiple advantages resembling the ideal islet transplantation sites, which is a promising replacement site for islet transplantation.

Renal capsule metastasis from renal pelvic cancer: a case report.

BACKGROUND: Metastatic renal cancers are relatively common. Most are metastases to the renal parenchyma via a hematogenous route and are derived from lung, breast, and gastrointestinal cancer, malignant melanoma, and hematologic malignant cancer. However, little is known about renal capsule metastasis from other cancers. CASE PRESENTATION: We report a 71-year-old woman with breast cancer who was treated with endocrine therapy. She presented with gross hematuria and was diagnosed as having right renal pelvic cancer and renal cell cancer. She underwent right laparoscopic radical nephroureterectomy. Pathological findings revealed right pelvic cancer and renal capsule metastasis. CONCLUSION: Renal capsule metastasis derived from renal pelvic cancer is very rare. When diagnosing renal capsule cancer, we believe that renal capsule metastasis should also be taken into consideration. Clinical and radiological differential diagnosis of renal capsule metastasis from renal cell cancer and primary renal capsule cancer is difficult. Assessment of the histopathological findings of the surgical specimens seems to be the only realistic approach to achieving the correct diagnosis.

Leiomyoma of the renal capsule: case report and literature review.

INTRODUCTION: Mesenchymal tumors are an exceptional finding in the urinary tract and renal leiomyoma is even more rare. They are usually discovered incidentally during ultrasonography examinations or autopsy. Sometimes they are clinically symptomatic with hematuria, flank pain, or palpable mass. Till today, it is still difficult to make a diagnosis of leiomyoma using the radiological examinations. Although conventional imaging has a high sensitivity and specificity in the detection of both retroperitoneal and renal masses, the diagnosis is based on histological examination, due to the poor discrimination accuracy between different retroperitoneal tumors. CASE DESCRIPTION: We report a case of renal leiomyoma in a 47-year-old woman, who incidentally discovered a retroperitoneal mass with an abdominal ultrasound scheduled for a conventional follow-up schedule of a mammary neoplasm. Partial nephrectomy was carried out with an open flank surgical approach and the diagnosis was "leiomyoma of the renal capsule". Four years after surgery, the patient is disease-free. CONCLUSIONS: Renal leiomyomas are rare, benign, nonmetastasizing tumors with a good prognosis after surgical treatment. At present, the differential diagnosis is still possible by histopathological examination.

Use of sub-renal capsule transplantation in developmental biology.

The sub-renal capsule graft site for in vivo growth and development of developing organs can be used to great advantage in the "rescue" of organ rudiments from "embryonic" or "birth" lethal mutant mice, which permits examination of the full impact of gene knockout in all phases of development from morphogenesis to adult functional differentiation. Another use of the sub-renal capsule graft site is the examination of normal and "chemically perturbed" development of human fetal organs. Tissue recombinants composed of various types of epithelium and mesenchyme, when grafted under the renal capsule undergo normal development and in 3-4 weeks achieve full adult functional cytodifferentiation. The investigator can control many of the developmental parameters of the graft such as endocrine status of the host and treatment of the host with a variety of biologically active agents to assess their effects on development and differentiation.