Predictive Factors of Renal Recovery and Progression to End-Stage Kidney Disease in Patients With Antineutrophil Cytoplasmic Autoantibody-Associated Vasculitis With Severe Kidney Disease.

Introduction: A significant number of patients with antineutrophil cytoplasmic antibodies (ANCA)- associated vasculitis (AAV) with glomerulonephritis (AAV-GN) still progress to end-stage kidney disease (ESKD, estimated glomerular filtration rate [eGFR] <15 ml/min per 1.73 m2) despite advances in remission-induction treatment. Methods: This is a retrospective cohort study on myeloperoxidase (MPO)-ANCA or proteinase 3 (PR3)-ANCA positive patients with AAV (microscopic polyangiitis, MPA; or granulomatosis with polyangiitis, GPA) and eGFR <15 ml/min per 1.73 m2 or ESKD at presentation. Renal recovery, dialysis discontinuation, and persistence of ESKD after standard remission-induction, with or without the use of plasma exchange (PLEX) were analyzed. Results: We analyzed 166 patients with biopsy-proven active AAV-GN and eGFR <15 ml/min per 1.73 m2 at the time of diagnosis. Patients received glucocorticoids with cyclophosphamide (CYC) (n = 84) or with rituximab (RTX) (n = 72) for remission-induction, and 49 received PLEX. The predictors of renal recovery were erythrocyte sedimentation rate, serum creatinine (SCr) at diagnosis, and minimal or mild chronicity changes. We further analyzed 71 patients who started dialysis with or without PLEX within 4 weeks of AAV-GN diagnosis. The predictors of dialysis discontinuation were minimal chronicity changes in kidney biopsy at diagnosis (odds ratio = 6.138; 95% confidence interval [CI]: 1.389-27.118; P = 0.017). Predictors of persistence of ESKD within 12 months included higher SCr at diagnosis (incidence rate ratio [IRR] = 1.086; 95% CI: 1.005-1.173; P = 0.037), and moderate (IRR = 3.797; 95% CI: 1.090-13.225; P = 0.036), or severe chronicity changes in kidney biopsy (IRR = 5.883; 95% CI: 1.542-22.439; P =0.009). Conclusion: In our cohort, kidney recovery, dialysis discontinuation, and persistence of ESKD in patients with AAV-GN and eGFR <15 ml/min per 1.73 m2 depended on SCr and histologic findings on kidney biopsies at the time of diagnosis and was not affected by the addition of PLEX.

Peritoneal dialysis related peritonitis: insights from a long-term analysis of an Italian center.

BACKGROUND: Peritonitis is a common and severe complication of peritoneal dialysis (PD). For comparative analysis standardized definitions as well as measurements and outcomes are crucial. However, most PD-related peritonitis studies have been using heterogenous definitions and variable methods to measure outcomes. The ISPD 2022 guidelines have revised and clarified numerous definitions and proposed new peritonitis categories and outcomes. METHODS: Between 1st January 2009 and 31st May 2023, 267 patients who started PD at our institution were included in the study. All PD-related peritonitis episodes that occurred in our unit during the study period were collected. The new definitions and outcomes of ISPD 2022 recommendations were employed. RESULTS: The overall peritonitis rate was 0.25 episode/patient year. Patient cumulative probability of remaining peritonitis-free at one year was 84.2%. The medical cure and refractory peritonitis rates were equal to 70.3 and 22.4%, respectively. Culture-negative peritonitis accounted for 25.6% of all specimens. The rates of peritonitis associated death, hemodialysis transfer, catheter removal and hospitalization were 6.8%, 18.3%, 18.7% and 64.4%, respectively. Relapsing, repeat, recurrent and enteric peritonitis accounted for 7.8%, 6.8%, 4.1% and 2.7% of all episodes, respectively. Catheter insertion, catheter related and pre-PD peritonitis were 4.2, 2.1 and 0.5%. CONCLUSIONS: The implementation of PD-related peritonitis reports using standardized definitions and outcome measurements is of paramount importance to enhance clinical practice and to allow comparative studies.

Are Kidneys Affected by SARS-CoV-2 Infection? An Updated Review on COVID-19-Associated AKI.

BACKGROUND: Human kidneys are an important target of SARS-CoV-2 infection, and many renal abnormalities have been found in patients with SARS-CoV-2 infection, including proteinuria, hematuria, and acute kidney injury. Acute kidney injury is now considered a common complication of COVID-19, and the epidemiology of AKI in SARS-CoV-2-infected patients continues to be controversial. AIM AND METHODS: We have carried out a narrative review to evaluate the frequency and risk factors for AKI among patients hospitalized due to COVID-19, and the latest surveys on this topic have been included. The mechanisms by which AKI occurs in COVID-19 patients have also been reviewed. RESULTS: Multiple risk factors for the development of AKI in patients with SARS-CoV-2 infection have been identified; these have been classified in various groups (management and background factors, among others). SARS-CoV-2 targets the kidneys by indirect activity, but SARS-CoV-2 infects tubular epithelial cells and podocytes. We retrieved 24 reports (n = 502,593 unique patients with SARS-CoV-2 infection) and found an incidence of AKI of 31.8% (range, 0.5% to 56.9%). Only a minority (n = 2) of studies had a prospective design. We found that the AKI risk was greater in SARS-CoV-2 patients who underwent in-hospital deaths vs. those who survived; the summary estimate of the unadjusted RR of AKI was 2.63 (95% CI, 2.37; 2.93) (random-effects model). A stratified analysis showed that the incidence of AKI was greater in those reports where the frequency of COVID-19-positive patients having comorbidities (diabetes mellitus, arterial hypertension, and advanced age) was high. The unadjusted relative risk (aRR) of AKI was greater in SARS-CoV-2 patients who underwent ICU admission vs. those who did not; the pooled estimate of AKI risk was 2.64 (95% CI, 1.96; 3.56) according to the random-effects model. CONCLUSIONS: AKI is a common complication of hospitalized SARS-CoV-2-infected patients, and some comorbidities are important risk factors for it. The direct activity of the virus on the kidneys has been mentioned in the pathogenesis of AKI in SARS-CoV-2 patients. Further studies are ongoing in order to identify the mechanisms underlying the kidney injury in this population. The role of AKI on survival in SARS-CoV-2-infected patients is another area of active investigation.

Tunnel ultrasound can guide the use of peritoneal dialysis catheter exit site relocation by external splicing and cuff removal in refractory tunnel infection.

BACKGROUND: Peritoneal dialysis (PD) catheter related infections continue to be a major cause of morbidity and transfer to hemodialysis (HD) in PD patients. The treatment of tunnel infection (TI) could be challenging, especially when the infection involves the superficial cuff requiring the removal of the catheter. To spare the patient the loss of the catheter and the transfer to HD, several mini-invasive surgical techniques have been proposed as rescue therapy. Furthermore, nowadays, the rapid growth of digital technology has enormously increased the diagnostic sensibility of the echo signal allowing to accurately defines the extent of the infectious process along the PD catheter tunnel. METHODS: Between 1st January 2020 and 31st December 2021 seven patients who underwent exit-site relocation by external splicing and cuff removal at our institution due to refractory TI were included in the study. All patients were followed until 12 months after the procedure. As soon as TI was defined refractory to the medical therapy, an ultrasonographic examination of the catheter tunnel was performed to define the extent of the infectious episode. RESULTS: Among the 7 infectious episodes, 4 were caused by P. aeruginosa, and 3 by S. aureus. Around the superficial cuff the hypo/anechoic collections detected by ultrasounds showed a mean diameter of 3.05 ± 0.79 mm. The exit-site relocation by external splicing and cuff removal was successful in all cases (7/7, 100%). CONCLUSIONS: In our experience the use of exit site relocation by external splicing and cuff removal as rescue therapy for TI with positive ultrasounds for TI limited to superficial cuff involvement and without secondary peritonitis, yielded to promising results with a success rate of 100%. This preliminary experience underlines the paramount usefulness of tunnel echography in accurately defining the extent of TI and, consequently, guiding the choice of the therapeutical approach in refractory TI.

Corrigendum: Impact of hyperparathyroidism and its different subtypes on long term graft outcome: a single Transplant Center cohort study.

[This corrects the article DOI: 10.3389/fmed.2023.1221086.].

Relationship between number of daily exchanges at CAPD start with clinical outcomes.

BACKGROUND: Peritoneal dialysis (PD) continues to be demanding for patients affected by kidney failure. In kidney failure patients with residual kidney function, the employment of incremental PD, a less onerous dialytic prescription, could translate into a decrease burden on both health systems and patients. METHODS: Between 1st January 2009 and 31st December 2021, 182 patients who started continuous ambulatory peritoneal dialysis (CAPD) at our institution were included in the study. The CAPD population was divided into three groups according to the initial number of daily CAPD exchanges prescribed: one or two (50 patients, CAPD-1/2 group), three (97 patients, CAPD-3 group) and four (35 patients, CAPD-4 group), respectively. RESULTS: Multivariate analysis showed a difference in term of peritonitis free survival in CAPD-1/2 in comparison to CAPD-3 (hazard ratio (HR): 2.20, p = 0.014) and CAPD-4 (HR: 2.98, p < 0.01). A tendency towards a lower hospitalisation rate (CAPD-3 and CAPD-4 vs. CAPD-1/2, p = 0.11 and 0.13, respectively) and decreased mortality (CAPD-3 and CAPD-4 vs. CAPD-1/2, p = 0.13 and 0.22, respectively) in patients who started PD with less than three daily exchanges was detected. No discrepancy of the difference of the mean values between baseline and 24 months residual kidney function was observed among the three groups (p = 0.33). CONCLUSIONS: One- or two-exchange CAPD start was associated with a lower risk of peritonitis in comparison to three- or four-exchange start. Furthermore, an initial PD prescription with less than three exchanges may be associated with an advantage in term of hospitalisation rate and patient survival.

Impact of hyperparathyroidism and its different subtypes on long term graft outcome: a single Transplant Center cohort study.

Purpose: We studied the association between parathormone (PTH) levels and long-term graft loss in RTx patients (RTx-p). Methods: We retrospectively evaluated 871 RTx-p, transplanted in our unit from Jan-2004 to Dec-2020 assessing renal function and mineral metabolism parameters at 1, 6, and 12 months after RTx. Graft loss and death with functioning graft during follow-up (FU, 8.3[5.4-11.4] years) were checked. Results: At month-1, 79% had HPT, of which 63% with secondary HPT (SHPT) and 16% tertiary HPT (THPT); at month-6, HPT prevalence was 80% of which SHPT 64% and THPT 16%; at month-12 HPT prevalence was 77% of which SHPT 62% and THPT 15%. A strong significant correlation was found between HPT type, PTH levels and graft loss at every time point. Mean PTH exposure remained strongly and independently associated to long term graft loss (OR 3.1 [1.4-7.1], p = 0.008). THPT was independently associated with graft loss at month-1 when compared to HPT absence and at every time point when compared to SHPT. No correlation was found with RTx-p death. Discriminatory analyses identified the best mean PTH cut-off to predict long-term graft loss to be between 88.6 and 89.9 pg/mL (AUC = 0.658). Cox regression analyses highlighted that THPT was strongly associated with shorter long-term graft survival at every time-point considered. Conclusion: High PTH levels during 1st year of RTx seem to be associated with long term graft loss.

Heterogeneity of Target Antigens in Sarcoidosis-Associated Membranous Nephropathy.

Introduction: Membranous nephropathy (MN) is the most common glomerular disease associated with sarcoidosis. The target antigen M-type phospholipase A2 receptor 1 (PLA2R) has been identified in a subset of sarcoidosis-associated MN. The target antigen is not known in the remaining sarcoidosis-associated MN. Methods: Data of patients with history of sarcoidosis and biopsy-proven MN were retrieved and analyzed. Mass spectrometry (MS/MS) was performed on all kidney biopsies of sarcoidosis-associated MN to detect the target antigens. Immunohistochemistry (IHC) studies were performed to confirm and localize the target antigens along the glomerular basement membrane (GBM). Results: Eighteen patients with history of sarcoidosis and biopsy-proven MN were identified, of whom 3 were known to be PLA2R-negative, and in the remaining patients the target antigen was unknown. Thirteen (72%) patients were males; the median age at MN diagnosis was 54.5 years. The median proteinuria at presentation was proteinuria 9.8 g/24 h. Eight patients (44.4%) had concurrent sarcoidosis. Using MS/MS, we detected PLA2R and neural epidermal growth factor-like-1 protein (NELL1) in 7 (46.6%) and 4 (22.2%) patients, respectively. In addition, 1 case each (5.5%) was positive for thrombospondin type 1 domain-containing 7A (THSD7A), protocadherin-7 (PCDH7), and putative antigen Serpin B12. No known target antigen was detected in the remaining 4 patients (22.2%). Conclusion: Patients with sarcoidosis and MN exhibit heterogeneous target antigens. We identified, along with PLA2R, the presence of previously unreported antigens, including NELL1, PCDH7, and THSD7A. The incidence of the target antigens in sarcoidosis appears to mirror the overall incidence of target antigens in MN. MN in sarcoidosis may be the result of a heightened immune response and is not associated with a single target antigen.

Simultaneous removal and replacement of the peritoneal catheter in CAPD patient with refractory peritonitis sustained by P. aeruginosa: A case-report.

Pseudomonas peritonitis is often severe and associated with less than 50% complete cure rate, often requiring catheter removal, and transfer to HD. International guidelines recommend that peritoneal catheter should be removed if peritoneal dialysis (PD) effluent does not clear after 5 days of appropriate antibiotic therapy defining the episode as refractory peritonitis. To avoid the shift to hemodialysis (HD), the simultaneous removal and replacement of the peritoneal catheter (SCR) has been employed to treat recurrent peritonitis or tunnel infections associated with peritonitis, obtaining satisfactory outcomes. However, the use of SCR is still controversial in refractory episodes. At present there is growing evidence that refractory peritonitis can be sustained by bacterial adherence along the intraperitoneal portion of the catheter, especially when Pseudomonas species are involved. We describe a case of refractory peritonitis sustained by P. aeruginosa that after a partial response to antibiotics has been successfully treated by SCR.

Utility of ultrasonographic examination in catheter-related infections in peritoneal dialysis: a clinical approach.

Peritoneal dialysis- (PD) related infections continue to be a major cause of morbidity and mortality in patients on renal replacement therapy via PD. However, despite the great efforts in the prevention of PD-related infectious episodes, approximately one third of technical failures are still caused by peritonitis. Recent studies support the theory that ascribes to exit-site and tunnel infections a direct role in causing peritonitis. Hence, prompt exit site infection/tunnel infection diagnosis would allow the timely start of the most appropriate treatment, thereby decreasing the potential complications and enhancing technique survival. Ultrasound examination is a simple, rapid, non-invasive and widely available procedure for tunnel evaluation in PD catheter-related infections. In case of an exit site infection, ultrasound examination has greater sensitivity in diagnosing simultaneous tunnel infection compared to the physical exam alone. This allows distinguishing the exit site infection, which will likely respond to antibiotic therapy, from infections that are likely to be refractory to medical therapy. In case of a tunnel infection, the ultrasound allows localizing the catheter portion involved in the infectious process, thus providing significant prognostic information. In addition, ultrasound performed after two weeks of antibiotic administration allows monitoring patient response to therapy. However, there is no evidence of the usefulness of ultrasound examination as a screening tool for the early diagnosis of tunnel infections in asymptomatic PD patients.

Bone health in autosomal dominant polycystic kidney disease (ADPKD) patients after kidney transplantation.

ADPKD is caused by pathogenic variants in PKD1 or PKD2, encoding polycystin-1 and -2 proteins. Polycystins are expressed in osteoblasts and chondrocytes in animal models, and loss of function is associated with low bone mineral density (BMD) and volume. However, it is unclear whether these variants impact bone strength in ADPKD patients. Here, we examined BMD in ADPKD after kidney transplantation (KTx). This retrospective observational study retrieved data from adult patients who received a KTx over the past 15 years. Patients with available dual-energy X-ray absorptiometry (DXA) of the hip and/or lumbar spine (LS) post-transplant were included. ADPKD patients (n = 340) were matched 1:1 by age (±2 years) at KTx and sex with non-diabetic non-ADPKD patients (n = 340). Patients with ADPKD had slightly higher BMD and T-scores at the right total hip (TH) as compared to non-ADPKD patients [BMD: 0.951 vs. 0.897, p < 0.001; T-score: -0.62 vs. -0.99, p < 0.001] and at left TH [BMD: 0.960 vs. 0.893, p < 0.001; T-score: -0.60 vs. -1.08, p < 0.001], respectively. Similar results were found at the right femoral neck (FN) between ADPKD and non-ADPKD [BMD: 0.887 vs. 0.848, p = 0.001; T-score: -1.20 vs. -1.41, p = 0.01] and at left FN [BMD: 0.885 vs. 0.840, p < 0.001; T-score: -1.16 vs. -1.46, p = 0.001]. At the LS level, ADPKD had a similar BMD and lower T-score compared to non-ADPKD [BMD: 1.120 vs. 1.126, p = 0.93; T-score: -0.66 vs. -0.23, p = 0.008]. After adjusting for preemptive KTx, ADPKD patients continued to have higher BMD T-scores in TH and FN. Our findings indicate that BMD by DXA is higher in patients with ADPKD compared to non-ADPKD patients after transplantation in sites where cortical but not trabecular bone is predominant. The clinical benefit of the preserved cortical bone BMD in patients with ADPKD needs to be explored in future studies.

Simultaneous replacement and removal of the peritoneal catheter is effective in patients with refractory tunnel infections sustained by S. aureus.

BACKGROUND: In tunnel infection (TI) refractory to medical therapy or in case of TI that occurs simultaneously with peritonitis, the removal of the peritoneal catheter has been proposed. This approach requires the interruption of peritoneal dialysis (PD) and the creation of a temporary vascular access. However, simultaneous removal and reinsertion of the PD catheter (SCR) represents another possible therapeutic approach. METHODS: We analysed the outcome of 20 patients (10 men and 10 women, mean age 65.5 ± 16.3 years) treated by CAPD for a mean period of 24.3 ± 14.2 months who underwent to SCR for the treatment of TI unresponsive to medical therapy or TI that occurred simultaneously with peritonitis at Fondazione Ca' Granda Ospedale Maggiore Policlinico. All the patients restarted CAPD exchanges within 24 h from catheter placement. RESULTS: SCR was successful in 80% (16/20) of the cases. In particular, SCR was effective in 100% (11/11) of the TI with or without associated peritonitis sustained by S. aureus. However, SCR failed in 57% (4/7) of TI associated with relapsing peritonitis and in one patient with TI secondary to Enterobacter. No early mechanical complications (within 3 months after SCR) occurred when CAPD was restarted. CONCLUSIONS: SCR of the PD catheter through double-purse string technique represents an effective treatment for TI without or with simultaneously peritonitis sustained by S. aureus avoiding the patient the need for temporary hemodialysis and second surgical procedure. However, SCR could be contraindicated in case of relapsing peritonitis.

Incremental peritoneal dialysis allows to reduce the time spent for dialysis, glucose exposure, economic cost, plastic waste and water consumption.

BACKGROUND: Incremental peritoneal dialysis (incPD) as the initial PD strategy represents a convenient and resource-sparing approach, but its impact on patient, healthcare and environment has not been thoroughly evaluated. METHODS: This study includes 147 patients who started incPD at our institution between 1st January, 2009 and 31st December, 2021. Adequacy measures, peritoneal permeability parameters, peritonitis episodes, hospitalizations and increase in CAPD dose prescriptions were recorded. The savings related to cost, patient glucose exposure, time needed to perform dialysis, plastic waste, and water usage were compared to full-dose PD treatment. RESULTS: During the study follow-up 11.9% of the patients transitioned from incremental to full dose PD. Patient cumulative probability of remaining on PD at 12, 24, 36, 48 and 60 months was 87.6, 65.4, 46.1, 30.1 and 17.5%, respectively. The median transition time from 1 to 2 exchanges, from 2 to 3 and 3 to 4 exchanges were 5, 9 and 11.8 months, respectively. Compared to full dose PD, 1, 2, and 3 exchanges per day led to reduction in glucose exposure of 20.4, 14.8 or 8.3 kg/patient-year, free lifetime gain of 18.1, 13.1 or 7.4 day/patient-year, a decrease in cost of 8700, 6300 or 3540 €/patient-year, a reduction in plastic waste of 139.2, 100.8 or 56.6 kg/patient-year, and a decline in water use of 25,056, 18,144 or 10,196 L/patient-year. CONCLUSIONS: In comparison with full-dose PD, incPD allows to reduce the time spent for managing dialysis, glucose exposure, economic cost, plastic waste, and water consumption.

The use of mini-invasive surgical techniques to treat refractory exit-site and tunnel infections in peritoneal dialysis patients: a clinical approach.

Peritoneal dialysis-(PD) related infections continue to be a major cause of morbidity and mortality in patients on PD. Although great advances have been made in the prevention and treatment of infectious complications over the past two decades, catheter-related infections represent a significant cause of technical failure in PD. Recent studies support the role of exit-site/tunnel infections in causing peritonitis. Peritonitis secondary to tunnel infection led to catheter loss in most cases. Thus, removing the catheter when exit-site/tunnel infection is refractory to medical therapy has been recommended. This approach requires interrupting PD and, after the placement of a central venous catheter, and transferring the patient to haemodialysis. In order to continue PD, simultaneous catheter removal and replacement of the PD catheter has been suggested. Although simultaneous catheter removal and replacement avoids temporary haemodialysis, it implies the removal/reinsertion of the catheter and the immediate initiation of PD with the risk of mechanical complications, such as leakage and malfunction. Hence, several mini-invasive surgical techniques, such as curettage, cuff-shaving, removal of the superficial cuff, and partial reimplantation of the catheter, have been proposed as rescue treatments. These procedures may allow the rescue of the catheter with a success rate of 70-100%. Therefore, in case of refractory exit-site/tunnel infection, a mini-invasive surgical revision should be considered before removing the catheter.

Maintenance of Remission and Risk of Relapse in Myeloperoxidase-Positive ANCA-Associated Vasculitis with Kidney Involvement.

BACKGROUND: The optimal strategy for remission-maintenance therapy in patients with myeloperoxidase-ANCA (MPO-ANCA)-associated vasculitis is not established. Defining parameters to guide maintenance therapy is required. METHODS: This was a retrospective cohort study of all patients with MPO-ANCA-associated vasculitis (microscopic with polyangiitis and granulomatosis with polyangiitis) and GN followed at the Mayo Clinic between 1996 and 2015. Relapse rate, MPO-ANCA status, and remission-maintenance therapies were reviewed. Logistic regression models, Kaplan-Meier method, and Cox proportional hazards regression models were applied. RESULTS: We analyzed 159 patients with active MPO-ANCA-associated vasculitis with GN. Sixty-six (42%) patients had at least one relapse, and 52 (33%) relapsed before 60 months. Patients with MPO-ANCA who became persistently negative did not relapse (hazard ratio [HR], 0.03; 95% confidence interval [95% CI], 0.002 to 0.431; P =0.01). The reappearance of MPO-ANCA was associated with a higher risk of relapse (HR, 1.91; 95% CI, 1.109 to 3.293; P =0.02). Immunosuppression was withdrawn in 80 (50%) patients, and this was less likely in those who received cyclophosphamide for remission induction or in patients with persistently positive MPO-ANCA (odds ratio [OR], 0.44; 95% CI, 0.228 to 0.861; P =0.02 and OR, 0.42; 95% CI, 0.213 to 0.820; P =0.01, respectively). Relapse frequency was not different between patients with persistently positive MPO-ANCA and patients with MPO-ANCA reappearance (44% versus 39%, P =0.49), irrespective of remission-maintenance treatment. Ear, nose, and throat involvement (OR, 6.10; 95% CI, 1.280 to 29.010; P =0.02) and MPO-ANCA reappearance (OR, 9.25; 95% CI, 3.126 to 27.361; P <0.001) were independently associated with relapse after treatment withdrawal. CONCLUSIONS: Patients persistently MPO-ANCA negative are at low risk for relapse even without remission-maintenance therapy. Persistence or subsequent reappearance of MPO-ANCA is associated with a higher risk of relapse. PODCAST: This article contains a podcast at https://dts.podtrac.com/redirect.mp3/www.asn-online.org/media/podcast.aspx?p=CJASN&e=2023_01_10_CJN06460622.mp3.

Recent Information on Pan-Genotypic Direct-Acting Antiviral Agents for HCV in Chronic Kidney Disease.

BACKGROUND: Hepatitis C virus (HCV) is still common in patients with chronic kidney disease. It has been recently discovered that chronic HCV is a risk factor for increased incidence of CKD in the adult general population. According to a systematic review with a meta-analysis of clinical studies, pooling results of longitudinal studies (n = 2,299,134 unique patients) demonstrated an association between positive anti-HCV serologic status and increased incidence of CKD; the summary estimate for adjusted HR across the surveys was 1.54 (95% CI, 1.26; 1.87), (p < 0.0001). The introduction of direct-acting antiviral drugs (DAAs) has caused a paradigm shift in the management of HCV infection; recent guidelines recommend pan-genotypic drugs (i.e., drugs effective on all HCV genotypes) as the first-choice therapy for HCV, and these promise to be effective and safe even in the context of chronic kidney disease. AIM: The purpose of this narrative review is to show the most important data on pan-genotypic DAAs in advanced CKD (CKD stage 4/5). METHODS: We recruited studies by electronic databases and grey literature. Numerous key-words ('Hepatitis C' AND 'Chronic kidney disease' AND 'Pan-genotypic agents', among others) were adopted. RESULTS: The most important pan-genotypic combinations for HCV in advanced CKD are glecaprevir/pibrentasvir (GLE/PIB) and sofosbuvir/velpatasvir (SOF/VEL). Two clinical trials (EXPEDITION-4 and EXPEDITION-5) and some 'real-world' studies (n = 6) reported that GLE/PIB combinations in CKD stage 4/5 gave SVR12 rates ranging between 86 and 99%. We retrieved clinical trials (n = 1) and 'real life' studies (n = 6) showing the performance of SOF/VEL; according to our pooled analysis, the summary estimate of SVR rate was 100% in studies adopting SOF/VEL antiviral combinations. The drop-out rate (due to AEs) in patients on SOF/VEL ranged between 0 and 4.8%. CONCLUSIONS: Pan-genotypic combinations, such as GLE/PIB and SOF/VEL, appear effective and safe for HCV in advanced CKD, even if a limited number of studies with small sample sizes currently exist on this issue. Studies are under way to assess whether successful antiviral therapy with DAAs will translate into better survival in patients with advanced CKD.

Analysis of mechanical complications in urgent-start peritoneal dialysis.

BACKGROUND: Peritoneal dialysis (PD) is an excellent, but underutilized dialysis technique. Thus, its implementation may depend also on the chance to offer this modality of treatment to patients referred late to the nephologists. This approach has recently been named "urgent-start peritoneal dialysis" (UPD). The main barrier to this practice is represented by the fear of early mechanical complications. METHODS: All prevalent patients needing urgent-start PD at our institution between 1 January, 2009 and 31 December, 2019 were included in the study. During this period, 242 peritoneal catheters were inserted in 222 patients. In all patients, an anti-leakage/dislocation suture was made. PD was started within 24 h from catheter placement. RESULTS: The early incidence of leakages, catheter dislocations, omental wrappings, bleedings, peritonitis and exit-site infections was 11/242 (4.5%), 5/242 (2%), 3/242 (1.2%), 2/242 (0.8%), 6/242 (2.5%) and 4/242 (1.6%), respectively. No bowel perforations were observed. Nearly one third of the late complications (13/45; 35.2%) resulted in discontinuation of PD, while one fourth (11/45; 24.4%) required surgical revision. The remaining episodes (21/45; 46.6%) were successfully managed by a conservative approach. The survival of the catheter at 3, 6, 12, 24, 36 and 48 months was 93.6, 91.2, 84.8, 77.4, 65.5 and 59.3%, respectively. The technique survival at 3, 6, 12, 24, 36 and 48 months was 97.2, 94.9, 87.6, 78.9, 66.6 and 60.0%, respectively. The main causes of PD drop-out included infectious complications (36.8%) followed by mechanical complications (17.5%). CONCLUSIONS: A tight seal between deep cuff and surrounding tissues (double purse-string technique) in association with a starting low-volume exchange scheme allows to minimize early and late mechanical complication in UPD.

Peritoneal Dialysis for Potential Kidney Transplant Recipients: Pride or Prejudice?

Kidney transplantation (KT) is recognized as the gold-standard of treatment for patients with end-stage renal disease. Additionally, it has been demonstrated that receiving a pre-emptive KT ensures the best recipient and graft survivals. However, due to an overwhelming discrepancy between the organs available and the patients on the transplant waiting list, the vast majority of transplant candidates require prolonged periods of dialysis before being transplanted. For many years, peritoneal dialysis (PD) and hemodialysis (HD) have been considered competitive renal replacement therapies (RRT). This dualistic vision has recently been questioned by evidence suggesting that an individualized and flexible approach may be more appropriate. In fact, tailored and cleverly planned changes between different RRT modalities, according to the patient's needs and characteristics, are often needed in order to achieve the best results. While home HD is still under scrutiny in this particular setting, current data seems to favor the use of PD over in-center HD in patients awaiting a KT. In this specific population, the demonstrated advantages of PD are superior quality of life, longer preservation of residual renal function, lower incidence of delayed graft function, better recipient survival, and reduced cost.

[Is peritoneal dialysis the first-choice renal replacement therapy for patients waiting for a kidney transplant?]

Kidney transplantation is the gold-standard treatment of end-stage renal disease. Receiving a pre-emptive transplant ensures the best survival for both the recipient and the allograft. However, due to an overwhelming discrepancy between available donors and patients on the transplant waiting list, the vast majority of transplant candidates require prolonged periods of dialytic therapy before transplant. Peritoneal dialysis and hemodialysis have been traditionally considered as competitive renal replacement therapies. This dualistic vision has been recently questioned by emerging evidence suggesting that an individualized and flexible approach may be more appropriate. Tailored and cleverly planned shifts between different modalities, according to the patient's needs, represents the best option. Remarkably, recent data seem to support the use of peritoneal dialysis over hemodialysis in patients waiting for a kidney transplant. In this specific setting, the perceived advantages of PD are better overall recipient survival and quality of life, longer preservation of residual renal function, lower incidence of delayed graft function and reduced cost.

[Urgent-start PD: a viable approach].

Despite the many potential benefits of peritoneal dialysis (PD), the percentage of dialysis patients treated with PD is around 10% worldwide. Up to 70% of the subjects who progress to end-stage renal disease (ESRD) start dialysis without a well-defined therapy plan. Most of these patients are unaware of having chronic kidney disease, while others with stable CKD incur in unpredictable and acute worsening of kidney function. As a matter of fact, 80% of incident HD patients start dialysis with a central venous catheter (CVC) even though starting HD with a CVC is independently associated with increased mortality, high rates of bacteremia, and increased hospitalization rates. Thus, PD is an excellent but underused mode of dialysis. Offering it to patients who present late to dialysis therapy, due to uremic state or hypervolemia, may help increase its application in the future. This approach has been recently denominated "urgent-start peritoneal dialysis" (UPD). Based on the break-in period, it is possible to differentiate UPD from "early-start peritoneal dialysis" (EPD). The outcome of UPD depends on the right selection of patients, the appropriate placement of the catheter and the adequate education of the nursing and medical staff. Moreover, using modified catheter insertion technique aimed at creating a tight seal between the inner cuff and the abdominal tissues, as well as employing protocols that use low-volume exchanges in a supine posture, could minimize the occurrence of early mechanical complications. Although the probability of mechanical complications is higher in early-start PD patients, UPD/EPD show a mortality rate, a PD survival and an infectious complication rate comparable with conventional PD. In comparison to urgent-start hemodialysis via a CVC, UPD can be a safe and cost-effective alternative that decreases the incidences of catheter-related bloodstream infections and hemodialysis-related complications. Furthermore, UPD can promote the diffusion of PD.