Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Acute phosphate nephropathy
Frank P. Hurst
a,b
and Kevin C. Abbott
a,b
Introduction
Acute phosphate nephropathy (APN) was first described
in 2003 in a 71-year-old female patient who developed
acute kidney injury (AKI) after ingestion of oral sodium
phosphate (OSP). She presented with nonspecific
malaise 2 weeks after exposure to OSP with a serum
creatinine of 4.5 mg/dl up from a prior baseline of 1.0 mg/
dl. Renal biopsy showed numerous intratubular deposits
containing calcium and phosphate ions assembled as
hydroxyapatite crystals (Fig. 1). On the basis of appear-
ance of the biopsy, the authors postulated that OSP
ingestion led to obstructive calcium phosphate crystal-
luria and intraluminal nephrocalcinosis. This insult
resulted in chronic kidney disease (CKD) in that the
patient’s renal function did not return to prior baseline
1 year later (serum creatinine 1.7 mg/dl) [1].
Later, a large biopsy case series described more histo-
pathologic cases of APN, strengthening the association of
OSP ingestion to this pathologic finding. The authors
reviewed biopsies over a 5-year period, searching for
cases with the triad of unexplained AKI, OSP exposure,
and nephrocalcinosis (with normal serum calcium). A
total of 21 cases met criteria out of 7349 biopsies
(0.29%). The renal biopsy findings showed abundant
calcium phosphate deposits in the distal tubules and
collecting ducts often accompanied by tubular atrophy
and interstitial fibrosis. Most patients had normal renal
function prior to OSP exposure [mean baseline serum
creatinine of 1.0 mg/dl (range 0.6–1.7 mg/dl)], though
some patients had preexisting CKD. After a mean of
16.7 months of follow-up, no patient returned to baseline
creatinine [mean 2.4 mg/dl (range 1.3–3.4)], and 19%
were on permanent hemodialysis [2].
This study helped to confirm prior suspicions that APN
may be an underrecognized cause of both AKI and CKD.
With increased recognition of this disease and increasing
numbers of reported cases, the US Food and Drug
Administration (FDA) issued an alert in May 2006
describing APN as a rare but serious event associated
with the use of OSP for bowel cleansing. Cases continued
to surface, and several epidemiologic studies were pub-
lished in an attempt to quantify the risk of AKI with the
use of OSP. On 11 December 2008, the FDA issued a
boxed warning on prescription OSP products and
directed manufacturers to develop a risk evaluation
a
Nephrology Service, Walter Reed Army Medical
Center, Washington, District of Columbia and
b
Uniformed Services University of Health Sciences,
F. Edward Hebert School of Medicine, Bethesda,
Maryland, USA
Correspondence to Dr Frank P. Hurst, MD, Department
of Nephrology, Walter Reed Army Medical Center,
6900 Georgia Ave. NW, Washington, DC 20307, USA
Tel: +1 202 782 6462; fax: +1 202 782 0185;
e-mail: frank.hurst@us.army.mil
Current Opinion in Nephrology and
Hypertension 2009, 18:513–518
Purpose of review
Acute phosphate nephropathy (APN) has been identified in renal biopsy specimens of
patients exposed to oral sodium phosphate (OSP) bowel purgatives. Biopsy confirmed
cases presented with bland urinary sediment, low-grade proteinuria, and varying
degrees of creatinine elevation. Prospective identification of APN is difficult in that
definitive diagnosis requires renal biopsy, and biopsy is rarely performed for patients
with this clinical presentation.
Recent findings
Observational studies evaluating acute kidney injury after OSP exposure using interval
changes in creatinine as a surrogate for APN have reported conflicting results. Although
these studies have produced estimates of disease occurrence, they have been unable
to definitively quantify the overall risk of APN with OSP as compared with alternative
bowel-cleansing agents.
Summary
On the basis of association of APN and OSP, the US Food and Drug Administration
issued a boxed warning and manufacturers have ceased production and distribution of
some OSP products. As this is a temporary solution, more studies are needed to
delineate the pathophysiology of this disease and to better identify the subset of the
population at risk for APN.
Keywords
acute kidney injury, colonoscopy, nephrocalcinosis, phosphate nephropathy
Curr Opin Nephrol Hypertens 18:513–518
ß 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins
1062-4821
1062-4821 ß 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins DOI:10.1097/MNH.0b013e32833096af