Introduction
The protein‐energy wasting (PEW) syndrome is a common complication in hemodialysis (HD) patients associated to morbidity and mortality. Our objective was to assess the prevalence of PEW ...and its association with erythropoietin resistance index (ERI) score, body composition by impedance, health‐related quality of life, and muscle strength.
Methods
In this cross‐sectional, observational, multicenter study, we included data from 191 HD patients from three HD clinics located in Mexico City, Mexico. Clinical and biochemistry variables, body composition, handgrip strength, and the KDQOL‐SF36 questionnaire were collected for each patient.
Findings
Prevalence of PEW was 22% (n = 41/191), with a higher frequency in those with diabetes mellitus (59% vs. 49%, p = 0.04). Subjects with PEW had lower hemoglobin levels (9.5 + 1.6 g/dl vs. 10.3 + 1.7 g/dl; p = 0.005) and higher ERI scores (19.2 ± 11.2 vs. 15.6 ± 8.2; p = 0.04) compared with the non‐PEW group. In analysis of body composition, PEW was associated to higher overhydration status (42.2 vs. 24.9 OH/kg; p = 0.009), higher extracellular water (263 ± 40 vs. 246 ± 32 ml/kg; p = 0.019), lower lean tissue index (12.2 ± 3.2 vs. 14.1 ± 3.7 ml/m2; p = 0.021), and lower fat tissue index (9.6 ± 5.7 vs. 12.3 ± 6.2 ml/m2; p = 0.043). Handgrip strength was lower in PEW patients (22.5 vs. 28.1 kg; p = 0.002). Finally, no significant differences were observed between groups in quality‐of‐life assessment.
Discussion
In this study, PEW was associated to poor responsiveness to erythropoiesis‐stimulating agents, lower muscle strength, and higher overhydration status due to the increase in extracellular water which replaced the loss of tissue. Nevertheless, quality‐of‐life assessment was not different in patients with PEW compared with those without this complication.
Kidney replacement therapy (KRT) initiated in Latin America towards the second half of the 20th century, starting with dialytic therapies and, shortly thereafter, with kidney transplant. By the end ...of 2021, close to half a million Latin Americans were under KRT, with an overall unadjusted prevalence of 872 per million persons (pmp), yet with significant heterogeneity between nations. By treatment modality, 68% of prevalent patients were treated with hemodialysis (HD), 9% with peritoneal dialysis (PD), and 23% were living with a functioning kidney graft (LFG). In the last decade, HD is the KRT that has had the largest growth, and it also has incorporated newer and better technologies. Nevertheless, Latin America shows heterogeneity between countries, and as a region we are far from achieving full accessibility to all in need of KRT. While there has been growth and improvement in existing renal dialysis registries, and several countries that did not previously have these registries have implemented them, there are still some nations with limited or absent registry implementation. The number of nephrologists in the region is heterogeneous, with only four countries having an appropriate group of specialists. The remaining nations have an important need to expand nephrology training programs. SLANH is a major regional player in addressing these topics and supporting the expansion of appropriate nephrology programs to improve inequalities and patient care. (Rev Invest Clin. 2023;75(6):300-8).
La pandemia del SARS-CoV-2 representa un riesgo especial para los pacientes en hemodiálisis crónica por su estado de inmunosupresión, edad avanzada y coexistencia de comorbilidades importantes, en ...particular patología cardiovascular, diabetes mellitus y otras. Adicionalmente, esta población constituye un conglomerado cerrado ya que los pacientes acuden a tratamiento con regularidad y permanecen horas en los lugares de tratamiento, expuestos a una posible adquisición de la infección. El hecho de acudir necesaria y regularmente a su tratamiento impide que permanezcan en aislamiento domiciliario y con exposición potencial en el traslado. Las presentes recomendaciones resumen las intervenciones propuestas por tres organizaciones internacionales, a las que se agregan algunas sugeridas por expertos nacionales, con el objetivo de identificar precozmente a los pacientes y personal de la salud en riesgo para disminuir el riesgo de infección.
Abstract
Background
Insulin resistance (IR) is a pathophysiologic hallmark of type 2 diabetes and associated with the presence of chronic kidney disease (CKD). Experimental studies suggest that ...endothelin-1 increases IR. We assessed the association between IR and cardio-renal outcomes and the effect of the selective endothelin receptor antagonist atrasentan on IR in patients with type 2 diabetes and CKD.
Methods
We used data from the RADAR and SONAR trials that recruited participants with type 2 diabetes and CKD eGFR 25–75 mL/min/1.73 m², urine albumin-to-creatinine ratio of 300–5000 mg/g. IR was calculated using the homeostatic model assessment (HOMA-IR). The association between HOMA-IR and the pre-specified cardio-renal outcomes was assessed using multivariable Cox proportional hazards regression, and effects of atrasentan on HOMA-IR by a linear mixed effect model.
Results
In the SONAR trial, each log-unit increase in HOMA-IR was associated with an increased risk of the composite cardio-renal outcome hazard ratio 1.32 (95%CI 1.09,1.60; p = 0.004), kidney outcome hazard ratio 1.30 (95%CI 1.00,1.68; p-value = 0.048), and the kidney or all-cause mortality outcome hazard ratio 1.25 (95%CI 1.01,1.55; p-value = 0.037). After 12 weeks treatment in the RADAR trial (N = 123), atrasentan 0.75 mg/day and 1.25 mg/day compared to placebo reduced HOMA-IR by 19.1 (95%CI -17.4, 44.3) and 26.7% (95%CI -6.4, 49.5), respectively. In the SONAR trial (N = 1914), atrasentan 0.75 mg/day compared to placebo reduced HOMA-IR by 9.6% (95%CI 0.6, 17.9).
Conclusions
More severe IR is associated with increased risk of cardio-renal outcomes. The endothelin receptor antagonist atrasentan reduced IR.
Trial registration
RADAR trial (Reducing Residual Albuminuria in Subjects With Diabetes and Nephropathy With AtRasentan): NCT01356849.
SONAR trial (The Study Of Diabetic Nephropathy With AtRasentan) NCT01858532.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Mineralocorticoid receptor antagonists (MRAs) and sodium–glucose cotransporter-2 (SGLT2) inhibitors reduce the risk of kidney failure in chronic kidney disease (CKD). We performed an analysis of the ...Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease (DAPA-CKD) trial by baseline conventional MRA (spironolactone and eplerenone) prescription.
Participants with CKD (estimated glomerular filtration rate eGFR 25–75 ml/min per 1.73 m2; urinary albumin-to-creatinine ratio 200–500 mg/g), with or without type 2 diabetes, were randomized 1:1 to dapagliflozin 10 mg or placebo, once daily. The primary outcome was a composite of sustained ≥50% eGFR decline, end-stage kidney disease, or kidney or cardiovascular (CV) death. A prespecified kidney-specific secondary outcome was as the primary outcome but without CV death. Hyperkalemia (serum potassium ≥6.0 mmol/l) was an exploratory end point. Time-to-event analyses (proportional hazards Cox regression) assessed dapagliflozin versus placebo in patient subgroups defined by baseline conventional MRA use.
A total of 229 of 4304 DAPA-CKD participants (5.3%) were receiving conventional MRAs at baseline (dapagliflozin n = 109, placebo n = 120). The effect of dapagliflozin on the primary outcome was consistent in participants prescribed (hazard ratio HR 0.76, 95% CI 0.40–1.47) and not prescribed (HR 0.60, 95% CI 0.50–0.72, P-interaction = 0.59) MRAs. This consistency was maintained for the kidney-specific outcome. The effect of dapagliflozin on hyperkalemia (HR 0.87, 95% CI 0.70–1.09) was consistent among those prescribed (HR 0.94, 95% CI 0.41–2.20) and not prescribed (HR 0.87, 95% CI 0.69–1.10, P-interaction = 0.96) MRAs. Adverse events (AEs) leading to discontinuation and serious AEs were similar between treatment groups, regardless of baseline MRA prescription.
Dapagliflozin was similarly safe and efficacious in reducing major adverse kidney outcomes in participants with CKD who were or were not prescribed MRAs at baseline.
It is known that one of the leading causes of morbidity in chronic kidney disease (CKD) is the anemic syndrome. Although the pathogenic mechanisms of anemia are multiple, erythropoietin deficiency ...appears as the dominant factor. Patients in hemodialysis (HD) have a high prevalence of protein energy wasting (PEW) that may explains the poor response to Erythropoietin (EPO).
Retrospective cohort study of patients on HD from January to December 2014. The participants were classified according to a diagnostic of PEW using the "Malnutrition Inflammation Score" (MIS) and bioimpedance analysis (BIA) measurement of body composition at the start of erythropoietin therapy and after 3 months of follow up. We performed descriptive statistics and analyzed the differences between groups with and without PEW considering their responsiveness. In addition, we calculated the relative risk of EPO resistance, considering p value < 0.05 as statistically significant.
Sixty-one patients ended the follow up. Both groups were similar in basal hemoglobin, hematocrit and other hematopoiesis markers (p = NS). Patients without PEW have a decrease risk for poor response to treatment with EPO (RR = 0.562 95% CI, 0.329-0.961-) than those with PEW. Finally, hemoglobin concentrations were evaluated at baseline and every four weeks until week 12, finding a statistically significant improvement only in patients without PEW according MIS (p < 0.05).
PEW is an incremental predictor of poor responsiveness to EPO in HD patients, thus, it is important to consider correcting malnutrition or wasting for a favorable response to treatment with EPO.
Summary
Experimental studies have shown that rabbit antithymocyte polyclonal globulin (ATG) can expand human CD4+CD25++Foxp3+ cells (Tregs). We investigated the major biological effects of a ...self‐manufactured rabbit polyclonal anti‐rat thymoglobulin (rATG) in vitro, as well as its effects on different peripheral T‐cell subsets. Moreover, we evaluated the allogeneic suppressive capacity of rATG‐induced Tregs in an experimental rat renal transplant model. Our results show that rATG has the capacity to induce apoptosis in T lymphocyte lymphocytes as a primary mechanism of T‐cell depletion. Our in vivo studies demonstrated a rapid but transient cellular depletion of the main T cell subsets, directly proportional to the rATG dose used, but not of the effector memory T cells, which required significantly higher rATG doses. After rATG administration, we observed a significant proliferation of Tregs in the peripheral blood of transplanted rats, leading to an increase in the Treg/T effector ratio. Importantly, rATG‐induced Tregs displayed a strong donor‐specific suppressive capacity when assessed in an antigen‐specific allogeneic co‐culture. All of these results were associated with better renal graft function in rats that received rATG. Our study shows that rATG has the biological capacity immunomodulatory to promote a regulatory alloimmune milieu during post‐transplant homeostatic proliferation.
In order to change the current state of chronic kidney disease knowledge and therapeutics, a fundamental improvement in the understanding of genetic and environmental causes of chronic kidney disease ...is essential. This article first provides an overview of the existing knowledge gaps in our understanding of the genetic and environmental causes of chronic kidney disease, as well as their interactions. The second part of the article formulates goals that should be achieved in order to close these gaps, along with suggested timelines and stakeholders that are to be involved. A better understanding of genetic and environmental factors and their interactions that influence kidney function in healthy and diseased conditions can provide novel insights into renal physiology and pathophysiology and result in the identification of novel therapeutic or preventive targets to tackle the global public health care problem of chronic kidney disease.
Aims
The selective endothelin (ET) A receptor antagonist atrasentan has been shown to lower albuminuria in North American and Asian patients with type 2 diabetes and nephropathy. As drug responses to ...many drugs may differ between North American and Asian populations, we assessed the influence of geographical region on the albuminuria and fluid retention response to atrasentan.
Materials and methods
Two 12‐week double‐blind randomised controlled trials were performed with atrasentan 0.75 or 1.25 mg/d vs placebo in patients with type 2 diabetes and nephropathy. The efficacy endpoint was the percentage change in albuminuria. Bodyweight change, a proxy of fluid retention, was used as a safety endpoint. Pharmacodynamics were determined in Asians (N = 77) and North Americans (N = 134). Atrasentan plasma concentration was measured in 161 atrasentan‐treated patients.
Results
Mean albuminuria reduction in Asian, compared to North American, patients was, respectively, −34.4% vs −26.3% for 0.75 mg/d (
P
= .44) and −48.0% vs −28.9% for 1.25 mg/d (
P
= .035). Bodyweight gain did not differ between North American and Asian populations. Atrasentan plasma concentrations were higher in Asians compared to North Americans and correlated with albuminuria response (7.2% albuminuria reduction per doubling atrasentan concentration;
P
= .024). Body surface area (β = −1.09 per m2;
P
< .001) and bilirubin, as a marker of hepatic organic anion transporter activity, (β = 0.69 per mg/dL increment;
P
= .010) were independent determinants of atrasentan plasma concentration; correction by body surface area and bilirubin left no significant difference in plasma concentration between Asian and North American populations.
Conclusion
The higher exposure and albuminuria reduction of atrasentan in Asian patients is not associated with more fluid retention, suggesting that Asian patients are less sensitive to atrasentan‐induced sodium retention.
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