BackgroundHeterogeneous progression of chronic kidney disease (CKD) toward dialysis advocates improving in renal care management. Diagnosis and staging of CKD relies on estimated glomerular filtration rate (eGFR) and albuminuria. Tubular biomarkers emerged as new predictors of worsening renal function (WRF), due to partial inaccuracy of eGFR and existing WRF in non-proteinuric patients. Active vitamin D is synthesized in renal tubules and participates to mineral adaptation in CKD. Circulating 1,25-dihydroxyvitamin D [1,25(OH)2D] was poorly investigated as a biomarker of endocrine tubular function and predictor of WRF.ObjectiveInvestigate capability of 1,25(OH)2D to predict parathormone (PTH) increase and WRF in CKD stage 3–4.MethodsPASCaL-1,25D was an observational, prospective, monocentric study. Primary outcomes were absolute and 20% increase in PTH, and WRF defined as 20% reduction in eGFR or dialysis initiation at 6 months.ResultsSeventy-one patients completed follow up. Absolute increase in PTH (1–84) was independently predicted by lower 1,25(OH)2D levels (p = 0.0134). No association was detected between 1,25(OH)2D and iPTH increase. Higher 1,25(OH)2D was associated with reduced risk of WRF at univariate analysis [OR 0.89 (95% CI 0.86–0.93), p = 0.006]. The 1,25(OH)2D/PTH (1–84) ratio was associated with non-significant 84% risk reduction for WRF [OR 0.16 (95% CI 0.06–0.41), p = 0.05]. Low 1,25(OH)2D reached 100% sensitivity in predicting WRF in CKD stage 3 (AUC 9.909, p < 0.0001) and non-elderly patients (AUC 0.883, p < 0.0001). Machine learning models retained 1,25(OH)2D/PTH (1–84) as relevant predictor of WRF together with eGFR and albuminuria. Age influenced interaction between renal and mineral biomarkers.Conclusion1,25(OH)2D deserves attention as biomarker of tubular health, and sensible predictor of WRF on the short run among non-elderly patients affected by stage 3 CKD. The 1,25(OH)2D/PTH (1–84) ratio may represent a composite biomarker of tubular reserve/endocrine response to the transition from adaptive to maladaptive equilibrium in CKD-MBD.
Background. Secondary hyperparathyroidism (SHPT) is a major risk factor for cardiovascular events and all-cause mortality in hemodialysis (HD) patients. The purpose of our study was to evaluate the effects and tolerability of etelcalcetide in HD patients with SHPT. Methods. An observational study was conducted on 16 hemodialysis patients with SHPT treated with etelcalcetide. All patients were followed up for a duration of 6 months. The primary endpoints were the reduction in mean PTH ≥ 30% and ≥40% from baseline after 6 months of etelcalcetide. All patients were divided into two groups (group A versus group B) based on baseline serum PTH level prior to etelcalcetide: above and below the median serum PTH (1300 pg/mL), respectively. Results. After 6 months, a significant decrease in PTH levels was achieved by all patients receiving etelcalcetide (p = 0.015). Both primary endpoint of reduction in PTH ≥ 40% at 6 months (p = 0.01), and the secondary endpoint of reduction in median PTH values (p = 0.0001) and median percentage reduction in PTH values (p = 0.009) were significantly achieved in group A. In contrast, a greater decline of calcium (p = 0.028) and phosphorus was reached in group B than group A. Dialysis vintage ≥ 36 months, arteriovenous fistula (AVF)-based hemodialysis, post-diluition hemodiafiltration (HDF) method, and baseline values of PTH < 1300 pg/mL can positively influence the achievement of the endpoints. Furthermore, the baseline PTH < 1300 pg/mL, among these variables, was the only one showing statistically significant relevance (OR 2.28, 95% CI 1.32–3.96, p = 0.015). The history of cinacalcet use negatively correlated with the possibility to reach therapeutic targets with etelcalcetide (OR 0.47, 95% CI 0.26–0.85, p = 0.031). Treatment with etelcalcetide was well tolerated and no adverse effects were observed. Conclusions. In our study, patients with low baseline PTH levels showed a better response to etelcalcetide than patients with higher PTH levels. Consequently, the possibility to reach desirable therapeutic targets could depend on SHPT severity at the time of initiation of therapy.
Background and Aims The variable deterioration of patients with chronic kidney disease poses an omnipresent need for improved renal care management. At present, renal function in CKD patients is measured or estimated using the glomerular filtration rate (mGFR and eGFR). While mGFR affords the most objective and accurate evaluation of kidney function, it is not routinely used for repeated assessment due to its expense and difficulty to execute. Although eGFR provides the most diffuse approach for the monitoring of renal function, its commonality does not come without limitations: above 60mL/min*1.73m2, serum creatinine, and therefore eGFR variability are increasingly impacted by muscle metabolism/mass, age, gender, diet and fluid imbalances. eGFR can neither anticipate nor predict kidney damage. In CKD, deficiency of 1,25-dihydroxyvitamin D (1,25(OH)2D) develops during the progression of kidney failure, due to the decreased capability of renal proximal tubule cells to mediate the final hydroxylation step of 25-hydroxyvitamin D to 1,25(OH)2D. While not measured routinely in the clinic, new methods make the measurement of 1,25(OH)2D possible and reliable, and data on its performance as a biomarker are emerging. The aim of this study is to describe the ability of the LIAISON® XL 1,25 Dihydroxyvitamin D measurement to predict worsening renal function in conjunction with other relevant analytes. Method This monocentric study was observational, prospective and descriptive, with a longitudinal approach. 71 patients were assessed for mGFR determination by 99mTc-diethylenetriamine-pentaacetic acid at baseline. Twenty percent worsening of renal function, based on eGFR, provided the primary endpoint which was evaluated at 3 and 6 months. In addition, serum levels of 1,25(OH)2D, 25(OH)D, 1-84 PTH, intact FGF23, sclerostin, alkaline phosphatase (bone-specific and total) and calcium/phosphorus along with 24h urine levels of creatinine, phosphorus, calcium and sodium were measured. Endpoint analyses were performed by receiver operating characteristics, univariate, and multivariate logistic regressions. Results ROC analyses of 1,25(OH)2D and the 1,25(OH)2D/1-84PTH ratio for patients with early CKD (stage 3) showed very good performance in predicting worsening of renal function with AUCs of 0.916 (p<0.0001, criterion ≤29 pg/mL) and 0.791 (p<0.0005, criterion ≤0.844), respectively. Significance was lost for both markers’ outcome prediction with CKD4 subjects. Of interest, endpoint prediction by 1,25(OH)2D was also better in all patients <70 years old (AUC=0.883. p<0.0001). In univariate logistic regression analysis, 1,25(OH)2D is the single and strongest predictor of WRF (p=0.0029) corroborating the ROC analysis. In backward-elimination multi-variate regression, the 1,25(OH)2D/1-84PTH ratio and 1-84PTH are the final variables in the regression model (p=0.00013). Interestingly, while the ratio correlates well with mGFR (R=0.541), 1,25(OH)2D does not (R=0.116). Conclusion 1,25(OH)2D and the ratio of 1,25(OH)2D/1-84PTH are strong predictors of outcome in CKD3 patients, and thus these measurements may indicate improved clinical care for this important class of patients. Further research of these biomarkers is needed to expand the observations to larger numbers and more diverse populations.
Monitoring venous congestion by ultrasound assessment of hepatic venogram allowed individualized fluid management in severe cardiorenal syndrome type 5 due to light chain myeloma, preserving residual renal function and avoiding heart failure.
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