DIETARY FACTORS ASSOCIATED WITH THE PROGRESSION OF AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE
Introduction: Dietary factors (sodium, protein, acid precursors, and fluid) have been observed to influence cyst growth in human and animal studies of autosomal dominant polycystic kidney disease (ADPKD). However, no studies have been conducted to control such dietary constituents. Body mass index (BMI) and high-density lipoprotein (HDL), factors associated with dietary behaviors, have also been reported to associate with ADPKD progression and warrant further examination. The following series of studies aimed to (1) determine whether patients could adhere to a low sodium, low protein, low acid precursor diet with increased fluid intake; (2) understand participants’ experiences and perspectives as they attempted to follow the diet; (3) reveal potential barriers that may reduce the likelihood of long-term adherence; (4) determine if data obtained from the electronic health record (EHR) can be used to identify risk factors associated with ADPKD progression (BMI and HDL). Methods: A four-week dietary intervention was conducted to determine if a relatively complex dietary prescription targeting salt, protein, acid precursors, and fluid intake would be adopted by adult patients with ADPKD. Consecutive 24-hour urine collections were analyzed for sodium, urea, net acid excretion (NAE), urine volume, and osmolality. Three-day diet records were analyzed for sodium, protein, net endogenous acid production (NEAP), and fluid intake. A basic metabolic panel was obtained from blood samples. Blood pressure, height, and weight were obtained by a nurse at each visit. Outcomes were measured at baseline, two weeks, and four weeks. Following the dietary intervention, interviews and a Nutrition Hassles Questionnaire (NHQ) were conducted with participants to determine how difficult it was for them to follow the diet. Finally, we collected BMI and HDL levels from the EHRs of ADPKD patients seen at the University of Kansas Medical Center and determined their associations with the age of reaching kidney failure (estimated glomerular filtration rate (eGFR) ≤ 15ml/min/1.73m2). Results: The dietary changes caused a decrease in daily sodium excretion (-20%), urea excretion (-28%), and NAE (-46%) while increasing urine volume 35% above baseline. Subjects eating the experimental diet reached the daily goals for sodium (≤ 1.5 mmol/kg), protein (≤ 1 g/kg), and fluid intake (mean 24h urine osmolality ≤ 285 mosm/kg) prescribed for each patient and were sustained for four weeks. NEAP decreased 58 mEq/d from baseline. Only one participant reported hassles on the NHQ as “moderately severe” and no hassles were reported as “extremely severe”. The NHQ also showed that 10 out of 11 individuals were “somewhat confident” or “very confident” that they could manage the new diet. The interviews conducted following the dietary intervention found a general consensus that reducing portion sizes of meat and increasing intake of fruits and vegetables were the easiest components of the diet while keeping track of what they ate and reaching the prescribed goal amount for fruits and vegetables each day were the most difficult components. Participants met their fluid goal and believed it to be an attainable amount long-term. Travel and meals away from home made following and tracking the diet more difficult. Participants stated a cell phone app may have mitigated some of these issues. Data collected from the EHR did not show an association of BMI with age at kidney failure (p=0.69, HR=1.096, 95% CI 0.697-1.724). By contrast, those with a desirable HDL (Men & Women: ≥60 mg/dL) had a significantly slower disease progression compared to individuals with low (Men: <40 mg/dL; Women <50 mg/dL) (p=0.0147, HR=0.271, 95% CI 0.095-0.774) and acceptable (Men: 40-59 mg/dL; Women 50-59 mg/dL) HDL levels (p=0.0436, HR=0.319, 95% CI 0.105-0.968). Conclusion: Dietary sodium, protein, and acid precursors can be effectively reduced while increasing fluid intake, and sustained for at least four weeks in patients with ADPKD. Eight out of twelve participants reported they could follow the diet over a much longer period of time. It is reasonable to suppose that our experimental diet could be used to ameliorate cyst growth in patients with ADPKD; however, long-term, adequately powered studies that evaluate structural and functional changes in kidney function need to be examined. Furthermore, participants reported that to move forward to a long-term dietary trial, the development of an app to help monitor and track dietary intake in individuals with ADPKD is necessary. Participants thought an app would help them be successful tracking and adhering to the diet long-term. The results of these studies provide new ways worthy of more robust, long-term testing to determine the efficacy of slowing disease progression. Additionally, analysis of ADPKD histories in the EHR confirms that HDL is positively associated with the age at kidney failure whereas BMI is not. Monitoring and improving HDL levels through dietary and lifestyle behaviors may provide additional benefits when included as part of a comprehensive lifestyle intervention. Collaborative efforts that would permit the mining of EHR data from multiple centers would allow for assessment of large-scale laboratory and clinical measurements to determine if additional risk factors for ADPKD progression should be routinely monitored in patients. If successful, these modifiable risk factors could be targeted in clinical trials in an effort to halt disease progression through dietary, lifestyle, or behavioral modifications.
Nutrition, Health sciences, dietary acid load, net acid excretion, net endogenous acid production, polycystic kidney disease, potential renal acid load, renal nutrition
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