Nephrology Dialysis Transplantation

2001

DOI: 10.1093/ndt/16.4.765

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Clinicopathological correlation in biopsy‐proven atherosclerotic nephropathy: implications for renal functional outcome in atherosclerotic renovascular disease

Julian Wright¹,

et al.

Abstract: In patients with atherosclerotic nephropathy the severity of histopathological damage is an important determinant and predictor of renal functional outcome.

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Cited by 98 publications

(56 citation statements)

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“…22,23 However, there is still a shortage of techniques that can accurately determine the severity of renal damage pre-PTRAS and therefore, define its role in the responses to therapy. It is possible that there is a tipping point at which irreversible renal damage may render any intervention futile.…”

Section: Discussionmentioning

confidence: 99%

Endothelin-A Receptor Antagonism after Renal Angioplasty Enhances Renal Recovery in Renovascular Disease

et al. 2015

Journal of the American Society of Nephrology

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Percutaneous transluminal renal angioplasty/stenting (PTRAS) is frequently used to treat renal artery stenosis and renovascular disease (RVD); however, renal function is restored in less than one half of the cases. This study was designed to test a novel intervention that could refine PTRAS and enhance renal recovery in RVD. Renal function was quantified in pigs after 6 weeks of chronic RVD (induced by unilateral renal artery stenosis), established renal damage, and hypertension. Pigs with RVD then underwent PTRAS and were randomized into three groups: placebo (RVD+PTRAS), chronic endothelin-A receptor (ET-A) blockade (RVD+PTRAS+ET-A), and chronic dual ET-A/B blockade (RVD+PTRAS+ET-A/B) for 4 weeks. Renal function was again evaluated after treatments, and then, ex vivo studies were performed on the stented kidney. PTRAS resolved renal stenosis, attenuated hypertension, and improved renal function but did not resolve renal microvascular rarefaction, remodeling, or renal fibrosis. ET-A blocker therapy after PTRAS significantly improved hypertension, microvascular rarefaction, and renal injury and led to greater recovery of renal function. Conversely, combined ET-A/B blockade therapy blunted the therapeutic effects of PTRAS alone or PTRAS followed by ET-A blockade. These data suggest that ET-A receptor blockade therapy could serve as a coadjuvant intervention to enhance the outcomes of PTRAS in RVD. These results also suggest that ET-B receptors are important for renal function in RVD and may contribute to recovery after PTRAS. Using clinically available compounds and techniques, our results could contribute to both refinement and design of new therapeutic strategies in chronic RVD. Chronic renovascular disease (RVD) increases the risk of cardiovascular morbidity and mortality and may progressively induce renal injury, leading to ESRD. 1 Percutaneous transluminal renal angioplasty/stenting (PTRAS) is a frequently used therapeutic strategy to treat patients with chronic RVD. Targeting the renal stenosis is a logical choice for treating RVD, because the resolution of the vascular obstruction followed by restoration of blood flow to the site of injured tissues should play an important role to initiate successful repairing responses. The use of PTRAS in RVD grew significantly during the past 20 years, 2 with tremendous progress in successfully resolving renal stenosis and restoring blood flow (.95% of the cases). 3 However, despite the high technical success of PTRAS, improvement in renal function is still observed in a relatively small portion of the cases. 4 The reasons for the persistent poor outcomes after PTRAS in RVD are still unclear. Furthermore, the dissociation between the technical success of PTRAS and renal outcomes underscores a pressing need to identify more effective therapeutic strategies in RVD.Endothelin-1 (ET-1) is a powerful renal vasoconstrictor and mitogenic peptide that plays important roles in controlling BP and renal function.

“…22,23 However, there is still a shortage of techniques that can accurately determine the severity of renal damage pre-PTRAS and therefore, define its role in the responses to therapy. It is possible that there is a tipping point at which irreversible renal damage may render any intervention futile.…”

Section: Discussionmentioning

confidence: 99%

Endothelin-A Receptor Antagonism after Renal Angioplasty Enhances Renal Recovery in Renovascular Disease

et al. 2015

Journal of the American Society of Nephrology

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Percutaneous transluminal renal angioplasty/stenting (PTRAS) is frequently used to treat renal artery stenosis and renovascular disease (RVD); however, renal function is restored in less than one half of the cases. This study was designed to test a novel intervention that could refine PTRAS and enhance renal recovery in RVD. Renal function was quantified in pigs after 6 weeks of chronic RVD (induced by unilateral renal artery stenosis), established renal damage, and hypertension. Pigs with RVD then underwent PTRAS and were randomized into three groups: placebo (RVD+PTRAS), chronic endothelin-A receptor (ET-A) blockade (RVD+PTRAS+ET-A), and chronic dual ET-A/B blockade (RVD+PTRAS+ET-A/B) for 4 weeks. Renal function was again evaluated after treatments, and then, ex vivo studies were performed on the stented kidney. PTRAS resolved renal stenosis, attenuated hypertension, and improved renal function but did not resolve renal microvascular rarefaction, remodeling, or renal fibrosis. ET-A blocker therapy after PTRAS significantly improved hypertension, microvascular rarefaction, and renal injury and led to greater recovery of renal function. Conversely, combined ET-A/B blockade therapy blunted the therapeutic effects of PTRAS alone or PTRAS followed by ET-A blockade. These data suggest that ET-A receptor blockade therapy could serve as a coadjuvant intervention to enhance the outcomes of PTRAS in RVD. These results also suggest that ET-B receptors are important for renal function in RVD and may contribute to recovery after PTRAS. Using clinically available compounds and techniques, our results could contribute to both refinement and design of new therapeutic strategies in chronic RVD. Chronic renovascular disease (RVD) increases the risk of cardiovascular morbidity and mortality and may progressively induce renal injury, leading to ESRD. 1 Percutaneous transluminal renal angioplasty/stenting (PTRAS) is a frequently used therapeutic strategy to treat patients with chronic RVD. Targeting the renal stenosis is a logical choice for treating RVD, because the resolution of the vascular obstruction followed by restoration of blood flow to the site of injured tissues should play an important role to initiate successful repairing responses. The use of PTRAS in RVD grew significantly during the past 20 years, 2 with tremendous progress in successfully resolving renal stenosis and restoring blood flow (.95% of the cases). 3 However, despite the high technical success of PTRAS, improvement in renal function is still observed in a relatively small portion of the cases. 4 The reasons for the persistent poor outcomes after PTRAS in RVD are still unclear. Furthermore, the dissociation between the technical success of PTRAS and renal outcomes underscores a pressing need to identify more effective therapeutic strategies in RVD.Endothelin-1 (ET-1) is a powerful renal vasoconstrictor and mitogenic peptide that plays important roles in controlling BP and renal function.

“…However, recent studies have also shown that proteinuria and severe renal failure are predictors of poor outcome in patients with ARVD (11,12). Proteinuria is a marker of hypertension-related renal parenchymal damage, and this, rather than purely the extent of proximal renal artery stenosis (RAS) lesions, is often the most important determinant of renal functional outcome (13,14). It is likely that microvascular disease also occurs in the heart of patients with ARVD and contributes to their "cardiomyopathy.…”

mentioning

confidence: 99%

Left Ventricular Morphology and Function in Patients with Atherosclerotic Renovascular Disease

¹

,

²

,

³

et al. 2005

Journal of the American Society of Nephrology

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“…We suspect that functional glomerulopenia of this magnitude could be sufficient to evoke the remnant kidney phenomenon. This could be especially dangerous in aging individuals who are prone to superimposition of the renovasculopathies associated with the development of hypertension (13) or bilateral renal artery stenosis (32,37,41), two common causes of end-stage renal failure in the elderly.…”

Section: Discussionmentioning

confidence: 99%

Adaptive hyperfiltration in the aging kidney after contralateral nephrectomy

¹

,

²

,

³

et al. 2006

American Journal of Physiology-Renal Physiology

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We examined the magnitude of adaptive hyperfiltration in the remaining kidney of 16 aging (Ͼ57 yr) and 16 youthful (Ͻ55 yr) individuals who had undergone a contralateral nephrectomy. Healthy volunteers who were youthful (n ϭ 143) or aging (n ϭ 37) provided control values for the binephric condition. One-kidney glomerular filtration rate (GFR; ϩ42%), renal plasma flow (ϩ38%), plasma oncotic pressure (ϩ2.8 mmHg), and mean arterial pressure (ϩ7.0 mmHg) were all higher in youthful uninephric vs. binephric subjects. Corresponding excesses in aging uninephric vs. binephric subjects were by 38 and 36% and 1.4 and 14.0 mmHg, respectively. Modeling of these data revealed that an isolated increase in either the glomerular ultrafiltration coefficient (Kf) by 110% or in the transcapillary hydraulic pressure gradient (⌬P) by 7 mmHg, could account for the observed level of hyperfiltration in youthful uninephric subjects. Corresponding increases for aging uninephric subjects were 61% for Kf and 5 mmHg for ⌬P. We conclude that the magnitude of adaptive hyperfiltration is similar in aging to that in youthful uninephric subjects, albeit at a lower absolute GFR level. Isolated increases in either Kf or ⌬P or a combination of smaller increases in both can account for the hyperfiltration. Greater adaptive arterial hypertension in aging than youthful uninephric subjects raises the possibility of a disproportionate role for glomerular hypertension and ⌬P elevation in aging compared with youthful uninephric subjects. Glomerular hypertension could exacerbate the sclerosing glomerulopathy of senescence and lead to renal insufficiency. We recommend that living donors of a kidney transplantation in or beyond the seventh decade be used with caution.living kidney donor; uninephrectomy; glomerular filtration A SHORTAGE OF KIDNEYS FOR transplantation (Tx) in the United States has resulted in a recipient waiting list in excess of 50,000 and a median waiting time of 1,131 days (38). One measure adopted to lower the donor deficit has been the increasing use of unrelated, living donor transplants (35,36,38). Another recent source of additional donors has been deceased donors who meet the so-called "expanded" criteria for donation, the most prominent of which is a donor age in the seventh or even eighth decade (38). Although the expanded criteria have been recommended for deceased donors, the use of living donors over 60 yr of age has, in fact, more than doubled during the past decade (38), suggesting a possible trend toward the increasing use of aging donors, be they deceased or living.A large body of evidence indicates that both the short-term and long-term risks of living kidney donation are minimal and that the ensuing uninephric state is safe for the living donor (9,22,25,26). Donors above age 60 yr at the time of nephrectomy have been few, however, and a comparison between their course and outcome and those of younger donors has not been reported. A relative paucity of aging donors reflects an inverse relationship between graft survival and d...

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