Autoimmune haemolytic anaemia associated with Epstein Barr virus infection as a severe late complication after kidney transplantation and successful treatment with rituximab: case report.

BACKGROUND: Autoimmune haemolytic anaemia (AIHA) is a rare complication following kidney transplantation and usually occurs early in its course. It is characterised by autoantibodies or alloantibodies directed against red blood cells (RBCs). CASE PRESENTATION: We describe a 44 year old woman who presented 5 years after kidney transplantation with profound transfusion dependent warm AIHA. Investigations confirmed an IgG autoantibody against RBCs and high titre Epstein-Barr virus (EBV) viraemia. The patient was at higher risk for EBV disease being seronegative at the time of transplantation but had detectable EBV capsid IgG antibody at the time of presentation. The haemolysis was refractory to high dose steroid and intravenous immunoglobulin. There was a rapid and complete resolution of both the anaemia and the viraemia following rituximab therapy, with no adverse events. Twenty-six units of blood were required during the course of treatment. CONCLUSIONS: To our knowledge this is the first reported case of EBV associated AIHA in a renal transplant recipient. It highlights a rare pathology associated with post-transplant EBV infection, of broad interest to transplant physicians, haematologists, and microbiologists, and the effective novel use of monoclonal anti-CD20 therapy.

Chapter 8 Haemoglobin, ferritin and erythropoietin amongst UK adult dialysis patients in 2010: national and centre-specific analyses.

BACKGROUND: The UK Renal Association (RA) and National Institute for Health and Clinical Excellence (NICE) have published clinical practice guidelines which include recommendations for management of anaemia in established renal failure. AIM: To determine the extent to which the guidelines for anaemia management are met in the UK. METHODS: Quarterly data were obtained regarding haemoglobin (Hb) and factors that influence Hb from renal centres in England, Wales, Northern Ireland (EWNI) and the Scottish Renal Registry for the incident and prevalent renal replacement therapy (RRT) cohorts for 2010. RESULTS: In the UK, in 2010 53.6% of patients commenced dialysis therapy with Hb ≥ 10.0 g/dl (median Hb 10.1 g/dl). The median Hb of haemodialysis (HD) patients was 11.5 g/dl with an interquartile range (IQR) of 10.5-12.3 g/dl. Of HD patients 84.6% had Hb ≥ 10.0 g/dl. The median Hb of peritoneal dialysis (PD) patients in the UK was 11.6 g/dl (IQR 10.6-12.5 g/dl). Of UK PD patients, 87.2% had Hb ≥ 10.0 g/dl. The median ferritin in HD patients in EWNI was 444 µg/L (IQR 299-635) and 96% of HD patients had a ferritin ≥ 100 µg/L. The median ferritin in PD patients was 264 µg/L (IQR 148-426) with 86% of PD patients having a ferritin ≥ 100 µg/L. In EWNI the mean Erythropoietin Stimulating Agent (ESA) dose was higher for HD than PD patients (9,020 vs. 6,202 IU/week). CONCLUSIONS: Of prevalent HD patients, 52.7% had Hb ≥ 10 and ≤ 12 g/dl. Of prevalent PD patients, 54.3% had Hb 10.5-12.5 g/dl.

Chapter 10 Blood pressure profile of prevalent patients receiving renal replacement therapy in England, Wales and Northern Ireland in 2010: national and centre-specific analyses.

BACKGROUND: The UK Renal Registry (UKRR) assesses blood pressure (BP) control annually for patients receiving renal replacement therapy (RRT) at renal centres in England, Wales and Northern Ireland. METHODS: Patients receiving RRT on 31st December 2010 with a BP reading in either the fourth or third quarter of 2010 were included. Summary statistics were calculated for each renal centre and country. RESULTS: Data completeness for BP measurements submitted to the UKRR for all modalities were little changed from previous years: it was better for HD patients (64% for pre-HD measurements) than for PD patients (44%) or transplant recipients (36%). In 2010, the median pre-and post-HD SBP were 140 mmHg and 128 mmHg respectively. The median SBP of patients on PD was 138 mmHg. Transplant recipients had a median SBP of 134 mmHg. Median DBP were 71 mmHg (pre-HD), 67 mmHg (post-HD), 80 mmHg (PD ) and 79 mmHg (transplant). Only 25.6% of PD patients achieved the Renal Association guideline of SBP <130 mmHg and DBP <80 mmHg. Amongst transplant patients, 27.7% achieved the Renal Association guideline of SBP <130 mmHg and DBP <80 mmHg. CONCLUSION: In 2010 there continued to be significant variation in the achievement of BP standards between UK renal centres.

Chapter 3 Demographic and biochemistry profile of kidney transplant recipients in the UK in 2010: national and centre-specific analyses.

INTRODUCTION: National transplant registries routinely focus on centre-specific patient and graft survival rates following renal transplantation. However other outcomes such as graft function (as measured by eGFR), haemoglobin and blood pressure are also important quality of care indicators. METHODS: Renal transplant activity, incident graft survival data and donor information were obtained from NHS Blood and Transplant. Laboratory and clinical variables and prevalent survival data were obtained from the UK Renal Registry. Data were analysed separately for prevalent and one year post-transplant patients. RESULTS: The numbers of live and deceased kidney donors increased in 2010. The death-censored graft failure rate fell slightly to 2.4% and the transplant patient death rates remained stable at 2.5 per 100 patient years. There was centre variation in outcomes including eGFR and haemoglobin in prevalent and 1 year post-transplant patients. Analysis of prevalent transplants by chronic kidney disease stage showed 13.7% with an eGFR <30 ml/min/1.73 m(2) and 1.5% with an eGFR <15 ml/min/1.73 m(2). Of those with CKD stage 5 T, 36.1% had haemoglobin concentrations <10.5 g/dl, 22.9% phosphate concentrations ≥ 1.8 mmol/L and 6.2% adjusted calcium concentrations ≥ 2.6 mmol/L. Malignancy (23%) and infection (22%) remained the commonest two causes of death in prevalent transplant patients. CONCLUSION: Significant variations in clinical outcomes (unadjusted for patient-specific variables) amongst kidney transplant recipients continued to exist in the UK and may reflect differences in healthcare delivery between renal centres.

Chapter 4 Comorbidities and current smoking status amongst patients starting renal replacement therapy in England, Wales and Northern Ireland from 2009 to 2010.

INTRODUCTION: Comorbidities are an important determinant of survival for patients requiring renal replacement therapy (RRT) and influence other care processes such as dialysis access formation and transplant wait-listing. The prevalence of comorbidities in incident RRT patients changes with age and varies between ethnic groups. This study describes these associations and the independent effect of comorbidities on outcomes. METHODS: Incident patients reported to the UK Renal Registry (UKRR) with comorbidity data in 2009 and 2010 (n = 6,130) were included in analyses exploring the association of comorbidities with patient demographics, treatment modality, haemoglobin and renal function at start of RRT. For analyses examining association between comorbidities and survival, adult patients starting RRT between 2005 and 2010 in centres reporting to the UKRR with comorbidity data (n = 17,184) were included. The relationship between comorbidities and mortality at 90 days and one year after 90 days from start of RRT were explored using Cox regression. RESULTS: Completeness of comorbidity data was 49.1% in 2010 compared with 48.9% in 2005. Of patients with data, 55.4% had one or more comorbidities. Diabetes mellitus and ischaemic heart disease were the most common conditions, observed in 33.3% and 21.1% of patients respectively. 13.2% of incident RRT patients in the 2-year period were recorded as current smokers. The prevalence of comorbidity increased with increasing age across all ethnic groups. In multivariable survival analysis, malignancy and the presence of ischaemic/neuropathic ulcers were strong independent predictors of poor survival at 1 year after 90 days from the start of RRT in patients <65 years. CONCLUSION: Differences in prevalence rates of comorbid illnesses in incident RRT patients may reflect variation in access to health care or competing risk prior to commencing treatment. The generalisability of these analyses continues to be limited by poor data completeness.

Hypogammaglobulinemia and bronchiectasis in mycophenolate mofetil-treated renal transplant recipients: an emerging clinical phenomenon?

BACKGROUND: Mycophenolate mofetil (MMF) inhibits T- and B-cell proliferation and can cause acquired or secondary hypogammaglobulinemia. This finding and the subsequent development of opportunistic infection, including pneumonia, have been reported in patients receiving MMF. Chronic pulmonary infection and hypogammaglobulinemia predispose to bronchiectasis, and we aimed to establish the incidence and clinical pattern of this condition within our MMF-treated renal transplant population. METHODS: We performed a retrospective analysis of MMF-treated transplant recipients. Two hundred and eighty-nine patients were identified and for each, demographic, clinical, radiological and laboratory data from case notes and electronic records were collected. RESULTS: Twenty-three of 289 patients had recurrent severe chest infections (>2 episodes) between 12 and 95 months after the introduction of MMF. The mean age was 53 ± 17yr. Pulmonary lesions fulfilled clinical, radiographic and computerized tomography criteria for bronchiectasis in 7/289 (2.4%). All seven patients with bronchiectasis had low serum IgG levels. Three patients had sufficient samples available for B-cell phenotype analysis but no conclusive results emerged. No cases of post-transplant bronchiectasis were identified in our transplant population not receiving MMF. DISCUSSION: We report seven cases of bronchiectasis in renal transplant patients receiving MMF. We speculate that low immunoglobulin levels may contribute to the development of this significant pulmonary disease.

UK Renal Registry 13th Annual Report (December 2010): Chapter 8: adequacy of haemodialysis in UK adult patients in 2009: national and centre-specific analyses.

BACKGROUND: Outcome in patients treated with haemodialysis (HD) is influenced by the delivered dose of dialysis. The UK Renal Association (RA) publishes Clinical Practice Guidelines which include recommendations for dialysis dose. The urea reduction ratio (URR) is a widely used measure of dialysis dose. AIM: To determine the extent to which patients received the recommended dose of HD in the UK. METHODS: All seventy-two UK renal centres submitted data to the UK Renal Registry (UKRR). Two groups of patients were included in the analyses: the prevalent patient population on 31st December 2009 and the incident patient population for 2009. Centres returning data on <50% of their patient population were excluded from centre-specific comparisons. RESULTS: Data regarding URR were available from 63 renal centres in the UK. Fifty-one centres provided URR data on more than 90% of prevalent patients. The proportion of patients in the UK who met the UK Clinical Practice Guideline for URR (>65%) increased from 56% in 1998 to 85.5% in 2009. There was considerable variation between centres, with 19 centres attaining the RA clinical practice guideline in >90% of patients and 5 centres attaining the guideline in <70% of patients. The delivered HD dose (URR) was lower in patients who had just commenced dialysis treatment compared to patients who had survived longer on HD. CONCLUSIONS: The delivered dose of HD for patients with established renal failure has increased over the last decade. Whilst the majority of UK patients achieved the target URR there was considerable variation between centres in the percentage of patients achieving the guideline.

UK Renal Registry 13th Annual Report (December 2010): Chapter 9: haemoglobin, ferritin and erythropoietin amongst UK adult dialysis patients in 2009: national and centre-specific analyses.

BACKGROUND: The UK Renal Association (RA) and National Institute for Health and Clinical Excellence (NICE) have published Clinical Practice Guidelines which include recommendations for management of anaemia in established renal failure. AIMS: To determine the extent to which the guidelines for anaemia management are met in the UK. METHODS: Quarterly data were obtained regarding haemoglobin (Hb) and factors that influence Hb from renal centres in England, Wales, Northern Ireland (EWNI) and the Scottish Renal Registry for the incident and prevalent renal replacement therapy (RRT) cohorts for 2009. RESULTS: In the UK, in 2009 55% of patients commenced dialysis therapy with Hb x10.0 g/dl (median Hb 10.2 g/dl). The median Hb of haemodialysis (HD) patients was 11.6 g/dl with an interquartile range (IQR) of 10.6 - 12.4 g/dl. Of HD patients 85% had Hb ≥ 10.0 g/dl. The median Hb of peritoneal dialysis (PD) patients in the UK was 11.7 g/dl (IQR 10.7-12.6 g/dl). Of UK PD patients, 88% had Hb ≥ 10.0 g/dl. The median ferritin in HD patients in EWNI was 441 mg/L (IQR 289-629) and 96% of HD patients had a ferritin ≥ 100 mg/L. The median ferritin in PD patients was 249 mg/L (IQR 142-412) with 86% of PD patients having a ferritin 5100 mg/L. In EWNI the mean Erythropoietin Stimulating Agent (ESA) dose was higher for HD than PD patients (9,507 vs. 6,212 IU/week). CONCLUSIONS: In 2009, 56% of prevalent HD patients had a Hb ≥ 10.5 and ≤ 12.5 g/dl compared with 54% in 2008 and 53% in 2007. Fifty-four percent of prevalent PD patients had a Hb ≥10.5 and ≤12.5 g/dl compared to 55% in 2008.

UK Renal Registry 13th Annual Report (December 2010): Chapter 4: comorbidities and current smoking status amongst patients starting renal replacement therapy in England, Wales and Northern Ireland from 2008 to 2009.

INTRODUCTION: Comorbidity is an important determinant of survival for renal replacement therapy patients and impacts other care processes such as dialysis access creation and transplant wait-listing. The prevalence of comorbidities in incident patients on renal replacement therapy (RRT) changes with age and varies between ethnic groups. This study describes these associations and the independent effect of comorbidities on outcomes. METHODS: Incident patients reported to the UK Renal Registry (UKRR) with comorbidity data in 2008 and 2009 (n = 5,617) were included in analyses exploring the association of comorbidity with patient demographics, treatment modality, haemoglobin and renal function at start of RRT. For analyses examining comorbidity and survival, adult patients starting RRT between 2004 and 2009 in centres reporting to the UKRR with comorbidity data (n = 16,527) were included. The relationship between comorbidities and mortality at 90 days and one year after 90 days from start of RRT was explored using Cox regression. RESULTS: Completeness of comorbidity data was 44.4% in 2009 compared with 52.1% in 2004. Of patients with data, 56.5% had one or more comorbidities. Diabetes mellitus and ischaemic heart disease were the most common conditions seen in 32.9% and 22.5% of patients respectively. Current smoking was recorded for 12.4% of incident RRT patients in the 2-year period. The presence of comorbidities in patients <75 years became more common with increasing age in all ethnic groups. In multivariable survival analysis, malignancy and the presence of ischaemic/neuropathic ulcers were the strongest independent predictors of poor survival at 1 year after 90 days from the start of RRT in patients <65 years. CONCLUSION: Differences in prevalence rates of comorbid illnesses in incident RRT patients may reflect variation in access to health care or competing risk prior to commencing treatment. The interpretation of analyses continues to be limited by poor data completeness.

UK Renal Registry 13th Annual Report (December 2010): Chapter 3: demographic and biochemistry profile of kidney transplant recipients in the UK in 2009: national and centre-specific analyses.

INTRODUCTION: National transplant registries routinely focus on centre-specific patient and graft survival rates following renal transplantation. However other outcomes such as graft function (as measured by eGFR), haemoglobin, biochemical variables and blood pressure are also important quality of care indicators. METHODS: Renal transplant activity, incident graft survival data and donor information were obtained from NHS Blood and Transplant. Laboratory and clinical variables and prevalent survival data were obtained from the UK Renal Registry. Data were analysed separately for prevalent and one year post-transplant patients. RESULTS: Increasing live and donor after cardiac death donors were responsible for the increasing transplant activity within the UK. During 2009, 2.9% of prevalent transplant patients experienced graft failure and transplant patient death rates remained stable at 2.5 per 100 patient years. There was centre variation in outcomes including eGFR, haemoglobin and biochemical variables in prevalent and 1 year posttransplant patients. Analysis of prevalent transplants by chronic kidney disease stage showed 14.3% with an eGFR <30 ml/min/1.73 m(2) and 1.9% with an eGFR <15 ml/min/1.73 m(2). Of those with CKD stage 5T, 33.3% had haemoglobin concentrations <10.5 g/dl, 22.4% phosphate concentrations ≥ 1.8 mmol/L and 7.7% adjusted calcium concentrations ≥ 2.6 mmol/L. CONCLUSION: Significant variations in clinical outcomes (unadjusted for patient-specific variables) amongst kidney transplant recipients continued to exist in the UK, and may reflect differences in healthcare delivery between renal centres.

UK Renal Registry 13th Annual Report (December 2010): Chapter 11: blood pressure profile of prevalent patients receiving renal replacement therapy in England, Wales and Northern Ireland in 2009: national and centre-specific analyses.

BACKGROUND: The UK Renal Registry (UKRR) assesses blood pressure (BP) control annually for patients receiving Renal Replacement Therapy (RRT) at renal centres in England, Wales and Northern Ireland. METHODS: Patients alive and receiving RRT on 31st December 2009 with a BP reading in either the fourth or third quarter of 2009 were included. Summary statistics were calculated for each renal centre and country. RESULTS: Data completeness for BP measurements submitted to the UKRR for all modalities improved from the previous year and was better for HD patients (67% for pre-HD measurements) than for PD patients (44%) or transplant recipients (37%). In 2009, the median pre-and post-HD SBP were 142 mmHg and 129 mmHg respectively. The median SBP of patients on PD was 137 mmHg. Transplant recipients had a median SBP of 134 mmHg. Median DBP were 74 mmHg (pre-HD), 68 mmHg (post-HD), 79 mmHg (PD) and 79 mmHg (transplant). Only 26.7% of PD patients achieved the Renal Association guideline of SBP <130 mmHg and DBP <80 mmHg. Amongst transplant patients, 27.2% achieved the Renal Association guideline of SBP <130 mmHg and DBP <80 mmHg. CONCLUSION: In 2009 there continued to be significant variation in the achievement of BP standards between UK renal centres.

UK Renal Registry 13th Annual Report (December 2010): Chapter 13: centre variation in access to renal transplantation in the UK (2004-2006).

BACKGROUND: Renal transplantation is recognised as being the optimal treatment modality for many patients with end stage renal disease. This analysis aimed to explore the equity of access to renal transplantation in the UK. METHODS: Transplant activity and waiting list data were obtained from NHS Blood and Transplant, demographic and laboratory data were obtained from the UK Renal Registry. All incident RRT patients starting treatment between 1st January 2004 and 31st December 2006 from 65 renal centres were considered for inclusion. The cohort was followed until 31st December 2008 (or until transplantation or death, whichever was earliest). RESULTS: Age, ethnicity and primary renal diagnosis were associated with both accessing the kidney transplant waiting list and receiving an organ. A patient starting dialysis in a non-transplanting renal centre was less likely to be registered for transplantation (OR 0.90, 95% CI 0.82-0.99) or receive a transplant from a donor after cardiac death or a living kidney donor (OR 0.69, 95% CI 0.60-0.79) compared with patients cared for in transplanting renal centres. Once registered for kidney transplantation, patients in both transplanting and nontransplanting renal centres had an equal chance of receiving a transplant from a donor after brain stem death (OR 0.92, 95% CI 0.78-1.08). CONCLUSION: There is wide variation in access to kidney transplantation between UK renal centres which cannot be explained by differences in case mix.

UK Renal Registry 12th Annual Report (December 2009): chapter 6: comorbidities and current smoking status amongst patients starting renal replacement therapy in England, Wales and Northern Ireland from 2003 to 2008: national and centre-specific analyses.

INTRODUCTION: The prevalence of comorbidities in incident renal replacement therapy (RRT) patients changes with age and varies between ethnic groups. This study describes these associations and the independent effect of comorbidities on outcomes. METHODS: Adult patients starting RRT between 2003 and 2008 in centres reporting to the UK Renal Registry (UKRR) with data on comorbidity (n (1/4) 14,909) were included. The UKRR studied the association of comorbidity with patient demographics, treatment modality, haemoglobin, renal function at start of RRT and subsequent listing for kidney transplantation. The relationship between comorbidities and mortality at 90 days and one year after 90 days from start of RRT was explored using Cox regression. RESULTS: Completeness of comorbidity data was 40.0% compared with 54.3% in 2003. Of patients with data, 53.8% had one or more comorbidities. Diabetes mellitus and ischaemic heart disease were the most common conditions seen in 30.1% and 22.7% of patients respectively. Current smoking was recorded for 14.5% of incident RRT patients in the 6-year period. Comorbidities became more common with increasing age in all ethnic groups although the difference between the 65-74 and 75+ age groups was not significant. Within each age group, South Asians and Blacks had lower rates of comorbidity, despite higher rates of diabetes mellitus. In multivariate survival analysis, malignancy and ischaemic/neuropathic ulcers were the strongest independent predictors of poor survival at 1 year after 90 days from the start of RRT. CONCLUSION: Differences in prevalence of comorbid illnesses in incident RRT patients may reflect variation in access to health care or competing risk prior to commencing treatment. At the same time, smoking rates remained high in this 'at risk' population. Further work on this and ways to improve comorbidity reporting should be priorities for 2010-11.

UK Renal Registry 12th Annual Report (December 2009): chapter 5: demographic and biochemistry profile of kidney transplant recipients in the UK in 2008: national and centre-specific analyses.

INTRODUCTION: National renal transplant registries routinely report on centre-specific patient and graft survival following renal transplantation. However, other outcomes such as graft function (as measured by eGFR), haemoglobin and blood pressure are also important indicators of quality of care. METHODS: Transplant activity and incident graft survival data were obtained from NHS Blood and Trans-plant, laboratory and clinical variables and prevalent survival data were obtained from the UK Renal Registry. Data were analysed separately for prevalent and one year post-transplant patients. RESULTS: Increasing live and nonheartbeating donors were responsible for the increasing transplant activity. Graft failure occurred in 2.9% of prevalent transplant patients and death rates remained stable at 2.4/100 patient years. In transplant recipients with a specified cause of death, 21% died due to malignancy and 21% as a consequence of cardiac disease. There was centre variation in outcomes including eGFR and haemoglobin in prevalent and 1 year post-transplant recipients. Analysis of prevalent transplants by chronic kidney disease stage showed 14.7% with an eGFR <30 ml/min/1.73 m(2) and 2.1% <15 ml/min/1.73 m(2). Of those with CKD stage 5T, 40.4% had Hb concentrations <10.5 g/dl, 25.9% phosphate concentrations >or=1.8 mmol/L, 9.0% adjusted calcium concentrations >or=2.6 mmol/L and 40.8% PTH concentrations >or=32 pmol/L. With the exception of PTH, transplant recipients with CKD stage 5T were less likely to achieve the UK standards compared to prevalent dialysis patients. CONCLUSION: Wide variations in clinical and biochemical outcomes amongst transplant recipients continue to exist and may reflect differences in healthcare delivery across the UK.