ABSTRACT
The demographic evolution of patients with advanced chronic kidney disease (CKD) has led to the advent of an alternative treatment option to kidney replacement therapy in the past couple of ...decades. The KDIGO controversies on Kidney Supportive Care called this approach “comprehensive conservative care” (CCC) and defined it as planned holistic patient-centered care for patients with CKD stage 5 that does not include dialysis. Although the benefit of this treatment option is now well-recognized, especially for the elderly, and comorbid and frail patients, its development remains limited in practice. While shared decision-making and advance care planning represent the cornerstones of the CCC approach, one of the main barriers in its development is the perfectible communication between nephrologists and patients, but also between all healthcare professionals involved in the care of advanced CKD patients. As a result, a significant gap has opened up between what doctors say and what patients hear. Indeed, although CCC is reported by nephrologists to be widely available in their facilities, few of their patients say that they have actually heard of it. The objectives of this review are to explore discrepancies between what doctors say and what patients hear, to identify the factors underlying this gap, and to formulate practical proposals for narrowing this gap in practice.
Graphical Abstract
Graphical Abstract
The Spin-D (Safety and Cardiovascular Efficacy of Spironolactone in Dialysis-Dependent End-Stage Renal Disease) and MiREnDa (Mineralocorticoid Receptor Antagonists in End-Stage Renal Disease) trials ...taken together provide the reassuring demonstration that up to 25 mg/d spironolactone is reasonably safe, provided maintenance hemodialysis patients are properly monitored and investigators use a per-protocol therapeutic algorithm to manage hyperkalemia. These results should encourage and reassure the investigators of the 2 currently ongoing, large, international, major-outcome clinical trials, both of which are using spironolactone up to 25 mg/d: ACHIEVE (Aldosterone bloCkade for Health Improvement EValuation in End-stage Renal Disease trial; NCT03020303) and ALCHEMIST (ALdosterone antagonist Chronic HEModialysis Interventional Survival Trial; NCT01848639).
If any benefit is to be derived from the use of the health-related quality of life (HRQoL) questionnaires in chronic kidney disease (CKD) patients, they should be validated and culturally adapted to ...the target population. We aimed to critically appraise the psychometric properties of HRQoL questionnaires used in African populations with CKD.
Web of Science, Embase, PubMed and PsycINFO databases were searched. Psychometric validation studies of HRQoL questionnaires reporting at least one psychometric property of the COSMIN checklist in CKD African population, published up to October 16, 2023 were included and independently assessed for methodological quality and level of measurement properties by using the COSMIN methodology.
From 1163 articles, 5 full-text were included. Only the Kidney Disease Quality-of-Life questionnaire was translated and cross-culturally adapted for studies of patients with CKD. Internal consistency was of doubtful quality in 4 studies and very good in 1. Its measurement was sufficient in 1 study and insufficient in 4. Test-retest reliability was of doubtful quality in 4 studies. Its measurement was sufficient in 3 studies and insufficient in 1. Structural validity was of inadequate quality in 1 study and very good quality in 1. Its measurement was sufficient in both. Construct validity was of inadequate quality in all studies. Their measurement was insufficient in 4 studies and sufficient in 1.
This review highlighted that only one HRQoL questionnaire used in studies of African populations with CKD underwent a small number of cultural adaptations and psychometric validations, generally of poor methodological quality. HRQoL validation studies in African CKD populations are needed to better take advantage of the benefits in patient care, population health management, and research.
The kidney function monitoring is recommended in routine practice to detect 5-aminosalicylic acid (5-ASA) related nephrotoxicity, although is not standardized. The optimal monitoring is unknown, ...especially the best timing and which tests to perform. We summarized why, how, and when to perform the monitoring for patients treated with 5-ASA and provided an overview of the current guidelines on this topic.
Relevant studies on this topic were searched in PubMed, Embase, and Web of Science databases from July to August 2020.
Serum creatinine, the estimated glomerular filtration rate, and 24-h proteinuria are the 3 main tests used for the monitoring in daily practice. Regarding the timing, several monitoring strategies have been proposed and guidelines are available too, but they provide conflicting information. To date, there is no medical evidence-based that one strategy is better than another. Comorbidities, chronic renal disease, use of nephrotoxic drugs or concomitant steroid therapy also impact the nephrotoxicity risk. Based on the literature review we proposed a kidney function monitoring strategy to guide physicians in clinical practice.
A baseline assessment should be performed in all patients treated with 5-ASA. The monitoring should be carried out according to the other nephrotoxic factors. A tight monitoring may reduce morbidity and mortality of drug nephrotoxicity.
Epidemiologic studies suggest that higher serum phosphaturic hormone fibroblast growth factor 23 levels are associated with increase morbidity and mortality. The aim of the FGF23 Reduction Efficacy ...of a New Phosphate Binder in CKD Trial was to evaluate the effect of sevelamer carbonate on serum C-terminal fibroblast growth factor 23 levels in normophosphatemic patients with CKD stage 3b/4.
Patients with CKD, eGFR between 45 and 15 ml/min per 1.73 m
, fasting serum phosphate concentration >3.1 mg/dl, and serum C-terminal fibroblast growth factor 23 >80 relative units/ml were included in our double-blind, placebo-controlled, randomized multicenter study. All patients received 100,000 IU cholecalciferol at time of randomization. Participants received either placebo or sevelamer carbonate 4.8 g daily during a 12-week period. Biologic parameters, including serum C-terminal fibroblast growth factor 23, intact fibroblast growth factor 23, and
-klotho, were evaluated at baseline and 12 weeks after inclusion.
Of 96 screened patients, 78 (mean±SD age: 63±13 years old; 70% men; mean eGFR: 27±9 ml/min per 1.73 m
) met the inclusion criteria. At baseline, mean eGFR was 27±9 ml/min per 1.73 m
, mean serum phosphate level was 3.8±0.5 mg/dl, and median (interquartile range) serum C-terminal fibroblast growth factor 23 level was 157 (120-241) relative units/ml. After 12 weeks of treatment, urinary phosphate-to-creatinine ratio fell significantly in the sevelamer group. The sevelamer and placebo groups did not differ significantly in terms of median change in serum C-terminal fibroblast growth factor 23 levels: the median (interquartile range) change was 38 (-13-114) relative units/ml in the placebo group and 37 (-1-101) relative units/ml in the sevelamer group (
=0.77). There was no significant difference in serum intact fibroblast growth factor 23,
-klotho, or phosphate levels changes between the two groups. Serum total and LDL cholesterol levels fell significantly in the sevelamer group.
In our double-blind, placebo-controlled, randomized study performed in normophosphatemic patients with CKD, a 12-week course of sevelamer carbonate significantly reduced phosphaturia without changing serum phosphorus but did not significantly modify serum C-terminal fibroblast growth factor 23 and intact fibroblast growth factor 23 or
-klotho levels.
Abstract
Background
International variation in anemia assessment and management practices in chronic kidney disease (CKD) is poorly understood.
Methods
We performed a cross-sectional analysis of ...anemia laboratory monitoring, prevalence and management in the prospective Chronic Kidney Disease Outcomes and Practice Patterns Study (CKDopps). A total of 6766 participants with CKD Stages 3a–5ND from nephrology clinics in Brazil, France, Germany and the USA were included.
Results
Among patients with anemia (hemoglobin <12 g/dL), 36–58% in Brazil, the USA and Germany had repeat hemoglobin measured and 40–61% had iron indices measured within 3 months of the index hemoglobin measurement. Anemia was more common in the USA and Brazil than in France and Germany across CKD stages. Higher ferritin and lower iron saturation (TSAT) levels were observed with lower hemoglobin levels, and higher ferritin with more advanced CKD. The proportion of anemic patients with ferritin <100 ng/mL or TSAT <20% ranged from 42% in Brazil to 53% in France and Germany, and of these patients, over 40% in Brazil, Germany and the USA, compared with 27% in France, were treated with oral or intravenous iron within 3 months after hemoglobin measurement. The proportion of patients with hemoglobin <10 g/dL treated with erythropoiesis-stimulating agents ranged from 28% in the USA to 57% in Germany.
Conclusions
Hemoglobin and iron stores are measured less frequently than per guidelines. Among all regions, there was a substantial proportion of anemic patients with iron deficiency who were not treated with iron, highlighting an area for practice improvement in CKD care.
We investigated the shape of the relationship between longitudinal uric acid (UA) and the hazard of kidney failure and death in chronic kidney disease (CKD) patients, and attempted to identify ...thresholds associated with increased hazards. We included CKD stage 3-5 patients from the CKD-REIN cohort with one serum UA measurement at cohort entry. We used cause-specific multivariate Cox models including a spline function of current values of UA (cUA), estimated from a separate linear mixed model. We followed 2781 patients (66% men, median age, 69 years) for a median of 3.2 years with a median of five longitudinal UA measures per patient. The hazard of kidney failure increased with increasing cUA, with a plateau between 6 and 10 mg/dl and a sharp increase above 11 mg/dl. The hazard of death had a U-shape relationship with cUA, with a hazard twice higher for 3 or 11 mg/dl, compared to 5 mg/dl. In CKD patients, our results indicate that UA above 10 mg/dl is a strong risk marker for kidney failure and death and that low UA levels below 5 mg/dl are associated with death before kidney failure.
Abstract
Background
Recent data have shown that severe acute respiratory syndrome coronavirus 2 can infect renal proximal tubular cells via Angiotensin Converting Enzyme 2 (ACE2) . Our objective was ...to determine whether Fanconi syndrome is a frequent clinical feature in coronavirus disease 2019 (COVID-19) patients.
Methods
A retrospective cohort of 42 laboratory-confirmed COVID-19 patients without history of kidney disease hospitalized in University Hospital of Nancy was investigated. Patients were admitted to the intensive care unit (ICU) (n = 28) or the Medical department (n = 14) and were screened at least once for four markers of proximal tubulopathy.
Results
The mean (standard deviation) follow-up was 19.7 (±12.2) days. Of the patients, 75% (30/40) showed at least two proximal tubule abnormalities (incomplete Fanconi syndrome). The main disorders were proteinuria (88%, n = 35), renal phosphate leak defined by renal phosphate threshold/glomerular filtration rate (TmPi/GFR) <0.77 (55%, n = 22), hyperuricosuria (43%, n = 17) and normoglycaemic glycosuria (30%, n = 12). At the time of the first renal evaluation, ICU patients presented more frequent (96 versus 62%, P = 0.0095) and more severe (844 ± 343 versus 350 ± 221 mg/g, P = 0.0001) proteinuria, and a trend for an increased number of proximal tubule abnormalities (P = 0.038). During follow-up, they presented a lower nadir of serum phosphate median (interquartile range) 0.68 (0.43–0.76) versus 0.77 (0.66–1.07) mmol/L, P = 0.044 and Acute kidney Injury (AKI) during the hospitalization (P = 0.045). Fanconi syndrome preceded severe AKI KDIGO Stages 2 and 3 in 88% (7/8) of patients. Proximal tubular abnormalities (such as proteinuria, TmPi/GFR and glycosuria in five, two and two patients, respectively) were not detected anymore in recovering patients before hospital discharge.
Conclusion
Incomplete Fanconi syndrome is highly frequent in COVID-19 patients and precedes AKI or disappears during the recovery phase.
Introduction: Adjusting drug dose levels based on equations that standardize the estimated glomerular filtration rate (eGFR) to a body surface area (BSA) of 1.73 m 2 can pose challenges, especially ...for patients with extremely high or low body mass index (BMI). The objective of the present study of patients with CKD and diabetes was to assess the impact of deindexing creatinine-based equations on estimates of kidney function and on the frequency of inappropriate prescriptions of oral antidiabetic drugs (OADs). Methods: The prospective CKD-REIN cohort is comprised of patients with eGFR <60 mL/min/1.73 m 2 . The inclusion criteria for this study were the use of OADs and the availability of data on weight, height and serum creatinine. We compared data for three BMI subgroups (group 1 <30 kg/m 2 ; group 2 30–34.9 kg/m 2 ; group 3 ≥35 kg/m 2 ). Inappropriate prescriptions (contraindicated or over-dosed drugs) were assessed with regard to the summary of product characteristics and the patient’s kidney function estimated with the 2009 Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation, the 2021 CKD-EPI equation, the Modification of Diet in Renal Disease (MDRD) equation, the European Kidney Function Consortium (EKFC) equation, their deindexed estimates, and the Cockcroft-Gault (CG) formula. The impact of deindexing the equations was evaluated by assessing 1) the difference between the indexed and deindexed eGFRs, and 2) the difference in the proportion of patients with at least one inappropriate OAD prescription between the indexed and deindexed estimates. Results: At baseline, 694 patients were receiving OADs. The median BMI was 30.7 kg/m 2 , the mean BSA was 1.98 m 2 , and 90% of patients had a BSA >1.73 m 2 . Deindexing the kidney function estimates led to higher eGFRs, especially in BMI group 3. The proportion of patients with at least one inappropriate prescription differed greatly when comparing indexed and deindexed estimates. The magnitude of the difference increased with the BMI: when comparing BMI group 1 with BMI group 3, the difference was respectively −4% and −10% between deindexed 2021 CKD-EPI and indexed CKD-EPI. Metformin and sitagliptin were the most frequent inappropriately prescribed OADs. Conclusion: We highlight significant differences between the BSA-indexed and deindexed versions of equations used to estimate kidney function, emphasizing the importance of using deindexed estimates to adjust drug dose levels - especially in patients with an extreme BMI.
Abstract
Background
Most studies comparing the efficacy of hypothermic machine perfusion (HMP) versus static cold storage (SCS) are based on short-term outcomes. We aimed to better evaluate the ...mid-term impact of HMP in patients receiving expanded criteria donor (ECD) kidneys.
Methods
The analyses were based on the French Données Informatisées et VAlidées en Transplantation (DIVAT) observational cohort. Patients aged ≥45 years transplanted for the first or second times from an ECD donor since 2010 were studied. Our study reported the graft and/or patient survivals and the incidence of acute rejection episode. The Cox models and the Kaplan–Meier estimators, weighted on the propensity score, were used to study the times-to-events.
Results
Among the 2019 included patients, 1073 were in the SCS group versus 946 in the HMP group. The mean life expectancy with functioning graft was 5.7 years 95% confidence interval (CI) 5.4–6.1 for the HMP cohort followed-up for 8 years post-transplantation versus 6.0 years (95% CI 5.7–6.2) for the SCS group. These mid-term results were comparable in the patients receiving grafts from donors aged ≥70 years and in the transplantations with cold ischaemia time ≥18 h.
Conclusions
Our study challenges the utility of using HMP to improve mid-term patient and graft survival. Nevertheless, the improvement of the short-term outcomes is indisputable. It is necessary to continue technological innovations to obtain long-term results.
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