Faculty Bibliography

PURPOSE: The combination of sepsis and ureteral calculus is a urological emergency. Traditional teaching advocates urgent decompression with nephrostomy tube or ureteral stent placement, although published outcomes validating this treatment are lacking. National practice patterns for such scenarios are currently undefined. Using a retrospective study design, we defined the surgical decompression rate in patients admitted to the hospital with severe infection and ureteral calculi. We determined whether a mortality benefit is associated with this intervention. MATERIALS AND METHODS: Patient demographics and hospital characteristics were extracted from the 2007 to 2009 Nationwide Inpatient Sample. We identified 1,712 patients with ureteral calculi and sepsis. Multivariate logistic regression was performed to determine the association between mortality and surgical decompression. RESULTS: Of the patients 78% underwent surgical decompression. Mortality was higher in those not treated with surgical decompression (19.2% vs 8.82%, p <0.001). Lack of surgical decompression was independently associated with an increased OR of mortality even when adjusting for patient demographics, comorbidities and geographic region of treatment (OR 2.6, 95% CI 1.9-3.7). CONCLUSIONS: Absent surgical decompression is associated with higher odds of mortality in patients with sepsis and ureteral calculi. Further research to determine predictors of surgical decompression is necessary to ensure that all patients have access to this life saving therapy.

This article reviews the data on pharmacologic treatment of kidney stone disease, with a focus on prophylaxis against stone recurrence. One of the most effective and important therapies for stone prevention, an increase in urine volume, is not discussed because this is a dietary and not a pharmacologic intervention. Also reviewed are medical expulsive therapy used to improve the spontaneous passage of ureteral stones and pharmacologic treatment of symptoms associated with ureteral stents. The goal is to review the literature with a focus on the highest level of evidence (ie, randomized controlled trials).

Evaluation of stone formers should include careful attention to medications, past medical history, social history, family history, dietary evaluation, occupation, and laboratory evaluation. Laboratory evaluation requires at least serum chemistries and urinalysis. Twenty-four-hour urine collections are most appropriate for patients with recurrent stones or complex medical histories. However, these collections may be appropriate for some first-time stone formers, including those with comorbidities or large stones. Although twin studies demonstrate that heritability accounts for at least 50% of the kidney stone phenotype, the responsible genes are not clearly identified, and so genetic testing is rarely indicated.

BACKGROUND: Assessment of adherence to study medications is a common challenge in clinical research. Counting unused study medication is the predominant method by which adherence is assessed in outpatient clinical trials but it has limitations that include questionable validity and burdens on research personnel. PURPOSE: To compare capsule counts, patient questionnaire responses, and plasma drug levels as methods of determining adherence in a clinical trial that had 2056 participants and used centralized drug distribution and patient follow-up. METHODS: Capsule counts from study medication bottles returned by participants and responses to questions regarding adherence during quarterly telephone interviews were averaged and compared. Both measures were compared to plasma drug levels obtained at the 3-month study visit of patients in the treatment group. Counts and questionnaire responses were converted to adherence rates (doses taken divided by days elapsed) and were categorized by stringent (>/=85.7%) and liberal (>/=71.4%) definitions. We calculated the prevalence-adjusted bias-adjusted kappa to assess agreement between the two measures. RESULTS: Using a pre-paid mailer, participants returned 76.0% of study medication bottles to the central pharmacy. Both capsule counts and questionnaire responses were available for 65.8% of participants and were used to assess adherence. Capsule counts identified more patients who were under-adherent (18.8% by the stringent definition and 7.5% by the liberal definition) than self-reports did (10.4% by the stringent definition and 2.1% by the liberal definition). The prevalence-adjusted bias-adjusted kappa was 0.58 (stringent) and 0.83 (liberal), indicating fair and very good agreement, respectively. Both measures were also in agreement with plasma drug levels determined at the 3-month visit (capsule counts: p = 0.005 for the stringent and p = 0.003 for the liberal definition; questionnaire: p = 0.002 for both adherence definitions). LIMITATIONS: Inconsistent bottle returns and incomplete notations of medication start and stop dates resulted in missing data but exploratory missing data analyses showed no reason to believe that the missing data resulted in systematic bias. CONCLUSIONS: Depending upon the definition of adherence, there was fair to very good agreement between questionnaire results and capsule counts among returned study bottles, confirmed by plasma drug levels. We conclude that a self-report of medication adherence is potentially comparable to capsule counts as a method of assessing adherence in a clinical trial, if a relatively low adherence threshold is acceptable, but adherence should be confirmed by other measures if a high adherence threshold is required

Recent work has highlighted the strong relationships among obesity, diabetes, and the metabolic syndrome as causes of low urinary pH. Low urinary pH in turn is the major urinary risk factor for uric acid stones. Unlike calcium stones, uric acid stones can be dissolved and easily prevented with adequate urinary alkalinization. Recognizing the relevant risk factors should lead to increased identification of these radiolucent stones. The cornerstone of therapy is raising urinary pH; xanthine dehydrogenase inhibitors should be used only when urinary alkalinization cannot be achieved.

BACKGROUND: The EXtracorporeal TReatments In Poisoning (EXTRIP) workgroup was formed to provide recommendations on the use of extracorporeal treatment (ECTR) in poisoning. To test and validate its methods, the workgroup reviewed data for thallium (Tl). METHODS: After an extensive search, the co-chairs reviewed the articles, extracted the data, summarized findings, and proposed structured voting statements following a predetermined format. A two-round modified Delphi method was chosen to reach a consensus on voting statements and RAND/UCLA Appropriateness Method to quantify disagreement. Blinded votes were compiled, returned, and discussed during a conference call. A second vote determined the final recommendations. RESULTS: Forty-five articles met inclusion criteria. Only case reports and case series were identified, yielding a very low quality of evidence for all recommendations. Data on 74 patients, including 11 who died, were abstracted. The workgroup concluded that Tl is slightly dialyzable and made the following recommendations: ECTR is recommended in severe Tl poisoning (1D). ECTR is indicated if Tl exposure is highly suspected on the basis of history or clinical features (2D) or if the serum Tl concentration is >1.0 mg/L (2D). ECTR should be initiated as soon as possible, ideally within 24-48 hours of Tl exposure (1D), and be continued until the serum Tl concentration is <0.1 mg/L for a minimal duration of 72 hours (2D). CONCLUSION: Despite Tl's low dialyzability and the limited evidence, the workgroup strongly recommended extracorporeal removal in the case of severe Tl poisoning.

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.

Kidney stones composed predominantly (50% or more) of calcium phosphate constitute up to 10% of all stones and 15%-20% of calcium stones, 80% of which are composed of calcium oxalate. Calcium phosphate is a minor component of up to 30% of calcium oxalate stones as well. The cause of calcium phosphate stones is often obscure but most often related to a high urine pH. Some patients with calcium phosphate stones may have incomplete renal tubular acidosis. Others have distal renal tubular acidosis characterized by hyperchloremic acidosis, hypocitraturia, and high urine pH. The use of carbonic anhydrase inhibitors such as acetazolamide, topiramate, and zonisamide leads to a similar picture. Treatment options to specifically prevent calcium phosphate stone recurrence have not been tested in clinical trials. Increases in urine volume and restriction of sodium intake to limit calcium excretion are important. Citrate supplementation is probably effective, although the concomitant increase in urine pH may increase calcium phosphate supersaturation and partially offset the inhibition of crystallization resulting from the increased urine citrate excretion and the alkali-associated reduction in urine calcium excretion. Thiazides lower urine calcium excretion and may help ensure the safety of citrate supplementation.