Acute Phosphate Nephropathy

1. Acute Phosphate Nephropathy AM Report Emily Jenkins 7.28.08

2. Which would you prefer? GoLytely: Gold Standard of Bowel Preparation 4L of volume, 5-15 % of pts do not complete NaP: low-volume hyperosmotic solution that contains 48 g or 400 mmol of monobasic NaP and 18 g (130 mmol) of dibasic NaP per 100 ml Bowel prep of choice among most patients

3. NaP Preparations osmotically draws plasma water into bowel lumen to promote colonic cleansing Aqueous NaP: Fleet�s phosphosoda NaP tablets contain monobasic and dibasic NaP and microcrystalline cellulose as tablet binder.� Amount of active ingredient is similar to standard aqueous NaP regimen Visicol: 40 tablets of NaP OsmoPrep: 32 tablets (20 night before, 12 morning of), developed as residue-free NaP preparation for better colon mucosal visualization�

4. June 2006: A consensus statement from GI surgeons and endoscopists �NaP is associated with physiologically significant but rarely clinically meaningful changes in volume status and electrolyte abnormalities� Usually asymptomatic, hyperphosphatemia is seen in as many as 40% of healthy pts receiving NaP preparations and may be significant in patients with renal failure� As many as 20% of patients who use NaP develop hypokalemia Also shown to cause elevated BUN, decreased exercise capacity, increased plasma osmolality, hypocalcemia, and significant hyponatremia and seizures Nephrocalcinosis has been reported in pts with ARF, particularly in those pts with HTN receiving ACEi or ARBs In addendum to consensus statement: APhN has been reported in 21 pts receiving OSP solution, and in one pt who used Visicol No cases of APhN have been reported with OsmoPrep

5. Contraindications for NaP Bowel Preparations Serum electrolyte imbalances Advanced hepatic dysfunction Acute and chronic renal failure Recent MI USA CHF Ileus Malabsorption Ascites

6. Acute Phosphate Nephropathy: Diagnostic Criteria absence of hypercalcemia ARF pathologic findings of acute and/or chronic tubular injury with abundant tubular calcium deposition recent exposure to an oral sodium phosphate bowel purgative **Irreversible

7. Risk Factors for APhN Use of Ace inhibitors or ARBs Use of diuretics NSAIDs Age Chronic kidney disease

8. Fleet Enemas: Hometown Pride for Lynchburg VA Fleet estimated risk of adverse events from using its products to be 1-5 per million doses sold as reported to Fleet, FDA or published literature per calendar year Proactive in commissioning an independent advisory panel to weigh in on risk of APhN and to reword package labels

9. References 1. Wexner SD, DE Beck, TH Baron, RD Fanelli et al. (June 2006) A consensus document on bowel preparation before colonoscopy: prepared by a task force from the American Society of Colon and Rectal Surgeons (ASCRS), the American Society for Gastrointestinal Endoscopy (ASGE), and the Society of American Gastrointestinal and Endoscopic Surgeons (SAGES), Diseases of the colon and Rectum, vol 49, no. 6, pg 793-809.� 2. JF Johanson, JW Pepp, LE Bohen, SR Lottes et al. A randomized, multicenter study comparing the safety and efficacy of sodium phosphate tablets with 2L polyethylene glycol solution plus bisacodyl tablets for colon cleansing.� American journal of gastroenterology 2007; 102: 2238-2246.� 3. Rex DK, Schwartz H, Goldstein M et al.� Safety and colon-cleansing efficacy of a new residue-free formulation of sodium phosphate tablets.� Am J Gastroenterol 2006; 101: 2594-604. 4. Markowitz GS, Stokes MB, Radhakrishnan J et al.� Acute phosphate nephropathy following oral sodium phosphate bowel purgative: an under-recognized cause of chronic renal failure.� K Am Soc Nephrol 2005; 15: 3389-96.� 5. DE Carl, Sica DA. Acute phosphate nephropathy following colonoscopy preparation. (Sept 2007) Am J of Med Sci Vol 334 No 3: 151-154. 6. GS Markowitz, Radhakrishnan J, VD D'Agati.� Toward the incidence of acute phosphate nephropathy (2007) J Am Soc Nephrol 18: 3020-3022. 7. FP Hurst, EM Bohen, EM Osgard et al.� Association of oral sodium phosphate purgative use with acute kidney injury.� (2007) J Am Soc Nephrol 18: 3192-3198. 8. S Desmeules, MJ Bergeron, P I Senring. Acute phosphate nephropathy and renal failure.� (Sept 2003)� N Eng J Med 349 (10) 1006-1007.� 9. A Beyea, C Block, A Schned.� Acute phosphate nephropathy following oral sodium phosphate solution to cleanse the bowel for colonoscopy. American journal of kidney diseases (Jul 2007) Vol 50(1):151-4. 10.� SM Brunelli, JD Lewis, M Gupta et al.� Risk of kidney injury following oral phosphosoda bowel preparations.� J Am Soc Nephrol 18 (2007) : 3199-3205. 11. C Ell, W Fischbach, R Keller et al.� A randomized, prospective trial to compare the safety and efficacy of three bowel-cleansing solutions for colonoscopy.� Endoscopy (Apr 2003) 35 (4): 300-4.� 12. A Rostom, E Joicoeur, C Dube et al.� A randomized prospective trial comparing different regimens of oral sodium phosphate and polyethylene glycol-base lavage solution in the preparation of patients for colonoscopy. 13. AK Singal, AS Rosman, JB Post et al.� The renal safety of bowel preparations for colonoscopy: a comparative study of oral sodium phosphate solution and polyethylene glycol.� Aliment Pharmacol Ther (2008 Jan 1): 27 (1): 41-7. 14. G Zuccaro, JT Connor, M Schreiber.� Colonoscopy preparation: are our patients at risk?� Am J Gastroenterol 2007; 102: 2664-2666. 15. S Russman, L Lamerato, A Marfatia et al.� Risk of impaired renal function after colonoscopy: a cohort study in patients receiving either oral sodium phosphate or polyethylene glycol.� Am J Gastroenterol 2007; 102: 2655-2663.� 16. DA Sica, D Carl, AM Zfass.� Acute phosphate nephropathy--an emerging issue.� Am J Gastroenterol 2007; 102: 1844-1847.