How to deal with renal toxicities from immune-based combination treatments in metastatic renal cell carcinoma. A nephrological consultation for Oncologists.

We are witnessing a revolution in the treatment of metastatic renal cell carcinoma (mRCC). Indeed, several immune-based combinations (ICI [immune checkpoint inhibitor] + ICI, or ICI + antiangiogenic agents) have been approved as first-line therapy for mRCC after demonstrating superior efficacy over the previous standard. Despite all the improvements made, safety remains a critical issue, adverse events (AEs) being the main reason for drug discontinuations or dose reductions, ultimately resulting in an increased risk of losing efficacy. Thus, a good understanding of the AEs associated with the use of immune-based combinations, their prevention, and management, are key in order to maximize therapeutic effectiveness. Among these AEs, renal ones are relatively frequent, but always difficult to be diagnosed, not to take into account that it is often difficult to determine which drug is to blame for such toxicities. Chronic kidney disease (CKD) is a common finding in patients with RCC, either as a pre-existing condition and/or as a consequence of cancer and its treatment; furthermore, CKD, especially in advanced stages and in patients undergoing dialysis, may influence the pharmacokinetics and pharmacodynamics properties of anticancer agents. Finally, managing cancer therapy in kidney transplanted patients is another challenge. In this review, we discuss the therapy management of immune-based combinations in patients with CKD, on dialysis, or transplanted, as well as their renal toxicities, with a focus on their prevention, detection and practical management, taking into account the crucial role of the consulting nephrologist within the multidisciplinary care of these patients.

Vascular access for hemodialysis in Italy: What a national survey reveals.

BACKGROUND: Since in Italy there are no official data on vascular access (VA) for hemodialysis the Vascular Access Project Group (VAPG) of the Italian Society of Nephrology (SIN) designed a national survey. METHODS: A 35-question survey was designed and sent it to the Italian facilities through the SIN website. The basic questions were the prevalence, the location, and the surveillance of VA, the bedside use of ultrasound, the use of fluoroscopy for central venous catheter (CVC) placement, and of buttonhole technique, the role of nephrologist in the access creation. RESULT: The questionnaire was completed in June 2022 by 161 facilities. The survey registered 15,499 patients, approximately one-third of the Italian dialysis population. The prevalence of arteriovenous fistula (AVF), arteriovenous Graft (AVG), and CVC were 61.8%, 3.7%, and 34.5% respectively. The AVF location was 50% in distal forearm, 20% in meanproximal forearm, 30% in upper arm. For AVF creation, nephrologists were involved in 72% of facilities while for CVC placement in 62%. As regards VA monitoring, 21% of the facilities did not have a surveillance protocol; 60% did not register AVF thrombosis and 53% did not register CVC infections. Most of facilities use the fluoroscope during CVC placement, 37% when needed, and 22% never. Ultrasound-guided puncture of complex AVFs was used by 80% of facilities. Buttonhole puncture was used in 5% of patients. CONCLUSIONS: Some considerations emerge from the survey data: (1) The increasing CVC prevalence compared to DOPPS 5 study. (2) The low rate of AVG prevalence. (3) The nephrologist is the operator in many VA procedures. (4) The fluoroscopy for CVC placement and the US-guide puncture of the complex AVF are widely used in most facilities. (5) The practice of the buttonhole is not widespread. (6) When the operator is the nephrologist more distal fistulas are performed.

Nephrology Partnership for Advancing Technology in Healthcare (N-PATH) program: the teachers' perspective.

The N-PATH (Nephrology Partnership for Advancing Technology in Healthcare) program concluded with the 60th European Renal Association 2023 Congress in Milan, Italy. This collaborative initiative aimed to provide advanced training in interventional nephrology to young European nephrologists. Funded by Erasmus+ Knowledge Alliance, N-PATH addressed the global burden of chronic kidney disease (CKD) and the shortage of nephrologists. CKD affects >850 million people worldwide, yet nephrology struggles to attract medical talent, leading to unfilled positions in residency programs. To address this, N-PATH focused on enhancing nephrology education through four specialized modules: renal expert in renal pathology (ReMAP), renal expert in vascular access (ReVAC), renal expert in medical ultrasound (ReMUS) and renal expert in peritoneal dialysis (RePED). ReMAP emphasized the importance of kidney biopsy in nephrology diagnosis and treatment, providing theoretical knowledge and hands-on training. ReVAC centred on vascular access in haemodialysis, teaching trainees about different access types, placement techniques and managing complications. ReMUS recognized the significance of ultrasound in nephrology, promoting interdisciplinary collaboration and preparing nephrologists for comprehensive patient care. RePED addressed chronic peritoneal dialysis, offering comprehensive training in patient selection, prescription, monitoring, complications and surgical techniques for catheter insertion. Overall, N-PATH's strategy involved collaborative networks, hands-on training, mentorship, an interdisciplinary approach and the integration of emerging technologies. By bridging the gap between theoretical knowledge and practical skills, N-PATH aimed to revitalize interest in nephrology and prepare proficient nephrologists to tackle the challenges of kidney diseases. In conclusion, the N-PATH program aimed to address the shortage of nephrologists and improve the quality of nephrology care in Europe. By providing specialized training, fostering collaboration and promoting patient-centred care, N-PATH aimed to inspire future nephrology professionals to meet the growing healthcare demands related to kidney diseases and elevate the specialty's status within the medical community.

Real-world usage of Chronic Kidney Disease - Mineral Bone Disorder (CKD-MBD) biomarkers in nephrology practices.

Background: Chronic kidney disease mineral bone disorder (CKD-MBD) is a condition characterized by alterations of calcium, phosphate, parathyroid hormone (PTH), and fibroblast growth factor 23 (FGF-23) metabolism that in turn promote bone disorders, vascular calcifications, and increase cardiovascular (CV) risk. Nephrologists' awareness of diagnostic, prognostic, and therapeutic tools to manage CKD-MBD plays a primary role in adequately preventing and managing this condition in clinical practice. Methods: A national survey (composed of 15 closed questions) was launched to inquire about the use of bone biomarkers in the management of CKD-MBD patients by nephrologists and to gain knowledge about the implementation of guideline recommendations in clinical practice. Results: One hundred and six Italian nephrologists participated in the survey for an overall response rate of about 10%. Nephrologists indicated that the laboratories of their hospitals were able to satisfy request of ionized calcium levels, 105 (99.1%) of both PTH and alkaline phosphatase (ALP), 100 (94.3%) of 25(OH)D, and 61 (57.5%) of 1.25(OH)2D; while most laboratories did not support the requests of biomarkers such as FGF-23 (intact: 88.7% and c-terminal: 93.4%), Klotho (95.3%; soluble form: 97.2%), tartrate-resistant acid phosphatase 5b (TRAP-5b) (92.5%), C-terminal telopeptide (CTX) (71.7%), and pro-collagen type 1 N-terminal pro-peptide (P1NP) (88.7%). As interesting data regarding Italian nephrologists' behavior to start treatment of secondary hyperparathyroidism (sHPT), the majority of clinicians used KDOQI guidelines (n = 55, 51.9%). In contrast, only 40 nephrologists (37.7%) relied on KDIGO guidelines, which recommended referring to values of PTH between two and nine times the upper limit of the normal range. Conclusion: Results point out a marked heterogeneity in the management of CKD-MBD by clinicians as well as a suboptimal implementation of guidelines in Italian clinical practice.

Variation in performing kidney biopsy amongst nephrologists in the Asia-Pacific region: A multinational survey.

AIM: Kidney biopsy (KB) is the gold standard procedure for diagnosing kidney diseases. Globally, nephrologists are trained to perform KB. However, the past few decades have witnessed a transition where interventional radiologists (IRs) are now preferentially performing the procedure. Our survey-based cross-sectional study aimed to investigate the current trends of KB operators in the Asia-Pacific region (APR) in practicing interventional nephrologists. MATERIAL AND METHODS: The Association of Vascular Access and intervenTionAl Renal Physicians (AVATAR) Foundation from India conducted a multinational online survey among interventional nephrologists from the APR to investigate who does KB, if the nephrology training curriculum includes KB, and whether nephrologists have access to ultrasound. RESULTS: Out of 21 countries from the APR that participated in our survey, 10 countries (47.4%) reported that more than 70% of their nephrologists performed KB, whereas in 11 countries (57.6%), KB was most likely done by an IR. The frequency of nephrologists performing KB ranged from 0% in Afghanistan to 100% in countries such as Pakistan, Singapore, and Thailand. Formal training for KB and access to ultrasound was available to nephrologists in 80% of the responding countries. CONCLUSION: Our study shows that despite the availability of training and access to USG, a significant number of nephrologists are not performing KB in the APR. Similar to the trends observed in Western countries, the observed pattern in the APR could be due to lack of time, less incentive, hospital policy, or interest of nephrologists in other aspects of intervention nephrology.

Long-term safety and efficacy of left atrial appendage occlusion in dialysis patients with atrial fibrillation: a multi-center, prospective, open label, observational study.

Background: The prevalence of atrial fibrillation (AF) in end stage kidney disease (ESKD) patients undergoing dialysis is high, however, the high risk of bleeding often hampers with a correct anticoagulation in ESKD patients with AF, despite high thromboembolic risk. Left atrial appendage (LAA) occlusion is a anticoagulation (OAT) for thromboembolism prevention in AF populations with high hemorrhagic risk. Methods and Results: The purpose of the study was to evaluate the efficacy and safety of LAA occlusion in a cohort of dialysis patients undergoing the procedure (LAA occlusion cohort, n = 106), in comparison with two other ESKD cohorts, one taking warfarin (Warfarin cohort, n = 114) and the other without anticoagulation therapy (No-OAT cohort, n = 148). After a median follow-up of 4 years, a Cox regression model, adjusted for possible confounding factors, showed that the hazard ratios (HRs) of thromboembolic events in the LAA occlusion cohort were 0.19 (95%CI 0.04-0.96; p = 0.045) and 0.16 (95%CI 0.04-0.66; p = 0.011) as compared with Warfarin and No-OAT cohorts, respectively. The HR of bleeding in the LAA occlusion cohort was 0.37 (95%CI 0.16-0.83; p = 0.017) compared to Warfarin cohort, while there were no significant differences between the LAA occlusion and the No-OAT cohort (HR 0.51; 95%CI 0.23-1.12; p = 0.094). Adjusted Cox regression models showed lower mortality in patients undergoing LAA occlusion as compared with both the Warfarin cohort (HR 0.60; 95%CI 0.38-0.94; p = 0.027) and no-OAT cohort (HR 0.52; 95%CI 0.34-0.78; p = 0.002). Thromboembolic events in the LAA occlusion cohort were lower than expected according to the CHA2DS2VASc score (1.7 [95%CI 0.3-3.0] vs 6.7 events per 100 person/years, p < 0.001). Conclusion: In ESKD patients with AF, LAA occlusion is safe and effective and is associated with reduced mortality compared with OAT or no therapy.

Assisted PD throughout Europe: advantages, inequities, and solution proposals.

BACKGROUND: Peritoneal dialysis provides several benefits for patients and should be offered as first line kidney replacement therapy, particularly for fragile patients. Limitation to self-care drove assisted peritoneal dialysis to evolve from family-based care to institutional programs, with specialized care givers. Some European countries have mastered this, while others are still bound by the availability of a volunteer to become responsible for treatment. METHODS: A group of leading nephrologists from 13 European countries integrated real-life application of such therapy, highlighting barriers, lessons learned and practical solutions. The objective of this work is to share and summarize several different approaches, with their intrinsic difficulties and solutions, which might helpperitoneal dialysis units to develop and offer assisted peritoneal dialysis. RESULTS: Assisted peritoneal dialysis does not mean 4 continuous ambulatory peritoneal dialysis exchanges, 7 days/week, nor does it exclude cycler. Many different prescriptions might work for our patients. Tailoring PD prescription to residual kidney function, thereby maintaining small solute clearance, reduces dialysis burden and is associated with higher technique survival. Assisted peritoneal dialysis does not mean assistance will be needed permanently, it can be a transitional stage towards individual or caregiver autonomy. Private care agencies can be used to provide assistance; other options may involve implementing PD training programs for the staff of nursing homes or convalescence units. Social partners may be interested in participating in smaller initiatives or for limited time periods. CONCLUSION: Assisted peritoneal dialysis is a valid technique, which should be expanded. In countries without structural models of assisted peritoneal dialysis, active involvement by the nephrologist is needed in order for it to become a reality.

Practice of dialysis access interventional nephrology procedures in the Asia-Pacific region: Getting lay of the land.

AIM: This cross-sectional survey aimed to determine the prevalence of Interventional Nephrology (IN) practice amongst nephrologists in the Asia-Pacific Region (APR), specifically related to dialysis access (DA). METHODS: The Association of VA and intervenTionAl Renal physicians (AVATAR) Foundation from India conducted a multinational online survey amongst nephrologists from the Asia-Pacific to determine the practice of IN in the planning, creation, and management of dialysis access. The treatment modalities, manpower and equipment availability, monthly cost of treatment, specifics of dialysis access interventions, and challenges in the training and practice of IN by nephrologists were included in the survey. RESULTS: Twenty-one countries from the APR participated in the survey. Nephrologists from 18 (85.7%) countries reported performing at least one of the basic dialysis access-related IN procedures, primarily the placement of non-tunnelled central catheters (n-TCC; 71.5%). Only 10 countries (47.6%) reported having an average of <4% of nephrologists performing any of the advanced IN access procedures, the most common being the placement of a peritoneal dialysis (PD) catheter (20%). Lack of formal training (57.14%), time (42.8%), incentive (38%), institutional support (38%), medico-legal protection (28.6%), and prohibitive cost (23.8%) were the main challenges to practice IN. The primary obstacles to implementing the IN training were a lack of funding and skilled personnel. CONCLUSION: The practice of dialysis access-related IN in APR is inadequate, mostly due to a lack of training, backup support, and economic constraints, whereas training in access-related IN is constrained by a lack of a skilled workforce and finances.

Vascular access hands-on training for young nephrologists: The fellows' experience of the N-PATH project REVAC module.

Chronic kidney disease is a major public health problem, as population studies record a prevalence of 7.2% in individuals over 30 years and is expected to increase in the future. Many of them will end up undergoing hemodialysis treatment, and vascular access is not only an essential requirement for the technique, but also a determining factor in their prognosis; for all these reasons, every nephrologist should have both theoretical and practical knowledge of vascular access; however, the practical training is generally uneven and dependent on the hospital in which you train. It is within this context that the N-PATH (Nephrology Partnership for Advancing Technology in Healthcare) program was born with the objective of training 40 young European nephrologists in theoretical and practical aspects of Interventional Nephrology. To fulfill its mission, the 2-year program is composed of four modules of 6 months each including theoretical courses and hands-on training: Renal Expert in Molecular Pathology (REMAP), Renal Expert in Vascular Access (REVAC), Renal Expert in Medical Ultrasound (REMUS), and Renal Expert in Peritoneal Dialysis (REPED). By bringing together young nephrologists from all over Europe, the goal is also to create a strong network and promote Nephrology career at the European level. This publication highlights the experience of fellows who attended the REVAC hands-on training in Milan, focused on simulation and virtual reality for vascular access, and its impact on their nephrology training.

A decision-making algorithm proposal for PICCs and midlines insertion in patients with advanced kidney disease: A pilot study.

INTRODUCTION: Kidney Disease Outcomes Quality Initiative clinical practice guidelines recommend avoiding placement of peripherally inserted vascular access devices in patients with an estimated glomerular filtration rate (eGFR) <45 ml/min. On the other hand, many patients with severe chronic kidney disease (CKD) have poor prognosis.This study carried out a global assessment of mortality at 2 years through Charlson Comorbidity Index (CCI) and Beclap score in patients with PICCs or Midlines, assuming that in those with an estimated high mortality rate at 2 years, it could be acceptable to implant a peripheral vascular access device (PVAD) despite the presence of CKD. METHODS: We analyzed data on patients with PICCs or Midlines inserted from October 2018 to November 2019. CCI, Beclap score, and eGFR were calculated for each patient at the time of the catheter insertion. We then followed patients for 2 years to assess 2-year mortality for each. RESULTS: One hundred and thirty-one patients were enrolled, 49 (37.4%) had eGFR<45 ml. The 2-year mortality rate was 57.3%. The cut off derived from ROC curve analysis of 15 for Beclap score and 5 for CCI, showed good sensitivity and specificity in predicting mortality of the total population, patients without an oncological disease and patients with eGFR<45 ml/min. CONCLUSION: CCI and Beclap score are good predictors of mortality at 2 years.Physicians and nurses can use these tools in the evaluation of patients at risk for future dialysis, instead of relying exclusively on renal function to decide whether implanting PICCs, Midlines, or other vascular access devices.

Alleviating symptoms in patients undergoing long-term hemodialysis: a focus on chronic kidney disease-associated pruritus.

Since the breakthrough of kidney replacement therapy, increases in life expectancy for patients with end-stage kidney disease have been limited. However, patients have become increasingly vocal that, although mortality and life expectancy matter to them, the quality of their life, and particularly the relief of symptoms associated with their treatment, are in many cases more important. The majority of dialysis-associated symptoms and adverse effects do not currently have any approved treatments in this patient population, with the few treatments that are available used off-label, frequently without proven efficacy, yet still potentially adding further adverse effects to patients' current symptom burden. This article will illustrate how understanding the pathophysiology of a single, particularly burdensome symptom of dialysis (chronic kidney disease-associated pruritus) resulted in the design, development and regulatory approval of a treatment for that symptom. The pathway described here can be applied to other symptoms associated with dialysis, meaning that if we cannot add years to patients' lives, we can at least add life to their remaining years.

Magnetic Resonance Visibility, Artifacts, and Overall Safety of the Self-Locating Peritoneal Dialysis Catheter with a Tungsten Tip.

Background: The self-locating peritoneal dialysis (PD) catheter, contains a tungsten tip. The effects of magnetic resonance (MR) on the catheter were evaluated, emphasizing its MR signal, artifacts, ferromagnetism, and possible heating production during the MR sequences. Methods: The catheter was studied in an ex vivo model using a 1.5T MR system and placed into a plastic box containing saline solution. Acquisitions on coronal and axial planes were obtained on fast gradient-echo T1-weighted and fast spin-echo T2-weighted. In vivo abdominal MR exams were also carried out. Results: Overall, the catheter had good visibility. In all sequences, an extensive paramagnetic blooming artifact was detected at the level of the tip tungsten ballast, with a circular artifact of 5 cm in diameter. The catheter showed no magnetic deflection, rotation, or movements during all MR sequences. After imaging, the temperature of the saline solution did not change compared to the basal measurement. Patients safely underwent abdominal MR. Conclusions: The results point to the possibility of safely performing MR in PD patients carrying the self-locating catheter. The self-locating PD catheter is stable when subjected to a 1.5T MR system. However, it creates some visual interference, preventing an accurate study of the tissues surrounding the tungsten tip.

Predictors of hypogammaglobulinemia in ANCA-associated vasculitis after a rituximab-based induction: a multicentre study.

OBJECTIVES: Rituximab has become the cornerstone of induction treatment in ANCA-associated vasculitis (AAV). B-cell depletion may increase the risk of hypogammaglobulinemia, potentially leading to severe infections. This study aims to assess factors associated with hypogammaglobulinemia in AAV patients treated with rituximab. METHODS: This retrospective cohort study included AAV patients treated with rituximab induction in 14 European centres. Severe adverse events (SAEs) were defined as episodes requiring hospitalization or intravenous antibiotics, malignancies, or death. Linear and logistic regression were used to identify predictors of IgG levels and of the risk of hypogammaglobulinemia, defined as IgG ≤7 g/l at 6 months. RESULTS: The study included 227 patients. IgG levels at 6 months were lower than baseline (P < 0.001). Patients requiring intravenous antibiotics during the first 6 months had lower IgG levels at 6 months (P = 0.004). Age [ß (95% CI): -0.23 (-0.38, -0.08) per 10 years, P = 0.003], oral glucocorticoid dose at induction [ß (95% CI): -0.37 (-0.51, -0.24) per sqrt-transformed mg prednisone, P < 0.001] and concomitant use of intravenous glucocorticoid pulses [ß (95% CI): -0.88 (-1.73, -0.02), P = 0.044] were associated with IgG levels at 6 months. Hypogammaglobulinemia was identified in 97 (42.7%) patients. In multivariable logistic regression, factors associated with the risk of hypogammaglobulinemia were age [OR (95% CI): 1.46 (1.15, 1.86) per 10 years, P = 0.002] and oral glucocorticoid dose at induction [OR (95% CI): 1.52 (1.23, 1.89) per 10 mg prednisone, P < 0.001]. CONCLUSIONS: In AAV patients treated with rituximab, hypogammaglobulinemia at 6 months after induction is common, and lower IgG levels are associated with serious infections. The risk of hypogammaglobulinemia in these patients increases with age and higher glucocorticoid doses.

α-Gal A missense variants associated with Fabry disease can lead to ER stress and induction of the unfolded protein response.

Anderson-Fabry Disease (FD) is an X-linked lysosomal disorder caused by mutations in GLA, the gene encoding the lysosomal hydrolase α-galactosidase A (α-Gal A), leading to accumulation of glycosphingolipids in the lysosomes. FD is a multisystemic disorder leading to progressive cardiovascular, cerebrovascular and kidney dysfunction. Phenotypes are divided in two main classes, classic or non-classic, depending on substrate accumulation, age at onset, disease manifestation, severity and progression. The more severe classical phenotype is generally associated with mutations leading to absent or strongly reduced α-Gal A activity, while mutations with higher residual activity generally lead to the non-classical one. Approximately 70% of the over 1,000 Fabry disease-associated mutations are missense mutations, some leading to endoplasmic reticulum (ER) retention of mutant protein. We hypothesized that such mutations could be associated, besides the well-known absence of α-Gal A function/activity, to a possible gain of function effect due to production of a misfolded protein. We hence expressed α-Gal A missense mutations in HEK293 GLA -/- cells and investigated the localization of mutant protein and induction of ER stress and of the unfolded protein response (UPR). We selected a panel of 7 missense mutations, including mutants shown to have residual or no activity in vitro. Immunofluorescence analysis showed that mutants with residual activity have decreased lysosomal localization compared with wild type, and partial retention in the ER, while missense mutants with no residual activity are fully retained in the ER. UPR (ATF6 branch) was significantly induced by all but two mutants, with clear correlation with the extent of ER retention and the predicted mutation structural effect. These data identify a new molecular pathway, associated with gain of function effect, possibly involved in pathogenesis of FD.

[Itching in dialysis, from the patient's point of view].

Itching is an annoying symptom, which afflicts patients with chronic renal failure. To assess the diffusion of itching in the dialysis population in Italy, we carried out a questionnaire, which was distributed to patients of various Italian dialysis centers. The purpose of this investigation was to bring out all those aspects, which make itching a state of chronic suffering, which daily undermines the quality of life of patients. The questionnaire had 16 questions on the intensity of itching, the timing of appearance, the report to doctors and nurses, and any suggested remedies, in addition to some other concerning age, sex, and dialysis age. The questionnaires were distributed to 153 Dialysis Centers and received 1905 responses. In 46.7% of the answered questionnaires, the patients declared the absence of itching. Instead, 53.3% of the patients interviewed reported having itching with varying degrees of intensity. We used for quantifying the intensity of itching the numerical rating scale (NRS). Among the interviewees, those (20.4%) who reported a greater intensity and severity of the symptom described it as often present always, even at night, so as to heavily condition sleep. Only 32.5% of patients solved the problem by contacting their nephrologist or dialysis nurse, and a lower percentage by contacting the dermatologist or general practitioner.

Living Well With Kidney Disease and Effective Symptom Management: Consensus Conference Proceedings.

Chronic kidney disease (CKD) confers a high burden of uremic symptoms that may be underrecognized, underdiagnosed, and undertreated. Unpleasant symptoms, such as CKD-associated pruritus and emotional/psychological distress, often occur within symptom clusters, and treating 1 symptom may potentially alleviate other symptoms in that cluster. The Living Well with Kidney Disease and Effective Symptom Management Consensus Conference convened health experts and leaders of kidney advocacy groups and kidney networks worldwide to discuss the effects of unpleasant symptoms related to CKD on the health and well-being of those affected, and to consider strategies for optimal symptom management. Optimizing symptom management is a cornerstone of conservative and preservative management which aim to prevent or delay dialysis initiation. In persons with kidney dysfunction requiring dialysis (KDRD), incremental transition to dialysis and home dialysis modalities offer personalized approaches. KDRD is proposed as the preferred term given the negative connotations of "failure" as a kidney descriptor, and the success stories in CKD journeys. Engaging persons with CKD to identify and prioritize their personal values and individual needs must be central to ensure their active participation in CKD management, including KDRD. Person-centered communication and care are required to ensure diversity, equity, and inclusion; education/awareness that considers the health literacy of persons with CKD; and shared decision-making among the person with CKD, care partners, and providers. By putting the needs of people with CKD, including effective symptom management, at the center of their treatment, CKD can be optimally treated in a way that aligns with their goals.

The Role of Rituximab in Primary Focal Segmental Glomerular Sclerosis of the Adult.

Introduction: Primary focal segmental glomerular sclerosis (FSGS) is a rare, likely immune-mediated disease. Rituximab (RTX) may play a role in management, although data in adults are scanty. Methods: We collected cases of RTX-treated primary FSGS within the Italian Society of Nephrology Immunopathology Working Group and explored response rate (24-hour proteinuria <3.5 g and <50% compared with baseline, stable estimated glomerular filtration rate). Results: A total of 31 patients were followed for at least 12 months; further follow-up (median 17 months, interquartile range [IQR] 15-33.5) was available for 11. At first RTX administration, median creatinine and 24-hour proteinuria were 1.17 mg/dl (IQR 0.83-1.62) and 5.2 g (IQR 3.3-8.81), respectively. Response rate at 3, 6, and 12 months was 39%, 52%, and 42%, respectively. In the first 12 months, creatinine level remained stable whereas proteinuria and serum albumin level improved, with an increase in the proportion of patients tapering other immunosuppressants. There were 6 patients who were retreated with RTX within 12 months, either for proteinuria increase or refractory disease; only the 2 responders to the first RTX course experienced a further response. At univariate analysis, 6-month response was more frequent in steroid-dependent patients (odds ratio [OR] 7.7 [95% CI 1.16-52.17]) and those with proteinuria <5 g/24 h (OR 8.25 [1.45-46.86]). During long-term follow-up, 4 of 5 responders at 12 months maintained a sustained response, either without further immunosuppression (2 of 4) or with pre-emptive RTX (2 of 4); 1 relapsed and responded to RTX retreatment. Conclusion: RTX may be an option in primary FSGS, especially in steroid-dependent patients, with 24-hour proteinuria <5 g and previously responders to RTX. Optimal long-term management for responders is unclear, with some patients experiencing sustained remission and others requiring RTX retreatment, either preemptive or after rising proteinuria.