Prevalence and risk factors of diabetic kidney disease in Malagasy patients with diabetes mellitus: a cross-sectional study at a University Hospital Center in Antananarivo, Madagascar

Abstract

Background

Diabetic kidney disease (DKD) is the most serious microvascular complication of diabetes mellitus (DM), responsible for significant morbidity and mortality. Its incidence is increasing in parallel with the epidemiological evolution of DM. Its management is primarily preventive, with specific attention paid to the identification and management of associated risk factors. The study’s objectives were to determine the prevalences and risk factors of DKD and glomerular hyperfiltration (GHF) in Malagasy patients with DM.

Methods

This cross-sectional study was conducted on 248 patients with DKD seen in the Cardiovascular Diseases and Internal Medicine departments of the Soavinandriana Hospital Center in Antananarivo over a 2-year period. The diagnosis of DKD was confirmed by an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m² and/or albuminuria ≥ 30 mg/24 h. GHF was defined as a value ≥ 100 mL/min/1.73 m².

Results

The prevalence of DKD was 36.3% and GHF was 31.0%. In bivariate analysis, risk factors for DKD included age ≥ 60 years (aOR 2.08 [1.14–3.88]), hypertension (aOR 2.21 [1.07–4.78]), dyslipidemia (aOR 2.91 [1.53–5.77]), smoking (aOR 1.94 [1.09–3.49]) and DM duration ≥ 10 years (aOR 2.99 [1.64–5.53]). After multivariate analysis, the independent risk factors for DKD were dyslipidemia (aOR 2.23 [1.11–4.46]) and duration of diabetes ≥ 10 years (aOR 2.82 [1.55–5.14]). Peripheral neuropathy (aOR 4.93 [2.67–9.11]), retinopathy (aOR 28.3 [12.0-66.8]) and carotid atherosclerosis (aOR 1.86 [1.00-3.51]) were significantly associated with DKD. Independent risk factors for GHF were age ≤ 50 years (aOR 5.48 [2.37–12.7]) and glycated hemoglobin ≥ 10% (aOR 1.89 [1.01–3.21]).

Conclusion

DKD and GHF were common among Malagasy diabetics. Their management should primarily focus on prevention by achieving optimal control of blood glucose levels and other risk factors, using cardioprotective and renoprotective medications. The presence of DKD should prompt a search for other diabetic complications, and vice versa.

Introduction

Diabetes mellitus (DM) is a major cause of morbidity and mortality due to its microvascular and macrovascular complications [1, 2]. It also imposes significant economic costs on households and societies in both developed and low-income countries [3–5].

The term “diabetic nephropathy” is traditionally based the presence of histological evidence. However, when there is suspicion of diabetic nephropathy, the term “diabetic kidney disease” (DKD) is more suitable [6, 7]. Indeed, other factors contributing to renal dysfunction are often present in DM [8]. DKD can be defined by reduced renal function or by the presence of permanent renal damage (at least three months), regardless of renal function, often associated with hypertension. Renal damage is determined by an increase in urinary markers, such as albuminuria, or by abnormal urine sediment, abnormal imaging, or renal biopsy [9].

DKD is the most serious microangiopathic complication of diabetes [10]. Its incidence is increasing in parallel with the epidemiological evolution of diabetes. Approximately 40% of diabetic patients are affected by DKD, which can lead to end-stage renal disease (ESRD) (relative risk 6.2 to 62.0), cardiovascular disease and an increased risk of morbidity and mortality [11–13]. Consequently, DKD represents an expanding and growing challenge, not only for patients, their families and caregivers, but also for healthcare systems and governments [14]. Risk factors of DKD include age, obesity, smoking, hypertension, dyslipidemia, duration of diabetes, glycated hemoglobin (Hb A1c) and diabetic retinopathy [8, 9, 15]. Additionally, DKD usually starts with glomerular hyperfiltration (GHF), which subsequently progresses to persistent micro- and macroalbuminuria, accompanied by hypertension and a decline in glomerular filtration rate (GFR). GHF frequently remains unrecognized and under-diagnosed. However, at this stage, it is important to implement management strategies to prevent the progression to overt DKD [9].

In Africa, as well as in Madagascar, DKD appears to be more prevalent (overall prevalence ranging from 11 to 83.7%) and more severe (34.7% ESRD at 5 years and 18.4% mortality at 20 years), and its risk factors are similar to those described above [16–18]. To consolidate the existing databases on this subject in Madagascar, the objectives of the present study were to determine the prevalences and risk factors of DKD and glomerular hyperfiltration in Malagasy patients with DM.

Methods

Study design and setting

This cross-sectional study was conducted in the cardiovascular diseases and internal medicine departments of the Soavinandriana Hospital Center. This is a tertiary-level hospital located in the 3rd arrondissement of Antananarivo, the capital of Madagascar. These departments offer comprehensive care, encompassing the full spectrum of metabolic and endocrine pathologies, internal medicine and cardiovascular diseases. The study spanned over a two-year period, from November 1, 2021 to October 31, 2023.

Study participants

The study participants consisted of patients with diabetes mellitus who were being followed up in these departments. The inclusion criteria encompassed all patients with a known or newly diagnosed diagnosis of type 2 DM, as well as those with a confirmed type 1 DM lasting at least 10 years. These individuals underwent a comprehensive evaluation that entailed 24-hours albuminuria assessment, serum creatinine measurement, and a fundus examination. Patients were excluded if they were pregnant, had incomplete records, infections, congestive heart failure, or other obvious associated nephropathies, based on long-term intake of nephrotoxic drugs and substances (decoctions) and the presence of previously diagnosed systemic autoimmune diseases (such as systemic lupus erythematosus, vasculitides). It is noteworthy that none of the patients had undergone a biopsy.

Exhaustive sampling was used to determine the sample size, which was calculated using a single population proportion formula: n = (Z1-α/2)² P (1-P)/d². This calculation was made assuming a 95% confidence level (Z1-α/2 = 1.96), a 5% margin of error, and a 20,4% prevalence of DKD [19]. The study’s sample size was 250 patients with DM who consented to participate.

Clinical and laboratory data

The study examined various variables including socio-demographic data (gender, age), cardiovascular risk factors (hypertension, dyslipidemia, overweight/obesity, smoking), DM (types 1 and 2, duration, fasting blood glucose, glycated hemoglobin or Hb A1c, diabetic retinopathy, diabetic neuropathy, ischemic stroke, carotid atherosclerosis, coronary heart disease and lower limb arteriopathy), DKD (estimated glomerular filtration rate (eGFR), albuminuria), treatment (antidiabetics, antihypertensives, statins and antiplatelet agents, extra-renal purification).

Hypertension was confirmed by a blood pressure ≥ 140/90 mmHg on two occasions or the use of an antihypertensive drug. Dyslipidemia was defined by a low-density lipoprotein cholesterol (LDLc) level outside the targets recommended by the European Society of Cardiology [20] or the use of a lipid-lowering agent.

The diagnosis of DM was made in accordance with the diagnostic criteria established by the American Diabetes Association. Type 2 DM was diagnosed when the patient was over 35 years of age, overweight or obese, had a family history of type 2 DM, and did not have any obvious secondary causes, such as chronic pancreatitis, endocrinopathies, or long-term glucocorticoid use. Conversely, type 1 DM was considered when the patient was under 35 years of age, had a thin or normal body mass index, was non-responsive to oral antidiabetic medications, and/or had positive autoantibodies [21]. Fasting blood glucose levels (after at least 8 h of fasting) and HbA1c levels were determined using a colorimetric assay on the Alinity C 8502 and a high-performance liquid chromatography method, respectively.

The diagnosis of retinopathy was confirmed by abnormalities found during vitreous and fundus examinations, performed by an experienced ophthalmologist [22]. Diabetic peripheral neuropathy was indicated by symmetrical distal sensory symptoms starting in the lower limbs, assessed using the DN4 questionnaire, as well as impaired foot sensitivity on 10 g monofilament examination and reduced or absent Achilles reflex [22]. The diagnosis of ischemic stroke was made based on sudden onset focal neurological signs, such as motor and/or sensory deficits affecting all or part of one side of the body, and further confirmed by parenchymal hypodensity corresponding to the affected arterial territories on cerebral CT scan [23]. Carotid atherosclerosis was defined as the presence of a carotid plaque or diffuse thickening of the carotid wall with an intima-media thickness ≥ 1.1 mm [24]. The diagnosis of coronary heart disease was made in the presence of typical or atypical chest pain and/or other atypical signs, necrotizing Q waves and negative T waves in one or more defined territories on the electrocardiogram, and segmental akinesia or hypokinesia on transthoracic echocardiography [25]. Lower limb arteriopathy was confirmed through lower limb arterial doppler ultrasound, whether in the form of stenosing or non-stenosing atherosclerosis, and/or mediacalcosis.

Serum creatinine levels (µmol/L) were assessed by colorimetric assay on Alinity C 8502. The eGFR (mL/min/1.73 m²) was calculated using the Chronic Kidney Disease – Epidemiology Collaboration (CKD-EPI) equation. Albuminuria levels were quantitatively determined in the laboratory. The categorization of CKD and albuminuria followed the criteria established by Vassalotti et al. [26] and adopted by the American Diabetes Association [27]. DKD diagnosis was made in the presence of albuminuria (≥ 30 mg/24 hours) and/or reduced eGFR (< 60 mL/min/1.73 m²) in the absence of signs or symptoms of other primary causes of kidney damage, associated with long-term diabetes, with or without diabetic retinopathy [26, 27]. As there is no clear cut-off value, GHF was defined by an eGFR ≥ 100 mL/min/1.73 m² in both the present study and in the study of Naqvi et al. [28].

Statistical analysis

Data were collected from patient files using a pre-established form and then analyzed using IBM SPSS^® software version 26.0. Qualitative and quantitative variables were expressed as percentage and median with interquartile ranges (IQR). Crude (cOR) and adjusted odds ratios (aOR) with their respective 95% confidence intervals (CI) were calculated. Candidate risk factors for multivariate analysis were identified in bivariate analysis. Multivariable analysis was used to control confounding variables and determine independent risk factors for DKD and GHF. Statistical significance was set at a p-value of < 0.05.

Results

Among the 250 patients with DM who consented to participate, two were excluded due to incomplete records. Following the application of the eligibility criteria, 248 patients were retained for the study. Females predominated in 57.3% of cases, with a median age of 64 years (IQR 56–69). The most prevalent cardiovascular risk factors were hypertension (77.4%) and dyslipidemia (64.3%). A patient could have one or more cardiovascular risk factors. Only 2.8% of patients had type 1 DM. The medians for diabetes duration, fasting plasma glucose and Hb A1c were 6 years (IQR 4–11), 7.93 mmol/L (IQR 6.62–11.41) and 8.3% (IQR 6.8–10.4), respectively. Neuropathy was the most prevalent degenerative complication (37.1%), followed by carotid atherosclerosis (28.2%) and retinopathy (27.4%). A total of 188 patients were prescribed oral antidiabetic drugs, with or without insulin. A patient could be taking one or more classes of oral antidiabetics. The general characteristics of the study population are shown in Table 1.

Table 1.

General characteristics of the study population

Variables	Frequency	Percentage
Male gender	106	42.7
Age ≥ 60 years	159	64.1
Cardiovascular risk factors
Hypertension	192	77.4
Dyslipidemia	167	67.3
Overweight/obesity	120	48.4
Smoking	81	32.7
Diabetes mellitus
Type 2	241	97.2
Type 1	7	2.8
Newly diagnosed	39	15.7
Duration ≥ 10 years	71	28.6
Glycated hemoglobin ≥ 7%	180	72.6
Diabetes complications
Peripheral neuropathy	92	37.1
Carotid atherosclerosis	70	28.2
Retinopathy	68	27.4
Lower limb arteriopathy	46	18.5
Coronary heart disease	37	14.9
Ischemic stroke	20	8.1
Treatment
Oral antidiabetics	188	75.8
Insulin	88	35.5
Metformin	148	59.7
Sulfonylurea	78	31.5
Dipeptidyl peptidase 4 inhibitor	38	15.3
Sodium–glucose cotransporter 2 inhibitor	38	15.3
Glucagon-like peptide 1 receptor agonist	4	1.6
RAAS blockers	186	75.0
Calcium channel blockers	117	47.2
Diuretics	63	25.4
Statins	162	65.3
Antiplatelet agent	98	39.5
Hemodialysis	8	3.2

RAAS: renin angiotensin aldosterone system

The respective medians for urea, serum creatinine, eGFR and albuminuria were 3.5 mmol/L (IQR 3-4.6), 78 µmol/L (IQR 65–98), 88.3 mL/min/1.173 m² (IQR 65.92-102.26) and 12.72 mg/24 h (IQR 5-64.45). eGFR < 60 mL/min/1.73 m² and albuminuria ≥ 30 mg/24 h were found in 22.2% and 35.1% of cases, respectively. Table 2 represents the distribution of patients according to eGFR and albuminuria categories. Overall, ninety patients (36.3%) had DKD and seventy-seven patients (31.0%) had GHF.

Table 2.

Estimated glomerular filtration rate and albuminuria categories in Malagasy patients with diabetes mellitus

Variables	Categories	Frequency	Percentage
Estimated glomerular filtration rate (ml/min/1.73 m²)	G1 (≥ 90)	122	49.2
	G2 (60–89)	71	28.6
	G3a (45–59)	24	9.7
	G3b (30–44)	16	6.5
	G4 (15–29)	8	3.2
	G5 (< 15)	7	2.8
Albuminuria (mg/24h)	A1 (< 30)	161	64.9
	A2 (30–299)	48	19.4
	A3 (≥ 300)	39	15.7

In bivariate analysis, the risk factors for DKD were as follows: age ≥ 60 years (cOR 2.08 [1.14–3.88]), hypertension (crude odds ratio [cOR] 2.21 [1.07–4.78]), dyslipidemia (cOR 2.91 [1.53–5.77]), smoking (cOR 1.94 [1.09–3.49]) and DM duration ≥ 10 years (cOR 2.99 [1.64–5.53]). The remaining diabetic complications showed a significant correlation with DKD. Logistic regression analysis indicated that dyslipidemia (adjusted odds ratio [aOR] 2.23 [1.11–4.46]), DM duration of at least 10 years (aOR 2.82 [1.55–5.14]), peripheral neuropathy (aOR 4.93 [2.67–9.11]), retinopathy (aOR 28.3 [12.0-66.8]) and carotid atherosclerosis (aOR 1.86 [1.00-3.51]) were identified as independent risk factors for DKD (see Table 3).

Table 3.

Risk factors for diabetic kidney disease in Malagasy patients with diabetes mellitus

Variables	Diabetic kidney disease		Bivariate analysis		Multivariate analysis
	No (n1 = 158)	Yes (n2 = 90)	cOR [95% CI]	p value	aOR [95% CI]	p value
Male gender, n (%)	65 (41.1)	41 (45.6)	1.19 [0.68–2.08]	0.2934
Age ≥ 60 years, n (%)	92 (58.2)	67 (74.4)	2.08 [1.14–3.88]	0.0072*	1.25 [0.65–2.42]	0.4957
Hypertension, n (%)	115 (72.8)	77 (85.6)	2.21 [1.07–4.78]	0.0141*	1.29 [0.58–2.88]	0.5250
Dyslipidemia, n (%)	94 (59.5)	73 (81.1)	2.91 [1.53–5.77]	0.0003*	2.23 [1.11–4.46]	0.0226*
Overweight or obesity, n (%)	73 (46.2)	47 (52.2)	1.27 [0.73–2.21]	0.2177
Smoking, n (%)	43 (27.2)	38 (42.2)	1.94 [1.09–3.49]	0.0116*	1.74 [0.97–3.12]	0.0596
Type 2 DM, n (%)	152 (96.2)	89 (98.9)	3.49 [0.41–163]	0.2086
Type 1 DM, n (%)	6 (3.8)	1 (1.1)	Reference
DM duration ≥ 10 years, n (%)	32 (20.3)	39 (43.3)	2.99 [1.64–5.53]	0.0001*	2.82 [1.55–5.14]	0.0007*
Glycated hemoglobin ≥ 7%, n (%)	112 (70.9)	68 (75.6)	1.29 [0.68–2.42]	0.2609
Peripheral neuropathy, n (%)	36 (22.8)	56 (62.2)	5.53 [3.05–10.2]	< 0.0001*	4.93 [2.67–9.11]	< 0.0001*
Retinopathy, n (%)	9 (5.7)	59 (65.6)	30.8 [13.5–78.6]	< 0.0001*	28.3 [12.0-66.8]	< 0.0001*
Carotid atherosclerosis, n (%)	32 (20.3)	38 (42.2)	2.86 [1.56–5.29]	0.0002*	1.86 [1.00-3.51]	0.0462*
Ischemic stroke, n (%)	11 (7.0)	9 (10.0)	1.48 [0.52–4.12]	0.2699
Lower limb arteriopathy, n (%)	23 (14.6)	23 (25.6)	2.01 [1.04–4.05]	0.0254*	1.22 [0.59–2.51]	0.5869
Coronary heart disease, n (%)	18 (11.4)	19 (21.1)	2.07 [1.01–4.48]	0.0315*	1.23 [0.57–2.65]	0.5812
Oral antidiabetics, n (%)	124 (78.5)	64 (71.1)	0.67 [0.36–1.28]	0.1256
Insulin, n (%)	46 (29.1)	42 (46.7)	2.12 [1.19–3.77]	0.0031*	1.78 [0.98–3.79]	0.0572
Statin, n (%)	93 (58.9)	69 (76.7)	2.28 [1.24–4.33]	0.0032*	1.15 [0.47–2.82]	0.7499

aOR: adjusted odds ratio, CI: Confidence interval, cOR: crude odds ratio, DM: diabetes mellitus

*Significant p value < 0.05

Independent risk factors for GFH were age ≤ 50 years and glycated hemoglobin ≥ 10% with aOR 5.48 [2.37–12.7] and 1.89 [1.01–3.21], respectively (see Table 4).

Table 4.

Risk factors for glomerular hyperfiltration in Malagasy patients with diabetes mellitus

Variables	Glomerular hyperfiltration		Bivariate analysis		Multivariate analysis
	No (n1 = 171)	Yes (n2 = 77)	cOR [95% CI]	p value	aOR [95% CI]	p value
Male gender, n (%)	67 (39.2)	39 (50.6)	1.59 [0.89–2.83]	0.0607
Age ≤ 50 years	11 (6.4)	26 (33.8)	7.34 [3.24–17.7]	< 0.0001*	5.48 [2.37–12.7]	0.0001*
Type 1 DM, n (%)	1 (0.6)	6 (7.8)	14.2 [1.68–664]	0.0041*	2.94 [0.30–28.6]	0.3533
Type 2 DM, n (%)	170 (99.4)	71 (92.2)	Reference
Newly diagnosed DM, n (%)	20 (11.7)	19 (24.7)	2.46 [1.15–5.26]	0.0092*	1.77 [0.81–3.83]	0.1460
Glycated hemoglobin ≥ 10%, n (%)	43 (25.1)	31 (40.3)	2.00 [1.08–3.68]	0.0127*	1.89 [1.01–3.21]	0.0483*

aOR: adjusted odds ratio, CI: Confidence interval, cOR: crude odds ratio, DM: diabetes mellitus

*Significant p value < 0.05

Discussion

Prevalence of diabetic kidney disease

The prevalence of DKD in the present study (36.3%) was similar to those found in studies conducted in Uganda (33.7%) [29], Kenya (39.0%) [30] and China (35.5%) [31]. However, it was less prevalent in South Africa (24.5%) [32], Ethiopia (14.3%) [33] and Taiwan (17.92%) [34]. It was higher in studies carried out in Jordan (43.5%) [35] and Nepal (86.6%) [36]. The proportions of eGFR and albuminuria categories varied across different studies [29–31]. Other studies in Madagascar [18] and Nepal [36] found that DKD was more severe (stage G5 at 47% and 30.8%, respectively). Pathological albuminuria was more frequent, found in 39.7% of cases in Switzerland [37], 44.8% in Jordan [35] and up to 79.9% in Tanzania [38].

Indeed, the study populations, study settings, diagnostic criteria for DKD and methods used to assess albuminuria (laboratory quantitative, urine dipstick), differed between the studies. Patients in advanced stages will be referred to and managed in the nephrology department. Although albuminuria testing using urine dipsticks has been validated [26, 27], there are a number of practical conditions to be met, such as storage of dipsticks, preservation of box color, and reading time. In any case, DKD is most prevalent and must be systematically and appropriately screened.

Risk factors for diabetic kidney disease

The present study identified age ≥ 60 years, hypertension, dyslipidemia, smoking, and DM duration ≥ 10 years as risk factors for DKD. Other authors have also noted that being over 60 years old predicts of DKD [39, 40]. In the study by De Cosmo et al., an increase in age of five years was associated with a 37% increased risk of eGFR impairment and a 7.5% increased risk of albuminuria [41]. Other studies have shown that hypertension, dyslipidemia, and smoking contribute to the occurrence of DKD [32, 40, 42]. The risk of developing DKD increases after a period of ten years with diabetes [32, 40], and even after five years [30]. Indeed, DKD follows a natural history over time with chronic hyperglycemia.

According to the literature, males are more predisposed to developing diabetic kidney disease (DKD) than females. Testosterone accelerates the onset and progression of DKD through activation of the renin angiotensin aldosterone system, while estrogen attenuates the vasoconstrictor effect of angiotensin II reducing tubular fibrosis [43]. The role of overweight and obesity in DKD risk varied between studies [29, 31]. However, an Italian study demonstrated that a 1% increase in Hb A1c was associated with a 7% increase in the risk of developing albuminuria [41].

The significant associations between DKD and other degenerative complications of diabetes found in the present study were consistent with the findings of several studies [33, 35]. Indeed, the microvascular complications of diabetes shares the same pathophysiological mechanism, which is primarily linked to chronic hyperglycemia resulting in chronic inflammation and endothelial dysfunction [44, 45]. It has also been established that DKD is a cardiovascular risk factor and that most causes of death in patients with DKD are cardiovascular diseases [46].

Prevalence and risk factors for glomerular hyperfiltration

The prevalence of GHF varied depending on the eGFR cut-off value. It was 42.9% (eGFR ≥ 100 ml/min/1.73 m²) in a Pakistani study [28], 24% (eGFR ≥ 140 ml/min/1.73 m²) in the DCCT/EDIC study [47] and 20.1% (age- and sex-specific GFR above the 80th percentile) in an Italian study [48]. In the present study, as in others, young age and major uncontrolled diabetes were identified as risk factors for GHF [48]. Indeed, an increase in blood glucose levels is associated with a corresponding rise in osmotic diuresis. According to the literature, 10–67% of type 1 diabetics and 6–73% of type 2 diabetics present with GHF [49].

Study strengths and limitations

To our knowledge, the present study is among the first to focus specifically on this subject in Madagascar. Hospital prevalences and risk factors for DKD and GFH were identified in a sample of Malagasy diabetics. This will help streamline the country’s databases and improve patient management. Despite its contributions, the present study was conducted in a tertiary hospital, which may limit the generalizability of the results to patients treated in primary care facilities, where access to specialized care is often more limited. The cross-sectional design of the study may have influenced the identification of risk factors. Certain potential risk factors for DKD, including decoction intake and a family history of DKD, were not documented in all medical records. Access to renal biopsy and hemodialysis remains very limited, and renal transplantation is not yet standard practice in our country.

Conclusion

DKD and GHF were common among Malagasy diabetics and theirs risk factors consistent with those found in the literature. The findings emphasize the pivotal role of primary prevention of DKD through the implementation of effective management for diabetes and associated risk factors. Screening for GHF is also essential, particularly in young patients with poorly controlled diabetes. The early use of cardioprotective and renoprotective medication is of paramount importance in this context. The present study supports the need to enhance the therapeutic arsenal available in our country.

Abbreviations

aOR

Adjusted odds ratio

cOR

Crude odds ratio

CI

Confidence interval

CKD-EPI

Chronic kidney Disease – epidemiology collaboration

DCCT/EDIC

Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications

DKD

Diabetic kidney disease

DM

Diabetes mellitus

eGFR

Estimated glomerular filtration rate

ESRD

End-stage renal disease

GFR

Glomerular filtration rate

GHF

Glomerular hyperfiltration

Hb A1c

Glycated hemoglobin

IQR

Interquartile ranges

LDLc

Low density lipoprotein cholesterol

RAAS

Renin angiotensin aldosterone system

Author contributions

S.A.R contributed to the conception and design of the study; the acquisition, analysis, and interpretation of data for the study; and the drafting the work. MAR, SJNR and FRR participated in the interpretation of data for the study and the revision of the draft. ADPR review it critically for important intellectual content. All authors read and approved the final manuscript, and agree to be accountable for all aspects of the work.

Funding

No funding.

Data availability

The data used/analyzed during the current study available from the corresponding author on reasonable request.

Declarations

Ethics approval and consent to participate

The study adhered to the principles outlined in the Declaration of Helsinki. Patients’ anonymity and confidentiality were maintained. The Review Board of Soavinandriana Hospital approved this study, on October 28, 2021 (No. 73/CENHOSOA/DG/DT). Informed consents were obtained from all of the participants in the study.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.