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.

Statins are widely used to decrease cholesterol and improve morbidity and mortality associated with coronary artery disease. Myopathy constitutes a rare but potentially life-threatening adverse reaction, which is related to plasma HMG-CoA reductase inhibitory activity. Therefore, the incidence of rhabdomyolysis increases dramatically when statins are co-administered with drugs that inhibit their hepatic transformation, such as cyclosporine or azoles. We present a case of severe rhabdomyolysis and acute renal failure induced by itraconazole in a heart transplant recipient chronically treated with cyclosporine and simvastatin. The literature with regard to the pathogenetic mechanisms and the clinical implications are reviewed. To avoid severe myopathy, cyclosporine levels should be monitored sooner than weekly intervals and statins should be discontinued or their dosage should be reduced, as long as azoles need to be prescribed in transplant recipients. Rhabdomyolysis and acute renal insufficiency should be promptly recognized and aggressively treated.

Although polycythemia has been considered a common adverse event in COPD, anemia is reported more often and has gained more importance than polycythemia over the last thirty years. Factors considered to be associated with the development of anemia in COPD have included: Aging and kidney dysfunction with erythropoietin deficiency and bone marrow suppression due to uremic toxins; heart failure (HF), which is often encountered in COPD and is accompanied by anemia in one third of the cases; Low-grade chronic inflammation, which can directly suppresses the bone marrow and diminish iron absorption and utilization via increased hepcidin levels; long-term oxygen therapy (LTOT), which ameliorates chronic hypoxia, and most important, RAS inhibitors, which are widely used for the co-morbidities associated with COPD (hypertension, HF, CKD, diabetes) and have previously been shown to lower hematocrit values or cause anemia in various clinical conditions. Introduction of LTOT in COPD and especially the established use of RAS inhibitors form the basis for the shift from polycythemia to anemia in COPD. Interestingly, when the SGLT2 inhibitors are introduced for cardiorenal protection in COPD, one could anticipate correction of anemia or even reemergence of polycythemia, since this new class of drugs can augment erythropoietin secretion and increase hematocrit values.