Erythrocytosis and CKD.

Erythrocytosis or polycythemia is defined as an increase in red blood cell concentration above the age- and sex-specific normal levels. Unlike anemia that is very common in chronic kidney disease (CKD) patients, erythrocytosis is less frequent but requires specific understanding by healthcare professionals in order to provide the best care. Erythrocytosis, especially when undiagnosed and untreated, can lead to serious thrombotic events and higher mortality. Classical causes of erythrocytosis associated with CKD include cystic kidney diseases, kidney or other erythropoietin-secreting neoplasms, high-altitude renal syndrome, overdosage of erythropoietin-stimulating agents, androgen therapy, heavy smoking, chronic lung disease, obstructive sleep apnea, IgA nephropathy, post-kidney transplant erythrocytosis, renal artery stenosis and congenital etiologies. After ruling out the common acquired causes of erythrocytosis, and/or in the presence of suggestive parameters, primary erythrocytosis or polycythemia vera (PV) should be considered and patients screened for JAK2V617F somatic mutation. The newest entity inducing erythrocytosis is linked to the use of sodium-glucose cotransporter-2 (SGLT2) inhibitors that hypothetically activate hypoxia-inducible factor 2-alpha (HIF-2α), and in some cases unmask PV. This review focusses on the pathogenesis, renal manifestations and management of PV, the pathophysiology of erythrocytosis induced by SGLT2 inhibitors and the relevance of timely JAK2 mutation screening in these patients.

Oxalate nephropathy after pancreaticoduodenectomy: a case report.

A 75-year-old male developed acute kidney injury KDIGO stage 3 a few weeks after Whipple surgery was performed for a distal cholangiocarcinoma. Kidney biopsy revealed oxalate nephropathy. This was attributed to post-Whipple malabsorption, poor compliance with pancreatic enzyme replacement therapy, and daily intake of vitamin C supplements. Pancreatic enzyme replacement therapy was resumed and calcium carbonate initiated, with an improvement in glomerular filtration rate. Unfortunately, due to oncological progression, best supportive care was initiated.We review the pathophysiology and conditions predisposing to secondary hyperoxaluria and oxalate nephropathy. This diagnosis should be considered among the main causes of acute kidney injury following pancreatectomy, with important therapeutic implications.

Prevention, Diagnosis, Evaluation, and Treatment of Hepatitis C in Chronic Kidney Disease: Synopsis of the Kidney Disease: Improving Global Outcomes 2022 Clinical Practice Guideline.

DESCRIPTION: The Kidney Disease: Improving Global Outcomes (KDIGO) 2022 clinical practice guideline on prevention, diagnosis, evaluation, and treatment of hepatitis C in chronic kidney disease (CKD) is an update of the 2018 guideline from KDIGO. METHODS: The KDIGO Work Group (WG) updated the guideline, which included reviewing and grading new evidence that was identified and summarized. As in the previous guideline, the WG used the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach to appraise evidence and rate the strength of recommendations and used expert judgment to develop recommendations. New evidence led to updating of recommendations in the chapters on treatment of hepatitis C virus (HCV) infection in patients with CKD (Chapter 2), management of HCV infection before and after kidney transplant (Chapter 4), and diagnosis and management of kidney disease associated with HCV infection (Chapter 5). Recommendations in chapters on detection and evaluation of hepatitis C in CKD (Chapter 1) and prevention of HCV transmission in hemodialysis units (Chapter 3) were not updated because of an absence of significant new evidence. RECOMMENDATIONS: The 2022 updated guideline includes 43 graded recommendations and 20 ungraded recommendations, 7 of which are new or modified on the basis of the most recent evidence and consensus among the WG members. The updated guidelines recommend expanding treatment of hepatitis C with sofosbuvir-based regimens to patients with CKD glomerular filtration rate categories G4 and G5, including those receiving dialysis; expanding the donor pool for kidney transplant recipients by accepting HCV-positive kidneys regardless of the recipient's HCV status; and initiating direct-acting antiviral treatment of HCV-infected patients with clinical evidence of glomerulonephritis without requiring kidney biopsy. The update also addresses the use of immunosuppressive regimens in such patients.

Heart rate variability at rest and in response to stress: Comparative study between hemodialysis and peritoneal dialysis patients.

Cardiac arrhythmias and sudden death are the leading causes of mortality in end-stage kidney disease (ESKD). Autonomic nervous system (ANS) dysfunction contributes to this arrhythmogenic background. This study compared heart rate variability (HRV) indices between hemodialysis (HD) and peritoneal dialysis (PD) patients, both at rest and in response to mental and physical stimulation maneuvers. Thirty-four HD and 34 PD patients matched for age, sex, and dialysis vintage, and 17 age- and sex-matched controls were studied. ANS function was examined by linear and non-linear HRV indices. Heart rate was recorded continuously (Finometer-PRO) at rest and during ANS maneuvers (orthostatic, mental-arithmetic, sit-to-stand, handgrip exercise tests). At rest, no significant differences between HD and PD were observed in HRV (root mean square of successive differences [RMSSD]: HD = 57.1 ± 81.1 vs PD = 69.6 ± 113.4 ms; P = 0.792), except for detrended fluctuation analysis (DFA-α1) (HD = 0.87 ± 0.40 vs PD = 0.70 ± 0.20; P = 0.047). DFA-α1 was significantly lower in PD than controls (1.00 ± 0.33; P < 0.05). All HRV indices during the mental-arithmetic test (RMSSD: HD = 128.2 ± 346.0 vs PD = 87.5 ± 150.0 ms; P = 0.893) and the physical stress tests were similar between HD and PD. The standard deviation along the line-of-identity (SD2)/the standard deviation perpendicular to the line-of-identity (SD1) ratio during mental-arithmetic was marginally lower in HD and significantly lower in PD than controls (PD = 1.31 ± 0.47 vs controls = 1.79 ± 0.64; P < 0.05). Both dialysis groups presented similar patterns in HRV responses during orthostatic and handgrip exercise tests. After the sit-to-stand, RMSSD, SD1, SD2, and DFA-α2 were higher compared to rest only in HD (RMSSD = 57.1 ± 81.1 vs 126.7 ± 185.7 ms; P = 0.028), suggesting a greater difficulty of HD patients in recovering normal ANS function in response to physical stress. In conclusion, HRV indices at rest and after mental and physical stimulation did not differ between HD and PD; however, the ANS responses following the sit-to-stand test were more impaired in HD. These findings suggest that ANS dysfunction is not largely affected by dialysis modality, but small differences in normal ANS recovery may exist.

Infectious Complications Associated to Buttonhole Cannulation of Native Arteriovenous Fistulas: A 22-year follow-up.

BACKGROUND AND HYPOTHESIS: Buttonhole cannulation of native arteriovenous fistulas (AVFs) appears associated with an increased infectious risk. We previously reported a dramatic increase in the incidence of infectious events after shift to buttonhole in an in-center hemodialysis unit, largely reduced after staff (re)education regarding strict respect of the procedure. We assessed the evolution over the following 12-years period in our center. METHODS: In this prospective follow-up of a previous, pre (rope-ladder)-post (buttonhole) comparison (2001-2010), all in-center hemodialysis patients with a native AVF were included from July 1st, 2010 to December 31st, 2022. Primary and secondary outcomes were infectious events (unexplained bacteraemia due to skin bacteria and/or local AVF infection) and complicated infectious events (metastatic infection, AVF surgery, death). Overall, the impact of several quality improvement strategies was tested according to the events rate over 6 periods: 1: Rope-ladder in all; 2: switch to buttonhole; 3: buttonhole in all, before workshops; 4: buttonhole in all, after workshops; 5: buttonhole withdrawal in problematic AVFs; 6: additional procedural changes. RESULTS: This extended observation period allowed adding 195,180 AVF-days to our previous report. Overall, 381,661 AVF-days (366 AVFs, 345 patients) were analysed. After an increase of the infectious events rate in 2012, the shift to rope-ladder in problematic AVFs during Period 5 did not have a significant impact. The incidence of infectious events decrease significantly during Period 6 compared to Periods 3, 4 and 5 [IRR 0.24 (95%CI 0.09-0.52) p=0.0001, IRR 0.22 (95%CI 0.09-0.47) p<0.0001, and IRR 0.29 (95%CI 0.11-0.66) p=0.001, respectively] and became eventually for the first time comparable to Period 1 [IRR 0.59 (95%CI 0.21-1.62) p=0.27]. CONCLUSION: The constant observance of reinforced hygiene protocols by trained staff and central coordination succeeded in significantly mitigating the infectious risk associated with buttonhole.

Impact of thrice-weekly cotrimoxazole prophylaxis on creatinine and potassium plasma levels in kidney transplant recipients.

INTRODUCTION: Cotrimoxazole (CTX) 800/160 mg daily or thrice-weekly is recommended as prophylaxis of Pneumocystis jirovecii pneumonia in kidney transplant recipients. Cotrimoxazole 800/160 daily elevates plasma creatinine and potassium levels but whether the thrice-weekly regimen does so is unknown. METHODS: Medical records of 225 kidney transplant recipients at Cliniques Universitaires Saint-Luc were analyzed retrospectively. All received thrice-weekly CTX 800/160 for 6 months after transplantation. Monthly laboratory results, co-medications, and tacrolimus trough levels were compared. Standard statistical tests were used. RESULTS: One month after CTX stop, creatinine level decreased by 0.11 mg/dl (8%, p = 0.029). This contrasts with its stability in previous and subsequent months. No co-medication change accounted for this decrease. The decrease averaged 0.17 mg/dl (p < 0.01) in the highest initial creatinine tertile. The higher the initial creatinine level, the greater the decrease after CTX stop (p < 0.001), and urea levels remained stable after CTX stop. Potassium levels decreased by 0.09 mmol/L (p = 0.021) one month after CTX stop, and decreased by 0.23 mmol/L (p < 0.01) in the highest initial potassium level tertile. CONCLUSIONS: Our study pinpoints the impact of CTX 800/160 thrice-weekly on creatinine and potassium levels in kidney transplant recipients. This should be considered when interpreting the evolution of plasma creatinine over time, especially in patients with graft dysfunction. Thus, creatinine levels of cohorts with 6 months versus lifelong CTX require different interpretations.

Managing the symptom burden associated with maintenance dialysis: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference.

Individuals with kidney failure undergoing maintenance dialysis frequently report a high symptom burden that can interfere with functioning and diminish life satisfaction. Until recently, the focus of nephrology care for dialysis patients has been related primarily to numerical targets for laboratory measures, and outcomes such as cardiovascular disease and mortality. Routine symptom assessment is not universal or standardized in dialysis care. Even when symptoms are identified, treatment options are limited and are initiated infrequently, in part because of a paucity of evidence in the dialysis population and the complexities of medication interactions in kidney failure. In May of 2022, Kidney Disease: Improving Global Outcomes (KDIGO) held a Controversies Conference-Symptom-Based Complications in Dialysis-to identify the optimal means for diagnosing and managing symptom-based complications in patients undergoing maintenance dialysis. Participants included patients, physicians, behavioral therapists, nurses, pharmacists, and clinical researchers. They outlined foundational principles and consensus points related to identifying and addressing symptoms experienced by patients undergoing dialysis and described gaps in the knowledge base and priorities for research. Healthcare delivery and education systems have a responsibility to provide individualized symptom assessment and management. Nephrology teams should take the lead in symptom management, although this does not necessarily mean taking ownership of all aspects of care. Even when options for clinical response are limited, clinicians should focus on acknowledging, prioritizing, and managing symptoms that are most important to individual patients. A recognized factor in the initiation and implementation of improvements in symptom assessment and management is that they will be based on locally existing needs and resources.

Trends and perspectives for improving quality of chronic kidney disease care: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference.

Chronic kidney disease (CKD) affects over 850 million people globally, and the need to prevent its development and progression is urgent. During the past decade, new perspectives have arisen related to the quality and precision of care for CKD, owing to the development of new tools and interventions for CKD diagnosis and management. New biomarkers, imaging methods, artificial intelligence techniques, and approaches to organizing and delivering healthcare may help clinicians recognize CKD, determine its etiology, assess the dominant mechanisms at given time points, and identify patients at high risk for progression or related events. As opportunities to apply the concepts of precision medicine for CKD identification and management continue to be developed, an ongoing discussion of the potential implications for care delivery is required. The 2022 KDIGO Controversies Conference on Improving CKD Quality of Care: Trends and Perspectives examined and discussed best practices for improving the precision of CKD diagnosis and prognosis, managing the complications of CKD, enhancing the safety of care, and maximizing patient quality of life. Existing tools and interventions currently available for the diagnosis and treatment of CKD were identified, with discussion of current barriers to their implementation and strategies for improving the quality of care delivered for CKD. Key knowledge gaps and areas for research were also identified.

Evaluation of the effect of sodium zirconium cyclosilicate on arrhythmia-related cardiovascular outcomes in patients receiving chronic haemodialysis with hyperkalaemia: protocol for the multicentre, randomised, controlled DIALIZE-Outcomes study.

INTRODUCTION: Patients with kidney failure receiving chronic haemodialysis have elevated risk of arrhythmias potentially increasing the likelihood of sudden cardiac death, stroke and hospitalisation. The DIALIZE study (NCT03303521) demonstrated that sodium zirconium cyclosilicate (SZC) was an efficacious and well-tolerated treatment for predialysis hyperkalaemia in patients undergoing haemodialysis. The DIALIZE-Outcomes study evaluates the effect of SZC on sudden cardiac death and arrhythmia-related cardiovascular outcomes in patients receiving chronic haemodialysis with recurrent hyperkalaemia. METHODS AND ANALYSIS: International, multicentre, randomised, double-blind, placebo-controlled study conducted at 357 study sites across 25 countries. Adults (≥18 years) receiving chronic haemodialysis three times per week with recurrent predialysis serum potassium (K+) ≥5.5 mmol/L post long interdialytic interval (LIDI) are eligible. Patients (~2800) will be randomised 1:1 to SZC or placebo, starting at 5 g orally once daily on non-dialysis days and titrated weekly in 5 g increments (maximum 15 g) to target predialysis serum K+ 4.0-5.0 mmol/L post LIDI. The primary objective is to evaluate efficacy of SZC versus placebo in reducing occurrence of the primary composite endpoint of sudden cardiac death, stroke or arrhythmia-related hospitalisation, intervention or emergency department visit. Secondary endpoints include efficacy of SZC versus placebo in maintaining normokalaemia (serum K+ 4.0-5.5 mmol/L post LIDI) at the 12-month visit, preventing severe hyperkalaemia (serum K+ ≥6.5 mmol/L post LIDI) at the 12-month visit and reducing the incidence of individual cardiovascular outcomes. Safety of SZC will be evaluated. The study is event driven, with participants remaining in the study until 770 primary endpoint events have occurred. Average time in the study is expected to be ~25 months. ETHICS AND DISSEMINATION: Approval was obtained from the relevant institutional review board/independent ethics committee from each participating site (approving bodies in supplementary information). The results will be submitted to a peer-reviewed journal. TRIAL REGISTRATION NUMBERS: EudraCT 2020-005561-14 and clinicaltrials.gov identifier NCT04847232.

Novel anemia therapies in chronic kidney disease: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference.

Anemia is common in patients with chronic kidney disease and is associated with a high burden of morbidity and adverse clinical outcomes. In 2012, Kidney Disease: Improving Global Outcomes (KDIGO) published a guideline for the diagnosis and management of anemia in chronic kidney disease. Since then, new data from studies assessing established and emerging therapies for the treatment of anemia and iron deficiency have become available. Beginning in 2019, KDIGO planned 2 Controversies Conferences to review the new evidence and its potential impact on the management of anemia in clinical practice. Here, we report on the second of these conferences held virtually in December 2021, which focused on a new class of agents-the hypoxia-inducible factor-prolyl hydroxylase inhibitors (HIF-PHIs). This report provides a review of the consensus points and controversies from this second conference and highlights areas that warrant prioritization for future research.

Challenges in the management of the kidney allograft: from decline to failure: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference.

In March 2022, Kidney Disease: Improving Global Outcomes (KDIGO) held a virtual Controversies Conference to address the important but rarely examined phase during which the kidney transplant is failing or has failed. In addition to discussing the definition of a failing allograft, 4 broad areas were considered in the context of a declining functioning graft: prognosis and kidney failure trajectory; immunosuppression strategies; management of medical and psychological complications, and patient factors; and choice of kidney replacement therapy or supportive care following graft loss. Identifying and paying special attention to individuals with failing allografts was felt to be important in order to prepare patients psychologically, manage immunosuppression, address complications, prepare for dialysis and/or retransplantation, and transition to supportive care. Accurate prognostication tools, although not yet widely available, were embraced as necessary to define allograft survival trajectories and the likelihood of allograft failure. The decision of whether to withdraw or continue immunosuppression after allograft failure was deemed to be based most appropriately on risk-benefit analysis and likelihood of retransplantation within a few months. Psychological preparation and support was identified as a critical factor in patient adjustment to graft failure, as was early communication. Several models of care were noted that enabled a medically supportive transition back to dialysis or retransplantation. Emphasis was placed on the importance of dialysis-access readiness before initiation of dialysis, in order to avoid use of central venous catheters. The centrality of the patient to all management decisions and discussions was deemed to be paramount. Patient "activation," which can be defined as engaged agency, was seen as the most effective way to achieve success. Unresolved controversies, gaps in knowledge, and areas for research were also stressed in the conference deliberations.

Kidney Transplantation From Hepatitis C Virus-Infected Donors to Uninfected Recipients: A Systematic Review for the KDIGO 2022 Hepatitis C Clinical Practice Guideline Update.

RATIONALE & OBJECTIVE: Direct-acting antiviral (DAA) treatment of hepatitis C virus (HCV) infection in patients with chronic kidney disease (CKD) has made transplantation of kidneys from HCV-infected donors to uninfected recipients (D+/R-) feasible. To facilitate an update to the 2018 KDIGO guideline for patients with CKD and HCV, we conducted a systematic review of HCV D+/R-kidney transplantation coupled with DAA treatment. STUDY DESIGN: Systematic review and meta-analysis. SETTING & STUDY POPULATIONS: We included studies of HCV D+/R-kidney transplantations that used any DAA protocol. SELECTION CRITERIA FOR STUDIES: Based on a search of PubMed, Embase, Cochrane, CINAHL, and ClinicalTrials.gov through February 1, 2022, conferences from 2019 to 2021, and the 2018 KDIGO HCV guideline we identified single-group (D+/R-) or comparative studies of D+/R-versus D-/R-kidney transplantation. DATA EXTRACTION: Conducted in SRDR-Plus with review by a second researcher. ANALYTICAL APPROACH: Maximum likelihood meta-analyses; the certainty of evidence was assessed per GRADE (Grading of Recommendations Assessment, Development and Evaluation). RESULTS: We identified 16 studies (N=557). A sustained viral response at 12 weeks after treatment (SVR12) was observed in 97.7% (95% CI, 96.3%-98.8%). Ultrashort duration treatment (≤8 days) resulted in viremia requiring standard-course DAA treatment in some patients, all of whom achieved SVR12 after 1 or rarely 2 DAA courses. Serious adverse events from DAA treatment were rare after D+/R-transplantation (0.4% [95% CI, 0.1%-2.8%]). At≥1 year after D+/R-transplantation, recipient death occurred in 2.1% (95% CI, 0.9-3.7) and allograft survival was 97.6% (95% CI, 95.7%-98.9%). Estimated glomerular filtration rate 1 year after transplantation ranged from 46 to 74mL/min/1.73m2. LIMITATIONS: Analyses were generally based on low-certainty evidence. Uncertainty exists about the long-term safety and efficacy of D+/R-transplantation. Few studies investigated ultrashort treatment courses. CONCLUSIONS: Kidney transplantation from HCV-infected donors to uninfected recipients followed by DAA treatment appears to be safe and associated with excellent 1-year clinical outcomes. PLAIN-LANGUAGE SUMMARY: Due to the high efficacy of direct-acting antivirals (DAA), the use of kidneys from HCV-infected deceased donors may increase rates of kidney transplantation. We conducted a systematic review for the 2022 KDIGO Clinical Practice Guideline on Hepatitis C to evaluate the safety and efficacy of kidney transplantation from HCV-infected donors to uninfected recipients (D+/R-) followed by DAA therapy. Sixteen studies comprising 557 patients revealed high rates of sustained viral response, low rates of adverse events, and excellent patient and allograft survival 1 year after transplantation. Kidney transplantation from HCV-infected deceased donors to uninfected recipients treated with DAA appears safe and effective. Future studies should investigate shorter treatment durations, monitor safety, and obtain longer-term efficacy data.

Home dialysis: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference.

Home dialysis modalities (home hemodialysis [HD] and peritoneal dialysis [PD]) are associated with greater patient autonomy and treatment satisfaction compared with in-center modalities, yet the level of home-dialysis use worldwide is low. Reasons for limited utilization are context-dependent, informed by local resources, dialysis costs, access to healthcare, health system policies, provider bias or preferences, cultural beliefs, individual lifestyle concerns, potential care-partner time, and financial burdens. In May 2021, KDIGO (Kidney Disease: Improving Global Outcomes) convened a controversies conference on home dialysis, focusing on how modality choice and distribution are determined and strategies to expand home-dialysis use. Participants recognized that expanding use of home dialysis within a given health system requires alignment of policy, fiscal resources, organizational structure, provider incentives, and accountability. Clinical outcomes across all dialysis modalities are largely similar, but for specific clinical measures, one modality may have advantages over another. Therefore, choice among available modalities is preference-sensitive, with consideration of quality of life, life goals, clinical characteristics, family or care-partner support, and living environment. Ideally, individuals, their care-partners, and their healthcare teams will employ shared decision-making in assessing initial and subsequent kidney failure treatment options. To meet this goal, iterative, high-quality education and support for healthcare professionals, patients, and care-partners are priorities. Everyone who faces dialysis should have access to home therapy. Facilitating universal access to home dialysis and expanding utilization requires alignment of policy considerations and resources at the dialysis-center level, with clear leadership from informed and motivated clinical teams.

A Systematic Review of Direct-Acting Antivirals for Hepatitis C in Advanced CKD.

Introduction: Direct-acting antivirals (DAAs) have improved treatment of hepatitis C virus (HCV) infection in patients with chronic kidney disease (CKD). To facilitate the 2022 update of the Kidney Disease: Improving Global Outcomes (KDIGO) guideline for CKD patients with HCV, we systematically reviewed DAA regimens in patients with CKD stages G4 and G5 nondialysis (G4-G5ND), CKD stage G5 on dialysis (G5D), and kidney transplant recipients (KTRs). Methods: We conducted a systematic review by searching PubMed, Embase, Cochrane, CINAHL, and ClinicalTrials.gov through February 1, 2022, and conferences from 2019 to 2021. Studies of HCV-infected patients with CKD G4-G5ND, G5D, and KTRs treated with specified DAA regimens were included. Outcomes included death at 6 months or later, sustained virologic response at 12 weeks (SVR12), serious adverse events (SAEs) attributed to DAA, and treatment discontinuation because of adverse events. Maximum likelihood meta-analyses were determined; certainty of evidence was assessed per GRADE (Grading of Recommendations Assessment, Development, and Evaluation). Results: We identified 106 eligible studies (22 reported on CKD G4-G5ND, 69 on CKD G5D, and 29 on KTRs). In each population, the majority of DAA regimens achieved SVR12 ≥ 93%. We found generally low quality of evidence of low risk of SAEs (mostly 0%, up to 2.9%) and low risk of discontinuation because of adverse events (mostly 0%-5%). Across 3 unadjusted observational studies in KTRs, the risk of death after DAA treatment was substantially lower than without treatment (summary odds ratio, 0.16; 95% CI, 0.04-0.61). Conclusion: Combination DAA regimens are safe and highly effective in patients with advanced CKD, on dialysis, and with kidney transplants.