Distal ureteral atresia – an embryological dilemma

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

Kidney-Draining Lymph Node Fibrosis Following Unilateral Ureteral Obstruction

Although the primary organ has been the subject of intense investigation in the field of organ fibrosis over the past several decades, the presence of lymph node fibrosis due to persistent activation of the immune response in its partner organ remains largely unknown. Previously, we demonstrated that activation of the immune response following ischemia-reperfusion injury (IRI) and crescentic glomerulonephritis (CGN) in the kidney was associated with extracellular matrix (ECM) production by fibroblastic reticular cells (FRCs) of the kidney-draining lymph node (KLN). Here, we sought to determine whether FRCs in the KLN become similarly fibrogenic following unilateral ureteral obstruction (UUO) of the kidney. We subjected 6–8-week-old C57BL/6J mice to UUO for 2, 7, and 14 days. We examined the microarchitecture of the kidney and KLN by immunofluorescence staining at each timepoint, and we quantified immune cell populations in the KLN by flow cytometry. The contralateral kidney unaffected by UUO and its partner KLN were used as controls. We found through immunofluorescence staining that FRCs increased production of ECM fibers and remodeled the microarchitecture of the UUO KLN, contributing to fibrosis that mirrored the changes in the kidney. We also observed by flow cytometry that the populations of CD11b+ antigen-presenting cells, CD11c+ dendritic cells, and activated CD4+ and CD8+ T cells were significantly higher in the UUO KLN than the KLN draining the unaffected contralateral kidney. Expression of the TGFβ/TGFβR signaling pathway was upregulated and colocalized with FRCs in the UUO KLNs, suggesting a possible mechanism behind the fibrosis. Both release of ureteral ligation at 2 days following UUO and depletion of FRCs at the time of injury onset halted the progression of fibrosis in both the kidney and the KLN. These findings for the first time highlight the association between fibrosis both in the kidney and the KLN during UUO, and they lay the groundwork for future studies that will investigate more deeply the mechanisms behind the connection between FRCs and KLN fibrosis.

Development of renal adenocarcinoma in a ferret with renal cortical cysts (Mustela putorius furo)

CASE DESCRIPTION A 5.5-year-old 0.929-kg spayed female domestic ferret (Mustela putorius furo) underwent serial abdominal ultrasonographic and clinicopathologic examinations after multiple renal cysts were detected bilaterally during a routine examination. CLINICAL FINDINGS The ferret was apparently healthy at the start of the monitoring period and had no clinical signs for > 20 months. Four months after the initial examination, the largest cyst became increasingly mineralized; 17 months after detection, it had increased in size and become amorphous, and the ferret’s plasma BUN concentration was mildly high. Within 21 months after the first visit, a nodule was detectable, and hydronephrosis developed in the kidney with the largest cyst. Findings for fine-needle aspirates from the nodule were consistent with renal carcinoma. TREATMENT AND OUTCOME Contrast-enhanced CT revealed severe unilateral nephromegaly with no contrast uptake in the affected ureter. Following surgical removal of the affected kidney, histologic examination identified renal adenocarcinoma replacing the entire renal cortex and medulla. The ferret was euthanized postoperatively because of declining condition. On necropsy, metastasis to a mesenteric lymph node was identified; comorbidities included 2 other neoplasms and acute, severe injury of the contralateral kidney. CLINICAL RELEVANCE Neoplastic transformation of a renal cyst was suspected in the ferret of this report on the basis of observed ultrasonographic changes over time and extensive infiltration of the neoplasm throughout the affected kidney. Renal cysts are linked to renal neoplasia in other species, and the findings for this patient supported the need for periodic monitoring of renal cysts in ferrets.

Curcumin Protects against Renal Ischemia/Reperfusion Injury by Regulating Oxidative Stress and Inflammatory Response

Objective. The aim of this study was to explore the pharmacological effects of curcumin on oxidative stress and inflammatory response of renal dysfunction induced by renal ischemia/reperfusion (RIRI). Methods. Fifty male SD rats (Sprague Dawley) were randomly divided into the sham group, RIRI group, and curcumin group (low, medium, and high). The RIRI model was established by clipping the left renal artery for 45 min and then reperfusion for 24 h and resection of the contralateral kidney. In the curcumin group, curcumin was intraperitoneally injected once a day for 3 consecutive days using different dosage regimens. The RIRI group was intraperitoneally administered with normal saline. Renal injury was evaluated by measuring the concentration of creatinine (Cr) and urea nitrogen (BUN) in serum. Oxidative stress was assessed by assessing the level of malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione (GSH), and iron reduction/antioxidant capacity (FRAP) in tissues. In addition, the protective effect of RIRI was investigated by measuring Paller scores, the level of serum inflammatory factors and caspase-3, and the number of apoptotic cells. Results. Ischemia/reperfusion resulted in increased levels of Cr and BUN in serum and MDA in tissues and decreased levels of SOD, CAT, GPx, GSH, and FRAP. Curcumin pretreatment strikingly increased the level of SOD, CAT, GPx, GSH, IL-10, IFN-γ, and FRAP and significantly decreased MDA, Cr, BUN, IL-8, TNF-α, IL-6, and myeloperoxidase (MPO) expressions in tissues. Conclusion. Curcumin can relieve the degree of renal injury and improve renal function in ischemia-reperfusion, which may be related to the fact that curcumin can increase SOD content in serum and reduce MDA and FRAP levels in the rat model.

Hemodynamics and functional state of the contralateral kidney in the early postoperative period after surgical treatment of kidney cancer

AIM:To study the hemodynamics and functional state of the renal tissue of the contralateral kidney in the early postoperative period after surgical treatment of kidney cancer. MATERIALS AND METHODS:The prospective study included 58 patients with renal cell carcinoma, 36 (62.1%) of whom underwent radical nephrectomy, and 22 (37.9%) underwent partial nephrectomy. Tumor sizes ranged from 1.0 to 12.0 cm. All patients before surgery and in the early postoperative period underwent ultrasound examination of the structure and size of the kidneys, Doppler ultrasonography of the renal vessels, biomicroscopy of the bulbar conjunctiva, measured peripheral blood pressure, determined the glomerular filtration rate (GFR) and performed a coagulogram. The control group included 16 healthy adults. RESULTS:In 83.3% of patients after radical nephrectomy and in 13.6% of patients after partial nephrectomy a tendency towards an increase in blood pressure compared with the initial values was noted by the 2-4th day after the operation. By the 5th day after surgery, the volume of the only kidney remaining after radical nephrectomy increased by an average of 4% (from 126.1 1.4 to 131.2 2.1 cm3,p 0.05), while after partial nephrectomy has not changed reliably. After surgery, a decrease in GFR was detected in 34 (58.6%;p 0.05) patients, including after radical nephrectomy (n= 28) up to 73.4 8.2 ml / min / 1.73 m2, after partial nephrectomy (n= 6) up to 98.2 3.4 ml / min / 1.73 m2. Doppler ultrasonography of the vessels of a single kidney in patients after radical nephrectomy showed a moderate increase in linear blood flow, an increase in the resistance index in the main trunk of the renal artery, and a decrease in the pulsation index in the segmental and arc arteries. In patients after partial nephrectomy in the contralateral kidney these changes were not observed. When performing biomicroscopy of the bulbar conjunctiva in 83.3% of patients after radical nephrectomy and in 13.6% of patients after partial nephrectomy, changes in the microvasculature were revealed: narrowing of arterioles, expansion of venules, slowing of venular and capillary blood flow. Before the operation and in the early postoperative period, the content of fibrinogen and soluble fibrin-monomer complex in the blood of patients with renal cell carcinoma was significantly higher than in the control group. CONCLUSIONS:In patients with renal cell carcinoma, changes in the contralateral kidney in the early postoperative period after radical nephrectomy are significantly more pronounced than after partial nephrectomy, and are accompanied by changes in systemic and local hemodynamics and kidney function. The results of the study confirm the feasibility of performing organ-preserving surgeries in patients with renal cell carcinoma.

The changes of the tubular epithelium phenotype in the contralateral kidney nephrons while developing unilateral ureteral obstruction: an experimental study

Introduction. The high prevalence of renal diseases caused by urinary tract obstruction led to the need for experimental research of compensatory and pathological processes with kidney injury. It is also of relevance to study key mechanisms providing a compensatory function of the contralateral kidney for early diagnosis, treatment, and prognosis of obstructive renal diseases.Purpose of the study. To examine epithelial nephron cells phenotype dynamics changes in contralateral kidney using unilateral ureteral obstruction experimental model.Materials and methods. Model of unilateral ureteral obstruction was established using adult rabbits. The studies were carried out on days 7, 14 and 21 of complete obstruction of the left ureter. Immunophenotyping was performed on contralateral kidney tissue samples using epithelial (cytokeratin 7, E-cadherin) and mesenchymal (vimentin, α-smooth muscle actin) markers.Results. The contralateral kidney under additional load can maintain the morphological and functional characteristics of the nephron for a long time. The first transmogrify signs in the nephron epithelium phenotype were detected by day 21 as the diffuse appearance of mesenchymal marker vimentin with unaltered visualization of epithelial phenotype markers.Conclusion. The results obtained allow us to assume that the compensatory reserve of the contralateral kidney is gradually decreasing when the duration of the obstruction increases. Thus, the likelihood of developing negative disorders increases.

Huge Renal Angiomyolipoma in a Child with Tuberous Sclerosis Complex: A Diagnostic and Therapeutic Dilemma

Tuberous Sclerosis Complex (TSC) is a rare neuro-cutaneous disorder that is associated with the development of benign hamartomas including renal angiomyolipoma (RAML). TSC associated RAML are usually asymptomatic, but it carries a life-threatening bleeding risk. We are sharing a case of a 5-year-old girl who was diagnosed to have TSC with associated subependymal giant cell astrocytoma, cardiac rhabdomyoma and autism. She presented with a history of worsening abdominal distension over 3 weeks duration and clinically noted to be pale with a ballotable left flank mass. Ultrasound and CT scan found to have multiple RAML in both kidneys with a huge mass on the left side. The mass represented a huge RAML (8cm) with aneurysmal formation with suspicion of intratumoral bleeding. The option of conservative management with mammalian target of rapamycin inhibitor followed with partial nephrectomy has been questioned with its life-threatening risk of bleeding and inability to do biopsy to rule out the possibility of renal cell carcinoma. Decision for nephrectomy was then made clearer following a MAG-3 scan which revealed only 11% differential function of the left kidney. She underwent a total left nephrectomy uneventfully and intraoperatively noted to have an enlarging lesion as compared to the previous imaging; 15cm in largest diameter. Histopathological finding was consistent with multifocal angiomyolipoma with intratumoral haematoma. Decision for nephrectomy in TSC-associated RAML need to be justified carefully in view of its risk of losing the contralateral kidney following the disease progression which may end up with life-long renal replacement therapy.International Journal of Human and Health Sciences Supplementary Issue-2: 2021 Page: S26

sGC stimulation lowers elevated blood pressure in a new canine model of resistant hypertension

Therapy-resistant hypertension is a serious medical problem, causing end-organ damage, stroke, and heart failure if untreated. Since the standard of care fails in resistant hypertension patients, there is still a substantial unmet medical need for effective therapies. Active stimulation of soluble guanylyl cyclase via novel soluble guanylyl cyclase stimulators might provide an effective treatment option. To test this hypothesis, we established a new experimental dog model and investigated the effects of the soluble guanylyl cyclase-stimulator BAY 41-2272. In beagle dogs, a resistant hypertension phenotype was established by combining unilateral renal wrapping with the occlusion of the renal artery in the contralateral kidney. The most frequently used antihypertensive drugs were administered orally, either alone or in combination, and their acute effect on telemetric measured blood pressure was assessed and compared with that of BAY 41-2272. The chosen disease stimulus led to a moderate and stable increase in blood pressure. Even high doses of standard-of-care antihypertensives only slightly decreased blood pressure. In contrast, the administration of the soluble guanylyl cyclase stimulator BAY 41-2272 as standalone therapy led to a dose-dependent reduction in blood pressure (−14.1 ± 1.8 mmHg). Moreover, BAY 41-2272 could also further decrease blood pressure in addition to a triple combination of standard-of-care antihypertensives (−28.6 ± 13.2 mmHg). BAY 41-2272 was highly efficient as a standalone treatment in resistant hypertension but was also effective in addition to standard-of-care treatment. These data strongly suggest that soluble guanylyl cyclase stimulators might provide an effective pharmacologic therapy for patients with resistant hypertension.

Unilateral renal artery stenosis causing hypertensive flash pulmonary oedema

Flash pulmonary oedema can occur as a result of multiple triggers that may act independently or in concert. One such precipitating factor is bilateral renal artery stenosis which can be treated either with revascularisation or with medical therapy. Unilateral renal artery stenosis, however, is a rare cause of flash pulmonary oedema, especially when the contralateral kidney is still functional. We describe a case of an elderly woman with a history of heart failure with preserved ejection fraction and multiple hospitalisations for hypertensive crisis and flash pulmonary oedema who was found to have right, ostial renal artery stenosis that was treated with stent placement.