Background: Anaemia is a common finding in diabetes, particularly in those patients with albuminuria or renal dysfunction and is associated with impaired erythropoietin (EPO) secretion. This review focuses on mechanisms involved in the regulation of erythropoiesis in diabetic patients in an effort to elucidate the competing effects of the renin angiotensin system (RAS) blockade and sodium-glucose cotransporter-2 (SGLT2) inhibitors on haemoglobin concentration and hematocrit values. Summary: The RAS shows significant activation in diabetic subjects. Angiotensin II, its active octapeptide, causes renal tubulointerstitial hypoxia, which stimulates hypoxia-inducible factors (HIF) and increases EPO secretion and erythropoiesis. As expected, drugs that inactivate RAS, such as angiotensin converting enzyme inhibitors or angiotensin receptor blockers (ACEi/ARB) are associated with a significant hematocrit-lowering effect and/or anaemia in various clinical conditions, including diabetes. Dual blockade by a combination of ACEi and ARB in diabetic patients achieves a better RAS inhibition, but at the same time a worse drop of haemoglobin concentration. Increased glucose reabsorption by SGLTs in diabetic subjects generates a high-glucose environment in renal tubulointerstitium, which may impair HIF-1, damage renal erythropoietin-producing cells (REPs) and decrease EPO secretion and erythropoiesis. SGLT2 inhibitors, which inhibit glucose reabsorption, may attenuate glucotoxicity in renal tubulointerstitium, allowing REPs to resume their function and increase EPO secretion. Indeed, EPO levels increase within a few weeks after initiation of therapy with all known SGLT2 inhibitors, followed by increased reticulocyte count and a gradual elevation of haemoglobin concentration and hematocrit level, which reach zenith values after 2-3 months. Key Messages: The competing effects of RAS blockade and SGLT2 inhibitors on erythropoiesis may have important clinical implications. The rise of hematocrit values by SGLT2 inhibitors given on top of RAS blockade in recent outcome trials may significantly contribute to the cardiorenal protection attained. The relative contribution of each system to erythropoiesis and outcome remains to be revealed in future studies.

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Aims: Therapy with either angiotensin converting enzyme inhibitors and angiotensin receptor blockers (ACEI/ARB) or thiazolidinediones (TZD) is associated with dose-dependent decrements in hematocrit and hemoglobin levels. We aimed to investigate the impact of the coadministration of TZD and ACEI/ARB on hematocrit and hemoglobin values in uncomplicated patients with type 2 diabetes mellitus and normal serum creatinine. Methods: Data from patients with type 2 diabetes currently followed, were reviewed and patients treated with ACEI/ARB and/or TZD were identified. For the purpose of this study the following 4 groups of 30 stable non-anemic diabetic patients each matched for age, gender, and BMI were formed. Group ACEI/ARB included patients on ACEI/ARB without TZD, group TZD included patients on TZD and antihypertensive agents other than ACEI/ARB, group ACEI/ARB/TZD consisted of patients on combined therapy with ACEI/ARB and TZD and the control group C included patients never exposed to ACEI/ARB or TZD. Clinical and laboratory data were collected prior to initiation of treatment and after 6 months. Results: Neither hematocrit nor hemoglobin showed any significant change from baseline at the end of the study in group C. In both group ACEI/ARB and group TZD a small, but statistically significant reduction in hematocrit (~?1% point) and hemoglobin levels (~?0.3 g/dl) was seen. A greater statistically and clinically important reduction in hematocrit (~?3% points) and hemoglobin (~?1?g/dl) levels was observed in group ACEI/ARB/TZD. Furthermore, incident anemia at the end reached 7% in group TZD and 23% in group ACEI/ARB/TZD. Conclusions: Coadministration of RAS inhibitors and PPAR-? agonists should be considered in the differential diagnosis of hematocrit lowering and anemia in uncomplicated type 2 diabetic patients with normal serum creatinine. Further studies are required to clarify the mechanism(s), the cardiovascular consequences and the cost utility of anemia workup in such patients.

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Sevelamer hydrochloride (HCl) contains multiple amines that may cause a significant dietary acid load. To evaluate the impact of sevelamer on arterial blood gases, we followed two groups of stable hemodialysis patients for 24 months. The Sevelamer Group (n = 7) did not achieve the National Kidney Foundation Kidney Disease Outcomes Quality Initiative (K/DOQI) goals for phosporus and Ca x P product and was switched from a calcium-based to sevelamer-based regimen. The Calcium Group (n = 7) achieved those goals and remained on calcium salts. Following sevelamer administration, a deterioration of chronic metabolic acidosis was revealed, which lasted throughout the study. Sevelamer therapy was associated with reduced cholesterol levels, improved serum phosphate, and Ca x P product, which facilitated the management of secondary hyperparathyroidism. No significant changes in acid-base status or other parameter tested were found in the Control Group. In conclusion, sevelamer intake caused small but persistent acid-base disturbances, which did not neutralize sevelamer's beneficial effects on mineral and lipid metabolism.

Introduction. The aim of the study was to examine the impact of adherence to a Mediterranean-style diet (MD) on left ventricular hypertrophy (LVH) and cardiac geometry in chronic kidney disease patients on dialysis (CKD-5D), given the high prevalence of cardiovascular morbidity in this population. Methods. n = 127 (77 men and 50 women) CKD-5D patients (69 on hemodialysis and 58 on peritoneal dialysis) with a mean age of 62 ± 15 years were studied. An MD adherence score (MDS) (range 0–55, 55 representing maximal adherence) was estimated with a validated method. Echocardiographic LVH was defined by LV mass index (LVMI) > 95 g/m2 in women and > 115 g/m2 in men. Based on LVMI and relative wall thickness (RWT), four LV geometric patterns were defined: normal (normal LVMI and RWT), concentric remodeling (normal LVMI and increased RWT > 0.42), eccentric LVH (increased LVMI and normal RWT), and concentric LVH (increased LVMI and RWT). Results. Patients with LVH (n = 81) as compared to patients with no LVH (n = 46) were older in age (66 ± 13 vs. 55 ± 16 years; p < 0.001) had lower MDS (24 ± 2.7 vs. 25 ± 4.3; p < 0.05) and higher malnutrition-inflammation score (5.0 ± 2.7 vs. 3.9 ± 1.9; p < 0.05), body mass index (27.5 ± 4.9 vs. 24.1 ± 3.5 kg/m2; p < 0.001), prevalence of diabetes (79% vs. 20%; p < 0.05), coronary artery disease (78% vs. 20%; p < 0.05) and peripheral vascular disease (78% vs. 20%; p < 0.01). In a multivariate logistic regression analysis adjusted for all factors mentioned above, each 1-point greater MDS was associated with 18% lower odds of having LVH (OR = 0.82, 95% CI: 0.69–0.98; p < 0.05). MDS was inversely related to LVMI (r = −0.273; p = 0.02), and in a multiple linear regression model (where LVMI was analyzed as a continuous variable), MDS emerged as a significant (Β = −2.217; p < 0.01) independent predictor of LVH. Considering LV geometry, there was a progressive decrease in MDS from the normal group (25.0 ± 3.7) to concentric remodeling (25.8 ± 3.0), eccentric (24.0 ± 2.8), and then concentric (23.6 ± 2.7) group (p < 0.05 for the trend). Conclusions. The greater adherence to an MD is associated with lesser LVH, an important cardiovascular disease risk factor; MD preserves normal cardiac geometry and may confer protection against future cardiac dysfunction in dialysis patients.

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Background/Aims: Peritoneal dialysis solutions (PDS), new and conventional, do not yet have a clinical biocompatibility profile. We aimed at a comparative laboratory profile based on the effect of PDS on peripheral blood mononuclear cell (PBMC) cytokine release. Method: PBMCs from 19 healthy volunteers were incubated at a concentration of 10⁶/ml in fresh PDS and control medium (RPMI 1640), and stimulated or not with 10μg/ml Escherichia coli lipopolysaccharide. The tested PDS were glucose/lactate 1.5 and 4.25%, glucose/pyruvate 1.0 and 4.0%, icodextrin and amino acid solutions. The initial incubation in culture flasks for 15 min was followed by 1:1 dilution with RPMI and by additional incubation for 22 h as a ‘recovery period’. At the end, the supernatants were tested for cytokines IL-6 and TNFα by ELISA. Results: The hypertonic glucose solutions, irrespective of the buffer, had the most adverse effect on PBMC cytokine release. The icodextrin and amino acid solutions seemed close to the isotonic glucose PDS. The substitution of pyruvate for lactate buffer seemed to offer an advantage only for the hypertonic glucose-based solutions. Conclusions: Icodextrin and amino acid solutions seem to offer an advantage only compared to hypertonic glucose PDS.