Paradigm shift in activity assessment of IgA nephropathy - optimizing the next generation of diagnostic and therapeutic maneuvers via glycan targeting.

INTRODUCTION: IgA nephropathy (IgAN) is the most common glomerular disease and has a poor prognosis. Appropriate therapeutic strategies are not currently available due to the lack of information regarding IgAN pathogenesis and the absence of appropriate tools to assess disease activity in IgAN, a long-term chronic disease. However, recent evidence revealed that aberrantly glycosylated serum IgA1, mostly galactose-deficient IgA1 (Gd-IgA1) and immune complexes (ICs) with autoantibodies against glycan-containing epitopes on Gd-IgA1 are essential effector molecules. AREAS COVERED: Assessing disease activity by urinalysis/renal biopsy has some limitations, resulting in conflicts regarding the efficacy of possible IgAN-specific therapies. We summarize the characteristics and molecular basis of Gd-IgA1 and related ICs, their clinical application for activity assessment and early diagnosis, and discuss glycan as a potent target of therapeutic agents based on glycan engineering in IgAN. EXPERT OPINION: Recently, Gd-IgA1 and related ICs have shown clinical value for disease activity assessment and IgAN diagnosis. This suggests a paradigm shift in IgAN treatment thus allowing development of appropriate clinical trials of patients with IgAN stages and objective evaluation of the efficacy of future treatments. Early screening and diagnosis may increase therapeutic options, including quantitative regulation of nephritogenic Gd-IgA1 using therapeutic antibodies and selective depletion of Gd-IgA1-producing cells via glycan engineering.

Prognostic factors and therapy assessment of IgA nephropathy: report from a single unit in iran.

BACKGROUND: Immunoglobulin A (IgA) nephropathy is the most common cause of primary glomerulonephritis with slow progression to end-stage renal disease (ESRD) in up to 40% of patients. METHODS: A retrospective cohort study of patients with biopsy-proven IgA nephropathy was performed in our center from 1998 to 2009. We tried to determine the clinical and pathological factors which affect patients progressing to ESRD. We also compared the impact of renin-angiotensin system (RAS) blockers therapy alone or in combination with prednisone on baseline proteinuria and glomerular filtration rate (GFR) after 6 months of treatment in patients with proteinuria>1 g/d and GFR>30 mL/min. RESULTS: There were 70 IgA nephropathy patients of whom 46 were men. The average age of patients at biopsy was 39 ± 12.1 years. During the median 23.5 (6-130) months of follow-up, 10 patients progressed to ESRD and no patient died. Five-year renal survival following biopsy was 88%. By multivariate analysis, age more than 50 years (p = 0.003) and baseline serum creatinine level (p = 0.012) were independent predictors of progressing to ESRD and poor prognosis. Although there was no significant difference in proteinuria reduction after 6 months of treatment, kidney function was less preserved in RAS inhibitors therapy alone than in the combination treatment with prednisone. CONCLUSION: We showed that late diagnosis of patients with IgA nephropathy might be associated with poor outcome. Our results also suggest that addition of prednisone to RAS blockers may lead to better preservation of kidney function.

Successful three-way kidney paired donation with cross-country live donor allograft transport.

Providing transplantation opportunities for patients with incompatible live donors through kidney paired donation (KPD) is seen as one of the important strategies for easing the crisis in organ availability. It has been estimated that an additional 1000-2000 transplants per year could be accomplished if a national KPD program were implemented in the United States. While most of these transplants could be arranged within the participants' local or regional area, patients with hard-to-match blood types or broad HLA sensitization would benefit from matching across larger geographic areas. In this case, either patients or organs would need to travel in order to obtain maximum benefit from a national program. In this study, we describe how a triple KPD enabled a highly sensitized patient (PRA 96%) to receive a well-matched kidney from a live donor on the opposite coast. The kidney was removed in San Francisco and transported to Baltimore where it was reperfused 8 h later. The patient had prompt function and 1 year later has a serum creatinine of 1.1 mg/dl. This case provides a blueprint for solving some of the complexities that are inherent in the implementation of a national KPD program in a large country like the United States.

Evidence-based assessment of treatment options for children with IgA nephropathies.

We present an evidence-based evaluation of published data on therapy for children with various presentations of the IgA nephropathies--idiopathic IgA nephropathy (IgAN) and Henoch-Schonlein purpura nephritis (HSPN). Particular attention has been paid to the outcome markers used in the studies reviewed, with the best evidence provided by markers highly associated with progressive renal failure. No treatment modality for either IgAN or HSPN in pediatric patients has been shown to be effective by a properly designed and administered randomized controlled trial (i.e., the highest level of evidence--level 1). Lower levels of evidence support the use of a variety of corticosteroid regimens, often in combination with other agents, although there are some conflicting studies in this area. No convincing evidence has been published to date to support the use of fish oil, angiotensin-converting enzyme inhibitors or tonsillectomy for the treatment of children with IgAN or HSPN. Well designed randomized controlled trials in children with the IgA nephropathies need to be undertaken.

A cost analysis of the prevention of end-stage renal disease: immunoglobulin therapy for IgA nephropathy.

A cost analysis was used to evaluate three possible immunoglobulin (IgG) treatment protocols for end-stage renal disease due to IgA nephropathy. The perspective chosen for the cost analysis was that of the health-care delivery system. The baseline strategy was the absence of IgG treatment, and alternative strategies corresponded to three protocols presently on trial: all three included a high initial dose of intravenous IgG. Protocol 1 followed with intramuscular IgG injections only, protocol 2 with intramuscular plus intravenous injections, and protocol 3 with intravenous injections only. The costs of treatment included the costs of immunoglobulins, outpatient hospital costs, and the costs of tests; the saving (costs averted) resulted from kidney dialysis averted. The bottom line for the health-care system is a net savings of $233,000, $213,000, or $83,000, depending on the protocol chosen. The computation of costs did not value physical and psychological health benefits. Thus, any subjective benefit, such as improved comfort, or objective benefit, such as longer life expectancy, would be an improvement over the results presented here.