Silent Renal Stones in Primary Hyperparathyroidism
Silent Renal Stones in Primary Hyperparathyroidism
Our data confirmed the increased prevalence of silent nephrolithiasis among PHPT patients compared with controls, and in addition, our data shed light on some clinical features of this subset of PHPT patients. To date, only 1 study has been published of an investigation of silent nephrolithiasis in PHPT patients. Suh et al retrospectively reviewed renal US data for 271 patients with surgically proven PHPT and 500 unmatched controls. A total of 19 (7.0%) patients and 8 (1.6%) controls had asymptomatic renal stones, with a significant difference in prevalence between the 2 groups (P<.0001). Our study confirms an increased prevalence of silent nephrolithiasis in PHPT patients relative to controls but shows higher percentages in both groups (11.35% vs. 2.13%, respectively; P = .003). Our findings may partially depend on the difference between the 2 populations and on the methods used to collect data. In fact, the influence of ethnicity, lifestyle, and socio-economic and environmental factors in the development of nephrolithiasis has been widely demonstrated. Moreover, we reviewed US reports rather than US images, in contrast with Suh et al.
In both studies, the prevalence of silent nephrolithiasis was lower in the control group than that reported by Lorenz et al with CT scanning in the general population (9.7%). CT scanning is currently regarded as the gold standard for diagnosing renal stones, with sensitivity and specificity levels in symptomatic patients of 96 and 97%, respectively. The diagnostic performance of US is lower than CT, but without the burden of exposure to radiation associated with CT (1 to 1.5 mSv). Moreover, US is a low-cost procedure and is widely available. Both CT and US are used, depending on the availability of resources and choices of referring physicians in different centers. Though US could lead to an underestimation of silent nephrolithiasis, we believe that it is appropriate and proportionate to assess silent renal calculi in PHPT as a potentially harmful but not life-threatening clinical problem.
In our series, most PHPT patients and controls had small stones (≤5 mm), without a predominance of monoor bilateral disease. These data are in contrast with those of Suh et al, who reported a greater percentage of large stones (>5 mm in 57%) and unilateral stone disease in each PHPT patient. In our series, the characteristics usually linked to overt nephrolithiasis did not differ between cases and controls, except for higher serum calcium levels, thus confirming the role of PHPT as a risk factor for nephrolithiasis, even when asymptomatic. Age and sex differed between subjects affected by silent stones with and without PHPT. The younger age of PHPT patients is in line with the reported young age at diagnosis of PHPT as a risk factor of nephrolithiasis. As for gender, there were more females among PHPT patients with silent renal stones than in the control group, in contrast to the widely accepted involvement of male sex as a risk factor of symptomatic nephrolithiasis in patients with and without PHPT.
To the best of our knowledge, our study is the first to compare clinical characteristics of PHPT patients with and without silent renal stones. We did not observe a difference in bone disease. The relationship between stone and bone disease in PHPT is still debated. Bone damage was previously considered less marked among patients with renal stones. However, in agreement with our findings, more recent studies have reported no differences in bone disease among patients with and without renal stones. No differences in GFR were observed between the 2 groups, in agreement with data for the general population.
Our data suggest that silent nephrolithiasis could identify a subgroup of PHPT patients with a more severe disease than that observed in PHPT patients without renal stones. Biochemical markers in subjects affected by PHPT and silent renal calculi pointed to a more active disease (higher levels of total and ionized calcium and higher levels of PTH), in contrast with results reported in a recent clinical review. However, the review included studies that compared PHPT patients with overt renal stone disease and those without clinical signs of renal stones, not considering PHPT patients with asymptomatic renal stone disease. Moreover, PHPT patients with asymptomatic renal stones met surgical indication more frequently than PHPT without stones—even without considering nephrolithiasis— and 1 PHPT patient (6.25%) gained surgical indication due to asymptomatic nephrolithiasis.
Finally, we did not observe any differences in urinary calcium excretion between PHPT patients with and without silent renal stones. In the general population, no data are available on urinary calcium excretion as a risk factor for silent nephrolithiasis. However, our data are in line with the concept that urinary calcium excretion in PHPT is not a risk factor for stones in subjects who have never had a kidney stone.
Discussion
Our data confirmed the increased prevalence of silent nephrolithiasis among PHPT patients compared with controls, and in addition, our data shed light on some clinical features of this subset of PHPT patients. To date, only 1 study has been published of an investigation of silent nephrolithiasis in PHPT patients. Suh et al retrospectively reviewed renal US data for 271 patients with surgically proven PHPT and 500 unmatched controls. A total of 19 (7.0%) patients and 8 (1.6%) controls had asymptomatic renal stones, with a significant difference in prevalence between the 2 groups (P<.0001). Our study confirms an increased prevalence of silent nephrolithiasis in PHPT patients relative to controls but shows higher percentages in both groups (11.35% vs. 2.13%, respectively; P = .003). Our findings may partially depend on the difference between the 2 populations and on the methods used to collect data. In fact, the influence of ethnicity, lifestyle, and socio-economic and environmental factors in the development of nephrolithiasis has been widely demonstrated. Moreover, we reviewed US reports rather than US images, in contrast with Suh et al.
In both studies, the prevalence of silent nephrolithiasis was lower in the control group than that reported by Lorenz et al with CT scanning in the general population (9.7%). CT scanning is currently regarded as the gold standard for diagnosing renal stones, with sensitivity and specificity levels in symptomatic patients of 96 and 97%, respectively. The diagnostic performance of US is lower than CT, but without the burden of exposure to radiation associated with CT (1 to 1.5 mSv). Moreover, US is a low-cost procedure and is widely available. Both CT and US are used, depending on the availability of resources and choices of referring physicians in different centers. Though US could lead to an underestimation of silent nephrolithiasis, we believe that it is appropriate and proportionate to assess silent renal calculi in PHPT as a potentially harmful but not life-threatening clinical problem.
In our series, most PHPT patients and controls had small stones (≤5 mm), without a predominance of monoor bilateral disease. These data are in contrast with those of Suh et al, who reported a greater percentage of large stones (>5 mm in 57%) and unilateral stone disease in each PHPT patient. In our series, the characteristics usually linked to overt nephrolithiasis did not differ between cases and controls, except for higher serum calcium levels, thus confirming the role of PHPT as a risk factor for nephrolithiasis, even when asymptomatic. Age and sex differed between subjects affected by silent stones with and without PHPT. The younger age of PHPT patients is in line with the reported young age at diagnosis of PHPT as a risk factor of nephrolithiasis. As for gender, there were more females among PHPT patients with silent renal stones than in the control group, in contrast to the widely accepted involvement of male sex as a risk factor of symptomatic nephrolithiasis in patients with and without PHPT.
To the best of our knowledge, our study is the first to compare clinical characteristics of PHPT patients with and without silent renal stones. We did not observe a difference in bone disease. The relationship between stone and bone disease in PHPT is still debated. Bone damage was previously considered less marked among patients with renal stones. However, in agreement with our findings, more recent studies have reported no differences in bone disease among patients with and without renal stones. No differences in GFR were observed between the 2 groups, in agreement with data for the general population.
Our data suggest that silent nephrolithiasis could identify a subgroup of PHPT patients with a more severe disease than that observed in PHPT patients without renal stones. Biochemical markers in subjects affected by PHPT and silent renal calculi pointed to a more active disease (higher levels of total and ionized calcium and higher levels of PTH), in contrast with results reported in a recent clinical review. However, the review included studies that compared PHPT patients with overt renal stone disease and those without clinical signs of renal stones, not considering PHPT patients with asymptomatic renal stone disease. Moreover, PHPT patients with asymptomatic renal stones met surgical indication more frequently than PHPT without stones—even without considering nephrolithiasis— and 1 PHPT patient (6.25%) gained surgical indication due to asymptomatic nephrolithiasis.
Finally, we did not observe any differences in urinary calcium excretion between PHPT patients with and without silent renal stones. In the general population, no data are available on urinary calcium excretion as a risk factor for silent nephrolithiasis. However, our data are in line with the concept that urinary calcium excretion in PHPT is not a risk factor for stones in subjects who have never had a kidney stone.