Nomenclature in Palliative and Kidney Supportive Care: Not Just at the End-of-Life.

The multidimensional view of disease is fundamental in the care of complex diseases such as chronic kidney disease (CKD). It is appropriate to define and unify concepts that allow the different professionals involved in care to provide a multidisciplinary approach tailored to the needs of each individual. Given the increasing incidence of CKD worldwide and the fact that the disease may progress at different rates, there is a need to establish personalized, comprehensive approaches for each patient and their families at an earlier stage. This approach goes beyond the simple control of uremic symptoms or congestion and consists of addressing not only symptomatic but also functional, social and coping problems at an early stage, facilitating decision making both in the CKD and in acute situations, potentially irreversible or interventions that do not improve life expectancy. To ensure excellence in care, it is important to assess indicators of palliative care and kidney support, such as the presence of advance and shared care planning, the inclusion of psychosocial, ethical, spiritual and bereavement care. This enables the provision of comprehensive, humanized, and high-quality care for patients and their families. Palliative and kidney care is not just about patients in the last days of life. Defining, unifying, and evaluating the concepts will allow them to be applied in a timely manner at each specific moment of the CKD trajectory.

Vertebral fractures in patients with CKD and the general population: a call for diagnosis and action.

Vertebral fractures (VFs) are the most common osteoporotic fractures in the general population, and they have been associated with high mortality, decreased quality of life, and high risk of subsequent fractures, especially when recent, multiple, or severe. Currently, VF diagnosis and classification determine fracture risk and the most appropriate anti-osteoporotic treatment. However, VFs are clearly underdiagnosed, especially in patients with chronic kidney disease (CKD), and CKD-associated osteoporosis has been disregarded until recently. VFs are associated with higher morbidity and mortality, and their prevalence and incidence differ depending on the grade of renal dysfunction (CKD G1-G5) and/or the type of renal replacement therapy (dialysis or transplantation). In addition to classical risk factors [such as higher age, female sex, reduced bone mineral density, diabetes and steroid use], various other factors have been associated with an increased risk of VFs in CKD, including CKD grade, haemodialysis vintage, time since renal transplantation, low or high intact parathyroid hormone and phosphate levels, and/or vitamin D and K1 deficiencies. Importantly, several clinical societies have recently modified their algorithms according to the fracture risk classification (including the presence of VFs) and determined the most appropriate anti-osteoporotic treatment for the general population. However, there are no specific guidelines addressing this topic in patients with CKD despite an important paradigm shift regarding the prognostic value of bone mineral density in 2017 after the publication of the CKD-Mineral and Bone Disorder Kidney Disease: Improving Global Outcomes guidelines. A proactive attitude towards diagnosis, treatment, and research is proposed to avoid therapeutic nihilism.

Urinary Cell Cycle Arrest Biomarkers and Diuretic Efficiency in Acute Heart Failure.

INTRODUCTION: This study aimed to evaluate the association between the NephroCheck® test AKIRisk® score, diuretic efficiency (DE), and the odds of worsening kidney function (WKF) within the first 72 h of admission in patients hospitalized for acute heart failure (AHF). METHODS: The study prospectively enrolled 125 patients admitted with AHF. NephroCheck® test was obtained within the first 24 h of admission. DE was defined as net fluid urine output per 40 mg of furosemide equivalents. RESULTS: The median AKIRisk® score was 0.11 (IQR 0.06-0.34), and 38 (30.4%) patients had an AKIRisk® score >0.3. The median cumulative DE at 72 h was 1,963 mL (IQR 1317-3,239 mL). At 72 h, a total of 10 (8%) patients developed an absolute increase in sCr ≥0.5 mg/dL (WKF). In a multivariable setting, there was an inverse association between the AKIRisk® score and DE within the first 72 h. In fact, the highest the AKIRisk® score (centered at 0.3), the higher the likelihood of poor DE (below the median) and WKF at 72 h (odds ratio [OR] 2.04; 95%; CI: 1.02-4.07; p = 0.043, and OR 3.31, 95% CI: 1.30-8.43; p = 0.012, respectively). CONCLUSION: In patients with AHF, a higher NephroCheck® AKIRisk® score is associated with poorer DE and a higher risk of WKF at 72 h. Further research is needed to confirm the role of urinary cell cycle arrest biomarkers in the AHF scenario.

Trajectories of Kidney Function in Heart Failure Over a 15-Year Follow-Up: Clinical Profiling and Mortality.

BACKGROUND: Limited data are available on the long-term trajectory of estimated glomerular filtration rate (eGFR) in patients with chronic heart failure. OBJECTIVES: The authors evaluated eGFR dynamics using the 2009 Chronic Kidney Disease Epidemiology Collaboration equation and its prognostic significance in a real-world cohort over a 15-year follow-up. METHODS: A prospective observational registry of ambulatory heart failure outpatients was conducted, with regular eGFR assessments at baseline and on a 3-month schedule for ≤15 years. Urgent kidney function assessments were excluded. Locally weighted error sum of squares curves were plotted for predefined subgroups. Multivariable longitudinal Cox regression analyses were conducted to assess associations with all-cause and cardiovascular death. RESULTS: A total of 2,672 patients were enrolled consecutively between August 2001 and December 2021. The average age was 66.8 ± 12.6 years, and 69.8% were men. Among 40,970 creatinine measurements, 28,634 were used for eGFR analysis, averaging 10.7 ± 8.5 per patient. Over the study period, a significant decline in eGFR was observed in the entire cohort, with a slope of -1.70 mL/min/1.73 m2 per year (95% CI: -1.75 to -1.66 mL/min/1.73 m2 per year). Older patients, those with diabetes, a preserved ejection fraction, a higher baseline eGFR, elevated hospitalization rates, and those who died during follow-up experienced more pronounced decreases in the eGFR. Moreover, the decrease in kidney function correlated independently with all-cause mortality and cardiovascular death. CONCLUSIONS: These findings highlight the sustained decline in eGFR over 15 years in patients with heart failure, with variations based on clinical characteristics, and emphasize the importance of regular eGFR monitoring in this population.

Osteoporosis management in patients with chronic kidney disease (ERCOS Study): A challenge in nephrological care.

Fracture risk assessment in patients with chronic kidney disease (CKD) has been included in the CKD-MBD ("Chronic Kidney Disease-Mineral and Bone Disorders") complex in international and national nephrology guidelines, suggesting for the first time the assessment of bone mineral density (BMD) if the results can influence therapeutic decision-making. However, there is very little information on actual clinical practice in this population. The main objective of the ERCOS (ERC-Osteoporosis) study is to describe the profile of patients with CKD G3-5D with osteoporosis (OP) and/or fragility fractures treated in specialized nephrology, rheumatology and internal medicine clinics in Spain. Fifteen centers participated and 162 patients (mostly women [71.2%] postmenopausal [98.3%]) with a median age of 77 years were included. Mean estimated glomerular filtration rate (eGFR) was 36 mL/min/1.73 m2 and 38% of the included patients were on dialysis. We highlight the high frequency of prevalent fragility fractures [37.7%), mainly vertebral (52.5%) and hip (24.6%)], the disproportionate history of patients with glomerular disease compared to purely nephrological series (corticosteroids) and undertreatment for fracture prevention, especially in nephrology consultations. This study is an immediate call to action with the dissemination of the new, more proactive, clinical guidelines, and underlines the need to standardize a coordinated and multidisciplinary care/therapeutic approach to these patients in an efficient way to avoid current discrepancies and therapeutic nihilism.

Evaluating Osteoporosis in Chronic Kidney Disease: Both Bone Quantity and Quality Matter.

Bone strength is determined not only by bone quantity [bone mineral density (BMD)] but also by bone quality, including matrix composition, collagen fiber arrangement, microarchitecture, geometry, mineralization, and bone turnover, among others. These aspects influence elasticity, the load-bearing and repair capacity of bone, and microcrack propagation and are thus key to fractures and their avoidance. In chronic kidney disease (CKD)-associated osteoporosis, factors traditionally associated with a lower bone mass (advanced age or hypogonadism) often coexist with non-traditional factors specific to CKD (uremic toxins or renal osteodystrophy, among others), which will have an impact on bone quality. The gold standard for measuring BMD is dual-energy X-ray absorptiometry, which is widely accepted in the general population and is also capable of predicting fracture risk in CKD. Nevertheless, a significant number of fractures occur in the absence of densitometric World Health Organization (WHO) criteria for osteoporosis, suggesting that methods that also evaluate bone quality need to be considered in order to achieve a comprehensive assessment of fracture risk. The techniques for measuring bone quality are limited by their high cost or invasive nature, which has prevented their implementation in clinical practice. A bone biopsy, high-resolution peripheral quantitative computed tomography, and impact microindentation are some of the methods established to assess bone quality. Herein, we review the current evidence in the literature with the aim of exploring the factors that affect both bone quality and bone quantity in CKD and describing available techniques to assess them.

Albuminuria, Forgotten No More: Underlining the Emerging Role in CardioRenal Crosstalk.

Kidneys have an amazing ability to adapt to adverse situations, both acute and chronic. In the presence of injury, the kidney is able to activate mechanisms such as autoregulation or glomerular hyperfiltration to maintain the glomerular filtration rate (GFR). While these adaptive mechanisms can occur in physiological situations such as pregnancy or high protein intake, they can also occur as an early manifestation of diseases such as diabetes mellitus or as an adaptive response to nephron loss. Although over-activation of these mechanisms can lead to intraglomerular hypertension and albuminuria, other associated mechanisms related to the activation of inflammasome pathways, including endothelial and tubular damage, and the hemodynamic effects of increased activity of the renin-angiotensin-aldosterone system, among others, are recognized pathways for the development of albuminuria. While the role of albuminuria in the progression of chronic kidney disease (CKD) is well known, there is increasing evidence of its negative association with cardiovascular events. For example, the presence of albuminuria is associated with an increased likelihood of developing heart failure (HF), even in patients with normal GFR, and the role of albuminuria in atherosclerosis has recently been described. Albuminuria is associated with adverse outcomes such as mortality and HF hospitalization. On the other hand, it is increasingly known that the systemic effects of congestion are mainly preceded by increased central venous pressure and transmitted retrogradely to organs such as the liver or kidney. With regard to the latter, a new entity called congestive nephropathy is emerging, in which increased renal venous pressure can lead to albuminuria. Fortunately, the presence of albuminuria is modifiable and new treatments are now available to reverse this common risk factor in the cardiorenal interaction.

Real-world usage of Chronic Kidney Disease - Mineral Bone Disorder (CKD-MBD) biomarkers in nephrology practices.

Background: Chronic kidney disease mineral bone disorder (CKD-MBD) is a condition characterized by alterations of calcium, phosphate, parathyroid hormone (PTH), and fibroblast growth factor 23 (FGF-23) metabolism that in turn promote bone disorders, vascular calcifications, and increase cardiovascular (CV) risk. Nephrologists' awareness of diagnostic, prognostic, and therapeutic tools to manage CKD-MBD plays a primary role in adequately preventing and managing this condition in clinical practice. Methods: A national survey (composed of 15 closed questions) was launched to inquire about the use of bone biomarkers in the management of CKD-MBD patients by nephrologists and to gain knowledge about the implementation of guideline recommendations in clinical practice. Results: One hundred and six Italian nephrologists participated in the survey for an overall response rate of about 10%. Nephrologists indicated that the laboratories of their hospitals were able to satisfy request of ionized calcium levels, 105 (99.1%) of both PTH and alkaline phosphatase (ALP), 100 (94.3%) of 25(OH)D, and 61 (57.5%) of 1.25(OH)2D; while most laboratories did not support the requests of biomarkers such as FGF-23 (intact: 88.7% and c-terminal: 93.4%), Klotho (95.3%; soluble form: 97.2%), tartrate-resistant acid phosphatase 5b (TRAP-5b) (92.5%), C-terminal telopeptide (CTX) (71.7%), and pro-collagen type 1 N-terminal pro-peptide (P1NP) (88.7%). As interesting data regarding Italian nephrologists' behavior to start treatment of secondary hyperparathyroidism (sHPT), the majority of clinicians used KDOQI guidelines (n = 55, 51.9%). In contrast, only 40 nephrologists (37.7%) relied on KDIGO guidelines, which recommended referring to values of PTH between two and nine times the upper limit of the normal range. Conclusion: Results point out a marked heterogeneity in the management of CKD-MBD by clinicians as well as a suboptimal implementation of guidelines in Italian clinical practice.

Sevelamer Use and Mortality in People with Chronic Kidney Disease Stages 4 and 5 Not on Dialysis.

Rationale and objective: Data suggest that non-calcium-based binders, and specifically sevelamer, may lead to lower rates of death when compared with calcium-based binders in end-stage renal disease (ESRD) patients. However, the association between sevelamer use and mortality for those with non-dialysis-dependent chronic kidney disease (NDD-CKD) patients has been uncertain. Study design: Our research is presented in a prospective cohort study. Setting and participants: A total of 966 participants with NDD-CKD stages 4-5 were enrolled in the PECERA study from 12 centers in Spain. Exposure: The participants were treated with sevelamer. Outcome: This study yielded all-cause and cardiovascular mortality outcomes. Analytical approach: We conducted an association analysis between mortality and sevelamer use with time-dependent Cox proportional hazards models. Results: After a median follow-up of 29 months (IQR: 13-36 months), death occurred in 181 participants (19%), with cardiovascular (n = 95, 53%) being the leading cause of death. In a multivariable model, the adjusted hazard ratios (HRs) for patients under sevelamer treatment were 0.44 (95% CI, 0.22 to 0.88) and 0.37 (95% CI, 0.18 to 0.75) for all-cause and cardiovascular mortality, respectively, compared with those of untreated patients. Limitations: Some limitations include potential confusion via indication bias; causal statements about these associations cannot be made due to the observational nature of this study. Conclusions: In this prospective NDD-CKD cohort study, the administration of sevelamer was independently associated with lower all-cause and cardiovascular mortality, suggesting that non-calcium-based phosphate binders might be the first-line therapy for phosphate lowering in this population. Further interventional studies clarifying the risks and benefits of phosphate binders in NDD-CKD are warranted.

La enfermedad cardiovascular en pacientes con insuficiencia renal crónica: el eje cardiorrenal / Cardiovascular Disease in Patients with Chronic Renal Failure: the Cardiorenal Axis

La enfermedad renal crónica se ha relacionado con un incremento de la morbimortalidad cardiovascular. Es una patología muy frecuente en la actualidad y constituye un factor de riesgo cardiovascular independiente, en el que el metabolismo del calcio-fósforo y la hipertrofia miocárdica tienen un papel relevante. La consecuencia de la alteración de la función renal sobre el incremento del riesgo cardiovascular se ha demostrado en estudios clínicos previos. Los pacientes con enfermedad renal crónica moderada a grave tienen un incremento exponencial de la mortalidad por enfermedad cardiovascular, incluso mucho antes de desarrollar la falla renal. En el presente trabajo se resume la información experimental básica sobre el tema del eje cardiorrenal y se plantea la necesidad de contar con modelos en animales para el estudio de los factores interrelacionados en este eje.

Chronic renal disease has been associated with an increase in cardiovascular morbidity and mortality. It is currently a very frequent disorder in which calcium and phosphate metabolism and myocardial hypertrophy play an outstanding role, and it constitutes an independent risk factor for cardiovascular disease. Previous clinical studies have demonstrated the consequences of the alteration in renal function on the increase of cardiovascular risk. Patients with moderate to severe renal chronic disease have an exponential increase in cardiovascular mortality, even before developing renal failure. The present study summarizes the information of basic research on the cardiorenal axis, and establishes the need of animal models to study the factors interrelated with this axis.