Cigarette Smoking is Associated with Decreased Bone Gla-protein (BGP) Levels in Hemodialysis Patients.

BACKGROUND: Bone Gamma-carboxyglutamic acid (Gla)-protein (BGP or osteocalcin) is a vitamin K-dependent protein involved in the regulation of bone mineralization. Smoking is a risk factor for osteoporosis. METHODS: We carried out a secondary analysis of the Vitamin K Italian (VIKI) study to investigate the association between cigarette smoking and BGP levels in patients with end stage renal disease. Data were collected in 370 haemodialysis patients, 37% (136) smokers (or ex-smokers) and 63% (234) nonsmokers. Vascular calcifications and vertebral fractures (quantitative morphometry) were identified on spine radiographs. RESULTS: Smokers had significantly lower BGP levels (152 vs. 204 µg/L, p=0.003). Smokers had lower plasma phosphate levels (4.2 vs. 4.7 mg/dl, p<0.01). Lower BGP levels were associated with aortic calcification (p<0.001), iliac calcification (p=0.042) and vertebral fractures (p=0.023). In addition, the regression model showed that smoking is associated with a significant reduction of total BGP levels by about 18% (p=0.01). CONCLUSION: This is the first clinical study in a haemodialysis population, which identifies cigarette smoking as a potential factor that can lower BGP levels, a protective agent in bone and vascular health.

Carnitine-mediated improved response to erythropoietin involves induction of haem oxygenase-1: studies in humans and in an animal model.

BACKGROUND: Carnitine improves erythropoetin (EPO) response and anaemia in haemodialysis patients (HD); however, the mechanism(s) responsible remain unidentified. We have reported that carnitine induces haem oxygenase (HO)-1, which is an antioxidant and antiapoptotic that acts via pathways shared with EPO. Therefore carnitine's effect on these pathways may account for the improved EPO response. This study evaluates carnitine's effect on protein expression of HO-1 in unexplained EPO resistant HD. Carnitine's effect was assessed by HO-1 expression in patients and compared to its antiapoptotic effect via HO-1 induction in a rat model of carnitine-treated heart failure. METHODS: Unexplained EPO resistant HD mononuclear cell HO-1 and rat gastrocnemious muscle HO-1 and Bcl-2 protein expression were evaluated by western blot. RESULTS: HD's haemoglobin (Hb) and haematocrit (Ht) were not different before carnitine treatment: 8.8 +/- 0.4 mg/dl versus 8.98 +/- 0.13 and 30.20% +/- 0.84 versus 30.72 +/- 1.14, respectively. Carnitine increased HO-1, Hb and Ht compared with patients not treated with carnitine: 2.40 +/- 0.58 versus 1.49 +/- 0.41, P = 0.02; 11.22 +/- 0.54 versus 8.90 +/- 0.15, P < 0.0001; 32.72 +/- 1.77 versus 30.66 +/- 0.43, P = 0.035, respectively. Carnitine-treated HD's HO-1 significantly correlated with haemoglobin. HO-1 and Bcl-2 protein levels in untreated heart failure rat's gastrocnemious muscle were reduced when compared with controls: 3.41 +/- 0.49 versus 5.32 +/- 0.38 and 0.69 +/- 0.11 versus 1.65 +/- 0.37, respectively, but were higher in carnitine-treated heart failure rats: 4.8 +/- 0.32 versus 3.41 +/- 0.49, P < 0.0002 and 1.09 +/- 0.08 versus 0.69 +/- 0.11, P = 0.0007, respectively. CONCLUSIONS: These results are consistent with an involvement of HO-1 in carnitine's effect on erythropoiesis. The initial signals or effectors responsible for carnitine's effect remain to be identified.

Soluble transferrin receptors and reticulocyte hemoglobin concentration in the assessment of iron deficiency in hemodialysis patients.

BACKGROUND: Diagnosing iron deficiency in hemodialysis (HD) patients is crucial for correct anemia management. Hypochromic erythrocytes appear to be the best available marker, but they are often unavailable. Transferrin saturation (TSAT) and ferritin are also indicated as reference markers by guidelines. We evaluated the usefulness of soluble transferrin receptor (s-TfR) and reticulocyte hemoglobin concentration (CHr), which have been recently proposed as more sensitive functional iron deficiency indicators. METHODS: A single-center unselected cohort of 39 chronic HD patients underwent a cross-sectional determination of hemoglobin (Hb), hematocrit (Hct), CHr, transferrin, iron, TSAT, ferritin, folate, vitamin B12 and s-TfR. Twenty-nine patients (74.4%) were treated with subcutaneous erythropoietin (EPO) at a dose of 122 +/- 98 U/kg/week and 24 patients (61.5%) were treated with intravenous (i.v.) iron gluconate, 62.5 mg/week. RESULTS: Hb was 11.1 +/- 1.2 g/dL, Hct 34.4 +/- 3.7%, CHr 32.7 +/- 3.8 pg, transferrin 170 +/- 31 mg/dL, iron 60.2 +/- 25.9 mg/dL, TSAT 30 +/- 18%; ferritin 204 +/- 219 ng/mL, folate 4.2 +/- 1.0 mcg/L, vitamin B12 0.58 +/- 0.15 mcg/L, and s-TfR 1.94 +/- 0.83 mg/L. Both TSAT and s-TfR significantly correlated with CHr, but no relationship could be found between s-TfR and TSAT or between s-TfR and ferritin. Dividing the population into two groups based on iron repletion (ferritin >100 ng/mL and TSAT >20%) we found no differences for CHr levels and significantly lower levels of s-TfR in the replete group (s-TfR 1.71 +/- 0.70 vs. 2.29 +/- 0.90 mg/L; p=0.033). Analysis of 2x2 tables demonstrated that 44% of patients with TSAT >20% had elevated (>1.5 mg/L) s-TfR, indicating a possible functional iron deficiency, but covariance analysis showed that TSAT had a better correlation to CHr. CONCLUSIONS: No clear-cut advantages in the use of CHr content and s-TfR levels as single diagnostic tests could be demonstrated by this cross-sectional study. However, our results suggest that the combined use of TSAT <20% and s-TfR >1.5 mg/L (therefore, including all patients with low TSAT, but also patients with high s-TfR despite normal TSAT) could improve functional iron deficiency detection in dialysis patients suspected of having inflammatory conditions.

Are the baseline chances of survival comparable between the candidates for kidney transplantation who actually receive a graft and those who never get one?

BACKGROUND: The superiority of kidney transplantation over dialysis for patient survival often is assessed by comparing the survival rate of candidates who get a graft to that of those on the waiting list who do not. This study tries to ascertain if the two groups are comparable in terms of their chances of surviving. METHODS: Of the 187 non-diabetic patients who entered our waiting list during 1998 and 1999 for first cadaveric kidney transplants, 81 received a graft and 106 did not. We compared the two groups for factors which could affect survival and that were present at the moment of acceptance on the list. As one of those factors was the clinical score quantifying health status, as given by the transplant team and rated from 1 (high risk) to 4 (very good), we assessed its reliability by evaluating the survival of the patients we transplanted between 1988 and 1996, grouped according to that score. RESULTS: Transplanted patients had been immunized less frequently (2 vs 13%; P=0.02), had a lower dialytic age (16.9+/-2.1 vs 22.9+/-2.1 months; P<0.05), and better clinical scores (2.9+/-0.1 vs 2.6+/-0.1; P<0.05). The two groups did not differ in age, gender, or the presence of single specific diseases. Logistic regression analysis confirmed the results of univariate analysis. The clinical score was a very strong predictor of patient survival, as the survival of patients transplanted from 1988 to 1996 progressively improved with better scores (P<0.0001). CONCLUSIONS: Transplanted patients actually differ from non-transplanted candidates with respect to various factors potentially affecting survival. The difference is highly relevant clinically, yet it is not easily detected when considering mainly the presence or absence of specific diseases. A global quantitative clinical parameter based on a thorough medical evaluation is required to identify differences.