Patients undergoing chronic hemodialysis suffer large morbidity and mortality rates even with application of modern techniques. Although comorbidities due to age, diabetes and hypertension contribute to this situation, a """"""""residual syndrome"""""""" derives from the imperfect nature of dialysis. Multiple solutes are retained in high levels even with dialysis judged to be adequate by urea removal. The HEMO trial points to several classes as particularly poorly removed by high flux or high KT/V and therefore worthy of consideration- protein bound ones and those sequestered in cells and poorly equilibrating across the cellular- extracellular interface. Small aliphatic amines, trimethylamine , dimethylamine and monomethylamine are disproportionately located in the cellular compartment, accumulate in uremia and have toxicities. Thus, as a class, they are strong candidates for contributors to the residual syndrome. Their normal handling by the kidney is poorly understood. The efficacy of dialysis in their removal has not been measured. Their metabolism in ESRD and their pathways of production are also obscure. We propose the following specific aims: 1) Measure the normal renal handling of these compounds and quantitate their daily urinary excretion in normal adult subjects. 2) Measure their clearance by hemodialysis and calculate their distribution and intercompartmental exchange in subjects with ESRD. 3) Measure the production and non renal clearance of monomethylamine in normal and ESRD subjects. 4) Removal of MMA, DMA, TMA and TMAO compared with urea at standard and extended dialysis durations Currently dialysis is prescribed based on urea's behavior. If this treatment is to be improved, the biochemistry, physiology and dialysis characteristics of other classes of uremic retention solutes different from urea must be understood. The aliphatic amines constitute members of one such class of compounds and we propose to develop the critical description of their behavior in uremia. Currently dialysis is prescribed based on urea's behavior. If this treatment is to be improved, the biochemistry, physiology and dialysis characteristics of other classes of uremic retention solutes different from urea must be understood. The aliphatic amines constitute members of one such class of compounds and we propose to develop the critical description of their behavior in uremia. ? ? ?
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