Nature Reviews Nephrology

Publications in this journal

• Article: Hypertension: Role of renal ACE in response to hypertensive stimuli.

  Susan J Allison
  Nature Reviews Nephrology 05/2013;
• Article: Vesicoureteral reflux: Association of TNXB mutations with vesicoureteral reflux.

  Rebecca Kelsey
  Nature Reviews Nephrology 05/2013;
• Article: Iron metabolism in the pathogenesis of iron-induced kidney injury.

  A M F Martines, R Masereeuw, H Tjalsma, J G Hoenderop, J F M Wetzels, D W Swinkels
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  ABSTRACT: In the past 8 years, there has been renewed interest in the role of iron in both acute kidney injury (AKI) and chronic kidney disease (CKD). In patients with kidney diseases, renal tubules are exposed to a high concentration of iron owing to increased glomerular filtration of iron and iron-containing proteins, including haemoglobin, transferrin and neutrophil gelatinase-associated lipocalin (NGAL). Levels of intracellular catalytic iron may increase when glomerular and renal tubular cells are injured. Reducing the excessive luminal or intracellular levels of iron in the kidney could be a promising approach to treat AKI and CKD. Understanding the role of iron in kidney injury and as a therapeutic target requires insight into the mechanisms of iron metabolism in the kidney, the role of endogenous proteins involved in iron chelation and transport, including hepcidin, NGAL, the NGAL receptor and divalent metal transporter 1, and iron-induced toxic effects. This Review summarizes emerging knowledge, which suggests that complex mechanisms of iron metabolism exist in the kidney, modulated directly or indirectly by cellular iron content, inflammation, ischaemia and oxidative stress. The potential exists for prevention and treatment of iron-induced kidney injury by customized iron removal or relocation, aided by detailed insight into the underlying pathological mechanisms.
  Nature Reviews Nephrology 05/2013;
• Article: Peritoneal changes in patients on long-term peritoneal dialysis.

  Raymond T Krediet, Dirk G Struijk
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  ABSTRACT: Long-term peritoneal dialysis can lead to morphological and functional changes in the peritoneum. Although the range of morphological alterations is known for the peritoneal dialysis population as a whole, these changes will not occur in every patient in the same sequence and to the same extent. Longitudinal studies are therefore required to help identify which patients might develop the changes. Although longitudinal studies using peritoneal biopsies are not possible, analyses of peritoneal effluent biomarkers that represent morphological alterations could provide insight. Longitudinal studies on peritoneal transport have been performed, but follow-up has often been too short and an insufficient number of parameters have been investigated. This Review will firstly describe peritoneal morphology and structure and will then focus on peritoneal effluent biomarkers and their changes over time. Net ultrafiltration will also be discussed together with the transport of small solutes. Data on the peritoneal transport of serum proteins show that serum protein levels do not increase to the same extent as levels of small solutes with long-term peritoneal dialysis. Early alterations in peritoneal transport must be distinguished from alterations that only develop with long-term peritoneal dialysis. Early alterations are related to vasoactive mediators, whereas later alterations are related to neoangiogenesis and fibrosis. Modern peritoneal dialysis should focus on the early detection of long-term membrane alterations by biomarkers-such as cancer antigen 125, interleukin-6 and plasminogen activator inhibitor 1-and the improved assessment of peritoneal transport.
  Nature Reviews Nephrology 05/2013;
• Article: Transplantation: Alloantibodies in simultaneous liver-kidney transplantation.

  Andrew L Singer, Dorry L Segev
  Nature Reviews Nephrology 05/2013;
• Article: Acute kidney injury: Perioperative sodium bicarbonate infusion for prevention of acute kidney injury-no benefit and possible harm.

  Ellen F Carney
  Nature Reviews Nephrology 05/2013;
• Article: Three feasible strategies to minimize kidney injury in 'incipient AKI'

  Mark A Perazella, Steven G Coca
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  ABSTRACT: Acute kidney injury (AKI) is common and increasing in hospitalized patients. The earlier recognition of renal injury, at a stage described as 'incipient AKI', may allow renoprotective strategies to be initiated at a time when more kidney tissue is salvageable. 'Incipient AKI' represents renal injury as manifested by new-onset proteinuria, cellular activity on urine microscopy, or elevated novel biomarkers of kidney injury in the absence of clinical data that meet current diagnostic criteria for AKI. We propose three strategies to preserve kidney function and minimize further kidney injury in patients with 'incipient AKI'. These include-when appropriate for the prevailing cause of 'incipient AKI'-use of low-chloride-containing intravenous solutions, continued use of renin-angiotensin system antagonists, and use of diuretics to achieve adequate control of intravascular volume. The combined approach of the early diagnosis of AKI and early employment of feasible therapeutic strategies may slow the growth of clinical AKI, AKI requiring renal replacement therapy and chronic kidney disease, and might reduce AKI-associated mortality.
  Nature Reviews Nephrology 05/2013;
• Article: Diabetes: Pre-eclampsia: association with increased risk of diabetes.

  Susan J Allison
  Nature Reviews Nephrology 05/2013;
• Article: Risk factors: Body fat distribution and renal risk.

  Rebecca Kelsey
  Nature Reviews Nephrology 04/2013;
• Article: Diabetic nephropathy: FRMD3 in diabetic nephropathy-guilt by association.

  Nicholette D Palmer, Barry I Freedman
  Nature Reviews Nephrology 04/2013;
• Article: Renin-angiotensin system: Meta-analyses can misdirect decisions on treatment.

  Piero Ruggenenti, Giuseppe Remuzzi
  Nature Reviews Nephrology 04/2013;
• Article: Chronic kidney disease: How effective and safe are antiplatelet agents in CKD?

  Jürgen Floege, Georg Schlieper
  Nature Reviews Nephrology 04/2013;
• Article: End-stage renal disease: A bioengineered kidney with excretory function.

  Susan J Allison
  Nature Reviews Nephrology 04/2013;
• Article: Chronic kidney disease: Renal adenosine in hypertensive CKD.

  Ellen F Carney
  Nature Reviews Nephrology 04/2013;
• Article: The role of the podocyte in albumin filtration.

  Paul Thomas Brinkkoetter, Christina Ising, Thomas Benzing
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  ABSTRACT: In the past decade, our understanding of the role of podocytes in the function of the glomerular filtration barrier, and of the role of podocyte injury in the pathogenesis of proteinuric kidney disease, has substantially increased. Landmark genetic studies identified mutations in genes expressed by podocytes as a cause of albuminuria and nephrotic syndrome, leading to breakthrough discoveries from many laboratories. These discoveries contributed to a dramatic change in our view of the glomerular filtration barrier of the kidney and of the role of podocyte injury in the development of albuminuria and progressive kidney disease. In the past several years, studies have demonstrated that podocyte injury is a major cause of marked albuminuria and nephrotic syndrome, and have confirmed that podocytes are important for the maintenance of an intact glomerular filtration barrier. An essential role of loss of these cells in the pathogenesis of glomerulosclerosis and progressive proteinuric kidney disease has also been identified. In this Review, we discuss the importance of podocytes for the maintenance of an intact glomerular filtration barrier and their role in albumin handling.
  Nature Reviews Nephrology 04/2013;
• Article: Chronotherapy improves blood pressure control and reduces vascular risk in CKD.

  Ramón C Hermida, Diana E Ayala, Michael H Smolensky, Artemio Mojón, José R Fernández, Juan J Crespo, Ana Moyá, María T Ríos, Francesco Portaluppi
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  ABSTRACT: In patients with chronic kidney disease (CKD), the prevalence of increased blood pressure during sleep and blunted sleep-time-relative blood pressure decline (a nondipper pattern) is very high and increases substantially with disease severity. Elevated blood pressure during sleep is the major criterion for the diagnoses of hypertension and inadequate therapeutic ambulatory blood pressure control in these patients. Substantial, clinically meaningful ingestion-time-dependent differences in the safety, efficacy, duration of action and/or effects on the 24 h blood pressure pattern of six different classes of hypertension medications and their combinations have been substantiated. For example, bedtime ingestion of angiotensin-converting-enzyme inhibitors and angiotensin-receptor blockers is more effective than morning ingestion in reducing blood pressure during sleep and converting the 24 h blood pressure profile into a dipper pattern. We have identified a progressive reduction in blood pressure during sleep-a novel therapeutic target best achieved by ingestion of one or more hypertension medications at bedtime-as the most significant predictor of decreased cardiovascular risk in patients with and without CKD. Recent findings suggest that in patients with CKD, ambulatory blood pressure monitoring should be used for the diagnosis of hypertension and assessment of cardiovascular disease risk, and that therapeutic strategies given at bedtime rather than on awakening are preferable for the management of hypertension.
  Nature Reviews Nephrology 04/2013;
• Article: The effect of vitamin D status on risk factors for cardiovascular disease.

  Sujana S Gunta, Ravi I Thadhani, Robert H Mak
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  ABSTRACT: Vitamin-D-related pathways are implicated in various endocrine, inflammatory and endothelial functions. An estimated 1 billion people in the world have vitamin D deficiency or insufficiency, and undiagnosed vitamin D deficiency is common. Vitamin D deficiency is associated with substantial increases in the incidence of hypertension, hyperlipidaemia, myocardial infarction and stroke, as well as in diseases such as chronic kidney disease and type 2 diabetes. Low vitamin D levels also upregulate the renin-angiotensin-aldosterone system, increase inflammation and cause endothelial dysfunction. However, the role of vitamin D deficiency in cardiovascular morbidity and mortality is an emerging and hotly debated topic. Epidemiological studies suggest an association between low vitamin D levels and risk factors for cardiovascular disease, but a causal relationship has not been established, and clinical trials and meta-analyses have not demonstrated convincing evidence that vitamin D therapy improves cardiovascular outcomes. Some evidence suggests that vitamin D status is a biomarker of lifestyle, since unhealthy and sedentary lifestyles are associated with vitamin D insufficiency or deficiency and are also risk factors for cardiovascular complications.
  Nature Reviews Nephrology 04/2013;
• Article: Pre-eclampsia: Podocyturia predicts pre-eclampsia.

  Ellen F Carney
  Nature Reviews Nephrology 04/2013;
• Article: Vascular access in haemodialysis: strengthening the Achilles' heel.

  Miguel C Riella, Prabir Roy-Chaudhury
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  ABSTRACT: Despite all the progress achieved since Scribner first introduced the arteriovenous (AV) shunt in 1960 and Cimino and Brescia introduced the native AV fistula in 1962, we have continued to face a conundrum in vascular access for dialysis, in that dialysis vascular access is at the same time both the 'lifeline' and the 'Achilles' heel' of haemodialysis. Indeed, findings from a multitude of published articles in this area, unfortunately mainly observational studies, reflect both our frustration and our limited knowledge in this area. Despite improved understanding of the pathophysiology of stenosis and thrombosis of the vascular access, we have unfortunately not been very successful in translating these advances into either improved therapies or a superior process of care. As a result, we continue to face an epidemic of arteriovenous fistula (AVF) maturation failure, a proliferation of relatively ineffective interventions such as angioplasty and stent placement, an extremely high incidence of catheter use, and more doubts rather than guidance with regard to the role (or lack thereof) of surveillance. An important reason for these problems is the lack of focused translational research and robust randomized prospective studies in this area. In this Review, we will address some of these critical issues, with a special emphasis on identifying the best process of care pathways that could reduce morbidity and mortality. We also discuss the potential use of novel therapies to reduce dialysis vascular access dysfunction.
  Nature Reviews Nephrology 04/2013;
• Article: Chronic kidney disease: Cystatin-C-based eGFR: what is it telling us?

  Kristen L Jablonski, Michel Chonchol
  Nature Reviews Nephrology 04/2013;