Effects of rare kidney diseases on kidney failure: a longitudinal analysis of the UK National Registry of Rare Kidney Diseases (RaDaR) cohort.

BACKGROUND: Individuals with rare kidney diseases account for 5-10% of people with chronic kidney disease, but constitute more than 25% of patients receiving kidney replacement therapy. The National Registry of Rare Kidney Diseases (RaDaR) gathers longitudinal data from patients with these conditions, which we used to study disease progression and outcomes of death and kidney failure. METHODS: People aged 0-96 years living with 28 types of rare kidney diseases were recruited from 108 UK renal care facilities. The primary outcomes were cumulative incidence of mortality and kidney failure in individuals with rare kidney diseases, which were calculated and compared with that of unselected patients with chronic kidney disease. Cumulative incidence and Kaplan-Meier survival estimates were calculated for the following outcomes: median age at kidney failure; median age at death; time from start of dialysis to death; and time from diagnosis to estimated glomerular filtration rate (eGFR) thresholds, allowing calculation of time from last eGFR of 75 mL/min per 1·73 m2 or more to first eGFR of less than 30 mL/min per 1·73 m2 (the therapeutic trial window). FINDINGS: Between Jan 18, 2010, and July 25, 2022, 27 285 participants were recruited to RaDaR. Median follow-up time from diagnosis was 9·6 years (IQR 5·9-16·7). RaDaR participants had significantly higher 5-year cumulative incidence of kidney failure than 2·81 million UK patients with all-cause chronic kidney disease (28% vs 1%; p<0·0001), but better survival rates (standardised mortality ratio 0·42 [95% CI 0·32-0·52]; p<0·0001). Median age at kidney failure, median age at death, time from start of dialysis to death, time from diagnosis to eGFR thresholds, and therapeutic trial window all varied substantially between rare diseases. INTERPRETATION: Patients with rare kidney diseases differ from the general population of individuals with chronic kidney disease: they have higher 5-year rates of kidney failure but higher survival than other patients with chronic kidney disease stages 3-5, and so are over-represented in the cohort of patients requiring kidney replacement therapy. Addressing unmet therapeutic need for patients with rare kidney diseases could have a large beneficial effect on long-term kidney replacement therapy demand. FUNDING: RaDaR is funded by the Medical Research Council, Kidney Research UK, Kidney Care UK, and the Polycystic Kidney Disease Charity.

The epidemiology of primary FSGS including cluster analysis over a 20-year period.

INTRODUCTION: Focal segmental glomerulosclerosis (FSGS) is one of the leading causes of nephrotic syndrome in adults. This epidemiological study describes a renal centre's 20-year experience of primary FSGS. METHODS: Patients were identified with a diagnosis of primary FSGS after exclusion of known secondary causes. In this retrospective observational study, data was collected for baseline demographics, immunosuppression and outcomes. A two-step cluster analysis was used to identify natural groupings within the dataset. RESULTS: The total cohort was made up of 87 patients. Those who received immunosuppression had lower median serum albumin than those who did not- 23g/L vs 40g/L (p<0.001) and higher median urine protein creatinine ratios (uPCR)- 795mg/mmol vs 318mg/mmol (p <0.001). They were more likely to achieve complete remission (62% vs 40%, p=0.041), but relapsed more 48.6% vs 22% (p=0.027). Overall 5 year mortality was 10.3% and 5 year progression to RRT was seen in 17.2%. Complete remission was observed in 49.4%. The 2-step cluster analysis separated the cohort into 3 clusters: cluster 1 (n=26) with 'nephrotic-range proteinuria'; cluster 2 (n=43) with 'non-nephrotic-range proteinuria'; and cluster 3 (n=18) with nephrotic syndrome. Immunosuppression use was comparable in clusters 1 and 3, but lower in cluster 2 (77.8% and 69.2% vs 11.6%, p<0.001). Rates of complete remission were greatest in clusters 1 and 3 vs cluster 2: 57.7% and 66.7% vs 37.2%. CONCLUSION: People who received immunosuppression had lower serum albumin and achieved remission more frequently, but were also prone to relapse. Our cluster analysis highlighted 3 FSGS phenotypes: a nephrotic cluster that clearly require immunosuppression; a cohort with preserved serum albumin and non-nephrotic range proteinuria who will benefit from supportive care; and lastly a cluster with heavy proteinuria but serum albumin > 30g/L. This group may still have immune mediated disease and thus could potentially benefit from immunosuppression. TRIAL REGISTRATION: This study protocol was reviewed and approved by the 'Research and Innovation committee of the Northern Care Alliance NHS Group', study approval number (Ref: ID 22HIP54).

Frontiers in hemodialysis: Innovations and technological advances.

As increasing demand for hemodialysis (HD) treatment incurs significant financial burden to healthcare systems and ecological burden as well, novel therapeutic approaches as well as innovations and technological advances are being sought that could lead to the development of purification devices such as dialyzers with improved characteristics and wearable technology. Novel knowledge such as the development of more accurate kinetic models, the development of novel HD membranes with the use of nanotechnology, novel manufacturing processes, and the latest technology in the science of materials have enabled novel solutions already marketed or on the verge of becoming commercially available. This collaborative article reviews the latest advances in HD as they were presented by the authors in a recent symposium titled "Frontiers in Haemodialysis," held on 12th December 2019 at the Royal Society of Medicine in London.

Motion correction of free-breathing magnetic resonance renography using model-driven registration.

INTRODUCTION: Model-driven registration (MDR) is a general approach to remove patient motion in quantitative imaging. In this study, we investigate whether MDR can effectively correct the motion in free-breathing MR renography (MRR). MATERIALS AND METHODS: MDR was generalised to linear tracer-kinetic models and implemented using 2D or 3D free-form deformations (FFD) with multi-resolution and gradient descent optimization. MDR was evaluated using a kidney-mimicking digital reference object (DRO) and free-breathing patient data acquired at high temporal resolution in multi-slice 2D (5 patients) and 3D acquisitions (8 patients). Registration accuracy was assessed using comparison to ground truth DRO, calculating the Hausdorff distance (HD) between ground truth masks with segmentations and visual evaluation of dynamic images, signal-time courses and parametric maps (all data). RESULTS: DRO data showed that the bias and precision of parameter maps after MDR are indistinguishable from motion-free data. MDR led to reduction in HD (HDunregistered = 9.98 ± 9.76, HDregistered = 1.63 ± 0.49). Visual inspection showed that MDR effectively removed motion effects in the dynamic data, leading to a clear improvement in anatomical delineation on parametric maps and a reduction in motion-induced oscillations on signal-time courses. DISCUSSION: MDR provides effective motion correction of MRR in synthetic and patient data. Future work is needed to compare the performance against other more established methods.

A randomised controlled trial to examine the effects of cinacalcet on bone and cardiovascular parameters in haemodialysis patients with advanced secondary hyperparathyroidism.

BACKGROUND: Secondary hyperparathyroidism may lead to increased cardiovascular risk. The use of cinacalcet may improve bone and cardiovascular health with improved parathormone (PTH) and phosphate control. METHODS: This is an open-label prospective randomised controlled trial to compare progression of cardiovascular and chronic kidney disease mineral and bone disorder (CKD-MBD) parameters. Patients were randomised to receive cinacalcet alongside standard therapy or standard therapy alone. Thirty-six haemodialysis patients who had > 90 days on dialysis, iPTH > 300 pg/mL, calcium > 2.1 mmol/L and age 18-75 years were included. Following randomization, all 36 patients underwent an intensive 12-week period of bone disease management aiming for iPTH 150-300 pg/mL. The primary outcome was change in vascular calcification using CT agatston score. Secondary outcomes included pulse wave velocity (PWV), left ventricular mass index (LVMI), carotid intima-media thickness (CIMT), augmentation index (Aix) and bone measurements. The above measurements were obtained at baseline and 12 months. RESULTS: There was no evidence of a group difference in the progression of calcification (median change (IQR) cinacalcet: 488 (0 to1539); standard therapy: 563 (50 to 1214)). In a post hoc analysis combining groups there was a mean (SD) phosphate reduction of 0.3 mmol/L (0.7) and median (IQR) iPTH reduction of 380 pg/mL (- 754, 120). Regression of LVMI and CIMT was seen (P = 0.03 and P = 0.001) and was significantly associated with change of phosphate on multi-factorial analyses. CONCLUSIONS: With a policy of intense CKD-MBD parameter control, no significant benefit in bone and cardiovascular markers was seen with the addition of cinacalcet to standard therapy over one year. Tight control of hyperphosphataemia and secondary hyperparathyroidism may lead to a reduction in LVMI and CIMT but this needs further investigation. Although the sample size was small, meticulous trial supervision resulted in very few protocol deviations with therapy.

Safely reducing haemodialysis frequency during the COVID-19 pandemic.

BACKGROUND: Patients undergoing haemodialysis (HD) are at higher risk of developing worse outcomes if they contract COVID-19. In our renal service we reduced HD frequency from thrice to twice-weekly in selected patients with the primary aim of reducing COVID 19 exposure and transmission between HD patients. METHODS: Dialysis unit nephrologists identified 166 suitable patients (38.4% of our HD population) to temporarily convert to twice-weekly haemodialysis immediately prior to the peak of the COVID-19 pandemic in our area. Changes in pre-dialysis weight, systolic blood pressure (SBP) and biochemistry were recorded weekly throughout the 4-week project. Hyperkalaemic patients (serum potassium > 6.0 mmol/L) were treated with a potassium binder, sodium bicarbonate and received responsive dietary advice. RESULTS: There were 12 deaths (5 due to COVID-19) in the HD population, 6 of which were in the twice weekly HD group; no deaths were definitively associated with change of dialysis protocol. A further 19 patients were either hospitalised and/or developed COVID-19 and thus transferred back to thrice weekly dialysis as per protocol. 113 (68.1%) were still receiving twice-weekly HD by the end of the 4-week project. Indications for transfer back to thrice weekly were; fluid overload (19), persistent hyperkalaemia (4), patient request (4) and compliance (1). There were statistically significant increases in SBP and pre-dialysis potassium during the project. CONCLUSIONS: Short term conversion of a large but selected HD population to twice-weekly dialysis sessions was possible and safe. This approach could help mitigate COVID-19 transmission amongst dialysis patients in centres with similar organisational pressures.

Cardiac structure and function after revascularization versus medical therapy for renal artery stenosis: the ASTRAL heart echocardiographic sub-study.

BACKGROUND: The ASTRAL trial showed no difference in clinical outcomes between medical therapy and revascularization for atherosclerotic renal vascular disease (ARVD). Here we report a sub-study using echocardiography to assess differences in cardiac structure and function at 12 months. METHODS: ASTRAL patients from 7 participating centres underwent echocardiography at baseline and 12 months after randomisation. Changes in left ventricular ejection fraction (LVEF), left ventricular mass (LVM), left atrial diameter (LAD), aortic root diameter (AoRD), E:A, and E deceleration time (EDT) were compared between study arms. Analyses were performed using t-tests and multivariate linear regression. RESULTS: Ninety two patients were included (50 medical versus 42 revascularization). There was no difference between arms in any baseline echocardiographic parameter. Comparisons of longitudinal changes in echocardiographic measurements were: δLVEF medical 0.8 ± 8.7% versus revascularization - 2.8 ± 6.8% (p = 0.05), δLVM - 2.9 ± 33 versus - 1.7 ± 39 g (p = 0.9), δLAD 0.1 ± 0.4 versus 0.01 ± 0.5 cm (p = 0.3), δAoRD 0.002 ± 0.3 versus 0.06 ± 0.3 cm (p = 0.4), δE:A - 0.0005 ± 0.6 versus 0.03 ± 0.7 (p = 0.8), δEDT - 1.1 ± 55.5 versus - 9.0 ± 70.2 ms (p = 0.6). In multivariate models, there were no differences between treatment groups for any parameter at 12 months. Likewise, change in blood pressure did not differ between arms (mean δsystolic blood pressure medical 0 mmHg [range - 56 to + 54], revascularization - 3 mmHg [- 61 to + 59], p = 0.60). CONCLUSIONS: This sub-study did not show any significant differences in cardiac structure and function accompanying renal revascularization in ASTRAL. Limitations include the small sample size, the relative insensitivity of echocardiography, and the fact that a large proportion of ASTRAL patient population had only modest renal artery stenosis as described in the main study.

The effect of revascularization in patients with anatomically significant atherosclerotic renovascular disease presenting with high-risk clinical features.

Background: Patients with atherosclerotic renovascular disease (ARVD) and high-risk clinical presentations have largely been excluded from randomized controlled trials comparing renal revascularization and optimal medical therapy. Here, we explore the effect of revascularization on death, progression to end-stage kidney disease (ESKD) and cardiovascular events (CVE) in a highly selected cohort of patients with ARVD. Methods: All patients with a radiological diagnosis of ARVD referred to our tertiary centre have been recruited into a single-centre cohort study between 1986 and 2014. Patients with ≥70% unilateral or bilateral ARVD together with one or more of the following putative high-risk presentations were designated 'high-risk': flash pulmonary oedema (FPE), severe hypertension, rapidly deteriorating renal function. The effect of revascularization on clinical outcomes in high-risk patients, patients with bilateral severe ARVD and those with <1 g proteinuria at baseline was compared with 'control' patients who had the same degree of renal artery stenosis (RAS) but did not exhibit these features. Results: Median follow-up was 58.4 months [interquartile range (IQR) 25.4-97.3]. Revascularization was associated with a reduced risk of progression to ESKD, CVE and all combined events in patients with rapidly deteriorating renal function [ESKD: hazard ratio (HR) 0.47 (95% confidence interval, CI, 0.25-0.85), P = 0.01; CVE: HR 0.51 (95% CI 0.29-0.91), P = 0.02; Any: HR 0.51 (95% CI 0.29-0.90), P = 0.02]. High-risk patients with bilateral ≥70% RAS and those with <1 g/day baseline proteinuria also had significantly better renal and cardiovascular outcomes post-revascularization when compared with controls. Conclusion: Our results indicate that revascularization may be of benefit in patients with anatomically significant RAS who present with rapidly deteriorating renal function, especially in the presence of severe bilateral ARVD or <1 g/day proteinuria.

Revascularization of atherosclerotic renal artery stenosis for chronic heart failure versus acute pulmonary oedema.

AIM: The aim of the study is to determine whether the apparent benefit of revascularization of renal artery stenosis for 'flash' pulmonary oedema extends to heart failure patients without a history of prior acute pulmonary oedema. METHODS: A prospective study of patients with renal artery stenosis and heart failure at a single centre between 1 January 1995 and 31 December 2010. Patients were divided into those with and without previous acute pulmonary oedema/decompensation. Survival analysis compared revascularization versus medical therapy in each group using Cox regression adjusted for age, estimated glomerular filtration rate, blood pressure and co-morbidities. RESULTS: There were 152 patients: 59% male, 36% diabetic, age 70 ± 9 years, estimated glomerular filtration rate 29 ± 17 mL/min per 1.73 m2 ; 52 had experienced previous acute pulmonary oedema (34%), whereas 100 had no previous acute pulmonary oedema (66%). The revascularization rate was 31% in both groups. For heart failure without previous acute pulmonary oedema, the hazard ratio for death after revascularization compared with medical therapy was 0.76 (0.58-0.99, P = 0.04). In heart failure with previous acute pulmonary enema, the hazard ratio was 0.73 (0.44-1.21, P = 0.22). For those without previous acute pulmonary oedema, the hazard ratio for heart failure hospitalization after revascularization compared with medical therapy was 1.00 (0.17-6.05, P = 1.00). In those with previous acute pulmonary oedema, it was 0.51 (0.08-3.30, P = 0.48). CONCLUSION: The benefit of revascularization in heart failure may extend beyond the current indication of acute pulmonary oedema. However, findings derive from an observational study.

Revascularisation of renal artery stenosis as a therapy for heart failure: an observational cohort study.

BACKGROUND: Heart failure contributes to 5% of all hospital admissions, and mortality is more than 50% at 4 years. 54% of patients with a left ventricular ejection fraction of less than 40% have renal artery stenosis. The potential benefit of revascularisation for heart failure is not established. We aimed to compare clinical outcomes for renal artery revascularisation with medical therapy for renal artery stenosis associated with heart failure as the first step towards validating revascularisation as a therapeutic option in heart failure. METHODS: In a prospective, longitudinal observational study at a single UK nephrology centre, we recruited patients with atherosclerotic renal artery stenosis (>50% as judged by CT, MR, or direct angiography). Endpoints were all-cause mortality and hospital admission for heart failure. Survival analyses were performed with Cox proportional hazard model adjusted for age, estimated glomerular filtration rate (eGFR), and cardiovascular comorbidities. Ethics approval was granted by South Manchester Research Ethics Committe. FINDINGS: 611 patients (152 [25%] with and 459 [75%] without heart failure) were recruited. Mean age was 70 years (SD 9), 348 (57%) were men, 183 (30%) had diabetes, and mean eGFR was 33 mL/min per 1·73 m(2) (SD 19). Patients with and without heart failure were similar with to sex, diabetes, and eGFR. 367 participants (60%) died over a follow-up of a mean of 4·3 years (SD 3·6). 87 patients without heart failure (19%) underwent revascularisation compared with 47 with heart failure (31%). The adjusted hazard ratio (HR) for death in heart failure compared with no heart failure was 1·9 (95% CI 1·5-2·5, p<0·0001). For patients without heart failure, the adjusted HR for death in revascularisation compared with receiving medical therapy was 0·8 (0·5-1·1, p=0·16). For heart failure, the HR was 0·6 (0·3-0·9, p=0·01). The HR for hospital admission for heart failure in revascularised patients was 0·2 (0·0-1·1, p=0·06). INTERPRETATION: Revascularisation of renal artery stenosis in heart failure is associated with a substantial reduction in all-cause mortality and hospital admission, although such observational data might be complicated by hidden confounders. These findings are encouraging for the development of a randomised trial of renal artery revascularisation versus medical therapy in heart failure, and suggest that investigation for renal artery stenosis should be considered more frequently in heart failure clinics. FUNDING: None.

Three Decades of Atherosclerotic Reno-vascular Disease Management - Changing Outcomes in an Observational Study.

BACKGROUND/AIMS: Optimized medical therapy has improved cardiovascular outcomes in the general population. To investigate whether changes in the management of atherosclerotic renovascular disease (ARVD) have had an impact on clinical outcomes. METHODS: Recruitment into this single-center prospective cohort study started in 1986. Data was analyzed retrospectively. Patients were divided into four groups based on relationship of diagnosis year to landmark randomized controlled trials (RCT); group 1 - pre-large RCT data (1986-2000); group 2 - post-early RCT (2001-2004); group 3 - ASTRAL study recruitment era (2004-2009); group 4 - post-ASTRAL (2009-2014). RESULTS: In total, 872 patients were followed for a median 54.9 months (IQR 20.2-96.2). Over successive time-periods, there was an increase in baseline utilization of renin angiotensin blockade (RAB) (group 4: 69% vs. group 1: 31%, p<0.001), statins (74% vs 20%, p<0.001) and beta-blockers (43% vs 30%, p=0.024). Median time to death, end-stage kidney disease and cardiovascular events improved except in group 4, which displayed more baseline cardiovascular comorbidities. The number of investigative angiograms performed decreased from 139 per year between 2006 and 2008 to 74 per year in group 4. CONCLUSIONS: Although fewer patients are being investigated for ARVD in our center, these have more cardiovascular comorbidities. Nonetheless, optimized medical therapy may have contributed towards improved proteinuria, renal function and clinical outcomes in patients diagnosed with ARVD.

The importance of proteinuria and prior cardiovascular disease in all major clinical outcomes of atherosclerotic renovascular disease - a single-center observational study.

BACKGROUND: Identification of patients at risk of developing adverse events would enable aggressive medical therapy and possibly targeted revascularization. The aim of this study is to characterize the determinants of long-term outcomes in atherosclerotic renovascular disease (ARVD). METHODS: Patients with a radiological diagnosis of ARVD were recruited into this single-center prospective cohort study between 1986 and 2014. Data collected included baseline co-morbid conditions, annualized prescribed medications and laboratory data (serum creatinine [υmol/L], proteinuria [g/24 h]). Multivariable Cox regression analysis was used to explore association with these end-points: death, end-stage kidney disease (ESKD), cardiovascular event (CVE) and the first of any of these events. RESULTS: A total of 872 patients were recruited into this study. However, 42 patients were excluded due to missing baseline data and hence case records for 830 patients were reviewed. Over median follow-up of 57.1 months (interquartile range: 21.7-96.9), incidence per 100 patient years of death, ESKD, CVE and any event was 13.5, 4.2, 8.9 and 21.0 respectively. Macrovascular disease (MVD), congestive heart failure (CHF), flash pulmonary oedema (FPE) and greater proteinuria at baseline were individually associated with increased risk for all end-points in multivariable analysis (Death: MVD -HR 1.24 [95% CI 1.02-1.50]; CHF -HR 1.33 [95% CI 1.08-1.64]; FPE - HR 2.10 [95% CI 1.50-2.92]; proteinuria - HR 1.14 [95% CI 1.08-1.20]). Higher estimated glomerular filtration rate at time of diagnosis was significantly associated with reduced risk of all end-points (Death: HR 0.92 [95% CI 0.89-0.94])., Administration of statins and renin angiotensin blockade (RAB) at baseline were also associated with reduced adverse events, especially death (RAB: HR 0.83 [95% CI 0.70-0.98]; statins: HR 0.79 [95% CI 0.66-.94]) and ESKD (RAB: HR 0.84 [95% CI 0.71-1.00]; statins: HR 0.79 [95% CI 0.66-0.93]). Revascularization was associated with reduced risk of death (HR 0.65 [95% CI 0.51-0.83]) and ESKD (HR 0.59 [95% CI 0.46-0.76]). CONCLUSION: All patients with ARVD require intensive vascular protection therapy to help mitigate systemic atherosclerosis, optimize cardiovascular risk and improve clinical outcomes. More effort is required to identify the minority of patients who may benefit from revascularization.

High-risk clinical presentations in atherosclerotic renovascular disease: prognosis and response to renal artery revascularization.

BACKGROUND: Current trial data may not be directly applicable to patients with the highest risk presentations of atherosclerotic renovascular disease, including flash pulmonary edema, rapidly declining kidney function, and refractory hypertension. We consider the prognostic implications of these presentations and response to percutaneous revascularization. STUDY DESIGN: Single-center prospective cohort study; retrospectively analyzed. SETTING & PARTICIPANTS: 467 patients with renal artery stenosis ≥50%, managed according to clinical presentation and physician/patient preference. PREDICTORS: Presentation with flash pulmonary edema (n = 37 [7.8%]), refractory hypertension (n = 116 [24.3%]), or rapidly declining kidney function (n = 46 [9.7%]) compared to low-risk presentation with none of these phenotypes (n = 230 [49%]). Percutaneous revascularization (performed in 32% of flash pulmonary edema, 28% of rapidly declining kidney function, and 28% of refractory hypertension patients) compared to medical management. OUTCOMES: Death, cardiovascular (CV) event, end-stage kidney disease. RESULTS: During a median follow-up of 3.8 (IQR, 1.8-5.8) years, 55% died, 33% had a CV event, and 18% reached end-stage kidney disease. In medically treated patients, flash pulmonary edema was associated with increased risk of death (HR, 2.2; 95% CI, 1.4-3.5; P < 0.001) and CV event (HR, 3.1; 95% CI, 1.7-5.5; P < 0.001), but not end-stage kidney disease, compared to the low-risk phenotype. No increased risk for any end point was observed in patients presenting with rapidly declining kidney function or refractory hypertension. Compared to medical treatment, revascularization was associated with reduced risk for death (HR, 0.4; 95% CI, 0.2-0.9; P = 0.01), but not CV event or end-stage kidney disease, in patients presenting with flash pulmonary edema. Revascularization was not associated significantly with reduced risk for any end point in rapidly declining kidney function or refractory hypertension. When these presentations were present in combination (n = 31), revascularization was associated with reduced risk for death (HR, 0.15; 95% CI, 0.02-0.9; P = 0.04) and CV event (HR, 0.23; 95% CI, 0.1-0.6; P = 0.02). LIMITATIONS: Observational study; retrospective analysis; potential treatment bias. CONCLUSIONS: This analysis supports guidelines citing flash pulmonary edema as an indication for renal artery revascularization in atherosclerotic renovascular disease. Patients presenting with a combination of rapidly declining kidney function and refractory hypertension also may benefit from revascularization and may represent a subgroup worthy of further investigation in more robust trials.

Improving outcomes in atherosclerotic renovascular disease: importance of clinical presentation and multi-disciplinary review.

BACKGROUND AND OBJECTIVES: Atherosclerotic renal artery stenosis may cause hypertension, chronic kidney disease and heart failure, but large randomized control trials to date have shown no major additional benefit of renal revascularization over optimal medical management. However, these trials did not consider outcomes specifically in relation to clinical presentations. Given that atherosclerotic renal artery stenosis is a heterogenous condition, measures of success likely differ according to the clinical presentation. Our retrospective study objectives were to determine the effects of revascularization when applied to specific clinical presentations and after careful multi-disciplinary team review. METHODS: All patients presenting to our centre and its referring hospitals with radiological findings of at least one renal artery stenosis > 50% between January 2015 and January 2020 were reviewed at the renovascular multi-disciplinary team meeting with revascularization considered in accordance with international guidelines, notably for patients with anatomically significant renal artery stenosis, adequately sized kidney and presentations with any of; deteriorating kidney function, heart failure syndrome, or uncontrollable hypertension. Optimal medical management was recommended for all patients which included lipid lowering agents, anti-platelets and anti-hypertensives targeting blood pressure ≤ 130/80 mmHg. The effect of revascularization was assessed according to the clinical presentation; blood pressure and number of agents in those with renovascular hypertension, delta glomerular filtration rate in those with ischaemic nephropathy and heart failure re-admissions in those with heart failure syndromes. RESULTS: During this 5-year period, 127 patients with stenosis ≥ 50% were considered by the multidisciplinary team, with 57 undergoing revascularization (17 primarily for severe hypertension, 25 deteriorating kidney function, 6 heart failure syndrome and 9 for very severe anatomical stenosis). Seventy-nine percent of all revascularized patients had a positive outcome specific to their clinical presentation, with 82% of those with severe hypertension improving blood pressure control, 72% with progressive ischaemic nephropathy having attenuated GFR decline, and no further heart failure admissions in those with heart failure. Seventy-eight percent of patients revascularized for high grade stenosis alone had better blood pressure control with 55% also manifesting renal functional benefits. CONCLUSIONS: Multi-disciplinary team discussion successfully identified a group of patients more likely to benefit from revascularization based on 3 key factors: clinical presentation, severity of the renal artery lesion and the state of the kidney beyond the stenotic lesion. In this way, a large proportion of patients can clinically improve after revascularization if their outcomes are considered according to the nature of their clinical presentation.

Prediction and assessment of responses to renal artery revascularization with dynamic contrast-enhanced magnetic resonance imaging: a pilot study.

The aim of this study was to assess the potential of dynamic contrast-enhanced (DCE) MRI to predict and evaluate functional outcomes after renal artery revascularization for renal artery stenosis (RAS). The single-kidney glomerular filtration rate (SK-GFR) was measured in 15 patients with atherosclerotic RAS with DCE-MRI and radioisotopes at baseline and 4 mo after revascularization. DCE-MRI also produced measurements of blood flow, blood volume, extraction fraction, tubular transit time, and functional volume. Stented kidneys (n = 22) were divided into three response groups on the basis of the changes in radioisotope SK-GFR: improved (n = 5), stable (n = 13), and deteriorated (n = 4). A good agreement was found between SK-GFR values from DCE-MRI and radioisotopes (correlation coefficient: 0.91). Before intervention, kidneys that improved had lower extraction fraction, higher blood volume, longer tubular transit time, and lower SK-GFR. After intervention, improved kidneys had increased functional volume, and deteriorated kidneys had reduced functional volume and extraction fraction. Revascularization improved blood flow and blood volume in all groups. This pilot study led to the hypothesis that well-vascularized kidneys with reduced extraction fractions are most likely to benefit from revascularization. More generally, DCE-MRI has the potential to replace radioisotope measurement of SK-GFR and may improve patient management by providing additional information on tissue perfusion.

Reverse cardiac remodelling and renal functional improvement following bilateral renal artery stenting for flash pulmonary oedema.

Acute flash pulmonary oedema (AFPO) is a life-threatening syndrome almost unique to patients with atheromatous renovascular disease (ARVD). Although recurrent AFPO is a widely accepted indication to consider renal revascularization, this is based on a number of case reports/series describing a successful outcome post-procedure. There is limited literature on the pathophysiological mechanisms and treatment effects of revascularization to support this clinical decision making. We report the case of a 65-year-old lady who presented with three episodes of AFPO. Investigations revealed severe bilateral renal artery stenosis. Post-revascularization, she experienced substantial improvement in energy levels and New York Heart Association class, with improvement in her blood pressure and renal function. Post-procedure, there were dramatic improvements in her cardiac morphology and function that were sustained at 1 year (ejection fraction improved from 39 to 65%, left ventricular mass decreased from 161 to 116 g) as well as renal function (isotopic glomerular filtration rate increased from 22.4 to 34.2 mL/min). This report provides new insights into the pathophysiological relationships between renal and cardiac changes in AFPO; the extent of the cardiac morphological changes was striking and unexpected.

Dispelling the myth: the use of renin-angiotensin blockade in atheromatous renovascular disease.

BACKGROUND: Many physicians retain reservations regarding the routine prescription of renin-angiotensin blockade (RAB) in patients with atheromatous renovascular disease (ARVD). Conversely, these patients are in most need of the cardio- and renal protection offered by RAB. This reservation is mostly because of fear of precipitating acute renal deterioration. We aimed to study whether RAB can be used safely in ARVD patients and whether it altered their outcome. METHODS: Prospective observational study of all ARVD patients presenting to our tertiary referral centre from 1999-2009. Data capture included usage and tolerability of RAB, and correlation with endpoints of cardiovascular events, dialysis or death. RESULTS: Six hundred and twenty-one subjects were available for analysis. Mean age (SD) of the cohort was 71.3 (8.8) years, median (interquartile range) follow-up 3.1 (2.1, 4.8), range 0.2-10.61 years. Seventy-four patients had an intolerance to RAB at study entry. When utilized prospectively, RAB was tolerated in 357 of 378 patients (92%), and this was even seen in 54/69 (78.3%) patients with bilateral>60% renal artery stenosis (RAS) or occlusion. Patients (4/21) who were intolerant of RAB during follow-up (and 12 retrospectively intolerant), underwent renal revascularization which facilitated safe use of these medications post-procedure. On multivariate time-adjusted analysis, patients receiving RAB were significantly less likely to die (P=0.02). CONCLUSION: RAB is well tolerated even in patients with bilateral severe RAS and reduced mortality in a large group of ARVD patients. We recommend all ARVD patients be considered for RAB therapy unless an absolute contra-indication exists. Intolerance of these agents due to renal dysfunction should be considered an emerging indication for renal revascularization to facilitate their re-introduction.

BOLD imaging: a potential predictive biomarker of renal functional outcome following revascularization in atheromatous renovascular disease.

BACKGROUND: Stenting of the stenosed renal artery is commonly employed in atheromatous renovascular disease (ARVD) in order to revascularize the affected kidney. However, it is still far from clear which patient subgroups should be revascularized as stenting carries small but significant risks. We have previously demonstrated that the ratio of magnetic resonance-measured renal volume to isotopic single kidney glomerular filtration rate (isoSK-GFR) is higher in kidneys which show functional improvement after revascularization. Blood oxygen level-dependent (BOLD) magnetic resonance imaging (MRI) does not require contrast administration and is sensitive to changes in tissue concentration of deoxyhaemoglobin. METHODS: In this study, we test the hypothesis that baseline BOLD R2* map signal and R2*:isoSK-GFR ratio will provide an additional independent predictive biomarker of response to revascularization. RESULTS: Studies were performed in 28 subjects (16 ARVD and 12 controls). All subjects had R2* mapping and isoSK-GFR measured at baseline and at 4-month follow-up. MRI data were collected on a 3 T whole-body MRI scanner using a coronal dual-echo, 2D gradient-echo breath-hold acquisition. Parenchymal regions of interest (ROIs) were drawn on a representative slice through the middle of the kidney. Parametric maps of R2* were generated and mean values of R2* were calculated for every ROI. The ratio of R2*:isoSK-GFR at baseline was significantly greater in kidneys where renal function improved (5.91 ± 6.51) versus stable (1.78 ± 1.11), deteriorated (2.15 ± 1.79) or controls (1.5 ± 0.91), P = 0.003. R2*:isoSK-GFR ratio that was greater than 95% confidence interval of the control kidneys was 66.7% sensitive, but 85.7% specific in predicting a positive renal functional outcome. CONCLUSIONS: These pilot data show that BOLD R2* imaging, presumably by detecting intra-renal deoxyhaemoglobin in still viable 'hibernating' parenchyma, coupled with isoSK-GFR may provide an effective predictive biomarker for positive renal functional response to revascularization. R2* imaging is non-invasive, quick to perform and could provide further insight into reversible parenchymal changes in ARVD kidneys.

A low rate of end-stage kidney disease in membranous nephropathy: A single centre study over 2 decades.

INTRODUCTION: Membranous nephropathy is the commonest cause of nephrotic syndrome in non-diabetic Caucasian adults over the age of 40 years. Primary membranous nephropathy is limited to the kidneys. Clinical management aims to induce remission, either spontaneously with supportive care, or with immunosuppression. Here, we describe the natural history of this condition in a large tertiary centre in the UK. METHODS: 178 patients with primary membranous nephropathy were identified over 2 decades. We collected data on demographics, baseline laboratory values, treatment received and outcomes including progression to renal replacement therapy and death. Analysis was performed on the whole cohort and specific subgroups. Univariate and multivariate Cox regression was also performed. RESULTS: Median age was 58.3 years with 63.5% male. Median baseline creatinine was 90µmol/L and urine protein-creatinine ratio 664g/mol. Remission (partial or complete) was achieved in 134 (75.3%), either spontaneous in 60 (33.7%) or after treatment with immunosuppression in 74 (41.6%), and of these 57 (42.5%) relapsed. Progression to renal replacement therapy was seen in 10.1% (much lower than classically reported) with mortality in 29.8%. Amongst the whole cohort, those who went into remission had improved outcomes compared to those who did not go into remission (less progression to renal replacement therapy [4.5% vs 28%] and death [20.1% vs 67%]. Those classified as high-risk (based on parameters including eGFR, proteinuria, serum albumin, PLA2R antibody level, rate of renal function decline) also had worse outcomes than those at low-risk (mortality seen in 52.6% vs 10.8%, p<0.001). The median follow-up period was 59.5 months. CONCLUSION: We provide a comprehensive epidemiologic analysis of primary membranous nephropathy at a large tertiary UK centre. Only 10.1% progressed to renal replacement therapy. For novelty, the KDIGO risk classification was linked to outcomes, highlighting the utility of this classification system for identifying patients most likely to progress.