Post-Kidney Transplant Cancer: A Real-World Retrospective Analysis From a Single Italian Center.

We describe the epidemiology of cancer after kidney transplantation (KTx), investigating its risk factors and impact on therapeutic management and survival in KTx recipients (KTRs). The association between modification of immunosuppressive (IS) therapy after cancer and survival outcomes was analyzed. We collected data from 930 KTRs followed for 7 [1-19] years. The majority of KTRs received KTx from a deceased donor (84%). In total, 74% of patients received induction therapy with basiliximab and 26% with ATG. Maintenance therapy included steroids, calcineurin inhibitors, and mycophenolate. Patients with at least one cancer (CA+) amounted to 19%. NMSC was the most common tumor (55%). CA+ were older and had a higher BMI. Vasculitis and ADPKD were more prevalent in CA+. ATG was independently associated with CA+ and was related to earlier cancer development in survival and competing risk analyses (p = 0.01 and <0.0001; basiliximab 89 ± 4 vs. ATG 40 ± 4 months). After cancer diagnosis, a significant prognostic impact was derived from the shift to mTOR inhibitors compared to a definitive IS drug suspension (p = 0.004). Our data confirm the relevance of cancer as a complication in KTRs with ATG as an independent risk factor. An individualized choice of IS to be proposed at the time of KTx is crucial in the prevention of neoplastic risk. Finally, switching to mTORi could represent an important strategy to improve patient survival.

Hepatitis C virus infection is associated with proteinuria according to a systematic review with meta-analysis.

INTRODUCTION AND AIM: Hepatitis C virus infection and chronic kidney disease are major public health issues all over the world. It has been suggested a role of HCV as a risk factor for the development and progression of chronic kidney disease (defined by reduced glomerular filtration rate and/or detectable proteinuria) in the general population but conflicting findings have been given. MATERIAL AND METHODS: A systematic review of the published medical literature was conducted to assess whether positive HCV serologic status is associated with greater rate of proteinuria in the adult general population. We used a random-effect model to generate a summary estimate of the relative risk of proteinuria with HCV across the published studies. RESULTS: We identified 23 studies (n=198,967 unique patients) and performed separate meta-analyses according to the study design. Overall effect estimate was significant in cross-sectional (OR, 1.47, 95%CI, 1.3; 1.66) (P<0.001) and obvious between-study heterogeneity was observed (Q value by Chi-squared [χ2] test 27.3, P=0.02). The risk of proteinuria after exposure to HCV was also consistent among longitudinal studies (HR, 1.79, 95% CI, 1.17; 2.74) (P<0.001) and between-study heterogeneity occurred (Q value, 27.82 by X2 test, P=0.0001). Stratified analysis did not report heterogeneity in several comparisons-pooling studies based on urine protein/creatinine ratio (UACR) showed that the adjusted OR with HCV was 1.64 (95% CI, 1.41; 1.91, P<0.001) without heterogeneity (Q value by Chi-squared [χ2] test 9.98, P=NS). Meta-regression recorded a link between greater prevalence of proteinuria in males with HCV exposure (P=0.03). Studies based on univariate analysis (n=6, n=72, 551 unique patients) gave similar results, pooled OR 1.54 (95% CI, 1.08; 2.19) (P=0.0001). CONCLUSIONS: An important relationship between HCV infection and higher risk of proteinuria in the general population exists. Research aimed to understand the biological mechanisms underlying such association is under way. We encourage to screen all patients with HCV exposure for proteinuria.

Frailty Is Associated with Malnutrition-Inflammation Syndrome in Older CKD Patients.

Patients affected by chronic kidney disease (CKD) are generally considered to be frailer than those with preserved renal function. We cross-sectionally evaluated the associations between frailty, malnutrition-inflammation syndrome and circulating inflammatory cytokines in 115 older individuals with advanced CKD. As for frailty definition, we adopted Fried's frailty phenotype (FP), while malnutrition-inflammation syndrome was assessed using the Malnutrition-Inflammation Score (MIS) and circulating inflammatory cytokines (IL-6; TNFα; MCP-1). A total of 48 patients were frail, and mean eGFR was comparable in both frail and non-frail patients (24 ± 10 vs. 25 ± 11 mL/min/1.73 m2; p = 0.63). Frail patients had higher MIS (6 [4-11] vs. 4 [3-5]; p < 0.0001) but cytokine concentrations were comparable in both groups. At multivariate regression, FP was independently associated with MIS, age, gender and pre-albumin but not with cytokines. However, we found some associations between inflammatory cytokines and some specific frailty criteria: weight loss and slowness were associated with MCP-1 (respectively p = 0.049 and p < 0.0001) and weakness with IL-6 (p = 0.005); in conclusion, in older patients with advanced CKD, frailty is strictly associated with malnutrition-inflammation syndrome but not with circulating inflammatory cytokines.

What Not to Overlook in the Management of Patients with Type 2 Diabetes Mellitus: The Nephrological and Hepatological Perspectives.

Diabetes mellitus (DM) significantly impacts renal and hepatic function, necessitating comprehensive understanding and management strategies. Renal involvement, namely diabetic kidney disease (DKD), presents a global challenge, with increasing prevalence paralleling DM rates. Lifestyle modifications and pharmacotherapy targeting hypertension and glycemic control have pivotal roles in DKD management. Concurrently, hepatic involvement in DM, characterized by metabolic dysfunction-associated steatotic liver disease (MASLD), presents a bidirectional relationship. DM exacerbates MASLD progression, while MASLD predisposes to DM development and worsens glycemic control. Screening for MASLD in DM patients is of high importance, utilizing non-invasive methods like ultrasound and fibrosis scores. Lifestyle modifications, such as weight loss and a Mediterranean diet, mitigate MASLD progression. Promising pharmacotherapies, like SGLT2 inhibitors and GLP-1 agonists, demonstrate efficacy in both DM and MASLD management. Special populations, such as diabetic individuals undergoing hemodialysis or kidney transplant recipients, demand special care due to unique clinical features. Similarly, DM exacerbates complications in MASLD patients, elevating the risks of hepatic decompensation and hepatocellular carcinoma. Recognizing the interconnectedness of DM, renal, and hepatic diseases underscores the need for multidisciplinary approaches for optimal patient outcomes. The present review aims to present the main characteristics and crucial points not to be overlooked regarding the renal and hepatic involvement in DM patients focusing on the inter-relationships between the renal and the hepatic involvements.

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.

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.

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.

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.

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.

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.

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.