The complement system is a vital component of innate immunity, known for its role in pathogen defense. It has been increasingly recognized as a mediator of homeostatic clearance, tissue repair, and immune-metabolic crosstalk. In the kidney, unique anatomical and hemodynamic features predispose to aberrant complement activation, rendering glomerular structures particularly vulnerable. Complement dysregulation is implicated in a broad spectrum of kidney diseases – ranging from primary complement-driven disorders (atypical hemolytic uremic syndrome, C3 glomerulopathy, and emergent C4 glomerulopathy) to secondary complement disorders, with special emphasis on classical immune complex diseases, podocytopathies, and kidney transplantation. Within glomeruli, complement activation triggers non-lytic cellular activation (including calcium influx, kinase signaling, cytokine release, and cytoskeletal remodeling), inflammation, cytotoxic injury, and maladaptive remodeling via effectors such as C3a, C5a, and the membrane attack complex (C5b-9). Genetic and autoantibody–mediated defects in complement regulators amplify this risk. Recent advances in complement-targeted therapies—including inhibitors of C3, C5, factor B, and MASP-2—are entering glomerular disease trials, with early evidence of efficacy in proteinuria reduction and slowing of glomerular injury. Nevertheless, key challenges remain: balancing infection risk, defining appropriate durations, selecting responsive patient populations based on complement pathway profiling, and achieving cost-effectiveness. Looking ahead, integration of genetic, proteomic, and histopathologic biomarkers will be essential to implement a precision-medicine approach. Complement remains a frontier in glomerular disease research, bridging fundamental immunology to translational nephrology and offering new pathways to modify disease progression.
Peritoneal dialysis effluent should be clear and any changes in aspect require further investigation. We report a case of a spontaneous milky white effluent (chyloperitoneum) associated with calcium channel blockers in a peritoneal dialysis patient. Our case is a 43-year-old man that presents with milky white peritoneal dialysis effluent 9 days after starting peritoneal dialysis. He didn't have any other complaints and he wasn't prescribed any new medications. In the effluent sample we found high triglycerides (1.8 mmol/L) thus confirming the chyloperitoneum. We suspended lercanidipine and within a few days the peritoneal dialysis effluent was clear. Currently the patient is well adjusted to the technique and had no further episodes of chyloperitoneum.
Kidney disease is a global health priority affecting >850 million people worldwide. This number is projected to increase over the coming decades given the increasing prevalence of diabetes, hypertension and obesity and the aging population. Chronic kidney disease (CKD) can reduce both life expectancy and quality of life and is intricately linked with cardiac and metabolic health-the cardiovascular-kidney-metabolic multimorbidity syndrome. With early recognition of risk, CKD can be prevented and with timely case finding, early diagnosis and early intervention, its progression can be halted or slowed. The European Renal Association has established the Strong Kidneys Task Force, with the main purpose of creating awareness about the importance of kidney health for individual and population health. In collaboration with the European Kidney Health Alliance and the European Kidney Patients Federation, the ABCDE campaign will empower communities and individuals to remind their healthcare providers to assess their risk of kidney disease. ABCDE asks five simple questions about health status that only the healthcare system can provide: A) Do I have Albumin in my urine? B) What is my Blood pressure? C) What is my Cholesterol? D) Do I have Diabetes? E) What is my current kidney function (Estimated glomerular filtration rate)? This advocacy text aims to inform individuals, communities and front line healthcare workers that capturing the risk of kidney, cardiac and metabolic health is simple, makes sense, is logical and will save lives. Although making meaningful change will take time and involve major personal and societal changes, the first step really is as easy as ABCDE!
Abstract Background and Aims Prior abdominal surgery may result in peritoneal membrane adhesions and fibrosis, compromising the success of peritoneal dialysis (PD). The impact of this factor on peritoneal membrane function and PD technique survival has not been adequately investigated. The aim of our study was to disclosure the effect of prior abdominal surgical procedures on PD technique survival (main outcome), efficacy rates and also evaluate the risk of infectious complications (secondaries outcomes). Method We performed a retrospective, longitudinal study, that included 155 PD patients followed at our unit, since September 2018 to September 2022. Two groups were created: G1 (without previous abdominal surgery) and G2 (with previous abdominal surgery). Demographic and clinical characteristics, such as age, gender, chronic kidney disease (CKD) etiology, time on PD program, dialytic efficacy (Kt/V), peritoneal equilibration test results and episodes of peritonitis were registered from our unit database. Statistical analyses were performed using SPSS statistics version 23,0. The statistical hypothesis tests with p-value <0,05 were considered significant. Results One-hundred and fifty-five patients (female: 50,9%) with a mean age of 55,4 ± 7 years were selected. The main CKD cause was glomerular diseases (n = 43, 27,7%), followed by uncertain etiology (n = 32, 20,6%) and autosomal dominant polycystic kidney disease (n = 21, 13,5%). G1 (n = 87; 56,1%) and G2 (n = 68; 43,9%) had similar distributions of gender (female: 50,6% vs 47,1%, p = 0,061), age (50,4± 9 vs 55,4 ±10 years, p = 0,076) and dialysis vintage (27,9 vs 28,2 months, p = 0,081). In G1, 62,1% of patients were on continuous ambulatory peritoneal dialysis (vs 55,9% in G2). The majority of patients were high-average transporters in both groups (58,6% vs 54,4%, p = 0,066). Previous comorbidities were (G1 vs G2): arterial hypertension (95,4% vs. 98,5%, p = 0,87), diabetes (27,6% vs. 26,5%, p = 0,83), heart failure (25,3% vs. 26,5%, p = 0,64), peripheral arterial disease (28,7% vs 35,3%, p = 0,082), body mass index >30 kg/m2 (20,7% vs 29,4%, p = 0,072) and dyslipidemia (64,4% vs. 64,7%, p = 0,91). In G1, Kt/V was inferior a 1,7 in 36,8% of patients (vs 66,2% in G2, p<0,001). Seven patients (8,1%) have reported more than one peritonitis during time in PD in group 1 (vs 32,4% in G2, p<0,001). We found no differences in PD technique survival between both groups. Transition to hemodialysis happened in 26,4% of patients in G1 (vs 26,5% in G2, p = 0,092). Mortality rate was similar in both groups (6,9% vs 10,3%, p = 0,063). Conclusion According to our results, prior abdominal surgical procedures do not appear to compromise technique survival in patients on PD. Although, abdominal surgical events places PD patients in a higher risk of infectious complications and lower efficacy rates. Thus, this group of patients deserve a more detailed evaluation before starting PD, in order to understand if they are good candidates for the technique, as this may not be the most advantageous for them in the long term.
Introduction: Sleep disorders affect up to 70% of peritoneal dialysis (PD) patients and appear to have significant negative effects on their quality of life (QoL). We compared life and sleep quality between patients on automated PD (APD) and continuous ambulatory PD (CAPD). Material and Methods: Cross-sectional study in chronic PD patients followed in our Dialysis Unit in February 2022. We evaluated sleep quality with the Pittsburgh Sleep Quality Index (PSQI) and the Epworth Sleepiness Scale (ESS) and QoL with EUROHIS-QOL-8. Results: Fifty-two patients, mostly men (65.4%, n=32), with a mean age of 52.7±14.2 years and PD vintage of 24.3±17.1 months. Our sample had similar distribution between APD and CAPD; we found no difference between groups regarding demographic data, PD-related quality parameters or prevalence of previous sleep disturbances. Mean QoL index was 69.9%±9.3% and similar between APD and CAPD patients; EUROHIS-QOL-8 negatively correlated with the scores on ESS (p=0.004) and PSQI (p=0.011). Regarding sleep quality, the mean ESS was 8.8±4.2 and PSQI was 7.6±3.6. APD patients had similar scores on ESS, but higher prevalence of severe daytime sleepiness (ESS≥18) (p=0.04) and higher scores on PSQI (p=0.002). Within the PSQI, sleep’ latency (p=0.003), duration (p=0.002) and efficiency (p=0.013) were the most affected parameters. Higher PSQI scores also correlated with worse blood pressure control; a cut-off value for PSQI of 6 was found to increase the risk of uncontrolled hypertension. Conclusion: In our series, APD patients had worse global sleep quality (PSQI) when compared to ACPD patients. This difference was mainly due to worse sleep latency, duration and efficiency. The assessment of the quality of life showed no difference between groups, however there was a clear link between quality of life and sleep quality.
Abstract Background and Aims Control of extracellular volume in peritoneal dialysis (PD) patients requires both removal of sodium and water. Hypervolemia occurs more frequently in PD patients and is associated with greater morbidity and mortality. Dietary salt restriction (Na+ < 2g) is recommended in all PD patients. Most patients do not comply with this recommendation (prevalence difficult to assess). Bioimpedance spectroscopy (BIS) devices can help assess volume overload in patients receiving maintenance PD. The aim of our study was to determine the association between fluid status as measured using BIS to BP and salt consumption in continuous ambulatory peritoneal dialysis (CAPD) patients. Method We performed a retrospective, longitudinal study, that included 60 PD patients followed at our unit. Demographic and clinical characteristics, such as age, gender, chronic kidney disease (CKD) etiology, time on PD program, dialytic efficacy (Kt/V), peritoneal equilibration test results, BIS results and episodes of peritonitis were registered from our unit database. We measured total sodium removal and estimated daily sodium intake using dietary recall for one day, during the assessment of dialysis adequacy. Based on a 2017 study of 87 patients on PD that sought a correlation between effective daily sodium intake (memory recollection) and urinary + peritoneal sodium sieving. It allowed, through logistic regression, the creation of equations for patients with and without renal residual function (RRF) (Pearson's 0.6). Statistical analyses were performed using SPSS statistics version 23.0. The statistical hypothesis tests with p-value <0.05 were considered significant. Results Sixty patients (male: 60%) with a mean age of 55,9 ± 9 years were selected. Mean time on dialysis was 24,8 months ± 11,9 (min. 2, max. 63). The most common etiology of CKD was glomerular diseases (n = 16, 26.7%), followed by uncertain etiology (n = 11, 18.3%) and diabetic kidney disease (n = 9, 15%). In total, 71,7% of patients were on continuous ambulatory peritoneal dialysis (CAPD). Mean Kt/V was 2,2 ± 0,6 and the majority of patients were high-average transporters. Previous comorbidities were arterial hypertension (n = 60, 100%), diabetes (n = 16, 26,7%), heart failure (n = 13, 21,7%), body mass index >30 kg/m2 (n = 22, 36,7%) and dyslipidemia (n = 40, 66,7%). According to European Society of Cardiology we define three stages of hypertension: stage 1 (140–159/90–99 mmHg) with 15 patients (25%), stage 2 (160–179/100–109 mmHg) with 14 patients (23,3%) and stage 3 (≥180/≥110 mmHg) with 4 patients (6,7%). In total, we have 27 patients (45%) with hypertension under control. A statistically significant positive correlation was found between a status of overhydration (≥2liters) with salt consumption (Na+ >2g) (p = 0,01) and also of hypertension stages 2 and 3 (p = 0,03). Conclusion In PD patients, BIS is a reliable method for evaluating volume status. We found that stable CAPD patients with uncontrolled BP had higher overhydration and salt consumption compared to patients whose BP was controlled. Control of hypervolemia and blood pressure is associated with better cardiac condition. Thus, it is important to encourage patients on peritoneal dialysis to significantly restrict salt intake.
Introduction: Optimal fluid balance in peritoneal dialysis requires adequate urinary and peritoneal water and sodium removal and restriction of dietary sodium intake (<2 g/day). We aim to study the relationship between sodium intake, blood pressure control and medication burden in peritoneal dialysis patients. Methods: Observational, cross-sectional study of chronic peritoneal dialysis patients followed in our hospital in March 2022. We estimated patient’s sodium intake according to the equations proposed by Kim et al. Mean ambulatory blood pressure was categorized in controlled, stage one, stage two and stage three hypertension. A qualitative evaluation of sodium intake was done by asking patients about their compliance with a low-salt diet. Results: Eighty-two patients: mostly men, with a mean age of 54.1±14.7 years and dialysis vintage of 26.2±18.7 months. Most patients were on continuous ambulatory peritoneal dialysis (63.4%) and the mean weekly Kt/V was 2.2±0.4. A percentage of 85.4% of our patients had residual diuresis, averaged at 1257±867 mL/day. Mean dietary sodium intake was 3.5±1.1 g; it was higher in men and patients with uncontrolled hypertension, regardless of age, dialysis vintage and other comorbidities. We found a strong correlation between dietary sodium intake and residual diuresis, systolic blood pressure, diastolic blood pressure and the number of anti-hypertensive drugs. Patients with a sodium intake ≥ 3.3 g had higher risk of uncontrolled BP and higher medication burden. Qualitative evaluation of this sub-population revealed that only 2.3% (n=1) admitted non-compliance with a low-sodium diet. Conclusion: We found a strong correlation between estimated dietary sodium consumption, blood pressure control and medication burden. Most importantly, there was a striking difference between patient’s perception of sodium consumption and the actual results. Our results highlight the importance of dietary salt restriction in blood pressure control and reinforce the need for a dietary consultation in peritoneal dialysis patients.
Background: The gap between offer and need for a kidney transplant (KT) has been increasing. The Kidney Donor Profile Index (KDPI) is a measure of "organ quality" and allows estimation of graft survival, but could not apply to all populations. Knowledge of our kidney donor and recipient population is vital to adjust transplant strategies. Methods: We performed a retrospective evaluation of donors and recipients of KT regarding two kidney transplant units: Centro Hospitalar Universitario de Coimbra, CHUC (Coimbra, Portugal) and Centro Hospitalar Universitario de Sao Joao, CHUSJ (Porto, Portugal), between 2013 and 2018. We then did statistical analysis and modeling, correlating these KT outcomes with donor and recipient characteristics, including KDPI. Artificial intelligence methods were performed to determine the best predictors of graft survival. Results: We analyzed a total of 808 kidney donors and 829 recipients of KT. The association between KDPI and graft dysfunction was only moderate. The decision tree machine learning algorithm proved to be better at predicting graft failure than artificial neural networks. Multinomial logistic regression revealed recipient age as an important prognostic factor for graft loss. Conclusions: In this Portuguese cohort, KDPI was not a good measure of KT survival, although it correlated with GFR 1 year post-transplant. The decision tree proved to be the best algorithm to predict graft failure. Age of the recipient was the most important predictor of graft dysfunction.
Abstract Background and Aims Post-transplant lymphoproliferative disorders (PTLD) are a group of heterogeneous lymphoid proliferations in chronic immunosuppressed recipients of solid organ and hematopoietic stem cell transplantation. Due to rarity of this disease, retrospective studies from transplant centers have been the main source to provide knowledge and treatment guidelines, which are still in evolution. This study examined the clinical outcomes and identified the predictors of mortality in adult renal transplant recipients who developed PTLD. Method We have studied the incidence of PTLD in adult renal transplant recipients who were transplanted in our hospital from 1996 to 2019. Data was collected for demographics, transplant and immunosuppression history, EBV and CMV serostatus, diagnosis, treatment and outcomes of PTLD. We performed univariate and multivariate analysis to identify prognostic factors. PTLD was classified according to 2018 WHO lymphoma classification. Results Twenty-four patients (12 males and 12 females) were eligible for the analysis. Mean age at time of the transplant was 43.1 ± 16.9 years, with a time between grafting and PTLD of 66 months (IQR 36-98 months). Mean follow-up time was 87 months (IQR 61-117 months). 25% of patients received a living donor renal transplant. 12,5% of patients received induction therapy with thymoglobulin. Mean age at time of PTLD diagnosis was 48,8 ± 17,9 years. Five cases were from Epstein-Barr virus (EBV) mismatched (D+/R-) transplants and there was seroconversion at time of PTLD diagnosis. 25% of patients had central nervous system involvement. 19 patients have monomorphic PTLD and the most common histological diagnosis was diffuse large B cell lymphoma. We identified that age >30 years at time of the transplant was predictor of mortality (HR 33.01; 95% CI: 3.24-336.14; p=0.003). Surprisingly, presence of B symptoms at time of PTLD diagnosis confer a better prognosis (HR 0,143; 95% CI: 0,035-0,579; p=0.006). All cases were managed with reduction in immunosuppression and converted to everolimus. 8 patients were treated with rituximab and there was no significant difference in the survival of these patients. By the end of follow-up, 7 patients went into remission, 1 returned to chronic dialysis, and 16 patients died (15 of them due to the disease). Mean time between PTLD and death was 3 months (IQR 1-6 months). Conclusion PTLD is an infrequent disease with a poor prognosis in renal transplant patients. Some cases have a close relationship with EBV, but it can also develop in the absence of the classical risk factors. The factor affecting mortality in our population was age >30 years at time of the transplant. Presence of B symptoms at time of PTLD diagnosis seems to confer a better prognosis probably due to early investigation and diagnosis of the disease.
ABSTRACT Background: A well-functioning vascular access is vital to patients on regular hemodialysis. Banding the access is indicated in high-flow-associated steal syndrome. It allows for the reduction of access flow while maintaining distal limb perfusion. Nonetheless, this procedure has some limitations as it can cause hemorrhage, infection, aneurysm formation, thrombosis of access in cases of overbanding, or otherwise insufficient reduction of vascular flow. Other surgical techniques to achieve the same benefit would be useful. Methods: We performed a modified banding technique without endovascular placement of the angioplasty balloon, which is a viable alternative to other techniques. This surgery was performed in patients on chronic dialysis with steal syndrome. Pre- and post-operative access flows were measured and resolution of symptoms was recorded. Primary patency rate was defined as the intervention-free access survival from the operative time. Results: We verified that this technique allowed for access flow reduction in all our six patients, with total resolution of symptoms in all patients. Primary patency rate at 12 months was 100%. No major complications were noted during our follow-up. Conclusions: This technique allows for correction of high-flow arteriovenous fistulas in an efficient and safe way, and can be a viable alternative to other banding procedures.
functions.In this study, we therefore, aimed to evaluate the effects of a standardized treatment approach on KTRs with AMR.METHODS: Since 2010, a two-week standardized protocol including 6 sessions of plasmapheresis (PP), a total dose of 2 g/kg IVIG, and 1-2 weekly doses of rituximab (375 mg/m2) has been administered to KTRs with acute or chronic AMR in our tertiary care center.Adjunct to this protocol, all eligible patients have been converted to triple immunosuppressive maintenance regimen consisting of tacrolimus, a mycophenolic acid derivative and low-dose prednisolone.Overall, 41 KTRs, who were followed-up for a median duration of 124 (IQR: 108-179.5)months and treated according to this regimen, were included in the study.Demographic, clinical, laboratory and histopathological characteristics of patients were analyzed.Study outcome was defined as returning to dialysis due to graft failure or death with a functioning graft.HLA antibodies were measured using single antigen bead assays, and MFI values exceeding 1000 were considered as positive. RESULTS:Demographic, clinical, laboratory and histopathological features at the time of AMR diagnosis are shown in Table 1.A great majority of patients (38, 92.7%) were characterized by chronic AMR.Seventeen patients (41.5%) reached the study outcome over a median of 17 (6-26) months.One, two and five year graft survival rates were 82.9%, 65.9% and 58.5%, respectively.Three modalities of PP were used in this cohort: Immunoadsorption (22, 53.7%), regular PP (12, 29.3%), and double filtration PP (7, 17.1%).Modality of PP (p=0.384),presence of DSA (p=0.178),C4d deposition (p=0.144), and presence of high MFI values (5000) (p=0.198)showed no difference between patients with and without experiencing the study outcome.However, patients with high Banff ct+ci scores (3) had worse 2 (50% vs. 69.7%,p=0.045) and 5-year graft survival rates (37.5% vs. 63.6%,p=0.021) in Kaplan-Meier analysis (Figures 1a and1b).In multivariate Cox regression analysis, only Banff ct scores [p=0.047,HR: 6.214 (1.028-37.571)]and serum albumin levels [p=0.001,HR: 0.016 (0.001-0.197)] predicted the outcome (Table 2).CONCLUSIONS: Response to a standardized treatment protocol, which includes PP, IVIG and rituximab, is quite low in the treatment of both acute and chronic AMR.Hypoalbuminemia and high Banff ct scores are predictors of a worse outcome.
Hepatitis C virus (HCV) is widely prevalent worldwide, with an estimated 180 million people infected.Its manifestations are not limited to hepatic disease, as it has widely known immunomodulator and oncogenic effects.Most HCV associated autoimmune and lymphoproliferative diseases have been shown to subside after successful antiviral treatment.However, viral eradication doesn't always equal lymphoma cure.In some cases, the oncogenic effect lasts well beyond viral elimination.Although the new direct anti -viral agents (DAA) have proved to be safe and effective in treating HCV (with sustained viral responses of 91-95%), this treatment has inherent toxicities.Further, immunologic manifestations of HCV -associated diseases, when present, may require broad immunosuppression in association with the antiviral treatment.We present a case that illustrates the complexities of treating these viral mediated immunologic and lymphoproliferative diseases.
A 39-year-old patient who had kidney transplant presented at the emergency department with pain in his right flank that was ongoing for 15 days. It had started suddenly when he was driving his taxi, after a coughing effort. No haematuria and no history of trauma. He had had a deceased donor kidney
Systemic lupus erythematosus is a heterogeneous and unpredictable autoimmune disease which can be complicated to approach and treat. Hemophagocytic lymphohistiocytosis and diffuse alveolar hemorrhage are rare disease complications. The authors describe a clinical case of a 32-year-old woman with lupus and fever of unknown origin. From the investigations performed, the myelogram revealed hemophagocytosis and Leishmania parasites, therefore liposomal amphotericin B was then started. In addition to directed therapy, she maintained fever that evolved with diffuse alveolar hemorrhage. The myelogram was repeated and showed that she still had hemophagocytosis but now without parasites. Corticotherapy was increased and intravenous Immunoglobulin was started, with improvement. Rituximab was started as a result of macrophage activation syndrome and diffuse alveolar hemorrhage. Months after discharge, she began once again to have sustained fever and Leishmania parasites were found again, therefore liposomal amphotericin B was started once more associated with miltefosine. She continues being followed-up as she is asymptomatic and using steroids in weaning scheme.
INTRODUCTION AND AIMS: Atypical hemolytic-uremic syndrome has ill-defined ethyopathogenesis, and may affect multiple organs. It results from complement alternative pathway dysregulation and its consequences can be catastrophic if not timely detected, as it can be life-threatening. Discovery of new pathogenic mutations which can help to detect this disease sooner is of utmost importance. Here we present one of these new pathogenic mutations of CFI gene.