Rhythmanalysis

The SUPCR had a high correlation (r=0.734) with 24HUP for all groups, a high correlation (r=0.748) for Group 1 (normal renal function without proteinuria), a high correlation (0.949) for Group 3 (renal impairment and proteinuria) and Group 4 (renal impairment without

proteinuria), respectively, in HIV subjects. The SUPOR correlated moderately (0.417, 0.548, 0.437, 0.389 and 0.274) with 24HUP for all groups, Groups 1, 2, 3 and 4 respectively in HIV

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subjects. In the controls, both SUPCR and SUPOR had moderate positive correlation with the 24HUP. These were lower than the values noted by Wilson et al⁸ in which they found higher correlation r=91 of SUPCR with 24HUP, and that of Farahnak et al¹³⁵ in which SUPOR correlated highly (r=0.92, p<0.01), with 24HUP. However, a high correlation (0.949) of 24HUP with SUPCR observed in Group 3 of HIV subjects in this study was similar to the findings of Wilson et al mentioned previously. This difference may be due to the categorization of the subjects according to their renal function and proteinuria status used in our study in contrast to the grouping according to levels of proteinuria used in their study.

The linear regression analysis showed that both SUPCR and SUPOR had a linear relationship with the 24HUP. This agrees with the reports of some studies in which SUPCR and 24HUP were found to have a linear relationship.^8,9 It is also similar to the findings of some studies in which SUPOR and 24HUP were reported to have a linear relationship.^8,135

The accuracy of the SUPCR and SUPOR in predicting patients with abnormal proteinuria (24HUP≥0.150g) was assessed in this study. The values obtained with the different methods were 76.8% for SUPCR and 70.6% for SUPOR in HIV subjects. Furthermore, accuracy for Group 2 (normal renal function and proteinuria) was 60.3% for SUPCR and 64.6% for SUPOR. For Group 3 (renal impairment and proteinuria) accuracy was 79.4% for SUPCR and 68.0% for SUPOR.

Although the values obtained in both groups of patients were above average, a very high result (90% and above) is required for the method used in assessing the 24-hour urine protein to be classified as having a good predictive accuracy. ¹³⁶ The values for accuracy obtained for the control group were high: 84.5% for SUPCR and 86.0% for SUPOR for all groups. Further, for Group 1, accuracy was 91.6% for both SUPCR and SUPOR methods, Group 2 83.0% and 84.9%

respectively, and Group 3 69.6% and 71.1% respectively. The results showed that the two methods have a poor predictive accuracy in HIV subjects, but have a good predictive accuracy in the control group. In these controls, the predictive accuracy was good for Group 1. The results also showed that SUPOR as a method of assessing 24-hour urine protein, both in those with normal renal function and those with renal impairment, was slightly better than the SUPCR in the controls than in the HIV subjects.

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The sensitivity of the different methods of assessing 24-hour urine protein in overall HIV subjects were 43.$% and 11.4% for SUPCR and SUPOR respectively. Sensitivity in Group 1 was 10.9% and 30.0% for SUPCR and SUPOR methods respectively. The results showed that the sensitivity of the SUPCR method was 61.2% in Group 3 (renal impairment and proteinuria) compared with sensitivity of 12.2% for SUPOR method in the same Group 3. Therefore, sensitivity pattern of the methods was poor in those with normal renal function. This is much lower than the sensitivity pattern noted by Serdaroglu et al.¹⁰¹ They reported sensitivity of 82%

for SUPOR against 24HUP. The low sensitivity in our study may be due to the difference in cutoff points for abnormal proteinuria. Different studies used different cutoff points for abnormal proteinuria. Wilson et al⁸ used a cutoff point of 0.12 with SUPOR method and had a sensitivity of 96%, specificity 93%. With a cutoff point of 0.05 with SUPCR method, they had a sensitivity of 96%, specificity 90% in their study of 24-hour urine protein excretion. In our study, a cutoff point of 0.150 was used for 24HUP, SUPCR and SUPOR for abnormal proteinuria.

Specificity, overall for all HIV groups, of the different methods was 92.9% and 99.2% for SUPCR and SUPOR respectively. In Group 2 the specificity was 100% and 92.3% for SUPCR and SUPOR respectively, and in Group 3 89.0% and 97.8% for SUPCR and SUPOR respectively. This showed that both methods used in this study had high specificity in both the normal renal function group and the impaired renal function group, and that for patients in both groups with 24-hour protein<0.150g, the chances of their being classified as having 24-hour urine ≥0.150g by these methods is very low. This is a good attribute of a screening test or formula.

The positive predictive value, overall, of the methods used in this study was 74.6% and 87.5% for SUPCR and SUPOR respectively. In Group 2, positive predictive value was 100% and 75% for SUPCR and SUPOR respectively. Overall, the positive predictive value was higher with the SUPOR method than with the SUPCR. The high positive predictive values for both methods in Group 2 and Group 3 compensate for the slightly lower sensitivity values.

The negative predictive value of the methods used in this study was 92.8% and 69.9% for SUPCR and SUPOR respectively, overall. The negative predictive value of SUPCR was high, whereas that of SUPOR was average. The negative predictive value of SUPCR was much better

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than that of SUPOR. In Group 2 the negative predictive value was 58.3% and 67.2% for the SUPCR and SUPOR respectively. In Group 3 the negative predictive value was 81.8% and 67.2%

for SUPCR and SUPOR respectively and this showed that the negative predictive value was higher with SUPCR than with SUPOR method in Group 3. Also, the negative predictive value was higher with SUPCR in Group 3 than in Group 2. The pattern was the same with SUPOR method in which the negative predictive value was higher in Group 3 than in Group 2.

The sensitivity pattern in the controls was 20.0% and 15.0% for SUPCR and SUPOR respectively, overall. For both methods the sensitivity was very low, but lower still with the SUPOR method. In Group 1 the sensitivity of the SUPCR and SUPOR could not be worked out as the true positive was zero for both. In Group 2 the sensitivity was 22.2% for both SUPCR and SUPOR methods. The results do not agree with the reports of a study in which the sensitivity was high in both those with renal impairment and those with normal renal function.¹³⁵ The specificity in the controls was 95.6% and 98.2% for SUPCR and SUPOR respectively, overall. These were very high specificity values. In Group 1, 2 and 3, as in the overall controls, the specificity was very high for both SUPCR and SUPOR methods. These results did not differ from those of other study.¹⁰¹

The positive predictive value in the controls was 44.4% and 60.0% for SUPCR and SUPOR respectively, overall. This showed a moderate positive predictive value for SUPCR and a poor value for SUPOR. In Group 1 and Group 4, the value could not be elucidated as the true positive was zero for both methods. In Group 2 the specificity was 50.0% and 66.6% for SUPCR and SUPOR respectively, and in Group 3 50.0% and 100% for SUPCR and SUPOR respectively. These showed a fair positive predictive value for both SUPCR and SUPOR in Group 2 and a fair value for SUPCR in Group 3. In this study, SUPOR had a much better positive predictive value than the SUPCR method in those controls with renal impairment and proteinuria than in those patients with normal renal function and proteinuria. These results agree with those of Serdaroglu et al.¹⁰¹

The negative predictive value for both SUPCR and SUPOR methods was 87.0%, indicating a high value. In Group 1 the value was 95.6%for both SUPCR and SUPOR methods, but in Group 2

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it was 85.6% for SUPCR and 86.0% for SUPOR. The value was lower in Group 3: 72.4% for SUPCR and 71.0% for SUPOR.

Both the SUPCR and the SUPOR had similar poor sensitivity in the controls.

Based on ROC Curves comparison, our study did not show any difference between SUPCR and SUPOR methods in predicting abnormal proteinuria in HIV subjects and non-HIV subjects, similar to the findings of some studies.^100,137 In contrast, in one study, it was reported that SUPCR was superior to SUPOR.¹³⁸

Based on Bland Altman plots, our study showed that 24HUP and SUPCR methods of

assessing quantitative proteinuria may be used interchangeably in both HIV subjects and in the non-HIV control subjects. In contrast, 24HUP and SUPOR may not be used interchangeably in both the HIV subjects and the non-HIV subjects. This disagrees with the report of Yang et al in which they demonstrated no significant difference in the overall performance of SUPCR and SUPOR.¹³⁷

5.5 Analysis of relationship between SUCr and SUOsm

Our study showed there was significant positive correlation between SUCr and SUOsm in HIV subjects and in the controls, not influenced by renal function and level of proteinuria. There was a linear relationship between urine creatinine and urine osmolality. This is similar to the report of Godevthanage et al¹³⁹ in which they found that spot urine osmolality/creatinine ratio of healthy humans was consistent in the steady state.

75 CHAPTER SIX 6.1 CONCLUSIONS

1. Abnormal proteinuria is common among newly diagnosed HIV patients in FMC, Owerri, occurring in 32.5% of subjects.

2. CKD is common in newly diagnosed HIV patients, occurring in 37.8% of subjects.

3. Factors that predispose to CKD in HIV patients include low waist circumference, high serum creatinine, high SUPCR, high 24HUPCR, high 24HUPOR, and they are positive predictors, while only low waist circumference is a negative predictor, of CKD in HIV subjects.

4. There is a linear relationship between urine creatinine and urine osmolality, not influenced by renal function status and levels of proteinuria.

5. From correlation analysis, both SUPCR and SUPOR are sensitive in assessing 24-hour urine protein in HIV subjects, with SUPCR being more sensitive than SUPOR.

6. Based on the sensitivity, specificity, accuracy and LHR analysis, both SUPCR and SUPOR are poor diagnostic methods for detecting abnormal proteinuria in HIV subjects, but SUPCR is superior to SUPOR.

7. Based on the ROC Curves analysis, both SUPCR and SUPOR are poor diagnostic but good screening methods of assessing quantitative proteinuria in HIV subjects, with SUPCR method being slightly better in non-HIV subjects.

8. Based on Bland Altman’s plots analysis, SUPCR and 24HUP may be used interchangeably in HIV subjects and non-HIV subjects whereas SUPOR and 24HUP will not be used interchangeably in both groups.

9. Overall, the performance of SUPCR is better than SUPOR in HIV subjects and non-HIV subjects.

76 STRENGTHS OF THE STUDY INCLUDE

1. The study was in 100% black African population.

2. Availability of PEPFAR clinics facilitated study access to large HIV patient population.

3. Materials for protein and creatinine analyses were readily available.

4. Use of automated machines made it, overall, cheaper and more convenient to run SUPCR and SUPOR for estimation of 24-hour urine protein than the standard protein measurement based on 24-hour urine collection.

5. The study was done in a high endemic HIV African population.

6. Measured GFR was used and not estimated GFR for both HIV subjects and no-HIV subjects in this study.

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