The Severity of Secondary Hyperparathyroidism in Chronic Renal Insufficiency is GFR-Dependent, Race-Dependent, and Associated with Cardiovascular Disease

Abstract

Abstract. Secondary hyperparathyroidism (SHPT) is an important complication of end-stage renal disease. However, SHPT begins during earlier stages of chronic renal insufficiency (CRI), and little is known about risk factors for SHPT in this population. This study evaluated 218 patients in an ethnically diverse ambulatory nephrology practice at the University of California San Francisco during calendar years 1999 and 2000. Demographic data, comorbid diseases, medications, and laboratory parameters were collected, and independent correlates of intact parathyroid hormone (PTH) were identified by using multiple linear regression. The mean estimated GFR was 34 ml/min per 1.73 m 2 (10%-90% range, 13 to 61 ml/min per 1.73 m 2 ); PTH was inversely related to GFR (P Ͻ 0.0001). The adjusted mean PTH was higher among African Americans and lower among Asian/Pacific Islanders compared with white patients (233 versus 95 versus 139 pg/ml; P Ͻ 0.0001). Moreover, among the 196 patients with GFR Ͻ60 ml/min per 1.73 m 2 , the slope of GFR versus PTH was significantly steeper among African Americans than among white patients (10.6 versus 3.9 pg/ml per ml per min per 1.73 m 2 ; P ϭ 0.01). After adjusting for age and diabetes, PTH was associated with a history of myocardial infarction (OR, 1.6; 95% CI, 1.1 to 2.3 per unit natural log PTH) and congestive heart failure (OR, 2.0; 95% CI, 1.3 to 2.9 per unit natural log PTH) and not associated with other co-morbid conditions. These factors should be considered when screening and managing SHPT in CRI.Secondary hyperparathyroidism (SHPT) is a common, important, and treatable complication of chronic renal insufficiency (CRI) and end-stage renal disease (ESRD). Although its exact pathogenesis is unknown, hyperphosphatemia, (1,2), hypocalcemia (3), deficiency of 1,25-dihydroxyvitamin D 3 (4), decreased expression of calcium and vitamin D receptors (5,6), and parathyroid hormone (PTH) resistance (7) may each play a part. Longstanding SHPT results in osteitis fibrosa cystica (a high turnover bone lesion) and increases the risks for bone pain and fracture. Osteitis fibrosa cystica (OFC) may be present in 30 to 50% of CRI patients before the initiation of dialysis (8 -12).The prevalence and severity of SHPT have been shown to increase with declining renal function in CRI (13-17). Drug therapy with 1,25-dihydroxyvitamin D 3 and calcium salts have been reported to retard the progression of SHPT (18,19), improve BMD (20), and reverse abnormal bone histology (19,21,22).In the dialysis population, the degree of SHPT varies widely, although higher PTH has been associated with African American race, female gender, younger age, and lack of diabetes mellitus (23,24), along with higher serum phosphorus and lower serum calcium concentrations. We hypothesized that, in CRI, the degree of SHPT would be correlated inversely with GFR and the serum concentrations of calcium and bicarbonate and directly with the use of loop diuretics.

A Randomized, Double-Blind, Placebo-Controlled Trial of Niacinamide for Reduction of Phosphorus in Hemodialysis Patients

“…Hyperphosphatemia is linked to cardiovascular risk as well as bone disease (19,20), and the hyperphosphatemic milieu may promote vascular calcification through cellular changes in vascular smooth muscle cells (21). Previous open-label studies by Takahashi et al (10) and Sampathkumar et al (22) demonstrated that niacinamide lowers serum phosphorus levels in maintenance hemodialysis patients when traditional binding agents are withheld.…”

Mineral Metabolites and CKD Progression in African Americans

“…For example, at comparable levels of estimated GFR, African Americans manifest lower levels of 25-hydroxyvitamin D and higher levels of parathyroid hormone (PTH), serum phosphate, and fibroblast growth factor-23 (FGF23). [6][7][8] Abnormal levels of these individual mineral metabolites have been associated with greater risks of mortality and cardiovascular disease, [9][10][11][12][13][14][15][16] but analyses of risk of progression to ESRD yielded less consistent results, perhaps because of methodological limitations. [13][14][15][16][17][18][19][20] Foremost among these limitations is difficulty discerning whether abnormal levels of mineral metabolites are true risk factors for CKD progression, or instead, if they simply identify individuals with more advanced and rapidly progressive CKD.…”

Obesity Is Associated with Secondary Hyperparathyroidism in Men with Moderate and Severe Chronic Kidney Disease

“…Elevated parathyroid hormone (PTH) levels develop early in the course of CKD and worsen with advancing stages of this disease (6,(11)(12)(13)(14)(15)(16). Studies exploring SHPT in patients with CKD have characterized the physiologic factors governing the relationship between PTH level and other components of bone and mineral metabolism, such as calcium, phosphorus, and vitamin D, mostly in the context of alterations in these factors occurring as a function of the level of severity of CKD (11)(12)(13)(14)(15)(16).…”