Interventional Nephrology: Opportunities and Challenges.

The nephrologist has a pivotal role as the leader of multidisciplinary teams to optimize vascular access care of the patient on dialysis and to promote multidisciplinary collaboration in research, training, and education. The continued success of interventional nephrology as an independent discipline depends on harnessing these efforts to advance knowledge and encourage innovation. A comprehensive curriculum that encompasses research from bench to bedside coupled with standardized clinical training protocols are fundamental to this expansion. As we find ourselves on the threshold of a much-awaited revolution in nephrology, there is great opportunity but also formidable challenges in the field - it is up to us to work together to realize the enormous potential of our discipline.

Lessons for the clinical nephrologist: recurrence of nephrotic syndrome induced by SARS-CoV-2.

SARS-CoV-2 is characterized by a multiorgan tropism including the kidneys. Recent autopsy series indicated that SARS-CoV-2 can infect both tubular and glomerular cells. Whereas tubular cell infiltration may contribute to acute kidney injury, data on a potential clinical correlative to glomerular affection is rare. We describe the first case of nephrotic syndrome in the context of COVID-19 in a renal transplant recipient. A 35 year old male patient received a kidney allograft for primary focal segmental glomerulosclerosis (FSGS). Three months posttransplant a recurrence of podocytopathy was successfully managed by plasma exchange, ivIG, and a conversion from tacrolimus to belatacept (initial proteinuria > 6 g/l decreased to 169 mg/l). Six weeks later he was tested positive for SARS-CoV-2 and developed a second increase of proteinuria (5.6 g/l). Renal allograft biopsy revealed diffuse podocyte effacement and was positive for SARS-CoV-2 in RNA in-situ hybridation indicating a SARS-CoV-2 associated recurrence of podocytopathy. Noteworthy, nephrotic proteinuria resolved spontaneously after recovering from COVID-19. The present case expands the spectrum of renal involvement in COVID-19 from acute tubular injury to podocytopathy in renal transplant recipients. Thus, it may be wise to test for SARS-CoV-2 prior to initiation of immunosuppression in new onset glomerulopathy during the pandemic.

ASDIN white paper: Assessment and management of hemodialysis access-induced distal ischemia by interventional nephrologists.

Although not common, hemodialysis access-induced distal ischemia is a serious condition resulting in significant hemodialysis patient morbidity. Patients with signs and symptoms suggestive of hand ischemia frequently present to the general and interventional nephrologist for evaluation. In order to care for these cases, it is necessary to understand this syndrome and its management. Most cases can be managed conservatively without intervention. Some cases requiring intervention may be treated using techniques within the scope of practice of the interventional nephrologists while other cases require vascular surgery. In order for the interventional nephrologists to evaluate and manage these cases in a timely and appropriate manner, practice guidelines are presented.

Surgeon Characteristics and Dialysis Vascular Access Outcomes in the United States: A Retrospective Cohort Study.

RATIONALE & OBJECTIVE: An arteriovenous fistula (AVF) is the preferred access for most patients receiving maintenance hemodialysis, but maturation failure remains a challenge. Surgeon characteristics have been proposed as contributors to AVF success. We examined variation in AVF placement and AVF outcomes by surgeon and surgeon characteristics. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: National Medicare claims and web-based data submitted by dialysis facilities on maintenance hemodialysis patients from 2009 through 2015. EXPOSURES: Patient characteristics, including demographics and comorbid conditions; surgeon characteristics, including specialty, prior volume of AVF placements, and years since medical school graduation. OUTCOMES: Percent of access placements that were an AVF from 2009 to 2015 (designated AVF placement), and percent of AVFs with successful use within 6 months of placement (maturation) from 2013 to 2014. ANALYTICAL APPROACH: Multilevel logistic regression models examining the association of surgeon characteristics with the outcomes, adjusted for patient characteristics and dialysis facilities as random effects. RESULTS: Among 4,959 surgeons placing 467,827 accesses, median AVF placement was 71% (IQR, 59%-84%). More recent year of medical school graduation and general surgery specialty (vs vascular, cardiothoracic, or transplantation surgery) were associated with higher odds of AVF placement. Among 2,770 surgeons placing 49,826 AVFs, the median AVF maturation rate was 59% (IQR, 44%-71%). More recent year of medical school graduation, but not surgical specialty, was associated with higher odds of AVF maturation. Greater prior volume of AVF placement was associated with higher odds of AVF maturation: OR of 1.46 (95% CI, 1.37-1.57) for highest (>84 AVF placements in 2years) versus lowest (<14) volume quintile. LIMITATIONS: The study relied on administrative data, limiting capture of some factors affecting access outcomes. CONCLUSIONS: There is substantial surgeon-level variation in AVF placements and AVF maturation. Surgeons' prior volume of AVF placements is strongly associated with AVF maturation.

[Is apheresis still a useful tool in the treatment of nephrological diseases?]

Therapeutic apheresis is by now a century-old extracorporeal procedure, but it is still very much relevant thanks to advances in medical device technology. In addition to the classic plasma exchange, we now have double filtration techniques, plasma absorption, immunoadsorption, leuko and cyto-apheresis, LDL apheresis. The application of these highly selective techniques has opened up new perspectives in the treatment of various nephrological diseases. Unfortunately, renal diseases that can be treated with apheretic techniques are often relatively rare and this prevents us from carrying out extensive studies aimed at demonstrating the real benefits of these methods. Every three years, the American Society of Apheresis provides solid recommendations regarding the diseases that can be treated with apheresis. New immunosuppressants, immuno-modulating substances and monoclonal antibodies are becoming extremely selective and sophisticated weapons against diseases with a clearly identified causal agent. This does not exclude the fact that, due to economic reasons or even to minimize the side effects of these new drugs, apheretic techniques could still retain an important, if ancillary, role.

Decision making for the initiation and termination of dialysis in patients with advanced cancer.

Age is a risk factor for both cancer and end-stage renal disease (ESRD). Newer cancer treatments are allowing patients to live longer with their cancer, the renal toxicity from the cancer itself or from the therapies that was used to treat the malignancy. Consequently, nephrologists will increasingly be asked to evaluate and counsel patients with ESRD and advanced cancer regarding the initiation of dialysis. Data on morbidity, mortality, and quality of life (QOL) outcomes in this population are sparse. Expectations regarding what dialysis can reasonably accomplish in this cohort can be unrealistically high among patients, their family members and the rest of the health care team. This article will discuss some results from the available studies on mortality and QOL outcomes in this cohort and advise the nephrologist about how to approach these challenging discussions.

Beyond chronic kidney disease: the diagnosis of Renal Disease in the Elderly as an unmet need. A position paper endorsed by Italian Society of Nephrology (SIN) and Italian Society of Geriatrics and Gerontology (SIGG).

The dramatic increase in prevalence of chronic kidney disease (CKD) with ageing makes the recognition and correct referral of these patients of paramount relevance in order to implement interventions preventing or delaying the development of CKD complications and end-stage renal disease. Nevertheless, several issues make the diagnosis of CKD in the elderly cumbersome. Among these are age related changes in structures and functions of the kidney, which may be difficult to distinguish from CKD, and multimorbidity. Thus, symptoms, clinical findings and laboratory abnormalities should be considered as potential clues to suspect CKD and to suggest screening. Comprehensive geriatric assessment is essential to define the clinical impact of CKD on functional status and to plan treatment. Correct patient referral is very important: patients with stage 4-5 CKD, as well as those with worsening proteinuria or progressive nephropathy (i.e. eGFR reduction > 5 ml/year) should be referred to nephrologist. Renal biopsy not unfrequently may be the key diagnostic exam and should not be denied simply on the basis of age. Indeed, identifying the cause(s) of CKD is highly desirable to perform a targeted therapy against the pathogenetic mechanisms of CKD, which complement and may outperform in efficacy the general measures for CKD.

Can increased vigilance for chronic kidney disease in hospitalised patients decrease late referral and improve dialysis-free survival?

BACKGROUND: Insufficient vigilance for renal insufficiency is associated with late referral, increased morbidity and mortality. The present study examines whether increased vigilance for chronic kidney disease (CKD) leads to quicker referral to and better follow-up by a nephrologist, and whether it is associated with an improved outcome. METHODS: Patients with an eGFR < 45 ml/min/1.73 m2 during hospitalisation at the Ghent University Hospital were enrolled during a period of 100 days. The patients were interviewed about their awareness of CKD. Both the patients and their general practitioner were subsequently informed about CKD. The primary endpoint was the number of patients referred for nephrological follow-up within three months. The secondary endpoint was need for dialysis and mortality from any cause one year after inclusion. RESULTS: Of the 72 included patients, 54 had proven CKD, with eGFR consistently < 45 ml/min/1.73 m2 during at least three months before inclusion. Merely 65% was aware of having CKD and only 41% was in regular nephrological follow-up. After intervention, the percentage of patients with CKD in follow-up increased from 41% to 71% (p = 0.002). The proportion reaching the secondary endpoint was significant lower in the patients who were referred quickly than in those who were not (p = 0.015). Similarly, the proportion was significant lower in the patients who received nephrological follow-up than in those who did not (p = 0.006). CONCLUSION: Vigilance for CKD is poor. Simple interventions to augment the vigilance for CKD, as presented in this study, lead to a quicker referral to and follow-up by a nephrologist, which may result in better outcome.

Biomarker research to improve clinical outcomes of peritoneal dialysis: consensus of the European Training and Research in Peritoneal Dialysis (EuTRiPD) network.

Peritoneal dialysis (PD) therapy substantially requires biomarkers as tools to identify patients who are at the highest risk for PD-related complications and to guide personalized interventions that may improve clinical outcome in the individual patient. In this consensus article, members of the European Training and Research in Peritoneal Dialysis Network (EuTRiPD) review the current status of biomarker research in PD and suggest a selection of biomarkers that can be relevant to the care of PD patients and that are directly accessible in PD effluents. Currently used biomarkers such as interleukin-6, interleukin-8, ex vivo-stimulated interleukin-6 release, cancer antigen-125, and advanced oxidation protein products that were collected through a Delphi procedure were first triaged for inclusion as surrogate endpoints in a clinical trial. Next, novel biomarkers were selected as promising candidates for proof-of-concept studies and were differentiated into inflammation signatures (including interleukin-17, M1/M2 macrophages, and regulatory T cell/T helper 17), mesothelial-to-mesenchymal transition signatures (including microRNA-21 and microRNA-31), and signatures for senescence and inadequate cellular stress responses. Finally, the need for defining pathogen-specific immune fingerprints and phenotype-associated molecular signatures utilizing effluents from the clinical cohorts of PD patients and "omics" technologies and bioinformatics-biostatistics in future joint-research efforts was expressed. Biomarker research in PD offers the potential to develop valuable tools for improving patient management. However, for all biomarkers discussed in this consensus article, the association of biological rationales with relevant clinical outcomes remains to be rigorously validated in adequately powered, prospective, independent clinical studies.

Outcomes of Vascular Access Care and Surgery Managed by Interventional Nephrologists: A Twelve-Year Experience.

BACKGROUND: Optimizing vascular access outcomes is still a challenge, since 30-60% of arteriovenous fistulas fail or do not mature and catheters are widely used in contemporary patients. METHODS: This study reports on strategies and outcomes in a single center in which access planning, surgery and maintenance are managed by a team of nephrologists. We retrospectively analyzed 305 fistulas and 61 grafts created in 270 consecutive patients between 2002 and 2013. RESULTS: The percentage of patients receiving a fistula or graft who initiated hemodialysis with a mature access was 68.6%. Among prevalent patients, 71.7% used a fistula, 15.7% a graft and 12.6% a catheter. Rates of primary failure and revision before cannulation were 14.4 and 1.6% for fistulas vs. 4.9 and 3.3% for grafts. After maturation, complications (1.040 vs. 0.188 per patient-year (py)) and interventions (0.743 vs. 0.066 per py) were greater for grafts than for fistulas (p < 0.001). Secondary patency did not significantly differ between grafts and fistulas (median survival 34.8 vs. 57.3 months, p = 0.36), unless primary failures were excluded from Kaplan-Meier analysis (median survival 34.9 vs. 70.9 months, p = 0.03). CONCLUSIONS: High fistula prevalence, low access-related morbidity and catheter dependence were achieved using individualized strategies, including mid-forearm or perforating vein fistula creation and selective graft placement in high risk patients. Direct involvement of nephrologists throughout all steps of access care can improve access outcomes, by promoting a patient-centered approach.