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Treatments administered to patients with primary IgA nephropathy (IgAN) and those with Henoch–Schönlein nephritis are largely based on opinion or weak evidence, and the recent KDIGO Clinical Practice Guidelines for Glomerulonephritis assigned low levels of evidence for the majority of recommendations and suggestions related to these two diseases. In this Review, Floege and Feehally describe an algorithm for structuring the treatment of IgAN depending on the clinical scenario, and discuss ongoing studies to investigate treatments.

In this Viewpoint, five members of theNature Reviews Nephrologyadvisory board reflect on the progress and frustrations of the past decade in basic and clinical nephrology research. They comment on areas where effort and money should be invested and the challenges that remain to be overcome, as well as give their predictions for progress in the next decade.

A recent study demonstrated the superiority of prednisone plus ramipril in preventing progression of IgA nephropathy compared with ramipril alone in a group of patients at high risk of progressive renal damage. However, future clinical trials need to clarify whether more aggressive supportive therapy may match the benefits of immunosuppression.

A relationship between IgA nephropathy (IgAN) and the mucosa has long been recognized with evidence from clinical observations and genetic studies suggesting that abnormalities in the IgA mucosal immune system could be a key element in the pathogenesis of IgAN. In this Review, Jürgen Floege and John Feehally describe current evidence that links the mucosa, in particular the gastrointestinal mucosa, and IgA produced in the bone marrow with IgAN.

Cinacalcet, a calcimimetic drug, is an attractive treatment for renal transplant patients who experience persistent hyperparathyroidism and hypercalcemia. In this article, however, Seikrit et al. present the case of a 47-year-old man who experienced fulminant renal allograft failure after receiving cinacalcet soon after transplantation. The authors also discuss the possible pathophysiological connection between cinacalcet administration and failure of the transplanted kidney.

Corticosteroids are frequently used to treat patients with IgA nephropathy (IgAN) despite a paucity of data to support their use in individuals with substantially reduced renal function. A retrospective study provides evidence that these agents may slow the rate of decline in renal function in high-risk patients with IgAN.

Surprising new randomized trial data showed no clinically relevant decrease in bone mineral density at various skeletal sites 12 months after kidney transplantation in patients receiving baseline calcitriol and calcium therapy as well as ibandronate or placebo. These data raise important questions regarding strategies to prevent bone loss after renal transplantation.

Renal fibrosis is the common end point of virtually all progressive kidney diseases and a detailed understanding of the underlying mechanisms is required for the development of effective therapeutic strategies. In this Review, Boor and colleagues discuss the most recent advances in renal, or more specifically, tubulointerstitial fibrosis. Consideration is given to novel mechanisms as well as potential treatment targets based on different cell types.

Aspirin and other antiplatelet agents are widely used in patients with chronic kidney disease. However, their use is often based on data obtained in patients with normal renal function. A recent Cochrane Collaboration systematic review analysed the benefits and risks of these agents in patients with chronic kidney disease.

As IgA nephropathy (IgAN) is considered to result in part from autoimmune processes, B-cell depletion using rituximab might be a plausible therapy. However, a small randomized, controlled trial in patients at risk of progressive IgAN reports that this therapy failed to reduce proteinuria over 1 year and was associated with more adverse events per patient.

In a phase 2 trial involving patients with kidney failure who were undergoing hemodialysis, treatment with osocimab—an antibody targeting coagulation factor XIa—did not lead to increased rates of clinically relevant bleeding or an increased risk of adverse events as compared to placebo, suggesting the possibility that factor XIa inhibitors may be safer in this patient population than currently available anticoagulants.

Genome-wide association analyses identify 30 risk loci for IgA nephropathy. Functional annotations of putative causal genes converge on inflammatory signaling pathways and cytokine ligand–receptor pairs, prioritizing potential new drug targets.

Time-averaged proteinuria (TAP) is thought to be the most reliable predictor of outcomes in IgA nephropathy (IgAN). New data suggest that corticosteroids reduce TAP and presumably improve outcomes in IgAN, but increase the risk of adverse effects. Whether TAP is a good surrogate end point for clinical trials remains unclear.

Pathology diagnostics still rely on tissue morphology assessment by trained experts. Here, the authors perform deep-learning-based segmentation followed by large-scale feature extraction of histological images, i.e., next-generation morphometry, to enable outcome-relevant and disease-specific pathomics analysis of non-tumor kidney pathology.

The new Oxford classification of IgA nephropathy has been developed as a pathological classification system to reliably predict the risk of disease progression. Future studies need to demonstrate the value of this classification in directing individualized therapeutic decisions for patients with IgA nephropathy.

Ali Gharavi and colleagues report a genome-wide association analysis of IgA nephropathy in over 20,000 individuals of European and East Asian ancestry. They identify genome-wide significant signals at three new loci near VAV3, CARD9 and ITGAM-ITGAX and correlations between genetic risk and pathogen diversity.

Immunoglobulin A protects against infectious disease and contributes to autoimmune and inflammatory disorders. Here, the authors perform a genome-wide association study for serum IgA levels, identifying 20 genome-wide significant loci, providing new insights into the genetic regulation of IgA levels.

Adult kidney organoids, or tubuloids, originate from CD24⁺ epithelial cells. Tubuloids represent a functional kidney tubule and can be used to model autosomal dominant polycystic kidney disease and study drug response.

A meta-analysis of individual-level patient data from 66 clinical studies supports the utility of glomerular filtration rate as a surrogate endpoint in clinical trials for chronic kidney disease, with potential to enable detection of events earlier in the disease course.

A range of techniques are used to investigate the molecular landscape of chronic kidney disease, and the results suggest that distinct populations of pericytes and fibroblasts are the main source of myofibroblasts in kidney fibrosis.

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.

IgA nephropathy (IgAN) is an inflammatory disease of the glomerulus that can lead to kidney failure. In this Primer, Stamellou et al. discuss the prevalence and pathophysiological mechanisms of IgAN, summarize diagnosis and management of the disease, and provide an outlook on required future research.

This Review discusses advances in the understanding of WNT–β-catenin signalling and its regulation during kidney injury, along with its potential diagnostic and therapeutic implications.

In vivo non-invasive molecular imaging techniques have potential to improve clinical research and practices in nephrology. Here, the authors discuss the benefits and challenges of preclinical and clinical applications of molecular imaging to acute kidney injury and chronic kidney disease, transplantation and kidney cancer.

Dysregulated expression of metalloproteinases is observed in many forms of kidney disease. Here, the authors focus on the roles of the matrix metalloproteinase and a disintegrin and metalloproteinase families of proteins, as well as their regulators, in kidney disease processes and explore the therapeutic potential of novel metalloproteinase inhibitors.