Clinical evidence indicates that the melanocortin peptide ACTH is effective in inducing remission of nephrotic glomerulopathies like minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS), including those resistant to steroids. This suggests that a steroid-independent melancortinergic mechanism may contribute. However, the type of melanocortin receptor (MCR) that conveys this beneficial effect as well as the underlying mechanisms remain controversial. Burgeoning evidence suggests that MC5R is expressed in glomeruli and may be involved in glomerular pathobiology. This study aims to test the effectiveness of a novel highly selective MC5R agonist (MC5R-A) in puromycin aminonucleoside (PAN) nephrosis. Upon PAN injury, rats developed evident proteinuria on day 5, denoting an established nephrotic glomerulopathy. Following vehicle treatment, proteinuria continued to persist on day 14 with prominent histologic signs of podocytopathy, marked by ultrastructural glomerular lesions, including extensive podocyte foot process effacement. Concomitantly, there was loss of podocyte homeostatic markers, such as synaptopodin and podocin, and de novo expression of the podocyte injury marker desmin. Treatment with MC5R-A attenuated urine protein excretion and mitigated the loss of podocyte marker proteins, resulting in improved podocyte ultrastructural changes. In vitro in cultured podocytes, MC5R-A prevented the PAN-induced disruption of actin cytoskeleton integrity and apoptosis. MC5R-A treatment in PAN-injured podocytes also reinstated inhibitory phosphorylation and thus averted hyperactivity of GSK3β, a convergent point of multiple podocytopathic pathways. Collectively, pharmacologic activation of MC5R by using the highly selective small-molecule agonist is likely a promising therapeutic strategy to improve proteinuria and glomerular injury in protenuric nephropathies.

The average age of renal transplant recipients in the United States has increased over the past decade. The implications, however, have not been fully investigated. We explored predictors of success and demographic variables related to outcomes in elderly live donor transplantation. Retrospective analysis was performed using the UNOS database between 2001 and 2016. Donor characteristics and the graft failure rate of recipients above and below 70 years of age were compared across four eras: 2001‐2004, 2005‐2008, 2009‐2012, and 2013‐2016. There was a steady increase in average donor age from the first era to the fourth era (40‐44) which was more evident among the septuagenarian patients (43‐50) (P < .001). The 2‐year graft survival rate improved from 92% in the first era to 96% in the fourth era (P < .001), and this was also more prominent in the >70 population (87%‐93%) (P < .001). The >70 recipients were more likely to be non‐Hispanic white (80.1% vs 65.1%, P < .001) and male (70.1% vs 61.0% P < .001), respectively. The donors were more likely to be non‐Hispanic white and female in the >70 population. Live donation in the elderly is justified based on graft survival and patient survival. However, racial and gender differences exist in septuagenarian recipients and their donors.

The present study was performed to determine the ANG II‐dependence of distal nephron sodium reabsorption in Cyp1a1‐Ren2 transgenic rats [strain name: TGR(Cyp1a1‐Ren2)] with inducible ANG II‐dependent malignant hypertension. To assess distal nephron sodium reabsorptive function, we compared sodium excretion before and after blockade of the two main distal nephron sodium transporters by intravenous administration of amiloride (AMIL; 25 μg) plus bendroflumethiazide (BFTZ; 25 μg) in pentobarbital sodium‐anesthetized male Cyp1a1‐Ren2 transgenic rats (n=5). Cyp1a1‐Ren2 transgenic rats induced with 0.3% I3C for 8–10 days exhibited a markedly elevated mean arterial pressure (MAP; 185±5 vs. 131±3 mmHg, P<0.001) compared with non‐induced rats (n=5). Administration of AMIL+BFTZ did not alter MAP in either group, but elicited a greater increase in urinary sodium excretion in the non‐induced control rats than in the hypertensive rats (6.36±1.08 vs. 3.13±0.42 μEq/min, P<0.05). Distal nephron sodium delivery was not different between the two groups (7.43±1.41 vs. 5.24±0.86 μEq/min). However, absolute distal nephron sodium reabsorption and fractional reabsorption of distal nephron sodium delivery were markedly lower in the hypertensive rats than in the normotensive rats (3.13±0.42 vs. 6.36±1.08 μEq/min and 63.37±7.86 vs. 87.97±4.58 %, respectively, P<0.05 in both cases). These findings demonstrate that distal nephron sodium reabsorptive function is markedly decreased in Cyp1a1‐Ren2 rats with ANG II‐dependent malignant hypertension. Such impaired distal nephron sodium reabsorptive function suggests that ANG II‐dependent stimulation of distal nephron sodium reabsorption does not contribute substantively to the hypertension in these rats.

Outcomes of vaccination against SARS-COV-2 in organ transplant recipients are unclear. Recent studies have investigated outcomes for patients who are several years post-transplant. There hasn't been much data in peri-transplant patients. This is important because patients are highly immunosuppressed during this period due to induction immunosuppression and thus susceptible to infection. We looked at 6 patients who were transplanted at our center after receiving their first dose of mRNA vaccines. We assessed their antibody response after one, two and in a few cases, three doses of the vaccine. Two patients received their third booster dose, one of whom had a detectable antibody level after the third dose. We report that the overall antibody response to vaccination was weaker in transplant patients compared to the general population with a rapid attrition of antibody response over time. There is a need for more studies which follow-up antibody levels in transplant patients over time, especially those in the peri-transplant period to help guide the vaccination plan and frequency for immunosuppressed transplant patients.