High Risk of ESRD in Type 1 Diabetes: New Strategies Are Needed to Retard Progressive Renal Function Decline

Królewski, Andrzej S.; Bonventre, Joseph V.

doi:10.1016/j.semnephrol.2012.07.002

Cited by 37 publications

(27 citation statements)

References 52 publications

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“…Unfortunately, the ONTARGET and ALTITUDE studies have further highlighted the limitations of RAAS inhibition, since combination therapies with multiple RAAS blockers increase the risk of serious adverse events 29, 30 . Therefore, a large residual DN risk remains despite current evidence-based intervention strategies and novel therapies to safely complement glucose and RAAS inhibition are urgently needed 3, 26 .…”

Section: Limitations Of Current Approaches To Prevent Esrd In Diabetesmentioning

confidence: 99%

“…While such improvements in clinical care have been effective at delaying the development of diabetic complications 1 , the overall incidence of end-stage renal disease (ESRD) due to diabetes has not declined 2, 3 and diabetic nephropathy (DN) remains a major cause of morbidity and mortality among diabetic patients 4–6 . Thus, novel strategies are urgently needed to complement the existing ones in order to prevent kidney function loss in diabetes.…”

Section: Introductionmentioning

confidence: 99%

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Uric Acid Lowering to Prevent Kidney Function Loss in Diabetes: The Preventing Early Renal Function Loss (PERL) Allopurinol Study

et al. 2013

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Diabetic kidney disease causes significant morbidity and mortality among people with type 1 diabetes (T1D). Intensive glucose and blood pressure control have thus far failed to adequately curb this problem and therefore a major need for novel treatment approaches exists. Multiple observations link serum uric acid levels to kidney disease development and progression in diabetes and strongly argue that uric acid lowering should be tested as one such novel intervention. A pilot of such a trial, using allopurinol, is currently being conducted by the Preventing Early Renal Function Loss (PERL) Consortium. Although the PERL trial targets T1D individuals at highest risk of kidney function decline, the use of allopurinol as a renoprotective agent may also be relevant to a larger segment of the population with diabetes. As allopurinol is inexpensive and safe, it could be cost-effective even for relatively low-risk patients, pending the completion of appropriate trials at earlier stages.

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Section: Limitations Of Current Approaches To Prevent Esrd In Diabetesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Uric Acid Lowering to Prevent Kidney Function Loss in Diabetes: The Preventing Early Renal Function Loss (PERL) Allopurinol Study

et al. 2013

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“…New effective therapies are desperately needed to reduce risk of ESRD in T1D as it was discussed in the recent issue of Seminars in Nephrology [53]. In designing therapies for T1D it is important to put aside the previous proteinuria-centric model of diabetic nephropathy and fully appreciate the features of progressive renal decline.…”

Section: Progressive Renal Decline and Considerations For Therapeuticmentioning

confidence: 99%

Progressive renal decline as the major feature of diabetic nephropathy in type 1 diabetes

2013

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Despite almost universal implementation of reno-protective therapies over the last 25 years, risk of ESRD in type 1 diabetes (T1D) is not decreasing, and ESRD remains the major cause of excess morbidity and premature mortality [1]. Such a state of affairs prompts a call to action. In this review we re-evaluated the proteinuria-centric model of diabetic nephropathy and showed its deficiencies. On the basis of the extensive studies that we have been conducting in the population of the Joslin Clinic, we propose that progressive renal decline, not abnormalities in urinary albumin excretion, should be considered as the major feature of disease processes leading to ESRD in T1D. Etiology of diabetic nephropathy should be reconsidered in light of our new findings so our perspective can be broadened regarding new therapeutic targets available for interrupting the progressive renal decline in T1D. Reduction in the rate of GFR loss, not reduction of AER, should become the measure for evaluating the effectiveness of new therapeutic interventions. We need new accurate methods for early diagnosis of patients at risk of progressive renal decline or, better yet, for detecting in advance which patients will have rapid, moderate or minimal rate of progression to ESRD.

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“…12 Studies demonstrated that early hyperglycemia stimulates the production of ECM components, mainly fibronectin and collagen IV, and this effect appears to be mediated by transforming growth factor beta 1 (TGF-b1) in streptozotocin (STZ)-induced diabetic rats, 13,14 as well as, in other models of renal injury. 15,16 Currently, no specific therapy is available to inhibit the progression of renal diabetic disease, and although some studies have demonstrated the renoprotective action of pharmacological therapies that target the glycemic and blood pressure controls, 17,18 the incidence of diabetic nephropathy continues to increase. 1 Regular exercise training is considered an unquestionable component of a healthy lifestyle and widely accepted in the management and prevention of several chronic diseases.…”

Section: Introductionmentioning

confidence: 99%

Beneficial effects of previous exercise training on renal changes in streptozotocin-induced diabetic female rats

Amaral

Silva

Correia

et al. 2015

Exp Biol Med (Maywood)

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This study evaluated the effects of aerobic exercise performed both previously and after the induction of diabetes mellitus on changes of renal function and structure in streptozotocin-induced diabetic rats. Female wistar rats were divided into five groups:The previous exercise consisted of treadmill running for four weeks before the induction of diabetes mellitus. After induction of diabetes mellitus with streptozotocin, the D þ PEx, D þ Ex and C þ Ex groups were submitted to eight weeks of aerobic exercise. At the end of the training protocol, we evaluate the serum glucose, insulin and 17b-estradiol levels, renal function and structure, proteinuria, and fibronectin, collagen IV and transforming growth factor beta 1 (TGF-b1) renal expressions. Induction of diabetes mellitus reduced the insulin and did not alter 17b-estradiol levels, and exercise did not affect any of these parameters. Previous exercise training attenuated the loss of body weight, the blood glucose, the increase of glomerular filtration rate and prevented the proteinuria in the D þ PEx group compared to D þ Se group. Previous exercise also reduced glomerular hypertrophy, tubular and glomerular injury, as well as the expressions of fibronectin and collagen IV. These expressions were associated with reduced expression of TGF-b1. In conclusion, our study shows that regular aerobic exercise especially performed previously to induction of diabetes mellitus improved metabolic control and has renoprotective action on the diabetic kidney.

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High Risk of ESRD in Type 1 Diabetes: New Strategies Are Needed to Retard Progressive Renal Function Decline

Cited by 37 publications

References 52 publications

Uric Acid Lowering to Prevent Kidney Function Loss in Diabetes: The Preventing Early Renal Function Loss (PERL) Allopurinol Study

Uric Acid Lowering to Prevent Kidney Function Loss in Diabetes: The Preventing Early Renal Function Loss (PERL) Allopurinol Study

Progressive renal decline as the major feature of diabetic nephropathy in type 1 diabetes

Beneficial effects of previous exercise training on renal changes in streptozotocin-induced diabetic female rats

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