Aldosterone Rapidly Enhances Levels of the Striatin and Caveolin-1 Proteins in Rat Kidney: The Role of the Mineralocorticoid Receptor

BACKGROUND: Striatin and caveolin-1 (cav-1) are scaffolding/regulating proteins that are associated with salt-sensitive high blood pressure and promote renal sodium and water reabsorption, respectively. The mineralocorticoid receptor (MR) interacts with striatin and cav-1, while aldosterone increases striatin and cav-1 levels. However, no in vivo data have been reported for the levels of these proteins in the kidney. METHODS: Male Wistar rats were intraperitoneally injected with normal saline solution, aldosterone alone (Aldo: 150 µg/kg body weight), or aldosterone after pretreatment with eplerenone, an MR blocker, 30 minutes before the aldosterone injection (eplerenone [Ep.]+Aldo). Thirty minutes after the aldosterone injection, the amount and localization of striatin and cav-1 were determined by Western blot analysis and immunohistochemistry, respectively. RESULTS: Aldosterone increased striatin levels by 150% (P<0.05), and cav-1 levels by 200% (P<0.001). Eplerenone had no significant effect on striatin levels, but partially blocked the aldosterone-induced increase in cav-1 levels. Aldosterone stimulated striatin and cav-1 immunoreactivity in both the cortex and medulla. Eplerenone reduced cav-1 immunostaining in both areas; however, striatin intensity was reduced in the cortex, but increased in the medulla. CONCLUSION: This is the first in vivo study demonstrating that aldosterone rapidly enhances renal levels of striatin and cav-1. Aldosterone increases striatin levels via an MR-independent pathway, whereas cav-1 is partially regulated through MR.

Effects of vanadate and potassium depletion on renal H, K-ATPase protein expression

Background: Vanadate (V) inhibits while potassium (K) depletion stimulates collecting tubule H, K-ATPase activity. In the presence of V, K depletion could not restore the decreased H,K-ATPase activity. The effects of V and K depletion on renal H,K-ATPase protein expression might explain such observation.Objective: To examine the effects of V and K depletion on renal H,K-ATPase protein expression. Methods: Rats treated with normal saline solution (NSS) or V (5 mg/kg body weight) received either normal potassium (NK) or low potassium (LK) diet for 10 days. Protein expressions of renal H,K-ATPase \α₁ and \α₂ isoforms were determined by immunohistochemistry.Results: Both NK and LK animals treated with V had significantly increased vanadium levels in serum, urine, and renal tissues. LK diet caused hypokalemia. Animals treated with LK and V showed progressive hypokalemia. LK stimulated renal H,K-ATPase \α₁ protein expression in both cortex and medulla but enhanced H,K-ATPase \α₂ protein expression only in the cortex. Vanadate did not affect H,K-ATPase \α₁ protein expression in both NK and LK groups. Vanadate unaltered H,K-ATPase \α₂ protein expression in NK animals but could attenuate the increased expression in LK group.Conclusion: The magnitude of direct inhibitory effect of V on renal H,K-ATPase activity with small suppressive effect on protein expression is greater than the stimulatory effect of K depletion on H,K-ATPase activity and protein expression.

Beneficial effect of pioglitazone in proteinuric IgA nephropathy with concomitant ACEI/ARB treatment

Background: Proteinuria is a major predictor for renal progression in IgA nephropathy (IgAN). Thiazolidinediones were demonstrated to reduce proteinuria in patients with diabetic nephropathy.Objective: To investigate the effect of pioglitazone (PGZ) in proteinuric IgAN using randomized, double-blinded approach.Methods: Forty-one biopsy-proven IgAN patients with proteinuria (≥ 0.5g/day) who were currently treated with renin angiotensin system inhibitors and had at least two out of four risk factors for progressive disease (male gender, blood pressure \>150/90 mmHg, creatinine clearance of 20-80 mL/min/1.73m², and chronicity index \> 1) were randomly assigned to receive either PGZ 30 mg/day (PGZ group; n=21) or placebo (control group, n=20) for 16 weeks.Results: Baseline characteristics of patients in both groups were comparable. Following 16-week treatment, proteinuria in the PGZ group was significantly lower than the control group, [1.2 vs. 2.1 g/day (p \< 0.05)]. Patients in the PGZ group also showed a significant reduction in urinary excretion of TGF-β (from 361.4 to 234.4 ng/gCr) and VEGF (from 1353.1 to 765.1 ng/gCr) after 16-week treatment (p \< 0.05, both).Conclusion: PGZ significantly reduced proteinuria, urinary TGF-β, and urinary VEGF in IgAN patients. These findings suggest that PGZ could have a role in the treatment of proteinuric IgAN. Further studies with larger cases and longer follow-up time are warranted.

Mid-dilution on-line hemodiafiltration: technology and efficiency outcome

Background: The standard pre- and post-dilution methods of fluid substitution in on-line hemodiafiltration (OL-HDF) have limitations in removal of uremic toxins. Objective: To review the technique and efficiency outcomes of mid-dilution OL-HDF. Results: Mid-dilution OL-HDF could provide comparable or better efficiency with pre- and post-dilution modes. There are no serious adverse effects or technical complications. Conclusion: It appears that mid-dilution OL-HDF could combine the advantages and overcome the disadvantages of pre- and post-dilution modes.

Living-donor kidney transplantation across ABO barriers: the first case in Thailand

Background: Transplantation among ABO blood group incompatibility was considered an absolute contraindication until recent development of successful protocols. A living-donor across ABO barriers may provide another option for end-stage kidney disease patients. Objective: To report the first case of ABO-incompatible living-donor kidney transplantation (ABOi-LKT) in Thailand. Patients and method: The kidney transplantation across ABO barriers was performed following the Japanese recommended protocol. The kidney recipient was a thirty-four years old woman with blood group-O, whereas the kidney donor was her brother with blood group A. To reduce anti-donor (anti-blood group-A antibody) blood levels, the patient underwent double filtration plasmapheresis and received an intravenous anti-CD20 monoclonal antibody. A maintenance immunosuppressive regimen was similar to the one of ABO-compatible setting. Results: The kidney allograft had immediate good function. The transplantation was uneventful, and the patient went home within two weeks. Kidney allograft biopsies were performed on a protocol-driven basis at time-zero, the first and sixth month post-transplantation. Histologic studies showed unremarkable findings. The patient is now twelve months after transplantation and has achieved excellent kidney function. Conclusion: ABOi-LKT provides an alternative treatment for end-stage kidney disease patients. A multi-center study of ABOi-LKT in Thailand is ongoing, and this may change the national policy of organ donation in the near future.

Renal replacement therapy in patients with acute kidney injury: comparison of intermittent and continuous dialysis

Background: Despite dialysis being performed in critically ill patients for more than 30 years, it is still controversial whether intermittent or continuous dialysis yields superior end results. Objective: To compare intermittent renal replacement therapy (RRT) and continuous RRT to establish which is superior to the other in patients with acute kidney injury. Results: With respect to hemodynamic stability, continuous RRT seems to be superior to intermittent RRT although there are no significant differences between the two modalities in terms of survival and recovery of renal function. Conclusion: More severe patients might obtain greater benefit from continuous RRT while the less severe patients might take advantage from daily extended or intermittent dialysis.