Complement activation in wasp venom-induced acute kidney injury.

Previous studies have highlighted the significant role of complement activation in kidney injuries induced by rhabdomyolysis, intravascular hemolysis, sepsis, and ischemia-reperfusion. Nevertheless, the specific role and mechanism of complement activation in acute kidney injury (AKI) caused by wasp venom remain unclear. The aim of this study was to elucidate the specific complement pathway activated and investigate complement activation in AKI induced by wasp venom. In this study, a complement-depleted mouse model was used to investigate the role of complement in wasp venom-induced AKI. Mice were randomly categorized into control, cobra venom factor (CVF), AKI, and CVF + AKI groups. Compared to the AKI group, the CVF + AKI group showed improved pathological changes in kidneys and reduced blood urea nitrogen (BUN) levels. The expression levels of renal complement 3 (C3), complement 5 (C5), complement 1q (C1q), factor B (FB), mannose-binding lectin (MBL), and C5b-9 in AKI group were upregulated compared with the control group. Conversely, the renal tissue expression levels of C3, C5, C1q, FB, MBL, and C5b-9 were decreased in the CVF + AKI group compared to those in the AKI group. Complement activation occurs through all three pathways in AKI induced by wasp venom. Furthermore, complement depletion by CVF attenuates wasp venom-induced nephrotoxicity, suggesting that complement activation plays a primary role in the pathogenesis of wasp venom-induced AKI.

STING deficiency protects against wasp venom-induced acute kidney injury.

OBJECTIVE: Recent evidence suggests a key role of the inflammatory responses in wasp venom-induced acute kidney injury (AKI). However, the potential regulatory mechanisms underlying the inflammatory responses in wasp venom-induced AKI remain unclear. STING reportedly plays a critical role in other AKI types and is associated with inflammatory responses and diseases. We aimed to investigate the involvement of STING in inflammatory responses associated with wasp venom-induced AKI. METHODS: The role of the STING signaling pathway in wasp venom-induced AKI was studied in vivo using a mouse model of wasp venom-induced AKI with STING knockout or pharmacological inhibition and in vitro using human HK2 cells with STING knockdown. RESULTS: STING deficiency or pharmacological inhibition markedly ameliorated renal dysfunction, inflammatory responses, necroptosis, and apoptosis in wasp venom-induced AKI in mice. Moreover, STING knockdown in cultured HK2 cells attenuated the inflammatory response, necroptosis, and apoptosis induced by myoglobin, the major pathogenic factor in wasp venom-induced AKI. Urinary mitochondrial DNA upregulation has also been observed in patients with wasp venom-induced AKI. CONCLUSIONS: STING activation mediates the inflammatory response in wasp venom-induced AKI. This may offer a potential therapeutic target for the management of wasp venom-induced AKI.

Wasp venom-induced acute kidney injury: current progress and prospects.

Wasp venom can trigger local and systemic reactions, with the kidneys being commonly affected, potentially causing acute kidney injury (AKI). Despite of the recent advances, our knowledge on the underlying mechanisms of toxicity and targeted therapies remain poor. AKI can result from direct nephrotoxic effects of the wasp venom or secondary rhabdomyolysis and intravascular hemolysis, which will release myoglobin and free hemoglobin. Inflammatory responses play a central role in these pathological mechanisms. Noteworthily, the successful establishment of a suitable experimental model can assist in basic research and clinical advancements related to wasp venom-induced AKI. The combination of therapeutic plasma exchange and continuous renal replacement therapy appears to be the preferred treatment for wasp venom-induced AKI. In addition, studies on cilastatin and varespladib for wasp venom-induced AKI treatment have shown their potential as therapeutic agents. This review summarizes the available evidence on the mechanisms and treatment of wasp venom-induced AKI, with a particular focus on the role of inflammatory responses and potential targets for therapeutic drugs, and, therefore, aiming to support the development of clinical treatment against wasp venom-induced AKI.

A retrospective observational study of patients on maintenance hemodialysis receiving parathyroidectomy by ultrasonic scalpel.

BACKGROUND: Secondary hyperparathyroidism (SHPT) remains a common complication in many patients on maintenance hemodialysis. Kidney Disease Improve Global Outcomes (KDIGO) 2017 guidelines suggest that parathyroidectomy (PTX) should be performed in severe SHPT patients with chronic kidney disease stage 3a-stage 5D. In the present study, we observed the efficacy of ultrasonic scalpel for PTX in SHPT patients on maintenance hemodialysis. METHODS: A total of 74 patients on maintenance hemodialysis who underwent PTX (34 with traditional electrocautery and 40 with an ultrasonic scalpel) were observed between August 2020 and August 2021 at Xiangyang Central Hospital (Hubei University of Arts and Science). Baseline demographic and clinic characteristics were collected pre- and post-PTX. Moreover, the postoperative complications and operation time were assessed between the two groups. RESULTS: The univariate analysis showed that there was no statistical significance in weight, dialysis duration, serum potassium, serum calcium, serum magnesium, alkaline phosphate, triglyceride, and intact parathyroid hormone (iPTH) before and after PTX between the two groups (P > 0.05). The operation time in the ultrasonic scalpel group was significantly decreased compared with the traditional electrocautery group (P < 0.05). Compared with the traditional electrocautery group, the drainage amount was significantly reduced in the ultrasonic scalpel group, and the number of days with drain and postoperative hospital stay were also remarkably decreased (P < 0.05). CONCLUSIONS: The use of ultrasonic scalpel significantly reduced the operation time and postoperative hospital stay in patients on maintenance hemodialysis undergoing PTX.

Clinical Features and Outcomes of Acute Kidney Injury in Patients Infected with COVID-19 in Xiangyang, China.

BACKGROUND: In December 2019, pneumonia associated with COVID-19 has spread from Wuhan to other areas in China. In the present study, we aimed to further clarify the clinical features and outcomes of acute kidney injury (AKI) in patients infected with COVID-19 in Xiangyang, Hubei, China. METHODS: All confirmed cases of COVID-19 with AKI in Xiangyang Central Hospital from January 22 to May 31, 2020, were included in this retrospective study. Data of epidemiological, clinical, laboratory, radiological tests, treatment, complication, and outcomes were collected and analyzed. Patients were divided into intensive care unit (ICU) group and isolation ward (non-ICU) group. RESULTS: Of the total patients, 33.3% in the non-ICU group and 85.7% in the ICU group had chronic diseases. In addition, 85.7% of patients in the ICU group died. The most common symptoms were fever, cough, and fatigue. The lymphocyte count in the ICU group was significantly reduced compared with the non-ICU group. The chest computed tomography (CT) images appeared showed multiple mottles and ground-glass opacity. Strip shadow could be found in chest CT images of some recovered patients. All patients received antiviral treatment. Most patients in the ICU group were given methylprednisolone, immunoglobulin, antibiotics, and mechanical ventilation and 35.7% of patients in the ICU group received continuous renal replacement therapy. CONCLUSIONS: Elderly with chronic comorbidities were more susceptible to COVID-19, showing a higher mortality rate due to multiple organ damage, and 35.7% of patients with AKI in ICU received renal replacement therapy. Moreover, part of the cured patients might need additional time to recover for poor lung function.

A retrospective cohort study comparing high and low balloon inflation pressure on technical success and patency for treating central venous lesions in patients on chronic hemodialysis.

BACKGROUND: We aimed to analyze the success rates and the access patency rates at 12 months between patients on chronic hemodialysis with symptomatic central venous stenosis (CVS) or occlusion (CVO), receiving high or low balloon inflation pressure for treatment. METHODS: We performed a retrospective study in which angioplasty balloons were inflated using a low-pressure or a high-pressure for the management of hemodialysis patients with CVS/CVO. The outcomes of this study were the success rate and the access patency rates at 12 months after balloon angioplasty, and the differences between groups were compared. RESULTS: We included a total of 74 patients on hemodialysis and assigned them to the low-pressure or the high-pressure groups. Success rates in patients of the high-pressure group (94.12%) were higher than those in patients of the low-pressure group (67.50%) (p = 0.005). With a total of 59 patients with technical success, at 6 and 12 months after angioplasty, the rates of access patency in the low-pressure group were 68 and 48%, respectively; on the other hand, the primary patency rates in the high-pressure group were 86.67% (6-months) and 76.67% (12-months). The 6 and 12 months post-interventional patency rates were higher in patients of the high-pressure group than those in patients of the low-pressure group (p = 0.10 at 6 months and p = 0.03 at 12 months). CONCLUSIONS: Compared to balloon angioplasty using a low inflation pressure, hemodialysis patients with CVS/CVO receiving angioplasty using a high inflation pressure have significantly higher technical success and 12-month patency rates.

Coronavirus Disease 2019 in a Hemodialysis Patient.

There has been a global outbreak of the coronavirus disease 2019 (COVID-19) since December 2019. Here, we describe the case of a 49-year-old male undergoing maintenance hemodialysis (HD) who got infected with COVID-19 and our experience in performing HD for him. The patient's symptoms and lung imaging changes were atypical. However, his lymphocyte range decreased upon admission and the polymerase chain reaction of the pharyngeal swab for the -COVID-19 nucleic acid was positive. The patient developed respiratory failure and required mechanical ventilation 8 days after admission. In the end, he died from multiple organ dysfunction syndrome. The difficulties in diagnosis, infection control, and treatment of COVID-19 in maintenance HD patients are discussed in this report.

Serum Surfactant Protein D is Associated with Atherosclerosis of the Carotid Artery in Patients on Maintenance Hemodialysis.

BACKGROUND: Surfactant protein-D (SP-D) is an inflammatory modulator that has been associated with cardiovascular disease-related mortality, estimated glomerular filtration rate, and major adverse cardiac events in patients with chronic kidney disease. The aim of this study was to investigate the link between SP-D level and atherosclerosis in patients on hemodialysis. METHODS: A total of 116 patients undergoing maintenance hemodialysis were recruited to this cross-sectional study. As a marker of atherosclerosis, the carotid artery intima-media thickness (CA-IMT) was measured by high-resolution ultrasonography, and the coronary artery calcification (CAC) score was determined by multislice computed tomography. Serum SP-D levels were measured by a commercial enzyme-linked immunosorbent assay kit. RESULTS: In patients on long-term hemodialysis, the mean serum SP-D level was 192.9 +/- 89.6 pg/mL (range: 89-537 pg/mL). The serum SP-D level exhibited positive correlations with CA-IMT (r = 0.497, p < 0.0001) and severe CAC (r = 0.352, p = 0.02), which persisted after multivariate adjustment. CONCLUSIONS: The SP-D level showed positive correlations with carotid CA-IMT and CAC in patients on long-term hemodialysis. Therefore, SP-D may be a novel marker of atherosclerosis in patients with hemodialysis.

Efficacy of Two Combinations of Blood Purification Techniques for the Treatment of Multiple Organ Failure Induced by Wasp Stings.

BACKGROUND/AIMS: The aim of this study was to explore the clinical efficacy of 2 combinations of blood purification techniques in patients with sting venom-induced multiple organ dysfunction syndrome (MODS). METHODS: A total of 23 patients received 35 sessions of hemoperfusion (HP) + continuous veno-venous hemodiafiltration (CVVHDF) treatment and 22 sessions of plasma exchange (PE) + CVVHDF treatment, respectively. RESULTS: Both HP + CVVHDF and PE + CVVHDF reduced the levels of inflammation, thus improving our patients' health condition. Moreover, PE + CVVHDF was found to be significantly more effective in reducing the levels of specific liver function markers and inflammatory mediators, as well as shortening prothrombin time and increasing the levels of serum albumin. CONCLUSION: Both combinations of blood purification techniques were capable of improving MODS. However, the PE + CVVHDF approach was more efficient for the removal of wasp venom and inflammatory mediators from the blood.

The role and mechanism of NLRP3 in wasp venom-induced acute kidney injury.

BACKGROUND: Inflammation and pyroptosis have crucial impacts on the development of acute kidney injury (AKI) and have been validated in a variety of existing AKI animal models. However, the mechanisms underlying wasp venom-induced AKI are still unclear. The involvement of nucleotide-binding oligomerization domain (NOD)-like receptor protein 3 (NLRP3) in some mouse models of AKI has been extensively documented, and its crucial function in controlling inflammation and pyroptosis has been highlighted. The objective of our study was to investigate the role and mechanism of NLRP3 in inflammation and pyroptosis associated with wasp venom-induced AKI. METHODS: A mouse model of AKI induced by wasp venom pre-injected with an NLRP3 inhibitor was used to study the role and mechanism of NLRP3. To verify the importance of NLRP3, western blotting was performed to assess the expression of NLRP3, caspase-1 p20, and gasdermin D (GSDMD)-N. Additionally, quantitative real-time polymerase was used to determine the expression of NLRP3, caspase-1, and GSDMD. Furthermore, enzyme-linked immunosorbent assay was utilized to measure the levels of interleukin (IL)-1ß and IL-18. RESULTS: NLRP3 was found to be the downstream signal of the stimulator of interferon genes in the wasp sting venom-induced AKI model. The administration of wasp venom in mice significantly upregulated the expression of NLRP3, leading to renal dysfunction, inflammation, and pyroptosis. Treatment with an NLRP3 inhibitor reversed the renal damage induced by wasp venom and attenuated pathological injury, inflammatory response, and pyroptosis. CONCLUSION: NLRP3 activation is associated with renal failure, inflammatory response and pyroptosis in the hyper early phase of wasp venom-induced AKI. The inhibition of NLRP3 significantly weakened this phenomenon. These findings could potentially offer a viable therapeutic approach for AKI triggered by wasp venom.

Design of a 140 GHz waveguide notch filter for millimeter-wave receiver module protection in fusion plasma diagnostics.

A carefully designed waveguide-based millimeter-wave notch filter, operating at 140 GHz, safeguards plasma diagnostic instruments from gyrotron leakage. Utilizing cylindrical cavity resonators with aperture coupling, the filter efficiently resonates 140 GHz wave-power into the TE11p mode, optimizing various geometrical parameters for practical fabrication and high-yield production. Thorough thermal analysis ensures its ability to handle power. The filter achieves outstanding performance with over 90 dB rejection at 140 GHz while providing low insertion loss over the passband (110-138 GHz), which is ideally suited for system-on-chip approach F-band diagnostic system applications.

Enhanced liver autophagic activity improves survival of septic mice lacking surfactant proteins A and D.

Autophagy is a protective cellular mechanism in response to various stresses, including sepsis. Sepsis is defined as systemic inflammation by infection. Surfactant protein A and D (SP-A and SP-D) are involved in host defense, regulation of inflammation, and homeostasis, but their roles in the autophagic activity and relevant gene expression in sepsis are unclear. In this study, mice lacking SP-A and SP-D (SP-A/D KO mice) and background-matched wild-type (WT) C57BL/6 mice underwent either cecal ligation and puncture (CLP) or sham surgery. The results showed that SP-A/D KO mice had lower mortality than WT mice in CLP sepsis. Liver tissues showed marked pathological changes in both septic SP-A/D KO and WT mice 24 hrs after CLP treatment; and quantitative analysis of liver histopathology revealed significant difference between septic SP-A/D and septic WT mice. SP-A/D KO mice had higher basal and sepsis-induced level of autophagy than WT mice (p < 0.05), as judged by Western blot and electron microscopic analyses. The expression of 84 autophagy-related genes revealed differential basal and sepsis-induced gene expression between SP-A/D KO and WT mice. The expression increased in three genes and decreased in four genes in septic WT mice, as compared to septic SP-A/D KO mice (p < 0.05). Furthermore, differential responses to sepsis between SP-A/D KO and WT mice were found in six signaling pathways related to autophagy and apoptosis. Therefore, enhanced autophagic activity improves the survival of septic SP-A/D KO mice through the regulation of liver autophagy/apoptosis-related gene expression and signaling pathway activation.

A rat model of acute kidney injury caused by multiple subcutaneous injections of Asian giant hornet (Vespa mandarina Smith) venom.

A model of acute kidney injury (AKI) caused by multiple subcutaneous injections of Asian giant hornet (Vespa mandarina Smith) venom was developed in male Wistar rats. The rats were injected subcutaneously at multiple sites in the dorsal region with a total venom dose of 5 mg/kg. Blood samples were obtained 8, 24 and 48 h after venom injection for the quantification of various biochemical parameters and assessment of renal function. Wasp venom caused significant increases in all biochemical parameters (aspartate aminotransferase, creatine kinase, free hemoglobin, lactate dehydrogenase, myoglobin, and plasma creatinine) within 8 h of venom administration, as well as marked alterations in renal function (a decrease in glomerular filtration rate leading to oliguria). The biochemical parameters showed varying degrees of recovery but remained elevated to varying degrees after 48 h, whereas the glomerular filtration rate showed no recovery during this period. The histopathological alterations consisted primarily of acute tubular necrosis, with tubular epithelial cell sloughing and loss of tubule brush border. This profile of biochemical and functional alterations was similar to that seen in human envenomations by this species, suggesting that this animal model may be useful for understanding the pathophysiology of AKI caused by this wasp venom.

Impact of enhanced recovery after surgery program for hungry bone syndrome in patients on maintenance hemodialysis undergoing parathyroidectomy for secondary hyperparathyroidism.

Purpose: Hungry bone syndrome after parathyroidectomy is an important clinical problem in patients on maintenance hemodialysis. We examined the effect of an enhanced recovery after surgery (ERAS) program on the incidence of hungry bone syndrome after parathyroidectomy in this population. Methods: This single-institution, retrospective study analyzed 108 patients on hemodialysis who underwent parathyroidectomy for secondary hyperparathyroidism. Patients were classified into the pre-ERAS (n = 52) and post-ERAS (n = 56) groups. The ERAS program identified high-risk patients and enforced aggressive measures to normalize calcium levels following parathyroidectomy. Results: There was no significant difference in age, sex, body weight, presenting symptoms, preoperative calcium and alkaline phosphatase levels, postoperative intact parathyroid levels, postoperative calcium levels at 1 and 24 hours after parathyroidectomy, and 30-day readmission rates between the groups. The post-ERAS group had significantly higher levels of postoperative calcium at 48 and 72 hours after parathyroidectomy, but a lower incidence of hungry bone syndrome and shorter postoperative length of stay. Patients with hungry bone syndrome had higher preoperative levels of alkaline phosphatase and intact parathyroid, longer postoperative length of stay, and were less likely to have been part of the ERAS program. High preoperative alkaline phosphatase levels and absence of the ERAS program were independent risk factors for hungry bone syndrome after parathyroidectomy. Conclusion: The ERAS program reduced the incidence of hungry bone syndrome and shortened the postoperative length of stay in patients on maintenance hemodialysis who underwent parathyroidectomy for secondary hyperparathyroidism.

Megalin blockade with cilastatin ameliorates multiple wasp sting-induced acute kidney injury in rats.

Cilastatin has been shown to prevent various drug-induced nephrotoxicities and confer renoprotection in a mouse model of glycerol-mediated rhabdomyolysis-induced acute kidney injury (AKI). The present study aimed to investigate whether cilastatin attenuates wasp sting-induced AKI in rats. Male Wistar rats were divided into the control, cilastatin, AKI, and AKI + cilastatin groups. Nephrotoxicity was assessed using renal function, rhabdomyolysis (creatine kinase, CK) and intravascular hemolysis (lactate dehydrogenase, LDH) markers, and histological changes. In addition, tubular injury biomarkers, apoptosis, oxidative stress markers, complement C3 expression, and urine and blood myoglobin levels were examined. Compared with the control or cilastatin group, the AKI group showed significant histological damage, increased levels of CK, LDH, and creatinine, and increased mRNA expression of tubular injury biomarkers. Cilastatin ameliorated wasp venom-induced kidney injury by attenuating oxidative stress and apoptosis. Cilastatin also reduced C3 expression in the renal tubular cells. In addition, cilastatin reduced serum myoglobin levels and increased urine myoglobin concentrations. Therefore, megalin blockade with cilastatin attenuates wasp venom-induced AKI owing to its antioxidative and antiapoptotic properties.

Phospholipase A2 inhibitor varespladib prevents wasp sting-induced nephrotoxicity in rats.

This study aimed to clarify whether varespladib, a phospholipase A2 (PLA2) inhibitor, can be used as a therapeutic agent for wasp sting-induced acute kidney injury (AKI). Rats were divided into control, AKI, and AKI + varespladib groups. The AKI model was established by subcutaneously injecting wasp venom at five different sites in rats. Varespladib treatment showed a significant inhibitory effect on wasp venom PLA2in vitro and in vivo. Moreover, we observed that varespladib decreased the levels of rhabdomyolysis and hemolysis markers compared with that in the AKI group. Histopathological changes in the kidney decreased significantly, and rat serum creatinine levels were reduced after varespladib administration. The significantly regulated genes in the kidney of the AKI group were mostly involved in inflammatory response pathway, and the administration of varespladib remarkably attenuated the expression of these genes. Therefore, varespladib inhibited wasp sting-induced functional and pathological damage to the kidneys. We propose that the PLA2 inhibitor varespladib protects the kidney tissue in a wasp sting-induced AKI model by inhibiting PLA2 activity.

An integrative proteomics metabolomics based strategy reveals the mechanisms involved in wasp sting induced acute kidney injury.

The pathophysiological mechanisms involved in wasp-sting-induced acute kidney injury (AKI) remain largely unknown. Here, we combined proteomics and metabolomics to investigate the mechanisms behind multiple wasp sting-induced AKI. Interestingly, we found many differentially abundant proteins in the serum of AKI group compared with that of the non-AKI and control groups, involved in several metabolic pathways and the regulation of cellular processes. In addition, we also detected differentially abundant metabolites in the AKI group; among them many were involved in the glycerophospholipid metabolic pathway (the key pathway in the context of AKI): 50 metabolites, all downregulated in the AKI group. Importantly, the convergent analysis of metabolomics and proteomics data revealed that biomarkers of rhabdomyolysis (CA 3, MYL3, and LDH) and hemolysis (ALT and LDH) were integrated into a regulatory network with phospholipid metabolism products in the AKI group, indicating that wasp sting-induced AKI is secondary to rhabdomyolysis and intravascular hemolysis. Of note, such a phenotype suggests the disruption of the membrane of skeletal muscle cells and red blood cells mediated by the phospholipase A1 (PLA1), PLA2, and mastoparan in the wasp venom, via the disruption of membrane glycerophospholipids. Overall, our results highlight a potential new mechanism behind wasp sting-induced AKI and suggest that PLA inhibitors may be potential agents for the treatment of this condition.

Disparate effects of eplerenone, amlodipine and telmisartan on podocyte injury in aldosterone-infused rats.

BACKGROUND: Several studies in patients with primary aldosteronism (PA) have suggested that aldosterone (ALD) is directly contributing to albuminuria. However, there are limited data pertaining to the direct role of ALD in in vivo models in regard to the induction of renal injury and the involved mechanisms. In the present study, we established a high-dose ALD-infused rat model to evaluate urinary albumin excretion rate (UAER) and podocyte damage. Moreover, we studied the effect of eplerenone (EPL), telmisartan (TEL) and amlodipine (AML) on ALD-induced renal structural and functional changes. METHODS: Immunohistochemical and real-time PCR analyses, and TUNEL assays were performed to evaluate nephrin expression and podocyte injury. RESULTS: ALD-receiving rats (ARR) showed a progressive increase in BP, UAER and proteinuria when compared with control rats (CR). Conversely, BP was significantly reduced in ALD + EPL (A/ERR)-, ALD + AML (A/ARR)- and ALD + TEL (A/TRR)-treated rats. However, UAER and proteinuria were decreased only in A/ERR and A/TRR, but not in A/ARR. Only EPL administration provided protection against ALD-induced podocyte apoptosis. Renal tissue of ARR revealed enhanced expression of nephrin protein and mRNA. This effect of ALD was inhibited by EPL, but not by TEL or AML. Conclusions. ALD induces direct glomerular injury independent of its haemodynamic effects; this effect of ALD is, at least in part, mediated through activation of the mineralocorticoid receptor.

Role of collectin-11 in innate defence against uropathogenic Escherichia coli infection.

Classical collectins (surfactant protein A and D) play a significant role in innate immunity and host defence in uropathogenic Escherichia coli (UPEC)-induced urinary tract infection (UTI). However, the functions of collectin-11 (CL-11) with respect to UPEC and UTI remain largely unexplored. This study aimed to investigate the effect of CL-11 on UPEC and its role in UTI. We further examined its modulatory effect on inflammatory reactions in proximal tubular epithelial cells (PTECs). The present study provides evidence for the effect of CL-11 on the growth, agglutination, binding, epithelial adhesion and invasion of UPEC. We found increased basal levels of phosphorylated p38 MAPK and human cytokine homologue (keratinocyte-derived chemokine) expression in CL-11 knockdown PTECs. Furthermore, signal regulatory protein α blockade reversed the increased basal levels of inflammation associated with CL-11 knockdown in PTECs. Additionally, CL-11 knockdown effectively inhibited UPEC-induced p38 MAPK phosphorylation and cytokine production in PTECs. These were further inhibited by CD91 blockade. We conclude that CL-11 functions as a mediator of innate immunity via direct antibacterial roles as well as dual modulatory roles in UPEC-induced inflammatory responses during UTI. Thus, the study findings suggest a possible function for CL-11 in defence against UTI.

Polymorphisms in the surfactant protein a gene are associated with the susceptibility to recurrent urinary tract infection in chinese women.

Some risk factors for susceptibility to recurrent urinary tract infection (r-UTI) are well known, but the genetic role in acquiring the disease is poorly understood. Surfactant protein A and D (SP-A and SP-D) play an important role in modulation of lung inflammatory processes. The SP-A1 and SP-A2 genes encoding SP-A and the SP-D gene are highly polymorphic, and some of polymorphisms are associated with several infective diseases, including pyelonephritis. In the present study, we investigated whether some of these polymorphisms are associated with the risk of r-UTI in Chinese population. Genomic DNA was extracted from blood samples of 32 female patients with r-UTI and 30 age-matched, unrelated healthy female subjects. Genotyping of gene polymorphisms was analyzed by PCR. Among 11 single nucleotide polymorphisms (SNPs) (five of SP-A1, four of SP-A2 and two of SP-D) observed in the enrolled subjects, Ala19Val of SP-A1 and Lys223Gln of SP-A2 were associated with susceptibility to r-UTI. The frequencies of 19Ala allele of SP-A1 gene (p = 0.038) and 223Gln allele of SP-A2 gene (p = 0.012) in the patients were significantly higher than those in healthy subjects. The serum SP-A and SP-D levels were increased and the urine SP-A and SP-D levels were decreased in r-UTI patients compared with control subjects (p < 0.05). r-UTI patients with 19Ala/Ala or 223Gln/Gln genotype were associated with high serum and low urine SP-A levels (p < 0.01). Therefore, the 19Ala allele of SP-A1 gene and the 223Gln allele of SP-A2 gene are risk factors for r-UTI.