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A critical gap in the field of transplantation tolerance is the lack of available tests or biomarkers to indicate when a patient has become partially or totally tolerant to their graft. Here, Hernandez-Fuentes and Lechler discuss advances in the development of biomarkers of transplantation tolerance and describe the potential utility of such biomarkers for the modification of protocols in clinical practice.
Promoting the development and maintenance of regulatory responses through the promotion of regulatory T (TREG) cells represents a promising approach for the induction of transplantation tolerance. In this Review, Li and Turka provide an overview of TREG cells, focusing on the challenges, opportunities, and emerging approaches in exploiting FOXP3+ TREGcells for the induction of transplant tolerance.
Various molecules, such as components of the slit diaphragm and the glomerular basement membrane strictly orchestrate the integrity of the glomerular filtration barrier. Genetic defects in these components have the potential to cause glomerular disease. In this Review, Chiang and Inagi summarize genetic abnormalities that affect the structural and functional integrity of the glomerulus. The authors also discuss some of the therapeutic avenues that are being explored for the treatment of genetic forms of glomerular disease.
Although continuous renal replacement therapy (CRRT) is widely used for the treatment of acute kidney injury in intensive care units, controversy in the clinical application of this therapy continues. Results of two recently published randomized controlled trials—the ATN study and the RENAL trial—have now provided an unparalleled quantity of information to guide clinicians. Here, Prowle and Bellomo discuss the results of these trials, explain the controversies that still exist regarding the use of CRRT, and describe the questions that remain to be answered.
Autosomal dominant polycystic kidney disease is a common disorder that is caused by mutations inPKD1 and PKD2. The proteins that these genes encode, polycystin 1 and polycystin 2, are thought to be involved in the sensing of shear stress and pressure through the regulation of calcium influx, nucleotide release and purinergic stimulation. This Review summarizes our current understanding of the role of polycystins in mechanosensory transduction and describes the potential role of altered mechanosensory transduction in the etiology of polycystic kidney disease.
Gastrointestinal complications commonly occur in patients with renal failure. Upper gastrointestinal lesions, gastrointestinal bleeding, pancreatitis, and ischemic colitis are more common in patients with renal failure than in the general population. This Review describes the prevalence, etiologies, and treatment of the most common gastrointestinal complications associated with renal failure. The renal consequences of common gastrointestinal procedures are also discussed.
Cardiovascular disease is the most frequent cause of death in patients on peritoneal dialysis. In this Review, Krediet and Balafa describe cardiovascular risk factors that may affect the general population, those that are related to end-stage renal disease, and those that are specific to patients on peritoneal dialysis. The authors also discuss how these factors may be modified by changes in residual kidney function and/or peritoneal dialysis.
Cognitive impairment, delirium and depression are common in patients with renal disease. As all of these conditions are associated with prolonged hospitalization and an increased risk of mortality, a good understanding of these conditions is key to their prevention, early intervention and management. In this Review, McQuillan and Jassal summarize the main clinical features of the neuropsychiatric complications that occur in individuals with renal disease and describe the evidence for the high burden of neuropsychiatric disease in such patients.
Acute interstitial nephritis (AIN) is a common cause of acute kidney injury. The most common etiology of AIN is drug-induced disease, which results from a reaction to certain medications. Multiple classes of drugs can induce AIN, resulting in a range of clinical presentations and laboratory findings. This Review describes the clinical features of drug-induced AIN, with a particular focus on the different features that are induced by different agents. The pathology, diagnosis and management of drug-induced AIN are also discussed.
Cystinuria is an inherited disease characterized by the failure to reabsorb filtered cystine and dibasic amino acids in the proximal tubule that leads to the formation of cystine stones. In this Review, Chillarón and colleagues discuss the genetic mutations that lead to cystinuria, the molecular mechanisms by which some of these mutations may cause the disease, and the current and prospective treatment options for recurrent cystine lithiasis.
New-onset diabetes after transplantation (NODAT) is a common complication following kidney transplantation and is associated with adverse patient and graft outcomes. This Review discusses the current understanding of the risk factors associated with NODAT and transplant-associated hyperglycemia. The authors suggest that a dynamic approach to the surveillance and attenuation of transplantation-associated hyperglycemia may help to improve the outcomes of patients with NODAT.
The endothelium has a central role in the development of kidney disease and vascular lesions. In this Review, Ton Rabelink and colleagues discuss the biology of endothelial activation at a molecular level and the relevance of this process in the context of clinical outcomes. The authors also discuss markers of endothelial injury and repair in patients with renal disease and the potential for these markers to improve patient care.
Angiotensin II and other components of the renin–angiotensin–aldosterone system (RAAS) have a central role in the pathogenesis and progression of diabetic renal disease. In this Review, Ruggenenti and colleagues describe the roles of angiotensin II and other effectors of the RAAS—such as aldosterone and renin—in the pathogenesis and progression of diabetic renal disease. In addition, they discuss the renoprotective and cardioprotective effects that inhibition of these effectors may have in individuals with diabetes.
Improved understanding of the pathogenesis of fibrosis associated with diabetic kidney disease has led to the identification of several novel targets for treatment. In this Review, Declèves and Sharma discuss the clinical and experimental evidence supporting various novel pharmacological approaches aimed at controlling the progression of diabetic nephropathy. The potential therapeutic agents discussed include direct renin inhibitors, statins, and antifibrotic drugs.
A large body of evidence suggests that excess amounts of lipoproteins and lipids can induce glomerular injury and tubulointerstitial fibrosis, and may accelerate the progression of nephropathy in patients with diabetes. In this Review, John Rutledge and colleagues describe the influence of lipoproteins, specifically triglyceride-rich lipoproteins, on the development and perpetuation of diabetic nephropathy.
The receptor for advanced glycation endproducts (RAGE) was first identified as a signal transduction receptor for the advanced glycation endproducts (AGEs) of proteins and lipids. Experiments using transgenic mouse models, pharmacological blockade of RAGE and genetic modification or deletion of RAGE indicate a key role for RAGE in the pathogenesis of various nephropathies including diabetic nephropathy. In this Review, D'Agati and Schmidt discuss the evidence linking RAGE to diabetic nephropathy and chronic kidney disease.
Nuclear hormone receptors are transcription factors that regulate multiple biological pathways and may provide protection against metabolic, inflammatory and cardiovascular diseases. In this Review, Wang and colleagues discuss the evidence that supports a role for nuclear hormone receptors in the pathogenesis of diabetic nephropathy and describe how the manipulation of these receptors may provide new avenues for the treatment of this disease.
Chronic hyperglycemia is associated with the presence and evolution of diabetic complications in type 1 and type 2 diabetes. Intensive glycemic control can have beneficial effects on such complications, particularly diabetic nephropathy. This Review discusses the phenomenon of 'metabolic memory', in which the beneficial effects of intensive glycemic control persist after a return to more usual (often worse) glycemic control. This phenomenon is not well understood, but preliminary studies indicate that biochemical mechanisms such as advanced glycation and molecular pathways involving epigenetic events might have a role.
Liver disease can negatively affect clinical outcomes of patients with chronic kidney disease and patients who have undergone renal transplantation. Hepatitis B virus and hepatitis C virus infections are the most common form of liver disease in such patients. In this article, Fabrizi and colleagues discuss the natural history, clinical course, diagnosis and management of liver disorders associated with hepatitis B virus and hepatitis C virus infection in patients with chronic kidney disease and in renal transplant recipients, and also briefly describe other causes of liver disease in such patients.
Metabolic acidosis is a common acid–base disorder that can occur acutely (lasting minutes to several days) or chronically (lasting weeks to years). Both forms can have considerable adverse effects on cellular function and can contribute to increased morbidity and mortality. This Review summarizes current views on the pathogenesis, diagnosis, adverse effects, and management of different forms of metabolic acidosis.
