Continuum of therapy in progressive renal diseases (from predialysis to transplantation): analysis of a new organizational model.

In the aging of Western populations, decreased mortality is counterbalanced by an increase in morbidity, particularly involving chronic diseases such as most renal diseases. The price of the successful care of chronic conditions, such as cardiovascular diseases or diabetes, is a continuous increase in new dialysis patients. However, the increased survival of patients on chronic renal replacement therapies poses new challenges to nephrologists and calls for new models of care. Since its split from internal medicine, nephrology has seen a progressive trend toward super specialization and the differentiation into at least 3 major branches (nephrology, dialysis, and transplantation), following a path common to several other fields of internal medicine. The success in the care of chronic patients is owed not only to a careful technical prescription, but also to the ability to teach self-care and attain compliance; this requires good medical practice and a sound patient-physician relationship. In this context, the usual models of care may fail to provide adequate coordination and, despite valuable single elements, could end up as an orchestra without a conductor. We propose an integrated model of care oriented to the type of patient (tested in our area especially for diabetic patients): the patient is followed-up by the same team from the first signs of renal disease to eventual dialysis or transplantation. This model offers an interesting alternative both for patients, who usually seek continuity of care, and for nephrologists who prefer a holistic and integrated patient-physician approach.

Low-dose continuous iron therapy leads to a positive iron balance and decreased serum transferrin levels in chronic haemodialysis patients.

BACKGROUND: Iron balance is critical for adequate erythropoiesis, but its optimal therapeutic regimen remains to be defined. Continuous maintenance therapy with iron has been proposed for dialysis patients on recombinant human erythropoietin (rHuEpo) in the hope that the regimen is adequate and safe. METHODS: We determined serum ferritin, transferrin, transferrin saturation (TSAT), serum transferrin receptors, albumin and C-reactive protein (CRP) in a 3-year prospective study in 30 chronic haemodialysis patients on dialysis treatment for 132+/-111 months (18 males, 12 females; mean age 56+/-14 years). Beginning in the year 2000, they regularly received low-dose maintenance iron supplementation (i.v. iron gluconate 31.25 mg/week) for 12 months (Period 1 or first treatment phase), followed by a 6-month withdrawal (Period 2 or stop phase) and then by continuous maintenance iron therapy (i.v. iron gluconate 31.25 mg/week) for another 9 months (Period 3 or re-challenge phase). RESULTS: A significant increase in serum ferritin and TSAT was observed, with values exceeding 500 ng/ml and 50% in 10/30 (33%) and 7/30 (23%) of subjects, respectively, in Period 1, and in 11 and 5% in Period 3. A significant decrease in serum transferrin was documented during Period 1, followed by an increase in Period 2 and a decrease in Period 3. Serum albumin remained stable. Serum transferrin was always negatively correlated with ferritin (r = -0.41, P<0.001) and weakly correlated with serum transferrin receptors (r = 0.178, P<0.05), but was not correlated with serum albumin or CRP. Regression equations based on pre-treatment serum ferritin values were developed for predicting the value of serum ferritin at any time following the beginning of continuous iron supplementation. They fitted a linear relationship for males (y = 81 + 21.5 x time) and for females (y = 65 + 22 x time). Percentile charts for quantitative tracking of serum ferritin increases and decreases in patients have also been developed from values measured at different times. These charts show box-plot distributions of expected ferritin against time. CONCLUSIONS: Even continuous low-dose maintenance iron therapy, with only 31.25 mg weekly over 1 year, cannot prevent the risk of iron overload in patients with moderate anaemia. Furthermore, this treatment is responsible for decreases in serum transferrin, unrelated to changes in serum albumin, possibly of concern for hypo-transferrinaemia as an independent risk factor for iron toxicity.

Validation of serum ferritin values by magnetic susceptometry in predicting iron overload in dialysis patients.

BACKGROUND: Guidelines for treating anemia in dialysis patients accept, as high-end range of serum ferritin useful to optimize erythropoietin therapy, values high as 500 to 900 microg/L, on the hypothesis that ferritin might be not representative of iron overload. METHODS: A superconducting quantum interference device (SQUID) was used to make direct noninvasive magnetic measurements of nonheme hepatic iron content in 40 dialysis patients treated with intravenous iron, and liver iron content was compared with biochemical markers of iron status. RESULTS: Only 12/40 (30%) patients showed normal hepatic iron content (SQUID <400 microg/g), while 32.5% had mild (400 to 1000 microg/g) and 37.5% severe (>1000 microg/g) iron overload, although 28/40 patients (70%) had serum ferritin below 500 microg/L. Among many parameters, hepatic iron content was only correlated with ferritin (r= 0.324, P= 0.04). The receiver operating characteristic (ROC) analysis showed the best specificity/sensitivity ratio to identify iron overload for ferritin >340 microg/L (W = 0.716). Multivariate logistic regression analysis demonstrated that an increase in serum ferritin of 100 microg/L and female gender were independent variables associated with moderate to severe hepatic iron overload: OR 1.71 (95% CI 1.10 to 2.67) and OR 10.68 (95% CI 1.81 to 63.15), respectively. CONCLUSION: Hepatic iron overload is frequent in dialysis patients with ferritin below currently proposed high-end ranges, and the diagnostic power of ferritin in indicating true iron stores is better than presumed. Safety concerns should prompt a reevaluation of acceptable iron parameters, focusing on potential gender-specific differences, to avoid potentially harmful iron overload in a majority of dialysis patients, mainly females.