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Quiz Page February 2010
QUIZ PAGE FEBRUARY 2010 A Hemodialysis Patient With Muscle Cramps and Malaise After Virtual Colonoscopy
CLINICAL PRESENTATION A 58-year-old woman with endstage renal disease caused by AA amyloidosis on hemodialysis therapy for the past 7 years presents with severe malaise, nausea, vomiting, and diffuse muscle cramps. Symptoms began the previous evening after the patient
underwent a virtual colonoscopy required for her maintenance on the kidney transplant waiting list. The procedure had been uneventful. On evaluation, the patient is in obvious distress. Blood pressure is 120/80 mm Hg, heart
rate is 82 beats/min with a regular rhythm, and weight is 1 kg greater than her postdialysis weight from 2 days earlier. Her abdomen is diffusely tender, and she mentions pain in the hand and forearm during blood pressure measurement.
Which clues are important in the presentation? What tests are required for confirmation? What is the best therapeutic approach?
xxxv
QUIZ PAGE
American Journal of Kidney Diseases, Vol 55, No 2 (February), 2010: pp xxxv-xxxvii
QUIZ PAGE FEBRUARY 2010 ANSWERS DISCUSSION
QUIZ PAGE
f Which clues are important in the presentation? The temporal relationship between the patient’s virtual colonoscopy and presentation is an important clue. Although weight gain and normal blood pressure rule out severe volume depletion, a side effect of the bowel preparation may be suspected. The severe cramps occurring during blood pressure measurement suggest the possibility of hypocalcemia. After questioning, the patient reports having replaced the “usual” bowel preparation with “a new one” that did not require ingestion of a large quantity of fluid. On further investigation, the compound was a sodium phosphate bowel preparation containing 48 g (400 mmol) of monobasic sodium phosphate and 18 g (130 mmol) of dibasic sodium phosphate per 100 mL; in other words, ⬃34 times the amount of sodium, 2,000 times the amount of phosphate, and ⬎30 times the osmolarity of normal human plasma. The standard dose recommended for intestinal cleaning is 90 mL, taken in 2 doses the day before the imaging procedure.1,2 Severe hypocalcemia can develop from intravascular precipitation of calcium phosphate, a very dangerous event that can lead to death if left untreated.3-5 f What tests are required for confirmation? Severe calcium and phosphate imbalance was detected, with a total xxxvi
Figure 1. Main laboratory parameters at diagnosis and subsequent daily dialysis sessions. Conversion factors for units: phosphorus in mg/dL to mmol/L, ⫻0.3229; calcium in mg/dL to mmol/L, ⫻0.2495; calcium ion in mEq/L to mmol/L, ⫻0.5.
serum calcium level of 6.63 mg/dL (1.66 mmol/L), ionized calcium level of 1.30 mEq/L (0.65 mmol/ L), and serum phosphate level of 25.09 mg/dL (8.1 mmol/L). Levels of other electrolytes were normal, with sodium, 140 mEq/L (140 mmol/L); potassium, 5.3 mEq/L (5.3 mmol/L); bicarbonate, 23.2 mEq/L (23.2 mmol/L); and magnesium, 1.70 mEq/L (0.85 mmol/L). Of note, the patient’s usual predialysis reference levels are total serum calcium, 10 mg/dL (2.5 mmol/L); ionized calcium, 2 mEq/L (1 mmol/ L); and serum phosphate, 6-6.5 mg/dL (1.8-2.2 mmol/L). Amylase, lipase, and liver enzyme levels were normal; total blood cell count showed a white blood cell count of 13.9 ⫻ 103/L with neutrophilia; and hemoglobin level was 11 g/dL. f What is the best therapeutic approach? Daily dialysis treatment was initiated because phosphate is highly
compartmentalized and its removal is the highest during the first hours of treatment. The first dialysis session was prolonged for 5 hours, and daily treatments were performed until normalization of calcium and phosphate levels was achieved after the third session (Fig 1). Dialysate calcium concentration was 3 mEq/L (1.5 mmol/L). The phosphate levels recorded in this case are among the highest reported in the literature.3-5 Although phosphate-containing bowel preparations are contraindicated in dialysis patients, they are widely available over the counter, and awareness of the potential dangers is low, as suggested by recent studies in the general population6-8 and case reports in dialysis or transplant patients.3-5 A review of these reports shows wide variability in phosphate absorption, which may be why this toxicity has
American Journal of Kidney Diseases, Vol 55, No 2 (February), 2010: pp xxxv-xxxvii
xxxvii
been underappreciated in our patients. Use of bowel preparation with compounds containing oral sodium phosphate should be avoided in patients with chronic kidney disease and possibly also in the general population.9 Phosphatecontaining enemas have been recognized in the development of de novo nephrocalcinosis, in addition to acute kidney injury.6-8 Current recommendations are to avoid oral sodium phosphate–containing preparations in patients with known underlying kidney disease, aged ⬎65 years, or treated using diuretics, angiotensin-converting enzyme inhibitors, or angiotensin receptor blockers.1,2,8 Alternative bowel preparations containing magnesium citrate bear a risk of severe and even fatal hypermagnesemia in patients with kidney disease because the major excretion route of magnesium is through the kidney.1,2 The safest option in dialysis patients may be low-volume polyethylene glycol, a nonabsorbable compound.1,2,8 Severe side effects are rare and include pulmonary aspiration, Mallory-Weiss tear, pancreatitis or colitis, and exacerbation of chronic heart failure. Severe and even lethal dysnatremia have been reported in patients with chronic kidney disease stage 5 and those treated with diuretics.1 Furthermore, acute kidney injury caused by volume depletion has been reported with all the common preparations.1,2 Despite increasing warnings, many physicians and nurses may not be aware of groups of patients who are at high risk. Hence, this rather unusual problem should be
considered in the differential diagnosis of malaise occurring after bowel preparation, especially in patients with advanced chronic kidney disease.
FINAL DIAGNOSIS Severe hypocalcemia caused by intravascular calcium phosphate precipitation after sodium phosphate–containing bowel preparation.
ACKNOWLEDGEMENTS The authors thank Professor Giuseppe Paolo Segoloni for critical support and Dr P. Christie for careful language revision.
REFERENCES 1. Barkun A, Chiba N, Enns R, et al. Commonly used preparations for colonoscopy: efficacy, tolerability, and safety—a Canadian Association of Gastroenterology position paper. Can J Gastroenterol. 2006;20(11):699710. 2. Wexner SD, Beck DE, Baron TH, 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). Dis Colon Rectum. 2006;49(6):792-809. 3. Mendoza J, Legido J, Rubio S, Gisbert JP. Systematic review: the adverse effects of sodium phosphate enema. Aliment Pharmacol Ther. 2007;26(1):9-20. 4. Woo YM, Crail S, Curry G, Geddes CC. A life threatening complication after ingestion of sodium phosphate bowel preparation. BMJ. 2006; 333(7568):589-590.
5. Heher EC, Thier SO, Rennke H, Humphreys BD. Renal and metabolic effects associated with oral sodium phosphate bowel preparation. Clin J Am Soc Nephrol. 2008;3(5): 1494-1503. 6. 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(12): 2655-2663. 7. Markovitz 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(11):3389-3396. 8. Lien YH. Is bowel preparation before colonoscopy a risky business for the kidney? Nat Clin Pract Nephrol. 2008;4(11):606-614. CASE PROVIDED AND AUTHORED BY Giorgina Barbara Piccoli, MD,1 Federica Neve Vigotti, MD,2 Valentina Consiglio, MD,1 and Maria Chiara Deagostini, MD,1 1Nephrology Unit, SCDU Urology, University of San Luigi, Orbassano; and 2 Department of Internal Medicine, University of Turin, Turin, Italy. Address correspondence to Giorgina Barbara Piccoli, MD. Nephrology Unit of the University of San Luigi, Orbassano, Torino, Regione Gonzole, Orbassano, Torino, Italy. E-mail: [email protected] or [email protected] © 2010 by the National Kidney Foundation, Inc. doi:10.1053/j.ajkd.2009.09.012 SUPPORT: None. FINANCIAL DISCLOSURE: None.
QUIZ PAGE
CLINICAL PRESENTATION A 58-year-old woman with endstage renal disease caused by AA amyloidosis on hemodialysis therapy for the past 7 years presents with severe malaise, nausea, vomiting, and diffuse muscle cramps. Symptoms began the previous evening after the patient
underwent a virtual colonoscopy required for her maintenance on the kidney transplant waiting list. The procedure had been uneventful. On evaluation, the patient is in obvious distress. Blood pressure is 120/80 mm Hg, heart
rate is 82 beats/min with a regular rhythm, and weight is 1 kg greater than her postdialysis weight from 2 days earlier. Her abdomen is diffusely tender, and she mentions pain in the hand and forearm during blood pressure measurement.
Which clues are important in the presentation? What tests are required for confirmation? What is the best therapeutic approach?
xxxv
QUIZ PAGE
American Journal of Kidney Diseases, Vol 55, No 2 (February), 2010: pp xxxv-xxxvii
QUIZ PAGE FEBRUARY 2010 ANSWERS DISCUSSION
QUIZ PAGE
f Which clues are important in the presentation? The temporal relationship between the patient’s virtual colonoscopy and presentation is an important clue. Although weight gain and normal blood pressure rule out severe volume depletion, a side effect of the bowel preparation may be suspected. The severe cramps occurring during blood pressure measurement suggest the possibility of hypocalcemia. After questioning, the patient reports having replaced the “usual” bowel preparation with “a new one” that did not require ingestion of a large quantity of fluid. On further investigation, the compound was a sodium phosphate bowel preparation containing 48 g (400 mmol) of monobasic sodium phosphate and 18 g (130 mmol) of dibasic sodium phosphate per 100 mL; in other words, ⬃34 times the amount of sodium, 2,000 times the amount of phosphate, and ⬎30 times the osmolarity of normal human plasma. The standard dose recommended for intestinal cleaning is 90 mL, taken in 2 doses the day before the imaging procedure.1,2 Severe hypocalcemia can develop from intravascular precipitation of calcium phosphate, a very dangerous event that can lead to death if left untreated.3-5 f What tests are required for confirmation? Severe calcium and phosphate imbalance was detected, with a total xxxvi
Figure 1. Main laboratory parameters at diagnosis and subsequent daily dialysis sessions. Conversion factors for units: phosphorus in mg/dL to mmol/L, ⫻0.3229; calcium in mg/dL to mmol/L, ⫻0.2495; calcium ion in mEq/L to mmol/L, ⫻0.5.
serum calcium level of 6.63 mg/dL (1.66 mmol/L), ionized calcium level of 1.30 mEq/L (0.65 mmol/ L), and serum phosphate level of 25.09 mg/dL (8.1 mmol/L). Levels of other electrolytes were normal, with sodium, 140 mEq/L (140 mmol/L); potassium, 5.3 mEq/L (5.3 mmol/L); bicarbonate, 23.2 mEq/L (23.2 mmol/L); and magnesium, 1.70 mEq/L (0.85 mmol/L). Of note, the patient’s usual predialysis reference levels are total serum calcium, 10 mg/dL (2.5 mmol/L); ionized calcium, 2 mEq/L (1 mmol/ L); and serum phosphate, 6-6.5 mg/dL (1.8-2.2 mmol/L). Amylase, lipase, and liver enzyme levels were normal; total blood cell count showed a white blood cell count of 13.9 ⫻ 103/L with neutrophilia; and hemoglobin level was 11 g/dL. f What is the best therapeutic approach? Daily dialysis treatment was initiated because phosphate is highly
compartmentalized and its removal is the highest during the first hours of treatment. The first dialysis session was prolonged for 5 hours, and daily treatments were performed until normalization of calcium and phosphate levels was achieved after the third session (Fig 1). Dialysate calcium concentration was 3 mEq/L (1.5 mmol/L). The phosphate levels recorded in this case are among the highest reported in the literature.3-5 Although phosphate-containing bowel preparations are contraindicated in dialysis patients, they are widely available over the counter, and awareness of the potential dangers is low, as suggested by recent studies in the general population6-8 and case reports in dialysis or transplant patients.3-5 A review of these reports shows wide variability in phosphate absorption, which may be why this toxicity has
American Journal of Kidney Diseases, Vol 55, No 2 (February), 2010: pp xxxv-xxxvii
xxxvii
been underappreciated in our patients. Use of bowel preparation with compounds containing oral sodium phosphate should be avoided in patients with chronic kidney disease and possibly also in the general population.9 Phosphatecontaining enemas have been recognized in the development of de novo nephrocalcinosis, in addition to acute kidney injury.6-8 Current recommendations are to avoid oral sodium phosphate–containing preparations in patients with known underlying kidney disease, aged ⬎65 years, or treated using diuretics, angiotensin-converting enzyme inhibitors, or angiotensin receptor blockers.1,2,8 Alternative bowel preparations containing magnesium citrate bear a risk of severe and even fatal hypermagnesemia in patients with kidney disease because the major excretion route of magnesium is through the kidney.1,2 The safest option in dialysis patients may be low-volume polyethylene glycol, a nonabsorbable compound.1,2,8 Severe side effects are rare and include pulmonary aspiration, Mallory-Weiss tear, pancreatitis or colitis, and exacerbation of chronic heart failure. Severe and even lethal dysnatremia have been reported in patients with chronic kidney disease stage 5 and those treated with diuretics.1 Furthermore, acute kidney injury caused by volume depletion has been reported with all the common preparations.1,2 Despite increasing warnings, many physicians and nurses may not be aware of groups of patients who are at high risk. Hence, this rather unusual problem should be
considered in the differential diagnosis of malaise occurring after bowel preparation, especially in patients with advanced chronic kidney disease.
FINAL DIAGNOSIS Severe hypocalcemia caused by intravascular calcium phosphate precipitation after sodium phosphate–containing bowel preparation.
ACKNOWLEDGEMENTS The authors thank Professor Giuseppe Paolo Segoloni for critical support and Dr P. Christie for careful language revision.
REFERENCES 1. Barkun A, Chiba N, Enns R, et al. Commonly used preparations for colonoscopy: efficacy, tolerability, and safety—a Canadian Association of Gastroenterology position paper. Can J Gastroenterol. 2006;20(11):699710. 2. Wexner SD, Beck DE, Baron TH, 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). Dis Colon Rectum. 2006;49(6):792-809. 3. Mendoza J, Legido J, Rubio S, Gisbert JP. Systematic review: the adverse effects of sodium phosphate enema. Aliment Pharmacol Ther. 2007;26(1):9-20. 4. Woo YM, Crail S, Curry G, Geddes CC. A life threatening complication after ingestion of sodium phosphate bowel preparation. BMJ. 2006; 333(7568):589-590.
5. Heher EC, Thier SO, Rennke H, Humphreys BD. Renal and metabolic effects associated with oral sodium phosphate bowel preparation. Clin J Am Soc Nephrol. 2008;3(5): 1494-1503. 6. 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(12): 2655-2663. 7. Markovitz 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(11):3389-3396. 8. Lien YH. Is bowel preparation before colonoscopy a risky business for the kidney? Nat Clin Pract Nephrol. 2008;4(11):606-614. CASE PROVIDED AND AUTHORED BY Giorgina Barbara Piccoli, MD,1 Federica Neve Vigotti, MD,2 Valentina Consiglio, MD,1 and Maria Chiara Deagostini, MD,1 1Nephrology Unit, SCDU Urology, University of San Luigi, Orbassano; and 2 Department of Internal Medicine, University of Turin, Turin, Italy. Address correspondence to Giorgina Barbara Piccoli, MD. Nephrology Unit of the University of San Luigi, Orbassano, Torino, Regione Gonzole, Orbassano, Torino, Italy. E-mail: [email protected] or [email protected] © 2010 by the National Kidney Foundation, Inc. doi:10.1053/j.ajkd.2009.09.012 SUPPORT: None. FINANCIAL DISCLOSURE: None.
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