News & Views in 2018

New findings implicate sodium transport in α-cell secretory dysfunction, leading to impaired counter-regulatory responses in diabetes. However, these findings also raise important questions about the tissue-specific roles of sodium transport and suggest that inhibitors of sodium transport may have potentially divergent roles in the pancreas, kidney and heart.

A new study discovered thousands of expression quantitative trait loci (eQTLs) in the renal glomerular and tubulointerstitial compartments and integrated these data with other omics data sets to identify genes with roles in the pathogenesis of chronic kidney disease. This report reinforces the necessity of using compartment-derived eQTLs to advance kidney genomic discovery.

The IDEAL-ICU study reports no mortality benefit of early versus delayed initiation of renal replacement therapy (RRT) in patients with early septic shock and acute kidney injury. In the delayed initiation group, 17% of patients required emergency RRT but more than one-third spontaneously recovered renal function and did not require RRT.

A genetic study using a Mendelian randomization approach provides evidence that albuminuria — as well as being the result of hypertension — might also cause hypertension and cardiometabolic disease. We suggest that a mechanism behind these findings could involve sodium retention by urinary protein-induced activation of the epithelial sodium channel in the distal tubule.

The polycystin complex structure has been solved at near-atomic resolution. Its surprising architecture provides new insights into the transient receptor potential (TRP) family of cation channels and the pathogenesis of autosomal dominant polycystic kidney disease. This discovery should have a transformative impact on the development of treatment strategies to cure the disease.

A new study reports that genome-wide polygenic risk scores can identify individuals at risk of common complex diseases, such as coronary artery disease or type 2 diabetes, with comparable performance to that of monogenic mutation screens. These findings support the potential clinical utility of genome-wide association study (GWAS)-based risk stratification; however, several issues need to be addressed before this approach can be applied to kidney disease.

The AWARD-7 trial shows that the glucagon-like peptide 1 (GLP1) receptor agonist dulaglutide, which is not cleared by the kidney, seems to be renoprotective, ameliorates albuminuria and slows estimated glomerular filtration rate decline in patients with type 2 diabetes mellitus and chronic kidney disease, without increasing the risk of hypoglycaemia.

A recent observational study reports that after cardiac surgery, clinical outcomes differ significantly between patients with the same stage of acute kidney injury (AKI) depending on the diagnosis criteria used: urine output, serum creatinine or both. This finding emphasizes the limitations of current criteria for AKI risk stratification and diagnosis.

Many considered the failure of the SYMPLICITY HTN-3 trial to represent the end of therapeutic renal denervation. However, promising preliminary data from the SPYRAL HTN-OFF MED study and more recently the SPYRAL HTN-ON MED and RADIANCE-HTN SOLO studies support the efficacy of this intervention for blood pressure lowering in patients with hypertension.

Cytoreductive nephrectomy is the current treatment paradigm for metastatic renal cell carcinoma (RCC). However, the introduction of targeted therapies has dramatically changed the treatment landscape and may limit the role of nephrectomy in this disease. The recent CARMENA trial supports initial medical treatment of patients with RCC and synchronous metastases.

Intensive lowering of blood pressure can decrease the risk of death and cardiovascular events in individuals with hypertension. However, a reanalysis of data from the SPRINT and ACCORD trials suggests that intensive blood pressure lowering increases the risk of chronic kidney disease.

Three reports from the TRACERx Renal study delineate the precise origin and evolution of clear cell renal cell carcinoma in minute detail. The insights gained from these studies might provide improved disease prognostics and identify novel therapeutic targets.

Technologies such as proteomics provide a snapshot of a specific cellular state but are unable to directly record successive signalling events. Two new CRISPR-mediated analogue multi-event recording apparatus (CAMERA) systems enable sequential recording of endogenous and exogenous signalling events by targeted DNA modifications, thereby allowing systematic interrogation of different cellular states.

A new subclassification of diabetes based on quantitative traits, including age, body mass index, insulin resistance and β-cell function suggests five clusters with distinct phenotypes and prognoses. This approach may offer a novel way to classify diabetes by providing more information on risks and potential therapeutic strategies.

An unbiased functional gene knockout screen to identify genes implicated in Hedgehog signalling in primary cilia detected most components of the ciliary machinery and ciliopathy-associated genes, but no kidney-related ciliopathy genes. The 472 hits are a tremendous resource for identifying potential ciliopathy genes and for analysing ciliary function and signalling pathways.

Two new clinical trials together involving nearly 30,000 patients support previous observational evidence that the most common solution used for intravenous fluid therapy in the world is associated with kidney damage. Both trials found that 0.9% saline was inferior to solutions with more physiological chloride concentrations and resulted in greater rates of major adverse kidney events.

A recent observational study reports that implantable cardioverter defibrillators were not associated with improved survival in patients with heart failure, reduced left ventricular ejection fraction and chronic kidney disease. Further studies are needed to identify which of these high-risk patients are most likely to benefit from this potentially life-saving therapy.

A genome-wide association study (GWAS) of quantitative traits that incorporated data from GWAS of complex diseases provides clues regarding the relationships between genetic loci, intermediate phenotypes and diseases. Together, the data demonstrate pleiotropy, genetic correlation and cell-type specificity of quantitative traits as predictors of multiple complex diseases.

Advances in precision medicine have greatly improved outcomes for patients with cancer. New findings that demonstrate a substantial contribution of major chronic diseases and disease markers to the risk of cancer incidence and mortality highlight the impact of chronic disease on cancer risk and suggest that chronic diseases should be targeted in cancer prevention strategies.

The cellular origins of angiomyolipoma and other tuberous sclerosis complex-associated neoplasms are unknown. Now, two studies show that these neoplasms derive from cancer stem cells that originate from multipotent renal epithelial cells. The new findings provide a link between stemness and tumorigenesis in the kidney.