Looking into the Eyes to See the Heart of Chronic Kidney Disease Patients.

In patients with chronic kidney disease (CKD), the main cause of morbidity and mortality is cardiovascular disease (CVD). Both coronary artery calcium scoring by computed tomography (CT) and optical coherence tomography (OCT) are used to identify patients at increased risk for ischemic heart disease, thereby indicating a higher cardiovascular risk profile. Our study aimed to investigate the utility of these techniques in the CKD population. In patients with CKD, OCT was used to measure the choroidal thickness (CHT) and the thickness of the peripapillary retinal nerve fiber layer (pRNFL). A total of 127 patients were included, including 70 men (55%) with an estimated glomerular filtration rate (eGFR) of 39 ± 30 mL/min/1.73 m2. Lower pRNFL thickness was found to be related to high-sensitivity troponin I (r = -0.362, p < 0.001) and total coronary calcification (r = -0.194, p = 0.032). In a multivariate analysis, pRNFL measurements remained associated with age (ß = -0.189; -0.739--0.027; p = 0.035) and high-sensitivity troponin I (ß = -0.301; -0.259--0.071; p < 0.001). Severe coronary calcification (Agatston score ≥ 400 HU) was related to a worse eGFR (p = 0.008), a higher grade of CKD (p = 0.036), and a thinner pRNFL (p = 0.011). The ROC curve confirmed that the pRNFL measurement could determine the patients with an Agatston score of ≥400 HU (AUC 0.638; 95% CI 0.525-0.750; p = 0.015). Our study concludes that measurement of pRNFL thickness using OCT is related to the markers associated with ischemic heart disease, such as coronary calcification and high-sensitivity troponin I, in the CKD population.

Treatment of Chronic Heart Failure in Advanced Chronic Kidney Disease: The HAKA Multicenter Retrospective Real-World Study.

INTRODUCTION: Chronic heart failure (HF) has high rates of mortality and hospitalization in patients with advanced chronic kidney disease (aCKD). However, randomized clinical trials have systematically excluded aCKD population. We have investigated current HF therapy in patients receiving clinical care in specialized aCKD units. METHODS: The Heart And Kidney Audit (HAKA) was a cross-sectional and retrospective real-world study including outpatients with aCKD and HF from 29 Spanish centers. The objective was to evaluate how the treatment of HF in patients with aCKD complied with the recommendations of the European Society of Cardiology Guidelines for the diagnosis and treatment of HF, especially regarding the foundational drugs: renin-angiotensin system inhibitors (RASi), angiotensin receptor blocker/neprilysin inhibitors (ARNI), beta-blockers (BBs), mineralocorticoid receptor antagonists (MRAs), and sodium-glucose cotransporter-2 inhibitors (SGLT2i). RESULTS: Among 5,012 aCKD patients, 532 (13%) had a diagnosis of HF. Of them, 20% had reduced ejection fraction (HFrEF), 13% mildly reduced EF (HFmrEF), and 67% preserved EF (HFpEF). Only 9.3% of patients with HFrEF were receiving quadruple therapy with RASi/ARNI, BB, MRA, and SGLT2i, but the majority were not on the maximum recommended doses. None of the patients with HFrEF and CKD G5 received quadruple therapy. Among HFmrEF patients, approximately half and two-thirds were receiving RASi and/or BB, respectively, while less than 15% received ARNI, MRA, or SGLT2i. Less than 10% of patients with HFpEF were receiving SGLT2i. CONCLUSIONS: Under real-world conditions, HF in aCKD patients is sub-optimally treated. Increased awareness of current guidelines and pragmatic trials specifically enrolling these patients represent unmet medical needs.

Clonal Hematopoiesis of Indeterminate Potential and Cardiovascular Risk in Patients with Chronic Kidney Disease without Previous Cardiac Pathology.

Clonal hematopoiesis of indeterminate potential (CHIP) is defined by the clonal expansion of hematopoietic stem cells carrying certain genes associated with an increased risk of hematological malignancies. Our study analyzes the influence of CHIP on the risk of heart disease and cardiovascular events in a population with chronic kidney disease (CKD). A total of 128 patients were prospectively followed up for 18 months to detect major cardiovascular events (MACE). To detect the presence of silent heart disease, troponin I, NT-Pro-BNP, and coronary calcification were measured. A massive sequencing was performed to detect CHIP. A total of 24.2% of the patients presented CHIP, including that which was only pathogenic. The most frequently affected gene was TET2 (21.1%). Using multivariate logistic regression analysis, the presence of CHIP was not related to coronary calcification (OR 0.387, 95% CI 0.142-1.058, p = 0.387), nor was it related to troponin I or NT-Pro-BNP. A total of nine patients developed major cardiovascular events. Patients with CHIP did not have a higher risk of major cardiovascular events, although patients with DNMT3A did have a higher risk (HR 6.637, 95% CI 1.443-30.533, p = 0.015), independent of other variables. We did not find that CHIP was associated with a greater risk of silent heart disease or cardiovascular events, although those affected by DNMT3a, analyzed independently, were associated with a greater number of cardiovascular events.

Oral Anticoagulation in Patients with Chronic Kidney Disease and Non-Valvular Atrial Fibrillation: The FAERC Study.

Atrial fibrillation (AF) is the most common arrhythmia in patients with chronic kidney disease (CKD), and its presence is associated with a higher risk of stroke and mortality. MATERIAL AND METHODS: The FAERC study performed a retrospective multicentre analysis of historical cohorts in which data were collected from arrhythmia diagnosis onwards. RESULTS: We analysed a Spanish cohort of 4749 patients with CKD (mean eGFR 33.9 mL/min) followed up in the nephrology clinic, observing a 12.2% prevalence of non-valvular AF. In total, 98.6% of these patients were receiving anticoagulant treatment, mainly with coumarins (79.7%). Using direct-acting oral anticoagulants (DOACs) was associated with fewer cerebrovascular events than using acenocoumarol, but in contrast with other studies, we could not corroborate the association of risk of bleeding, coronary events, or death with a type of anticoagulant prescribed. CONCLUSIONS: Atrial fibrillation is highly prevalent in renal patients. Direct-acting anticoagulants seem to be associated with fewer ischemic-embolic complications, with no differences in bleeding, coronary events, or mortality rates.

Lower Time in Therapeutic Range Relates to a Worse Kidney Graft Outcome.

Tacrolimus has a narrow therapeutic margin. Maintaining tacrolimus blood levels in the appropriate range is difficult because of its intrapatient variability. In fact, greater blood level variability has been related to worse kidney graft outcome, but only measuring variability does not consider the therapeutic range goal. Determining the time in therapeutic range (TTR) using the Rosendaal method allows dose optimization by considering the adverse events associated with both supratherapeutic and subtherapeutic doses. Some previous studies in kidney and lung transplantation have shown that the measurement of TTR has been related to the subsequent graft outcome. We performed a single-center, observational study including 215 consecutive kidney transplants performed in our center. The percentage of time that the patient remained with levels above 6 ng/mL between months 3 and 12 (%TTR3-12) was calculated using the Rosendaal method. A lower %TTR3-12 was associated with a higher risk of acute rejection (area under the receiver operating characteristic curve, 0.614; 95% confidence interval [CI], 0.513-0.714; P = .018) and with a higher risk of having a 1-year glomerular filtration rate < 30 mL/min/1.73 m2 (area under the receiver operating characteristic curve, 0.676; 95% CI, 0.542-0.811; P = .014). The lowest tertile of %TTR3-12 was independently associated with a higher risk of death-censored graft loss (hazard ratio, 10.773; 95% CI, 1.315-88.264; P = .027) after adjusting by 1-year glomerular filtration rate, expanded criteria donation, and acute rejection throughout the first year. To conclude, measuring TTR after kidney transplant is an easy way to estimate the time of exposure to adequate levels of tacrolimus and relates to kidney graft outcome.

Growth Differentiation Factor 15 Is Superior to Troponin I in the Evaluation of Kidney Transplant Candidates.

INTRODUCTION: Pretransplant cardiac troponin I (cTNI) has demonstrated its predicting value in survival after kidney transplant. Growth differentiation factor 15 (GDF-15) is a biomarker currently studied as a predictor of mortality and cardiovascular events (CVE) in different scenarios. The aim of this study was to compare the utility of these two biomarkers in the prediction of events after kidney transplant. METHODS: We included 359 kidney transplants performed in our center between 2005 and 2015. cTNI and GDF-15 were measured on stored serum samples obtained pretransplant. RESULTS: Median GDF-15 was 5,346.4 pg/mL, and cTNI was 5.6 ng/L. After follow-up, 77 (21.5%) patients died, and the incidence of cerebrovascular accident (CVA), acute coronary syndrome (ACS), and major adverse CVEs (MACE) was 6.38%, 12.68%, and 20.56%, respectively. Patients were stratified in tertiles according to GDF-15 and cTNT levels. By multivariate cox regression analysis including both biomarkers and different clinical characteristics, we found a significant relation between GDF-15 and mortality, CVAs, and MACE (highest tertile hazard ratio [HR] 2.2 95% confidence interval [CI] [1.2-4.1], p = 0.01, HR 9.7 CI 95% [2.2-43.1], p = 0.003 and HR 2.7 CI 95% [1.4-5.1], p = 0.002). On the contrary, posttransplant ACS was related to cTNI (highest cTNI tertile HR 3.2 CI 95% [1.5-7.3], p = 0.003). DISCUSSION: Our study indicates the potential utility of GDF-15 as a mortality and CVE predictor after kidney transplant and its superiority compared to cTNI. By contrast, probably due to its tissue specificity, cardiac troponin showed a stronger correlation with acute coronary events. Although more studies are needed to confirm our findings, these two molecules could be used in conjunction with other tools to predict adverse events after transplant and ideally find strategies to minimize them.

Controlled Donation After Circulatory Death Program: Analysis and Results at a Tertiary Care Hospital.

BACKGROUND: The objective of the study was to evaluate the impact in organs obtained and transplanted from controlled donation after circulatory death (cDCD). METHODS: Transplants from cDCD donors performed at the Hospital Universitario Marqués de Valdecilla from the beginning of the program (December 2013) to December 2020 were evaluated. All procedures were performed with normothermic regional perfusion. Donors after brain death (DBDs) during the same period were used as a control group. RESULTS: A total of 95 donors after cardiac death and 152 DBDs were included. Age was similar in both groups (60 years [IQR, 53-68 years vs 62 years {IQR, 51-79 years]; P = .390). The number of organs recovered per donor was higher in the DBD group (4 [IQR, 3-5] vs 3 [IQR, 2-4], P < .001], as well as the number of transplanted organs (4 [IQR, 2-4] vs 2 [IQR, 2-4]; P = .002]. However, the number of noneffective donors was similar. DBDs presented a higher rate of liver donation (30.5% vs 46.7%; P = .012), lung donation (25.3% vs 38.2%; P = .036), and cardiac donation (1.1% vs 21.7%; P < .001) with respect to the donors after cardiac death group, but kidney and pancreatic donation were similar. CONCLUSIONS: The cDCD with normothermic regional perfusion program is fully established in our center. The age of the cDCD donor has increased with experience and it is currently identical to the control group (DBD). After overcoming the learning curve, cDCD is a multiorgan donation that presents an excellent profitability in the number of organs extracted and transplanted.

"Epigenome-wide methylation profile of chronic kidney disease-derived arterial DNA uncovers novel pathways in disease-associated cardiovascular pathology."

Chronic kidney disease (CKD) related cardiovascular disease (CVD) is characterized by vascular remodelling with well-established structural and functional changes in the vascular wall such as arterial stiffness, matrix deposition, and calcification. These phenotypic changes resemble pathology seen in ageing, and are likely to be mediated by sustained alterations in gene expression, which may be caused by epigenetic changes such as tissue-specific DNA methylation. We aimed to investigate tissue specific changes in DNA methylation that occur in CKD-related CVD. Genome-wide DNA methylation changes were examined in bisulphite converted genomic DNA isolated from the vascular media of CKD and healthy arteries. Methylation-specific PCR was used to validate the array data, and the association between DNA methylation and gene and protein expression was examined. The DNA methylation age was compared to the chronological age in both cases and controls. Three hundred and nineteen differentially methylated regions (DMR) were identified spread across the genome. Pathway analysis revealed that DMRs associated with genes were involved in embryonic and vascular development, and signalling pathways such as TGFß and FGF. Expression of top differentially methylated gene HOXA5 showed a significant negative correlation with DNA methylation. Interestingly, DNA methylation age and chronological age were highly correlated, but there was no evidence of accelerated age-related DNA methylation in the arteries of CKD patients. In conclusion, we demonstrated that differential DNA methylation in the arterial tissue of CKD patients represents a potential mediator of arterial pathology and may be used to uncover novel pathways in the genesis of CKD-associated complications.

Investigation of iron deficiency in patients with congestive heart failure: A medical practice that requires greater attention. / Estudio de la deficiencia de hierro en pacientes con insuficiencia cardiaca congestiva: una práctica clínica que precisa mayor atención.

INTRODUCTION: Iron deficiency in congestive heart failure (CHF), with or without concomitant anaemia, is associated with health-related quality of life, NYHA functional class, and exercise capacity. Prospective, randomised studies have demonstrated that correcting iron deficiency improves the quality of life and functional status of patients with CHF, including those who do not have anaemia. OBJECTIVE: The aim of this study was to analyse how frequently these iron parameters are tested and thus determine the extent to which this quality improvement tool has been implemented in patients admitted with CHF. METHODS: Retrospective observational study of patients from a university hospital diagnosed with CHF on admission between 01/01/2012 and 11/06/2013. RESULTS: Iron parameters were tested in 39% (324) of the 824 patients analysed. There was no significant difference in age between the patients whose iron was tested and those whose iron was not tested, but the difference in terms of gender was significant (P=.007). Glomerular filtration rate and haemoglobin, were significantly lower in the group of patients whose iron was tested (P<.001). The proportion of patients with anaemia, renal failure or both was significantly higher in the group of patients who had iron tests (P<.001). Of the 324 patients whose iron parameters were tested, 164 (51%) had iron deficiency. There were no differences between patients with and without iron deficiency in terms of age or gender. The iron parameters in both groups, ferritin and transferrin saturation index were significantly lower among the patients with iron deficiency (P<.001). The glomerular filtration rate values were significantly lower in patients with no iron deficiency (P<.001). Significant differences were also observed between those with and without iron deficiency in the proportion of patients with renal failure (79 vs. 66%, respectively, P=.013), but not in terms of haemoglobin concentration. CONCLUSION: Congestive heart failure is very frequently associated with anaemia, iron deficiency and renal failure. Despite the fact that correcting iron deficiency is known to improve symptoms, testing of iron parameters in patients admitted with CHF is not performed as often as it should be.

Haemodialysis session: the perfect storm for vascular calcification.

INTRODUCTION: Vascular calcification (VC) associated to chronic kidney disease (CKD) is a complex phenomenon closely related to mineral bone metabolism disorders. Many are the factors implicated, as the drugs used in the treatment of CKD. Some in vitro studies suggest that electrolyte and acid-base disorders induced by hemodialysis (HD) may play a key role in VC. METHODS: We analyzed electrolyte and acid-base disorders that occur during an HD session in 26 patients randomly assigned to 1,25 mM or 1,5 mM calcium bath. RESULTS: There is a calcium load in all the patients, independently of calcium bath concentration or basal serum calcium levels. At the end of the session, 100% of the patients dialyzed with 1,5 mM calcium bath have calcium serum levels > 1,3 mM. However, this only occurs in 15% of the patients dialysed with 1,25 mM calcium bath. During this calcium load, phosphorus levels persist uncontrolled. Besides, there is a progressive alkalinization in all the patients. In the end of the session 50% have serum bicarbonate > 30 mM and 23% pH > 7,5. CONCLUSIONS: During HD sessions occur electrolyte and acid-base disorders that induce VC: Calcium load and alkalization in presence of elevated phosphorus levels. It is necessary to perform studies with kinetic models of calcium load and alkalinization different from the actual ones.

Effect of calcium acetate/magnesium carbonate in the treatment of hyperphosphataemia in dialysis patients in real clinical practice. One year follow up.

BACKGROUND: This observational study was conducted to investigate the use and effectiveness of calcium acetate/magnesium carbonate (CaMg) in the treatment of hyperphosphataemia in dialysis patients in real-world clinical practice. METHODS: 120 adult CKD patients on dialysis who received CaMg alone or in combination with other phosphate binders were followed-up for 3-12 months. Serum phosphorus, calcium, magnesium, parathyroid hormone and albumin concentration was measured at baseline and after 3, 6 and 12 months respectively. In addition, CaMg dosage, use of concurrent phosphate binders, vitamin D and cinacalcet was documented. Patients were evaluated in 2 subgroups – CaMg alone (n=79) vs. CaMg + concurrent phosphate binder (n=41). RESULTS: In both subgroups serum phosphorus levels decreased significantly from baseline at 3, 6 and 12 months of CaMg treatment. The percentage achievement of recommended serum phosphorus targets improved after CaMg initiation. At month 6, a total of 78% were within the Kidney Disease Outcomes Quality Initiative (K/DOQI) target range. Total corrected serum calcium increased during CaMg treatment, but mildly exceeded the upper limit of normal in three patients only. Asymptomatic significant increases in magnesium (p<0.001) were observed in the monotherapy group at 3, 6 and 12 months. A total of 80 patients (67%) experienced episodes of mild hypermagnesaemia (>2.6mg/mL, 1.05mmol/L). CONCLUSIONS: This analysis of current clinical practice shows that – consistent with findings from a randomised controlled trial – CaMg treatment leads to marked improvement in serum phosphorus levels, helping patients in trying to achieve K/DOQI and KDIGO (Kidney Disease Improving Global Outcome) targets.

Renal function, nephrogenic systemic fibrosis and other adverse reactions associated with gadolinium-based contrast media.

Nephrogenic systemic fibrosis is a fibrosing disorder that affects patients with impaired renal function and is associated with the administration of gadolinium-based contrast media used in MRI. Despite being in a group of drugs that were considered safe, report about this potentially serious adverse reaction was a turning point in the administration guidelines of these contrast media. There has been an attempt to establish safety parameters to identify patients with risk factors of renal failure. The close pharmacovigilance and strict observation of current regulations, with special attention being paid to the value of glomerular filtration, have reduced the published cases involving the use of gadolinium-based contrast media. In a meeting between radiologists and nephrologists we reviewed the most relevant aspects currently and recommendations for its prevention.

Strokes in patients on haemodialysis: incidence, onset time and associated factors.

The incidence of stroke is higher substantially among hemodialysis patients than in the overall population. In this observational cohort study, we analysed data from incident hemodialysis patients at Valdecilla University Hospital in Santander (Spain) during a 40-year period (1971-2011). A total number of 1453 patients were started on hemodialysis The total follow-up period was 4982.22 patients/year, with 84 patients having stroke. The cumulative incidence of stroke in our patients was 5.8%, with an incidence rate of 1686 strokes per 100 000 patient-years. The incidence rate in the first year was 1803 strokes per 100 000 patients-year, 6.5% higher than its average over the period studied. In the remaining period, the rates ranged between 356 and 1626 strokes per 100 000 patients-year. Significative factors related to stroke were: diabetes, myocardial infarction or angina, hypertension, arteriosclerosis/intermittent claudication, history of stroke before the HD and atrial fibrillation. Haemoglobin levels in the cohort stroke were virtually identical to those of the not stroke cohort (11.92±2.07 g/dL, compared to 11, 68±2.12 g/dL). Finally, 60.7% of the population of the stroke cohort received erythropoietin with mean dose of 9611 IU/week, compared to 51.9% and a dose of 9544 IU/week in the not stroke cohort, without significative differences among groups. In conclusion, in haemodialysis population the incidence of stroke is 7-10 times higher than in the general population. It is associated with well known factors for stroke but not with haemoglobin levels or erythropoietin dose.