UK experience of ofatumumab in recurrence of focal segmental glomerulosclerosis post-kidney transplant.

BACKGROUND: Steroid-resistant nephrotic syndrome (SRNS), commonly caused by focal segmental glomerulosclerosis (FSGS), is associated with progression to stage 5 chronic kidney disease, requirement for kidney replacement therapy and a risk of disease recurrence post-kidney transplantation. Ofatumumab (OFA) is a fully humanised monoclonal antibody to CD20, with similar mechanisms of action to rituximab (RTX). METHODS: We report a case series of seven UK patients (five paediatric, two adult), all of whom developed FSGS recurrence after kidney transplantation and received OFA as part of their therapeutic intervention. All also received concomitant plasmapheresis. The 2-year outcome of these seven patients is reported, describing clinical course, kidney function and proteinuria. RESULTS: Four patients (all paediatric) achieved complete urinary remission with minimal proteinuria 12 months post-treatment. Three of those four also had normal graft function. Two patients showed partial remission-brief improvement to non-nephrotic proteinuria (197 mg/mmol) in one patient, maintained improvement in kidney function (estimated glomerular filtration rate 76 ml/min/1.73 m2) in the other. One patient did not demonstrate any response. CONCLUSIONS: OFA may represent a useful addition to therapeutic options in the management of FSGS recurrence post-transplantation, including where RTX has shown no benefit. Concomitant plasmapheresis in all patients prevents any definitive conclusion that OFA was the beneficial intervention.

Clinical factors associated with severe hypophosphataemia after kidney transplant.

BACKGROUND: The mechanism by which hypophosphataemia develops following kidney transplantation remains debated, and limited research is available regarding risk factors. This study aimed to assess the association between recipient and donor variables, and the severity of post-transplantation hypophosphataemia. METHODS: We performed a single-centre retrospective observational study. We assessed the association between demographic, clinical and biochemical variables and the development of hypophosphataemia. We used linear regression analysis to assess association between these variables and phosphate nadir. RESULTS: 87.6% of patients developed hypophosphataemia. Patients developing hypophosphataemia were younger, had a shorter time on renal replacement therapy, were less likely to have had a parathyroidectomy or to experience delayed graft function, were more likely to have received a living donor transplant, from a younger donor. They had higher pre-transplantation calcium levels, and lower alkaline phosphatase levels. Receipt of a living donor transplant, lower donor age, not having had a parathyroidectomy, receiving a transplant during the era of tacrolimus-based immunosuppression, not having delayed graft function, higher pre-transplantation calcium, and higher pre-transplantation phosphate were associated with lower phosphate nadir by multiple linear regression. CONCLUSIONS: This analysis demonstrates an association between variables relating to better graft function and hypophosphataemia. The links with biochemical measures of mineral-bone disease remain less clear.

Predicting outcome in acute interstitial nephritis: a case-series examining the importance of histological parameters.

AIMS: The clinical significance of common histological parameters in acute interstitial nephritis (AIN) is uncertain. We aimed to evaluate the utility of histology in predicting clinical outcomes in patients with AIN. METHODS AND RESULTS: Adult renal biopsies yielding a diagnosis of AIN between 2000 and 2015 were re-examined. Patients were divided into groups based on: (i) the percentage of non-fibrotic cortex containing inflammation (NFI score) (NFI-1 = 0-24%; NFI-2 = 25-74%; NFI-3 = 75-100%) and (ii) the percentage of cortex containing tubular atrophy (TA score) (TA1 = 0-9%; TA2 = 10-24%; TA3 = 25-100%). The primary outcome was a composite of ≥50% reduction in serum creatinine (sCr) or an estimated glomerular filtration rate (eGFR) > 60 ml/min/1.73 m2 1 year post-biopsy. From a total of 2817 native renal biopsies, there were 120 patients with AIN and adequate data for analysis. Of these, 66 (56%) achieved the primary outcome. On univariable logistic regression, NFI-3 was associated with a 16 times increased likelihood of achieving the primary outcome compared to NFI-1 [odds ratio (OR) = 16, 95% confidence interval (CI) = 5.2-50)]. In contrast, TA3 was associated with a 90% reduced likelihood of achieving the primary outcome compared to TA1 (OR = 0.10, 95% CI = 0.0-0.3). Maximal clinical utility was achieved by combining TA and NFI into a single prognostic 'TANFI' score, which had an independent predictive effect on the primary outcome in a multivariable regression model consisting of age, sex, baseline sCr and identified drug cause. CONCLUSIONS: In patients with biopsy-proven AIN, a lower percentage of cortical tubular atrophy and, paradoxically, a higher percentage of inflammation in non-fibrosed cortex were associated with an increased likelihood of a positive clinical outcome.

Interaction between socioeconomic deprivation and likelihood of pre-emptive transplantation: influence of competing risks and referral characteristics - a retrospective study.

Socioeconomic deprivation (SED) influences likelihood of pre-emptive kidney transplantation (PET), but the mechanisms behind this are unclear. We explored the relationships between SED and patient characteristics at referral, which might explain this discrepancy. A retrospective cohort study was performed. SED was measured by Scottish Index of Multiple Deprivation (SIMD). Logistic regression evaluated predictors of PET. A competing risks survival analysis evaluated the interaction between SED and progression to end-stage kidney disease (ESKD) and death. Of 7765 patients with follow-up of 5.69 ± 6.52 years, 1298 developed ESKD requiring RRT; 113 received PET, 64 of which were from live donors. Patients receiving PET were "less deprived" with higher SIMD (5 ± 7 vs. 4 ± 5; P = 0.003). This appeared independent of overall comorbidity burden. SED was associated with a higher risk of death but not ESKD. Higher SIMD decile was associated with a higher likelihood of PET (OR 1.14, 95% CI 1.06, 1.23); the presence of diabetes and malignancy also reduced PET. SED was associated with reduced likelihood of PET after adjustment for baseline comorbidity, and this was not explained by risk of death or faster progression to ESKD. Education and outreach into transplantation should be augmented in areas with higher deprivation.

Obesity is not associated with progression to end stage renal disease in patients with biopsy-proven glomerular diseases.

BACKGROUND: Body mass index (BMI) is associated with renal disease progression in unspecified CKD. The relationship between BMI and primary glomerular disease (GN) may be more complex. We aimed to evaluate the association between BMI and renal disease progression in patients with primary glomerular disease (GN). METHODS: This was a single-centre retrospective cohort study performed in adult patients with biopsy-proven primary GN (excluding minimal change disease) from January 2000 to December 2015, with follow-up data until June 2017. BMI at time of biopsy was categorised as ≤25 kg/m2, > 25 to ≤30 kg/m2 and > 30 kg/m2. We used univariate and multivariate survival analyses to evaluate factors associated with progression to a composite endpoint of stage 5 CKD or renal replacement therapy (Major Adverse Renal Event - MARE) censoring for competing risk of death using Fine and Gray subdistribution hazards model. RESULTS: We included 560 patients with biopsy-proven primary GN and available BMI data: 66.1% were male with median age 54.8 (IQR 41.1-66.2) years and BMI 28.2 (IQR 24.9-32.1) kg/m2. Those with BMI 25-30 kg/m2 (n = 210) and with BMI > 30 kg/m2 (n = 207) were older (p = 0.007) with higher systolic and diastolic blood pressures (p = 0.02 and 0.004 respectively) than those with BMI < 25 kg/m2 (n = 132). There was a greater proportion of focal segmental glomerulosclerosis in those with higher BMI (3.9% in BMI < 25 kg/m2, 7.9% in BMI 25-30 kg/m2 and 10.7% in BMI > 30 kg/m2 of biopsies (p = 0.01)), but similar proportions of other GN diagnoses across BMI groups. Baseline eGFR (p = 0.40) and uPCR (p = 0.17) were similar across BMI groups. There was no interaction between BMI and time to MARE (log-rank p = 0.98) or death (log-rank p = 0.42). Censoring for competing risk of death, factors associated with progression to MARE were: younger age, lower baseline eGFR and higher uPCR, but not BMI (SHR 0.99, 95%CI 0.97-1.01, p = 0.31) nor blood pressure or GN diagnosis. CONCLUSION: BMI was not associated with progression to MARE in this patient cohort with primary GN. Efforts should be directed to managing other known risk factors for CKD progression.

The utility of anti-Müllerian hormone in women with chronic kidney disease, on haemodialysis and after kidney transplantation.

Women with renal disease have menstrual and gonadal dysfunction manifesting as hormonal imbalance. Anti-Müllerian hormone (AMH) is a potential measure of ovarian reserve. We examined circulating AMH concentrations in young women with renal failure, determined associations with clinical characteristics, and compared AMH with age-matched healthy individuals. AMH was measured in 77 women: 26 had chronic kidney disease (CKD), 26 were on haemodialysis (HD), and 25 had a kidney transplant. Random AMH levels were highest in women on HD [HD 2.9 (1.1-5.2), CKD 1.6 (0.7-2.2), transplant 1.5 (1.0-4.2) ng/ml]. On multiple linear regression, AMH was 53% higher [95% CI 0.20-0.98, P = 0.002] in women on HD and decreased by 20% per 5-year increase in age (P < 0.001). AMH was 43% lower in women with renal failure compared with 600 age-matched controls [1.7 (0.9-3.8) versus 3.0 (1.9-5.0) ng/ml, P < 0.001]; however, we found no difference in AMH between those on HD and healthy individuals [2.9 (1.1-5.2) versus 3.0 (1.9-5.0) ng/ml]. AMH may be a useful biomarker in female renal patients with non-dialysis dependent renal disease pursuing pregnancy. In contrast, AMH levels are higher in HD but unlikely to reflect ovarian reserve.

Continued monitoring of acute kidney injury survivors might not be necessary in those regaining an estimated glomerular filtration rate >60 mL/min at 1 year.

Background: Severe acute kidney injury (AKI) among hospitalized patients often necessitates initiation of short-term dialysis. Little is known about the long-term outcome of those who recover to normal renal function. The aim of this study was to determine the long-term renal outcome of patients experiencing AKI requiring dialysis secondary to hypoperfusion injury and/or sepsis who recovered to apparently normal renal function. Methods: All adult patients with AKI requiring dialysis in our centre between 1 January 1980 and 31 December 2010 were identified. We included patients who had estimated glomerular filtration rate (eGFR) >60 mL/min/1.73 m 2 12 months or later after the episode of AKI. Patients were followed up until 3 March 2015. The primary outcome was time to chronic kidney disease (CKD) (defined as eGFR persistently <60 mL/min/1.73 m 2 ) from first dialysis for AKI. Results: Among 2922 patients with a single episode of dialysis-requiring AKI, 396 patients met the study inclusion criteria. The mean age was 49.8 (standard deviation 16.5) years and median follow-up was 7.9 [interquartile range (IQR) 4.8-12.7] years. Thirty-five (8.8%) of the patients ultimately developed CKD after a median of 5.3 (IQR 2.8-8.0) years from first dialysis for AKI giving an incidence rate of 1 per 100 person-years. Increasing age, diabetes and vascular disease were associated with higher risk of progression to CKD [adjusted hazard ratios (95% confidence interval): 1.06 (1.03, 1.09), 3.05 (1.41, 6.57) and 3.56 (1.80, 7.03), respectively]. Conclusions: Recovery from AKI necessitating in-hospital dialysis was associated with a very low risk of progression to CKD. Most of the patients who progressed to CKD had concurrent medical conditions meriting monitoring of renal function. Therefore, it seems unlikely that regular follow-up of renal function is beneficial in patients who recover to eGFR >60 mL/min/1.73 m 2 by 12 months after an episode of AKI.

Symptomatic fracture risk in the renal replacement therapy population.

BACKGROUND: Bone fractures are an important cause of morbidity and mortality in patients on renal replacement therapy (RRT). The aim of this multicentre observational study was to quantify the incidence of radiologically proven bone fracture by anatomical site in prevalent RRT groups and study its relationship to potential risk factors. METHODS: We performed a retrospective analysis of electronic records of all 2096 adults prevalent on RRT in the West of Scotland on 7 July 2010 across all hospitals (except one where inception was 1 August 2011) to identify all subsequent radiologically proven fractures during a median 3-year follow-up. RESULTS: There were 340 fractures, with an incidence of 62.8 per 1000 patient-years. The incidences were 37.6, 99.2 and 57.6 per 1000 patient-years in the transplant, haemodialysis (HD) and peritoneal dialysis (PD) groups, respectively (P < 0.05). In the multivariable model, age and HD (relative to transplant or PD) were independently associated with increased risk of fractures, while primary glomerular disease, increasing serum albumin and taking alfacalcidol or lanthanum were associated with decreased risk. In a multivariable model of only HD patients, age was independently associated with an increased risk of fractures, while glomerular disease, high serum albumin and being on alfacalcidol and lanthanum were associated with decreased risk. In a multivariable model in transplant patients, there were no significant independent predictors of fracture. CONCLUSIONS: The risk of symptomatic bone fracture is high in RRT patients and is ∼2.5 times higher in HD than in renal transplant patients, with the increased risk being independent of baseline factors. Fracture risk increases with age and lower serum albumin and is reduced if the primary renal diagnosis is glomerular disease. The possible protective role of alfacalcidol and lanthanum in HD patients deserves further exploration.

Obstetric and long-term kidney outcomes in renal transplant recipients: a 40-yr single-center study.

Female renal transplant recipients of childbearing age may ask what the outcomes are for pregnancy and whether pregnancy will affect graft function. We analyzed obstetric and transplant outcomes among renal transplant recipients in our center who have been pregnant between 1973 and 2013. A case-cohort study was performed identifying 83 pairs of pregnant and non-pregnant controls matched for sex, age, transplant vintage, and creatinine. There were 138 pregnancies reported from 89 renal transplant recipients. There were live births in 74% of pregnancies with high prevalence of prematurity (61%), low birth weight (52%), and pre-eclampsia (14%). Lower eGFR (OR 0.98; p = 0.05) and higher uPCR (OR 1.86; p = 0.02) at conception were independent predictors for poor composite obstetric outcome. Lower eGFR (OR 0.98; p = 0.04), higher uPCR (OR 1.50; p = 0.04), and live organ donation (OR 0.35; p = 0.02) were predictors of ≥20% loss of eGFR between immediately pre-pregnancy and one yr after delivery. There was no difference in eGFR at one, five, and 10 yr in pregnant women compared with non-pregnant controls and a pregnancy was not associated with poorer 10-yr transplant or 20-yr patient survival. Despite high rates of obstetric complications, most women had successful pregnancies with good long-term transplant function.

Risk factors and outcome of stroke in renal transplant recipients.

Stroke incidence is high in end-stage renal disease, and risk factors differ between the dialysis and general populations. However, risk factors and outcomes following renal transplantation remain unclear. We analyzed all adult patients with a functioning renal transplant from 01/01/2007 to 12/31/2012. Data were extracted from the electronic patient record. Variables associated with stroke were identified by survival analyses; demographic, clinical, and imaging and laboratory variables were assessed and case fatality determined. Follow-up was until 05/12/2013. A total of 956 patients were identified (median age 40.1 years, 59.9% male). Atrial fibrillation (AF) prevalence was 9.2%, and 38.2% received a transplant during follow-up. A total of 26 (2.7%) experienced a stroke during 4409 patient-years of follow-up (84.6% ischemic). Stroke incidence was 5.96/1000 patient-years. Factors associated with stroke on regression analysis were prior stroke, diabetes, age, systolic hypertension, and hemoglobin. Atrial fibrillation was associated with time to stroke (P<0.001). Warfarin did not associate with ischemic stroke risk in those with AF. Fatality was 19.2% at 7, 23.1% at 28, and 42.3% at 365 days after stroke. Patients with a functioning renal transplant have a high stroke incidence and case fatality. Unlike those on hemodialysis, risk factors are similar to the general population. We did not demonstrate benefit from warfarin use in those with AF.

Risk Factors of Ischemic Stroke and Subsequent Outcome in Patients Receiving Hemodialysis.

BACKGROUND AND PURPOSE: End-stage renal disease (ESRD) requiring hemodialysis carries up to a 10-fold greater risk of stroke than normal renal function. Knowledge on risk factors and management strategies derived from the general population may not be applicable to those with ESRD. We studied a large ESRD population to identify risk factors and outcomes for stroke. METHODS: All adult patients receiving hemodialysis for ESRD from January 1, 2007, to December 31, 2012, were extracted from the electronic patient record. Variables associated with stroke were identified by survival analysis; demographic, clinical, imaging, and dialysis-related variables were assessed, and case-fatality was determined. Follow-up was until December 31, 2013. RESULTS: A total of 1382 patients were identified (mean age, 60.5 years; 58.5% men). The prevalence of atrial fibrillation was 21.2%, and 59.4% were incident hemodialysis patients. One hundred and sixty patients (11.6%) experienced a stroke during 3471 patient-years of follow-up (95% ischemic). Stroke incidence was 41.5/1000 patient-years in prevalent and 50.1/1000 patient-years in incident hemodialysis patients. Factors associated with stroke on regression analysis were prior stroke, diabetes mellitus, and age at starting renal replacement therapy. Atrial fibrillation was not significantly associated with stroke, and warfarin did not affect stroke risk in warfarin-treated patients. Fatality was 18.8% at 7 days, 26.9% at 28 days, and 56.3% at 365 days after stroke. CONCLUSIONS: Incidence of stroke is high in patients with ESRD on hemodialysis with high case-fatality. Incident hemodialysis patients had the highest stroke incidence. Many, but not all, important risk factors commonly associated with stroke in the general population were not associated with stroke in patients receiving hemodialysis.

Teaching percutaneous renal biopsy using unfixed human cadavers.

BACKGROUND: Percutaneous renal biopsy (PRB) is an important diagnostic procedure. Despite advances in its safety profile there remains a small but significant risk of bleeding complications. Traditionally, operators train to perform PRB through tutor instruction and directly supervised PRB attempts on real patients. We describe an approach to teaching operators to perform PRB using cadaveric simulation. METHODS: We devised a full day course hosted in the Clinical Anatomy Skills Centre, with places for nine candidates. Course faculty consisted of two Consultant Nephrologists, two Nephrology trainees experienced in PRB, and one Radiologist. Classroom instruction included discussion of PRB indications, risk minimisation, and management of complications. Two faculty members acted as models for the demonstration of kidney localisation using real-time ultrasound scanning. PRB was demonstrated using a cadaveric model, and candidates then practised PRB using each cadaver model. RESULTS: Written candidate feedback was universally positive. Faculty considered the cadaveric model a realistic representation of live patients, while the use of multiple cadavers introduced anatomical variation. CONCLUSIONS: Our model facilitates safe simulation of a high risk procedure. This might reduce serious harm associated with PRB and improve patient safety, benefiting trainee operators and patients alike.

The incidence of biopsy-proven IgA nephropathy is associated with multiple socioeconomic deprivation.

Chronic kidney disease is more common in areas of socioeconomic deprivation, but the relationship with the incidence and diagnosis of biopsy-proven renal disease is unknown. In order to study this, all consecutive adult patients undergoing renal biopsy in West and Central Scotland over an 11-year period were prospectively analyzed for demographics, indication, and histologic diagnosis. Using the Scottish Index of Multiple Deprivation, 1555 eligible patients were separated into quintiles of socioeconomic deprivation according to postcode. Patients in the most deprived quintile were significantly more likely to undergo biopsy compared with patients from less deprived areas (109.5 compared to 95.9 per million population/year). Biopsy indications were significantly more likely to be nephrotic syndrome, or significant proteinuria without renal impairment. Patients in the most deprived quintile were significantly more likely to have glomerulonephritis. There was a significant twofold increase in the diagnosis of IgA nephropathy in the patients residing in the most compared with the least deprived postcodes not explained by the demographics of the underlying population. Thus, patients from areas of socioeconomic deprivation in West and Central Scotland are significantly more likely to undergo native renal biopsy and have a higher prevalence of IgA nephropathy.

Predictors of sustained arteriovenous access use for haemodialysis.

BACKGROUND: Guidelines encourage early arteriovenous (AV) fistula (AVF) planning for haemodialysis (HD). The aim of this study was to estimate the likelihood of sustained AV access use taking into account age, sex, comorbidity, anatomical site of first AVF and, for pre-dialysis patients, eGFR and proteinuria. METHODS: 1,092 patients attending our centre who had AVF as their first AV access procedure between January 1, 2000 and August 23, 2012 were identified from the electronic patient record. The primary end-point was time to first sustained AV access use, defined as use of any AV access for a minimum of 30 consecutive HD sessions. RESULTS: 52.9% (n = 578) of the patients ultimately achieved sustained AV access use. The main reasons for AV access non-use were AVF failure to mature and death. The 3-year Kaplan-Meier probability of sustained AV access use was 68.8% for those not on renal replacement therapy (RRT) (n = 688) and 74.2% for those already on RRT (n = 404) at the time of first AVF. By multivariate analysis in patients not on RRT, male sex (HR 2.22; p < 0.001), uPCR (HR 1.03; p = 0.03) and eGFR (hazard ratio, HR 0.85; p < 0.001) were independent predictors of AV access use. In patients already on RRT, age (HR 0.98; p < 0.001) and peripheral vascular disease (HR 0.48; p = 0.02) were independent predictors of AV access use. CONCLUSION: Our data suggest that refinement of the current guideline for timing of AV access creation in planning RRT is justified to take into account individual factors that contribute to the likelihood of technical success and clinical need.

Incidence of fatal and non-fatal pulmonary thromboembolism after removal of tunnelled central venous haemodialysis catheters without ultrasound scan and anticoagulation.

BACKGROUND: Catheter related thrombosis is a common complication of tunnelled central venous catheter (TCVC) usage. There are concerns that TCVC removal could dislodge a thrombus to cause pulmonary thromboembolism (PE). The incidence of PE following TCVC removal is unclear and so the aim of this study was to investigate the incidence of PE and whether it is high enough to warrant screening with ultrasound with a view to systemic anticoagulation prior to TCVC removal. METHODS: 1102 consecutive TCVC removals without ultrasound and systemic anticoagulation were included in this retrospective study. Data were extracted from electronic health records. Measures to identify PE events included: deaths, computed tomography pulmonary angiogram (CT-PA), isotope lung perfusion scans and D-dimers blood tests within 7 days of removal. RESULTS: Of the 1102 TCVC removals, the mean age of patients was 56.9 years and 57.3% were male. The primary renal diagnosis for 24.5% of patients was diabetic nephropathy. There were seven deaths following removal, none of which had PE as a contributing cause on review of their clinical history and death certificates. Five CT-PAs and one isotope lung perfusion scan were carried out in the 7 days after TCVC removal and none had a positive finding of PE. Three patient had D-dimers measured in blood within 7 days and none of these patients were subsequently diagnosed with PE. CONCLUSIONS: There was no evidence of fatal or non-fatal PE's occurring in the 7 days following TCVC removal. This would support the practice of removing TCVCs without the need for ultrasound screening and without a period of systemic anticoagulation.

Outcomes in ANCA-Associated Vasculitis in Scotland: Validation of the Renal Risk Score in a Complete National Cohort.

Introduction: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) causes autoimmune-mediated inflammation of small blood vessels in multiple organs, including the kidneys. The ability to accurately predict kidney outcomes would enable a more personalized therapeutic approach. Methods: We used our national renal biopsy registry to validate the ability of ANCA Renal Risk Score (ARRS) to predict end-stage kidney disease (ESKD) for individual patients. This score uses histopathological and biochemical data to stratify patients as high, medium, or low risk for developing ESKD. Results: A total of 288 patients were eligible for inclusion in the study (low risk n = 144, medium risk n = 122, high risk n = 12). Using adjusted Cox proportional hazard models with the low-risk group as reference, we show that outcome differs between the categories: high-risk hazard ratio (HR) 16.69 (2.91-95.81, P = 0.002); medium risk HR 4.14 (1.07-16.01, P = 0.039). Incremental multivariable-adjusted Cox proportional hazards models demonstrated that adding ARRS to a model adjusted for multiple clinical parameters enhanced predictive discrimination (basic model C-statistic 0.864 [95% CI 0.813-0.914], basic model plus ARRS C-statistic 0.877 [95% CI 0.823-0.931]; P <0.01). Conclusion: The ARRS better discriminates risk of ESKD in AAV and offers clinicians more prognostic information than the use of standard biochemical and clinical measures alone. This is the first time the ARRS has been validated in a national cohort. The proportion of patients with high-risk scores is lower in our cohort compared to others and should be noted as a limitation of this study.

Idiopathic membranous nephropathy and nephrotic syndrome: outcome in the era of evidence-based therapy.

BACKGROUND: Contemporary studies analysing the long-term outcomes of patients with idiopathic membranous nephropathy and nephrotic syndrome in the era of evidence-based antiproteinuric and immunosuppressive therapies are sparse. Controversy also persists regarding which immunosuppression (IS) regimen to use. In this retrospective cohort study, we aimed to characterize time to partial remission (PR), complete remission (CR), requirement for renal replacement therapy (RRT) or death. We aimed to assess which factors predicted RRT or death and determine the impact of IS on outcome. METHODS: Ninety-five consecutive adult patients attending two centres between 1997 and 2008 were identified. Baseline demographics and subsequent treatment and outcome were recorded. RESULTS: Ninety-five percent of patients were prescribed angiotensin-converting enzyme inhibitors and/or angiotensin-receptor blocker (ACEI/ARB) therapy, 78% statin therapy, 70% antiplatelets and 38% IS. The 5-year actuarial rates for PR, CR, RRT and death were 76.4, 24.4, 11.9 and 16.8%, respectively. In patients achieving at least one PR, the 5-year actuarial risk of relapse was 32.8%. Using multivariate survival analysis, achievement of remission was the factor most strongly associated with reduced risk of RRT or death. There was no significant difference in outcomes between patients who did or did not receive IS, although patients receiving IS had more severe disease. Contrary to published findings, 81.8% of patients treated with the Ponticelli regimen (6 months of alternating prednisolone and cyclophosphamide or chlorambucil) suffered significant treatment-related complications compared with 19% of patients prescribed the Cattran regimen (prolonged combined low-dose prednisolone and cyclosporine). CONCLUSIONS: Using an approach of widespread ACEI/ARB treatment and targeted IS, 76% of patients can expect to have achieved at least one PR by 5 years. Achievement of remission is the factor most strongly associated with reduced risk of RRT and death. Treatment with IS is associated with significant treatment complications.

Early measurement of pulsatility and resistive indexes: correlation with long-term renal transplant function.

PURPOSE: To correlate pulsatility index (PI) and resistive index (RI) measured at early specific intervals after transplantation with 1-year estimated glomerular filtration rate (eGFR) and death-censored transplant survival to assess the long-term prognostic value of these Doppler indexes. MATERIALS AND METHODS: The local ethics committee was consulted, and no formal approval was required. This retrospective review included 178 consecutive patients (111 male, 67 female; mean age, 43.9 years ± 13.4 [standard deviation]; age range, 16-72 years) undergoing first deceased-donor renal transplantation between 1997 and 2000. All patients were identified from a prospectively maintained database. Spectral Doppler analysis was performed within 1 week after transplantation in all patients and between 1 week and 3 months after transplantation in 124 patients. Average PI and RI were determined from measurements obtained in the upper, lower, and interpolar regions. For statistical analysis, the χ(2) test, analysis of variance, the Student t test, Kaplan-Meier survival plots, and Cox proportional hazards models were used. RESULTS: Within 1 week after transplantation, there was a significant association between PI and 1-year eGFR when analyzed as tertiles (P = .02). Between 1 week and 3 months after transplantation, there was a significant relationship between 1-year eGFR and both PI and RI when comparing the lowest and highest tertiles (47.5 mL/min/1.73 m(2) for PI <1.26 vs 32.7 mL/min/1.73 m(2) for PI >1.49 [P = .01], 42.8 mL/min/1.73 m(2) for RI <0.69 vs 32.3 mL/min/1.73 m(2) for RI >0.74 [P = .03]). Both PI and RI were independent predictors of death-censored transplant survival (hazard ratio, 1.68 per unit [P < .001] and 260.4 per unit, respectively [P = .02]). CONCLUSION: PI and RI in the early posttransplantation period correlate with long-term transplant function and can potentially be used as prognostic markers to aid risk stratification for future transplant dysfunction.