Can Exercise during pregnancy protect against gestational diabetes?

Gestational diabetes complicates about 4-12% of the pregancies and puts baby’s and mothers at risk to develop both short- and long-term complications. The benefits of exercise to improve glucose metabolism have been well established in pre-diabetes patients but few studies have been performed on the safety and efficacy of structured exercise to improve maternal glucose tolerance and reduce maternal weight gain during pregnancy. A total of 83 healthy pregnant women were randomly assigned to either an exercise group (n=40) or a control group (n=43). Although no significant differences were observed in maternal weight gain, pregnancy outcome or cases of gestational diabetes, maternal glucose levels were significantly lower in the exercise intervention group. Interestingly, 3 cases of gestational diabetes were found in the control group, with none in the exercise group (p>0.05). Importantly, in the intervention group twice as many caesarian sections were reported, but this seemed to be related to more primiparous women. So, although this study is clearly underpowered to assess the risk-reduction for gestational diabetes, the improved glucose tolerance suggests a protective effect of structured exercise against gestational diabetes.


Exercise during pregnancy improves maternal glucose screen at 24–28 weeks: a randomised controlled trial


Objective The influence of an exercise programme performed by healthy pregnant women on maternal glucose tolerance was studied. Study design A physical activity (PA, land/aquatic activities) programme during the entire pregnancy (three sessions per week) was conducted by a qualified instructor. 83 healthy pregnant women were randomly assigned to either an exercise group (EG, n=40) or a control (CG, n=43) group. 50 g maternal glucose screen (MGS), maternal weight gain and several pregnancy outcomes were recorded. Results Significant differences were found between study groups on the 50 g MGS. Values corresponding to the EG (103.8±20.4 mg/dl) were better than those of the CG (126.9±29.5 mg/dl), p=0.000. In addition, no differences in maternal weight gain and no cases of gestational diabetes in EG versus 3 in CG (7%) (p>0.05) were found. Conclusion A moderate PA programme performed during pregnancy improves levels of maternal glucose tolerance.

Source: BMJ




Laser microdissection and mass spectrometry–based proteomics aids the diagnosis and typing of renal amyloidosis.

Accurate diagnosis and typing of renal amyloidosis is critical for prognosis, genetic counseling, and treatment. Laser microdissection and mass spectrometry are emerging techniques for the analysis and diagnosis of many renal diseases. Here we present the results of laser microdissection and mass spectrometry performed on 127 cases of renal amyloidosis during 2008–2010. We found the following proteins in the amyloid deposits: immunoglobulin light and heavy chains, secondary reactive serum amyloid A protein, leukocyte cell–derived chemotaxin-2, fibrinogen-α chain, transthyretin, apolipoprotein A-I and A-IV, gelsolin, and β-2 microglobulin. Thus, laser microdissection of affected areas within the kidney followed by mass spectrometry provides a direct test of the composition of the deposit and forms a useful ancillary technique for the accurate diagnosis and typing of renal amyloidosis in a single procedure.

Source: Kidney international





Mycophenolate and lower graft function reduce the seroresponse of kidney transplant recipients to pandemic H1N1 vaccination.

In late 2009 transplant organizations recommended that kidney recipients be vaccinated for pandemic H1N1 influenza (pH1N1); however, the vaccine efficacy was unknown. We had offered a monovalent non-adjuvanted pH1N1 vaccine to transplant recipients. Here we compared the pre- and post-vaccination seroresponses of 151 transplant recipients to that of 71 hemodialysis patients and 30 healthy controls. Baseline seroprotection was similar between groups but was significantly different at 1 month (44, 56, and 87%, respectively). Seroconversion was significantly less common for transplant recipients (32%) than dialysis patients (45%) and healthy controls (77%). After adjusting for age and gender, dialysis patients were significantly more likely (2.7-fold) to achieve new seroprotection than transplant recipients. The likelihood of seroprotection in transplant recipients was significantly reduced by mycophenolate use (adjusted odds ratio 0.24), in a dose-dependent manner, and by reduced eGFR (adjusted odds ratio 0.16 for worst to best). Seroprotection and geometric mean antibody titers increased substantially in 49 transplant recipients who subsequently received the 2010 seasonal influenza vaccine. Thus, patients requiring renal replacement therapy had reduced seroresponses to vaccination with the monovalent vaccine compared with healthy controls. Transplant recipient responses were further reduced if they were receiving mycophenolate or had significantly lower graft function.

Source: Kidney international




Poly(ADP-ribose) polymerase 1 activation is required for cisplatin nephrotoxicity.

Apoptosis, necrosis, and inflammation are hallmarks of cisplatin nephrotoxicity; however, the role and mechanisms of necrosis and inflammation remains undefined. As poly(ADP-ribose) polymerase 1 (PARP1) inhibition or its gene deletion is renoprotective in several renal disease models, we tested whether its activation may be involved in cisplatin nephrotoxicity. Parp1 deficiency was found to reduce cisplatin-induced kidney dysfunction, oxidative stress, and tubular necrosis, but not apoptosis. Moreover, neutrophil infiltration, activation of nuclear factor-κB, c-Jun N-terminal kinases, p38 mitogen-activated protein kinase, and upregulation of proinflammatory genes were all abrogated by Parp1 deficiency. Using proximal tubule epithelial cells isolated from Parp1-deficient and wild-type mice and pharmacological inhibitors, we found evidence for a PARP1/Toll-like receptor 4/p38/tumor necrosis factor-α axis following cisplatin injury. Furthermore, pharmacological inhibition of PARP1 protected against cisplatin-induced kidney structural/functional damage and inflammation. Thus, our findings suggest that PARP1 activation is a primary signal and its inhibition/loss protects against cisplatin-induced nephrotoxicity. Targeting PARP1 may offer a potential therapeutic strategy for cisplatin nephrotoxicity.

Source: Kidney international





Anti-DNA autoantibodies initiate experimental lupus nephritis by binding directly to the glomerular basement membrane in mice.

The strongest serological correlate for lupus nephritis is antibody to double-stranded DNA, although the mechanism by which anti-DNA antibodies initiate lupus nephritis is unresolved. Most recent reports indicate that anti-DNA must bind chromatin in the glomerular basement membrane or mesangial matrix to form glomerular deposits. Here we determined whether direct binding of anti-DNA antibody to glomerular basement membrane is critical to initiate glomerular binding of anti-DNA in experimental lupus nephritis. Mice were co-injected with IgG monoclonal antibodies or hybridomas with similar specificity for DNA and chromatin but different IgG subclass and different relative affinity for basement membrane. Only anti-DNA antibodies that bound basement membrane bound to glomeruli, activated complement, and induced proteinuria whether injected alone or co-injected with a non-basement-membrane–binding anti-DNA antibody. Basement membrane–binding anti-DNA antibodies co-localized with heparan sulfate proteoglycan in glomerular basement membrane and mesangial matrix but not with chromatin. Thus, direct binding of anti-DNA antibody to antigens in the glomerular basement membrane or mesangial matrix may be critical to initiate glomerular inflammation. This may accelerate and exacerbate glomerular immune complex formation in human and murine lupus nephritis.

Source: Kidney international




The intrinsic prostaglandin E2–EP4 system of the renal tubular epithelium limits the development of tubulointerstitial fibrosis in mice.

Inflammatory responses in the kidney lead to tubulointerstitial fibrosis, a common feature of chronic kidney diseases. Here we examined the role of prostaglandin E2 (PGE2) in the development of tubulointerstitial fibrosis. In the kidneys of wild-type mice, unilateral ureteral obstruction leads to progressive tubulointerstitial fibrosis with macrophage infiltration and myofibroblast proliferation. This was accompanied by an upregulation of COX-2 and PGE2 receptor subtype EP4 mRNAs. In the kidneys of EP4 gene knockout mice, however, obstruction-induced histological alterations were significantly augmented. In contrast, an EP4-specific agonist significantly attenuated these alterations in the kidneys of wild-type mice. The mRNAs for macrophage chemokines and profibrotic growth factors were upregulated in the kidneys of wild-type mice after ureteral obstruction. This was significantly augmented in the kidneys of EP4-knockout mice and suppressed by the EP4 agonist but only in the kidneys of wild-type mice. Notably, COX-2 and MCP-1 proteins, as well as EP4 mRNA, were localized in renal tubular epithelial cells after ureteral obstruction. In cultured renal fibroblasts, another EP4-specific agonist significantly inhibited PDGF-induced proliferation and profibrotic connective tissue growth factor production. Hence, an endogenous PGE2–EP4 system in the tubular epithelium limits the development of tubulointerstitial fibrosis by suppressing inflammatory responses.

Source: Kidney international



Hemodialysis effect on platelet count and function and hemodialysis-associated thrombocytopenia.

Substantial activation of platelets can occur in the course of hemodialysis. Platelet surface markers show evidence of platelet degranulation. Some activation occurs due to exposure of blood to the roller pump segment and microbubbles may play a role. Platelet activation seems to be reduced with reused dialyzers or with those containing synthetic versus cellulosic membranes. Nevertheless, a substantial degree of platelet activation can be demonstrated with polysulfone and other synthetic membranes; the amount of activation may differ substantially among polysulfone membranes, depending on the manufacturer and the polyvinylpyrrolidone content. Platelet–platelet and platelet–leukocyte aggregates have been detected in the dialyzer blood outflow line and the consequences of these to the microcirculation are unknown. Typically, the platelet count decreases slightly during the first hour of dialysis, but mostly returns to initial values by the end of dialysis. A number of chronic hemodialysis patient cases have been reported in which a marked decrease in platelet count (50% or more) during dialysis was observed, resulting in mild degrees of predialysis thrombocytopenia. In only one case was the decrease in platelet count associated with bleeding. Dialyzer hypersensitivity symptoms are infrequently associated with a fall in platelet count. Most recent cases of dialysis-associated thrombocytopenia have been with polysulfone membranes, especially polysulfone membranes sterilized by electron beam. The exact cause of these reactions remains unknown.

Source: Kidney international

Reprogramming the kidney: a novel approach for regeneration.

Nuclear reprogramming has reshaped stem cell science and created new avenues for cell-based therapies. The ability to bestow any given phenotype upon adult cells regardless of their origin is an exciting possibility. How can this powerful tool be harnessed for the treatment of kidney disease? Many approaches, including induced pluripotent stem cell (iPSC) production, direct lineage conversion, and reprogramming to a kidney progenitor, are now possible. Indeed, the generation of iPSC lines from adult kidney–derived cells has been successfully achieved. This, however, is just the beginning of the challenge. This review will discuss the fundamental concepts of transcription factor–based reprogramming in its various forms, highlighting recent advances in the field and how these are applicable to the kidney. The relative merits of each approach will be discussed in the context of what is a realistic and feasible strategy for kidney regeneration via reprogramming.

Source: Kidney international


EP4: a new piece in the fibrotic puzzle.

Most progressive and severe acute kidney diseases lead to renal fibrosis, for which we still lack effective treatment options. Prostaglandin E2 (PGE2) is one of the most abundant prostanoids, exerting its pleiotropic functions via four receptors, EP1 through EP4. Recent studies indicate that the PGE2–EP4 pathway is a potent endogenous renoprotective system that limits renal fibrosis by acting on multiple cellular targets.


Source: kidney International

Dietary sodium and clinical outcome in hemodialysis: where do we stand and what is next?

The association of dietary sodium and outcome is widely studied in the general population, but less is known in hemodialysis patients. The evidence supporting daily dietary sodium intake of 2 g on hemodialysis is not strong. Mc Causland et al. found that higher dietary sodium intake was marginally associated with a higher ultrafiltration requirement and mortality, but not with blood pressure. Well-designed clinical trials are needed to examine the association of dietary sodium modification and outcomes in hemodialysis patients.

Source: kidney International