Acute phosphate nephropathy

Authors:
Glen S Markowitz, MD
Mark A Perazella, MD, FACP
Section Editor:
Paul M Palevsky, MD
Deputy Editor:
Shveta Motwani, MD, MMSc, FASN
All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Apr 2020. | This topic last updated: Jan 14, 2019.

INTRODUCTION 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). 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
[3]. 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 [12]. The
warning was incorporated into a consensus document on bowel preparation by the
American Society of Colon and Rectal Surgeons (ASCRS), the American Society of
Gastrointestinal Endoscopy (ASGE), and the Society of American Gastrointestinal and
Endoscopic Surgeons (SAGES) [13]. In December 2008, the FDA required that a boxed
warning be added to labeling of Visicol and OsmoPrep, which are still available by
prescription [14]. 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counter preparations that contain OSP were voluntarily withdrawn from the market by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" [15].

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".)
 PATHOGENESIS The mechanism underlying acute phosphate nephropathy

most likely relates to a transient but potentially severe increase in serum phosphate
coupled with volume depletion, both of which may occur following the administration of
bowel purgatives that contain oral sodium phosphate (OSP).

Hyperphosphatemia — Hyperphosphatemia occurs in a large number of patients

following OSP ingestion [1,16,17]. In one study, 28 percent of patients who underwent
elective colonoscopy had serum phosphate concentrations >8 mg/dL (2.6 mmol/L;
normal range 2.5 to 4.5 mg/dL [0.8 to 1.5 mmol/L]) following OSP administration [16].

The high rate of hyperphosphatemia following the use of OSP as a bowel purgative
reflects the ingestion of a large amount of phosphate over a short period of time; this
leads to a marked increase in phosphate absorption since the intestinal sodium-
phosphate cotransporters that mediate absorption cannot be rapidly downregulated
[18,19].

Until reports were published describing acute phosphate nephropathy, the

recommended dose as a bowel preparation provided 11.6 grams of phosphorus within
24 hours, an amount that far exceeds the usual dietary intake of 1 g/day. Subsequent to
reports of kidney injury, a phosphate dose reduction of 17 to 20 percent has been
instituted [20].

Hyperphosphatemia is more likely to occur in patients with renal insufficiency, who have
decreased excretion of phosphate [17,20-23]. As a result, OSP is contraindicated in
patients with clinically significant acute or chronic impairment in renal function.

However, hyperphosphatemia also occurs in patients with normal renal function, as

illustrated in a study of 70 patients with creatinine clearances >70 mL/min [17]. After
OSP administration, 37 percent had serum phosphate levels >8 mg/dL (2.6 mmol/L). In
this study, there was a strong correlation between patient age and the degree of
hyperphosphatemia, suggesting that age-related factors (including decreased total body
water, abnormal bowel motility, enhanced gastrointestinal absorption) unrelated to
kidney function promote hyperphosphatemia. As a result, advanced age may increase
the risk for the development of acute phosphate nephropathy. (See 'Risk
factors' below.)

Hyperphosphatemia is more likely to occur in patients who have impaired

gastrointestinal motility, which leads to increased phosphate absorption.
Gastrointestinal obstruction is a contraindication to the use of OSP.

Nephrocalcinosis — The mechanism by which hyperphosphatemia causes kidney

injury is not known, although hypotheses have been raised based on observed
histology. The predominant (though not exclusive) finding on renal biopsy is widespread
deposition of calcium phosphate in tubular lumina, tubular epithelia, and the interstitium.
There is also evidence of tubular epithelial injury and inflammation.
(See 'Pathology' below.)

One hypothesis to explain the pathogenesis is that transient hyperphosphatemia leads

to an increased intratubular phosphate concentration, resulting in the precipitation and
tissue deposition of calcium phosphate salts that cause luminal obstruction, direct
tubular epithelial injury, and activation of the immune response [20,24].
Although tubular injury is noted in all nephron segments, calcium phosphate deposition
is limited to the distal tubule and collecting duct [25]. The delivery of phosphate to these
sites is enhanced by the decrease in proximal tubular phosphate absorption that occurs
within minutes of OSP ingestion.

Volume depletion — The intraluminal calcium phosphate deposition is probably

worsened by volume depletion, which often results from the OSP-induced osmotic
diarrhea in the setting of reduced oral intake prior to the procedure. Conditions that
cause effective volume depletion, such as heart failure and ascites, are
contraindications to the use of OSP.

True or effective volume depletion results in increased sodium chloride and water
reabsorption in the proximal tubule. This effect, combined with ongoing water
reabsorption in the descending limb of the loop of Henle, raises the calcium phosphate
product within the tubular lumen in the fluid presented to the ascending limb and distal
tubule [26]. Volume depletion may also increase the adherence of calcium phosphate
crystals to the distal tubule epithelium via an increase in surface expression of
hyaluronan and osteopontin [27].

Angiotensin-converting enzyme inhibitors and angiotensin receptor

blockers — Patients who are on angiotensin-converting enzyme (ACE) inhibitors and
angiotensin II receptor blockers (ARBs) appear to be at increased risk for acute
phosphate nephropathy [8,28,29]. (See 'Risk factors' below.)

ACE inhibitors and ARBs worsen the prerenal state caused by OSP-induced volume
depletion by promoting the loss of angiotensin II-mediated efferent arteriolar
constriction, which reduces glomerular filtration. In addition, ACE inhibitors and ARBs
decrease angiotensin II-dependent proximal tubule bicarbonate reabsorption, which
leads to an increase in distal tubular bicarbonate concentration. The increase in
intraluminal pH promotes precipitation of calcium phosphate crystals [30,31].

PATHOLOGY The chief pathologic characteristic of acute phosphate

nephropathy is extensive deposition of calcium phosphate in the tubular lumina, within

tubular epithelial cells, and, less commonly, in the peritubular interstitium [25]. Calcium
phosphate deposits are distinguished from calcium oxalate deposits by positive staining
with the "von Kossa stain" and the absence of birefringence under polarized light
(picture 1).

Other findings observed on renal biopsy depend upon the elapsed time between
oral sodium phosphate (OSP) exposure and the time at which the biopsy was
performed. Early biopsies show tubular degenerative changes similar to those seen in
acute tubular necrosis [25]. These changes 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.

In contrast, renal biopsies performed more than three weeks following OSP use show
chronic changes, including tubular atrophy and interstitial fibrosis. The tubular
degenerative changes are less severe and more localized and resemble changes seen
in repeat renal biopsies from patients with nonresolving acute tubular necrosis.
 INCIDENCE There are no reliable data on the incidence of acute phosphate

nephropathy in patients with previously intact renal function. A number of retrospective

studies have examined this issue by evaluating the frequency or magnitude of reduction
in estimated glomerular filtration rate (eGFR) at 6 to 12 months after the administration
of bowel purgatives that contain oral sodium phosphate (OSP) [28,29,32,33].

However, all of these studies are limited in a variety of ways, including lack of
confirmation of the diagnosis by renal biopsy. This is an important issue since many
patients who develop acute kidney injury (AKI) following OSP administration do not
have acute phosphate nephropathy. (See 'Acute and reversible kidney injury' below.)

The following observations illustrate the range of findings:

●The largest study is an observational analysis of 9799 Department of

Defense beneficiaries who underwent colonoscopy between 2002 and 2006
[32]. AKI, defined as a >50 percent increase in serum creatinine from baseline
within one year following colonoscopy, was observed in 114 patients. After
adjusting for putative risk factors, OSP was the strongest risk factor for AKI
(risk ratio [RR] 2.35, 95% CI 1.51-3.66).
●A retrospective case-control study evaluated 2237 patients who had
outpatient colonoscopy [29]. AKI, defined as a 25 percent or a 0.5 mg/dL
(44.2 micromol/L) increase in serum creatinine over six months
postcolonoscopy, was identified in 141 patients (6.3 percent). An association
between OSP and AKI was only seen in patients who received an
angiotensin-converting enzyme (ACE) inhibitor or angiotensin II receptor
blocker (ARB).
However, interpretation of this study is limited by the small sample size and
the permissive definition of AKI [34]. When a stricter definition of AKI (which
required an increase in creatinine of 1 mg/dL [88.4 micromol/L]) was
employed, the number of cases of kidney injury fell from 116 to 3.

Risk factors — The following potential risk factors for the development of acute
phosphate nephropathy have been identified. However, since only the series from
Columbia University had biopsy confirmation of the disease [8], one cannot be certain
how many of the patients with impaired renal function in other series had acute
phosphate nephropathy.
●Phosphate dosing – The degree of hyperphosphatemia is directly related to
the total amount of administered OSP, and a greater degree of
hyperphosphatemia is likely to increase the risk of acute phosphate
nephropathy [3,35-37]. A wider interval between the administration of the two
doses of OSP (ie, 24 versus 12 hours) is associated with a lesser degree of
hyperphosphatemia and, therefore, is likely to be safer [20,34].
●Chronic kidney disease (CKD) – Reduced GFR increases the risk of
hyperphosphatemia following OSP administration. A retrospective study on
the safety of bowel preparations in patients with an eGFR <60 mL/min/1.73
m2 found an adjusted relative risk of AKI for OSP-exposed patients of 12.6
relative to polyethylene glycol (PEG)-exposed patients [38]. OSP is
contraindicated in patients with a clinically significant impairment in renal
function.
 ●ACE inhibitors and ARBs – In the series from Columbia, 14 of 21 patients
with acute phosphate nephropathy were being treated with one of these two
agents [8]. The increased risk conferred by these agents has been confirmed
in observational studies [28,29].
●Age – Advanced age has been identified as an independent risk factor in
multiple studies [17,32,33,39]. An absolute age at which the risk is increased
has not been determined.
●Drugs – The use of diuretics, nonsteroidal anti-inflammatory agents
(NSAIDs), and lithium has been suggested as a possible risk factor [20,39].
●Female gender – The majority of reported cases of acute phosphate
nephropathy have occurred in women [8,29]. A possible contributing factor is
that female subjects are generally smaller and have a lower GFR than men
but receive the same dose of OSP.
●Comorbid conditions – Hypertension and diabetes have been suggested as
risk factors by several studies [8,28,33].

Risk with sodium phosphate enemas — Acute phosphate nephropathy also has been
rarely reported following the administration of sodium phosphate enemas (SPEs),
although the majority of these reports have followed the use of excessive doses [40-42].
●One report highlights the occurrence of acute phosphate nephropathy
following the use of a 250 mL dose of SPEs in older patients. In this report, 11
older patients with a mean age of 80 years (range 61 to 89 years) developed
AKI following the administration of Fleet enemas; of these, three individuals
had received large doses of 500 to 798 mL, and eight had received standard
doses of 250 to 266 mL. Four patients had normal baseline renal function
(defined as eGFR >60 mL/min/1.73 m2), and seven had reduced renal
function (eGFR between 25 to 57 mL/min/1.73 m2). Although renal functional
outcomes are not provided, five patients expired. Histologic confirmation of
the diagnosis of acute phosphate nephropathy was available for a single
patient in whom tubular calcium phosphate deposits were found at autopsy
[2]. Of note, fluid volume and phosphorus content of the SPE used in this
study are substantially greater than the Fleet SPE that is marketed in the US
(133 mL).
●In a retrospective cohort study that included 70,499 Veterans Affairs (VA)
patients who underwent colonoscopy, compared with PEG oral solution alone
(n = 64,092), the use of SPE (with or without oral PEG; n = 6407) was
associated with increased risk for a 50 percent increase in serum creatinine
within 15 months of use (odds ratio [OR] 1.3, 95% CI 1.2-1.5) [42]. There was
no difference between groups in the risk for an acute eGFR decline (ie, over
six weeks).

However, in the absence of an increased risk for an acute decline in eGFR, the causal
relationship of sodium phosphate-containing enemas to a decline in eGFR is not clear
[43]. In addition, SPE alone was not associated with either acute or long-term eGFR
changes in a sensitivity analysis in which the subjects were broken into three groups:
PEG (90.9 percent), PEG and SPE (8.1 percent), and SPE alone (1 percent). The
authors may have obtained misleading results by using variables in their multivariate
model that were in the causal pathway between exposure and outcome (ie, baseline
CKD and anemia) and by using variables that are not associated with eGFR decline (ie,
asthma and chronic obstructive pulmonary disease [COPD]).

The impact of SPE on eGFR is unclear. Further studies are required to

address this issue.
 CLINICAL PRESENTATION AND PROGNOSIS Two different clinical

patterns of kidney injury have been described following the administration of bowel
purgatives that contain oral sodium phosphate (OSP): an acute form that is reversible
and may not represent acute phosphate nephropathy, and a delayed onset that is due
to acute phosphate nephropathy and is generally irreversible [44].

Acute and reversible kidney injury — In some patients, acute kidney injury (AKI)
occurs within hours of the administration of OSP. This presentation is mainly associated
with excessive dosing of OSP or other risk factors for hyperphosphatemia [44-46]. AKI
occurs in the setting of severe hyperphosphatemia and hypocalcemia, leading to tetany,
cardiac arrest, and, in some cases, death. Patients who survive the immediate event
typically return to normal or near-normal renal function. As a result, renal biopsy was not
performed.

It appears likely that the AKI in these patients was due to prerenal factors or acute
tubular necrosis rather than acute phosphate nephropathy. (See "Etiology and
diagnosis of prerenal disease and acute tubular necrosis in acute kidney injury in
adults".)

Acute phosphate nephropathy — In contrast, acute phosphate nephropathy is

characterized by increases in serum creatinine that occur in asymptomatic patients and
are documented days to months following OSP administration. The serum phosphate
and calcium concentrations are typically normal when kidney injury is discovered. The
majority of reports of acute phosphate nephropathy have been confirmed by renal
biopsy.

The largest series on acute phosphate nephropathy is a retrospective review of biopsies

processed by the renal pathology laboratory at Columbia University from 2000 to 2004
[8]. This study identified 21 patients who had biopsy-confirmed acute phosphate
nephropathy and a compatible history of OSP ingestion. The following observations
were noted:

●Seventeen of the 21 patients were Caucasian, 17 were women, and the

mean age was 64 years. Sixteen patients had a history of hypertension, and
14 of the 16 were taking either an angiotensin-converting enzyme (ACE)
inhibitor or angiotensin II receptor blocker (ARB). (See 'Risk factors' above.)
●The mean baseline (within four months of the procedure) serum creatinine
was 1.0 mg/dL (88.4 micromol/L). In contrast, the mean value at the time of
presentation with AKI was 3.9 mg/dL (345 micromol/L) at a median of one
month after colonoscopy.
●The urinalysis was bland in 13 patients; hematuria was observed in three
patients and pyuria in five patients. Twenty-four-hour protein excretion was
<600 mg/day in 13 of 14 patients in whom quantification was performed. In
the seven other patients, urinalysis showed 0 to 1+ proteinuria on dipstick
testing. Protein excretion exceeded 1 g/day in only one patient who had
concurrent diabetic glomerulosclerosis on renal biopsy.
●Most patients appear to have taken OSP at the correct dose and in the
absence of clear contraindications.

At mean follow-up of 16.7 months, four patients progressed to end-stage renal disease
(ESRD), and the remaining 17 patients had a decline in serum creatinine to a mean of
2.4 mg/dL (212 micromol/L). No patient returned to baseline renal function. Similar
findings have been noted by others; complete recovery of renal function, if it occurs,
appears to be a rare event [44,47-49]. In the Department of Defense study cited above,
16 percent of patients returned to their baseline serum creatinine [32]. However, renal
biopsies were not performed, and some or many of these patients may have had acute
tubular necrosis rather than acute phosphate nephropathy.

Given the poor prognosis, identification of patients at risk and preventive measures are
important.

DIAGNOSIS The diagnosis of acute phosphate nephropathy is suggested by

the temporal association between acute kidney injury (AKI) and the administration of
bowel purgatives that contain oral sodium phosphate (OSP). However, some patients
present late after the exposure with chronic kidney disease (CKD).

The diagnosis of phosphate nephropathy is supported by a benign sediment on

urinalysis and modest proteinuria. By definition, all patients with phosphate nephropathy
should be normocalcemic since hypercalcemia may also cause nephrocalcinosis.
(See "Nephrocalcinosis".)

There are no reports of the use of imaging to demonstrate nephrocalcinosis in acute

phosphate nephropathy. As a result, the diagnosis can be confirmed only by renal
biopsy, which may not be required in patients with AKI diagnosed shortly after using an
OSP purgative. (See 'Pathology' above.)

Differential diagnosis — For the patient who presents days to months following

colonoscopy with an elevated creatinine, minimal proteinuria, and a relatively bland
urine sediment, the differential diagnosis includes acute and chronic tubular and
interstitial diseases. These include acute and chronic forms of interstitial nephritis,
ischemic and toxic forms of acute tubular necrosis, and myeloma cast nephropathy, to
name a few. (See "Diagnostic approach to adult patients with subacute kidney injury in
an outpatient setting".)

Once a renal biopsy is obtained, all causes of nephrocalcinosis should be considered,

including conditions associated with hypercalcemia, hypercalciuria without
hypercalcemia, or hyperphosphatemia with hyperphosphaturia.
(See 'Nephrocalcinosis' above.)

PREVENTION AND TREATMENT The single, most important preventive

strategy is to identify patients who are at higher risk for the development of acute
phosphate nephropathy and then avoid the administration of bowel purgatives that
contain oral sodium phosphate (OSP), if possible. Specific recommendations for the
choice of bowel preparation are discussed elsewhere. (See 'Risk factors' above
and "Bowel preparation before colonoscopy in adults".)

There is no specific treatment for established acute phosphate nephropathy. However,

acute hemodialysis is likely to be beneficial in the infrequent patient who is diagnosed
within 12 to 24 hours after OSP administration and still has marked hyperphosphatemia.
As noted above, most patients are diagnosed later, and, since complete recovery of
renal function is rare, these patients should be treated the same as others with chronic
kidney disease (CKD). (See 'Acute phosphate nephropathy' above and "Overview of the
management of chronic kidney disease in adults".)

SOCIETY GUIDELINE LINKS Links to society and government-sponsored

guidelines from selected countries and regions around the world are provided
separately. (See "Society guideline links: Acute kidney injury in adults".)

SUMMARY AND RECOMMENDATIONS

●Acute phosphate nephropathy is a clinicopathologic entity that results from

colonic cleansing with bowel purgatives that contain oral sodium
phosphate (OSP). Acute phosphate nephropathy has also been reported
following the administration of sodium phosphate-containing enemas. Acute
phosphate nephropathy is usually detected days to months following OSP
administration. This entity is complicated by the development of chronic
kidney disease (CKD). (See 'Introduction' above.)
●The pathogenesis of acute phosphate nephropathy is related to volume
depletion and transient OSP-induced hyperphosphatemia and involves
precipitation of calcium phosphate crystals in the distal tubule.
(See 'Pathogenesis' above.)
●Renal biopsy reveals an acute and chronic tubulointerstitial nephropathy with
the distinctive finding of abundant tubular and interstitial deposits of calcium
phosphate. In biopsies performed within three weeks of OSP exposure,
findings of acute tubular injury predominate and resemble changes seen in
acute tubular necrosis. Later biopsies exhibit findings of chronicity, including
tubular atrophy and interstitial fibrosis. (See 'Pathology' above.)
●The incidence of acute phosphate nephropathy remains unknown. Acute
phosphate nephropathy can occur in patients with normal renal function.
(See 'Incidence' above.)
●Apparent risk factors for acute phosphate nephropathy include advanced
age, hypertension, renal dysfunction, volume depletion, and the use of
angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor
blockers (ARBs). Possible additional risk factors include the use of diuretics,
nonsteroidal anti-inflammatory agents (NSAIDs) or lithium, the presence of
diabetes, and female gender. (See 'Risk factors' above.)
●Careful review of all contraindications to the use of OSP should be done prior
to selection of a bowel purgative for an individual patient. (See 'Prevention
and treatment' above.)
●Specific recommendations for the choice of bowel preparation are discussed
elsewhere. (See "Bowel preparation before colonoscopy in adults".)
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REFERENCES
1. Markowitz GS, Perazella MA. Acute phosphate nephropathy. Kidney Int 2009;
76:1027.
2. 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.
3. 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.
4. Cohen SM, Wexner SD, Binderow SR, et al. Prospective, randomized,
endoscopic-blinded trial comparing precolonoscopy bowel cleansing methods. Dis
Colon Rectum 1994; 37:689.
5. 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.
6. Tan JJ, Tjandra JJ. Which is the optimal bowel preparation for colonoscopy - a
meta-analysis. Colorectal Dis 2006; 8:247.
7. Desmeules S, Bergeron MJ, Isenring P. Acute phosphate nephropathy and renal
failure. N Engl J Med 2003; 349:1006.
8. 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.
9. Markowitz GS, Whelan J, D'Agati VD. Renal failure following bowel cleansing
with a sodium phosphate purgative. Nephrol Dial Transplant 2005; 20:850.
10. Demoulin N, Jadoul M, Cosyns JP, Labriola L. An easily overlooked iatrogenic
cause of renal failure. Clin Nephrol 2008; 70:176.
11. 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.
12. Oral sodium phosphate (OSP) products for bowel cleansing. US Government
Printing Office; Center of Drug Evaluation Research, DC 2006.
13. 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.
14. 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.
15. http://www.fda.gov/Drugs/DrugSafety/ucm380757.htm?
source=govdelivery&utm_medium=email&utm_source=govdelivery.
16. 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.
17. 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.
18. 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.
19. Forster IC, Hernando N, Biber J, Murer H. Proximal tubular handling of
phosphate: A molecular perspective. Kidney Int 2006; 70:1548.
20. 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.
21. 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.
22. 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.
23. Fass R, Do S, Hixson LJ. Fatal hyperphosphatemia following Fleet Phospo-Soda
in a patient with colonic ileus. Am J Gastroenterol 1993; 88:929.
24. 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.
25. 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.
26. Asplin JR, Mandel NS, Coe FL. Evidence of calcium phosphate supersaturation
in the loop of Henle. Am J Physiol 1996; 270:F604.
27. 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.
28. 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.
29. Brunelli SM, Lewis JD, Gupta M, et al. Risk of kidney injury following oral
phosphosoda bowel preparations. J Am Soc Nephrol 2007; 18:3199.
30. 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.
31. 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.
32. 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.
33. 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.
34. Markowitz GS, Radhakrishnan J, D'Agati VD. Towards the incidence of acute
phosphate nephropathy. J Am Soc Nephrol 2007; 18:3020.
35. 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.
36. 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.
 37. 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.
38. 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.
39. 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.
40. Martin RR, Lisehora GR, Braxton M Jr, Barcia PJ. Fatal poisoning from sodium
phosphate enema. Case report and experimental study. JAMA 1987; 257:2190.
41. 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.
42. 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.
43. Markowitz GS, Bomback AS, Perazella MA. Phosphate enemas and GFR
decline: it's premature to sound the alarm. Kidney Int 2016; 90:13.
44. 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.
45. 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.
46. Orias M, Mahnensmith RL, Perazella MA. Extreme hyperphosphatemia and
acute renal failure after a phosphorus-containing bowel regimen. Am J Nephrol
1999; 19:60.
47. Manley P, Somerfield J, Simpson I, et al. Bilateral uraemic optic neuritis
complicating acute nephrocalcinosis. Nephrol Dial Transplant 2006; 21:2957.
48. Aasebø W, Scott H, Ganss R. Kidney biopsies taken before and after oral
sodium phosphate bowel cleansing. Nephrol Dial Transplant 2007; 22:920.
49. 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.

Topic 7218 Version 18.0

GRAPHICS
Light microscopy demonstrating acute phosphate nephropathy
(A) A low-power view shows abundant tubular and focal interstitial calcium phosphate deposits. The

calcifications are confined to distal tubules, with sparing of proximal tubules (hematoxylin and eosin).

(B) The tubular calcifications exhibit a positive histochemical reaction with the von Kossa stain,

diagnostic of calcium phosphate.

Courtesy of Glen S Markowitz, MD.

Graphic 55578 Version 3.