Chronic kidney disease and the risk for cardiovascular disease, renal replacement, and death in the United States Medicare population, 1998 to 1999

Knowledge of the excess risk posed by specific cardiovascular syndromes could help in the development of strategies to reduce premature mortality among patients with chronic kidney disease (CKD). The rates of atherosclerotic vascular disease, congestive heart failure, renal replacement therapy, and death were compared in a 5% sample of the United States Medicare population in 1998 and 1999 (n = 1,091,201). Patients were divided into the following groups: 1, no diabetes, no CKD (79.7%); 2, diabetes, no CKD (16.5%); 3, CKD, no diabetes (2.2%); and 4, both CKD and diabetes (1.6%). During the 2 yr of follow-up, the rates (per 100 patient-years) in the four groups were as follows: atherosclerotic vascular disease, 14.1, 25.3, 35.7, and 49.1; congestive heart failure, 8.6, 18.5, 30.7, and 52.3; renal replacement therapy, 0.04, 0.2, 1.6, and 3.4; and death, 5.5, 8.1, 17.7, and 19.9, respectively (P < 0.0001). With use of Cox regression, the corresponding adjusted hazards ratios were as follows: atherosclerotic vascular disease, 1, 1.30, 1.16, and 1.41 (P < 0.0001); congestive heart failure, 1, 1.44, 1.28, and 1.79 (P < 0.0001); renal replacement therapy, 1, 2.52, 23.1, and 38.9 (P < 0.0001); and death, 1, 1.21, 1.38, and 1.56 (P < 0.0001). On a relative basis, patients with CKD were at a much greater risk for the least frequent study outcome, renal replacement therapy. On an absolute basis, however, the high death rates of patients with CKD may reflect accelerated rates of atherosclerotic vascular disease and congestive heart failure.     

Anemia and Cardiovascular Disease,Hospitalization, End Stage Renal Disease,and Death in Older Patients with Chronic Kidney Disease

Background: Large observational studies examining the association between anemia and “hard” clinical outcomes are rare in patients with chronic kidney disease (CKD).Methods: We used the General Medicare 5% Denominator Files to identify patients aged 67 years or more with CKD on December 31, 1999. Outcomes in the ensuing 2 years were compared in patients with and those without anemia (entry period, 1998–1999; follow-up period, 2000–2001).Results: Of 41,522 CKD patients identified, 49.0% had claims of anemia diagnosis. The factors associated (p< 0.0001) with anemia included older age, female gender, black race, and all 10 comorbid conditions studied; adjusted odds ratios (ORs) exceeded 1.5 for age 80 years old or older (OR, 1.54 compared to <70 years), for black race (OR, 1.52), and for co-existing diagnoses of congestive heart failure (OR, 1.64), gastrointestinal bleeding (OR, 3.65), and liver disease (OR, 2.16). During the follow-up period, outcome event rates (expressed per 1000 patient-years) were as follows: renal replacement therapy, 23.5; death, 186.4; congestive heart failure, 390.0; atherosclerotic vascular disease, 410.5; and first hospitalization, 552.6. Using proportional hazards modeling, the presence of anemia was associated (p < 0.0001) with the following adjusted hazards ratios: atherosclerotic vascular disease, 1.09; congestive heart failure, 1.14; renal replacement therapy, 2.61 and death, 1.40. Conclusion: A diagnosis of anemia is present in nearly half of all patients with CKD, aged 67 years or more, a group at very high risk of cardiovascular disease, hospitalization, end-stage renal disease, and death. Anemia is associated with each of these events.     

Surgical management of atherosclerotic renovascular disease

OBJECTIVE: This review describes the clinical outcome of surgical intervention for atherosclerotic renovascular disease in 500 consecutive patients with hypertension. METHODS: From January 1987 to December 1999, 626 patients underwent operative renal artery (RA) repair at our center. A subgroup of 500 patients (254 women and 246 men; mean age, 65 plus minus 9 years) with hypertension (mean blood pressure, 200 plus minus 35/104 plus minus 21 mm Hg) and atherosclerotic RA disease forms the basis of this report. Hypertension response was determined from preoperative and postoperative blood pressure measurements and medication requirements. Change in renal function was determined with estimated glomerular filtration rates (EGFRs) calculated from serum creatinine levels. Proportional hazards regression models were used for the examination of associations between selected preoperative parameters, blood pressure and renal function response, and eventual dialysis-dependence or death. RESULTS: Two hundred three patients underwent unilateral RA procedures, 297 underwent bilateral RA procedures, and 205 patients underwent combined renal and aortic reconstruction. After surgery, there were 23 deaths (4.6%) in the hospital or within 30 days of surgery. Significant and independent predictors of perioperative death included advanced age (P <.0001; hazard ratio [HR], 3.23; 95% confidence interval [CI], 1.85 to 5.70) and clinical congestive heart failure (P =.013; HR, 3.05; 95% CI, 1.26 to 7.34). Among the patients who survived surgery, hypertension was considered cured in 12%, improved in 73%, and unchanged in 15%. For the entire group, renal function increased significantly after operation (preoperative versus postoperative mean EGFR, 41.1 plus minus 23.9 versus 48.2 plus minus 25.5 mL/min/m(2); P <.0001). For individual patients, with a 20% or more change in EGFR considered significant, 43% had improved renal function (including 28 patients who were removed from dialysis-dependence), 47% had unchanged function, and 10% had worsened function. Preoperative renal insufficiency (P <.001; HR, 2.35; 95% CI, 1.86 to 2.98), diabetes mellitus (P =.007; HR, 2.14; 95% CI, 1.15 to 3.97), prior stroke (P =.042; HR, 1.50; 95% CI, 1.02 to 2.22), and severe aortic occlusive disease (P =.003; HR, 1.69; 95% CI, 1.19 to 2.31) showed significant and independent associations with death or dialysis during the follow-up examination period. After operation, blood pressure cured (P =.014; HR, 0.52; 95% CI, 0.30 to 0.88) and improved renal function (P =.011; HR, 0.40; 95% CI, 0.19 to 0.81) showed significant and independent associations with improved dialysis-free survival rate. All categories of function response and time to death or dialysis showed significant interactions with preoperative EGFR. CONCLUSION: The surgical correction of atherosclerotic renovascular disease resulted in blood pressure benefit and retrieval of renal function in selected patients with hypertension. The patients with cured hypertension or improved EGFR after operation showed increased dialysis-free survival as compared with other patients who underwent surgery.     

Mortality, kidney disease and cardiac procedures following acute coronary syndrome.

BACKGROUND: Cardiac interventions are underutilized in patients with chronic kidney disease (CKD) following acute coronary syndrome (ACS) partly due to nephrotoxicity concerns. METHODS: We analyzed outcomes of 4631 subjects with ACS enrolled in the Blockade of the Glycoprotein IIb/IIIa Receptor to Avoid Vascular Occlusion trial, including time to death, time to reduced renal function (50% reduction in estimated glomerular filtration rate (eGFR) or development of end-stage renal disease (ESRD)) and percent change in eGFR from baseline. RESULTS: Subjects with a lower baseline eGFR were more likely to be older, female and have diabetes, hypertension, congestive heart failure or peripheral vascular disease (all P < 0.0001); they were less likely to be taking aspirin > or = 162 mg or to have undergone a percutaneous coronary intervention (PCI) prior to enrollment (P < 0.0001). As eGFR declined, the proportion of subjects experiencing death versus reduced eGFR or ESRD qualitatively increased. In adjusted analyses, every 10 ml/min/1.73 m(2) decrease in eGFR < or = 90 was associated with a 15% increased hazard of death (HR 1.15, P = 0.01). In adjusted analyses of predictors of percent change in eGFR, catheterization (cath) with or without PCI compared to medical therapy during follow-up was not associated with significant differences in long-term eGFR (P = 0.09). CONCLUSIONS: Among CKD subjects in this study, the risk of death greatly outweighed the risk of reduced eGFR or development of ESRD following ACS and the occurrence of cath +/- PCI was not associated with significant differences in long-term renal function. The presence of CKD should not preclude potentially beneficial interventions and research should focus on reducing the high cardiovascular burden in this population.     

Ischemic nephropathy: where are we now?

Identification and reversing the loss of kidney function beyond occlusive disease of the renal arteries poses a major clinical challenge. Recent studies indicate that atherosclerotic renal artery stenosis develops as a function of age and is commonly associated with other microvascular disease, including nephrosclerosis and diabetic nephropathy. The risks of renal artery stenosis are related both to declining kidney function and to accelerated cardiovascular disease, with increased morbidity and mortality. Newer drugs, including agents that block the renin-angiotensin system, have improved the level of BP control for renovascular hypertension. Progressive renovascular disease during medical therapy can produce refractory hypertension, congestive heart failure, and renal failure with tubulointerstitial fibrosis. Recent studies indicate a complex interplay of oxidative stress, endothelial dysfunction, and activation of fibrogenic cytokines as a result of experimental atherosclerosis and renal hypoperfusion. Advances in imaging and interventional devices offer major new opportunities to prevent progressive loss of kidney function. Recent series indicate that although 25 to 30% of patients with impaired renal function can recover glomerular filtration after revascularization, many have no apparent change in kidney function and 19 to 25% experience a significant loss of kidney function, in some cases as a result of atheroemboli. To select patients who are most likely to benefit from vascular intervention, clinicians should understand the pathophysiology of developing ischemic nephropathy and the potential hazards of revascularization in the setting of diffuse atherosclerotic disease. Further research should be directed toward identification of critical disease, regulation of fibrogenesis, and the interaction with other atherosclerotic processes.     

Renal artery stenosis and chronic ischemic nephropathy: epidemiology and diagnosis

Atherosclerotic renal artery stenosis (RAS) is the most common primary disease of the renal arteries and results in renovascular hypertension and ischemic nephropathy. Ischemic nephropathy from atherosclerotic RAS is increasingly recognized as a cause of chronic kidney disease (CKD) and in severe cases can lead to end-stage renal disease. The exact prevalence of atherosclerotic RAS is unknown because the disease is often asymptomatic and few are screened unless they have significant traditional cardiac risk factors or symptoms. A high prevalence of atherosclerotic RAS is seen in patients with advanced age, congestive heart failure, and extrarenal atherosclerosis. The primary reason for diagnosing ischemic nephropathy from renovascular disease is that the loss of kidney function is potentially reversible through treatment of the occlusion with surgical revascularization or percutaneous transluminal renal angioplasty. However, the benefits of revascularization have to be considered in the context of other comorbid disease and remain controversial. There are several tests available for the screening and diagnosis of atherosclerotic RAS; however, the diagnostic test of choice should be based on patient factors and institutional expertise because the best test is the one performed most often at the individual medical facility.     

Revascularization to preserve renal function in patients with atherosclerotic renovascular disease

There are a significant number of patients with advanced atherosclerotic renovascular disease whose blood pressure is well controlled with medical therapy but in whom such vascular disease poses a grave risk to overall renal function. This article reviews current concepts regarding screening, evaluation, and selection of patients with this disease for revascularization to preserve renal function. The underlying rationale for this approach is an increasing awareness that, in selected patients, atherosclerotic renovascular disease represents a surgically correctable cause of progressive renal failure.     

Management of ischemic nephropathy: dialysis-free survival after surgical repair

PURPOSE: This retrospective review describes the surgical management of consecutive patients with severe hypertension and ischemic nephropathy due to atherosclerotic renovascular disease. METHODS: From January 1987 through December 1998, a total of 590 patients underwent operative renal artery repair at our center. A subgroup of 232 hypertensive patients (97 women, 135 men; mean age, 66 +/- 8 years) with atherosclerotic renovascular disease and preoperative serum creatinine levels of 1.8 mg/dL or more forms the basis of this report. Change in renal function was determined from glomerular filtration rates estimated from preoperative and postoperative serum creatinine. The influence of selected preoperative parameters and renal function response on time to dialysis and dialysis-free survival was determined by a proportional hazards regression model. RESULTS: In all, 83 patients underwent unilateral renal artery repair and 149 patients underwent bilateral repair, including repair to a solitary kidney in 17 cases. A total of 332 renal arteries were reconstructed, and 32 nephrectomies were performed in these patients. After surgery, there were 17 deaths (7.3%) in the hospital or within 30 days of surgery. Advanced patient age (P =.001; hazard ratio, 1.1; 95% CI [1.1, 1.2]) and congestive heart failure (P =.04; hazard ratio, 2.9 CI [1.0, 8.6]) demonstrated significant and independent associations with perioperative mortality. With a change of 20% or more in EGFR being considered significant, 58% of patients had improved renal function, including 27 patients removed from dialysis dependence; function was unchanged in 35% and worsened in 7%. Follow-up death from all causes or progression to dialysis dependence demonstrated a significant and independent association with early renal function response. Both patients whose function was unchanged (P =.005; hazard ratio, 6.0; CI [2.2, 16.6]) and patients whose function was worsened (P =.03; hazard ratio, 2.2; CI [1.1, 4. 5]) remained at increased risk of death or dialysis dependence. For patients with unchanged renal function after operation, risk of death or dialysis demonstrated a significant interaction with preoperative renal function. In addition to severe preoperative renal dysfunction, diabetes mellitus demonstrated a significant and independent association with follow-up death or dialysis. CONCLUSION: Surgical correction of atherosclerotic renovascular disease can retrieve excretory renal function in selected hypertensive patients with ischemic nephropathy. Patients with improved renal function had a significant and independent increase in dialysis-free survival in comparison with patients whose function was unchanged and patients whose function was worsened after operation. These results add further evidence in support of a prospective, randomized trial designed to define the value of renal artery intervention in patients with ischemic nephropathy.     

Smoking and cardiovascular outcomes in dialysis patients: the United States Renal Data System Wave 2 study

BACKGROUND: Smoking has received surprisingly little research attention in dialysis populations, a group at monumental cardiovascular risk. METHODS: Medicare claims data were used to study associations between smoking and new-onset cardiovascular outcomes, and death in the prospective, inception Wave 2 cohort (N = 4024), assembled in 1996 and 1997. RESULTS: Of the participants, 56.4% were lifetime nonsmokers, 3.6% were smokers with unknown current status, 20.0% had quit for more than 1 year, 5.8% had quit less than 1 year ago, and 14.2% were current smokers. Subjects with cardiovascular disease at baseline were more likely to be former smokers, less likely never to have smoked and less likely to be current smokers (P < 0.001). Patients were followed until December 31, 1998. When adjustment was made for baseline age, demographic variables, mode of dialysis therapy, and comorbidity, smoking status was associated with new-onset congestive heart failure (adjusted hazards ratio 1.59 comparing current to nonsmokers, P = 0.004), new-onset peripheral vascular disease (adjusted hazards ratio 1.68, P < 0.001), and mortality (adjusted hazards ratio 1.37, P < 0.001). Former smokers, in contrast, had adjusted event risks similar to lifelong nonsmokers. CONCLUSION: Smoking is a major, modifiable, cardiovascular risk factor in patients starting dialysis therapy.     

Is renal revascularization in diabetic patients worthwhile?

Purpose: This retrospective review describes surgical management of atherosclerotic renovascular disease (RVD) in hypertensive adults with diabetes mellitus.Methods: From July 1987 through July 1995, 54 consecutive hypertensive diabetics (mean 213/103 mm Hg; mean medications three drugs) requiring either insulin (16 patients) or oral hypoglycemic therapy (38 patients) had operative repair of atherosclerotic RVD. Renal dysfunction (serum creatinine [SCr] ≥1.3 mg/dl) was present in 82% of patients (mean SCr 2.4 mg/dl). Associations between blood pressure and renal function response to operation and preoperative parameters were examined. Clinical characteristics, response to operation, and dialysis-free survival were compared with those of 291 nondiabetic patients.Results: Four (7.4%) operative deaths occurred. Among 50 survivors blood pressure response was considered cured or improved in 72% and unchanged in 28%. Of 42 patients with renal dysfunction 40% had improved function including three patients removed from dialysis. No preoperative parameter examined demonstrated a significant association with blood pressure or renal function response. During follow-up 10 additional patient deaths occurred, and eight patients progressed to dialysis dependence. Time to death or dialysis was associated with preoperative estimates of glomerular filtration (p = 0.03) and the change in estimates of glomerular filtration after operation (p = 0.01). Compared with 291 nondiabetics, the diabetic group had no statistical difference in improved function response (40% vs 51%, p = 0.21); however, diabetics had a significantly lower rate of beneficial blood pressure response (72% vs 89%, p = 0.01) and an increased risk of dialysis or death during follow-up (p = 0.02). By multivariate analysis independent predictors of time to death or dialysis included the presence of diabetes mellitus, patient age, history of congestive heart failure, and increased serum creatinine.Conclusions: Most of the selected diabetic patients had a beneficial blood pressure response after undergoing operative repair of atherosclerotic RVD, albeit at a lower rate compared with nondiabetics. In diabetics poor renal function before and after operation was associated with progression to dialysis and death. Improved renal function after operation was associated with improved survival; however, function response to renal revascularization was difficult to predict. (J Vasc Surg 1996;24:383-93.)     

Surgery after failed percutaneous renal artery angioplasty.

PURPOSE: This retrospective review describes the surgical management of 51 patients after failed percutaneous renal artery angioplasty (F-PTRA). METHODS: From January 1987 through June 1998, 51 consecutive patients underwent surgical repair of either atherosclerotic (32 patients) or fibromuscular dysplastic (FMD; 19 patients) renovascular vascular disease after F-PTRA. These patients form the basis of this report. Surgical repair was performed for hypertension (29 patients with atherosclerosis: mean blood pressure, 205 +/- 34/110 +/- 23 mm Hg; 18 patients with FMD: mean blood pressure, 194 +/- 24/118 +/- 18 mm Hg) or ischemic nephropathy (20 patients with atherosclerosis: mean serum creatinine level, 2.0 +/- 0.8 mg/dL; three patients with FMD: mean serum creatinine level, 2.0 +/- 1.1 mg/dL). Emergency operation was required in four patients for acute renal artery thrombosis (one patient with atherosclerosis, one patient with FMD), renal artery rupture (one patient with atherosclerosis), or infected pseudoaneurysm (one patient with atherosclerosis). Operative management, blood pressure and renal function response to operation, and dialysis-free survival rate were examined and compared with 487 patients (441 patients with atherosclerosis, 46 patients with FMD) treated by operation alone. RESULTS: Among the patients with atherosclerotic renovascular disease, there were three postoperative deaths (9.4%) after repair for F-PTRA. Secondary operative repair was associated with emergent repair or nephrectomy in 16% of cases, while more extensive renal artery exposure and more complex operative management was required in 50% of patients with atherosclerosis and 65% of patients with FMD repaired electively. Among the 28 operative survivors with hypertension and atherosclerotic renovascular disease, blood pressure benefit after F-PTRA was significantly lower when compared with patients with atherosclerosis who underwent treatment with operation only (57% vs 89%; P <.001). However, blood pressure benefit in the 19 patients with FMD did not differ (89% vs 96%). Among the 28 patients with atherosclerosis, preoperative estimated glomerular filtration rate (EGFR) as compared with postoperative EGFR was significantly increased (47.4 +/- 4.2 mL/min/1.73m(2) vs 56. 6 +/- 5.1 mL/min/1.73m(2); P =.002). However, EGFR prior to PTRA was not significantly different from postoperative EGFR (51.6 +/- 3.4 mL/min/1.73m(2) vs 56.6 +/- 4.9 mL/min/1.73m(2); P =.121). As compared with patients with atherosclerosis who underwent treatment with operation alone, there was no difference in the dialysis-free survival rate. CONCLUSION: Operative repair after F-PTRA was altered in 59% of the patients with atherosclerosis and in 68% of patients with FMD. Blood pressure benefit for patients with FMD was unchanged after F-PTRA. However, the blood pressure benefit was significantly decreased among patients with atherosclerosis. Decreased EGFR after F-PTRA was recovered with operative renal artery repair. However, postoperative EGFR as compared with EGFR prior to PTRA was unchanged. Blood pressure and renal function response after F-PTRA for atherosclerotic renovascular disease warrants further study.     

Management of renovascular hypertension in the elderly population

This article summarizes our experience with the operative management of renovascular hypertension in a contemporary population of elderly patients. During a recent 18-month period 35 of 74 patients (47%) undergoing an operation for renovascular hypertension at our center were in their seventh (21 patients) or eighth (14 patients) decade of life (mean age, 68 years). There were 17 men and 18 women with blood pressures ranging from 176/90 mm Hg to 280/215 mm Hg (mean, 213/121 mm Hg). Twenty-seven patients (77%) had renal insufficiency (serum creatinine greater than or equal to 1.3 mg/dl). Nineteen patients had severe insufficiency (serum creatinine greater than or equal to 2.0 mg/dl), with five of these patients being dependent on dialysis. Thirty-three of 35 patients (94%) had evidence of organ-specific atherosclerotic damage as manifested by cardiac disease (72%), cerebrovascular disease (37%), or renal insufficiency (77%). Operative management consisted of unilateral revascularization in 17 patients (includes three contralateral nephrectomies), bilateral renal revascularization in 17 patients, and primary nephrectomy in one. Simultaneous aortic replacement was performed in nine patients. There were two operative deaths (5.7%) and two postoperative graft thromboses (4%). Hypertension was cured (three) or improved (27) in 30 of the 33 survivors (91%). Renal function was improved in six and worsened in two patients with severe non-dialysis-dependent renal insufficiency. Three of five patients who were dependent on dialysis before surgery were removed from dialysis after renal revascularization. On follow-up (mean, 10.3 months) we found that five patients had died. This article emphasizes the complexity of atherosclerosis in the current population presenting for operative management of renovascular hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)     

The clinical epidemiology and course of the spectrum of renal diseases associated with HIV infection

BACKGROUND: While an understanding of the epidemiology and clinical course of HIV-associated nephropathy (HIVAN) is growing, little is known about the risk factors and clinical course of the other renal diseases that may also occur as a complication of HIV infection. This study was undertaken to compare HIVAN to the spectrum of other kidney diseases seen among HIV-infected patients. METHODS: This retrospective cohort study included all HIV-infected patients who underwent renal biopsy during the course of their clinical care at six major medical centers. Demographic and clinical information were abstracted from each patient's clinical record. Time to initiation of renal replacement therapy was compared for patients with lesions other than HIVAN to patients with HIVAN using Cox proportional hazards regression. RESULTS: Eighty-nine patients (47 with lesions other than HIVAN and 42 with HIVAN) were available for inclusion. Patients with lesions other than HIVAN were less likely to be black (37/47 vs. 42/42, P= 0.02), more likely to have a positive hepatitis B surface antigen (10/37 vs. 4/42, P= 0.04), less likely to have the diagnosis of hypertension (24/46 vs. 31/42, P= 0.03), more likely to have a greater creatinine clearance at time of biopsy (60.6 vs. 39.0 cc/min, P= 0.008), and have a greater CD4 lymphocyte count at time of biopsy (287 vs. 187 cells/mL, P= 0.04) compared to patients with HIVAN. Lesions other than HIVAN were associated with a longer time to initiation of renal replacement therapy compared with HIVAN (HR 0.33, 95% CI 0.15-0.71, P= 0.005). Other factors associated with a longer time to renal replacement therapy included higher creatinine clearance at time of biopsy, greater CD4(+) lymphocyte count, the absence of hepatitis C antibody, and the use of an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker. The type of renal disease (HIVAN vs. other) interacted significantly with HIV-1 RNA level and the use of antiretroviral therapy (P= 0.0001 and 0.006, respectively). Among patients with lesions other than HIVAN, the presence of nondetectable HIV-1 RNA was not associated with a greater risk of progression of renal disease (HR 0.27, P= 0.24). Among patients with HIVAN, because all patients had detectable virus at the time of institution of renal replacement therapy, this highly significant association could not be quantified. Among patients with lesions other than HIVAN, the use of antiretroviral therapy was not associated with the progression to renal replacement therapy (HR 3.29, P= 0.06). Among patients with HIVAN, the use of antiretroviral therapy was associated with a slower progression to renal replacement therapy (HR 0.24, P= 0.03). CONCLUSION: Among HIV-infected patients with renal disease other than HIVAN, viral suppression and the use of antiretroviral therapy are not associated with a beneficial effect on renal function; thus, additional therapeutic strategies may need to be utilized. Because renal histology is associated with prognostic differences, these data provide outcomes information that will improve the clinical utility of renal biopsy among HIV-infected patients with renal disease.     

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.     

Incidental renal artery stenosis in peripheral vascular disease: a case for treatment?

BACKGROUND: Renal artery stenosis (RAS) is frequently encountered as an incidental finding in peripheral vascular disease. We assessed whether revascularization is indicated to prevent the practical consequences of end-stage renal failure, that is, the need for renal replacement therapy. METHODS: In a retrospective study, a cohort of consecutive patients was followed who had undergone angiography 8 to 10 years previously for peripheral artery disease. Patients with untreated incidental RAS of > or =50% diameter stenosis (68.8 +/- 9.8 years, mean +/- SD) were compared with regard to the prevalence of renal replacement therapy to controls without RAS who were matched for age and gender. RESULTS: RAS was present in 126 of 386 evaluable patients (33%). None of these patients required renal replacement therapy during the 10-year follow-up. Serum creatinine values remained stable during follow-up. CONCLUSIONS: Incidental RAS is frequently seen in patients with peripheral vascular disease. If left untreated, incidental RAS seems not to result in end-stage renal failure or in a need for renal replacement therapy. Revascularization with the aim to prevent end-stage renal failure seems less indicated, and further prospective studies are indicated to elucidate this issue.     

Race and sex differences in the identification of candidates for renal transplantation.

The availability of renal transplantation to individuals with end-stage renal disease (ESRD) is an issue of considerable concern. The role of age, race, sex, socioeconomic status, illness severity, and comorbidity in determining access to this therapy remains unclear. We examined the influence of these factors on transplant candidacy in 8,315 patients receiving dialysis treatment for ESRD in North Carolina, South Carolina, and Georgia. We found important race-sex differences in the likelihood of being identified as a transplant candidate. These differences persisted after adjustment for other patient characteristics, including illness severity and certain comorbid conditions. Characteristics found to be positively associated with candidacy included age less than 30 years (P less than 0.00001), living with a spouse and children (P = 0.004), and employment status (P = 0.006). Characteristics and comorbid conditions that were negatively associated with candidacy included 8 years or less of formal education (P = 0.001), cancer (P = 0.0006), visual impairment (P = 0.006), congestive heart failure (P = 0.008), and peripheral vascular disease (P = 0.01). Compared with white males, after adjustment for these factors, the likelihood (95% confidence interval) of being identified as a transplant candidate was: white females, 0.88 (0.65 to 1.18); black males, 0.77 (0.59 to 0.99); and black females, 0.66 (0.51 to 0.87). We conclude that although socioeconomic and medical factors are strongly associated with transplant candidacy, these associations do not adequately explain the observed race-sex differences in transplant candidacy status.     

Prospective multicentre study of the natural history of atherosclerotic renal artery stenosis in patients with peripheral vascular disease

BACKGROUND: Many patients with peripheral vascular disease have coincident renal artery stenosis. The present study characterized the natural history of the condition. METHODS: Some 98 patients (71 men) with more than 50 per cent atherosclerotic renal artery stenosis (unilateral 64, bilateral 34) were recruited prospectively. Measurements of serum creatinine, blood pressure and renal size were recorded at baseline and every 6 months, for a minimum of 2 years. RESULTS: Data were available for 85 patients with a minimum follow-up of 2 years. The mean age was 71 (range 51-87) years. All 52 patients with unilateral renal artery stenosis were managed conservatively (group 1); 21 of the 33 patients with bilateral disease had no intervention (group 2) and the remaining 12 had angioplasty or reconstruction (group 3). The overall mortality rate was 32 per cent at 2 years (27 patients) and this was similar in all three groups. In only three patients was death related directly to renovascular disease; coronary disease accounted for the majority of deaths. All three patients who needed dialysis died within 1 year. In survivors from groups 1 and 3 there was a significant increase in serum creatinine concentration at follow-up. Blood pressure did not increase significantly. CONCLUSION: Patients with renal artery stenosis and peripheral vascular disease had a poor prognosis, but this was not directly attributable to renal failure.     

Late incidence and predictors of persistent or recurrent heart failure in patients with mitral prosthetic valves

OBJECTIVE: The study's objective was to examine factors associated with persistent or recurrent congestive heart failure after mitral valve replacement. METHODS: Patients who underwent mitral valve replacement with contemporary prostheses (N = 708) were followed with annual clinical assessment and echocardiography. Cox proportional hazard models were developed to evaluate the impact of demographic, comorbid, and valve-related variables on the occurrence of congestive heart failure after mitral valve replacement, defined as the composite outcome of New York Heart Association class III or IV symptoms or death caused by congestive heart failure postoperatively. Factors associated with all-cause mortality were also examined. Models were bootstrapped 1000 times. RESULTS: The total follow-up was 3376 patient-years (mean 4.8 +/- 3.7 years, range 60 days to 17.1 years). Freedom from New York Heart Association III or IV symptoms or death caused by congestive heart failure was 96.1% +/- 0.8%, 82.7% +/- 1.7%, 66.4% +/- 3.0%, and 38.8% +/- 6.9% at 1, 5, 10, and 15 years, respectively. Preoperative New York Heart Association class, left ventricular grade, atrial fibrillation, coronary artery disease, smoking, persistent tricuspid regurgitation, and redo status predicted congestive heart failure postoperatively (all P <.05). Patients who underwent mitral valve replacement for pure mitral stenosis had less congestive heart failure events after surgery than those with regurgitation or mixed disease. Prosthesis size and elevated transprosthesis gradients were not predictive of freedom from congestive heart failure after mitral valve replacement. Atrial fibrillation, persistent tricuspid regurgitation, and surgical referral for mitral valve replacement at an advanced functional stage were also risk factors for all-cause mortality. CONCLUSIONS: This study identifies the incidence of and risk factors for congestive heart failure and death late after mitral valve replacement. Although prosthesis size has no effect, other potentially modifiable factors such as atrial fibrillation, persistent tricuspid regurgitation, and late surgical referral have a negative impact on freedom from congestive heart failure and overall survival after mitral valve replacement.     

Evidence-based medicine in renal artery stenting

Atherosclerotic renovascular disease is an increasingly recognized cause of severe hypertension and declining kidney function. Patients with atherosclerotic renovascular disease have been demonstrated to have an increased risk of adverse cardiovascular events. Over the course of the last two decades renal artery revascularization for treatment of atherosclerotic renal artery stenosis (RAS) has gained great increase via percutaneous techniques. However the efficacy of contemporary revascularization therapies in the treatment of renal artery stenosis is unproven and controversial. The indication for renal artery stenting is widely questioned due to a not yet proven benefit of renal revascularization compared to best medical therapy. Many authors question the efficacy of percutaneous renal revascularization on clinical outcome parameters, such as preservation of renal function and blood pressure control. None of the so far published randomized controlled trials could prove a beneficial outcome of RAS revascularization compared with medical management. Currently accepted indications for revascularization are significant RAS with progressive or acute deterioration of renal function and/or severe uncontrollable hypertension, renal function decline with the use of agents blocking the renin-angiotensin system and recurrent flash pulmonary edema. The key point for success is the correct selection of the patient. This article summarizes the background and the limitations of the so far published and still ongoing controlled trials.     

Atherosclerotic renovascular disease causing renal impairment--a case for treatment

Renovascular disease is a potentially curable cause of renal failure. In a prospective survey over an eighteen month period atherosclerotic renal artery disease was the cause of renal failure in 14% of patients over the age of fifty years accepted for renal replacement therapy at this hospital. Ten patients were found to be suffering from atherosclerotic renovascular disease causing renal failure but in only one was treatment able to reverse renal failure. The major problem with this group of patients is the widespread nature of their disease affecting many other organs. Significant morbidity is associated with their investigation. Although potentially curable, atherosclerotic renovascular disease is a frequent cause of renal failure in patients over the age of fifty years but is also difficult to treat.