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Prediction of microalbuminuria from proteinuria in chronic kidney disease due to non-diabetic lifestyle-related diseases: comparison with diabetes.
Ogi, M, Seto, T, Wakabayashi, Y
Clinical and experimental nephrology. 2021;(7):727-750
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Abstract
BACKGROUND To suppress increases in kidney failure and cardiovascular disease due to lifestyle-related diseases other than diabetes, early intervention is desirable. We examined whether microalbuminuria could be predicted from proteinuria. METHODS The participants consisted of adults who exhibited a urinary protein-to-creatinine ratio (uPCR) of < 0.5 g/gCr and an eGFR of ≥ 15 ml/min/1.73 m2 in their spot urine at their first examination for lifestyle-related disease. Urine was tested three times for each case, with microalbuminuria defined as a urinary albumin-to-creatinine ratio (uACR) of 30-299 mg/gCr, at least twice on three measurements. Youden's Index was used as an index of the cut-off value (CO) according to the ROC curve. RESULTS A single uPCR was useful for differentiating normoalbuminuria and micro- and macroalbuminuria in patients with non-diabetic lifestyle-related diseases. Regarding the GFR categories, the CO of the second uPCR was 0.09 g/gCr (AUC 0.89, sensitivity 0.76, specificity 0.89) in G1-4 (n = 197) and 0.07 g/gCr (AUC 0.92, sensitivity 0.85, specificity 0.88) in G1-3a (n = 125). Using the sum of two or three uPCR measurements was more useful than a single uPCR for differentiating microalbuminuria in non-diabetic lifestyle disease [CO, 0.16 g/gCr (AUC 0.91, sensitivity 0.85, specificity 0.87) and 0.23 g/gCr (AUC 0.92, sensitivity 0.88, specificity 0.84), respectively]. CONCLUSION Microalbuminuria in Japanese individuals with non-diabetic lifestyle-related diseases can be predicted from the uPCR, wherein the CO of the uPCR that differentiates normoalbuminuria and micro- and macroalbuminuria was 0.07 g/gCr for G1-3a, while that in G3b-4 was 0.09 g/gCr.
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Simvastatin maintains steady patterns of GFR and improves AER and expression of slit diaphragm proteins in type II diabetes.
Tonolo, G, Velussi, M, Brocco, E, Abaterusso, C, Carraro, A, Morgia, G, Satta, A, Faedda, R, Abhyankar, A, Luthman, H, et al
Kidney international. 2006;(1):177-86
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The factors determining the course of glomerular filtration rate (GFR) and albumin excretion rate (AER) and the expression of mRNA of slit diaphragm (SD) and podocyte proteins in microalbuminuric, hypertensive type II diabetic patients are not fully understood. GFR, AER, and SD protein mRNA were studied in 86 microalbuminuric, hypertensive, type II diabetics at baseline and after 4-year random double-blind treatment either with 40 mg simvastatin (Group 1) or with 30 g cholestyramine (Group 2) per day. Both groups had at baseline a GFR decay per year in the previous 2-4 years of 3 ml/min/1.73 m(2). Both Groups 1 and 2 showed a significant decrease of low-density lipoprotein cholesterol levels after simvastatin and cholestyramine treatment (P<0.01). No change from base line values was observed as for hs-C-reactive protein and interleukin-6. A significant decrease of 8-hydroxydeoxyguanosine urinary excretion was observed after simvastatin treatment. GFR did not change from baseline with simvstatin, whereas a decrease was observed with cholestyramine treatment (simvastatin vs cholestyramine: -0.21 vs -2.75 ml/min/1.73 m(2), P<0.01). AER decreased in Group 1 (P<0.01), but not in Group 2 patients. Real-time polymerase chain reaction measurement of mRNA SD proteins (CD2AP, FAT, Actn 4, NPHS1, and NPHS2) significantly increased in kidney biopsy specimens after simvastatin, but not cholestyramine treatment. Simvastatin, but not cholestyramine, 4-year treatment maintains steady patterns of GFR, and improves AER and expression of SD proteins in type II diabetes, despite similar hypocholesterolemic effects in circulation.
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On the nature of proteinuria with acute renal injury in patients with chronic kidney disease.
Agarwal, R
American journal of physiology. Renal physiology. 2005;(2):F265-71
Abstract
Albuminuria is an excellent marker of cardiovascular and renal prognosis. Commercially available tests of immunodetectable albumin in the urine may not identify posttranslationally modified albumin that makes it undetectable to antibodies. Also, it is unclear whether albumin is degraded to smaller fragments, such as through proteolysis, in the course of acute renal injury. In 20 men with chronic kidney disease, we measured excretion rates of urinary protein (pyragallol red), immundetectable urinary albumin (immunoturbidimetry), and urinary total intact albumin (HPLC) after a single dose of 100 mg intravenous iron sucrose administered over 5 min. Fragmentation of urinary albumin and carbonylation of urinary proteins were assessed by immunoblotting. Results showed that iron infusion increased carbonylation of plasma and urinary proteins in a time-dependent manner. A transient increase in urinary excretion rates of total protein, immunodetectable urinary albumin, and total intact albumin was seen. Fragmentation and loss of immunoreactivity of albumin paralleled the changes in total protein excretion. In conclusion, fragmentation, loss of immunoreactivity, and oxidation of albumin in a time-dependent manner may underestimate the extent of injury with the immunoreactive microalbumin assay. Measurement of total intact albumin may better quantify acute renal injury.
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The effect of acute normovolaemic haemodilution on the inflammatory response and clinical outcome in abdominal aortic aneurysm repair--results of a pilot trial.
Wolowczyk, L, Nevin, M, Day, A, Smith, FC, Baird, RN, Lamont, PM
European journal of vascular and endovascular surgery : the official journal of the European Society for Vascular Surgery. 2005;(1):12-9
Abstract
OBJECTIVES To determine the effect of acute normovolaemic haemodilution (ANH) on the inflammatory response and clinical outcome in elective open abdominal aortic aneurysm (AAA) repair. DESIGN Randomised controlled clinical trial. METHODS Thirty-six patients were randomised to undergo ANH or act as controls. Cell salvage was permitted in both groups. Heterologous blood was transfused according to pre-determined triggers. Outcome measures were markers of the systemic inflammatory response in serum and urine observed at multiple time points, and clinical recovery. RESULTS Median 890 (range 670-1620) ml of blood was removed at ANH in 16 patients. There were no differences in peri-operative changes in neutrophil count ( P = 0.13), serum C-reactive protein ( P = 0.38), interleukin-6 ( P = 0.50), total antioxidant capacity ( P = 0.73), urinary secretion of albumin ( P = 0.97) or retinol binding protein ( P = 0.41). There were no differences in the mortality and morbidity rates, systemic inflammatory response syndrome, ITU or hospital stay. CONCLUSIONS ANH, when used in combination with cell salvage, made no impact on systemic inflammatory response and clinical outcome when compared to cell salvage alone after AAA repair. ANH cannot be recommended for routine use in patients undergoing abdominal aortic aneurysm surgery when cell salvage is available.
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Framingham score and microalbuminuria: combined future targets for primary prevention?
Asselbergs, FW, Hillege, HL, van Gilst, WH
Kidney international. Supplement. 2004;(92):S111-4
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BACKGROUND Risk assessment is the cornerstone of primary prevention of cardiovascular disease. Our objective was to evaluate the prognostic value of the Framingham score in microalbuminuric subjects without a history of cardiovascular disease and whether this risk score can predict the benefit of treatment with fosinopril or pravastatin. METHODS Subjects were randomized to fosinopril 20 mg or matching placebo, and to pravastatin 40 mg or matching placebo (mean age 51 +/- 12 years, 65% men, N = 830). Prediction of 10-year risk for coronary heart disease by the Framingham score was performed using the risk factor categories with LDL cholesterol. RESULTS Albuminuria was correlated with Framingham score at baseline (P < 0.001). In the population with a Framingham risk score <20%, both albuminuria and Framingham risk score were independent predictors of the primary end point. A two-fold increase of albuminuria or the Framingham risk score was associated with a hazard ratio of 1.60 (95% CI 1.10-2.31), P = 0.013 and 3.00 (95% CI 1.40-6.44), P = 0.005, respectively. In contrast to fosinopril, pravastatin showed a significant beneficial effect on Framingham risk score after 4 years of follow-up (P < 0.001). Furthermore, the observed absolute risk reduction in cardiovascular events was greater than calculated by the Framingham risk score. CONCLUSION The Framingham score is useful in microalbuminuric subjects as a prognostic tool. In addition, when considering the risk score as a target of intervention, the beneficial effects of therapies might be underestimated. Combining the Framingham score with the level of urinary albumin excretion is suggested as a primary prevention strategy with higher efficiency.
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Preventing microalbuminuria in type 2 diabetes.
Ruggenenti, P, Fassi, A, Ilieva, AP, Bruno, S, Iliev, IP, Brusegan, V, Rubis, N, Gherardi, G, Arnoldi, F, Ganeva, M, et al
The New England journal of medicine. 2004;(19):1941-51
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BACKGROUND The multicenter double-blind, randomized Bergamo Nephrologic Diabetes Complications Trial (BENEDICT) was designed to assess whether angiotensin-converting-enzyme inhibitors and non-dihydropyridine calcium-channel blockers, alone or in combination, prevent microalbuminuria in subjects with hypertension, type 2 diabetes mellitus, and normal urinary albumin excretion. METHODS We studied 1204 subjects, who were randomly assigned to receive at least three years of treatment with trandolapril (at a dose of 2 mg per day) plus verapamil (sustained-release formulation, 180 mg per day), trandolapril alone (2 mg per day), verapamil alone (sustained-release formulation, 240 mg per day), or placebo. The target blood pressure was 120/80 mm Hg. The primary end point was the development of persistent microalbuminuria (overnight albumin excretion, > or =20 microg per minute at two consecutive visits). RESULTS The primary outcome was reached in 5.7 percent of the subjects receiving trandolapril plus verapamil, 6.0 percent of the subjects receiving trandolapril, 11.9 percent of the subjects receiving verapamil, and 10.0 percent of control subjects receiving placebo. The estimated acceleration factor (which quantifies the effect of one treatment relative to another in accelerating or slowing disease progression) adjusted for predefined baseline characteristics was 0.39 for the comparison between verapamil plus trandolapril and placebo (P=0.01), 0.47 for the comparison between trandolapril and placebo (P=0.01), and 0.83 for the comparison between verapamil and placebo (P=0.54). Trandolapril plus verapamil and trandolapril alone delayed the onset of microalbuminuria by factors of 2.6 and 2.1, respectively. Serious adverse events were similar in all treatment groups. CONCLUSIONS In subjects with type 2 diabetes and hypertension but with normoalbuminuria, the use of trandolapril plus verapamil and trandolapril alone decreased the incidence of microalbuminuria to a similar extent. The effect of verapamil alone was similar to that of placebo.
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Effects of aggressive blood pressure control in normotensive type 2 diabetic patients on albuminuria, retinopathy and strokes.
Schrier, RW, Estacio, RO, Esler, A, Mehler, P
Kidney international. 2002;(3):1086-97
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BACKGROUND Although several important studies have been performed in hypertensive type 2 diabetic patients, it is not known whether lowering blood pressure in normotensive (BP <140/90 mm Hg) patients offers any beneficial results on vascular complications. The current study evaluated the effect of intensive versus moderate diastolic blood pressure (DBP) control on diabetic vascular complications in 480 normotensive type 2 diabetic patients. METHODS The current study was a prospective, randomized controlled trial in normotensive type 2 diabetic subjects. The subjects were randomized to intensive (10 mm Hg below the baseline DBP) versus moderate (80 to 89 mm Hg) DBP control. Patients in the moderate therapy group were given placebo, while the patients randomized to intensive therapy received either nisoldipine or enalapril in a blinded manner as the initial antihypertensive medication. The primary end point evaluated was the change in creatinine clearance with the secondary endpoints consisting of change in urinary albumin excretion, progression of retinopathy and neuropathy and the incidence of cardiovascular disease. RESULTS The mean follow-up was 5.3 years. Mean BP in the intensive group was 128 +/- 0.8/75 +/- 0.3 mm Hg versus 137 +/- 0.7/81 +/- 0.3 mm Hg in the moderate group, P < 0.0001. Although no difference was demonstrated in creatinine clearance (P = 0.43), a lower percentage of patients in the intensive group progressed from normoalbuminuria to microalbuminuria (P = 0.012) and microalbuminuria to overt albuminuria (P = 0.028). The intensive BP control group also demonstrated less progression of diabetic retinopathy (P = 0.019) and a lower incidence of strokes (P = 0.03). The results were the same whether enalapril or nisoldipine was used as the initial antihypertensive agent. CONCLUSION Over a five-year follow-up period, intensive (approximately 128/75 mm Hg) BP control in normotensive type 2 diabetic patients: (1) slowed the progression to incipient and overt diabetic nephropathy; (2) decreased the progression of diabetic retinopathy; and (3) diminished the incidence of stroke.
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Effects of lisinopril and nitrendipine on urinary albumin excretion and renal function in patients with mild to moderate essential hypertension.
Ogawa, Y, Haneda, T, Hirayama, T, Ide, H, Obara, A, Maruyama, J, Morimoto, H, Tanaka, H, Kato, J, Hayakawa, T, et al
Hypertension research : official journal of the Japanese Society of Hypertension. 2000;(6):607-12
Abstract
The present study was designed to evaluate the effects of an ACE inhibitor, lisinopril, and a calcium antagonist, nitrendipine, on urinary albumin excretion (UAE) and renal function in mild to moderate essential hypertensive patients with microalbuminuria. After the 4-week drug-free period, 17 patients were randomly divided into two groups. The first group (group 1: n=8) received lisinopril 10-20 mg daily for 8 weeks followed by nitrendipine 5-10 mg daily for another 8 weeks. The second group (group 2: n=9) received nitrendipine 5-10 mg daily for 8 weeks followed by lisinopril 10-20 mg daily for another 8 weeks. The mean blood pressure (MBP) significantly decreased in a similar manner in both groups. UAE significantly decreased after 8 weeks of treatment with lisinopril in group 1 and after 8 weeks of subsequent treatment with lisinopril in group 2. On the other hand, UAE was not altered by treatment with nitrendipine. The changes in UAE were significantly correlated with changes in MBP after 8 weeks of treatment with nitrendipine, but not after 8 weeks of treatment with lisinopril. No significant changes in creatinine clearance, urinary excretion of sodium or urinary N-acetyl-beta-D-glucosaminide were observed by any treatment in either group. These results suggest that lisinopril, not nitrendipine, reduces UAE in essential hypertensive patients with microalbuminuria independently of its effective antihypertensive properties.
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Effect of combination therapy of angiotensin-converting enzyme inhibitor plus calcium channel blocker on urinary albumin excretion in hypertensive microalbuminuric patients with type II diabetes.
Shigihara, T, Sato, A, Hayashi, K, Saruta, T
Hypertension research : official journal of the Japanese Society of Hypertension. 2000;(3):219-26
Abstract
It has been demonstrated that antihypertensive treatment of hypertensive diabetic patients is quite effective in preventing macrovascular and microvascular complications and improving prognosis. Nevertheless, the target blood pressure level of antihypertensive treatment in hypertensive diabetic patients with microalbuminuria (i.e., with early diabetic nephropathy) remains to be established. In this study, we evaluated the effect of intensive blood pressure control (diastolic blood pressure <80 mmHg) on urinary albumin excretion in hypertensive, type II diabetic patients with microalbuminuria. We examined the effects of a combination therapy using an angiotensin-converting enzyme (ACE) inhibitor plus a long-acting calcium channel blocker (amlodipine), and compared them with the effect of an ACE inhibitor alone. Thirty hypertensive, type II diabetic patients with microalbuminuria were treated with either an ACE inhibitor alone (group I, n=17) or an ACE inhibitor plus amlodipine (group II, n=13) for 32 weeks. With treatment, blood pressures in both groups were significantly reduced, and diastolic blood pressure was lowered to a much greater extent in group II (76 +/- 2 mmHg) than in group I (83 +/- 2 mmHg, p < 0.05). Although the urinary albumin excretion rate was decreased in both groups, the decrease attained statistical significance only in group II (from 141 +/- 25 mg/day to 69 +/- 18 mg/day, p < 0.05); the extent of reduction in microalbuminuria during antihypertensive treatment was significantly greater in group II (50 +/- 10%) than in group I (14 +/- 13%, p < 0.05). In conclusion, this study showed that in hypertensive microalbuminuric type II diabetic patients, the combination of an ACE inhibitor plus amlodipine resulted in a more pronounced decreased in blood pressure (diastolic blood pressure <80 mmHg) and a greater reduction in urinary albumin excretion than did use of an ACE inhibitor alone. This combination strategy should thus be a more effective tool for obtaining optimal blood pressure control in patients with diabetic nephropathy.