Pravastatin Therapy and Biomarker Changes in Children and Young Adults with Autosomal Dominant Polycystic Kidney Disease

Klawitter, Jelena; McFann, Kim; Pennington, Alexander; Wang, Wei; Klawitter, Jost; Christians, Uwe; Schrier, Robert W.; Gitomer, Berenice; Cadnapaphornchai, Melissa A.

doi:10.2215/cjn.11331114

Cited by 26 publications

(10 citation statements)

References 58 publications

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“…As expected, eGFR did not differ between the groups. Although LDL and total cholesterol levels did not correlate directly with clinical outcome variables (htTKV, albuminuria and LVMI), the statininduced change in urinary biomarkers of endothelial dysfunction was associated with prospective change in htTKV 115 . Routine statin treatment for cardiovascular indications is more prevalent in adults than in children.…”

Section: Statinsmentioning

confidence: 68%

International consensus statement on the diagnosis and management of autosomal dominant polycystic kidney disease in children and young people

et al. 2019

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Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic disease in adults, with an estimated prevalence of 1 in 500-2,500 (refs 1-4). Cyst development starts early in life, and macroscopic cysts can become detectable in childhood. Substantial disease burden with massively enlarged kidneys or decreased glomerular filtration rate (GFR) usually does not occur until adulthood 5 ; however, approximately 3% of children who carry ADPKD-causing mutations have either very-early-onset or unusually rapid progressive disease 5-7. Thus, the absolute incidence of symptomatic ADPKD in childhood is thought to be higher than that of other severe paediatric kidney diseases such as autosomal recessive polycystic kidney disease (~1 in 20,000), nephrotic syndrome (~1 in 50,000) 8 or haemolytic uraemic syndrome (~1 in 100,000 children) 9. The past 25 years have seen remarkable progress in knowledge of ADPKD. Advances have been made in unravelling the genetic origins of the disease, in noninvasive monitoring and in predicting disease progression; multiple large-scale clinical trials have been conducted; and the first pharmacological treatment for

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Section: Statinsmentioning

confidence: 68%

International consensus statement on the diagnosis and management of autosomal dominant polycystic kidney disease in children and young people

et al. 2019

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“…Renal interstitial inflammation and oxidative stress are prominent features of ADPKD, resulting in dense fibrosis, tubular atrophy and glomerulosclerosis 45–48 . Statin treatment was associated with less renal interstitial and systemic inflammation in the Han:SPRD rat model 14,16 ; likewise in the pediatric ADPKD trial, plasma levels of inflammatory and oxidative stress biomarkers declined during pravastatin treatment but not with placebo 49 . However, any anti-inflammatory effects did not translate into slower decline of eGFR in our post-hoc analysis of either Study A or Study B.…”

Section: Discussionmentioning

confidence: 90%

Effect of Statin Therapy on the Progression of Autosomal Dominant Polycystic Kidney Disease. A Secondary Analysis of the HALT PKD Trials

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Rahbari-Oskoui

et al. 2018

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Background Autosomal dominant polycystic kidney disease (ADPKD) commonly results in end-stage renal disease (ESRD), yet a long-term treatment that is well tolerated is still lacking. In a small randomized trial in children and adolescents pravastatin administration for 3 years was associated with reduced renal cyst growth, but no large trial has tested the effect of statins in adults. Methods We performed a post-hoc analysis of the HALT PKD trials to compare outcomes of participants who never used statins with those who used statin for at least 3 years. Because statins were not randomly allocated we used propensity score models with inverse probability of treatment weighting to account for imbalances between the groups. For subjects in Study A (preserved renal function, n=438) relevant outcomes were percent change in total kidney and liver volume and the rate of decline in estimated glomerular filtration rate (eGFR); for those in Study B (reduced renal function, n=352) we compared time to the composite endpoint of death, ESRD or 50% decline in eGFR. Follow-up was 5–8 years. Results There was no difference in any outcome between the 2 groups. However, limitations of this analysis are the small number of statin users in Study A, different statin drugs and doses used, non-randomized allocation and advanced disease stage in Study B. Conclusions Although this post-hoc analysis of the HALT PKD trials does not demonstrate a benefit of statin therapy, conclusions remain preliminary. A larger randomized trial in young people with ADPKD is necessary to answer the question whether statins can slow renal cyst growth and preserve kidney function.

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“…The inflammatory and OS biomarkers used were 9hydroxyoctadecadienoic acid (9-HODE), 13-HODE, and 15hydroxyeicosatetraenoic acid . Furthermore, the urinary 8-HETE, 9-HETE, and 11-HETE were positively associated with the change in HtTKV in the pravastatin group [94].…”

Section: Pravastatin In Young Adpkd Patients-nct00456365mentioning

confidence: 85%

Oxidative stress in autosomal dominant polycystic kidney disease: player and/or early predictor for disease progression?

et al. 2018

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Autosomal dominant polycystic kidney disease (ADPKD), caused by mutations in PKD1 or PKD2 genes, is the most common hereditary renal disease. Renal manifestations of ADPKD are gradual cyst development and kidney enlargement ultimately leading to end-stage renal disease. ADPKD also causes extrarenal manifestations, including endothelial dysfunction and hypertension. Both of these complications are linked with reduced nitric oxide levels related to excessive oxidative stress (OS). OS, defined as disturbances in the prooxidant/antioxidant balance, is harmful to cells due to the excessive generation of highly reactive oxygen and nitrogen free radicals. Next to endothelial dysfunction and hypertension, there is cumulative evidence that OS occurs in the early stages of ADPKD. In the current review, we aim to summarize the cardiovascular complications and the relevance of OS in ADPKD and, more specifically, in the early stages of the disease. First, we will briefly introduce the link between ADPKD and the early cardiovascular complications including hypertension. Secondly, we will describe the potential role of OS in the early stages of ADPKD and its possible importance beyond the chronic kidney disease (CKD) effect. Finally, we will discuss some pharmacological agents capable of reducing reactive oxygen species and OS, which might represent potential treatment targets for ADPKD.

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Pravastatin Therapy and Biomarker Changes in Children and Young Adults with Autosomal Dominant Polycystic Kidney Disease

Cited by 26 publications

References 58 publications

International consensus statement on the diagnosis and management of autosomal dominant polycystic kidney disease in children and young people

International consensus statement on the diagnosis and management of autosomal dominant polycystic kidney disease in children and young people

Effect of Statin Therapy on the Progression of Autosomal Dominant Polycystic Kidney Disease. A Secondary Analysis of the HALT PKD Trials

Oxidative stress in autosomal dominant polycystic kidney disease: player and/or early predictor for disease progression?

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