Phosphate nephropathy

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Overview

Pathophysiology

Causes

Epidemiology and Demographics

Risk Factors

Natural History, Complications and Prognosis

Diagnosis

Diagnostic Criteria

History and Symptoms

Physical Examination

Laboratory Findings

Biopsy

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Ayesha Javid, MBBS[2]

Overview

Phosphate nephropathy is a clinical manifestation of irreversible kidney injury after the consumption of phosphate-containing bowel preparations such as oral sodium phosphate (OSP), leading to acute kidney injury followed by chronic renal failure. It is characterized by diffuse tubular injury with abundant calcium phosphate deposits in the tubules due to which it is also called acute nephrocalcinosis.

Historical Perspective

Pathophysiology

Hyperphosphatemia

Oral sodium phosphate consumption leads to hyperphosphatemia. Particularly, those patients who have to consume a large amount of Oral Sodium Phosphate as a bowel purgative before an elective colonoscopy have markedly elevated phosphate levels in the blood.[5] This is due to increase phosphate absorption from the small intestine and lack of downregulation of sodium-phosphate cotransporters in the small intestine even when a large amount of phosphate has already been absorbed.[6]

Hyperphosphatemia affects the kidneys by increasing the intratubular phosphate concentration, resulting in the deposition of calcium phosphate in the distal tubule and collecting duct. It directly damages the tubular epithelial cells and leads to luminal obstruction. The calcium phosphate crystals activate the innate immune system due to recognition by the epithelial TLRs leading to to tubular injury.[7] [8] [9]

Volume depletion

Differentiating Acute Phosphate Nephropathy from other Diseases

Epidemiology and Demographics

Gender

Age

Several epidemiological studies have identified advanced age as an independent risk factor of acute phosphate nephropathy, particularly age 55 and more.[2] [16] [18]

Ethnicity

A higher prevalence has been seen among Caucasians.[16] [2]

Risk Factors

Dose of Oral Sodium Phosphate administered

The risk of acute phosphate nephropathy is directly related to the dose of Oral Sodium Phosphate (OSP) administered. The higher the dose administered, more will be blood phosphate levels and hence there would be a higher chance of harming kidneys and resulting in nephropathy.[19]

Chronic Kidney disease

A chronic kidney disease patient will have a decrease glomerular filtration rate (GFR). Oral Sodium Phosphate (OSP) administration is seen to increase the creatinine levels further worsening their kidney functions. Therefore, Oral Sodium Phosphate is contraindicated in chronic renal disease patients. Instead, polyethylene glycol (PEG) has been found to be a good alternative. [20]

Advanced age

Researchers agree that advanced age is an independent risk factor for acute phosphate nephropathy. One research shows the median age to be 64 years, however, although most studies agree on the advanced age is a strong risk factor, but are unable set a particular age limit.

Co-morbid conditions

Co-morbidities such as hypertension and diabetes mellitus have been found to further increase a patient's risk to acute phosphate nephropathy. [15] [21] [22]

Drugs

The following drugs have been found to be a risk factor for acute phosphate nephropathy:[7] [23]

Natural History, Complications and Prognosis

Diagnosis

Diagnostic Criteria

  • The diagnosis of acute phosphate nephropathy is made when the following diagnostic criteria is met:[13] [27]

Symptoms

  • Acute phosphate nephropathy could be asymptomatic due to which it can be undiagnosed until chronic kidney failure occurs.
  • The following symptoms can occur after consumption of oral sodium phosphate which gives a strong suspicion of acute phosphate nephropathy:

Physical Examination

  • Patients with [disease name] usually appear [general appearance].
  • Physical examination may be remarkable for:

Laboratory Findings

Laboratory findings diagnostic of acute phosphate nephropathy include:

Electrolyte disturbances

Following electrolyte abnormalities are diagnostic of acute phosphate nephropathy after the consumption of oral sodium phosphate bowel purgative.

Urinanalysis

Renal function test

Imaging Findings

Renal biopsy

Early findings (<3 weeks)

The early biopsies show tubular degenerative changes, similar to acute tubular necrosis. Findings include

Late finding (>3 weeks)

Acute Phosphate Nephropathy-Calcium Phosphate deposition dark blue coloured on H&E stain[34]

Treatment

Prevention

Prevention of acute phosphate nephropathy could be achieved by:

  • Advice good amount of hydration before, during and after the use of oral sodium phosphate.
  • Increase the time gap between the doses.
  • Ask patient to avoid the following drugs on the day before and the day after the colonoscopy procedure:

References

  1. Vanner SJ, MacDonald PH, Paterson WG, Prentice RS, Da Costa LR, Beck IT (1990). "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. 85 (4): 422–7. PMID 2183591 PMID: 2183591 Check |pmid= value (help).
  2. 2.0 2.1 2.2 2.3 2.4 2.5 Markowitz GS, Perazella MA (2009). "Acute phosphate nephropathy". Kidney Int. 76 (10): 1027–34. doi:10.1038/ki.2009.308. PMID 19675530 PMID: 19675530 Check |pmid= value (help).
  3. Davies MRP, Williams D, Niewiadomski OD (2018). "Phosphate nephropathy: an avoidable complication of bowel preparation for colonoscopy". Intern Med J. 48 (9): 1141–1144. doi:10.1111/imj.14015. PMID 30182391 PMID: 30182391 Check |pmid= value (help).
  4. "International colloquy on the management of intrauterine fetal death". Int J Gynaecol Obstet. 25 (3): 185–97. 1987. PMID 2886377 PMID: 2886377 Check |pmid= value (help).
  5. Lieberman DA, Ghormley J, Flora K (1996). "Effect of oral sodium phosphate [[colon]] preparation on [[serum]] [[electrolytes]] in patients with normal serum [[creatinine]]". Gastrointest Endosc. 43 (5): 467–9. doi:10.1016/s0016-5107(96)70287-0. PMID 8726759 PMID 8726759 Check |pmid= value (help). URL–wikilink conflict (help)
  6. Murer H, Hernando N, Forster L, Biber J (2001). "Molecular mechanisms in proximal tubular and small intestinal phosphate reabsorption (plenary lecture)". Mol Membr Biol. 18 (1): 3–11. doi:10.1080/09687680010019357. PMID 11396609 PMID 11396609 Check |pmid= value (help).
  7. 7.0 7.1 Heher EC, Thier SO, Rennke H, Humphreys BD (2008). "Adverse renal and metabolic effects associated with oral sodium phosphate bowel preparation". Clin J Am Soc Nephrol. 3 (5): 1494–503. doi:10.2215/CJN.02040408. PMC 4571150. PMID 18596115 PMID 18596115 Check |pmid= value (help).
  8. Hebert LA, Lemann J, Petersen JR, Lennon EJ (1966). "Studies of the mechanism by which phosphate infusion lowers serum calcium concentration". J Clin Invest. 45 (12): 1886–94. doi:10.1172/JCI105493. PMC 292874. PMID 5953818 PMID 5953818 Check |pmid= value (help).
  9. 9.0 9.1 9.2 9.3 Heher EC, Thier SO, Rennke H, Humphreys BD (2008). "Adverse renal and metabolic effects associated with oral sodium phosphate bowel preparation". Clin J Am Soc Nephrol. 3 (5): 1494–503. doi:10.2215/CJN.02040408. PMC 4571150. PMID 18596115 PMID: 18596115 Check |pmid= value (help).
  10. Parra-Blanco A, Ruiz A, Alvarez-Lobos M, Amorós A, Gana JC, Ibáñez P; et al. (2014). "Achieving the best bowel preparation for colonoscopy". World J Gastroenterol. 20 (47): 17709–26. doi:10.3748/wjg.v20.i47.17709. PMC 4273122. PMID 25548470 PMID: 25548470 Check |pmid= value (help).
  11. Asplin JR, Mandel NS, Coe FL (1996). "Evidence of calcium phosphate supersaturation in the loop of Henle". Am J Physiol. 270 (4 Pt 2): F604–13. doi:10.1152/ajprenal.1996.270.4.F604. PMID 8967338 PMID 8967338 Check |pmid= value (help).
  12. Verhulst A, Asselman M, De Naeyer S, Vervaet BA, Mengel M, Gwinner W; et al. (2005). "Preconditioning of the distal tubular epithelium of the human kidney precedes nephrocalcinosis". Kidney Int. 68 (4): 1643–7. doi:10.1111/j.1523-1755.2005.00584.x. PMID 16164641 PMID 16164641 Check |pmid= value (help).
  13. 13.0 13.1 13.2 13.3 13.4 13.5 13.6 13.7 Markowitz GS, Stokes MB, Radhakrishnan J, D'Agati VD (2005). "Acute phosphate nephropathy following oral sodium phosphate bowel purgative: an underrecognized cause of chronic renal failure". J Am Soc Nephrol. 16 (11): 3389–96. doi:10.1681/ASN.2005050496. PMID 16192415 PMID: 16192415 Check |pmid= value (help).
  14. Alon U, Donaldson DL, Hellerstein S, Warady BA, Harris DJ (1992). "Metabolic and histologic investigation of the nature of nephrocalcinosis in children with hypophosphatemic rickets and in the Hyp mouse". J Pediatr. 120 (6): 899–905. doi:10.1016/s0022-3476(05)81957-2. PMID 1317418 PMID: 1317418 Check |pmid= value (help).
  15. 15.0 15.1 15.2 15.3 Markowitz GS, Stokes MB, Radhakrishnan J, D'Agati VD (2005). "Acute phosphate nephropathy following oral sodium phosphate bowel purgative: an underrecognized cause of chronic renal failure". J Am Soc Nephrol. 16 (11): 3389–96. doi:10.1681/ASN.2005050496. PMID 16192415 PMID 16192415 Check |pmid= value (help).
  16. 16.0 16.1 16.2 16.3 Abcar A, Hever A, Momi JS, Sim JJ (2009). "Acute phosphate nephropathy". Perm J. 13 (3): 48–50. doi:10.7812/tpp/08-069. PMC 2911810. PMID 20740089 PMID: 20740089 Check |pmid= value (help).
  17. Fenton A, Montgomery E, Nightingale P, Peters AM, Sheerin N, Wroe AC; et al. (2018). "Glomerular filtration rate: new age- and gender- specific reference ranges and thresholds for living kidney donation". BMC Nephrol. 19 (1): 336. doi:10.1186/s12882-018-1126-8. PMC 6249883. PMID 30466393 PMID: 30466393 Check |pmid= value (help).
  18. Hurst FP, Bohen EM, Osgard EM, Oliver DK, Das NP, Gao SW; et al. (2007). "Association of oral sodium phosphate purgative use with acute kidney injury". J Am Soc Nephrol. 18 (12): 3192–8. doi:10.1681/ASN.2007030349. PMID 17978311 PMID 17978311 Check |pmid= value (help).
  19. Vanner SJ, MacDonald PH, Paterson WG, Prentice RS, Da Costa LR, Beck IT (1990). "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. 85 (4): 422–7. PMID 2183591 PMID 2183591 Check |pmid= value (help).
  20. Russmann S, Lamerato L, Motsko SP, Pezzullo JC, Faber MD, Jones JK (2008). "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. 103 (11): 2707–16. doi:10.1111/j.1572-0241.2008.02201.x. PMID 18945285 PMID 18945285 Check |pmid= value (help).
  21. Russmann S, Lamerato L, Marfatia A, Motsko SP, Pezzullo JC, Olds G; et al. (2007). "Risk of impaired renal function after colonoscopy: a cohort study in patients receiving either oral sodium phosphate or polyethylene glycol". Am J Gastroenterol. 102 (12): 2655–63. doi:10.1111/j.1572-0241.2007.01610.x. PMID 17970832 PMID 17970832 Check |pmid= value (help).
  22. Khurana A, McLean L, Atkinson S, Foulks CJ (2008). "The effect of oral sodium phosphate drug products on renal function in adults undergoing bowel endoscopy". Arch Intern Med. 168 (6): 593–7. doi:10.1001/archinte.168.6.593. PMID 18362251 PMID: 18362251 Check |pmid= value (help).
  23. Ainley EJ, Winwood PJ, Begley JP (2005). "Measurement of serum electrolytes and phosphate after sodium phosphate colonoscopy bowel preparation: an evaluation". Dig Dis Sci. 50 (7): 1319–23. doi:10.1007/s10620-005-2780-9. PMID 16047480 PMID 16047480 Check |pmid= value (help).
  24. Santos P, Branco A, Silva S, Paiva A, Baldaia J, Maximino J; et al. (2010). "Acute phosphate nephropathy after bowel cleansing: still a menace". Nefrologia. 30 (6): 702–4. doi:10.3265/Nefrologia.pre2010.Jul.10544. PMID 21113224 . PMID: 21113224 . Check |pmid= value (help).
  25. 25.0 25.1 "StatPearls". 2020. PMID 29939592 PMID 29939592 Check |pmid= value (help).
  26. Tan JJ, Tjandra JJ (2006). "Which is the optimal bowel preparation for colonoscopy - a meta-analysis". Colorectal Dis. 8 (4): 247–58. doi:10.1111/j.1463-1318.2006.00970.x. PMID 16630226 PMID: 16630226 Check |pmid= value (help).
  27. Markowitz GS, Whelan J, D'Agati VD (2005). "Renal failure following bowel cleansing with a sodium phosphate purgative". Nephrol Dial Transplant. 20 (4): 850–1. doi:10.1093/ndt/gfh718. PMID 15772276 PMID: 15772276 Check |pmid= value (help).
  28. 28.0 28.1 28.2 28.3 Santos P, Branco A, Silva S, Paiva A, Baldaia J, Maximino J; et al. (2010). "Acute phosphate nephropathy after bowel cleansing: still a menace". Nefrologia. 30 (6): 702–4. doi:10.3265/Nefrologia.pre2010.Jul.10544. PMID 21113224 PMID: 21113224 Check |pmid= value (help).
  29. 29.0 29.1 Pálmadóttir VK, Gudmundsson H, Hardarson S, Arnadóttir M, Magnússon T, Andrésdóttir MB (2010). "Incidence and outcome of acute phosphate nephropathy in Iceland". PLoS One. 5 (10): e13484. doi:10.1371/journal.pone.0013484. PMC 2957439. PMID 20976065 PMID: 20976065 Check |pmid= value (help).
  30. Ori Y, Herman M, Tobar A, Chernin G, Gafter U, Chagnac A; et al. (2008). "Acute phosphate nephropathy-an emerging threat". Am J Med Sci. 336 (4): 309–14. doi:10.1097/MAJ.0b013e318167410c. PMID 18854672 PMID: 18854672 Check |pmid= value (help).
  31. Russmann S, Lamerato L, Marfatia A, Motsko SP, Pezzullo JC, Olds G; et al. (2007). "Risk of impaired renal function after colonoscopy: a cohort study in patients receiving either oral sodium phosphate or polyethylene glycol". Am J Gastroenterol. 102 (12): 2655–63. doi:10.1111/j.1572-0241.2007.01610.x. PMID 17970832 PMID: 17970832 Check |pmid= value (help).
  32. Joo WC, Lee SW, Yang DH, Han JY, Kim MJ (2012). "A case of biopsy-proven chronic kidney disease on progression from acute phosphate nephropathy". Kidney Res Clin Pract. 31 (2): 124–7. doi:10.1016/j.krcp.2012.04.320. PMC 4715133. PMID 26889420 PMID: 26889420 Check |pmid= value (help).
  33. Markowitz GS, Nasr SH, Klein P, Anderson H, Stack JI, Alterman L; et al. (2004). "Renal failure due to acute nephrocalcinosis following oral sodium phosphate bowel cleansing". Hum Pathol. 35 (6): 675–84. doi:10.1016/j.humpath.2003.12.005. PMID 15188133 PMID 15188133 Check |pmid= value (help).
  34. "Case 514 -- Case".
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  36. 36.0 36.1 Hurst FP, Bohen EM, Osgard EM, Oliver DK, Das NP, Gao SW; et al. (2007). "Association of oral sodium phosphate purgative use with acute kidney injury". J Am Soc Nephrol. 18 (12): 3192–8. doi:10.1681/ASN.2007030349. PMID 17978311 PMID: 17978311 Check |pmid= value (help).
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