Important medical discoveries frequently begin as simple observations. Examples include small reports of troglitazone-associated hepatotoxicity and pulmonary hypertension resulting from treatment with Fen-Phen, both ultimately leading to drug withdrawal. In 2004, we published a series of 5 patients with acute nephrocalcinosis following oral sodium phosphate (OSP) bowel cleansing (Hum Pathol 2004;35:675–684). We subsequently evaluated all renal biopsies processed at Columbia University Medical Center between 2000 and 2004 and found at least 16 additional cases of what we now more appropriately refer to as “acute phosphate nephropathy” (APhN) (J Am Soc Nephrol 2005;16:3389–3396). Dr. Koretz incorrectly states that Dr. Markowitz is a nephrologist. In fact, this study originates from a renal pathology laboratory, and 3 of the 4 authors are anatomic pathologists. Until recently, APhN was virtually unrecognized. Nephrology and renal pathology textbooks devote chapters to the entity of nephrocalcinosis. Based on the experience of one of the largest renal pathology referral centers in the United States, up to two thirds of nephrocalcinosis cases are caused by something that is not even mentioned in these chapters—the use of OSP bowel purgatives. Patients with APhN are typically older and present with acute renal failure, minimal proteinuria, bland urine sediment, and negative serologies. Based on this presentation, they may or may not be referred to a nephrologist. If they are referred, they are unlikely to undergo renal biopsy. Thus, the 21 cases in the numerator likely represents only a fraction of the cases of APhN occurring at the hospitals that send their renal biopsies to our laboratory, and it is a number that represents the experience of only a single center. Considering these facts, the most appropriate quote from the NY Times article is the one where Dr. Markowitz describes the results as “alarming.” Dr. Koretz quotes the NY Times article by saying that “Dr. Markowitz … does not think the risk is worth it and wants to make sure that every patient understands that the risk exists.” This is a direct quote from the article, not a direct quote from Dr. Markowitz. When choosing a bowel purgative for colonoscopy, the gastroenterologist should not adhere rigidly to a single preferred choice for use in all patients. The gastroenterologist should be aware that OSP is not meant for use in patients with kidney disease or certain electrolyte disorders, and that APhN is a potential complication. Risk factors that predispose to APhN include inadequate hydration, increased patient age, hypertension, concurrent use of ACE inhibitors, ARBs, diuretics, and NSAIDs, and possibly female gender. Until the denominator is known, it seems prudent to inform patients of the potential risk and advise them that safer alternatives exist. In the end, we agree with Dr. Koretz that: (1) we do not know the true incidence of APhN; (2) large prospective trials are needed; and (3) it is premature to establish public policy regarding this issue. Nonetheless, the finding of 21 cases on renal biopsy from a single center makes for quite a devilish numerator. The devil is in the denominatorGastroenterologyVol. 130Issue 7PreviewMarkowitz GS, Stokes MB, Radharkrishnan J, D’Agati VD (Departments of Pathology and Medicine, Division of Nephrology, Columbia College of Physicians and Surgeons, New York, New York). Acute phosphate nephropathy following oral sodium phosphate bowel purgative: an underrecognized cause of chronic renal failure. J Am Soc Nephrol 2005;16:3389–3396. Full-Text PDF