This Month in AJKD

Article Outline

• Massry Lecture: Clinical Transplantation Tolerance
• NGAL in Diagnosis and Prognosis of AKI
• Soluble CD14 in Hemodialysis Patients
• Proteinuria in Kidney Transplant Recipients

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Massry Lecture: Clinical Transplantation Tolerance 

See Azzi and Sayegh, pages 1005-1011.

Establishment of the Immune Tolerance Network, a clinical research consortium founded by National Institutes of Health in 1999, changed the approach to achieving clinical tolerance by translating advances in the field of immunology in general and in tolerance in particular from experimental animal strategies into human clinical trials. Despite these promising advances, scientific and operational challenges still face the transplantation community. In this issue's Massry Lecture, Drs Azzi and Sayegh highlight recent advances in the field of immunologic tolerance in organ transplantation. They conclude that achieving tolerance could not only revolutionize the field of transplantation through avoidance of toxicity associated with immunosuppressive agents, but also influence the treatment of autoimmune diseases, in which the immune system attacks itself, as well as cancer, in which tolerance of the immune system toward malignant cells may permit disease development and progression.

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• Credit: T. Triche, National Cancer Institute.

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NGAL in Diagnosis and Prognosis of AKI 

See Hasse et al, pages 1012-1024; and Parikh and Garg, pages 987-989.

Neutrophil gelatinase-associated lipocalin (NGAL) appears to be a promising biomarker for the early diagnosis of acute kidney injury (AKI); however, a wide range in its diagnostic accuracy has been reported. In this issue, Haase et al perform a meta-analysis where data from 19 studies and 8 countries involving 2,538 patients, of whom 487 (19.2%) developed AKI, was analyzed. In these studies, NGAL was tested across a broad range of clinical settings, in both adults and children. Haase et al were able to conclude from their results that urine and serum NGAL are useful as early markers of AKI, and that NGAL levels are also associated with clinical outcomes, such as requirement of dialysis and mortality. An editorial by Drs Parikh and Garg acknowledges that some important limitations to this study exist, but it allows the nephrology community to reflect on their understanding of AKI biomarker testing and guides their next research priorities.

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Soluble CD14 in Hemodialysis Patients 

See Raj et al, pages 1062-1071 and 1072-1080; and Jaber and colleagues, pages 990-992.

CD14 is a pattern-recognition receptor and a key molecule in innate immunity that mediates cell activation and signaling in response to endotoxin and other bacterial wall–derived components. The correlates of soluble CD14 (sCD14) in individuals undergoing maintenance hemodialysis are not known. In this issue, Raj et al contribute 2 prospective cohort studies exploring the relationship of circulating endotoxin and sCD14 levels to adverse clinical outcomes in prevalent patients undergoing maintenance hemodialysis. The studies were conducted in the United States (n = 310) and Sweden (n = 211). Follow-up was close to 2.5 years for both studies, and mean time on dialysis therapy was 50 months and 29 months, respectively. Both studies showed higher sCD14 levels were associated with higher mortality, possibly reflecting activation by endotoxin. An editorial by Jaber and colleagues argues that while one might call for the inclusion of sCD14 for risk stratification in clinical trials aimed at reducing endotoxin exposure, elucidating the role of sCD14 in the host inflammatory cascade should be a priority.

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Proteinuria in Kidney Transplant Recipients 

See Knoll, pages 1131-1144.

Proteinuria is highly prevalent after kidney transplantation. In this issue, Dr Knoll reviews the measurement, prevalence, pathological findings, prognostic significance, and evidence-based management of proteinuria in kidney transplant recipients. In addition to glomerulonephritis, proteinuria in kidney transplant recipients is associated commonly with such transplant-specific diagnoses on biopsy as allograft nephropathy, transplant glomerulopathy, and acute rejection, and is associated with decreased patient and allograft survival, as well as an increased risk of cardiovascular events. In proteinuric transplant recipients, treatment with an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker can decrease proteinuria. Dr Knoll concludes that there is no evidence from randomized trials that this strategy improves patient or graft survival, but awaits the results of an ongoing randomized trial.

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