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      Patterns of progression of chronic kidney disease at later stages

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          Abstract

          Background

          At later stages of chronic kidney disease (CKD), a pattern of linear and irreversible renal function decline is thought to be the most common. The objective of this study was to describe the characteristics of the different patterns of CKD progression, and to investigate potentially modifiable factors associated with the rate of decline of renal function.

          Methods

          This was a retrospective, observational study in a cohort of adult patients with CKD Stage 4 or 5 not on dialysis. Decline in renal function was estimated as the slope of the individual linear regression line of estimated glomerular filtration rate (eGFR) over time. The following patterns of CKD progression were considered: unidentifiable, linear, nonlinear (curvilinear) and positive (improvement of renal function).

          Results

          The study group consisted of 915 patients (mean ±SD age 65 ± 14 years, 48% females, median follow-up time 16 months). A linear pattern was observed in 38%, unidentifiable in 23%, nonlinear in 24% and positive in 15% of the study patients. The mean eGFR slope was: −3.35 ± 4.45 mL/min/year. Linear and unidentifiable patterns were associated with more rapid loss of renal function. By multiple linear and logistic regression analysis, the magnitude of proteinuria, the systolic blood pressure and the treatment with dual renin–angiotensin system blockade were associated with more rapid CKD progression. On the contrary, older age and discontinuation of commonly prescribed medication with potential influence on renal function or eGFR measurements were associated with slower CKD progression.

          Conclusions

          A majority of patients with advanced CKD show patterns of renal function decline different from linear, and several of the main determinants of CKD progression are potentially modifiable.

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          Most cited references25

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          Renal Aging: Causes and Consequences.

          Individuals age >65 years old are the fastest expanding population demographic throughout the developed world. Consequently, more aged patients than before are receiving diagnoses of impaired renal function and nephrosclerosis-age-associated histologic changes in the kidneys. Recent studies have shown that the aged kidney undergoes a range of structural changes and has altered transcriptomic, hemodynamic, and physiologic behavior at rest and in response to renal insults. These changes impair the ability of the kidney to withstand and recover from injury, contributing to the high susceptibility of the aged population to AKI and their increased propensity to develop subsequent progressive CKD. In this review, we examine these features of the aged kidney and explore the various validated and putative pathways contributing to the changes observed with aging in both experimental animal models and humans. We also discuss the potential for additional study to increase understanding of the aged kidney and lead to novel therapeutic strategies.
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            Selective vitamin D receptor activation with paricalcitol for reduction of albuminuria in patients with type 2 diabetes (VITAL study): a randomised controlled trial.

            Despite treatment with renin–angiotensin–aldosterone system (RAAS) inhibitors, patients with diabetes have increased risk of progressive renal failure that correlates with albuminuria. We aimed to assess whether paricalcitol could be used to reduce albuminuria in patients with diabetic nephropathy. In this multinational, placebo-controlled, double-blind trial, we enrolled patients with type 2 diabetes and albuminuria who were receiving angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. Patients were assigned (1:1:1) by computer-generated randomisation sequence to receive 24 weeks’ treatment with placebo,1 μg/day paricalcitol, or 2 μg/day paricalcitol. The primary endpoint was the percentage change in geometric mean urinary albumin-to-creatinine ratio (UACR) from baseline to last measurement during treatment for the combined paricalcitol groups versus the placebo group. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00421733. Between February, 2007, and October, 2008, 281 patients were enrolled and assigned to receive placebo(n=93), 1 μg paricalcitol (n=93), or 2 μg paricalcitol (n=95); 88 patients on placebo, 92 on 1 μg paricalcitol, and 92 on2 μg paricalcitol received at least one dose of study drug, and had UACR data at baseline and at least one timepoint during treatment, and so were included in the primary analysis. Change in UACR was: –3% (from 61 to 60 mg/mmol;95% CI –16 to 13) in the placebo group; –16% (from 62 to 51 mg/mmol; –24 to –9) in the combined paricalcitol groups, with a between-group difference versus placebo of –15% (95% CI –28 to 1; p=0.071); –14% (from 63 to 54 mg/mmol; –24 to –1) in the 1 μg paricalcitol group, with a between-group difference versus placebo of –11%(95% CI –27 to 8; p=0.23); and –20% (from 61 to 49 mg/mmol; –30 to –8) in the 2 μg paricalcitol group, with a between-group difference versus placebo of –18% (95% CI –32 to 0; p=0.053). Patients on 2 μg paricalcitol showed a nearly, sustained reduction in UACR, ranging from –18% to –28% (p=0.014 vs placebo). Incidence of hypercalcaemia,adverse events, and serious adverse events was similar between groups receiving paricalcitol versus placebo. Addition of 2 μg/day paricalcitol to RAAS inhibition safely lowers residual albuminuria in patients with diabetic nephropathy, and could be a novel approach to lower residual renal risk in diabetes. Abbott.
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              Predictors of the progression of renal disease in the Modification of Diet in Renal Disease Study.

              The Modification of Diet in Renal Disease (MDRD) Study examined the effects of dietary protein restriction and strict blood pressure control on the decline in glomerular filtration rate (GFR) in 840 patients with diverse renal diseases. We describe a systematic analysis to determine baseline factors that predict the decline in GFR, or which alter the efficacy of the diet or blood pressure interventions. Univariate analysis identified 18 of 41 investigated baseline factors as significant (P < 0.05) predictors of GFR decline. In multivariate analysis, six factors--greater urine protein excretion, diagnosis of polycystic kidney disease (PKD), lower serum transferrin, higher mean arterial pressure, black race, and lower serum HDL cholesterol--independently predicted a faster decline in GFR. Together with the study interventions, these six factors accounted for 34.5% and 33.9% of the variance between patients in GFR slopes in Studies A and B, respectively, with proteinuria and PKD playing the predominant role. The mean rate of GFR decline was not significantly related to baseline GFR, suggesting an approximately linear mean GFR decline as renal disease progresses. The 41 baseline predictors were also assessed for their interactions with the diet and blood pressure interventions. A greater benefit of the low blood pressure intervention was found in patients with higher baseline urine protein. None of the 41 baseline factors were shown to predict a greater or lesser effect of dietary protein restriction.
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                Author and article information

                Journal
                Clin Kidney J
                Clin Kidney J
                ckj
                Clinical Kidney Journal
                Oxford University Press
                2048-8505
                2048-8513
                April 2018
                28 July 2017
                28 July 2017
                : 11
                : 2
                : 246-253
                Affiliations
                Nephrology Department, Hospital Infanta Cristina, Badajoz, Spain
                Author notes
                Correspondence and offprint requests to: Fernando Caravaca-Fontán; E-mail: fcaravacaf@ 123456gmail.com
                Article
                sfx083
                10.1093/ckj/sfx083
                5888389
                29644066
                0e13225f-c5b3-429c-b5f2-9254e675473b
                © The Author 2017. Published by Oxford University Press on behalf of ERA-EDTA.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com

                History
                : 02 April 2017
                : 19 June 2017
                Page count
                Pages: 8
                Categories
                CKD

                Nephrology
                chronic kidney disease,dual blockade renin–angiotensin system,patterns of ckd progression,proteinuria

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