Year in Review

Studies published in 2016 provide insights that bring us closer to achieving the goal of personalized therapy for primary glomerular diseases. Moreover, promising renal outcome data with new classes of glucose-lowering agents — SGLT2 inhibitors and GLP-1 agonists — offer new hope for patients with diabetic nephropathy.

Kidney transplantation was the focus of numerous publications in 2016. Key studies demonstrated a survival advantage of HLA-incompatible kidney transplantation and suggested that novel approaches such as co-stimulation blockade using belatacept and treatment of antibody-mediated rejection using a C1 esterase inhibitor might prove to be future game changers.

The genetic background of many kidney diseases is complex and involves multiple genes, genetic variants and molecular pathways. Here, we look at how researchers tackled this challenging topic in 2016, focusing on studies that used ingenious data-integration tactics, which led to new insights into kidney disease aetiology and renal disease progression.

Tyrosine kinase inhibitors that target pro-angiogenic pathways improve progression-free and overall survival in patients with metastatic kidney cancer and were thus tested in the adjuvant setting in studies published this past year. 2016 also saw the emergence of new inhibitors of pro-angiogenic pathways that might represent the next step in kidney cancer therapy.

Blood pressure (BP) goals and the management of BP in patients with chronic kidney disease (CKD) remain controversial topics. Key articles in the past year have addressed BP goals in CKD, the use of new agents to slow CKD progression and the effects of visit-to-visit variability in systolic BP on cardiovascular events and renal progression in patients with CKD.

The year 2015 has seen great progress in the renal fibrosis field, as key studies began to build a consensus on the importance of epithelial-to-mesenchymal transition, cell cycle arrest, and defective metabolism in the pathogenesis of kidney fibrosis. New findings also point to a role of developmental signalling in renal fibrogenesis.

2015 saw the publication of several important studies in the renal stem cell and developmental biology fields. Key studies provided insights into the ageing of nephron progenitors and optimal conditions to stimulate the expansion of nephron progenitors, and reported the in vitro generation of kidney organoids.

Podocyte biologists can boast of some important advances in 2015. Some of the key developments include defining the transcriptional targets of the Wilms' tumour protein on a genome-wide scale, the identification of new mitochondria-centred pathways for maintaining podocyte homeostasis, and new insights into the regulation and pathogenic activation of TRPC6.

Combination therapy with optimal doses of multiple antihypertensive drugs fails to achieve blood pressure (BP) control in up to 15% of hypertensive patients. Key studies in 2015 highlighted the risks of uncontrolled hypertension and evaluated new therapeutic modalities designed to achieve satisfactory BP control in patients with treatment-resistant hypertension.

Numerous studies in 2015 focused on therapeutic immune modulation and immunosuppression. Trials of budenoside in patients with IgA nephropathy who are unresponsive to supportive therapy, and of low-dose IL-2 to enforce regulatory T-cell-mediated immunosuppression in autoimmune disease all produced promising results.

Knowledge of the pathogenesis of glomerular disease and approaches to therapy continued to advance in 2014. Key studies identified thrombospondin type-1 domain-containing protein 7A as an antigenic target in primary membranous nephropathy, and demonstrated efficacy of rituximab as maintenance therapy in relapsing or steroid-dependent nephrotic syndrome and antineutrophil cytoplasmic antibody-associated vasculitis.

In 2014, key articles in the field of acute kidney injury highlighted the importance of tubular homeostasis in renal regeneration. Cell cycle regulators, inflammatory signals and progenitors were identified as important factors that mediate the balance between inflammation and tubular regeneration necessary for renal repair.

Several studies published in 2014 might facilitate improvements in the treatment and long-term care of renal transplant recipients. The potential risks of living kidney donation, the efficacy and safety of alemtuzumab-based induction therapy, and the treatment of chronic hepatitis E virus infection have been addressed.

Chronic kidney disease (CKD) is an established independent risk factor for increased cardiovascular events and cardiovascular mortality. During 2014, several research efforts focused on clarifying the complex pathophysiology, assessing the prognostic associations and improving the treatment of cardiovascular disease in patients with CKD.

In 2014, key studies in the field of diabetic nephropathy highlighted the importance of albuminuria as a predictor of cardiovascular risk and showed that the incidence of renal and cardiovascular complications is decreasing. Promising efficacy data were obtained with atrasentan, whereas a trial of bardoxolone methyl led to safety concerns.

In 2013, four important papers were published that provide new insights on biomarkers in acute kidney injury (AKI). These studies demonstrate the potential for biomarkers to aid clinicians in improving the therapeutic management of patients with AKI and potentially improve patient outcomes.

In 2013, a key theme of research in renal transplantation was the diagnosis of rejection. Data from key studies published in the past year highlight aspects of rejection that warrant further investigation and should prompt the consideration of adjunctive tests to complement traditional histological assessment of allograft biopsy samples.

During 2013, a meta-analysis provided evidence that cystatin C improves estimated glomerular filtration rate in cardiovascular risk categorization in chronic kidney disease (CKD). Another study showed that low diastolic blood pressure (DBP) is harmful in patients with CKD, challenging the paradigm of treating elevated systolic blood pressure regardless of DBP. Overall, mortality rates in CKD have decreased but further improvement is required.

2013 saw the publication of numerous studies that identified resident renal stem or progenitor cells, induced pluripotent stem cells and strategies based on stem cell paracrine action, which all might be suitable for kidney regeneration after injury.

In 2013, substantial progress was made in uncovering the genetic basis of a variety of kidney and urological disorders, including congenital and developmental diseases. The new findings will lead to an increased understanding of the pathophysiology of these diseases, improved risk prediction and the development of novel therapies.