Faculty Bibliography

Abstract Extracorporeal treatments (ECTRs), such as hemodialysis and hemoperfusion, are used in poisoning despite a lack of controlled human trials demonstrating efficacy. To provide uniform recommendations, the EXTRIP group was formed as an international collaboration among recognized experts from nephrology, clinical toxicology, critical care, or pharmacology and supported by over 30 professional societies. For every poison, the clinical benefit of ECTR is weighed against associated complications, alternative therapies, and costs. Rigorous methodology, using the AGREE instrument, was developed and ratified. Methods rely on evidence appraisal and, in the absence of robust studies, on a thorough and transparent process of consensus statements. Twenty-four poisons were chosen according to their frequency, available evidence, and relevance. A systematic literature search was performed in order to retrieve all original publications regardless of language. Data were extracted on a standardized instrument. Quality of the evidence was assessed by GRADE as: High = A, Moderate = B, Low = C, Very Low = D. For every poison, dialyzability was assessed and clinical effect of ECTR summarized. All pertinent documents were submitted to the workgroup with a list of statements for vote (general statement, indications, timing, ECTR choice). A modified Delphi method with two voting rounds was used, between which deliberation was required. Each statement was voted on a Likert scale (1-9) to establish the strength of recommendation. This approach will permit the production of the first important practice guidelines on this topic.

OBJECTIVE: Many older adults have decreased kidney function. Practitioners should be informed that no single clinical assessment method is validated in predicting their kidney function. DATA SOURCES: Primary literature identified through MEDLINE/PubMed (1950-2010) and EMBASE (1980-2010) databases. The search was limited to English language, human subjects, and individuals 65 years of age and older. STUDY SELECTION AND DATA EXTRACTION: Research, review articles, and additional publications related to geriatric, elderly, kidney function assessment, and cystatin C. DATA SYNTHESIS: Screening and diagnosing chronic kidney disease are a challenge in older adults partially because of muscle loss and frailty. The various tools used to estimate creatinine clearance (Clcr) are not validated and may lead to under- or overdiagnosis of kidney function. The clinician must be cautious when using and interpreting results from these values. RESULTS: Estimating the glomerular filtration rate (eGFR) with either the Modification of Diet in Renal Disease (MDRD) or Cockcroft-Gault (Clcr) formulae yielded better predictions of kidney function when compared with creatinine alone, or to measured Clcr. These estimation methods should be used in clinical practice to provide a better estimation of kidney function in older adults until a more valid assessment tool becomes available. CONCLUSIONS: There is no proven valid method for eGFR in older adults; however, the CG and MDRD equations are routinely applied in clinical practice. Kidney function assessment in older adults remains a challenge, and practitioners should know their limitations.

BACKGROUND AND OBJECTIVES: Despite the important role of vitamin D in maintaining bone health, many clinicians are reluctant to treat vitamin D deficiency in kidney stone formers because of the theoretical risk of increasing urinary calcium excretion. This study examined the effect of vitamin D repletion on urinary calcium excretion among stone formers. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Participants (n=29) were recruited from urology clinics affiliated with New York Presbyterian Hospital. Enrollment criteria included a history of nephrolithiasis, urinary calcium excretion between 150 and 400 mg/d, and a serum 25-hydroxyvitamin D level <30 ng/ml. Participants were given oral ergocalciferol (50,000 IU/wk) for 8 weeks. Serum and 24-hour urine tests were repeated after 8 weeks. RESULTS: Levels of 25-hydroxyvitamin D increased significantly after vitamin D repletion (17+/-6 and 35+/-10 ng/ml, P<0.001), but mean 24-hour urinary calcium excretion did not change (257+/-54 and 255+/-88 mg/d at baseline and follow-up, respectively, P=0.91). However, 11 participants had an increase in urinary calcium excretion >/=20 mg/d; these participants also had an increase in urine sodium excretion, likely reflecting dietary variability. No participant experienced adverse effects from vitamin D, including hypercalcemia. CONCLUSIONS: Among stone formers with vitamin D deficiency, a limited course of vitamin D repletion does not seem to increase mean urinary calcium excretion, although a subset of individuals may have an increase. These data suggest that vitamin D therapy, if indicated, should not be withheld solely on the basis of stone disease, but 24-hour urinary calcium excretion should be monitored after repletion.

Genetics plays an important role in establishing susceptibility to nephrolithiasis, although diet and other environmental factors make major contributions. In a small number of patients, the genetic causes of stones are more clearly established. Four of these hereditary diseases include primary hyperoxaluria, Dent disease, cystinuria, and adenine phosphoribosyltransferase deficiency, which results in 2,8-dihydroxyadenine stones. Patients with these disorders often experience recurring stones from early childhood, requiring frequent hospitalizations and procedures. They are at risk of kidney damage and chronic kidney disease. Because of their rarity, these four disorders are difficult to study and recognize. This in turn slows progress toward effective therapies and increases the risk of misdiagnosis or diagnosis late in the course of the disease. Therefore, patients may experience unnecessary and harmful treatments and accelerated loss of kidney function. In this article, we will review the pathogenesis, clinical presentation, diagnosis of and treatments for these four disorders. 2011 Springer Science+Business Media, LLC

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

Abstract Background and Purpose: Oxalobacter formigenes (OF) may play a protective role in preventing calcium oxalate stones. This is the first prospective study to evaluate the effect of antibiotics on OF colonization. Intestinal colonization by OF is associated with reduced urinary oxalate excretion. Exposure to antibiotics may be an important factor determining rates of colonization. Materials and Methods: The effect of antibiotics on OF colonization was compared in two groups: A group receiving antibiotics for gastric infection with Helicobacter pylori (HP) and a group without HP whose members were not receiving antibiotics. OF colonization in stool was detected by oxalate degradation at baseline and after 1 and 6 months. Results: The prevalence at baseline of intestinal colonization with OF was 43.1% among all patients screened. Among the 12 patients who were positive for OF who did not receive antibiotics, 11 (92%) had OF on stool tests at 1 month and 6 months. Of the 19 participants who were positive for OF and who received antibiotics for HP, only 7 (36.8%) continued to be colonized by OF on follow-up stool testing at 1 and 6 months (P=0.003 by Fisher exact test). Amoxicillin and clarithromycin caused 62.5% of subjects to become negative for OF at 1 month; 56.2% remained negative for OF at 6 months. Conclusions: Antibiotics for HP infection effectively reduced colonization with OF, an effect present at 1 and 6 months after treatment. The lasting elimination of OF could be associated with hyperoxaluria and be a factor in recurrent kidney stone disease

After nearly 50 years, new drugs are now available or in development for gout. Febuxostat (approved 2009) selectively inhibits xanthine oxidase, preventing uric acid formation and lowering serum urate. Pegloticase (approved 2010) is a recombinant chimeric mammalian uricase that corrects the intrinsic human uricase deficiency. Pegloticase reduces serum urate, and may have particular efficacy against tophi. IL-1beta is now understood to be a central actor in acute gouty inflammation. Three IL-1beta antagonists - anakinra, rilonacept and canakinumab (all US FDA approved for other uses) - are being evaluated for gout treatment and/or prophylaxis. The renal urate resorbing transporters URAT1 and GLUT9 have been recently characterized as targets of uricosuric drugs; two pipeline drugs, RDEA594 and tranilast, inhibit these transporters and are promising urate-lowering therapies. 2011 Future Science Ltd

Two new potential pharmacologic therapies for recurrent stone disease are described. The role of hyperuricosuria in promoting calcium stones is controversial with only some but not all epidemiologic studies demonstrating associations between increasing urinary uric acid excretion and calcium stone disease. The relationship is supported by the ability of uric acid to 'salt out' (or reduce the solubility of) calcium oxalate in vitro. A randomized, controlled trial of allopurinol in patients with hyperuricosuria and normocalciuria was also effective in preventing recurrent stones. Febuxostat, a nonpurine inhibitor of xanthine oxidase (also known as xanthine dehydrogenase or xanthine oxidoreductase) may have advantages over allopurinol and is being tested in a similar protocol, with the eventual goal of determining whether urate-lowering therapy prevents recurrent calcium stones. Treatments for cystinuria have advanced little in the past 30 years. Atomic force microscopy has been used recently to demonstrate that effective inhibition of cystine crystal growth is accomplished at low concentrations of l-cystine methyl ester and l-cystine dimethyl ester, structural analogs of cystine that provide steric inhibition of crystal growth. In vitro, l-cystine dimethyl ester had a significant inhibitory effect on crystal growth. The drug's safety and effectiveness will be tested in an Slc3a1 knockout mouse that serves as an animal model of cystinuria