| Abstract|| |
Testing for proteinuria is used to screen for diabetic nephropathy. However, significant proportion of diabetics has normal urine protein excretion despite impaired renal function. We aimed to determine the factors predicting increased urine protein excretion in patients with type 2 diabetes. This was a cross-sectional study of 358 type 2 diabetics attending the diabetes clinic of a teaching hospital in Lagos. Data regarding patients’ demographic characteristics, and disease history were retrieved. Clinical measurement and samples for determination of plasma creatinine, and urine protein/creatinine ratio were obtained. Comparison of means was by student’s t-test, while for percentages, Chi-square test was used. Relationship between glomerular filtration rate (GFR) and urine protein excretion was assessed using linear regression while factors associated with increased urine protein was determined excretion logistic regression analysis. Level of statistical significance was set at P <0.05. Mean age was 57.84 + 11.12 years and mean duration of diabetes was 8.63 + 7.53 years. Urine protein excretion was increased in 191 (53.4%) of the patients. Patients with increased urine protein excretion were more likely to be hypertensive, to be on an angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker had a higher mean systolic blood pressure, and a lower mean GFR. Patients with a GFR <60 mL/min/1.73 m2 had a six-fold increased odds of having increased urine protein excretion, while patients on an inhibitor of the renin-angiotensin-aldosterone system had a 50% reduced odds of having increased urine protein excretion. Proteinuria and reduced GFR are common among sub-Saharan African patients with type 2 diabetes. GFR below 60 mL/min/1.73 m2 and not receiving an inhibitor of the renin-angiotensin-aldosterone system predict increased urine protein excretion in them.
|How to cite this article:|
Bello BT, Amira CO. Pattern and predictors of urine protein excretion among patients with type 2 diabetes attending a single tertiary hospital in Lagos, Nigeria. Saudi J Kidney Dis Transpl 2017;28:1381-8
|How to cite this URL:|
Bello BT, Amira CO. Pattern and predictors of urine protein excretion among patients with type 2 diabetes attending a single tertiary hospital in Lagos, Nigeria. Saudi J Kidney Dis Transpl [serial online] 2017 [cited 2019 Jul 23];28:1381-8. Available from: http://www.sjkdt.org/text.asp?2017/28/6/1381/220869
| Introduction|| |
Diabetes mellitus (DM) is the leading cause of end-stage renal disease (ESRD) world-wide., Even in sub-Saharan Africa where DM was, in the past, not considered a major cause of kidney disease, its contribution to the burden of ESRD is increasingly being.,, Diabetic nephropathy (DN) has traditionally been classified based on urine protein excretion into incipient and overt nephropathy. This has led to the routine evaluation of the urine for protein or albumin as a screening tool for detecting the presence of nephropathy in patients with DM.
However, there is evidence to suggest that significant proportions of diabetic patients with impaired renal function may have normal urine protein excretion. The first report of impaired renal function and normal urine albumin excretion in patients with type 1 diabetes was made in 1992. Since then, several studies have shown that patients with both type 1 and type 2 diabetes can have normal urinary protein excretion despite significantly impaired renal function.,,,, This suggests that factors other than the degree of renal dysfunction may influence urine protein excretion in patients with DN.
There is limited data from sub-Saharan Africa on the urinary protein excretion patterns in patients with DM. The aim of this study is to describe the pattern of urinary protein excretion as well as determine the factors predicting increased urine protein excretion in a sub-Saharan population of patients with type 2 DM.
| Subjects and Methods|| |
This was a cross-sectional study of 358 patients with type 2 diabetes who were attending the diabetes outpatient clinic of the Lagos University Teaching Hospital. Patients were included in the study if they were 18 years of age or older, had type 2 diabetes and gave informed consent. The exclusion criteria for the study included; age <18 years, a diagnosis of type 1 diabetes, an axillary temperature at the time of recruitment above 37.3°C, presence of a symptomatic urinary tract infection, severe intercurrent illness or malignancy and refusal to give consent. The study protocol was approved by the research and ethics committee of the hospital.
Data were retrieved from the patients using a structured, interviewer-administered questionnaire. Information retrieved included the patients’ demographic characteristics, lifestyle, personal and disease history, current drug therapy and a family history of kidney disease. All patients had their blood pressure measured in the sitting position after a 10 min rest using a mercury sphygmomanometer (Accusson®). The mean of two separate readings was taken as the patient’s blood pressure. Patients’ weights were measured in kilograms using an electronic weighing scale (Avery®) while height was measured in meters using a stadiometer (Seca®). The body mass index (BMI) was determined for each patient by dividing the weight expressed in kilograms by the square of the height in meters. The waist circumference of each patient was measured with the subjects standing using a nonstretch metric tape.
Each patient had ophthalmoscopic examination of the retinal fundus following pupillary dilatation using tropicamide. The presence of any retinal changes attributable to diabetes was documented. A 10 mL sample of early morning urine was obtained from each patient for determination of urine protein and urine creatinine concentration. The urine protein/ creatinine ratio (in g/g) was then calculated by dividing the urine protein concentration by the urine creatinine concentration. A 5 mL sample of blood was obtained for the determination of plasma creatinine concentration. The glomerular filtration rate (GFR) for each patient was then estimated from the plasma creatinine, using the abbreviated (four variable) version of the equation developed from the Modification of Diet in Renal Disease study., Both plasma and urine creatinine were measured using the modified Jaffe’s method while the urine protein concentration was measured using sulfosalicylic acid/sodium sulfate turbidimetry.
Definition of terms
- Hypertension was said to be present if systolic blood pressure was >140 mm Hg, diastolic blood pressure was >90 mm Hg or the patient required antihypertensive medication to control blood pressure
- Obesity was defined as a BMI >25 Kg/m2 while truncal obesity was defined as a waist circumference >88 cm in men and 102 cm in women
- Retinopathy was documented as present if any retinal changes attributable to diabetes were found on ophthalmoscopy according to the international clinical disease severity scale for diabetic retinopathy
- Increased urine protein excretion was defined as a urine protein/creatinine ratio >0.2 g/g
- Reduced GFR was defined as an estimated GFR <60 mL/min/1.73 m2.
Data obtained were analyzed using Epi-info statistical software version 7.0. (Centers for Disease Control and Prevention, Atlanta, USA). Continuous variables are presented as means and standard deviation while categorical variables are presented as percentages. The patients were stratified into two groups based on their urine protein excretion. Patients with a urine protein/creatinine ratio <0.2 were defined as having normal urine protein excretion while patients with urine protein/creatinine ratio of 0.2 or greater were defined as having increased urine protein excretion. A comparison of the clinical characteristics of both groups was then carried out. For continuous variables, student t-test was used to compare the differences between means, while for categorical variables comparisons was done using Chi-square test.
Linear regression analysis was carried out to determine the relationship between GFR and urine protein excretion while logistic regression analysis was used to determine the factors associated with increased urine protein excretion. For the purpose of logistic regression analysis, GFR and systolic blood pressure were modeled as categorical variables and patients with GFR <60 mL/min/1.73 m2 were compared with patients with GFR of 60 mL/min/ 1.73 m2 or greater while patients with systolic blood pressure of 140 mm Hg of higher were compared with patients with systolic blood pressure <140 mm Hg. The level of statistical significance was set at a P<0.05.
| Results|| |
Of the 358 patients who were recruited into the study, 221 (61.7%) were females. The mean age of the study population was 57.84 + 11.12 years (range: 30–87 years), and the patients had been diabetic for a mean duration of 8.63 + 7.53 years. [Figure 1] shows the distribution of GFR in the study population while [Figure 2] shows the relationship between estimated GFR and urine protein excretion.
|Figure 1: Glomerular filtration rate distribution of the study population.|
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|Figure 2: Relationship between glomerular filtration rate and urine protein excretion.|
r: coefficient of correlation, r2: Coefficient of determination, P: P-value.
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A total of 191 (53.4%) of the 358 patients studied had increased urine protein excretion. [Table 1] shows the clinical and laboratory characteristics of the study population as well as a comparison of the clinical and laboratory characteristics of patients with and without proteinuria. Compared to patients with normal urine protein excretion, patients with increased urine protein excretion were more likely to be hypertensive, and to be receiving angiotensin converting enzyme inhibitor (ACEI) or angiotensin II receptor blocker (ARB) therapy. They also had a higher mean systolic blood pressure, and a lower mean GFR. [Table 2] shows the logistic regression analysis of the factors predicting increasing urine protein excretion in the study population.
|Table 2: Logistic regression analysis of factors predicting increased urine protein excretion in patients with type 2 diabetes.|
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| Discussion|| |
In this sub-Saharan African population of patients with type 2 diabetes, we observed high rates of both reduced GFR (45.3%) and increased urine protein excretion (53.4%) as well as low rates of retinopathy (20.1%). The rates of both reduced GFR and increased urine protein excretion found in this study are significantly higher than those reported in previous studies carried out in non-African populations of patients with type 2 diabetes,,, but similar to that reported in studies of African type 2 diabetic patients.,, Unlike reduced GFR and proteinuria rates, however, the rate of retinopathy observed in this study is similar to that reported from studies of non-African populations of patients with type 2 diabetes., This finding is in keeping with the widely held belief that kidney disease is generally more severe in black populations than the nonblacks., In fact, Blacks with diabetes have been shown to have higher urine protein excretion for any degree of kidney injury when compared to Caucasians and other non-Hispanic whites.,
We observed an inverse, but nonsignificant, relationship between the amount of protein excreted in the urine and the GFR, with the amount protein in the urine increasing progressively as GFR decreased. However, when compared with patients who had normal protein excretion, patients with increased urine protein excretion had lower mean GFR and were more likely to have a GFR <60 mL/ min/1.73 m2, this finding is consistent with the documented natural history of DN in which the development of microalbuminuria, eventually leads to macroalbuminuria and then progressive loss of GFR. Although derived from observation of patients with type 1 DM, it has been suggested that a similar process occurs in patients with type 2 diabetes although in patients with type 2 diabetes, micro- or macro-albuminuria may be present at diagnosis of DM.
Hypertension has long been documented as an important risk factor for the development and progression of nephropathy in patients with diabetes.,,, In this study, we observed that patients with increased urine protein excretion were more likely to have a history of hypertension and had higher mean systolic blood pressures compared to those with normal urine protein excretion. There was, however, no significant difference in mean diastolic blood pressures between both groups of patients. Systolic blood pressure was associated with both microvascular and macrovascular complications in the United Kingdom prospective diabetes study, and the association of systolic blood pressure with proteinuria observed in this study has been reported by other studies of patients with type 2 DM.,,
We also observed that patients with increased urine protein excretion were more likely to be receiving ACEI or ARB therapy. ACEIs and ARBs have consistently been shown to offer benefits beyond blood pressure control. These benefits include reduction in urine protein excretion as well as retarding the rate of deterioration in GFR.,,,,,, Thus, this finding of ours is not surprising since it would be expected that physicians caring for those diabetic patients with proteinuria would be obliged to ensure that these patients benefit from the “renoprotective” effects of ACEIs and ARBs.
Logistic regression analysis however identified only two factors; a GFR <60 mL/min/1.73 m2 and therapy with an ACEI/ARB; that were associated with the presence of proteinuria in this population of patients with type 2 DM. Patients with GFR <60 mL/min/1.73 m2 were six times more likely than those with GFR of 60 mL/min/1.73 m2 or higher to have proteinuria, while patients who were receiving an ACEI or ARB were 50% less likely, than those who were not, to have proteinuria. This finding is in keeping with what has traditionally been known about the natural history of proteinuria in patients with DN; that overt proteinuria usually heralds and predicts the onset of progressive decline in GFR and that inhibitors of the renin-angiotensin-aldosterone system,, particularly, ACEIs and ARBs are usually prescribed by physicians for their “renoprotective” effects.,,,,,,,
One limitation of our study is that we did not take into consideration the effect of glycemia on proteinuria. Current guidelines recommend the routine use of glycosylated hemoglobin concentration in the assessment of glycemic control in patients with diabetes and this is standard practice in most developed. However, in resource settings such as ours its routine use in patient care and research have been hindered by it relatively high cost, “out-of-pocket” payment for care by patients and limited funding for research.,
| Conclusion|| |
Proteinuria is common among sub-Saharan African patients with type 2 DM. A GFR <60 mL/min/1.73 m2 is significantly associated with the presence of proteinuria in sub-
Saharan African patients with type 2 DM.
Conflict of interest: None declared.
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Babawale T Bello
Department of Medicine, College of Medicine, University of Lagos, Idi-Araba, Lagos
[Figure 1], [Figure 2]
[Table 1], [Table 2]