Controversy on the CONVINCE study findings: the PRO take / Controvérsia sobre os achados do estudo CONVINCE: a perspectiva PRO

ABSTRACT The CONVINCE study, recently published in the New England Journal of Medicine, reveals a groundbreaking 23% reduction in the relative risk of all-cause mortality among end-stage kidney patients undergoing high convective volume hemodiafiltration. This significant finding challenges the conventional use of high-flux hemodialysis and offers hope for improving outcomes in chronic kidney disease patients. While some controversies surround the study's findings, including concerns about generalizability and the causes of death, it is essential to acknowledge the study's design and its main outcomes. The CONVINCE study, part of the HORIZON 2020 project, enrolled 1360 patients and demonstrated the superiority of hemodiafiltration in reducing all-cause mortality overall, as well as in specific patient subgroups (elderly, short vintage, non-diabetic, and those without cardiac issues). Interestingly, it was shown that hemodiafiltration had a protective effect against infection, including COVID-19. Future research will address sustainability, dose scaling effects, identification of subgroups especially likely to benefit and cost-effectiveness. However, for now, the findings strongly support a broader adoption of hemodiafiltration in renal replacement therapy, marking a significant advancement in the field.

RESUMO O estudo CONVINCE, publicado recentemente no New England Journal of Medicine, revela uma redução inovadora de 23% no risco relativo de mortalidade por todas as causas entre pacientes renais em estágio terminal submetidos à hemodiafiltração de alto volume de convecção. Esse achado significativo desafia o uso convencional da hemodiálise de alto fluxo e oferece esperança de melhoria dos desfechos em pacientes com doença renal crônica. Embora algumas controvérsias cerquem os achados do estudo, incluindo preocupações sobre a generalização e as causas de óbito, é essencial reconhecer o desenho do estudo e seus principais desfechos. O estudo CONVINCE, parte do projeto HORIZON 2020, inscreveu 1.360 pacientes e demonstrou a superioridade da hemodiafiltração na redução da mortalidade por todas as causas em geral, bem como em subgrupos específicos de pacientes (idosos, HD de curta duração, não diabéticos e aqueles sem problemas cardíacos). Curiosamente, demonstrou-se que a hemodiafiltração teve um efeito protetor contra infecções, incluindo a COVID-19. Pesquisas futuras abordarão sustentabilidade, efeitos de escalonamento da dose, identificação de subgrupos especialmente propensos a se beneficiar e a relação custo-benefício. No entanto, por ora, os achados apoiam fortemente uma adoção mais ampla da hemodiafiltração na terapia renal substitutiva, marcando um avanço significativo na área.

High volume online hemodiafiltration: a global perspective and the Brazilian experience / Hemodiafiltração on-line de alto volume: uma perspectiva global e a experiência brasileira

ABSTRACT Online hemodiafiltration (HDF) is a rapidly growing dialysis modality worldwide. In Brazil, the number of patients with private health insurance undergoing HDF has exceeded the number of patients on peritoneal dialysis. The achievement of a high convection volume was associated with better clinical imprand patient - reported outcomes confirming the benefits of HDF. The HDFit trial provided relevant practical information on the implementation of online HDF in dialysis centers in Brazil. This article aims to disseminate technical information to improve the quality and safety of this new dialysis modality.

RESUMO A hemodiafiltração (HDF) on-line é uma modalidade dialítica em rápido crescimento no mundo. No Brasil, o número de pacientes com planos de saúde privados tratados por HDF já ultrapassa aquele de pacientes em diálise peritoneal. O alcance de um alto volume convectivo associado à redução de desfechos clínicos e do risco de morte confirmam os benefícios da HDF. Dados nacionais do estudo HDFit forneceram informações práticas relevantes sobre a implementação da HDF on-line em clínicas de diálise no Brasil. O objetivo desta publicação é a disseminação de informações técnicas que possam auxiliar na utilização, com qualidade e segurança, dessa nova modalidade dialítica.

EXPRESS: Clinical Outcomes and Clinico-Pathological Correlations in Children with MPO-ANCA-Associated Glomerulonephritis Showing Renal Arteritis.

OBJECTIVE: The aim of this study was to evaluate the clinical features, pathological characteristics and prognosis in myeloperoxidase (MPO)-antineutrophil cytoplasmic antibodies-associated glomerulonephritis (AAGN) with renal arteritis. METHODS: The study involved 97 children from five pediatric clinical centers with MPO-AAGN who exhibited distinct clinical features. The patients were divided into AAGN-A+ and AAGN-A-, based on the presence or absence of arteritis, and the disparities in clinical, histopathological characteristics, and prognosis between the two groups were evaluated. RESULT: In contrast to the AAGN-A- group, the children in the AAGN-A+ group exhibited more pronounced clinical symptoms and renal pathological injury. Arteritis positively moderately correlated with the serum creatinine (Scr), IL-6 (interleukin-6), urinary neutrophil gelatinase-associated lipocalin (NGAL), negatively moderately correlated with serum complement C3. The renal survival rate in the AAGN-A+ group was significantly poorer than AAGN-A- group (χ2=4.278, P=0.039). Arteritis showed a good predictive value for end-stage kidney disease (ESKD), and C3 deposition and arteritis were independent risk factors for the development of ESKD in children with MPO-AAGN. CONCLUSION: Arteritis is a significant pathological change observed in children with MPO-AAGN, and the formation of arteritis may be related to the inflammatory response and activation of the complement system.

Identification of patients undergoing chronic kidney replacement therapy in primary and secondary care data: validation study based on OpenSAFELY and UK Renal Registry.

Objective: To validate primary and secondary care codes in electronic health records to identify people receiving chronic kidney replacement therapy based on gold standard registry data. Design: Validation study using data from OpenSAFELY and the UK Renal Registry, with the approval of NHS England. Setting: Primary and secondary care electronic health records from people registered at 45% of general practices in England on 1 January 2020, linked to data from the UK Renal Registry (UKRR) within the OpenSAFELY-TPP platform, part of the NHS England OpenSAFELY covid-19 service. Participants: 38 745 prevalent patients (recorded as receiving kidney replacement therapy on 1 January 2020 in UKRR data, or primary or secondary care data) and 10 730 incident patients (starting kidney replacement therapy during 2020), from a population of 19 million people alive and registered with a general practice in England on 1 January 2020. Main outcome measures: Sensitivity and positive predictive values of primary and secondary care code lists for identifying prevalent and incident kidney replacement therapy cohorts compared with the gold standard UKRR data on chronic kidney replacement therapy. Agreement across the data sources overall, and by treatment modality (transplantation or dialysis) and personal characteristics. Results: Primary and secondary care code lists were sensitive for identifying the UKRR prevalent cohort (91.2% (95% confidence interval (CI) 90.8% to 91.6%) and 92.0% (91.6% to 92.4%), respectively), but not the incident cohort (52.3% (50.3% to 54.3%) and 67.9% (66.1% to 69.7%)). Positive predictive values were low (77.7% (77.2% to 78.2%) for primary care data and 64.7% (64.1% to 65.3%) for secondary care data), particularly for chronic dialysis (53.7% (52.9% to 54.5%) for primary care data and 49.1% (48.0% to 50.2%) for secondary care data). Sensitivity decreased with age and index of multiple deprivation in primary care data, but the opposite was true in secondary care data. Agreement was lower in children, with 30% (295/980) featuring in all three datasets. Half (1165/2315) of the incident patients receiving dialysis in UKRR data had a kidney replacement therapy code in the primary care data within three months of the start date of the kidney replacement therapy. No codes existed whose exclusion would substantially improve the positive predictive value without a decrease in sensitivity. Conclusions: Codes used in primary and secondary care data failed to identify a small proportion of prevalent patients receiving kidney replacement therapy. Codes also identified many patients who were not recipients of chronic kidney replacement therapy in UKRR data, particularly dialysis codes. Linkage with UKRR kidney replacement therapy data facilitated more accurate identification of incident and prevalent kidney replacement therapy cohorts for research into this vulnerable population. Poor coding has implications for any patient care (including eligibility for vaccination, resourcing, and health policy responses in future pandemics) that relies on accurate reporting of kidney replacement therapy in primary and secondary care data.

Study of therapeutic patient education practices in French renal transplantation centres.

OBJECTIVES: Therapeutic patient education (TPE) plays a critical role in the management of kidney transplant recipients. However, discrepancies exist in the guidance provided regarding the usage of immunosuppressants across different kidney transplant centres in France. METHODS: To assess the current landscape of TPE practices in this patient population, an online questionnaire consisting of 51 questions was distributed to 32 French renal transplantation centres. RESULTS: The participation rate in our survey was 96.9%, (31 of the 32 centres contacted). The respondents had diverse professions: they were nurses (15/31), physicians (9/31) and pharmacists (7/31). Virtually all institutions have implemented TPE initiatives, with an implementation rate of 93.5% (29/31). The topic of anti-rejection medication was consistently addressed, with only one centre not providing support at the conclusion of these sessions. However, the content of the sessions varied significantly from one centre to another, particularly regarding the proper management of anti-rejection medications. Only 19.4% (6/31) of the centres provided the correct recommendation regarding fasting when taking tacrolimus. Dietary guidance was a topic covered in 89.7% (26/29) of the centres, but significant divergences were also observed. TPE teams primarily consisted of nurses, with pharmacists present in only 51.6% (16/31) of the centres. We also observed limited involvement of patient partners, with just 9.7% (3/31) of the centres including them in their programme. CONCLUSION: These findings highlight considerable variability in the approach towards TPE among kidney transplant centres. Addressing counselling variability and increasing pharmacist and patient partner involvement is an essential step to improving the quality and effectiveness of TPE. By establishing a standardised and comprehensive approach to patient education, healthcare providers can ensure that kidney transplant recipients receive information that will ultimately help them improve their health and well-being.

Psychometric properties of the Kidney Disease Quality of Life short form 36 (KDQOL-36) scale for the assessment of quality of life in Colombian patients with chronic kidney disease on dialysis.

PURPOSE: Considering the importance of incorporating quality of life (QoL) construct during the health care of patients with stage 5 chronic kidney disease (CKD) on dialysis, it is necessary to have evidence on the clinimetric properties of the instruments used for its measurement. This study aimed to establish the clinimetric properties of the Kidney Disease Quality of Life Short Form 36 (KDQOL-36) scale in patients with stage 5 CKD on dialysis in Colombia. METHODS: A scale validation study was conducted using the classical test theory methodology. The statistical analysis included exploratory factor analysis (EFA) and confirmatory (CFA) techniques performed on two independent subsamples; concurrent criterion validity assessments; internal consistency using four different coefficients; test-retest reliability; and sensitivity to change using mixed model for repeated measures. RESULTS: The KDQOL-36 scale was applied to 506 patients with a diagnosis of stage 5 CKD on dialysis, attended in five renal units in Colombia. The EFA endorsed the three-factor structure of the scale, and the CFA showed an adequate fit of both the original and empirical models. Spearman's correlation coefficient values ≥0.50 were found between the domains of the CKD-specific core of the KDQOL-36 scale and the KDQ. Cronbach's alpha, McDonald's omega, Greatest lower bound (GLB), and Guttman's lambda coefficients were ≥0.89, indicating a high degree of consistency. A high level of concordance correlation was found between the two moments of application of the instrument, with values for Lin's concordance correlation coefficient ≥0.7. The application of the instrument after experiencing an event that could modify the quality of life showed statistically significant differences in the scores obtained. CONCLUSION: The KDQOL-36 scale is an adequate instrument for measuring QoL in Colombian patients with stage 5 CKD on dialysis.

Burden of impaired awareness of hypoglycemia in people with diabetes undergoing hemodialysis.

INTRODUCTION: Impaired awareness of hypoglycemia (IAH) refers to a diminished capacity to detect hypoglycemia. IAH can result in severe and even life-threatening outcomes for individuals with diabetes, especially those in advanced stages of the disease. This study aimed to assess the prevalence of IAH in people with diabetes on hemodialysis. RESEARCH DESIGN AND METHODS: We conducted a single-center audit to assess the prevalence of IAH using the Clarke questionnaire. Simultaneously, we measured fear of hypoglycemia with an adapted version of the Hypoglycemia Survey and recorded the incidence of severe hypoglycemia. Data were presented as mean±SD or counts/percentages. Logistic regression was then employed to analyze the association between IAH and various sociodemographic and clinical factors. RESULTS: We included 56 participants with diabetes on hemodialysis, with a mean age of 67.2 years (±12.9), of whom 51.8% were male. The ethnic distribution was 23.2% white, 23.2% black, 19.6% Asian, and 33.9% unspecified. The mean HbA1c was 52 mmol/mol (±18.6). The majority (91.1%) had a diagnosis of type 2 diabetes, and 55.4% of those were treated with insulin. The use of diabetes technology was low, with 2.8% of the participants using a continuous glucose monitor. IAH prevalence was 23.2%, and among the 57 participants, 23.6% had a history of severe hypoglycemia, and 60.6% reported fear of hypoglycemia. There were no significant differences in sociodemographic and clinical characteristics between those with IAH and normal hypoglycemia awareness. CONCLUSIONS: We observed that 23.2% of individuals with diabetes undergoing hemodialysis had IAH. IAH was more prevalent in people who reported a fear of hypoglycemia and had a history of severe hypoglycemia episode. The study highlights the unmet needs and disparities in access to diabetes technology within this population.

[Immunoglobulin A nephropathy-New treatment possibilities]. / Immunglobulin-A-Nephropathie ­ neue therapeutische Möglichkeiten.

Immunoglobulin A (IgA) nephropathy is the most frequent glomerulonephritis in adults in Central Europe. It is characterized by microhematuria and occasionally macrohematuria, proteinuria and a chronic loss of kidney function. The diagnosis is made based on a kidney biopsy. The progressive kidney damage must always be slowed down by normalizing blood pressure, using angiotensin inhibitors and consistently avoiding additional toxic substances. In many cases this is not sufficient and then sodium-glucose transporter 2 (SGLT-2) inhibitors and immunomodulators are used. In particular, the SGLT-2 inhibitors show a very significant reduction in proteinuria and slow down the deterioration of the estimated glomerular filtration rate (eGFR). While systemic corticosteroids are now only indicated in rare cases, a special budesonide formulation shows good effects. Further pathophysiologically based pharmacotherapies are currently being tested in clinical studies. These include, among others, the dual endothelin type A receptor and angiotensin II receptor antagonist sparsentan, which has already been shown to reduce proteinuria as well as inhibitors of complement activation, which is important for kidney damage. Initial findings for these as well as for the B­lymphocyte proliferation inhibitor sibeprenlimab, suggest that they could enrich the armamentarium for the treatment of IgA nephropathy in the future.

Risk Prediction and Management of Chronic Kidney Disease in People Living with Type 2 Diabetes Mellitus.

People with type 2 diabetes mellitus have increased risk of chronic kidney disease and atherosclerotic cardiovascular disease. Improved care delivery and implementation of guideline-directed medical therapy have contributed to the declining incidence of atherosclerotic cardiovascular disease in high-income countries. By contrast, the global incidence of chronic kidney disease and associated mortality is either plateaued or increased, leading to escalating direct and indirect medical costs. Given limited resources, better risk stratification approaches to identify people at risk of rapid progression to end-stage kidney disease can reduce therapeutic inertia, facilitate timely interventions and identify the need for early nephrologist referral. Among people with chronic kidney disease G3a and beyond, the kidney failure risk equations (KFRE) have been externally validated and outperformed other risk prediction models. The KFRE can also guide the timing of preparation for kidney replacement therapy with improved healthcare resources planning and may prevent multiple complications and premature mortality among people with chronic kidney disease with and without type 2 diabetes mellitus. The present review summarizes the evidence of KFRE to date and call for future research to validate and evaluate its impact on cardiovascular and mortality outcomes, as well as healthcare resource utilization in multiethnic populations and different healthcare settings.

Is There a Two-Way Risk between Decreased Testosterone Levels and the Progression and Prognosis of Chronic Kidney Disease? A Cohort Study Based on the National Health and Nutrition Examination Survey Database.

PURPOSE: The causal relationship between the incidence and prognosis of chronic kidney disease (CKD) and serum testosterone levels in patients is not yet fully understood. This study aims to use the National Health and Nutrition Examination Survey (NHANES), a large-scale nationally representative sample, to investigate the relationship between CKD and testosterone. MATERIALS AND METHODS: This study included six NHANES cycles for linear regression analysis, verified by multiple imputation methods. Stratified analysis and subgroup analysis were used to demonstrate the stability of CKD's effect on testosterone. Furthermore, we used Kaplan-Meier plots and log-rank tests to evaluate differences in survival rates between CKD male patients with low and normal levels of testosterone. RESULTS: From a total of 71,163 subjects, the cohort selected 28,663 eligible participants. Results showed that CKD patients had testosterone levels 28.423 ng/mL (24.762, 32.083) lower than non-CKD patients. The results of multiple imputations (ß=27.700, 95% confidence interval: 23.427, 31.974) were consistent with those of linear regression analysis, and the numerical match was good. Stratified regression analysis, and subgroup analysis results showed that CKD had a significant impact on testosterone at different dimensions. Kaplan-Meier plots showed significantly reduced survival rates in low testosterone CKD male patients (p<0.0001). CONCLUSIONS: The results of this big data analysis suggest that there may be a two-way risk between low levels of testosterone and CKD. The testosterone levels of CKD patients were significantly lower than those of the non-CKD population, and CKD patients with low testosterone levels had poorer prognoses. These results suggest that correcting testosterone levels in a timely manner can have preventive and therapeutic effects on the progression of CKD.

A Synopsis of the Evidence for the Science and Clinical Management of Cardiovascular-Kidney-Metabolic (CKM) Syndrome: A Scientific Statement From the American Heart Association.

A growing appreciation of the pathophysiological interrelatedness of metabolic risk factors such as obesity and diabetes, chronic kidney disease, and cardiovascular disease has led to the conceptualization of cardiovascular-kidney-metabolic syndrome. The confluence of metabolic risk factors and chronic kidney disease within cardiovascular-kidney-metabolic syndrome is strongly linked to risk for adverse cardiovascular and kidney outcomes. In addition, there are unique management considerations for individuals with established cardiovascular disease and coexisting metabolic risk factors, chronic kidney disease, or both. An extensive body of literature supports our scientific understanding of, and approach to, prevention and management for individuals with cardiovascular-kidney-metabolic syndrome. However, there are critical gaps in knowledge related to cardiovascular-kidney-metabolic syndrome in terms of mechanisms of disease development, heterogeneity within clinical phenotypes, interplay between social determinants of health and biological risk factors, and accurate assessments of disease incidence in the context of competing risks. There are also key limitations in the data supporting the clinical care for cardiovascular-kidney-metabolic syndrome, particularly in terms of early-life prevention, screening for risk factors, interdisciplinary care models, optimal strategies for supporting lifestyle modification and weight loss, targeting of emerging cardioprotective and kidney-protective therapies, management of patients with both cardiovascular disease and chronic kidney disease, and the impact of systematically assessing and addressing social determinants of health. This scientific statement uses a crosswalk of major guidelines, in addition to a review of the scientific literature, to summarize the evidence and fundamental gaps related to the science, screening, prevention, and management of cardiovascular-kidney-metabolic syndrome.

Effect of night shift work on the reduction of glomerular filtration rate using data from Korea Medical Institute (2016-2020).

Background: Shift work increases the risk of chronic diseases, including metabolic diseases. However, studies on the relationship between shift work and renal function are limited. The aim of this study was to investigate the association between shift work and a decreased glomerular filtration rate (GFR). Methods: Data were evaluated for 1,324,930 workers who visited the Korean Medical Institute from January 1, 2016 to December 31, 2020 and underwent a health checkup. Daytime workers were randomly extracted at a ratio of 1:4 after matching for age and sex. In total, 18,190 workers aged over 40 years were included in the analyses; these included 3,638 shift workers and 14,552 daytime workers. Participants were categorized into the shift work group when they underwent a specific health checkup for night shift work or indicated that they were shift workers in the questionnaire. The odds ratio was calculated using a conditional logistic regression to investigate the relevance of shift work for changes in GFR. Results: 35 workers in the shift group and 54 in the daytime group exhibited an estimated GFR (eGFR) value of < 60 mL/min/1.73m2 (p < 0.01). The difference in eGFR values between two checkups differed significantly depending on the type of work (p < 0.01); the difference in the shift work group (-9.64 mL/min/1.73 m2) was larger than that in the daytime work group (-7.45 mL/min/1.73 m2). The odds ratio for eGFR reduction to < 60 mL/min/1.73 m2 in the shift group versus the daytime group was 4.07 (95% confidence interval: 2.54-6.52), which was statistically significant. Conclusions: The results of this study suggest that eGFR decreases by a significantly larger value in shift workers than in daytime workers; thus, shift work could be a contributing factor for chronic kidney disease (CKD). Further prospective studies are necessary to validate this finding and identify measures to prevent CKD in shift workers.

Association of Reversal of Renin Suppression With Long-Term Renal Outcome in Medically Treated Primary Aldosteronism.

BACKGROUND: Renin suppression in primary aldosteronism indicates mineralocorticoid receptor activation via excessive aldosterone secretion, inducing renal damage. We investigated whether the reversal of renin suppression after the initiation of mineralocorticoid receptor antagonist therapy was associated with long-term renal outcomes in medically treated patients with primary aldosteronism. METHODS: This retrospective cohort study included 318 patients with primary aldosteronism treated with mineralocorticoid receptor antagonist between 2008 and 2020 at the Yokohama Rosai Hospital in Japan. The posttreatment renin status was defined as unsuppressed (ie, reversal of renin suppression) when individual plasma renin activity after the initiation of mineralocorticoid receptor antagonist (post-plasma renin activity) was ≥1.0 ng/mL per hour; otherwise, it was defined as suppressed. We analyzed the association of posttreatment renin status with subsequent longitudinal estimated glomerular filtration rate changes using linear mixed-effects models for repeated measurements, adjusting for potential confounders. RESULTS: The posttreatment renin status of 119 patients was unsuppressed (median post-plasma renin activity, 1.7 ng/mL per hour) and that of 199 patients was suppressed (median post-PRA, 0.5 ng/mL per hour). Through the median follow-up period of 3.1 years, the decline in estimated glomerular filtration rate was milder among patients with the unsuppressed posttreatment renin (-0.46 [95% CI, -0.63 to -0.28] mL/min per 1.73 m2 per year) than those with suppressed posttreatment renin (-1.41 [95% CI, -1.56 to -1.27] mL/min per 1.73 m2 per year; difference, 0.96 [95% CI, 0.72-1.20] mL/min per 1.73 m2 per year). CONCLUSIONS: Our findings may highlight the importance of reversing renin suppression with optimal mineralocorticoid receptor antagonist titration in medically treated primary aldosteronism, which could mitigate adverse renal outcomes.

The Association between Apolipoprotein E Genotypes and Serum Malondialdehyde Level with End-Stage Renal Disease.

Background: The Apolipoprotein E (ApoE) polymorphism plays an important role in the pathophysiology of end-stage renal disease (ESRD). Additionally, ApoE may contribute to the progression of oxidative stress. Thus, this study aimed to determine the ApoE gene polymorphism and evaluate the malondialdehyde (MDA) level in ESRD patients and healthy individuals. Methods: The present cross-sectional study was conducted at 2010 at Kermanshah University of Medical Sciences (Kermanshah, Iran). The study population comprised ESRD patients (n=136) and healthy individuals (n=137). The MDA level was assessed using high-performance liquid chromatography (HPLC), and the frequencies of ApoE gene alleles were analyzed using restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR). The data were analyzed using Statistical Package for Social Sciences (SPSS), version 13. The significant differences of ApoE genotypes in case and control groups were assessed using Pearson's Chi square tests, and two-tailed Student's tests. A logistic regression model was used to calculate the odd ratio. P<0.05 was considered statistically significant. Results: According to the results, ESRD patients had a higher frequency of the E2/E3 genotype than the healthy group (P<0.001). The results indicated that E3/E4 genotype frequency in the patients' group was higher than that of the control group (P=0.026). Furthermore, the E3/E2 (OR=5.7, 95% CI=2.68-12.14) (P<0.001) and E3/E4 (OR=1.57, 95% CI=1.05-2.34) (P=0.029) genotypes were found to increase the risk of ESRD. Moreover, the MDA level in ESRD patients was higher than the healthy individuals (P<0.001). The patients with E3/E2 (P<0.001) and E3/E4 (P<0.001) genotypes had a higher level of MDA than the control group. Conclusion: According to the findings, patients with ESRD had higher genotypes of E3/E2 and E3/E4, which suggests a higher risk of developing ESRD.

Referral Criteria to Specialist Palliative Care for People with Advanced Chronic Kidney Disease: A Systematic Review.

CONTEXT: People with advanced chronic kidney disease (CKD) have significant morbidity, yet for many, access to palliative care occurs late, if at all. OBJECTIVES: This study sought to examine criteria for referral to specialist palliative care for adults with advanced CKD with a view to improving use of these essential services. METHODS: Systematic review of studies detailing referral criteria to palliative care in advanced CKD conducted and reported according to the Preferred Reporting Items for Systematic Reviews and Meta Analyses (PRISMA) guideline and registered (PROSPERO: CRD42021230751). DATA SOURCES: Electronic databases (Ovid, MEDLINE, Ovid Embase, and PubMed) were used to identify potential studies, which were subjected to double review, data extraction, thematic coding, and descriptive analyses. RESULTS: Searches yielded 650 unique titles ultimately resulting in 56 studies addressing referral criteria to specialist palliative care in advanced CKD. Of 10 categories of referral criteria, most commonly discussed were: Critical times of treatment decision making (n = 23, 41%); physical or emotional symptoms (n = 22, 39%); limited prognosis (n = 18, 32%); patient age and comorbidities (n = 18, 32%); category of CKD/ biochemical criteria (n = 13, 23%); functional decline (n = 13, 23); psychosocial needs (n = 9, 16%); future care planning (n = 9, 16%); anticipated decline in illness course (n = 8, 14%); and hospital use (n = 8, 14%). CONCLUSION: Clinicians consider referral to specialist palliative care for a wide range of reasons, with many related to care needs. As palliative care continues to integrate with nephrology, our findings represent a key step towards developing consensus criteria to standardize referral for patients with chronic kidney diseases.

Cardiorenal protective effects of canagliflozin in CREDENCE according to glucose lowering.

INTRODUCTION: Relationships between glycemic-lowering effects of sodium glucose co-transporter 2 inhibitors and impact on kidney and cardiovascular outcomes are uncertain. RESEARCH DESIGN AND METHODS: We analyzed 4395 individuals with prebaseline and postbaseline hemoglobin A1c (HbA1c) randomized to canagliflozin (n=2193) or placebo (n=2202) in The Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation trial. Effects on HbA1c were assessed using mixed models. Mediation of treatment effects by achieved glycemic control was analyzed using proportional hazards regression with and without adjustment for achieved HbA1c. End points included combined kidney or cardiovascular death, end-stage kidney disease or doubling of serum creatinine (primary trial outcome), and individual end point components. RESULTS: HbA1c lowering was modified by baseline estimated glomerular filtration rate (eGFR). For baseline eGFR 60-90, 45-59, and 30-44 mL/min/1.73 m2, overall HbA1c (canagliflozin vs placebo) decreased by -0.24%, -0.14%, and -0.08% respectively and likelihood of >0.5% decrease in HbA1c decreased with ORs of 1.47 (95% CI 1.27 to 1.67), 1.12 (0.94 to 1.33) and 0.99 (0.83 to 1.18), respectively. Adjustment for postbaseline HbA1c marginally attenuated canagliflozin effects on primary and kidney composite outcomes: unadjusted HR 0.67 (95% CI 0.57 to 0.80) and 0.66 (95% CI 0.53 to 0.81); adjusted for week 13 HbA1c, HR 0.71 (95% CI 0.060 to 0.84) and 0.68 (95% CI 0.55 to 0.83). Results adjusted for time-varying HbA1c or HbA1c as a cubic spline were similar and consistent with preserved clinical benefits across a range of excellent and poor glycemic control. CONCLUSIONS: The glycemic effects of canagliflozin are attenuated at lower eGFR but effects on kidney and cardiac end points are preserved. Non-glycemic effects may be primarily responsible for the kidney and cardioprotective benefits of canagliflozin.22.

Predictive performance of glomerular filtration rate equations based on cystatin C, creatinine and their combination in critically ill patients.

OBJECTIVE: 24-hour urine creatinine clearance (ClCr 24 hours) remains the gold standard for estimating glomerular filtration rate (GFR) in critically ill patients; however, simpler methods are commonly used in clinical practice. Serum creatinine (SCr) is the most frequently used biomarker to estimate GFR; and cystatin C, another biomarker, has been shown to reflect GFR changes earlier than SCr. We assess the performance of equations based on SCr, cystatin C and their combination (SCr-Cyst C) for estimating GFR in critically ill patients. METHODS: Observational unicentric study in a tertiary care hospital. Patients with cystatin C, SCr and ClCr 24 hours measurements in ±2 days admitted to an intensive care unit were included. ClCr 24 hours was considered the reference method. GFR was estimated using SCr-based equations: Chronic Kidney Disease Epidemiology Collaboration based on creatinine (CKD-EPI-Cr) and Cockcroft-Gault (CG); cystatin C-based equations: CKD-EPI-CystC and CAPA; and Cr-CystC-based equations: CKD-EPI-Cr-CystC. Performance of each equation was assessed by calculating bias and precision, and Bland-Altman plots were built. Further analysis was performed with stratified data into CrCl 24 hours <60, 60-130 and ≥130 mL/min/1.73 m2. RESULTS: We included 275 measurements, corresponding to 186 patients. In the overall population, the CKD-EPI-Cr equation showed the lowest bias (2.6) and best precision (33.1). In patients with CrCl 24 hours <60 mL/min/1.73 m2, cystatin-C-based equations showed the lowest bias (<3.0) and CKD-EPI-Cr-CystC was the most accurate (13.6). In the subgroup of 60≤ CrCl 24 hours <130mL/min/1.73 m2, CKD-EPI-Cr-CystC was the most precise (20.9). However, in patients with CrCl 24 hours ≥130mL/min/1.73 m2, cystatin C-based equations underestimated GFR, while CG overestimated it (22.7). CONCLUSIONS: Our study showed no evidence of superiority of any equation over the others for all evaluated parameters: bias, precision and Lin's concordance correlation coefficient. Cystatin C-based equations were less biased in individuals with impaired renal function (GFR <60 mL/min/1.73 m2). CKD-EPI-Cr-CystC performed properly in patients with GFR from 60-130 mL/min/1.73 m2 and none of them were accurate enough in patients ≥130 mL/min/1.73 m2.