Arginine, dimethylated arginine and homoarginine in relation to cardiovascular risk in patients with moderate chronic kidney disease.

OBJECTIVES: Arginine, asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA), arginine/ADMA ratio and homoarginine could potentially affect nitric oxide production and have been studied in relation to cardiovascular risk (CVR) in various clinical populations. Prospective studies on the CVR associated with arginine/ADMA ratio and homoarginine in patients with moderate chronic kidney disease (CKD) are still scarce. We have studied how arginine, homoarginine and dimethylated arginine can predict cardiovascular events in such a population. DESIGN AND METHODS: We measured plasma concentrations of arginine (P-arginine), ADMA (P-ADMA), SDMA (P-SDMA), homoarginine (P-homoarginine) and other covariates in 160 patients with predialytic CKD (mean age 57 years and mean eGFR 43 mL/min/1.73 m(2)) and followed them for 58 months in median. The risks of fatal and non-fatal cardiovascular events associated with the predictors were evaluated with multivariable Cox proportional hazard analysis. RESULTS: There were 31 cardiovascular events during the observation period. In a multivariable model adjusted for age, sex, previous cardiovascular disease, P-cystatin C and P-homoarginine, the hazard ratio (HR) associated with an increase in arginine/ADMA ratio by 10 was 0.83 (P=0.03). The HR of a 1 µmol/L increase in P-homoarginine in the same model was 1.78 (P=0.01). A statistically significant interaction between P-homoarginine and P-cystatin C was found in an extended multivariable model. P-SDMA was not associated with increased CVR after adjustment for basic covariates. CONCLUSION: This study demonstrates a negative association between arginine/ADMA ratio and CVR in CKD patients and a positive association between P-homoarginine and CVR. The latter is in contrast to what has been demonstrated by others.

Vitamin B6 in plasma - sample stability and the reference limits.

Quantitatively, the most important B6 vitamer in plasma is pyridoxal-5'-phosphate (p-PLP). The prerequisite for the use of p-PLP measurements in patients with poor nutritional status is an appropriate reference interval, together with knowledge of the stability of vitamin B6 in plasma samples. We used blood samples from healthy blood donors to derive the reference limits for p-PLP, and to examine its stability for 24 hours at room temperature and at 4-8°C. P-PLP was measured using high performance liquid chromatography (HPLC). The reference interval in adults was 23-223 nmol/L. P-PLP was stable for 24 h at room temperature and at 4-8°C, allowing time for normal specimen transport.

Arginine/asymmetric dimethylarginine ratio and cardiovascular risk factors in patients with predialytic chronic kidney disease.

OBJECTIVES: Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide synthase (NOS) that accumulates in patients with chronic kidney disease (CKD) and predicts cardiovascular outcome. Arginine is the substrate for NOS and a low arginine/ADMA ratio may lead to a reduced NO production and a worse prognosis. We have studied how other important CKD variables predict the arginine/ADMA ratio. DESIGN AND METHODS: The population is 160 predialytic CKD patients (median age 61 years). We used backward stepwise regression to identify the best predictors of p-arginine, p-ADMA and arginine/ADMA ratio. RESULTS: P-ADMA was predicted by estimated GFR (eGFR) (adjusted R(2)=0.17, p>0.00). Arginine/ADMA ratio was predicted by gender, eGFR, use of renin angiotensin aldosteron (RAAS) inhibitors, current smoking and use of platelet inhibitors (adjusted R(2)=0.18, p<0.00). CONCLUSIONS: Reduced eGFR is associated with reduced arginine/ADMA ratio. The use of RAAS inhibitors and male gender may be protective against a low arginine/ADMA ratio.

[A 40-year-old woman with anemia]. / En 40 år gammel kvinne med anemi.

BACKGROUND: Normally the body is unable to regulate its own iron content effectively by excretion. Urinary excretion of iron is about 10% of total daily loss. CASE PRESENTATION: A 40-year-old woman was admitted to hospital because of anaemia that turned out to be caused by iron deficiency. In spite of extensive investigations no cause of her iron deficiency was identified. The urine was then tested for iron and showed excessive urinary loss as the cause of her anaemia. To our knowledge, extensive urinary iron loss as the cause of iron deficiency has not been reported before.