Faculty Bibliography

PURPOSE: Extended warm ischemia during partial nephrectomy can lead to considerable renal injury. Using a rat model of renal ischemia we examined the ability of a unique renoprotective cocktail to ameliorate warm ischemia-reperfusion injury. MATERIALS AND METHODS: A warm renal ischemia model was developed using 60 Sprague-Dawley(R) rats. The left renal artery was clamped for 40 minutes, followed by 48 hours of reperfusion. A renoprotective cocktail of a mixture of specific growth factors, mitochondria protecting biochemicals and Manganese-Porphyrin (MnTnHex-2-PyP(5+)) was given intramuscularly at -24, 0 and 24 hours after surgery. At 48 hours the 2 kidneys were harvested and examined with hematoxylin and eosin, and periodic acid-Schiff stains. Protein and gene expression were also analyzed to determine ischemia markers and the antioxidant response. RESULTS: Compared to ischemic controls, kidneys treated with the renoprotective cocktail showed significant reversal of morphological changes and a significant decrease in the specific ischemic markers lipocalin-2, mucin-1 and galectin-3. Quantitative reverse transcriptase-polymerase chain reaction revealed up-regulation of several antioxidant genes in treated animals. CONCLUSIONS: According to histopathological and several molecular measures our unique renoprotective cocktail mitigated ischemia-reperfusion injury

Idiopathic uric acid nephrolithiasis appears to be increasing in prevalence. While it has long been known that low urine pH is associated with uric acid stones, only recently has the pathophysiological basis for this disease emerged. Excessively acidic urine is the decisive risk for uric acid lithogenesis, and patients with diabetes and the metabolic syndrome often hold the company of low urine pH. While association does not imply causation, interesting insights have been made regarding insulin's influence on acid-base physiology. We review recent evidence from both the molecular and clinical realms to underline the importance of [H+] in the development and treatment of uric acid nephrolithiasis

Gout recently passed rheumatoid arthritis to become the most common inflammatory arthritis in the United States (US). However, epidemiologic studies indicate that the quality of gout management is suboptimal owing to both patient and physician issues. Only three options for urate-lowering therapy are currently available in the US: allopurinol, probenecid, and recently, febuxostat. Probenecid is generally safe except for the occurrence of urolithiasis, but is only effective for the subset of patients with better kidney function. Allopurinol use is limited due to its side effects, potential toxicity of uncertain magnitude in patients with renal disease, and failure to achieve targeted serum urate levels. In part this failure may be due to the necessity for it to be titrated for optimal therapeutic effect. Febuxostat is a new medication that may offer several advantages and can be given as an alternative to allopurinol. We review the basic biology and clinical performance of febuxostat, and consider the potential utility of this agent in comparison to the older, better-established gout therapeutics

PURPOSE: Citrate is a known inhibitor of calcium stone formation. Dietary citrate and alkali intake may have an effect on citraturia. Increasing alkali intake also increases urine pH, which can help prevent uric acid stones. We determined citrate, malate and total alkali concentrations in commonly consumed diet sodas to help direct dietary recommendations in patients with hypocitraturic calcium or uric acid nephrolithiasis. MATERIALS AND METHODS: Citrate and malate were measured in a lemonade beverage commonly used to treat hypocitraturic calcium nephrolithiasis and in 15 diet sodas. Anions were measured by ion chromatography. The pH of each beverage was measured to allow calculation of the unprotonated anion concentration using the known pK of citric and malic acid. Total alkali equivalents were calculated for each beverage. Statistical analysis was done using Pearson's correlation coefficient. RESULTS: Several sodas contained an amount of citrate equal to or greater than that of alkali and total alkali as a lemonade beverage commonly used to treat hypocitraturic calcium nephrolithiasis (6.30 mEq/l citrate as alkali and 6.30 as total alkali). These sodas were Diet Sunkist(R) Orange, Diet 7Up(R), Sprite Zero, Diet Canada Dry(R) Ginger Ale, Sierra Mist(R) Free, Diet Orange Crush(R), Fresca(R) and Diet Mountain Dew(R). Colas, including Caffeine Free Diet Coke(R), Coke Zero, Caffeine Free Diet Pepsi(R) and Diet Coke with Lime, had the lowest total alkali (less than 1.0 mEq/l). There was no significant correlation between beverage pH and total alkali content. CONCLUSIONS: Several commonly consumed diet sodas contain moderate amounts of citrate as alkali and total alkali. This information is helpful for dietary recommendations in patients with calcium nephrolithiasis, specifically those with hypocitraturia. It may also be useful in patients with low urine pH and uric acid stones. Beverage malate content is also important since malate ingestion increases the total alkali delivered, which in turn augments citraturia and increases urine pH

Extracorporeal removal of drugs and other poisons is occasionally indicated in the management of intoxications. The available modalities include hemodialysis and several methods of continuous renal replacement therapy (CRRT), including continuous venovenous hemofiltration with or without dialysis augmenting drug removal. A growing literature promoting CRRT for extracorporeal removal has been published and is reviewed here. Estimates of clearance achieved by these techniques uniformly demonstrate that hemodialysis achieves higher clearances. CRRT may be appropriate for more hypotensive and unstable patients, though these might be the patients most in need of a more rapidly effective technique. For the most part, these case reports have not demonstrated that CRRT was necessary because of hemodynamic instability. Hemodialysis remains the first choice among modalities of extracorporeal removal with CRRT reserved for patients who truly cannot tolerate hemodialysis

U. Rappo, J.R. Beitler, J.R. Faulhaber, B. Firoz, J.S. Henning, K.M. Thomas, M. Maslow, D.S. Goldfarb, H.W. Horowitz. Expanding the horizons of histoplasmosis: disseminated histoplasmosis in a renal transplant patient after a trip to Bangladesh. Transpl Infect Dis 2009. All rights reserved Abstract: Histoplasmosis is recognized to occur in the Ohio and Mississippi River Valleys of the United States, but less widely appreciated is its worldwide distribution. We report a case of disseminated histoplasmosis with disease involving skin, lungs, and epiglottis in a renal transplant patient 6 months after a trip to Bangladesh, to highlight the potential risk of acquisition of this infection in the Indian subcontinent

BACKGROUND AND OBJECTIVES: Autosomal dominant polycystic kidney disease (ADPKD) leads to kidney failure in half of those affected. Increased levels of adenosine 3;:5;-cyclic monophosphate (cAMP) play a critical role in disease progression in animal models. Water loading, by suppressing arginine vasopressin (AVP)-stimulated cAMP production, is a proposed therapy for ADPKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: The effects of acute and sustained water loading on levels of urine osmolality (Uosm) and cAMP in 13 subjects with ADPKD and 10 healthy controls were studied. Uosm and cAMP concentrations were measured before and after water loading. RESULTS: Urine [cAMP] indexed to Uosm significantly decreased with acute water loading in both groups (58% in controls and 35% in ADPKD). Chronic water loading resulted in a nonsignificant 13% decrease in 24-hour urine cAMP excretion in ADPKD participants, despite an increase in 24-hour urine volume by 64% to 3.14 +/- 0.32 L and decrease in mean Uosm by 46%, to below that of plasma (270 +/- 21 mOsm/L). CONCLUSIONS: Increased water intake of 3 L per day decreased Uosm in most ADPKD subjects. While urine [cAMP] accurately reflects changes in Uosm during acute water loading in ADPKD subjects, chronic water loading did not lower 24-hour urine cAMP excretion, although subjects with higher baseline [cAMP] (>2 nmol/mg Cr) responded best. Decreases in urine [cAMP] and osmolality are consistent with decreased AVP activity. These results support the need for a larger study to evaluate the effect of chronic water loading on ADPKD progression