Serum 25-hydroxyvitamin D deficiency; a risk factor for chronic kidney disease in ambulatory indigent patients.

OBJECTIVE: To assess whether 25-hydroxyvitamin D (25[OH]D) deficiency is a risk factor for chronic kidney disease (CKD) in ambulatory indigent patients. METHODS: Data for all serum 25(OH)D concentrations measured during 2010 in our ambulatory nondialysis-dependent patients were analyzed along with CKD-related parameters. Patients were stratified into groups based on 25(OH)D levels of <10, 10 to 19, 20 to 29, and ≥30 ng/mL. CKD was defined by estimated glomerular filtration rate (eGFR; Chronic Kidney Disease-Epidemiology Collaboration [CKD-EPI] equation) and abnormal urine protein to creatinine ratios. CKD-associated parameters included serum parathyroid hormone (PTH), 1,25-dihydroxyvitamin D (1,25[OH]2D), alkaline phosphatase, albumin, corrected calcium, and total CO2 levels. RESULTS: A total of 2,811 patients had 25(OH)D levels measured. Patients with 25(OH)D levels <10 ng/mL had significantly increased relative risk (RR) of an eGFR <15 mL/min/1.73 m2 (RR, 4.0), an eGFR of 15 to 29 mL/min/1.73 m2 (RR, 2.6), urine protein to creatinine ratio >3.5 g/g (RR, 5.6), and serum PTH >100 pg/mL (RR, 2.8) compared to patients with a 25(OH)D level ≥30 ng/mL. Patients with 25(OH)D levels of 10 to19 ng/mL had significantly increased RR of a urine protein to creatinine ratio >3.5 g/g (RR, 4.8) and serum PTH >100 pg/mL (RR, 1.5) compared to patients with 25(OH)D levels ≥30 ng/mL. CONCLUSION: 25(OH)D deficiency (<10 ng/mL) was associated with reduced eGFR, nephrotic-range proteinuria, and increased PTH levels in our population of ambulatory urban indigent patients.

Vitamin D deficiency in urban indigent patients in Southern California.

OBJECTIVE: To determine the prevalence of 25-hydroxy (OH) vitamin D deficiency in ambulatory and hospitalized patients from a large urban county medical center in Southern California, and assess the effects of season, ethnicity, age, location of care, and comorbidities on prevalence. METHODS: Data for all serum 25(OH)-D2 and -D3 concentrations measured during 2010, along with associated demographic characteristics and comorbidity data, were analyzed. 25(OH) D concentrations were measured using liquid chromatography-tandem mass spectrometry. RESULTS: Of 210,695 patients, serum 25(OH) D concentrations were measured for 3,276 (1.6%), 78% of whom were Hispanic, 69% female, 14% hospitalized, and 86% ambulatory. Median patient age was 54 years. Prevalence of 25(OH) D <10 ng/mL was 6.5% overall, 5.5% in Hispanics, 6.7% in Asians, 15.5% in African Americans, and 8.9% in whites. Prevalence was significantly higher in African Americans than in Hispanics (relative risk (RR): 2.79), males (RR: 2.07), hospitalized patients (RR: 4.96), and winter (RR: 1.34). Prevalence of 25(OH) D <20 ng/mL was 35% overall, 34% in Hispanics, 32% in Asians, 49% in African Americans, and 33% in whites, and was significantly higher in African Americans than Hispanics (RR: 1.45), males (RR: 1.32), hospitalized patients (RR: 2.02), and younger patients (RR: 1.21, age ≤30; 1.16, age 31-50) versus those age 51 to 70 years, and in winter (RR: 1.21). CONCLUSION: Our study estimated the prevalence of 25(OH) D deficiency and identified at-risk patient groups in Southern California; 25(OH) D deficiency should be suspected, diagnosed, and adequately treated to improve the health status in at-risk urban indigent patient populations.

Investigation of hypercalcemia.

Hypercalcemia is a relatively common clinical finding. Primary hyperparathyroidism, hypercalcemia associated with malignancy and chronic renal failure (with calcium and vitamin D metabolite treatment or tertiary hyperparathyroidism) are the most common causes. Less common causes of hypercalcemia include vitamin D-related (granulomatous diseases, lymphoma, vitamin D intoxication), other endocrine (thyrotoxicosis), medications (milk-alkali, thiazides, lithium) and other causes (immobilization, familial hypocalciuric hypercalcemia). The clinical laboratory is central to the diagnosis and differential diagnosis of hypercalcemia. Its role has expanded from measuring routine chemistry tests such as total calcium, phosphate, creatinine and alkaline phosphate to include quantification of ionized calcium, parathyroid hormone (PTH) and vitamin D metabolites. In spite of this progress, the diagnosis and differential diagnosis of hypercalcemia can be significantly improved by: 1) increasing the availability and utilization of ionized calcium since total and corrected calcium are often inaccurate; 2) establishing more accurate reference intervals for parathyroid hormone by excluding individuals who are vitamin D insufficient or deficient; and 3) harmonizing intact PTH immunoassays.

Comparison of fresh frozen serum to traditional proficiency testing material in a College of American Pathologists survey for ferritin, folate, and vitamin B12.

CONTEXT: Comparison of different analytical methods in proficiency surveys may be affected by the artificial nature of the survey material. OBJECTIVE: To compare intermethod differences in proficiency survey results between 2 types of survey material, conventional proficiency testing material (PTM) and fresh frozen human serum (FFS), for 3 markers of anemia: ferritin, folate, and vitamin B12. DESIGN: Data were gathered from a 2003 survey event in the College of American Pathologists Ligand ("K") Series, in which the specimens to be tested by each participating laboratory included 1 vial of FFS and 2 vials of PTM with different analyte concentrations. The more than 1600 laboratories subscribing to the survey were not advised as to the nature of the specimens. MAIN OUTCOME MEASURES: The bias of each method relative to the median of method means for each analyte and each type of survey material, and the interlaboratory coefficient of variation for each method. RESULTS: For each of the 3 analytes, moderate to large method biases were observed. For ferritin, method biases correlated strongly between comparable PTM and FFS specimens (Spearman r = 0.863, P < .001), whereas virtually no correlation was found for folate (r = -0.224, P = .48), and a marginally significant correlation existed for B12 (r = 0.55, P = .049). CONCLUSIONS: With ferritin, proficiency survey performance of PTM is similar to that of FFS, implying that method biases relate mainly to calibration. With folate and to a lesser extent with B12, PTM and FFS exhibit different method biases, implying that the biases reflect analyte heterogeneity and/or matrix effects.

Comparison of fresh frozen serum to proficiency testing material in College of American Pathologists surveys: alpha-fetoprotein, carcinoembryonic antigen, human chorionic gonadotropin, and prostate-specific antigen.

CONTEXT: Most proficiency testing materials (PTM) contain an artificial matrix that may cause immunoassays to perform differently with this material than with clinical samples. We hypothesized that matrix effects would be reduced by using fresh frozen serum (FFS). OBJECTIVE: To compare the performance of an FFS pool to standard PTM for measurement of alpha-fetoprotein, carcinoembryonic antigen, human chorionic gonadotropin (hCG), and prostate-specific antigen (PSA). DESIGN: One FFS specimen and 4 different admixtures of PTM were distributed in the 2003 College of American Pathologists K/KN-A (for alpha-fetoprotein, carcinoembryonic antigen, hCG, and total and free PSA) and C-C (hCG only) Surveys. PARTICIPANTS: The number of laboratories that participated in the surveys varied from a low of 288 (free PSA, K/KN-A Survey) to a high of 2659 (hCG, C-C Survey). MAIN OUTCOME MEASURES: Method imprecision and method bias were compared between the FFS specimen and the standard PTM specimen with the closest value. Method imprecision was determined by calculating the coefficients of variation for each method and for all methods combined. Bias was defined as the proportional difference between peer-group mean and the median of all method means. RESULTS: The FFS specimen gave significantly higher imprecision than PTM for the analytes alpha-fetoprotein, carcinoembryonic antigen, total PSA, and free PSA. For hCG, no substantial imprecision differences were observed in both surveys. Bias was significantly greater for the alpha-fetoprotein, carcinoembryonic antigen, and total PSA assays and significantly lower for the hCG and free PSA assays when comparing the FFS with the PTM. CONCLUSIONS: Fresh frozen serum did not provide consistently lower imprecision or bias than standard PTM in a survey of commonly ordered tumor markers.

Limitations of direct estradiol and testosterone immunoassay kits.

Estradiol (E2) and testosterone (T) are biologically active hormones that serve as important diagnostic markers in serum of premenopausal and postmenopausal women and in men. These hormones are measured frequently by immunoassay in clinical laboratories and the test results are used in the diagnosis and treatment of patients. For measuring the hormones by immunoassay, most laboratories utilize commercially available reagents that are packaged in the form of a kit and are used either in an automated instrument or manually. However, both the diagnostic kit manufacturer and testing laboratory seldom thoroughly validate the assay methods generated with these kits. This deficiency may lead to unreliable test results that could affect clinical evaluation and treatment of patients. The purpose of the present study was to assess the reliability of immunoassays that quantify serum E2 and T levels with commercial diagnostic kits. The data generally show wide differences in the apparent levels of each hormone in a given sample obtained with kits from different manufacturers. This was especially true when measuring postmenopausal E2 and T levels. However, a purification step, which included organic solvent extraction, prior to radioimmunoassay (RIA) of E2 gave values that compared well with those obtained by conventional RIA (with preceding extraction/chromatographic steps). Our results point out the importance of more thoroughly validating assays performed with commercial immunoassay kits, especially with respect to sensitivity and specificity, prior to their use for measuring hormone levels in patient samples.

Immunoreactive parathyroid hormone levels in platyrrhini and catarrhini: A comparative analysis with three different assays.

Serum concentrations of the hormonal form of vitamin D3-1,25-dihydroxy-vitamin D3 [1,25-(OH)2-D3]-are elevated in many genera of platyrrhines when compared to catarrhines; this elevation is presumed to result from a decrease in the ability of the target cell receptor effectively to recognize 1,25-(OH)2-D3. The activity of the renal 25-hydroxyvitumin D3-1α-hydroxylase, the mammalian enzyme which synthesizes the majority of the circulating 1,25-(OH)2-D3, is accelerated by parathyroid hormone (PTH). In order to determine whether the elevated serum concentrations of 1,25-(OH)2-D3 in platyrrhines were the result of relative hyperparathyroidism, we measured serum levels of immunoreactive parathyroid hormone (iPTH) in normocalcemic platyrrhines, catarrhines, and human subjects with assays that recognize different domains of the human PTH molecule. Antisera directed against the biologically active, aminoterminus of PTH yielded comparable mean values for iPTH among three test groups. The mean concentration of iPTH as assessed by a "proximal" midregion assay was significantly reduced in platyrrhine serum when compared to either human or catarrhine serum. A "distal" midregion assay yielded a reduced mean value for iPTH in both platyrrhine and catarrhine serum when compared to human serum. These data suggest that 1) high circulating levels of 1,25-(OH)2-D3 in New World primates are not the result of hyperparathyroidism; and 2) structural homology between human and primate PTH diminishes progressively as one moves toward the carboxyterminus of the molecule and is lost more rapidly in the platyrrhine than in the catarrhine hormone.