Tubulointerstitial nephritis and uveitis in Northern Ireland.

OBJECTIVES: This paper looks at patients with a diagnosis of tubulointerstitial nephritis and uveitis (TINU) presenting to the Northern Ireland regional adult and paediatric uveitis service in the Belfast Health and Social Care Trust. The demographic distribution, treatment required and the visual and renal outcomes of these patients are documented. METHODS: Data were collected retrospectively on 24 patients with TINU using the Northern Ireland Electronic Care Record, central pathology records alongside the adult and paediatric uveitis databases from 2011 to 2021. Patients were categorised into two groups using the Mandeville classification system. Standard Uveitis Nomenclature (SUN) was used to classify the uveitis. RESULTS: The population prevalence is at least 12.6 cases per million based on a population of 1.9 million. Nineteen of 24 cases were definite TINU and five of 24 probable. Seventeen out of 24 had biopsy-positive TIN, all of which met all of the Mandeville clinical diagnostic features required for a definite diagnosis. All but one presented with acute bilateral anterior uveitis. The paediatric cases ranged from age 12 to 18 at age of onset with a mean age of 14. Of the 18 adult onset cases, the age ranged from 20 to 76 years. The mean age of onset for the adult cases was 53 years. Of these patients 71% were female; 42% required second-line immunosuppression for ocular disease. Visual acuity was maintained. Follow-up time ranged from 3 months to 16 years. No patient developed long-term renal impairment. CONCLUSIONS: TINU is a cause of uveitis in both the paediatric and adult populations. In Northern Ireland average age with TINU was older than much of the published literature. Long-term immunosuppression for uveitis may be required as ongoing ocular, rather than renal inflammation seemed to require treatment.

Understanding the holistic experiences of living with a kidney transplant: an interpretative phenomenological study (protocol).

BACKGROUND: Currently very little is known about the perceptions and experiences of kidney transplant recipients from a qualitative perspective. As highlighted by the European Kidney Health Alliance recommendations, providing holistic care to kidney patients is important however this is currently an unmet care need in renal disease. It is imperative to understand patient experiences to ensure that they are included in key strategies and future renal service planning. Ignoring these important patient views means that there is a significant risk of inappropriate renal service provision and lack of adequate support impacting on overall health. METHOD: A purposive sampling strategy will recruit individuals currently living with a kidney transplant, 6 months to 5 years post-transplant. A maximum of 30 patients will be recruited between two Regional Nephrology units within the United Kingdom via clinical gatekeepers. In-depth interviews will be undertaken with participants living with a kidney transplant across the two sites. Interviews will be digitally-recorded, transcribed verbatim and subjected to interpretative phenomenological analysis. DISCUSSION: Renal healthcare professionals need to understand more than the biological impact of receiving a kidney transplant. Understanding the holistic and multi-domain experiences that these patients experience will help healthcare professionals to recognize the needs of this group and ensure more responsive care.

Introduction of an enhanced recovery protocol into a laparoscopic living donor nephrectomy programme.

INTRODUCTION: Living-donor renal transplantation is the optimal treatment for patients with end-stage renal disease. The rate of living donation in the UK is sub-optimal, and potential donor concerns regarding postoperative recovery may be contributory. Enhanced recovery programmes are well described for a number of surgical procedures, but experience in living-donor surgery is sparse. This study reports the impact of introducing an enhanced recovery protocol into a living-donor renal transplant programme. MATERIALS AND METHODS: All consecutive patients undergoing laparoscopic living-donor nephrectomy over a 25-month period were included. The principles of enhanced recovery were fluid restriction, morphine sparing and expectation management. Outcome measures were postoperative pain scores and complications for donor and recipients. RESULTS: Standard care was provided for 24 (30%) patients and 57 (70%) followed an enhanced recovery pathway. The latter group received significantly less preoperative intravenous fluid (0ml vs 841ml p < 000.1) and opiate medication (14.83mg vs 23.85mg p = 0.001). Pain scores, postoperative complications and recipient transplant outcomes were comparable in both groups. CONCLUSIONS: Enhanced recovery for living-donor nephrectomy is a safe approach for donors and recipients. Application of these techniques and further refinement should be pursued to enhance the experience of living donors.

The Timing of Application and Inclusion of a Surfactant Are Important for Absorption and Translocation of Foliar Phosphoric Acid by Wheat Leaves.

Introduction: Foliar applied phosphorus (P) has the potential to provide a more tactical approach to P fertilization that could enhance P use efficiency. The aims of this study were to investigate the influence of adjuvant choice and application timing of foliar applied phosphoric acid on leaf wettability, foliar uptake, translocation, and grain yield of wheat plants. Materials and Methods: We measured the contact angles of water and fertilizers on wheat leaves, and the uptake, translocation and wheat yield response to isotopically-labelled phosphoric acid in combination with five different adjuvants when foliar-applied to wheat at either early tillering or flag leaf emergence. Results: There was high foliar uptake of phosphoric acid in combination with all adjuvants that contained a surfactant, but only one treatment resulted in a 12% increase in grain yield and two treatments resulted in a decrease in grain yield. Despite the wettability of all foliar fertilizers being markedly different, foliar uptake was similar for all treatments that contained a surfactant. The translocation of phosphorus from foliar sources was higher when applied at a later growth stage than when applied at tillering despite the leaf surface properties that affect wettability being similar across all leaves at both growth stages. Discussion: Both the timing of foliar application and the inclusion of a surfactant in the formulation are important for absorption and translocation of phosphoric acid by wheat leaves, however high foliar uptake and translocation will not always translate to a yield increase.

Is big bad or bearable? Long-term renal transplant outcomes in obese recipients.

BACKGROUND: The global obesity epidemic has implications for kidney transplantation. There are conflicting reports regarding the impact of obesity on long-term post-transplant outcomes. AIM: To explore the impact of body mass index (BMI) on long-term outcomes after kidney transplantation. DESIGN: The association between BMI and cardiovascular disease, cancer, post-transplant diabetes mellitus, graft and recipient survival was investigated in recipients who had been transplanted at least ten years previously. METHODS: All consecutive adult renal transplant recipients who received first, deceased donor, transplants between 1986 and 2005 in Northern Ireland were followed-up until 2016. RESULTS: A total of 328 patients were eligible. Of them, 96 were overweight with a BMI 25.0-29.9 kg/m2, and 56 were obese with a BMI exceeding 29.9 kg/m2. Median follow-up time was 16.7 years. In multivariate analysis recipient BMI was associated with the development of post-transplant diabetes mellitus (P=0.003), but not with new cardiovascular disease (P=0.78). Cancer was less common in recipients with a higher BMI (hazard ratio (HR) 0.58, P < 0.001). BMI at the time of transplantation did not significantly influence graft (P=0.28) or recipient survival (P=0.13). CONCLUSIONS: Increased BMI at time of transplantation is associated with an increased risk of post-transplant diabetes mellitus but not new cardiovascular disease or malignancy. Long-term graft and recipient survival is not impacted. Potential recipients should not be excluded from transplantation solely on the basis of obesity, rather it should be considered as one part of an individualized risk stratification, based on comorbidity and considering the risk of death on maintenance dialysis.

Uptake of phosphorus from surfactant solutions by wheat leaves: spreading kinetics, wetted area, and drying time.

The delivery and uptake of nutrients at the surface of plant leaves is an important physicochemical phenomenon that depends on leaf surface morphology and chemistry, fertilizer formulation chemistry (including adjuvant and associated surfactants), wetting dynamics, and many other physical, chemical and biological factors. In this study, the role of spreading dynamics in determining uptake of the macronutrient phosphorus from phosphoric acid fertilizer solution in combination with three different adjuvants was measured in the absence of droplet run-off and splashing. When run-off and splashing losses were zero, spreading and drying rates had a small to negligible effect on the uptake efficiency. The results suggest that uptake may be much less sensitive to the specific choice of adjuvant and long time-scale spreading behaviour than one might intuitively expect.

The clinical course of kidney transplant recipients after 20 years of graft function.

There is a growing population of kidney transplant recipients who have survived 20 years with a functioning graft. This study identified the factors associated with prolonged survival and described the clinical course of recipients after two decades of transplant function. All recipients transplanted in Northern Ireland between 1968 and 1993 were included (n = 706) and data were collected prospectively. At 20 years, 25% had a functioning transplant; in multivariate analysis younger recipient age and living donation were associated with 20-year survival. The median recipient survival beyond two decades was 13.3 years; cancer was the commonest cause of death. De novo malignancy developed in 37% of recipients and cardiovascular disease in 27% after 20 years of graft function. The median graft survival after 20 years was 9.3 years; 69% of graft loss was due to death with a functioning transplant. Advances in kidney transplantation have improved the long-term survival of both graft and recipient. After two decades the majority of patients die with a functioning graft. The focus of management in long-term survivors may need to be on the prevention of cancer and cardiovascular disease to allow further improvements in graft and recipient survival.

Four decades of chronic haemodialysis: lessons from the past and implications for the future.

BACKGROUND: There have been substantial changes in the provision of chronic haemodialysis (HD) therapy over time, yet data regarding the impact of these differences on clinical outcomes are limited. AIM: To identify factors which have significantly changed over the last 40 years in relation to patients receiving maintenance HD therapy. METHODS: All 2,647 patients who were established on the chronic HD programme in Northern Ireland between 1970 and 2010 were included. Clinical data and survival outcomes were obtained from a prospectively recorded database. The study period was divided into four decades in order to assess the temporal changes. RESULTS: The total number of patients receiving HD therapy has risen, and the mean age of the HD population has increased significantly (39.0 years in the 1970s vs. 66.8 years in the 2000s, p < 0.001). Diabetic nephropathy has emerged as the commonest aetiology for ESRD (0% in the 1970s to 20.3% in the 2000s, p < 0.001). The median survival of patients on HD has improved significantly over time from 5.2 months (95% CI 2.6-15.5) in the 1970s to 41.7 months (95% CI 38-45.2) in the 2000s (p < 0.0001). Factors that remained significant in determining survival were age, primary renal diagnosis, and decade of commencement of dialysis. CONCLUSIONS: Survival on HD has significantly improved despite older patients with multiple co-morbidities being accepted for treatment reflecting both increased dialysis frequency and better management of cardiovascular risk factors. The increasing age of HD patients and their improved survival have implications for future planning and delivery of dialysis.

Recurrent dense deposit disease after renal transplantation: an emerging role for complementary therapies.

Dense deposit disease is a rare glomerulonephritis caused by uncontrolled stimulation of the alternative complement pathway. Allograft survival after kidney transplantation is significantly reduced by the high rate of disease recurrence. No therapeutic interventions have consistently improved outcomes for patients with primary or recurrent disease. This is the first reported case of recurrent dense deposit disease being managed with eculizumab. Within 4 weeks of renal transplantation, deteriorating graft function and increasing proteinuria were evident. A transplant biopsy confirmed the diagnosis of recurrent dense deposit disease. Eculizumab was considered after the failure of corticosteroid, rituximab and plasmapheresis to attenuate the rate of decline in allograft function. There was a marked clinical and biochemical response following the administration of eculizumab. This case provides the first evidence that eculizumab may have a place in the management of crescentic dense deposit disease. More information is necessary to clarify the effectiveness and role of eculizumab in dense deposit disease but the response in this patient was encouraging. The results of clinical trials of eculizumab in this condition are eagerly awaited.

Chronic kidney disease and bisphosphonate treatment: are prescribing guidelines unnecessarily restrictive?

The prevalence of both osteoporosis and chronic kidney disease (CKD) increases with advancing age. Bisphosphonates are effective in the prevention and treatment of osteoporosis but current recommendations limit their use in patients with renal impairment because of concern regarding the safety profile of these agents in the setting of reduced renal function. The appropriateness of bisphosphonate treatment for patients with CKD is also in question since CKD is independently associated with a variety of skeletal abnormalities, collectively termed renal osteodystrophy, including pre-existing low bone turnover. The evidence to support the current prescribing restrictions is not robust and there are some data to suggest both that bisphosphonate treatment reduces fracture risk without an increase in adverse events in patients with CKD, and that in clinical practice there is underutilisation of this treatment in early CKD. Appropriate prospective trial data with clinically important end points in CKD patients is awaited.

The evolution of renal transplantation in clinical practice: for better, for worse?

BACKGROUND: Kidney transplantation is the optimal form of renal replacement therapy for most patients with end-stage renal disease. Attempting to improve graft and recipient survival remains challenging in clinical practice. AIM: To identify the factors that have significantly changed over the past four decades and assess their impact on renal transplant outcomes. DESIGN: Retrospective review of all renal transplant procedures in a single UK region. METHODS: All 1346 renal transplant procedures performed between 1 January 1967 and 31 December 2006 were reviewed. Clinical data, histological reports and outcomes were available from a prospectively recorded database. The study period was divided into four decades to assess the changes in renal transplantation over time. RESULTS: Significant changes that have occurred include an increase in donor and recipient ages, a greater proportion of recipients with diabetic nephropathy, a longer wait before the first transplant procedure, a fall in the incidence and impact of acute rejection, a smaller proportion of deaths due to cardiovascular disease, (P < 0.001 for all) and a trend to increased deaths from malignancy (P = 0.06) over time. In multivariate analysis, death censored graft survival was significantly influenced by the era of transplantation, donor and recipient ages, living vs. deceased donor status, and histological evidence of acute rejection, chronic allograft nephropathy, or disease recurrence. Significant factors in recipient survival were the era of transplantation, recipient age, a primary renal diagnosis of diabetic nephropathy or unspecified chronic renal failure, and biopsy proven acute rejection. CONCLUSION: There have been major changes in the clinical practice related to renal transplantation over the past four decades; some have been beneficial and others detrimental to survival. Regular review of outcomes is essential to guide renal services development and maximize graft and recipient survival.

Critiques of clinical guidelines in nephrology: anaemia.

Chronic kidney disease (CKD) is characterised by reduced erythropoietin production and anaemia. The introduction in the late 1980s of recombinant human erythropoietin transformed the quality of life and the blood transfusion requirements of patients with advanced CKD, and several erythropoietin analogues or derivatives with the collective name of erythropoiesis-stimulating agents (ESAs) are now available. However, despite the treatment of hundreds of thousands of patients with ESAs there have still been relatively few randomised controlled trials comparing outcomes at pre-specified haemoglobin (Hb) concentrations. Several unanswered questions remain regarding the optimal use of ESAs, including the ideal target Hb level for an individual and a CKD population. The conclusion from the available interventional studies is that there is no evidence for a beneficial effect of complete correction of Hb and there is weak evidence of harm with an increase in cardiovascular events and mortality. This has prompted some renal advisory bodies to modify their guidance on ESA prescribing. This critique reviews current clinical guidelines and recommendations, their scientific basis, and identifies areas of controversy including the role of newer agents, the long-term safety of ESAs, the influence of the pharmaceutical industry, and the associated healthcare costs.

Influence of prolonged hospitalization on overall bed occupancy: a five-year single-centre study.

BACKGROUND: Effective bed use is crucial to an efficient NHS. Current targets suggest a decrease in mean occupancy as the most appropriate method of improving overall efficiency. The elderly and those suffering from complex medical problems are thought to account for a high proportion of overall bed occupancy. AIM: To assess the effect of prolonged hospital stay (>100 days) on overall bed occupancy in a modern teaching hospital. DESIGN: Retrospective analysis. METHODS: Analysis of all admission episodes (n = 117,178) over a five-year period in a large teaching hospital in a single UK region, serving a population of approximately 200,000. A logistic regression multi-factorial model was used to assess the effect of demographic and diagnostic variables on duration of stay. RESULTS: A prolonged stay (>100 days) was seen in 648 admission episodes (0.6%). These accounted for 11% of the overall bed occupancy over the 5-year period. Excluding all prolonged admission episodes from our analysis made no difference to the overall median length of stay. DISCUSSION: Prolonged hospitalizations have a significant impact on bed occupancy. Targeting these very long (>100 days) hospital stays may better improve overall efficiency, compared to targeting mean or median length of stay.

Association of functional heme oxygenase-1 gene promoter polymorphism with renal transplantation outcomes.

Heme oxygenase-1 (HO-1) is a cytoprotective molecule and increased expression in experimental transplant models correlates with reduced graft injury. A functional dinucleotide repeat (GT)(n) polymorphism, within the HO-1 promoter, regulates gene expression; a short number of repeats (S-allele <25) increases transcription. The role of this HO-1 gene promoter polymorphism on renal transplant outcomes was assessed. DNA from 707 donor/recipient pairs (n = 1414) of first deceased donor renal transplants (99% Caucasian) was genotyped. Graft survival was not significantly impacted by carriage of an S-allele by the donor (hazard ratio 0.89, 95% CI 0.71-1.11; p = 0.28) or recipient (hazard ratio 1.19, 95% CI 0.95-1.48; p = 0.13). Similarly neither donor nor recipient genotype influenced recipient survival (hazard ratio 0.89, 95% CI 0.67-1.18; p = 0.41, and hazard ratio 1.22, 95% CI 0.93-1.62; p = 0.16). The hazard ratios changed only minimally in multivariate analysis including significant survival factors. Genotype did not alter the incidence of acute rejection or chronic allograft nephropathy. There is no evidence of a protective effect for the S-allele of the HO-1 gene promoter polymorphism on graft or recipient survival in clinical renal transplantation.

Proposed risk stratification in upper gastrointestinal haemorrhage: is hospitalisation essential?

AIMS: Patients with upper gastrointestinal haemorrhage (UGIH) are usually admitted to hospital regardless of the severity of the bleed. The aim of this study was to identify patients who could be safely managed without hospitalisation and immediate inpatient endoscopy. METHODS: Based on a literature review, a protocol was devised using clinical and laboratory data regarded as being of prognostic value. A retrospective observational study of consecutive patients who attended the emergency department (ED) with UGIH was conducted during one calendar month. RESULTS: Fifty four patients were identified of whom 44 (81%) were admitted. Twelve suffered an adverse event. One of the 10 patients (10%) initially discharged from the ED was later admitted. Strict implementation of the protocol would have resulted in safe discharge of a further 15 patients, (34% of those admitted), and a saving of an estimated 37 bed days per month. CONCLUSIONS: Patients at low risk from UGIH may be identified in the ED. If validated, this protocol may improve patient management and resource utilisation.

Human immunoglobulin for diabetic amyotrophy--a promising prospect?

Diabetic neuropathies are universally recognised and cause significant morbidity. At present improving glycaemic control is the only recognised treatment. A man with type 2 diabetes presented with disabling asymmetric lower limb proximal neuropathy. Rapid clinical, functional, and electrical improvement followed treatment with intravenous immunoglobulin. The aetiology of diabetic amyotrophy remains controversial but there is evidence for an immune mediated process and this case suggests a role for immunoglobulin in the management of this debilitating condition.