Epidemiology of primary hypercalciuria: Distribution of values

According to Robertson et al. the distribution of values of urinary calcium excretion seems to be a continuous trait. However, calcium excretion rate values are skewed with a long tail of high values that represents a group of subjects with “ab­normal” calcium excretion that should be classified as “hyper- calciuric”. cialis professional 20 mg online pharmacy

Holmes et al. recognized in the distribution of urinary calci­um excretion of healthy subjects a group with definitely high calcium excretion above 0.18 mg/mg creatinine. In their opinion the distribution of calcium excretion in the remaining population was broad and did not appear to fit a normal distribution. On this basis they suggested that the non-hypercalciuric group could more appropriately divided into two groups: one with low excretion (< 0.1 mg/mg creatinine) and the other with an inter­mediate calcium excretion (0.1-0.18 mg/mg creatinine). The identification of these two subpopulations depended on the col­lection of three urinary specimens and the subdivision of the calcium excretion into smaller intervals. These results could in­dicate that a pair of co-dominant alleles exert a major influence on urinary calcium excretion.

Genetics

Two familial studies have attributed hypercalciuria to the pres­ence of an autosomal dominant gene. More recently mutations in the CLCN5 chloride channel gene and mutations affecting the calcium-sensing receptor have been identified in rare forms of hypercalciuria. Over-expression of the vitamin D receptor and deficiencies in renal tubule enzymes may be in­volved in idiopathic hypercalciuria.

Table II – Urinary excretion of calcium (mmol/24 hour) related to di-etary nutrients in white and black healthy subjects (HS) and renal stone formers (RSF).

Table

Black HS

White HS

Black RSF

White RSF

CaU

1.27±0.84

4.03±1.73

3.65±2.01

5.83±2.70

Cadiet

635±341

644±397

854±460

Nadiet

3809±1718

3183±1337

4437±2144

Protdiet

ND

99±28

113±39

Ethnicity

In a population-based study of South-African adults, black healthy controls showed a significantly lower excretion of calci­um than white healthy controls. The lower urinary calcium out­put in blacks probably reflects a lower calcium, sodium and protein intake (Table II). In an another study, after adjust­ment for counfounders including age and gender, 24 hour uri­nary calcium was significantly and independentely associated with ethnic origin: mean 24 hour urinary calcium (mmol) was 4.62±0.11 in whites, 3.33±0.12 in Asians and 3.16±0.13 in blacks (p<0.001). These differences may reflect ethnic differ­ences in renal tubular handling as they are present also after an overnight fast.

Table III – Age dependent 95th percentile of urinary Ca/Cr values for Caucasian, Afro-American and Thai children.

Thai

Caucasian

Afro-American

< 6 months

0.75

0.70

0.38

6-12 months

0.64

0.50

1-2 years

0.40

2-5 years

0.38

0.28

0.24

5-10 years

0.29

0.20

10-15 years

0.26

Worldwide variations of the urine calcium/creatinine ratio were reported also in children. Two recent studies were under­taken to set normal values of random non-fasting U Ca/Cr by age and race in the pediatric population of Hat-Yai (Thailand) and Kansas City (United States).

The 95th percentile for U Ca/Cr by age are shown in Table III. The data showed a strong inverse correlation between urinary Ca/Cr and age; urinary Ca/Cr of Caucasian and Thai children exceeded the corresponding value in African-Americans. Uri­nary Na/K ratio was correlated with urinary Ca/Cr in Thai chil­dren, whereas no significant correlation was observed in Cau­casian and Afro-American children.

It has been, therefore, concluded that the child’s age, ethnicity and geographic location should be taken into consideration when assessing U Ca/Cr ratio.