Patient Survey of current water Intake practices in autosomal dominant Polycystic kidney disease: the SIPs survey

Background: Autosomal dominant polycystic kidney disease (ADPKD) affects 12.5 million worldwide. Vasopressin drives cysts growth and in animal models can be suppressed through high water intake. A randomized controlled trial of ‘high’ versus ‘standard’ water intake in ADPKD is essential to determine if this intervention is beneficial. We conducted an ADPKD patient survey to gain an understanding of current fluid intake practices and the design challenges of a randomized water intake trial. Methods: In collaboration with the PKD Charity, we developed and distributed an online survey to ADPKD patients over age 16 years and not on renal replacement therapy. Results: Of the 2377 invited, 89 ADPKD patients completed the Survey of current water Intake practices in autosomal dominant Polycystic kidney disease (SIPs) online questionnaire. Most were female (65, 73%) and white (84, 94%), with a median age group of 45–49 years. The risk of contamination between treatment arms was highlighted by the survey as the majority (70, 79%) routinely discussed ADPKD management with family despite only 17% sharing the same household. More participants reported drinking beyond thirst (65, 73%) than those actually indicating a daily fluid intake of >2 L (54, 61%). This discrepancy emphasizes inaccuracies of fluid intake estimates and the requirement for objective methods of measuring water intake. Overall, only 51% believed high water intake was beneficial, while 91% were willing to participate in research evaluating this. Conclusion: ADPKD poses unique design challenges to a randomized water intake trial. However, the trial is likely to be supported by the ADPKD community and could impact significantly on PKD management and associated healthcare costs.We thank the PKD Charity for their help with the survey. R.E.-D. is supported by the PKD Charity and the Addenbrooke’s Charitable Trust. T.F.H. and F.E.K.F. are supported by the National Institute for Health Research (NIHR) and the Cambridge Biomedical Research Centre. This work was also supported by the British Renal Society and the British Kidney Patient Association

Vitamin K antagonists predispose to calciphylaxis in patients with end-stage renal disease.

BACKGROUND/AIMS: Calciphylaxis is associated with a poor prognosis in dialysis patients, and its pathogenesis remains incompletely understood. Although the use of vitamin K antagonists (VKA) has been implicated, previous reports are conflicting. We aimed to determine if vitamin K antagonists conferred an increased risk of calciphylaxis in patients on dialysis. METHODS: We performed a single-centre, retrospective cohort study of 2,234 patients receiving dialysis, and compared the characteristics of those with and without calciphylaxis. RESULTS: We identified 5 cases of calciphylaxis (all female) between January 2009 and December 2013. Overall, 142 patients (6.4%) were treated with VKA during the study period. Calciphylaxis was more common in the VKA group (4 of 142 patients, OR = 61, 95% CI 6.7-546, p = 0.0001). VKA was withdrawn in all cases and treatment instituted with sodium thiosulphate, cinacalcet and supportive measures. All patients recovered, although there was one sudden cerebrovascular death during follow-up. CONCLUSION: Treatment with VKA predisposes to the development of calciphylaxis.TFH is funded by the Cambridge BRC and NIHR.This is the accepted manuscript for a paper published in Nephron Clinical Practice, Vol. 129, No. 3, 2015, DOI:10.1159/00037144

High water vs. ad libitum water intake for autosomal dominant polycystic kidney disease: a randomized controlled feasibility trial.

BACKGROUND: Vasopressin stimulates cyst growth in autosomal dominant polycystic kidney disease (ADPKD) and is a key therapeutic target. Evaluation of high water intake as an alternative to pharmacological vasopressin blockade is supported by patients. However feasibility, safety and adherence-promoting strategies required to deliver this remain unknown. AIMS: Assess the feasibility of a definitive randomized high water intake trial in ADPKD. METHODS: In this prospective open-label randomized trial, adult ADPKD patients with eGFR ≥ 20 ml/min/1.73 m2 were randomized to prescribed high water (HW) intake targeting urine osmolality (UOsm) ≤270 mOsm/kg, or ad libitum (AW) intake (UOsm >300 mOsm/kg). Self-management strategies including home-monitoring of urine-specific gravity (USG) were employed to promote adherence. RESULTS: We enrolled 42 participants, baseline median eGFR (HW 68.4 [interquartile range (IQR) 35.9-107.2] vs. AW 75.8 [IQR 59.0-111.0 ml/min/1.73 m2, P = 0.22) and UOsm (HW 353 [IQR 190-438] vs. AW 350 [IQR 240-452] mOsm/kg, P = 0.71) were similar between groups. After 8 weeks, 67% in the HW vs. 24% in AW group achieved UOsm ≤270 mOsm/kg, P = 0.001. HW group achieved lower UOsm (194 [IQR 190-438] vs. 379 [IQR 235-503] mOsm/kg, P = 0.01) and higher urine volumes (3155 [IQR 2270-4295] vs. 1920 [IQR 1670-2960] ml/day, P = 0.02). Two cases of hyponatraemia occurred in HW group. No acute GFR effects were detected. In total 79% (519/672) of USG were submitted and 90% (468/519) were within target. Overall, 17% withdrew during the study. CONCLUSION: DRINK demonstrated successful recruitment and adherence leading to separation between treatment arms in primary outcomes. These findings suggest a definitive trial assessing the impact of high water on kidney disease progression in ADPKD is feasible

Establishing a core outcome set for autosomal dominant polycystic kidney disease : report of the Standardized Outcomes in Nephrology–Polycystic Kidney Disease (SONG-PKD) consensus workshop

The omission of outcomes that are of relevance to patients, clinicians and regulators across trials in autosomal dominant polycystic kidney disease (ADPKD) limits shared decision-making. The Standardized Outcomes in Nephrology – Polycystic Kidney Disease (SONG-PKD) Initiative convened an international consensus workshop on 25th October 2018, to discuss the identification and implementation of a potential core outcome set for all ADPKD trials. This article summarizes the discussion from the workshops and the SONG-PKD core outcome set. Key stakeholders including 11 patients/caregivers and 47 health professionals (nephrologists, policymakers, industry and researchers) attended the workshop. Four themes emerged: Relevance of trajectory and impact of kidney function included concerns about a patient’s prognosis and uncertainty of when they may need to commence kidney replacement therapy, and the lack of an early prognostic marker to inform long-term decisions; Discerning and defining pain specific to ADPKD highlighted the challenges in determining the origin of pain, adapting to the chronicity and repeated episodes of pain, the need to place emphasis on pain management and to have a validated measure for pain; Highlighting ADPKD consequences encompassed cyst-related complications and reflected patient’s knowledge because of family history and the hereditary nature of ADPKD; Risk of life-threatening but rare consequences such as cerebral aneurysm meant considering both frequency and severity of the outcome. Kidney function, mortality, cardiovascular disease and pain were established as the core outcomes for ADPKD

Supplementary Material for: Vitamin K Antagonists Predispose to Calciphylaxis in Patients with End-Stage Renal Disease

<b><i>Background/Aims:</i></b> Calciphylaxis is associated with a poor prognosis in dialysis patients, and its pathogenesis remains incompletely understood. Although the use of vitamin K antagonists (VKA) has been implicated, previous reports are conflicting. We aimed to determine if vitamin K antagonists conferred an increased risk of calciphylaxis in patients on dialysis. <b><i>Methods:</i></b> We performed a single-centre, retrospective cohort study of 2,234 patients receiving dialysis, and compared the characteristics of those with and without calciphylaxis. <b><i>Results:</i></b> We identified 5 cases of calciphylaxis (all female) between January 2009 and December 2013. Overall, 142 patients (6.4%) were treated with VKA during the study period. Calciphylaxis was more common in the VKA group (4 of 142 patients, OR = 61, 95% CI 6.7-546, p = 0.0001). VKA was withdrawn in all cases and treatment instituted with sodium thiosulphate, cinacalcet and supportive measures. All patients recovered, although there was one sudden cerebrovascular death during follow-up. <b><i>Conclusion:</i></b> Treatment with VKA predisposes to the development of calciphylaxis