Acute phosphate nephropathy
- Glen S Markowitz, MD
Glen S Markowitz, MD
- Professor of Clinical Pathology
- Columbia University Medical Center
- Mark A Perazella, MD, FACP
Mark A Perazella, MD, FACP
- Professor of Medicine
- Yale University School of Medicine
Acute phosphate nephropathy is a form of kidney injury that occurs following the use of bowel purgatives that contain oral sodium phosphate (OSP) and has been reported following the administration of sodium phosphate-containing enemas [1,2]. OSP was formerly sold without prescription under the brand name "Fleet Phospho-soda" (C.B. Fleet Inc.). Fleet no longer distributes OSP; however, generic versions of OSP are still available without prescription. OSP is also available by prescription in a pill form (Visicol, OsmoPrep; Salix Pharmaceuticals). In both pill and liquid form, OSP is a hyperosmotic laxative that acts by drawing water into the gastrointestinal tract.
Although long used as a laxative, OSP began to be used as a purgative for colonoscopy in 1990 . It is frequently given in favor of standard polyethylene glycol (PEG)-based lavage solutions because of the smaller required volume, which results in better patient compliance and improved colonic cleansing [4-6].
However, there have been multiple cases of OSP-induced acute kidney injury (AKI) with defining histologic features on biopsy [7-11]. This clinicopathologic entity has been referred to as acute phosphate nephropathy.
In 2006, in response to published reports, the US Food and Drug Administration (FDA) issued a warning regarding the potential for AKI in patients who received OSP . The warning was incorporated into a consensus document on bowel preparation by the American Society of Colon & Rectal Surgeons (ASCRS), the American Society of Gastrointestinal Endoscopy (ASGE), and the Society of American Gastrointestinal & Endoscopic Surgeons (SAGES) . In December 2008, the FDA required that a boxed warning be added to labeling of Visicol and OsmoPrep, which are still available by prescription . At the same time, following the recommendation of the FDA, over-the-counter preparations that contain OSP were voluntarily withdrawn from the market by Fleet; but, as noted above, generic versions are still available. In 2014, the FDA issued another warning that using more than one dose in 24 hours of OSP to treat constipation can cause "rare but serious harm to the kidneys and heart, and even death" .
This topic provides a review of the clinical features of acute phosphate nephropathy. AKI associated with an increased phosphate load has also been described in tumor lysis syndrome, especially with alkalinization of the urine by bicarbonate-containing intravenous (IV) fluids. Tumor lysis syndrome is discussed elsewhere. (See "Tumor lysis syndrome: Definition, pathogenesis, clinical manifestations, etiology and risk factors".)
- Markowitz GS, Perazella MA. Acute phosphate nephropathy. Kidney Int 2009; 76:1027.
- Ori Y, Rozen-Zvi B, Chagnac A, et al. Fatalities and severe metabolic disorders associated with the use of sodium phosphate enemas: a single center's experience. Arch Intern Med 2012; 172:263.
- Vanner SJ, MacDonald PH, Paterson WG, et al. A randomized prospective trial comparing oral sodium phosphate with standard polyethylene glycol-based lavage solution (Golytely) in the preparation of patients for colonoscopy. Am J Gastroenterol 1990; 85:422.
- Cohen SM, Wexner SD, Binderow SR, et al. Prospective, randomized, endoscopic-blinded trial comparing precolonoscopy bowel cleansing methods. Dis Colon Rectum 1994; 37:689.
- Golub RW, Kerner BA, Wise WE Jr, et al. Colonoscopic bowel preparations--which one? A blinded, prospective, randomized trial. Dis Colon Rectum 1995; 38:594.
- Tan JJ, Tjandra JJ. Which is the optimal bowel preparation for colonoscopy - a meta-analysis. Colorectal Dis 2006; 8:247.
- Desmeules S, Bergeron MJ, Isenring P. Acute phosphate nephropathy and renal failure. N Engl J Med 2003; 349:1006.
- Markowitz GS, Stokes MB, Radhakrishnan J, D'Agati VD. Acute phosphate nephropathy following oral sodium phosphate bowel purgative: an underrecognized cause of chronic renal failure. J Am Soc Nephrol 2005; 16:3389.
- Markowitz GS, Whelan J, D'Agati VD. Renal failure following bowel cleansing with a sodium phosphate purgative. Nephrol Dial Transplant 2005; 20:850.
- Demoulin N, Jadoul M, Cosyns JP, Labriola L. An easily overlooked iatrogenic cause of renal failure. Clin Nephrol 2008; 70:176.
- Steinman TI, Samir AE, Cornell LD. Case records of the Massachusetts General Hospital. Case 27-2008. A 64-year-old man with abdominal pain, nausea, and an elevated level of serum creatinine. N Engl J Med 2008; 359:951.
- Oral sodium phosphate (OSP) products for bowel cleansing. US Government Printing Office; Center of Drug Evaluation Research, DC 2006.
- American Society of Colon and Rectal Surgeons (ASCRS), American Society for Gastrointestinal Endoscopy (ASGE), Society of American Gastrointestinal and Endoscopic Surgeons (SAGES), et al. 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). Surg Endosc 2006; 20:1147.
- Oral sodium phosphate (OSP) products for bowel cleansing (marketed as Visicol and OsmoPrep), and oral sodium phosphate products available without a prescription. US Govenrment Printing Office; Center of Drug Evaluation Research. US Food and Drug Administration, Washington, DC 2008.
- Lieberman DA, Ghormley J, Flora K. Effect of oral sodium phosphate colon preparation on serum electrolytes in patients with normal serum creatinine. Gastrointest Endosc 1996; 43:467.
- Gumurdulu Y, Serin E, Ozer B, et al. Age as a predictor of hyperphosphatemia after oral phosphosoda administration for colon preparation. J Gastroenterol Hepatol 2004; 19:68.
- Murer H, Hernando N, Forster L, Biber J. Molecular mechanisms in proximal tubular and small intestinal phosphate reabsorption (plenary lecture). Mol Membr Biol 2001; 18:3.
- Forster IC, Hernando N, Biber J, Murer H. Proximal tubular handling of phosphate: A molecular perspective. Kidney Int 2006; 70:1548.
- Heher EC, Thier SO, Rennke H, Humphreys BD. Adverse renal and metabolic effects associated with oral sodium phosphate bowel preparation. Clin J Am Soc Nephrol 2008; 3:1494.
- Mishra R, Kaufman D, Mattern J 3rd, Dutta SK. Severe hyperphosphatemia and hypocalcemia caused by bowel preparation for colonoscopy using oral sodium phosphate in end-stage renal disease. Endoscopy 2005; 37:1259.
- Wechsler A, Schneider R, Sapojnikov M, et al. Bowel cleansing in patients with chronic renal failure--an often overlooked hazard. Nephrol Dial Transplant 2006; 21:1133.
- Fass R, Do S, Hixson LJ. Fatal hyperphosphatemia following Fleet Phospo-Soda in a patient with colonic ileus. Am J Gastroenterol 1993; 88:929.
- Hebert LA, Lemann J Jr, Petersen JR, Lennon EJ. Studies of the mechanism by which phosphate infusion lowers serum calcium concentration. J Clin Invest 1966; 45:1886.
- Markowitz GS, Nasr SH, Klein P, et al. Renal failure due to acute nephrocalcinosis following oral sodium phosphate bowel cleansing. Hum Pathol 2004; 35:675.
- Asplin JR, Mandel NS, Coe FL. Evidence of calcium phosphate supersaturation in the loop of Henle. Am J Physiol 1996; 270:F604.
- Verhulst A, Asselman M, De Naeyer S, et al. Preconditioning of the distal tubular epithelium of the human kidney precedes nephrocalcinosis. Kidney Int 2005; 68:1643.
- Khurana A, McLean L, Atkinson S, Foulks CJ. The effect of oral sodium phosphate drug products on renal function in adults undergoing bowel endoscopy. Arch Intern Med 2008; 168:593.
- Brunelli SM, Lewis JD, Gupta M, et al. Risk of kidney injury following oral phosphosoda bowel preparations. J Am Soc Nephrol 2007; 18:3199.
- Tenenhouse HS, Gauthier C, Martel J, et al. Na+ -phosphate cotransport in mouse distal convoluted tubule cells: evidence for Glvr-1 and Ram-1 gene expression. J Bone Miner Res 1998; 13:590.
- Hesse A, Heimbach D. Causes of phosphate stone formation and the importance of metaphylaxis by urinary acidification: a review. World J Urol 1999; 17:308.
- Hurst FP, Bohen EM, Osgard EM, et al. Association of oral sodium phosphate purgative use with acute kidney injury. J Am Soc Nephrol 2007; 18:3192.
- Russmann S, Lamerato L, Marfatia A, 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.
- Markowitz GS, Radhakrishnan J, D'Agati VD. Towards the incidence of acute phosphate nephropathy. J Am Soc Nephrol 2007; 18:3020.
- Barclay RL. Safety, efficacy, and patient tolerance of a three-dose regimen of orally administered aqueous sodium phosphate for colonic cleansing before colonoscopy. Gastrointest Endosc 2004; 60:527.
- Hookey LC, Depew WT, Vanner SJ. A prospective randomized trial comparing low-dose oral sodium phosphate plus stimulant laxatives with large volume polyethylene glycol solution for colon cleansing. Am J Gastroenterol 2004; 99:2217.
- Rostom A, Jolicoeur E, Dubé C, et al. A randomized prospective trial comparing different regimens of oral sodium phosphate and polyethylene glycol-based lavage solution in the preparation of patients for colonoscopy. Gastrointest Endosc 2006; 64:544.
- Russmann S, Lamerato L, Motsko SP, et al. Risk of further decline in renal function after the use of oral sodium phosphate or polyethylene glycol in patients with a preexisting glomerular filtration rate below 60 ml/min. Am J Gastroenterol 2008; 103:2707.
- Ainley EJ, Winwood PJ, Begley JP. Measurement of serum electrolytes and phosphate after sodium phosphate colonoscopy bowel preparation: an evaluation. Dig Dis Sci 2005; 50:1319.
- Martin RR, Lisehora GR, Braxton M Jr, Barcia PJ. Fatal poisoning from sodium phosphate enema. Case report and experimental study. JAMA 1987; 257:2190.
- Korzets A, Dicker D, Chaimoff C, Zevin D. Life-threatening hyperphosphatemia and hypocalcemic tetany following the use of fleet enemas. J Am Geriatr Soc 1992; 40:620.
- Schaefer M, Littrell E, Khan A, Patterson ME. Estimated GFR Decline Following Sodium Phosphate Enemas Versus Polyethylene Glycol for Screening Colonoscopy: A Retrospective Cohort Study. Am J Kidney Dis 2016; 67:609.
- Markowitz GS, Bomback AS, Perazella MA. Phosphate enemas and GFR decline: it's premature to sound the alarm. Kidney Int 2016; 90:13.
- Gonlusen G, Akgun H, Ertan A, et al. Renal failure and nephrocalcinosis associated with oral sodium phosphate bowel cleansing: clinical patterns and renal biopsy findings. Arch Pathol Lab Med 2006; 130:101.
- Fine A, Patterson J. Severe hyperphosphatemia following phosphate administration for bowel preparation in patients with renal failure: two cases and a review of the literature. Am J Kidney Dis 1997; 29:103.
- Orias M, Mahnensmith RL, Perazella MA. Extreme hyperphosphatemia and acute renal failure after a phosphorus-containing bowel regimen. Am J Nephrol 1999; 19:60.
- Manley P, Somerfield J, Simpson I, et al. Bilateral uraemic optic neuritis complicating acute nephrocalcinosis. Nephrol Dial Transplant 2006; 21:2957.
- Aasebø W, Scott H, Ganss R. Kidney biopsies taken before and after oral sodium phosphate bowel cleansing. Nephrol Dial Transplant 2007; 22:920.
- Beyea A, Block C, Schned A. Acute phosphate nephropathy following oral sodium phosphate solution to cleanse the bowel for colonoscopy. Am J Kidney Dis 2007; 50:151.
- Volume depletion
- Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers
- Risk factors
- Risk with sodium phosphate enemas
- CLINICAL PRESENTATION AND PROGNOSIS
- Acute and reversible kidney injury
- Acute phosphate nephropathy
- Differential diagnosis
- PREVENTION AND TREATMENT
- SUMMARY AND RECOMMENDATIONS