Review Articles

  • Review Article |

    This short article is an introduction to the histology of damage to transplanted kidneys caused by the immunosuppressants tacrolimus and ciclosporin. Aimed at trainee pathologists and nephrologists wishing to enhance their understanding of the histological basis of the diseases they manage, this beautifully illustrated paper describes the key features, differential diagnosis and clinical implications of nephrotoxicity induced by calcineurin inhibitors.

    • Peter Liptak
    •  & Bela Ivanyi
  • Review Article |

    The existence of several different definitions of acute renal failure makes it difficult to determine the true epidemiological characteristics of this condition. Nonetheless, there have been notable variations in its epidemiology during the past few decades. Norbert Lameire and colleagues present an overview of these changes and their causative factors, including geography, patient setting and ageing populations.

    • Norbert Lameire
    • , Wim Van Biesen
    •  & Raymond Vanholder
  • Review Article |

    This Review focuses on the role of drugs such as cinacalcet in the treatment of uremic secondary hyperparathyroidism. The authors present evidence to support their assertion that cinacalcet plus higher doses of calcium-based oral phosphate binders is a safe and efficacious alternative to currently recommended regimens. Other indications for calcimimetic drugs, such as predialysis secondary hyperparathyroidism and hypercalcemic hyperparathyroidism following kidney transplantation, are also discussed.

    • Irina Shahapuni
    • , Matthieu Monge
    • , Roxana Oprisiu
    • , Hakim Mazouz
    • , Pierre-François Westeel
    • , Philippe Morinière
    • , Ziad Massy
    • , Gabriel Choukroun
    •  & Albert Fournier
  • Review Article |

    Since the latest K/DOQI guidelines were formulated, new data on drugs such as lanthanum carbonate and calcimimetics have become available. In light of this new information, Matthieu Monge and colleagues believe that current practice can be updated. In this Review, the authors outline their recommendations regarding drug selection, dosing regimens, and monitoring of hyperparathyroidism in dialysis patients.

    • Matthieu Monge
    • , Irina Shahapuni
    • , Roxana Oprisiu
    • , Najeh El Esper
    • , Philippe Morinière
    • , Ziad Massy
    • , Gabriel Choukroun
    •  & Albert Fournier
  • Review Article |

    In the third article of our series on secondary hyperparathyroidism in renal disease, Joachim Ix and colleagues comment on the recommendations put forth by Matthieu Monge et al. on page 326. Ix et al. contend that the changes to current practice proposed by Monge and colleagues are supported by insufficient evidence and should be revisited only when more data from high-quality trials become available.

    • Joachim H Ix
    • , L Darryl Quarles
    •  & Glenn M Chertow
  • Review Article |

    Existing treatments for amyloidosis aim to perturb production of pathogenic fibrils by limiting the supply of precursor proteins. Recent insights into processes involved in fibrillogenesis have opened new therapeutic avenues. In this short Review, the authors provide an update on the development of drugs to stabilize precursor proteins, promote clearance of amyloid or enhance regression of fibrils.

    • Julian D Gillmore
    •  & Philip N Hawkins
  • Review Article |

    This is a practical guide to viruses that perturb renal function, with an emphasis on those that affect glomeruli. Touching on the mechanisms that underlie viral nephropathy before focusing on clinical presentation, diagnosis and treatment, this article covers HIV, hepatitis B and C, parvovirus B19, hantavirus and the coronavirus that causes severe acute respiratory syndrome.

    • Andrew SH Lai
    •  & Kar Neng Lai
  • Review Article |

    The slit diaphragm spans podocyte foot processes, effacement of which is a feature common to all glomerular diseases. Recent work in nephrotic syndrome and focal segmental glomerulosclerosis has led to identification of mutations in several gene products that function at the slit diaphragm, such as nephrin, Neph1 and podocin. Johnstone and Holzman predict that these molecular insights will facilitate disease classification and optimization of therapy.

    • Duncan B Johnstone
    •  & Lawrence B Holzman
  • Review Article |

    Introduced in the late 1990s for non-Hodgkin's lymphoma, the anti-CD20 monoclonal antibody rituximab has had anecdotal success in several renal settings. Here, Salama and Pusey compile and evaluate the data supporting use of rituximab to manage post-transplantation lymphoproliferative disorder, graft rejection, and ABO- and HLA-incompatibility. The drug's potential utility in autoimmune conditions that affect the kidney, including focal segmental glomerulosclerosis and systemic lupus erythematosus, is also assessed.

    • Alan D Salama
    •  & Charles D Pusey
  • Review Article |

    Production of nitric oxide (NO) is reduced in chronic kidney disease and end-stage renal disease. Data support the conclusion that low NO levels, probably a function of perturbed endothelial synthesis, contribute to progressive kidney dysfunction. Chris Baylis outlines the mechanisms by which NO deficiency can develop in renal disease states, and discusses the potential for developing new treatments by manipulating NO biosynthetic pathways.

    • Chris Baylis
  • Review Article |

    Primary aldosteronism is found in about one-tenth of people with hypertension. Following diagnosis, effective treatment is based on identification of the specific subtype of this condition. Of the various causes underlying primary aldosteronism, bilateral idiopathic hyperplasia and aldosterone-producing adenoma are the most common. In this Review, the authors describe the optimal approaches to detection and management of subtypes of aldosterone hypersecretion.

    • Cecilia Mattsson
    •  & William F Young Jr
  • Review Article |

    After outlining the mechanisms of phosphorous homeostasis—in which the kidney has a central role—Amanzadeh and Reilly explain how perturbation of this regulatory system can lead to hypophosphatemia. The authors then critically evaluate the clinical sequelae of this condition, and round out their review with advice on managing hypophosphatemia of varying severity in different patient populations.

    • Jamshid Amanzadeh
    •  & Robert F Reilly Jr
  • Review Article |

    The author comprehensively reviews novel data on the molecular mechanisms that underlie progression of kidney damage secondary to urinary tract obstruction. Encompassing inflammation, tubular cell apoptosis and interstitial fibrosis, the potential for the new findings to give rise to predictive biomarkers and molecular therapies for this leading cause of pediatric chronic renal failure is explored.

    • Robert L Chevalier
  • Review Article |

    In critical care units, acute renal failure is less common in premature infants than in more mature individuals. Recent studies indicate a role for the heat shock response in this clinical phenomenon. Distilled here, these new data could lead to strategies for identifying patients at greatest risk of developing acute renal failure.

    • Michael Riordan
    • , Rajasree Sreedharan
    • , Michael Kashgarian
    •  & Norman J Siegel
  • Review Article |

    Currently, there is little that can be done to treat fibrosis of the kidney. Recent advances in renal pathophysiology are yielding insight into the derivation of fibroblasts and their role in this inflammatory disease. Eric Neilson reviews this progress, catalogs the new targets for intervention that have been identified, and asserts that the future for clinical management of fibrosis is bright.

    • Eric G Neilson
  • Review Article |

    Optimal management of anemia in patients with end-stage renal disease on hemodialysis usually demands intravenous iron supplementation. Michael et al. review the current safety data for the nondextran intravenous iron formulation sodium ferric gluconate complex, and examine the emerging concerns related to use of intravenous iron, including the risks of infection, oxidative stress and cell toxicity.

    • Beckie Michael
    • , Steven Fishbane
    • , Daniel W Coyne
    • , Rajiv Agarwal
    •  & David G Warnock
  • Review Article |

    If detected early, damage to the kidneys caused by medications can be reversed in most instances. Physician awareness of which drugs have pathogenic potential is therefore essential. This article synthesizes current knowledge of the mechanisms by which commonly used drugs induce renal injury. Comprehensive summary tables that present the drug types associated with each mechanism, clinical findings and recommended management strategies are included.

    • Devasmita Choudhury
    •  & Ziauddin Ahmed
  • Review Article |

    There is no specific treatment for kidney damage secondary to deposition of polymeric IgA. Nephrologists' opinions on the optimal management strategy for IgA nephropathy therefore vary widely, encompassing perturbation of the renin–angiotensin system, tonsillectomy, fish oil, steroids and cytotoxic agents. The data supporting these and other therapeutic options are presented in this critical analysis.

    • Francesco Locatelli
    • , Lucia Del Vecchio
    •  & Claudio Pozzi
  • Review Article |

    Maintaining cardiovascular stability while eliminating toxins is the challenge that confronts intensivists managing critically ill patients whose kidneys have failed. Generally treated with continuous venovenous hemofiltration or intermittent hemodialysis, evidence is emerging that prolonged dialysis at low flow rates has equivalent safety and efficacy in acute renal failure, plus the advantages of flexible treatment timing and reduced costs.

    • Danilo Fliser
    •  & Jan T Kielstein
  • Review Article |

    The mutations ofPKD1 and PKD2, and PKHD1, which cause autosomal dominant and autosomal recessive polycystic kidney disease, respectively, disrupt the function of polycystins and fibrocystin in tubular epithelial cells. The cellular consequences of these perturbations are reviewed here by Torres and Harris, with emphasis on the affected signaling pathways.

    • Vicente E Torres
    •  & Peter C Harris
  • Review Article |

    Does erythropoietin have the potential to ameliorate renal injury in humans? This article addresses this question in the context of our current understanding of the pathophysiology of acute renal failure. Recent findings from experimental models are presented, and their relevance to mechanisms of acute renal failure—including endothelial and tubular cell injury, and inflammation—are discussed.

    • Edward J Sharples
    • , Christoph Thiemermann
    •  & Magdi M Yaqoob
  • Review Article |

    The escalating burden of diabetic nephropathy is largely a function of the increased frequency of type 2 diabetes, which is associated with obesity and the metabolic syndrome. Prevention is dependent on elucidation of causal mechanisms. Here, Richard Johnson and colleagues present evidence for a mechanism that might form the basis of novel intervention strategies.

    • Takahiko Nakagawa
    • , Katherine R Tuttle
    • , Robert A Short
    •  & Richard J Johnson
  • Review Article |

    In this comprehensive review, Giuseppe Remuzzi and colleagues present a hypothesis for the pathophysiology of pre-eclampsia that unifies findings from a recent flurry of research. These new insights should spur the development of novel treatments for the hypertension and proteinuria that are hallmarks of this leading cause of fetal and maternal morbidity.

    • Marina Noris
    • , Norberto Perico
    •  & Giuseppe Remuzzi
  • Review Article |

    Age-related decline in the capacity of the kidney to repair itself is a significant contributor to mortality associated with acute renal failure. In this well-balanced overview of renal and bone-marrow stem cells, Lloyd Cantley summarizes current knowledge and speculates on mechanisms of regeneration that have therapeutic potential.

    • Lloyd G Cantley
  • Review Article |

    Despite the implications of the term 'focal segmental glomerulosclerosis', subtypes of this form of idiopathic nephrotic syndrome are not always focal, segmental or sclerotic. Here, Alain Meyrier presents a comprehensive update of our understanding of the processes that underlie the development of variants of this condition, with emphasis on the unifying role of the podocyte.

    • Alain Meyrier
  • Review Article |

    Thiazolidinediones are synthetic agonists of peroxisome proliferator-activated receptors that have shown promise inin vitroand animal models of nephropathy. Encouraging early-stage data have also been generated in patients with diabetic nephropathy. Carol Pollock and colleagues outline what we know and what we need to find out before thiazolidinediones such as pioglitazone and rosiglitazone can fulfill their clinical potential.

    • Usha Panchapakesan
    • , Xin-Ming Chen
    •  & Carol A Pollock