Faculty Bibliography

A subgroup of hemodialysis patients experience high serum ferritin and low tansferrin saturation for reasons not clearly understood. Here we determined the economic impact of administering sodium ferric gluconate complex to patients with serum ferritin levels higher than 500 ng/ml and a transferrin saturation less than 25% based on the Dialysis Patients Response to IV Iron with Elevated Ferritin (DRIVE) study and its extension, DRIVE II. A cost effectiveness model was developed, consistent with the DRIVE studies, using decision analysis with a 12-week time horizon. The primary effectiveness measure was the mean hemoglobin increase in the intent to treat patient groups comparing epoetin with or without sodium ferric gluconate complex. Costs were computed using projected 2007 US Medicare reimbursements for the treatments and for serious adverse events, with the effectiveness factored by the increase in hemoglobin. The net savings for sodium ferric gluconate complex plus epoetin treatment was $1390 compared to epoetin alone for each g/dl hemoglobin increase over 12 weeks of study. Sensitivity analyses were performed to test the impact of change in the variables (using medians or means and actual 2005 or projected 2007 Medicare reimbursements) and these affirmed the robustness of the model. Our study shows that treatment of patients with high ferritin and low transferrin saturation levels, as defined in DRIVE, with sodium ferric gluconate complex and epoetin resulted in significant savings compared to epoetin alone

Cystinuria is an inherited disorder characterized by the impaired reabsorption of cystine in the proximal tubule of the nephron and the gastrointestinal epithelium. The only clinically significant manifestation is recurrent nephrolithiasis secondary to the poor solubility of cystine in urine. Although cystinuria is a relatively common disorder, it accounts for no more than 1% of all urinary tract stones. Thus far, mutations in 2 genes, SLC3A1 and SLC7A9, have been identified as being responsible for most cases of cystinuria by encoding defective subunits of the cystine transporter. With the discovery of mutated genes, the classification of patients with cystinuria has been changed from one based on phenotypes (I, II, III) to one based on the affected genes (I and non-type I; or A and B). Most often this classification can be used without gene sequencing by determining whether the affected individual's parents have abnormal urinary cystine excretion. Clinically, insoluble cystine precipitates into hexagonal crystals that can coalesce into larger, recurrent calculi. Prevention of stone formation is the primary goal of management and includes hydration, dietary restriction of salt and animal protein, urinary alkalinization, and cystine-binding thiol drugs

Kidney stones affect hypertensive patients disproportionately compared to normotensive individuals. On the other hand, some prospective data suggest that a history of nephrolithiasis was associated with a greater tendency to develop hypertension. Newer epidemiologic data also link obesity and diabetes, features of the metabolic syndrome, with nephrolithiasis. In this review, the association of hypertension, diabetes, and obesity with nephrolithiasis is reviewed, and possible pathogenic mechanisms are discussed. Patients with hypertension may have abnormalities of renal calcium metabolism, but data confirming this hypothesis are inconsistent. Higher body mass index and insulin resistance (i.e., the metabolic syndrome) may be etiologic in uric acid nephrolithiasis as increasing body weight is associated with decreasing urinary pH. The possibility that common pathophysiologic mechanisms underly these diseases is intriguing, and if better understood, could potentially lead to better therapies for stone prevention. Both hypertension and stones might be addressed through lifestyle modification to prevent weight gain. Adoption of a lower sodium diet with increased fruits and vegetables and low-fat dairy products, (for example, the dietary approaches to stop hypertension(DASH) diet), may be useful to prevent both stones and hypertension. In those patients in whom dietary modification and weight loss are ineffective, thiazide diuretics are likely to improve blood pressure control and decrease calciuria.American Journal of Hypertension (2008) doi:10.1038/ajh.2007.62American Journal of Hypertension (2008) doi:10.1038/ajh.2007.62

Extracorporeal removal techniques such as hemodialysis, charcoal hemoperfusion, and peritoneal dialysis have been used to remove toxins from the body. To define trends in the use of these techniques for toxin removal, we analyzed the 19,351 cases requiring extracorporeal removal reported to U.S. poison centers from 1985-2005. The number of such patients who received hemodialysis, excluding those with other medical indications, (normalized per million calls) increased from 231 to 707 whereas hemoperfusion decreased from 53 to 12 in the years 1985-2005. Peritoneal dialysis decreased from 2.2 in 1985 to 1.6 in 1991. The most common toxins removed by hemodialysis were lithium and ethylene glycol. There were more dialysis treatments for poisonings with valproate and acetaminophen in 2001-2005 than for methanol and theophylline, although hemodialysis for acetaminophen removal is generally not recommended. Theophylline was the most common toxin removed by hemoperfusion from 1985-2000, but carbamazepine became the most frequent toxin for removal during 2001-2005. Our study shows that the profile of toxins and the type of extracorporeal technique used to remove the toxins have changed over the years.Kidney International advance online publication, 17 September 2008; doi:10.1038/ki.2008.462

Acetazolamide, a potent carbonic anhydrase (CA) inhibitor, is the most commonly used and best studied agent for the amelioration of acute mountain sickness (AMS). The actual mechanisms by which acetazolamide reduces symptoms of AMS, however, remain unclear. Traditionally, acetazolamide's efficacy has been attributed to inhibition of CA in the kidneys, resulting in bicarbonaturia and metabolic acidosis. The result is offsetting hyperventilation-induced respiratory alkalosis and allowance of chemoreceptors to respond more fully to hypoxic stimuli at altitude. Studies performed on both animals and humans, however, have shown that this explanation is unsatisfactory and that the efficacy of acetazolamide in the context of AMS is likely due to a multitude of effects. This review summarizes the known systemic effects of acetazolamide, and incorporates them into a model encompassing several factors that are likely to play a key role in the drug's efficacy. Such factors include not only metabolic acidosis resulting from renal CA inhibition, but also improvements in ventilation from tissue respiratory acidosis, improvements in sleep quality from carotid body CA inhibition, and effects of diuresis. Key words: carbonic anhydrase, periodic breathing, hypercapnic ventilatory response, metabolic acidosis, altitude sickness

PURPOSE: Thiazide use to prevent recurrent calcium nephrolithiasis is supported by randomized, controlled trials. Concerns regarding adverse metabolic effects of thiazides, which are also used to treat hypertension, have reemerged with analysis of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial. The risks posed by thiazide induced hyperglycemia, hyperuricemia, hypokalemia and dyslipidemia may decrease the expected cardiovascular benefit of lowering blood pressure in hypertensive patients. Whether these side effects occur and are clinically significant in nonhypertensive patients with kidney stones treated with thiazides is unclear. MATERIALS AND METHODS: A review of the literature was performed for randomized, controlled trials with thiazides for calcium nephrolithiasis. We sought data regarding metabolic effects in this population, including hyperglycemia, hyperuricemia, hypokalemia and dyslipidemia. RESULTS: Nine randomized, controlled trials of thiazide treatment for kidney stones were included. Mean patient age was 42 years and followup was 2.6 years. Only 2 of the 9 studies measured glucose and lipid levels, which did not significantly change with treatment. Three studies measured serum potassium and 2 showed a significant decrease. Three of the 9 studies measured serum uric acid levels, which increased in all 3. None of the trials studied the development of diabetes mellitus or cardiovascular disease. CONCLUSIONS: There is a lack of data on the metabolic effects of thiazides used to prevent recurrent calcium nephrolithiasis. It remains unclear if metabolic effects occur and increase the risk of cardiovascular disease in otherwise healthy patients with recurrent nephrolithiasis on thiazide prophylaxis. Further research is needed to elucidate other alternatives for the treatment of recurrent nephrolithiasis

The diagnosis of medullary sponge kidney traditionally was established by means of intravenous pyelography. Beginning in the mid-1990s, intravenous pyelography rapidly was supplanted by computed axial tomography as the preferred imaging study for evaluating patients with renal stone disease. Conventional computed tomographic imaging has not been satisfactory for diagnosing medullary sponge kidney. The introduction of multidetector-row computed tomography in 1999 allowed radiologists to acquire images composed of elements allowing the creation of high-resolution 3-dimensional displays. Computed tomographic urography is an imaging technique that provides both cross-sectional displays and images of the contrast-filled renal collecting systems, ureters, and urinary bladder that are the equivalent of intravenous pyelography. We report a case of medullary sponge kidney diagnosed by means of 3-dimensional multidetector-row computed tomographic urography.