European Journal of Cardiovascular Medicine

Sickle cell anaemia (SCA) is a hereditary haemoglobin disorder characterized by abnormal haemoglobin S (HbS), leading to chronic haemolysis, vaso-occlusion, and a variety of systemic complications. The persistent release of free haemoglobin and iron during haemolysis causes oxidative stress, leading to glomerular injury. (1)

Vernon Ingram and colleagues later identified the culprit amino acid in the β chain of hemoglobin. Sickle cell hemoglobin, or hemoglobin S, has a valine for glutamic acid substitution at position 6 of the β chain. The hemoglobin can be identified as α2 β2 6Glu→Val. (2)

The phrase sickle cell trait refers to heterozygosity for the sickle cell gene (ββS). Sickle cell trait is asymptomatic in most people.

Individuals with sickle cell disease (SCD) possess two copies of the mutated gene (HbSS), resulting in the characteristic sickling of red blood cells.

Sickle cell anemia (SCA) is a significant public health concern in India, particularly in certain regions.

In Assam, located in Northeast India, the prevalence of sickle cell disease (SCD) is notably higher due to the presence of tribal populations with a higher carrier rate.

Studies indicate that the prevalence of SCD in Assam ranges from 1% to 10% in various tribal communities. (3)

The prevalence rate of proteinuria in patients with Hb SS has been reported to vary from 17 to 33% in studies in which proteinuria was determined by the dipstick method. (4)

The urinary albumin-to-creatinine ratio (ACR) is a sensitive marker for detecting microalbuminuria, a precursor to overt kidney disease, which can significantly affect morbidity and mortality in SCA.

This study explores the significance of urinary ACR in assessing renal involvement in adults with both sickle cell disease (SCD) and trait (SCT). Studies suggest that adults with SCD exhibit higher rates of albuminuria compared to those with SCT.

AIMS AND OBJECTIVE:

Aims: To evaluate the significance of the urinary albumin-to-creatinine ratio (ACR) as a marker for renal involvement in adults diagnosed with sickle cell anemia (both sickle cell disease and sickle cell trait) in a tertiary care hospital setting.

Objectives:

1. PRIMARY: To estimate the level Urinary Albumin-Creatinine Ratio in adult patients with sickle cell anemia (both disease and trait) screened with HPLC.
2. SECONDARY: To compare the levels of urinary ACR between patients with sickle cell disease and those with sickle cell trait and also with the increasing age.

In this cross-sectional study total 40 spot urine samples (20 trait and 20 disease) of patients attending outpatient department (OPD) /In patient department (IPD) of medicine in Assam Medical College and Hospital enrolled over a period of 6 months (May 15, 2024 to October 15, 2024).

Random urine sample was taken and urine micro albumin, urine creatinine analysis done on Vitros 5600 Autoanalyzer and urinary ACR was calculated by dividing the urine micro albumin to urine creatinine.

T test and SD, mean are used to compare between trait and disease.

CALCULATION OF URINARY ALBUMIN - CREATININE RATIO

Calculation of urinary albumin-creatinine ratio (mg/g) using the following formula –

URINARY MICROALBUMIN (mg/l)

URINARY CREATININE(g/l)

• The range for the albumin-creatinine ratio in urine described below

Normal - < 30

Microalbuminuria- 30–300

Clinical albuminuria > 300

INCLUSION ANS EXCLUSION CRITERIA:

INCLUSION CRITERIA:

Patients aged 13-60 years of both genders with sickle cell anaemia group screened with HPLC in Assam medical college and hospital.

EXCLUSION CRITERIA:

Patients documented with acute or chronic infection (e.g., active hepatitis B or C infections etc).

Patients with a systemic condition that could result in a glomerulopathy not related to Hemoglobinopathy (Systemic lupus erythematosus, inflammatory arthropathies).

Known casses of chronic kidney disease or acute kidney injury.

Pregnant and Lactating women.

Patients not willing to give informed consent.

Sickle cell homozygous people have considerably greater urine ACR activity than trait people; the mean±sd for trait people is 26.33±20.74, whereas the mean for homozygous people is 61.04±42.79, shown in table 1 and fig 1. The P value is similarly significant (0.0023).

Additionally, the urinary ACR is higher in patients aged 31–40 (71.66±50.96) than in those aged 21–30 (41.74±6.83), or in those aged ≤20 (19.00±6.73) for all the study participants. And the p value is significant (0.0021), shown in table 2 and fig 2.

TABLE 1: UACR IN SICKLE CELL ANAEMIA

FIGURE 1: UACR IN SICKLE CELL ANAEMIA

TABLE 2: AGE WISE DISTRIBUTION OF UACR

FIGURE 2: AGE WISE DISTRIBUTION OF UACR

Patients with hemoglobin SS may experience several renal dysfunctions, including hyposthenuria, hematuria, proteinuria, nephrotic syndrome, acidosis, urinary tract infection, renal failure, and changes in arterial blood pressure. Sickle cell nephropathy, including Hb AS, is characterized by an inability to concentrate urine appropriately. (5)

In our study the mean value of homozygous group was in the microalbuminuria range which was significant for impaired renal function, whereas for heterozygous group it was in the normal range.

Also, in the last two age group the value was significantly higher than normal range.

Similar type of study conducted by Sesso et al.(6) , where microalbuminuria was significantly higher in homozygous compared to heterozygous. Possible mechanisms of microalbuminuria are related to a reduction of ultrafiltration coefficient and loss of glomerular perm selectivity.

Clinical Implications:

Regular screening for albuminuria in SCA patients is critical for early detection and management of renal impairment. The elevated UACR values observed in our study indicate that interventions such as hydration, blood pressure control, and possibly the use of ACE inhibitors may be beneficial. (7)

Urinary ACR serves as a valuable marker for assessing renal dysfunction in adults with sickle cell disease and trait.

Since ACR increases with age, it could be a useful monitoring tool in adults with sickle cell related hemoglobinopathies.

Monitoring Urinary ACR in such patients may improve the overall management of patients affected by sickle cell-related renal complications.