An interleukin 6-based genetic risk score strengthened with interleukin 10 polymorphisms associated with long-term kidney allograft outcomes.

Of all kidney transplants, half are still lost in the first decade after transplantation. Here, using genetics, we probed whether interleukin 6 (IL-6) could be a target in kidney transplantation to improve graft survival. Additionally, we investigated if a genetic risk score (GRS) based on IL6 and IL10 variants could improve prognostication of graft loss. In a prospective cohort study, DNA of 1271 donor-recipient kidney transplant pairs was analyzed for the presence of IL6, IL6R, IL10, IL10RA, and IL10RB variants. These polymorphisms and their GRS were then associated with 15-year death-censored allograft survival. The C|C-genotype of the IL6 polymorphism in donor kidneys and the combined C|C-genotype in donor-recipient pairs were both associated with a reduced risk of graft loss (p = .043 and p = .042, respectively). Additionally, the GRS based on IL6, IL6R, IL10, IL10RA, and IL10RB variants was independently associated with the risk of graft loss (HR 1.53, 95%-CI [1.32-1.84]; p < .001). Notably, the GRS improved risk stratification and prediction of graft loss beyond the level of contemporary clinical markers. Our findings reveal the merits of a polygenic IL-6-based risk score strengthened with IL-10- polymorphisms for the prognostication and risk stratification of late graft failure in kidney transplantation.

Effects of the Seed Oil of Carica papaya Linn on Food Consumption, Adiposity, Metabolic and Inflammatory Profile of Mice Using Hyperlipidic Diet.

BACKGROUND: Studies indicate that different parts of Carica papaya Linn have nutritional properties that mean it can be used as an adjuvant for the treatment of various pathologies. METHODS: The fatty acid composition of the oil extracted from the seeds of Carica papaya Linn was evaluated by gas chromatography, and an acute toxicity test was performed. For the experiment, Swiss mice were fed a balanced or high-fat diet and supplemented with saline, soybean oil, olive oil, or papaya seed oil. Oral glucose tolerance and insulin sensitivity tests were performed. After euthanasia, adiposity, glycemia, total cholesterol and fractions, insulin, resistin, leptin, MCP-1, TNF-α, and IL-6 and the histology of the liver, pancreas, and adipose tissue were evaluated. RESULTS: Papaya seed oil showed predominance of monounsaturated fatty acids in its composition. No changes were observed in the acute toxicity test. Had lower food intake in grams, and caloric intake and in the area of adipocytes without minimizing weight gain or adiposity and impacting the liver or pancreas. Reductions in total and non-HDL-c, LDL-c, and VLDL-c were also observed. The treatment had a hypoglycemic and protective effect on insulin resistance. Supplementation also resulted in higher leptin and lower insulin and cytokine resistance. CONCLUSIONS: Under these experimental conditions, papaya seed oil led to higher amounts of monounsaturated fatty acids and had hypocholesterolemic, hypotriglyceridemic, and hypoglycemic effects.

Arteriolar C4d in IgA Nephropathy: A Cohort Study.

RATIONALE & OBJECTIVE: Glomerular C4d (C4dG) as an indicator of the lectin pathway of complement activation in immunoglobulin A nephropathy (IgAN) has been associated with more severe kidney damage. Recent studies have suggested that vascular lesions in IgAN biopsy specimens with complement deposition are also associated with disease progression. We aimed to study the clinical significance of arteriolar C4d (C4dA) in IgAN kidney biopsy tissue. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: Kidney biopsy specimens from 126 adults with IgAN diagnosed by Oxford classification criteria were stained using immunohistochemistry and classified according to C4dG and C4dA deposition. Additionally, vascular lesions including acute and chronic microangiopathy, arteriolar hyalinosis, and arterial intima fibrosis were characterized. PREDICTOR: C4dA. OUTCOME: Progressive kidney disease, defined as a decline in estimated glomerular filtration rate by≥50% or occurrence of kidney failure. ANALYTICAL APPROACH: The association of C4dA and C4dG with baseline clinical and histologic characteristics, as well as progressive kidney disease, were assessed with survival analysis using multivariable Cox regression analysis. RESULTS: C4dA was identified in 21 (17%) patients and was associated with mean arterial pressure, arterial intima fibrosis, and chronic microangiopathy. C4dA was also significantly associated with C4dG and both were associated with progressive kidney disease. In regression analysis, C4dA remained significantly associated with progressive kidney disease after adjusting for other significant predictors, including baseline estimated glomerular filtration rate, mean arterial pressure, and the presence of crescents. LIMITATIONS: Findings based on the retrospective evaluation of a single center's experience, limited number of events, a small number of patients with a broad range of kidney disease stages, and use of immunohistochemistry rather than immunofluorescence to detect C4d. CONCLUSIONS: C4dA is a potential biomarker for disease progression in IgAN. It should be further investigated in larger cohorts to determine the value of C4dA in improving prediction of IgAN disease progression.

Caryocar brasiliense Cambess. Pulp Oil Supplementation Reduces Total Cholesterol, LDL-c, and Non-HDL-c in Animals.

The fruit of Caryocar brasiliense Cambess. is a source of oil with active compounds that are protective to the organism. In our work, we analyzed the physicochemical characteristics and evaluated the effects of supplementation with C. brasiliense oil in an animal model. We characterized the oil by indices of quality and identity, optical techniques of absorption spectroscopy in the UV-Vis region and fluorescence, and thermogravimetry/derived thermogravimetry (TG/DTG). For the animal experiment, we utilized mice (Mus musculus) supplemented with lipidic source in different dosages. The results demonstrated that C. brasiliense oil is an alternative source for human consumption and presents excellent oxidative stability. Primarily, it exhibited oleic MFA (53.56%) and palmitic SFA (37.78%). The oil level of tocopherols and tocotrienols was superior to the carotenoids. The supplementation with C. brasiliense oil reduced the levels of total cholesterol, LDL-c, and non-HDL-c. Regarding visceral fats and adiposity index, the treatment synergically supplemented with olive oil and C. brasiliense oil (OO + CO) obtained the best result. Therefore, C. brasiliense oil is a high quality product for consumption. Its supplementation promotes beneficial effects mainly on the lipidic profile.

Systemic and local complement activation in peritoneal dialysis patients via conceivably distinct pathways.

BACKGROUND: Despite several advantages compared to haemodialysis (HD), peritoneal dialysis (PD) remains an underused dialysis technique due to its high technique failure rate related to membrane fibrosis and peritonitis events. Previous work has suggested a harmful role for the complement system in these processes, highlighting the need for a more comprehensive examination in PD. METHODS: Plasma levels of C1q, mannose-binding lectin (MBL), Properdin, Factor D, C3d/C3-ratio and soluble membrane attack complex (sC5b-9) were determined in PD patients (n = 55), HD patients (n = 41), non-dialysis chronic kidney disease (CKD) patients (n = 15) and healthy controls (n = 14). Additionally, C1q, MBL, Properdin, Factor D and sC5b-9 levels were assessed in the peritoneal dialysis fluid (PDF). In a subgroup, interleukin-6, matrix metalloproteinase-2 (MMP-2), myeloperoxidase (MPO) and elastase were measured in the PDF. RESULTS: PD patients had significantly higher systemic levels of sC5b-9 compared to healthy controls, CKD and HD patients (p < 0.001). Plasma levels of C1q and C3d/C3-ratios were significantly associated with systemic sC5b-9 levels (p < 0.001). Locally, sC5b-9 was detected in the PDF of all PD patients, and levels were approximately 33% of those in matched plasma, but they did not correlate. In the PDF, only Properdin levels remained significantly associated with PDF sC5b-9 levels in multivariate analysis (p < 0.001). Additionally, PDF levels of sC5b-9 positively correlated with elastase, MPO and MMP-2 levels in the PDF (p < 0.01). CONCLUSIONS: Our data reveal both systemic and local complement activation in PD patients. Furthermore, these two processes seem independent considering the involvement of different pathways and the lack of correlation.

C3 Glomerulonephritis Presenting With Nephritic and Nephrotic Syndromes: Spontaneous Remission After Six Months on Dialysis.

C3 glomerulopathy is a rare and complex renal disease driven by complement dysregulation, with variable presentation and pathophysiology. We report the case of a middle-aged male patient presenting with nephritic and nephrotic syndromes and low serum C3, whose biopsy established the diagnosis of C3 glomerulonephritis. He was found to be homozygous for the complement factor H-related protein (CFHR)3-CFHR1 deletion, which has been associated with the development of anti-factor H autoantibodies. However, the lack of consistent and accessible nephritic factor assays prevented full clarification of the mechanisms involved in the disease. Interestingly, despite not receiving treatment due to suspicion of malignancy and perceived poor renal prognosis, there was spontaneous recovery after six months on hemodialysis. This case reflects the enduring challenges in establishing the diagnosis and prognosis of C3 glomerulonephritis.

A non-muscle myosin heavy chain 9 genetic variant is associated with graft failure following kidney transplantation.

BACKGROUND: Despite current matching efforts to identify optimal donor-recipient pairs for kidney transplantation, alloimmunity remains a major source of late transplant failure. Additional genetic parameters in donor-recipient matching could help improve longterm outcomes. Here, we studied the impact of a non-muscle myosin heavy chain 9 gene (MYH9) polymorphism on allograft failure. METHODS: We conducted an observational cohort study, analyzing the DNA of 1,271 kidney donor-recipient transplant pairs from a single academic hospital for the MYH9 rs11089788 C>A polymorphism. The associations of the MYH9 genotype with risk of graft failure, biopsy-proven acute rejection (BPAR), and delayed graft function (DGF) were estimated. RESULTS: A trend was seen in the association between the MYH9 polymorphism in the recipient and graft failure (recessive model, p = 0.056), but not for the MYH9 polymorphism in the donor. The AA-genotype MYH9 polymorphism in recipients was associated with higher risk of DGF (p = 0.03) and BPAR (p = 0.021), although significance was lost after adjusting for covariates (p = 0.15 and p = 0.10, respectively). The combined presence of the MYH9 polymorphism in donor-recipient pairs was associated with poor long-term kidney allograft survival (p = 0.04), in which recipients with an AA genotype receiving a graft with an AA genotype had the worst outcomes. After adjustment, this combined genotype remained significantly associated with 15-year death-censored kidney graft survival (hazard ratio, 1.68; 95% confidence interval, 1.05-2.70; p = 0.03). CONCLUSION: Our results reveal that recipients with an AA-genotype MYH9 polymorphism receiving a donor kidney with an AA genotype have significantly elevated risk of graft failure after kidney transplantation.

Computed tomography fluoroscopy-guided percutaneous biopsy of pulmonary nodules ≤ 10 mm: retrospective analysis of procedures performed during the COVID-19 pandemic.

Objective: To evaluate the diagnostic performance of computed tomography (CT) fluoroscopy-guided percutaneous transthoracic needle biopsy (PTNB) in pulmonary nodules ≤ 10 mm during the coronavirus disease 2019 pandemic. Materials and Methods: Between January 1, 2020 and April 30, 2022, a total of 359 CT fluoroscopy-guided PTNBs were performed at an interventional radiology center. Lung lesions measured between 2 mm and 108 mm. Of the 359 PTNBs, 27 (7.5%) were performed with an 18G core needle on nodules ≤ 10 mm in diameter. Results: Among the 27 biopsies performed on nodules ≤ 10 mm, the lesions measured < 5 mm in four and 5-10 mm in 23. The sensitivity and overall diagnostic accuracy of PTNB were 100% and 92.3%, respectively. The mean dose of ionizing radiation during PTNB was 581.33 mGy*cm (range, 303-1,129 mGy*cm), and the mean biopsy procedure time was 6.6 min (range, 2-12 min). There were no major postprocedural complications. Conclusion: CT fluoroscopy-guided PTNB appears to provide a high diagnostic yield with low complication rates.

Effects of Ethanolic and Aqueous Extracts of Garcinia gardneriana Leaves in an In Vivo Experimental Model Induced by a Hyperlipidic Diet.

The study of medicinal plants, such as the genus Garcinia (Clusiaceae), in the treatment of non-communicable chronic diseases has aroused the interest of researchers. However, there are no studies in the literature that have investigated the effects of Garcinia gardneriana in experimental models of obesity for possible metabolic alterations. Swiss mice receiving a high-fat diet were supplemented with aqueous or ethanolic extract of G. gardneriana at doses of 200 or 400 mg/kg/day. It was found that there was a reduction in food consumption in experimental groups compared with the control groups, and the group supplemented with aqueous extract at a dose of 200 mg/kg/daydisplayed a reduction in weight. The results showed an increase in the values of high density lipoprotein (HDL-c), total cholesterol, triglycerides and fasting blood glucose. G. gardneriana did not protect against insulin resistance, and caused in an increase in monocyte chemoattractant protein-1 (MCP-1) concentrations and a reduction in interleukin 10 (IL-10). In addition, hepatic steatosis and microvesicular steatosis were indicated. It was revealed that, under the experimental conditions in the study, G. gardneriana did not prevent weight gain or comorbidities; that is, a different behavior was obtained from that described in the literature with regard to the medicinal potential of the Garcinia species, which is probably related to the phytochemical properties.

Physical examination of dysfunctional arteriovenous fistulae by non-interventionalists: a skill worth teaching.

BACKGROUND: Physical examination (PE) of arteriovenous fistulae (AVF) has recently emerged as an important element in the detection of stenotic lesions. This study examines the accuracy of PE in the assessment of AVF dysfunction by non-interventionalists in comparison with angiography. METHODS: A total of 177 consecutive patients who had AVF dysfunction and were referred to our centre by general nephrologists for angioplasty between November 2009 and July 2010 were included in this analysis. Eleven referring general nephrologists completed a form reporting the PE findings regarding their patients' AVFs. Before angiography examination was carried out, a trained nephrology resident performed a PE in all the cases. Angiography of the AVFs was then performed by an interventionalist. Cohen's κ value was used as the measurement of the level of agreement beyond chance between the diagnosis made on PE and angiography. RESULTS: There was a moderate agreement beyond chance between the general nephrologists' PE and angiography in the detection of AVF inflow stenosis (κ = 0.49), outflow stenosis (κ = 0.58) and thrombosis (κ = 0.52). On the other hand, PE performed by the trained nephrology resident strongly agreed with angiography in the detection of AVF inflow stenosis (κ = 0.84), outflow stenosis (κ = 0.92) and thrombosis (κ = 0.98). The agreement between PE and angiography in the detection of co-existing AVF inflow-outflow stenosis was poor for the general nephrologists and moderate for the trained nephrology resident (κ = 0.14 versus κ = 0.55, respectively). CONCLUSION: PE may provide an accurate means of diagnosis of AVF dysfunction. Theoretical and hands-on training in PE of dysfunctional AVFs should be provided for nephrologists in-training and for the dialysis staff.

Tumor Necrosis Factor-α Gene Polymorphism is Associated with Short- and Long-Term Kidney Allograft Outcomes.

Introduction: Kidney transplantation has excellent short-term results with current immunosuppression regimes, but long-term outcomes have barely improved over the past two decades. Hence, there is a need for new therapeutic options to increase long-term survival of kidney grafts. Drug development for kidney transplantation has slowly plateaued, limiting progress while making drug repurposing an attractive alternative. We, therefore, investigated the impact of tumor necrosis factor-alpha (TNF-α) gene (TNF) polymorphisms on kidney graft survival after transplantation. Methods: We performed a prospective cohort study to assess the association of TNF polymorphisms (rs1800629 G>A and rs3093662 A>G) with primary non-function and death-censored kidney allograft survival in 1271 kidney transplant pairs from the University Medical Center Groningen in The Netherlands. Results: The G-allele of the TNF rs3093662 polymorphism in donor kidneys was associated with a higher risk of immediate graft loss (odds ratio: 2.05; 95%-CI: 1.06-3.97; P = 0.032). Furthermore, the G-allele of this TNF rs3093662 polymorphism in the donor was also associated with worse 5-year, 10-year, and 15-year death-censored kidney graft survival (P < 0.05). The cumulative incidence of graft loss was 15.9% in the reference AA-genotype group and 25.2% in the AG/GG-genotype group, respectively. In multivariable analysis, the association between the TNF rs3093662 polymorphism in the donor and 15-year death-censored kidney graft survival remained significant (hazard ratio: 1.51; 95%-CI: 1.05-2.19, P = 0.028). Discussion: In conclusion, kidney allografts possessing a high-producing TNF polymorphism have a greater risk of immediate and late graft loss. Our study adds to a growing body of literature indicating the potential of TNF-α blockade in improving kidney transplantation outcomes.

A functional TGFB1 polymorphism in the donor associates with long-term graft survival after kidney transplantation.

BACKGROUND: Improvement of long-term outcomes in kidney transplantation remains one of the most pressing challenges, yet drug development is stagnating. Human genetics offers an opportunity for much-needed target validation in transplantation. Conflicting data exist about the effect of transforming growth factor-beta 1 (TGF-ß1) on kidney transplant survival, since TGF-ß1 has pro-fibrotic and protective effects. We investigated the impact of a recently discovered functional TGFB1 polymorphism on kidney graft survival. METHODS: We performed an observational cohort study analysing recipient and donor DNA in 1271 kidney transplant pairs from the University Medical Centre Groningen in The Netherlands, and associated a low-producing TGFB1 polymorphism (rs1800472-C > T) with 5-, 10- and 15-year death-censored kidney graft survival. RESULTS: Donor genotype frequencies of rs1800472 in TGFB1 differed significantly between patients with and without graft loss (P = 0.014). Additionally, the low-producing TGFB1 polymorphism in the donor was associated with an increased risk of graft loss following kidney transplantation (hazard ratio = 2.12 for the T-allele; 95% confidence interval 1.18-3.79; P = 0.012). The incidence of graft loss within 15 years of follow-up was 16.4% in the CC-genotype group and 31.6% in the CT-genotype group. After adjustment for transplant-related covariates, the association between the TGFB1 polymorphism in the donor and graft loss remained significant. In contrast, there was no association between the TGFB1 polymorphism in the recipient and graft loss. CONCLUSIONS: Kidney allografts possessing a low-producing TGFB1 polymorphism have a higher risk of late graft loss. Our study adds to a growing body of evidence that TGF-ß1 is beneficial, rather than harmful, for kidney transplant survival.

Diagnosis Methods for COVID-19: A Systematic Review.

At the end of 2019, the coronavirus appeared and spread extremely rapidly, causing millions of infections and deaths worldwide, and becoming a global pandemic. For this reason, it became urgent and essential to find adequate tests for an accurate and fast diagnosis of this disease. In the present study, a systematic review was performed in order to provide an overview of the COVID-19 diagnosis methods and tests already available, as well as their evolution in recent months. For this purpose, the Science Direct, PubMed, and Scopus databases were used to collect the data and three authors independently screened the references, extracted the main information, and assessed the quality of the included studies. After the analysis of the collected data, 34 studies reporting new methods to diagnose COVID-19 were selected. Although RT-PCR is the gold-standard method for COVID-19 diagnosis, it cannot fulfill all the requirements of this pandemic, being limited by the need for highly specialized equipment and personnel to perform the assays, as well as the long time to get the test results. To fulfill the limitations of this method, other alternatives, including biological and imaging analysis methods, also became commonly reported. The comparison of the different diagnosis tests allowed to understand the importance and potential of combining different techniques, not only to improve diagnosis but also for a further understanding of the virus, the disease, and their implications in humans.

Linseed, Baru, and Coconut Oils: NMR-Based Metabolomics, Leukocyte Infiltration Potential In Vivo, and Their Oil Characterization. Are There Still Controversies?

Different fatty acid proportions produce potential inflammatory and metabolic changes in organisms. However, the evidence for how each fatty acid mediates the metabolic pathway, and its lipid stability remains controversial. To resolve this controversy, the present study investigated the metabolic effects of cold-pressed linseed (LG), coconut (CG), and baru (BG) oils in comparison to those of soybean oil (SG) in mice, in terms of their oil characterization and stability. The quality analysis showed less oxidative behavior among PUFA-rich oils (SO, BO, and LO, with induction periods lower than 2 h compared to 39.8 h for CG), besides the high contents of tocopherols and carotenoids in SG and LG. In the experimental study, CG presented higher triglyceride (257.93 ± 72.30) and VLDL-cholesterol levels (51.59 ± 14.46, p < 0.05), while LG reduced LDL levels (59.29 ± 7.56, p < 0.05) when compared to SG (183.14 ± 22.06, 36.63 ± 4.41 and 131.63 ± 29.0, respectively). For visceral fats, the adiposity index was lower for BG (7.32 ± 3.13) and CG (9.58 ± 1.02, p < 0.05) in relation to SG (12.53 ± 2.80), and for leukocyte recruitment, CG presented lower polymorphonuclear (PMN) (p < 0.0001) and mononuclear (MN) (p < 0.05) cell infiltration, demonstrating anti-inflammatory potential. In NMR-based metabolomics, although CG presented higher values for the glucose, lactate, and LDL/VLDL ratio, this group also evidenced high levels of choline, a lipotropic metabolite. Our study emphasized the controversies of saturated fatty acids, which impair serum lipids, while alfa-linolenic acid presented cardioprotective effects. However, coconut oil also has a positive immunomodulatory pathway and was found to reduce visceral bodyfat in mice. Therefore, for future applications, we suggest a combination of lauric and al-fa-linolenic acid sources, which are present in coconut and linseed oil, respectively. This combination could be less obesogenic and inflammatory and exert cardioprotective action.

Characterization of Buriti (Mauritia flexuosa) Pulp Oil and the Effect of Its Supplementation in an In Vivo Experimental Model.

Mauritia flexuosa (Buriti) pulp oil contains bioactive substances and lipids that are protective against cardiovascular and inflammatory diseases. We performed physical and chemical analyses to verify its quality and stability. Buriti oil was stable according to the Rancimat test, presenting an induction period of 6.6 h. We evaluated the effect of supplementation with crude buriti oil and olive oil on metabolic parameters in 108 Swiss mice for 90 days. We investigated six groups: extra virgin olive oil (EVOO) 1 and 2 (1000 and 2000 mg/kg), buriti oil (BO) 1 and 2 (1000 and 2000 mg/kg), synergic (S) (BO1 + EVOO1), and control (water dose 1000 mg/kg). The animals were euthanized to examine their blood, livers, and fats. The supplementation did not interfere with food consumption, weight gain, and histological alterations in the liver. Group S showed the strongest relationship with the fractions HDL-c and non-HDL-c, indicating a possible cardioprotective effect. Moreover, we observed significantly higher IL-6 levels in the control, EVOO2, and BO1 groups than in the EVOO1 group. Resistin was also significantly higher for the synergic treatment than for the control. We conclude that BO combined with EVOO could be an excellent food supplement for human consumption.

Atheroembolic renal disease with rapid progression and fatal outcome.

Atheroembolic renal disease is caused by foreign-body reaction to cholesterol crystals flushed from the atherosclerotic plaques into the small-vessel system of the kidneys. It is an underdiagnosed entity, mostly related to vascular procedures and/or anticoagulation, and prognosis is considered to be poor. Besides the benefit of aggressive medical prevention of further embolic events, use of steroid therapy has been associated with greater survival. Here we report a case of a patient with a multisystemic presentation of the disease days after performance of percutaneous coronary intervention and anticoagulation initiation due to an episode of myocardial infarction. Renal, cutaneous, ophthalmic, neurological, and possibly muscular and mesenteric involvement was diagnosed. Although medical treatment with corticosteroids and avoidance of further anticoagulation was applied, the patient rapidly progressed to end-stage renal disease requiring hemodialysis and died 6 months after diagnosis. This is a case of catastrophic progression of the disease resistant to therapeutic measures. Focus on diagnosis and more efficient preventive and therapeutic protocols are therefore needed.

Peritoneal dialysis in transplant recipient patients: outcomes and management.

Transplant recipient patients performing dialysis represent a growing population in the integrated model of renal replacement therapy. This includes both patients with kidney allograft loss and non-renal organ transplant recipients requiring dialysis. Although a number of possible advantages of peritoneal dialysis over haemodialysis could hypothetically favour its choice when starting dialysis, peritoneal dialysis penetration is relatively residual in this population. Questions about its safety and adequacy in these patients can explain this fact. The purpose of this review is to address unfounded fears and document evidence that peritoneal dialysis should be considered a viable and safe choice in patients returning to dialysis. Specific issues that still need further investigation are also discussed.

The Contribution of Complement to the Pathogenesis of IgA Nephropathy: Are Complement-Targeted Therapies Moving from Rare Disorders to More Common Diseases?

Primary IgA nephropathy (IgAN) is a leading cause of chronic kidney disease and kidney failure for which there is no disease-specific treatment. However, this could change, since novel therapeutic approaches are currently being assessed in clinical trials, including complement-targeting therapies. An improved understanding of the role of the lectin and the alternative pathway of complement in the pathophysiology of IgAN has led to the development of these treatment strategies. Recently, in a phase 2 trial, treatment with a blocking antibody against mannose-binding protein-associated serine protease 2 (MASP-2, a crucial enzyme of the lectin pathway) was suggested to have a potential benefit for IgAN. Now in a phase 3 study, this MASP-2 inhibitor for the treatment of IgAN could mark the start of a new era of complement therapeutics where common diseases can be treated with these drugs. The clinical development of complement inhibitors requires a better understanding by physicians of the biology of complement, the pathogenic role of complement in IgAN, and complement-targeted therapies. The purpose of this review is to provide an overview of the role of complement in IgAN, including the recent discovery of new mechanisms of complement activation and opportunities for complement inhibitors as the treatment of IgAN.

Soluble CD59 in peritoneal dialysis: a potential biomarker for peritoneal membrane function.

INTRODUCTION: Various studies have reported the importance of complement regulators in preventing mesothelial damage during peritoneal dialysis (PD). Its assessment, however, is limited in clinical practice due to the lack of easy access to the peritoneal membrane. Recently, a soluble form of the complement regulatory protein CD59 (sCD59) has been described. We therefore aimed to investigate the role of sCD59 in PD. METHODS: Plasma sCD59 was measured in 48 PD patients, 41 hemodialysis patients, 15 non-dialysis patients with chronic kidney disease and 14 healthy controls by ELISA (Hycult; HK374-02). Additionally, sCD59 and sC5b-9 were assessed in the peritoneal dialysate. RESULTS: sCD59 and sC5b-9 were detectable in the peritoneal dialysate of all patients, and marginally correlated (r = 0.27, P = 0.06). Plasma sCD59 levels were significantly higher in PD patients than in patients with chronic kidney disease and healthy controls, but did not differ from hemodialysis patients. During follow-up, 19% of PD patients developed peritoneal membrane failure and 27% of PD patients developed loss of residual renal function. In adjusted models, increased sCD59 levels in the dialysate (HR 3.44, 95% CI 1.04-11.40, P = 0.04) and in plasma (HR 1.08, 95% CI 1.01-1.17, P = 0.04) were independently associated with the occurrence of peritoneal membrane failure. Higher plasma levels of sCD59 were also associated with loss of residual renal function (HR 1.10, 95% CI 1.04-1.17, P < 0.001). CONCLUSIONS: Our study suggests that sCD59 has potential as a biomarker to predict peritoneal membrane function and loss of residual renal function in PD, thereby offering a tool to improve patient management.

Percutaneous access for the diagnosis of urothelial neoplasms: pictorial essay with anatomopathological correlation.

Urothelial carcinoma is a rare malignant neoplasm, accounting for only 5% to 7% of kidney tumors and 5% of urothelial tumors. During the management of urothelial carcinoma, anatomopathological evaluation is used for stratifying the tumors into different prognostic groups to aid in the evaluation of treatment results and to optimize the management of patients. Percutaneous image-guided biopsy is a safe and feasible procedure, with high sensitivity and accuracy rates. Although image-guided percutaneous biopsy of the urinary tract is a relatively uncommon procedure, it can be considered an option in selected cases or when traditional methods, such as the ureteroscopic technique, are not possible.

O carcinoma urotelial é uma neoplasia maligna rara, responsável por apenas 5% a 7% dos tumores renais e 5% dos tumores uroteliais. No manejo do carcinoma urotelial, a determinação anatomopatológica tem por objetivo estratificar os tumores em diferentes grupos prognósticos, para permitir avaliar resultados do tratamento e otimizar o gerenciamento dos pacientes. Biópsia percutânea guiada por imagem é um procedimento seguro e tecnicamente viável, com alta sensibilidade e taxa de precisão. Apesar de as biópsias percutâneas guiadas por imagem do trato urinário serem um procedimento relativamente incomum, podem ser consideradas como opção em casos selecionados ou quando os métodos tradicionais, como o a técnica ureteroscópica, não são possíveis.