Inflammatory Renal Disease Research Articles

Pyeloduodenal fistula: a review of the current literature.

Pyeloduodenal fistula (PDF) is a communication between the renal pelvis and the duodenum. It is often secondary to other diseases. It is a rare condition and therefore infrequently described in the literature. The aim is to present a review of the current literature on PDF and to give an update of its aetiology, symptoms, investigations and treatments. Pubmed, Cochrane Library and Embase were used to search for existing literature in English and Scandinavian languages with available abstracts in the period Jan 2000-Dec 2023. No meta-analysis or reviews were found. In total, 24 original articles were found, including 25 cases all in all of both traumatic and spontaneous pyeloduodenal fistulas. Only four cases (15%) represented traumatic pyeloduodenal fistulas, and all of the spontaneous cases involved the right kidney and occurred due to calculi and pyonephrosis in 81% and 76% of the cases, respectively. Fever and flank pain were reported in 67% and 57% of the cases, respectively. Diagnosis was done by a CT urography or antegrade pyelography in 80% of the cases. More than 50% of all cases were managed by nephrectomy. Total parenteral nutrition (TPN) was administered alongside the nephrectomy in 28% of all cases. A pyeloduodenal fistula often involves the right kidney and often occurs as a result of chronic renal inflammatory disease. The fistulas are most efficiently diagnosed with a CT scanning with contrast or retrograde pyelography. The most frequently used management of pyeloduodenal fistula is nephrectomy after closure of the duodenum with somatostatin and TPN.

Growth arrest-specific protein 6 as a marker of nephritis in systemic sclerosis and juvenile systemic lupus erythematosus patients.

Background: Renal impairments commonly occur as a complication of autoimmune connective tissue diseases (CTDs). Therefore, early nephritis prediction is vital for patient outcomes. Growth Arrest-Specific Protein 6 (GAS6) was found to be upregulated in many types of inflammatory renal disease, including diabetic nephropathy.Aim: To evaluate GAS6 as a predictor of renal impairment in adults with systemic sclerosis (SSc) and children with systemic lupus Erythematosus (SLE).Methods: The study included 60 patients with SSc and 40 children with SLE. The serum level of GAS6 was measured using the ELISA technique. In adults with SSc, total proteins in 24-h urine concentration of >300mg/24 h indicated renal inflammation, while in children with SLE, nephritis was diagnosed by abnormal renal pathology.Results: In SSc patients, GAS6 significantly increased in patients with proteinuria. GAS6 is an independent predictor of nephritis with an odds ratio (OR) of 1.06 and a 95% confidence interval (CI) of 1.0-1.1. at cutoff 12.2ng/mL GAS6 predicted proteinuria with sensitivity 86.7% (95% CI: 59.5% to 98.3%), specificity 57.8% (95% CI: 42.1% to 72.3%), positive predictive value 40.6% (95% CI: 31.5% to 50.4%), negative predictive value 92.9% (95% CI: 77.7% to 97.73%), and accuracy 65.0% (95% CI: 51.6% to 76.9%). In SLE patients, Serum GAS6 did not differ significantly between children with and without lupus nephritis.Conclusion: GAS6 is an independent predictor of nephritis in patients with SSc. However, there is no association between GAS6 and nephritis in juvenile patients with SLE.

Adaptor protein 14-3-3zeta promotes corneal wound healing via regulating cell homeostasis, a potential novel therapy for corneal injury

Severe corneal injury can lead to blindness even after prompt treatment. 14-3-3zeta, a member of an adaptor protein family, contributes to tissue repair by enhancing cellular viability and inhibiting fibrosis and inflammation in renal disease or arthritis. However, its role in corneal regeneration is less studied. In this study, filter disc of 2-mm diameter soaked in sodium hydroxide with a concentration of 0.5 N was placed at the center of the cornea for 30 s to establish a mouse model of corneal alkali injury. We found that 14-3-3zeta, which is mainly expressed in the epithelial layer, was upregulated following injury. Overexpression of 14-3-3zeta in ocular tissues via adeno-associated virus-mediated subconjunctival delivery promoted corneal wound healing, showing improved corneal structure and transparency. In vitro studies on human corneal epithelial cells showed that 14-3-3zeta was critical for cell proliferation and migration. mRNA-sequencing in conjunction with KEGG analysis and validation experiments revealed that 14-3-3zeta regulated the mRNA levels of ITGB1, PIK3R1, FGF5, PRKAA1 and the phosphorylation level of Akt, suggesting the involvement of the PI3K-Akt pathway in 14-3-3zeta-mediated tissue repair. 14-3-3zeta is a potential novel therapeutic candidate for treating severe corneal injury.

Establishment, optimization and validation of a fluorescence polarization-based high-throughput screening assay targeting cathepsin L inhibitors

Cathepsin L (CTSL), a lysosomal cysteine proteinase, is primarily dedicated to the metabolic turnover of intracellular proteins. It is involved in various physiological processes and contributes to pathological conditions such as viral infection, tumor invasion and metastasis, inflammatory status, atherosclerosis, renal disease, diabetes, bone diseases, and other ailments. The coronavirus disease 2019 (COVID-19), with its rapid global spread and significant mortality, has been a worldwide epidemic since the late 2019s. Notably, CTSL plays a role in the processing of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein, providing a potential avenue to block coronavirus host cell entry and thereby inhibit SARS-CoV-2 infection in humans. In this study, we have developed a novel method using fluorescence polarization (FP) for screening CTSL inhibitors in a high-throughput format. The optimized assay demonstrated its appropriateness for high-throughput screening (HTS) with a Z-factor of 0.9 in a 96-well format. Additionally, the IC50 of the known inhibitor, Z-Phe-Tyr-CHO, was determined to be 188.50 ± 46.88 nM. Upon screening over 2000 small molecules, we identified, for the first time, the anti-CTSL properties of a benzothiazoles derivative named IMB 8015. This work presents a novel high-throughput approach and its application in discovering and evaluating CTSL inhibitors.

Effect of empagliflozin use on monocyte high-density lipoprotein ratio and plasma atherogenic index in obese and non-obese type 2 diabetic patients.

Diabetes mellitus (DM) is a metabolic disorder marked by hyperglycemia, caused by impaired insulin secretion and activity. Chronic inflammation holds a significant role in the development, progression, and complications of DM and obesity. There are publications reporting that the monocyte/ high-density lipoprotein (HDL)-C ratio (MHR) and plasma atherogenic index (PAI) could be used as indicators of systemic inflammation. In the present study, we aimed to explore the effect of empagliflozin, an inhibitor of sodium-glucose co-transporter 2 (SGLT2), on MHR and PAI in obese and non-obese type 2 diabetes mellitus (T2DM) patients. A total of 125 patients who presented to the outpatient clinics of Tokat Gaziosmanpasa University Hospital between January 2019 and January 2023 with a diagnosis of T2DM and were started on 25 mg empagliflozin and used for a minimum of 24 weeks were included in the study. The patients' age varied between 18-75 years, were without chronic liver disease, chronic renal failure, infection, or inflammatory disease, and were not on drugs affecting bone marrow. The patients were categorized into two groups, obese and non-obese, according to their body mass index (BMI). The data obtained were statistically analyzed using the IBM SPSS Statistics 25 software package. The mean age of the patients was 57.5 ± 10.9 years. Of the patients, 59.2% (n = 74) were female, and 40.8% (n = 51) were male. The mean HbA1c percentage was 8.99 ± 2.18% prior to empagliflozin treatment and significantly decreased to 7.68 ± 1.80% after empagliflozin use (p < 0.05). The mean monocyte HDL-C ratio (MHR) pre- and post-empagliflozin treatment was 16.22 ± 6.31 and 13.77 ± 5.29, respectively, and these values significantly differed from each other (p < 0.05). The mean plasma atherogenic index (PAI) of the patients before empagliflozin treatment was 0.62 ± 0.28, whereas, after the treatment, it significantly reduced to 0.52 ± 0.27 (p < 0.05). While MHR and PAI statistically significantly decreased with the use of empagliflozin, there was no difference between the obese and non-obese patient groups in terms of MHR and PAI results. Studies in the literature show that the decrease in MHR and PAI leads to a decline in inflammation. MHR and PAI are inexpensive and practical markers to assess cardiovascular disease risk and inflammation in diabetic patients. This finding indicates that MHR and PAI can be used as inflammation markers in patients on empagliflozin treatment.

Stem cell-based therapy for systemic sclerosis

Abstract Autoimmune diseases, including SSc, are prevalent, affecting autologous connective tissues and caused by the breakdown of self-tolerance mechanisms of the immune system. During the last 2 decades, stem cell therapy has been increasingly considered as a therapeutic option in various diseases, including Parkinson’s disease, Alzheimer’s disease, stroke, spinal cord injury, multiple sclerosis, inflammatory bowel disease, liver disease, diabetes, heart disease, bone disease, renal disease, respiratory disease and haematological abnormalities such as anaemia. This is due to the unique properties of stem cells that both divide and differentiate to the specialized cells in the damaged tissue. Moreover, they impose immunomodulatory properties affecting the diseases caused by immunological abnormalities such as SSc. In the present review, the efficacy of stem cell therapy with two main types of stem cells, including mesenchymal stem cells and hematopoietic stem cells, will be reviewed. Moreover, other related issues, including safety, changes in immunological parameters, suitable choice of stem cell origin, conditioning regimen and complications of stem cell treatment will be discussed.

MDCT Diagnosis and Staging of Xanthogranulomatous Pyelonephritis.

Background: Benign nephrectomy to treat patients with renal inflammatory disease in cases of severe urinary infection represents a diagnostic and management challenge because of significant inflammatory, fibrotic, and infectious components. Among renal inflammatory diseases, fistulization and invasiveness to adjacent structures are some of the hallmarks of xanthogranulomatous pyelonephritis (XGP). The aims of this study were as follows 1. to retrospectively determine key demographic and clinical features of XGP among benign nephrectomies; 2. to assess the CT preoperative diagnostic accuracy; and 3. to define the imaging characteristics of the CT stage. Material and Methods: A retrospective review of clinical, laboratory, and radiological features and operative methods of patients who underwent benign nephrectomy with histologically proven XGP was performed. Results: XPG was diagnosed in 18 patients over a 4-year (2018-2022) period. XGP represented 43.90% among benign nephrectomies. The mean age of the patients was 63 years, and the sex prevalence was higher in women (72.22%). Symptoms were vague and not specifically referrable to urinary tract disorders and unilateral (100%), with the left kidney affected in 61.11% of cases. Staghorn calculi and stone disease were the most common underlying cause (72.22%). All patients underwent CT. The preoperative CT imaging accuracy for renal inflammatory disease was 94.44% and indeterminate in 5.56%. A suspected diagnosis of XGP was formulated in 66.67% (12/18; 2 stage II/10 stage III), meanwhile, in 33.33% (6 patients with stage I), a non-specific diagnosis of renal inflammatory disease was formulated. CT was reported according to the Malek and Elder classification and staged in the stage I nephric form (33.33%), stage II perinephric form (11.11%), stage III paranephric form (55.56%). Conclusions: The CT diagnostic accuracy for kidney inflammatory disease was extremely high, whereas the suspected diagnosis of XGP was formulated preoperatively in only 66.67% of high-stage disease, where the hallmarks of invasiveness and fistulization of the pathology increased the diagnostic confidence.

A new era of genetic diagnosis for short stature children: A review

Children with short stature are often presented to pediatric endocrinologists. Short stature is defined as the height that is more than two standard deviations below the corresponding mean height for a specific age and sex in a reference population. Endocrine dysfunctions, including growth hormone deficiency/insensitivity, hypothyroidism, cortisol excess, precocious puberty, chronic disease (renal disease, diabetes mellitus, or inflammatory disease), and genetic disorders, should be assessed in patients presenting with short stature. In addition to medical history, physical examination, endocrine study, skeletal survey, and genetic testing are important for identifying the cause of short stature. Based on the next-generation sequencing analysis in patients with short stature, different genes that are unrelated to syndromic or non-syndromic short stature were identified. In particular, the genetic causes of short stature disrupting the growth plates and the pituitary-insulin-like growth factor axis have expanded. In recent years, the molecular level of chondrogenesis in the growth plates, including paracrine signals, extracellular matrix, and fundamental intracellular signals, has been reported. Moreover, new insights into the molecular pathogenesis of short stature are emerging. This article aimed to review the genetic causes of primary growth impairment in idiopathic short stature conditions.

The Role of Microbiome-Based Therapeutics in Clostridioides difficile Infection: Durable, Long-Term Results of RBX2660.

A recently published manuscript described findings from a phase 2 open label study of the microbiota-based live biotherapeutic product RBX2660 in patients with two or more previous recurrent Clostridioidesdifficile infection (rCDI) episodes, and described long-term safety and sustained treatment success through 24months. As previous studies have typically focused on short-term clinical outcomes, these new data provide insight into the tolerability, safety, and efficacy of RBX2660 over the long term. When microbiota-based products were first evaluated, the long-term efficacy and safety were principal concerns of the United States Food and Drug Administration. Microbiota-based live biotherapeutic products (LBPs) represent an emerging approach to the management of CDI and perhaps other gastrointestinal and medical conditions whose pathogenesis is defined by microbial dysbiosis. RBX2660 is a human-derived, broad consortium microbiota-based LBP that consists of a population of microbes obtained from healthy stool donors and may reflect the symbiotic nature of a healthy colonic microbiome. RBX2660 is rectally administered and does not require sedation or special preparation of the recipient. Potential advantages of the rectal administration of RBX2660 include the ease of administration and lack of need for any bowel preparation, which may benefit those who are frail, have swallowing issues, or cannot take bowel laxative preparations. In this multicenter prospective trial of rCDI, patients who achieved treatment success 8weeks after receiving RBX2660 continued to have a sustained clinical response over the course of long-term follow-up, with more than 90% of treatment responders remaining CDI-free at 6, 12, and 24months. Following receipt of RBX2660, the gut microbiota of those with treatment success were restored from a dysbiotic state to become more diverse and similar to RBX2660 composition. The restoration of the microbiota occurred as early as 7days after RBX2660 administration and remained stable through the 24-month analysis. No new adverse outcomes were observed during the prospective assessment, and the safety profile of RBX2660 was consistent with previous studies. Based on the clinical studies, RBX2660 will most likely benefit those with ≥ 1 rCDI episode or those who are at a high risk of subsequent rCDI, such as patients who have comorbid conditions including renal disease, heart disease, or inflammatory bowel disease, or who are immunosuppressed. The role of microbiome-based therapeutics in 47 Clostridioides difficile infection: Durable, long-term results of RBX2660 (MP4 511833 KB).

Axl Expression in Renal Mesangial Cells Is Regulated by Sp1, Ap1, MZF1, and Ep300, and the IL-6/miR-34a Pathway.

Axl receptor tyrosine kinase expression in the kidney contributes to a variety of inflammatory renal disease by promoting glomerular proliferation. Axl expression in the kidney is negligible in healthy individuals but upregulated under inflammatory conditions. Little is known about Axl transcriptional regulation. We analyzed the 4.4 kb mouse Axl promoter region and found that many transcription factor (TF)-binding sites and regulatory elements are located within a 600 bp fragment proximal to the translation start site. Among four TFs (Sp1, Ap1, MZF1, and Ep300) identified, Sp1 was the most potent TF that promotes Axl expression. Luciferase assays confirmed the siRNA results and revealed additional mechanisms that regulate Axl expression, including sequences encoding a 5′-UTR mini-intron and potential G-quadruplex forming regions. Deletion of the Axl 5′-UTR mini-intron resulted in a 3.2-fold increases in luciferase activity over the full-length UTR (4.4 kb Axl construct). The addition of TMPyP4, a G-quadruplex stabilizer, resulted in a significantly decreased luciferase activity. Further analysis of the mouse Axl 3′-UTR revealed a miRNA-34a binding site, which inversely regulates Axl expression. The inhibitory role of miRNA-34a in Axl expression was demonstrated in mesangial cells using miRNA-34a mimicry and in primary kidney cells with IL-6 stimulated STAT3 activation. Taken together, Axl expression in mouse kidney is synergistically regulated by multiple factors, including TFs and secondary structures, such as mini-intron and G-quadruplex. A unique IL6/STAT3/miRNA-34a pathway was revealed to be critical in inflammatory renal Axl expression.

Role of T-lymphocytes in Kidney Disease.

BackgroundThe role of T-regulatory cells (Tregs) in inflammatory renal disease is not yet established. We attempted to study peripherally circulating T-cells expressing RORγt+Foxp3+ dynamics in acute kidney injury (AKI) and chronic kidney disease (CKD).AimTo determine the role of T-regulatory cells in AKI and CKD.Research methodology This is a cross-sectional study conducted between January 2019 to January 2021 at a single tertiary care centre in Pune, India. Candidates enrolled in the study were either patients with CKD not on maintenance hemodialysis or newly diagnosed cases of AKI. Kidney transplant recipients, patients with autoimmune diseases like systemic lupus erythematosus (SLE), IgA nephropathy, or those receiving immuno-suppressants were excluded. T-lymphocytes were analyzed using a flow cytometer. ResultsWe studied 80 patients with kidney injury, 40 each belonging to the AKI and CKD study groups and 10 healthy volunteers as controls. The rationale behind having a small control group was to merely get an idea of T helper 17 (Th17):Treg ratio and different immune cell-phenotype profiles in healthy volunteers without kidney injury, diabetes, hypertension or any other risk factors. The ratio of RORγt:Foxp3 was ≤ 1 in these individuals (control group) while this ratio was significantly altered (MFI RORγt:Foxp3 ≥1) in the AKI/CKD study arm. We examined peripherally circulating T-lymphocytes in acute kidney injury and chronic kidney disease, comparing their activity to healthy volunteers. Biopsy-proven kidney injury patients (29/80) were also included in this study. We found that the ratio of RORγt:Foxp3 was altered in patients with kidney injury (acute and chronic) and was statistically significant compared to controls, indicating that injury may be attributed to T-cell dysfunction. ConclusionOur study provides some evidence of T-cell dysfunction in the pathology of kidney injury in acute and chronic kidney disease via activity of Foxp3 and RORγt. We found that there is evidence of altered Th17/Treg activity in kidney injury, more prevalent in acute than chronic, when compared to healthy volunteers.

Use of Rifaximin in Irritable Bowel Syndrome Treatment

Introduction and purpose of the work: Irritable Bowel Syndrome (IBS) affects up to 10% of the population. The deterioration in health-related quality of life in IBS patients has been shown to be comparable to, and perhaps even more severe than, other serious chronic organic diseases such as inflammatory bowel disease, diabetes, hypertension, and end-stage renal disease. The aim of the study is to present a new method of IBS treatment.State of knowledge: There are four main types of IBS: Constipation-predominant IBS (IBS-C), Diarrhea-predominant IBS (IBS-D), Fluctuating IBS (IBS-M), and the unclassified form of IBS (IBS-U). Disturbances in entero-brain interactions play a key role in its multifactorial etiopathogenesis. In patients with IBS, quantitative and qualitative disturbances in the composition of the intestinal microbiota can be found. So far, it has not been possible to clearly establish the cause of the disease, so there is no possibility of causal therapy and effective cure. Both non-pharmacological methods and drugs, including rifaximin α, have been used in IBS therapy.Summary: Rifaximin has a positive effect on the symptoms of IBS. In clinical trials conducted in patients with IBS, the use of rifaximin for 2 weeks was associated with a reduction in the severity of joint symptoms, bloating, abdominal pain and discomfort, and an improvement in stool consistency within 4 and 12 weeks, and did not increase the risk of side effects. In the forms: with predominant diarrhea, mixed and unclassified, in order to reduce the overall symptoms as well as reduce the severity of flatulence and / or diarrhea, a 14-day therapy with rifaximin α is recommended.

Pyeloduodenal Fistula in Xanthogranulomatous Pyelonephritis

Xanthogranulomatous pyelonephritis (XGP) is a rare but severe form of inflammatory renal disease associated with renal stones and results in granulomatous tissue invading and destroying normal parenchyma. A serious complication of XGP is fistulization to surrounding structures. We present a case of XGP with pyeloduodenal fistula (PDF) in a 48-year-old female with a history of hypertension and recurrent urinary infections but no previous stones.

The Restoration of Vitamin D Levels Slows the Progression of Renal Ischemic Injury in Rats Previously Deficient in Vitamin D.

Chronic kidney disease (CKD) remains a global public health problem. The initial damage after ischemia/reperfusion (I/R) injury plays an important role in the pathogenesis of acute kidney injury (AKI) and predisposition to CKD. Several studies have been showing that nontraditional risk factors such as AKI and hypovitaminosis D could also be involved in CKD progression. Vitamin D deficiency (VDD) is associated with hemodynamic changes, activation of inflammatory pathways and renal disease progression (RDP) following I/R-AKI. Strategies for prevention and/or slowing RDP have been determined and the sufficiency of vitamin D has been emerging as a renoprotective factor in many diseases. Therefore, we investigated the effect of the restoration of vitamin D levels in the progression of I/R injury (IRI) in rats previously deficient in vitamin D. On day 30, male Wistar rats were submitted to bilateral 45 min IRI and divided into three groups: IRI, standard diet for 120 days; VDD+IRI, vitamin D-free diet for 120 days; and VDD+IRI+R, vitamin D-free diet in the first 30 days and just after I/R, we reintroduced the standard diet in the last 90 days. After the 120-day protocol, VDD+IRI+R rats presented an improvement in the renal function and renal protein handling followed by a smaller fractional interstitial area. Furthermore, those animals exhibited a reestablishment regarding the hemodynamic parameters and plasma levels of aldosterone, urea and PTH. In addition, the restoration of vitamin D levels reestablished the amount of MCP1 and the renal expressions of CD68+ and CD3+ cells in the VDD+IRI+R rats. Also, VDD+IRI+R rats showed a restoration regarding the amount of collagen type III and renal expressions of fibronectin, vimentin and α-SMA. Such changes were also accompanied by a reestablishment on the renal expression of VDR, Klotho, JG12, and TGF-β1. Our findings indicate that the restoration of vitamin D levels not only improved the renal function and hemodynamics but also reduced the inflammation and fibrosis lesions observed in I/R-AKI associated with VDD. Thus, monitoring of vitamin D status as well as its replacement in the early stages of kidney injury may be a therapeutic alternative in the mitigation of renal disease progression.

Role of Multidetector Computed Tomography in Evaluation of Renal Infections Hayam A. Abdellatif, Hager S. Sakr, El-Sayed M. El-Sayed

Background: Imaging plays a very important role in the diagnosis of renal infection. It assists diagnosis and differentiates between different types of renal infection. It also helps to detect and manage the associated complications through image-guided drainage and aspiration. Contrast-enhanced CT is the most useful study. A contrast-enhanced study is essential for a complete evaluation of patients with renal inflammatory disease to demonstrate alterations in the renal parenchymal perfusion and excretion of the contrast material, which occur as a result of the inflammatory process. Objective: To detect the role of multidetector CT in diagnosis of renal infection. Materials and methods: This prospective study was conducted on sixty patients. The study was carried out at Diagnostic Radiology Departments of Menoufia University Hospital. The patients were presenting with fever (< 38°C) mainly and loin pain. Results: From 60 patients with renal infection, 18 cases were diagnosed as pyonephrosis, 16 cases were diagnosed as renal abscess, 12 cases were diagnosed as pyelonephritis, 4 cases were diagnosed as xanthogranulomatous pyelonephritis, 4 cases were diagnosed as perinephric abscess, 2 cases were diagnosed as emphysematous pyelonephritis, 2 cases were diagnosed as fungal ball, 2 cases were diagnosed as urinoma. The mean age was (39.4 ± 15.7). Conclusion: Contrast enhanced computed tomography is a perfect diagnostic modality to assess the severity of inflammatory process and reaching the diagnosis of renal infection. It also helps to reach the cause, predisposing factors, associations, complications and the extent of the disease.

Lipidomics Revealed Aberrant Metabolism of Lipids Including FAHFAs in Renal Tissue in the Progression of Lupus Nephritis in a Murine Model.

Lupus nephritis (LN) is an inflammatory renal disease of patients with systemic lupus erythematosus with lots of immune complexes deposited in kidneys. Accumulated studies have demonstrated the close relationships among dyslipidaemia, inflammation, and autoimmune response, and oxidative stress in the patients. Lipids play numerous important roles in biological process and cellular functions. Herein, shotgun lipidomics was employed to quantitatively analyze cellular lipidomes in the renal tissue of MRL/lpr mice in the progression of LN (including pre-LN and LN state) with/without treated with glucocorticoids (GCs). The levels of cytokines (i.e., TNF-α (Tumor necrosis factor alpha) and IL-6 (Interleukin 6)) in the serum were measured by ELISA (enzyme-linked immunosorbent assay) kits. Renal histopathological changes and C3 deposition in the glomeruli of the mice were also determined. Lipidomics analysis revealed that the ectopic fat deposition and the aberrant metabolism of lipids that were relevant to oxidative stress (e.g., 4-hydroxyalkenal, ceramide, lysophospholipid species, etc.) always existed in the development of LN. Moreover, the anti-inflammatory FAHFA (fatty acid ester of hydroxyl fatty acid) species in the kidney tissue could largely reflect the severity of LN. Thus, they were a potential early biomarker for LN. In addition, the study also revealed that treatment with GCs could prevent the progression of LN, but greatly aggravate the aberrant metabolism of the lipids, particularly when used for a long time.

CDK9 inhibition improves diabetic nephropathy by reducing inflammation in the kidneys

Diabetic nephropathy (DN) is a chronic inflammatory renal disease induced by hyperglycemia. Recent studies have implicated cyclin-dependent kinase 9 (CDK9) in inflammatory responses and renal fibrosis. In this study, we explored a potential role of CDK9 in DN by using cultured mouse mesangial cell line SV40 MES-13 and streptozotocin-induced type 1 mouse model of diabetes. We inhibited CDK9 in mice and in cultured cells by a highly selective CDK9 inhibitor, LDC000067 (LDC), and evaluated inflammatory and fibrogenic outcome by mRNA and protein analyses. Our studies show that treatment of diabetic mice with LDC significantly inhibits the levels of inflammatory cytokines and fibrogenic genes in kidney specimens. These reductions were associated with improved renal function. We also found that LDC treatment suppressed MAPK-AP1 activation. We then confirmed the involvement of CDK9 in cultured SV40 MES-13 cells and showed that deficiency in CDK9 prevents glucose-induced inflammatory and fibrogenic proteins. This protection was also afforded by suppression of MAPK-AP1. Taken together, our results how that hyperglycemia activates CDK9-MAPK-AP1 axis in kidneys to induce inflammation and fibrosis, leading to renal dysfunction. Our findings also suggest that CDK9 may serve as a potential therapeutic target for DN.

Comparison of laparoscopic and hand-assisted laparoscopic nephrectomy for inflammatory renal disease: which is the preferred approach?

Aims:Management of inflammatory renal disease (IRD) can still be technically challenging for laparoscopic procedures. The aim of the present study was to compare the safety and feasibility of laparoscopic and hand-assisted laparoscopic nephrectomy in patients with IRD.Patients and methods:We retrospectively analyzed the data of 107 patients who underwent laparoscopic nephrectomy (LN) and hand-assisted laparoscopic nephrectomy (HALN) for IRD from January 2008 to March 2020, including pyonephrosis, renal tuberculosis, hydronephrosis, and xanthogranulomatous pyelonephritis. Patient demographics, operative outcomes, and postoperative recovery and complications were compared between the LN and HALN groups. Multivariable logistic regression analysis was conducted to identify the independent predictors of adverse outcomes.Results:Fifty-five subjects in the LN group and 52 subjects in the HALN group were enrolled in this study. In the LN group, laparoscopic nephrectomy was successfully performed in 50 patients (90.9%), while four (7.3%) patients were converted to HALN and one (1.8%) case was converted to open procedure. In HALN group, operations were completed in 51 (98.1%) patients and conversion to open surgery was necessary in one patient (1.9%). The LN group had a shorter median incision length (5 cm versus 7 cm, p < 0.01) but a longer median operative duration (140 min versus 105 min, p < 0.01) than the HALN group. There was no significant difference in blood loss, intraoperative complication rate, postoperative complication rate, recovery of bowel function, and hospital stay between the two groups. Multivariable logistic regression revealed that severe perinephric adhesions was an independent predictor of adverse outcomes.Conclusion:Both LN and HALN appear to be safe and feasible for IRD. As a still minimally invasive approach, HALN provided an alternative to IRD or when conversion was needed in LN.

Challenges and management of laparoscopic treatment of pyonephrosis caused by calculi

BackgroundCalculous pyonephrosis is a disease characterized by infectious hydronephrosis associated with pyogenic destruction of the renal parenchyma, with complete or almost complete loss of renal function.MethodsThe clinical data of laparoscopic nephrolithotomy performed at Peking University People’s Hospital from May 2017 to June 2020 were analyzed retrospectively. Eight patients (2 men; 6 women) aged 27 to 65 years (average age, 45.8 years) were included. Among them, 7 patients were treated with retroperitoneal approach and 1 patient by transperitoneal approach. All patients had received more than one endoscopic lithotripsy before nephrectomy. Renal dynamic imaging and computed tomography revealed the absence of function in pyonephrosis before nephrectomy. General clinical data and perioperative data were recorded. All nephrectomies were performed by the same physician.ResultsLaparoscopic surgery was successfully performed in 7 patients; however, 1 patient underwent open surgery because of bleeding. The operation time, average operation time, and blood loss were 1.5–4.5 h, 3.4 h, and 100–1000 ml (average, 300 ml), respectively. The postoperative pathology showed inflammatory renal disease in 6 patients, xanthogranulomatous pyelonephritis in 1 patient, and high-grade urothelial cancer in 1 patient. The average postoperative hospital stay was 5.3 days. One patient had a Clavien–Dindo Grade IIIb complication (severe hematuria), which required laparotomy, and was found that there was bleeding of ureteral stump. None of the patients experienced poor healing of endoscopic wounds.ConclusionFor patients with complicated calculous pyonephrosis, renal inflammation could not be effectively controlled, and renal function was seriously damaged. Thus, kidneys should be immediately resected. With laparoscopy, patients may recover quickly, but surgeons require enough experience when performing laparoscopy to achieve safety.

Podocytes present antigen to activate specific T cell immune responses in inflammatory renal disease.

Infiltration of activated T cells into renal tissue plays an essential role in inflammatory nephropathy. However, the mechanism enabling the renal recruitment and activation of T cells remains elusive. Here we report that inflammatory cytokine-promoted antigen presentation by podocytes is a key for recruiting and activating specific T cells. Our results showed that diabetes-associated inflammatory cytokines IFNγ and IL-17 all upregulated expression of MHC-I, MHC-II, CD80 and CD86 on the podocyte surface. Both IFNγ and IL-17 stimulated the uptake and processing of ovalbumin (OVA) by mouse podocytes, resulting in presentation of OVA antigen peptide on the cell surface. OVA antigen presentation by podocytes was also validated using human podocytes. Furthermore, OVA antigen-presenting mouse podocytes were able to activate OT-I mouse T cell proliferation and inflammatory cytokine secretion, which in turn caused podocyte injury and apoptosis. Finally, OT-I mice subjected to direct renal injection of OVA plus IFNγ/IL-17 but not OVA alone exhibited OVA antigen presentation by podocytes and developed nephropathy in 4 weeks. In conclusion, antigen presentation by podocytes under inflammatory conditions plays an important role in activating T cell immune responses and facilitating immune-mediated glomerular disease development. © 2020 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.