Acute Phosphate Nephropathy After Oral Sodium Phosphate Bowel Preparation: A Clinically Underrecognized Entity Illustrated by a Series of Biopsy‐Proven Cases

1. Introduction

Acute phosphate nephropathy (APhN) is a form of crystal-induced tubulointerstitial kidney injury that has been described after exposure to oral sodium phosphate (OSP) preparations used for bowel cleansing before colonoscopy. Histologically, APhN is characterized by calcium phosphate deposition within renal tubules and the tubulointerstitium, accompanied by tubular injury and, in more advanced cases, tubular atrophy and interstitial fibrosis [1,2,3,4].

Although OSP-associated nephrotoxicity is well documented, APhN may be difficult to recognize in routine clinical practice. Kidney dysfunction may be detected only after a delay, serum calcium and phosphate concentrations can be unremarkable at the time of evaluation, and renal ultrasonography may fail to demonstrate nephrocalcinosis [3,5]. Consequently, the association with a preceding bowel preparation may not become apparent until kidney biopsy identifies characteristic crystal deposits.

We describe three patients with biopsy-proven APhN following documented OSP bowel preparation. The cases illustrate delayed clinical recognition, the potential discrepancy between imaging and histopathology, and the risk of persistent or irreversible loss of kidney function. They also highlight practical opportunities for prevention and earlier diagnosis.

2. Materials and Methods

This retrospective case series included three patients with biopsy-proven APhN following documented exposure to OSP bowel preparation between 2020 and 2025. APhN was diagnosed on the basis of the exposure history together with characteristic histopathological findings, particularly von Kossa-positive calcium phosphate microcalcifications associated with tubulointerstitial injury [1,2,3].

Clinical records were reviewed for demographic information, baseline and follow-up kidney function, timing of colonoscopy and OSP exposure, urinary findings, renal imaging, kidney biopsy findings, and subsequent clinical course. The demographic, clinical, laboratory, histopathological, and outcome characteristics of the three patients are summarized in Supplementary Table S1. Estimated glomerular filtration rate (eGFR) values shown in the clinical timeline were calculated using the CKD-EPI equation.

Renal biopsy specimens were evaluated by standard histopathological techniques. Representative findings include von Kossa staining for calcium phosphate deposits, hematoxylin and eosin (H&E) staining, and periodic acid–Schiff (PAS) staining. The clinical timeline of OSP exposure, first documented kidney function decline, kidney biopsy, and subsequent course is summarized in Figure 1.

3. Results

3.1. Case 1

A 77-year-old man underwent colonoscopy after OSP bowel preparation. Before the procedure, kidney function was only mildly impaired, with a serum creatinine concentration of 1.05 mg/dL and an eGFR of 73 mL/min/1.73 m². Urinary findings, including assessment of proteinuria, were not available. Eight weeks later, severe acute kidney injury was identified, with serum creatinine of 4.5 mg/dL and eGFR of 13 mL/min/1.73 m². Two kidney biopsies revealed nephrocalcinosis with extensive tubular injury and von Kossa-positive calcium phosphate microcalcifications, consistent with APhN. Despite supportive management, kidney function progressively deteriorated over the following months and ultimately resulted in end-stage kidney disease requiring maintenance hemodialysis.

3.2. Case 2

A 56-year-old man with pre-existing chronic kidney disease (CKD) secondary to immunoglobulin A nephropathy underwent colonoscopy with documented OSP bowel preparation. Several weeks later, routine laboratory testing revealed a marked deterioration in kidney function, with serum creatinine increasing from a stable baseline of 3.2 mg/dL to 4.7 mg/dL. Kidney biopsy demonstrated focal von Kossa-positive microcalcifications consistent with phosphate-related crystal nephropathy. Kidney function continued to decline thereafter, and the patient was subsequently evaluated for kidney transplantation.

3.3. Case 3

A 42-year-old man presented with progressive kidney dysfunction of initially unclear etiology. Kidney biopsy revealed moderate crystal nephropathy characterized by tubulointerstitial calcium phosphate and calcium oxalate deposits. Retrospective review of the medical history identified a colonoscopy approximately 18 months earlier with documented OSP bowel preparation, thereby establishing the diagnosis of APhN. Before colonoscopy, baseline kidney function had been mildly impaired, with eGFR between 58 and 62 mL/min/1.73 m². Nearly two years after the procedure, a marked decline in kidney function was first documented, with eGFR of 35 mL/min/1.73 m². The biopsy findings together with the documented OSP exposure strongly suggest that kidney injury most likely occurred at the time of phosphate exposure approximately 1.5 years before biopsy and remained clinically unrecognized thereafter.

3.4. Shared Clinical and Diagnostic Features

In all three patients, the relationship between OSP exposure and subsequent kidney dysfunction was recognized only retrospectively after kidney biopsy had demonstrated nephrocalcinosis or phosphate-related crystal deposition. Two of the three patients had pre-existing CKD, whereas Case 1 had only mildly impaired kidney function before exposure. Urinalysis provided additional evidence of tubular injury: apart from Case 2, in whom glomerular proteinuria was attributable to underlying IgA nephropathy, the patients did not have relevant glomerular proteinuria. In contrast, urinary α1-microglobulin was elevated in all three patients, consistent with persistent tubulointerstitial injury.

Figure 2. Representative renal ultrasonography demonstrating a normal-sized kidney with preserved corticomedullary differentiation and unusually well-defined medullary pyramids. No sonographic evidence of nephrocalcinosis was identified.

Figure 2. Representative renal ultrasonography demonstrating a normal-sized kidney with preserved corticomedullary differentiation and unusually well-defined medullary pyramids. No sonographic evidence of nephrocalcinosis was identified.

Figure 3. Histopathological findings in Case 1. (A) Von Kossa staining demonstrates extensive intratubular calcium phosphate crystal deposition accompanied by chronic tubulointerstitial injury. In the appropriate clinical context of OSP exposure, these findings are consistent with APhN. (B) Hematoxylin and eosin (H&E) staining shows chronic tubulointerstitial injury with tubular atrophy and interstitial fibrosis. (C) Periodic acid–Schiff (PAS) staining highlights tubular injury and tubular atrophy. Original magnification ×200.

Figure 3. Histopathological findings in Case 1. (A) Von Kossa staining demonstrates extensive intratubular calcium phosphate crystal deposition accompanied by chronic tubulointerstitial injury. In the appropriate clinical context of OSP exposure, these findings are consistent with APhN. (B) Hematoxylin and eosin (H&E) staining shows chronic tubulointerstitial injury with tubular atrophy and interstitial fibrosis. (C) Periodic acid–Schiff (PAS) staining highlights tubular injury and tubular atrophy. Original magnification ×200.

4. Discussions and Conclusions

Our case series highlights a central clinical problem in APhN: the renal injury may occur in temporal association with OSP exposure but remain clinically unrecognized for weeks or months. In each of our three patients, the causal relationship between bowel preparation and subsequent loss of kidney function was reconstructed only after kidney biopsy demonstrated nephrocalcinosis or phosphate-related crystal deposition.

Gonlusen et al. described two clinical patterns of kidney injury following OSP bowel preparation [3]. One subgroup developed acute kidney injury within hours to several days and presented with severe hydroelectrolytic disturbances. In a second subgroup, kidney injury was identified incidentally on kidney biopsy three days to eight weeks after OSP administration; these patients generally had mild, nonspecific symptoms and near-normal serum calcium and phosphate levels. Our patients resemble this less conspicuous pattern, although in Case 3 the interval between exposure and diagnostic recognition was considerably longer. Importantly, delayed recognition should not be interpreted as delayed onset of the renal injury, which most likely occurs much earlier following phosphate exposure.

A second important observation is the potential discordance between routine imaging and histopathology. Renal ultrasonography may be unrevealing despite histologically confirmed nephrocalcinosis. Davies et al. similarly reported normal renal ultrasonography in a patient with biopsy-proven phosphate nephropathy [5]. Thus, absence of sonographic nephrocalcinosis does not exclude APhN. When kidney dysfunction remains otherwise unexplained, a careful exposure history—including prior colonoscopy and the specific bowel preparation used—may be diagnostically more informative than routine imaging alone. Kidney biopsy can be pivotal when clinical suspicion persists.

Baseline kidney function appears relevant to susceptibility. Two of our three patients had pre-existing CKD, supporting previous observations that impaired renal function may increase the risk of APhN following OSP exposure. However, Case 1 demonstrates that severe and irreversible injury can also occur in a patient with only mildly impaired baseline kidney function, ultimately culminating in dialysis-dependent end-stage kidney disease. The factors determining individual susceptibility and severity remain incompletely understood.

Urinary findings may provide an additional clue. Urinary α1-microglobulin was elevated in all three patients, whereas relevant glomerular proteinuria was absent except in the patient with pre-existing IgA nephropathy. Although none of the biopsies was obtained during the immediate acute phase, persistent α1-microglobulin elevation is compatible with ongoing tubular and tubulointerstitial injury. This observation is hypothesis-generating and should not be considered a specific diagnostic marker of APhN.

Histopathology also provides insight into pathogenesis. Wiech et al. showed that phosphate-associated nephrocalcinosis is characterized predominantly by globular and shell-like calcium phosphate deposits, in contrast to the clumpy or finely granular calcifications typically seen in hypercalciuric disorders [4]. The authors proposed that phosphate-related crystals initially form within the tubular lumen and may subsequently migrate into the interstitium after tubular epithelial injury and disruption of the tubular basement membrane, a process termed “exotubulosis”. This process may contribute to tubular atrophy, interstitial fibrosis, and chronic tubulointerstitial damage. The findings in our patients are consistent with this proposed model.

These observations have direct implications for prevention. Current endoscopy guidance recommends polyethylene glycol (PEG)-based bowel preparations for patients at increased risk of kidney injury or electrolyte disturbances, including those with CKD, congestive heart failure, and liver cirrhosis with ascites [6,7]. Nevertheless, OSP-containing preparations continue to be used in clinical practice. Careful assessment of patient-specific risk factors and avoidance of OSP in susceptible patients may prevent avoidable kidney injury. If OSP is used, timely monitoring of kidney function and serum electrolytes should be considered to facilitate earlier recognition of renal injury and electrolyte disturbances.

This report has limitations. It is a small retrospective case series, and the timing of laboratory follow-up and kidney biopsy was determined by routine clinical care rather than a standardized protocol. In particular, the exact onset of kidney injury cannot be established in patients in whom renal function was not measured shortly after OSP exposure. The association with OSP is therefore supported by the documented exposure history and characteristic biopsy findings rather than by prospective post-exposure monitoring. Conversely, this diagnostic delay is itself clinically informative and illustrates why APhN may remain underrecognized.

APhN should be considered in patients with otherwise unexplained acute kidney injury or apparent CKD progression, particularly when there is a history of colonoscopy with OSP bowel preparation. The diagnosis may be delayed because clinical findings are nonspecific and renal ultrasonography may remain normal despite histological nephrocalcinosis. Careful exposure history, attention to tubular urinary markers, and kidney biopsy in selected patients can facilitate recognition. Prevention remains paramount: OSP should be avoided in patients at increased renal risk, and kidney function should be assessed in a timely manner when exposure has occurred.