Prediction of renal crystalline size distributions in space using a PBE analytic model. 2. Effect of dietary countermeasures

Abstract

is used to assess the efficacy of citrate, pyrophosphate, and augmented fluid intake as dietary countermeasures aimed at reducing the risk of renal stone formation for astronauts. The model uses the measured biochemical profile of the astronauts as input and predicts the steady-state size distribution of the nucleating, growing, and agglomerating renal calculi subject to biochemical changes brought about by administration of these dietary countermeasures. Numerical predictions indicate that an increase in citrate levels beyond its average normal groundbased urinary values is beneficial but only to a limited extent. Unfortunately, results also indicate that any decline in the citrate levels during space travel below its normal urinary values on Earth can easily move the astronaut into the stone-forming risk category. Pyrophosphate is found to be an effective inhibitor since numerical predictions indicate that even at quite small urinary concentrations, it has the potential of shifting the maximum crystal aggregate size to a much smaller and plausibly safer range. Finally, our numerical results predict a decline in urinary volume below 1.5 liters/day can act as a dangerous promoter of renal stone development in microgravity while urinary volume levels of 2.5-3 liters/day can serve as effective space countermeasures.nephrolithiasis; gravity; weightlessness; crystal nucleation; crystal growth; agglomeration; inhibition; dietary countermeasures NEPHROLITHIASIS IS NOT ONLY a problem within the general population on Earth but is also a risk to the astronauts' health and survival during future long-duration missions where exposure to microgravity and other space conditions are likely to increase the risk of renal stone formation. The concern seems to be justified since a recent survey of renal stone formation in US astronauts has revealed 14 recorded postflight episodes (13, 26). Whether on Earth or in space, the development of calcium oxalate (CaOx) renal stones is initiated with nucleation of the sparingly soluble salt from a supersaturated urine as the necessary first step, followed by simultaneous growth and agglomeration of the crystals as two effective stone size-enhancing mechanisms. While the extent of urinary CaOx supersaturation in the nephron changes continuously depending on the level of hydration and the extent of other dietary intake, the urine of most individuals, healthy or stone former, remains supersaturated under normal everyday conditions.The progression from crystal nucleation and growth to a clinical colic situation is not yet well understood, but it is thought to occur by either free-or fixed-particle mechanisms (13, 32). Recent studies by Kim et al. (14) and Evan et al. (7) using advanced endoscopic imaging and comprehensive physiological biopsies suggest three possible free/fixed pathways to stone formation: 1) nucleation and growth on the Randall plaque deposits in the papillae; 2) growth after adherence to a possibly injured section of collecting or Bellini ducts; and 3) homogeneous nucleatio...

Prediction of renal crystalline size distributions in space using a PBE analytic model. 1. Effect of microgravity-induced biochemical alterations

“…Since citrate is an important natural inhibitor in urine, the value of these rate constants have to be adjusted for the citrate content of the urine. This direct inhibitory effect of citrate on the rate constants is accounted for in the present work through adjustment of the rate constants based on the published data in the literature as discussed in detail in our companion paper (8). Here, the inhibited rate constants for each subject as adjusted based on their reported 24-h urinary citrate concentrations (see Table 1) are included in Table 2.…”

“…The situation is, again, further exacerbated by the scarcity of data on how the agglomeration constant is altered due to the direct inhibitive effect of certain constituents of urine such as citrate (11). The value of the agglomeration kernel for the microgravity astronaut as included in Table 2 includes an adjustment due to the citrate content of the subject's urine (8,11). Without the citrate inhibition effect, the magnitude of ␤ is given by its nominal value of 2.87(10) Ϫ14 m 3 /s in Table 2.…”

“…Some of the kinetic inhibitory properties of urine have been considered in the present model, and the effects of citrates and pyrophosphates are specifically examined in more detail in the companion paper (8). However, the list of constituents that may act as urinary inhibitors to CaOx precipitation are exhaustive, and data and an understanding of their inhibitive properties and mechanisms are not yet sufficiently complete to make their inclusion into deterministic mathematical models, even on a phenomenological basis, feasible at this point.…”

“…In part 1 of our study presented here, the model is used to assess the potential risks of renal stone development during space travel by predicting the population and size distributions of renal calculi for normal and stone-forming subjects on Earth and for astronauts after short-and long-duration space missions. In part II of our study presented in an accompanying paper (8), the model will be used to perform a comparative assessment of the efficacy of several possible dietary countermeasures in reducing the risk of renal stone development during space travel. The main inputs to the model for these simulations are the published urine biochemical data representing each of the subjects.…”

Medicina humana espacial: Performance fisiológico y contramedidas para mejorar la salud del astronauta

“…La alternativa efectiva para evitar la formación de cálculos renales, aparte del citrato de potasio y el pirofosfato añadido a la dieta del astronauta, es una adecuada y constante hidratación que mantenga el nivel urinario entre 2,5 a 3 litros/día (64) . En consecuencia, para minimizar el riesgo de enfermedad renal en el espacio se requiere desarrollar nuevas técnicas no invasivas, más seguras y rentables para la prevención, diagnóstico, control y tratamiento (22,65,66) .…”