The Effect of Dietary Intervention on Autosomal-Dominant Polycystic Kidney Disease (ADPKD) Patients on Tolvaptan and Their Quality of Life.

Background and objective Autosomal-dominant polycystic kidney disease (ADPKD) is the most common inherited renal disorder; it affects people of all ethnic groups and is found in up to 10% of patients with end-stage renal disease (ESRD). Dietary intervention is important in people with renal disease, and it has been linked to greater estimated glomerular filtration rate (eGFR) preservation. Tolvaptan, an orally-active nonpeptide, selective arginine vasopressin (AVP) V2R antagonist, was recently licensed in numerous countries for the treatment of ADPKD. The aim of this study was to assess the role of dietary intervention in decreasing the osmotic load on the urine volume and its impact on the quality of life (QOL) of patients with ADPKD on tolvaptan. Methods This prospective cohort study was carried out at a Hamilton nephrology genetics clinic. ADPKD patients on well-tolerated doses of tolvaptan for three months were included in the study. Gitelman and Bartter Symptom Health-related QOL questionnaire was used among the study participants. Results Our study consisted of nine adult patients with ADPKD who were on a stable dose of tolvaptan therapy. Patients had laboratory values for urine volume, sodium (Na), and urea. No significant difference was found between pre- and post-diet intervention values in 24-hour urine volume (5.9 vs. 5.49 L/d; p=0.423), urine Na (p=0.174), and 24-hour urine urea (p=0.404). Conclusion Dietary intervention in ADPKD patients on tolvaptan therapy can play a vital role in improving their QOL. Further research including interventional studies and clinical trials with larger sample sizes is needed to gain deeper insight into the subject.

A Case Report of Tolvaptan Therapy for ADPKD Patients With COVID-19. The Need for Appropriate Counselling for Temporary Drug Discontinuation.

BACKGROUND: Patients with autosomal dominant polycystic kidney disease (ADPKD) may require specific therapy with vasopressin receptor antagonists to slow the progression of renal disease. Because of its mechanism of action, the most common side effects are polyuria, nocturia, and polydipsia. Elevations of liver enzyme levels can also occur during treatment with Tolvaptan. Temporary drug withdrawal may be indicated if the patient is unable to hydrate adequately or if there are concomitant causes of dehydration, including major infectious events. During the Coronavirus Disease 2019 (COVID-19) pandemic, this should be considered in the management of patients on Tolvaptan therapy. CASE REPORT: We present the clinical case of a 51-year-old male with severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2) infection and ADPKD receiving Tolvaptan therapy with particular reference to the medical management of the patient during the infectious event. The patient was instructed to discontinue promptly Tolvaptan as soon as symptoms appeared. He was treated with forced hydration and symptomatic therapy. Nevertheless, a transient elevation of liver enzyme levels was detected. The timely discontinuation of Tolvaptan therapy avoided the risk of potential hepatotoxicity in a condition of known susceptibility. CONCLUSION: Tolvaptan therapy of patients with ADPKD is safe even during SARS-CoV-2 infection. There is need for appropriate and prompt patient counseling to avoid potentially adverse side effects.

Autosomal Dominant Polycystic Kidney Disease Does Not Significantly Alter Major COVID-19 Outcomes among Veterans.

Autosomal dominant polycystic kidney disease (ADPKD) was not a significant, independent risk factor for the four major outcomes studied among veterans with confirmed coronavirus disease 2019 (COVID-19).ADPKD did not significantly increase the risk for newly starting dialysis (after controlling for CKD) among veterans positive for COVID-19.The established risk factors for severe COVID-19 illness had significant effects in this cohort (e.g., type 2 diabetes and Black race).

The Impact of COVID-19 on Patients With ADPKD.

PURPOSE OF REVIEW: Patients with autosomal dominant polycystic kidney disease (ADPKD) have kidney cysts and kidney enlargement decades before progressing to advanced chronic kidney disease (CKD), meaning patients live most of their adult life with a chronic medical condition. The coronavirus disease 2019 (COVID-19) pandemic has created common questions among patients with ADPKD. In this review, we discuss COVID-19 concerns centered around a patient with a common clinical vignette. SOURCES OF INFORMATION: We performed PubMed and Google scholar searches for English, peer-reviewed studies related to "COVID-19," "ADPKD," "CKD," "tolvaptan," "angiotensin-converting enzyme inhibitors" (ACEi), "angiotensin receptor blockers" (ARB), and "vaccination." We also evaluated transplant data provided by the Ontario Trillium Gift of Life Network. METHODS: Following an assessment of available literature, this narrative review addresses common questions of patients with ADPKD in the context of the COVID-19 pandemic. KEY FINDINGS: Data regarding the risk of developing COVID-19 and the risk of adverse COVID-19 outcomes in patients with ADPKD remain limited, but patients with ADPKD with impaired estimated glomerular filtration rate (eGFR), kidney transplants, or on dialysis are likely at similar increased risk as those with generally defined CKD. We provide strategies to improve virtual care, which is likely to persist after the pandemic. Current evidence suggests ACEi, ARB, and tolvaptan treatment should be continued unless contraindicated due to severe illness. When available, and in the absence of a severe allergy, vaccination is recommended for all patients with ADPKD. LIMITATIONS: This narrative review is limited by a paucity of high-quality data on COVID-19 outcomes in patients specifically with ADPKD. IMPLICATIONS: Patients with ADPKD who have developed advanced CKD, require dialysis, or who have received a kidney transplant are at elevated risk of COVID-19 complications.

mtor Haploinsufficiency Ameliorates Renal Cysts and Cilia Abnormality in Adult Zebrafish tmem67 Mutants.

BACKGROUND: Although zebrafish embryos have been used to study ciliogenesis and model polycystic kidney disease (PKD), adult zebrafish remain unexplored. METHODS: Transcription activator-like effector nucleases (TALEN) technology was used to generate mutant for tmem67, the homolog of the mammalian causative gene for Meckel syndrome type 3 (MKS3). Classic 2D and optical-clearing 3D imaging of an isolated adult zebrafish kidney were used to examine cystic and ciliary phenotypes. A hypomorphic mtor strain or rapamycin was used to inhibit mTOR activity. RESULTS: Adult tmem67 zebrafish developed progressive mesonephric cysts that share conserved features of mammalian cystogenesis, including a switch of cyst origin with age and an increase in proliferation of cyst-lining epithelial cells. The mutants had shorter and fewer distal single cilia and greater numbers of multiciliated cells (MCCs). Absence of a single cilium preceded cystogenesis, and expansion of MCCs occurred after pronephric cyst formation and was inversely correlated with the severity of renal cysts in young adult zebrafish, suggesting a primary defect and an adaptive action, respectively. Finally, the mutants exhibited hyperactive mTOR signaling. mTOR inhibition ameliorated renal cysts in both the embryonic and adult zebrafish models; however, it only rescued ciliary abnormalities in the adult mutants. CONCLUSIONS: Adult zebrafish tmem67 mutants offer a new vertebrate model for renal cystic diseases, in which cilia morphology can be analyzed at a single-nephron resolution and mTOR inhibition proves to be a candidate therapeutic strategy.