Anton Schoolwerth

The development of many electrolyte disturbances in the ICU can be prevented by attention to the use of intravenous fluids and nutrition. Hyponatremia is a relative contraindication to the use of hypotonic intravenous fluids and hypernatremia calls for the administration of water. Formulae have been devised to guide the therapy of severe hyponatremia and hypernatremia. All formulae regard the patient as a closed system, and none takes into account ongoing fluid losses that are highly variable between patients. Thus, therapy of severe hyponatremia and hypernatremia must be closely monitored with serial electrolyte measurements. The significance of hypocalcemia in the critically ill is controversial. Hypokalemia, hypophosphatemia, and hypomagnesemia should be corrected.

For a health problem or condition to be considered a public health issue, four criteria must be met: 1) the health condition must place a large burden on society, a burden that is getting larger despite existing control efforts; 2) the burden must be distributed unfairly (i.e., certain segments of the population are unequally affected); 3) there must be evidence that upstream preventive strategies could substantially reduce the burden of the condition; and 4) such preventive strategies are not yet in place. Chronic kidney disease meets these criteria for a public health issue. Therefore, as a complement to clinical approaches to controlling it, a broad and coordinated public health approach will be necessary to meet the burgeoning health, economic, and societal challenges of chronic kidney disease.

Losartan is one of several angiotensin-receptor blockers currently in clinical use. Losartan is given as an active prodrug with subsequent conversion to a long-acting E-3174 metabolite. The clearance of losartan in predominantly hepatic whereas its E-3174 metabolite undergoes equal hepatic and renal clearance. To date, although the renal clearance mechanism for losartan/E-3174 have not been delineated the extensive protein binding of both losartan and E-3174 would suggest that tubular secretion is important to the renal eliminatin of both of these substances. This study was designed to evaluate the renal handling of losartan/E-3174 with and without the co-administration of the organic anion transport inhibitor probenecid. 8 healthy males and females were studied in a four-way crossover single losartan dose pharmacokinetic study. Limb A: losartan 100-mg; Limb B: probenecid 500-mg twice daily for 4 days (including the study day) and losartan 100-mg; Limb C: placebo; Limb D:probenecid ...

Acute renal failure of an abdominal aortic aneurysm is associated with an extremely poor chance of survival. We reviewed the cases of ruptured abdominal aortic aneurysm presenting between January 1, 1976 and June 1, 1979. Four patients developed oliguric acute renal failure and required hemodialysis. All patients survived despite multiple life-threatening complications. The prognosis for acute renal failure after ruptured abdominal aortic aneurysm is better than previously recognized.

We sought to conduct a meta-analysis to compare N-acetylcysteine (NAC) in combination with sodium bicarbonate (NaHCO(3)) for the prevention of contrast-induced acute kidney injury (AKI). Contrast-induced AKI is a serious consequence of cardiac catheterizations and percutaneous coronary interventions (PCI). Despite recent supporting evidence for combination therapy, not enough has been done to prevent the occurrence of contrast-induced AKI prophylactically. Published randomized controlled trial data were collected from OVID/PubMed, Web of Science, and conference abstracts. The outcome of interest was contrast-induced AKI, defined as a >or=25% or >or=0.5 mg/dl increase in serum creatinine from baseline. Secondary outcome was renal failure requiring dialysis. Ten randomized controlled trials met our criteria. Combination treatment of NAC with intravenous NaHCO(3) reduced contrast-induced AKI by 35% (relative risk: 0.65; 95% confidence interval: 0.40 to 1.05). However, the combination of N-acetylcysteine plus NaHCO(3) did not significantly reduce renal failure requiring dialysis (relative risk: 0.47; 95% confidence interval: 0.16 to 1.41). Combination prophylaxis with NAC and NaHCO(3) substantially reduced the occurrence of contrast-induced AKI overall but not dialysis-dependent renal failure. Combination prophylaxis should be incorporated for all high-risk patients (emergent cases or patients with chronic kidney disease) and should be strongly considered for all interventional radio-contrast procedures.

Puromycin aminonucleoside (PAN) nephropathy is a widely studied model of glomerular sclerosis (GS) in the rat, and cholesterol feeding exacerbates the injury induced by PAN. The importance of the interaction of angiotensin II (Ang II) with the AT2 receptor is unclear. We investigated the role of the renin-angiotensin system, particularly with regard to AT1 and AT2 receptor dynamics, in PAN and cholesterol-mediated GS. Sprague-Dawley rats were given a 4% cholesterol diet (group II), subcutaneous PAN (group III), or a 4% cholesterol diet and PAN (group IV) and compared with a control group given PAN vehicle (group I). After 16 weeks, kidneys were harvested and tissue Ang II concentration, angiotensin-converting enzyme (ACE) activity, and ACE, AT1, and AT2 mRNA levels were determined. Compared with control rats, proteinuria was significantly higher in groups II to IV. Kidney ACE activity and ACE mRNA levels in groups III and IV were 2- and 3-fold higher than in groups I and II, respectively. Kidney Ang II concentration also was increased in the experimental groups. Whereas kidney AT1 mRNA was significantly lower in groups III and IV, kidney AT2 mRNA was significantly increased in groups II to IV. In these experimental models of GS, there is significant activation of the tissue-based renin-angiotensin system. Puromycin with and without cholesterol decreased the AT1 receptor mRNA and increased the AT2 receptor mRNA. Up-regulation of AT2 receptors may be important in ameliorating the proliferative effects of Ang II, which presumably occur through the AT1 receptor.

The case of a 25-year-old man who had periosteal osteogenic sarcoma with intravascular metastases in unusual locations is reported. The patient presented with acute renal failure, unilateral pulmonary edema, functional mitral stenosis, and low cardiac output. After successful surgical removal of a left atrial metastasis with subsequent improvement in cardiac output, renal function improved only transiently and urinary output varied markedly. At autopsy, metastatic osteogenic sarcoma was discovered within the lumen of the abdominal aorta obstructing both renal arteries. The case is the first report of a neoplasm metastatic to the aorta causing intermittent bilateral renal arterial obstruction; it illustrates the diagnostic difficulties presented by intravascular metastatic disease.

Microalbuminuria screening may detect chronic kidney disease in its early stages, allowing for treatment that delays or prevents disease progression. The cost-effectiveness of microalbuminuria screening has not been determined. A cost-effectiveness model simulating disease progression and costs. US patients. MODEL, PERSPECTIVE, AND TIMEFRAME: The microsimulation model follows up disease progression and costs in a cohort of simulated patients from age 50 to 90 years or death. Costs are evaluated from the health care system perspective. Microalbuminuria screening at 1-, 2-, 5-, or 10-year intervals followed by treatment with angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers. We considered universal screening, as well as screening targeted at persons with diabetes, persons with hypertension but no diabetes, and persons with neither diabetes nor hypertension. Costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios. For the full model population, universal screening increases costs and increases QALYs. Universal annual screening starting at age 50 years has a cost-effectiveness ratio of $73,000/QALY relative to no screening and $145,000/QALY relative to usual care. Cost-effectiveness ratios improved with longer screening intervals. Relative to no screening, targeted annual screening has cost-effectiveness ratios of $21,000/QALY, $55,000/QALY, and $155,000/QALY for persons with diabetes, those with hypertension, and those with neither current diabetes nor current hypertension, respectively. Results necessarily are based on a microsimulation model because of the long time horizon appropriate for chronic kidney disease. The model includes only health care costs. Microalbuminuria screening is cost-effective for patients with diabetes or hypertension, but is not cost-effective for patients with neither diabetes nor hypertension unless screening is conducted at longer intervals or as part of existing physician visits.

A cost-effectiveness model that accurately represents disease progression, outcomes, and associated costs is necessary to evaluate the cost-effectiveness of interventions for chronic kidney disease (CKD). We developed a microsimulation model of the incidence, progression, and treatment of CKD. The model was validated by comparing its predictions with survey and epidemiologic data sources. US patients. The model follows up disease progression in a cohort of simulated patients aged 30 until age 90 years or death. The model consists of 7 mutually exclusive states representing no CKD, 5 stages of CKD, and death. Progression through the stages is governed by a person's glomerular filtration rate and albuminuria status. Diabetes, hypertension, and other risk factors influence CKD and the development of CKD complications in the model. Costs are evaluated from the health care system perspective. Usual care, including incidental screening for persons with diabetes or hypertension. Progression to CKD stages, complications, and mortality. The model provides reasonably accurate estimates of CKD prevalence by stage. The model predicts that 47.1% of 30-year-olds will develop CKD during their lifetime, with 1.7%, 6.9%, 27.3%, 6.9%, and 4.4% ending at stages 1-5, respectively. Approximately 11% of persons who reach stage 3 will eventually progress to stage 5. The model also predicts that 3.7% of persons will develop end-stage renal disease compared with an estimate of 3.0% based on current end-stage renal disease lifetime incidence. The model synthesizes data from multiple sources rather than a single source and relies on explicit assumptions about progression. The model does not include acute kidney failure. The model is well validated and can be used to evaluate the cost-effectiveness of CKD interventions. The model also can be updated as better data for CKD progression become available.