Samuel O. Thier

Anticystinuric Effects of Glutamine and of Dietary Sodium Restriction

We studied four patients with cystinuria to assess the effects of glutamine and dietary sodium on the urinary excretion of dibasic amino acids. In Patient 1, at an ad libitum dietary sodium intake of about 300 mmol per day, oral administration of glutamine led to reproducible and marked anticystinuria and antiornithinuria, whereas the excretion of lysine and arginine was not significantly affected. In Patient 2, at an ad libitum dietary sodium intake of about 150 mmol per day, no effect of glutamine could be demonstrated in studies lasting up to three weeks. Since the principal difference between Patients 1 and 2 was their dietary intake of sodium, Patient 3 was studied during dietary sodium intakes of 150 and 300 mmol per day. His cystine excretion was found to be higher at 300 than at 150 mmol per day. Glutamine suppressed his cystine excretion at a sodium intake of 300 mmol per day but had no effect at 150 mmol per day. When the effect of a further reduction in sodium intake alone was studied in a fourth patient, a decrease of 150 to 50 mmol per day was found to reduce cystine excretion markedly within 17 days. The low-sodium diet alone also reduced the excretion of lysine, arginine, and ornithine. We conclude that glutamine may reduce the excretion of dibasic amino acids at a high sodium intake but not at an intake of about 150 mmol per day. However, since a sodium-dependent excretion of the dibasic amino acids occurs at an intake down to about 50 mmol of sodium per day, dietary restriction of sodium can provide a safe approach to the treatment of cystinuria.

CYSTINURIA: IN VITRO DEMONSTRATION OF AN INTESTINAL TRANSPORT DEFECT.

A defect in the transport of L-cystine and L-lysine has been found in the intestinal mucosa of patients with cystinuria. Transport studies in normal intestinal mucosa, in contrast to similar studies in the kidney, show that cystine and lysine are mutually inhibitory.

Adverse Renal and Metabolic Effects Associated with Oral Sodium Phosphate Bowel Preparation

Colorectal cancer can be prevented by the removal of adenomatous polyps during screening colonoscopy, but adequate bowel preparation is required. Oral sodium phosphate (OSP), an effective bowel purgative, is available over the counter and requires a substantially lower volume than polyethylene glycol-based preparative agents. Accumulating reports implicate OSP in electrolyte disturbances as well as acute kidney injury (AKI) in a syndrome termed phosphate nephropathy (a form of nephrocalcinosis). Despite published case reports and case series, the actual incidence, risk factors, and natural history of phosphate nephropathy remain largely undefined. Several recent observational studies have provided new information on these important issues while supporting a link between OSP and acute phosphate nephropathy as well as the development of chronic kidney disease in elderly patients, many of whom had a normal serum creatinine at the time of OSP ingestion. This review summarizes current knowledge about the renal complications of OSP, risk factors for its development, and the pathophysiology of acute and chronic kidney damage in nephrocalcinosis.

Metabolic Basis of Renal-Stone Disease

URINARY calculi form when the concentration of the crystal-forming substances of which they are composed exceeds solubility. That even this apparent truism generates discussion and requires clarifi...

Forces motivating the use of health status assessment measures in clinical settings and related clinical research.

The subject is obviously an interesting one. I can see that the attendees represent a very broad set of interests and expertise. Those facts reflect the growing sense that assessing health status functional outcomes has something of an inevitability to it: people are beginning to think that they had best begin to understand and participate in this field. It is important to understand, however, that something that is inevitable does not necessarily have to happen during your lifetime. Just because there is a logic behind this inevitability does not mean that you can avoid spending a lot of time on strategic and practical aspects of translating health status measurement into real use. This conference is intended to address a

The Physiologic Approach to Hyperuricemia

HYPERURICEMIA is an easily detected and common chemical abnormality. Since the clinical importance of this abnormality has not been well defined, hyperuricemia presents a confusing problem for the ...

Breast-Cancer Screening: A View from outside the Controversy

IN its highest form medical controversy provides the energy for inquiry and progress. When controversy descends from the intellectual to the emotional plane, participants become more the advocates ...

The Continuing Dilemma in Clinical Investigation and the Future of American Health Care: A System-Wide Problem Requiring Collaborative Solutions.

American medicine faces a paradox: on the one hand, decades of basic science research have produced fundamental insights into disease mechanisms. On the other, there has rarely been a more difficult environment for the training and employment of clinical investigators, who perform the research that translates basic biomedical knowledge into practical advances in patient care. The authors explain the historical roots of this crisis and the lack of data about specific workforce needs for clinical investigators, discuss long-standing difficulties of recruiting, training, and retaining these scientists (e.g., time-consuming training, inadequate emphasis on clinical research in medical school, fewer role models) and why these processes are becoming more difficult (e.g., a coming flattening of federal support for research; the impact of managed care on academic health centers). In confronting this problem, the authors stress the importance of (1) carefully defining the major subtypes of clinical investigation (i.e., physiologic investigation, outcomes research, and clinical trials) and noting which are and which are not endangered; (2) understanding the potential solutions to the problem that have been offered in the past; and (3) defining and hopefully marshaling a coalition of those institutions whose resources are currently available to address the problem and that have an important stake in its solution: academic health centers, the National Institutes of Health, health care providers, foundations and educational societies, medical schools, and industry. The authors stress that finding solutions to the current problem are a shared responsibility that must be carried out, for without well-trained and innovative clinical investigators, the social contract of biomedical research-to keep society well-cannot be fulfilled.

Amino acid accumulation in the toad bladder relationship to transepithelial sodium transport

Abstract Amino acid accumulation has been studied in the toad bladder. The mucosal surface of the epithelial cells is impermeable to amino acid movement in either direction. Concentrative uptake of amino acid occurs through the serosal surface. The uptake of the neutral amino acid α-aminoisobutyric acid is sodium dependent, ouabain sensitive and unaffected by anaerobiosis. The concentrative uptake of amino acids may be independent of processes for transepithelial sodium transport, though the energy-requiring steps for both processes are thought to be in the serosal surface of the mucosal epithelial cells. The last observation makes unlikely the postulate that sodium serves a non-specific role in the production of energy for transport.

The effect of extracellular sodium concentration on the kinetics of α-aminoisobutyric acid transport in the rat kidney cortex slice

Abstract The kinetics of α-aminoisobutyric acid (AIB) accumulation by the rat kidney cortex slice under conditions of varying extracellular sodium concentration were investigated. Reduced extracellular sodium concentration resulted in a diminished initial uptake of amino acid and reduced influx under steady-state conditions. Efflux was accelerated under steady-state conditions and initial efflux was accelerated by reducing extracellular sodium concentration to below intracellular concentration. These findings are consistent with the concept of a linked sodium and amino acid transport mechanism.