DISCUSSION AND CONCLUSION
8.2. STUDY LIMTATIONS
The cross-sectional design used in the studies contained in this thesis was useful in the evaluation of key epidemiological aspects of CKD in our study patient population, in the absence of population data. Various associations were reported and several hypotheses for future studies were generated. However, causal inferences cannot be made from the observed associations, which is the major limitation of this study design. Selection bias is a potential limitation of the study setting in hospital-based clinics since the study participants are unlikely to be representative of the general population. Misdiagnosis in assigning comorbidities might have occurred with the use of self-reported diagnosis, current medication, prior clinical and pharmacy records. Another potential source of misclassification is the use of eGFR equations, leading to errors in CKD staging. The small sample size of the studies and absence of appropriate control groups in each of the studies, as a consequence of limited funding, might affect the reliability of the results thus, are further limitations. Future studies are needed, with sufficient power and control groups, e.g. healthy controls as well as rural/urban patients to overcome theidentified limitations.
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This work provides evidence that CKD affects relatively young patients and is associated with multiple comorbidities in adults seen at two regional hospital-based clinics, with limited access to nephrologists, cardiologists or diabetologists or other subspecialists. We confirmed that hypertension remains the commonest CKD risk factor, which is prevalent across the CKD spectrum, often with comorbidities like diabetes, HIV, CVD and obesity. This calls for intensified efforts aimed at early diagnosis and effective management of hypertension. Lessons could be obtained from the successful National Blood Pressure Education Program in USA, a private-public partnership designed to motivate the public, physicians, nurses, pharmacists and other health workers to do a better job of managing hypertension, which resulted in markedly improved hypertension awareness, treatment and control as well as reduced mortality (89).
Diabetes and HIV were shown to be emerging in our setting as important contributors to the CKD burden. Both are likely to change the epidemiology of ESRD in future due to recent favourable changes in RRT acceptance criteria in South Africa, which are now more inclusive of diabetic and HIV patients.
We have also shown that CKD-related metabolic and endocrine complications were prevalent, mainly from CKD stage ≥3b but also at normal GFR levels, with patients often untreated for these complications. This could either reflect resource-management policies that restrict treatment availability only to subspecialty clinics or lack of awareness of treatment and/or the resultant benefits, except in the case of hyperuricaemia, where evidence on the benefits of urate- lowering is inconclusive. The observed unexpected negative association of gout with African ancestry needs further evaluation. We further suggest PEW as another complication that might occur early, especially in males, who were found to have reduced lean and fat mass from CKD stage ≥3b however, we could not assess longitudinal changes in lean and fat mass with the present study design.
This observation in males as well as that of mGFR underestimation by eGFR in stages 4 and 5 CKD patients in the two GFR estimation studies, raises a possibility of increased catabolism in our population that could affect GFR estimation; a potential subject for future research. In addition, we found that eGFR overestimated mGFR in earlier CKD stages in both studies. These extremes in GFR estimation were substantially minimized, by the equation that was developed in
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8 Africans, albeit not eliminated. Nevertheless, we have concluded that the improved accuracy seen with the new equation, which showed better GFR prediction than existing ones, warrants more effort to further develop and validate it in a large study sample comprising a wide range of GFR values. Attempts to build on this innovation by establishing a network of investigators and planning a large multicentre study of Africans are underway. A major hurdle is the unavailability of radioisotope studies in many public healthcare centres in South Africa and lack of uniformity in the clearance agent used in the few that offer radioisotope GFR. This will necessitate collaboration with the private healthcare sector and researchers in other African countries.
The antiretroviral therapy roll-out program provides a practical framework through which training of primary healthcare doctors and nurses was performed successfully in South Africa.
The program, based at primary healthcare level with minimal specialist/subspecialist support, has delivered much needed treatment to multitudes of HIV patients many of whom likely had complex co-existing diseases, including infections and malignancies. We recommend adoption of a similar national strategy to train primary and regional level healthcare practitioners in primary, secondary as well as tertiary prevention, which we plan to propose to relevant health stakeholders to reduce the impact of CKD. Specialist outreach programs bring valuable expertise to primary healthcare practitioners and patients; hence it is commendable that outreach services to northern KwaZulu-Natal by specialists from both public and private healthcare sector in Durban have slowly gained traction over the last two years. Lobbying of health authorities, to extend provision of effective therapies to lower levels of care is indeed warranted, especially to areas without specialists/subspecialists or where there is no option for up-referral and/or RRT.
Lastly, the data presented underscore a need for population studies and registries to provide data on the various aspects of CKD. Studies of high-risk individuals are valuable to obtain epidemiological data, to understand disease patterns and distribution as well as guide resource allocation, where population studies are not feasible. A diagnostic method developed and validated in the population in which it will be used is necessary to provide a more accurate estimate of the GFR level.
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