Hypertension is a double common in diabetic patients in comparison with nondiabetics ⁽¹⁾ , Diabetic hypertensive patients report a significantly higher risk for both macrovascular and microvascular complications including renal disorder. Diabetic nephropathy has a cumulative prevalence of 30%-40% in T2DM, and is usually developed 15 years after the beginning of diabetes .⁽²⁾ It is documented that renin-angiotensin system has a direct effect on kidney function causing renal vasoconstriction and salts and water retention .⁽³⁾ The renin-angiotensin system can have nonhemodynamic effects through several pathways, including autocrine and paracrine actions and systemic and local hemodynamic effects. 

Their ability to stimulate cell proliferation in the kidneys and release growth factors and cytokines may contribute to diabetic kidney damage. ⁽⁴⁾. Diabetic patients, especially those with diabetic nephropathy, have higher serum angiotensin-converting enzyme activity compared to those without nephropathy.⁽⁵⁾ The formation of extracellular matrix and the enhancement of fibrosis are directly impacted by TGF-ſ and PAI, an inhibitor of fibrinolysis. Angiotensin II has significant effects on PAI-1 and TGF- β, leading to an aggravation of fibrosis. Research has shown that the angiotensin II receptor blockers losartan and enalapril reduce glomerular matrix deposition by lowering levels of PAI-1. ^{(6, 7)}, In terms of preserving kidney function in both diabetic and non-diabetic patients, research shows that angiotensin-converting enzyme (ACE) inhibitors like lisinopril are better than other antihypertensive medications. Better results in treating insulin resistance and dyslipidemia, as well as improved renal function, are achieved with telmisartan compared to other ARBs due to its greater effect on PPAR-γ. Stimulation of PPAR-γ by ARBs and direct inhibition of AT1 receptors leads to a significant reduction in vascular smooth muscle cells. ⁽⁷⁾ The proto-oncogene protein kinase B (AKT) controls cell formation and differentiation; telmisartan blocks this enzyme, inhibiting vascular smooth muscle cells. ⁽⁸⁾ . A couple of studies demonstrated that telmisartan was better than some other ARBs such as losartan in improving proteinuria. ⁽⁹⁾ 

Hyperuricemia is common in adult diabetes hypertensive individuals and is linked to obesity and insulin resistance. ⁽¹⁰⁾ . Uric acid (UA) is linked to elevated renal glomerular pressure and heightened renal salt reabsorption. It encourages the growth of smooth muscle in blood vessels and causes a malfunction in the inner lining of blood vessels, leading to inflammation and damage to arteries. This process increases the likelihood of developing diabetes and atherosclerosis. ⁽¹¹⁾ . Uric acid is a valid indicator of renal function, according to this data. Creatinine and urea are widely accepted as the most reliable indicators for evaluating kidney function and are commonly employed for this specific purpose. Plasma creatinine is a more sensitive indicator of renal function than plasma urea level. Creatinine meets most criteria for an ideal filtration marker. ⁽¹²⁾ .

Patients with chronic kidney disease were effectively protected against renal function loss by lisinopril and telmisartan, regardless of blood pressure levels, according to studies. These agents have many benefits because of their long-lasting pharmacological effects and low toxicity. However, these trials lack a comparison analysis of the effects of both medicines.

The study involved thirty-three men and twenty-one women, ranging in age from thirty-five to seventy-one, with an average age of fifty-two years and nineteen points. Each participant took one 5 mg tablet of lisinopril (Lisino®) from Jamjoom Pharma in Saudi Arabia every day for a month. A cohort of 21 men and 18 women, aged 37 to 68 and a mean age of 48.99 ± 10.15, consumed one tablet of telmisartan 40 mg (Telmi®, Diamond Pharma, Syria) daily for a month. A control group consisting of twenty-five males and twenty-three females, with comparable demographic characteristics to the patient groups, was incorporated into the study. The age of the control group varied between 35 and 69 years, with an average age of 49.16 ± 10.51. The level of serum uric acid was measured using the uricase method. ⁽¹³⁾ , They were utilizing the kit provided by Biolabo (France). The serum creatinine levels were determined using the Biolabo creatinine kit from France. Serum urea levels were determined using an enzymatic colourimetric technique. ⁽¹⁴⁾ . use the Urea-kit S provided by BioMerieux (France).

Ethical approval: patient's medical history was gathered with their consent.

Statistical analysis: 

Using SPSS, version 17, the researchers performed statistical analyses on the study's data. To make sense of continuous data, standard deviations and means were used. Various parameters were statistically analyzed using paired and unpaired t-tests and linear regression analysis (r). P-value of 0.05 or less was deemed statistically significant. ⁽¹⁵⁾

The study comprised 82 type-2 diabetes patients and 48 healthy controls. Diabetes patients were divided into two groups: 43 received lisinopril, and 39 received telmisartan. Additionally, 48 healthy subjects were controls.

Study results demonstrated no significant difference between diabetic patients in the group planning to get antihypertensive medicines and healthy individuals in control groups prior to the administration of the medication. Table (1).

Table (1). Comparing renal function parameters in diabetic patients and controls

a: Data presented a Mean ± SD, b: Paired t-test, CI:confidence interval, *: significant, N.S: non-significant, (P < 0.05).

There was no significant difference in renal function parameters between diabetic individuals who planned to be treated with lisinopril and those who intended to be treated with telmisartan, as indicated by the data. table (2).

Table (2). Comparing several renal parameters in diabetic patients treated with either lisinopril or telmisartan.

a: Data presented a Mean ± SD, b: Paired t-test, CI: confidence interval, *: significant, N.S: non-significant, (P < 0.05).

Research findings showed that diabetic patients who received lisinopril treatment had a significant reduction in serum creatinine levels, but those who received telmisartan did not. Table (3). 

Table (3). Before and after lisinopril and telmisartan treatment serum creatinine comparison.

a: Data presented a Mean ± SD, b: Paired t-test, CI:confidence interval, *: significant, N.S: non-significant, (P < 0.05).

While Patients treated with telmisartan showed significantly reduced serum urea levels, those treated with another medication did not.in the same time telmisartan elevate the level of uric acid significantly, while Lisinopril did not table (4.5).

Table (4). Lisinopril and telmisartan patients' pre- and post-treatment serum urea alterations.

a: Data presented a Mean ± SD, b: Paired t-test, CI:confidence interval, *: significant, N.S: non-significant, (P < 0.05).

Table (5). Compared serum uric acid levels before and after lisinopril and telmisartan medication.

a: Data presented a Mean ± SD, b: Paired t-test, CI:confidence interval, *: significant, N.S: non-significant, (P < 0.05).

Although serum creatinine and urea are considered as primary parameters in the routine test of renal function, interest in including serum uric acid has recently been increased. Serum uric acid was concluded to be primarily association with several other CV factors, such as blood pressure, renal function and lipoprotein levels. ^{(16, 17)} and it is strongly associated with diabetes mellites and its common complications (18) .Different works including “The LIFE research demonstrated that angiotensin II receptor blocker medications may be more effective than other antihypertensive regimens in treating hyperuricemia. The LIFE study indicated that serum uric acid (SUA) is a conventional independent risk factor for cardiovascular morbidity. ₍₁₉₎ . Angiotensin-converting enzyme inhibitors and calcium-channel blockers have uricosuric effects. ⁽²⁰⁾ . Diuretics elevate serum uric acid (SUA) levels, while b-blockers had no significant impact on SUA concentration. ⁽¹⁹⁾ Thus, using the uric acid parameter with creatinine and urea in the present investigation seemed logical.     Performed data showed a significant decrease in the serum levels of creatinine and some decrease in serum urea levels (although it was insignificant) with lisinopril. However, there was a minimally insignificant increase in serum uric acid (SUA) levels in lisinopril group. Telmisartan, on the other hand altered creatinine levels insignificantly (small minute increase) and produces a significant decrease in urea levels (so, both creatinine and urea gave rise to a significant mean difference between lisinopril and telmisartan). It also caused a significant increase in serum uric acid measurements after treatment. These data came along with many earlier works sometimes performed with same and sometimes different agents within RAAS. In early 1995, Fogari et al. discovered that lisinopril (20 mg over eight weeks) had no impact on plasma glucose or uric acid levels but positively affected the serum lipid profile. ⁽²¹⁾, while other studies exhibited telmisartan therapy caused a significant elevation in uric acid levels. ⁽²¹⁾ Creatinine levels were found to lower from 0.96 to 0.91 mg/dl, in contrast, other study results corresponded to 85 and 80 mmol/l respectively, in which lisinopril doses of 5-10 mg over 4- and 8-week periods were conducted. ⁽²¹⁾ On the other side, a study done by Khurana et al. revealed that treatment with lisinopril markedly reduced the elevated levels of serum creatinine in rat models. ⁽²¹⁾, Small increases in serum creatinine levels due to telmisartan treatment were recorded by both Weinbergova et al. (telmisartan 40-80 mg used over 1 year study) and Singh et al. (animal rats model was used), but these did not reach statistical significance. ^{(22, 23)}  It is important to mention that, normally there might be a temporary rise in serum creatinine several days after therapy with ACEIs or ARBs, creatinine levels then usually decrease to baseline or lower. ⁽²¹⁾  Minimal increases in urea levels were observed in studies conducted by Cleland et al. over a six-week trial using lisinopril (10 mg/day) and by Tuominen et al. over one year using 15 mg of lisinopril. ^{(22, 23)} Adapting telmisartan regimen in rat model, a significant reduction in serum urea levels was reached through studies done by Fouad et al. and thereafter by Fouad and Jresat .^{(24, 25)} Renal protective effect of ACIEs concluded by lower creatinine (and protein urea) had been studied since 1990s ⁽²⁶⁾ , However, there is little recent work in this regard for newly introduced ACEIs or ARBs such as lisinopril and telmisartan. This study highlights the benefit of lisinopril in lowering creatinine levels and therefore possible renal reserving effects in as small dose as 5mg of lisinopril and in a relatively short follow up course of 1 month.  The activation of the renin-angiotensin system (RAS) is significantly linked to the development of renal impairment in diabetic nephropathy. At first, angiotensin II elevates oxidative stress. Secondly, angiotensin II increases pressure in the capillaries of the glomerulus, which in turn enhances the ability of macromolecules to pass through the glomerular membrane. ARB and ACEI reduce glomerular hypertension by counteracting the effects of angiotensin II on the efferent arterioles, which helps prevent glomerular sclerosis. Thirdly, angiotensin II stimulates the secretion of chemokines, cytokines, and other inflammatory indicators. The drop in creatinine levels induced by lisinopril may result from reducing angiotensin II's adverse effects through one or more of the stated processes. If this is the case, a modest dose of lisinopril would be sufficient. ACE inhibition decreases the breakdown of bradykinin, which can lead to specific widening of efferent arterioles and promote the production of endothelial nitric oxide. ^(27-30), As ACEIs and ARBs belong to the same group, effects beyond the blockage of angiotensin II such as PPAR-γ or other mediated mechanisms are working in both cases and this suggests further work to investigate possible relations. Other studied mechanism of nephroprotective effects of ACEI and ABRs is obviously complex, Free radical scavenging, antioxidant, anti-inflammatory and anti-proteinurea effects, all contribute to renoprotevtive action of these agents. ⁽²⁷⁾

Lisinopril may be better than telmisartan regarding renal function preserving despite imperfect succeed.

Author Contributions:

Conception and design: Osama Abdullah Hassan, Fadhel Abbas Al-hammami.

Collection and assembly of data: Osama Abdullah Hassan, Ahmed Mohammed Abdullah             

Analysis and interpretation of data: Osama Abdullah Hassan, Rasool Khalid Mohammed.

Drafting of the article: Osama Abdullah Hassan, Youssef Shakuri Yasin.

Critical revision of article for important intellectual content: Osama Abdullah Hassan, Anowar Suhad Waad.

Statistical expertise: Osama Abdullah Hassan, Youssef Shakuri Yasin.

Final approval and guarantor of the article: Osama Abdullah Hassan, Youssef Shakuri Yasin.

Acknowledgments:

I want to thank everyone at Al Wafa Diabetes Center/Mosul Health Department in Mosul Governorate, Iraq, for their assistance and resources during my research.

Self-funded

There is complete impartiality.

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