Comparative Efficacy of Pharmacological Treatments for Adults With Autosomal Dominant Polycystic Kidney Disease: A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials

Abstract

Background: Tolvaptan is the gold standard treatment for autosomal dominant polycystic kidney disease (ADPKD), while several other drugs have the potential to inhibit the progression of ADPKD. However, individual clinical trials may not show sufficient differences in clinical efficacy due to small sample sizes. Furthermore, the differences in therapeutic efficacy among drugs are unclear. Herein, we investigated the effect of the ADPKD treatments.Methods: We systematically searched PubMed, Medline, EMBASE, and the Cochrane Library through January 2022 to identify randomized controlled trials in ADPKD patients that compared the effects of treatments with placebo or conventional therapy. A network meta-analysis was performed to compare the treatments indirectly. The primary outcomes were changes in kidney function and the rate of total kidney volume (TKV) growth.Results: Sixteen studies were selected with a total of 4,391 patients. Tolvaptan significantly preserved kidney function and inhibited TKV growth compared to the placebo {standardized mean difference (SMD) [95% confidence interval (CI)]: 0.24 (0.16; 0.31) and MD: −2.70 (−3.10; −2.30), respectively}. Tyrosine kinase inhibitors and mammalian target of rapamycin (mTOR) inhibitors inhibited TKV growth compared to the placebo; somatostatin analogs significantly inhibited TKV growth compared to the placebo and tolvaptan [MD: −5.69 (−7.34; −4.03) and MD: −2.99 (−4.69; −1.29), respectively]. Metformin tended to preserve renal function, although it was not significant [SMD: 0.28 (−0.05; 0.61), p = 0.09].Conclusion: The therapeutic effect of tolvaptan was reasonable as the gold standard for ADPKD treatment, while somatostatin analogs also showed notable efficacy in inhibiting TKV growth.Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42022300814.

A Novel COL4A5 Pathogenic Variant Joins the Dots in a Family with a Synchronous Diagnosis of Alport Syndrome and Polycystic Kidney Disease

“…The differential diagnosis of cystic kidney disease at early stages is especially important for the selection of patients who will benefit the most from current therapeutic approaches. While the administration of the selective vasopressin V2 receptor (V2R) antagonist, tolvaptan, is considered the gold standard treatment for ADPKD [40,41], clinical practice recommendations for the treatment of individuals with AS encourage the early use of angiotensinconverting enzyme (ACE) inhibitors that have proven efficient to reduce lifetime risk for ESRD [42,43]. In addition, as discussed above, COL4A5 genotype data can suggest the renal prognosis and partially predict the timing of ESRD, thus guiding the timing and intensity of intervention [44].…”

Manejo integral del síndrome cardiorrenal tipo 2

“…Por otro lado, existen antagonistas selectivos de la vasopresina tipo 2 (tolvaptán), que ha sido estudiado en los efectos de ICC, obteniendo beneficios favorables a corto plazo, como un incremento de los niveles séricos de sodio, TFG conservada y una recuperación clínica, si bien ayuda con la sintomatología, este medicamento no presenta mejoría en las tasas de morbimortalidad (34,35).…”