Effects of Octreotide–Long-Acting Release Added-on Tolvaptan in Patients with Autosomal Dominant Polycystic Kidney Disease: Pilot, Randomized, Placebo-Controlled, Cross-Over Trial

Trillini, Matias; Caroli, Anna; Perico, Norberto; Remuzzi, Andrea; Brambilla, Paolo; Villa, Giulia; Perna, Annalisa; Peracchi, Tobia; Rubis, Nadia; Martinetti, Davide; Caruso, Mariarosa; Leone, Valentina Fanny; Cugini, Daniela; Carrara, Fabiola; Remuzzi, Giuseppe; Ruggenenti, Piero

doi:10.2215/cjn.0000000000000049

Cited by 12 publications

(4 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A recent small, randomized trial in 19 participants with ADPKD showed that 4 weeks of treatment with octreotide combined with tolvaptan may reduce eGFR more effectively than octreotide and placebo. Octreotide reduced total and cystic kidney volumes and attenuated the aquaretic effect of tolvaptan [51]. This trial was too small, and the outcome was too short to allow conclusions.…”

Section: Adpkd Treatmentmentioning

confidence: 92%

Autosomal Dominant Polycystic Kidney Disease: Is There a Role for Autophagy?

Ponticelli,

Moroni,

Reggiani

2023

IJMS

View full text Add to dashboard Cite

Autosomal-Dominant Polycystic Kidney Disease (ADPKD) is a monogenic disorder initiated by mutations in either PKD1 or PKD2 genes, responsible for encoding polycystin 1 and polycystin 2, respectively. These proteins are primarily located within the primary cilia. The disease follows an inexorable progression, leading most patients to severe renal failure around the age of 50, and extra-renal complications are frequent. A cure for ADPKD remains elusive, but some measures can be employed to manage symptoms and slow cyst growth. Tolvaptan, a vasopressin V2 receptor antagonist, is the only drug that has been proven to attenuate ADPKD progression. Recently, autophagy, a cellular recycling system that facilitates the breakdown and reuse of aged or damaged cellular components, has emerged as a potential contributor to the pathogenesis of ADPKD. However, the precise role of autophagy in ADPKD remains a subject of investigation, displaying a potentially twofold impact. On the one hand, impaired autophagy may promote cyst formation by inducing apoptosis, while on the other hand, excessive autophagy may lead to fibrosis through epithelial to mesenchymal transition. Promising results of autophagy inducers have been observed in preclinical studies. Clinical trials are warranted to thoroughly assess the long-term safety and efficacy of a combination of autophagy inducers with metabolic and/or aquaferetic drugs. This research aims to shed light on the complex involvement of autophagy in ADPKD, explore the regulation of autophagy in disease progression, and highlight the potential of combination therapies as a promising avenue for future investigations.

show abstract

Section: Adpkd Treatmentmentioning

confidence: 92%

Autosomal Dominant Polycystic Kidney Disease: Is There a Role for Autophagy?

Ponticelli,

Moroni,

Reggiani

2023

IJMS

View full text Add to dashboard Cite

show abstract

“…All patients provided written informed consent to the procedures and to the use of their clinical laboratory data. According to the March 31, 2008 determination of the Agenzia Italiana del Farmaco ( https://www.gazzettaufficiale.it/eli/id/2008/03/31/08A02109/sg ), no specific patient informed consent and Ethical Committee approval was required because of the retrospective, purely observational nature of the study that was based on already available data–that had been already used for previous studies [ 9 , 10 , 26 ]—and did not require any additional clinical or laboratory data from considered patients.…”

Section: Methodsmentioning

confidence: 99%

GFR measurement in patients with CKD: Performance and feasibility of simplified iohexol plasma clearance techniques

Carrara,

Gaspari,

Trillini

et al. 2024

PLoS ONE

View full text Add to dashboard Cite

Implementing shortened one-compartment iohexol plasma clearance models for GFR measurement is crucial since the gold standard inulin renal clearance technique and the reference two-compartment, 10-hour, 16-samplings iohexol plasma clearance method are clinically unfeasible. Inulin may precipitate anaphylactic shock. Four-hour and 8-hour one-compartment iohexol plasma clearance models with Bröchner-Mortensen correction provide accurate GFR measurements in patients with estimated GFR (eGFR) > or ≤40 mL/min/1.73m2, respectively. We compared the performance of the simplified 5-hour, 4-samplings, two-compartment population pharmacokinetic model (popPK) with the performance of the reference two-compartment 10-hour iohexol method in 16 patients with GFR 15.2 to 56.5 mL/min/1.73 m2. We also compared the performance of shortened (5, 6 and 7-hour) one-compartment models with the performance of the standard 8-hour one-compartment model in 101 patients with eGFR ≤40 mL/min/1.73 m2. The performance of popPK and shortened methods versus reference methods was evaluated by total deviation index (TDI), concordance correlation coefficient (CCC) and coverage probability (CP). TDI <10%, CCC ≥0.9 and CP >90% indicated adequate performance. TDI, CCC and CP of popPK were 11.11%, 0.809 and 54.10%, respectively. All shortened, one-compartment models overestimated the GFR (p <0.0001 for all) as compared to the 8-hour model. TDI, CCC and CP were 7.02%, 0.815, and 75.80% for the 7-hour model, 7.26%, 0.803, and 74.20% for the 6-hour model, and 8.85%, 0.729 and 64.70% for the 5-hour model. The agreement of popPK model was comparable to that obtained with the Chronic-Kidney-Disease-Collaboration-Epidemiology (CKD-Epi) and the Modification-of-Diet-in-Renal-Disease (MDRD) serum-creatinine based equations for GFR estimation. PopPK model is remarkably unreliable for GFR measurement in stage III-IV CKD patients. In patients with eGFR ≤40 mL/min/1.73m2, shortened one-compartment models, in particular the 5-hour model, are less performant than the reference 8-hour model. For accurate GFR measurements, the iohexol plasma clearance should be measured with appropriate protocols. Over-simplified procedures should be avoided.

show abstract

“…The TKV can also serve as an indicator to evaluate the efficacy of candidate therapeutic agents that target cyst formation and growth in ADPKD patients [30][31][32][33][34][35][36][37][38]. Clinical studies have highlighted that drug treatment in these patients could limit kidney enlargement earlier, and to a greater extent, than slowing the renal function decline [11].…”

Section: Total Kidney Volumementioning

confidence: 99%

Abdominal Imaging in ADPKD: Beyond Total Kidney Volume

Caroli

Kline

2023

JCM

Self Cite

View full text Add to dashboard Cite

In the context of autosomal dominant polycystic kidney disease (ADPKD), measurement of the total kidney volume (TKV) is crucial. It acts as a marker for tracking disease progression, and evaluating the effectiveness of treatment strategies. The TKV has also been recognized as an enrichment biomarker and a possible surrogate endpoint in clinical trials. Several imaging modalities and methods are available to calculate the TKV, and the choice depends on the purpose of use. Technological advancements have made it possible to accurately assess the cyst burden, which can be crucial to assessing the disease state and helping to identify rapid progressors. Moreover, the development of automated algorithms has increased the efficiency of total kidney and cyst volume measurements. Beyond these measurements, the quantification and characterization of non-cystic kidney tissue shows potential for stratifying ADPKD patients early on, monitoring disease progression, and possibly predicting renal function loss. A broad spectrum of radiological imaging techniques are available to characterize the kidney tissue, showing promise when it comes to non-invasively picking up the early signs of ADPKD progression. Radiomics have been used to extract textural features from ADPKD images, providing valuable information about the heterogeneity of the cystic and non-cystic components. This review provides an overview of ADPKD imaging biomarkers, focusing on the quantification methods, potential, and necessary steps toward a successful translation to clinical practice.

show abstract

Effects of Octreotide–Long-Acting Release Added-on Tolvaptan in Patients with Autosomal Dominant Polycystic Kidney Disease: Pilot, Randomized, Placebo-Controlled, Cross-Over Trial

Cited by 12 publications

References 21 publications

Autosomal Dominant Polycystic Kidney Disease: Is There a Role for Autophagy?

Autosomal Dominant Polycystic Kidney Disease: Is There a Role for Autophagy?

GFR measurement in patients with CKD: Performance and feasibility of simplified iohexol plasma clearance techniques

Abdominal Imaging in ADPKD: Beyond Total Kidney Volume

Contact Info

Product

Resources

About