Cardiac Biomarkers are Associated with Incident Fracture Risk in Advanced Chronic Kidney Disease.

Cardiovascular disease is associated with increased fracture risk in the general population. Few data exist on the association between cardiovascular health and incident fracture risk in patients with advanced CKD, a high-risk population for fractures. We aimed to assess the link between fracture risk and cardiovascular health in a prospective cohort of 210 patients with CKD stage G4-5. Incident fractures were recorded during a prospective follow-up of 5 years. Laboratory parameters, abdominal aortic calcification score, echocardiography, ultrasound assessment of brachial artery flow-mediated dilatation and carotid intima-media thickness, and maximal stress ergometry were obtained at baseline. A total of 51 fractures were observed in 40 (19%) patients during follow-up. In separate multivariable Cox proportional hazards models adjusted for age, gender, and baseline eGFR, TnT (HR 1.007, CI 95% 1.003-1.010, p < 0.001) and ProBNP (HR 1.000, CI 95% 1.000-1.000, p = 0.017) were associated with incident fractures and the association persisted after adjusting for coronary artery disease (CAD). The patients unable to perform the ergometry test had a higher risk of incident fractures compared to others (36.1% vs 15.5%, p = 0.009). A cardiovascular composite risk score summarizing TnT, ProBNP, and ergometry data was independently associated with incident fractures in a multivariable Cox model (HR 1.373, CI 95% 1.180-1.599, p < 0.001). Patients with the lowest score were observed with no fractures, while patients with the highest score were observed with a fracture risk of 40.5% during follow-up. Risk of incident fractures is associated with biomarkers of cardiovascular health and a composite cardiovascular risk score in patients with advanced CKD.

Evolution of Quality of Life in Chronic Kidney Disease Stage 4-5 Patients Transitioning to Dialysis and Transplantation.

INTRODUCTION: Chronic kidney disease (CKD) has a profound effect on patients' health-related quality of life (QoL). Longitudinal studies on QoL in CKD are scarce and have explored selected patients on renal replacement therapy (RRT). We studied the evolution of QoL in patients with advanced CKD transitioning to dialysis and transplantation in a prospective follow-up study. METHODS: A total of 100 participants of the Chronic Arterial Disease, Quality of Life, and Mortality in Chronic Kidney Injury (CADKID) study were enrolled in the study. Kidney Disease Quality of Life Short Form, biochemistry, and echocardiography were obtained at baseline and after a median interval of 33 (range 12-85) months. RESULTS: At the time of the follow-up QoL assessment, 32 patients were not receiving RRT, 30 were on hemodialysis (HD), 19 on peritoneal dialysis (PD), and 19 had received a kidney transplant. Among kidney transplant recipients (KTRs), "Burden of Kidney Disease" and "General Health" domains improved compared to patients who initiated HD (p < 0.0001 and p = 0.007, respectively), PD (p = 0.0005 and p = 0.03, respectively), or remained in predialysis care (p = 0.009 and p = 0.003, respectively) while "Effects of Kidney Disease" improved compared to those who started HD (p = 0.004) or PD (p = 0.002). The change in Short Form-36 (SF-36) Physical Component Summary was not different between patients on different treatment modalities. Higher plasma albumin and cholesterol levels were associated with improved QoL in "Symptoms/Problems" (r = 0.28, p = 0.005, and r = 0.30, p = 0.004, respectively) and "Effects of Kidney Disease" (r = 0.27, p = 0.008, and r = 0.24, p = 0.03, respectively). CONCLUSION: QoL improved in KTRs in kidney disease-specific domains compared to patients initiating dialysis or those without RRT. Plasma albumin and lipids were associated with QoL over time.

Progression of Aortic Calcification in Stage 4-5 Chronic Kidney Disease Patients Transitioning to Dialysis and Transplantation.

BACKGROUND AND AIMS: Abdominal aortic calcification (AAC) is common in chronic kidney disease (CKD) patients and associated with increased mortality. Comparative data on the AAC score progression in CKD patients transitioning from conservative treatment to different modalities of renal replacement therapy (RRT) are lacking and were examined. METHODS: 150 study patients underwent lateral lumbar radiograph to study AAC in the beginning of the study before commencing RRT (AAC1) and at 3 years of follow-up (AAC2). We examined the associations between repeated laboratory tests taken every 3 months, echocardiographic and clinical variables and AAC increment per year (ΔAAC), and the association between ΔAAC and outcomes during follow-up. RESULTS: At the time of AAC2 measurement, 39 patients were on hemodialysis, 39 on peritoneal dialysis, 39 had a transplant, and 33 were on conservative treatment. Median AAC1 was 4.8 (0.5-9.0) and median AAC2 8.0 (1.5-12.0) (p < 0.0001). ΔAAC was similar across the treatment groups (p = 0.19). ΔAAC was independently associated with mean left ventricular mass index (LVMI) (log LVMI: ß = 0.97, p = 0.02) and mean phosphorus through follow-up (log phosphorus: ß = 1.19, p = 0.02) in the multivariable model. Time to transplantation was associated with ΔAAC in transplant recipients (per month on the waiting list: ß = 0.04, p = 0.001). ΔAAC was associated with mortality (HR 1.427, 95% confidence interval 1.044-1.950, p = 0.03). CONCLUSION: AAC progresses rapidly in patients with CKD, and ΔAAC is similar across the CKD treatment groups including transplant recipients. The increment rate is associated with mortality and in transplant recipients with the time on the transplant waiting list.

Maximal Exercise Capacity in Chronic Kidney Disease Stage 4-5 Patients Transitioning to Renal Replacement Therapy or Continuing Conservative Care: A Longitudinal Follow-Up Study.

INTRODUCTION: Chronic kidney disease (CKD) is associated with impaired maximal exercise capacity (MEC). However, data are scarce on the development of MEC in CKD stage 4-5 patients transitioning to renal replacement therapy (RRT). METHODS: We explored the change in MEC measured in watts (Wlast4) with 2 consecutive maximal bicycle stress ergometry tests in 122 CKD stage 4-5 patients transitioning to dialysis and transplantation in an observational follow-up study. RESULTS: Mean age was 58.9 ± 13.9 years and 43 (35.2%) were female. Mean time between the baseline and follow-up ergometry tests was 1,012 ± 327 days and 29 (23.8%) patients had not initiated RRT, 50 (41.0%) were undergoing dialysis, and 43 (35.2%) had received a kidney transplant at the time of the follow-up ergometry test. The mean Wlast4 was 91 ± 37 W and 84 ± 37 W for the baseline and follow-up ergometry tests, respectively (p < 0.001). The mean Wlast4 declined between the baseline and follow-up ergometry tests in patients not requiring RRT (p = 0.001) and transplant recipients (p = 0.005), but not in dialysis patients (p = 0.478). There were no differences in the ratio of Wlast4 of the follow-up to the baseline ergometry tests (∆Wlast4) between patients on different treatment modalities at the time of the follow-up test (p = 0.097). Mean capillary blood bicarbonate was significantly associated with ∆Wlast4 after adjusting for age and treatment modality in the multivariate linear regression analysis (ß = 0.226, p = 0.012). CONCLUSION: MEC declined or remained poor in advanced CKD patients transitioning to RRT or continuing conservative care in this observational study. Mean capillary blood bicarbonate was independently associated with the development of MEC.

Dental health assessed using panoramic radiograph and adverse events in chronic kidney disease stage 4-5 patients transitioning to dialysis and transplantation-A prospective cohort study.

BACKGROUND AND AIMS: Oral health could potentially be a modifiable risk factor for adverse outcomes in chronic kidney disease (CKD) patients transitioning from predialysis treatment to maintenance dialysis and transplantation. We aimed to study the association between an index of radiographically assessed oral health, Panoramic Tomographic Index (PTI), and cardiovascular and all-cause mortality, major adverse cardiovascular events (MACEs) and episodes of bacteremia and laboratory measurements during a three-year prospective follow-up in CKD stage 4-5 patients not on maintenance dialysis at baseline. METHODS: Altogether 190 CKD stage 4-5 patients without maintenance dialysis attended panoramic dental radiographs in the beginning of the study. The patients were followed up for three years or until death. MACEs and episodes of bacteremia were recorded during follow-up. Laboratory sampling for C-reactive protein and leukocytes was repeated tri-monthly. RESULTS: PTI was not associated with baseline laboratory parameters or C-reactive protein or leukocytes examined as repeated measures through the 3-year follow-up. During follow-up, 22 patients had at least one episode of bacteremia, but only 2 of the bacteremias were considered to be of oral origin. PTI was not associated with incident bacteremia during follow-up. Thirty-six patients died during follow-up including 17 patients due to cardiovascular causes. During follow-up 42 patients were observed with a MACE. PTI was independently associated with all-cause (HR 1.074 95% CI 1.029-1.122, p = 0.001) and cardiovascular (HR 1.105, 95% CI 1.057-1.157, p<0.0001) mortality, as well as, incident MACEs (HR 1.071 95% CI 1.031-1.113, p = 0.0004) in the multivariable Cox models adjusted for age and kidney transplantation or CKD treatment modality during follow-up. CONCLUSIONS: Radiographically assessed dental health is independently associated with all-cause and cardiovascular mortality and MACEs but not with the incidence of bacteremia in CKD stage 4-5 patients transitioning to maintenance dialysis and renal transplantation during follow-up.

Association of maximal stress ergometry performance with troponin T and abdominal aortic calcification score in advanced chronic kidney disease.

BACKGROUND: Cardiac biomarkers Troponin T (TnT) and N-terminal pro-B-type natriuretic peptide (proBNP) and abdominal aortic calcification score (AAC) are associated with cardiovascular events and mortality in patients with chronic kidney disease (CKD). The effects of cardiac biomarkers and AAC on maximal exercise capacity in CKD are unknown and were studied. METHODS: One hundred seventy-four CKD 4-5 patients not on maintenance dialysis underwent maximal bicycle ergometry stress testing, lateral lumbar radiograph to study AAC, echocardiography and biochemical assessments. RESULTS: The subjects with proportional maximal ergometry workload (WMAX%) less than 50% of the expected values had higher TnT, proBNP, AAC, left ventricular end-diastolic diameter, left ventricular mass index, E/e' and pulse pressure, and lower global longitudinal strain compared to the better performing patients. TnT (ß = - 0.09, p = 0.02), AAC (ß = - 1.67, p < 0.0001) and diabetes (ß = - 11.7, p < 0.0001) remained significantly associated with WMAX% in the multivariable model. Maximal ergometry workload (in Watts) was similarly associated with TnT and AAC in addition to age, male gender, hemoglobin and diastolic blood pressure in a respective multivariate model. AAC and TnT showed fair predictive power for WMAX% less than 50% of the expected value with AUCs of 0.70 and 0.75, respectively. CONCLUSIONS: TnT and AAC are independently associated with maximal ergometry stress test workload in patients with advanced CKD. TRIAL REGISTRATION: http://www.ClinicalTrials.gov NCT04223726.

Quality of Life Is Associated with Cardiac Biomarkers, Echocardiographic Indices, and Mortality in CKD Stage 4-5 Patients Not on Dialysis.

INTRODUCTION: Patients with CKD have an impaired health-related quality of life (QoL). Most studies have been conducted on dialysis patients, and less is known about QoL and its determinants in predialysis patients. We studied the association between QoL and comorbidities, cardiac biomarkers, echocardiography, and mortality in patients with CKD stage 4-5 not on dialysis. METHODS: A total of 140 patients enrolled in the Chronic Arterial Disease, Quality of Life and Mortality in Chronic Kidney Injury (CADKID) study filled the Kidney Disease Quality of Life Short Form (KDQOL-SF) at the beginning of the study. Echocardiography and biochemical parameters were obtained at baseline. Patients were followed up for at least 2 years or until death. RESULTS: The median age was 66 years, and 51 (36%) patients were female. The median estimated glomerular filtration rate was 13 mL/min per 1.73 m2. Obesity, diabetes, atrial fibrillation, and congestive heart failure were associated with lower QoL scores in multiple KDQOL-SF domains. Cardiac biomarkers, troponin T (p = 0.02), N-terminal pro-B-type natriuretic peptide (p = 0.006), and the echocardiographic parameter of cardiac systolic function left ventricular global longitudinal strain (p = 0.02) were significant predictors of lower physical component summary (PCS) score in multivariable regression models after controlling for age, BMI, and diabetes. A low PCS score predicted mortality in a multivariable Cox proportional hazards model [HR 0.96 (95% CI 0.92-0.99), p = 0.03]. QoL was not associated with kidney disease progression. CONCLUSION: Impaired QoL in CKD stage 4-5 patients not on dialysis is associated with cardiac biomarker levels, echocardiographic indices, and mortality.

Elevated Troponin T and Enlarged Left Atrium Are Associated with the Incidence of Atrial Fibrillation in Patients with CKD Stage 4-5.

INTRODUCTION: Atrial fibrillation (AF) and CKD are commonly coexisting conditions. However, data on epidemiology of AF in patients with CKD stage 4-5 is scarce. METHODS: We prospectively enrolled 210 consecutive non-dialysis patients with CKD stage 4-5 between 2013 and 2017. Follow-up data on AF incidence along with medical history, laboratory tests, and echocardiography at baseline were gathered. RESULTS: At baseline, mean age was 62 years, estimated glomerular filtration rate 12.8 mL/min, and 73/210 (34.8%) participants were female. Altogether, 41/210 (19.5%) patients had a previous diagnosis of AF. After median follow-up of 46 [IQR 27] months, new-onset AF occurred in 33/169 (19.5%) patients (69.9 events/1,000 person-years). In the Cox proportional hazard model, age >60 years (HR 4.27, CI 95% 1.57-11.64, p < 0.01), elevated troponin T (TnT) >50 ng/L (HR 3.61, CI 95% 1.55-8.37, p < 0.01), and left atrial volume index (LAVI) >30 mL/m2 (HR 4.82, CI 95% 1.11-21.00, p = 0.04) were independently associated with the incidence of new-onset AF. CONCLUSION: The prevalence and incidence of AF was markedly high in this prospective study on patients with CKD stage 4-5. Elevated TnT and increased LAVI were independently associated with the occurrence of new-onset AF in patients with severe CKD.

Arterial endothelial function, carotid artery intima-media thickness and abdominal aortic calcification in diabetic and nondiabetic CKD stage 4-5 patients not on dialysis.

AIMS: We aimed to study the effect of diabetes (DM) on endothelial dysfunction assessed by flow-mediated vasodilatation (FMD), carotid intima-media thickness (cIMT) and abdominal aortic calcification score (AAC) in chronic kidney disease (CKD) stage 4-5 patients not on dialysis. METHODS: Altogether 199 non-dialysis CKD stage 4-5 patients enrolled in the Chronic Arterial Disease, quality of life and mortality in chronic KIDney injury (CADKID) study with plain lumbar radiograph for the assessment of AAC were included. Data on cIMT and FMD were available for 172 and 161 patients, respectively. RESULTS: Median age was 65 (IQR 54-76) years, 88 (44.2%) patients had DM and median eGFR was 12 (IQR 10-14) ml/min/1.73 m2 in the study. FMD [controls: 3.3(2.0-6.7)% vs. DM-patients: 4.3(1.3-6.6)%, p = 0.73] and cIMT [controls: 0.65(0.58-0.87)mm vs. DM-patients: 0.67(0.59-0.81)mm, p = 0.65], were similar between the groups. AAC was higher in patients with DM [controls: 5(1-9) vs. DM-patients: 7(2-13), p = 0.01]. The significant multivariate determinants for AAC were older age (ß = 0.22, p < 0.0001), pulse pressure (ß = 0.05, p < 0.0001), DM (ß = 1.33, p = 0.04) and ProBNP (per µg/l ß = 0.18, p = 0.0008). AAC and cIMT were associated with incident cardiovascular death independent of DM. CONCLUSIONS: DM is associated with increased AAC but not increased cIMT or attenuated FMD in advanced CKD patients.

Interatrial block, P terminal force or fragmented QRS do not predict new-onset atrial fibrillation in patients with severe chronic kidney disease.

BACKGROUND: The prevalence of left atrial enlargement (LAE) and fragmented QRS (fQRS) diagnosed using ECG criteria in patients with severe chronic kidney disease (CKD) is unknown. Furthermore, there is limited data on predicting new-onset atrial fibrillation (AF) with LAE or fQRS in this patient group. METHODS: We enrolled 165 consecutive non-dialysis patients with CKD stage 4-5 without prior AF diagnosis between 2013 and 2017 in a prospective follow-up cohort study. LAE was defined as total P-wave duration ≥120 ms in lead II ± > 1 biphasic P-waves in leads II, III or aVF; or duration of terminal negative portion of P-wave > 40 ms or depth of terminal negative portion of P-wave > 1 mm in lead V1 from a baseline ECG, respectively. fQRS was defined as the presence of a notched R or S wave or the presence of ≥1 additional R waves (R') or; in the presence of a wide QRS complex (> 120 ms), > 2 notches in R or S waves in two contiguous leads corresponding to a myocardial region, respectively. RESULTS: Mean age of the patients was 59 (SD 14) years, 56/165 (33.9%) were female and the mean estimated glomerular filtration rate was 12.8 ml/min/1.73m2. Altogether 29/165 (17.6%) patients were observed with new-onset AF within median follow-up of 3 [IQR 3, range 2-6] years. At baseline, 137/165 (83.0%) and 144/165 (87.3%) patients were observed with LAE and fQRS, respectively. Furthermore, LAE and fQRS co-existed in 121/165 (73.3%) patients. Neither findings were associated with the risk of new-onset AF within follow-up. CONCLUSION: The prevalence of LAE and fQRS at baseline in this study on CKD stage 4-5 patients not on dialysis was very high. However, LAE or fQRS failed to predict occurrence of new-onset AF in these patients.

Cardiovascular Determinants of Mortality in Advanced Chronic Kidney Disease.

BACKGROUND: Patients with advanced chronic kidney disease (CKD stage 4-5) have an increased risk of death. To study the determinants of all-cause mortality, we recruited 210 consecutive CKD stage 4-5 patients not on dialysis to the prospective Chronic Arterial Disease, quality of life and mortality in chronic KIDney injury (CADKID) study. METHODS: One hundred seventy-four patients underwent maximal bicycle ergometry stress testing and lateral lumbar radiography to study abdominal aortic calcification score and echocardiography. Carotid and femoral artery intima-media thickness and elasticity and brachial artery flow-mediated dilatation were measured in 156 patients. RESULTS: The duration of follow-up was 42 ± 17 months (range 134-2,217 days). The mean age was 61 ± 14 years, and the estimated glomerular filtration rate was 12 (11-15) mL/min/1.73 m2. Thirty-six (21%) patients died during follow-up (time to death 835 ± 372 days). Seventy-five and 21 patients had diabetes and coronary artery disease, respectively, and all but one had hypertension. In the respective multivariate proportional hazards models adjusted for age, sex, and coronary artery disease, the significant determinants of mortality were troponin T, N-terminal pro-B-type natriuretic peptide, maximal ergometry performance, abdominal aortic calcification score, E/e' ratio, and albumin. CONCLUSION: Stress ergometry performance, abdominal aortic calcification score, E/e' of echocardiography, and plasma cardiac biomarkers and albumin predict mortality in advanced CKD.