Faculty Bibliography

Tubulocystic renal cell carcinoma (TC-RCC) is a rare renal tumor composed of well-differentiated tubules and cysts lined by neoplastic cells with eosinophilic cytoplasm and prominent nucleoli. The origin of the tumor cells is still controversial. TC-RCC typically arises unilaterally. Involvement of both kidneys by multifocal TC-RCC has not been reported. In this study we report the first case of bilateral and multifocal TC-RCC. Immunohistochemical, cytogenetic and ultrastructural studies suggest TC-RCC is closely related to papillary RCC.

Introduction. Minimal Change Disease (MCD) is the most common cause of nephrotic syndrome in children, while IgA nephropathy is the most common cause of glomerulonephritis worldwide. MCD is responsive to glucocorticoids, while the role of steroids in IgA nephropathy remains unclear. We describe a case of two distinct clinical and pathological findings, raising the question of whether MCD and IgA nephropathy are separate entities or if there is a common pathophysiology. Case Report. A 19-year old man with no medical history presented to the Emergency Department with a 20-day history of anasarca and frothy urine, BUN 68 mg/dL, Cr 2.3 mg/dL, urinalysis 3+ RBCs, 3+ protein, and urine protein : creatinine ratio 6.4. Renal biopsy revealed hypertrophic podocytes on light microscopy, podocyte foot process effacement on electron microscopy, and immunofluorescent mesangial staining for IgA. The patient was started on prednisone and exhibited dramatic improvement. Discussion. MCD typically has an overwhelming improvement with glucocorticoids, while the resolution of IgA nephropathy is rare. Our patient presented with MCD with the uncharacteristic finding of hematuria. Given the improvement with glucocorticoids, we raise the question of whether there is a shared pathophysiologic component of these two distinct clinical diseases that represents a clinical variant.

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.

Kidney stones are listed among the complications of eating disorders; however, very few cases have been reported. We present an additional case of nephrolithiasis associated with laxative abuse, including detailed results of the patient's urine metabolic profiles, in a patient with idiopathic hypercalciuria. We review the literature and provide an explanation for the paucity of cases of nephrolithiasis associated with these disorders. Despite low urine volumes resulting from extracellular fluid volume depletion and hypocitraturia resulting from hypokalemia, both of which would tend to favor the formation of kidney stones, most patients with eating disorders are likely to be protected from stone formation by the hypocalciuric effect of extracellular fluid volume depletion and increased proximal tubular sodium reabsorption. However, patients with underlying idiopathic hypercalciuria who develop eating disorders may be at increased risk of stone formation in the setting of low urine volume and therefore high supersaturation of calcium oxalate and phosphate.

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.

Studies have shown that certain beverages decrease urinary lithogenicity by increasing urine citrate excretion. Diet Sunkist Orange soda had the highest concentration of citrate and total alkali content among 12 diet sodas previously assayed. We studied the effect of Diet Sunkist Orange soda consumption on urinary chemistry. Nine healthy men and women ages 26-54 years completed the study. During the control period, subjects drank 36 oz of water for 3 days in addition to their own, self-selected diet and recorded a food diary. During the study period, the subjects drank three 12-oz cans of Diet Sunkist Orange soda a day instead of water, and replicated their diets from the control period. In each period, the subjects performed 24-h urine collections on days 2 and 3. Urine chemical analysis was performed, including urinary citrate levels and pH. Diet Sunkist Orange soda increased urinary citrate excretion by 60 mg/day, which was not statistically significant (95% CI -75 to 195, P value 0.34). There was no significant change in pH from the control period to the study period (pH: 6.29-6.21; 95% CI: -0.09 to 0.25, P = 0.30). Urine volumes and creatinine excretions were not significantly different between the control and study periods. Despite the relatively high citrate and total alkali content of Diet Sunkist Orange soda, the volume consumed in this study (36 oz per day) did not provide sufficient potential base to significantly alter urine composition in healthy subjects with normocitraturia. The effect of Diet Sunkist Orange soda on urinary chemistry in patients with hypocitraturia and nephrolithiasis is not likely to have a clinically significant effect to prevent calcium or uric acid stones.

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.