Reviews & Analysis

Lupus nephritis is a complication of systemic lupus erythematosus, a heterogeneous autoimmune syndrome that involves multiple pathogenetic pathways. Here, Adriana Migliorini and Hans-Joachim Anders summarize accumulating data from the fields of genetics, clinical science, transcriptomics and basic immunology which indicate that antiviral immunity is involved in the pathogenesis of lupus nephritis. The authors also discuss the potential implications for innovative therapeutic strategies.

Identification of effective therapies for nephrotic syndrome is challenging. The pituitary adrenocorticotropic hormone (ACTH) has been shown to be renoprotective in patients with proteinuric neuropathies, but its mechanism of action is unknown. In this Perspectives, Runjun Gong provides an overview of the biophysiology of ACTH, the effects of ACTH on proteinuric renal diseases and the mechanisms likely to be involved in its therapeutic activity. The potential therapeutic role of ACTH for nephrotic glomerulopathies is also discussed.

Several studies have indicated that an intensive continuous renal replacement therapy (CRRT) dose has no benefit over a standard CRRT dose. However, treatment-related factors may have influenced these findings. In this article, Macedo et al. discuss the assumption that delivered dialysis dose is equivalent to the effluent volume and highlight the importance of assessing filter efficacy and dose parameters in patients receiving CRRT.

Use of thiazide diuretics leads to decreased urinary calcium excretion, which in turn reduces the recurrence rate of calcium-containing stones. Whether the hypocalciuria results from increased calcium reabsorption in the proximal or distal nephron is still a matter of debate. In this Perspectives article, the authors discuss the evidence supporting the hypocalciuric effects of NaCl cotransporter inhibition in the proximal and distal nephron.

Several mechanisms in critically ill patients make them susceptible to augmented renal clearance (ARC). The authors of this Perspectives article focus on the causes, risk factors and monitoring of ARC in these patients, and examine the clinical consequences of ARC with regard to achieving target therapeutic concentrations of renally excreted drugs.

Extensive rhabdomyolysis is often lethal unless treated immediately, owing to hypovolemic shock, hyperkalemia, acidosis and myoglobinuric acute kidney injury. In patients with rhabdomyolysis caused by muscle crush syndrome, the use of early fluid resuscitation at the scene of injury has reduced mortality from ∼100% to <20% over the past 70 years. In this article, Better and Abassi discuss the lifesaving and limb-saving potential of early vigorous fluid resuscitation in patients with extensive traumatic and nontraumatic rhabdomyolysis.

Attempts to achieve pharmacological suppression of the renin–angiotensin–aldosterone system (RAAS) fall short of complete success, owing to the existence of accessory enzyme pathways. In this article, the therapeutic targets and limitations of RAAS inhibition are discussed, and the use of combination therapy and the direct renin inhibitor, aliskiren, are described.

Although the relationship between asymptomatic hyperuricemia and chronic kidney disease is not fully understood, data from small studies indicate that reducing high serum urate level may slow disease progression. In this Perspectives article, Badve and colleagues propose that a multicenter pilot randomized controlled trial be performed to investigate the effects of uric-acid-lowering therapy in patients with CKD.

Proteinuria is a prognostic indicator of renal function loss, and understanding the mechanisms underlying proteinuric nephropathy is a topic of intense interest. In this Perspectives article, Richard Baines and Nigel Brunskill consider the importance of megalin, cubilin, and other receptors in the handling of filtered proteins by PTECs and describe how these factors could contribute to the development of proteinuric nephropathy.

Increased uric acid has often been associated with pre-eclampsia in pregnant women, an issue re-examined in this Perspective by Martin and Brown. The authors call for further examination of the relationship between maternal plasma uric acid levels and maternal endothelial dysfunction and utero-placental bloodflow in pre-eclampsia, and suggest that uric acid is a pathogenic amplifier of this condition.

Several distinct pathological patterns of glomerular disorders are associated with abnormal regulation of the complement system. Some of these conditions are characterized by glomerular deposits of complement C3 in the absence or in the presence of marginal deposits of immunoglobulin. In this Perspectives article, the authors suggest that glomerular pathologies where isolated complement C3 deposition is found should be classified by the term 'C3 glomerulopathy'.

New hypoglycemic agents that inhibit renal glucose reabsorption are valuable in the constant search for therapeutic tools that achieve glycemic control in patients with diabetes mellitus. In this Perspectives article, Amanda Mather and Carol Pollock discuss novel agents that inhibit the principal glucose transporter in the kidney, which can be added to the armamentarium against hyperglycemia.

Acute kidney injury (AKI) is a common and potentially serious clinical complication that can be associated with poor outcomes and progression to chronic kidney disease. In this Perspectives article, Tögel and Westenfelder describe the preclinical data demonstrating the ability of mesenchymal stem cells (MSCs) to effectively improve outcome after AKI in experimental models and discuss the promising preliminary clinical data on MSC use in patients at risk of AKI.

The development of new biomarkers that enable the early diagnosis of acute kidney injury (AKI) should facilitate early intervention and reduce the mortality associated with this disease. In this Perspectives article, Robert Schrier discusses the need to develop interventions to attenuate or prevent AKI and the requirement for such interventions to selectively improve renal hemodynamics, increase tubular flow rates, and decrease inflammation without causing systemic vasodilation.

Calcific uremic arteriolopathy (CUA), a condition associated with high mortality, is most common among patients on dialysis. In this opinion article, Georg Schlieper and his colleagues discuss the evidence on the efficacy of administering sodium thiosulfate in the treatment of CUA. Given the lack of large clinical trials, the authors also evaluate the consultation of internet-accessible CUA case registries as a strategy to inform the treatment of this disease and to design future studies.

Weibel–Palade bodies, organelles of storage and secretion in endothelial cells, harbor a range of bioactive substances, including von Willebrand factor, angiopoietin 2, and interleukin 8. The authors of this Perspectives article examine the biogenesis and exocytosis of Weibel–Palade bodies and propose that these organelles could have key roles in the development of endothelial dysfunction and as a first-line response to acute stressors such as ischemia.