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□ CASE REPORT □

Acute with Diffuse Tubular Injury Despite Limited Phosphate Deposition

Yosuke Yamada 1, Makoto Harada 1, Akinori Yamaguchi 1, Mai Sugiyama 1,TaroKanno1, Koji Hashimoto 1, Takashi Ehara 2, Hisashi Shimojo 3, Hidekazu Shigematsu 3 and Yuji Kamijo 1

Abstract

An 86-year-old woman developed acute injury after . A renal showed diffuse tu- bular injury with minimal calcium phosphate deposits (CPDs), which were thought to be caused by an oral sodium phosphate bowel purgative before colonoscopy. According to these findings, she was diagnosed with acute phosphate nephropathy (APhN). In contrast to previous reports of diffuse tubular injury associated with tubular CPDs in APhN, this case demonstrated diffuse tubular injury despite a limited distribution of CPDs, suggesting that calcium phosphate can cause tubular injury without deposition. This case thus supports the hypothesis that urinary calcium phosphate crystals may cause tubular injury via other mechanisms, including inflammatory cytokines.

Key words: acute phosphate nephropathy, oral sodium phosphate, colonoscopy, acute and reversible kidney injury, calcium phosphate crystal, drug-induced

(Intern Med 55: 2229-2235, 2016) (DOI: 10.2169/internalmedicine.55.5864)

CPD-induced luminal obstruction and inflammation, fol- Introduction lowed by tubulointerstitial injury. We herein report a patient with APhN who showed diffuse tubular injury despite the Acute kidney injury (AKI) can be induced by various limited presence of CPDs. This case thus suggests that high drugs, including nonsteroidal anti-inflammatory drugs concentrations of calcium phosphate in the urine may result (NSAIDs), antibiotics, cisplatin, and contrast media. Oral in direct injury of the tubular epithelial cells, even in the ab- sodium phosphate (OSP) is used as a bowel purgative before sence of CPDs. colonoscopy and has also been shown to result in AKI, though this cause is not widely recognized. Desmeules et al. Case Report first described acute phosphate nephropathy (APhN) as a novel cause of drug-induced AKI in 2003 (1). Risk factors An 86-year-old woman underwent a routine colonoscopy for APhN include older age, female sex, , dia- checkup at a local hospital. She took 50 OSP tablets (50 g) betes mellitus, chronic (CKD), and treatment as a bowel purgative prior to the examination. She became with angiotensin-converting enzyme inhibitors, angiotensin aware of general fatigue and oliguria shortly after the ex- receptor blockers (ARBs), NSAIDs, and (Table 1). amination and visited the hospital 6 days after colonoscopy. However, there have been few detailed pathological studies At that time, a physical examination showed mild edema of of APhN. Markowitz et al. described the detailed pathologi- the face and legs and laboratory data showed severe kidney cal findings of APhN in 21 patients (2) (Table 2-4). Accord- dysfunction (serum , 5.3 mg/dL; blood nitro- ing to representative pathological findings of diffuse and gen, 82 mg/dL). No obvious signs of were de- abundant calcium phosphate deposits (CPDs) in the kidney tected by physical or laboratory examinations (fractional ex- tubule lumens, APhN is thought to develop as a result of cretion of sodium, 3.5%) (Table 5, 6). She was admitted to

１Department of , Shinshu University School of Medicine, Japan, ２Department of Health and Sport Science, Matsumoto University Graduate School of Medicine, Japan and ３Department of Pathology, Shinshu University School of Medicine, Japan Received for publication May 29, 2015; Accepted for publication December 15, 2015 Correspondence to Dr. Yuji Kamijo, [email protected]

2229 Intern Med 55: 2229-2235, 2016 DOI: 10.2169/internalmedicine.55.5864

Table 1. Risk Factors for Acute Phosphate Nephropa- basement membrane, and flattening of tubular epithelial thy. cells were detected (Fig. 2). The interstitial area was found Risk factor Reference to have increased and it occupied 51% of the total cortical [12] area, with tubular atrophy, interstitial edema, and fibrosis. RABs (ACE-Is and ARBs) [13] Tubular basophilic deposits accompanied by tubular epithe- Advanced age [12] [14] lial cell injury were also detected in several tubules (Fig. 3). Drugs (diuretics, NSAIDs) [12] [15] Female sex [16] These deposits were positive for von Kossa stain, indicating Comorbidity (hypertension, ) [12] [14] that they were CPDs (Fig. 4A). These CPDs were located in ACE-I: angiotensin-converting enzyme inhibitor, ARB: angiotensin the distal tubules, rather than the proximal tubules, and were receptor blocker, NSAID: nonsteroidal anti-inflammatory drug, RAB: renin-angiotensin blocker distributed focally, only occurring in 2% of tubular lumens (19/673), whereas damaged tubules with tubular vacuolation and dilation and detachment and flattening of tubular epithe- the hospital and administered intravenous fluids for 3 days, lial cells occurred diffusely in 53% (357/673) of tubular lu- however, her serum creatinine levels remained elevated (5.02 mens (Fig. 4B). Arterial lesions, including fibrous intimal mg/dL). Ten days after colonoscopy, she was transferred to thickening and hyaline changes, were scarce in the kidney our hospital for detailed examinations, including a kidney biopsy sample. Immunofluorescence results were negative biopsy. The patient had a past history of CKD (serum cre- for IgG, IgM, IgA, C3, and fibrinogen. No glomeruli were atinine, 0.83 mg/dL; estimated glomerular filtration rate, 49 detected in the electron microscopy specimen. According to mL/min/1.73 m2 at 6 months prior to this admission), hyper- the patient’s clinical course and pathological findings she tension, hyperlipidemia, and osteoarthritis of the knees, was diagnosed with APhN. which was treated with an ARB, calcium channel blocker, The patient’s serum creatinine levels gradually decreased fibrate, and NSAIDs. On admission to our hospital, her with rest and a low-sodium, low-protein diet for 1 week. blood pressure was 162/82 mmHg and her body temperature She was discharged from the hospital 8 days after admis- was 35.7℃. A physical examination only showed mild leg sion, with a serum creatinine level of 2.6 mg/dL, which had edema. Laboratory tests showed kidney dysfunction (blood further decreased to 1.6 mg/dL 1 year later. urea nitrogen, 45 mg/dL; serum creatinine, 3.49 mg/dL). Her electrolyte balance was normal, and no hypercalcemia Discussion or was detected. Similarly, no inflamma- tory reaction, serum monoclonal protein, or autoimmune ab- Several studies have reported that the administration of normalities was detected. Urinary protein was 0.76 g daily OSP can result in AKI. Choi et al. investigated the relation- and there was no sign of . Urinary N-acetyl-beta- ship between OSP and AKI in a case-crossover study de- D-glucosaminidase and urinary β-2 microglobulin levels signed to remove confounding factors and concluded that were increased (33.1 U/L and 29,660 μg/L, respectively), OSP could cause AKI independent of any complications (3). suggesting tubulointerstitial damage. Fractional excretion of Furthermore, Haut et al. reported that a high-phosphate diet sodium was 2.4%. Urinary Bence Jones protein was nega- caused marked tubular injury in a rat nephrectomy CKD tive. A renal ultrasound examination showed bilateral, mild model, the pathological findings of which included damaged kidney swelling (left, 112×56 mm; right, 113×52 mm) with tubules with CPDs, interstitial fibrosis, tubular dilation and increased renal cortical echogenicity, indicating acute kidney inflammatory cell infiltration, resembling those in the cur- dysfunction (Fig. 1). No or was rent clinical case (4). These studies support the suggestion detected. that AKI in the current case was caused by OSP administra- An ultrasound-guided kidney biopsy was performed 15 tion. days after colonoscopy to determine the cause of her kidney Previous studies have reported two different clinical pat- dysfunction. The specimen was processed and terns of kidney injury following the administration of OSP examined by light microscopy, immunofluorescence, and bowel purgatives: acute and reversible kidney injury (ARKI) electron microscopy. Light microscopy sections were stained and APhN, which shows a delayed onset and is generally ir- with Hematoxylin and Eosin, periodic acid-Schiff, periodic reversible. ARKI occurs less than 1 day after the administra- acid-methenamine silver, Masson’s trichrome, and von tion of OSP and is accompanied by severe hyperphos- Kossa. Twelve glomeruli were observed, two of which re- phatemia and leading to tetany, cardiac arrest, vealed global sclerosis, while no signs of glomerular hyper- and possible death. However, serum creatinine levels typi- cellularity, necrosis, crescent formation, mesangial cell pro- cally return to normal or near-normal levels. The renal- liferation, or thickening of the basement membrane were de- pathology findings of ARKI have not been reported to date. tected in the other 10 glomeruli. There was no evidence of In contrast, typical APhN progresses asymptomatically, and acute glomerular injury; however, obvious tubulointerstitial kidney dysfunction may thus remain undetected until several changes, including interstitial edema, focal inflammatory-cell days or even months after OSP administration. Patients with infiltration, mild interstitial fibrosis, tubular vacuolation, tu- APhN show little sign of hyperphosphatemia or hypocalce- bular dilation, detachment of tubular cells from the tubular mia, and the diagnosis of APhN is confirmed by renal bi-

2230 Intern Med 55: 2229-2235, 2016 DOI: 10.2169/internalmedicine.55.5864

Table 2. Clinical Findings of Current and Previously Reported Cases of APhN.

Source Patient Age (yr) Sex HTN Diabetes RAB Diuretics NSAIDs [2] 1 69 M Y Y 282MY 355FY YYY 464FY YYY 576FY Y 653MY Y 781F Y 882FY Y 957FY Y 10 76 F Y Y 11 74 F Y Y 12 57 F Y 13 43 F Y Y Y Y Y 14 39 F Y 15 69 F Y Y 16 66 F Y Y Y 17 51 F Y Y 18 79 F Y 19 44 M Y Y Y 20 62 F 21 64 F Y Y

Current case 22 86 F Y Y Y F: female, HTN: hypertension, M: male, RAB: renin-angiotensin receptor blocker, NSAID: nonsteroidal anti-inflammatory drug, Y: yes

Table 3. Serum Creatinine Levels (mg/dL) in Current and Previously Reported Cases of APhN.

Cre at Patient Baseline Cre at ARF Interval time of Interval Final [2] Cre diagnosis post-colonoscopy the renal post-colonoscopy Cre biopsy 1 1.2 6.7 1 month 6.3 7 weeks ESRD 2 0.9 5.2 1 week 4.9 4 weeks ESRD 30.64.513days 4 4months2.7 4 0.9 2.3 2 months 3 7 months ESRD 5 0.9 6 3 days 8 6 days 1.9 6 1 4.8 12 days 2.2 3 months 1.3 7 0.9 3.3 4.5 months 3.3 5 months 2.6 8 1.1 4.4 3 weeks 3.3 13 months 3.1 9 0.7 1.8 1 day 3.1 3 weeks 2.7 10 0.9 3.8 2 months 3.6 6 months 2.1 11 1.5 3.9 1 month 3 4 months 3 12 1 3.8 2 days 3.1 14 days 1.5 13 0.9 2.2 2 months 2.3 6 months 1.8 14 0.7 4.5 5 days 4.117days2.7 15 1.3 4.2 5 months 4.6 7 months ESRD 16 1.4 3.7 19 days 3.9 4 months 3.4 17 0.9 3 5 weeks 2.7 2 months 2.1 18 0.7 3.4 3 months 3.2 4 months 2.8 19 1.7 2.6 2 months 2.3 5 months 2.2 20 0.9 5.9 8 days 3.6 17 days 3.4 21 0.9 2.6 2 months 2.3 4 months 1.8

22 0.83 5.3 5 days 3.4 15 days 1.6 Cre: creatinine, ESRD: end-stage renal disease opsy findings, characterized by diffuse tubular injury with of severe hyperphosphatemia or hypocalcemia, and CPDs abundant tubular CPDs. Kidney dysfunction is irreversible in were detected in the tubular lumen in the renal biopsy speci- most cases of APhN, and patients may progress to end-stage men. These findings support the diagnosis of APhN; how- renal disease (5). ever, there were some discrepancies compared with typical In the current patient, kidney dysfunction was detected 5 APhN. First, the patient’s clinical course showed a relatively days after colonoscopy. Her laboratory data showed no signs acute, symptomatic onset, with the development of general

2231 Intern Med 55: 2229-2235, 2016 DOI: 10.2169/internalmedicine.55.5864

Table 4. Pathological Findings in Current and Previously Reported Cases of APhN.

Patient No. of Tubular Tubular %TA and Interstitial Histopathologic No. of SG [2] glomeruli injury CPDs IF inflammation pattern 1 53 5 (9%) Diffuse Diffuse 30% Mild A/C TIN 2 30 15 (50%) Diffuse Diffuse 40% Mild A/C TIN 3 47 4 (8%) Diffuse Diffuse 60% Minimal A/C TIN 4 6 1 (16%) Mild Diffuse 50% Moderate A/C TIN, NDGS 5 22 2 (9%) Diffuse Diffuse None Minimal ATN 6 19 1 (5%) Mild Diffuse 25% Mild A/C TIN 7 20 2 (10%) Mild Diffuse 60% Moderate A/C TIN 8 32 9 (28%) Mild Diffuse 60% Mild A/C TIN 9 17 2 (11%) Diffuse Diffuse 30% Moderate A/C TIN A/C TIN, 10 9 1 (11%) Mild Diffuse 60% Moderate segmental MG 11 16 1 (6%) Mild Diffuse 50% Minimal A/C TIN 12 16 2 (12%) Diffuse Diffuse 10% Mild ATN 13 17 2 (11%) Mild Diffuse 60% Mild A/C TIN 14 32 2 (6%) Diffuse Diffuse 5% Minimal ATN 15 17 6 (35%) Mild Diffuse 70% Mild A/C TIN 16 19 4 (21%) Mild Diffuse 70% Moderate A/C TIN 17 13 2 (15%) Mild Diffuse 40% Mild A/C TIN 18 17 1 (5%) Mild Diffuse 20% Minimal A/C TIN 19 20 3 (15%) Mild Diffuse 15% Minimal A/C TIN 20 16 1 (6%) Diffuse Diffuse None Minimal ATN 21 40 2 (5%) Mild Diffuse 60% Mild A/C TIN

Diffuse Partial 22 12 2 (16%) 51% Moderate A/C TIN (53%) (2%) A/C TIN: acute and chronic tubulointerstitial nephropathy, ATN: , MG: membranous , NDGS: nodular diabetic glomerulopathy, SG: sclerotic glomeruli, TA and IF: tubular atrophy and interstitial fibrosis

Table 5. Laboratory Data at First Admission to a Local Hospital.

Investigation Value Reference value Complete blood count White blood cells (per mm2) 4,630 4,000–9,000 Hemoglobin (g/dL) 11.1 12.0–16.0 Hematocrit (%) 33.9 35.0–48.0 Platelets (×104 per mm2) 24.6 12.0–35.0 Serum chemistry Total protein (g/dL) 6.4 6.5–8.3 Albumin (g/dL) 3.9 3.8–5.2 Blood urea nitrogen (mg/dL) 82 7–24 Creatinine (mg/dL) 5.3 0.45–0.80 Plasma blood urea nitrogen to serum creatinine ratio 15.4 Aspartate aminotransferase (IU/L) 24 11–40 Alanine aminotransferase (IU/L) 16 7–45 Lactic dehydrogenase (IU/L) 255 120–235 Sodium (mEq/L) 143 135–147 Potassium (mEq/L) 4.2 3.5–5.0 Chloride (mEq/L) 106 96–110 Calcium (mg/dL) 9.6 8.5–10.5 Phosphate (mg/dL) 5.2 2.4–4.6

fatigue and oliguria just after colonoscopy. These symptoms cal findings are believed to demonstrate acute ischemic may have been caused by hyperphosphatemia, hypocalce- changes or acute tubular epithelial injury without CPDs re- mia, or acute kidney dysfunction; however, we were unable lated to its acute and reversible clinical course, compared to confirm these conditions due to a lack of laboratory data with diffuse tubular damage associated with abundant insol- just after colonoscopy. Second, the patient’s final reported uble CPDs in APhN related to its chronic and irreversible serum creatinine level decreased to lower than the levels re- course. The characteristics of the current case thus demon- ported in other APhN cases (Table 3). Third, her kidney bi- strate similarities to both ARKI and APhN, suggesting that opsy findings revealed the presence of diffuse tubular injury, the differentiation of these two conditions may be unclear, despite only partial CPDs (Table 4). Although the biopsy with the current case illustrating an intermediate condition. findings of ARKI have not yet been reported, its pathologi- The mechanisms underlying the development of APhN af-

2232 Intern Med 55: 2229-2235, 2016 DOI: 10.2169/internalmedicine.55.5864

Table 6. Urinalysis Results at First Admission to a Local Hospital.

Investigation Value Reference range pH 5.5 Specific gravity 1.010 Screening dipstick test Protein ± - Glucose - - Bilirubin - - Urobilinogen - - Ketones - - Sediment Granular casts 3+ - Figure 1. A renal ultrasound image of the left kidney show- Hyaline casts 1+ - ing bilateral mild nephromegaly (left: 112×56 mm, right: Leukocyte casts 1+ - Red cells (high-power field) 1–4 113×52 mm) with increased cortical echogenicity. There was no White cells (high-power field) 10–19 hydronephrosis or visible calcification. Urinary chemistry Urine protein (mg/dL) 47 Urine urea nitrogen (mg/dL) 544 Urine creatinine (mg/dL) 93.6 Urine sodium (mEq/L) 91 Urine ȕ-microglobulin (μg/dL) 8,040 0–50 Urine N-acetyl-ȕ-D-glucosaminidase (U/L) 50.9 0.0–10.0 Osmolality (mOsm/kgh) 503 50–1,300 Ratio of U-protein to U-creatinine 0.50 Fractional excretion of sodium 3.5

ϭϬϬʅŵ

Figure 3. Histological staining of the kidney with Hematoxy- lin and Eosin staining showing vacuolation of tubular cells (ar- rows) and flattening of epithelial cells (thick arrow). Renal tu- bules with epithelial injury containing tubular basophilic deposits (asterisk) can be seen. Most of the tubules with calci- um phosphate deposits were distal tubules.

ϭϬϬʅŵ following OSP administration in all patients who underwent Figure 2. Histological staining of the kidney with periodic colonoscopy (7). The excess absorbed phosphate is then fil- acid-methenamine silver showing widespread dilation of the trated through the glomeruli, passed through the tubules, and tubular lumen resulting from degenerative atrophy and des- is excreted into the urine, except when the concentration of quamation of epithelial cells. Interstitial edema (arrows) and phosphate in the primary urine exceeds its solubility, in focal inflammatory cell infiltration (thick arrow) can be seen in which case calcium phosphate crystals are formed. These the interstitium, while the glomerulus is well preserved. crystals form CPDs on tubular epithelial cells, leading to lu- minal obstruction (8) and also causing an immune reaction, tubular inflammation, and damage to the tubulointerstitial ter OSP administration remain unclear. The phosphate de- area (9). Previous studies of APhN reported diffuse, abun- rived from OSP administration is mainly excreted in the fe- dant CPDs obstructing the tubular lumens, thus supporting ces, though some is absorbed into the blood through the this hypothesis (Table 4). In the current case, CPDs were small intestine. Phosphate absorption in the small intestine is only detected in 2% of the tubular lumen, despite the pres- loosely controlled and does not respond to excess phosphate ence of diffuse tubulointerstitial injury, suggesting that CPD exposure, resulting in a transient increase in serum phos- obstruction is not essential for the development of APhN. phate levels following OSP administration (6). Unfortu- Aihara et al. reported that the presence of calcium phosphate nately, we were unable to measure the serum phosphate lev- crystals increased oxidative stress and cellular damage in els in the current case because the blood sample taken just cultured renal tubular cells (10), while Kuro-o et al. showed after OSP administration was not stored. However, a previ- that the formation of urinary calcium phosphate nanoparti- ous study demonstrated increased serum phosphate levels cles, as a result of dietary phosphate overload, exerted cyto-

2233 Intern Med 55: 2229-2235, 2016 DOI: 10.2169/internalmedicine.55.5864

A APhN. caused by OSP-induced or -induced polyuria, as well as age-related decreases in body fluid, may thus contribute to the risk of APhN. Al- though there were no physical or laboratory findings that in- dicated dehydration in the current case, the patient may nonetheless have had a reduced body fluid volume related to her age. Some epidemiological studies have identified risk factors for APhN, and OSPs should thus be avoided in high- ϭϬϬʅŵ risk patients. Physicians must evaluate individual patients B according to APhN risk factors prior to colonoscopy and se- lect an appropriate bowel preparation for high-risk patients. In conclusion, we reported a patient with APhN who showed diffuse tubular injury and severe kidney dysfunction, despite a limited distribution of CPDs. APhN with partial CPDs may demonstrate a relatively acute onset and revers- ible course compared with APhN with more diffuse and 1mm widespread CPDs. This case suggests that calcium phos- phate crystals in the primary urine may cause direct tubular Figure 4. (A) Histological staining of the kidney with von injury even in the absence of deposits in the tubular lumen. Kossa stain showing tubular deposits composed of calcium APhN should thus be considered as a possible diagnosis in phosphate. (B) Histological staining of the kidney with von patients with diffuse interstitial injury after OSP administra- Kossa stain at low magnification showing calcium phosphate tion, even those with only limited CPDs in kidney samples. deposits (arrows) focally distributed in the renal parenchyma. Tubules with deposits only occupied 2% of the tubules in the The authors state that they have no Conflict of Interest (COI). section.

References toxic effects via inflammatory cytokines, leading to tubule 1. Desmeules S, Bergeron MJ, Isenring P. Acute phosphate nephropa- cell injury and tubulointerstitial fibrosis (11). Calcium phos- thy and renal failure. N Engl J Med 349: 1006-1007, 2003. phate in the primary urine might thus also have caused di- 2. Markowitz GS, Stokes MB, Radhakrishnan J, D’Agati VD. Acute phosphate nephropathy following oral sodium phosphate bowel rect tubule cell damages without deposition in the current purgative: an under recognized cause of chronic renal failure. J case. Am Soc Nephrol 16: 3389-3396, 2005. Existing kidney dysfunction is an important risk factor for 3. Choi NK, Lee J, Chang Y, et al. Acute renal failure following oral the development of APhN. Haut et al. reported that previous sodium phosphate bowel preparation: a nationwide case-crossover nephrectomy increased high-phosphate diet-induced tubu- study. Endoscopy 46: 465-470, 2014. 4. Haut LL, Alfrey AC, Guggenheim S, Buddington B, Schrier N. lointerstitial injury in the residual kidney in a rat model (4). Renal toxicity of phosphate in rats. Kidney Int 17: 722-731, 1980. Kidney dysfunction increases serum phosphate concentra- 5. Gonlusen G, Akugun H, Ertan A, Olivero J, Truong LD. Renal tions by reducing the phosphate excretion ability, resulting failure and associated with oral sodium phosphate in phosphate overload in functionally preserved in bowel cleansing: clinical patterns and renal biopsy findings. Arch an attempt to compensate for dysfunctional nephrons. Dam- Pathol Lab Med 130: 101-106, 2006. 6. Murer H, Hernando N, Forster L, Biber J. Molecular mechanisms age to nephrons may then rapidly spread, leading to APhN. in proximal tubular and small intestinal phosphate reabsorption. CKD and various factors that affect the kidney function, Mol Membr Biol 18: 3-11, 2001. such as aging, hypertension, and treatment with renin- 7. Lieberman DA, Ghormley J, Flora K. Effect of oral sodium phos- angiotensin blockers and/or NSAIDs, thus appear to facili- phate colon preparation on serum electrolytes in patients with nor- tate the development of APhN. Potential kidney dysfunction mal serum creatinine. Gastrointest Endosc 43: 467-469, 1996. 8. Markowitz GS, Perazella MA. Acute phosphate nephropathy. Kid- associated with CKD, aging, hypertension, and the use of ney Int 76: 1027-1034, 2009. ARBs and NSAIDs might thus have been an important risk 9. Heher EC, Their SO, Rennke H, Humphreys BD. Adverse renal factor affecting the development of APhN in the current and metabolic effects associated with oral sodium phosphate case. The proportion of global sclerosis (a form of non- bowel preparation. Clin J Am Soc Nephrol 3: 1494-1503, 2008. specific pathological damage) and the baseline serum cre- 10. Aihara K, Byer KJ, Khan SR. Calcium phosphate-induced renal epithelial injury and stone formation: involvement of reactive oxy- atinine level in the current patient were similar to those in gen species. Kidney Int 64: 1283-1291, 2003. previous cases, and arterial sclerotic changes were mild, 11. Kuro-o M. Klotho, phosphate and FGF-23 in ageing and disturbed suggesting similar contributions of existing kidney dysfunc- mineral metabolism. Nat Rev Nephrol 9: 650-660, 2013. tion (Table 4). 12. Russmann S, Lamerato L, Marfatia A, Motsko SP, Pezzullo JC, A decreased body fluid volume leading to an increased Jones JK. Risk of impaired renal function after colonoscopy: a co- hort study in patients receiving either oral sodium phosphate or urine concentration is another apparent risk factor promoting

2234 Intern Med 55: 2229-2235, 2016 DOI: 10.2169/internalmedicine.55.5864

. Am J Gastroenterol 102: 2655-2663, 2007. 15. Singal AK, Rosman AS, Post JB, Bauman WA, Spungen AM, 13. Khurana A, McLean L, Atkinson S, Foulks CJ. The effect of so- Korsten MA. The renal safety of bowel preparations for colono- dium phosphate drug products on renal function in adults undergo- scopy: a comparative study of oral sodium phosphate solution and ing bowel endoscopy. Arch Intern Med 168: 593-597, 2008. polyethylene glycol. Aliment Pharmacol Ther 27: 41-47, 2008. 14. Hurst FP, Bohen EM, Osgard EM, et al. Association of sodium 16. Brunelli SM, Lewis JD, Gupta M, Latif SM, Weiner MG, phosphate purgative use with acute kidney injury. J Am Soc Neph- Feldman HI. Risk of kidney injury oral phosphosoda bowel prepa- rol 18: 3192-3198, 2007. rations. J Am Soc Nephrol 18: 3199-3205, 2007.

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