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

AbstractSickle 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.

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Renal manifestations of sickle cell disease in children

International Journal of Contemporary Pediatrics ◽

10.18203/2349-3291.ijcp20202609 ◽

2020 ◽

Vol 7 (7) ◽

pp. 1524

Author(s):

Milind B. Kamble ◽

Vidhya S. Totewad

Keyword(s):

Risk Factors ◽

Steady State ◽

Sickle Cell Disease ◽

Sickle Cell ◽

Renal Involvement ◽

Screening Tests ◽

Age Group ◽

Coagulation Test ◽

Cell Disease ◽

Homozygous State

Background: Sickle cell disease prevalence is more in central part of India. This study tries to find extent of renal involvement, risk factors and screening tests in sickle cell disease.Methods: Study was Cross sectional observational study. Demographic and clinical findings were recorded. Renal function tests like serum creatinine, blood urea nitrogen, eGFR were studied. Presence of microalbuminuria was checkeed. Ultrasonography abdomen was done to see the texture and corticomedullary differentiation of kidney.Results: Total 143 patients were studied. Out of which, 117 homozygous (SS type), 26 heterozygous (AS type). Majority belonged to school going age group (i.e. 5 to 10 year age group) with male preponderance in homozygous state. Microalbuminuria was more common in crisis state (61.84% in SS pattern and 83.33% in AS pattern) as compared to steady state in both SS and AS pattern patients. Dipstic method detected more proteinuria than heat coagulation suggesting dipstick method superior to heat coagulation test. Low eGFR was common in patients with SS pattern as compared to patients with AS pattern and was significantly associated with microalbuminuria in both steady state and crisis state. Abnormal USG was seen 3.44% in patients with SS pattern. Renal involvement started below 5 years of age and then increases with age, homozygous childrens in crisis state are affected more.Conclusions: Renal involvement is common in sickle cell anemia i.e it is seen in 50% of the patients. Increasing age, male sex and homozygous state were risk factors. Simple test like dipstic method and heat coagulation test can be used as screening test to detect microalbumiburia, with dipstic method being superior. Presence of microalbuminuria can detect early renal involvement in sickle cell disease. This will help in early diagnosis and management of such patients which avoids further renal complications and thus prevents mortality and morbidity.

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Haemostasis Alterations in Sickle Cell Disease.

Blood ◽

10.1182/blood.v106.11.4026.4026 ◽

2005 ◽

Vol 106 (11) ◽

pp. 4026-4026

Author(s):

Patrick Van Dreden ◽

Aurelie Rousseau ◽

Thomas Exner ◽

Marc Vasse ◽

Agnes Lahary ◽

...

Keyword(s):

Steady State ◽

Sickle Cell Disease ◽

Platelet Activation ◽

Sickle Cell ◽

Factor Xa ◽

Screening Tests ◽

Plasma Samples ◽

Cell Disease ◽

Membrane Phospholipids ◽

Small Pilot Study

Abstract Sickle cell disease (SCD) is considered by many workers to be a hypercoagulable state. The vaso-occlusion in sickle cell disease is complex, involving adhesive processes between sickle red blood cells, leukocytes, and the activated endothelium. Loss of normal membrane phospholipids asymetry with the appearance of phosphatidylserine on the erythrocyte surface has been documented as promoting an exacerbation of the anaemia and an activation of coagulation. The aim of this study was to monitor changes in coagulation and platelet activation (monitored by measuring the levels of procoagulant phospholipids microparticles - PPM) in SCD (both in steady state and crisis). Coagulation screening tests (PT, APPT), Protein S (PS), D-Dimer (D-Di) and PPM were measured in plasma samples obtained from 18 patients with SCD (8 in crisis state and 10 in steady state) and in twenty one normal volunteers as control. All blood samples were collected and the plasma prepared in the same hospital using the same conditions. All plasma samples were stored at -80°C until assayed. PT, aPTT, PS and D-dimers were measured using reagents from Diagnostica Stago, Asniéres, France. PPM was monitored with a novel factor Xa-based coagulation assay. In this assay shortened clotting times are associated with increased levels of PPM and thus platelet activation. APTT Sec. PT % PPM Sec PS % D-Di μg/l Controls 34.6 (29.4–39.6) 93.1 (79–109) 57.5 (51.1–74.9) 88.8 (62–112) 0.22 (0.22–0.45) Sickle cell – in crisis 37.3 (33.4–47.4) 71.1 (56.5–86.5) 44.6 (34.0–60.0) 48.9 (25.0–89.5) 1.6 (0.6–2.6) Sickle cell – steady state. 38.0 (33.0–47.5) 75.0 (61.0–93.0) 52.2 (42.5–62.8) 84.7 (76.5–103.0) 0.7 (0.2–1.0) In sickle cell crisis a significant increase in both coagulation and platelet activation, as monitored by PPM, was found (all at p < 0.001). The decrease in % PT and PS levels confirms the findings of others. In steady state only DDi levels are significantly higher than controls. Further studies are needed to explain these findings. Although this was a small pilot study and further studies are needed it is interesting to speculate on the possible usefulness of the PPM assay in monitoring SCD crisis.

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Effects of Genotypes and Treatment on Oxygenscan Parameters in Sickle Cell Disease

Cells ◽

10.3390/cells10040811 ◽

2021 ◽

Vol 10 (4) ◽

pp. 811

Author(s):

Camille Boisson ◽

Minke A. E. Rab ◽

Elie Nader ◽

Céline Renoux ◽

Celeste Kanne ◽

...

Keyword(s):

Steady State ◽

Sickle Cell Disease ◽

Blood Cell ◽

Sickle Cell ◽

Red Blood Cell ◽

Cell Disease ◽

Oxygen Gradient ◽

Acute Complication ◽

Adults And Children ◽

The Difference

(1) Background: The aim of the present study was to compare oxygen gradient ektacytometry parameters between sickle cell patients of different genotypes (SS, SC, and S/β+) or under different treatments (hydroxyurea or chronic red blood cell exchange). (2) Methods: Oxygen gradient ektacytometry was performed in 167 adults and children at steady state. In addition, five SS patients had oxygenscan measurements at steady state and during an acute complication requiring hospitalization. (3) Results: Red blood cell (RBC) deformability upon deoxygenation (EImin) and in normoxia (EImax) was increased, and the susceptibility of RBC to sickle upon deoxygenation was decreased in SC patients when compared to untreated SS patients older than 5 years old. SS patients under chronic red blood cell exchange had higher EImin and EImax and lower susceptibility of RBC to sickle upon deoxygenation compared to untreated SS patients, SS patients younger than 5 years old, and hydroxyurea-treated SS and SC patients. The susceptibility of RBC to sickle upon deoxygenation was increased in the five SS patients during acute complication compared to steady state, although the difference between steady state and acute complication was variable from one patient to another. (4) Conclusions: The present study demonstrates that oxygen gradient ektacytometry parameters are affected by sickle cell disease (SCD) genotype and treatment.

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Is there a role for selective vasodilation in the management of sickle cell disease?

Blood ◽

10.1182/blood.v71.3.597.597 ◽

1988 ◽

Vol 71 (3) ◽

pp. 597-602 ◽

Cited By ~ 18

Author(s):

GP Rodgers ◽

MS Roy ◽

CT Noguchi ◽

AN Schechter

Keyword(s):

Blood Flow ◽

Steady State ◽

Sickle Cell Disease ◽

Sickle Cell ◽

Sickle Cell Anemia ◽

Microvascular Obstruction ◽

Controlled Study ◽

Control Group ◽

Cell Disease ◽

Retinal Arteriolar

Abstract To test the hypothesis that microvascular obstruction to blood flow at the level of the arteriole may be significant in individuals with sickle cell anemia, the ophthalmologic effects of orally administered nifedipine were monitored in 11 steady-state patients. Three patients with evidence of acute peripheral retinal arteriolar occlusion displayed a prompt reperfusion of the involved segment. Two other patients showed fading of retroequatorial red retinal lesions. Color vision performance was improved in six of the nine patients tested. The majority of patients also demonstrated a significant decrease in the amount of blanching of the conjunctiva which reflects improved blood flow to this frequently involved area. Such improvements were not observable in a control group of untreated stable sickle cell subjects. These findings support the hypothesis that inappropriate vasoconstriction or frank vasospasm may be a significant factor in the pathogenesis of the microvascular lesions of sickle cell disease and, further, that selective microvascular entrapment inhibition may offer an additional strategy to the management of this disorder. We believe a larger, placebo-controlled study with nifedipine and similar agents is warranted.

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Acute phase proteins and interleukins in steady state sickle cell disease

European Journal Of Haematology ◽

10.1111/j.1600-0609.1998.tb01060.x ◽

2009 ◽

Vol 61 (1) ◽

pp. 49-54 ◽

Cited By ~ 67

Author(s):

Konstantinos L. Bourantas ◽

Georgios N. Dalekos ◽

Alexandres Makis ◽

Aristidis Chaidos ◽

Stavroula Tsiara ◽

...

Keyword(s):

Steady State ◽

Sickle Cell Disease ◽

Sickle Cell ◽

Acute Phase ◽

Acute Phase Proteins ◽

Cell Disease

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Normal Non-HDL Cholesterol, Low Total Cholesterol, and HDL Cholesterol Levels in Sickle Cell Disease Patients in the Steady State: A Case-Control Study of Tema Metropolis

Journal of Lipids ◽

10.1155/2016/7650530 ◽

2016 ◽

Vol 2016 ◽

pp. 1-5 ◽

Cited By ~ 5

Author(s):

Richard K. D. Ephraim ◽

Patrick Adu ◽

Edem Ake ◽

Hope Agbodzakey ◽

Prince Adoba ◽

...

Keyword(s):

Blood Pressure ◽

Steady State ◽

Sickle Cell Disease ◽

Total Cholesterol ◽

Sickle Cell ◽

Density Lipoprotein ◽

Hdl Cholesterol ◽

Lipoprotein Cholesterol ◽

Cell Disease ◽

Cross Sectional

Background.Abnormal lipid homeostasis in sickle cell disease (SCD) is characterized by defects in plasma and erythrocyte lipids and may increase the risk of cardiovascular disease. This study assessed the lipid profile and non-HDL cholesterol level of SCD patients.Methods.A hospital-based cross-sectional study was conducted in 50 SCD patients, in the steady state, aged 8–28 years, attending the SCD clinic, and 50 healthy volunteers between the ages of 8–38 years. Serum lipids were determined by enzymatic methods and non-HDL cholesterol calculated by this formula: non-HDL-C = TC-HDL-C.Results.Total cholesterol (TC) (p=0.001) and high-density lipoprotein cholesterol (HDL-C) (p<0.0001) were significantly decreased in cases compared to controls. The levels of non-HDL-C, low-density lipoprotein cholesterol (LDL-C), and triglyceride (TG) were similar among the participants. The levels of decrease in TC and HDL were associated with whether a patient was SCD-SS or SCD-SC. Systolic blood pressure and diastolic blood pressure were each significantly associated with increased VLDL [SBP,p=0.01, OR: 0.74 (CI: 0.6–0.93); DBP,p=0.023, OR: 1.45 (CI: 1.05–2.0)].Conclusion.Dyslipidemia is common among participants in this study. It was more pronounced in the SCD-SS than in SCD-SC. This dyslipidemia was associated with high VLDL as well as increased SBP and DBP.

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Hematological and Biochemical Reference Ranges for the Population with Sickle Cell Disease at Steady State in Tanzania

Hemato ◽

10.3390/hemato3010007 ◽

2022 ◽

Vol 3 (1) ◽

pp. 82-97

Author(s):

Anna Daniel Fome ◽

Raphael Z. Sangeda ◽

Emmanuel Balandya ◽

Josephine Mgaya ◽

Deogratius Soka ◽

...

Keyword(s):

Steady State ◽

Sickle Cell Disease ◽

General Population ◽

Sickle Cell ◽

Age Groups ◽

Mean Corpuscular Hemoglobin ◽

Reference Ranges ◽

Cell Disease ◽

Laboratory Reference ◽

Males And Females

Hematological and biochemical reference values in sickle cell disease (SCD) are crucial for patient management and the evaluation of interventions. This study was conducted at Muhimbili National Hospital (MNH) in Dar es Salaam, Tanzania, to establish laboratory reference ranges among children and adults with SCD at steady state. Patients were grouped into five age groups and according to their sex. Aggregate functions were used to handle repeated measurements within the individual level in each age group. A nonparametric approach was used to smooth the curves, and a parametric approach was used to determine SCD normal ranges. Comparison between males and females and against the general population was documented. Data from 4422 patients collected from 2004–2015 were analyzed. The majority of the patients (35.41%) were children aged between 5–11 years. There were no significant differences (p ≥ 0.05) in mean corpuscular hemoglobin concentration (MCHC), lymphocytes, basophils, and direct bilirubin observed between males and females. Significant differences (p < 0.05) were observed in all selected parameters across age groups except with neutrophils and MCHC in adults, as well as platelets and alkaline phosphatase in infants when the SCD estimates were compared to the general population. The laboratory reference ranges in SCD at steady state were different from those of the general population and varied with sex and age. The established reference ranges for SCD at steady state will be helpful in the management and monitoring of the progress of SCD.

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Decreased Hepcidin Levels Are Associated with Low Steady-state Hemoglobin in Children With Sickle Cell Disease in Tanzania

EBioMedicine ◽

10.1016/j.ebiom.2018.07.024 ◽

2018 ◽

Vol 34 ◽

pp. 158-164 ◽

Cited By ~ 2

Author(s):

Nathaniel Lee ◽

Julie Makani ◽

Furahini Tluway ◽

Abel Makubi ◽

Andrew E. Armitage ◽

...

Keyword(s):

Steady State ◽

Sickle Cell Disease ◽

Sickle Cell ◽

Cell Disease

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Sickle cell crisis as evaluated from measurements of hydroxybutyrate dehydrogenase and myoglobin in plasma.

Clinical Chemistry ◽

10.1093/clinchem/27.2.314 ◽

1981 ◽

Vol 27 (2) ◽

pp. 314-316 ◽

Cited By ~ 9

Author(s):

E F Roth ◽

P A Bardfeld ◽

S J Goldsmith ◽

E Radel ◽

J C Williams

Keyword(s):

Steady State ◽

Sickle Cell Disease ◽

Sickle Cell ◽

High Specificity ◽

Mean Value ◽

Cell Disease ◽

Sickle Cell Crisis ◽

The Mean ◽

Low Sensitivity ◽

Sickle Cell Crises

Abstract Data on plasma hydroxybutyrate dehydrogenase activity (I) and myoglobin concentration were used to evaluate painful sickle cell crises. I was increased during non-crisis steady state in patients with sickle cell disease as compared to normal values (232, SD 79.7 vs 85, SD 33 Sigma units/mL). During crisis, the mean value for I increased further to 379 (SD 139) Sigma units/mL. For 12 patients evaluated both during steady state and crisis, there was a mean increase in plasma I of 131% (SD 76%). Repeated determinations of I in sickle cell disease patients during several months while they were in steady state showed that baseline I varied by no more than 20% from the mean. Plasma myoglobin in patients with sickle cell disease was not above normal, but during crisis 21 of 39 patients tested had increased plasma myoglobin concentrations. Our data suggest that I may be a useful indicator of sickle cell crisis when the patient's own baseline value is available for comparison. Plasma myoglobin measurements give evidence of muscle damage during crisis with high specificity but low sensitivity.

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