Proteinuria reduction and progression to renal failure in patients with type 2 diabetes mellitus and overt nephropathy

Department of Nephrology, Monash Medical Centre, Victoria, Australia. <>
American Journal of Kidney Diseases (Impact Factor: 5.9). 03/2005; 45(2):281-7. DOI: 10.1053/j.ajkd.2004.10.019
Source: PubMed


Little is known of the effects of blood pressure reduction by specific classes of antihypertensive drugs on the association between proteinuria reduction and progression of kidney insufficiency and development of end-stage kidney disease in patients with overt diabetic nephropathy in type 2 diabetes mellitus.
Associations between baseline proteinuria and proteinuria reduction by either irbesartan, amlodipine, or control for similar decrements in blood pressure and the cumulative incidence of renal end points were examined using the Kaplan-Meier method in patients enrolled in the Irbesartan Diabetic Nephropathy Trial.
Risk for kidney failure doubled for each doubling of baseline proteinuria level (hazard ratio, 2.04; 95% confidence interval, 1.87 to 2.22; P < 0.001). For each halving of proteinuria level between baseline and 12 months with treatment, risk for kidney failure was reduced by more than half (hazard ratio, 0.44; 95% confidence interval, 0.40 to 0.49; P < 0.001). For the same proportional change in proteinuria, the reduction in risk for kidney failure was significantly greater for irbesartan compared with amlodipine ( P = 0.048), but not control ( P = 0.245). Proteinuria reduction in the first 12 months of therapy with irbesartan is associated with 36% of the total renoprotective effect observed.
Baseline proteinuria is an important risk factor for kidney failure and provides a means to identify patients at greatest risk. Halving proteinuria halves the kidney risk. Proteinuria reduction using an angiotensin receptor-blocking agent, such as irbesartan, should be regarded as an important therapeutic goal in renoprotective strategies.

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    • "Thus hypertension is probably both a cause and an effect of diabetic nephropathy. Epidemiological studies have shown that identifying and monitoring patients with microalbuminuria is important because its treatment can prevent or postpone overt nephropathy.17,24 Higher values of Systolic blood pressure and diastolic blood pressure in microalbuminuric than in normoalbuminuric patients suggests that hypertension is associated with microalbuminuria.25 "
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    ABSTRACT: Background: Hypertension is commonly found in patients with Diabetic Kidney Disease (DKD). Microalbuminuria is the first clinical sign of involvement of kidneys in patients with type 2 diabetes. Uncontrolled hypertension induces a higher risk of cardiovascular events, including death, increasing proteinuria and progression to kidney disease. Objectives: To determine the correlation between microalbuminuria and hypertension and their association with other risk factors in type 2 diabetic patients. Methods: One hundred and thirteen type 2 diabetic patients attending the diabetic clinic of Shaikh Zayed Postgraduate Medical Institute, Lahore, Pakistan were screened for microalbuminuria and raised blood pressure. The study was conducted from November 2012 to June 2013. Results: Patients were divided into two groups. Group 1, those with normoalbuminuria (n=63) and Group 2, those having microalbuminuria (n=50). Group 2 patients showed higher blood pressure values as compared to Group 1. The results were statistically significant and showed poor glycemic control as a contributing risk factor. Conclusion: The study concluded that there is high frequency of hypertension among type 2 diabetics but still much higher among those having microalbuminuria. So, early recognition of renal dysfunction through detection of microalbuminuria and to start treatment without any delay will confer future protection from end stage renal disease as well as hypertension and its complications in type 2 diabetic patients.
    Pakistan Journal of Medical Sciences Online 05/2014; 30(3):511-4. DOI:10.12669/pjms.303.5042 · 0.23 Impact Factor
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    • "The magnitude of systolic blood pressure reduction as well as the degree of proteinuria reduction has been related to renal outcome in patients with non diabetic CKD, with greater renal protection being obtained when these two variables are lowered to a range of 110–130 mmHg and below 1.5 g/day, respectively [16–18]. Furthermore, results of the RENAAL and IDNT trials [19] indicate that residual blood pressure and urine protein excretion levels, i.e. those that can be achieved under optimal antihypertensive treatment, are far more important for long term renal protection as compared to baseline values. Specifically, the prognostic power of residual proteinuria seems to outweigh that of blood pressure since a graded relationship between the degree of proteinuria and the risk of reaching ESRD was observed for each systolic blood pressure strata [20]. "
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    ABSTRACT: The prevalence of chronic kidney disease, currently estimated to vary between 8 and 12 % in the general population, is steadily rising due to aging and to the ongoing epidemic of hypertension and type 2 diabetes. Even in its early stages, chronic kidney disease entails a greater risk for cardiovascular mortality, and its prevention and treatment is rapidly becoming a key medical issue for many health care systems worldwide. Adequate blood pressure control and reduction of urine protein excretion, preferably obtained by the use of renin-angiotensin-aldosterone system inhibitors, have traditionally been considered the mainstay of therapeutic strategies in patients with renal disease. Given the pivotal role of renin-angiotensin-aldosterone system activity in the pathogenesis and progression of renal and cardiovascular damage, a more profound inhibition of the system, either by the use of multiple agents or by a single agent at high dosage has recently been advocated, especially in the presence of proteinuria. Recent trials, however have failed to confirm the usefulness of this therapeutic approach, at least in unselected patients. This article will critically review the current literature and will discuss the clinical implications of targeting the renin-angiotensin-aldosterone system in order to provide the greatest renal protection.
    High Blood Pressure & Cardiovascular Prevention 10/2013; 20(4). DOI:10.1007/s40292-013-0027-y
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    • "Proteinuria, a useful marker for kidney damage associated with hypertension, is itself a risk factor for the progression of renal disease. 29,30 The accumulation of filtered proteins in the proximal tubular cells triggers proinflammatory, profibrogenic, and cytotoxic pathways that contribute to tubulointerstitial injury and renal scarring.31 In our experiments, the TEM revealed an increase in the spaces between the interdigitations in the convoluted proximal tubule and in the convoluted distal tubule, and the basal membranes of the tubules exhibited a thickened appearance in the SED-SHR compared to the EX-SHR and the SED-WKY and EX-WKY control groups. "
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    ABSTRACT: Kidney disorders can cause essential hypertension, which can subsequently cause renal disease. High blood pressure is also common among those with chronic kidney disease; moreover, it is a well-known risk factor for a more rapid progression to kidney failure. Because hypertension and kidney function are closely linked, the present study aimed to observe the beneficial effects of low-intensity physical activity on structural and ultrastructural renal morphology and blood pressure in normotensive and spontaneously hypertensive rats. Male Wistar-Kyoto rats and spontaneously hypertensive rats were randomly allocated into four groups: sedentary or exercised Wistar-Kyoto and sedentary or exercised spontaneously hypertensive rats. The exercise lasted 20 weeks and consisted of treadmill training for 1 hour/day, 5 days/week. The exercised, spontaneously hypertensive rats showed a significant blood pressure reduction of 26%. The body masses of the Wistar-Kyoto and spontaneously hypertensive strains were significantly different. There were improvements in some of the renal structures of the animals treated with physical activity: (i) the interdigitations of the proximal and distal convoluted tubules; (ii) the basal membrane of the proximal and distal convoluted tubules; and (iii) in the basal membrane, slit diaphragm and pedicels of the glomerular filtration barrier. The spontaneously hypertensive rats also showed a decreased expression of connexin-43. Physical exercise could be a therapeutic tool for improving kidney ultrastructure and, consequently, renal function in hypertensive individuals.
    Clinics (São Paulo, Brazil) 05/2011; 66(5):855-63. DOI:10.1590/S1807-59322011000500024 · 1.19 Impact Factor
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