Within both the kidney and the small intestine, phosphate absorption occurs mainly via sodium-dependent phosphate cotransporter proteins that are members of the SLC34 gene family [2-3]. NaPi-IIa (SLC34A1) and NaPi-IIc (SLC34A3) are expressed in the brush border of the proximal tubule and their expression is down regulated by increases in serum phosphate and parathyroid hormone (PTH). As such, NaPi-IIa knock-out mice have significant hyperphosphaturia and develop early and severe nephrocalcinosis [4]. NaPi-IIb (SLC34A2) has a broader distribution that includes the brush border of the small intestine and levels of this protein increase in response to hypophosphatemia and vitamin D. While expression of NaPi-IIa is acutely controlled over short time periods (i.e. minutes), NaPi-IIb expression in the intestine is slower, requiring days to respond to physiologic changes. Interestingly, recent studies have shown that there is a direct signaling axis by which intestinal phosphate absorption rapidly increases fractional phosphate excretion in the kidney. This effect is apparent within 10 minutes of phosphate ingestion and is independent of serum phosphate concentration or PTH [5].
In the usual state, between 60-80% of ingested phosphate is absorbed in the small intestine. In the kidney, phosphate is freely filtered at the level of the glomerulus. Approximately 80% of phosphate is reabsorbed in the proximal tubule, with smaller amounts reabsorbed in the distal tubule and collecting duct [6-7]. Oral phosphate ingestion has the potential to increase serum levels when the intake is at higher than usual levels or occurs over short periods of time. Similarly hyperphosphatemia may follow phosphate ingestion when it occurs in the setting of impaired gastrointestinal motility leading to increased absorption or with renal dysfunction leading to decreased excretion. Hyperphosphatemia may also result from massive intracellular phosphate release in the setting of tumor lysis syndrome or rhabdomyolysis.
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Keywords
- Acute Kidney Injury
- Renal Biopsy
- Angiotensin Converting Enzyme Inhibitor
- Calcium Phosphate
- Bowel Preparation
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References
Klemm KM, Klein MJ. Biochemical markers of bone metabolism. In: Henry’s Clinical Diagnosis and Management by Laboratory Methods. 21st Edition. McPherson RA, Pincus MR (editors). Saunders Elsevier 2007: p. 170-184.
Murer H, Hernando N, Forster L, Biber J. Molecular mechanisms in proximal tubular and small intestinal phosphate reabsorptio. Mol Membr Biol 2001; 18: 3-11.
Forster IC, Hernando N, Biber J, Murer H: Proximal tubular handling of phosphate: A molecular perspective. Kidney Int. 2006; 70: 1548-1559.
Chau H, El-Maadawy S, McKee MD, Tenenhouse HS: Renal calcification in mice homozygous for the disrupted type IIa Na/Pi cotransporter gene Npt2. J Bone Miner Res. 2003; 18: 644-657.
Berndt T, Thomas LF, Craig TA, Sommer S, Li X, Bergstralh EJ, Kumar R: Evidence for a signaling axis by which intestinal phosphate rapidly modulates renal phosphate absorption. Proc Natl Acad Sci USA 2007; 104: 11085-11090.
Tenenhouse HS, Gauthier C, Martel J, Gesek FA, Coutermarsh BA, Friedman PA. Na+-phosphate cotransport in mouse distal convoluted tubule cells: Evidence for Glvr-1 and Ram-1 gene expression. J Bone Miner Res 1998; 13: 590-7.
Sayer JA, Carr G, Simmons NL. Nephrocalcinosis: Molecular insights into calcium precipitation within the kidney. Clinical Science 2004; 106: 549-561.
Vanner SJ, MacDonald PH, Paterson WG, Prentice RS, Da Cost LR, Beck IT. 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: 422-7.
Cohen SM, Wexner SD, Binderow SR, Nogueras JJ, Daniel N, Ehrenpreis ED, Jensen J, Bonner GF, Ruderman WB. Prospective, randomized, endoscopic-blinded trial comparing precolonoscopy bowel cleansing methods. Dis Colon Rectum 1994; 37: 689-696.
Golub RW, Kerner BA, WiseWE, Meesig DM, Hartmann RF, Khanduja KS, Aguilar PS. Colonoscopic Bowel Preparations - Which One? A Blinded, Prospective, Randomized Trial. Dis Colon Rectum 1995; 38: 594-599.
Tan JJ, Tjandra JJ: Which is the optimal bowel preparation for colonoscopy - a meta-analysis. Colorectal Dis 2006; 8: 247-258.
Chan A, Depew W, Vanner S. Use of oral sodium phosphate colonic lavage solution by Canadian colonoscopists: pitfalls and complications. Can J Gastroenterol 1997; 11: 334-8.
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 Kidn Dis 1997; 29: 103-105.
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: 1259-60.
Kastenberg D, Chasen R, Cuckoo C, Riff D, Steinberg S, Weiss E, Wruble L: Efficacy and safety of sodium phosphate tablets compared with PEG solution in colon cleansing: two identically designed, randomized, controlled, parallel group multicenter phase III trials. Gastrointestinal Endoscopy 2001; 54: 705-712.
Carson FL: Histotechnology: A self-instructional text. Second Edition, Chicago, USA, ASCP Press, 1997.
Gwinner W, Suppa S, Mengel M, Hoy L, Kreipe HH, Haller H, Schwarz A. Early calcifications in renal allografts detected by protocol biopsies: Causes and clinical implications. Am J Transplant. 2005; 5:1934-1941.
Nankivell BJ, Borrows RJ, Fung CL, O’Connell PJ, Allen RD, Chapman JR. The natural history of chronic allograft nephropathy. N Engl J Med. 2003; 349:2326-2333.
Gonlusen G, Akgun H, Ertan A, Olivero J, Truong L. Renal Failure and Nephrocalcinosis Associated with Oral Sodium Phosphate Bowel Cleansing. Arch Patholo Lab Med 2006; 130: 101-6.
Zipser RD, Bischel MD, Abrams DE. Hypocalcemic tetany due to sodium phosphate ingestion in acute renal failure. Nephron 1975; 14: 378-381.
Fass R, Do S, Hixson LJ: Fatal Hyperphosphatemia following Fleet Phospho-Soda in a Patient with Colonic Ileus. Am J Gastroenterol 1993; 88: 929-932.
Ahmed M, Raval P, Buganza G. Oral sodium phosphate catharsis and acute renal failure. Am J Gastroenterol 1996; 6: 1261-2.
Orias M, Mahnensmith RL, Perazella MA. Extreme hyperphosphatemia and acute renal failure after a phosphorus-containing bowel regimen. Am J Nephrol 1999; 19: 60-3.
Tan HL, Liew QY, Loo S, Hawkins R. Severe hyperphosphatemia and associated electrolyte and metabolic derangement following the administration of sodium phosphate for bowel preparation. Anesthesia 2002; 57: 478-483.
Ullah N, Yeh R, Ehrinpreis M. Fatal Hyperphosphatemia From a Phosphosoda Bowel Preparation. J Clin Gastroenterol 2002; 34: 457-458.
Azzam I, Kovalev Y, Storch S, Elias N. Life threatening hyperphosphatemia after administration of sodium phosphate in preparation for colonoscopy. Postgrad Med J 2004; 80: 487-488.
Aydogan T, Kanbay M, Uz B, Kaya A, Bozalan R, Isik A, Bozalan R, Erkman M, Akcay A. Fatal hyperphosphatemia secondary to phosphosoda bowel preparation in a geriatric patient with normal renal function. J. Clin Gastroenterol 2006; 40: 177.
Ma RC, Chow CC, Yeung VT, So WY, Kong AP, Tong PC, Cockram CS, Chan JC. Acute renal failure following oral sodium phosphate bowel preparation in diabetes. Diabetes Care 2007; 30: 182-3.
Desmeules S. Gergeron MJ, Isenring P: Acute phosphate nephropathy and renal failure. N Engl J Med 2003; 349: 1006-7.
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: 3389-3396.
Manley P, Somerfield J, Simpson I, Barber A, Zwi J. Bilateral uraemic optic neuritis complicating acute nephrocalcinosis. Nephrol Dial Transplant 2006; 21: 2957-8.
Aasebo W, Scott H, Ganss R. Kidney biopsies taken before and after sodium phosphate bowel cleansing. Nephrol Dial Transplant 2006; 22: 920-922.
Beyea A, Block C, Schned A. Acute phosphate nephropathy following oral sodium phosphate solution to cleanse the bowel for colonoscopy. Am J Kidn Dis 2007; 50: 151-4, 2007.
McConnell TH. Fatal hypocalcemia from phosphate absorption from laxative preparation. JAMA 1971; 216: 147-8.
Markowitz GS, Nasr SH, Klein P, Anderson H. Stack JI, Alterman L, Price B, Radhakrishnan J, D’Agati VD. Renal failure and acute nephrocalcinosis following oral sodium phosphate bowel cleansing. Human Pathol 2004; 35: 675-684.
Markowitz GS, Whelan, J, D’Agati, VD: Renal failure following bowel cleansing with a sodium phosphate purgative. Nephrol Dial Transplant 2005; 20: 850-851.
Bulger HA, Dixon HH, Barr DP, Schregardus O. The functional pathology of hyper-parathyroidism. J Clin Invest 1930; 9:143-190.
Albright F, Bauer W, Claflin D, Cockrill JR. Studies in parathyroid physiology III: The effect of phosphate ingestion in clinical hyperparathyroidism. J Clin Invest 1932; 11:411-435.
Goldsmith RS, Ingbar SH. Inorganic Phosphate Treatment of Hypercalcemia of Diverse Etiologies. N Eng J Med 1966; 274: 1-7.
Breuer I, LeBauer. Caution in the Use of Phosphates in the Treatment of Severe Hypercalcemia. J Clin Endocr 1967; 27: 695-8.
Carey RW, Schmitt GW, Kopald HH, Kantrowitz PA. Massive Extraskeletal Calcification During Phosphate Treatment of Hypercalcemia. Arch Intern Med 1968; 122: 150-5.
Shackney S, Hasson J. Preciptious Fall In Serum Calcium, Hypotension, and Acute Renal Failure After Intravenous Phosphate Therapy for Hypercalcemia. Ann of Intern Med 1967; 5:906-16.
Ayala G, Chertow BS, Shah JH, Williams GA, Kukreja SC. Acute Hyperphosphatemia and Acute Persistent Renal Insufficiency Induced by Oral Phosphate Therapy. Ann of Intern Med 1975; 83: 520-1.
Dudley FJ, Blackburn CRB. Extraskeletal Calcification Complicating Oral Neutral- Phosphate Therapy. Lancet 1970; 26: 628-630.
Hebert LA, Lemann J, Petersen JR, Lennon EJ. Studies of the mechanism by which phosphate infusion lowers the serum calcium concentration. J Clin Invest 1966; 45: 1886-1894.
Verge CF, Lam A, Simpson JM, Cowell CT, Howard NJ, Silink M. Effects of therapy in X-linked hypophosphatemic rickets. N Eng J Med 1991; 325: 1843-8.
Alon U, Donaldson DL, Hellerstein S, Warady BA, Harris DJ. Metabolic and histologic investigation of the nature of nephrocalcinosis in children with hypophosphatemic rickets and the Hyp mouse. J Pediatr 1992; 120: 899-905.
Schnell-Feith E, Kist-van Holthe J, Conneman N, van Zwietne PHT, Holscher HC, Zonderland HM, Brand R, van der Heijden BJ. Etiology of nephrocalcinosis in preterm neonates: Association of nutritional intake and urinary parameters. Kidney Int 2000; 58: 2102-2110.
Pfitzer A, Nelle M, Rohrschneider W, Linderkamp O, Troger J. Incidence of typical nephrocalcinosis ultrasound findings in premature infants during enteral calcium and phosphate administration. Z Geburtshilfe Neonatol 1998; 202: 159-163.
Ritkes-Hoitinga J, Lemmens AG, Danse LHJC, Beynen AC. Phosphorous-induced nephrocalcinosis and kidney function in female rats. J Nutr 1989; 119: 1423-1431.
Ritkes-Hoitinga J, Mathot JNJJ, Van Zutphen LFM, Beynen AC. Inbred strains of rats have differential sensitivity to dietary phosphorus-induced nephrocalcinosis. J Nutr 1992; 122: 1682-1692.
Cramer B, Husa L. Pushpanathan C: Nephrocalcinosis in rabbits - Correlation of ultrasound, computed tomography, pathology and renal function. Pediatr Radiol 1998; 28: 9-13.
Cramer B, Husa L. Pushpanathan C: Pattern and permanence of phosphate-induced nephrocalcinosis in rabbits. 1998; 28: 14-19.
Schneider P, Ober KM, Ueberberg H. Contribution to the phosphate-induced nephropathy in the dog. Comparative light and electron microscopic investigations on the proximal tubule after oral application of K2HPO4, Na2HPO4, KC1, and NaC1. Exp Patholol 1981; 19: 53-65.
Patel VK, Emmett M, Santa Ana C, Fordtran JS. Pathogenesis of nephrocalcinosis after sodium phosphate catharsis to prepare for colonoscopy; Intestinal phosphate absorption and its effect on urine mineral and electrolyte excretion. Human Pathol 2007; 38: 193-4.
Asplin JR, Mandel NS, Coe FL. Evidence of calcium phosphate supersaturation in the loop of Henle. Am J Physiol 1996; 270: F604- F613.
Verhulst A, Asselman M, De Naeyer S, Vervaet BA, Mengel M, Gwinner W, D’Haese PC, Verkoelen CF, DeBroe ME. Preconditioning of the distal tubular epithelium of the human kidney precedes nephrocalcinosis. Kidney Int. 2005; 68:1643-7.
Haithcock D, Jiao H, Cui XL, Hopfer U, Douglas JG. Renal proximal tubular AT2 receptor: Signaling and transport. J Am Soc Nephrol 1999; 10: S69-S74.
Hesse A, Heimbach D: Causes of phosphate stone formation and the importance of metaphylaxis by urinary acidification: A review. World J Urol 1999; 17: 308-315.
Ainley EJ, Winwood PJ, Begley JP. Measurement of Serum Electrolytes and Phosphate After Sodium Phosphate Colonoscopy Bowel Preparation. Digestive Dis and Sci 2005; 50: 1319-1323.
Gumurdulu Y, Serin E, Ozer B, Gokcel A, Boyacioglu S. Age as a predictor of hyperphosphatemia after oral phosphosoda admin- istration for colon preparation. J Gastroenterol Hepatol 2004; 19: 68-72.
Beloosesky Y, Grinblat J, Weiss A, Grosman B, Gafter U, Chagnac A: Electrolyte disorders following oral sodium phosphate ad- ministration for bowel cleansing in elderly patients. Arch Intern Med 2003; 163: 803-8.
Geary CP, Cousins FB. An oestrogen-linked nephrocalcinosis in rats. Br J Exp Pathol 1969; 50:507-515.
Fuiano G, Maza G, Comi N, Caglioti A, De Nicola L, Iodice C, Andreucci M, Andreucci VE. Current indications for renal biopsy: A questionnaire-based survey. Am J Kidn Dis 2000; 35: 448-457.
Wexner S, Beck D, Baron T, Fanelli RD, Hyman N, Shen BS, Wasco KE. A consensus document on bowel preparation before colonoscopy: Prepared by 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: 1147-1161.
Post, S: Changes to Professional Labeling of Fleet Phospho-Soda. 2006. http://www.phosphosoda.com/professionals/pdf/ 2006DearDrLetter.pdf
Abaskharoun R, Depew W, Vanner S. Changes in renal function following administration of oral sodium phosphate or polyeth- ylene glycol cleansing before colonoscopy. Can J Gastroenterol. 2007; 21: 227-231.
Brunelli SM, Lewis JD, Gupta M, Latif SM, Weiner MG, Feldman HI. Risk of kidney injury following use of oral phosphosoda bowel preparations. J Am Soc Nephrol. 2007; 18:3199-3205.
Hurst FP, Bohen EM, Osgard EM, Oliver DK, Das NP, Gao SW, Abbott KC. Acute kidney injury associated with oral sodium phosphate purgative use: An observational retrospective cohort study. J Am Soc Nephrol. 2007; 18:3192-8.
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: 527-533.
Rex DK, Chasen R, Pochapin MB. Safety and efficacy of two reduced dosing regimens of sodium phosphate tablets for prepara- tion following colonoscopy. Aliment Pharmacol Ther. 2002; 16: 937-944.
Hookey LC, Depew WT, Vanner SJ. A Prospective Randomized Low-Dose Oral Sodium Phosphate Plus Stimulant Laxatives with Large Volume Polyethylene Glycol Solution for Colon Cleansing. Am J Gastroenterol 2004: 99: 2217-2222.
Vanner SJ, MacDonald PH, Paterson WG, Prentice RSA, DaCosta LR, Beck IT: 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: 422-7.
Rostom A, JolicoeurE, Dube C, Gregoire S, Patel D, Saloojee N, Lowe C. A randomized prospective trial comparing different regi- mens of oral sodium phosphate and polyethylene glycol-based lavage solution in the preparation of patients for colonoscopy. Gastrointest Endosc 2006; 64: 544-552.
Seeff LC, Richards TB, Shapiro JA, Nadel MR, Manninen DL, Given LS, Dong FB, Winges LD, McKenna MT. How many endoscopies are performed for colorectal cancer screening? Results from the CDC’s survey of endoscopic capacity. Gastroenterol 2004; 127: 1670-7.
Hookey LC, Vanner S. A review of current issues underlying colon cleansing before colonoscopy. Can J Gastroenterol. 2007; 21: L105-11.
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Markowitz, G.S. (2008). Oral sodium phosphate bowel purgatives and acute phosphate nephropathy. In: De Broe, M.E., Porter, G.A., Bennett, W.M., Deray, G. (eds) Clinical Nephrotoxins. Springer, Boston, MA. https://doi.org/10.1007/978-0-387-84843-3_26
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