Progressive survival improvement of incident dialysis patients in a tertiary center, Ireland.

BACKGROUND: The survival of incident dialysis patients' end-stage kidney disease in some European and American has been reported to improve in modern era compared to earlier periods. However, in Ireland, this has not been well documented. AIM: To investigate the survival outcomes of incident end-stage kidney failure dialysis patients in a tertiary center over a 24-year period, 1993-2017. METHODS: A retrospective analysis was carried out utilizing the Beaumont Hospital Renal Database. Consecutive adults with incident dialysis were analyzed. Kaplan-Meier methods and the estimated mean survival times were used to evaluate survival at successive 4-year periods of time. RESULTS: In total, 2106 patients were included, of whom 830 underwent subsequent renal transplantation during follow-up. During the study period, from 1993 up to 2017, the mean patients' age increased from 56.3 ± 17.4 in 1993-1996 to 60.6 ± 18.3 in 2014-2017. There was an overall decrement in mortality over successive time intervals which were mirrored by the improvements in median survival after commencement of dialysis treatment from 6.14 years during 1993-1996 to 8.01 years during 2009-2012. Patients' survival has steadily improved, with the 5-year survival has risen over time, by almost 15%. This positive signal persisted and became more pronounced after adjusting Kaplan-Meier curve to age, where the 5-year survival estimates were exceeding 80% in 2014-2017. CONCLUSION: Survival rates among incident dialysis patients have improved progressively between 1993 and 2017 in Beaumont Hospital in Dublin, Ireland. The factors which led to this improvement are not entirely clear, but likely to be multifactorial.

Improved graft survival in highly sensitized patients undergoing renal transplantation after the introduction of a clinically validated flow cytometry crossmatch.

BACKGROUND: Flow cytometric techniques are increasingly used in pretransplant crossmatching, although there remains debate regarding the clinical significance and predictive value of donor-specific antibodies detected by flow cytometry. At least some of the discrepancies between published studies may arise from differences in cutoffs used and lack of standardization of the test. METHODS: We selected cut-off values for pretransplant flow cytometric crossmatching (FCXM) based on the correlation of retrospective results with the occurrence of antibody-mediated rejection. The impact on long-term renal graft survival of prospective FCXM was determined by comparing graft survival between patients crossmatched with complement-dependent cytotoxicity (CDC) only with those prospectively crossmatched with both CDC and FCXM. RESULTS: Chosen cut-off values gave a positive predictive value of FCXM for antibody-mediated rejection of 83%, and a negative predictive value of 90%. After the introduction of prospective B- and T-cell crossmatching by flow cytometry in addition to CDC in our center, there was a significant improvement in renal graft survival in highly sensitized patients (P=0.017). Four-year graft survival in highly sensitized patients after the introduction of FCXM was 89%, which did not differ significantly from that seen in nonsensitized patients (93%; P=0.638). CONCLUSIONS: Our data demonstrate that prospective FCXM improves renal transplant outcome in highly sensitized patients, provided that cut-off values are carefully validated and results interpreted in the context of sensitization history and antibody screening results.

Factors influencing general practitioner referral of patients developing end-stage renal failure: a standardised case-analysis study.

BACKGROUND: To understand why treatment referral rates for ESRF are lower in Ireland than in other European countries, an investigation of factors influencing general practitioner referral of patients developing ESRF was conducted. METHOD: Randomly selected general practitioners (N = 51) were interviewed using 32 standardised written patient scenarios to elicit referral strategies. MAIN OUTCOME MEASURES: General practitioner referral levels and thresholds for patients developing end-stage renal disease; referral routes (nephrologist vs other physicians); influence of patient age, marital status and co-morbidity on referral. RESULTS: Referral levels varied widely with the full range of cases (0-32; median = 15) referred by different doctors after consideration of first laboratory results. Less than half (44%) of cases were referred to a nephrologist. Patient age (40 vs 70 years), marital status, co-morbidity (none vs rheumatoid arthritis) and general practitioner prior specialist renal training (yes or no) did not influence referral rates. Many patients were not referred to a specialist at creatinine levels of 129 micromol/l (47% not referred) or 250 micromol/l (45%). While all patients were referred at higher levels (350 and 480 micromol/l), referral to a nephrologist decreased in likelihood as scenarios became more complex; 28% at 129 micromol/l creatinine; 28% at 250 micromol/l; 18% at 350 micromol/l and 14% at 480 micromol/l. Referral levels and routes were not influenced by general practitioner age, sex or practice location. Most general practitioners had little current contact with chronic renal patients (mean number in practice = 0.7, s.d. = 1.3). CONCLUSION: The very divergent management patterns identified highlight the need for guidance to general practitioners on appropriate management of this serious condition.

Reduced graft function (with or without dialysis) vs immediate graft function--a comparison of long-term renal allograft survival.

BACKGROUND: Delayed graft function (DGF) is a common complication in cadaveric kidney transplants affecting graft outcome. However, the incidence of DGF differs widely between centres as its definition is very variable. The purpose of this study was to define a parameter for DGF and immediate graft function (IGF) and to compare the graft outcome between these groups at our centre. METHODS: The renal allograft function of 972 first cadaveric transplants performed between 1990 and 2001 in the Republic of Ireland was examined. The DGF and IGF were defined by a creatinine reduction ratio (CRR) between time 0 of transplantation and day 7 post-transplantation of <70 and >70%, respectively. Recipients with reduced graft function (DGF) not requiring dialysis were defined as slow graft function (SGF) patients. The serum creatinine at 3 months, 6 months, 1, 2 and 5 years after transplantation was compared between these groups of recipients. The graft survival rates at 1, 3 and 5 years and the graft half-life for DGF, SGF and IGF recipients were also assessed. RESULTS: Of the 972 renal transplant recipients, DGF was seen in 102 (10.5%) patients, SGF in 202 (20.8%) recipients and IGF in 668 (68.7%) patients. Serum creatinine levels were significantly different between the three groups at 3 and 6 months, 1, 2 and 5 years. Graft survival at 5 years for the DGF patients was 48.5%, 60.5% for SGF recipients and 75% for IGF patients with graft half-life of 4.9, 8.7 and 10.5 years, respectively. CONCLUSION: This study has shown that the CRR at day 7 correlates with renal function up to 5 years post-transplantation and with long-term graft survival. We have also demonstrated that amongst patients with reduced graft function after transplantation, two groups with significantly different outcomes exist.

The impact of donor spontaneous intracranial haemorrhage vs. other donors on long-term renal graft and patient survival.

BACKGROUND: Donor cause of death has a significant impact on transplant survival in heart transplants recipients. The objective of this study was to determine if long-term renal allograft and patient survival differed between grafts donated by donors who died of spontaneous intracranial haemorrhage (SIH) compared with those with other causes of death (OCOD). METHODS: Between 1990 and 2001, 1526 renal transplants were performed (711 SIH donors and 815 OCOD donors) at our unit. Serum creatinine levels at 1 yr, graft half-life and annual graft failure rate were measured for both groups. Renal graft and patient survivals between the groups were compared. Relative risk for SIH donors and other confounding variables was measured using Cox proportional hazards models. RESULTS: Graft half-life results were obtained for SIH (8 yr) and OCOD (10.13 yr) recipients. Graft and patient survival at 5 and 10 yr was 68.5% and 39.3% respectively for the SIH group vs. 76.8% and 51.9% respectively for the OCOD group (p < 0.001). However, SIH graft recipients were significantly older with more females. After adjustment for differences in baseline variables between the groups, donor cause of death did not have an independent effect on long-term graft or patient survival. CONCLUSION: Spontaneous intracranial haemorrhage as a cause of donor death, failed to have a significant independent effect on long-term allograft and patient survival.

Pretransplant cardiac investigations in the Irish renal transplant population--the effectiveness of our current screening techniques in predicting cardiac events.

BACKGROUND: Coronary artery disease (CAD) is prevalent among endstage renal failure patients and remains the major cause of mortality following renal transplantation. Death with a functioning transplant institute remains the most common cause of kidney graft failure. In this study we attempt to evaluate the effectiveness of the clinical history and current screening techniques available in predicting posttransplant CAD and also assess the role of coronary angiography as a pretransplant screening technique. METHODS: Clinical data of 190 renal transplant patients was analyzed. Any clinical history of cardiac disease and all preoperative cardiac screening data was recorded for each patient. The study endpoints were the subsequent development of myocardial infarction (MI), undergoing coronary artery bypass graft (CABG) or death. RESULTS: Factors that were significantly associated with reaching a study endpoint included: age at transplant [Hazard Ratio (HR) 1.91, P<0.001], history of heart failure (HR 8.22, P<0.001), presence of CAD on coronary angiography (HR 5.55, P=0.033), anterior Q wave on electrocardiograph (ECG) (HR 8.6, P<0.001), carotid artery disease (HR 3.74, P=0.030) and history of a cerebrovascular accident (HR of 4.32, P=0.008). The screening techniques of exercise stress testing and echocardiography were not conclusive as predictive variables of outcome. CONCLUSION: Clinical history and ECG results are good, practical and low-cost screening methods. In our study exercise stress testing and echocardiography were found to be of limited value. Coronary angiography is appropriate in certain high-risk groups but not necessary as part of screening in all potential renal transplant recipients.

Acute interstitial nephritis: clinical features and response to corticosteroid therapy.

BACKGROUND: Acute interstitial nephritis (AIN) is a recognized cause of reversible acute renal failure characterized by the presence of an interstitial inflammatory cell infiltrate. METHODS: In order to evaluate the clinical characteristics and management of this disorder, we performed a retrospective study of all cases of AIN found by reviewing 2598 native renal biopsies received at our institution over a 12 year period. Presenting clinical, laboratory and histological features were identified, as was clinical outcome with specific regard to corticosteroid therapy response. RESULTS: AIN was found in 2.6% of native biopsies, and 10.3% of all biopsies performed in the setting of acute renal failure during the period analysed (n = 60). The incidence of AIN increased progressively over the period observed from 1 to 4% per annum. AIN was drug related in 92% of cases and appeared to be idiopathic in the remainder. The presenting symptoms included oliguria (51%), arthralgia (45%), fever (30%), rash (21%) and loin pain (21%). Median serum creatinine at presentation was 670 micromol/l [interquartile range (IQR) 431-1031] and 58% of cases required acute renal replacement therapy. Corticosteroid therapy was administered in 60% of cases. Serum creatinine at baseline was similar in the corticosteroid-treated and conservatively managed groups; 700 micromol/l (IQR 449-1031) vs 545 micromol/l (IQR 339-1110) P = 0.4. In this, the largest retrospective series to date, we did not detect a statistically significant difference in outcome, as determined by serum creatinine, between those patients who received corticosteroid therapy and those who did not, at 1, 6 and 12 months following presentation. CONCLUSION: The results of this study do not support the routine administration of corticosteroid therapy in the management of AIN.

Plasmapheresis as rescue therapy in accelerated acute humoral rejection.

Accelerated acute humoral rejection (AHR) continues to occur in renal transplantation despite improved crossmatching, with potentially devastating consequences. Between 1 June 1998 and 31 December 2000, 440 renal transplants were performed in our center. AHR was diagnosed by the demonstration of typical pathological features on renal histology and positive direct immunofluorescence or detection of anti-HLA antibodies in serum. AHR developed in 20 (4.5%) of our renal transplant recipients, nine male and eleven female at an average of 16.3 days post transplantation. All of these patients had a negative current cytotoxic crossmatch prior to transplantation. The median serum creatinine at diagnosis was 5.96 mg/dL, and 83% of these individuals developed oliguric renal failure requiring dialysis after having initially attained good graft function (median of best serum creatinine before AHR was 2.64 mg/dL). The 18 recipients who had not infarcted their grafts at the time of diagnosis of AHR received plasmapheresis in conjunction with intensification of their immunosuppressive regimen. This regimen was successful in reversing AHR in 78% of those treated with apheresis. In the 14 responders, graft survival at 6 months was 100% and at 12 months was 91%. Median serum creatinine at 6 and 12 months was 1.26 and 1.33 mg/dL, respectively. Patients received an average of 8.1 plasma exchanges. However, responders received a significantly higher frequency of plasmapheresis (P =.0053), despite undergoing a similar number of exchanges overall. Plasmapheresis appears to be an effective modality for reversing AHR and maintaining graft function.

Reversal of pulmonary hypertension after ligation of a brachiocephalic arteriovenous fistula.

The arteriovenous (AV) fistula is the access method of choice for long-term hemodialysis according to DOQI guidelines. Among the recognized complications of upper extremity AV fistulae fashioned for hemodialysis are infection, aneurysm formation, and high-output left ventricular failure. We describe a novel cardiopulmonary complication--secondary pulmonary hypertension resulting from an aneurysmal brachiocephalic AV fistula. The clinical presentation, investigation, management, and pathophysiology of this complication are discussed.

The effect of pre-existing ischaemic heart disease on renal dysfunction in cardiac transplant recipients.

Renal dysfunction is a recognized complication of cardiac transplantation and can impact on the life expectancy of an already fragile population. A large proportion of these patients require transplantation because of the consequences of ischaemic heart disease (IHD) which, in turn, is often associated with ischaemic nephropathy. We studied the effect of IHD, diagnosed prior to transplantation, on the renal function of recipients who survived more than 6months after surgery. Of the 168 patients transplanted in a single centre over 15 years, 132 were included in the study. Renal dysfunction was defined as a serum creatinine consistently above 200 micromol/L (2.26 mg/dL). Analysis confirmed that IHD was an independent risk factor for developing renal impairment. In transplant recipients with IHD, closer monitoring is warranted to detect and prevent renal dysfunction or to retard its progression.