Chronic renal denervation prevents glomerular hyperfiltration in diabetic rats

Luippold, Gerd; Beilharz, Martina; Mühlbauer, Bernd

doi:10.1093/ndt/gfg584

Cited by 65 publications

(59 citation statements)

References 13 publications

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“…In young patients with type 1 diabetes, SNS activity causes early, preclinical BP changes that are in turn associated with increased glomerular basement membrane thickness and mesangial matrix expansion (38). Autonomic dysfunction also correlates with higher-range normoalbuminuria in patients with type 1 diabetes, suggesting a possible role for SNS activation in the transition from normo-to microalbuminuria (39) and activation of intrarenal RAAS, intraglomerular hypertension, and hyperfiltration in animals and in humans with type 1 diabetes (40)(41)(42). Therapeutic interventions using pharmacologic SNS blockade in type 1 diabetes resulted in lower BP and improved HRV (43).…”

Section: Discussionmentioning

confidence: 99%

“…Therapeutic interventions using pharmacologic SNS blockade in type 1 diabetes resulted in lower BP and improved HRV (43). Meanwhile, in streptozotocin-induced diabetic rats, renal hyperfiltration can be prevented with sympathetic renal denervation (40). Similar strategies for renal sympathetic denervation have been targeted in humans with treatment-resistant hypertension (44), although their long-term utility in preventing CKD is unknown.…”

Section: Discussionmentioning

confidence: 99%

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Cardiac Autonomic Neuropathy and Early Progressive Renal Decline in Patients with Nonmacroalbuminuric Type 1 Diabetes

Orlov

Cherney

Pop‐Busui

et al. 2015

Clinical Journal of the American Society of Nephrology

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Background and objectives Cardiac autonomic neuropathy predicts future adverse renal outcomes in the general population. This study sought to determine its relationship with early progressive renal decline in type 1 diabetes.Design, setting, participants, & measurements A subset of participants with normoalbuminuria (n=204) or microalbuminuria (n=166) from the First Joslin Kidney Study underwent assessment for cardiac autonomic neuropathy using heart rate variability during baseline visits performed from January 1991 to April 1992. Cardiac autonomic neuropathy was defined as an R-R variation (mean circular resultant) ,20. Participants also had baseline and follow-up measurement of eGFR. Early progressive renal decline was evaluated according to two definitions: early GFR loss (slope of eGFR estimated by cystatin C ,23.3%/year) and incident advanced CKD (stage $3, defined by eGFR [calculated by Modification of Diet in Renal Disease method] ,60 ml/min per 1.73 m 2 ). Association with baseline cardiac autonomic neuropathy was assessed by adjusted logistic regression and Cox proportional hazards.Results Among the 370 participants, 47 (13%) had baseline cardiac autonomic neuropathy, 51 (14%) had early GFR loss, and 68 (18%) had incident advanced CKD over a median 14-year follow-up. Early GFR loss occurred in 15 (32%) of the 47 patients with baseline autonomic neuropathy and in 32 (10%) of the 323 without baseline autonomic neuropathy (P,0.001). Baseline autonomic neuropathy was strongly associated with odds of early GFR loss (adjusted odds ratio, 4.09; 95% confidence interval, 1.65 to 10.12; P=0.002). Incident advanced CKD was observed in 22 (47%) of those with baseline autonomic neuropathy and 46 (14%) of those without baseline autonomic neuropathy (P,0.001). Autonomic neuropathy was independently associated with incident advanced CKD (adjusted hazard ratio, 2.76; 95% confidence interval, 1.44 to 5.30; P=0.002).Conclusions Cardiac autonomic neuropathy was a strong independent predictor of the long-term risk of early progressive renal decline in type 1 diabetes. Future research should explore the mechanisms by which autonomic neuropathy may be associated with renal function loss.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Cardiac Autonomic Neuropathy and Early Progressive Renal Decline in Patients with Nonmacroalbuminuric Type 1 Diabetes

Orlov

Cherney

Pop‐Busui

et al. 2015

Clinical Journal of the American Society of Nephrology

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“…52 This preclinical model used bilateral surgical renal denervation before the induction of diabetes mellitus with streptozotocin in rats. Functional and anatomic studies were performed 2 weeks after the onset of diabetes mellitus.…”

Section: Chronic Kidney Diseasementioning

confidence: 99%

Renal Denervation as a Therapeutic Approach for Hypertension

et al. 2009

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“…63 However, there are reports that renal nerves are protective against the progression of diabetic nephropathy. 64 Increases in the glomerular filtration rate in response to amino acid load are also reduced by sectioning renal nerves.…”

Section: Time Course Of Changes In Renal Function and Activation Of Tmentioning

confidence: 99%

Lewis K. Dahl Memorial Lecture

Diz

2008

Hypertension

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identified many of the relationships that underlie our current thinking and focus of research on hypertension. Among the first to establish the interactions between salt and hypertension, the realization that genetic factors played a major role in how the kidney responded to salt loads 1 led to development of the genetically predisposed Dahl salt-sensitive rat. His research, although not specifically directed toward aging, recognized that the effects of high-salt diets were not necessarily immediate. In fact, he suggested that at least one third of the life span was required for salt-induced changes in systolic blood pressure (SBP).I am very grateful for the honor of presenting the Dahl lectureship on work, which, over the past several years, has had aging as the focus. The emphasis has been on the autonomic nervous system, as influenced by the renin-angiotensin system (RAS), specifically, the balance between angiotensin (Ang) II and Ang-(1-7) and the contributions of brain cardiovascular areas to the constellation of changes occurring with advancing age. The overall message derived is that, although the brain RAS plays a major role in all of the age-related changes in cardiovascular and metabolic function, neither the SBP nor the metabolic changes appear to be initiating factors in the activation of the intrarenal RAS or the decline in kidney function during aging ( Figure 1). Differential Regulation of the Circulating and Intrarenal RAS During AgingComponents of the classical circulating RAS, in particular, renin release from the juxtaglomerular cells of the kidney, undergo a decline in older animals. This includes reductions in renal tissue renin mRNA, juxtaglomerular cell renin content, responsiveness of renin release to various challenges, and plasma renin and angiotensin (Ang) II. [2][3][4][5][6][7][8][9] The renal vasoconstrictor responses to exogenously administered Ang II are increased in older animals, 6 perhaps resulting from the reductions in the circulating system. In striking contrast, however, kidney Ang II content increases in older animals. 6This latter finding is not surprising, because all of the components of the RAS are synthesized locally within the kidney, 10 -12 and local production of Ang peptides is regulated independent of the circulating system. 11,13-16 Thus, whereas the juxtaglomerular cell renin and its release into the circulation are considered representative of the circulating/hormonal RAS, renal tissue content, tubular fluid, or urinary RAS components are considered representative of the intrarenal RAS.The concept of differential regulation of the circulating and intrarenal or other tissue RAS is not new.12 One possibility for these differences relate to the increase in SBP. An increase in arterial pressure during aging may lead to a baromediated reduction in renin release from the kidney, contributing to the decline in the circulating RAS. In contrast, for the intrarenal system, there is evidence that the regulation of tubular renin may be opposite to or at least different fro...

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Chronic renal denervation prevents glomerular hyperfiltration in diabetic rats

Abstract: Renal nerves appear to be significantly involved in the mediation of glomerular hyperfiltration in experimental DM. If the kidney is prevented from sympathetic nerve stimulation, structural changes due to early diabetic nephropathy, i.e. glomerular enlargement, are abolished.

Cited by 65 publications

References 13 publications

Cardiac Autonomic Neuropathy and Early Progressive Renal Decline in Patients with Nonmacroalbuminuric Type 1 Diabetes

Cardiac Autonomic Neuropathy and Early Progressive Renal Decline in Patients with Nonmacroalbuminuric Type 1 Diabetes

Renal Denervation as a Therapeutic Approach for Hypertension

Lewis K. Dahl Memorial Lecture

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