Acute renal failure in pregnancy

Acute renal failure is a most challenging clinical problem when it occurs in pregnancy. It requires an understanding of the normal physiology of the kidney in pregnancy and the natural history of different underlying renal diseases when pregnancy occurs. Because patients with chronic renal disease may present with worsening proteinuria, hypertension, and renal function, these disorders must be excluded from those conditions that cause acute deterioration of renal failure in otherwise normal women during pregnancy. As in all patients who develop acute renal failure, prerenal and obstructive causes must be excluded. Particularly important causes of prerenal azotemia in pregnancy include hyperemesis gravidarum and uterine hemorrhage, especially if it is unsuspected as in abruptio placentae. Infectious causes of acute renal failure in the pregnant woman include acute pyelonephritis and septic abortion. The clinical presentation of both these conditions should be apparent, and appropriate diagnosis and treatment can then be promptly instituted. Renal cortical necrosis is another cause of renal failure that occurs more frequently in pregnancy, and it must be differentiated from the many causes of acute tubular necrosis that may be associated with pregnancy. Those conditions that cause renal failure unique to pregnancy must always be considered when renal function deteriorates in the last trimester or the postpartum period. Severe preeclampsia, acute fatty liver of pregnancy, and idiopathic postpartum acute renal failure may all present similar complications, but the approach to each of these clinical disorders must be individualized. By understanding the causes of renal functional deterioration in pregnancy, a logical differential diagnosis can be established, allowing appropriate therapeutic decisions to preserve both maternal and fetal well-being.     

Reliability and validity of a new classification of MIH based on severity

To describe a new molar-incisor hypomineralization (MIH) severity scoring system (MIH-SSS) that focuses on the defects’ severity and to assess the sy     

The effect of spironolactone on diastolic function in haemodialysis patients

Heart failure with preserved ejection fraction (HFpEF) is highly prevalent in patients on maintenance haemodialysis (HD) and lacks effective treatment. We investigated the effect of spironolactone on cardiac structure and function with a specific focus on diastolic function parameters. The MiREnDa trial examined the effect of 50 mg spironolactone once daily versus placebo on left ventricular mass index (LVMi) among 97 HD patients during 40 weeks of treatment. In this echocardiographic substudy, diastolic function was assessed using predefined structural and functional parameters including E/e’. Changes in the frequency of HFpEF were analysed using the comprehensive ‘HFA-PEFF score’. Complete echocardiographic assessment was available in 65 individuals (59.5?±?13.0 years, 21.5% female) with preserved left ventricular ejection fraction (LVEF?>?50%). At baseline, mean E/e’ was 15.2?±?7.8 and 37 (56.9%) patients fulfilled the criteria of HFpEF according to the HFA-PEFF score. There was no significant difference in mean change of E/e’ between the spironolactone group and the placebo group (+?0.93?±?5.39 vs.?+?1.52?±?5.94, p?=?0.68) or in mean change of left atrial volume index (LAVi) (1.9?±?12.3 ml/m² vs. 1.7?±?14.1 ml/m², p?=?0.89). Furthermore, spironolactone had no significant effect on mean change in LVMi (+?0.8?±?14.2 g/m² vs.?+?2.7?±?15.9 g/m²; p?=?0.72) or NT-proBNP (p?=?0.96). Treatment with spironolactone did not alter HFA-PEFF score class compared with placebo (p?=?0.63). Treatment with 50 mg of spironolactone for 40 weeks had no significant effect on diastolic function parameters in HD patients.

The trial has been registered at clinicaltrials.gov (NCT01691053; first posted Sep. 24, 2012).

     

Expression of hypoxia‐inducible factor‐1α and hepatocyte growth factor in development of fibrosis in the transplanted kidney

Late renal graft loss is associated with interstitial fibrosis. Hypoxia‐inducible factor‐1α (HIF‐1α) is thought to facilitate fibrosis through interaction with TGF‐β1, while hepatocyte growth factor (HGF) may act antifibrotic in the kidney allograft. The aim of this study was to investigate the expression of HIF‐1α and HGF in protocol biopsies as possible prognostic biomarkers for renal fibrosis. Thirty‐nine renal transplant recipients were included in the study. Protocol biopsies performed 1 and 2 years after transplantation were used for immunohistochemistry analysis. The correlation between HIF‐1α/HGF and the Banff score was analysed. In addition, progression in renal fibrosis and graft survival among recipients with high or low expression of HIF‐1α/HGF after transplantation was compared. There was no significant correlation between fibrosis and the HIF‐1α expression 1 and 2 years after transplantation, but an inverse significant correlation between the HGF expression and the fibrosis score 1 year after transplantation was shown. Even when adjusting for human leucocyte antigen mismatches, there was a significant relationship between fibrosis and HGF expression. Graft survival was not significantly correlated to HIF‐1α or HGF at 1 year, although the trend was towards better graft survival with high HGF. HGF may have antifibrotic effects in human renal transplants. (Central.Denmark.Region.Committee number: 1‐10‐72‐318‐13)     

Clonal dominance among T-lymphocyte infiltrates in arthritis

Synovial membranes in patients with rheumatoid arthritis as well as other types of chronic destructive inflammatory arthritis contain infiltrates of activated T lymphocytes that probably contribute to the pathogenesis of the disease. In an effort to elucidate the nature of these infiltrates, interleukin 2 (IL-2)-responsive T lymphocytes were grown out of synovial fragments from 14 patients undergoing surgery for advanced destructive inflammatory joint disease. Eleven of the samples examined were from patients with classical rheumatoid arthritis, while three others were obtained from individuals with clinical osteoarthritis. Southern blot analysis of T-cell receptor (TCR) beta-chain genes in 13 of 14 cultures showed distinct rearrangements, indicating that each culture was characterized by the predominance of a limited number of clones. T-cell populations from peripheral blood stimulated with a variety of activators and expanded with IL-2 did not demonstrate evidence of similar clonality in long-term culture. These results suggest that a limited number of activated T-cell clones predominate at the site of tissue injury in rheumatoid synovial membranes as well as in other types of destructive inflammatory joint disease. Further characterization of these T-cell clones may aid our understanding of the pathogenesis of these rheumatic disorders.     

A high-affinity, dimeric inhibitor of PSD-95 bivalently interacts with PDZ1-2 and protects against ischemic brain damage

Inhibition of the ternary protein complex of the synaptic scaffolding protein postsynaptic density protein-95 (PSD-95), neuronal nitric oxide synthase (nNOS), and the N-methyl-D-aspartate (NMDA) receptor is a potential strategy for treating ischemic brain damage, but high-affinity inhibitors are lacking. Here we report the design and synthesis of a novel dimeric inhibitor, Tat-NPEG4(IETDV)(2) (Tat-N-dimer), which binds the tandem PDZ1-2 domain of PSD-95 with an unprecedented high affinity of 4.6 nM, and displays extensive protease-resistance as evaluated in vitro by stability-measurements in human blood plasma. X-ray crystallography, NMR, and small-angle X-ray scattering (SAXS) deduced a true bivalent interaction between dimeric inhibitor and PDZ1-2, and also provided a dynamic model of the conformational changes of PDZ1-2 induced by the dimeric inhibitor. A single intravenous injection of Tat-N-dimer (3 nmol/g) to mice subjected to focal cerebral ischemia reduces infarct volume with 40% and restores motor functions. Thus, Tat-N-dimer is a highly efficacious neuroprotective agent with therapeutic potential in stroke.