3.2 Part B: Proposed Methods
3.2.3 Method III
CHAPTER SIX
Albuminuria may be a marker of widespread vascular abnormalities including those of the glomerular capillary wall. This is an early evidence of nephropathy which can be tested for in our laboratory. Also, albuminuria can be used as a mass screening test at the community level, this had been done else where57. Renal dysfunction may enhance intermediate risk factors such as hypertension, hyperhomocysteinemia, and abnormalities of thrombogenic factors. This study58 had shown that proteinuria is not only a risk factor for cardiovascular disease but also a strong indicator of progression to end stage renal disease in the general population, the blood pressure difference between the subjects and the controls was not significant but there was a significant difference in their GFR. The presence of proteinuria generally indicates the existence of established renal parenchymal damage29.
In this study, the rise in blood pressure, associated with the development of microalbuminuria was not evaluated, because, the patients recruited were people with overt albuminuria. Also it had been reported that microalbuminuria is associated with a failure of nocturnal dipping in blood pressure, insulin resistance and abnormal vascular response to various stimuli64.
There was positive correlation between the Body mass index (BMI), proteinuria, and the GFR.
Perry and colleagues 65 reported no association between baseline BMI and future risk of ESRD.
Iseki25 and colleagues found that baseline BMI predicted future risk for ESRD in men but not in women. Ramirez and colleagues,66 noted that among a sample of participants from Singapore, the relationship between GFR, proteinuria and BMI was J-shaped, because those with a BMI of 18kg/m² or less and those with BMI 25kg/m² were more likely to have proteinuria than those with a BMI of 18.01 to 22.99kg/m2. That was a cross-sectional study in which preceding illness may lead to both proteinuria and malnutrition66. In the present study, the bulk of the patients were overweight, and the numbers that were obese was small, however
there was significant correlation between the BMI and the albumin-creatinine ratio. This finding is congruent with the submission that low birth weight is associated with many non communicable diseases; diabetes mellitus, kidney disease etc. This fact also supports the notion that obesity is also a risk factor for chronic kidney disease, and its associated increase morbidity and mortality rate.
There was a negative correlation between the BMI and the GFR, among the subjects studied.
This finding has been corroborated by earlier observers who had documented that obesity leads to renal hyperperfusion which in turn causes proteinuria and focal segmental glomerulosclerosis .47 Some investigators had suggested that leptin produced from adipose tissue may directly lead to renal fibrosis and reduction in GFR 49. The exact mechanism(s) by which excessive weight leads to kidney disease are still been investigated. 46, 47
There was correlation between the left renal length and the GFR in both the subjects and the controls but in the case of the right renal length, there was no association in the controls but that of the subjects was still sustained. This obvious discrepancy may be as a result of human error in the measurement or the placement of the probe. This is one of the limitations in the use of ultrasound in the measurement of renal dimensions, however, this findings is in keeping with Emanian et al, who found correlation between renal length and creatinine clearance in 665 adult volunteers52. This association was greater for the kidney length than for the kidney volume. Although there was significant correlation between renal length and GFR, the usefulness, in clinical practice, of renal length in estimating GFR remains a problem due to a low sensitivity in detecting renal impairment. None of the control had a renal length below 9cm. This may suggest that kidney length <9 centimeter correlates well with albuminuria and
so, may be suggestive of renal impairment. In clinical practice, the usefulness of this is limited by the wide variation and low sensitivity of kidney length in predicting GFR as stated earlier.
Both GFR and proteinuria are independent risk factors for adverse cardiovascular outcome.
Reduced GFR was associated with high prevalence of cardiovascular disease. Several studies across a broad spectrum of populations, such as the HOPE study72, the Cardiovascular Health study (CHS) 73, Hypertension Optimal Treatment study71 et al have shown that levels of systolic blood pressure, total cholesterol and low HDL, are greater in subjects with diabetes, left ventricular hypertrophy, ischeamic heart disease and heart failure. These entire adverse outcomes are also prevalent in patient with decreased GFR. This is true in the elderly patients in whom even mild reduction of kidney function is associated with worse outcomes.57 This had also been demonstrated in studies of hypertensive subjects.69
There was significant number of the controls (44.2%) with grade I echogenicity, and this group of patients had no albuminuria. It could be that grade I echogenicity is not sensitive for screening for albuminuria. However, none of the controls had grade II renal parenchymal echogenicity which is likely more suggestive of nephropathy. Therefore, it is not surprising that there was no correlation between renal parenchymal Echogenicity and the severity of hypertension for both the subjects and the controls.68This findings could also mean that some controls had renal disease without proteinuria. They may infarct have microalbuminuria which was not tested for in this study.
The analysis of variance showed that, there was a significant association between the mean renal parenchymal echogenicities and the GFR in both the subjects and the controls. This finding of correlation between the renal echogenicity and the GFR was not surprising, because,
‘increase in cortical echoes have been described in cases of diabetes mellitus
glomerulosclerosis, and in glomerulonephritis70. The normal medullary pyramid is relatively echo poor as compared with the cortex, and it becomes more prominent in advance glomerulosclerosis69. The increase in echogenicity had been well documented as an evidence of renal parenchymal disease70.
Early detection and treatment of chronic kidney disease may reduce the social burden of cardiovascular disease. It is also important to appreciate the association between the investigations done in this regard. The association between the kidney function and the renal ultrasound findings will be an important step in this regard.
CONCLUSION
The following conclusions could be reached from this study:
1. The ANOVA between the GFR and the renal echogenicities in both the subjects and the controls is significant. The renal echogenicity could be used to predict the GFR in both the hypertensives with albuminuria and the controls, it then follows that increase renal echogenicity is predictive evidence of nephropathy.
2. There was positive correlation between the renal length and the GFR in both groups.
The renal length may be used to predict the level of renal impairment, as none of the controls had renal length less than 9cm.
3. There was negative correlation between the BMI and the GFR of the subjects but not that of the controls, despite the fact that there was no significant difference in their BMI. This shows that the proteinuria in the subjects contributed significantly to their adverse outcome.
4. There was no correlation between the degree of hypertension and renal
echogenicity. The severity of the blood pressure could not be predicted from the renal echogenicity. And also, the renal length has no association with the degree of blood pressure level.
5. There was no correlation between albumin-creatinine ratio and the GFR,echogenicity, and the degree of SBP and DBP in both the subjects and the controls.
LIMITATIONS:
1. The study was hospital based, and single centred for the recruitment of the respondents, therefore selection bias can not be completely ruled out. This is because the participants recruited were all patients attending University College Hospital, Ibadan, and as such may not be representative of the general population.
2. The non probability sampling technique was employed for this study and the degree to which the sample differs from the population remains unknown.
3. The degree of albuminuria in hypertensive patient could not be comprehensively ascertained because the bulk of the people with microalbuminuria were not screened for in these subjects.
4. The rate of urinary albumin excretion varies by as much as 40% in a day, and there is an interindividual and intraindividual variation. The appropriate method will have been an average urinary albumin excretion. In this study, the sample for albumin-creatinine ratio was not repeated for logistics reasons.
IMPLICATIONS AND RECOMMENDATIONS
The study shows that there was no correlation between renal ultrasound findings and the severity of blood pressure reading. In this study there was correlation between the renal length and the GFR in both the subjects and the controls. There was also correlation between the renal echogenicity and the GFR in both the subjects and the controls.
The preponderance of overweight patients in this study and the correlation of this with reduced GFR in the subjects but not in the controls, suggests that attention should be focused on life style modification in hypertensive patients with or without proteinuria. Overweight is a strong and potentially modifiable risk factor for the development of ESRD. Conversely kidney failure should be added to the list of adverse consequence of obesity, given the rapidly increasing incidence of obesity and ESRD.
The correlation between the albumin-creatinine ratio and renal echogenicity suggest that increase in echogenicity is an evidence of renal parenchymal disease, but there were no correlation between the renal length and protein excretion.
The screening of the patient’s urine for albuminuria should be extended to include the search for microalbuminuria.
This study been hospital based and a small sample size has a limitation in terms of the strength of the study, nevertheless, it constitutes a background for analytical study to test some of the hypothesis generated.
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Ethical
APPENDIX II
DEMOGRAPHIC INFORMATION ON CORRELATION OF ULTRASOUND FINDINGS WITH RENAL FUNCTION IN HYPERTENSIVE PATIENT WITH PROTEINURIA
A
Name (Initials) ………..
Serial No………
Age ………
Hospital No………
Occupation ………
Sex……….
Tribe………..
Religion ……….
B
Age at Diagnosis : <20yrs 21-30yrs 31-40yrs 41-50yrs 51-60yrs 61-70yrs > 71yrs
Duration of the illness: <1yr 1-4.9yrs 5-9.9yrs >10yrs C
Risk factors for hypertension
Family history of hypertension Yes No
Family history of diabetes Yes No
History of steroid use >3/12 Yes No
Drugs
α methyldopa Yes No
Calcium channel blocker Yes No
Moduretics Yes No