Microbiological and molecular studies on a multidrug-resistant Pseudomonas aeruginosa from a liver transplant patient with urinary tract infection in Egypt.

BACKGROUND: Pseudomonas aeruginosa is an opportunistic pathogen responsible for complicated UTIs and exhibits high antibiotic resistance, leading to increased mortality rates, especially in cases of multidrug-resistant strains. This study aimed to investigate the antibiotic susceptibility patterns and genomic characterization of XDR strains identified in end-stage liver disease patients who underwent liver transplants. METHODS: In this study, a number of 30 individuals who underwent liver transplants were registered. Ninety urine and 60 wound site swab samples were collected and processed for culturing, identification, and antimicrobial sensitivity. Extensively drug-resistant strain EMARA01 was confirmed through Sanger sequencing and was then processed for whole genome sequencing to characterize the genomic pattern. Sequencing data were processed for de novo assembly using various tools and databases, including genome annotation, serotype identification, virulence factor genes, and antimicrobial resistance gene. Pangenome analysis of randomly selected 147 reference strains and EMAR01 sequenced strain was performed using the Bacterial Pan Genome Analysis (BPGA) software. RESULTS: Of these total examined samples, nosocomial infection due to P. aeruginosa was detected in twelve patients' samples. AST analysis showed that P. aeruginosa strains exhibit resistance to tobramycin, erythromycin, and gentamicin, followed by piperacillin and ofloxacin, and no strains exhibit resistance to meropenem and imipenem. The CARD database identified 59 AMR genes similar to the EMAR01 strain genome and mostly belong to the family involved in the resistance-nodulation-cell division (RND) antibiotic efflux pump. Five genes; nalC, nalD, MexR, MexA, and MexB, exhibit resistance to 14 classes of antibiotics, while two AMR; CpxR, and OprM, exhibit resistance to 15 classes of drugs. Pangenome analysis revealed that the pan-genome remained open, suggesting the potential for acquiring accessory and unique genes. Notably, the genes predominantly involved in amino acid transport metabolism were identified using the KEGG database. CONCLUSIONS: This study provides valuable insights into the antimicrobial resistance profile, genetic features, and genomic evolution of P. aeruginosa strains causing UTIs in liver transplant patients. The findings emphasize the significance of comprehending AMR mechanisms and genetic diversity in P. aeruginosa for developing effective treatment strategies and infection control measures.

Nitric Oxide Levels as a Marker of Intradialytic Hypertension in End-Stage Renal Disease Patients.

Intradialytic hypertension (IDH) is an important emerging complication in hemodialysis patients. No study has examined the diagnostic markers of various risk factors for the occurrence of IDH in chronic hemodialysis patients. Therefore, our study aimed to assess the use of nitric oxide (NO) as a marker of IDH among end-stage renal disease patients. The patients were divided into two groups: Group I (40 patients) with IDH and Group II (40 patients) without IDH. For all participants, a full medical history was taken, followed by laboratory examinations to measure the level of NO and a clinical examination. The dose of erythropoietin per week, the level of intact parathyroid hormone, and platelet count were significantly higher in Group I than in Group II, whereas the mean level of NO (2.10 ± 1.23 pmol/L) was highly significantly lower in patients with IDH (P < 0.001). Multivariate analysis showed that hypertension (odds ratio: 1.824, 95% confidence interval: 1.273-2.982) and the level of NO (odds ratio: 1.68, 95% confidence interval: 1.13-2.97) were independent risk factors for IDH. The receiver operating characteristic curve showed that the cutoff point of NO was 2.52 µmol/L to differentiate between cases with and without IDH (area under the curve = 0.844). Our findings support previous research regarding the involvement of endothelial dysfunction and a higher sodium level in the pathogenesis of IDH. We also found that the NO level had a good diagnostic value for the occurrence of IDH at a cutoff of 2.52 µmol/L.

Angiotensinogen Gene Missense Polymorphisms (rs699 and rs4762): The Association of End-Stage Renal Failure Risk with Type 2 Diabetes and Hypertension in Egyptians.

Type 2 diabetes mellitus (T2DM) and hypertension are common chronic diseases mainly associated with the development and progression of end-stage renal disease (ESRD) leading to morbidity and mortality. Gene polymorphisms linked to the renin-angiotensin (AGT)-aldosterone system (RAAS) were broadly inspected in patients with diabetic nephropathy (DN) and hypertension. This study aimed to investigate the association of AGT gene polymorphisms (rs699 and rs4762) with ESRD in T2DM hypertensive Egyptian patients. Genotyping of rs699 and rs4762 was conducted using the tetra-primers amplification refractory mutation system (ARMS-PCR). The allelic distribution analysis was performed on 103 healthy control subjects, 97 non-ESRD patients, and 104 patients with ESRD. The allelic frequencies of AGT gene polymorphisms (rs4762 and rs699) in all study participants were assessed. For the non-ESRD group, the frequencies of the alleles of AGT-rs4762 (χ2 = 31.88, p < 0.001, OR = 5.17, CI 95%: 2.81-9.51) and AGT-rs699 (χ2 = 4.85, p = 0.027, OR = 1.56, CI 95%: 1.05-2.33) were significantly associated with the non-ESRD group. However, for the ESRD group, the T allele was significantly higher than that in the controls (χ2 = 24.97, p < 0.001, odds ratio (OR) = 4.35, CI 95%: 2.36-8.02). Moreover, AGT (rs699) genotypes showed no significant difference between the ESRD group and controls. In conclusion, AGT gene polymorphisms rs699 and rs4762 were associated with non-ESRD versus controls, without any significant risk observed in all patient groups. However, the AGT (rs4762) variant showed a significant risk in the ESRD group in comparison to controls in Egyptians.

Platelet indices as an assessment tool of septic acute kidney injury.

Platelet (PLT), one of blood cells, plays a major role in physiological and pathological processes such as coagulation, thrombosis, inflammation, and keeping the integrity of vascular endothelium. There are a group of parameters that are used to measure the total amount of PLTs, PLTs morphology, and proliferation. PLT indices are associated with the severity of illness and patients' prognosis. It was reported that mean platelet volume (MPV) was raising synchronously with interleukin (IL)-6 and C-reactive protein in sepsis, and was correlated to the severity of the disease. We aimed to study PLT indices and its changes in sepsis and septic acute kidney injury (AKI) patients to assess the disease and its severity. The present study is a cross-sectional study, had been carried out at Menoufia University hospitals from August 2017 to August 2019. The various platelet indices [MPV, platelet distribution width (PDW) and plateletcrit (PCT)] are considered as outcome variables were compared among controls, cases with sepsis, and cases with sepsis associated AKI. Group I (31) cases with the clinical diagnosis of septic AKI, Group II (33) cases with the diagnosis of sepsis, and Group III (28) consecutive persons marked as negative in the output of the cell counter were taken as controls. Data were tabulated and statistically analyzed. There were 15 men and 15 women for Group I (septic AKI), 17 males and 16 females for Group II (sepsis) and 15 men and 13 women healthy controls as a control group. According to PLT indices MPV, there was a significant statistical difference (P1 <0.01) between Group I and II of patients as it were12.06 ± 1.23, 11.01 ± 1.20, respectively, and PDW also there was a significant statistical difference (P1 <0.01) as it were16.01 ± 2.33, 13.97 ± 2.14, respectively, and PCT there was no significant difference between the two groups. Furthermore, there was a significant statistical difference between Group I and II of patients according to procalcitonin, TNF-α and IL-10. From these results, we conclude that there were a statistical significant difference between the patient groups of critically ill.

The Human Genetic Variants CYP2J2 rs2280275 and EPHX2 rs751141 and Risk of Diabetic Nephropathy in Egyptian Type 2 Diabetic Patients.

BACKGROUND: Diabetic nephropathy (DN), the primary driver of end-stage kidney disease, is a problem with serious consequences for society's health. Single nucleotide polymorphisms (SNPs) can define differences in susceptibility to DN and aid in development of personalized treatment. Giving the importance of epoxyeicosatrienoic acids (EETs) in kidney health, we aimed to study the association between two SNPs in the genes controlling synthesis and degradation of EETs (CYP2J2 rs2280275 and EPHX2 rs751141 respectively) and susceptibility of type 2 diabetes mellitus (T2DM) patients to develop DN. PATIENTS AND METHODS: Two hundred subjects were enrolled and categorized into three groups: group I (80 T2DM patients with DN), group II (60 T2DM patients without DN) and group III (60 healthy controls). Urea, creatinine, albumin/creatinine ratio (ACR), and eGFR were measured for all participants. Genotyping of CYP2J2 rs2280275 and EPHX2 rs751141 was done by real time PCR. RESULTS: There was no significant difference between the studied groups regarding CYP2J2 rs2280275. In contrast, EPHX2 rs751141 was associated with increased risk of DN under a dominant model (GG vs GA+AA: OR=0.375; 95% CI (0.19-0.75), P=0.006) in unadjusted model and after adjustment for age and sex (OR=0.440; 95% CI (0.21-0.92), P=0.029), recessive model (AA vs GG+GA: OR=0.195; 95% CI (0.05-0.74), P=0.017) and additive model (GA vs GG+AA): OR=0.195; 95% CI (0.05-0.74), P=0.017). CONCLUSION: CYP2J2 rs2280275 was not associated with DN predisposition. However, EPHX2 rs751141 could be a genetic marker for development and progression of DN among Egyptian T2DM patients.

Study the Association of Tumor Necrosis Factor Promoter Polymorphism with Type 2 Diabetic Nephropathy.

Type 2 Diabetes Mellitus (T2DM) is well known to include an inflammatory component that has been considered to be related to diabetic complications. Diabetic nephropathy (DN) is one of the significant complications as it constitutes the most frequent cause of end-stage renal disease. Tumor Necrosis Factor-α (TNF-α) is known as a multifunctional proinflammatory cytokine which is associated with some pathological processes such as immunoregulation, proliferation, inflammation, and apoptosis. The aim was to explore the association between the TNF-α promoter -1031T/C single nucleotide polymorphism (SNP) and the serum TNF-α level in addition to nephropathy among type 2 diabetic patients. The study included 38 T2DM subjects without nephropathy (DM group), 40 subjects with DN, and 20 controls. Identification of TNF-α promoter gene polymorphism -1031T/C was done by PCR-RFLP, and genotyping was confirmed by direct sequencing. The serum TNF-α level was assessed by ELISA. Correlations were tested by Pearson's correlation analysis. Logistic regression was used to detect the most independent factor for development of DN. The serum level of TNF-α in the DM group was significantly higher than controls (p < 0.001); also, the DN group was considerably higher than controls and DM without nephropathy (p < 0.001). Also, there was a significant positive correlation between serum levels of TNF-α with FBG (fasting blood glucose), creatinine, total cholesterol, LDL-C, HbA1c, and microalbumin/creatinine ratio (ACR) among the DN group (p = 0.042, <0.001, <0.001, <0.001, 0.027, and 0.043, respectively). Mutant homozygous CC and heterozygous TC genotypes were higher in DN than in DM and controls. C allele was more represented in DN than in DM and controls (p = 0.003) while T allele was higher in controls than in DM and DN patients. The levels of TNF-α were higher in subjects who had mutant CC than the wild TT genotype among DN (p < 0.001). C allele was more risky for DN than T allele between DN and controls by 5.4-fold (CI: 1.75-16.68) as well as between DN and DM by 2.25-fold (CI: 1.1-4.59). Conclusion. Serum levels of TNF-α were higher in individuals with mutant CC genotype of -1031T/C TNF-α gene, and C allele could be associated with increased risk for nephropathy among patients with T2DM.

Improvement of Bi doping in ZnO nanocrystals by co-doping with Al: crystal geometry calculations and photocatalytic activity.

In this work we demonstrate enhancement in visible-light photocatalytic activity (PCA) of ZnO nanoparticles (NPs) with minimal attenuation of visible light transmittance. This approach can benefit numerous optoelectronic and photocatalytic applications. ZnO NPs were p-n co-doped with Al and Bi to improve Bi doping into the ZnO crystal. Al- and/or Bi-doped ZnO was coprecipitated by ammonia from aqueous nitrate solutions of Zn2+, Al3+, and Bi3+, followed by microwave heating. Doping concentrations in Al- and Bi- doped ZnO (AZO and BZO) and Al/Bi co-doped ZnO (ABZO) were 1, 3, 5, and 7 mole %. The resulting NPs were characterized by XRD, TEM, EDS, BET, and UV-visible absorption. While EDS shows that almost all added Bi was incorporated into the ZnO, XRD analysis of BZO reveals formation of α-Bi2O3 as a secondary phase due to the poor Bi solubility in ZnO. Co-doping of Al with Bi suppressed α-Bi2O3 formation and increased Bi solubility in ZnO. XRD-based calculations of the lattice constants and deformation strain, stress, and energy all show insertion of Al and/or Bi into the crystal with different extents according to the dopants' solubilities into ZnO. AZO and BZO NPs had E g lowered by 0.05-1.39 eV and 0.30-0.70 eV, respectively, relative to ZnO. On the other hand, ABZO had E g reductions of only 0.01-0.20 eV due to formation of acceptor-donor complex through co-doping. ABZO gave higher PCA enhancements with respect to E g reductions (Δk photo/-ΔE g) than either AZO and BZO, with values up to 370, 126, and 13 min-1 eV-1, respectively.

Relation of neuropeptide Y gene expression and genotyping with hypertension in chronic kidney disease.

OBJECTIVES: The prognosis of high-risk patients might be greatly ameliorated using genetic predisposition risk factors. Sympathetic activity and innate immunity related to neuropeptide Y function may be related to dyslipidemia and atherosclerosis. The aim of this study is to detect the correlation between Neuropeptide Y (NPY) SNP rs16147 and its gene expression in chronic kidney disease with and without hypertension. METHODS: This study carried out on 150 subjects who were divided into 3 main groups group (I) 50 CKD patients with hypertension, group (II) 50 CKD patients without hypertension and group (III) 50 healthy individuals. Carotid intima media thickness (CIMT) was measured by Ultrasound. Kidney function test and lipid profile were performed. Genotyping and gene expression of neuropeptide Y (NPY) were performed using real time PCR. RESULTS: There was a significant increase in number and percentage of CC genotype and C allele of NPY SNP distribution in CKD patients with and without hypertension when compared to controls. A significant association was found between CC genotype and C allele and the risk of CKD with hypertension with odd ratio 3.26 and 1.77, respectively. There is a significant positive correlation between NPY gene expression level and CIMT among chronic kidney disease patients with highest level of TC, LDLc and CIMT among CC genotype of NPY gene. CONCLUSION: A significant association was found between CC genotype and C allele of NPY at rs16147 with increase NPY gene expression and risk of developing hypertension in CKD.

Studying alternative approaches for placement of cuffed hemodialysis catheters in hemodialysis patients with bilateral internal jugular vein occlusion.

INTRODUCTION: Internal jugular vein occlusion often makes necessary the use of less desirable routes as external jugular, subclavian, and femoral vein approaches in addition to inferior vena cava approaches. This a prospective cross-sectional follow-up study of the alternative approaches for placement of cuffed hemodialysis catheters in end-stage renal disease patients with bilateral internal jugular vein occlusion from the interventional nephrology point of view. METHOD: The study was conducted on 134 end-stage renal disease patients who were referred for insertion of a challenging hemodialysis catheter due to bilateral internal jugular vein occlusion. Ultrasound Doppler guided catheter insertion was used as a routine practice in addition to fluoroscopy or post insertion X-ray to localize catheter tip position and exclude complications. Follow-up of patients was conducted until the end of the study or catheter removal. FINDINGS: The most highly prevalent alternative approach is the trans-external iliac vein inferior vena cava approach (43.28%) followed by external jugular vein approach (14.93%), innominate vein approach (10.18%), internal jugular vein collaterals by interventional radiology (7.46%), femoral vein approach (7.46%), transhepatic approach (5.97%), subclavian vein approach (5.22%), and finally the retrograde femoral vein approach (1.49%). DISCUSSION: End-stage renal disease patients maintained on regular hemodialysis who have bilateral internal jugular vein obstruction and non-functioning arteriovenous fistula/graft is a daily scenario in nephrology practice. Our study showed that there is a variety of approaches for the insertion of cuffed hemodialysis catheters other than occluded internal jugular veins. Interventional nephrologists have a major role in solving the problem of poor hemodialysis vascular access. These alternative approaches can conserve the anatomically limited number of percutaneous access sites in each patient.

First versus second trimester mean platelet volume and uric acid for prediction of preeclampsia in women at moderate and low risk.

OBJECTIVE: To determine if second trimester mean platelet volume (MPV) and serum uric acid are reasonable predictors of preeclampsia (PE) or not, in patients at moderate and low risk. METHODS: This prospective study was conducted on 9522 women at low or moderate risk for developing PE who underwent dual measurements of MPV and serum uric acid at late first trimester (10-12 weeks) and at second trimester (18-20 weeks) and subsequently divided into two groups; PE group (n = 286) who later developed PE and non-PE group (n = 9236). Test validity of MPV and serum uric acid was the primary outcome measure. Data were collected and analyzed. RESULTS: Second trimester MPV is a good predictor for development of PE at a cutoff value of 9.55 fL with area under the curve (AUC) of 0.86, sensitivity of 95.2%, specificity of 66.7%, positive predictive value (PPV) of 87%, negative predictive value (NPV) of 85.7%, and accuracy of 86.7%. Second trimester serum uric acid is a good predictor for development of PE at a cutoff value of 7.35 mg/dL, with AUC of 0.85, sensitivity of 95.2%, specificity of 55.6%, PPV of 83.3%, NPV of 83.3%, and accuracy of 83.3%. Combination of both tests has a sensitivity of 100%, specificity of 22.2%, PPV of 75%, NPV of 100%, and accuracy of 76.7%. CONCLUSION: Second trimester MPV and serum uric acid alone or in combination could be used as a useful biochemical markers for prediction of PE based on their validity, simplicity, and availability.

Improved pregnancy outcome following earlier splenectomy in women with immune thrombocytopenia: a 5-year observational study.

OBJECTIVE: To assess prospectively the maternal and fetal outcome in women with immune thrombocytopenic purpura (ITP) who undergone earlier splenectomy compared to women on medical therapy. METHODS: A 5-year observational study included pregnant women in the first trimester previously diagnosed with primary ITP with 74 patients underwent splenectomy before pregnancy and 86 patients on medical therapy. Patients were followed throughout pregnancy and labour to record their obstetric outcome. Data were collected and tabulated. RESULTS: There was a higher platelet count in the splenectomy group at enrollment (p < .05) and at delivery (p < .001). Higher number of patients in the medical group experienced bleeding episodes (p < .001), severe thrombocytopenia (p < .001), need for therapy (p < .001), complications of steroid therapy (p < .05), postpartum hemorrhage (p < .05), and defective lactation (p < .001) compared to patients in the splenectomy group. Higher rates of small for gestational age, preterm labour, and admission to neonatal intensive care unit (NICU) were observed in patients in the medical group (p < .05) compared to patients in the splenectomy group. CONCLUSION: Earlier splenectomy in patients with ITP may have a beneficial impact on obstetric outcome and should be explained to patients wishing to get pregnant. Further larger multicenter studies are warranted to confirm or refute our findings.

How assembly matters to catalysis and thermal conductivity mediated by CuO nanoparticles.

CuO nanostructures (NSs) of different morphologies were prepared, applied as catalysts for the pyrolysis of sugarcane bagasse (PSCB), and applied for thermally-conductive nanofluids. Both size and shape of the prepared NSs ranged from 5 to 1000 nm, and from nanodots (NDs) to spindle nano-aggregates (NAs), respectively. The catalytic activity of these NSs towards the PSCB was followed up by thermogravimetric analysis (TGA), where they increased the percentage of total weight loss, and lowered the decomposition temperatures of PSCB. The Coats-Redfern kinetic model showed a decline in activation energy by 57 and 9-43 kJ mol-1 for NDs and NAs, respectively. Colloidal dispersions of CuO NDs and NAs in monoethylene glycol (MEG) were prepared with volume fractions ([Formula: see text]) of 0.01-0.04%, where thermal conductivity improved with increasing [Formula: see text]. At all values of [Formula: see text], the best enhancements were exerted by NDs. The nature of assembly impacted the catalyzed PSCB and the thermal conductivity of MEG. This behavior depends to a large extent on the NAs that expose a different fraction of crystal facets of different reactivities and surface areas, not on the constituent nanorods (NRs).

Maternal and fetal morbidity following discontinuation of antihypertensive drugs in mild to moderate chronic hypertension: A 4-year observational study.

OBJECTIVE: To assess maternal and fetal morbidity in women with mild to moderate chronic hypertension on antihypertensive drug therapy compared to cessation of therapy. METHODS: This was a prospective observational study included 222 women with mild to moderate chronic hypertension (systolic blood pressure of 140-159mmHg or diastolic blood pressure of 90-109mmHg) who were divided into two groups based on antihypertensive drug intake, treatment group (n=104) who received methyl dopa, and non-treatment group (n=118) who used only low dose aspirin. Patients were followed to assess maternal and fetal outcome. RESULTS: There were significant differences between the two groups regarding the development of severe hypertension (p<0.001), renal impairment (p<0.001), ECG changes (p<0.001), placental abruption (p<0.05), repeated hospital admissions (p<0.001), preterm delivery (p<0.05) and neonatal ICU admission (p<0.05) with higher occurrence in the non-treatment group. There were no significant differences between the two groups in terms of the development of preeclampsia, hepatic impairment, mode of delivery, venous thromboembolism, small for gestational age, intrauterine fetal demise or neonatal mortality (p>0.05). CONCLUSION: Maternal and fetal morbidity is increased following cessation of antihypertensive drug use in patients with mild to moderate chronic hypertension. Further larger studies are warranted to confirm or refute our findings.

Histopathological Assessment of Dyspepsia in the Absence of Endoscopic Mucosal Lesions.

INTRODUCTION: Dyspepsia is a common symptom with an extensive differential diagnosis. Endoscopy alone may miss serious mucosal lesions in about 15 to 30% of cases. The aim was to determine histopathological features of gastric and duodenal mucosal biopsies in patients with dyspepsia and normal looking upper gastrointestinal (GI) endoscopy. MATERIALS AND METHODS: One hundred and five adult patients presenting with dyspepsia with no endoscopic mucosal lesions in the upper GI tract were included. Gastric biopsy specimens according to Sydney-Houston system for grading gastritis and biopsy from duodenum were taken. The histopathological features were graded according to the Sydney-Houston system classification for grading gastritis. RESULTS: The histological lesions were found in 65.7% (69 out of 105 endoscopy free dyspeptic patients). Chronic inflammation was the commonest finding. Neutrophilic activity, glandular atrophy, and mild degree of intestinal metaplasia were present in 27, 45, and 6 patients (22.8, 42.8, and 5.7% respectively). Helicobacter pylori was present in 54 patients with histopathological lesions and in 6 patients without histopathological lesions, and the difference was significant (p = 0.045). CONCLUSION: The endoscopic diagnosis of dyspepsia correlated poorly with histopathological findings. The histopathological examination allowed detection and grading of gastric pathology in dyspepsia with normal endoscopy and the commonest finding was the moderate chronic gastritis. HOW TO CITE THIS ARTICLE: Dawod HM, Emara MW. Histopathological Assessment of Dyspepsia in the Absence of Endoscopic Mucosal Lesions. Euroasian J Hepato-Gastroenterol 2016;6(2):97-102.

Maternal and fetal outcome in de novo preeclampsia in comparison to superimposed preeclampsia: a two-year observational study.

AIM: To assess the maternal and fetal outcome in women with de novo preeclampsia (PE) in comparison to superimposed PE. STUDY DESIGN: This was a prospective 2-year observational study carried out at Menoufia University Hospital, Egypt, in which 164 patients out of 6472 pregnant women were diagnosed with PE (78 with de novo PE and 86 with superimposed PE). Enrolled patients were followed to assess the maternal and fetal outcome. RESULTS: There was a significant higher women with liver impairment and delivery by caesarean section in the de novo PE group (p < 0.05), with more women with renal impairment and ECG changes in the superimposed PE group (p < 0.05). No significant difference between the two groups regarding the occurrence of eclampsia, blood transfusion, admission to ICU and venous thromboembolism (p > 0.05). There was a significantly higher small for gestational age, prematurity, NICU admission and perinatal mortality in the superimposed PE group (p < 0.05). No significant difference between the two groups regarding the occurrence of placental abruption and intrauterine fetal demise (p > 0.05). CONCLUSIONS: Women with de novo PE have higher risks of liver impairment and delivery by cesarean section. On the other hand, women with superimposed PE have higher risks of poorer fetal outcome.

Comparing measures of cystatin C in human sera by three methods.

BACKGROUND: Cystatin C (Cys C) is measured by particle-enhanced nephelometric immunoassay (PENIA), particle-enhanced turbidimetric immunoassay (PETIA) and ELISA. AIM: To determine differences among these methods. METHOD: 80 normal human sera and 20 from patients with renal and/or heart disease were simultaneously assayed. Statistical analyses including receiver operating characteristics (ROC) of the three methods were compared. RESULTS: There was a highly significant correlation across the assay range between the ELISA and PENIA (r(2) = 0.94) and PETIA methods (r(2) = 0.95). Analysis of variance and bias were poor between the ELISA and the other two methods. Mean difference between ELISA and PETIA was 0.65 +/- 0.63 microg/ml, while it was 0.58 +/- 0.53 microg/ml between ELISA and PENIA. Accuracy (at 30% range) was 17 and 11% between ELISA and PETIA and ELISA and PENIA, respectively. Normalization of the ELISA by a factor of 0.66 improved this relationship. AUC of ROC curves of PENIA, ELISA and normalized ELISA to predict Cys C levels measured from PETIA were all above 0.87 (p = not significant between curves). Criterion values of ELISA*.66 method was close to PETIA measurements. CONCLUSION: There is a significant difference in measured human Cys C levels among the three methods, and normalization of ELISA narrows these differences.

How to best define patients with moderate chronic kidney disease.

BACKGROUND: The objective of this study was to identify which formula may best identify moderate chronic kidney disease (CKD) (glomerular filtration rate (GFR) cut-off of 60 ml/min/1.73 m(2)). METHODS: We compared the performances of 14 serum creatinine (S(cr)) and 11 cystatin C (Cys C) estimated GFR equations using inulin clearance (Cl(in)) as the reference test in a stable CKD population of 101 patients. Scatter, coefficient of variation, bias, precision, accuracy within 30% ranges from the reference method, agreements and receiving operating characteristics (ROC) of each test were compared. RESULTS: ROC analysis identified Davis, Salzar, Virga and Cockcroft-Gault as the most sensitive (>or=85%) and the isotope dilution mass spectrometry (IDMS), Edwards, MacIsaac as the most specific (95%) to define the GFR cut-off level of 60 ml/min/1.73 m(2). Area under the ROC curve (AUC) was generally >0.8 (p

Evidence for a need to mandate kidney transplant living donor registries.

Kidney disease is a global public health problem of growing proportions. Currently the best treatment for end-stage renal failure is transplantation. Living organ donation remains a complex ethical, moral and medical issue. It is based on a premise that kidney donation is associated with short-term minimal risks to harm the donor, and is outweighed by the definite advantages to the recipient. A growing number of patients with end-stage renal disease and shortage of kidney donors poses a pressing need to expand the criteria needed to accept kidney donors. The current donor registries are structured and are driven to expand donor pool. As living kidney donation is not without risks, more attention should be given to protect the donor health. After kidney donation, mild to moderate renal insufficiency may occur. Renal insufficiency, even mild, is associated with increased risks of hypertension, proteinuria and cardiovascular morbidity. We, therefore, foresee a need to mandate the establishment of renal transplant donor registries at all transplanting programs as a prerequisite to protect the long-term well being of kidney donors. These registries can collect the database necessary to develop standards of practice and guidelines for future kidney donation.

Accuracy to estimate rates of decline in glomerular filtration rate in renal transplant patients.

BACKGROUND: We examined the use of the Cockroft Gault (C-G) test, Modified Diet in Renal Disease 2 (MDRD2) test, and inverse serum creatinine (Delta1/Scr) to estimate rates of decline in renal transplant function using isotope glomerular filtration rate (GFR) as a reference test. METHODS: Percent changes in estimated GFR (DeltaeGFR) were compared to simultaneous changes in isotope GFR (DeltaiGFR) in 72 patients. RESULTS: The number of iGFR was 508 with a mean of 7.15+/-3.15 scans per patient. There was a decline in iGFR of 16.14+/-21.37 ml/min over the study duration of 88.9+/-57.6 months. DeltaeGFR and Delta1/Scr correlated significantly with DeltaiGFR. Accuracy to predict DeltaiGFR from the eGFRs was limited to <65% concordance within 30% range from changes in iGFR. Slope analyses showed a significantly lower percent annual loss in mean iGFR of 6.03% than that of the C-G of 8.62% and MDRD2 of 8.96% (P<0.001). The within patient variability measured from the standard deviation (ml/min) of root mean square of 4.69 for iGFR was significantly higher than that for C-G and MDRD2 of 2.46 and 2.94, respectively. iGFR and eGFR at first observation correlated significantly (P<0.001) with last observation. CONCLUSIONS: iGFR is significantly more variable within patient than the other predictors, and the two estimators predict the iGFR with a high sensitivity but low specificity. This is a clinically reasonable combination. Predicted percent of annual loss in iGFR appears to be smaller than that using the two estimators.

Impact of Schistosoma mansoni co-infection on serum profile of interferon-gamma, interleukin-4 and interleukin-10 in patients with chronic hepatitis C virus infection.

T cell immunoregulatory cytokines may play a crucial role in the host response to hepatitis C virus infection. While T-helper type 1 (Th1) cytokines are required for host antiviral immune responses, T-helper type 2 (Th2) cytokines can inhibit the development of these effector mechanisms. The aim of this study was to investigate the serum levels of IFN-gamma, IL-4 and IL-10 and their roles in the pathogenesis of chronic HCV infection. Also, to explore the influence of Schistosoma mansoni co-infection on that profile of cytokines. Serum levels of IFN- gamma, IL-4 and IL-10 were measured by ELISA in 15 healthy control subjects (group 1), 18 patients with chronic HCV infection (group II) and 17 patients with chronic HCV co-infected with S. mansoni (group III). Routine liver function tests were performed for all groups. All patients had positive HCV RNA by reverse transcription polymerase chain reaction and elevated alanine amino transferase (ALT) levels for more than 6 months. Diagnosis of S. mansoni infection was based on detection of the parasite in the stools and/or rectal snips and seropositivity for schistosomal antibodies by ELISA. Hematoxylin and eosin stained liver biopsy sections were available and were examined for 25 patients (12 of group II and 13 of group III). There was no statistical difference in serum IFN- gamma levels between patients with chronic HCV infection and healthy controls. IL-4 and IL-10 serum levels were significantly elevated in chronic HCV patients compared to controls (P < 0.05). Chronic HCV patients co-infected with S. mansoni had significantly lower IFN-gamma and significantly higher IL-4 and IL-10 serum levels compared to the other groups (P < 0.05). Serum levels of IL-4 and IL-10 did not correlate to each others in both groups of patients (r = 0.29, P > 0.05 for group II, r = 0.30, P > 0.05 for group III). Patients co-infected with HCV and S. mansoni had necro-inflammatory scores significantly higher in comparison to patients infected with HCV alone (P < 0.05). Serum levels of IFN-gamma, IL-4 and IL-10 did not correlate with the different laboratory parameters, histological activity index or HCV-RNA viral load for all patients population (P > 0.05 for all comparisons). In Conclusions, Th1/Th2 cytokines imbalance is probably involved in the pathogenesis of chronic HCV infection. S. mansoni co-infection induces more alteration in the cytokine milieu, along with more-severe liver disease.