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Lower serum calcium is independently associated with CKD progression.

ABSTRACT: Disturbances in calcium metabolism are common in individuals with chronic kidney disease (CKD), but whether they are associated with subsequent kidney function decline is less clear. In a CKD 3-5 cohort of 15,755 adult citizens of Stockholm with creatinine tests taken during 2006-2011 and concurrent calcium testing at cohort entry, we investigated the association between baseline serum calcium and the subsequent change in estimated glomerular filtration rate (eGFR, by CKD-EPI) decline using linear mixed models. Mean (SD) baseline corrected serum calcium was 9.6 (0.5) mg/dL. Mean (95%-confidence interval [CI]) eGFR decline was -0.82 (-0.90; -0.74) mL/min/1.73 m²/year. In advanced CKD stages, higher baseline serum calcium was associated with less rapid kidney function decline. The adjusted change (95%-CI) in eGFR decline associated with each mg/dL increase in baseline serum calcium was -0.10 (-0.28; 0.26), 0.39 (0.07; 0.71), 0.34 (-0.02; 0.70) and 0.68 (0.36; 1.00) mL/min/1.73 m²/year for individuals in CKD stage 3a, 3b, 4, and 5, respectively. In a subgroup of patients using vitamin D supplements, the association between baseline serum calcium and CKD progression was eliminated, especially in CKD stage 3b and 4. To conclude, in individuals with CKD stage 3b to 5, lower baseline corrected serum calcium, rather than higher baseline serum calcium, associated with a more rapid CKD progression. Lower serum corrected calcium seems to be indicative for vitamin D deficiency.

SUBMITTER: Janmaat CJ

PROVIDER: S-EPMC5980097 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

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Lower serum calcium is independently associated with CKD progression.

Janmaat Cynthia J CJ van Diepen Merel M Gasparini Alessandro A Evans Marie M Qureshi Abdul Rashid AR Ärnlöv Johan J Barany Peter P Elinder Carl-Gustaf CG Rotmans Joris I JI Vervloet Marc M Dekker Friedo W FW Carrero Juan Jesus JJ

Scientific reports 20180326 1

Disturbances in calcium metabolism are common in individuals with chronic kidney disease (CKD), but whether they are associated with subsequent kidney function decline is less clear. In a CKD 3-5 cohort of 15,755 adult citizens of Stockholm with creatinine tests taken during 2006-2011 and concurrent calcium testing at cohort entry, we investigated the association between baseline serum calcium and the subsequent change in estimated glomerular filtration rate (eGFR, by CKD-EPI) decline using line ...[more]

PMID: 29581540

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Project description:Background and objectivesStudies of adults have demonstrated an association between metabolic acidosis, as measured by low serum bicarbonate levels, and CKD progression. We evaluated this relationship in children using data from the Chronic Kidney Disease in Children study.Design, setting, participants, & measurementsThe relationship between serum bicarbonate and a composite end point, defined as 50% decline in eGFR or KRT, was described using parametric and semiparametric survival methods. Analyses were stratified by underlying nonglomerular and glomerular diagnoses, and adjusted for demographic characteristics, eGFR, proteinuria, anemia, phosphate, hypertension, and alkali therapy.ResultsSix hundred and three participants with nonglomerular disease contributed 2673 person-years of follow-up, and 255 with a glomerular diagnosis contributed 808 person-years of follow-up. At baseline, 39% (237 of 603) of participants with nonglomerular disease had a bicarbonate level of ≤22 meq/L and 36% (85 of 237) of those participants reported alkali therapy treatment. In participants with glomerular disease, 31% (79 of 255) had a bicarbonate of ≤22 meq/L, 18% (14 of 79) of those participants reported alkali therapy treatment. In adjusted longitudinal analyses, compared with participants with a bicarbonate level >22 meq/L, hazard ratios associated with a bicarbonate level of <18 meq/L and 19-22 meq/L were 1.28 [95% confidence interval (95% CI), 0.84 to 1.94] and 0.91 (95% CI, 0.65 to 1.26), respectively, in children with nonglomerular disease. In children with glomerular disease, adjusted hazard ratios associated with bicarbonate level ≤18 meq/L and bicarbonate 19-22 meq/L were 2.16 (95% CI, 1.05 to 4.44) and 1.74 (95% CI, 1.07 to 2.85), respectively. Resolution of low bicarbonate was associated with a lower risk of CKD progression compared with persistently low bicarbonate (≤22 meq/L).ConclusionsIn children with glomerular disease, low bicarbonate was linked to a higher risk of CKD progression. Resolution of low bicarbonate was associated with a lower risk of CKD progression. Fewer than one half of all children with low bicarbonate reported treatment with alkali therapy. Long-term studies of alkali therapy's effect in patients with pediatric CKD are needed.

Project description:To estimate the discriminative value of serum P1NP/βCTX ratio and albumin levels in hospitalized orthogeriatric patients with and without nonvertebral fractures.In 1,239 orthogeriatric patients (mean age 78.1±9.52 years, 69.1% women) including 854 (68.9%) with osteoporotic nonvertebral fractures (455 [36.7%] with hip fracture [HF]) and 385 (31.1%) without fractures, markers of bone formation (procollagen type 1 N-terminal propeptide [P1NP], osteocalcin [OC], and bone resorption (beta-C-terminal cross-linking telopeptide of type 1 collagen [βCTX]), indices of mineral metabolism, and parameters of liver and renal functions were assessed; data on clinical and laboratory characteristics were collected prospectively.Both lower serum P1NP/βCTX ratio and albumin concentration (as continuous or categorical variables) were independently associated with fracture presence in multivariate logistic regressions. Compared with the highest P1NP/βCTX tertile, the prevalence of HF, after adjustment for multiple covariates, was 3-fold higher in the lowest tertile and 1.5 times higher in the middle tertile; presence of any fracture was 2.3- and 1.6-fold higher, respectively; patients with albumin levels in the lowest tertile had multivariate odds ratio (OR) of 4.6 for HF and 2.8 for any fracture, in the middle tertile the ORs were 2.2 and 1.3, respectively. The P1NP/βCTX <100.0 (median) and hypoalbuminemia (<33 g/L) demonstrated area under the curve values for HF of 0.802 and 0.806, respectively, and for any fractures of 0.711 and 0.706, respectively. When both characteristics were combined, the ORs for HF or any fracture, compared with the nonfractured group, were 7.8 and 3.2, respectively, with an accuracy of 79.6% and 71.6%, respectively.In orthogeriatric patients, both serum P1NP/βCTX ratio and albumin levels demonstrated an inverse dose-effect relationship with the prevalence of nonvertebral fractures and independently indicated fracture presence with acceptable discriminatory power. Lower P1NP/βCTX (<100) and hypoalbuminemia could be useful simple additive prognostic tools for fracture risk stratification in the elderly.

Project description:Background and objectivesData are scarce on blood metabolite associations with proteinuria, a strong risk factor for adverse kidney outcomes. We sought to investigate associations of proteinuria with serum metabolites identified using untargeted profiling in populations with CKD.Design, setting, participants, & measurementsUsing stored serum samples from the African American Study of Kidney Disease and Hypertension (AASK; n=962) and the Modification of Diet in Renal Disease (MDRD) study (n=620), two rigorously conducted clinical trials with per-protocol measures of 24-hour proteinuria and GFR, we evaluated cross-sectional associations between urine protein-to-creatinine ratio and 637 known, nondrug metabolites, adjusting for key clinical covariables. Metabolites significantly associated with proteinuria were tested for associations with CKD progression.ResultsIn the AASK and the MDRD study, respectively, the median urine protein-to-creatinine ratio was 80 (interquartile range [IQR], 28-359) and 188 (IQR, 54-894) mg/g, mean age was 56 and 52 years, 39% and 38% were women, 100% and 7% were black, and median measured GFR was 48 (IQR, 35-57) and 28 (IQR, 18-39) ml/min per 1.73 m2. Linear regression identified 66 serum metabolites associated with proteinuria in one or both studies after Bonferroni correction (P<7.8×10-5), 58 of which were statistically significant in a meta-analysis (P<7.8×10-4). The metabolites with the lowest P values (P<10-27) were 4-hydroxychlorthalonil and 1,5-anhydroglucitol; all six quantified metabolites in the phosphatidylethanolamine pathway were also significant. Of the 58 metabolites associated with proteinuria, four were associated with ESKD in both the AASK and the MDRD study.ConclusionsWe identified 58 serum metabolites with cross-sectional associations with proteinuria, some of which were also associated with CKD progression.PodcastThis article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2019_02_07_CJASNPodcast_19_03_.mp3.

Project description:Rationale & objectiveTo evaluate progression patterns and associated economic outcomes, using estimated glomerular filtration rate (eGFR) and urine albumin-creatinine ratio (UACR) based on the Kidney Disease: Improving Global Outcomes (KDIGO) risk categories, among patients with type 2 diabetes (T2D) and chronic kidney disease (CKD).Study designPatients with T2D and moderate- or high-risk CKD were selected from the Optum electronic health records database (January 2007-December 2019). Progression patterns and post-progression economic outcomes were assessed.Setting & participantsAdults with T2D and CKD in clinical settings.PredictorBaseline KDIGO risk categories.OutcomesProgression to a more severe KDIGO risk category; healthcare resource utilization and medical costs.Analytical approachProgression probability was estimated using cumulative incidence. Healthcare resource utilization and costs were compared across progression groups.ResultsOf 269,187 patients (mean age 65.6 years) with T2D and CKD of moderate or high baseline risk, 18.9% progressed to the very high-risk category within 5 years. Among moderate-risk patients, 17.8% of CKD stage G1-A2, 44.0% of stage G2-A2, and 61.3% of stage G3a-A1 patients progressed to a higher KDIGO risk category. Among high-risk patients, 63.9% of stage G3b-A1/G3a-A2 and 56.0% of stage G2-A3 patients progressed to very high risk. Within the same eGFR stage, a higher UACR stage was associated with 4- to 7-times higher risk of progressing to very high risk and faster eGFR decline. Nonprogressors had lower annual medical costs ($16,924) than patients who progressed from moderate risk to high risk ($22,117, P < 0.05), from high risk to very high risk ($32,204, P < 0.05), and from moderate risk to very high risk ($35,092, P < 0.05).LimitationsInfrequent lab testing might have caused lags in identifying progression; medical costs were calculated using unit costs.ConclusionsPatients with T2D and CKD of moderate or high risk per KDIGO risk categories had high probabilities of progression, incurring a substantial economic burden. The results highlight the value of UACR in CKD management.

Project description:Background and objectivesHyperlipidemia is common in patients with CKD. The objective of this study was to evaluate whether measures of plasma lipids and lipoproteins predict progression of kidney disease in patients with CKD.Design, setting, participants, & measurementsProspective cohort study in adults (n=3939) with CKD aged 21-74 years recruited between 2003 and 2008 and followed for a median of 4.1 years. At baseline, total cholesterol, triglycerides, very-low-density lipoprotein cholesterol (VLDL-C), LDL cholesterol (LDL-C), HDL cholesterol (HDL-C), apoA-I , apoB, and lipoprotein(a) [Lp(a)] were measured. The outcomes were composite end point of ESRD or 50% decline in eGFR from baseline (rate of change of GFR).ResultsMean age of the study population was 58.2 years, and the mean GFR was 44.9 ml/min per 1.73 m(2); 48% of patients had diabetes. None of the lipid or lipoprotein measures was independently associated with risk of the composite end point or rate of change in GFR. However, there were significant (P=0.01) interactions by level of proteinuria. In participants with proteinuria<0.2 g/d, 1-SD higher LDL-C was associated with a 26% lower risk of the renal end point (hazard ratio [HR], 0.74; 95% confidence interval [95% CI], 0.59 to 0.92; P=0.01), and 1-SD higher total cholesterol was associated with a 23% lower risk of the renal end point (HR, 0.77; 95% CI, 0.62 to 0.96; P=0.02). In participants with proteinuria>0.2 g/d, neither LDL-C (HR, 0.98; 95% CI, 0.98 to 1.05) nor total cholesterol levels were associated with renal outcomes. Treatment with statins was reported in 55% of patients and was differential across lipid categories.ConclusionsIn this large cohort of patients with CKD, total cholesterol, triglycerides, VLDL-C, LDL-C, HDL-C, apoA-I, apoB, and Lp(a) were not independently associated with progression of kidney disease. There was an inverse relationship between LDL-C and total cholesterol levels and kidney disease outcomes in patients with low levels of proteinuria.

Dataset Information

Lower serum calcium is independently associated with CKD progression.

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Lower serum calcium is independently associated with CKD progression.

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