In patients on maintenance dialysis with severe hyperparathyroidism, studies have demonstrated an association between parathyroid hormone (PTH) and anemia. However, it remains unclear whether there is an association between PTH and hemoglobin in patients with chronic kidney disease not on dialysis.
Domenico Russo, MD, Luigi Morrone, MD, and colleagues recently conducted a retrospective observational cohort analysis designed to assess the association between PTH and hemoglobin in CKD patients without severe secondary hyperparathyroidism. The researchers reported results of the study online in the Journal of Nephrology [doi:10.1007/s40620-014-0129-1].
The study utilized data on hospitalized patients and outpatients who had been referred to a single nephrology unit from 2002 to 2009. Inclusion criteria were >18 years of age, a minimum of 6 months of follow-up prior to the collection of data of interest, and two assays of PTH and hemoglobin performed by the same laboratory.
Exclusion criteria were stage 5 CKD requiring dialysis treatment; rapidly progressive glomerulonephritis; polycystic kidney disease; past or recent therapy with iron, erythropoietin stimulating agents, or vitamin D sterols; presence of bleeding and/or need for blood transfusion in the previous medical history; and current treatment with warfarin that may cause unapparent blood loss.
Of the 1093 screened patients, 114 were excluded; ineligibility factors were chronic lung disease (n=35), inability to give reliable personal history (n=30), severe liver disease (n=25), chronic therapy with nonsteroidal anti-inflammatory drugs (n=15), and hemorrhoids (n=9).
Data on 979 patients were analyzed. The primary renal diagnoses were hypertensive nephropathy (26%), glomerulonephritis (16%), diabetes (11%), ischemic nephropathy (6%), minor urinary abnormalities (4%), interstitial nephritis (4%), and CKD of unknown cause (34%).
The majority of the patients included in the analysis did not have severe derangement of PTH levels (upper normal limit, 75 pg/mL). Twenty-one percent of patients (n=207) had PTH >150 pg/mL and 0.3% (n=3) had PTH >1000 pg/mL.
Patients were stratified into quartiles based on PTH levels. Those in the highest quartile (≥133 pg/mL) were more likely to have reduced glomerular filtration rate (GFR), serum albumin concentration, total cholesterol, and low-density lipoprotein cholesterol. They were also more likely to have increased serum concentration of fibrinogen and homocysteine and 24-hour urinary protein excretion.
On univariate analysis, there was a significant association (P=.001) between serum hemoglobin and age (correlation coefficient [r]=-0.21), sex (r=-0.20), diabetes (r=-0.27), PTH (r=0.42), GFR (r=0.32), serum calcium (r=-0.47), serum phosphorus (r=0.60), GFR (r=0.32), transferrin saturation (r=0.19), C-reactive protein (r=-0.34), homocysteine (r=-0.26), serum albumin (r=0.49), and serum cholesterol (r=0.24). There was no association between hemoglobin and ferritin (r=0.10) or body mass index (r=0.04).
There was an inverse association between PTH and hemoglobin in patients as a whole (r=-0.459; P=.000), in patients with serum hemoglobin <12.0 g/dL (r=-0.176; P=.000), and in patients with serum hemoglobin >12.0 g/dL (r=-374; P=.01).
In multivariate lineal regression analysis in patients as a whole, there was collinearity of fibrinogen and homocysteine with CRP; as a result, the researcher excluded those factors from the final model.
In the final model, the only significant predictor of low hemoglobin was high PTH (unstandardized coefficients beta -2.12; P=.005). There was a significant interaction between log-PTH and GFR (P=.006). However, despite this interaction, PTH remained the single significant (P=.000) predictor of low hemoglobin.
Among patients as a whole, there was an inverse association between PTH and hemoglobin levels (P=.001). In logistic regression, the risk of having hemoglobin levels <100.0 mg/dL was more than doubled for each increase of quartile of PTH (hazards ratio, 2.79; 95% confidence interval [CI], 2.00-3.88; P=.001). PTH ≥122 pg/mL had a sensitivity of 67% and a specificity of 75% in predicting hemoglobin level <10.0 g/dL with area under the curve of 0.758 (95% CI, 0.73-0.78).
Regardless of the level of hemoglobin used for the definition of anemia, the majority of anemic patients were found in the highest quartile of PTH. The percentage of anemic patients was higher in patients with diabetes and in patients with GFR ≤60 mL/min/1.73 m2. At hemoglobin levels of <12.0, <11.0, and <10.0 g/dL, the percentages of anemic patients were 63, 37, and 21, respectively. At those same hemoglobin levels, the percentages of anemic patients with GFR ≤60 mL/min/1.73 m2 were 84, 43, and 31, respectively.
The researchers cited some limitations to the study. The design did not allow the establishment of causality, only an association between PTH and hemoglobin levels. The researchers were also unable to identify the exact mechanisms explaining the association between PTH and serum hemoglobin levels. Residual confounding could not be ruled out. In addition, the study did not assess the levels of vitamin D.
“This study shows a significant inverse association between PTH and hemoglobin levels across the whole spectrum of non-dialysis CKD and a doubled risk of having serum hemoglobin <10.0 mg/dL in the absence of severely deranged PTH concentration. These findings may have clinical relevance in ascertaining the cause of unexplained low hemoglobin in CKD patients,” the researchers said.
- This study was designed to evaluate the association between parathyroid hormone (PTH) and hemoglobin in patients with chronic kidney disease without severe secondary hyperparathyroidism.
- Among the study population as a whole, there was an inverse association observed between PTH and hemoglobin, an association that was also seen in patients with diabetes and glomerular filtration rate (GFR) ≤60 mL/min/1.73 m2.
- PTH was the single predictor of low hemoglobin in the patients as a whole, as well as in patients with diabetes and those with GFR ≤60 mL/min/1.73 m2.