The burden of diabetes mellitus is relentlessly increasing. Diabetic nephropathy is the most common cause of end-stage renal disease (ESRD) worldwide and a major cause of morbidity and mortality in patients with diabetes. The current standard therapy of diabetic nephropathy involves intensive treatment of hyperglycemia and strict blood pressure control, mainly via blockade of the renin-angiotensin system (RAS). Attention has been drawn to additional beneficial effects of oral hypoglycemic drugs and fibrates on other aspects of diabetic nephropathy. On the other hand, antiproteinuric effects of RAS combination therapy do not seem to enhance the prevention of renal disease progression, and it has been associated with an increased rate of serious adverse events. Novel agents, such as bardoxolone methyl, pentoxifylline, inhibitors of protein kinase C (PKC), sulodexide, pirfenidone, endothelin receptor antagonists, vitamin D supplements, and phosphate binders have been associated with controversial outcomes or significant side effects. Although new insights into the pathogenetic mechanisms have opened new horizons towards novel interventions, there is still a long way to go in the field of DN research. The aim of this review is to highlight the recent progress made in the field of diabetes management based on the existing evidence. The article also discusses novel targets of therapy, with a special focus on the major pathophysiologic mechanisms implicated in the initiation and progression of diabetic nephropathy.
Background: Hemodiafiltration with online preparation of the substitution [online high-flux hemodiafiltration (OHDF)] and hemodiafiltration with prepared bags of substitution (HDF) are important, recently widely used renal replacement therapies in patients with end-stage renal disease. However, there is little information on the comparative impacts of these modalities versus conventional low-flux hemodialysis (HD) on the quality of life (QoL) of HD patients. This study investigates the effect of dialysis modality on QoL in chronic HD patients. Methods: In this prospective, randomized, cross-over, open label study, 24 patients were enrolled. Their age were 62 AE 13.34 years (mean AE SD), with the duration of dialysis of 31 AE 23.28 months (mean AE SD). Five of the patients were women. QoL was measured by the Short-Form Health Survey with 36 questions (SF-36) and subscale scores were calculated. Each patient received HD, OHDF, and HDF for 3 months, with the dialysis modality subsequently being altered. They completed the questionnaire of QoL at the end of each period. Results: There were statistical significant differences in QoL for the total .7) and 40.7 (30.2-62.8)], for classic low-flux HD and high-flux hemodiafiltration, for bodily pain [45 (26.9-66.9) and 55 (35.6-87.5)], and for role limitations due to emotional functioning [0 (0-33.3) and 33.3 (0-100)], respectively. The scores did not differ significantly between the two types of hemodiafiltration. Conclusions: Our study indicates that QoL differs significantly among patients receiving low-flux HD and high-flux hemodiafiltration, on total SF-36, bodily pain, and role limitations due to emotional functioning. Convective modalities may offer better QoL than diffusive HD.
We studied the concentration of serum estradiol and serum and follicular fluid leptin in 200 women undergoing their first in vitro fertilization with embryo transfer (IVF-ET) program at the time of human chorionic gonadotrophin administration and oocyte retrieval, in an attempt to assess their concerted role on embryo quality and the prognosis of IVF outcome. Low serum (46.49 6 8.4 ng/ml) and follicular fluid (52 6 9.8 ng/ml) leptin levels were associated with a high number of 'good-quality' embryos (73.6%) and high implantation (11.2%) and pregnancy (35.8%) rates and were observed in women with normal peak estradiol levels of between 1000 and 2000 pg/ml. It appears that leptin and estradiol interact coordinately in a concentration-dependent manner to control IVF outcome. Further studies will be required to substantiate and clarify the mechanism of proposed conditional interaction between the two hormonal systems.
Vascular access (VA) survival is a crucial issue associated with morbidity and mortality of patients undergoing maintenance hemodialysis. The development of stenosis is the major factor that leads to VA failure. Strategies for early detection of lesions within a VA system before serious complications arise are therefore crucial. The implementation of a VA surveillance program could lead to timely detection of VA dysfunction and referral for correction, reduction in central venous catheter use and decrease in hospitalization and VA-related cost. Suggested methods for arteriovenous fistulae and grafts surveillance include blood flow measurement, static pressure evaluation and duplex ultrasonography. Physical examination is an accepted method in contrast to nonstandardized dynamic pressure measurement for grafts. Access recirculation (not urea based) and dynamic pressure measurements are accepted methods for fistulae. Decreasing URR or Kt/V (otherwise unexplained) and increased (negative) arterial pressure in the dialysis machine are methods of limited sensitivity and specificity for both fistulae and grafts. Measurement of access blood flow has been proposed as the gold standard for the screening of all types of VA. Access flow can be measured by various techniques which are direct or indirect. Several studies about VA surveillance programs have demonstrated conflicting results. Larger, randomized controlled trials need to be carried out in order to clarify whether surveillance programs are necessary and which is the best surveillance strategy for each type of VA.
The use of Automated Peritoneal Dialysis (APD) in its various forms has increased over the past few years mainly in developed countries. This could be attributed to improved cycler design, apparent lifestyle benefits and the ability to achieve adequacy and ultrafiltration targets. However, the dilemma of choosing the superior modality between APD and Continuous Ambulatory Peritoneal Dialysis (CAPD) has not yet been resolved. When it comes to fast transporters and assisted PD, APD is certainly considered the most suitable Peritoneal Dialysis (PD) modality. Improved patients' compliance, lower intraperitoneal pressure and possibly lower incidence of peritonitis have been also associated with APD. However, concerns regarding increased cost, a more rapid decline in residual renal function, inadequate sodium removal and disturbed sleep are APD's setbacks. Besides APD superiority over CAPD in fast transporters, the other medical advantages of APD still remain controversial. In any case, APD should be readily available for all patients starting PD and the most important indication for its implementation remains patient's choice.
We aimed to investigate the possible association of the inactive, dephosphorylated, uncarboxylated matrix Gla protein (dp-ucMGP) with oxidized low-density lipoprotein (ox-LDL) and all-cause/cardiovascular (CV) mortality and renal function in diabetic chronic kidney disease (CKD). Ox-LDL and dp-ucMGP were determined in 66 diabetic CKD patients. All patients were prospectively followed for seven years, or until the occurrence of death, or a composite renal outcome of 30% estimated glomerular filtration rate (eGFR) reduction or progression to end-stage renal disease (ESRD) requiring dialysis occurred. Secondary outcomes were the occurrence of CV events. Kaplan–Meier curves showed that patients with plasma dp-ucMGP levels above the median (≥656 pM) had a significantly higher risk for all study endpoints. After adjustment for several well-known cofounders, multivariate Cox analysis showed that high plasma dp-ucMGP levels were associated with all-cause mortality (Hazard ratio-HR = 2.63, 95% Confidence Interval-CI = 1.17–5.94, p = 0.02), CV mortality (HR = 2.82, 95% CI = 1.07–7.49, p = 0.037) and progression of CKD (HR = 4.02, 95% CI = 1.20–13.46, p = 0.024). Circulating dp-ucMGP is associated with mortality and decreased renal function in diabetic CKD.
The response of intraocular pressure (IOP) to hemodialysis procedure has been a subject of research throughout many decades. Several studies that evaluated the impact of hemodialysis (HD) on IOP have reported conflicting results and have drawn varied conclusions. Some studies have described an IOP elevation during HD, a finding they attributed to the osmotic disequilibrium between serum and aqueous humor induced by the HD procedure, especially when the facility of the outflow system is already compromised. On the other hand, several studies have reported a significant IOP decrease during HD. The majority of these studies supported the notion that the increase in plasma colloid pressure induced by fluid removal during the HD session is the underlying cause of decreased IOP. Finally, recent investigations did not establish a significant change in IOP measurements during HD. They have therefore suggested that improved dialysis techniques, such as high-flux HD, or hemofiltration and better urea control, maintain better osmolar balance and prevent a marked IOP elevation. Nevertheless, specific preventive measures are still necessary in HD patients with ocular pathologies (e.g., glaucoma) whose vision may be adversely influenced by significant IOP fluctuation.
Renal adaptation in space has been studied during various space missions since the early 70s. Technical and financial disadvantages of performing experiments under real microgravity conditions have warranted the conductance of relative studies under simulated weightlessness on earth. Arriving in microgravity leads to a redistribution of body fluids to the upper part of the body and an exaggerated extravasation very early in-flight. Plasma volume as well as skin evaporation and oral hydration are reduced, while total body water seems to remain stable. Urinary sodium is diminished and a substantial amount of sodium is retained outside the intravascular space. Glomerular filtration rate shows a transient mild increase. Urinary albumin excretion is reduced although initial studies had demonstrated the opposite. Examination of renal histopathology after exposure to simulated microgravity in rats revealed glomerular atrophy, interstitial edema, and degeneration of renal tubular cells. Acute urinary retention which has been reported during spaceflights can lead to certain medical complications that could compromise an entire mission. Kidney stone formation is another important potential hazard for any manned spaceflight. Increased kidney stone formation in space is attributed to several factors including reduced fluid intake, hypercalciuria, and the presence of nanobacteria. Nutritional and pharmacological interventions are currently recommended as preventive measures against renal stone formation in space travelers.
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