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Incidence and predictors of chronic kidney disease in type-II diabetes mellitus patients attending at the Amhara region referral hospitals, Ethiopia: A follow-up study.
Ahmed, MA, Ferede, YM, Takele, WW
PloS one. 2022;(1):e0263138
Abstract
BACKGROUND Chronic kidney disease (CKD) is the severest form of kidney disease characterized by poor filtration. The magnitude of chronic kidney disease is trending upward in the last few years linked with the rapidly escalating cases of non-communicable chronic diseases, particularly diabetes mellitus. However, little is known about when this problem may occur, the incidence as well as predictors of chronic kidney disease among type-II diabetes mellitus patients. Thus, this study was conducted to determine the incidence, time to the occurrence, and predictors of chronic kidney disease in type-II diabetic patients attending the Amhara region referral hospitals, Ethiopia. METHODS A retrospective follow-up study was conducted involving 415 participants with type-II diabetes mellitus that enrolled in the chronic follow-up from 2012 to 2017. Multivariable shared Frailty Weibull (Gamma) survival model was employed considering the hospitals as a clustering variable. Model fitness was checked by both the Akaike information criteria (AIC) and log-likelihood. Factors having a p-value of ≤0.2 in the bi-variable analysis were considered to enter the multivariable model. Variables that had a p-value of <0.05 with its corresponding 95% confidence level were deemed to be significant predictors of chronic kidney disease. RESULTS The overall cumulative incidence of chronic kidney disease was 10.8% [95%; CI: 7.7-14.0%] with a median occurrence time of 5 years. The annual incidence rate was 193/10,000 [95%; CI: 144.28-258.78]. Having cardiovascular disease/s [AHR = 3.82; 95%CI: 1.4470-10.1023] and hypercholesterolemia [AHR = 3.31; 95% CI: 1.3323-8.2703] were predictors of chronic kidney disease. CONCLUSION One out of every ten diabetic patients experienced chronic kidney disease. The median time to develop chronic kidney disease was five years. Hypercholesterolemia and cardiovascular diseases have escalated the hazard of developing CKD. Thus, health promotion and education of diabetic patients to optimize cholesterol levels and prevent cardiovascular disease is recommended to limit the occurrence of this life-threatening disease.
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Individual Atrasentan Exposure is Associated With Long-term Kidney and Heart Failure Outcomes in Patients With Type 2 Diabetes and Chronic Kidney Disease.
Koomen, JV, Stevens, J, Bakris, G, Correa-Rotter, R, Hou, FF, Kitzman, DW, Kohan, DE, Makino, H, McMurray, JJV, Parving, HH, et al
Clinical pharmacology and therapeutics. 2021;(6):1631-1638
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Atrasentan, an endothelin receptor antagonist, showed clinically significant albuminuria reduction with minimal signs of fluid retention in phase II trials. We evaluated whether plasma exposure was associated with long-term outcomes for kidney protection and heart failure in the phase III SONAR trial (n = 3668) in type 2 diabetics with chronic kidney disease. A population pharmacokinetic model was used to estimate plasma exposure of atrasentan 0.75 mg/day. Parametric time-to-event models were used to quantify the association between plasma exposure and long-term outcomes. Mean atrasentan plasma exposure was 41.4 ng.h/mL (2.5th to 97.5th P: 14.2 to 139.9). Compared with placebo, a mean atrasentan exposure translated in a hazard ratio of 0.76 (95% confidence interval (CI): 0.28-0.85) for kidney events and 1.13 (95% CI: 1.03-2.20) for heart failure events. At the mean atrasentan exposure, the kidney protective effect was larger than the increase in heart failure supporting the atrasentan 0.75 mg/day dose in this population.
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Longitudinal Assessment of the Effect of Atrasentan on Thoracic Bioimpedance in Diabetic Nephropathy: A Randomized, Double-Blind, Placebo-Controlled Trial.
Webb, DJ, Coll, B, Heerspink, HJL, Andress, D, Pritchett, Y, Brennan, JJ, Houser, M, Correa-Rotter, R, Kohan, D, Makino, H, et al
Drugs in R&D. 2017;(3):441-448
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BACKGROUND Fluid retention is a common adverse event in patients who receive endothelin (ET) receptor antagonist therapy, including the highly selective ETA receptor antagonist, atrasentan. OBJECTIVE We performed longitudinal assessments of thoracic bioimpedance in patients with type 2 diabetes mellitus and nephropathy to determine whether a decrease in bioimpedance accurately reflected fluid retention during treatment with atrasentan. STUDY DESIGN We conducted a randomized, double-blind, placebo-controlled study in 48 patients with type 2 diabetes mellitus and nephropathy who were receiving stable doses of renin angiotensin system inhibitors and diuretics. METHODS Patients were randomized 1:1:1 to placebo, atrasentan 0.5 mg, or atrasentan 1.25 mg once daily for 8 weeks. Thoracic bioimpedance, vital signs, clinical exams, and serologies were taken at weeks 1, 2, 4, 6, and 8, with the exception of serum hemoglobin, which was not taken at week 1, and serum brain natriuretic peptide, which was only taken at baseline, week 4, and week 8. RESULTS Alterations in bioimpedance were more often present in those who received atrasentan than in those who received placebo, though overall differences were not statistically significant. Transient declines in thoracic bioimpedance during the first 2 weeks of atrasentan exposure occurred before or during peak increases in body weight and hemodilution (decreased serum hemoglobin). CONCLUSIONS We conclude that thoracic bioimpedance did not reflect changes in weight gain or edema with atrasentan treatment in this study. However, the sample size was small, and it may be of interest to explore the use of thoracic bioimpedance in a larger population to understand its potential clinical use in monitoring fluid retention in patients with chronic kidney disease who receive ET receptor antagonists.
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HbA1c variability as an independent correlate of nephropathy, but not retinopathy, in patients with type 2 diabetes: the Renal Insufficiency And Cardiovascular Events (RIACE) Italian multicenter study.
Penno, G, Solini, A, Bonora, E, Fondelli, C, Orsi, E, Zerbini, G, Morano, S, Cavalot, F, Lamacchia, O, Laviola, L, et al
Diabetes care. 2013;(8):2301-10
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OBJECTIVE To examine the association of hemoglobin (Hb) A1c variability with microvascular complications in the large cohort of subjects with type 2 diabetes from the Renal Insufficiency And Cardiovascular Events (RIACE) Italian Multicenter Study. RESEARCH DESIGN AND METHODS Serial (3-5) HbA1c values collected in a 2-year period before enrollment were available from 8,260 subjects from 9 centers (of 15,773 patients from 19 centers). HbA1c variability was measured as the intraindividual SD of 4.52 ± 0.76 values. Diabetic retinopathy (DR) was assessed by dilated funduscopy. Chronic kidney disease (CKD) was defined based on albuminuria, as measured by immunonephelometry or immunoturbidimetry, and estimated glomerular filtration rate (eGFR) was calculated from serum creatinine. RESULTS Median and interquartile range of average HbA1c (HbA1c-MEAN) and HbA1c-SD were 7.57% (6.86-8.38) and 0.46% (0.29-0.74), respectively. The highest prevalence of microalbuminuria, macroalbuminuria, reduced eGFR, albuminuric CKD phenotypes, and advanced DR was observed when both HbA1c parameters were above the median and the lowest when both were below the median. Logistic regression analyses showed that HbA1c-SD adds to HbA1c-MEAN as an independent correlate of microalbuminuria and stages 1-2 CKD and is an independent predictor of macroalbuminuria, reduced eGFR, and stages 3-5 albuminuric CKD, whereas HbA1c-MEAN is not. The opposite was found for DR, whereas neither HbA1c-MEAN nor HbA1c-SD affected nonalbuminuric CKD. CONCLUSIONS In patients with type 2 diabetes, HbA1c variability affects (albuminuric) CKD more than average HbA1c, whereas only the latter parameter affects DR, thus suggesting a variable effect of these measures on microvascular complications.
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High doses of irbesartan offer long-term kidney protection in cases of established diabetic nephropathy.
Ros-Ruiz, S, Aranda-Lara, P, Fernández, JC, Martínez-Esteban, MD, Jironda, C, Hidalgo, P, Hernández-Marrero, D
Nefrologia : publicacion oficial de la Sociedad Espanola Nefrologia. 2012;(2):187-96
Abstract
BACKGROUND Hypothetically, the greater the blockade of angiotensin AT1 receptors from ultra-high doses of angiotensin receptors blockers (ARB), the greater the expected renoprotection effects. The aim of our study was to evaluate the effects of ultra-high doses of irbesartan on proteinuria and renal function in diabetics with established or overt diabetic nephropathy (ODN). MATERIAL AND METHOD Ours was a prospective, non-randomised 3-year follow-up study, using a multifactorial therapeutic approach based on irbesartan 600mg daily. Demographic variables, anthropometric data, and biochemical parameters were comparatively analysed at the beginning and end of the study. Forty patients (75% with type 2 diabetes) were included, average age 57.1 +/- 10, 29 male (72.5%). RESULTS SBP (157.6 +/- 27mm Hg vs 130.1 +/- 14mm Hg) and DBP (88.8 +/- 10mm Hg vs 76.2 +/- 8mm Hg) decreased significantly at the end of follow-up (P<.001). Serum creatinine increased by only 0.17mg/dl, although this was a statistically significant difference (P<.05). Proteinuria markedly decreased from 2.64 +/- 1.99 to 0.98 +/- 1.18 (P<.0001), i.e. 59.2%. Twenty-five percent of patients had normal albuminuria at the end of the follow-up period. Lipid profiles significantly improved. No patients withdrew from the study due to side effects, and serum potassium did not change significantly over the course of the study. Except for BMI and HbA1c, all other therapeutic targets set out by ADA recommendations improved significantly. CONCLUSIONS The treatment of ODN with ultra-high doses of irbesartan was highly effective and safe in reducing proteinuria and slowing the progressive course to ESRD.
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Effects of low dose ramipril on cardiovascular and renal outcomes in patients with type 2 diabetes and raised excretion of urinary albumin: randomised, double blind, placebo controlled trial (the DIABHYCAR study).
Marre, M, Lievre, M, Chatellier, G, Mann, JF, Passa, P, Ménard, J, ,
BMJ (Clinical research ed.). 2004;(7438):495
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OBJECTIVE To investigate whether a low dose of the angiotensin converting enzyme (ACE) inhibitor ramipril lowers cardiovascular and renal events in patients with type 2 diabetes who have microalbuminuria or proteinuria. DESIGN Randomised, double blind, parallel group trial comparing ramipril (1.25 mg/day) with placebo (on top of usual treatment) for cardiovascular and renal outcomes for at least three years. SETTING Multicentre, primary care study conducted mostly by general practitioners in 16 European and north African countries. PARTICIPANTS 4912 patients with type 2 diabetes aged >50 years who use oral antidiabetic drugs and have persistent microalbuminuria or proteinuria (urinary albumin excretion > or = 20 mg/l in two consecutive samples), and serum creatinine < or = 150 micromol/l. MAIN OUTCOME MEASURES The primary outcome measure was the combined incidence of cardiovascular death, non-fatal myocardial infarction, stroke, heart failure leading to hospital admission, and end stage renal failure. RESULTS Participants were followed for 3 to 6 (median 4) years. There were 362 primary events among the 2443 participants taking ramipril (37.8 per 1000 patient years) and 377 events among the 2469 participants taking placebo (38.8 per 1000 patient years; hazard ratio 1.03 (95% confidence interval 0.89 to 1.20, P = 0.65)). None of the components of the primary outcome was reduced. Ramipril lowered systolic and diastolic blood pressures (by 2.43 and 1.06 mm Hg respectively after two years) and favoured regression from microalbuminuria (20-200 mg/l) or proteinuria (> 200mg/l) to normal level (< 20 mg/l) or microalbuminuria (P < 0.07) in 1868 participants who completed the study. CONCLUSIONS Low dose (1.25 mg) ramipril once daily has no effect on cardiovascular and renal outcomes of patients with type 2 diabetes and albuminuria, despite a slight decrease in blood pressure and urinary albumin. The cardiovascular benefits of a daily higher dose (10 mg) ramipril observed elsewhere are not found with an eightfold lower daily dose.
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[Lercanidipine in diabetic patients with renal failure].
Robles, NR, Pastor, L, Manjón, M, Ocón, J, Gómez Campderá, F, Herrera, J, Villatoro, J, Calls, J, Torrijos, J, Rodríguez Villareal, I, et al
Nefrologia : publicacion oficial de la Sociedad Espanola Nefrologia. 2004;(4):338-43
Abstract
OBJECTIVE To evaluate the safe use of a new calcium channel blocker, lercanidipine, in diabetic chronic renal failure (CRF) patients. DESIGN AND METHODS The study recruited 42 diabetic CRF patients (creatinine > 1.4 mg/dl for males, creatinine > 1.2 mg/dl for females, or creatinine clearance < 70 ml/min). Mean age was 68.2 +/- 9.1 years. 53.8% were males and 46.2% females. Three patients were type 1 diabetics and 39 ones were type II. All patients were receiving ACE inhibitors (67.4%) or angiotensin II antagonist (32.6%) therapy but they had higher blood pressure than recommended for CRF patients (130/85 mmHg). No patients were under diuretic treatment. Patients were clinically evaluated 1, 3 and 6 months after starting treatment with lercanidipine. Samples for urine and blood examination were taken during the examination. When needed, a third drug was added to treatment, excluding diuretics. Creatinine clearance was measured using 24 h urine collection. RESULTS BP significantly decrease from 163 +/- 18/90 +/- 8 mmHg to 134 +/- 12/77 +/- 9 mmHg. One half of patients showed significant reduction of blood pressure, 26.7% reached the target blood pressure (< 130/85 mmHg) and 20.0% gets optimal BP control (< 130/85 mmHg). No one patient showed untoward effects. No edema was detected nor adverse effects related to vasodilatation were found. Plasmatic creatinine did not change (1.9 +/- 0.5 baseline vs 1.8 +/- 0.5 mg/dl) and creatinine clearance increased at the end visit (40.1 +/- 14.5 baseline vs 45.4 +/- 18.2 ml/min) but the difference was not significant. Proteinuria was unchanged. CONCLUSIONS Lercanidipine showed a good antihypertensive effect in diabetics CRF patients. It has a good tolerability profile and showed neutral effect on plasmatic lipids. Neither impairment of renal function nor increment in proteinuria were detected.
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Additive antiproteinuric effect of combination therapy with ACE inhibitor and angiotensin II receptor antagonist: differential short-term response between IgA nephropathy and diabetic nephropathy.
Kim, MJ, Song, JH, Suh, JH, Lee, SW, Kim, GA
Yonsei medical journal. 2003;(3):463-72
Abstract
In previous studies, the synergistic antiproteinuric effect of the combination therapy of ACE inhibitors and angiotensin II receptor antagonists (ATRAs) has been inconsistent in relation to underlying renal diseases. The influence from the blood pressure (BP) - reducing effect in some studies might also contribute to this inconclusiveness. To examine the possibility of the benefit being different according to underlying renal diseases, we undertook a crossover therapeutic trial of the combination therapy in two selected homogenous groups of patients with diabetic and non-diabetic renal diseases. The BP-reducing effect was excluded during the study. Nineteen biopsy-proven IgA nephropathy, as examples of non-diabetic renal diseases, and 24 type 2 diabetic nephropathy patients were selected as the study subjects. The subjects had to meet the follow criteria: a creatinine clearance (Ccr) between 25 - 90 ml/min/1.73 m2, 24-hr urinary protein excretion rate over 1.0 g/day and a BP maintained at less than 130/80 mmHg, with more than six-month therapy of ramipril, (5.7 +/- 0.4 mg/day, 13 +/- 2 month). The baseline data between the two groups showed no significantly differences. After a 12-week stabilization period (control period), 4 mg, once daily, dose of candesartan (combination period) followed by a placebo (placebo period), or vice versa, were administered in addition to the ramipril, for 12 weeks. The combination, with candesartan, did not change the Ccr, BP, serum and urinary electrolytes or the urea. The 24 hour urinary protein excretion rate was significantly reduced by the combination therapy in the patients with IgA nephropathy (3.1 +/- 0.3 g/day in combination, 4.2 +/- 0.3 in control, and 4.3 +/- 0.2 in placebo; p < 0.05). However, the patients with diabetic nephropathy showed no reduction in their proteinuria with the combination therapy (3.8 +/- 0.2 g/day in combination, 3.9 +/- 0.3 in control, and 4.1 +/- 0.3 in placebo; p=NS). The changes in proteinuria showed no relationship with the changes in the BP in IgA nephropathy. In conclusions, the benefit of combination therapy of its antiproteinuric effect was different between IgA and diabetic nephropathy over the 12-week trial. The difference in the pathophysiological role, and the importance of the renin- angiotensin system, between the two diseases might contribute to the discrepancy in the result. We suggest the discrimination of the underlying renal diseases in the study subjects is an important prerequisite for future studies on this issue.
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Dual blockade of the renin-angiotensin system versus maximal recommended dose of ACE inhibition in diabetic nephropathy.
Jacobsen, P, Andersen, S, Rossing, K, Jensen, BR, Parving, HH
Kidney international. 2003;(5):1874-80
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BACKGROUND Albuminuria and hypertension are predictors of poor renal and cardiovascular outcome in diabetic patients. We tested whether dual blockade of the renin-angiotensin system (RAS) with both an angiotensin-converting enzyme (ACE) inhibitor and an angiotensin II receptor blocker (ARB) is superior to maximal recommended dose of ACE inhibitor in type 1 diabetic patients with diabetic nephropathy (DN). METHODS We performed a randomized, double-blind, crossover trial with 8 weeks treatment with placebo and irbesartan 300 mg (once daily), added on top of enalapril 40 mg (once daily). We included 24 type 1 patients with DN. At the end of each treatment period, albuminuria, 24-hour blood pressure, and glomerular filtration rate (GFR) were measured. RESULTS Values on ACE inhibitors + placebo were: albuminuria [mean (95% CI)], 519 (342 to 789) mg/24 hours; blood pressure [mean (SEM)], 131 (3)/74 (1) mm Hg, and GFR [mean (SEM)], 65 (5) mL/min/1.73 m2. Dual blockade of the RAS induced a reduction in albuminuria [mean (95% CI)] of 25% (15, 34) (P < 0.001), a reduction in systolic blood pressure of 8 mm Hg (4, 12) (P = 0.002), and a reduction of 4 mm Hg (2, 7) (P = 0.003) in diastolic blood pressure. GFR and plasma potassium remained unchanged during both treatment regimes. Dual blockade was safe and well tolerated. CONCLUSION Dual blockade of the RAS is superior to maximal recommended dose of ACE inhibitors with regard to lowering of albuminuria and blood pressure in type 1 patients with DN. Long-term trials are needed to further establish the role of dual blockade of the RAS in renal and cardiovascular protection.
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Antiproteinuric effects of combined antihypertensive therapies in patients with overt type 2 diabetic nephropathy.
Kuriyama, S, Tomonari, H, Tokudome, G, Horiguchi, M, Hayashi, H, Kobayashi, H, Ishikawa, M, Hosoya, T
Hypertension research : official journal of the Japanese Society of Hypertension. 2002;(6):849-55
Abstract
Combined antihypertensive therapy plays a crucial role in achieving targeted blood pressure reductions and renoprotection. We therefore compared the antihypertensive and antiproteinuric effects of combined therapy with either a calcium channel blocker (CCB) plus an angiotensin II receptor blocker (ARB) or an angiotensin converting enzyme inhibitor (ACE-I) plus an ARB in patients with type 2 diabetes mellitus complicated by overt nephropathy and mild to moderate hypertension. After a 12-week dietary control period, diabetic patients with mildly to moderately impaired renal function were randomly assigned to either a CCB (amlodipine 5 mg once daily) or an ACE-I (temocapril 2 mg once daily) for 12 weeks (monotherapy period). Both groups then received add-on therapy with an ARB (candesartan 4 mg once daily) for an additional 12 weeks. During the monotherapy period, blood pressure was decreased equally well in both groups. Daily urinary protein excretion remained unchanged in the CCB-treated group (control period, 4.0 +/- 1.8 g/day vs. CCB period, 4.1 +/- 1.9 g/day; ns; n = 8), but decreased in the ACE-I-treated group (control period, 4.3 +/- 1.8 g/day vs. ACE-I period, 3.5 +/- 1.7 g/day; p < 0.05; n = 9). After the combined therapy period, blood pressure was decreased to the same degree in both groups. Although ARB plus CCB significantly reduced urinary protein excretion (to 3.5 +/- 1.5 g/day; p < 0.05 vs. control period; n = 8), a more profound reduction was achieved with ARB plus ACE-I (to 2.6 +/- 1.3 g/day; p < 0.01 vs. control period; n = 9). Monotherapy with the ACE-I increased the serum potassium concentration, and this elevation was sustained after addition of the ARB. In contrast, the serum potassium concentration was not influenced by monotherapy with the CCB, but was significantly increased after addition of the ARB. A decreased hematocrit was observed in the ARB plus ACE-I group. The present study suggests that combined antihypertensive therapy with either a CCB plus an ARB or an ACE-I plus an ARB exerts an antiproteinuric effect in patients with type 2 diabetic nephropathy with mildly impaired renal function. Although the latter combination had a more profound effect, it was associated with an increased serum potassium concentration and worsening of renal anemia. Thus, the combination of a CCB and an ARB should be the first line antihypertensive therapy in those with overt diabetic nephropathy. The long-term efficacy of these combined antihypertensive therapies will need to be further addressed in a future study.