Lupus nephritis: A historical appraisal of how a skin lesion became a kidney disease
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"Lupus nephritis", a serious complication of systemic lupus erythematosus (SLE), is an entity of recent vintage. The term "lupus", derived from Latin for wolf, was introduced in the Middle Ages to denote nondescript erosive skin lesions which resembled wolf bites that were known theretofore by their Greek name of "herpes esthiomenos", used in the Hippocratic Corpus for the spread of the lesions like a crawling snake. The specific dermatologic features of lupus were characterized as an "erythematous" butterfly rash in 1828 and dubbed "lupus erythematosus" in 1850. Their association with systemic manifestations was described in 1872 and termed "disseminated lupus erythematosus" by the close of the century. A preference for "systemic" rather than "disseminated" was suggested in 1904 but would not prevail until the 1960s. The generic term "nephritis", denoting "inflammation of the kidnies" dating to the 1580s, was first used to describe the renal lesions of SLE in 1902. Although albuminuria and abnormal urine sediment were often noted in SLE patients, the early study of their renal changes was limited to postmortem studies. Refinements in their identification came in the late 1950s after the introduction of kidney needle biopsies and refined thereafter by immunofluorescent and electron microscopic studies. Subsequent lupus nephritis studies paralleled the emerging discipline of immunology that identified autoimmunity as the cause of SLE. The varied lesions observed were classified by glomerular changes in 1975 and refined in 2003. Advances in genetic and molecular profiling have enriched the management of lupus nephritis based on kidney biopsies.

A comprehensive evaluation for the treatment of lupus nephritis.

Systemic lupus is the prototypic human autoimmune disease. It is a kaleidoscope of autoreactivities, with clear indications of both a genetic and environmental basis. Indeed, it is a disease that can manifest in virtually every tissue and organ and can also be found spontaneously in a number of animal species, including dogs, cats and horses. Moreover, there are multiple murine models of lupus, the first of which, New Zealand Black (NZB) mice, were discovered in 1959. Despite an enormous effort from scientists in multiple disciplines, the etiology of lupus remains elusive and the introduction of new therapies has been disappointing. Fortunately, significant advances have occurred to help patients through the general principles of internal medicine, including antibiotics, dialysis, and of course use of steroids and immunosuppressive agents. However, the magic bullet has yet to be discovered. One of the major causes of morbidity in lupus remains lupus nephritis and there has been significant effort and encouragement in understanding the pathogenesis, renal histologic classification, and use of therapeutic protocols to induce and sustain remission of lupus nephritis. Indeed, the first use of evidence-based clinical trials in lupus was initiated by Dr. Alfred D. Steinberg at NIH in pioneering studies involving either oral or intravenous pulses of cyclophosphamide, azathioprine or corticosteroids alone and/or some combination. Cyclophosphamide intravenously proved to be superior and the use of cyclophosphamide in combination with methylprednisolone remained the standard protocol for the treatment of lupus nephritis for decades. Although alternative therapies have been introduced, including mycophenolate mofetil, the use of therapies first pioneered at NIH may still be considered standard of care in the appropriate indications. More targeted therapies are much desired. In this review we provide a comprehensive overview of lupus nephritis and the evolution of clinical treatments.

Advances in the care of children with lupus nephritis.

The care of children with lupus nephritis (LN) has changed dramatically over the past 50 y. The majority of patients with childhood-onset systemic lupus erythematosus (cSLE) develop LN. In the 1960's, prognosis in children was worse than in adults; therapies were limited and toxic. Nearly half of cases resulted in death within 2 y. Since this time, several diagnostic recommendations and disease-specific indices have been developed to assist physicians caring for patients with LN. Pediatric researchers are validating and adapting these indices and guidelines for the treatment of LN in cSLE. Classification systems, activity, and chronicity indices for kidney biopsy have been validated in pediatric cohorts in several countries. Implementation of contemporary immunosuppressive agents has reduced treatment toxicity and improved outcomes. Biomarkers sensitive to LN in children have been identified in the kidney, urine, and blood. Multi-institutional collaborative networks have formed to address the challenges of pediatric LN research. Considerable variation in evaluation and treatment has been addressed for proliferative forms of LN by development of consensus treatment practices. Patient survival at 5 y is now 95-97% and renal survival exceeds 90%. Moreover, international consensus exists for quality indicators for cSLE that consider the unique aspects of chronic disease in childhood.

Henry Kunkel Festschrift.

This Festschift by his former trainees is dedicated to the memory of Dr Henry G Kunkel. Dr Kunkel spent most of his academic life at The Rockefeller University. He has been called the father of Clinical Immunology. His trainees became professors and leaders in this field. Dr Kunkel's laboratory led to the elucidation of the immunology of the LE cell, the significance of anti-DNA and immune deposits in lupus nephritis, the recognition of antibodies to other nucleic acids and cellular constituents, the role of complement, genetics, hormones and cellular immunology--in the area of lupus and other rheumatic diseases.