Attending Rounds A Woman with Recurrent Calcium Phosphate Kidney Stones David S. Goldfarb Summary Kidney stones composed predominantly (50% or more) of calcium phosphate constitute up to 10% of all stones and 15%–20% of calcium stones, 80% of which are composed of calcium oxalate. Calcium phosphate is a minor component of up to 30% of calcium oxalate stones as well. The cause of calcium phosphate stones is often obscure Nephrology Section, New York Harbor but most often related to a high urine pH. Some patients with calcium phosphate stones may have incomplete renal Department of tubular acidosis. Others have distal renal tubular acidosis characterized by hyperchloremic acidosis, hypocitraturia, Veterans Affairs and high urine pH. The use of carbonic anhydrase inhibitors such as acetazolamide, topiramate, and Healthcare System, zonisamide leads to a similar picture. Treatment options to specifically prevent calcium phosphate stone recur- New York, New York; Endourology Section, rence have not been tested in clinical trials. Increases in urine volume and restriction of sodium intake to limit Lenox Hill Hospital, calcium excretion are important. Citrate supplementation is probably effective, although the concomitant in- New York, New York; crease in urine pH may increase calcium phosphate supersaturation and partially offset the inhibition of crys- and Division of tallization resulting from the increased urine citrate excretion and the alkali-associated reduction in urine calcium Nephrology, New excretion. Thiazides lower urine calcium excretion and may help ensure the safety of citrate supplementation. York University Langone Medical Clin J Am Soc Nephrol 7: 1172–1178, 2012. doi: 10.2215/CJN.00560112 Center, New York, New York Introduction calcium was 9.4 mg/dl, potassium was 4.7 meq/L, Correspondence: Dr. A 22-year-old woman who had her first kidney stone HCO was 24 meq/L, 25-OH-vitamin D was 32 ng/ml, David S. Goldfarb, 3 423 East 23rd Street/ at age 15 years was seen in the Kidney Stone Prevention and intact parathyroid hormone (PTH) was 23 pg/ml. 111G, New York, NY Clinic because of recurrent calcium stones. In total, She performed 24-hour urine collections (Table 1). All 10010. Email: david. she has had five episodes of acute renal colic in 7 years. collections had similar creatinine excretion, indicating [email protected] Each episode was associated with more than one stone that the collections were comparable and consistent. causing at least temporary ureteral obstruction that At baseline, the results were notable for a very low required urologic intervention. She has had one unsuc- volume less than 1 L and normal calcium, oxalate, cessful shock-wave lithotripsy and five ureteroscopies. phosphate, and uric acid excretion, with relatively Stone composition has been variable: her first stone low sodium excretion and very low citrate excretion. was 80% calcium oxalate and 20% calcium phosphate; As expected in a calcium phosphate stone former, her 4 years later, 80% calcium phosphate and 20% calcium urine pH was relatively high. The calculated supersat- oxalate; 1 year later, a lab reported that one of her uration values indicated moderate risk of calcium oxa- stones was composed of 50% brushite, 20% hydroxy- late and calcium phosphate crystallization. apatite and 30% calcium oxalate; most recently a stone was reported to be 100% carbonate apatite. She had no Therapy history of urinary tract infections. She was prescribed potassium citrate 15 meq two She is physically active and does aerobic exercises. times per day and told to increase her fluid intake to at She has not been on any weight loss diets, and eats least 3 L (about 100 oz) per day. She was counseled to “everything”, including milk with cereal, and some continue to limit her sodium and oxalate intake and yogurt. She is not taking any medications but 1 year have two to three servings of dairy products with ago, had taken potassium citrate 15 meq two times meals per day, which she had been avoiding. A repeat per day for 5 months and then stopped it when she urine collection several months later (Table 1, Treat- concluded that it had not been effective. She has no ment 1) showed increased potassium, citrate, sodium, history of hypertension or diabetes. Both her father and calcium excretion, with a significant increase in and paternal grandfather had stones of uncertain com- urine volume and pH. Despite the increased calcium position. On physical exam, she had a seated blood excretion, the net effect was reduction in supersatura- pressure of 114/78 mmHg. She is 165 cm tall and tion of both calcium oxalate and calcium phosphate. weighs 74.8 kg, with body mass index of 27.5 kg/m2. Her increased sodium excretion was associated with an increase in calcium excretion and was probably Laboratory Evaluation more representative of her typical sodium intake. Al- Review of laboratory evaluations showed that serum though the resulting calciuria did not constitute hyper- creatinine was 0.8 mg/dl, uric acid was 5.2 mg/dl, calciuria and because she was highly motivated to 1172 Copyright © 2012 by the American Society of Nephrology www.cjasn.org Vol 7 July, 2012 Clin J Am Soc Nephrol 7: 1172–1178, July, 2012 Table 1. 24-Hour urine chemistries Supersaturation Supersaturation Uric Volume Sodium Potassium Calcium Oxalate Citrate Phosphorus Creatinine Calcium pH Calcium Acid (L) (meq) (meq) (mg) (mg) (mg) (mg) (mg) Oxalate Phosphate (mg) Normal 0.5–4.0 50–150 20–100 M,250; 20–40 8–10 M.450; 5.8–6.2 0.5–2.0 800–1200 M,800; M=18–24 values F,200 F.550 F,750 mg/kg; F=15–20 mg/kg Baseline 0.86 55 60 92 31 9.5 103 6.45 1.9 586 551 1379 Treatment 1 2.49 152 81 175 24 3.1 218 7.49 1.4 525 396 1412 Treatment 2 1.97 209 53 93 37 3.2 196 7.24 1.2 859 600 1352 Normal values apply to the general population but do not represent the optimal values to lower stone risk. Baseline represents the mean of two collections performed before the patient’s first clinic visit. M, male; F, female. for distal renal tubularDefective acidosis Renal (dRTA). Tubular Acidification A low serum phate to avoid inaccuracy. uncertainty, some labsliability simply report of basic thiscrystalline calcium determination phases, phos- (6). leading In tocium some recognition phosphate question stones of about reportedshow this different the that re- results different forwhich these laboratories is analyzing seencalcium the in phosphate same the stones cal- currentbonate not patient apatite (5). cansociated be Recent with present data urease-producing in organisms. patients However, with car- idiopathic growths on Randall the vast majoritystones of has calcium been oxalate highlightedimportance stones of by form calcium recent as phosphate workof over- as showing an up initiator that of to calcium calcium 30% oxalate. Calcium of phosphate calcium15% is a oxalate minor stones component of as calcium phosphate well constitute up (1). to 10% The of allOverview stones and of Calcium PhosphateCase Stones Discussion regarding restriction ofbaseline dietary value sodium. ofa 4.7 serum meq/L). potassium Sheand level was serum of again chemistry 3.9 counseled phosphate values meq/L were changed (lower unchanged, signi thanneither including her supersaturation ofsodium calcium excretion; oxalate urine norto volume calcium the was slightly indapamide,showed lower, despite a and reduction a in further urine1 calcium increase month excretion in attributable later urine one (Table time 1, each Treatmentavoid day 2). additional and That stones, repeated collection I the prescribed urine indapamide collection 2.5 mg the ammonium ruled out, particularlycomponent if it of exists stones combinedbrushite should is with not have struvite, known. urinarythe Patients with tract form carbonate infection of apatitehydroxyapatite. as hydroxyapatite a Why some and calcium othersis phosphate a take stones less take the stablehydrogen form crystal phosphate) structure of is that lesssame common, often crystal probably transforms form because into thatpresented it composes here. bones; The brushitein most (calcium kidney common stones, is and hydroxyapatite, these the forms occurredspeculative. in the patient defective urinary acidi otripsy (3,4). Lithotripsy hasbelow) been or hypothesized adverse effects to ofbeen lead extracorporeal attributed to shockwave to lith- treatmentin with prevalence. citrate If supplements true,data (see suggest the that reasons calcium are phosphatecrystals stones uncertain nucleate have and increased and have urothelium grow and becomes into exposed kidney toand urine; stones it calcium (2). oxalate growsphous Some until apatite that it forms ruptures in the through interstitium the of the papillary papillae, Calcium phosphate stone formers should be evaluated Kidney stones composed predominantly (50% or more) There are several forms of calcium phosphate that appear – 20% of calcium stones, 80% of which are composed of – Recurrent Calcium Phosphate Stones, Goldfarb 1173 magnesium ’ fi s plaque. Randall cation, but this effect is highly fi – cantly. Her blood pressure calcium phosphate crystal as- associated with infection, ’ splaqueisanamor- 1174 Clinical Journal of the American Society of Nephrology bicarbonate concentration, hyperchloremic metabolic aci- fasting and 24-hour urine pH compared with calcium dosis, and persistently alkaline urine pH of at least 5.5 stone formers who did not have incomplete dRTA. In an- is diagnostic. Hypokalemia is frequently present as well. other study, an inability to lower the urine pH below 5.25 Metabolic acidosis and hypokalemia both contribute to was present in calcium phosphate stone formers but not hypocitraturia. Hypercalciuria is frequent, and in the pres- calcium oxalate stone formers (11). Because appropriate ence of a consistently elevated urine pH, these urinary therapy addressing the specific urine chemistry abnormal- characteristics lead to calcium phosphate precipitation. ities will be the same whether incomplete RTA is diag- Nephrocalcinosis (calcification of the renal parenchyma) is nosed or not, ammoniuim chloride loading is rarely done often present and may lead to reduced GFR.