Principles of Kidney Pharmacotherapy for the Nephrologist: Core Curriculum 2021.

Medications are an important part of the management of patients with kidney disease. When used appropriately, pharmacotherapy can slow disease progression and reduce morbidity and mortality. Unfortunately, reduced kidney function can significantly alter the pharmacokinetics and pharmacodynamics of many medications, putting patients at risk for drug toxicity if modifications to therapy are not appropriately managed. Adding complexity to the appropriateness of medication and dosage selection is the difficulty in estimating kidney function and the discordance between the Cockcroft-Gault-derived dosing cut points in most medication package inserts and the estimations of glomerular filtration rate by newer and generally more accurate guideline-recommended equations. This installment of the AJKD Core Curriculum in Nephrology provides recent updates and practical considerations for designing optimal medication regimens. Given the prevalence of abnormal kidney function and its importance in medication selection and dose adjustment, additional focus and specific recommendations are provided for anticoagulant, anti-infective, analgesic, antidiabetic, and antihypertensive agents.

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.

Experiences of US Nephrologists in the Delivery of Conservative Care to Patients With Advanced Kidney Disease: A National Qualitative Study.

RATIONALE & OBJECTIVE: It is relatively unusual for US patients with advanced chronic kidney disease (CKD) to forgo initiation of maintenance dialysis. Our objective was to describe practice approaches of US nephrologists who have provided conservative care for members of this population. STUDY DESIGN: Qualitative study using semi-structured interviews. SETTING & PARTICIPANTS: A national sample of 21 nephrologists experienced in caring for patients with advanced CKD who decided not to start dialysis. ANALYTICAL APPROACH: Grounded theory methods to identify dominant themes reflecting nephrologists' experiences with and approaches to conservative care for patients with advanced CKD. RESULTS: Nephrologists who participated in this study were primarily from academic practices (n=14) and urban areas (n=15). Two prominent themes emerged from qualitative analysis reflecting nephrologists' experiences with and approaches to conservative care: (1) person-centered practices, which described a holistic approach to care that included basing treatment decisions on what mattered most to individual patients, framing dialysis as an explicit choice, being mindful of sources of bias in medical decision making, and being flexible to the changing needs, values, and preferences of patients; and (2) improvising a care infrastructure, which described the challenges of managing patients conservatively within health systems that are not optimally configured to support their needs. Participating nephrologists described cobbling together resources, assuming a range of different health care roles, preparing patients to navigate health systems in which initiation of dialysis served as a powerful default, and championing the principles of conservative care among their colleagues. LIMITATIONS: The themes identified likely are not generalizable to most US nephrologists. CONCLUSIONS: Insights from a select group of US nephrologists who are early adopters of conservative care signal the need for a stronger cultural and health system commitment to building care models capable of supporting patients who choose to forgo dialysis.

[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.

Achieving dialysis safety: The critical role of higher-functioning teams.

The potential for harm from errors and adverse events in dialysis is significant. Achieving a culture of safety in dialysis to reduce the potential harm to patients has been challenging. Recently, improving dialysis safety has been highlighted by Nephrologists Transforming Dialysis Safety (NTDS), a national initiative to eliminate dialysis infections. Other aspects of dialysis safety are important, though less measurable. Approaching dialysis safety from a systematic thinking view helps us to understand the need for leadership and high-functioning teams to deliver safe, reliable care in dialysis facilities. Resilience in healthcare is embodied by strong teamwork-interdependent professionals working together with clarity of goals and communication. This paper reframes the role of dialysis facility medical directors as leaders of these high-functioning teams. Alignment between nephrologists and dialysis management is necessary for these teams to function. This will require nephrologists to embrace their leadership roles as medical directors and for dialysis facility management to provide adequate operational support. The accountability for dialysis safety is shared between the nephrologists and dialysis organizations; coleadership is required for safety culture and high-functioning dialysis teams to develop.

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.

The 2018 ESC/ESH hypertension guidelines: Should nephrologists always stop at the lower boundary?

In patients with chronic kidney disease (CKD), hypertension is a major challenge because of its high prevalence, the consequent increase in cardiovascular morbidity and mortality, and the risk it confers specifically to the progression of kidney disease. Hence, establishing evidence-based blood pressure targets and treatment strategies is a clinical priority of paramount importance. Over the last few years, different guidelines have advocated different blood pressure treatment thresholds and goals in CKD patients, including a target < 140/90 mmHg and a more intensive target-lower than 130/80 mmHg-in the presence of albuminuria ≥ 300 mg/daily. Aim of this article is to critically appraise the evidence base of the freshly released 2018 ESC/ESH European Guidelines, which recommend to lower systolic BP to a range 130 to < 140 mmHg in patients with diabetic or non-diabetic CKD, also in view of the 2017 US guidelines, which favor a more intensive strategy with a BP target lower than 130/80 mmHg.

Clinicians' and researchers' perspectives on establishing and implementing core outcomes in haemodialysis: semistructured interview study.

OBJECTIVES: To describe the perspectives of clinicians and researchers on identifying, establishing and implementing core outcomes in haemodialysis and their expected impact. DESIGN: Face-to-face, semistructured interviews; thematic analysis. STETTING: Twenty-seven centres across nine countries. PARTICIPANTS: Fifty-eight nephrologists (42 (72%) who were also triallists). RESULTS: We identified six themes: reflecting direct patient relevance and impact (survival as the primary goal of dialysis, enabling well-being and functioning, severe consequences of comorbidities and complications, indicators of treatment success, universal relevance, stakeholder consensus); amenable and responsive to interventions (realistic and possible to intervene on, differentiating between treatments); reflective of economic burden on healthcare; feasibility of implementation (clarity and consistency in definition, easily measurable, requiring minimal resources, creating a cultural shift, aversion to intensifying bureaucracy, allowing justifiable exceptions); authoritative inducement and directive (endorsement for legitimacy, necessity of buy-in from dialysis providers, incentivising uptake); instituting patient-centredness (explicitly addressing patient-important outcomes, reciprocating trial participation, improving comparability of interventions for decision-making, driving quality improvement and compelling a focus on quality of life). CONCLUSIONS: Nephrologists emphasised that core outcomes should be relevant to patients, amenable to change, feasible to implement and supported by stakeholder organisations. They expected core outcomes would improve patient-centred care and outcomes.

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.

Warfarin anticoagulation in hemodialysis patients with atrial fibrillation: comparison of nephrologist-led and anticoagulation clinic-led management.

BACKGROUND: There is conflicting evidence of benefit versus harm for warfarin anticoagulation in hemodialysis patients with atrial fibrillation. This equipoise may be explained by suboptimal Time in Therapeutic Range (TTR), which correlates well with thromboembolic and bleeding complications. This study aimed to compare nephrologist-led management of warfarin therapy versus that led by specialized anticoagulation clinic. METHODS: In a retrospective cohort of chronic hemodialysis patients from two institutions (Institution A: Nephrologist-led warfarin management, Institution B: Anticoagulation clinic-led warfarin management), we identified patients with atrial fibrillation who were receiving warfarin for thromboembolic prophylaxis. Mean TTRs, proportion of patients achieving TTR ≥ 60%, and frequency of INR testing were compared using a logistic regression model. RESULTS: In Institution A, 16.7% of hemodialysis patients had atrial fibrillation, of whom 36.8% were on warfarin. In Institution B, 18% of hemodialysis patients had atrial fibrillation, and 55.5% were on warfarin. The mean TTR was 61.8% (SD 14.5) in Institution A, and 60.5% (SD 15.8) in Institution B (p-value 0.95). However, the proportion of patients achieving TTR ≥ 60% was 65% versus 43.3% (Adjusted OR 2.22, CI 0.65-7.63) and mean frequency of INR testing was every 6 days versus every 13.9 days in Institutions A and B respectively. CONCLUSIONS: There was no statistical difference in mean TTR between nephrologist-led management of warfarin and that of clinic-led management. However, the former achieved a trend toward a higher proportion of patients with optimal TTR. This improved therapeutic results was associated with more frequent INR monitoring.

Measuring patient experience in dialysis: a new paradigm of quality assessment.

Patients' experience of care (PEC) is as an important dimension in quality of care. As a distinct entity from patient satisfaction and patient health-related quality of life, PEC is defined as patients' perceptions of the range of interactions they have with the health care system, including care from providers, facilities, and health plans. While traditionally PEC may be ascertained via informal assessments, in recent years, especially in the United States, there has been a shift towards standardized surveillance of PEC amongst dialysis patients in order to: (1) set a normative expectation regarding the importance of PEC; (2) standardize the components of patients' experience that are assessed to minimize potential "blind spots"; (3) provide a direct "voice" to the patient in communicating perceptions of their care; (4) facilitate comparisons of quality across facilities; and (5) broaden accountability for PEC to the entire multidisciplinary dialysis care team. In this review, we will discuss the significance of PEC as a quality of care metric in dialysis patients; the history of PEC assessment across other health care arenas; the development of the In-Center Hemodialysis Consumer Assessment of Healthcare Provider and Systems survey as a means to standardize PEC assessment among US dialysis patients; experiences in PEC assessment across international dialysis populations; and future areas of research needed to refine the ascertainment of PEC and its impact upon patient outcomes.