Concept: Diabetic nephropathy
Clinical and experimental studies have shown that sodium glucose co-transporter 2 inhibitors (SGLT2i) contribute to the prevention of diabetic kidney disease progression. In order to clarify its pharmacological effects on the molecular mechanisms underlying the development of diabetic kidney disease, we administered different doses of the SGLT2i, ipragliflozin, to type 2 diabetic mice. A high-dose ipragliflozin treatment for 8 weeks lowered blood glucose levels and reduced urinary albumin excretion. High- and low-dose ipragliflozin both inhibited renal and glomerular hypertrophy, and reduced NADPH oxidase 4 expression and subsequent oxidative stress. Analysis of glomerular phenotypes using glomeruli isolation demonstrated that ipragliflozin preserved podocyte integrity and reduced oxidative stress. Regarding renal tissue hypoxia, a short-term ipragliflozin treatment improved oxygen tension in the kidney cortex, in which SGLT2 is predominantly expressed. We then administered ipragliflozin to type 1 diabetic mice and found that high- and low-dose ipragliflozin both reduced urinary albumin excretion. In conclusion, we confirmed dose-dependent differences in the effects of ipragliflozin on early diabetic nephropathy in vivo. Even low-dose ipragliflozin reduced renal cortical hypoxia and abnormal hemodynamics in early diabetic nephropathy. In addition to these effects, high-dose ipragliflozin exerted renoprotective effects by reducing oxidative stress in tubular epithelia and glomerular podocytes.
Background Combination therapy with angiotensin-converting-enzyme (ACE) inhibitors and angiotensin-receptor blockers (ARBs) decreases proteinuria; however, its safety and effect on the progression of kidney disease are uncertain. Methods We provided losartan (at a dose of 100 mg per day) to patients with type 2 diabetes, a urinary albumin-to-creatinine ratio (with albumin measured in milligrams and creatinine measured in grams) of at least 300, and an estimated glomerular filtration rate (GFR) of 30.0 to 89.9 ml per minute per 1.73 m(2) of body-surface area and then randomly assigned them to receive lisinopril (at a dose of 10 to 40 mg per day) or placebo. The primary end point was the first occurrence of a change in the estimated GFR (a decline of ≥30 ml per minute per 1.73 m(2) if the initial estimated GFR was ≥60 ml per minute per 1.73 m(2) or a decline of ≥50% if the initial estimated GFR was <60 ml per minute per 1.73 m(2)), end-stage renal disease (ESRD), or death. The secondary renal end point was the first occurrence of a decline in the estimated GFR or ESRD. Safety outcomes included mortality, hyperkalemia, and acute kidney injury. Results The study was stopped early owing to safety concerns. Among 1448 randomly assigned patients with a median follow-up of 2.2 years, there were 152 primary end-point events in the monotherapy group and 132 in the combination-therapy group (hazard ratio with combination therapy, 0.88; 95% confidence interval [CI], 0.70 to 1.12; P=0.30). A trend toward a benefit from combination therapy with respect to the secondary end point (hazard ratio, 0.78; 95% CI, 0.58 to 1.05; P=0.10) decreased with time (P=0.02 for nonproportionality). There was no benefit with respect to mortality (hazard ratio for death, 1.04; 95% CI, 0.73 to 1.49; P=0.75) or cardiovascular events. Combination therapy increased the risk of hyperkalemia (6.3 events per 100 person-years, vs. 2.6 events per 100 person-years with monotherapy; P<0.001) and acute kidney injury (12.2 vs. 6.7 events per 100 person-years, P<0.001). Conclusions Combination therapy with an ACE inhibitor and an ARB was associated with an increased risk of adverse events among patients with diabetic nephropathy. (Funded by the Cooperative Studies Program of the Department of Veterans Affairs Office of Research and Development; VA NEPHRON-D ClinicalTrials.gov number, NCT00555217 .).
The waiting list for kidney transplantation is long and growing. The creation of “vouchers” for future kidney transplants enables living donation to occur when optimal for the donor and transplantation to occur later, when and if needed by the recipient.
ACE Inhibitors (ACE-I) and Angiotensin-Receptor Antagonists (ARAs) are commonly prescribed but can cause acute kidney injury (AKI) during intercurrent illness. Rates of hospitalization with AKI are increasing. We aimed to determine whether hospital AKI admission rates are associated with increased ACE-I/ARA prescribing.
Abstract Objective. Many patients experience problems with sexual functioning after renal transplantation (RTx). Research on the sexual functioning of the partners of those patients and the consequences for relationship satisfaction and quality of life is lacking. This study sought to explore changes in sexual and relationship functioning from before to after RTx in patients and their partners. Material and methods. Twenty-nine patients (mean ± SD age 53.4 ± 14.2 years) and 13 partners (age 57.1 ± 11.6 years) provided data 12-15 months after RTx. They retrospectively evaluated sexual and relationship functioning as well as general life satisfaction before RTx and, in comparison, in the most recent months. Results. Among the patients, most items on sexual experience indicated deterioration in sexual functioning. Among their partners, the wish for sexual activity with the patient and the actual frequency of sexual activity decreased from before to after RTx. The rate of partners indicating high personal importance for intercourse decreased from 83.3% to 69.2%, as did the rate of partners stating high sexual satisfaction (from 63.6% to 41.7%). Despite these trends, most patients and partners reported high relationship and life satisfaction after RTx. Conclusions. Partners of patients who had received a kidney transplant seem to be affected by negative changes in the patients' sexual functioning. Nonetheless, many couples maintain high relationship and life satisfaction.
Podocyte injury plays a key role in the development of diabetic nephropathy (DN). We have recently shown that 11R-VIVIT, a cell-permeable nuclear factor of activated T cells (NFAT) inhibitor, abrogated podocyte apoptosis induced by high glucose in vitro, however, whether or not 11R-VIVIT has a protective effect on DN, especially for podocyte injury, under in vivo diabetic conditions is still unknown. This study examined the renoprotective effects of 11R-VIVIT in diabetic db/db mice. In addition, the possible mechanisms underlying the protective effects of 11R-VIVIT on podocyte injury were also investigated in these experimental animal models and in cultured podocytes.
: Since 2007, a number of transplantation centers have been routinely using an expert system for tacrolimus (TAC) dose adjustment in kidney allograft recipients, based on PK modeling and Bayesian estimation for area-under-the-curve (AUC) determination. This has allowed the setting up of a large database of TAC pharmacokinetic profiles and AUC values, a part of which was analyzed here.
We previously performed a preliminary 6-month controlled trial to examine the effect of a disease management education program on prolongation of the time to renal replacement therapy (RRT) and/or avoidance of RRT for patients with diabetic nephropathy. However, its duration was too short to follow the changes of renal function, so we performed the present study for 24 months.
Kidney transplantation in hiv-positive patients treated with a steroid-free immunosuppressive regimen
- Transplant international : official journal of the European Society for Organ Transplantation
- Published over 4 years ago
One of the main concerns associated with renal transplantation in HIV-infected patients is the high risk of acute rejection, which makes physicians reluctant to use steroid-free immunosuppressive therapy in this subset of patients. However, steroid therapy increases cardiovascular morbidity and mortality. The aim of this study was to define the efficacy of a steroid-sparing regimen in HIV-infected renal transplant recipients.
Predictors of Atrasentan-Associated Fluid Retention and Change in Albuminuria in Patients with Diabetic Nephropathy
- Clinical journal of the American Society of Nephrology : CJASN
- Published over 3 years ago
Endothelin A receptor antagonists (ERAs) decrease residual albuminuria in patients with diabetic kidney disease; however, their clinical utility may be limited by fluid retention. Consequently, the primary objective of this study was to identify predictors for ERA-induced fluid retention among patients with type 2 diabetes and CKD. A secondary objective was to determine if the degree of fluid retention necessarily correlated with the magnitude of albuminuria reduction in those patients receiving ERAs.