Nephrocalcinosis in Calcium Stone Formers Who Do Not have Systemic Disease

Abstract

Introduction and Objective Nephrocalcinosis (NC) is commonly present in primary hyperparathyroidism (HPT), distal renal tubular acidosis (dRTA), and medullary sponge kidney disease (MSKD) but has not been studied in patients with CaP stones who do not have systemic disease. Methods We studied patients undergoing percutaneous nephrolithotomy (PNL) who had CaP or CaOx stones and did not have HPT, dRTA, or MSKD. On post-op (PO) day 1, all patients underwent a non-contrast CT scan. If there were no residual calcifications, the patient was categorized as not having NC. If there were residual calcifications, the patient underwent a secondary PNL. If the calcifications were found to be stones then the patient was categorized as not having NC. If the calcifications were not stones then the patient was categorized as having NC. Patients were grouped based on the type of stones they formed: hydroxyapatite (HASF), brushite (BRSF), and idiopathic calcium oxalate (ICSF). The extent of NC was quantified: 0=absence of NC and 3=extensive NC. Patients with residual calcifications on PO day 1 NCCT scan who did not undergo secondary PNL were excluded. The presence or absence of NC was correlated with metabolic studies. Results 67 patients were studied (14 HASF, 19 BRSF, and 34 ICSF). NC was present in 10/14 (71.4%), 11/19 (57.9%) and 6/34 (17.6%) for the HASF, BRSF, and ICSF groups respectively (Chi-square (X2): p=0.01) (Table 1). The extent of NC per group was 1.98, 1.32, and 0.18 for HASF, BRSF, and ICSF respectively (p=<0.001). The presence of NC was positively correlated with urine calcium excretion (287.39±112.49 v. 223.68±100.67, p=0.03). Conclusions Patients without systemic disease who form hydroxyapatite and brushite stones commonly have coexistent NC. NC can occur in calcium oxalate stone formers but the quantity and frequency of NC in this group is dramatically less.

Mice with a Brd4 Mutation Represent a New Model of Nephrocalcinosis

“…Our studies have established a mouse model for an autosomal dominant form of renal calcification, designated RCALC1, which is due to a heterogeneous germline Met149Thr mutation of Brd4 and has phenotypic similarities to those observed in patients with NC . Thus, RCALC1 mutant mice ( Brd4 +/M149T ) had the interstitial renal papillary calcium deposits that were similar to the papillary calcification that accompanies Randall's plaque, a lesion observed in 85% to 95% of humans with calcium phosphate (apatite) and calcium oxalate deposits . Thus, in humans, Randall's plaque has been reported to contain interstitial apatite deposits that act as a nidus for urothelial surface deposition of calcium oxalate, although calcium oxalate has been reported to overlie and adhere to Randall's plaque in only 50% of stone formers .…”

“…(4) Thus, RCALC1 mutant mice (Brd4 +/M149T ) had the interstitial renal papillary calcium deposits that were similar to the papillary calcification that accompanies Randall's plaque, a lesion observed in 85% to 95% of humans with calcium phosphate (apatite) and calcium oxalate deposits. (4,5,46) Thus, in humans, Randall's plaque has been reported to contain interstitial apatite deposits that act as a nidus for urothelial surface deposition of calcium oxalate, (4,45) although calcium oxalate has been reported to overlie and adhere to Randall's plaque in only 50% of stone formers. (47) In addition, previous studies of plaque formation in patients with recurrent stones have demonstrated that most stones grow by remaining attached to papillae and that subsequent crystal deposition involves the stone-tissue interface becoming overlaid with osteopontin and THP.…”

“…Renal calcification may occur in the kidney parenchyma (nephrocalcinosis [NC]) or the collecting system (nephrolithiasis [NL], ie, kidney stones) . NL and NC affect ∼10% of the adult Western population by the age of 70 years, although such distinctions may be difficult in patients who may develop both NL and NC, and it has been reported that >50% to 70% of patients with kidney stones will have NC . The renal calcification in NL and NC results from deposition of calcium oxalate and calcium phosphate, which has a multifactorial etiology that involves environmental and genetic causes and may also be associated with several endocrine and metabolic disorders, including primary hyperparathyroidism, hypercalciuria, renal tubular acidosis, cystinuria, low urinary volume, and hyperoxaluria .…”

“…(1)(2)(3)(4) NL and NC affect $10% of the adult Western population by the age of 70 years, (1)(2)(3) although such distinctions may be difficult in patients who may develop both NL and NC, and it has been reported that >50% to 70% of patients with kidney stones will have NC. (5) The renal calcification in NL and NC results from deposition of calcium oxalate and calcium phosphate, (4) which has a multifactorial etiology that involves environmental and genetic causes and may also be associated with several endocrine and metabolic disorders, including primary hyperparathyroidism, hypercalciuria, renal tubular acidosis, cystinuria, low urinary volume, and hyperoxaluria. (1,6) Hypercalciuria is the commonest metabolic abnormality associated with NL and NC; however, around 30% of individuals with kidney stones have been reported to have no obvious underlying metabolic defect (idiopathic NL).…”

A Spectrum: Nephrocalcinosis-Nephrolithiasis

“…5 The goal was to characterize the burden and prevalence of nephrocalcinosis in a population "without systemic disease." 5 A total of 54 patients (67 renal units with calcium oxalate or calcium apatite) underwent a rigorous protocol to determine whether renal calcifications were in the parenchyma (nephrocalcinosis) or the collecting system (nephrolithiasis).…”