Haematological diseases articles within Nature Reviews Nephrology

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  • Review Article |

    Sickle cell syndromes are associated with kidney abnormalities and sickle cell nephropathy. Here, the authors discuss the pathological changes that occur in the kidney and their underlying mechanisms, as well as the detection, treatment and management of kidney disease in patients with sickle cell syndromes.

    • Kenneth I. Ataga
    • , Santosh L. Saraf
    •  & Vimal K. Derebail

  • News & Views |

    Erythropoiesis-stimulating agents (ESAs) are widely used to treat anaemia in patients with kidney disease. A potential alternative approach is to increase erythropoietin production using small-molecule inhibitors of prolyl hydroxylase domain (PHD) enzymes. Recent phase III trials of the PHD inhibitor roxadustat demonstrate similar efficacy and safety to ESAs.

    • Patrick H. Maxwell

  • Review Article |

    Intravascular haemolysis and the subsequent release of proinflammatory haemoglobin and haem into the circulation are characteristic of several diseases. This Review discusses the major pathophysiological mechanisms and consequences of intravascular haemolysis with a focus on the kidney, and highlights emerging therapeutic strategies to target haemolysis-related kidney injury.

    • Kristof Van Avondt
    • , Erfan Nur
    •  & Sacha Zeerleder

  • News & Views |

    The PIVOTAL trial shows that proactive intravenous (i.v.) iron administration reduces cardiovascular events and deaths, transfusions and erythropoiesis-stimulating agent doses and does not increase infections in patients on haemodialysis. These findings upend the warnings of guidelines and experts about the dangers of i.v. iron and prove that maintaining low iron stores is harmful.

    • Daniel W. Coyne

  • Review Article |

    Renal anaemia, resulting from impaired renal production of erythropoietin, is a common occurrence in patients with chronic kidney disease. Conventional erythropoiesis stimulating agents can be used to treat the condition, but small-molecule inhibitors of prolyl hydroxylase domain-containing (PHD) enzymes might provide a more efficient and tolerable approach to anaemia management. Here, Maxwell and Eckardt describe the rationale for targeting PHD enzymes to increase erythropoietin production. They also discuss other potential on-target consequences of HIF activation and possible off-target effects on enzymes that are structurally similar to PHD enzymes.

    • Patrick H. Maxwell
    •  & Kai-Uwe Eckardt

  • Review Article |

    Anaemia is a clinical hallmark of advanced kidney disease, characterized by insufficient erythropoiesis due to inadequate erythropoietin production in the kidney, inflammation and iron deficiency. Here, Mark Koury and Volker Haase discuss the hypoxic regulation of erythropoiesis and renal erythropoietin production, providing insight into the inter-relationships between erythropoietin synthesis, erythrocyte production, iron metabolism and inflammatory mediators. They also describe current clinical experience with pharmacologic activators of hypoxia-inducible factor signalling as an emerging approach to the treatment of renal anaemia.

    • Mark J. Koury
    •  & Volker H. Haase

  • Review Article |

    The complex vascular pathobiology of sickle cell disease leads to renal manifestations that affect almost all physiological process in the kidney. Renal complications are diverse, ranging from altered haemodynamics and impaired urinary concentrating ability to glomerulopathies, chronic kidney disease, acute kidney injury and renal medullary carcinoma. In this Review, Karl A. Nath and Robert P. Hebbel provide an overview of sickle cell disease and consider the underlying pathogenetic mechanisms of the renal manifestations.

    • Karl A. Nath
    •  & Robert P. Hebbel

  • News & Views |

    A new study has advanced our understanding of iron management in chronic kidney disease (CKD) by comparing oral iron to high-dose and low-dose intravenous ferric carboxymaltose (FCM) in patients with predialysis CKD. Intravenous FCM treatment to achieve a higher serum ferritin target improved patient haemoglobin levels and reduced initiation of other anaemia treatments.

    • Steven Fishbane
    •  & Azzour D. Hazzan

  • News & Views |

    Recently published data from four phase 3 safety and efficacy trials show that the synthetic peptide-based, erythropoietin mimetic, peginesatide, is noninferior to conventional erythropoiesis-stimulating agents in increasing haemoglobin levels in patients with chronic kidney disease (CKD). However, peginesatide therapy increased the risk of a combined cardiovascular end point in patients with CKD not on dialysis.

    • Kai-Uwe Eckardt

  • Review Article |

    Anaemia is common in patients with chronic kidney disease (CKD) and is associated with increased mortality and morbidity. This Review describes findings from randomized controlled trials and observational studies investigating how target haemoglobin level and erythropoiesis-stimulating agent (ESA) dose affect outcomes in patients with CKD and discusses whether high haemoglobin targets, high ESA dosage or ESA resistance are risk factors for adverse outcomes.

    • Walter H. Hörl

  • Opinion |

    Prospective cohort studies have shown that anaemia is an independent predictor of adverse outcomes in patients with chronic kidney disease. However, randomized controlled trials of the use of erythropoiesis-stimulating agents to correct moderate anaemia in this patient group have failed to show clinical benefit, and indicate that such treatment may even be harmful. Here, Patrick Parfrey discusses possible explanations for these seemingly contradictory results.

    • Patrick S. Parfrey

  • News & Views |

    The new KDIGO anaemia guidelines represent a bold, sensible, and patient-centred approach to anaemia management in patients with chronic kidney disease. Recommendations regarding haemoglobin targets, blood transfusions, and erythropoiesis-stimulating agent therapy are provided, and individualizing the management of anaemia is emphasized.

    • Ajay K. Singh

  • Review Article |

    Renal impairment is a common problem in patients with multiple myeloma. An early and rapid reduction in serum levels of free light chains (FLCs), achieved with the use of antimyeloma agents or direct removal of FLCs, has been shown to improve renal recovery in these patients. In this Review, the authors provide an update on new and current management approaches for reducing FLC levels in patients with myeloma-related acute kidney injury.

    • Colin A. Hutchison
    • , Joan Bladé
    •  & Christopher Winearls

  • Review Article |

    Anemia in children with chronic kidney disease (CKD) is associated with increased morbidity and mortality. In this Review, Atkinson and Furth outline the adverse effects associated with the anemia of CKD in children and discuss factors that contribute to the development of anemia in this population. Treatment strategies and the challenges of managing this condition in children with CKD are also discussed.

    • Meredith A. Atkinson
    •  & Susan L. Furth

  • Review Article |

    Iron deficiency is common in patients with chronic kidney disease (CKD) and administration of iron supplements could help maintain target levels of hemoglobin and reduce, or remove, the need for erythropoiesis-stimulating agents. In this Review, Besarab & Coyne discuss the efficacy, safety and practical recommendations for oral and intravenous therapy in the treatment of anemia in patients with CKD.

    • Anatole Besarab
    •  & Daniel W. Coyne

  • News & Views |

    Although anemia is a well-known risk factor for the development of cardiovascular disease in patients with chronic kidney disease, a number of prospective clinical trials have shown that treatment of anemia does not improve cardiovascular outcomes. The primary findings of TREAT, the largest trial to date investigating anemia treatment in patients with chronic kidney disease, have been eagerly awaited.

    • Andrzej Wiecek

  • News & Views |

    The findings of a secondary analysis of the CHOIR trial—which evaluated the beneficial and harmful effects of anemia correction with epoetin alfa in patients with chronic kidney disease and diabetes mellitus or heart failure—threaten to undermine the importance of anemia therapy in patients with chronic kidney disease.

    • Walter H. Hörl

  • Review Article |

    A wide range of erythropoiesis-stimulating agents to stimulate red blood cell production are currently in clinical use, but advances in our understanding of erythropoiesis have provided an ever-increasing array of potential therapeutic targets. Here, Robert Foley describes the desirable properties of erythropoiesis-stimulating agents and discusses various novel agents currently under assessment for the treatment of anemia in patients with chronic kidney disease. Such agents include proteins and peptides that activate erythropoietin receptors, non-protein agents, and strategies with targets other than erythropoietin receptors.

    • Robert N. Foley

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