The current practice of using angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers in diabetic hypertensive and non-hypertensive patients

Discussion

Our study showed that 48% of questionnaire respondents were aware that vitamin D can confer benefits to patients with DN.

Guidelines produced by National Kidney Foundation (NKF) and the American Diabetes Association (ADA) suggest screening patients with T2DM for microalbuminuria at diagnosis, as studies have found that 7% of patients present with kidney disease at diagnosis of T2DM. The NKF recommends serum creatinine for glomerular filtration rate (GFR) estimation, as well as urine albumin excretion to be monitored annually. American Diabetes Association recommends urine albumin excretion alone and subsequent serum creatinine for estimated GFR if the urine albumin is increased beyond 30 mg/L.17 Following positive screening for microalbuminuria, as per ADA guidelines, annual urine albumin should be checked to monitor DN and the response to therapy.18 In this multicenter cross-sectional study, the majority of respondents, ranging from medical practitioners of various specialties to master’s and PhD holders, thought that renal function should be monitored prior to and upon initiation of ACEi and/or ARBs in patients with diabetes, which is in line with the ADA guidelines.

One important reason for testing renal function post initiation of ACEi or ARBs is the risk of precipitating acute kidney failure. Should a clinician pick up a 30% increase in serum creatinine above baseline within 2 months of initiation of therapy or if serum potassium persists above 5.6 mEq/L, ACE inhibitors should be discontinued.19

Almost all questionnaire respondents agreed to the indication of ACE inhibitors and/or ARBs for microalbuminuria in normotensive individuals, following the Cochrane Systematic review, which recommends the use of these drugs as a first-line option to reduce the progression of the disease.20 Almost a third of the respondents, however, admitted to the use of ACEi and ARBs simultaneously, which in a double-blinded randomized control trial was discouraged due to increased risks without evidence of improved efficacy.21

The deficiency of vitamin D is linked to microvascular complications in patients with DM, perhaps facilitating the development of DN.13 The results of this study showed that only approximately 48% of questionnaire respondents were aware that vitamin D has been shown to confer benefits to patients with DN. This indicates a lack of awareness on the benefits of vitamin D and its effectiveness in DN. A systematic review and meta-analysis evaluating the role of vitamin D or its analogue in the management of DN showed a significant improvement of proteinuria in patients with DN and an overall improvement in renal function.22 A systematic review published in 2018 including 16 studies that met inclusion criteria showed that prevalence of vitamin D deficiency in Saudi Arabia (63%) and more specifically Riyadh (31%).23 Moreover, this study demonstrates that up to 52% of clinicians have not been incorporating vitamin D to their plan of care in a high risk population.

In this study, 41% of questionnaire respondents reported never using vitamin D in the treatment of DN, which could be partly explained by limited recommendations/guidelines. Most patients with DN have been receiving vitamin D supplements for vitamin D deficiency, as the 2 conditions commonly co-exist; therefore, clinicians may not consider modifying vitamin D regimens solely for the treatment of DN.

The major strength of this study is its uniqueness in comparison to other studies that solely focused on improving the use of ACEis and ARBs in the gulf region before evaluating the current practice. We used an instrument that was carefully constructed to examine physician’s current practice and attitude toward ACEi and ARBs. In addition, we explored the association between the demographic characteristics and working-experience with the ongoing clinical application of ACEi and ARBs.

On the other hand, the limitations were mostly due to participants being self-enrolled in the study which may lead to poor external validity to other hospitals in the region as well as worldwide and sample bias cannot be ruled out. Also, the questionnaires were in English, which for many respondents was not their first language resulting in a potential space for false interpretation. Furthermore, as with all cross-sectional studies carried out using paper-based questionnaires, they lack nuance and there is risk of unconscientious responses. We also did not stratify the results based on speciality of responder, level of experience or to what degree of clinical involvement they had with the management of diabetic nephropathy.

In overcoming these limitations, we successfully administered the survey to 80% of the physicians in the 3 hospitals under the specialties of interest. Although we used a convenience sampling we were able to cover the vast majority with a 92% response rate. Moreover, we specifically chose to implement an instrument that consisted of a broad range of items and practices on the application of ACEi and ARBS. We aim to conduct more studies to extract additional information that reflect the reasons for these practices and opinions. Of note, Saudi Arabia has not produced guidelines for the treatment of DN thus far, further investigation into the guidelines different providers refer to for implementing evidence based medicine could be beneficial. Moreover, expanding the study to include an intervention such as a didactics to residents that are involved in the care of diabetic nephropathic patients and re-distributing the questionnaire to see if their practice has been modified.

In conclusion, there seems to be a universal agreement regarding the use of ACE inhibitors and ARBs in the treatment of patients with DN. Renal function tests were used regularly to monitor the progression of DN and response to therapy. Physicians, however, were not fully aware of the benefit of using vitamin D in patients with DN. This is likely to be due to a lack of a local generating body for guidelines regarding the management of diabetic nephropathy. The literature lacks recent data on the incidence of diabetic nephropathy among the Saudi population. But, one study, showed Saudi to be one of the countries with the highest rate of T2DM and renal complications of diabetes in adult populations. “In 2011, it was estimated that 42.5% of end stage renal disease (ESRD) cases in Saudi Arabia were related to diabetes, and the cost for dialysis in this country amounts to SR173,784 (US$46,332) per patient per year.”24 This justifies the need for more research investigating the implementation of the best level of care for the adult population of diabetics.

While vitamin D deficiency is a common finding in patients with chronic kidney disease, there is a profound shortage of guidelines for its use in clinical practice. Thus, further research is warranted to establish the role of vitamin D in the prevention and treatment of DN. In addition, we recommend the development of clear, specified, and detailed guidelines for the use of vitamin D in the treatment of patients with DN that is tailored to a population that at least shares the characteristics of Saudi Arabia including but not limited to high deficiency of vitamin D and DN prevalence.

In conclusion, the burden of disease of diabetic nephropathy as well as -min D deficiency in Saudi Arabia is high. There is evidence for the benefits of supplementing diabetes complicated by nephropathy with vitamin D. Additionally, there is evidence for the no added benefit, but on the contrary added risk of using both ACEi and ARBs simultaneously. This study displayed the need for clearer guidelines for management of diabetes complicated by nephropathy.