Characteristics and clinical outcomes of patients with kidney failure of unknown aetiology from ANZDATA registry.

INTRODUCTION: Kidney failure of unknown aetiology (uESKD) is also heavily location dependent varying between 27% in Egypt to 54% in Aguacalientes, Mexico. There is limited information about the characteristics of people with uESKD in Australia and New Zealand, as well as their clinical outcomes on kidney replacement therapy. METHODS: Data on people commencing kidney replacement therapy 1989-2021 were received from the Australia and New Zealand Dialysis and Transplant (ANZDATA) registry. Primary exposure was cause of kidney failure-uESKD or non-uESKD (known-ESKD). Primary outcome was mortality. Secondary outcome was kidney transplantation. Dialysis and transplant cohorts were analysed separately. Cox Proportional Hazards Regression models were used to evaluate correlations between cause of kidney failure and mortality risk. Subgroup analyses were completed to compare mortality risk in people with uESKD to those with diabetic nephropathy, autosomal dominant polycystic kidney disease (ADPKD), glomerular disease and other kidney diseases. RESULTS: This study included 60,448 people on dialysis and 20,859 transplant recipients. 1-year, 3-year and 5-year mortality rates in people with uESKD on dialysis were 31.6%, 58.7% and 77.2%, respectively. 1-year, 3-year and 5-year mortality rates in transplant recipients with uESKD were 2.8%, 13.8% and 24.0%, respectively. People with uESKD on dialysis had a higher mortality risk compared to those without uESKD on univariable and multivariable analyses (adjusted hazard ratio [AHR] 1.10, 95% CI 1.06-1.16, p<0.001). Transplant recipients with uESKD have a higher mortality risk compared to those without uESKD on univariable and multivariable analyses (AHR 1.17, 95% CI 1.01-1.35, p<0.05). People with uESKD had similar likelihood of kidney transplantation compared to people with known-ESKD. CONCLUSION: People with uESKD on kidney replacement therapy have higher mortality risk compared to people with other kidney diseases. Further studies are required to identify contributing factors to these findings.

Arteriovenous Access for Hemodialysis: A Review.

Importance: Hemodialysis requires reliable vascular access to the patient's blood circulation, such as an arteriovenous access in the form of an autogenous arteriovenous fistula or nonautogenous arteriovenous graft. This Review addresses key issues associated with the construction and maintenance of hemodialysis arteriovenous access. Observations: All patients with kidney failure should have an individualized strategy (known as Patient Life-Plan, Access Needs, or PLAN) for kidney replacement therapy and dialysis access, including contingency plans for access failure. Patients should be referred for hemodialysis access when their estimated glomerular filtration rate progressively decreases to 15 to 20 mL/min, or when their peritoneal dialysis, kidney transplant, or current vascular access is failing. Patients with chronic kidney disease should limit or avoid vascular procedures that may complicate future arteriovenous access, such as antecubital venipuncture or peripheral insertion of central catheters. Autogenous arteriovenous fistulas require 3 to 6 months to mature, whereas standard arteriovenous grafts can be used 2 to 4 weeks after being established, and "early-cannulation" grafts can be used within 24 to 72 hours of creation. The prime pathologic lesion of flow-related complications of arteriovenous access is intimal hyperplasia within the arteriovenous access that can lead to stenosis, maturation failure (33%-62% at 6 months), or poor patency (60%-63% at 2 years) and suboptimal dialysis. Nonflow complications such as access-related hand ischemia ("steal syndrome"; 1%-8% of patients) and arteriovenous access infection require timely identification and treatment. An arteriovenous access at high risk of hemorrhaging is a surgical emergency. Conclusions and Relevance: The selection, creation, and maintenance of arteriovenous access for hemodialysis vascular access is critical for patients with kidney failure. Generalist clinicians play an important role in protecting current and future arteriovenous access; identifying arteriovenous access complications such as infection, steal syndrome, and high-output cardiac failure; and making timely referrals to facilitate arteriovenous access creation and treatment of arteriovenous access complications.

Survival of Infants With Severe Congenital Kidney Disease After ECMO and Kidney Support Therapy.

Congenital kidney failure not only affects the homeostatic functions of the kidney, but also affects neonatal respiratory integrity. Until recently, extracorporeal membrane oxygenation (ECMO) support was not used in this population because the need for ECMO clearly established nonviability. Since 2016, 31 neonates have been admitted to the NICU at Children's of Alabama with congenital kidney failure. Five patients were placed on ECMO for severe respiratory distress unresponsive to conventional interventions. We evaluated neonates with congenital kidney failure and pulmonary hypoplasia/hypertension refractory to conventional therapies who received ECMO support within the first 9 postnatal days. We describe the pre and postnatal diagnoses, ECMO course details, dialysis modalities, complications, procedures, and long-term outcomes of these patients. All 5 patients received kidney support therapy by postnatal day 7. Diagnoses included posterior urethral valves, bilateral renal dysplasia, and autosomal recessive polycystic kidney disease. Gestational age ranged from 35.6 to 37.1 weeks. Birth weight ranged from 2740 to 3140 g. Days on ECMO ranged from 4 to 23. Four survived and are living today. Pulmonary hypertension resolved in surviving patients. Three surviving patients require no oxygen support, and 1 patient requires nocturnal oxygen. Three survivors received a kidney transplant, and 1 awaits transplant evaluation. Patients with congenital kidney failure with severe pulmonary hypoplasia/pulmonary hypertension no longer warrant a reflexive assignment of nonviability. Meticulous ECMO, respiratory, nutritional, and kidney support therapies may achieve a favorable long-term outcome. Further investigation of strategies for optimal outcome is needed.

Anticoagulation with osocimab in patients with kidney failure undergoing hemodialysis: a randomized phase 2 trial.

Individuals with kidney failure undergoing hemodialysis are at elevated risk for thromboembolic events. Factor (F) XI, which is in the intrinsic pathway of coagulation, is emerging as an attractive target for new anticoagulants that may be safer than existing agents. Osocimab-an inhibitory FXIa antibody-is a potential treatment option for such patients. We conducted a phase 2b, double-blind, placebo-controlled trial, in which 704 participants (448 male, 256 female) with kidney failure undergoing hemodialysis were randomized to receive lower- or higher-dose osocimab or placebo. In total, 686 participants (436 male, 250 female) received treatment for ≤18 months (planned minimal treatment period of 6 months). The co-primary outcomes were clinically relevant bleeding (a composite of major and clinically relevant nonmajor bleeding) and a composite of the incidence of moderate, severe or serious adverse events. Clinically relevant bleeding occurred in 16/232 (6.9%) and 11/224 (4.9%) participants who received lower- and higher-dose osocimab, respectively, and in 18/230 participants (7.8%) who received a placebo. For the composite adverse event endpoint, incidences were 51%, 47% and 43% in the lower-dose osocimab, higher-dose osocimab and placebo groups, respectively. These results suggest that osocimab is associated with a low risk of bleeding and is generally well tolerated in this population; findings that require confirmation in larger trials. ClinicalTrials.gov identifier, NCT04523220 .

Adjuvant trastuzumab for triple-positive breast cancer with chronic renal failure: A case report and review of literature.

RATIONALE: Although the occurrence of combined renal insufficiency among patients with breast cancer is even rarer, it poses a significant challenge in the treatment of these patients. Treating such patients often requires both targeted and endocrine therapies. However, oncologists lack evidence-based guidelines for managing renal function in patients with renal insufficiency. PATIENTS CONCERN: A 56-year-old menopausal female with a history of renal failure was diagnosed with triple-positive breast cancer and administered endocrine therapy and targeted therapy associated with hemodialysis after surgery. OUTCOMES: Under the premise of regular dialysis, the patient successfully completed endocrine therapy and targeted therapy for 1 year. DISCUSSION: Patients with advanced triple-positive breast cancer, including those undergoing hemodialysis, require a combination of anti-human epidermal growth factor receptor-2 and endocrine therapies, The side effects of these 2 treatment methods are worth considering in patients with renal insufficiency. CONCLUSION: We report a case of triple-positive breast cancer in a patient undergoing hemodialysis. There was no difference in the treatment approach between patients with and without normal renal function.

Clearance and nutrition in neonatal continuous kidney replacement therapy using the Carpediem™ system.

BACKGROUND: Infants with kidney failure (KF) demonstrate poor growth partly due to obligate fluid and protein restrictions. Delivery of liberalized nutrition on continuous kidney replacement therapy (CKRT) is impacted by clinical instability, technical dialysis challenges, solute clearance, and nitrogen balance. We analyzed delivered nutrition and growth in infants receiving CKRT with the Cardio-Renal, Pediatric Dialysis Emergency Machine (Carpediem™). METHODS: Single-center observational study of infants receiving CKRT with the Carpediem™ between June 1 and December 31, 2021. We collected prospective circuit characteristics, delivered nutrition, anthropometric measurements, and illness severity Score for Neonatal Acute Physiology-II. As a surrogate to normalized protein catabolic rate in maintenance hemodialysis, we calculated normalized protein nitrogen appearance (nPNA) using the Randerson II continuous dialysis model. Descriptive statistics, Spearman correlation coefficient, Mann Whitney, Wilcoxon signed rank, receiver operating characteristic curves, and Kruskal-Wallis analysis were performed using SAS version 9.4. RESULTS: Eight infants received 31.9 (22.0, 49.7) days of CKRT using mostly (90%) regional citrate anticoagulation. Delivered nutritional volume, protein, total calories, enteral calories, nPNA, and nitrogen balance increased on CKRT. Using parenteral nutrition, 90 ml/kg/day should meet caloric and protein needs. Following initial weight loss of likely fluid overload, exploratory sensitivity analysis suggests weight gain occurred after 14 days of CKRT. Despite adequate nutritional delivery, goal weight (z-score = 0) and growth velocity were not achieved until 6 months after CKRT start. Most (5 infants, 62.5%) survived and transitioned to peritoneal dialysis (PD). CONCLUSIONS: Carpediem™ is a safe and efficacious bridge to PD in neonatal KF. Growth velocity of infants on CKRT appears delayed despite delivery of adequate calories and protein.

Default Palliative Care Consultation for Seriously Ill Hospitalized Patients: A Pragmatic Cluster Randomized Trial.

Importance: Increasing inpatient palliative care delivery is prioritized, but large-scale, experimental evidence of its effectiveness is lacking. Objective: To determine whether ordering palliative care consultation by default for seriously ill hospitalized patients without requiring greater palliative care staffing increased consultations and improved outcomes. Design, Setting, and Participants: A pragmatic, stepped-wedge, cluster randomized trial was conducted among patients 65 years or older with advanced chronic obstructive pulmonary disease, dementia, or kidney failure admitted from March 21, 2016, through November 14, 2018, to 11 US hospitals. Outcome data collection ended on January 31, 2019. Intervention: Ordering palliative care consultation by default for eligible patients, while allowing clinicians to opt-out, was compared with usual care, in which clinicians could choose to order palliative care. Main Outcomes and Measures: The primary outcome was hospital length of stay, with deaths coded as the longest length of stay, and secondary end points included palliative care consult rate, discharge to hospice, do-not-resuscitate orders, and in-hospital mortality. Results: Of 34 239 patients enrolled, 24 065 had lengths of stay of at least 72 hours and were included in the primary analytic sample (10 313 in the default order group and 13 752 in the usual care group; 13 338 [55.4%] women; mean age, 77.9 years). A higher percentage of patients in the default order group received palliative care consultation than in the standard care group (43.9% vs 16.6%; adjusted odds ratio [aOR], 5.17 [95% CI, 4.59-5.81]) and received consultation earlier (mean [SD] of 3.4 [2.6] days after admission vs 4.6 [4.8] days; P < .001). Length of stay did not differ between the default order and usual care groups (percent difference in median length of stay, -0.53% [95% CI, -3.51% to 2.53%]). Patients in the default order group had higher rates of do-not-resuscitate orders at discharge (aOR, 1.40 [95% CI, 1.21-1.63]) and discharge to hospice (aOR, 1.30 [95% CI, 1.07-1.57]) than the usual care group, and similar in-hospital mortality (4.7% vs 4.2%; aOR, 0.86 [95% CI, 0.68-1.08]). Conclusions and Relevance: Default palliative care consult orders did not reduce length of stay for older, hospitalized patients with advanced chronic illnesses, but did improve the rate and timing of consultation and some end-of-life care processes. Trial Registration: ClinicalTrials.gov Identifier: NCT02505035.

Management of multiple myeloma-related renal impairment: recommendations from the International Myeloma Working Group.

Here, the International Myeloma Working Group (IMWG) updates its clinical practice recommendations for the management of multiple myeloma-related renal impairment on the basis of data published until Dec 31, 2022. All patients with multiple myeloma and renal impairment should have serum creatinine, estimated glomerular filtration rate, and free light chains (FLCs) measurements together with 24-h urine total protein, electrophoresis, and immunofixation. If non-selective proteinuria (mainly albuminuria) or involved serum FLCs value less than 500 mg/L is detected, then a renal biopsy is needed. The IMWG criteria for the definition of renal response should be used. Supportive care and high-dose dexamethasone are required for all patients with myeloma-induced renal impairment. Mechanical approaches do not increase overall survival. Bortezomib-based regimens are the cornerstone of the management of patients with multiple myeloma and renal impairment at diagnosis. New quadruplet and triplet combinations, including proteasome inhibitors, immunomodulatory drugs, and anti-CD38 monoclonal antibodies, improve renal and survival outcomes in both newly diagnosed patients and those with relapsed or refractory disease. Conjugated antibodies, chimeric antigen receptor T-cells, and T-cell engagers are well tolerated and effective in patients with moderate renal impairment.

Patient involvement interventions for patients with kidney failure making end-of-life care decisions: a scoping review.

OBJECTIVE: The objective of this review was to investigate and map empirical evidence of patient involvement interventions to support patients with kidney failure making end-of-life care decisions in kidney services. INTRODUCTION: Clinical guidance integrating end-of-life care within kidney failure management pathways varies. Advance care planning interventions aimed at involving patients with kidney failure in their end-of-life care planning are established in some countries. However, there is limited evidence of the other types of patient involvement interventions integrated within services to support patients with kidney failure in making decisions about their end-of-life care. INCLUSION CRITERIA: This scoping review included studies exploring patient involvement interventions evaluated for patients with kidney failure considering end-of-life care, their relatives, and/or health professionals in kidney services. Studies of children under the age of 18 years were excluded. METHODS: The review was informed by JBI methodology and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Review guidelines. MEDLINE, Scopus, Embase, and CINAHL were searched for full-text studies in English, Danish, German, Norwegian, or Swedish. Two independent reviewers assessed the literature against the inclusion criteria. A relational analysis framework was used to synthesize the data extracted from the included studies, and to investigate and map different patient involvement interventions. RESULTS: The search identified 1628 articles, of which 33 articles met the inclusion criteria. A total of 23 interventions were described. Interventions targeted patients (n=3); health professionals (n=8); patients and health professionals (n=5); and patients, relatives, and health professionals (n=7). Intervention components included patient resources (eg, information, patient decision aids), consultation resources (eg, advance care planning, shared decision-making), and practitioner resources (eg, communication training). Patient involvement interventions were delivered within hospital-based kidney services. CONCLUSIONS: The review identified several ways to support patients with kidney failure to be involved in end-of-life care decisions. Future interventions may benefit from adopting a complex intervention framework to engage multiple stakeholders in the research and design of an intervention for shared decision-making between patients with kidney failure, their relatives, and health professionals about integrating end-of-life care options into their kidney disease management pathway.

DIALIZE China: A Phase IIIb, Randomized, Placebo-Controlled Study to Reduce Predialysis Hyperkalemia With Sodium Zirconium Cyclosilicate in Chinese Patients.

PURPOSE: The DIALIZE China study (Reduce Incidence of Pre-Dialysis Hyperkalaemia With Sodium Zirconium Cyclosilicate in Chinese Subjects) (NCT04217590) evaluated sodium zirconium cyclosilicate (SZC) for the management of hyperkalemia in Chinese patients undergoing hemodialysis. METHODS: In the double-blind, Phase IIIb DIALIZE China study, Chinese adults with kidney failure and predialysis hyperkalemia (predialysis serum potassium [sK+] concentration >5.4 mmol/L after the long interdialytic interval [LIDI] and >5.0 mmol/L after ≥1 short interdialytic interval) who were receiving hemodialysis 3 times weekly were randomized to placebo or SZC 5 g once daily on nondialysis days. Doses were titrated towards maintaining normokalemia for 4 weeks (titration period) in 5-g increments up to 15 g. Primary efficacy was the proportion of responders during the 4-week evaluation period following the titration period (ie, those with a predialysis sK+ of 4.0-5.0 mmol/L for at least 3 of 4 hemodialysis visits following the LIDI) who did not require urgent rescue therapy. FINDINGS: Overall, 134 adults (mean [SD] age, 55 [11.3] years) were randomized to SZC or placebo (n = 67 each). There were significantly more responders with SZC (37.3%) versus placebo (10.4%; estimated odds ratio [OR] = 5.10; 95% CI, 1.90-15.12; P < 0.001). The probability of all predialysis sK+ concentrations being 3.5 to 5.5 mmol/L was significantly higher with SZC versus placebo (estimated OR = 6.41; 95% CI, 2.71-15.12; P < 0.001). A greater proportion of patients achieved an sK+ of 3.5 to 5.5 mmol/L on at least 3 of 4 LIDI visits during evaluation with SZC (73.1%) versus placebo (29.9%). Serious adverse events occurred in 9.1% and 11.9% of patients in the SZC and placebo groups, respectively. IMPLICATIONS: SZC treatment for predialysis hyperkalemia is effective and well tolerated in Chinese patients with kidney failure receiving hemodialysis. CLINICALTRIALS: gov identifier: NCT04217590.

Long-term social and professional outcomes in adults after pediatric kidney failure.

BACKGROUND: Little is known about the long-term social and professional outcomes in adults after pediatric kidney replacement therapy (KRT). In this study, we described social and professional outcomes of adults after kidney failure during childhood and compared these outcomes with the general population. METHODS: We sent a questionnaire to 143 individuals registered in the Swiss Pediatric Renal Registry (SPRR) with KRT starting before the age of 18 years. In the questionnaire, we assessed social (partner relationship, living situation, having children) and professional (education, employment) outcomes. Logistic regression models adjusted for age at study and sex were used to compare outcomes with a representative sample of the Swiss general population and to identify socio-demographic and clinical characteristics associated with adverse outcomes. RESULTS: Our study included 80 patients (response rate 56%) with a mean age of 39 years (range 19-63). Compared to the general population, study participants were more likely to not have a partner (OR = 3.7, 95%CI 2.3-5.9), live alone (OR = 2.5, 95%CI 1.5-4.1), not have children (OR = 6.8, 95%CI 3.3-14.0), and be unemployed (OR = 3.9, 95%CI 1.8-8.6). No differences were found for educational achievement (p = 0.876). Participants on dialysis at time of study were more often unemployed compared to transplanted participants (OR = 5.0, 95%CI 1.2-21.4) and participants with > 1 kidney transplantation more often had a lower education (OR = 3.2, 95%CI 1.0-10.2). CONCLUSIONS: Adults after pediatric kidney failure are at risk to experience adverse social and professional outcomes. Increased awareness among healthcare professionals and additional psycho-social support could contribute to mitigate those risks. A higher resolution version of the Graphical abstract is available as Supplementary information.

Therapeutic plasma exchange for anti-glomerular basement membrane disease with dialysis-dependent kidney failure without diffuse alveolar hemorrhage.

BACKGROUND: Anti-glomerular basement membrane (anti-GBM) disease is treated with immunosuppressive medications and plasma exchange. However, whether plasma exchange, in addition to pulse glucocorticoid therapy, would benefit patients with anti-GBM disease with dialysis-dependent kidney failure without diffuse alveolar hemorrhage remains unclear. METHODS: Using the Japanese Diagnosis Procedure Combination database, we identified patients diagnosed with anti-GBM disease with dialysis-dependent kidney failure and without diffuse alveolar hemorrhage from July 2010 to March 2020. We compared in-hospital mortality within 10 days of hospitalization between patients who received therapeutic plasma exchange in addition to pulse glucocorticoid therapy and those who received pulse glucocorticoid therapy alone. Overlap weighting based on propensity score was performed to adjust for potential confounders. RESULTS: We identified 207 eligible patients; 168 patients received therapeutic plasma exchange plus pulse glucocorticoid therapy, while 39 patients received pulse glucocorticoid therapy alone. The mean dose of therapeutic plasma exchange was 52.2 ml/kg/day of albumin and/or fresh frozen plasma. Therapeutic plasma exchange in addition to pulse glucocorticoid therapy was associated with a lower in-hospital mortality risk in the unweighted (10.7% versus 28.2%; risk difference, 17.5%; 95% confidence interval, 2.6-32.4%; P = 0.02) and weighted analyses (11.5% versus 28.4%; risk difference, 17.0%; 95% confidence interval, 1.5-32.5%; P = 0.03) than pulse glucocorticoid therapy alone. CONCLUSIONS: This retrospective cohort study using a national database suggests that therapeutic plasma exchange may improve the in-hospital prognosis of anti-GBM disease with dialysis-dependent kidney failure and without diffuse alveolar hemorrhage.

Beyond Autonomy: Ethics of Decision Making About Treatments for Kidney Failure at the Extremes of Age.

Decisions around initiating and forgoing treatments for kidney failure are complex, and contemporary approaches to medical decision making are designed to uphold patients' own preferences and values when there are multiple clinically reasonable treatment options. When patients do not have cognitive capacity to make their own decisions, these models can be adapted to support the previously expressed preferences of older adults and to promote open futures as autonomous persons for young children. Nonetheless, an autonomy-focused approach to decision making may not align with other overlapping values and needs of these groups. Dialysis profoundly shapes life experience. Values framing decisions about this treatment extend beyond independence and self-determination and vary between life stages. Patients at the extremes of age may place a strong emphasis on dignity, caring, nurturing, and joy. Models of decision making tailored to support an autonomous individual may also discount the role of family as not only surrogate decision makers but stakeholders whose lives and experience are interwoven with a patient's and will be shaped by their treatment decisions. These considerations underline a need to more flexibly incorporate a diversity of ethical frameworks to support medical decisions, especially for the very young and old, when facing complex medical decisions such as initiating or forgoing treatments for kidney failure.

[Hyperkalemia]. / ABC om Hyperkalemi.

Hyperkalemia is a relatively common electrolyte abnormality that in serious cases can lead to life-threatening arrhythmias. There are a number of factors that can contribute to hyperkalemia, and in most cases some level of kidney failure is present. The management of hyperkalemia depends on the underlying cause and the level of potassium. This paper briefly examines the pathophysiological mechanisms behind hyperkalemia, with a special focus on treatment.