Impact of the Preintervention Rate of Renal Function Decline on Outcome of Renoprotective Intervention

Lely, A. Titia; Kleij, Frank G.H. van der; Kistemaker, Taco J.; Apperloo, Alfred J.; Jong, Paul E. de; Zeeuw, Dick de; Navis, Gerjan

doi:10.2215/cjn.01450307

Cited by 13 publications

(8 citation statements)

References 20 publications

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“…Although this would increase trial duration it would improve validity. 13 In addition, there may be heterogeneity within individual CKD patients. The balance between altered excretory and endocrine function may be quite different between individuals.…”

Section: Heterogeneity Of Patient Characteristics and Outcomesmentioning

confidence: 99%

“…There is much to be learned from those who do not progress: more focus on those individuals may reveal insights for therapy. 13 Currently a number of large cohort studies are underway, [66][67][68][69][70][71] which will collect clinical information and biological samples on large numbers of people in different regions of the world. There are significant biobanks already established from large observational and clinical trial cohorts: 66,72,73 we should soon be able to better characterize our patient populations and understand progressive and nonprogressive disease and cross validate findings through proteomic, metabolomic, and genomic studies that are planned.…”

Section: Interventions To Delay Ckd Progressionmentioning

confidence: 99%

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Targets, trends, excesses, and deficiencies: refocusing clinical investigation to improve patient outcomes

Levin

Lancashire

Fassett

2013

Kidney International

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Clinical trials in nephrology have focused on achieving targets, supplementing deficiencies, and correcting excesses in order to improve patient outcomes. The majority of interventions have failed to demonstrate benefit and some have caused harm. It may be that therapies aiming to 'normalize' parameters may actually disturb evolutionary adaptation, thus causing harm. By refocusing on the physiology of disease, and complexity of adaptation, we may design better trials. We review successful and unsuccessful trials in nephrology and other disciplines and suggest a set of principles by which to design future clinical trials:(1) acknowledge heterogeneity of chronic kidney disease populations and appropriately characterize populations for studies; (2) develop better validated biomarkers (through proteomics, genomics, and metabolomics) to identify responders and nonresponders to interventions; (3) design interventions that mimic physiological processes without collateral detrimental effects; (4) reconsider the status of the randomized-controlled trial as the only 'gold standard' and perform large-scale pragmatic trials comparing current care with the intervention(s) of interest, and (5) broaden nephrology research culture so that the majority of patients are enrolled into observational cohorts and intervention studies, which foster greater knowledge acquisition and dissemination. Improved understanding of pathophysiological mechanisms, in conjunction with more innovative but stringent clinical trial design, will ultimately lead to improved patient outcomes.

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Section: Heterogeneity Of Patient Characteristics and Outcomesmentioning

confidence: 99%

Section: Interventions To Delay Ckd Progressionmentioning

confidence: 99%

Targets, trends, excesses, and deficiencies: refocusing clinical investigation to improve patient outcomes

Levin

Lancashire

Fassett

2013

Kidney International

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“…A recent analysis in one of the contradicting trials [19] showed that the preintervention rate of renal function loss (measured as creatinine clearance) was significantly higher in the ACE DD group compared with the other genotype groups [34]. Taking this preintervention rate into account, ACEi therapy did in fact benefit patients with the ACE DD genotype, but not those with ACE II/ ID genotype [34]. Therefore, although the REIN trial was the largest trial on the subject, other studies seem to confirm the findings.…”

Section: Discussionmentioning

confidence: 99%

Cost-effectiveness of ACE inhibitor therapy to prevent dialysis in nondiabetic nephropathy: influence of the ACE insertion/deletion polymorphism

Vegter

Perna

Hiddema

et al. 2009

Pharmacogenetics and Genomics

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Introduction End-stage renal disease is associated with high health-care costs and low quality of life compared with chronic kidney disease. The renoprotective effectiveness of angiotensin-converting enzyme inhibitors (ACEi) is largely determined by the ACE insertion/deletion (I/D) polymorphism. We determined the cost-effectiveness of ACEi therapy in nondiabetic nephropathy for the ACE II/ID and for the ACE DD genotype separately. Furthermore, we considered a selective screen-and-treat strategy in which patients are prescribed alternative, more effective, therapy based on their ACE (I/D) polymorphism.Methods Time-dependent Markov models were constructed; cohorts of 1000 patients were followed for 10 years. Data were mainly gathered from the Ramipril Efficacy In Nephropathy trial. Both univariate and probabilistic sensitivity analyses were performed.Results ACEi therapy dominated placebo in both the ACE II/ID group (h15 826, and 0.091 quality-adjusted life years gained per patient) and the ACE DD group (h105 104 and 0.553 quality-adjusted life years gained). Sensitivity analyses showed 30.2% probability of ACEi being not cost-effective in the ACE II/ID group, against an almost 100% probability of cost-effectiveness in the ACE DD group. A selective screen-and-treat strategy should incorporate an alternative therapy for patients with the ACE II/ID genotype with an at least 9.1% increase in survival time compared with ACEi therapy to be cost-effective. Sensitivity analyses show that higher effectiveness and lower costs of the alternative therapy improve the cost-effectiveness of a screening strategy.Conclusion ACEi therapy is a cost-saving treatment compared with placebo in nondiabetic nephropathy, irrespective of ACE (I/D) genotype. However, ACEi therapy saved more costs and more health gains were achieved in the ACE DD genotype than in the ACE II/ID genotype. An alternative treatment featuring a modest increase in effectiveness compared with ACEi therapy for patients with the ACE II/ID genotype can be incorporated in a cost-effective or even cost-saving screen-and-treat strategy.

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“…While there is substantial evidence that introduction of RASI can slow the rate of loss of renal function, there is much less evidence that there is a greater benefit in those patients with an initial acute fall in GFR. The available studies are few and post hoc, not matching their patient groups for pre‐intervention rate of loss of GFR, which, if different, would impact on the outcomes . If there is an acute fall in GFR following intervention with RASI, the likelihood of a long‐term benefit in GFR can be calculated from the pre‐intervention rate of loss, and actual, GFR, the size of the initial fall in GFR and the impact of the RASI on the rate of fall in GFR (Table ).…”

Section: Evidence That An Acute Fall In Gfr Following Rasi Will Lead mentioning

confidence: 99%

Use of renin angiotensin system inhibitors in patients with chronic kidney disease

Adam

Wright

2016

Internal Medicine Journal

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Current guidelines recommend renin angiotensin system inhibitors (RASI) as key components of treatment of hypertension in patients with chronic kidney disease (CKD), because of their effect on reducing the future rate of loss of glomerular filtration rate (GFR). A common risk of RASI in CKD is a haemodynamically mediated, and reversible, fall in GFR of varying severity and duration, any time after commencement of the Inhibitors. A benefit of the acute reduction in filtration rate with RASI may be a reduction in the future rate of loss in GFR: the greatest benefit likely to be in those patients with a greater rate of loss of GFR prior to, and a lesser acute loss of GFR after, introduction of RASI; and in those patients with significant proteinuria. An acute loss of GFR of >25% following the introduction of RASI is an indication to cease the RASI. An acute loss of GFR < 25% requires consideration of the likely risks of the lower GFR and benefits of any future reduced rate of loss of GFR. A fall in GFR in patients while on RASI is usually associated with a remediable cause. When the cause for the fall in GFR is not revealed, and the fall is less than 25%, hopeful expectancy is recommended. Hyperkalaemia in patients with CKD on RASI is more common with more severe disease, potassium retaining diuretics and hypoaldosteronism. Treatment should be modified to maintain a plasma potassium <6 mmol/L.

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Impact of the Preintervention Rate of Renal Function Decline on Outcome of Renoprotective Intervention

Cited by 13 publications

References 20 publications

Targets, trends, excesses, and deficiencies: refocusing clinical investigation to improve patient outcomes

Targets, trends, excesses, and deficiencies: refocusing clinical investigation to improve patient outcomes

Cost-effectiveness of ACE inhibitor therapy to prevent dialysis in nondiabetic nephropathy: influence of the ACE insertion/deletion polymorphism

Use of renin angiotensin system inhibitors in patients with chronic kidney disease

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