PowerPoint Slides for: A Systematic Review and Meta-Analysis of Kidney and Pregnancy Outcomes in IgA Nephropathy

<i>Background:</i> The outcomes of pregnancy in immunoglobulin A nephropathy (IgAN) remain controversial. We sought to evaluate the effect of pregnancy on the progression of IgAN as well as the impact of IgAN on pregnancy outcomes. <i>Methods:</i>We systematically searched MEDLINE, Embase for cohort or case-control studies. OR reductions were calculated with a random-effects model, and kidney outcomes and adverse pregnancy events were analyzed. <i>Results:</i> Our literature search returned 652 relevant articles; 4 studies were included, providing data of 376 pregnancies in 273 patients with IgAN and that of 241 IgAN who did not become pregnant. Four hundred sixty seven patients with chronic kidney disease stages 1-2 were included. Pregnancy in patients with IgAN did not increase the risk of adverse renal events including doubling of serum creatinine, 50% decline in glomerular filtration rate (GFR) and end-stage kidney disease (OR 0.97, 95% CI 0.55-1.70; p = 0.90; I2 = 0.0%, p = 0.79). There was no significant difference in the change in estimated GFR at the end of follow-up in the pregnant and non-pregnant groups (weighted mean difference 0.1 ml/min/1.73 m2 (95% CI -4.85 to 5.04 ml/min/1.73 m2), p = 0.97; I2 = 0%, p = 0.95). Women with IgAN had high rates of infant loss (12.2, 7.4-19.4%), preterm delivery (8.5, 5.9-12.1%), low birth weight (9.5, 6.7-13.3%), and preeclampsia/severe preeclampsia (7.3, 4.9-10.6%). <i>Conclusions:</i> Pregnancy in IgAN patients with preserved kidney function did not accelerate deterioration of renal function. But pregnant women with IgAN are at higher risk of pregnancy complications

Supplementary Material for: The Inhibitory Effect of Eplerenone on Cell Proliferation in the Contralateral Kidneys of Rats with Unilateral Ureteral Obstruction

<p><b><i>Background:</i></b> The unilateral ureteral obstruction (UUO) model not only induces renal interstitial fibrosis in the obstructed kidney but also induces injury in the contralateral kidney. We hypothesized that activation of the mineralocorticoid receptor (MR) may induce fibrosis in the early stage of UUO. <b><i>Methods:</i></b> Thirty male Sprague-Dawley rats weighting 200 ± 10 g were used in this study and randomly divided into 3 groups: a UUO group, a UUO and eplerenone group, and a sham group. The contralateral kidney and plasma were harvested for further study 10 days after surgery. <b><i>Results:</i></b> The level of plasma aldosterone (869.95 ± 55.851 pg/mL) was significantly higher in the UUO group than that in the sham group (478.581 ± 36.186 pg/mL vs. UUO, <i>p</i> < 0.05). The infiltrated inflammatory cells (F4/80) and deposited collagens were increased significantly in the contralateral kidneys in the UUO group compared to those in the sham group, which were decreased by eplerenone. However, proliferating cell nuclear antigen was increased 2.47 times in the UUO group compared to the sham group in the contralateral kidney (<i>p</i> < 0.01), and those changes are attenuated by eplerenone. The expression of SGK-1 protein and mRNA was upregulated in the contralateral kidney in the UUO group, which is suppressed by eplerenone treatment. NF-κB pathway effecters were also changed markedly in the contralateral kidney in the UUO group and partly reversed by eplerenone. <b><i>Conclusion:</i></b> Aldosterone induces inflammatory cell proliferation via the MR/SGK-1 and NF-κB pathways and eventually leads to fibrosis in the contralateral kidney.</p

Supplementary Material for: Na⁺-Leak Channel, Non-Selective (NALCN) Regulates Myometrial Excitability and Facilitates Successful Parturition

<b><i>Background/Aims:</i></b> Uterine contractility is controlled by electrical signals generated by myometrial smooth muscle cells. Because aberrant electrical signaling may cause inefficient uterine contractions and poor reproductive outcomes, there is great interest in defining the ion channels that regulate uterine excitability. In human myometrium, the Na⁺ leak channel, non-selective (NALCN) contributes to a gadolinium-sensitive, Na⁺-dependent leak current. The aim of this study was to determine the role of NALCN in regulating uterine excitability and examine its involvement in parturition. <b><i>Methods:</i></b> Wildtype C57BL/6J mice underwent timed-mating and NALCN uterine expression was measured at several time points across pregnancy including pregnancy days 7, 10, 14, 18 and 19. Sharp electrode current clamp was used to measure uterine excitability at these same time points. To determine NALCN’s contribution to myometrial excitability and pregnancy outcomes, we created smooth-muscle-specific NALCN knockout mice by crossing NALCN<i>fx/fx</i> mice with myosin heavy chain Cre (MHC<i>CreeGFP</i>) mice. Parturition outcomes were assessed by observation via surveillance video recording cre control, flox control, smNALCN^+/-, and smNALCN^-/- mice. Myometrial excitability was compared between pregnancy day 19 flox controls and smNALCN^-/- mice. <b><i>Results:</i></b> We found that in the mouse uterus, NALCN protein levels were high early in pregnancy, decreased in mid and late pregnancy, and then increased in labor and postpartum. Sharp electrode current clamp recordings of mouse longitudinal myometrial samples from pregnancy days 7, 10, 14, 18, and 19 revealed day-dependent increases in burst duration and interval and decreases in spike density. NALCN smooth muscle knockout mice had reduced myometrial excitability exemplified by shortened action potential bursts, and an increased rate of abnormal labor, including prolonged and dysfunctional labor. <b><i>Conclusions:</i></b> Together, our findings demonstrate that the Na⁺ conducting channel NALCN contributes to the myometrial action potential waveform and is important for successful labor outcomes

Supplementary Material for: rs4711751 and rs1999930 Are Not Associated with Neovascular Age-Related Macular Degeneration or Polypoidal Choroidal Vasculopathy in the Chinese Population

<b><i>Purpose:</i></b> rs1999930 and rs4711751 have recently been identified as novel variants associated with advanced age-related macular degeneration (AMD) in populations of European ancestry. We aimed to investigate whether these two single nucleotide polymorphisms (SNPs) were associated with neovascular AMD (nAMD) or with polypoidal choroidal vasculopathy (PCV), a variant of AMD in Asians, using a Chinese case-control study. <b><i>Methods:</i></b> A total of 900 subjects, including 300 controls, 300 cases with nAMD and 300 cases with PCV, were included in the present study. Genomic DNA was extracted from venous blood leukocytes. The allelic variants of rs1999930 and rs4711751 were determined by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. The differences in allele distribution between cases and controls were tested by a χ² test, with additional adjustments for age and gender using logistic regression. The statistical power was also calculated. Values of p < 0.05 were considered statistically significant. <b><i>Results:</i></b> No statistically significant association was observed between the two polymorphisms of nAMD or PCV phenotype (p > 0.05 for all comparisons). The difference remained insignificant after correction for age and gender (p > 0.05 for all comparisons). The statistical powers to detect the association between these two SNPs and nAMD or PCV range from 0.05 to 0.36, assuming conventional levels of statistical significance. <b><i>Conclusions:</i></b> In the present study, we could not replicate the reported association of these two SNPs and either nAMD or PCV in a Chinese population, suggesting that they are unlikely to be a major AMD and PCV susceptibility gene locus in the Chinese population. Considering the low power value, a large sample size is required to draw more reliable conclusions