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Stephen C Textor

Publications and source records attributed to Stephen C Textor.

At least 19 recordsLinked to original sources
PubMed2006

Endothelin-a receptor blockade improves renal microvascular architecture and function in experimental hypercholesterolemia.

Hypercholesterolemia (HC) may trigger early renal injury, partly by impairing the function or the structure of renal microvessels (MV). The endothelin (ET) system is upregulated in HC and can have an impact on the renal microcirculation by regulating MV tone, growth factors, and remodeling. It was hypothesized that ET-A blockade would protect the HC kidney by improving the function and attenuating the damage of intrarenal MV. Single-kidney function and hemodynamic responses to endothelium-dependent challenge were assessed in pigs after 12 wk of experimental HC, HC and chronic supplementation with the ET receptor A blocker ABT-627 (HC+ET-A, 0.75 mg/kg per d), and normal controls. Renal MV architecture then was studied ex vivo using three-dimensional microcomputed tomography imaging, and growth factors and remodeling pathways were explored in renal tissue. The HC kidney showed increased MV density compared with normal (77.68 +/- 5.1 versus 62.9 +/- 4.8 vessels/cm(2); P = 0.04) but blunted endothelial function. Chronic ET-A blockade in HC upregulated renal vascular growth factors, further increased renal MV density (139.9 +/- 8.4 vessels/cm(2); P = 0.001 versus normal and HC), and decreased renal tissue and MV remodeling. Furthermore, ET-A blockade in HC decreased MV tortuosity and improved MV endothelial function, suggesting accelerated stabilization and maturation of neo-vessels. Modulation of renal MV architecture and function in HC is mediated partly by the endogenous ET system. Notably, ET-A blockade enhanced the proliferation and facilitated the maturation of renal MV in the HC kidney and improved renal MV remodeling and function. This study suggests novel renoprotective effects of ET-A blockers and supports further exploration of strategies that target the ET pathway in HC and atherosclerosis.

Animals↗
PubMed2006

Renovascular hypertension update.

Hypertension detected in patients with renovascular disease poses a major clinical challenge. The rapid expansion of noninvasive imaging, effective antihypertensive drug therapy, and endovascular interventional procedures combine to make optimal management a moving target. Renal arterial disease accelerates the development of hypertension associated with activation of multiple pressor systems and accelerated target organ injury. Younger individuals with fibromuscular lesions often respond well to renal revascularization with minor associated risks. Care must be taken in cases of complex vascular anomalies, such as renal artery aneurysms. Atherosclerotic renal artery stenosis is detected more commonly than ever before and affects more than 85% of patients referred for revascularization. Most are older patients with long-standing hypertension, diabetes, and pre-existing complications of vascular disease. The benefits of extensive workup and intervention in this group of patients are controversial. Antihypertensive drug therapy is most effectively achieved with drugs that block the renin-angiotensin system, but most require multiple agents. Selection of patients for renal revascularization in this group is far more controversial than with fibromuscular disease. Several small trials failed to identify major benefits with renal artery angioplasty as compared to closely monitored drug therapy, although crossover rates from medical to interventional arms were high. The Cardiovascular Outcomes in Renal Atherosclerotic Lesions (CORAL) seeks to randomly assign subjects with proven, high-grade renal artery lesions to optimal medical management with and without stenting. This important trial employs distal embolic protection to prevent deterioration of renal function. Understanding the optimal role for renal revascularization depends heavily upon the successful conduct of such trials.

Disease Progression↗
PubMed2005

Pathways of renal fibrosis and modulation of matrix turnover in experimental hypercholesterolemia.

Dyslipidemia often accompanies and accelerates renal disease, partly by promoting fibrosis. However, the mechanisms mediating this effect are unclear. We hypothesized that hypercholesterolemia modulates several interlinked pathways that promote deposition and blunt degradation of extracellular matrix, and that these could be manipulated by reversal of hypercholesterolemia. Fourteen pigs were fed a 16-week 2% high-cholesterol diet (HC-HC; n=7) or normal diet (n=7), whereas in 7 others, a 10-week HC was followed by a 6-week normal diet (HC-N). Renal endothelial function was assessed in vivo with electron-beam computed tomography, and renal tissue was then studied ex vivo using Western blot, real-time quantitative polymerase chain reaction, gelatin zymography, and immunostaining. HC-HC kidneys showed endothelial dysfunction, accompanied by increased intrarenal oxidative stress, inflammation, activation of the endothelin and transforming-growth factor-beta systems, and decreased matrix metalloproteinase expression and activity. Accordingly, HC-HC kidneys showed increased collagen IV expression and fibrosis. A lipid-lowering dietary intervention reversed most of these changes. In conclusion, this study indicates that renal fibrosis in early atherosclerosis is a result of a simultaneous increase in extracellular matrix deposition and blunted matrix metalloproteinase-mediated degradation, overall promoting perivascular and tubulointerstitial fibrosis. Notably, many of these pathways may be reversible in hypercholesterolemia, and crucial targets could potentially be identified for early interventions to preserve the kidney.

Animals↗
PubMed2005

Surgical management of renal fibromuscular dysplasia: challenges in the endovascular era.

Percutaneous transluminal renal angioplasty (PTRA) is the primary treatment for renal fibromuscular dysplasia (RFMD). Surgical revascularization is limited to patients who fail or are unsuitable for PTRA. All patients who were operated on with RFMD since the indications for renal PTRA were expanded in our institution were retrospectively reviewed. Outcome included patency, hypertension, and renal function. Twenty-six patients had reconstruction of 32 renal arteries between 1998 and 2004. The mean age was 47.1 +/- 14 years; the majority (81%) were female. Six patients had bilateral disease and three had a solitary kidney. Operations were done for hypertension in 25 patients, renal artery aneurysm in 8, and chronic dissection in 1, alone or in combination. Six patients had a failed PTRA and 20 were unsuitable for it. Aortorenal bypass was done most often (n = 28) and saphenous vein was the preferred conduit (n = 25). The distal anastomosis was to the main renal artery in 13 patients and to the branch arteries in 19. Ex vivo repair was needed in five patients. Five intraoperative revisions were done because of abnormalities on duplex scan. One patient died unexpectedly 42 days after operation from myocardial infarction. Extrarenal complications occurred in five patients. Median follow-up was 2.4 (range, 42 days to 6.3) years and was available in all but one patient (96%). Two bypasses occluded at 3 and 376 days, which resulted in loss of the kidneys. One graft stenosis was treated successfully with PTRA at 239 days. All failures occurred in men. One-year cumulative primary patency was 89 +/- 8% and was not adversely affected by prior PTRA or complex repair. Hypertension at 1 year was cured in 27% of the patients and improved in 60%. No patient developed acute or chronic renal failure. Surgical reconstruction for RFMD has excellent short-term patency. Failed PTRA or complex reconstructions did not adversely affect outcome.

Female↗
PubMed2005

Renovascular hypertension: current concepts.

Hypertension produced by renal artery occlusive disease is an important secondary form of hypertension. Clinicians commonly encounter forms of renal arterial disease of varying severity, many of which are of little hemodynamic significance when first detected. Experimental studies emphasize that transient activation of the renin-angiotensin-aldosterone system is necessary for initiation of renovascular hypertension. At some point, angiotensin II activates additional mechanisms responsible for sustained increased blood pressure including sodium retention, endothelial dysfunction, and vasoconstriction related to production of reactive oxygen species. Widespread application of agents that block the renin-angiotensin system, including angiotensin-converting enzyme inhibitors and angiotensin-receptor blockers, render many patients with unilateral renal arterial disease manageable primarily by medical means for many years. In the setting of high a priori likelihood of renovascular disease, recognizing the potential for disease progression during medical therapy and individually evaluating the risks and benefits of renal revascularization are important tasks. Recent prospective studies show limited, but real, benefit regarding blood pressure control for patients with atherosclerotic disease. Whether earlier renal revascularization offers benefits regarding improved morbidity and mortality from cardiovascular end point reduction is an important question to be addressed in multicenter, prospective, randomized trials. Our paradigm stresses the fact that patients with renovascular hypertension require intensive blood pressure control and cardiovascular risk factor intervention, both before and after revascularization. Hence, management of such patients requires close attention and periodic review regarding restenosis and progression of vascular disease.

Angioplasty↗
PubMed2005

Atherosclerotic renal artery stenosis: how big is the problem, and what happens if nothing is done?

Renal artery stenosis is a common problem, particularly for patients with other manifestations of atherosclerosis. Wide practice variations are apparent regarding how best to manage this disorder. Part of this variation is based on a broad range of clinical presentation, from incidentally identified disease of no clinical importance to rapidly progressive hypertension, renal failure, and refractory congestive heart failure. Advances in antihypertensive therapy, particularly as a result of angiotensin-converting enzyme inhibition and angiotensin receptor blockade, have led to improved blood pressure control and delayed recognition of renal artery disease. As a result, patients now sent for revascularization are older than before and have high comorbid disease risk, primarily related to cardiovascular events. Clinicians need to be vigilant for evidence of unsuspected renal artery stenosis as a cause of treatment-resistant hypertension and/or renal failure. Renal revascularization should be considered in viable individuals before the development of advanced renal insufficiency.

Atherosclerosis↗
PubMed2005

New onset hyperglycemia and diabetes are associated with increased cardiovascular risk after kidney transplantation.

BACKGROUND: Post-transplant diabetes (PTDM) is a common and serious complication of kidney transplantation. The implications of developing hyperglycemia of lesser severity are not well understood. METHODS: In this study we used American Diabetes Association (ADA) criteria to assess the incidence of abnormal glycemia post-transplant, the variables that relate to this complication, and the relationship between hyperglycemia and cardiovascular (CV) disease. Included in the study were 490 kidney recipients, transplanted from 1998 to 2003, without a history of diabetes, and with a pretransplant fasting glucose <126 mg/dL. RESULTS: Within one week post-transplant, 45% of recipients had impaired fasting glycemia (IFG, glucose 100-125 mg/dL), and 21% PTDM (glucose > or =126). One year post-transplant, 33% of patients had IFG, and 13% PTDM. Risk factors for hyperglycemia at one year included: older recipient, male gender, higher BMI, higher pretransplant glucose, and higher glucose one week post-transplant (all P < 0.002 by multivariable analyses). During a follow-up period of 40 +/- 14 months, 12% of recipients had CV events (cardiac, CVA, and/or peripheral). Increasing fasting glucose levels at one, four, and/or 12 months post-transplant were significantly related to CV events. Furthermore, these relationships were independent of other CV risk factors, including: older age, CV events pretransplant, male gender, dyslipidemia, and transplant year. Fasting glucose levels >100 mg/dL were associated with higher incidence of post-transplant cardiac (P= 0.001) and peripheral vascular disease events (P= 0.003). CONCLUSION: The incidence of post-transplant hyperglycemia and its CV impact have been underestimated. Pretransplant characteristics and, particularly, the glycemia during the first month post-transplant identified patients at risk of PTDM. Increasing glucose levels greater than 100 mg/dL, any time after the first month post-transplant, are associated with increasing CV risk. We postulate that aggressive detection and treatment of post-transplant hyperglycemia may significantly reduce CV morbidity and mortality after kidney transplantation.

Adult↗
PubMed2005

Obesity in living kidney donors: clinical characteristics and outcomes in the era of laparoscopic donor nephrectomy.

Acceptance of obese individuals as living kidney donors is controversial related to possible increased risk for surgical complications and concern that obesity may contribute to long-term renal disease. We retrospectively examined 553 consecutive hand-assisted laparoscopic living kidney donations between October 1, 1999 and April 1, 2003. We stratified donors into quartiles by baseline body mass index (BMI) assessing perioperative complications and 6-12 months post-donation metabolic and renal function. Compared to BMI <25 kg/m(2), high BMI donors (> or =35 kg/m(2)) had slightly longer operative times (mean increase 19 min), more overall perioperative complications (mostly minor wound complications), yet the same low rate of major surgical complications (conversion to open and re-operation) and similar length-of-stay (2.3 vs. 2.4 days). At 6-12 months after donation (mean 11 months), renal function and microalbuminuria did not differ with BMI. These results suggest that laparoscopic donor nephrectomy is generally safe in selected obese donors and does not result in a high rate of major perioperative complications. Obese donors have higher baseline cardiovascular risk and warrant risk reduction for long-term health. While early results are encouraging, we advocate careful study of obese donors and do not support their widespread use until longer follow-up is available.

Adult↗
PubMed2005

Kidney allograft fibrosis and atrophy early after living donor transplantation.

Kidney allograft failure is most often caused by chronic allograft nephropathy, a process of interstitial fibrosis (GIF) and tubular atrophy (TA). We assessed the pathology of living donor (LD) grafts compared to deceased donor (DD). Included are 321 recipients (245 LD; 76 DD) with protocol biopsies the first 2 years of transplant. In LD, GIF was present in 7%, 31%, 61% and 71% of grafts at 0, 4, 12 and 24 months. TA progressed in parallel to GIF. Compared to LD, more DD grafts had GIF at time 0 (29%, p = 0.002); thereafter the incidence of GIF was similar. In LD, GIF was associated with lower glomerular filtration rate (GFR)(1 year) (no GIF, 62 +/- 16; GIF, 49 +/- 15 mL/min/m(2) iothalamate clearance, p = 0.001) and reduced graft survival (HR = 2.2, p = 0.009). GIF in LD related to acute rejection (HR = 2.6, p = 0.01), polyoma nephropathy (OR = 4.4, p = 0.02) and lower levels of GFR 3 weeks post-transplant (HR = 0.961; p = 0.03, multivariate). However, GIF also developed in 53% of recipients lacking these covariates. Thus, GIF/TA develops in the majority of LD grafts, it is often mild but is associated with reduced function and survival. GIF frequently develops in the absence of risk factors. Lower GFR post-transplant identify patients at highest risk of GIF.

Adult↗
PubMed2005

Living donor kidney and autologous stem cell transplantation for primary systemic amyloidosis (AL) with predominant renal involvement.

Primary systemic amyloidosis (AL) is characterized by multiorgan deposition of monoclonal immunoglobulin light chain. Renal involvement is common and impaired kidney function is associated with reduced median survival. Autologous stem cell transplantation (SCT) for AL achieves superior response rates compared to chemotherapy alone but patients with end-stage renal disease (ESRD) may be excluded from consideration. A treatment approach consisting of living donor kidney transplantation (LDKTx) followed by autologous SCT was developed for AL with ESRD. Eight patients underwent LDKTx with immediate graft function. Two suffered unanticipated complications post-KTx and died 10 and 3 months later. Two cases of subclinical acute cellular rejection (ACR) and one case of clinical ACR occurred--all reversible with corticosteroid. Six patients had successful stem cell harvests performed and five of these underwent SCT with satisfactory trilineage engraftment. Renal function remained stable following SCT in four and was reduced in one due to infectious and bleeding complications. One patient, who has thus far elected not to undergo SCT, has proteinuria and histologic evidence of recurrent renal amyloidosis. This experience supports the feasibility of sequential living donor KTx and autologous SCT for carefully selected patients with ESRD due to AL.

Adolescent↗
PubMed2004

Blood pressure and renal function after kidney donation from hypertensive living donors.

BACKGROUND: Rising numbers of patients reaching end-stage kidney disease intensify the demand for expansion of the living-kidney-donor pool. On the basis of low risk in white donors with essential hypertension, our transplant center undertook a structured program of accepting hypertensive donors if kidney function and urine protein were normal. This study reports outcomes of hypertensive donors 1 year after kidney donation. METHODS: We studied detailed measurements of blood pressure (oscillometric, hypertensive therapy nurse [RN], and ambulatory blood pressure monitoring [ABPM]), clinical, and renal characteristics (iothalamate glomerular filtration rate [GFR], urine protein, and microalbumin) in 148 living kidney donors before and 6 to 12 months after nephrectomy. Twenty-four were hypertensive (awake ABPM>135/85 mm Hg and clinic/RN BP>140/90 mm Hg) before donation. RESULTS: After 282 days, normotensive donors had no change in awake ABPM pressure (pre 121 +/- 1/75 +/- 2 vs. post 120 +/- 1/ 5 +/- 1 mm Hg), whereas BP in hypertensive donors fell with both nonpharmacologic and drug therapy (pre 142 +/- 3/85 +/- 2 to post 132 +/- 2/80 +/- 1 mm Hg, P<.01). Hypertensive donors were older (53.4 vs. 41.4 years, P<.001) and had lower GFR after kidney donation (61 +/- 2 vs. 68 +/- 1 mL/min/1.73m, P<.01). After correction for age, no independent BP effect was evident for predicting GFR either before or after nephrectomy. Urine protein and microalbumin did not change in either group after donor nephrectomy. CONCLUSIONS: Our results indicate that white subjects with moderate, essential hypertension and normal kidney function have no adverse effects regarding blood pressure, GFR, or urinary protein excretion during the first year after living kidney donation. Although further studies are essential to confirm long-term safety, these data suggest that selected hypertensive patients may be accepted for living kidney donation.

Adult↗
PubMed2004

Decline in native renal function early after bladder-drained pancreas transplantation alone.

BACKGROUND: Pancreas transplant alone (PTA) has become accepted therapy for select nonuremic patients with type 1 diabetes mellitus. However, PTA may lead to significant complications including a decline in native renal function. This study examines trends in native renal function during the first posttransplant year in PTA recipients with a spectrum of pretransplant glomerular filtration rates (GFR). METHODS: Renal function was studied in 23 recipients of bladder-drained PTA who underwent transplantation from April 1998 through September 2001. GFR was measured by corrected iothalamate clearance at the time of transplant evaluation and 1 year posttransplant and also calculated using the Cockcroft-Gault method at the transplant evaluation; at the day of transplantation; and at 1, 6, and 12 months posttransplant. RESULTS: Iothalamate clearance decreased in the first year in 96% of patients (22 of 23). The mean measured GFR decreased from 84 +/- 33 mL/min/1.73 m2 pretransplant to 52 +/- 26 mL/min/1.73 m2 at 1 year (P <0.001). Calculated creatinine clearance declined in the majority of patients at both 1 and 12 months after PTA, but some patients, including a few with low GFR, maintained stable renal function. Calculated GFR generally correlated well with measured GFR in most patients, with a few notable exceptions. One patient (baseline GFR, 42 mL/min/1.73 m2) developed renal failure in the first year after transplant and required kidney transplantation. CONCLUSIONS: Bladder-drained PTA results in a decline in native renal function in the majority of patients regardless of the pretransplant GFR. These data suggest the need for strategies to prevent or minimize the decline in renal function after PTA.

Adult↗
PubMed2004

Pancreas-after-kidney transplantation: an increasingly attractive alternative to simultaneous pancreas-kidney transplantation.

BACKGROUND: Historically, the clinical acceptability of pancreas-after-kidney (PAK) transplantation has been hampered by relatively high acute rejection rates and lower pancreas graft survival rates when compared with the more commonly performed simultaneous pancreas-kidney (SPK) transplantation. The purpose of this study was to compare PAK transplantation to SPK transplantation in the Thymoglobulin induction era. METHODS: The authors reviewed all bladder-drained PAK (n=47) transplants receiving rabbit antithymocyte globulin induction from June 1998 to June 2002 and compared them with SPK (n=25) transplants during the same time period at their institution. The authors retrospectively studied data on demographics, patient survival, graft (pancreas and kidney) survival, complications, and biopsy-proven rejection episodes. RESULTS: The actuarial 1-year patient survival was 93% for the PAK group versus 100% for the SPK group (P =not significant [NS]). The actuarial 1-year pancreas graft survival was 87% for the PAK group versus 92% for the SPK group (P =NS). Waiting time for PAK was significantly shorter than for SPK (6.3 +/- 5.2 vs. 16.2 + -13.7 months, P <0.05). Clinical acute rejection rates were similar in the two groups (4.3% for PAK vs. 4.0% for SPK). PAK recipients demonstrated a greater decline in renal function after transplantation compared with SPK. A multivariate analysis failed to elucidate the cause. CONCLUSIONS: Newer immunosuppressive regimens allow PAK transplant patients to achieve immunologic outcomes similar to SPK transplant patients. Although the shorter waiting time and the ability to use living-donor kidneys make PAK an increasingly attractive alternative to SPK transplantation, its effect on renal allograft function deserves further attention.

Antilymphocyte Serum↗