Renal failure following bowel cleansing with a sodium phosphate purgative

Sir,

Visicol® (InKline Pharmaceutical Co., Inc., Blue Bell, PA, USA) is a tablet form of sodium phosphate used as a bowel purgative prior to colonoscopy. Patients are instructed to take three tablets with at least 8 oz (227 g) clear liquids every 15 min, for a total of 20 tablets, both the evening before and again the morning of colonoscopy. The cumulative dose of 40 tablets contains 44.08 g sodium phosphate monobasic monohydrate (USP) and 15.92 g sodium dibasic anhydrous (USP) for a total of 60 g sodium phosphate. Visicol has been shown to be an effective and safe bowel purgative [1,2]. We describe a case of acute renal failure (ARF) with sustained loss of renal function following use of Visicol.

A 44-year-old Caucasian male presented for evaluation of renal dysfunction. The patient had mild chronic renal insufficiency (CRI) with a creatinine of 1.5 mg/dl (normal range: 0.7–1.5 mg/dl) in August 2002 and 1.7 mg/dl in early December 2003. In early February 2004, the patient was found to have a creatinine of 2.6 mg/dl and was referred for nephrological consultation.

Past medical history was significant for coronary artery disease, requiring multiple percutaneous interventions (PCIs) and stent placements over the previous 2 years. The most recent PCI was in July 2003 and was not associated with a change in renal function. There was also a history of hypertension, gout and osteoarthritis, for which he had been treated with non-steroidal anti-inflammatory drugs (NSAID) for the past 10 years. There was no history of diabetes mellitus. Medications included meloxicam 15 mg QD and ramipril 10 mg QD. The patient experienced an episode of haematochezia in autumn 2003 and underwent colonoscopy in mid-December 2003. For bowel preparation, the patient was given Visicol, 20 tablets the evening before and 12 tablets the morning of the colonoscopy procedure.

Physical examination revealed a blood pressure of 138/82 mmHg, obesity [height: 5' 1'' (155 cm); weight: 238 lb (108 kg)] and no oedema. The patient had serum albumin of 4.4 g/dl (normal: 3.2–5.2 g/dl), calcium of 9.2 mg/dl (normal: 8.4–10.4 mg/dl), 24 h urine protein of 95 mg (normal: 0–150 mg) and bland urinary sediment. Serological evaluation revealed normal C3 and C4 complement levels, negative ANA and no evidence of a monoclonal serum or urine spike. Magnetic resonance angiography was negative for renal artery stenosis. The kidneys measured 11.7 and 12.0 cm in length by ultrasound. While the patient's mild CRI appeared to be related to chronic NSAID use, the aetiology of the superimposed ARF was unclear.

Renal biopsy revealed a tubulointerstitial nephropathy characterized by degenerative changes in proximal tubules and numerous distal tubular calcifications with staining properties of calcium phosphate (Figure 1), accompanied by mild tubular atrophy and interstitial fibrosis. The findings of ‘acute nephrocalcinosis’ were not associated with glomerular or vascular disease. No specific therapy was given and 4 months post-biopsy the patient's creatinine was 2.2 mg/dl.



View larger version (162K):
[in this window]
[in a new window]
 
Fig. 1. Multiple basophilic calcifications are seen in tubular lumina and adjacent interstitium. The calcifications did not polarize and were von Kossa positive, consistent with calcium phosphate. (Haematoxylin and eosin; original magnification: x400.)

 
Oral sodium phosphate solution (OSPS; Phospho-soda, CB Fleet, Lynchburg, PA, USA) is widely used for bowel cleansing prior to colonoscopy. The recommended regimen of two 45 ml doses taken 12 h apart contains 37.6 g monobasic sodium phosphate and 8.6 g dibasic sodium phosphate, for a total of 46.2 g sodium phosphate. This regimen is associated with a transient increase in serum phosphorus of 3.0–3.5 mg/dl and a transient decline in serum calcium of 0.2–0.3 mg/dl [3,4].

We recently reported the occurrence of renal failure and acute nephrocalcinosis following bowel cleansing with OSPS [5]. The five reported patients had a mean age of 69.2 years and a mean baseline serum creatinine of 0.9 mg/dl (with a mean interval from baseline creatinine determination to colonoscopy of 4 months). Patients presented with ARF and a mean creatinine of 4.9 mg/dl at 3 days to 2 months (mean: 3 weeks) post-colonoscopy. Renal biopsy revealed acute nephrocalcinosis with abundant distal tubular calcium phosphate deposition in all five patients. The close temporal relationship with colonoscopy, the presence of tubular calcium phosphate precipitates and previous reports of a similar lesion occurring after oral phosphate treatment of children with hypophosphataemic rickets [6], all strongly implicated OSPS as the precipitating factor. At 4 months post-colonoscopy, renal function was unchanged in four patients and slightly improved in one patient. Subsequent to this report, we have seen 10 additional cases of ARF due to biopsy-proven acute nephrocalcinosis following treatment with OSPS.

Visicol is a newer purgative preparation with a nearly identical composition to OSPS. While all purgatives have the potential for abuse, in the case of OSPS abuse is limited by its unpleasant taste. In contrast, Visicol tablets are virtually tasteless and, therefore, are only available by prescription [1]. Similar to OSPS, Visicol is associated with transient electrolyte abnormalities. At 3–5 h after the second dose of 20 tablets, patients experience a mean increase in serum phosphorus of 3.7 mg/dl and a mean decline in serum calcium of 0.5 mg/dl [1]. These changes resolve within 48–72 h. It is recommended that both agents be used with caution in patients who have electrolyte abnormalities or renal insufficiency.

This is the first report of ARF following the use of Visicol, a tablet form of sodium phosphate bowel purgative. The renal biopsy findings of acute nephrocalcinosis following Visicol administration are identical to those reported for OSPS. This observation reaffirms that ARF and acute nephrocalcinosis is a potential complication of all orally administered sodium phosphate purgatives, whether they are given in liquid or tablet form. Clinicians should be aware of this potential complication of sodium phosphate-containing purgative agents.

Conflict of interest statement. None declared.

Glen S. Markowitz1, Joseph Whelan2 and Vivette D. D'Agati1

1 Department of Pathology Columbia University, College of Physicians & Surgeons New York, NY2 Indiana Nephrology & Internal Medicine Indianapolis, IN USA Email: gsm17{at}columbia.edu

References

  1. Kastenberg D, Chasen R, Choudhary C et al. Efficacy and safety of sodium phosphate tablets compared with PEG solution in colon cleansing: two identically designed, randomized, controlled, parallel group, multicenter phase III trials. Gastrointest Endosc 2001; 54: 705–713[CrossRef][ISI][Medline]
  2. Rex DK, Chasen R, Pochapin MB. Safety and efficacy of two reduced dosing regimens of sodium phosphate tablets for preparation prior to colonoscopy. Aliment Pharmacol Ther 2002; 16: 937–944[CrossRef][ISI][Medline]
  3. Vanner SJ, MacDonald PH, Paterson WG, Prentice RS, Da Costa LR, Beck IT. 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: 422–427[ISI][Medline]
  4. Cohen SM, Wexner SD, Binderow SW et al. Prospective, randomized, endoscopic-blinded trial comparing precolonoscopy bowel cleansing methods. Dis Colon Rectum 1994; 37: 689–696[ISI][Medline]
  5. Markowitz GS, Nasr SH, Klein P et al. Renal failure and acute nephrocalcinosis following oral sodium phosphate bowel cleansing. Human Pathol 2004; 35: 675–684[CrossRef][ISI][Medline]
  6. Alon U, Donaldson DL, Hellerstein S, Warady BA, Harris DJ. Metabolic and histologic investigation of the nature of nephrocalcinosis in children with hypophosphatemic rickets and in the Hyp mouse. J Pediatr 1992; 120: 899–905[ISI][Medline]