Effects of Short-Term Pistachio Consumption on Phosphorus, Parathyroid Hormone, Fibroblast Growth Factor 23, and Malondialdehyde Concentrations in Patients With Chronic Kidney Disease: A Randomized Crossover Trial

Introduction Cardiovascular diseases (CVD) remain the leading cause of mortality in patients with chronic kidney disease (CKD), and targeted nutritional management plays a critical role in mitigating CVD risk in this population. While extensive epidemiological evidence underscores the cardioprotective benefits of nut consumption, dietary guidelines for patients with CKD typically mandate strict phosphorus and potassium restriction. Consequently, nut intake is frequently discouraged in this group. This restriction stems from the impaired renal capacity to excrete excess phosphorus and potassium; unmitigated dietary phosphorus loading can exacerbate secondary hyperparathyroidism, renal osteodystrophy, vascular calcification, and overall cardiovascular morbidity and mortality. Conversely, overly restrictive phosphorus diets often precipitate inadequate intake of essential cardioprotective nutrients.

Phytate (phytic acid or myo-inositol hexaphosphate) is a naturally occurring compound abundant in fiber-rich foods, including whole grains, legumes, and nuts. It acts as an effective dietary inhibitor of calcium salt deposition, thereby mitigating risks associated with nephrolithiasis and vascular calcification. Nuts are rich sources of both dietary fiber and phytate, with pistachios standing out among the highest botanical sources-averaging 1,562 mg (range: 0.29-2.83 g) of inositol phosphate per 100 g. Accumulating evidence indicates that pistachio consumption may attenuate cardiovascular risk through anti-inflammatory, antioxidant, and lipid-lowering mechanisms, alongside favorable effects on blood pressure.

Crucially, the majority of phosphorus in unprocessed nuts is organically bound as phytate, which resists enzymatic cleavage in the human gastrointestinal tract, substantially reducing its intestinal bioavailability and systemic absorption. Therefore, a large proportion of phosphorus derived from natural nuts may not be systemically bioavailable. Given these favorable phytochemical profiles, moderate pistachio consumption by patients with CKD could potentially improve specific cardiovascular risk factors without adversely altering mineral metabolism. Nevertheless, interventional data evaluating the clinical safety and efficacy of nut consumption in CKD populations remain sparse. This study aims to evaluate the short-term effects of incorporating pistachios into the diets of patients with CKD on circulating and urinary phosphorus levels, as well as serum concentrations of parathyroid hormone (PTH), fibroblast growth factor 23 (FGF23), and malondialdehyde (MDA).

Methods This study is designed as an open-label, randomized, controlled crossover clinical trial. Eligible patients with stage 4 and 5 non-dialysis CKD presenting to the nephrology clinic will be informed of the study objectives, and written informed consent will be obtained prior to enrollment.

Prior to randomization, all participants will undergo a 1-week run-in period. During this phase, participants will initiate the standardized, modified pre-dialysis renal diet (protein: 0.8 g/kg/day, potassium: 39 mg/kg/day, and phosphorus: 12 mg/kg/day). The primary purpose of this run-in phase is to ensure participant adherence to the dietary protocol and to stabilize baseline metabolic parameters before the initiation of the experimental periods.