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 & Osteoporosis

Individuals with osteoporosis and nephrolithiasis represent a special patient population. Calcium stone formers are well described to have decreased BMD and an increased risk of fractures,[44,45] yet bone disease is frequently overlooked in the care of patients with nephrolithiasis. Hypercalciuric stone formers exhibit decreased bone formation rates,[46,47] but this alone is insufficient to explain the pathogenesis of decreased BMD, so genetic and environmental or dietary factors are presumed to be involved.[48] Given a fourfold increase in fracture risk in stone-forming patients over a period of 19 years,[44] it seems prudent to evaluate stone patients for osteoporosis with a dual energy X-ray absortiometry and to treat if a decrement in BMD is detected, particularly in the older population where the prevalence of osteoporosis is also high.

Treatment options that have been demonstrated to improve BMD in hypercalciuric subjects of various ages include thiazide diuretics, alkali supplementation, low-sodium diet and, potentially, bisphosphonates. Thiazides have been shown to effectively increase BMD in a wide variety of patient populations including pre- and post-menopausal females,[49,50] healthy older men,[51] as well as elderly men with hypercalciuria.[52] In the latter population, thiazides appear to act by decreasing bone resorption.[53] Supplementation with alkali, such as potassium citrate, has also been shown to be effective in reducing bone loss associated with both postmenopausal osteoporosis[54,55] and hypercalciuric stone disease.[56,57] The mechanism by which alkali supplementation improves BMD is likely through a combination of decreased requirement for bone buffering of acid loads, leading to decreased urinary calcium excretion,[58] as well as via a likely direct stimulatory effect on osteoblast function.[59]

Another often overlooked intervention to decrease hypercalciuria in osteoporosis and in hypercalciuric stone formers is a low-sodium diet. In a cross-sectional study of 85 calcium stone formers (men and premenopausal women), high sodium intake was highly associated with decreased BMD.[60] In another trial focusing on postmenopausal women without hypercalciuria, Teucher et al. studied 11 subjects each on one of four diets: high sodium/high calcium, high sodium/low calcium, low sodium/high calcium, and low sodium/low calcium, and determined the impact on calcium bone balance.[61] Even with high calcium intake (1284 mg/day), patients on a high-sodium diet (11.9 g/day) were in negative calcium balance. The only permutation where positive bone calcium balance was achieved was in the low-sodium/high-calcium group.Despite this, it appears that the impact of the high-salt diet can be mitigated. In an intriguing trial, Sellmeyer et al. placed 60 postmenopausal females on a low-sodium diet (87 mmol/day) for 3 weeks, prior to randomizing them to either a high-salt diet (225 mmol/day) with placebo or with potassium citrate (90 mmol/day) for 4 weeks.[62] Predictably, urine calcium increased by 42 mg/day in the high-salt plus placebo group; however, surprisingly, patients in the alkali group actually demonstrated decreased urinary calcium excretion by 8 mg/day (p < 0.008). Although a low-sodium diet has been shown to decrease hypercalciuria, it is important to note that very little is known about the effect of these maneuvers on BMD, bone mineral structure, fracture rates or stone recurrence. Even so, the recommendation for a low-sodium diet is not imprudent, particularly in the older population with a high burden of hypertension and heart disease. Lastly, though counterintuitive given that the primary abnormality in hypercalciuric bone disease is decreased turnover,[46,47] bisphosphonates have also been shown to improve BMD in hypercalciuric stone-forming patients.[63] In an interesting recent report, alendronate therapy coupled with indapamide outperformed either therapy alone in improving BMD in osteoporotic hypercalciuric females in a 1-year trial.[64] In this trial, indapamide alone was not effective in increasing BMD. However, it should be noted that caution should be exercised with bisphosphonate use in patients with CKD, particularly those with advanced CKD (creatinine clearance <30–35 ml/min/1.73 m2) for whom treatment with bisphosphonates is generally contraindicated. This is largely based on concerns regarding the presence of CKD-mineral bone disorder (CKD-MBD) as the underlying etiology of bone disease, rather than osteoporosis. In patients with CKD stage 4 or greater with a fragility fracture for whom osteoporosis therapy is entertained, experts suggest a bone biopsy with histomorphometry as a prerequisite to bisphosphonate initiation.[65]