Altered Kidney Function Research Articles

Renin-Angiotensin System Induced Secondary Hypertension: The Alteration of Kidney Function and Structure

Long-term hypertension is known as a major risk factor for cardiovascular and chronic kidney disease (CKD). The Renin-angiotensin system (RAS) plays a key role in hypertension pathogenesis. Angiotensin II (Ang II) enhancement in Ang II-dependent hypertension leads to progressive CKD and kidney fibrosis. In the two-kidney one-clip model (2K1C), more renin is synthesized in the principal cells of the collecting duct than juxtaglomerular cells (JGCs). An increase of renal Ang I and Ang II levels and a decrease of renal cortical and medullary Ang 1–7 occur in both kidneys of the 2K1C hypertensive rat model. In addition, the activity of the angiotensin-converting enzyme (ACE) increases, while ACE2's activity decreases in the medullary region of both kidneys in the 2K1C hypertensive model. Also, the renal prolyl carboxypeptidase (PrCP) expression and its activity reduce in the clipped kidneys. The imbalance in the production of renal ACE, ACE2, and PrCP expression causes the progression of renal injury. Intrarenal angiotensinogen (AGT) expression and urine AGT (uAGT) excretion rates in the unclipped kidney are greater than the clipped kidney in the 2K1C hypertensive rat model. The enhancement of Ang II in the clipped kidney is related to renin secretion, while the elevation of intrarenal Ang II in the unclipped kidney is related to stimulation of AGT mRNA and protein in proximal tubule cells by a direct effect of systemic Ang II level. Ang II-dependent hypertension enhances macrophages and T-cell infiltration into the kidney which increases cytokines, and AGT synthesis in proximal tubules is stimulated via cytokines. Accumulation of inflammatory cells in the kidney aggravates hypertension and renal damage. Moreover, Ang II-dependent hypertension alters renal Ang II type 1 & 2 receptors (AT1R & AT2R) and Mas receptor (MasR) expression, and the renal interstitial fluid bradykinin, nitric oxide, and cGMP response to AT1R, AT2R, or BK B2-receptor antagonists. Based on a variety of sources including PubMed, Google Scholar, Scopus, and Science-Direct, in the current review, we will discuss the role of RAS-induced secondary hypertension on the alteration of renal function.

Association of Pesticides and Kidney Function among Adults in the US Population 2001-2010.

Chronic kidney disease of unknown cause is prevalent in a range of communities; however, its etiology remains unclear. We examined the association between pesticide exposures and the risk of kidney function loss using four waves of the National Health and Nutrition Examination Survey (NHANES) to identify a pathological pathway. We pooled data from four cross-sectional waves of NHANES, with 41,847 participants in total. Exposure to malathion increased the risk of low kidney function (aOR = 1.26, 95% CI = 1.01–1.56) in the adjusted model. Increased risk of low kidney function was not found among those exposed to 2,4-D (aOR = 0.88, 95% CI = 0.72–1.09), 3,5,6-trichloropyridinol (aOR = 0.96, 95% CI = 0.83–1.12), and 3-PBA (aOR = 1.03, 95% CI = 0.94–1.13). Our findings provide evidence of altered kidney function in people exposed to malathion, highlighting the potential of organophosphate pesticides’ role in renal injury.

Combined Untargeted and Targeted Metabolomics Approaches Reveal Urinary Changes of Amino Acids and Energy Metabolism in Canine Babesiosis With Different Levels of Kidney Function.

Canine babesiosis is a tick-borne disease with a worldwide distribution, caused by the haemoprotozoan parasites of the genus Babesia. One of the most prevalent complication is acute kidney injury, and an early diagnosis of altered kidney function remains a challenge for veterinary practice. The aim of this study was to assess the urine metabolic profile from dogs with babesiosis and different degree of kidney function using untargeted and targeted MS-based metabolomics approaches. In this study, 22 dogs naturally infected with Babesia canis and 12 healthy dogs were included. Untargeted metabolomics approach identified 601 features with a differential abundance between the healthy group and groups of dogs with babesiosis and different level of kidney function, with 27 of them identified as a match to known standards; while targeted approach identified 17 metabolites with significantly different concentrations between the groups. A pattern of significantly altered metabolites referring to the inflammatory host response, oxidative stress, and energy metabolism modulation in babesiosis was presented. Our findings have demonstrated that kidney dysfunction accompanying canine babesiosis was associated with changes in amino acid metabolism, energy metabolism, fatty acid metabolism, and biochemical pathways such as urea cycle and ammonia detoxication. These findings will enable the inclusion of urinary markers for the detection and monitoring of renal damage in babesiosis, as well as in other similar diseases.

Improving SIRT1 by trehalose supplementation reduces oxidative stress, inflammation, and histopathological scores in the kidney of aged rats.

The aging process leads to progressive loss of kidney function. Sirtuin1 (SIRT1) exerts renoprotective effects by conferring resistance to cellular stresses. Trehalose potentially displayed various beneficial effects to promote health span. In this study, we investigated the effects of trehalose on renal SIRT1 and kidney function in senescent rats. Trehalose (2% w/v) was administrated in drinking water for 1month to male aged rats (24months). Then, the level of SIRT1 mRNA and protein, malondialdehyde, total antioxidant capacity, tumor necrosis factor α as well as parameters related to the function and histology of the kidneys were evaluated. Trehalose supplementation increased the level of SIRT1, whereas alleviated the level of oxidative stress, inflammation, and histopathology scores in senescent tissues. However, trehalose administration did not alter kidney function indices in old rats. Collectively, these findings suggested that trehalose was an effective intervention to ameliorate some aspects of age-associated injury in the old kidneys. PRACTICAL APPLICATIONS: Aging is associated with impairment in renal structure and function. Trehalose is a natural disaccharide, which is widely distributed in many organisms. The consumption of trehalose as a dietary supplement is increasing worldwide. This study showed that trehalose administration to aged rats had renoprotective effects through reducing oxidative stress and inflammation, which was mediated by SIRT1. Our results provide useful information for individuals using this sugar as a supplement.

Metabolic Profiling Indicates Diversity in the Metabolic Physiologies Associated With Maternal Postpartum Depressive Symptoms.

Background: Postpartum depression (PPD) is a devastating disease requiring improvements in diagnosis and prevention. Blood metabolomics identifies biological markers discriminatory between women with and those without antenatal depressive symptoms. Whether this cutting-edge method can be applied to postpartum depressive symptoms merits further investigation.Methods: As a substudy within the Biology, Affect, Stress, Imagine and Cognition Study, 24 women with PPD symptom (PPDS) assessment at 6 weeks postpartum were included. Controls were selected as having a score of ≤ 6 and PPDS cases as ≥12 on the Edinburgh Postnatal Depression Scale. Blood plasma was collected at 10 weeks postpartum and analyzed with gas chromatography–mass spectrometry metabolomics.Results: Variations of metabolomic profiles within the PPDS samples were identified. One cluster showed altered kidney function, whereas the other, a metabolic syndrome profile, both previously associated with depression. Five metabolites (glycerol, threonine, 2-hydroxybutanoic acid, erythritol, and phenylalanine) showed higher abundance among women with PPDSs, indicating perturbations in the serine/threonine and glycerol lipid metabolism, suggesting oxidative stress conditions.Conclusions: Alterations in certain metabolites were associated with depressive pathophysiology postpartum, whereas diversity in PPDS physiologies was revealed. Hence, plasma metabolic profiling could be considered in diagnosis and pathophysiological investigation of PPD toward providing clues for treatment. Future studies require standardization of various subgroups with respect to symptom onset, lifestyle, and comorbidities.

MO003DISTAL RENAL TUBULAR ACIDOSIS IN PATIENTS WITH AUTOIMMUNE DISEASES

Abstract Background and Aims Distal renal tubular acidosis (DRTA) is characterized by hyperchloremic metabolic acidosis, with normal anion gap and with the inability to acidify the urine to a pH lower than 5.3. DRTA can evolve without symptoms and systemic acidosis, this form being defined as incomplete DRTA, that necessitates the use of a urinary acidification test like the Furosemide and Fludrocortisone test for establishing the diagnosis. There are several cases of type 1 DRTA reported in patients with autoimmune diseases, especially Sjögren syndrome and systemic lupus erythematosus (SLE), most of them being diagnosed due to severe symptoms caused by the associated hypokalemia. The prevalence of the DRTA in patients with autoimmune diseases is unknown, especially if we refer to the incomplete form. Method We conducted an observational prospective study in a selected cohort of 21 patients diagnosed with autoimmune diseases, who presented for evaluation in our clinic during December, 2020 and January, 2021. We included patients diagnosed with SLE, Sjögren syndrome, ANCA vasculitis, cryoglobulinemic vasculitis, who were submitted to Furosemide/Fludrocortisone test in our nephrology department. The urinary pH was evaluated hourly for 6 hours after the test began. The test was considered positive if the urinary pH did not decrease < 5.3. Results The study included 21 patients (16 females, 5 males, mean age 41.52 ± 17.58 years), diagnosed with SLE (13 patients, mean age 30.23 ± 10.34 years, eGFR 81.61±20.39 ml/min/1.73 m2), pANCA vasculitis (6 patients, mean age 60.83 ± 6.14, eGFR 40 ± 12.64 ml/min/1.73 m2), Sjogren syndrome (one 44 year-old patient, eGFR 39 ml/min/1.73 m2) and cryoglobulinemic vasculitis (one 69 year-old patient, eGFR 31 ml/min/1.73 m2). The test was positive for 4 patients out of 21 (3 females, one male; one with SLE, one with pANCA vasculitis, one with Sjogren syndrome and one with cryoglobulinemic vasculitis). Although 2 patients developed hypokalemia defined as a level of serum potassium lower than 3.5 mmol/l after the test and 1 patient augmented previous hypokalemia, there was not a significant change in kalemia (3.93 ± 0.32 mmol/l before the test vs 3.95 ± 0.49 mmol/l after the test, p=0.835). Although none of the patients developed metabolic alkalosis after the test, there was a significant increase in the level of serum bicarbonate (26.6 (2.2) mmol/l before the test vs 28.2 (2.7) mmol/l after the test, p=0.005) and also in the level of serum pH (7.36 ± 0.04 before the test vs 7.38 ± 0.04 after the test, p=0.018). None of the patients reported digestive or allergic side effects. It was interesting that the patients with vasculitis responded with delay to the treatment and urinary acidification under the pH of 5.3 occurred after a mean period of 3.2 hours in comparison to 1.5 hours in patients with SLE (p=0.014). Regarding the histological data, both the patients with vasculitis were elders, with an altered kidney function (both with a eGFR of 31 ml/min/1.73 m2) and severe tubular atrophy and interstitial fibrosis on kidney biopsy. The female patient with cryoglobulinemic vasculitis also had positive titers for antinuclear antibody, anti Ro-antibodies and anti-La antibodies. The patient with Sjögren syndrome was diagnosed with nephrocalcinosis and the kidney biopsy was not effectuated. The youngest patient with a positive test had preserved renal function, without tubular or interstitial lesions on kidney biopsy, but with a pattern of membranous lupus nephritis and with intense immunological activity (ANA, anti ds-DNA antibodies, anti RNP and Sm antibodies, antiphospholipid syndrome). Conclusion Incomplete DRTA was found in 4 out of 21 patients with autoimmune diseases, one with Sjogren syndrome and nephrocalcinosis, two with pANCA and cryoglobulinemic vasculitis with decreased eGFR and severe tubular atrophy and interstitial fibrosis and one young female with SLE.

Pesticide use and kidney function among farmers in the Biomarkers of Exposure and Effect in Agriculture study

BackgroundPesticides have been reported to be associated with malignant and non-malignant kidney disease. Few studies have examined the relationship between individual pesticides and kidney dysfunction. ObjectiveWe evaluated the associations of pesticide use with measured kidney function among male pesticide applicators in the Biomarkers of Exposure and Effect in Agriculture (BEEA) study, a subcohort in the Agricultural Health Study. MethodsSerum creatinine was measured in 1545 BEEA participants and estimated glomerular filtration rate (eGFR) was calculated with the chronic kidney disease epidemiology collaboration (CKD-EPI) equation. Using reported information on lifetime use of 41 pesticides, multivariable linear and logistic regression was used to examine associations with eGFR modeled continuously and with CKD (eGFR <60 mL/min/1.73 m2), respectively. Models were adjusted for possible confounding factors related to kidney function and correlated pesticides. ResultsLower eGFR was observed among pesticide applicators who ever used the herbicides pendimethalin (−3.7%, 95% confidence interval (CI): 5.8%, −1.5%), atrazine (−3.7%, 95% CI: 6.9%, −0.4%), and dicamba (−2.8%, 95% CI: 5.3%, −0.2%) compared with never users of each pesticide. Ever use of pendimethalin (odds ratio (OR)=1.6, 95% CI: 1.1, 2.2) and atrazine (OR=1.8, 95% CI: 1.0, 3.0) was also associated with elevated odds of CKD, with an exposure-response association between intensity-weighted lifetime days of pendimethalin use and CKD among active farmers (N=1302; ptrend=0.04). Atrazine use within the last year was associated with lower eGFR and elevated odds of CKD when compared with never users, and we observed exposure-response associations with intensity-weighted lifetime days among recent users. Use of several other pesticides was associated with higher eGFR. DiscussionThese results suggest that two widely used herbicides, pendimethalin and atrazine, may be associated with altered kidney function among pesticide applicators. Our findings for these herbicides are consistent with observed associations with end-stage renal disease in the Agricultural Health Study.

Epidemiology and Outcomes of Acute Kidney Diseases: A Comparative Analysis

Introduction: Acute kidney diseases and disorders (AKD) encompass acute kidney injury (AKI) and subacute or persistent alterations in kidney function that occur after an initiating event. Unlike AKI, accurate estimates of the incidence and prognosis of AKD are not available and its clinical significance is uncertain. Methods: We studied the epidemiology and long-term outcome of AKD (as defined by the KDIGO criteria), with or without AKI, in a retrospective cohort of adults hospitalized at a single centre for >24 h between 2012 and 2016 who had a baseline eGFR ≥60 mL/min/1.73 m² and were alive at 30 days. In patients for whom follow-up data were available, the risks of major adverse kidney events (MAKEs), CKD, kidney failure, and death were examined by Cox and competing risk regression analyses. Results: Among 62,977 patients, 906 (1%) had AKD with AKI and 485 (1%) had AKD without AKI. Follow-up data were available for 36,118 patients. In this cohort, compared to no kidney disease, AKD with AKI was associated with a higher risk of MAKEs (40.25 per 100 person-years; hazard ratio [HR] 2.51, 95% confidence interval [CI] 2.16–2.91), CKD (27.84 per 100 person-years); subhazard ratio [SHR] 3.18, 95% CI 2.60–3.89), kidney failure (0.56 per 100 person-years; SHR 24.84, 95% CI 5.93–104.03), and death (14.86 per 100 person-years; HR 1.52, 95% CI 1.20–1.92). Patients who had AKD without AKI also had a higher risk of MAKEs (36.21 per 100 person-years; HR 2.26, 95% CI 1.89–2.70), CKD (22.94 per 100 person-years; SHR 2.69, 95% CI 2.11–3.43), kidney failure (0.28 per 100 person-years; SHR 12.63, 95% CI 1.48–107.64), and death (14.86 per 100 person-years; HR 1.57, 95% CI 1.19–2.07). MAKEs after AKD were driven by CKD, especially in the first 3 months. Conclusions: These findings establish the burden and poor prognosis of AKD and support prioritisation of clinical initiatives and research strategies to mitigate such risk.

The spectrum of kidney function alterations in adolescents with a solitary functioning kidney.

A precise assessment of glomerular filtration rate is key to delineate the care of children with a solitary functioning kidney (SFK). Data regarding measured GFR (mGFR) in this population is restricted to a single study of 77 individuals, which suggested that a GFR estimation (eGFR) method based on creatinine and cystatin C (eGFR-CKiD2) performed better than Schwartz's equation (eGFR-Schwartz). We measured GFR in 210 consecutive adolescents (7 to 22 years old) with an SFK referred to our institution between 2014 and 2019 and in 43 young candidates for kidney donation (18 to 25 years old). We compared the distribution of mGFR in both groups and determined the factors associated with reduced mGFR in adolescents with an SFK. We further compared different eGFR formulas with mGFR and assessed the association of mGFR and eGFRs with PTH and FGF23, two early indicators of GFR reduction. While adolescents with an SFK had a similar median mGFR to healthy controls (103 ± 24ml/min/1.73m2 vs. 107 ± 12 ml/min/1.73m2), the fraction of individuals with an mGFR below 90ml/min/1.73m2 was higher in patients with SFK (23% vs. 5% in controls; P = 0.005). Multiple linear regression identified older age, ipsilateral abnormalities of the urinary tract, lack of compensatory hypertrophy, and treated hypertension as independent factors associated with reduced mGFR. A smaller bias using eGFR-Schwartz (95% confidence interval (95%CI): 3 to 7) was revealed when compared to other eGFR. Compared to eGFR-Schwartz, mGFR showed a stronger correlation with PTH (r=0.04 vs. r=0.1) and FGF23 (r =0.03 vs. r=0.05). SFK is not a benign condition, since 20% of the patients display altered kidney function. Our results raise caution regarding the use of the cystatin-based equation. mGFR shows a better ability than eGFR-Schwartz to differentiate patients showing early homeostatic adaptation to GFR reduction.

Renal dysfunctions and clinical correlates in adolescents with restrictive anorexia nervosa.

The alteration of kidney function in adolescents with anorexia nervosa (AN) is a frequent, but still poorly investigated, consequence of AN. In this study, we analyzed glomerular filtration rate with the Cockroft-Gault formula in a group of 148 adolescents with Anorexia Nervosa and correlated it to clinical and biochemical data collected at admission. A retrospective study was conducted on 148 patients hospitalized from 2016 to 2019 for severe malnutrition due to restrictive AN. We measured glomerular filtration rate and correlated it with the patients' anamnestic history, nutritional status and biochemical data. For the 148 AN patients, 40 (27%) resulted at admission at stage 1 of kidney damage (GFR>90mL/min), 88 patients (59%) at stage 2 (GFR 89-60mL/min), 17 patients (11%) at stage 3A (GFR 59-45mL/min) and 3 patients (2%) at stage 3B (GFR 44-30mL/min). Results outlined a correlation between the entity of kidney damage and BMI at admission and before illness onset, but not with the rapidity and entity of weight loss. Further, more severe renal damages corresponded to major biochemical and hormonal alterations. Results of our study confirm that kidney damage is a frequent condition in adolescents withrestrictive-type AN and support making kidney functionality tests part of routine care in patients with AN.

BK Virus Pneumonia with CMV Colitis in a Kidney Transplant Recipient: Successful Treatment with Non-Cidofovir Based Therapy

BK virus (BKV) pneumonia is a rare entity especially seen in immunosuppressed patients, for which cidofovir is the used treatment option. We describe a case of a young female patient who presented for altered kidney function six months following kidney transplantation for focal segmental glomerulosclerosis and was found to have BKV nephritis. Her in-hospital stay was complicated by BKV pneumonia requiring mechanical ventilation, in addition to CMV colitis. She was treated with leflunomide/ciprofloxacin and ganciclovir for her pneumonia and colitis, respectively. The patient improved clinically except that her kidney function deteriorated. Leflunomide/ciprofloxacin combination may constitute an effective and safe alternative to cidofovir for the treatment of BKV pneumonia, in particular when cidofovir is not available. J Microbiol Infect Dis 2021; 11(1):36-41.

Cerebral Blood Flow in Chronic Kidney Disease

The prevalence of mild cognitive impairment increases with age and is further exacerbated by chronic kidney disease (CKD). CKD is associated with (1) mild cognitive impairment, (2) impaired endothelial function, (3) impaired blood-brain barrier, (4) increased cerebral microhemorrhage burden, (5) increased cerebral blood flow (CBF), (6) impaired cerebral autoregulation, (7) impaired cerebrovascular reactivity, and (8) increased arterial stiffness. We report preliminary findings from our group that demonstrate altered cerebrovascular reactivity in a mouse model of CKD-associated vascular calcification. The CBF of CKD mice increased more quickly in response to hypercapnia (p < 0.05) but then decreased prematurely during hypercapnia challenge (p < 0.05). Together, these results indicate that altered kidney function can lead to alterations in the cerebral microvasculature, and hence brain health.

Drinking water salinity is associated with hypertension and hyperdilute urine among Daasanach pastoralists in Northern Kenya

Water salinity is a growing global environmental health concern. However, little is known about the relation between water salinity and chronic health outcomes in non-coastal, lean populations. Daasanach pastoralists living in northern Kenya traditionally rely on milk, yet are experiencing socioecological changes and have expressed concerns about the saltiness of their drinking water. Therefore, this cross-sectional study conducted water quality analyses to examine how water salinity, along with lifestyle factors like milk intake, was associated with hypertension (blood pressure BP ≥140 mm Hg systolic or ≥90 mm Hg diastolic) and hyperdilute urine (urine specific gravity <1.003 g/mL, indicative of altered kidney function). We collected health biomarkers and survey data from 226 non-pregnant adults (46.9% male) aged 18+ from 134 households in 2019 along with participant observations in 2020. The salinity (total concentration of all dissolved salts) of reported drinking water from hand-dug wells in dry river beds, boreholes, and a pond ranged from 120 to 520 mg/L. Water from Lake Turkana and standpipes, which was only periodically used for consumption when no other drinking sources are available, ranged from 1100 to 2300 mg/L. Multiple logistic regression models with standard errors clustered on households indicate that each additional 100 mg/L of drinking water salinity was associated with 45% (95% CI: 1.09–1.93, P = 0.010) increased odds of hypertension and 33% (95% CI: 0.97–1.83, P = 0.075) increased odds of hyperdilute urine adjusted for confounders. Results were robust to multiple specifications of the models and sensitivity analyses. Daily milk consumption was associated with 61–63% (P < 0.01) lower odds of both outcomes. This considerable protective effect of milk intake may be due to the high potassium, magnesium, and calcium contents or the protective lifestyle considerations of moving with livestock. Our study results demonstrate that drinking water salinity may have critical health implications for blood pressure and kidney function even among lean, active pastoralists.

NCAA Division I American football players with sickle cell trait have altered hematological responses and hydration status

Sickle cell trait (SCT) is a risk factor of collapse and sudden death in athletes. We conducted a longitudinal study to determine the hematological responses and hydration status in NCAA Division I American football players with SCT. The study took place over 2 years with 6 SCT and 6 position-matched controls (CON) in year 1; and 4 SCT and 4 CON in year 2. In year 2, three of the four SCT players were recruited and re-enrolled with new position-matched controls (total sample data = 10 SCT and 10 CON). Blood samples were taken at three visits: pre-camp, post-camp, and post-season to examine hemoglobin variants, complete blood counts, and chemistry panel 26. Hydration status was assessed by measuring body weight change, urine specific gravity, and urine and sweat electrolyte concentrations during the pre-season training camp. All SCT players were confirmed to have SCT (HbS = 37.9 ± 2.4%) and had greater red cell distribution width (RDW) compared to CON across all visits. Serum uric acid was higher in SCT (7.3 ± 1.0 mg/dL) compared to CON (6.1 ± 0.6 mg/dL; p = 0.001). Furthermore, serum creatine kinase levels were greater in SCT (1617.0 ± 1034.8 IU/L) at pre-camp compared to CON (1037.4 ± 602.8 IU/L; p = 0.03). SCT players exhibited lower pre- and post-practice urine electrolytes and urine specific gravity (SCT pre: 1.019 ± 0.005 vs. CON pre: 1.026 ± 0.008 p < 0.001; SCT post: 1.020 ± 0.005 vs. CON post: 1.030 ± 0.008 p < 0.01), whereas sweat sodium concentrations were higher in SCT players (55.4 ± 13.6 mmol/L) compared to CON (45.5 ± 10.6 mmol/L; p < 0.001). Given the evidence, greater uric acid and CPK levels in SCT players compared to CON may be an early indicator of altered kidney function and muscle damage, which could be added into NCAA guidelines for surveillance among SCT players. Consistent education and reinforcement of the importance of adequate fluid balance during exercise are critical for both SCT and CON players.

Adverse Maternal and Fetal Outcomes in a Novel Experimental Model of Pregnancy after Recovery from Renal Ischemia-Reperfusion Injury.

Recent clinical studies report that women with a history of AKI have an increased incidence of maternal and fetal adverse outcomes during pregnancy, despite fully recovering renal function prior to conception. The mechanisms contributing to such adverse outcomes in pregnancy after AKI are not yet understood. To develop a rodent model to investigate fetal and maternal outcomes in female animals with a history of AKI, we used ischemia-reperfusion injury as an experimental model of AKI in female Sprague Dawley rats. The 12-week-old animals underwent warm bilateral ischemia-reperfusion surgery involving clamping of both renal arteries for 45 minutes or sham surgery (control). Rats were allowed to recover for 1 month prior to mating. Recovery from ischemia-reperfusion injury was confirmed by measurements of plasma creatinine and urinary protein excretion. We assessed maternal and fetal outcomes during late pregnancy on gestational day 20. After recovery from ischemia-reperfusion injury, compared with healthy sham-surgery controls, dams exhibited pregnancy-induced renal insufficiency with increases in plasma creatinine and urea, along with increased urinary protein excretion. Additionally, recovered ischemia-reperfusion dams experienced worse fetal outcomes compared with controls, with intrauterine growth restriction leading to higher rates of fetal demise and smaller pups. In this rat model, despite biochemical resolution of ischemia-reperfusion injury, subsequent pregnancy resulted in maternal renal insufficiency and significant impairments in fetal growth. This mirrors findings in recent reports in the clinical population, indicating that this model may be a useful tool to further explore the alterations in kidney function after AKI in women.

Evaluation of kidney function in children with Hashimoto's Thyroiditis

Aim: Thyroid hormones have various effects on kidney function and both hypothyroidism and hyperthyroidism may result in clinically important alterations in kidney function. Therefore, we evaluated kidney functions and changes in kidney functions over time in children with Hashimoto thyroiditis (HT) who treated or not treated with thyroid hormone replacement therapy. Materials and Methods: The patients were divided into three groups. Group 1 included patients who had hypotroidism and received treatment, group 2 included patients who had euthyroid goiter and received treatment and group 3 consisted of patients who were clinically euthyroid and not received any treatment. All participants were followed prospectively. Serum creatinine (Cr), albumin and serum cystatin C (CysC) levels, estimated glomerular filtration rate eGFR, and urine protein to creatinine ratio (PCR) were measured at the time of diagnosis and one and six months after diagnosis Results: There were significant differences between baseline and follow-up characteristics of the group 1 in terms of serum Cr, urine PCR, CysC and eGFR. The baseline and follow-up characteristics of groups 2 and 3 were not statistically significant. Conclusion: Children with HT may present with kidney dysfunction and proteinuria, which improve with thyroid hormone replacement. We think that clinicians who follow children with HT should pay attention to this issue.

430. Frontline doctors infected with Covid-19 during a hospital outbreak in Veracruz, Mexico

BackgroundThe current Covid-19 pandemic has affected health workers, some estimates mention more than 90,000 affected, even with deaths throughout the world.Population characteristics General symptoms MethodsDescriptive, analytical and cross-sectional study. The cases of front-line doctors infected with Covid-19 during a hospitalary outbreak, in the General Hospital 71 “Lic. Benito Coquet Lagunes” of Veracruz, dependent on the Mexican Institute of Social Security, from April 1 to May 31, 2020.Treatments ResultsSeven doctors were entered into the study, with an average age of 42.4 years, all of them male. The affectation by service was: Internal medicine 5 of 17 doctors (29.4%), Emergencies 1 of 15 doctors (6.6%) and Intensive care 1 of 6 doctors (16.6%) infected by Covid-19. Laboratory studies were only performed in 5 cases, the presence of leukopenia in 1 case (20%), leukocytosis in 2 cases (40%), lymphopenia in 4 cases (80%) stand out. Impaired fasting glucose was reported in all cases. There was no alteration in kidney function; in liver function, transaminemia was reported in 80%. Regarding the acute phase reactants, the intake of these was very inconsistent since it was not uniform in all cases, but the most representative was elevated ESR in 4 of 4 cases (100%), positive PCR in 3 of 4 cases (75%), procalcitonin negative in 3 of 3 cases (100%), elevated DHL in 2 of 5 cases (40%), elevated D-dimer in 1 of 3 cases (33.3%), elevated ferritinemia in 1 of 2 cases (50 %). The rest of the characteristics in the table and graphs.ConclusionThe present cohort of doctors affected by Covid during a hospital outbreak shows that there are several factors to take into account, on the one hand, factors specific to the population (obesity, diabetes, hypertension), as well as the institutions that are in charge of medical personnel. they must identify the risk factors mentioned, influence them and protect said population that is vulnerable per se to a pandemic; Another constantly identified factor is occupational exposure to the pathogen without sufficient and adequate personal protective equipment.Disclosures All Authors: No reported disclosures

Epigenetic mechanisms involved in intrauterine growth restriction and aberrant kidney development and function.

Intrauterine growth restriction (IUGR) due to uteroplacental insufficiency results in a placenta that is unable to provide adequate nutrients and oxygen to the fetus. These growth-restricted babies have an increased risk of hypertension and chronic kidney disease later in life. In rats, both male and female growth-restricted offspring have nephron deficits but only males develop kidney dysfunction and high blood pressure. In addition, there is transgenerational transmission of nephron deficits and hypertension risk. Therefore, epigenetic mechanisms may explain the sex-specific programming and multigenerational transmission of IUGR-related phenotypes. Expression of DNA methyltransferases (Dnmt1and Dnmt3a) and imprinted genes (Peg3, Snrpn, Kcnq1, and Cdkn1c) were investigated in kidney tissues of sham and IUGR rats in F1 (embryonic day 20 (E20) and postnatal day 1 (PN1)) and F2 (6 and 12 months of age, paternal and maternal lines) generations (n = 6-13/group). In comparison to sham offspring, F1 IUGR rats had a 19% decrease in Dnmt3a expression at E20 (P < 0.05), with decreased Cdkn1c (19%, P < 0.05) and increased Kcnq1 (1.6-fold, P < 0.01) at PN1. There was a sex-specific difference in Cdkn1c and Snrpn expression at E20, with 29% and 34% higher expression in IUGR males compared to females, respectively (P < 0.05). Peg3 sex-specific expression was lost in the F2 IUGR offspring, only in the maternal line. These findings suggest that epigenetic mechanisms may be altered in renal embryonic and/or fetal development in growth-restricted offspring, which could alter kidney function, predisposing these offspring to kidney disease later in life.

High genetic diversity of paramyxoviruses infecting domestic cats in Western Brazil

Feline morbillivirus was discovered in 2012 in cats from Hong Kong, and it was initially found to be associated with chronic kidney disease. Although subsequent molecular surveys showed a common occurrence in cat populations from distinct countries, there were controversial results regarding the relationship between viral shedding through urine and reduced kidney function. In this study, 276 domestic cats of diverse origins from Western Brazil had their urine evaluated for the presence of paramyxoviral RNA by reverse transcription seminested PCR and direct sequencing. Additionally, a selected Brazilian feline morbillivirus strain was isolated in Crandell Rees feline kidney cells, and a nearly complete genome sequence was obtained. To assess the kidney function of all cats, serum biochemistry screening and standard urinalysis were performed. Our results revealed a relatively high paramyxovirus-positive rate (34.7%) in the evaluated cats although there was not a statistical association between the shedding of viral RNA through urine and kidney disease. Direct sequencing of partial fragments of the L gene demonstrated high genetic diversity among strains detected in cats in this study, since both feline morbillivirus RNA and feline paramyxovirus RNA were frequently shed in urine. Phylogenetic reconstruction based on partial amino acid sequences of the L gene showed that Brazilian feline paramyxovirus strains were genetically diverse since they grouped into two distinct subclusters; one subcluster contained three strains identified in Germany, while the second contained Japanese strain 163, which was recently classified in the Jeilongvirus genus of the Paramyxoviridae family. In contrast, the Brazilian feline morbillivirus strain FeMV/BR_Boni, herein characterized by nearly complete genome sequencing, was classified in the Morbillivirus genus with other strains previously identified as genotype 1. In conclusion, urinary excretion of diverse paramyxoviral RNA is frequent in cats of different origins from Western Brazil, but viral infection is not related to altered kidney function.

The effect of hyperfiltration mechanism on kidney function in Living-Donor Kidney Transplantation in Cipto Mangunkusumo Hospital, Jakarta, Indonesia: study on renal arterial resistive index, urinary vascular endothelial growth factor, neutrophil gelatinase-associated lipocalin, and heparan sulfate

Background: While adequate donors’ kidney function after donation is desired, some may recover incompletely and develop chronic kidney diseases. Hyperfiltration is an adapting mechanism to overcome nephrectomy-related kidney function loss. This study aims to explain adaptive and maladaptive hyperfiltration mechanism during the first 30 days postnephrectomy. Methods: Longitudinal observational study was conducted on 46 kidney donors in Cipto Mangunkusumo Hospital in April-De cember 2019. Estimated glomerular filtration rate (eGFR) and albumin-creatinine ratio (ACR) were examined serially. Subjects were divided into adaptive (eGFR >60 mL/min/1.73 ㎡ and/or ACR 30 mg/g on day 30). Kidney resistive index (RI), urinary vascular endothelial growth factor (VEGF), and heparan sulfate (HS) were examined prenephrectomy and on day-2, day-7, and day-30 postnephrectomy. Urinary neutrophil gelati nase-associated lipocalin (NGAL) level was measured before and 6-hour postnephrectomy. Donors’ characteristic variables were analyzed using chi-square or Fisher test and logistic regression. Difference of RI, VEGF, NGAL, and HS between two groups were analyzed using Mann-Whitney or independent t-test. Results: Out of 46 subjects, 40 were included in the final analysis. Nineteen donors (47.5%) underwent maladaptive hyperfil tration. Prenephrectomy eGFR was significantly different with value of 111.17 (11.38) mL/min/1.73 ㎡ and 92.94 (13.21) mL/ min/1.73 ㎡ and cutoff of 104.60 mL/min/1.73 ㎡. Outcomes of donors aged >45 years and arterial stiffness >50th percentile were significantly different (P=0.03 and P=0.01). Hyperfiltration was evidenced by significant changes in RI, VEGF, NGAL, and HS after nephrectomy. Significant difference between arcuate artery RI on day-2 and day-30 was found only in adaptive group. Conclusions: Hyperfiltration does not alter kidney function on day-30 postnephrectomy. Prenephrectomy eGFR, age >45 years, and arterial stiffness are associated with day-30 postnephrectomy kidney function. RI of arcuate artery changes more promi nently and rapidly in adaptive group. Further study evaluating kidney function and interfering variables within longer period is necessary.