Renal stenting for incidentally discovered renal artery stenosis: is there any outcome benefit?

We evaluated whether there was a clinical outcome benefit in patients incidentally discovered to have high-grade renal artery stenosis (RAS) and treated with percutaneous transluminal renal angioplasty and stenting (PTRAS) at the time of angiogram for another indicated procedure. A retrospective chart review was performed on all patients undergoing renal arteriography over 4 years at our academic tertiary-care referral center. Review of catheterization reports was used to identify patients diagnosed with high-grade RAS (reduction of > or =70% luminal diameter by arteriogram). Patients treated with PTRAS were identified. Baseline and postprocedure blood pressure (BP, an average of at least three independent measurements), glomerular filtration rate, serum creatinine, and antihypertensive medication regimen were compared for 12 months of follow-up. Over 4 years, 124 patients underwent renal arteriography and 78 (63%) were diagnosed with high-grade RAS. Fifty-eight patients (74% of those with high-grade RAS) received PTRAS. Patients treated with PTRAS had similar baseline characteristics to those with high-grade RAS with no intervention, with the exception of lower diastolic BP (DBP; 74 +/- 11.2 vs. 80 +/- 14.2 mm Hg, p = 0.04) and a higher proportion of hyperlipidemia (78 vs. 55%, p = 0.05). Thirty-eight out of 58 PTRAS patients (66%) received sufficient follow-up to assess outcomes. When baseline and postprocedure variables were compared in PTRAS patients with 12-month follow-up, there was a reduction in systolic BP (SBP, 153 +/- 20.8 vs. 136 +/- 27.2 mm Hg, p = 0.01) and mean arterial pressure (MAP, 103 +/- 11.2 vs. 95 +/- 14 mm Hg, p = 0.04). When these patients were stratified by those with an increase, decrease, or no change in postprocedure antihypertensive medications, significant reductions in SBP, MAP, and DBP were noted only in the patient population that also had an increase in the number of antihypertensive medications. No differences in renal insufficiency were detected. Patients with high-grade RAS incidentally discovered during arteriography performed for extrarenal disease and treated with PTRAS have a modest reduction in BP, which is significant only in those patients with an increased number of antihypertensive medications postprocedure. Caution must be taken in stenting patients with incidental RAS as outcome benefit may be minimal when compared to medical management only.     

Intrarenal hemodynamic alterations induced by anti-GBM antibody

An isolated perfused kidney system (IPK) was used to study the direct intrarenal hemodynamic effects of binding of anti-glomerular-basement membrane (anti-GBM) antibody in the absence of all other circulating humoral and cellular inflammatory mediators. Control IPK's (perfused with Krebs-Henseleit buffered 5% albumin solution containing non-immune globulin) had a renal vascular resistance (RVR) mean +/- SEM 3.10 +/- 0.47 mm Hg/ml/min and a GFR mean +/- SEM 0.63 +/- 0.8 ml/min/g. Anti-GBM antibody administration raised RVR (4.83 +/- 0.52 mm Hg/ml/min, P less than 0.01) and lowered GFR (0.34 +/- 0.04 ml/min/g, P less than 0.01). Perfusate renin activity was higher after antibody administration (684 +/- 87 ng AI/ml/hr compared with control 308 +/- 42 ngAI/ml/hr, P less than 0.01). Treatment with Sar1Ala8All (3 X 10(-6) M) or captopril (10 mg/ml) attenuated antibody-induced vasoconstriction (RVR mm Hg/ml/min, Sara1Ala8All = 3.78 +/- 0.13 captopril = 3.26 +/- 0.12, both P less than 0.05 compared with anti-GBM alone). Both inhibitors of the renin-angiotensin system (RAS) also aggrevated the decline in GFR seen after antibody administration (GFR ml/min/g, Sara1Ala8All = 0.24 +/- 0.05, Captopril = 0.18 +/- 0.03, both P less than 0.05 compared with anti-GBM alone). These IPK studies demonstrate that anti-GBM antibody itself may directly induce intrarenal hemodynamic alterations in the absence of complement activation, neutrophil infiltration, neural influences or circulating vasoactive substances. The results from perfusate renin sampling and blockade of the RAS provide evidence that anti-GBM antibody deposition activates the intrarenal RAS and thereby induces significant hemodynamic alterations.     

The management of renal artery atherosclerosis for renal salvage: does stenting help?

OBJECTIVE: The use of endovascular techniques to treat renal artery stenosis (RAS) has increased in recent years but remains controversial. The purpose of this study was to review the outcomes and durability of percutaneous transluminal angioplasty and stenting (PTA/S) for patients with RAS and decreasing renal function. METHODS: Between 1999 and 2004, 125 consecutive patients underwent angiography and intervention for renal salvage and formed the basis of this study. Inclusion criteria for this study included serum creatinine greater than 1.5 mg/dL, ischemic nephropathy, and high-grade RAS perfusing a single functioning kidney. Patients undergoing PTA/S for renovascular hypertension or fibromuscular dysplasia or in conjunction with endovascular stent grafting for aneurysm repair were excluded. The original angiographic imaging was evaluated for lesion grade and parenchymal kidney size. All medical records and noninvasive testing were reviewed. Preoperative and postoperative patient data were standardized and analyzed by using chi(2) tests for nominal values and t tests for continuous variables. The Modification of Diet in Renal Disease equation was used to estimate glomerular filtration rate (GFR), and univariate analysis was performed. RESULTS: Preoperative variables included the presence of coronary artery disease (93%), diabetes (44%), tobacco use (48%), and hypercholesterolemia (70%). RAS was suspected on the basis of preoperative duplex imaging or magnetic resonance angiography. Aortography and PTA/S were performed in 125 patients (mean age, 71 years; 59% male) with a mean baseline creatinine level of 2.2 mg/dL. There were two mortalities (1.6%) in the 30-day postoperative period, but there was no case of acute renal loss. Blood pressure decreased after PTA/S (151/79 mm Hg before vs 139/72 mm Hg after 1 month; P < .03). For all patients, the estimated GFR went from 33 +/- 12 mL . min(-1) . 1.73 m(-2) (mean +/- SD) to 37 +/- 19 mL . min(-1) . 1.73 m(-2) at 6 months (P = .10). Sixty-seven percent of treated patients had improvement (>10% increase in GFR) or stabilization of renal function. A rapid decline in GFR before intervention was correlated with improvement after PTA/S. Responders after PTA/S had a 27% decrease in GFR before intervention (44 +/- 13 mL . min(-1) . 1.73 m(-2) to 32 +/- 13 mL . min(-1) . 1.73 m(-2); P < .001) with a negative to positive slope change in GFR values. Ten patients underwent reintervention for in-stent restenosis. Cases without improvement in GFR after PTA/S were associated with eventual dialysis need (P = .01; mean follow-up, 19 months). Survival at 3 years was 76%, and dialysis-free survival was 63% as estimated by Kaplan-Meier analyses. CONCLUSIONS: Renal artery stenoses causing renal dysfunction can be safely treated via endovascular means. Rapidly decreasing renal function is associated with the response to renal artery angioplasty/stenting and helps identify patients for renal salvage.     

Renal function and blood pressure five years after puumala virus-induced nephropathy

BACKGROUND: Nephropathia epidemica (NE) is a mild form of hemorrhagic fever with renal syndrome caused by Puumala hantavirus. Its long-term prognosis is considered favorable. Some reports suggest, however, that a previous hantavirus infection increases the risk of hypertension. METHODS: We studied 46 previously healthy subjects (26 males and 20 females, mean age of 44 years) who had serologically confirmed NE three to seven years previously, and 38 healthy, seronegative controls (22 males and 16 females, mean age of 44 years). Ambulatory blood pressure (ABP) was monitored. Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were determined by 51CrEDTA and 131I-hippurate clearances, respectively. The filtration fraction (FF) was calculated. Quantitative 24-hour urinary protein excretion (UprotE) and timed overnight urinary excretion of alpha1-microglobulin were measured. RESULTS: The NE patients had a higher mean ambulatory systolic BP than the controls (123 +/- 13 vs. 117 +/- 9 mm Hg, P = 0. 008). GFR and FF were increased in patients compared with controls (GFR, 120 +/- 20 vs. 109 +/- 14 mL/min/1.73 m2, P = 0.006; FF, 19 +/- 3 vs. 18 +/- 3%, P = 0.030), but ERPF did not differ between the groups. The patients also had higher UPE than the controls (median 0. 18 g/day, range 0.12 to 0.38 vs. median 0.14 g/day, range 0.09 to 0. 24, P < 0.001, respectively). The overnight urinary excretion rate of alpha1-microglobulin exceeded 7 microg/min in nine patients. CONCLUSION: Three to seven years after NE, the patients had higher GFR and FF, more proteinuria, and higher ambulatory systolic BP compared with the healthy controls. NE may thus cause mild renal lesions and alterations in BP in some patients.     

Effects of enalapril and eprosartan on the renal vascular nitric oxide system in human essential hypertension

BACKGROUND: Experimental data in humans on the contribution of angiotensin-converting enzyme inhibitors and angiotensin II type 1 receptor blockers to the nitric oxide system of the renal vasculature are inconsistent. Enalapril and eprosartan, alone and in combination, were used to determine their short-term effects on the renal nitric oxide system and renal hemodynamics of human subjects with essential hypertension. METHODS: Twenty male, white patients (27 +/- 1 years) with mild essential hypertension (143 +/- 11/95 +/- 6 mm Hg) were included in a double-blind, randomized, placebo-controlled, fourfold cross-over study with placebo, enalapril (20 mg/day), eprosartan (600 mg/day), or combination of both drugs (10 and 300 mg/day, respectively) each over a one week period followed by a two-week washout phase. After each study phase the glomerular filtration rate (GFR) and renal plasma flow (RPF) were determined. Basal nitric oxide synthesis of the renal vasculature was assessed by the decrease in RPF after inhibition of nitric oxide synthase with NG-monomethyl-L-arginine (L-NMMA; 4.25 mg/kg). RESULTS: After one week of therapy, the combination therapy decreased casual blood pressure by 5 +/- 2/3 +/- 1 mm Hg versus placebo (P < 0.01). Neither enalapril alone (-2 +/- 2/1 +/- 2 mm Hg, NS vs. placebo) nor eprosartan alone (-1 +/- 1/0 +/- 2 mm Hg, NS vs. placebo) had a clear-cut significant effect on casual blood pressure. In the combination phase, RPF increased by 123 +/- 36 mL/min (P < 0.01). Neither enalapril alone (+59 +/- 46 mL/min, P = 0.21) nor eprosartan alone (+113 +/- 51 mL/min, P = 0.06) had a clear-cut significant effect on RPF. Changes of RPF induced by treatment correlated with the L-NMMA induced decrease in RPF in the combination (r = 0.70, P < 0.01) and eprosartan phase (r = 0.86, P < 0.001), but not in the enalapril phase (r = -0.44, P = 0.10). Renal vascular resistance was reduced by each active treatment with the most prominent reduction in the combination phase. GFR was unaffected by any treatment. CONCLUSIONS: In contrast to the effects of either substance alone, a combination of half the dose of eprosartan with half the dose of enalapril had a prominent effect on renal perfusion. The effects of eprosartan on RPF are mediated, at least in part, by an increased bioavailability of nitric oxide in the renal vasculature.     

Plasma renin activity and the renal response to nitric oxide synthesis inhibition.

Inhibition of systemic endothelium-derived relaxing factor (EDRF) synthesis with L-Nw-nitroarginine (L-NAME) results in decreased RBF, which can be reversed by acute blockade of angiotensin II (AII). Because AII is particularly elevated in the renal circulation, it was hypothesized that the degree of renal vasoconstriction produced by L-NAME in Inactin-anesthetized rats is related to PRA. To test this, PRA was chronically increased or suppressed by the manipulation of dietary sodium (eating 0.03% sodium chow or deoxycorticosterone acetate plus drinking 1% NaCl, respectively). After 10 days, rats were anesthetized for determination of blood pressure (BP) and RBF before and after L-NAME (10 mg/kg body wt). In rats with high PRA (61.6 +/- 10.4 ng of angiotensin I [Al]/mL/h; N = 8), L-NAME increased BP by 29 +/- 2 mm Hg (from 110 +/- 4 to 139 +/- 5 mm Hg; P < 0.001), decreased RBF by 27% (from 7.9 +/- 0.3 to 5.8 +/- 0.3 mL/min/g kidney wt; P < 0.001), and increased renal vascular resistance (RVR) by 67% (from 14.5 +/- 0.9 to 24.2 +/- 1.1 resistance units [RU]; P < 0.001). When rats with high PRA (N = 8) were treated with 10 mg/kg body wt of DuP 753, on AII receptor antagonist, L-NAME similarly increased BP by 30 +/- 5 mm Hg (from 81 +/- 3 to 111 +/- 5; P < 0.001) but RBF did not change and RVR increased by only 31% (from 10.9 +/- 0.8 to 13.3 +/- 0.7 RU; P < 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)     

Impact of combined mycophenolate mofetil and low-dose calcineurin inhibitor therapy on renal function, cardiovascular risk factors, and graft function in liver transplant patients: preliminary results of an open prospective study

As liver transplantation (LT) is now being performed with excellent 1-year graft survival rates of 85% to 90%, attention has been shifted to reducing long-term complications of calcineurin inhibitors (CNI). We randomized LT patients (2:1) who displayed renal dysfunction under CNI treatment to either mycophenolate mofetil (MMF) (1000 mg twice a day) followed by stepwise reduction of CNI (n = 21; Tac trough levels <4 ng/mL, CsA trough levels <50 ng/mL); or continue their current CNI dose (n = 11; control group). Three months after study entry, we observed significantly decreased mean values in the CNI reduction group of serum creatinine (1.88 +/- 0.36 versus 1.58 +/- 0.33 mg/dL, P < .001) and BUN (39.2 +/- 11.8 versus 29.9 +/- 9.59 mg/dL, P < .001) with a significantly increased GFR (51.4 +/- 10.8 versus 61.6 +/- 14.1 mL/min, P < .001). Improved renal function in these long-term LT recipients (5.6 +/- 3.6 years posttransplant; range, 2 to 13 years) suggests at least a partial reversibility of CNI-induced renal damage. Furthermore, we found an improved lipid profile as well as a significantly decreased mean systolic (140 +/- 19 versus 130 +/- 14 mm Hg, P < .01) and diastolic (82 +/- 9 to 74 +/- 8 mm Hg, P < .001) blood pressure 3 months after introduction of MMF therapy. Additionally, transaminases significantly improved in the CNI reduction group within this time period (ALT 37.9 +/- 25.9 versus 25.2 +/- 13.2, P < .05). MMF and CNI-reduced immunosuppressive regimens may improve long-term patient survival, suggesting a broad application within the liver transplant setting.     

Effect of valsartan on urinary protein excretion and renal function in patients with chronic renal allograft nephropathy

Chronic allograft nephropathy (CAN) remains a significant cause of late renal allograft loss. Although many factors may be involved in pathogenesis, the hemodynamic and fibrogenic consequences of long-term therapy with cyclosporine (CsA) have been implicated as important potentially reversible causes. CsA's effect on CAN is mediated in part through increased renal expression of TGF-beta, which can be modified by administration of angiotensin receptor blockers (ARBs). A pilot study was undertaken to evaluate the safety and efficacy of the ARB valsartan on renal function and proteinuira in patients with CAN. Ten patients on CsA-based therapy with evidence of CAN received valsartan in an initial dose of 80 mg/d, force titrated to 160 mg/d after 4 weeks, for a total of 52 weeks. Renal function was evaluated by serum creatinine, 24-hour creatinine clearance (CrCl), and isotope, GFR and urinary protein by 24-hour protein excretion. The 10 patients were aged 20 to 71 years and had been transplanted for 88.2 +/- 64.8 months at the time of study. After 52 weeks of valsartan therapy mean blood pressure (BP) fell from 152/88 mm Hg to 138/77 mm Hg (P =.06); serum creatinine rose from 206 +/- 55 micromol/L to 238 +/- 81 micromol/L (P =.22.); GFR fell from 39.8 +/- 17.6 to 31.9 +/- 19 mL/min (P =.23); and urine protein fell from 2.16 +/- 2.7 to 1.12 +/-.095 g/24 hours (P =.13). Side effects of valsartan therapy were few and included transient hyperkalemia in 2/10 patients. The small rise in serum creatinine and fall in GFR observed were not statistically significant. Urine protein fell by more than 50%, though the small patient numbers in this pilot study prevent this from achieving statistical significance. It is concluded that valasartan reduces BP and proteinuria in CAN patients without inducing a serious worsening in renal function. Valsartan may have a role to play in the management of patients with CAN.     

Antihypertensive and antiproteinuric efficacy of ramipril in children with chronic renal failure

BACKGROUND: While the antihypertensive and renoprotective potency of angiotensin-converting enzyme (ACE) inhibitors is well-established in adults with hypertension and/or chronic renal failure, little experience exists in pediatric chronic kidney disease. METHODS: As part of a prospective assessment of the renoprotective efficacy of ACE inhibition and intensified blood pressure (BP) control, 397 children (ages 3 to 18 years) with chronic renal failure [CRF; glomerular filtration rate (GFR) 11 to 80 mL/min/1.73 m2] and elevated or high-normal BP received ramipril (6 mg/m2) following a 6-month run-in period including a two-month washout of any previous ACE inhibitors. Drug efficacy was assessed by two monthly office BP and proteinuria assessments, and by ambulatory BP monitoring at start and after 6 months of treatment. RESULTS: In the 352 patients completing six months of treatment, 24-hour mean arterial pressure (MAP) had decreased by a mean of 11.5 mm Hg (-2.2 SDS) in initially hypertensive subjects, but only by 4.4 mm Hg (-0.8 SDS) in patients with initially normal BP. A linear correlation was found between MAP at baseline and the change of MAP during treatment (r= 0.51; P < 0.0001). The antihypertensive response was independent of changes in concomitant antihypertensive medication or underlying renal disease. BP was reduced with equal efficacy during day- and nighttime. Urinary protein excretion was reduced by 50% on average, with similar relative efficacy in patients with hypo/dysplastic nephropathies and glomerulopathies. The magnitude of proteinuria reduction depended on baseline proteinuria (r= 0.32, P < 0.0001), and was correlated with the antihypertensive efficacy of the drug (r= 0.22, P < 0.001). The incidence of rapid rises in serum creatinine and progression to end-stage CRF during treatment did not differ from the pretreatment observation period. Mean serum potassium increased by 0.3 mmol/L. Ramipril was discontinued in three patients due to symptomatic hypotension or hyperkalemia. Hemoglobin levels decreased by 0.6 g/dL in the first two treatment months and remained stable thereafter. CONCLUSION: Ramipril appears to be an effective and safe antihypertensive and antiproteinuric agent in children with CRF-associated hypertension. The BP lowering and antiproteinuric effects are greatest in severely hypertensive and proteinuric children.     

Effects of renal arterial angiotensin I infusion on glomerular dynamics in sodium replete dogs

During intrarenal infusion of angiotensin I (AI), conversion to angiotensin II (AII) within the kidney has been shown to occur early enough to decrease glomerular filtration rate (GFR). To evaluate further the mechanism by which AI decreases GFR, micropuncture studies were conducted in sodium replete dogs. Feedback-mediated alterations in glomerular function were minimized by reducing renal arterial pressure to 90 mm Hg. During infusion of AI (0.82 +/- 0.01 micrograms min-1), renal blood flow (3.91 +/- 0.25 ml min-1 g-1) and GFR (0.63 +/- 0.04 ml min-1 g-1) decreased by 36.7 +/- 6.1% and 18.9 +/- 6.1%, respectively. Similarly, single nephron GFR decreased from 66.4 +/- 3.8 to 40.0 +/- 3.2 nl min-1 and estimated glomerular plasma flow (280 +/- 49 nl min-1) decreased by 55 +/- 6%. Stop-flow pressure (40.5 +/- 3.6 mm Hg) did not change significantly, while proximal tubular (21.8 +/- 1.4 mm Hg) and peritubular capillary pressures (13.2 +/- 1.8 mm Hg) decreased by 25.5 +/- 2.8% and 49.4% +/- 5.1%, respectively. Glomerular capillary and effective filtration pressures were not altered significantly. There were increases in both preglomerular (168%) and efferent (203%) arteriolar resistances, along with a decrease in the glomerular filtration coefficient (Kf) from 4.6 +/- 0.6 to 2.5 +/- 0.5 nl mm Hg-1 min-1. These data indicate that augmented intrarenal conversion of circulating AI reduces GFR as a consequence of decreases in Kf as well as in glomerular plasma flow, the latter being due to concomitant increases in preglomerular and efferent arteriolar resistances.     

Efficacy and safety of valsartan, an angiotensin II receptor antagonist, in hypertension after renal transplantation: a randomized multicenter study

BACKGROUND: The prevalence of posttransplant hypertension is high, and it appears to be a major risk factor for graft and patient survival. The aim of this study was to assess the efficacy and safety of valsartan, an angiotensin-receptor blocker (ARB), in the treatment of posttransplant hypertension. METHODS: A multinational, multicenter, prospective, randomized, double-blind, placebo-controlled study was performed on the treatment of hypertension (systolic blood pressure [BP] >/= 140 and/or diastolic BP >/= 90 mm Hg) in adult cyclosporin-treated renal transplant recipients randomized to receive either valsartan (80 mg once daily) or a matching placebo for 8 weeks. After the first 4 weeks, furosemide 20 mg twice daily was added on a open basis if systolic BP remained >/= 130 mm Hg and/or diastolic BP remained >/= 85 mm Hg. RESULTS: One hundred fifteen (valsartan = 57, placebo = 58) uncontrolled hypertensive patients despite monotherapy for hypertension, other than angiotensin-converting enzyme inhibitor or ARB, were randomized. In the valsartan group, significant decreases were seen in systolic BP (from 153 +/- 11 to 140.9 +/- 18.35 mm Hg at 4 weeks, and 136.5 +/- 15 mm Hg at 8 weeks) and diastolic BP (from 93 +/- 9 to 85.2 +/- 11.28 mm Hg at 4 weeks, and 83.8 +/- 9.2 mm Hg at 8 weeks). There was no significant change in the placebo group. In the valsartan group, a statistically but not clinically significant reduction was observed in the mean hemoglobin concentration (12.9 +/- 1.6 g/dL versus 13.8 +/- 1.6 g/dL at 4 weeks, P < .01; and 12.3 +/- 1.6 versus 13.8 +/- 1.7 at 8 weeks; P < .001) as well as a significant increase in serum potassium (4.4 +/- 0.5 mmol/L versus 4.1 +/- 0.4 mmol/L at 4 weeks, P < .01) vs placebo. CONCLUSIONS: Valsartan is effective in the treatment of posttransplant hypertension and is well tolerated.     

Regression of left ventricular hypertrophy after conversion to nocturnal hemodialysis

BACKGROUND: Left ventricular hypertrophy (LVH) is an independent risk factor for mortality in the dialysis population. LVH has been attributed to several factors, including hypertension, excess extracellular fluid (ECF) volume, anemia and uremia. Nocturnal hemodialysis is a novel renal replacement therapy that appears to improve blood pressure control. METHODS: This observational cohort study assessed the impact on LVH of conversion from conventional hemodialysis (CHD) to nocturnal hemodialysis (NHD). In 28 patients (mean age 44 +/- 7 years) receiving NHD for at least two years (mean duration 3.4 +/- 1.2 years), blood pressure (BP), hemoglobin (Hb), ECF volume (single-frequency bioelectrical impedance) and left ventricular mass index (LVMI) were determined before and after conversion. For comparison, 13 control patients (mean age 52 +/- 15 years) who remained on self-care home CHD for one year or more (mean duration 2.8 +/- 1.8 years) were studied also. Serial measurements of BP, Hb and LVMI were also obtained in this control group. RESULTS: There were no significant differences between the two cohorts with respect to age, use of antihypertensive medications, Hb, BP or LVMI at baseline. After transfer from CHD to NHD, there were significant reductions in systolic, diastolic and pulse pressure (from 145 +/- 20 to 122 +/- 13 mm Hg, P < 0.001; from 84 +/- 15 to 74 +/- 12 mm Hg, P = 0.02; from 61 +/- 12 to 49 +/- 12 mm Hg, P = 0.002, respectively) and LVMI (from 147 +/- 42 to 114 +/- 40 g/m2, P = 0.004). There was also a significant reduction in the number of prescribed antihypertensive medications (from 1.8 to 0.3, P < 0.001) and an increase in Hb in the NHD cohort. Post-dialysis ECF volume did not change. LVMI correlated with systolic blood pressure (r = 0.6, P = 0.001) during nocturnal hemodialysis. There was no relationship between changes in LVMI and changes in BP or Hb. In contrast, there were no changes in BP, Hb or LVMI in the CHD cohort over the same time period. CONCLUSIONS: Reductions in BP with NHD are accompanied by regression of LVH.     

Treatment of atherosclerotic ostial renal artery stenosis with the intravascular stent

Traditional approaches to revascularization for atherosclerotic ostial renal artery stenosis (RAS) have been suboptimal because of the invasiveness and relatively high perioperative morbidity and mortality of surgery and the low rates of success and long-term patency with percutaneous renal angioplasty (PTRA). We report our 5-year (1991 to 1996) experience with the intravascular stent (Palmaz stent; Johnson & Johnson, Miami Lakes, FL) for the treatment of ostial RAS in 129 patients (63 men, 66 women) and 148 arteries. The mean age of the patients was 71+/-10 years; 98% were hypertensive and 57% had renal dysfunction. Angiographic characteristics of RAS were unilateral in 78%, bilateral in 15%, and single kidney in 7%. The technical success rates were 98% for stent versus 11% for PTRA in the ostial location. The stent restenosis rate (angiographic) was 14% at 8+/-5 months. Systolic and diastolic blood pressures were as follows: baseline, 158+/-3 and 84+/-2 mm Hg; 6 months, 149+/-3 and 81+/-2 mm Hg; 12 months, 149+/-3 and 79+/-2 mm Hg; and 24 months, 135+/-3 and 79+/-2 mm Hg. Follow-up values were significantly lower than baseline (P < 0.05). The number of medications for hypertension initially decreased from 2.2+/-0.1 at baseline to 1.6+/-0.1 and 1.8+/-0.1 at 1 and 3 months, respectively (P < 0.05). By 6 months, however, the number of medications had increased and was not significantly different from before stent placement. Renal function was stable in the group as a whole: Cockroft-Gault creatinine clearance (C-G CrCl) at baseline was 40+/-2 mL/min; at 6 months, 36+/-3 mL/min; at 12 months, 39+/-3 mL/min; and at 24 months, 39+/-4 mL/min. When stratified by degree of renal function, values were similarly stable. Patients with a baseline serum creatinine level of 2 mg/dL or less had C-G CrCl values as follows: baseline, 53+/-3 mg/dL; 6 months, 43+/-4 mg/dL; 12 months, 46+/-4 mg/dL; and 24 months, 52+/-5 mg/dL. Those with a baseline serum creatinine level greater than 2 mg/dL had C-G CrCl values as follows: baseline, 26+/-2 mg/dL; 6 months, 31+/-4 mg/dL; 12 months, 32+/-6 mg/dL; and 24 months, 23+/-3 mg/dL. Of eight patients who were dialysis dependent, four (50%) recovered renal function with a mean serum creatinine level of 2.3+/-0.5 mg/dL at 15+/-6 months (range, 9 to 24 months). Stent placement for the treatment of atherosclerotic ostial RAS has a high success rate and a low rate of restenosis. Control of hypertension improves in most patients. Renal function stabilizes or improves in the majority of patients, even those with severe renal failure. These favorable outcomes are maintained long term.     

A comparison of cerebral blood flow reactivity to CO2 during halothane versus isoflurane anesthesia for carotid endarterectomy

The effects of isoflurane or halothane on cerebral blood flow (CBF) reactivity to changes in arterial carbon dioxide tension (PaCO2) during carotid endarterectomy were compared using the intravenous method of 133Xe-CBF determination. Patients, aged 65 +/- 3 yr (mean +/- SE), received O2 and N2O (1:1) and either 0.75% isoflurane (n = 7) or 0.5% halothane (n = 7). Patient demographic and clinical data were similar for both groups and followed the expected strata of patients with ischemic cerebrovascular disease. Measurements were made during the period of temporary bypass shunting. In the isoflurane group, increasing PaCO2 from 33.3 +/- 1.4 to 43.4 +/- 1.3 mm Hg resulted in a significant (P less than 0.05) increase in CBF from 21 +/- 1 to 35 +/- 4 mL.100 g-1.min-1. In the halothane group, increasing PaCO2 from 31.1 +/- 1 to 39.4 +/- 1.6 mm Hg resulted in a significant increase in CBF from 26 +/- 3 to 37 +/- 3 mL.100 g-1.min-1. Mean CBF reactivity to changes in PaCO2 (mL.100 g-1.min-1.mm Hg-1) was 1.74 +/- 0.39 for isoflurane and 1.78 +/- 0.4 for halothane (not significant), corresponding to a relative change of 4.8% +/- 0.8% and 5.2% +/- 1.3% per mm Hg, respectively. There is no significant difference between halothane and isoflurane in their effects on CO2 reactivity in the mildly hypocapnic to normocapnic range.     

Glomerular filtration rate after left renal vein division and reconstruction during infrarenal aortic aneurysm repair

OBJECTIVES: The study assessed the effect on postoperative renal function of left renal vein (LRV) division and reconstruction by direct reanastomosis or graft interposition during infrarenal abdominal aortic aneurysm (AAA) repair. METHODS: Between January 2001 and March 2006, 1189 patients underwent elective open repair of infrarenal AAAs. LRV division was performed in 15 (1.3%) and its reconstruction in all but one (LRV group), where the LRV was occluded. Patients' glomerular filtration rates (GFRs) were retrospectively estimated through postoperative day 4 by using the Cockcroft-Gault equation and compared with the GFRs of 56 controls undergoing AAA repair without LRV division (control group) randomly identified from a prospectively compiled database in a 4:1 ratio. Post hoc 1:1 case-matched analysis was also performed. Statistical analyses were performed as appropriate. RESULTS: Comparison of demographics and risk factors revealed no statistically significant differences between the two groups with the exception of the following: AAAs were larger in LRV group (71.4 +/- 17.1 mm vs 56.0 +/- 14.6 mm; P = .003) and preoperative GFR was lower in LRV group (65.3 +/- 19.0 mL/min/1.73 m(2) vs 82.8 +/- 22.3 mL/min/1.73 m(2); P = .009). Postoperatively, the trend of GFR with time did not differ between groups (P = .33). The variation of GFR at day 4 after surgery compared with preoperative values was not different either (5.6 +/- 12.6 mL/min/1.73 m(2) vs 1.0 +/- 15.5 mL/min/1.73 m(2); P = .67). A further 1:1 case-matched multivariate analysis of variance, matching patients and controls by AAA size and preoperative GFR, showed no difference in trend of GFR with time between groups (P = .15). Operative time was not significantly longer in LRV group (148.4 +/- 35.8 minutes vs 131.0 +/- 40.3 minutes; P = .07). No differences between groups were found for blood loss (585.7 +/- 264.2 mL vs 567.7 +/- 222.5 mL; P = .88), perioperative complications (5 vs 8; P = .12), or hospital length of stay (6.2 +/- 1.8 days vs 5.5 +/- 1.2 days; P = .10). A 6-month follow-up of renal function available in 12 patients of LRV group showed no significant decrease in GFR compared with postoperative values (70.8 +/- 24.8 mL/min/1.73 m(2) vs 69.1 +/- 23.5 mL/min/1.73 m(2); P = .86). At duplex scan, the reconstructed LRV could be insonated in nine of these 12 patients and all were patent. CONCLUSIONS: LRV division during AAA repair was associated with larger aneurysms and preoperative subclinical renal function impairment. In these patients, LRV reconstruction was associated with the maintenance of preoperative renal functional status without significantly lengthening of operative time or increasing the complications from surgery.     

Dual blockade of the renin-angiotensin system versus maximal recommended dose of ACE inhibition in diabetic nephropathy

BACKGROUND: Albuminuria and hypertension are predictors of poor renal and cardiovascular outcome in diabetic patients. We tested whether dual blockade of the renin-angiotensin system (RAS) with both an angiotensin-converting enzyme (ACE) inhibitor and an angiotensin II receptor blocker (ARB) is superior to maximal recommended dose of ACE inhibitor in type 1 diabetic patients with diabetic nephropathy (DN). METHODS: We performed a randomized, double-blind, crossover trial with 8 weeks treatment with placebo and irbesartan 300 mg (once daily), added on top of enalapril 40 mg (once daily). We included 24 type 1 patients with DN. At the end of each treatment period, albuminuria, 24-hour blood pressure, and glomerular filtration rate (GFR) were measured. RESULTS: Values on ACE inhibitors + placebo were: albuminuria [mean (95% CI)], 519 (342 to 789) mg/24 hours; blood pressure [mean (SEM)], 131 (3)/74 (1) mm Hg, and GFR [mean (SEM)], 65 (5) mL/min/1.73 m2. Dual blockade of the RAS induced a reduction in albuminuria [mean (95% CI)] of 25% (15, 34) (P < 0.001), a reduction in systolic blood pressure of 8 mm Hg (4, 12) (P = 0.002), and a reduction of 4 mm Hg (2, 7) (P = 0.003) in diastolic blood pressure. GFR and plasma potassium remained unchanged during both treatment regimes. Dual blockade was safe and well tolerated. CONCLUSION: Dual blockade of the RAS is superior to maximal recommended dose of ACE inhibitors with regard to lowering of albuminuria and blood pressure in type 1 patients with DN. Long-term trials are needed to further establish the role of dual blockade of the RAS in renal and cardiovascular protection.     

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.     

Replacement of calcineurin-inhibitors with sirolimus as primary immunosuppression in stable cardiac transplant recipients

BACKGROUND: Calcineurin-inhibitor (CNI) nephrotoxicity is a major cause of morbidity and mortality after cardiac transplantation. The aim of this study was to assess over 2 years the safety and effect on renal function of withdrawal of CNI immunosuppression and replacement with sirolimus (SRL) in stable cardiac transplant recipients. METHODS: CNI was substituted with SRL in 78 cardiac transplant recipients (SRL group) of whom 58 (group A) had CNI-induced renal impairment (glomerular filtration rate [GFR] <50 mL/min) and 20 (group B) had preserved renal function (GFR >50 mL/min). Fifty-one patients (CNI group) with renal impairment (GFR < or =50 mL/min) maintained on CNI served as controls. Secondary immunosuppressants were unchanged. RESULTS: In the SRL group, GFR increased from 47.0+/-18.0 to 61.2+/-22.2 ml/min (P=0.0001) 24 months after SRL initiation. In Group A, GFR increased from 40.5+/-12.7 to 53.9+/-19.8 mL/min (P<0.0001). In Group B, GFR increased marginally from 67.2+/-15.8 to 83.5+/-27.8 mL/min (P=0.10). In the CNI group, GFR declined from 40.5+/-14.0 mL/min to 36.4+/-12.5 mL/min (P=0.23) after 24 months of follow up. There was no significant difference in cardiac rejection or cardiac allograft function. In SRL group, proteinuria increased from 299+/-622 mg/day to 517+/-795 mg/day (P=0.0002) 12 months after SRL initiation and then stabilized; it did not differ from CNI group at 24 months (637+/-806 vs. 514+/-744 mg/day, P=0.39). Uric acid decreased from 7.6+/-2.4 to 6.2+/-1.9 mg/dL (P=0.0007) in the SRL group. CONCLUSIONS: Graduated substitution of CNI with SRL in cardiac transplant recipients is safe and improves renal function, without cardiac compromise.     

Renal hemodynamics and reduction of proteinuria by a vasodilating beta blocker versus an ACE inhibitor.

The effects of a nonselective beta-adrenergic blocking drug with beta-2 agonist activity (dilevalol 200 mg) on proteinuria and renal hemodynamics were evaluated in a double-blind crossover study versus an ACE inhibitor (enalapril 5 mg) in eight patients with glomerulonephritis, moderate renal function impairment and proteinuria greater than 1 g/24 hr. Patients were studied after a one week placebo phase while off all other medications, except steroids in a few cases, and after three weeks of treatment. A 10-day placebo washout perod was included between the various drug treatments. During each period renal hemodynamics were measured by clearance techniques, and urinary protein excretion as well as fractional clearance of albumin and IgG were determined. Both drugs reduced mean arterial pressure and proteinuria to a similar extent [mean arterial pressure: placebo 108 +/- 13 mm Hg; dilevalol 103 +/- 11 mm Hg (P less than 0.05); enalapril 103 +/- 12 mm Hg (P less than 0.05); protein excretion: placebo 5.1 +/- 4.2 g/day; dilevalol 3.3 +/- 3.0 g/day (P less than 0.05); enalapril 2.8 +/- 2.8 g/day (P less than 0.05)]. The antiproteinuric effect was greater with enalapril than dilevalol. Dilevalol reduced GFR [baseline inulin clearance: 73.3 +/- 38 ml/min/1.73 m2; after dilevalol: 63.3 +/- 28 ml/min/1.73 m2 (P less than 0.05)] and the decrease of proteinuria correlated positively with the reduction of GFR. Enalapril did not significantly lower the GFR (inulin clearance during enalapril 66.8 +/- 23 ml/min/1.73 m2) and the reduction of proteinuria did not correlate with the lowering of the GFR.(ABSTRACT TRUNCATED AT 250 WORDS)     

Progression of diabetic nephropathy

BACKGROUND: Diabetic nephropathy is a major cause of renal failure. The decline in glomerular filtration rate (GFR) is highly variable, ranging from 2 to 20, with a median of 12 mL/min/year. The risk factors of losing filtration power (progression promoters) have not been clearly identified. Furthermore, information on optimal arterial blood pressure, glycemic control, and cholesterol levels are lacking. METHODS: We measured GFR with (51)Cr-EDTA plasma clearance technique, blood pressure, albuminuria, glycosylated hemoglobin A1c, and serum cholesterol every year for seven years (range 3 to 14 years) in 301 consecutive type 1 diabetic patients with diabetic nephropathy recruited consecutively during 1983 through 1997. Diabetic nephropathy was diagnosed clinically if the following criteria were fulfilled: persistent albuminuria> 200 microg/min, presence of diabetic retinopathy, and no evidence of other kidney or renal tract disease. In total, 271 patients received antihypertensive treatment at the end of the observation period. RESULTS: Mean arterial blood pressure was 102 +/- 0.4 (SE) mm Hg. The average decline in GFR was 4.0 +/- 0.2 mL/min/year and even lower (1.9 +/- 0.5 mL/min/year) in the 30 persistently normotensive patients, none of whom had ever received antihypertensive treatment (P < 0.01). A multiple linear regression analysis revealed a significant positive correlation between the decline in GFR and mean arterial blood pressure, albuminuria, glycosylated hemoglobin A(1c), and serum cholesterol during follow-up (R(adj)(2) = 0.29, P < or = 0.001). No threshold level for blood pressure, glycosylated hemoglobin A(1c), or serum cholesterol was demonstrated. A two-hit model with mean arterial blood pressure and glycosylated hemoglobin A(1c) below and above the median values (102 mm Hg and 9.2%, respectively) revealed a rate of decline in GFR of only 1.5 mL/min/year in the lowest stratum compared with 6.1 mL/min/year in the highest stratum (P < 0.001). CONCLUSIONS: The prognosis of diabetic nephropathy has improved during the past decades, predominantly because of effective antihypertensive treatment. Genuine normotensive patients have a slow progression of nephropathy. Several modifiable variables have been identified as progression promoters.