METHODS: To assess the effects of non-calcium-based phosphate binders on intermediate cardiovascular markers, we conducted a multicenter, double-blind trial, randomizing 278 participants with stage 3b or 4 CKD and serum phosphate >1.00 mmol/L (3.10 mg/dl) to 500 mg lanthanum carbonate or matched placebo thrice daily for 96 weeks. We analyzed the primary outcome, carotid-femoral pulse wave velocity, using a linear mixed effects model for repeated measures. Secondary outcomes included abdominal aortic calcification and serum and urine markers of mineral metabolism.
RESULTS: A total of 138 participants received lanthanum and 140 received placebo (mean age 63.1 years; 69% male, 64% White). Mean eGFR was 26.6 ml/min per 1.73 m2; 45% of participants had diabetes and 32% had cardiovascular disease. Mean serum phosphate was 1.25 mmol/L (3.87 mg/dl), mean pulse wave velocity was 10.8 m/s, and 81.3% had abdominal aortic calcification at baseline. At 96 weeks, pulse wave velocity did not differ significantly between groups, nor did abdominal aortic calcification, serum phosphate, parathyroid hormone, FGF23, and 24-hour urinary phosphate. Serious adverse events occurred in 63 (46%) participants prescribed lanthanum and 66 (47%) prescribed placebo. Although recruitment to target was not achieved, additional analysis suggested this was unlikely to have significantly affected the principle findings.
CONCLUSIONS: In patients with stage 3b/4 CKD, treatment with lanthanum over 96 weeks did not affect arterial stiffness or aortic calcification compared with placebo. These findings do not support the role of intestinal phosphate binders to reduce cardiovascular risk in patients with CKD who have normophosphatemia.
CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: Australian Clinical Trials Registry, ACTRN12610000650099.
MATERIALS AND METHODS: An e-mail invitation to participate in an online survey was sent to hospital laboratories in Malaysia (n=140). Questions regarding methods for measuring creatinine, equations for calculating eGFR, eGFR reporting, the terminology used in reporting urine albumin, types of samples and the cut-off values used for normal albuminuria.
RESULTS: A total of 42/140 (30%) laboratories answered the questionnaire. The prevalent method used for serum creatinine measurement was the Jaffé method (88.1%) traceable to isotope-dilution mass spectrometry. eGFR was reported along with serum creatinine by 61.9% of laboratories while 33.3% of laboratories report eGFR on request. The formula used for eGFR reporting was mainly MDRD (64.3%) and results were reported as exact numbers even when the eGFR was <60 ml/min/1.73m2. The term microalbumin is still used by 83.3% of laboratories. There is a large heterogeneity among the labs regarding the type of sample recommended for measuring urine albumin, reference interval and reporting units.
CONCLUSION: It is evident that the laboratory assessment of chronic kidney disease in Malaysia is not standardised. It is essential to provide a national framework for standardised reporting of eGFR and urine albumin. Recommendations developed by the MACB CKD Task Force, if adopted by all laboratories, will lead to a reduction in this variability.
METHODS: A multicentered, open-label, parallel group, prospective randomized controlled trial among patients suffering from CKD-associated pruritus with sleep disturbance, after randomization into control, and intervention group to be held at North West General Hospital and Research Center Peshawar, Pakistan and Institute of Kidney Diseases Peshawar, Pakistan.
RESULTS: The primary outcome is to investigate the effectiveness of zolpidem 10 mg and acupressure therapy on foot acupoints to improve the sleep quality and overall quality of life among hemodialysis patients suffering from CKD-associated pruritus. After baseline assessment by Urdu version of 5D itch scale and Urdu version of Pittsburgh Sleep Quality Index (PSQI) and Urdu EQ-5D 3L, the intervention group will be given zolpidem 10 mg oral tablets and control group with acupressure on both foots on KI-1 acupoints for total of 6 minutes. Assessment will be done at weeks 4 and 8 from baseline by using Urdu version of 5D itch scale and Urdu version of PSQI and Urdu EQ-5D 3L, whereas safety profiling of zolpidem 10 mg tablet at week 6 from baseline and acupressure acceptability at week 6 from baseline. Analysis of covariance will be used to examine the differences in treatment effects between the intervention and control groups.
CONCLUSION: Improvement of sleep quality and quality of life among patients with CKD-associated pruritus requires great importance. This study aims to improve the quality of sleep and quality of life among patients with hemodialysis suffering from CKD-associated pruritus.
Methods: This cross-sectional study included all gout patients who attended the rheumatology clinic from January 2013 to June 2018 and had received febuxostat as a second-line ULT. Analysis focused on the proportion of gout patients who achieved target serum urate (sUA) of <360 μmol/L, duration taken to achieve target sUA, and febuxostat dosage at achievement of target sUA. Safety assessments included comparison of serum creatinine, estimated glomerular filtration rate (eGFR), and serum alanine aminotransferase (ALT) at baseline, at achievement of target sUA, and at 12-monthly intervals.
Results: Majority (90.9%) of patients achieved target sUA. Median duration required to achieve target sUA was 5.5 months with IQR (interquartile range) of 8.5. Five (22.7%) patients achieved target sUA within one month of therapy with febuxostat 40 mg per day. Eleven (55%) patients achieved target sUA within six months and 16 (80%) by 12 months. Equal proportion of patients achieved target sUA with febuxostat 40 mg per day and 80 mg per day, respectively. There was no significant difference in the changes in serum creatinine level, eGFR and ALT from baseline and at achievement of target sUA, nor at 12-monthly intervals throughout the duration of febuxostat therapy. Apart from three patients who developed hypersensitivity reactions to febuxostat, no other adverse events were reported.
Conclusion: A significant proportion of gout patients with CKD managed to achieve target sUA with a lower dose of febuxostat at 40 mg per day and it is reasonable to maintain this dose for up to six months before considering dose escalation.
Methods: We evaluated commonly used surrogate and imputed baseline creatinine values against a "reference" creatinine measured during follow-up in an adult clinical trial cohort. Known AKI incidence (Kidney Disease: Improving Global Outcomes [KDIGO] criteria) was compared with AKI incidence classified by (1) back-calculation using the Modification of Diet in Renal Disease (MDRD) equation with and without a Chinese ethnicity correction coefficient; (2) back-calculation using the Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) equation; (3) assigning glomerular filtration rate (GFR) from age and sex-standardized reference tables; and (4) lowest measured creatinine during admission. Back-calculated distributions were performed using GFRs of 75 and 100 ml/min.
Results: All equations using an assumed GFR of 75 ml/min underestimated AKI incidence by more than 50%. Back-calculation with CKD-EPI and GFR of 100 ml/min most accurately predicted AKI but misclassified all AKI stages and had low levels of agreement with true AKI diagnoses. Back-calculation using MDRD and assumed GFR of 100 ml/min, age and sex-reference GFR values adjusted for good health, and lowest creatinine during admission performed similarly, best predicting AKI incidence (area under the receiver operating characteristic curves [AUC ROCs] of 0.85, 0.87, and 0.85, respectively). MDRD back-calculation using a cohort mean GFR showed low total error (22%) and an AUC ROC of 0.85.
Conclusion: Current methods for estimating baseline creatinine are large sources of potential error in acute infection studies. Preferred alternatives include MDRD equation back-calculation with a population mean GFR, age- and sex-specific GFR values corrected for "good health," or lowest measured creatinine. Studies using surrogate baseline creatinine values should report specific methodology.
Methods and results: An observational study of consecutive CKD patients (n = 276) undergoing comprehensive clinical cardiovascular magnetic resonance imaging. The relationship between aortic stiffness, myocardial fibrosis, left ventricular remodeling and the severity of chronic kidney disease was examined. Compared to age-gender matched controls with no known kidney disease (n = 242), CKD patients had considerably higher myocardial native T1 and central aortic PWV (p ≪ 0.001), as well as abnormal diastolic relaxation by E/e' (mean) by echocardiography (p ≪ 0.01). A third of all patients had LGE, with similar proportions for the presence and the (ischaemic and non-ischaemic) pattern between the groups. PWV was strongly associated with and age, NT-proBNP and native T1 in both groups, but not with LGE presence or type; the associations were amplified in severe CKD stages. In multivariate analyses, PWV was independently associated with native T1 in both groups (p ≪ 0.01) with near two-fold increase in adjusted R2 in the presence of CKD (native T1 (10 ms) R2, B(95%CI) CKD vs. non-CKD 0.28, 0.2(0.15-0.25) vs. 0.18, 0.1(0.06-0.15), p ≪ 0.01).
Conclusions: Aortic stiffness and interstitial myocardial fibrosis are interrelated; this association is accelerated in the presence of CKD, but independent of LGE. Our findings reiterate the significant contribution of CKD-related factors to the pathophysiology of cardiovascular remodeling.
Methods: We performed a longitudinal study in 30 children with CKD5-5D and 13 age-matched healthy controls (71 measurements) to determine a correlation between optimal weight by bioimpedance spectroscopy (Wt-BIS) and clinical assessment (Wt-CA). The accuracy of Wt-BIS [relative overhydration (Rel-OH)] was compared against indicators of fluid status and cardiovascular measures.
Results: There was poor agreement between Wt-CA and Wt-BIS in children on dialysis (P = 0.01), but not in CKD5 or control subjects. We developed a modified chart to plot Rel-OH against systolic blood pressure (SBP) z-score for the appropriate representation of volume status and blood pressure (BP) in children. In total, 25% of measurements showed SBP >90th percentile but not with concurrent overhydration. Rel-OH correlated with peripheral pulse pressure (P = 0.03; R = 0.3), higher N-terminal pro-brain natriuretic peptide (P = 0.02; R = 0.33) and left ventricular end-diastolic diameter (P = 0.05; R = 0.38). Central aortic mean and pulse pressure significantly associated with the left ventricular end-diastolic diameter (P = 0.03; R = 0.47 and P = 0.01; R = 0.50, respectively), but not with Rel-OH. SBP was positively associated with pulse wave velocity z-score (P = 0.04). In total, 40% of children on haemodialysis and 30% on peritoneal dialysis had increased left ventricular mass index.
Conclusions: BIS provides an objective method for the assessment of hydration status in children on dialysis. We noted a marked discrepancy between BP and hydration status in children on dialysis that warrants further investigation.