scholarly journals Kidney Injury Caused by Preeclamptic Pregnancy Recovers Postpartum in a Transgenic Rat Model

2021 ◽  
Vol 22 (7) ◽  
pp. 3762
Author(s):  
Sarah M. Kedziora ◽  
Kristin Kräker ◽  
Lajos Markó ◽  
Julia Binder ◽  
Meryam Sugulle ◽  
...  

Preeclampsia (PE) is characterized by the onset of hypertension (≥140/90 mmHg) and presence of proteinuria (>300 mg/L/24 h urine) or other maternal organ dysfunctions. During human PE, renal injuries have been observed. Some studies suggest that women with PE diagnosis have an increased risk to develop renal diseases later in life. However, in human studies PE as a single cause of this development cannot be investigated. Here, we aimed to investigate the effect of PE on postpartum renal damage in an established transgenic PE rat model. Female rats harboring the human-angiotensinogen gene develop a preeclamptic phenotype after mating with male rats harboring the human-renin gene, but are normotensive before and after pregnancy. During pregnancy PE rats developed mild tubular and glomerular changes assessed by histologic analysis, increased gene expression of renal damage markers such as kidney injury marker 1 and connective-tissue growth factor, and albuminuria compared to female wild-type rats (WT). However, four weeks postpartum, most PE-related renal pathologies were absent, including albuminuria and elevated biomarker expression. Only mild enlargement of the glomerular tuft could be detected. Overall, the glomerular and tubular function were affected during pregnancy in the transgenic PE rat. However, almost all these pathologies observed during PE recovered postpartum.

Hypertension ◽  
2020 ◽  
Vol 76 (Suppl_1) ◽  
Author(s):  
Sarah M Kedziora ◽  
Kristin Kraeker ◽  
Lajos Markó ◽  
Dominik N Mueller ◽  
Ralf Dechend ◽  
...  

Preeclamptic pregnancies involve mild renal injuries. However, there has been evidence that women with a history of preeclampsia (PE) have an increased risk to develop kidney disease in association to high blood pressure later in life. This study aims to characterize renal injury during pregnancy and postpartum in an established transgenic rat model for PE. Female Sprague-Dawley rats transgenic for the human angiotensinogen gene develop a PE phenotype in pregnancy, including cardiac remodeling, when mated with male rats harboring the human renin gene. Postpartum, blood pressure restores but cardiac remodeling persists. We hypothesize that PE during pregnancy mediates kidney injuries but does not fully restore after ending of the high blood pressure (postpartum). The renal alterations were analyzed by histological staining, gene expression and urine analysis. PE rats have elevated mean arterial blood pressure during pregnancy (PE d19 148.4 ± 20.7 mmHg) compared to normotensive values in control animals (WT d19 105.3 ± 4.6 mmHg). During PE increased expression of kidney injury marker 1 ( Kim-1/18S : PE d21 4.14 ± 3.26; WT d21 0.08 ± 0.02), neutrophil gelatinase associated lipocalin 2 ( Ngal/18S : PE d21 1.64 ± 0.83; WT d21 0.59 ± 0.28) and connective-tissue growth factor ( Ctgf/18S: PE d21 1.51 ± 0.46; WT d21 0.92 ± 0.32) were detected. Kidneys of PE rats showed mild glomerular (PAS-positive glomerular area PE d21 86.2 ± 4.4%; WT d21 79.1 ± 3.2%) and tubular changes during PE pregnancy resulting in albuminuria (albumin/creatinine ratio PE d19 2193.8 ± 1878.2; WT d19 290.4 ± 252.0). However, 4 weeks after pregnancy (approx. 2 years in humans) most of the PE related renal damages were absent including albuminuria and elevated expression of biomarkers ( Kim-1/18S : PE d50 0.09 ± 0.05; WT d50 0.23 ± 0.13; Ctgf/18S : PE d50 0.78 ± 0.25; WT d50 0.8 ± 0.25; Ngal/18S : PE d50 0.37 ± 0.17; WT 50 0.47 ± 0.11). Only mild enlargement of glomerular tuft area (PE d50 7523.8 ± 418.7 μm 2 ; WT d50 7058.4 ± 198.8 μm 2 ) was detected. Overall, the glomerular and tubular injuries are present during pregnancy in this transgenic PE rat. Most restore postpartum, speculating long-term kidney failure observed in humans is associated to hypertension and additional cardiovascular events.


BMJ Open ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. e041543
Author(s):  
Keiko Ikuta ◽  
Shunsaku Nakagawa ◽  
Kenji Momo ◽  
Atsushi Yonezawa ◽  
Kotaro Itohara ◽  
...  

ObjectivesThis study aimed to assess whether the combined use of proton pump inhibitors (PPIs) with non-steroidal anti-inflammatory drugs (NSAIDs) or antibiotics (penicillins, macrolides, cephalosporins or fluoroquinolones) was associated with an increased risk of acute kidney injury (AKI).DesignA nested case–control study.SettingA health insurance claims database constructed by the Japan Medical Data Center.ParticipantsPatients were eligible if they were prescribed a PPI, NSAID and antibiotic at least once between January 2005 and June 2017. The patients who were new PPI users and did not have any history of renal diseases before cohort entry were included (n=219 082). The mean age was 45 and 44% were women.InterventionsCurrent use of PPIs, NSAIDs, or antibiotics.Primary outcome measuresAcute kidney injury.ResultsDuring a mean follow-up of 2.4 (SD, 1.7) years, 317 cases of AKI were identified (incidence rate of 6.1/10 000 person-years). The current use of PPIs was associated with a higher risk of AKI compared with past PPI use (unadjusted OR, 4.09; 95% CI, 3.09 to 5.44). The unadjusted ORs of AKI for the current use of PPIs with NSAIDs, cephalosporins and fluoroquinolones, compared with the current use of PPIs alone, were 3.92 (95% CI, 2.40 to 6.52), 2.57 (1.43 to 4.62) and 3.08 (1.50 to 6.38), respectively. The effects of concurrent use of PPIs with NSAIDs, cephalosporins or fluoroquinolones remain significant in the adjusted model. The analyses on absolute risk of AKI confirmed the results from the nested case–control study.ConclusionsConcomitant use of NSAIDs with PPIs significantly increased the risk for AKI. Moreover, the results suggested that concomitant use of cephalosporins or fluoroquinolones with PPIs was associated with increased risk of incident AKI.


2018 ◽  
Vol 314 (1) ◽  
pp. R12-R21 ◽  
Author(s):  
Hershel Raff ◽  
Brian Hoeynck ◽  
Mack Jablonski ◽  
Cole Leonovicz ◽  
Jonathan M. Phillips ◽  
...  

Care of premature infants often requires parental and caregiver separation, particularly during hypoxic and hypothermic episodes. We have established a neonatal rat model of human prematurity involving maternal-neonatal separation and hypoxia with spontaneous hypothermia prevented by external heat. Adults previously exposed to these neonatal stressors show a sex difference in the insulin and glucose response to arginine stimulation suggesting a state of insulin resistance. The current study used this cohort of adult rats to evaluate insulin resistance [homeostatic model assessment of insulin resistance (HOMA-IR)], plasma adipokines (reflecting insulin resistance states), and testosterone. The major findings were that daily maternal-neonatal separation led to an increase in body weight and HOMA-IR in adult male and female rats and increased plasma leptin in adult male rats only; neither prior neonatal hypoxia (without or with body temperature control) nor neonatal hypothermia altered subsequent adult HOMA-IR or plasma adiponectin. Adult male-female differences in plasma leptin were lost with prior exposure to neonatal hypoxia or hypothermia; male-female differences in resistin were lost in the adults that were exposed to hypoxia and spontaneous hypothermia as neonates. Exposure of neonates to daily hypoxia without spontaneous hypothermia led to a decrease in plasma testosterone in adult male rats. We conclude that neonatal stressors result in subsequent adult sex-dependent increases in insulin resistance and adipokines and that our rat model of prematurity with hypoxia without hypothermia alters adult testosterone dynamics.


Author(s):  
Wenyan Liu ◽  
Yang Yan ◽  
Dan Han ◽  
Yongxin Li ◽  
Qian Wang ◽  
...  

Abstract Background Systemic inflammation contributes to cardiac surgery–associated acute kidney injury (AKI). Cardiomyocytes and other organs experience hypothermia and hypoxia during cardiopulmonary bypass (CPB), which induces the secretion of cold-inducible RNA-binding protein (CIRP). Extracellular CIRP may induce a proinflammatory response. Materials and Methods The serum CIRP levels in 76 patients before and after cardiac surgery were determined to analyze the correlation between CIRP levels and CPB time. The risk factors for AKI after cardiac surgery and the in-hospital outcomes were also analyzed. Results The difference in the levels of CIRP (ΔCIRP) after and before surgery in patients who experienced cardioplegic arrest (CA) was 26-fold higher than those who did not, and 2.7-fold of those who experienced CPB without CA. The ΔCIRP levels were positively correlated with CPB time (r = 0.574, p < 0.001) and cross-clamp time (r = 0.54, p < 0.001). Multivariable analysis indicated that ΔCIRP (odds ratio: 1.003; 95% confidence interval: 1.000–1.006; p = 0.027) was an independent risk factor for postoperative AKI. Patients who underwent aortic dissection surgery had higher levels of CIRP and higher incidence of AKI than other patients. The incidence of AKI and duration of mechanical ventilation in patients whose serum CIRP levels more than 405 pg/mL were significantly higher than those less than 405 pg/mL (65.8 vs. 42.1%, p = 0.038; 23.1 ± 18.2 vs. 13.8 ± 9.2 hours, p = 0.007). Conclusion A large amount of CIRP was released during cardiac surgery. The secreted CIRP was associated with the increased risk of AKI after cardiac surgery.


2020 ◽  
Vol 8 (1) ◽  
pp. 34-39
Author(s):  
Ave Olivia Rahman ◽  
Erny Kusdiyah ◽  
Herlambang Herlambang ◽  
Aldo Victoria

ABSTRACT Background: polyphenols and alkaloids in herbal plants could have aphrodisiac effect.  Betel nut (Areca catechu L) contain polyphenol and alkaloid. Alkaloid of betel nut has aphrodisiac effect, but also has side effect to many organs. Data of aphrodisiac effect of betel nut’s polyphenols is limited. This study aim to determine aphrodisiac effect of extraction of betel nut’s polyphenols in rats Method:  twelve rats, Sprague dawney, aged 2-3 months, weight 150-200 gram were divided into 2 group randomly. Group A were given  the extract with doses 100mg/kgWB and  group B were given extract with doses 200mg/kgWB  daily for 35 days. The aphrodisiacs effect determined by difference of mounting frequency before and after treatment. Male rats were mated with female rats which were in estrous phase and were recorded for 7 days.  Wilcoxon test were used for statistical analysis with p value < 0,05. Result: extract from extractio’s method that was used in this study had 39,8%(w/w) of polyphenols and 0,98% (w/w) of alkaloids. Both groups had decreasing of mounting’s frequency after treatment (p>0,05). Conclusions:  Extract of betel nut from this study had 39,8% (w/w) of polyphenols and had no aphrodisiacs effect in male rats. Keywords: Areca Catechu L, Betel nut, polyohenols, alkaloids, Rats, Aphrodisiac, Mounting.   ABSTRAK Latarbelakang: senyawa polifenol atau alkaloid suatu tanaman dapat mempunyai efek afrodisiak. Biji pinang (Areca catechu L) mempunyai kandungan polifenol dan alkaloid. Alkaloid biji pinang telah diketahui mempunyai efek afrodisiak, akan tetapi juga mempunyai banyak efek samping. Efek afrodisiak polifenol biji pinang belum diketahui. Penelitian ini bertujuan untuk melihat efek afrodisiak ekstrak polifenol biji pinang muda terhadap tikus putih. Metode: dua belas ekor tikus  Sprague dawney berumur 2-3 bulan, berat 150-200 gram dibagi secara random menjadi 2 kelompok yaitu Kelompok A diberikan ekstrak biji pinang dosis 100 mg/ kgBB, dan kelompok B diberikan dosis 200 mg/ kgBB setiap hari selama 35 hari. Efek afrodisiak dilihat dari perbedaan rerata frekuensi tunggangan sebelum dan sesudah perlakuan. Jantan dikawinkan dengan betina fase estrus dan direkam masing-masing selama 7 hari. Uji statistik menggunakan Wilcoxon dengan p<0,05. Hasil: ekstrak hasil ekstraksi yang digunakan pada penelitian ini mempunyai kandungan polifenol 39,8%(b/b) dan alkaloid 0,98% (b/b). Kedua kelompok terdapat penurunan rerata frekuensi  tunggangan setelah perlakuan (p >0,05). Kesimpulan: Ekstrak Biji Pinang Muda pada penelitian ini mempunyai kandungan 39,8% polifenol dan tidak mempunyai efek afrodisiak  pada tikus jantan. Kata kunci:  Areca Catechu L, biji pinang, polifenol, alkaloid, tikus, afrodisiak, tunggangan


2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Ayaka Domon ◽  
Kentaro Katayama ◽  
Yuki Tochigi ◽  
Hiroetsu Suzuki

A variety of animal models of diabetes mellitus (DM) are required to study the genetics and pathophysiology of DM. We established a novel rat strain showing nonobese type 2 diabetes with enlarged kidneys from the LEA.PET-pet congenic strain and named it Diabetes with Enlarged Kidney (DEK). The body growth of DEK affected rats was similar to that of normal rats before the development of DM but was attenuated with the deterioration of DM. There was a marked difference in the etiology of DEK by gender: DM phenotypes including polyuria, polydipsia, and hyperglycemia (nonfasting blood glucose over 300 mg/dl) were found in male rats aged over 10 weeks but not in female rats. The cumulative incidence of DM in DEK males at the age of 30 weeks was 44.8%. Oral glucose tolerance tests showed glucose intolerance and decreased insulin secretion in response to glucose loading in affected males, features which were exacerbated with age. Affected males exhibited disorganized architecture of pancreatic islets, decreased numbers of β cells, and markedly decreased expression of insulin, despite no pathological findings of hemorrhage or infiltration of inflammatory cells in the pancreatic islet. Age-related islet fibrosis appeared similar in normal and affected males. Affected males also showed enlarged kidneys with dilation of renal tubules in both the cortex and medulla, but no obvious glomerular lesions typical of diabetic nephropathy (DN) at the age of 30 weeks. Plasma levels of urea nitrogen and creatinine were normal, but hypoalbuminemia was detected. These pathophysiological features in affected males indicated that their renal function was almost maintained despite severe DM. Taken together, these findings indicate that the affected males of the DEK strain are a novel nonobese type 2 diabetes rat model useful for studying the mechanisms underlying β cell loss and identifying genetic factors protective against DN.


1998 ◽  
Vol 274 (2) ◽  
pp. R510-R516 ◽  
Author(s):  
Margaret P. Chandler ◽  
Stephen E. Dicarlo

Arterial pressure (AP), heart rate (HR), cardiac sympathetic tonus (ST), and parasympathetic tonus (PT) were determined in spontaneously hypertensive rats (SHR, 8 male and 8 female) and Wistar-Kyoto normotensive rats (WKY, 8 male and 12 female) before and after acute exercise. Before exercise, hypertensive rats (regardless of gender) had an increased ST (+15 beats/min), increased resting HR (+12 beats/min), and decreased PT (−11 beats/min). Similarly, female rats (regardless of strain) also had an increased ST (+15 beats/min), increased resting HR (+39 beats/min), and decreased PT (−14 beats/min). Hypertensive rats had a significant reduction in AP (−17 ± 3 mmHg), ST (−26 beats/min), PT (−7 beats/min), and HR (−14 beats/min) after exercise. In contrast, AP was not reduced in normotensive rats and ST (+18 beats/min) and HR (+42 beats/min) were increased in female normotensive rats after exercise. However, male normotensive rats had a postexercise reduction in ST (−14 beats/min) and HR (−19 beats/min). In summary, AP, ST, and resting HR were higher whereas PT was lower in hypertensive vs. normotensive rats. Furthermore, females had a higher resting HR, intrinsic HR, and ST and lower PT than male rats. These data demonstrate that gender and the resting level of AP influence cardiac autonomic regulation.


Hypertension ◽  
2020 ◽  
Vol 76 (Suppl_1) ◽  
Author(s):  
Justine M Abais-Battad ◽  
Hayley Lund ◽  
John Henry Dasinger ◽  
Daniel J Fehrenbach ◽  
David L Mattson

The immune system has a clear role in the development of hypertension and renal damage in male Dahl salt-sensitive (SS) rats, but far less is known about this phenotype in females, especially in regard to the contribution of immune-related mechanisms. The current study examined the hypertensive and kidney injury phenotype in response to a 3 week high salt challenge (HS, 4.0% NaCl, AIN-76A) in female versus male SS rats (n>10/group). Measured via radiotelemetry, there was no difference in low salt (LS, 0.4% NaCl) mean arterial pressure (MAP) between females and males (129±2 vs 124±2 mmHg, respectively). However, after 3 weeks of HS, females had a significant attenuation in the development of hypertension compared to males (161±3 vs 177±7 mmHg). This coincided with significantly less renal damage, evident by markedly reduced albuminuria (105±16 vs 183±16 mg/day) and medullary protein cast formation (7.0±0.7 vs 14.6±1.1%) in the females. Assessed via flow cytometry, there were fewer CD45+ total leukocytes (48% reduction), CD3+ T cells (51%), CD45R+ B cells (73%), and CD11b/c+ monocytes/macrophages (47%) in female versus male kidneys. To interrogate the contribution of adaptive immunity, specifically T cells, to the development of this sex difference, the same parameters were investigated in female and male SS CD247-/- rats which lack CD3+ T cells. The absence of functional T cells significantly reduced blood pressure in both females (147±6 vs 161±3 mmHg; SS CD247-/- vs SS) and males (157±8 vs 177±7 mmHg) after 3 weeks of HS, with no statistical difference between female and male SS CD247-/- rats. While a reduction in albuminuria (females: 37±12 vs 105±16 mg/day; males: 88±13 vs 183±16 mg/day, SS CD247-/- vs SS) and medullary protein cast formation (females: 1.8±0.4 vs 7.0±0.7%; males: 9.1±0.7 vs 14.6±1.1%) was observed in SS CD247-/- versus SS rats regardless of sex, there was greater protection from these measures of kidney damage in SS CD247-/- female versus SS CD247-/- males. Together, our data indicate that female SS rats are significantly protected from high salt-induced hypertension and renal disease compared to males rats. The deletion of T cells normalized high salt blood pressure between male and female rats but sex differences in renal damage still persisted.


2002 ◽  
Vol 88 (4) ◽  
pp. 399-409 ◽  
Author(s):  
G. Leung ◽  
I. F. F. Benzie ◽  
A. Cheung ◽  
S. W. Tsao ◽  
Y. C. Wong

Results of international correlation and migrant studies suggest that dietary fat promotes carcinogenesis in hormone-sensitive sites, but this is disputed. In the present study, we used a Noble rat model of sex hormone-induced cancers to examine the effect of a high-fat diet on the incidence and latency of prostate and mammary cancer in male (n 139) and female (n 72) animals respectively. We also measured α-tocopherol levels in female breast tissue to determine whether a high intake of polyunsaturated fatty acids depletes antioxidant defence in target tissues, providing a possible potentiating mechanism for carcinogenesis. Results showed a very high incidence of hormone-induced adenocarcinomas of prostate and mammary gland, irrespective of diet. There was no difference in the pattern of carcinogenesis in different prostatic locations, weight of the prostate, or weight gain between male rats on the high-fat diet compared with the control (standard, low-fat) diet. In female rats, the incidence of mammary cancer and the body-weight gain were the same in both dietary groups, and breast α-tocopherol was also unaffected by dietary fat intake. Our present results are supportive of recent cohort studies that reported no significant association between intake of fat and the development of human prostate and breast cancer, and do not support a role for dietary fat in promoting sex hormone-induced prostate and mammary carcinogenesis.


2018 ◽  
Vol 32 ◽  
pp. 205873841878551 ◽  
Author(s):  
Mohamed A Hamzawy ◽  
Yasmin B El-Ghandour ◽  
Sekena H Abdel-Aziem ◽  
Zoba H Ali

The aspect of treatment of autistic behaviour was investigated using valproic acid rat model of pregnant female rats. Two main groups (10 male rats/group) were treated for 6 days and then divided into six subgroups. The first group of normal rats was divided into three subgroups: (A) – control group, (B) – treated with camel milk (CAM; 2 mL/p.o) and (C) – treated with leptin (1000 µg/kg i.p) twice daily. The second group of autistic rats was randomly distributed into four subgroups as follows: (D) – positive control (autistics rats), (E) – treated with CAM, (F) – treated with a moderate dose of leptin and (G) – treated with a higher dose of leptin. Autistic behaviours of male offspring were checked by grooming and elevated pulz maze tests. Valproic acid (VPA)-induced autistic rats showed severe changes in oxidative stress markers, neurotransmitters and inflammatory cytokines, besides genotoxic manifestation of expression of tumour necrosis factor (TNF)-α, Bax and caspase-3. Leptin or CAM alone showed no signs of toxicity. CAM showed pronounced improvement in control rats than control itself. Leptin or CAM treatment of autistic animals showed a significant improvement of all measured parameters and genetic expression values. The improvement was pronounced in animals treated with CAM. These results suggest that CAM is a potential therapeutic candidate for autism via regulation of inflammatory and apoptotic pathways. Leptin plays an essential role in alleviation of autistic behaviour through antioxidant effects.


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