Faculty Bibliography

INTRODUCTION: Uremic syndrome consists of nitrogenous waste retention, deficiency in kidney-derived hormones, and reduced acid excretion, and, if untreated, may progress to coma and eventual death. Previous experience suggests that oral administration of a probiotic formulation of selected microbial strains may extend renoprotection via intraintestinal extraction of toxic waste solutes in patients with chronic kidney disease (CKD)stages 3 and 4. This report presents preliminary data from a pilot study. METHODS: This was a 6-month prospective, randomized, double-blind, placebo-controlled crossover trial of a probiotic bacterial formulation conducted in four countries, at five institutions, on 46 outpatients with CKD stages 3 an nd 4: USA (n=10), Canada (n=113), Nigeria (n=115), and Argentina (n=8). Outcomes were compared using biochemical parameters:blood urea nitrogen (BUN), serum creatinine, and uric acid. General well-being was assessed as a secondary parameter by a quality of life (QQOL) questionnaire on a subjective scale of 1-10. RESULTS: Oral ingestion of probiotics (90 billion colony forming units [CFUs]/day) was well tolerated and safe during the entire trial period at all sites. BUN levels decreased in 29 patients (63%, P<0.05), creatinine levels decreased in 20 patients (43%, no statistical significance), and uric acid levels decreased in 15 patients (33%, no statistical significance). Almost all subjects expressed a perceived substantial overall improvement in QOL (86%, P<0.05). CONCLUSION: The main outcomes of this preliminary trial include a significant reduction of BUN, enhanced well-being, and absence of serious adverse effects, thus supporting the use of the chosen probiotic formulation for bowel-based toxic solute extraction. QOL and BUN levels showed statistically significant differences in outcome (P<0.05) between placebo and probiotic treatment periods at all four sites (46 patients). A major limitation of this trial is the small sample size nd elated inconsistencies

Cystinuria is a primary inherited aminoaciduria caused by mutations in the genes that encode the two subunits (neutral and basic amino acid transport protein rBAT and b(0,+)-type amino acid transporter 1) of the amino acid transport system b(0,+). This autosomal recessive disorder (in which few cases show dominant inheritance) causes a failure in the reabsorption of filtered cystine and dibasic amino acids in the proximal tubule. The clinical symptoms of this disease are caused by the loss of poorly soluble cystine, which precipitates to form stones. Although rare, the prevalence of cystinuria is sufficiently high that the disease results in a substantial contribution to pediatric renal lithiasis. A thorough understanding of cystine transport processes over the past 15 years and the genetic abnormalities responsible for the disease has led to a new classification of cystinuria and recognition that some cases result from an autosomal dominant etiology with incomplete penetrance. This Review examines the molecular and mechanistic effects of some of the mutations that cause cystinuria based on our current understanding of the structural and cellular biology of system b(0,+). This Review also describes the current treatments to prevent recurrent cystine lithiasis

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

The kidney is able to rapidly eliminate many water-soluble xenobiotics (exogenous chemicals). However, in the face of extraordinary serum concentrations of these xenobiotics or renal dysfunction, alternative elimination techniques often become necessary. Extracorporeal removal (ECR) techniques are used to increase the clearance of xenobiotics. These techniques include hemodialysis (HD), charcoal hemoperfusion (HP), and modalities grouped under the heading of continuous renal replacement therapy (CRRT): continuous venovenous hemofiltration (CVVH) and continuous venovenous hemodiafiltration (CVVHDF). Extracorporeal removal is limited to patients with significant or potentially significant clinical poisoning because the resources required to perform ECR are great. Therefore, most patients who are treated with these techniques are being cared for in intensive care units (ICUs). Our goal in this review is to discuss the properties that make xenobiotics amenable to removal by ECR and the advantages and disadvantages of the individual techniques. We discuss xenobiotics that constitute clear indications for ECR, including the toxic alcohols, salicylates, and lithium. We review the use of CRRT, a modality for which clear indications for treatment of poisonings are currently lacking

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

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

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