Evaluation and Management of Nephrolithiasis in the Aging Population With Chronic Kidney Disease

Anna L Zisman; Fredric L Coe; Elaine M Worcester


Aging Health. 2011;7(3):423-433. 

In This Article

Nephrolithiasis as a Complication of Therapy of Osteoporosis

In total 15% of women over the age of 50 years have osteoporosis, with another 35–50% affected by low bone mass.[26] Menopause is the most common cause of osteoporosis and is associated with increased urinary calcium excretion, presumably as a result of bone loss.[27,28] Physicians must be aware that women require increased calcium with age, as successful management of osteoporosis hinges on adequate calcium availability for new bone formation. Decreased intestinal absorption of calcium with age, coupled with increased bone turnover secondary to the decreased availability of estrogen with menopause, lead to the increased need for calcium intake. However, prescribers must also be aware that calcium supplementation in postmenopausal women has been associated with complications such as nephrolithiasis, though this remains a point of contention in the literature.[29] In the Women's Health Initiative (WHI) study, which randomized 36,282 women aged 50–79 years to receive either 1000 mg of elemental calcium along with 400 IU of vitamin D3 daily or a placebo, there was a 17% increased risk for development of new stone disease in the calcium/vitamin D group.[30] Patients in both arms of the study had a baseline calcium intake of approximately 1150 mg per day, so it is possible that the stone complications developed due to supratherapeutic amounts of calcium being administered, as the recommended guidelines for postmenopausal women advocate intake of 1000–1500 mg/day of elemental calcium. Notably, in this study although the BMD was slightly improved in the supplemented group, no decrement in fracture risk could be documented. In a study of 91,731 females enrolled in the Nurses' Health Study, Curhan et al. showed that in addition to the total amount of calcium ingested, sources of calcium were important as well.[31] Women with high dietary calcium intake were less likely to report a stone event, while those with supplemental calcium use were at increased risk. The protective effect of dietary calcium intake on stone risk has been documented in men also.[32] The presumed reason for the divergent effects of dietary and supplemental calcium is thought to be the reciprocal relationship of dietary calcium to oxalate absorption, also a risk factor for nephrolithiasis.[33] While dietary calcium, by definition, is likely to be ingested concurrently with oxalate, calcium supplements may be taken away from meal times, leading to spikes in urinary calcium excretion without delivering the benefit of decreased oxalate absorption and excretion. Given the concerns regarding the impact of calcium supplements, it seems prudent to recommend that women obtain their recommended calcium intake from dietary sources. If there is a history of nephrolithiasis, this recommendation is particularly pertinent.

Adequate calcium absorption is dependent on the availability of vitamin D to promote intestinal absorption of calcium. Importantly, despite earlier concerns regarding potential increases in urinary calcium excretion with nutritional vitamin D repletion,[34] a recent report documented no increased urinary calcium excretion in postmenopausal women with normal renal function receiving aggressive vitamin D repletion (50,000 IU ergocalciferol daily for 15 days) while consuming a similar diet to that eaten prior to repletion.[35] Vitamin D (25-hydroxyvitamin D) concentrations in the blood increased from a mean of 22 to 63 ng/ml, while total daily urinary calcium excretion remained stable (212 to 195 mg/day; not statistically significant). It must be emphasized that though the female subjects were consuming a diet with a calcium content on a par with the average consumption across the country,[36] these amounts (average 830 mg/day) are below the target of 1000–1500 mg/day for postmenopausal women. So, since the fractional absorption of calcium from the gut was shown to increase slightly (3%), it is plausible that higher levels of dietary calcium intake could promote hypercalciuria. Interestingly, in the four patients in the study who were hypercalciuric at baseline (mean daily calcium excretion of 377 mg/day), no exacerbation of hypercalciuria was detected with vitamin D supplementation (mean daily calcium excretion 312 mg/day, not statistically significant). Also of note, none of the subjects had a history of kidney stones. The effect of aggressive vitamin D repletion in stone formers is unknown.

Until the recent publication of the WHI trial, postmenopausal women were commonly treated with estrogen or estrogen and progesterone hormone replacement therapy (HRT) for symptomatic relief as well as prevention of complications such as osteoporosis.[37] To date, there are conflicting data on whether HRT is linked to lithogenic risk. In the Nurses' Health Study, natural menopause and HRT conferred no increased risk of incident stone disease;[38] however, a small increased risk was seen with surgical menopause. In another study, stone-forming postmenopausal women receiving HRT had decreased urinary calcium excretion and higher urinary citrate excretion (resulting in lower supersaturations for calcium salts) than their counterparts not receiving HRT.[39] In contrast, a recent post hoc data analysis from the WHI hormone therapy trials comparing incidence of nephrolithiasis in the hormone (estrogen or estrogen/progesterone) group versus placebo group showed an increased risk of stone disease in the hormone-treated group.[40] At this time the data are inconclusive to definitively determine the role of HRT in stone risk.

A newer treatment option for management of osteoporosis is teriparatide, a recombinant form of 1–34 PTH.[41] In contrast to the commonly used bisphosphonate medication class that seeks to reduce bone turnover, teriparatide is an anabolic agent that promotes bone turnover. Whether through this increased bone turnover, increased gastrointestinal absorption of calcium or increased renal tubular reabsorption of calcium, serum calcium tends to increase during treatment with teriparatide.[41] Teriparatide has been shown to increase urinary calcium excretion in postmenopausal females, though in the short 1-year follow-up no increased incidence of nephrolithiasis was noted.[41,42] Treatment courses with teriparatide are limited to 24 months second to concerns regarding an increased risk of osteosarcoma seen in rat studies.[43] Teriparatide studies have specifically excluded patients with a history of stone disease, so the impact of teriparatide treatment in stone formers is also unknown.