Neutrophil gelatinase-associated lipocalin as a biomarker of nephropathy in sickle cell disease.

Sickle cell nephropathy (SCN) develops via altered hemodynamics and acute kidney injury, but conventional screening tests remain normal until advanced stages. Early diagnostic biomarkers are needed so that preventive measures can be taken. This study evaluates the role of neutrophil gelatinase-associated lipocalin (NGAL) as a biomarker of SCN in steady state and vaso-occlusive crisis (VOC). In this case-control study, 74 sickle cell disease (SCD) patients (37 in steady state and 37 in VOC) and 53 control subjects had hematological and biochemical measurements including plasma and urine NGAL. Univariate and logistic regression analyses were used to find the associations between variables. The receiver operating characteristic (ROC) curve was used to determine the diagnostic performance characteristics of plasma and urine NGAL for detection of VOC. Plasma and urine NGAL, urine microalbumin:creatinine ratio, and urine protein:creatinine ratio were significantly higher in VOC. Microalbuminuria was present in 17.1% steady state and 32.0% VOC patients. Microalbuminuria showed significant correlations with age, plasma NGAL, WBC, and hemolytic parameters. Area under the ROC curve for plasma NGAL was 0.69 (95%CI = 0.567-0.813; p = 0.006) and 0.86 (95%CI = 0.756-0.954; p < 0.001) for urine NGAL. Urine NGAL cut-off value of 12.0 ng/mL had 95% sensitivity and 65% specificity. These results confirm the presence of nephropathy during VOC and suggest that plasma and urine NGAL would be useful in the identification of SCN. Urine NGAL should be used as the screening biomarker, and patients with VOC and urine NGAL > 12.0 ng/mL should be selected for aggressive management to prevent progression of renal damage.

Correction to: A matched case-control study of risk factors associated with multiple sclerosis in Kuwait.

An amendment to this paper has been published and can be accessed via the original article.

A matched case-control study of risk factors associated with multiple sclerosis in Kuwait.

BACKGROUND: Genetic and environmental factors seem to have etiologic roles in multiple sclerosis (MS). Kuwait is regarded as medium to high risk country for MS. However, there is a paucity of published data on the risk factors for MS in Kuwait. Therefore, this matched case-control study examined the association between various factors including family history, stressful life events, exposure to tobacco smoke, vaccination history, comorbidities and MS risk in Kuwait. METHODS: Confirmed 110 MS cases and age (± 5 years), gender and nationality matched controls (1:1) were enrolled. A pre-tested structured questionnaire was used to collect the data through face-to-face interviews both from cases and controls. Conditional logistic regression was used to analyze the data. RESULTS: Among both cases and controls, majority were Kuwaiti (82.7%), and female (76.4%). Multivariable model showed that cases compared to controls were significantly more likely to have had a family history of MS (adjusted matched odds ratio (mORadj) = 5.1; 95% CI: 2.1-12.4; p < 0.001) or less likely to have been vaccinated against influenza A and B viruses before MS onset (mORadj = 0.4; 95% CI: 0.2-0.8; p = 0.010). None of the other variables considered were significantly related to MS status in this study. CONCLUSIONS: Family history of MS had significantly direct, whereas, vaccination against influenza A and B viruses had inverse associations with MS status. Future studies may contemplate to verify the observed results.

Transthoracic echocardiography and 6-minute walk test in Kuwaiti sickle cell disease patients.

OBJECTIVE: The aim of this study was to investigate cardiac abnormalities in Kuwaiti sickle cell disease (SCD) patients using markers such as tricuspid regurgitant jet velocity (TRJV), pulmonary artery systolic pressure (PASP), and the 6-minute walk (6MW) test and correlate these findings with clinical, hematological, and biochemical parameters. MATERIALS AND METHODS: Seventy-three patients with SCD and 70 matched controls were studied. The cardiac status was investigated using transthoracic echocardiography in 57 patients; the 6MW test was carried out in patients and controls. Complete blood counts and hemolytic parameters were assessed. RESULTS: Reticulocytes, bilirubin, and lactate dehydrogenase were significantly higher (p < 0.0001) in patients, while hemoglobin (Hb) and haptoglobin were lower (p < 0.0001) than in controls. The mean fetal Hb among patients was 15.85 ± 8.7%. Of the 57 patients, 14 (24.5%) and 15 (26%) had mild tricuspid and mitral regurgitation, respectively. The mean ejection fraction, TRJV, and PASP were 63.9 ± 6.3%, 1.7 ± 0.5 m/s, and 23.0 ± 7.3 mm Hg, respectively. Three (5.2%) patients had mildly raised TRJV (2.6-2.97 m/s, normal range <2.5 m/s) while 8 (14%) had high PASP (mean 35.3 ± 5.1 mm Hg, normal range <30 mm Hg). Hb, hematocrit, and reticulocytes were different (p = 0.010, p = 0.006, and p = 0.011, respectively) between patients with normal and high PASP. All 3 patients who had a high TRJV had a high PASP, and 2 of these patients died during follow-up. The systolic and diastolic blood pressure, oxygen saturation before and after the 6MW test, and distance walked were lower (p = 0.006, p = 0.000, p = 0.002, p = 0.000, and p = 0.000, respectively) in patients compared to controls. CONCLUSION: Raised PASP was common in Kuwaiti SCD patients while raised TRJV was not.

Recombinant hepatitis B vaccine uptake and multiple sclerosis risk: A marginal structural modeling approach.

BACKGROUND: There has been an ongoing debate regarding the association between uptake of recombinant vaccine against hepatitis B virus (HBV) and multiple sclerosis (MS) risk. This case-control study tested the hypothesis whether recombinant HBV vaccination status is causally associated with MS risk using targeted maximum likelihood estimation (TMLE) technique. METHODS: Confirmed 110 MS cases and age (± 5 years), sex and nativity matched (1:1) 110 controls were enrolled. Data were collected on sociodemographics, environmental factors, history of vaccinations and past morbidities through face-to-face interview both from cases and controls. To estimate the causal parameters including marginal odds ratio (OR), causal relative risk (RR), causal risk difference (RD) and their 95% confidence intervals (CIs), we implemented case-control-weighted TMLE for a matched design that uses data-adaptive flexible stacked ensemble-based machine learning system namely Super Learner. Additionally, population preventable fraction (PPF) of MS risk was computed. RESULTS: This study demonstrated a significant nonspecific protective effect of HBV vaccination against MS risk (marginal OR 0.44; 95% CI: 0.19-0.68; p = 0.006; causal RR 0.64, 95% CI: 0.46-0.89; p = 0.004). The significant causal RD showed that among the vaccinated 19% fewer MS cases occurred owing to their HBV vaccination (causal RD -0.19; 95% CI: -0.32 - -0.06; p = 0.014). In the source population, vaccination against HBV led to 17.4% reduced MS risk (PPF = 17.4%; 95% CI: 3.8%, 36.3%). CONCLUSION: The results suggest a significant nonspecific protective effect of recombinant HBV vaccine against MS risk. Future studies may contemplate to confirm these results.

Determinants and associations of homocysteine and prothrombotic risk factors in Kuwaiti patients with cerebrovascular accident.

OBJECTIVE: The objective of this study was to evaluate the determinants and associations of some prothrombotic risk factors in patients with cerebrovascular accidents (CVAs). SUBJECTS AND METHODS: In this case-control study, plasma total homocysteine (tHcy), lupus anticoagulant, protein C, protein S, activated protein C resistance (APC-R) and antithrombin were measured in 102 patients (60 males and 42 females) and 167 controls (87 males, 80 females). Serum vitamin B(12), folate, red cell folate, creatinine, lipid profile and glucose were also determined. Glomerular filtration rate (GFR) was calculated. RESULTS: 13 (22%) of the 60 male patients, and 16 (39%) of the 42 female patients had hyperhomocysteinemia. Median (interquartile range) tHcy was higher in male patients [11.22 micromol/l (9.60-15.40)] than female patients [10.05 micromol/l (8.72-17.54)]. On binary logistic regression analysis, the significant (p < 0.05) determinants of tHcy were urea, creatinine and GFR. Comparing patients with control subjects showed that tHcy, age, fasting glucose, urea, serum creatinine, white blood cell count, protein S, APC-R and factor VIII were significantly higher, while protein C, factor II, total cholesterol, high-density lipoprotein cholesterol and low-density lipoprotein cholesterol were significantly lower in patients. Lupus anticoagulant was not associated with tHcy and not detected in patients and controls. Low concentrations of vitamins B(12) and folate were not associated with tHcy. Logistic regression analysis showed a significant association of tHcy with CVA (OR = 9.55; p = 0.047) in males in the presence of other traditional CVA risk factors but tHcy is not independently associated with CVA in females. CONCLUSION: Hyperhomocysteinemia is common in Kuwaiti patients with CVA and tHcy probably interacts with prothrombotic factors (protein C, APC-R and factor VIII) to increase CVA risk. The main determinants, age and GFR markers, should be kept in mind when determining the risk associated with tHcy.