End-stage renal disease in autosomal dominant polycystic kidney disease: a comparison of dialysis-related utilization and costs with other chronic kidney diseases

Brunelli, Steven M.; Blanchette, Christopher M.; Claxton, Ami J.; Roy, Debosree; Rossetti, Sandro; Gutiérrez, Benjamín

doi:10.2147/ceor.s76269

Cited by 23 publications

(22 citation statements)

References 11 publications

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“…Nevertheless, the administration of Tolvaptan causes some side effects, such as polyuria and high activity of hepatic enzymes, increasing the management costs of patients [9]. Therefore, dialysis is still the main therapy for ADPKD patients, but it requires high healthcare and personnel costs and limits the life quality of patients [10]. To improve benefits and reduce healthcare costs, the use of combined compounds able to target different pathways could be an attractive purpose for the treatment of ADPKD [11].…”

Section: Introductionmentioning

confidence: 99%

Double inhibition of cAMP and mTOR signalling may potentiate the reduction of cell growth in ADPKD cells

et al. 2016

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Background ADPKD is a renal pathology caused by mutations of PKD1 and PKD2 genes, which encode for polycystin-1 (PC1) and polycystin-2 (PC2), respectively. PC1 plays an important role regulating several signal transducers, including cAMP and mTOR, which are involved in abnormal cell proliferation of ADPKD cells leading to the development and expansion of kidney cysts that are a typical hallmark of this disease. Therefore, the inhibition of both pathways could potentiate the reduction of cell proliferation enhancing benefits for ADPKD patients. Methods The inhibition of cAMP- and mTOR-related signalling was performed by Cl-IB-MECA, an agonist of A3 receptors, and rapamycin, respectively. Protein kinase activity was evaluated by immunoblot and cell growth was analyzed by direct cell counting. Results The activation of A3AR by the specific agonist Cl-IB-MECA causes a marked reduction of CREB, mTOR, and ERK phosphorylation in kidney tissues of Pkd1flox/−: Ksp-Cre polycystic mice and reduces cell growth in ADPKD cell lines, but not affects the kidney weight. The combined sequential treatment with rapamycin and Cl-IB-MECA in ADPKD cells potentiates the reduction of cell proliferation compared with the individual compound by the inhibition of CREB, mTOR, and ERK kinase activity. Conversely, the simultaneous application of these drugs counteracts their effect on cell growth, because the inhibition of ERK kinase activity is lost. Conclusion The double treatment with rapamycin and Cl-IB-MECA may have synergistic effects on the inhibition of cell proliferation in ADPKD cells suggesting that combined therapies could improve renal function in ADPKD patients.

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Section: Introductionmentioning

confidence: 99%

Double inhibition of cAMP and mTOR signalling may potentiate the reduction of cell growth in ADPKD cells

et al. 2016

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“…A total of 28 papers were classified initially as potentially relevant and the full papers retrieved. Of the 28 articles, 14 potential relevant papers were excluded for the following reasons: no associated endpoint events data [12,13,15,31,32]; did not compare PKD and Non-PKD patients [33][34][35]; not distinguish dialysis modalities, such as HD or PD [36,37]; only epidemiological studies about ESRD due to PKD on PD [2,4]; enrolled patients from the same cohorts [10,38]. Finally, the remaining 14 articles [9, 16-26, 39, 40] were included in our meta-analysis.…”

Section: Discussionmentioning

confidence: 99%

“…It may be gradually playing an important role on patients with PKD in ESRD that health care resource utilization and costs for those requiring dialysis were needed to be considered. Therapeutic interventions that can prevent or delay the progression in ESRD patients with PKD for increased dialysis-free life [33] were needed to be considered.…”

Section: Discussionmentioning

confidence: 99%

Is Peritoneal Dialysis a Suitable Renal Replacement Therapy Option for Polycystic Kidney Disease Patients?

Zhang¹,

Dou²,

Wang³

et al. 2018

Kidney Blood Press Res

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Background/Aims: Mounting clinical experience and evidence from scale observational studies have suggested that polycystic kidney disease (PKD) was not a contraindication for peritoneal dialysis (PD). Recent studies have reported that PD may be associated with a better prognosis in PKD than that of non-PKD patients. To solve the problem, we performed a systematic review and comprehensive meta-analysis to compare the outcomes between PKD and non-PKD patients on PD and the all-cause mortality between patients with PKD on PD and hemodialysis (HD). Methods: We conducted a systematic literature using electronic databases (PubMed, Ovid, Embase and Web of Science) to identify the studies reporting the endpoint events of PKD/non-PKD patients with PD and the all-cause mortality between patients with PKD on PD and HD, such as dialysis adequacy, technique failure, PD-related complications, the mode of RRT change, and all-cause mortality. We searched the literature published February 2018 or earlier. We used both fix-effects and random-effects models to calculate the overall effect estimate. A sensitivity analysis and subgroup analysis were performed to find the origin of heterogeneity. Results: 12 studies with a total of 17,040 patients reported the endpoint events of PKD/non-PKD patients with PD. No significant difference was observed on dialysis adequacy (Kt/V, SMD: -0.02, 95%CI: -0.12–0.08; D: Pcr (4h), SMD: -0.10, 95% CI: -0.26–0.06), technique failure (RR: 0.97, 95%CI: 0.78-1.20), RRT change (RR: 0.96, 95%CI: 0.77-1.19), total PD-associated complications (RR: 1.0, 95%CI: 0.91-1.09) and all-cause mortality (RR: 0.40, 95%CI: 0.33–0.47) in PKD patients, compared with non-PKD subjects undergoing PD. However, the proportion of renal transplantation in PKD patients was higher than that of non-PKD patients (RR: 2.04, 95%CI: 1.88–2.20) with significant heterogeneity (I2 =82.7%, P=0.000). 4 studies with a total of 5,762 patients reported that the all-cause mortality did not differ between the PKD patients on PD and HD (RR: 0.87, 95%CI: 0.72-1.06). Conclusion: Our meta-analysis found that the outcomes of given population of PKD patients on PD were at least not inferior as compared to those with other primary kidney diseases, and suggested that PKD might be not absolutely a contraindication for PD. Given the limitations of the proposed, it needs further large-scale studies to assess whether PD is a suitable RRT option for end-stage renal disease (ESRD) patients with PKD.

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“…[36][37][38][39] In a retrospective study in a large dialysis organization in the United States that included 1,274 patients with ADPKD and aimed to quantify healthcare expenditures and costs for ADPKD patients with ESRD, the total healthcare costs for those patients were considerable -at US$4,254 per patient per month or US$51,048 per patient-year. 37 However, the same study showed that the total costs for ESRD patients other than those with ADPKD were higher. Another study in the United States that reviewed the administrative records of a private health insurer and included 1,913 patients with ADPKD demonstrated that higher charges are associated with advanced kidney disease, as the annual medical charges …”

Section: Burden Of Adpkd Economic Burdenmentioning

confidence: 99%

Is the light at the end of the tunnel nigh? A review of ADPKD focusing on the burden of disease and tolvaptan as a new treatment

Barnawi¹,

Attar²,

Alfaer³

et al. 2018

IJNRD

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Abstract:Autosomal dominant polycystic kidney disease (ADPKD) causes pathological cystic changes to the kidney and is characterized by numerous renal and systemic manifestations. ADPKD is the fourth most common renal disease requiring renal replacement therapy. In this report, we present a detailed review of ADPKD, with a particular focus on its major economic, psychological, and social burden in affected patients. Treatment of this disease has been based on prophylactic and supportive measures. However, in recent years, new drugs have emerged as promising agents that may retard the progression of ADPKD, such as tolvaptan. In this report, we provide an in-depth discussion of tolvaptan, which has shown an effect in decreasing annual total kidney volume growth and renal function decline, thus slowing disease progression. The mechanism of action, side effects, and available data on cost-effectiveness are discussed together with the results of the first clinical trials and the most recent trials with regard to its efficacy and safety. Tolvaptan has recently received approval and been granted marketing authorization in Japan, Canada, Korea, Switzerland, and Europe. A demand for widely accepted guidelines for its use has emerged since its approval. The currently available series of recommendations and guidelines as to when to start treatment with tolvaptan, as well as which patients should be treated, are also reviewed in this report. We lastly offer some considerations for future trials, and raise unanswered questions.

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End-stage renal disease in autosomal dominant polycystic kidney disease: a comparison of dialysis-related utilization and costs with other chronic kidney diseases

Cited by 23 publications

References 11 publications

Double inhibition of cAMP and mTOR signalling may potentiate the reduction of cell growth in ADPKD cells

Double inhibition of cAMP and mTOR signalling may potentiate the reduction of cell growth in ADPKD cells

Is Peritoneal Dialysis a Suitable Renal Replacement Therapy Option for Polycystic Kidney Disease Patients?

Is the light at the end of the tunnel nigh? A review of ADPKD focusing on the burden of disease and tolvaptan as a new treatment

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