| Abstract|| |
There are no available data about the factors associated with diabetic nephropathy (DN) in Kuwaiti individuals with type 2 diabetes. This study was conducted on 154 consecutive Kuwaiti adults with type 2 diabetes who attended the diabetic out-patient clinic at Al-Sabah Hospital to determine the factors associated with albuminuria among them. Albuminuria was considered to be present if the urinary albumin:creatinine ratio test or 24-h collection was positive on two occasions. There were 102 (66.2%) women and 52 (33.8%) men, with a mean age of 49.1 ± 10.1 years and a median duration of diabetes for 6 years. Hypertension was found in 60.8% of the patients and 16.3% had an HbA 1c <7%. Albuminuria was found in 43.5% of the patients. The prevalence of microalbuminuria and macroalbuminuria was 27.3% and 16.2%, respectively. In the univariate analysis, the factors that were significantly associated with albuminuria were hypertension - both systolic and diastolic blood pressure levels, HbA 1c , retinopathy, duration of diabetes, and modality of treatment. Multiple logistic regression analysis indicated that hypertension was the main independent risk factor associated with albuminuria (OR 4.1, 95% CI 1.1- 15.0; P = 0.03). In conclusion, although albuminuria is common among Kuwaiti adults with type 2 diabetes, the prevalence is lower than that reported for other populations in spite of the poor glycemic control and the high prevalence of hypertension. Factors associated with albuminuria appear to be similar to other populations, and hypertension was the most independent factor. Early recognition and treatment of hypertension is an important strategy to prevent or delay DN as well as cardiovascular morbidity and mortality. A population-based study is warranted to confirm these findings and to search for genetic linkage for the development of DN.
|How to cite this article:|
Al-Adsani A. Risk factors associated with albuminuria in Kuwaiti adults with type 2 diabetes. Saudi J Kidney Dis Transpl 2012;23:860-5
|How to cite this URL:|
Al-Adsani A. Risk factors associated with albuminuria in Kuwaiti adults with type 2 diabetes. Saudi J Kidney Dis Transpl [serial online] 2012 [cited 2020 Aug 3];23:860-5. Available from: http://www.sjkdt.org/text.asp?2012/23/4/860/98189
| Introduction|| |
Diabetic nephropathy (DN) is a progressive kidney disease and, at present, in many countries, is the most common cause of end-stage renal disease (ESRD). It accounts for 40% of new ESRD cases in the United States. The risk of developing DN starts with albuminuria, progressing from micro- to macroalbuminuria.  Albuminuria in diabetes is strongly predictive of poor renal outcomes, cardiovascular morbidity and mortality. , The Developing Education on Microalbuminuria for Awareness of Renal and Cardiovascular risk in Diabetes (DEMAND), a multinational cross-sectional clinic/center-based study, revealed that approximately 50% of type 2 diabetic patients had micro- or macroalbuminuria, and Asians had a higher prevalence of albuminuria compared with Caucasian patients.  The main risk factors identified in DEMAND were HbA 1c , systolic blood pressure (BP), ethnicity, retinopathy, duration of diabetes, kidney function, body height, and smoking. In Kuwait, type 2 diabetes is a major public health problem, and cardiovascular disease is the leading cause of death.  National data have shown that DN is the leading cause of ESRD, accounting for 21.2% of the cases with ESRD. , The prevalence of DN and the associated risk factors are currently unknown. This study was conducted to identify the factors that are associated with albuminuria in Kuwaiti adults with type 2 diabetes and whether they are different from those reported for other populations.
| Patients and Methods|| |
One hundred and seventy consecutive Kuwaiti adults with type 2 diabetes attending the Diabetic Clinic at the Al-Sabah Hospital, between October 2000 and March 2005, were screened at their initial visit for albuminuria using the urinary albumin:creatinine ratio test (U-ACR) or 24-h urine collection. Albuminuria was measured by the immunoturbidimetric method and was defined as positive if U-ACR was ≥1.5 mg/mmol and/or 24-h collection was ≥20 mg on two occasions. Macroalbuminuria was defined if 24-h collection was ≥300 mg. Other data collected included age, gender, diagnosis of hypertension, smoking status, body mass index (BMI), BP, serum creatinine, and lipids. Diabetes-related data included diabetes duration and treatment, HbA 1c , and diabetic retinopathy. Hypertension was defined as BP ≥140/90 mmHg or as current use of anti-hypertensive drugs. BMI (kg/m 2 ) was calculated from weight and height measurements. HbA 1c was performed using turbidmetric inhibition immunoassay (Roche HB1c II kit). Gly-cemic control was diagnosed as good, acceptable, or poor when HbA 1c % was <7.0, 7.0- 8.0, or >8.0, respectively. Serum lipids were measured by the enzymatic method using Dade Dimension (Siemens, Becton-Dickinson, NJ, USA). Diabetic retinopathy was diagnosed using two-field fundus photography per eye, and results were presented as yes or no.
| Statistical Analysis|| |
Data management and analysis were conducted using the SPSS program. Continuous variables are presented as means ± SD, whereas categorical variables are presented as percentages. The χ2 test was used to test for differences in proportions between categorical variables, while the two-tailed t-test was used to compare between means. A P-value of <0.05 was considered to be statistically significant. Multiple logistic regression analysis was performed to adjust for the confounders and to determine independent effects of factors associated with diabetic albuminuria.
| Results|| |
Of the type 2 diabetics in the study, data was available for 154 patients. There were 102 (66.2%) women and 52 (33.8 %) men, with a mean age of 49.1 ± 10.1 years and a median duration of six years. Of the patients, 60.8% had hypertension, 38.3% had retinopathy, and 13.2% were current smokers. Mean systolic and diastolic BP were 135.5 ± 22.5 mmHg and 80.9 ± 10.3 mmHg, respectively. Systolic BP <130 mmHg and diastolic BP <80 mmHg were found in 35.7% and 26.6% of the patients, respectively. Mean HbA 1c was 9.4 ± 2.5%, and 16.3% of the patients had an HbA 1c <7%. Mean BMI was 33.2 ± 7.4 kg/m 2 , and BMI >30 was found in 65.5% of the patients. Mean total cholesterol and triglyceride level was 5.7 ± 1.2 mmol/L and 1.9 ± 1.3 mmol/L, respectively. Mean Low density lipo-proteins-(LDL) and High density lipo-proteins (HDL-cholesterol were 3.7 ± 1.0 mmol/L and 1.2 ± 0.3 mmol/L, respectively. Of the 154 patients, 22.1% were being treated by diet only, 8.4% by metformin, 25.3% by sulphonylurea, 14.3% by combination oral therapy, 19.5% by insulin only, and 10.4% by combination insulin/oral therapy.
Albuminuria and associated factors
Albuminuria was found in 43.5% of the patients. The prevalence of microalbuminuria and macroalbuminuria was 27.3% and 16.2%, respectively. Eleven patients (7.1%) had an impaired renal profile (non-diabetic nephropathy was excluded). Personal and clinical characteristics of those with albuminuria are presented in [Table 1]. The prevalence of albuminuria increased significantly with longer duration of diabetes (P <0.001). Of the newly diagnosed patients (n = 25), 20% had microalbuminuria. Albuminuria was significantly prevalent in patients with systolic BP ≥130 mmHg and diastolic BP ≥80 mmHg and in those with retinopathy (P <0.001). Patients with albuminuria had higher HbA 1c (10.4 ± 2.5% vs. 8.7 ± 2.2%; P <0.0001) compared with patients without albuminuria. The risk for albuminuria increased from 20.0% in patients with good glycemic control to 54.6% in patients with poor glycemic control (P <0.001).Patients with BMI ≥30 had a higher prevalence of albuminuria compared with those with BMI <30 (P <0.001). The prevalence of albuminuria was highest among those treated with insulin and/or oral therapy and lowest among those treated with metformin (P <0.0001). Multiple logistic regression analysis indicated that hypertension was the main independent factor associated with albuminuria (OR 4.1, 95% CI 1.1-15.0; P = 0.03). There were no significant differences between patients with and without micro-albuminuria with regard to gender, smoking status, triglyceride levels, or cholesterol levels.
|Table 1: Personal and clinical characteristics of diabetic patients with and without albuminuria.|
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| Discussion|| |
In this hospital-based study, the prevalence of albuminuria due to type 2 diabetes among Kuwaiti adults was 43.5%, and hypertension was the most independent risk factor. The DEMAND study revealed that Asian patients had the highest prevalence of albuminuria (55%) whereas Caucasian patients had the lowest prevalence (40.6%).  Among the Asian countries, Saudi Arabia was the only contributing country; all other patients were from the Far East countries. The prevalence of micro-albuminuria found in our study is lower than that reported for Asian populations in the DEMAND study. Asians in the DEMAND study had higher HbA 1c levels but lower prevalence of hypertension compared with Caucasians (7.8% vs. 7.2% and 53% vs. 68%, respectively). The patients in our study had higher HbA 1c levels (9.4%) and higher prevalence of hypertension (61%) than the Asian patients in the DEMAND study; however, the prevalence of albuminuria was lower. These findings suggest that several factors contribute to the variations in the prevalence of diabetic albuminuria among different populations, including the prevalence of hyperglycemia, hypertension, ethnicity, and a genetic predisposition.  Genetic linkage in the development of DN has been suggested.  The genetic correlation between urinary albumin excretion (UAE) and BP, particularly in the presence of diabetes, suggests that these traits may share common genetic determinants. 
In this study, 20% of the newly diagnosed type 2 diabetics were found to have micro-albuminuria. Mogensen et al reported that in newly diagnosed non-insulin dependant diabetes mellitus, about 40% of the patients showed a UAE rate above 15-20 μg/min. 
In this study, hypertension was the most significant independent factor associated with diabetic albuminuria. It is well documented that hypertension compounds and greatly increases the risk of microvascular complications, including the risk of ESRD.  Each 10 mmHg reduction in mean systolic BP led to 13% risk reduction of nephropathy.  Tight control of BP to keep it <130/80 mmHg, using renin- angiotensin-aldosterone system (RAAS) inhibitors, has been shown to prevent or delay renal complications as well as cardiovascular events in diabetic patients. 
Consistent with other studies, glycemic control, duration of diabetes, BMI, and presence of retinopathy were significantly associated with albuminuria. The relationship of hyper-glycemia to the development and progression of diabetic retinopathy is well documented. 
The UKPDS has shown that for every 10% decrease in HbA1c, there was a 9% reduction in the risk of development of diabetic micro-albuminuria.  Similarly, longer duration of the disease increases the risk of albuminuria in patients with type 2 diabetes.  The association between albuminuria and increased BMI in individuals with type 2 diabetes has been reported and attributed to the glomerular deposition of lipids and the activation of the RAAS.  For every 1 unit increase in BMI, there was an increase in UAE rate by 17%.  Studies have shown that weight loss is accompanied by reduction of proteinuria in chronic proteinuric nephropathies of different etiologies, including diabetes.  As reported,  we too found an association between diabetic retinopathy and albuminuria. Microalbuminuria in patients with type 2 diabetes is considered a marker of retinopathy. 
This study showed that albuminuria was found more frequently in patients treated with insulin or sulphonylurea as monotherapy and with combined insulin/oral therapy, and less frequently among those treated with metformin as mono-therapy or combined with other oral agents. The role of insulin in nephropathy was suggested by Klein et al.  The effect of metformin as monotherapy on UAE rate, compared with sulphonylurea, was inconsistent. ,
Inconsistent with other studies, , gender, smoking status, triglyceride levels, and cholesterol levels were not found to be significantly associated with albuminuria in this study. This may be attributed to the small sample size of our study.
There are two limitations that need to be addressed regarding the present study. The first limitation is the small sample size, which is due to the fact that the majority of diabetic patients in Kuwait are followed-up in primary health care. Although this may affect the prevalence of albuminuria, it should not affect the main objective of the study, which involves the factors associated with diabetic albuminuria. The second limitation is that the present study is a hospital-based study, which may have affected the results by showing a higher prevalence of albuminuria.
In conclusion, albuminuria is common among Kuwaiti adults with type 2 diabetes. Hypertension is the most independent factor associated with albuminuria. Therefore, early recognition and treatment of hypertension is an important strategy to prevent or delay diabetic nephropathy as well as cardiovascular morbidity and mortality. The findings of this study indicate that factors associated with albuminuria among Kuwaiti adults are similar to those reported in other studies. However, the impact of these factors on the prevalence of albuminuria probably varies among different populations, which suggests a genetic linkage for the development of DN. A population-based study is warranted to confirm these findings and to search for genetic linkage for the development of DN. 
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Diabetes Unit, Department of Medicine, Al-Sabah Hospital, P. O. Box 4078, Safat 13041