A Spectrum: Nephrocalcinosis-Nephrolithiasis

Abstract

A Spectrum: Nephrocalcinosis-Nephrolithiasis NEPHROCALCINOSIS is a diagnosis frequently associ- ated with referral to a urologist for treatment of stone disease. In the current era computerized to- mography (CT) has enhanced our ability to detect renal calcifications with high resolution. Not surprisingly we are seeing more patients with nephrocalcinosis who are referred for management of urinary stone disease. Strictly speaking the term nephrocalcinosis re- fers to calcifications in the kidney parenchyma. It has been most commonly used to describe the pattern of parenchymal calcifications in primary hyperparathyroidism, distal renal tubular acidosis and medullary sponge kidneyxl This is distinct from nephrolithiasis, which identifies a mineralized cal- culus bathed and surrounded in urine in the col- lecting system. Nephrocalcinosis is a diagnosis made on a radiographic image.2 Therefore, radiolo- gists rather than urologists more frequently and routinely make this diagnosis. If nephrocalcinosis also includes calcifications in the renal papillae, it is more prevalent than we think. Randall originally described calcified plaques on the papillae in 19.6% of human autopsies with gross examination and without the aid of CT.3 He proposed that circumferential calcification of the basement membrane of the collecting ducts erodes with time through the papillary surface. We now know that these plaques are composed of interstitial deposits of hydroxyapatite and are integral to the process of stone formation for most calcium stone formers.4 In a way the Randall plaque stands at the intersection between nephrocalcinosis and nephrolithiasis. In this issue of The Journal Bhojani et al (page 1308) evaluated nephrocalcinosis in calcium stone formers who did not have a concurrent diagnosis of distal renal tubular acidosis, medullary sponge kidney or primary hyperparathyroidism.5 The goal was to characterize the burden and prevalence of nephrocalcinosis in a population “without sys- temic disease.”5 A total of 54 patients (67 renal units with calcium oxalate or calcium apatite) underwent a rigorous protocol to determine whether renal 0022-5347/15/1945-1188/0 THE JOURNAL OF UROLOGY® © 2015 by AMERICAN UROLOGICAL ASSOCIATION EDUCATION AND RESEARCH, INC. 1188 www.jurology.com calcifications were in the parenchyma (neph- rocalcinosis) or the collecting system (neph- rolithiasis). Noncontrast CT was performed after percutaneous nephrolithotomy. If there were resid- ual calcifications, a second percutaneous nephros- copy was performed to determine whether the calcifications were truly in the parenchyma or were residual stones in the collecting system. Bhojani et al report that the main finding of the study was that nephrocalcinosis was common in this cohort that did not have “systemic disease.”5 Nephrocalcinosis was present in 71%, 58% and 18% of hydroxyapatite, brushite and idiopathic calcium oxalate stone formers, respectively. The extent of nephrocalcinosis was highest in hydroxyapatite stone formers, followed by brushite and then idiopathic calcium oxalate stone formers. Comparison of 24-hour urine collections showed higher mean urinary cal- cium excretion and supersaturation of calcium phos- phate but no differences in other urinary parameters. This study raises several important issues. First, what is it that initiates nephrocalcinosis in the first place? If the etiology were systemic, we would expect it to develop symmetrically. However, quite often nephrocalcinosis occurs unilaterally and even focally.6 One possible explanation lies in a potential mechanism involving differential renal and seg- mental perfusion combined with vascular injury to the renal papillary circulation.7 The microvascula- ture of the papilla comprises the smallest vessels in a hypoxic and hyperosmolar environment, where turbulent tubular flow occurs at or near the tip of the papilla. Repair of the damage results in an atherosclerotic—like calcification process, which grows into the interstitium and eventually becomes detectable on imaging. Other theories implicate deposition of hydroxyapatite at the thin loops of Henle, overgrowth of deposits extending from the ducts of Bellini and interstitial fibrosis with crystal deposition in the inner medullary collecting ducts.4 Because we frequently see the 2 conditions in com- bination, a better understanding of the etiology of nephrocalcinosis would help us understand the etiology of urinary stone disease. http://dx.doi.org/10.1016/j.juro.2015.08.018 Vol. 194, 1188-1189, November 2015 Printed in U.S.A.