The glomerular endothelial glycocalyx (GEnGlx) forms the first part of the glomerular filtration barrier. Previously we showed that mineralocorticoid receptor (MR) activation caused GEnGlx damage and albuminuria. Here we investigated whether MR antagonism could limit albuminuria in diabetes and studied the site of action. Streptozotocin-induced diabetic Wistar rats developed albuminuria, increased glomerular albumin permeability (Ps'alb) and increased glomerular matrix metalloproteinase (MMP) activity with corresponding GEnGlx loss. MR antagonism prevented albuminuria progression, restored Ps'alb, preserved GEnGlx and reduced MMP activity. Enzymatic degradation of the GEnGlx negated the benefits of MR antagonism, confirming their dependence on GEnGlx integrity. Exposing human glomerular endothelial cells (GEnC) to diabetic conditions in vitro increased MMPs and caused glycocalyx damage. Amelioration of these effects confirmed a direct effect of MR antagonism on GEnC. To confirm relevance to human disease, we used a novel confocal imaging method to show loss of GEnGlx in renal biopsy specimens from patients with diabetic nephropathy (DN). In addition, DN patients randomised to receive an MR antagonist had reduced urinary MMP2 activity and albuminuria compared with placebo and baseline levels. Taken together our work suggests MR antagonists reduce MMP activity and thereby preserve GEnGlx resulting in reduced glomerular permeability and albuminuria in diabetes.

Understanding and communicating the risk of pregnancy complications post‐living kidney donation is imperative as the majority of living kidney donors (LKD) are women of childbearing age. We aimed to identify all original research articles examining complications in post‐donation pregnancies and compared the quality and consistency of related guidelines. We searched Embase, MEDLINE, PubMed, society webpages, and guideline registries for English‐language publications published up until December 18, 2020. Ninety‐three articles were screened from which 16 studies were identified, with a total of 1399 post‐donation pregnancies. The outcome of interest, post‐donation pregnancy complications, was not calculable, and only a narrative synthesis of the evidence was possible. The absolute risk of pre‐eclampsia increased from ~1%–3% pre‐donation (lower than the general population) to ~4%–10% post‐donation (comparable to the general population). The risks of adverse fetal and neonatal outcomes were no different between post‐donation and pre‐donation pregnancies. Guidelines and consensus statements were consistent in stating the need to inform LKDs of their post‐donation pregnancy risk, however, the depth and scope of this guidance were variable. While the absolute risk of pregnancy complications remains low post‐donation, a concerted effort is required to better identify and individualize risk in these women, such that consent to donation is truly informed.

The renin angiotensin aldosterone system is a key regulator of blood pressure. Aldosterone is the final effector of this pathway, acting predominantly via mineralocorticoid receptors. Aldosterone facilitates the conservation of sodium and, with it, water and acts as a powerful stimulus for potassium excretion. However, evidence for the pathological impact of excess mineralocorticoid receptor stimulation is increasing. Here, we discussed how in the heart, hyperaldosteronism is associated with fibrosis, cardiac dysfunction, and maladaptive hypertrophy. In the kidney, aldosterone was shown to cause proteinuria and fibrosis and may contribute to the progression of kidney disease. More recently, studies suggested that aldosterone excess damaged endothelial cells. Here, we reviewed how damage to the endothelial glycocalyx may contribute to this process. The endothelial glycocalyx is a heterogenous, negatively charged layer on the luminal surface of cells. Aldosterone exposure alters this layer. The resulting structural changes reduced endothelial reactivity in response to protective shear stress, altered permeability, and increased immune cell trafficking. Finally, we reviewed current therapeutic strategies for limiting endothelial damage and suggested that preventing glycocalyx remodelling in response to aldosterone exposure may provide a novel strategy, free from the serious adverse effect of hyperkalaemia seen in response to mineralocorticoid blockade.

Abstract.1. Density‐dependent phase polyphenism occurs when changes in density during the juvenile stages result in a developmental shift from one phenotype to another. Density‐dependent phase polyphenism is common among locusts (Orthoptera: Acrididae).2. Previously, we demonstrated a longitudinal geographic cline in adult body size (western populations = small adults; eastern populations = large adults) in the eastern lubber grasshopper (Romalea microptera) in south Florida. As lubbers are confamilial with locusts, we hypothesised that the longitudinal size cline was partly due to density‐dependent phase polyphenism.3. We tested the effect of density, population, and density×population interaction on life‐history traits (pronotum length, mass, cumulative development time, growth rate) of, and proportion surviving to, each of the five instars and the adult stage in a 2 × 3 factorial laboratory experiment with two lubber populations, each reared from hatchling to adult at three different densities.4. The effect of density on life history and survival was independent of the effects of population on life history and survival. Higher densities led to larger adult sizes (pronotum, mass) and lower survivorship. The western population had smaller adult masses, fewer cumulative days to the adult stage, and higher survivorship than the eastern population.5. Our data suggest that lubber grasshoppers exhibit density‐dependent phase polyphenism initiated by the physical presence of conspecifics. However, the plastic response of adult size to density observed in the laboratory is not consistent with the relationship between phenotypes and adult density in the field. Genetic differences between populations observed in the laboratory could contribute to size and life‐history differences among lubber populations in the field.