Risk factors for progression of chronic kidney disease in the EPPIC trials and the effect of AST-120

Schulman, Gerald; Berl, Tomás; Beck, Gerald J.; Ritz, Eberhard; Shimizu, Miho; Kikuchi, Mami; Shobu, Yuko

doi:10.1007/s10157-017-1447-0

Cited by 30 publications

(32 citation statements)

References 18 publications

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“…Other studies have shown an association of microhaematuria with faster CKD progression [17]. Findings from the Chronic Renal Insufficiency Cohort (CRIC) study and the Evaluating Prevention of Progression in Chronic Kidney Disease (EPICC) trial, suggest an increased risk or ESRD after two years of follow-up in patients with baseline haematuria [18]. We now present the first study analysing the association of haematuria with disease severity and outcomes in a large population of biopsy-proven ATIN patients.…”

Section: Discussionmentioning

confidence: 89%

Hematuria Is Associated with More Severe Acute Tubulointerstitial Nephritis

Esteras

Fox

Geddes

et al. 2020

JCM

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Acute tubulointerstitial nephritis (ATIN) is a common cause of acute kidney injury. Although haematuria is a risk factor for the development of renal disease, no previous study has analyzed the significance of haematuria in ATIN. Retrospective, observational analysis of 110 patients with biopsy-proven ATIN was conducted. Results: Haematuria was present in 66 (60%) ATIN patients. A higher percentage of ATIN patients with haematuria had proteinuria than patients without haematuria (89.4% vs. 59.1%, p = 0.001) with significantly higher levels of proteinuria (median (interquartile range) protein:creatinine ratio 902.70 (513–1492) vs. 341.00 (177–734) mg/g, p <0.001). Moreover, those patients with more haematuria intensity had a higher urinary protein:creatinine ratio (1352.65 (665–2292) vs. 849.60 (562–1155) mg/g, p = 0.02). Those patients with higher proteinuria were more likely to need renal replacement therapy (22.7 vs. 0%, p = 0.03) and to suffer relapse (4 vs. 0%, p = 0.03). At the end of follow up, haematuric ATIN patients had higher serum creatinine levels (3.19 ± 2.91 vs. 1.91 ± 1.17 mg/dL, p = 0.007), and a trend towards a higher need for acute dialysis (7 vs. 1%, p = 0.09) and renal replacement therapy (12.1 vs. 2.3%, p = 0.12). Haematuria is common in ATIN and it is associated with worse renal function outcomes.

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Section: Discussionmentioning

confidence: 89%

Hematuria Is Associated with More Severe Acute Tubulointerstitial Nephritis

Esteras

Fox

Geddes

et al. 2020

JCM

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“…In experimental CKD, it reduces tissue accumulation of IS and pCS in diverse tissues, including the kidney and protected the kidneys in several animal models of AKI and CKD [ 122 ], However, two large multinational trials (EPPIC-1 and EPPIC-2), failed to show benefit on CKD progression [ 123 ]. However, a post-hoc, hypothesis-generating analysis observed that in the subgroup of high risk patients (urinary creatinine ratio ≥1.0 and haematuria) who were additionally treated with renin-angiotensin system blockade, AST-120 may have provided additional benefit in retarding CKD progression [ 124 ]. The large daily number of pills may negatively impact compliance and may be one of the underlying cause for the failure of clinical trials outside Japan.…”

Section: Nephroprotection Interventional Studies Targeting the Intmentioning

confidence: 99%

Impact of Altered Intestinal Microbiota on Chronic Kidney Disease Progression

Castillo-Rodríguez

Fernández-Prado

Esteras

et al. 2018

Toxins

120

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In chronic kidney disease (CKD), accumulation of uremic toxins is associated with an increased risk of CKD progression. Some uremic toxins result from nutrient processing by gut microbiota, yielding precursors of uremic toxins or uremic toxins themselves, such as trimethylamine N-Oxide (TMAO), p-cresyl sulphate, indoxyl sulphate and indole-3 acetic acid. Increased intake of some nutrients may modify the gut microbiota, increasing the number of bacteria that process them to yield uremic toxins. Circulating levels of nutrient-derived uremic toxins are associated to increased risk of CKD progression. This offers the opportunity for therapeutic intervention by either modifying the diet, modifying the microbiota, decreasing uremic toxin production by microbiota, increasing toxin excretion or targeting specific uremic toxins. We now review the link between nutrients, microbiota and uremic toxin with CKD progression. Specific focus will be placed on the generation specific uremic toxins with nephrotoxic potential, the decreased availability of bacteria-derived metabolites with nephroprotective potential, such as vitamin K and butyrate and the cellular and molecular mechanisms linking these toxins and protective factors to kidney diseases. This information provides a conceptual framework that allows the development of novel therapeutic approaches.

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“…A subanalysis in the patients enrolled in the study in the USA showed a delay in the treated group for reaching the primary endpoint which was a composite of RRT and doubling of serum creatinine [ 491 ], and this evolution was essentially observed in the group with diabetic nephropathy [ 491 ]. A further post hoc analysis showed that the benefit of AST-120 was limited to patients on ACEi/ARB with hematuria and urinary protein/creatinine ratio ≥ 1 [ 492 ], although this type of post hoc subgroup analysis is prone to substantial bias, especially as hematuria, as one of the parameters accounted for, is far from specific for intrinsic kidney disease.…”

Section: Pharmacological Treatmentmentioning

confidence: 99%

Deleting Death and Dialysis: Conservative Care of Cardio-Vascular Risk and Kidney Function Loss in Chronic Kidney Disease (CKD)

Vanholder

Laecke

Glorieux

et al. 2018

Toxins

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The uremic syndrome, which is the clinical expression of chronic kidney disease (CKD), is a complex amalgam of accelerated aging and organ dysfunctions, whereby cardio-vascular disease plays a capital role. In this narrative review, we offer a summary of the current conservative (medical) treatment options for cardio-vascular and overall morbidity and mortality risk in CKD. Since the progression of CKD is also associated with a higher cardio-vascular risk, we summarize the interventions that may prevent the progression of CKD as well. We pay attention to established therapies, as well as to novel promising options. Approaches that have been considered are not limited to pharmacological approaches but take into account lifestyle measures and diet as well. We took as many randomized controlled hard endpoint outcome trials as possible into account, although observational studies and post hoc analyses were included where appropriate. We also considered health economic aspects. Based on this information, we constructed comprehensive tables summarizing the available therapeutic options and the number and kind of studies (controlled or not, contradictory outcomes or not) with regard to each approach. Our review underscores the scarcity of well-designed large controlled trials in CKD. Nevertheless, based on the controlled and observational data, a therapeutic algorithm can be developed for this complex and multifactorial condition. It is likely that interventions should be aimed at targeting several modifiable factors simultaneously.

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Risk factors for progression of chronic kidney disease in the EPPIC trials and the effect of AST-120

Cited by 30 publications

References 18 publications

Hematuria Is Associated with More Severe Acute Tubulointerstitial Nephritis

Hematuria Is Associated with More Severe Acute Tubulointerstitial Nephritis

Impact of Altered Intestinal Microbiota on Chronic Kidney Disease Progression

Deleting Death and Dialysis: Conservative Care of Cardio-Vascular Risk and Kidney Function Loss in Chronic Kidney Disease (CKD)

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