Phosphate nephropathy: Difference between revisions
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===Co-morbid conditions=== | ===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. | Co-morbidities such as [[hypertension]] and [[diabetes mellitus]] have been found to further increase a patient's risk to acute phosphate nephropathy. <ref name="pmidPMID 16192415">{{cite journal| author=Markowitz GS, Stokes MB, Radhakrishnan J, D'Agati VD| title=Acute phosphate nephropathy following oral sodium phosphate bowel purgative: an underrecognized cause of chronic renal failure. | journal=J Am Soc Nephrol | year= 2005 | volume= 16 | issue= 11 | pages= 3389-96 | pmid=PMID 16192415 | doi=10.1681/ASN.2005050496 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16192415 }} </ref> | ||
===Drugs=== | ===Drugs=== | ||
The following drugs have been found to be a risk factor for acute phosphate nephropathy:<ref name="pmidPMID 18596115">{{cite journal| author=Heher EC, Thier SO, Rennke H, Humphreys BD| title=Adverse renal and metabolic effects associated with oral sodium phosphate bowel preparation. | journal=Clin J Am Soc Nephrol | year= 2008 | volume= 3 | issue= 5 | pages= 1494-503 | pmid=PMID 18596115 | doi=10.2215/CJN.02040408 | pmc=4571150 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18596115 }} </ref> <ref name="pmidPMID 16047480">{{cite journal| author=Ainley EJ, Winwood PJ, Begley JP| title=Measurement of serum electrolytes and phosphate after sodium phosphate colonoscopy bowel preparation: an evaluation. | journal=Dig Dis Sci | year= 2005 | volume= 50 | issue= 7 | pages= 1319-23 | pmid=PMID 16047480 | doi=10.1007/s10620-005-2780-9 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16047480 }} </ref> | The following drugs have been found to be a risk factor for acute phosphate nephropathy:<ref name="pmidPMID 18596115">{{cite journal| author=Heher EC, Thier SO, Rennke H, Humphreys BD| title=Adverse renal and metabolic effects associated with oral sodium phosphate bowel preparation. | journal=Clin J Am Soc Nephrol | year= 2008 | volume= 3 | issue= 5 | pages= 1494-503 | pmid=PMID 18596115 | doi=10.2215/CJN.02040408 | pmc=4571150 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18596115 }} </ref> <ref name="pmidPMID 16047480">{{cite journal| author=Ainley EJ, Winwood PJ, Begley JP| title=Measurement of serum electrolytes and phosphate after sodium phosphate colonoscopy bowel preparation: an evaluation. | journal=Dig Dis Sci | year= 2005 | volume= 50 | issue= 7 | pages= 1319-23 | pmid=PMID 16047480 | doi=10.1007/s10620-005-2780-9 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16047480 }} </ref> | ||
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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 the 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.
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.[1] 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.[2] 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.[3] [4] [5]
Volume depletion
- OSP preparations are osmotic purgatives which lead to osmotic diarrhoea.[5] Consumption of a large amount of oral Sodium Phosphate bowel purgative prior to elective colonoscopy leads to volume depletion. Also before elective colonoscopy, patients are advised not to consume anything by mouth.[6]
- The volume depletion leads to increased reabsorption of sodium chloride and water via the proximal tubule. Also, there is ongoing water reabsorption in the descending limb of the loop of Henle. The combined effect results in increased calcium phosphate in tubules.[7]
- The volume depletion increases the surface expression of hyaluronan and osteopontin which increases the adherence of calcium phosphate crystals to the distal tubule epithelium leading to precipitation and deposition of calcium phosphate in the lumen of the nephrons.[8]
Pathology
The characteristic finding on the renal biopsy is the extensive deposition of calcium phosphate, mostly in the tubular lumen and less commonly in the peritubular interstitium. The calcium phosphates can be identified using von Kossa stain, also they lack birefringence under polarized light.[9] Other findings can be divided on the basis of the time at which the biopsy is performed:
Early findings (<3 weeks)
The early biopsies show tubular degenerative changes, similar to acute tubular necrosis. Findings include
- luminal ectasia, cytoplasmic simplification, loss of brush border, shedding of cell fragments into the lumina, and enlarged nuclei with prominent nucleoli. The tubular degenerative changes and calcifications are accompanied by interstitial edema and mild to moderate interstitial inflammation that is not typically associated with significant tubulitis.[10]
Late finding (>3 weeks)
- If the time between consumption of Oral Sodium Phosphate and renal biopsy is more than 3 weeks, then less severe and more localized degenerative changes are observed.
- The findings include, chronic inflammation, extracellular matrix deposition, tubular atrophy and interstitial fibrosis.[10] [5]
Causes
Epidemiology and Demographics
Gender
Several studies report a higher incidence among females as compared to males.[11] [5] It could be related to their smaller heights and subsequently less GFR as compared to men. Hence the same amount of Oral Sodium Phsophate could be more harmful to the women than men.[12]
Age
Several epidemiological studies have identified advanced age as an independent risk factor of acute phosphate nephropathy. Mean age of 64 years has been identified.
Ethnicity
A higher prevalence has been seen in whites.
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.[13]
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. [14]
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. [11]
Drugs
The following drugs have been found to be a risk factor for acute phosphate nephropathy:[3] [15]
Natural History, Complications and Prognosis
Diagnosis
Diagnostic Criteria | History and Symptoms | Physical Examination | Laboratory Findings | Phosphate Nephropathy Biopsy | X ray | Ultrasound | Other Diagnostic Studies
Laboratory findings
Laboratory findings consistent with the diagnosis of Phosphate nephropathy include:
- Urinanalysis shows proteinuria and benign sediments.
- Serum creatinine is high.
Treatment
- In acute phosphate nephropathy, immediate hemodialysis is beneficial.
- However, in cases where diagnosis is made late, patients are treated the same way as chronic kidney disease.
Medical Therapy | Surgery | Primary Prevention | Secondary Prevention | Cost-Effectiveness of Therapy | Future or Investigational Therapies
Prevention
The most step of preventing phosphate nephropathy is to identify the higher risk group and avthen avoid oral sodium phosphate bowel purgative. PEG is a good alternative. OSP is contraindicated in the following patients:
References
- ↑ 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). - ↑ 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). - ↑ 3.0 3.1 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). - ↑ 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). - ↑ 5.0 5.1 5.2 5.3 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). - ↑ 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). - ↑ 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). - ↑ 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). - ↑ 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). - ↑ 10.0 10.1 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). - ↑ 11.0 11.1 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). - ↑ 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). - ↑ 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). - ↑ 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). - ↑ 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).