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Allison E Ashleykoch - One of the best experts on this subject based on the ideXlab platform.
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rna sequencing of isolated Cell populations expressing human apol1 g2 risk variant reveals molecular correlates of Sickle Cell Nephropathy in zebrafish podocytes
PLOS ONE, 2019Co-Authors: Joseph L Bundy, Blair R Anderson, Ludmila Francescatto, Melanie E Garrett, Karen L Soldano, Marilyn J Telen, Erica E Davis, Allison E AshleykochAbstract:Kidney failure occurs in 5–13% of individuals with Sickle Cell disease and is associated with early mortality. Two APOL1 alleles (G1 and G2) have been identified as risk factors for Sickle Cell disease Nephropathy. Both risk alleles are prevalent in individuals with recent African ancestry and have been associated with nephropathic complications in other diseases. Despite the association of G1 and G2 with kidney dysfunction, the mechanisms by which these variants contribute to increased risk remain poorly understood. Previous work in zebrafish models suggest that the G2 risk allele functions as a dominant negative, whereas the G1 allele is a functional null. To understand better the Cellular pathology attributed to APOL1 G2, we investigated the in vivo effects of the G2 risk variant on distinct Cell types using RNA sequencing. We surveyed APOL1 G2 associated transcriptomic alterations in podocytes and vascular endothelial Cells isolated from zebrafish larvae expressing Cell-type specific reporters. Our analysis identified many transcripts (n = 7,523) showing differential expression between APOL1 G0 (human wild-type) and APOL1 G2 exposed podocytes. Conversely, relatively few transcripts (n = 107) were differentially expressed when comparing APOL1 G0 and APOL1 G2 exposed endothelial Cells. Pathway analysis of differentially expressed transcripts in podocytes showed enrichment for autophagy associated terms such as “Lysosome” and “Phagosome”, implicating these pathways in APOL1 G2 associated kidney dysfunction. This work provides insight into the molecular pathology of APOL1 G2 Nephropathy which may offer new therapeutic strategies for multiple disease contexts such as Sickle Cell Nephropathy.
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rna sequencing of isolated Cell populations expressing human apol1 risk variants reveals molecular correlates of Sickle Cell Nephropathy in zebrafish podocytes
Blood, 2017Co-Authors: Joseph L Bundy, Blair R Anderson, Ludmila Francescatto, Melanie E Garrett, Karen L Soldano, Marilyn J Telen, Erica E Davis, Allison E AshleykochAbstract:Abstract Background: Kidney failure occurs in 5-13% of individuals with Sickle Cell disease (SCD), and is associated with early mortality. We have shown previously that genetic variation in apolipoprotein L1 (APOL1) is associated with increased risk for developing SCD Nephropathy (Ashley-Koch et al, 2011). Two APOL1 alleles (G1 and G2) have been identified as risk factors for SCD Nephropathy, as well as chronic kidney disease (CKD) in African Americans without SCD (Limou et al, 2014). Both risk alleles are highly prevalent in individuals of African descent. Despite the strong association of G1 and G2 with kidney dysfunction, the mechanisms by which these variants contribute to increased CKD risk remain poorly understood. However, the observation of podocyte effacement in CKD patients suggests that podocytes and/or endothelial Cells are likely implicated in pathogenesis. We established zebrafish models of these human risk alleles previously for the purpose of better understanding the underlying pathology contributing to SCD Nephropathy (Anderson et al, 2015). Here, we have utilized these models to explore further the Cell-type specific transcriptomic perturbations contributing to Nephropathy. Methods: To investigate the effects of the APOL1 G2 risk variant on Cell-type specific transcriptomes, we injected human APOL1 mRNA into embryos from 3 different zebrafish lines expressing Cell-type specific reporters to permit the isolation of podocytes (pod:NTR-mCherry), endothelial Cells (fli1:egfp), or peripheral neurons (hb9:gfp; control). Three populations from each line were utilized: (1) uninjected controls; (2) embryos injected with canonical human APOL1 (G0); and (3) embryos injected with human APOL1 (G2) mRNA. Larvae were dissociated at 4 days post-fertilization (4 dpf), and fluorescent Cell types were isolated via fluorescence activated Cell-sorting (FACS). Messenger RNA was extracted from sorted Cell populations (n=3 FACS sorted Cell populations per condition) and subsequently amplified to obtain a sufficient amount of RNA for sequencing. The amplified RNA was prepared into cDNA libraries, and sequenced on an Illumina HiSeq 2500. We performed pairwise comparisons between uninjected and G0 injected larvae in each Cell type to ascertain the effects of canonical human APOL1 on the zebrafish kidney transcriptome. Additionally, to measure the effects of APOL1 G2 expression on the transcriptome, we compared APOL1 G0 and APOL1 G2 samples. Transcripts were considered to be differentially expressed if they achieved an FDR-adjusted q-value of less than 0.05. To understand better the biological processes altered by injection condition, we conducted gene ontology enrichment analyses (GOEA) on sets of differentially expressed genes. Results: Our analysis of uninjected and APOL1 G0 libraries identified 38, 154, and 204 differentially expressed (DE) genes in endothelial Cells, podocytes, and motor neurons, respectively. No significant enrichment of gene ontology terms was detected, suggesting that canonical G0 APOL1 did not have a substantial impact on the zebrafish transcriptome. In contrast, the comparison of APOL1 G0 and APOL1 G2 samples found 95, 7400 (Figure below), and 652 DE genes in endothelial Cells, podocytes, and motor neurons, respectively. GOEA of the podocyte DE gene list showed enrichment for several autophagy-associated terms, including “Lysosome” and “Phagosome”. Close inspection of these autophagy-associated genes revealed that the majority are up-regulated in G2 relative to G0 (68/75 genes for “Lysosome” and 52/78 genes for “Phagosome”). Thus, the G2 allele appears to induce transcription of genes involved in autophagy in podocytes. Summary: Taken together, these data suggest that podocytes are the predominant Cell type affected by the expression of APOL1 G2. The comparison of podocytes injected with APOL1 G0 or APOL1 G2 yielded an order of magnitude more DE transcripts than any other comparison. The GOEA results of the podocyte comparison are consistent with a recent study of transgenic mice expressing the G1 or G2 APOL1 high risk variants, which showed alterations in endocytic vesicle content and autophagic flux (Beckerman et al 2017). Ongoing work includes molecular analysis to characterize the effects of the APOL1 G1 allele. This work will continue to shed light on the molecular pathology of SCD Nephropathy and provide insight into new therapeutic strategies. Download : Download high-res image (224KB) Download : Download full-size image Figure . Disclosures No relevant conflicts of interest to declare.
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evidence for a dominant negative effect conferred by the apol1 g2 Sickle Cell Nephropathy risk allele in an in vivo model
Blood, 2014Co-Authors: Blair R Anderson, Marilyn J Telen, Erica E Davis, Allison E AshleykochAbstract:BACKGROUND: Sickle Cell disease (SCD) patients have a heterogeneous clinical course, and as patient survival has improved, end-organ damage has become an emergent clinical priority. End stage renal disease (ESRD), occurring in 5-18% of SCD patients, is a particular concern, because it is a major risk factor for early mortality (Platt et al. 1994). Detection of SCD Nephropathy (SCDN) relies on relatively late-stage markers, namely proteinuria and reduced glomerular filtration rate (GFR). Consequently, at-risk SCD patients are not identified prior to end-organ damage. In non-SCD Nephropathy, ESRD risk among African American individuals has been attributed to coding variants (termed G1 and G2) in apolipoprotein L1 ( APOL1 ). The G1 allele consists of two nonsynonymous variants in perfect LD, rs73885319 and rs60910145 (encoding S384G and I384M), while the G2 variant consists of a six base pair deletion removing amino acids N388 and Y389 (~21% and ~13% allelic frequency in African Americans for G1 and G2, respectively). We demonstrated that these variants in APOL1 are strong predictors of risk for proteinuria in SCD (Ashley-Koch et al . 2011). Here, we use zebrafish as an in vivo model to both examine the role of apol1 in glomerular development and pronephric filtration and also to test the effects of APOL1 G1 and G2 expression in the developing kidney. METHODS: A morpholino (MO) was designed by Gene Tools, LLC (Philomath, OR) to target the translation initiation site of zebrafish apol1 . APOL1 G1 and G2 allelic constructs were synthesized from a wild-type (WT) APOL1 human open reading frame clone (GenBank: BC112943) using site-directed mutagenesis (Stratagene, QuikChange II), subsequently transcribed (mMESSAGE mMACHINE®, Life Technologies) into capped mRNA and co-injected with apol1 -MO into zebrafish embryos. To assay glomerular filtration, 70 kDa FITC-conjugated dextran was injected into the cardiac venous sinus of 48 hour post-fertilization embryos. The eye vasculature of individual fish was imaged at two, 12, and 36 hours after dextran injection. The average fluorescence intensity was measured across the eye, and changes in intensity relative to the 2-hour post-injection measurements were calculated for comparison. Electron microscopy sections of five days post-fertilization embryos were cut on a Leica-Reichert Ultracut E ultramicrotome, and semi-thin sections (1.0μm) were stained and examined on a Phillips CM12 electron microscope. RESULTS: As we showed previously (Anderson et al ., ASH 2013), MO-induced suppression of apol1 in zebrafish embryos results in pericardial edema, glomerular filtration defects, and extensive podocyte loss. Importantly, complementation of apol1 morphants with WT human APOL1 mRNA rescues the observed kidney defects. However, we now show that neither APOL1 G1 nor G2 risk alleles ameliorate defects caused by apol1 suppression. Notably, injection of APOL1 G2 alone results in renal defects, as indicated by increased dextran clearance and the presence of microvillus protrusions in the urinary space. Injection of APOL1 G1 alone, however, does not induce noticeable kidney dysfunction. Furthermore, when APOL1 G2 injected embryos were titrated with increasing concentrations of human APOL1 WT mRNA, we observed a significant reduction of edema formation in developing embryos, suggesting a possible dominant-negative effect of the altered protein. CONCLUSIONS: Unlike the WT APOL1 mRNA, neither the APOL1 G1 or G2 risk alleles could rescue kidney dysfunction due to knockdown of apol1 in zebrafish embryos, suggesting that these SCDN risk alleles impact the normal function of APOL1 in the kidney. Furthermore, development of edema with concomitant defects in glomerular ultrastructure in zebrafish embryos injected with APOL1 G2 mRNA alone suggest that this allele may act in a dominant-negative manner to induce kidney defects. Interestingly, it has been shown that APOL1 may cause toxic renal effects through programmed Cell death pathways leading to glomerulosclerosis (Wan et al. 2008). Thus, apol1 suppression could result in the dysregulation of autophagic pathways, causing podocyte malformation and thereby affecting the susceptibility of the pronephros to glomerular injury. In summary, these data provide essential insight into the biological mechanisms by which APOL1 variants confer disease risk in human SCDN and other nondiabetic nephropathies. Disclosures No relevant conflicts of interest to declare.
Karl Skorecki - One of the best experts on this subject based on the ideXlab platform.
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apol1 Nephropathy a population genetics and evolutionary medicine detective story
Seminars in Nephrology, 2017Co-Authors: Etty Kruzeldavila, Walter G Wasser, Karl SkoreckiAbstract:Summary: Common DNA sequence variants rarely have a high-risk association with a common disease. When such associations do occur, evolutionary forces must be sought, such as in the association of apolipoprotein L1 (APOL1) gene risk variants with nondiabetic kidney diseases in populations of African ancestry. The variants originated in West Africa and provided pathogenic resistance in the heterozygous state that led to high allele frequencies owing to an adaptive evolutionary selective sweep. However, the homozygous state is disadvantageous and is associated with a markedly increased risk of a spectrum of kidney diseases encompassing hypertension-attributed kidney disease, focal segmental glomerulosclerosis, human immunodeficiency virus Nephropathy, Sickle Cell Nephropathy, and progressive lupus nephritis. This scientific success story emerged with the help of the tools developed over the past 2 decades in human genome sequencing and population genomic databases. In this introductory article to a timely issue dedicated to illuminating progress in this area, we describe this unique population genetics and evolutionary medicine detective story. We emphasize the paradox of the inheritance mode, the missing heritability, and unresolved associations, including cardiovascular risk and diabetic Nephropathy. We also highlight how genetic epidemiology elucidates mechanisms and how the principles of evolution can be used to unravel conserved pathways affected by APOL1 that may lead to novel therapies. The APOL1 gene provides a compelling example of a common variant association with common forms of nondiabetic kidney disease occurring in a continental population isolate with subsequent global admixture. Scientific collaboration using multiple experimental model systems and approaches should further clarify pathomechanisms further, leading to novel therapies.
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Mini-Review Gene–Gene and Gene–Environment Interactions
2016Co-Authors: In Apolipoprotein Gene-associated L Nephropathy, Barry I. Freedman, Karl SkoreckiAbstract:Molecular genetics have revolutionized the understanding of susceptibility to the broad spectrum of kidney diseases with light microscopic appearance of FSGS, particularly in populations with recent African ancestry. These disorders include idiopathic FSGS, HIV-associated Nephropathy, severe lupus nephritis, Sickle Cell Nephropathy, and the primary kidney disorder focal global glomerulosclerosis, which had historically been ascribed to systemic hypertension. FSGS was once thought to include a multitude of unrelated disorders with similar histologic appearance. However, variation in the apolipoprotein L1 gene locus is now known to account for the vast majority of such cases in African Americans as well as nearly all the excess risk for FSGS and related forms of progressive nondiabetic Nephropathy in populations with recent African ancestry, relative to European ancestry. Inheriting two coding apolipoprotein L1 gene Nephropathy risk variants is necessary for susceptibility to CKD; however, these variants alone are insufficient to produce disease. Thiswork reviews the evidence supporting second hits or modifying factors that affect risk for apolipoprotein L1 gene-associated Nephropathy and produce the protean manifestations of this common and complex syndrome. Targeting modifiable second factors will lead to preventive therapies for slowing progression of nondiabetic Nephropathy in many patients possessing two apolipoprotein L1 gene risk variants. This model of genetic risk coupled with modifiable second hits will serve as a paradigm applicable to patients with CKD of various etiologies as well as a host of other complex disorders
P O Uadia - One of the best experts on this subject based on the ideXlab platform.
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association of oxidative stress markers with atherogenic index of plasma in adult Sickle Cell Nephropathy
Anemia, 2012Co-Authors: M A Emokpae, P O UadiaAbstract:This paper evaluates the association of oxidative stress and atherogenic index of plasma in order to assess the cardiovascular risk in Sickle Cell Nephropathy especially as lipoprotein levels are lower in SCD than non-SCD patients. Antioxidant enzymes, malondialdehyde(MDA), urea, creatinine, and glomerular filtration rate were evaluated in 110 confirmed Sickle Cell disease patients: 65 males in steady state, aged 21.1 ± 6.0 years, 30 males with macroalbuminuria, aged 24.5 ± 7.0, years and 15 with chronic kidney disease (CKD), aged 31.8 ± 2.0 years. The mean activity levels of glutathione peroxidase (GPx), superoxide dismutase (Cu/ZnSOD), and catalase (CAT) were significantly lower (P < 0.001) in SCD with macroalbuminuria and CKD while MDA was higher (P < 0.001) in SCD with macroalbuminuria and CKD compared with controls. There was negative correlation between GPx (P < 0.001), Cu/ZnSOD (P < 0.02), and Atherogenic index of plasma in SCD with CKD, while MDA shows a positive correlation (P < 0.001) with AIP in SCD with CKD. There was however no correlation between CAT and AIP. Decreased activity levels of antioxidant enzymes and low HDL-cholesterol concentration were confirmed in adult SCD with CKD in Nigerians. The increase oxidative stress and high atherogenic index in CKD may accelerate the process of cardiovascular complications in adult SCD patients. Atherogenic index of plasma was negatively correlated with antioxidant enzymes and positively with MDA.
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correlation of oxidative stress and inflammatory markers with the severity of Sickle Cell Nephropathy
Annals of African Medicine, 2010Co-Authors: M A Emokpae, P O Uadia, A A GadzamaAbstract:Background : Reactive oxygen species have been shown to mediate inflammatory process and may be involved in lipid peroxidation. Methods : This study evaluates superoxide dismutase, glutathione peroxidase, catalase, malondialdehyde, C- reactive protein and fibrinogen in the serum of patients with Sickle Cell disease and their correlation with renal insufficiency. Superoxide dismutase, glutathione peroxides and C - reactive protein were assayed using sandwich ELISA technique while malondialdehyde and fibrinogen were determined using thiobarbituric reactive substance and turbidometric technique, respectively. Results : The study group consisted of 40 patients with Sickle Cell disease along with macroalbuminuria, 16 with chronic kidney disease and 144 Sickle Cell disease controls. Superoxide dismutase, glutathione peroxidase and catalase were decreased while malondialdehyde, C-reactive protein and fibrinogen were increased in patients with Sickle Cell disease along with renal insufficiency. These parameters correlated with the severity of renal disease. Conclusion : Oxidative stress and inflammatory parameters correlate with Sickle Cell disease Nephropathy.
Lawrence Y Agodoa - One of the best experts on this subject based on the ideXlab platform.
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Sickle Cell Nephropathy at end stage renal disease in the united states patient characteristics and survival
Clinical Nephrology, 2002Co-Authors: Kevin C Abbott, Iman O Hypolite, Lawrence Y AgodoaAbstract:Background: The patient characteristics, including age at presentation to end-stage renal disease (ESRD) and mortality associated with Sickle Cell Nephropathy (SCN) have not been characterized for a national sample of patients. Methods: 375,152 patients in the United States Renal Data System were initiated on ESRD therapy between January 1, 1992 and June 30, 1997 and analyzed in an historical cohort study of SCN. Results: Of the study population, 397(0.11%) had SCN, of whom 93% were African-American. The mean age at presentation to ESRD was 40.68 ± 14.00 years. SCN patients also had an independently increased risk of mortality (hazard ratio 1.52, 95% CI: 1.27 - 1.82) even after adjustment for placement on the renal transplant waiting list, diabetes, hematocrit, creatinine, and body mass index. However, when receipt of renal transplantation was also included in the model, SCN was no longer significant (p = 0.51, HR = 1.10, 95% CI: 0.82 - 1.48). SCN patients were much less likely to be placed on the renal transplant waiting list or receive renal transplants in comparison to age and race matched controls, and results of survival analysis were similar in this model. Conclusions: SCN patients were much less likely to be listed for or receive renal transplantation than other comparable patients with ESRD. SCN patients were at independently increased of mortality compared with other patients with ESRD, including those with diabetes, but this increased risk did not persist when models adjusted for their low rates of renal transplantation.
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renal transplantation in end stage Sickle Cell Nephropathy
Transplantation, 1999Co-Authors: Akinlolu O Ojo, Timothy C Govaerts, Robert L Schmouder, Alan B Leichtman, Sean F Leavey, Robert A Wolfe, Philip J Held, Friedrich K Port, Lawrence Y AgodoaAbstract:Background. The role of renal transplantation as treatment for end-stage Sickle Cell Nephropathy (SCN) has not been well established. Methods. We performed a comparative investigation of patient and allograft outcomes among age-matched African-American kidney transplant recipients with ESRD as a result of SCN (n=82) and all other causes (Other-ESRD, n=22,565). Results. The incidence of delayed graft function and predischarge acute rejection in SCN group (24% and 26%) was similar to that observed in the Other-ESRD group (29% and 27%). The mean discharge serum creatinine (SCr) was 2.7 (± 2.5) mg/dl in the SCN recipients compared to 3.0 (± 2.5) mg/dl in the Other-ESRD recipients (P=0.42). There was no difference in the 1-year cadaveric graft survival (SCN: 78% vs. Other-ESRD : 77%), and the multivariable adjusted 1-year risk of graft loss indicated no significant effect of SCN (relative risk [RR]=1.39, P=0.149). However, the 3-year cadaveric graft survival tended to be lower in the SCN group (48% vs. 60%, P=0.055) and their adjusted 3-year risk of graft loss was significantly greater (RR=1.60, P=0.003). There was a trend toward improved survival in the SCN transplant recipients compared to their dialysis-treated, wait-listed counterparts (RR=0.14, P=0.056). In comparison to the Other-ESRD (RR=1.00), the adjusted mortality risk in the SCN group was higher both at 1 year (RR=2.95, P=0.001) and at 3 years (RR=2.82, P=0.0001) after renal transplantation. Conclusions. The short-term renal allograft result in recipients with end-stage SCN was similar to that obtained in other causes of ESRD, but the long-term outcome was comparatively diminished. There was a trend toward better patient survival with renal transplantation relative to dialysis in end-stage SCN.
M A Emokpae - One of the best experts on this subject based on the ideXlab platform.
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neutrophil to lymphocyte platelet to lymphocyte ratios and their association with atherogenic index of plasma in Sickle Cell Nephropathy
Journal of Applied Hematology, 2016Co-Authors: M A Emokpae, Aliyu Abdu, Baffa A GwaramAbstract:Background/Objectives: Neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios (NLR and PLR) were introduced as cheap and readily assessed biologic markers of subclinical inflammation. There are few studies that have evaluated NLR and PLR as prognostic markers of proteinuria in Sickle Cell anemia (SCA) patients. This study seeks to evaluate NLR and PLR in SCA patients with proteinuria, impaired kidney function and to ascertain whether there exist relationship between the leukocyte ratios and atherogenic index of plasma. Materials and Methods: The NLR, PLR, and atherogenic index were calculated from full blood count and lipid profile parameters determined from fasting blood specimens collected from 200 confirmed SCA patients and 100 control subjects with normal hemoglobin (Hb). Results: The NLR and PLR values were significantly higher (P < 0.001) in SCA patients compared with control subjects with normal Hb. Similarly, NLR and PLR values were significantly higher (P < 0.001) in SCA patients with proteinuria and those with impaired kidney function than without proteinuria and normal controls. A significantly positive association was observed between NLR and atherogenic index of plasma (AIP) in SCA patients with proteinuria (P < 0.05) and those with impaired kidney function (P < 0.02) while significant association was observed between PLR and AIP in SCA with impaired kidney function (P < 0.05). Conclusion: The leukocyte ratios may be useful as prognostic markers for the presence of proteinuria in SCA patients and impaired kidney function as well as cardiovascular risk event. The need to have reference cut-off values of NLR and PLR is hereby suggested to better identify those patients at risk in the management SCA patients.
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association of oxidative stress markers with atherogenic index of plasma in adult Sickle Cell Nephropathy
Anemia, 2012Co-Authors: M A Emokpae, P O UadiaAbstract:This paper evaluates the association of oxidative stress and atherogenic index of plasma in order to assess the cardiovascular risk in Sickle Cell Nephropathy especially as lipoprotein levels are lower in SCD than non-SCD patients. Antioxidant enzymes, malondialdehyde(MDA), urea, creatinine, and glomerular filtration rate were evaluated in 110 confirmed Sickle Cell disease patients: 65 males in steady state, aged 21.1 ± 6.0 years, 30 males with macroalbuminuria, aged 24.5 ± 7.0, years and 15 with chronic kidney disease (CKD), aged 31.8 ± 2.0 years. The mean activity levels of glutathione peroxidase (GPx), superoxide dismutase (Cu/ZnSOD), and catalase (CAT) were significantly lower (P < 0.001) in SCD with macroalbuminuria and CKD while MDA was higher (P < 0.001) in SCD with macroalbuminuria and CKD compared with controls. There was negative correlation between GPx (P < 0.001), Cu/ZnSOD (P < 0.02), and Atherogenic index of plasma in SCD with CKD, while MDA shows a positive correlation (P < 0.001) with AIP in SCD with CKD. There was however no correlation between CAT and AIP. Decreased activity levels of antioxidant enzymes and low HDL-cholesterol concentration were confirmed in adult SCD with CKD in Nigerians. The increase oxidative stress and high atherogenic index in CKD may accelerate the process of cardiovascular complications in adult SCD patients. Atherogenic index of plasma was negatively correlated with antioxidant enzymes and positively with MDA.
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correlation of oxidative stress and inflammatory markers with the severity of Sickle Cell Nephropathy
Annals of African Medicine, 2010Co-Authors: M A Emokpae, P O Uadia, A A GadzamaAbstract:Background : Reactive oxygen species have been shown to mediate inflammatory process and may be involved in lipid peroxidation. Methods : This study evaluates superoxide dismutase, glutathione peroxidase, catalase, malondialdehyde, C- reactive protein and fibrinogen in the serum of patients with Sickle Cell disease and their correlation with renal insufficiency. Superoxide dismutase, glutathione peroxides and C - reactive protein were assayed using sandwich ELISA technique while malondialdehyde and fibrinogen were determined using thiobarbituric reactive substance and turbidometric technique, respectively. Results : The study group consisted of 40 patients with Sickle Cell disease along with macroalbuminuria, 16 with chronic kidney disease and 144 Sickle Cell disease controls. Superoxide dismutase, glutathione peroxidase and catalase were decreased while malondialdehyde, C-reactive protein and fibrinogen were increased in patients with Sickle Cell disease along with renal insufficiency. These parameters correlated with the severity of renal disease. Conclusion : Oxidative stress and inflammatory parameters correlate with Sickle Cell disease Nephropathy.