Rituximab for rescue and maintenance therapy in rapidly progressive life-threatening antineutrophil cytoplasmic autoantibody-associated systemic vasculitis.

Antineutrophil cytoplasmic autoantibody (ANCA)-associated systemic vasculitides (AASV) consists of small-vessel systemic inflammatory disorders which commonly affect the kidneys and without treatment have a poor prognosis. Rituximab is a novel biological agent which is being used experimentally in the management of AASV. This report presents the case of a young woman with rapidly progressive life-threatening AASV. Despite prompt diagnosis and initial treatment with steroids and alkylating agents her condition became life threatening. With addition of rituximab therapy she showed an excellent sustained response. Rituximab appears an effective and safe treatment choice for the induction of remission in severe AASV that is not responding to standard agents, at the initial presentation and for maintenance therapy, without the development of common serious side-effects associated with immunosuppression.

Effects of renal volume and single-kidney glomerular filtration rate on renal functional outcome in atherosclerotic renal artery stenosis.

BACKGROUND: Renal functional outcome is unpredictable after revascularization of high-grade atherosclerotic renal artery stenosis (RAS). 'Hibernating' parenchyma describes acute parenchymal injury where renal dysfunction is potentially reversible with treatment of the stenosis. We analysed renal parenchymal volume (PV) and single-kidney glomerular filtration rate (SK-GFR) characteristics to identify kidneys with hibernating parenchyma and hence determine renal functional outcome after revascularization. METHODS: Fifty patients with > or =50% RAS underwent baseline analyses: (i) PV using magnetic resonance imaging; (ii) radioisotopic SK-GFR. Twenty-one patients (27 kidneys) underwent renal revascularization and 29 medical therapy alone. RESULTS: Patients with revascularized kidneys manifesting high PV:SK-GFR showed improvement in global estimated GFR compared to conservatively managed counterparts at 6 months and 1 year (6 months: 6.2 +/- 2.9 versus -3.7 +/- 6.8, P = 0.038; 1 year: 3.5 +/- 3.0 versus -5.1 +/- 5.1 ml/min/1.73 m(2), P = 0.021). Twelve revascularized patients (16 kidneys) underwent repeat SK-GFR 4 months post-revascularization. Six of 16 revascularized kidneys had high baseline PV:SK-GFR and showed improved SK-GFR compared to kidneys with low or normal PV:SK-GFR (6.3 +/- 2.0 versus -0.9 +/- 4.2 ml/min, P = 0.002). CONCLUSIONS: Our data suggest that, after revascularization, GFR improvement is likely if there is a disproportionately higher baseline PV:SK-GFR in the RAS kidney. Analysing these parameters can potentially identify these 'hibernating' kidneys and aid determination of renal functional outcome in RAS.

Progression of cardiac dysfunction in patients with atherosclerotic renovascular disease.

BACKGROUND: Patients with atherosclerotic renovascular disease (ARVD) are at increased risk of heart disease because of the association with hypertension, coronary artery disease, cardiac failure and chronic kidney disease (CKD). A previous echocardiographic cross-sectional study showed that only 5% of patients with ARVD had normal cardiac structure and function at baseline. In this longitudinal study of the same patient cohort the progression of cardiac dysfunction and factors which predict declining cardiac function in patients with ARVD were delineated. METHODS: Seventy-nine patients were available for baseline analysis, but 16 withdrew from follow-up during the study. Forty-three patients (27M and 16F, age at study entry [mean +/- SD] 69.7 +/- 8.0 years) who were managed conservatively and 8 (age 69.8 +/- 5.7) who were managed with renal revascularization underwent echocardiography and 24 h ambulatory blood pressure investigations at baseline and 12 months thereafter. The two data sets were interrogated to determine changes in blood pressure and cardiac status (morphological and functional); baseline factors which predicted such changes were ascertained. Twelve patients underwent baseline investigation but did not complete follow-up because of death (nine patients) or requirement of dialysis (three patients). RESULTS: Conservatively managed patients: At 12 months eGFR, (38.6 +/- 18.3 vs 35.0 +/- 18.5 ml/min; P = 0.001) had fallen whilst proteinuria had increased (0.3 +/- 0.4 vs 0.6 +/- 0.8 g/24 h; P = 0.001). Despite no increase in the number of blood pressure medications there was a fall in blood pressure between baseline and follow-up investigations (140.0 +/- 16.5/75.3 +/- 11.8, MAP 98.6 +/- 12.3 mmHg vs 135.7 +/- 16.1/69.6 +/- 9.1, MAP 92.5 +/- 10.2 mmHg; P < 0.001 for diastolic blood pressure and MAP). At 12 months, there was an increase in the number of patients with LVH (72.9% vs 81.4%). There were increases in left ventricular dimensions [left ventricular end diastolic diameter (5.1 +/- 0.8 vs 5.5 +/- 0.8 cm; P = 0.009), and left ventricular end diastolic volume (140.9 +/- 39.5 vs 163.3 +/- 61.0 ml; P = 0.01)]. There was no significant relationship of these changes in cardiac parameters to anatomical severity of renal artery disease but patients with severe renal dysfunction at baseline had an increase in left ventricular dilatation at follow-up. Linear regression analysis revealed an association between elevated time-averaged PTH and LV dilatation [beta-coefficient and 95% confidence intervals, 0.18 (0.04, 0.32); P = 0.01]. Revascularization: No significant changes in any biochemical or echocardiographic parameters were seen between baseline and 1 year investigations in this small sub-group. CONCLUSION: Patients with ARVD exhibit a high prevalence of LVH at diagnosis and progressive left ventricular dilatation over the first year after diagnosis. This dilatation is associated with severe renal impairment at baseline and not associated with anatomical severity of renal artery disease.

Measurement of single kidney function using dynamic contrast-enhanced MRI: comparison of two models in human subjects.

PURPOSE: To compare two methods for assessing the single kidney glomerular filtration rate (SK-GFR) in humans using dynamic contrast-enhanced (DCE)-MRI. MATERIALS AND METHODS: Images were acquired from 39 separate MR studies of patients with atherosclerotic renovascular disease (ARVD). Data from the kidneys and descending aorta were analyzed using both a Rutland-Patlak plot and a compartmental model. MR estimates of the SK-GFR were compared with standard radioisotope measures in a total of 75 kidneys. RESULTS: Estimates of renal function using both techniques correlated well with radioisotope-assessed SK-GFR (Spearman's rho=0.81, Rutland-Patlak; rho=0.71, compartmental model). The Rutland-Patlak approach provided a near one-to-one correspondence, while the compartmental method tended to overestimate SK-GFR. However, the compartmental model fits to the experimental data were significantly better than those obtained using the Rutland-Patlak approach. CONCLUSION: DCE-MRI of the kidneys provides data that correlate well with reference measures of SK-GFR. However, further work, including image registration, is needed to isolate measurement of glomerular filtration to the level of the renal cortex.

Left ventricular morphology and function in patients with atherosclerotic renovascular disease.

Atherosclerotic renovascular disease (ARVD) is associated with heart disease. There has been no systematic study of cardiac structure and function in patients with this condition. In this study, the epidemiology of cardiac changes and their relationship to renal function, renovascular anatomy, and BP are delineated. With the use of a cross-sectional design, 79 patients with ARVD and 50 control patients without ARVD underwent echocardiography and 24-h ambulatory BP monitoring. Clinical and biochemical data were collected. Results were analyzed according to renal function, residual renal artery patency, and unilateral or bilateral ARVD. Only 4 (5.1%) patients with ARVD had normal cardiac structure and function. Patients with ARVD (age 70.7 +/- 7.5 yr; estimated GFR 36 +/- 19 ml/min) had significantly more cardiovascular comorbidity (77.2 versus 42.0%; P < 0.001), greater prevalence of left ventricular (LV) hypertrophy (78.5 versus 46.0%; P < 0.001) and LV diastolic dysfunction (74.6 versus 40.0%; P < 0.001), and greater LV mass index (183 +/- 74 versus 116 +/- 33 g/m2; P < 0.001) and LV end-diastolic volume index (82 +/- 35 versus 34 +/- 16 ml/m2; P < 0.001) than control subjects. BP was similar for both patient groups. For patients with ARVD, neither renal function nor renal artery patency predicted a difference in echocardiographic or ambulatory BP monitoring parameters. Patients with bilateral ARVD had greater LV mass index and LV dilation than patients with unilateral disease. Patients with ARVD exhibit a high prevalence of cardiac morphologic and functional abnormalities at early stages of renal dysfunction. Such patients must be identified early in their disease course to allow risk factor modification.

A prospective study of the determinants of renal functional outcome and mortality in atherosclerotic renovascular disease.

Atherosclerotic renovascular disease (ARVD) commonly causes renal failure and hypertension and is accompanied by high cardiovascular comorbidity and mortality. Interrelationships between these factors remain poorly understood. Patients with ARVD presenting to a single center between 1995 and 1999 were followed up, with prospective collection of clinical and biochemical data. Fifty men and 48 women were identified. Mean age at entry was 68.7 +/- 8.3 (SD) years, and baseline creatinine clearance (CrCl) was 35.5 +/- 20.7 mL/min. During follow-up (27.7 +/- 18.7 months), 10 patients required dialysis therapy, 11 patients underwent revascularization, and 35 patients (36%) died. Patients in whom renal function deteriorated during follow-up (n = 61) had similar ages, baseline CrCls, blood pressures, and comorbidities compared to patients with stable function. Mortality (55.7% versus 27.0%; P < 0.01) and proteinuria (protein, 1.3 +/- 1.6 versus 0.3 +/- 0.4 g/24 h; P < 0.001) were greater in patients with declining function. Baseline renal function was not significantly related to blood pressure, proteinuria, or change in renal function during follow-up (change in CrCl), but patients with a lower CrCl had increased mortality. There was no increase in cardiovascular comorbidity in groups with lower renal function. Patients with the most severe anatomic ARVD had worse hypertension and increased mortality, but severity of ARVD was unrelated to extent of renal dysfunction and proteinuria at baseline. Lack of correlation between renal artery anatomy and baseline renal function or functional outcome and correlation between renal functional outcome and proteinuria suggest that renal parenchymal damage is a major determinant of renal dysfunction and outcome in ARVD.