The incidence of nephrotoxicity occurring with the nonionic contrast agent, iohexol, and the ionic contrast agent, meglumine/sodium diatrizoate, was compared in 1196 patients undergoing cardiac angiography in a prospective, randomized, double-blind multicenter trial. Patients were stratified into four groups: renal insufficiency (RI), diabetes mellitus (DM) both absent (N = 364); RI absent, DM present (N = 318); RI present, DM absent (N = 298); and RI and DM both present (N = 216). Serum creatinine levels were measured at -18 to 24, 0, and 24, 48, and 72 hours following contrast administration. Prophylactic hydration was administered pre- and post-angiography. Acute nephrotoxicity (increase in serum creatinine of > or = 1 mg/dl 48 to 72 hours post-contrast) was observed in 42 (7%) patients receiving diatrizoate compared to 19 (3%) patients receiving iohexol, P < 0.002. Differences in nephrotoxicity between the two contrast groups were confined to patients with RI alone or combined with DM. In a multivariate analysis, baseline serum creatinine, male gender, DM, volume of contrast agent, and RI were independently related to the risk of nephrotoxicity. Patients with RI receiving diatrizoate were 3.3 times as likely to develop acute nephrotoxicity compared to those receiving iohexol. Clinically severe adverse renal events were uncommon (N = 15) and did not differ in incidence between contrast groups (iohexol N = 6; diatrizoate N = 9). In conclusion, in patients undergoing cardiac angiography, only those with pre-existing RI alone or combined with DM are at higher risk for acute contrast nephrotoxicity.(ABSTRACT TRUNCATED AT 250 WORDS)

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Our previous studies have demonstrated that raising ambient glucose from 100 to 450 mg/dl significantly inhibited the proliferation of mouse renal proximal tubule cells in culture. This effect was demonstrated after a latent period of 24 to 48 hours. Because transforming growth factor-beta (TGF-beta) inhibits cell proliferation in most epithelial cell lines, we hypothesized that the inhibitory effect of high glucose levels on cell proliferation may be mediated by TGF-beta. The present studies were performed to test the hypothesis that TGF-beta is an autocrine cytokine whose activity can be modulated by ambient glucose. Exogenous TGF-beta inhibited [3H]-thymidine incorporation in a dose-dependent fashion and with high affinity (picomolar range), but with slightly lower potency in high versus normal glucose media. Northern analysis of mRNA demonstrated that proximal tubule cells constitutively express TGF-beta 1 transcripts, and that the steady state level of TGF-beta 1 mRNA was, on average, 63% higher in the cells grown for 48 hours in high versus normal glucose media. Furthermore, the conditioned media of cells exposed to 450 mg/dl glucose exhibited endogenous TGF-beta bioactivity as measured by inhibition of cell proliferation. The addition of a rabbit antiporcine TGF-beta neutralizing antibody significantly increased basal thymidine incorporation in high glucose media to levels approaching those of cells grown in normal glucose media. In contrast, the anti-TGF-beta antibody did not have a significant effect on the growth of cells in the normal glucose media.(ABSTRACT TRUNCATED AT 250 WORDS)

Once considered mostly a postsurgical condition, intra-abdominal hypertension (IAH) and the abdominal compartment syndrome (ACS) are now thought to increase morbidity and mortality in many patients receiving medical or surgical intensive care. Animal data and human observational studies indicate that oliguria and acute kidney injury are early and frequent consequences of IAH/ACS and can be present at relatively low levels of intra-abdominal pressure (IAP). Among medical patients at particular risk are those with septic shock and severe acute pancreatitis, but the adverse effects of IAH may also be seen in cardiorenal and hepatorenal syndromes. Factors predisposing to IAH/ACS include sepsis, large volume fluid resuscitation, polytransfusion, mechanical ventilation with high intrathoracic pressure, and acidosis, among others. Transduction of bladder pressure is the gold standard for measuring intra-abdominal pressure, and several nonsurgical methods can help reduce IAP. The role of renal replacement therapy for volume management is not well defined but may be beneficial in some cases. IAH/ACS is an important possible cause of acute renal failure in critically ill patients and screening may benefit those at increased risk.

Indiscriminate use of the terms dehydration and volume depletion, so carefully crafted by our predecessors, risks confusion and therapeutic errors. These two conditions should be distinguished at the bedside and in how we speak to one another. Dehydration largely refers to intracellular water deficits stemming from hypertonicity and a disturbance in water metabolism. The diagnosis of dehydration cannot be established without laboratory analysis of p[Na +] or calculation of serum tonicity. In contrast, volume depletion describes the net loss of total body sodium and a reduction in intravascular volume and is best termed extracellular fluid volume depletion. The diagnosis of this condition relies principally on history, careful physical examination, and adjunctive data from laboratory studies. The pathophysiology of both dehydration and extracellular fluid volume depletion must be understood if these conditions are to be recognized and appropriately treated when they occur separately or together. There is no inclusive therapy for all situations. For example, indiscriminate treatment with 0.45% saline cannot be recommended when these conditions coexist because extracellular fluid volume depletion is often treated rapidly with 0.9% saline and dehydration is often treated more slowly with 5% dextrose.

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Tubulointerstitial changes in the diabetic kidney correlate closely with the decline in glomerular filtration. In this study, we used a cell culture system of mouse proximal tubule epithelial cells to test the effects of glucose on cell growth, size, and matrix biosynthesis. [3H]thymidine incorporation was significantly inhibited in cells grown in 450 mg/dl glucose, compared with cells grown in 100 mg/dl glucose. The cells grown in the higher glucose concentration were slightly larger, their protein content and the total protein synthetic rate were significantly increased, and they secreted approximately twice as much procollagens type IV and type I. Concordantly, steady-state procollagen mRNA levels were also increased: 2.6-fold for the alpha 1(IV) and 2.2-fold for the alpha 2(I) procollagens. Additionally, nuclear run-off studies demonstrated that procollagen gene transcription rate was stimulated approximately 50%; beta-actin transcription rate was not altered. We used chloramphenicol acetyltransferase (CAT) reporter gene constructs to determine whether the increased transcription rate of alpha 2(I) gene was associated with activation of its enhancer sequence. Cells transfected with the enhancer demonstrated more than fivefold increase in CAT activity when cultured in the high-glucose medium. These studies demonstrate a multitude of effects of high ambient glucose concentrations on proximal tubule cell growth and collagen biosynthesis; cell proliferation is decreased although cell hypertrophy occurs. Procollagen gene transcription rate is stimulated and this response contributes to the observed increase in procollagen mRNA content. Activation of an enhancer sequence may be one possible mode through which high glucose levels increase the transcription of procollagen type I, presumably involving trans-acting factor(s).

Low dose (<3 mSv) noncontrast CT (NCCT) is the imaging study of choice for accurate evaluation of patients with acute onset of flank pain and suspicion of stone disease (sensitivity 97%, specificity 95%). NCCT can reliably characterize the location and size of an offending ureteral calculus, identify complications, and diagnose alternative etiologies of abdominal pain such as appendicitis. By comparison, the sensitivity of radiographs (59%) and ultrasound (24-57%) for the detection of renal and ureteral calculi is relatively poor. Ultrasound can accurately diagnose pelvicaliectasis and ureterectasis, but it may take several hours for these findings to develop. In the pregnant patient, however, ultrasound is a first line test as it does not expose the fetus to ionizing radiation. MR is an accurate test for the diagnosis of pelvicaliectasis and ureterectasis, but is less sensitive than CT for the diagnosis of renal and ureteral calculi. For patients with known stone disease whose stones are visible on radiographs, radiographs are a good tool for post-treatment follow-up.The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every two years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.