Deceased organ donor characteristics and clinical interventions associated with organ yield.

While the function of each organ is used by each transplant team to assess suitability for transplantation, little is known about the donor characteristics and clinical interventions that contribute toward overall organ transplantation potential. We conduct a retrospective review of United Network for Organ Sharing (UNOS) deceased donor registry data from January 2005 to December 2006. This registry contains all deceased donors from whom organs were recovered during this time period (n = 15,601). Ordinary least-squares (OLS) regression models using variables in the registry are estimated to predict the number of organs transplanted. Outcome is the number of organs transplanted per donor. Organ yield is found to depend significantly on donor age, anoxia as cause of death, history of myocardial infarction (MI), hypertension and/or diabetes, body mass index (BMI), B or AB blood type, cocaine and/or cigarette use and hepatitis infection (p < 0.01). In addition, the clinical interventions of steroid administration, desmopressin (DDAVP) and diuretic usage, as well as oxygenation, are associated with organ yield. Both intrinsic donor characteristics and medical management practice are observed to be highly variable across organ procurement organizations (OPOs). These findings may provide important information to explore and assess the efficacy of clinical interventions, compare OPO performance and point to best practices.

Renal sonography: can it be used more selectively in the setting of an elevated serum creatinine level?

The objectives of our study were to (1) assess the outcomes resulting from the use of sonography in patients referred to our institution's ultrasound laboratory for an elevated serum creatinine level and (2) determine relevant clinical parameters in these patients to better triage them for sonography. We retrospectively identified and determined outcomes of 60 patients (20 women, 40 men; mean age, 61 years; range, 33 to 100 years) referred for sonographic evaluation because of an increased serum creatinine level (> or = 1.3 mg/dL). Ultrasound findings (hydronephrosis, renal size, and echogenicity) were correlated with clinical outcomes. Twenty-one patients (35%) had hydronephrosis, with 14 of these patients confirmed to be obstructed and five not obstructed. Two were indeterminate for obstruction. Eight of 14 obstructed patients were successfully treated. All obstructed patients had a suggestive history for obstruction with at least one of the following: pelvic mass (n = 9), stone disease (n = 4), or flank pain (n = 1). Only 2 of 44 patients, who were not obstructed, had any of these parameters (statistically significant difference, P < 0.0001). Thirty of the patients, who were not obstructed, had more likely alternative causes for renal failure, with sonography having no effect on patient management. Renal size and echogenicity had little effect on patient management. Sonography was efficacious in guiding management in patients with a suggestive history for obstruction (eg, pelvic mass, stone disease, or flank pain) but not in most patients who had no suggestive history and other more likely causes for renal failure.

Potentiation of effects of weight loss by monounsaturated fatty acids in obese NIDDM patients.

Although moderate weight loss improves glycemic control in obese NIDDM patients, quite often it is not normalized. To determine whether the response to weight loss can be improved by altering the macronutrient composition of hypocaloric diets, 17 obese NIDDM patients were studied at I) baseline, 2) after dieting for 6 weeks on a formula diet enriched in either monounsaturated fatty acids (MUFAs, n = 9) or carbohydrates (CHOs, n = 8) at a 50% caloric deficit, and 3) after 4 weeks of postdiet refeeding on the respective formulas with caloric intake titrated to achieve weight maintenance. Fasting, 24-h, and oral glucose tolerance test (OGTT) blood glucose, plasma insulin, and C-peptide levels were measured. All prediet parameters were similar between groups. After dieting, although weight loss was similar between groups, the fasting glucose level decreased significantly more in the MUFA group (-4.6 +/- 0.7 mmol/l) than in the CHO group (-2.4 +/- 1.0 mmol/l; P < 0.05). Twenty-four-hour glycemia decreased in both groups after dieting, but the MUFA group had a greater decrease than the CHO group (P < 0.05, analysis of variance [ANOVA]). Although decreases in fasting glycemia were maintained in both groups after refeeding, postprandial glycemia deteriorated after refeeding with the CHO- but not the MUFA-enriched formula (P < 0.05). After dieting and refeeding, fasting C-peptide increased 204 +/- 47 pmol/l in the MUFA group, but the CHO group remained at prediet levels (P < 0.05). Twenty-four-hour C-peptide levels were similar between groups after dieting and refeeding, despite the lower glycemia and CHO content of the MUFA formula. However, when equal amounts of CHO were consumed during the OGTT, the MUFA group had significantly higher C-peptide levels after both dieting and refeeding (P < 0.05). Fasting, 24-h, and OGTT insulin levels were similar between groups throughout the study. These results indicate that macronutrient composition is an important determinant of the glycemic response to weight-loss therapy in obese NIDDM patients. Based on the C-peptide response during the OGTT, increased CHO-induced insulin secretion is one possible mechanism by which this occurs.

Preliminary assessment of captopril sonography in screening for renal artery stenosis.

RATIONALE AND OBJECTIVES: We assessed the usefulness of the resistive index (RI) and renal length in predicting a significant renal artery stenosis (RAS) and evaluated the effect of captopril on the RI in kidneys with and without a significant RAS. METHODS: The RIs and renal lengths of both kidneys were measured in 39 patients who were referred for captopril renography for suspected renovascular hypertension. The difference in RIs (delta RI), the smaller RI (SRI), the difference in lengths (delta L), and the shorter length (SL) of the patient's two kidneys were determined. The accuracy of each of these parameters was calculated using captopril renography (n = 39) and arteriography (n = 9) as the gold standards. RESULTS: There was a significant difference in the delta RI (P < .05), SRI (p < .001), and delta L (p < .05) in patients with a positive captopril renogram for a significant RAS. Captopril increased delta RI (p = .052) in patients with a positive captopril renogram (n = 6). Use of an SRI threshold of less than .55 resulted in ultrasound being as accurate as captopril renography in predicting an angiographically documented stenosis of greater than or equal to 50%. CONCLUSION: The RI and renal length are useful in detecting a significant RAS. In this preliminary study, captopril was shown to increase delta RI in patients with a significant RAS, but larger prospective studies are necessary to further assess the value of captopril sonography in detecting a significant RAS.

Water and nonelectrolyte permeabilities of apical membranes of toad urinary bladder granular cells.

Certain types of epithelial cells such as those lining the toad urinary bladder have been classified as "tight" because their apical membranes exhibit low permeabilities to water, ions, and small nonelectrolytes. However, the permeability properties and structural features of these specialized apical membranes remain unclear because these membranes have never been purified. To isolate toad bladder granular cell apical membranes, we derivatized the bladder apical surface with the membrane-impermeant bifunctional reagent N-hydroxysulfosuccinimydyl-S,S-biotin (NHS-SS-biotin). After cell disruption, these derivatized apical membranes were purified using streptavidin-coated magnetic beads in a magnetic field. With the use of lactoperoxidase-mediated radioiodination as a marker for apical membrane, this preparative procedure purified apical membrane 48- or 72-fold as compared with homogenate. Thin section electron microscopy revealed unilamellar vesicles with some nonvesiculated membranes, while fragments of organelles such as mitochondria were absent. Water and nonelectrolyte permeabilities of purified apical membrane vesicles were similar to those obtained in intact bladders in the absence of antidiuretic hormone stimulation. The results demonstrate that isolated apical vesicles do not contain water channels and confirm the applicability of Overton's rule to the apical membrane of the toad urinary bladder. The technique has general applicability to isolation of other plasma membranes, and the apical membranes obtained are suitable for structural analysis.

Vasopressin alters the mechanism of apical Cl- entry from Na+:Cl- to Na+:K+:2Cl- cotransport in mouse medullary thick ascending limb.

Experiments were performed using in vitro perfused medullary thick ascending limbs of Henle (MTAL) and in suspensions of MTAL tubules isolated from mouse kidney to evaluate the effects of arginine vasopressin (AVP) on the K+ dependence of the apical, furosemide-sensitive Na+:Cl- cotransporter and on transport-related oxygen consumption (QO2). In isolated perfused MTAL segments, the rate of cell swelling induced by removing K+ from, and adding one mM ouabain to, the basolateral solution [ouabain(zero-K+)] provided an index to apical cotransporter activity and was used to evaluate the ionic requirements of the apical cotransporter in the presence and absence of AVP. In the absence of AVP cotransporter activity required Na+ and Cl-, but not K+, while the presence of AVP the apical cotransporter required all three ions. 86Rb+ uptake into MTAL tubules in suspension was significant only after exposure of tubules to AVP. Moreover, 22Na+ uptake was unaffected by extracellular K+ in the absence of AVP while after AVP exposure 22Na+ uptake was strictly K(+)-dependent. The AVP-induced coupling of K+ to the Na+:Cl- cotransporter resulted in a doubling in the rate of NaCl absorption without a parallel increase in the rate of cellular 22Na+ uptake or transport-related oxygen consumption. These results indicate that arginine vasopressin alters the mode of a loop diuretic-sensitive transporter from Na+: Cl- cotransport to Na+: K+: 2Cl- cotransport in the mouse MTAL with the latter providing a distinct metabolic advantage for sodium transport. A model for AVP action on NaCl absorption by the MTAL is presented and the physiological significance of the coupling of K+ to the apical Na+: Cl- cotransporter in the MTAL and of the enhanced metabolic efficiency are discussed.

Sodium-coupled ion cotransport and the volume regulatory increase response.

In conclusion, maintenance of volume homeostasis is a fundamental requirement of all cells. For many cell types, this process requires expression of ion cotransport mechanisms as well as accumulation of osmotically-active organic compounds. Recent observations have indicated that the cellular mechanisms responsible for modulating hypertonic volume regulation are complex and appear to involve hormonal, biochemical and physico-chemical stimuli. Knowledge of the specific ion-transport mechanisms involved in the initial phase of VRI, the factors that control their expression, and the interrelationships between inorganic and organic solute accumulation will be required before an in depth understanding of hypertonic cell volume regulation in medullary nephron segments can be achieved.

Renal inner medullary choline dehydrogenase activity: characterization and modulation.

Betaine belongs to the trimethylamine class of osmolytes (osmotically active substances believed to play an important role in cell volume homeostasis) and has recently been identified in the inner medulla of the mammalian kidney. Trimethylamines accumulate in the renal inner medulla during hypertonic stress, and betaine content in the inner medulla has been shown recently to increase during hypernatremia, yet the mechanisms governing the modulation of trimethylamine content and, in particular, of betaine content are not well understood. In this study, we demonstrate the presence of choline dehydrogenase activity in the renal inner medullas of three separate rat strains. Choline dehydrogenase is the enzyme that catalyzes the first of two successive oxidation steps in the biosynthetic conversion of choline to betaine. The presence of choline dehydrogenase activity in the inner medulla suggests that betaine accumulation in the inner medulla may result, at least in part, through in situ synthesis. The Km and Vmax of the reaction in the inner medullas of Long-Evans rats are 4.7 +/- 0.5 mM and 36.9 +/- 5.0 nmol.mg protein-1.min-1, respectively. These values are similar to the characteristics of choline dehydrogenase in mammalian liver. During hypernatremia, when betaine content of the inner medulla has been shown to increase 1.5-fold, choline dehydrogenase activity remains unchanged (or slightly increased), whereas enzyme activity in the cortex increases approximately 50%. Possible mechanisms of inner medullary betaine accumulation are discussed.

Modulation of Na-K-ATPase activity in the mouse medullary thick ascending limb of Henle. Effects of mineralocorticoids and sodium.

This study investigates the effect of variations in mineralocorticoid as well as cell sodium delivery and uptake on Na-K-ATPase activity in the mouse medullary thick ascending limb of Henle (mTALH). Pharmacologic doses of the mineralocorticoid deoxycorticosterone acetate (DOCA) resulted in a 28% increase of Na-K-ATPase activity. Furosemide-induced inhibition of sodium uptake by the mTALH cell also resulted in Na-K-ATPase activity reduction (45%). Sodium deprivation did not cause a clear change in enzyme activity, either at 3 d or 2 wk, likely reflecting the result of the opposing influences of decreased sodium delivery and increased endogenous aldosterone. Finally, the behavior of Na-K-ATPase activity at 3 d of sodium deprivation in the mTALH contrasted with a 60% increase in activity observed in the cortical collecting tubule, a nephron segment known to be responsive to mineralocorticoid, and this heterogeneity of response may suggest an important role for the mTALH in maintaining salt homeostasis.

Effects of pH on bone calcium and proton fluxes in vitro.

Bone mineral is thought to decompose during acute and chronic metabolic acidosis and thereby contribute to buffering of the acid load. We cultured neonatal mouse calvariae for 3 h and found calcium efflux from bone when the medium pH was below 7.40, calcium influx into bone when the pH was above 7.40, and no net flux at pH 7.40. The calcium flux varied to the same extent when medium pH was altered by a primary change in the medium bicarbonate concentration or in the partial pressure of carbon dioxide. Calcium and proton fluxes were inversely correlated (r = -0.713, P less than 0.001), and the slope of the linear regression indicated that between 16 and 21 neq of proton entered the calvariae in exchange for each neq of calcium that left. In 24-h cultures, acid medium also caused net calcium efflux from bone, and alkaline medium caused net influx. PTH increased calcium efflux at acid but not at alkaline medium pH. Sodium azide resulted in net influx of calcium into bone at all values of medium pH. Calcium release by cultured calvariae in response to low medium pH is associated with proton buffering; over 3 h the stoichiometry indicates that little buffering is due to the dissolution of calcium-containing crystals. Effects of medium pH on calcium release are amplified by PTH, and calcium efflux can be prevented by the metabolic inhibitor sodium azide.