Development Of Kidney Dysfunction Research Articles

A novel imaging index for predicting adverse progression in acute-on-chronic liver failure related to hepatitis B virus: the low erector spine index

BackgroundIt is widely known that muscle mass influences the outcomes of many chronic diseases. Erector spine mass is a convenient parameter obtained from routine abdominal computed tomography (CT). The clinical application value of erector spine mass, and whether erector spine mass could predict the outcome of disease has not been studied.AimTo evaluate the role of the erector spine index (ESI) calculated based on abdominal CT imaging in the progression of acute-on-chronic liver failure related to the hepatitis B virus (HBV-ACLF).MethodsWe performed a retrospective study of 118 HBV-ACLF patients and calculated the ESI (the total erector spine area normalized for height2 in meters) for each patient through abdominal CT. The findings were analyzed regarding the progression of HBV-ACLF and the ESI at baseline, including mortality and the development of complications.ResultsThe ESI level was associated with mortality and the development of complications. During the 90-day follow-up period, patients with a low ESI (<12.05 cm2/m2) had higher mortality than those with a high ESI (≥ 12.05 cm2/m2) (51.7% vs. 26.7%), and the cumulative survival rates were 71.0%±4.6 and 85.8%±3.9, respectively (log-rank P = 0.003). The hazard ratios (HRs) calculated using univariable and multivariable analyses were 2.23(95% confidence interval (CI): 1.25–4.21, P = 0.005) and 2.52 (95% CI: 1.34–9.24, P = 0.011), respectively. Patients with a low ESI (<12.05 cm2/m2) had higher incidences of kidney dysfunction (43.5% vs. 23.2%, P = 0.029; log-rank P = 0.017) and hepatic encephalopathy (39.6% vs. 14.0%, P = 0.003; log-rank P = 0.010) than those with a high ESI. A low ESI was an independent risk factor for kidney dysfunction (adjusted HR = 1.36, 95% CI: 1.05–2.93, P = 0.043) and the development of hepatic encephalopathy (adjusted HR = 2.26; 95% CI: 2.05–3.13, P = 0.036). In addition, the presence of hepatic encephalopathy (the odds ratio (OR) = 2.26, 95% CI: 2.05–3.18, P = 0.006), spontaneous bacterial peritonitis (OR = 3.95, 95% CI: 1.01–5.46, P = 0.037), and kidney dysfunction (OR = 4.47, 95% CI: 1.02–9.64, P = 0.032) was independently associated with a low ESI in patients.ConclusionA low ESI is an independent risk factor for mortality in patients with HBV-ACLF, as well as the development of kidney dysfunction and hepatic encephalopathy.

Prevalence and associated factors for kidney dysfunction in hospitalized patients with COVID-19 pneumonia in Zambia

Background: A significant link has been reported between COVID-19 pneumonia, disease severity and development of kidney dysfunction. This study assessed the prevalence and correlated factors for kidney impairment in hospitalized patients with COVID-19 infection&#x0D; Methods: This nested retrospective study examined medical files of patients with confirmed COVID-19 pneumonia. The outcome variable was kidney dysfunction ( defined as functional renal indexes beyond the normal range) and associated factors. Multivariate logistic regression was employed to establish factors associated with renal dysfunction.&#x0D; Results: 179 patients were included in this nested study and the mean age was 58.3 years (SD 16.5) and 49.0% were female. The prevalence of renal dysfunction was 51.9% and 39.3% these patients renal had eGFR&lt;60 mL/min/1.73m2 The proportion of kidney impairment was higher in males than females (59.3% vs.44.3 %), patients with underlying hypertension than normotensive (60.5% vs. 39.5 %) and those with chronic kidney disease (CKD) than those without (90% vs. 10%). After adjusting for age, male gender, critical COVID-19 disease, and raised white cell count, hypertension was an independent predictor of kidney impairment with a AOR 1.54 (95% CI [1.06-2.23],p=0.022). Presence of HIV or diabetes mellitus showed a non statistical significance with renal dysfunction.&#x0D; Conclusion: The study demonstrated a high prevalence of kidney dysfunction in hospitalized patients with COVID-19 pneumonia and presence of hypertension predicted nearly 2-fold development renal impairment.

Prevalence and associated factors for kidney dysfunction in hospitalized patients with COVID-19 pneumonia in Zambia

Background: A significant link has been reported between COVID-19 pneumonia, disease severity and development of kidney dysfunction. This study assessed the prevalence and correlated factors for kidney impairment in hospitalized patients with COVID-19 infection&#x0D; Methods: This nested retrospective study examined medical files of patients with confirmed COVID-19 pneumonia. The outcome variable was kidney dysfunction ( defined as functional renal indexes beyond the normal range) and associated factors. Multivariate logistic regression was employed to establish factors associated with renal dysfunction.&#x0D; Results: 179 patients were included in this nested study and the mean age was 58.3 years (SD 16.5) and 49.0% were female. The prevalence of renal dysfunction was 51.9% and 39.3% these patients renal had eGFR&lt;60 mL/min/1.73m2 The proportion of kidney impairment was higher in males than females (59.3% vs.44.3 %), patients with underlying hypertension than normotensive (60.5% vs. 39.5 %) and those with chronic kidney disease (CKD) than those without (90% vs. 10%). After adjusting for age, male gender, critical COVID-19 disease, and raised white cell count, hypertension was an independent predictor of kidney impairment with a AOR 1.54 (95% CI [1.06-2.23],p=0.022). Presence of HIV or diabetes mellitus showed a non statistical significance with renal dysfunction.&#x0D; Conclusion: The study demonstrated a high prevalence of kidney dysfunction in hospitalized patients with COVID-19 pneumonia and presence of hypertension predicted nearly 2-fold development renal impairment.

Consequences of exposure to prenatal famine on estimated glomerular filtration rate and risk of chronic kidney disease among survivors of the great Ethiopian famine (1983\u201385): a historical cohort study

BackgroundThe impact of an adverse prenatal environment such as famine exposure on the development of adulthood non-communicable chronic illnesses, including diabetes and hypertension has been well articulated in the recent past and supported by evidence. However, there exist few longitudinal studies conducted on the long term consequences of prenatal famine exposure on adulthood kidney function. Hence, we set out to examine whether prenatal exposure to the Ethiopian Great Famine (1983–1985) was associated with changes in estimated glomerular filtration rate (eGFR) and the risk of developing chronic kidney disease (CKD) later in adult life.MethodsThe study was conducted in 219 famine exposed and 222 non exposed cohorts in Raya Kobo district, North Wollo Zone, Northern Ethiopia. Estimated GFR was computed from standardized serum creatinine using the CKD Epidemiology Collaboration (CKD-EPI) equation. The definition of CKD includes those with an eGFR of less than 60 ml/min/1.73 m2 on at least in two occasions of 90 days apart (with or without markers of kidney damage). Linear and logistic regression analyses were employed to examine the independent effect of prenatal famine exposure on eGFR and CKD respectively.ResultsThe mean (SD) serum creatinine of exposed and non-exposed groups were 0.78 (0.2) and 0.75 (0.2) respectively. The mean (SD) eGFR of exposed groups was 107.95 (27.49) while the non-exposed 114.48 (24.81) ml/min. In linear regression, the unadjusted model to examine the association between famine exposure and eGFR resulted in a significant negative beta coefficient (β = − 0.124: 95% CI: − 11.43, − 1.64). Adjusting the exposure for outstanding covariates of kidney health, including systolic blood pressure, fasting blood sugar and blood glucose did not alter the inverse relationship (β = −.114 95% CI: − 10.84, − 1.17). In the unadjusted bivariate logistic regression model, famine exposure resulted in nearly 2.7 times higher odds of developing CKD (OR: 2.68, 95% CI: 1.16, 6.2). The odds remained equivalent after adjusting for systolic blood pressure, fasting blood glucose and body mass index (OR = 2.61: 95% CI: 1.120, 6.09).ConclusionIn the study setting, prenatal exposure to the Great Ethiopian Famine was associated with decreased eGFR and higher risk of developing CKD among survivors. These findings may imply that famine in early life may play a significant role in the development of kidney dysfunction in adulthood.

Preventive effect of Artichoke (Cynara scolymus L.) in kidney dysfunction against high fat-diet induced obesity in rats

A high-fat diet (HFD) promotes oxidative stress, which contributes to the development of kidney dysfunction. We examined the protective effects of an ethanol extract of artichoke leaves (EEA) compared to Atorvastatin (ATOR) in the kidney of Wistar rats fed a high-fat diet. The experimental animals were divided into five groups: control (Cont), HFD, HFD treated with EEA (200 mg/kg), HFD treated with EEA (400 mg/kg), and HFD treated with ATOR. Organ weights, lipid profile, renal markers, and antioxidants enzymes were measured. Oral administration of EEA (200 and 400 mg/kg) for 60 days showed a significant decrease in organ weights and kidney markers levels accompanied by decreasing in oxidative stress biomarkers as compared to HFD groups. The histological findings showed a renoprotective effect of artichoke extract. These findings suggest that EEA exerts anti-oxidant kidney effects in HFD- induced obese rats.

The effect of dicarbonyl stress on the development of kidney dysfunction in metabolic syndrome \u2013 a transcriptomic and proteomic approach

Background and aimsDicarbonyl stress plays an important role in the pathogenesis of microvascular complications that precede the formation of advanced glycation end products, and contributes to the development of renal dysfunction. In renal cells, toxic metabolites like methylglyoxal lead to mitochondrial dysfunction and protein structure modifications.In our study, we investigated the effect of methylglyoxal on metabolic, transcriptomic, metabolomic and proteomic profiles in the context of the development of kidney impairment in the model of metabolic syndrome.Materials and methodsDicarbonyl stress was induced by intragastric administration of methylglyoxal (0.5 mg/kg bw for 4 weeks) in a strain of hereditary hypertriglyceridaemic rats with insulin resistance and fatty liver.ResultsMethylglyoxal administration aggravated glucose intolerance (AUC0–120p < 0.05), and increased plasma glucose (p < 0.01) and insulin (p < 0.05). Compared to controls, methylglyoxal-treated rats exhibited microalbuminuria (p < 0.01). Targeted proteomic analysis revealed increases in urinary secretion of pro-inflammatory parameters (MCP-1, IL-6, IL-8), specific collagen IV fragments and extracellular matrix proteins. Urine metabolomic biomarkers in methylglyoxal-treated rats were mainly associated with impairment of membrane phospholipids (8-isoprostane, 4-hydroxynonenal).Decreased levels of glutathione (p < 0.01) together with diminished activity of glutathione-dependent antioxidant enzymes contributed to oxidative and dicarbonyl stress. Methylglyoxal administration elevated glyoxalase 1 expression (p < 0.05), involved in methylglyoxal degradation. Based on comparative transcriptomic analysis of the kidney cortex, 96 genes were identified as differentially expressed (FDR < 0.05). Network analysis revealed an over-representation of genes related to oxidative stress and pro-inflammatory signalling pathways as well as an inhibition of angiogenesis suggesting its contribution to renal fibrosis.ConclusionOur results support the hypothesis that dicarbonyl stress plays a key role in renal microvascular complications. At the transcriptome level, methylglyoxal activated oxidative and pro-inflammatory pathways and inhibited angiogenesis. These effects were further supported by the results of urinary proteomic and metabolomic analyses.

Serum pigment epithelium-derived factor: Relationships with cardiovascular events, renal dysfunction, and mortality in the Veterans Affairs Diabetes Trial (VADT) cohort

BackgroundTo determine if serum pigment epithelium-derived factor (PEDF) levels predict cardiovascular events, renal dysfunction and mortality in the Veterans Affairs Diabetes Study (VADT). MethodsPEDF was evaluated in relation to subsequent cardiovascular outcomes, mortality, and renal dysfunction (defined as urinary albumin creatinine ratio (ACR) ≥300 mg/g), or chronic kidney disease (CKD) stages 3 (eGFR<60 ml/min) or 4 (eGFR<60 and <30 ml/min respectively). PEDF was measured by ELISA on sera from 881 participants collected a median (range) of 1.7 (0–5.0) years post-baseline, and later, from 832 participants 4.0 (1.5–6.9) years post-baseline. ResultsIn 743 participants, PEDF was measured at both time-points. PEDF increased over time from (mean ± SD) 10.5 ± 4.03 to 11.0 ± 4.86 ng/ml (paired t-test p = 0.0092). Lower eGFR (p < 0.01), higher serum creatinine (p < 0.01) and urinary ACR (p < 0.01) were associated with increasing PEDF. Multivariate event time models included either one or two follow-up windows (i.e., between first and second PEDF measures; and, when available, from second PEDF measure until study-end). PEDF tertiles were not associated with cardiovascular events, but were significantly associated with all-cause mortality [HR = 2.00 (1.03, 3.89) comparing first to third tertile] in models adjusted for age, minority status, VADT treatment arm and prior cardiovascular event status. Higher PEDF levels also associated with development of kidney dysfunction with adjusted HRs (95% CI comparing third to first PEDF tertiles: 2.74 (1.71, 4.39) for stage 3 CKD; and 3.84 (95% CI: 1.17, 12.5) for stage 4 CKD. ConclusionsOver 2-years, higher serum PEDF levels predicted advanced nephropathy in patients with type 2 diabetes.

MD2 blockade prevents oxLDL-induced renal epithelial cell injury and protects against high-fat-diet-induced kidney dysfunction

There is a strong epidemiological link between obesity, a growing worldwide concern, and kidney disease. Emerging evidence indicates that the pathogenic basis of obesity-related kidney disease may be attributed to Toll-like receptor 4 (TLR4) of the innate immune system. We hypothesized that renal epithelial cell injury in response to oxidized low-density lipoprotein (oxLDL) requires myeloid differentiation factor 2 (MD2), a co-receptor of TLR4. Moreover, we also hypothesized that renal dysfunction is MD2-dependent in the high-fat diet (HFD) mouse model. Results indicated that the MD2 selective inhibitor (L6H21) abrogated the oxLDL-induced formation of MD2-TLR4 dimerization in the renal proximal tubular epithelial cell line NRK-52E. Further, MD2 blockade in NRK-52E cells using siRNA target sequences or L6H21 prevented oxLDL-induced cell injury as indicated by expression of profibrotic molecules, autophagic activity and apoptosis. Similarly, TLR4 knockdown in NRK-52E cells using siRNA target sequences prevented oxLDL-induced cell injury. In the HFD mouse model, MD2 knockout protected against development of kidney dysfunction and renal tissue injury, corroborating the observations observed in NRK-52E cells. Thus, the oxLDL-induced renal tubular epithelial cell profibrotic responses, autophagy and apoptosis were dependent on MD2, as were the renal dysfunction and tissue impairment in HFD mice. These are new findings indicating that the MD2-TLR4 immune signaling complex is a critical pathogenic factor in the development of kidney disease related to obesity or metabolic syndrome.

The eNOS-NO pathway attenuates kidney dysfunction via suppression of inflammasome activation in aldosterone-induced renal injury model mice.

Hypertension causes vascular complications, such as stroke, cardiovascular disease, and chronic kidney disease (CKD). The relationship between endothelial dysfunction and progression of kidney disease is well known. However, the relationship between the eNOS–NO pathway and chronic inflammation, which is a common pathway for the progression of kidney disease, remains unexplored. We performed in vivo experiments to determine the role of the eNOS–NO pathway by using eNOS-deficient mice in a hypertensive kidney disease model. All mice were unilateral nephrectomized (Nx). One week after Nx, the mice were randomly divided into two groups: the aldosterone infusion groups and the vehicle groups. All mice also received a 1% NaCl solution instead of drinking water. The aldosterone infusion groups were treated with hydralazine to correct blood pressure differences. After four weeks of drug administration, all mice were euthanized, and blood and kidney tissue samples were collected. In the results, NLRP3 inflammasome activation was elevated in the kidneys of the eNOS-deficient mice, and tubulointerstitial fibrosis was accelerated. Suppression of inflammasome activation by knocking out ASC prevented tubulointerstitial injury in the eNOS knockout mice, indicating that the eNOS–NO pathway is involved in the development of kidney dysfunction through acceleration of NLRP3 inflammasome in macrophages. We revealed that endothelial function, particularly the eNOS–NO pathway, attenuates the progression of renal tubulointerstitial injury via suppression of inflammasome activation. Clinically, patients who develop vascular endothelial dysfunction have lifestyle diseases, such as hypertension or diabetes, and are known to be at risk for CKD. Our study suggests that the eNOS–NO pathway could be a therapeutic target for the treatment of chronic kidney disease associated with endothelial dysfunction.

Abstract P164: Inflammatory Cell Populations in a Mouse Model of Cardiorenal Syndrome

Objective: Renal dysfunction frequently coexists with heart disease, manifesting in a condition called cardiorenal syndrome (CRS). CRS results in accelerated failure of the heart and kidney via a complex combination of hemodynamic, neurohormonal, immunological and biochemical feedback pathways. Preliminary evidence suggests that inflammatory cells such as monocytes and macrophages may contribute to the pathogenesis of CRS. However, animal models of CRS remain limited and the roles of specific inflammatory cell subsets in CRS remains unclear. Here, we describe the establishment of a mouse model of CRS. Methods: Three-week-old C57BL/6J mice were subjected to sham uninephrectomy and normal-salt (SHAM/NS) diet or left uninephrectomy and high-salt (UNIX/HS) diet. After 4, 6 or 8 weeks, urine was collected for salt and protein analyses. The heart and kidney were collected for histochemical staining and analyses of inflammatory cell distribution by flow cytometry. Results: UNIX/HS mice had a higher kidney weight/body weight ratio and higher water intake than that of SHAM/NS mice. As early as 4 weeks post-surgery, UNIX/HS mice had higher urine creatinine levels (0.22 ± 0.02 mg/day c.f. 0.13 ± 0.02 mg/day) and higher proteinuria (0.46 ± 0.18 mg/day c.f. 5.37 ± 1.19 mg/day) than SHAM/NS mice. These results suggest the development of kidney dysfunction. Histological analysis revealed increased fibrosis in the heart and kidney at 8 weeks after UNIX/HS. Using flow cytometry, we characterized changes in the inflammatory cell populations in the heart and kidney that occur as CRS progresses. A significant increase in Ly6C hi monocyte (0.29 ± 0.06% c.f. 0.15 ± 0.02% of mean 1.0 x 10 6 total live cells) and neutrophil (1.00 ± 0.27% c.f. 0.41 ± 0.09%) proportions in the heart was observed 8 weeks after UNIX/HS. Conclusion: Therapeutic strategies targeting inflammatory signaling pathways and modulating specific inflammatory cell populations may reduce organ damage and improve prognosis in patients with CRS.

Recurrent urinary tract infection in females is a benign disease

BackgroundLittle is known about long-term consequences of recurrent urinary tract infections although 60% of women develop urinary tract infection during their lifetime and 20–40% of them have a recurrence. ObjectiveTo study the role of recurrent urinary tract infections in mortality or development of kidney dysfunction or hypertension in women. DesignRetrospective analysis of prospective, population-based 20-year follow-up study. SettingCommunity. SubjectsA birth cohort of 764 older females living in the defined geographical area in Southwestern Finland who were 70 years old at baseline. MethodsThe participants were examined and interviewed to assess health history, health behaviors, cardiovascular risk factors, morbidity and physical, social and psychocognitive functioning at the age of 70, 80, 85 and 90 years between 1991–2011. ResultsRecurrent urinary tract infections in females were not associated with increased mortality, development of hypertension or kidney dysfunction. Urinary incontinence predisposed females to receive antimicrobial treatment for recurrent urinary tract infections. ConclusionsThe results indicate that recurrent urinary tract infection in females is a benign disease in the absence of abnormalities of the urinary tract even in the older population.

Serum 1,25-Dihydroxyvitamin D and the Development of Kidney Dysfunction in a Japanese Community

Recent evidence indicates that vitamin D deficiency is associated with an increased risk of renal impairment, but studies addressing the influence of vitamin D deficiency on the development of chronic kidney disease (CKD) in the general Asian population have been few. A total of 2,417 community-dwelling individuals without CKD stage 3-5 aged ≥40 years were followed for 5 years (mean age, 60 years; women, 59.1%). The cumulative incidence of CKD stage 3-5, defined as estimated glomerular filtration rate (eGFR) <60ml·min(-1)·1.73m(-2), and the rate of decline in eGFR according to quartile of serum 1,25-dihydroxyvitamin D (1,25(OH)2D), were estimated. During follow-up, 378 subjects experienced CKD stage 3-5. The age- and sex-adjusted incidence of CKD stage 3-5 increased significantly with decreasing serum 1,25(OH)2D (P for trend <0.001). Compared with the highest quartile, the multivariate-adjusted odds ratio for the development of CKD stage 3-5 was 1.90 in the lowest quartile and 1.74 in the second lowest quartile, after adjusting for confounding factors. Additionally, lower serum 1,25(OH)2D was significantly associated with a greater change in eGFR (-0.10ml·min(-1)·1.73m(-2)·year(-1) per 10-pg/ml decrement in serum 1,25(OH)2D). Lower serum 1,25(OH)2D is a significant risk factor for the development of CKD stage 3-5 in the general Asian population.

Target blood pressure in sepsis: between a rock and a hard place

We acknowledge the constructive comments of Beloncle and colleagues [1] regarding our recently published study. We demonstrated that targeting a mean arterial blood pressure (MAP) between 50 and 60 mmHg (Low-MAP) in porcine fecal peritonitis was associated with increased incidence of acute kidney injury (AKI) in comparison to targeting a MAP between 75 and 85 mmHg (High-MAP), which resulted in increased net positive fl uid balance and vasopressor load [2]. Beloncle and colleagues argue that a dilution eff ect of the higher amount of fl uid resuscitation on creatinine concentrations cannot be ruled out. Nevertheless, we report total hemoglobin concentrations in our manuscript [1], and, at study end, they were actually higher in animals in the High-MAP group than in the Low-MAP group (10.0 g/dl versus 8.4 g/dl, respectively, P = 0.008; Table 3 in the original manuscript). � e assumption that the low incidence of AKI in animals allocated to the High-MAP group could be explained by a dilution eff ect is, therefore, unlikely [2]. We hypothesize that the circulating blood volume in the High-MAP group was lower at study end as a consequence of norepinephrineinduced vasoconstriction. Moreover, Beloncle and colleagues suspect that low baseline hemoglobin levels in the Low-MAP group may have contributed to the development of kidney dysfunction [2]. Nevertheless, since the values were virtually identical in the Low- and High-MAP groups (9.3 mg/dl and 9.2 mg/dl, respectively), it seems unlikely that low hemoglobin levels - which were normal for young pigs explain the observed diff erences in AKI. Abbreviations AKI, acute kidney injury; MAP, mean arterial blood pressure.

Transforming Growth Factor-β1-Gene Polymorphism in the Development of Kidney Disease After Liver Transplantation

The development of kidney dysfunction is one of the most important after liver transplantation (LT). Genetic variants of pathogenetically relevant cytokines may influence the development and course of the disease. The aim of our study was to evaluate the role of transforming growth factor-β1 (TGF-β1) polymorphism in this context. Four hundred eighty-six liver graft recipients were genotyped for TGF-β1 codon 25 (guanine → cytosine, G → C) by polymerase chain reaction. Renal function before and after LT was characterized by estimation of glomerular filtration rate (GFR) using four-parameter-modification of diet in renal disease formula on defined dates. GFR was compared among TGF-β1-genotype groups of the entire cohort within the median observation period of 7 years. For the assessment of renal function recovery after LT, patients were divided into three groups by GFR difference (ΔGFR = ± 10 mL/min). Mean pretransplant GFR differed significantly among TGF-β1-genotype groups (GG: 85.0 mL/min vs. GC/CC: 75.3 mL/min; P=0.016). The significance disappeared in the follow-up period. Although GG genotype demonstrated higher mean GFR levels, patients with GC/CC genotype tended to improve kidney function compared with GG genotype (P=0.013). Interestingly, lower mean GFR rates were observed among female compared with male recipients before (P=0.002), separately at all dates and cumulatively after LT (P<0.001). Genetic variants of one of the most important cytokine TGF-β1 at codon 25 may have an impact on kidney function, suggesting an unfavorable effect of C allele in pretransplant setting and serve as marker for the recovery of renal function after LT. The identification of further confounders seems to be promising.

Close bidirectional relationship between chronic kidney disease and atrial fibrillation: The Niigata preventive medicine study

Atrial fibrillation (AF) and chronic kidney disease share risk factors and pathophysiologic mechanisms, suggesting that two conditions have close relationships. This is a prospective community-based observational cohort study including 235,818 subjects based upon a voluntary annual health check-up program in Japan. We studied the association of kidney dysfunction at entry with subsequent new-onset AF and the association of AF at entry with the development of kidney disease. During a follow-up of 5.9 +/- 2.4 years, AF developed in 2947 subjects (1.3%). Baseline serum creatinine and estimated glomerular filtration rate (GFR) were associated with risk of subsequent AF. The HRs (95% CI) for AF were 1.32 (1.08-1.62) and 1.57 (0.89-2.77) for GFR 30 to 59 and <30 mL/min per 1.73 m(2), respectively. The effect of kidney disease on risk of new-onset AF remained significant in subjects without treated hypertension or diabetes. During the follow-up, 7791 subjects (3.3%) developed kidney dysfunction (GFR <60 mL/min per 1.73 m(2)), and 11 307 subjects (4.9%) developed proteinuria. Atrial fibrillation at entry was associated with development of kidney dysfunction (HRs [95% CI], 1.77 [1.50-2.10]) and proteinuria (HR [95% CI], 2.20 [1.92-2.52]). The association persisted in subjects without treated hypertension or diabetes. Kidney dysfunction increased the risk of new onset of AF, and AF increased the risk of development of kidney disease. This finding supports the concept that the two conditions share common abnormal molecular signaling pathways contributing to their pathogenesis.

Abstract 2152: Close Bidirectional Relationship Between Chronic Kidney Disease and Atrial Fibrillation: The Niigata Preventive Medicine Study

Atrial fibrillation (AF) and chronic kidney disease share risk factors including obesity, hypertension, diabetes, and the metabolic syndrome as well as pathophysiologic mechanisms including persistent inflammation and oxidative stress. We tested the hypothesis here that two conditions are risk factors for each other. This is a prospective community-based observational cohort study based upon an annual health check-up in Niigata prefecture, Japan. We studied the association of kidney dysfunction with new-onset AF and the association of AF with development of kidney disease in 235,818 subjects (mean age, 60.9 ± 11.7 years). Development of kidney dysfunction was defined by an elevation of serum creatinine level (≥1.4 mg/dL for men, ≥1.2 mg/dL for women) or an GFR reduction (&lt;60 ml/min/1.73 m 2 ) in subjects without baseline kidney dysfunction. Kidney disease as risk of AF During a follow-up of 5.9 ± 2.4 years, AF developed in 2,947 subjects (1.3%). Baseline serum creatinine and GFR were associated with risk of subsequent AF (adjusted hazard ratios, HRs [95% confidence interval, CI], 1.09 [1.02–1.17] for serum creatinine [1 mg/dL increment] and 1.02 [1.00 –1.03] for GFR [10 ml/min/1.73 m 2 decline]). The HRs for AF increased inversely with GFR: 1.32 (95% CI, 1.08 –1.62) for GFR 30 –59 ml/min/1.73 m 2 and 1.57 (95% CI, 0.89 –2.77) for GFR &lt;30 ml/min/1.73 m 2 . The effect of chronic kidney disease on risk of new-onset AF was significant after eliminating subjects with treated hypertension or diabetes. AF as risk of kidney disease During a 5.9 year follow-up, 7,791 subjects (4.0%) developed kidney dysfunction and 11,307 subjects (5.8%) developed proteinuria. Baseline AF was associated with development of kidney dysfunction (HRs [95% CI], 1.84 [1.30 –2.61] for serum creatinine-based model and 1.77 [1.50 –2.10] for GFR-based model) and proteinuria (HR [95% CI], 2.20 [1.92–2.52]). The association remained significant in subjects without treated hypertension and diabetes. Kidney dysfunction increased the risk of new-onset of AF and AF increased risk of development of kidney disease. This finding supports the concept that the two conditions share common abnormal molecular signaling pathways contributing to their pathogenesis.

Effects of Dexamethasone on the Development of Radiation Nephropathy in the Rat

Low-dose, chronic administration of the synthetic glucocorticoid, dexamethasone, to male CD-I rats in the drinking water or by osmotic minipumps implanted subcutaneously after supralethal irradiation of the kidneys (20 Gy) was studied. The effectiveness of treatment with dexamethasone in the drinking water at concentrations of 23 micrograms/l to 188 micrograms/l and treatment times varying from 33 to 166 days was evaluated. At monthly intervals kidney function was assayed by measuring the clearance of 51Cr-ethylenediaminetetraacetic acid. All dexamethasone treatment regimens increased survival times significantly and delayed the development of kidney dysfunction. The most effective combination of concentration of dexamethasone in drinking water and treatment interval after irradiation with respect to survival was 94 micrograms/l and 88 days. However, a slightly longer survival and a better functional result was obtained if an equivalent amount of dexamethasone was administered by minipumps. Shielding the adrenal glands during kidney irradiation did not prolong survival. This shows that the beneficial effect of dexamethasone is not due to compensation for reduced adrenal glucocorticoid production resulting from concomitant exposures of these glands during kidney irradiation.

Effects of Dexamethasone on Late Radiation Injury Following Partial-Body and Local Organ Exposures

Dexamethasone was evaluated as a treatment for radiation-induced lung, kidney, liver, and spinal cord injuries in rats. One experimental group was partial-body-irradiated (22.5 Gy) with the head, femur, and exteriorized intestine shielded to prevent acute mortality. Other animals received local irradiation to the kidney (20 Gy), liver (25 Gy), or a 1-cm segment of cervical spinal cord (18 to 40 Gy). Following irradiation half of the animals in each radiation group were given drinking water containing 188 micrograms/liter of dexamethasone. Tests were done to assess kidney function (hematocrit, plasma urea nitrogen, ethylenediaminetetraacetic acid clearance), liver function (rose bengal clearance, plasma glutamic oxaloacetic acid transaminase), or spinal cord injury (paralysis). The effectiveness of dexamethasone in preventing radiation injury was tissue specific. Dexamethasone eliminated lethal pleural fluid accumulation after partial-body irradiation and delayed development of kidney dysfunction after local kidney irradiation. As a result, dexamethasone increased the median survival time from 63 to 150 days after partial-body irradiation and from 126 to 175 days after local kidney irradiation. After whole-liver irradiation, development of hepatic functional injury was retarded by dexamethasone treatment but without significantly changing survival time. Dexamethasone had no effect on spinal cord tolerance but significantly shortened the latent period between radiation and paralysis.