Elevated soluble cellular adhesion molecules are associated with increased mortality in a prospective cohort of renal transplant recipients.

BACKGROUND: Increased plasma levels of cellular adhesion molecules (CAMs) have been shown to be predictors of all cause mortality in individuals with chronic renal failure 12 and patients with end-stage renal disease receiving haemodialysis 3. In renal transplant recipients the predictive value of CAMs has not been well characterised. The aim of this study was to assess the relationship between CAMs and all-cause mortality during prospective follow-up of a renal transplant cohort. METHODS: A total of 378 renal transplant recipients were recruited between June 2000 and December 2002. Soluble vascular CAM-1 (VCAM) and soluble intercellular CAM-1 (ICAM) were measured at baseline and prospective follow-up data was collected at a median of 2441 days after enrolment. RESULTS: In univariate survival analysis the renal transplant recipients with a VCAM or ICAM concentration in the lowest third were significantly more likely to have survived at follow-up (p < 0.001 and p = 0.009 respectively). In multivariate survival analysis VCAM and ICAM remained significant independent predictors of mortality following adjustment for traditional cardiovascular risk factors, hsCRP and estimated GFR (p = 0.030 and p = 0.037 respectively). CONCLUSIONS: The results of this prospective study are the first to show that the CAMs, ICAM and particularly VCAM, are significant independent predictors of mortality in patients with a renal transplant.

Patterns of hospitalisation before and following initiation of haemodialysis: a 5 year single centre study.

BACKGROUND The utilisation of healthcare resources by prevalent haemodialysis patients has been robustly evaluated with regard to the provision of outpatient haemodialysis; however, the impact of hospitalisation among such patients is poorly defined. Minimal information is available in the UK to estimate the health and economic burden associated with the inpatient management of prevalent haemodialysis patients. The aim of this study was to assess the pattern of hospitalisation among a cohort of haemodialysis patients, before and following their initiation of haemodialysis. In addition the study sought to assess the impact of their admissions on bed occupancy in a large tertiary referral hospital in a single region in the UK. METHODS All admission episodes were reviewed and those receiving dialysis with the Belfast City Hospital Programme were identified over a 5 year period from January 2001 to December 2005. This tertiary referral centre provides dialysis services for a population of approximately 700 000 and additional specialist renal services for the remainder of Northern Ireland. The frequency and duration of hospitalisation, and contribution to bed day occupancy of haemodialysis patients, was determined and compared to other common conditions which are known to be associated with high bed occupancy. In addition, the pattern and timing of admissions in dialysis patients in relation to their dialysis initiation date was assessed. RESULTS Over the 5 year study period, 798 haemodialysis patients were admitted a total of 2882 times. These accounted for 2.5% of all admissions episodes; the median number of admissions for these patients was 3 (2-5) which compared with 1 (1-2) for non-dialysis patients. The majority of first hospitalisations (54%) were within 100 days before or after commencement of maintenance dialysis therapy. In all clinical specialties the median length of stay for haemodialysis patients was significantly longer than for patients not on haemodialysis (p=0.004). In multivariate analysis with adjustment for age, gender, and other clinically relevant diagnostic codes, maintenance haemodialysis patients stayed on average 3.75 times longer than other patient groups (ratio of geometric means 3.75, IQR 3.46-4.06). CONCLUSIONS Maintenance haemodialysis therapy is an important risk factor for prolonged hospitalisation regardless of the primary reason for admission. Such patients require admission more frequently than the general hospital population, particularly within 100 days before and after initiation of their first dialysis treatment.

Elevated homocysteine is a predictor of all-cause mortality in a prospective cohort of renal transplant recipients.

BACKGROUND: In patients with chronic kidney disease, an elevated homocysteine concentration is associated with an increased incidence of cardiovascular events. AIM: The aim of this study was to investigate the relationship between homocysteine concentration and all-cause mortality during prospective follow-up of a renal transplant cohort. METHODS: A total of 378 renal transplant recipients were recruited between June 2000 and December 2002. Homocysteine was measured at baseline and mortality data was collected at a median of 2,441 days after enrolment. RESULTS: In univariate analysis, homocysteine was a significant predictor of mortality (p < 0.001). In multivariate analysis, homocysteine remained a significant independent predictor of mortality following adjustment for traditional cardiovascular risk factors (p = 0.01), vitamin B(12) and folate (p < 0.001) and estimated glomerular filtration rate (p = 0.03). CONCLUSIONS: In the renal transplant recipients enrolled in this study, homocysteine concentration was a significant predictor of mortality in univariate survival analysis and in multivariate survival analysis following adjustment for traditional cardiovascular risk factors and following adjustment for renal function. Assessing the effect of lowering homocysteine concentration on the survival of patients with a renal transplant is therefore worthy of further study.

The impact of admissions for the management of end-stage renal disease on hospital bed occupancy.

BACKGROUND: End-stage renal disease (ESRD) is increasingly prevalent but the inpatient costs associated with this condition are poorly defined due to limitations with data extraction and failure to differentiate between hospitalisation for renal and non-renal disease reasons. The impact of admissions primarily for the management of ESRD on hospital bed utilisation was assessed over a 5-year period in a large teaching hospital. METHODS: All admission episodes were reviewed and the ESRD group was identified by a primary International Classification of Diseases code for ESRD or a non-specific primary renal failure code with a secondary code for ESRD. The frequency and duration of hospitalisation and contribution to bed day occupancy of this group with ESRD was determined. RESULTS: There were 70,808 patients responsible for a total of 116,915 admissions and 919,212 bed days over the study period. Of these, 988 (1.4%) patients were admitted for the management of ESRD, accounting for 2,387 (2.0%) of admissions and utilisation of 23,011 (2.5%) bed days. After adjustment for age and gender, those admitted for ESRD management were significantly more likely to have a prolonged admission exceeding 30 days (odds ratio 1.46, 95% confidence interval 1.23-1.72, p < 0.001). When the admission was an emergency rather than an elective event, the patient was 4.6 times more likely to be hospitalised for over 30 days. CONCLUSIONS: Persons admitted for ESRD management are hospitalised more frequently and for longer than the overall inpatient population, occupying a substantial number of bed days.

The changing pattern of adult primary glomerular disease.

BACKGROUND: Published biopsy series have shown geographical and temporal variations in the patterns of primary glomerulonephritis (GN). IgA nephropathy is the most common type of GN in most European studies, but there is evidence suggesting that focal segmental glomerulosclerosis (FSGS) is increasingly common in the USA in all ethnic groups. We report the analysis of 30 years of native renal biopsies and the temporal pattern of primary glomerular disease in a single United Kingdom (UK) region. METHODS: All 1844 adult native kidney biopsies for 30 years (1976-2005 inclusive) were analysed. The data were divided into three 10-year time frames, and trends in the biopsy rate and diagnosis of primary glomerular disease were considered. RESULTS: Biopsy rates increased significantly from 2.02 to 7.08 per hundred thousand population per year (php/year) (chi(2) = 55.9, P < 0.001), and the mean patient age at biopsy rose from 33 to 49 years over the study period (F = 58, P < 0.001). Primary GN was documented in 49% of biopsies; the most common diagnoses within this group were IgA nephropathy (38.8%), membranous nephropathy (29.4%), minimal change disease (9.8%), membranoproliferative GN type 1 (9.6%) and FSGS (5.7%). There was a significant increase in the proportion of IgA nephropathy (chi(2) = 9.6, P = 0.008) and a decrease in membranous nephropathy (chi(2) = 7.2, P = 0.03) over time. The population incidence of FSGS was low and unchanged at 0.18 php/ year from 1986 to 2005. CONCLUSIONS: Consistent with several other European studies, IgA nephropathy was the most common primary glomerular disease in this UK region. The diagnosis of FSGS was uncommon with no evidence of a rise in incidence.

Elevated serum phosphate predicts mortality in renal transplant recipients.

BACKGROUND: High serum phosphate has been identified as an important contributor to the vascular calcification seen in patients with chronic kidney disease (Block et al., Am J Kidney Dis 1998; 31: 607). In patients on hemodialysis, elevated serum phosphate levels are an independent predictor of mortality (Block et al., Am J Kidney Dis 1998; 31: 607; Block, Curr Opin Nephrol Hypertens 2001; 10: 741). The aim of this study was to investigate whether an elevated serum phosphate level was an independent predictor of mortality in patients with a renal transplant. METHODS: Three hundred seventy-nine asymptomatic renal transplant recipients were recruited between June 2000 and December 2002. Serum phosphate was measured at baseline and prospective follow-up data were collected at a median of 2441 days after enrolment. RESULTS: Serum phosphate was significantly higher in those renal transplant recipients who died at follow-up when compared with those who were still alive at follow-up (P<0.001). In Kaplan-Meier analysis, serum phosphate concentration was a significant predictor of mortality (P=0.0001). In multivariate Cox regression analysis, serum phosphate concentration remained a statistically significant predictor of all-cause mortality after adjustment for traditional cardiovascular risk factors, estimated glomerular filtration rate, and high sensitivity C reactive protein (P=0.036) and after adjustment for renal graft failure (P=0.001). CONCLUSIONS: The results of this prospective study are the first to show that a higher serum phosphate is a predictor of mortality in patients with a renal transplant and suggest that serum phosphate provides additional, independent, prognostic information to that provided by traditional risk factors in the risk assessment of patients with a renal transplant.

The uptake of cervical cancer screening by renal transplant recipients.

BACKGROUND: Renal transplant recipients are at an increased risk of developing cervical cancer compared to women in the general population. At least annual cervical smear screening is currently recommended, but little information is available regarding the actual uptake of such screening. METHODS: All female renal transplant recipients in one United Kingdom region who were alive with a functioning graft were identified. The uptake and results of cervical smear testing over a 10-year period in this cohort were determined. RESULTS: Of the 173 women eligible for cervical cancer screening, 18 (10%) undertook the recommended number of screening procedures; 56 (32%) had never had a cervical smear performed. The year of transplantation, age at engraftment and the social deprivation status did not significantly influence the uptake of screening (P > 0.05). In those women who were screened, the incidence of smear test abnormalities was 20% in renal transplant recipients compared with 7% in the general population. The cytological findings in the positive smear tests ranged from borderline changes to grade III cervical intraepithelial neoplasia. CONCLUSIONS: The renal transplant population is at higher risk of abnormal cervical cytology, but the uptake of cervical cancer screening is low. The reasons for this low screening rate are unclear, and changes in practice are necessary to improve the uptake of cervical smear testing in women with renal transplants.

Association of functional haem oxygenase-1 gene promoter polymorphism with polycystic kidney disease and IgA nephropathy.

BACKGROUND: Haem oxygenase-1 (HO-1) is a cytoprotective molecule that is reported to have a protective role in a variety of experimental models of renal injury. A functional dinucleotide repeat (GT)(n) polymorphism, within the HO-1 promoter, regulates HO-1 gene expression; a short number of repeats (S-allele <25) increases transcription. We report the first assessment of the role of this HO-1 gene promoter polymorphism in chronic kidney disease due to autosomal dominant polycystic kidney disease (ADPKD) and IgA nephropathy (IgAN). METHODS: The DNA from 160 patients (99% Caucasian) on renal replacement therapy (RRT) was genotyped. The primary renal disease was ADPKD in 100 patients and biopsy-proven IgAN in 60 patients. RESULTS: Overall, the mean age at commencement of RRT was not significantly different between patients with and without an S-allele (44.1 years versus 45.0 years, P = 0.64). In patients with ADPKD, the age at commencement of RRT was comparable regardless of the HO-1 genotype (47.7 years versus 46.7 years, P = 0.59). The same was true in patients with IgAN (38.3 years versus 42.2 years, P = 0.28). CONCLUSION: This suggests that the functional HO-1 promoter polymorphism does not influence renal survival in CKD due to ADPKD or IgAN.

Troponin T is an independent predictor of mortality in renal transplant recipients.

BACKGROUND: Numerous reports have demonstrated an association between elevated Troponin T levels and adverse cardiovascular outcomes in patients with chronic kidney disease. However, whether raised Troponin T levels are an independent predictor of mortality in renal transplant recipients has not yet been established. The aim of this study was, therefore, to assess the use of Troponin T as a prognostic marker in a population of renal transplant recipients. METHODS: Three hundred and seventy-two asymptomatic renal transplant recipients were recruited between June 2000 and December 2002. Troponin T was measured at baseline and prospective follow-up data were collected at a median of 1739 days. RESULTS: In Kaplan-Meier analysis a Troponin T level > or = 0.03 microg/l was a significant predictor of mortality (P < 0.001). In Cox Regression analysis, an elevated Troponin T level remained a significant predictor of mortality following adjustment for traditional cardiovascular risk factors (P < 0.001) and following adjustment for estimated glomerular filtration rate and high sensitivity C reactive protein (P < 0.001). CONCLUSIONS: Elevated Troponin T level is a strong independent predictor of all cause mortality in patients with a renal transplant. Troponin T, therefore, represents a promising biochemical marker that identifies those renal transplant recipients who are most likely to benefit from aggressive cardiovascular risk factor modification.

Cost should be the principal determinant of choice of erythropoiesis-stimulating agent in chronic haemodialysis patients.

BACKGROUND/AIMS: Erythropoiesis-stimulating agents (ESAs) are effective in the management of the anaemia of chronic kidney disease but add substantially to the treatment costs. We performed a comparison cross-sectional analysis of ESA prescribing in 4 dialysis centres in Northern Ireland. METHODS: The ESA prescription and current haemoglobin (Hb) concentration for all patients on haemodialysis (HD) treatment for at least 3 months was extracted from the renal data system. RESULTS: A total of 403 patients were analysed, 184 (46%) were prescribed epoetin beta and 219 (54%) darbepoetin alpha. The mean Hb concentrations for both agents were comparable overall (Hb = 11.4 and 11.7 g/dl, p = 0.13), and for subcutaneous (SC) and intravenous (IV) administration: epoetin beta 11.5 g/dl (n = 119) and 11.4 g/dl (n = 65) (p = 0.70), and darbepoetin alpha 11.8 g/dl (n = 39) and 11.6 g/dl (n = 180) (p = 0.49). The mean weekly dose was 7,941 units of epoetin beta with SC and 9,200 units with IV administration (p = 0.10), and 45 mug SC and 46 mug IV of darbepoetin alpha (p = 0.94). The weekly cost of achieving equivalent Hb levels was GBP 61.86 (EUR 90.57/USD 115.68) with SC and GBP 71.67 (EUR 104.93/USD 134.02) with IV epoetin beta, and GBP 70.78 (EUR 103.63/USD 132.36) with SC and GBP 72.18 (EUR 105.68/USD 134.98) with IV darbepoetin alpha. CONCLUSIONS: Epoetin beta and darbepoetin alpha are equally effective ESAs and the choice of ESA prescribed in stable HD patients should be determined by cost.

Level of renal function and serum erythropoietin levels independently predict anaemia post-renal transplantation.

BACKGROUND: Post-renal transplant anaemia is a potentially reversible cardiovascular risk factor. Graft function, immunosuppressive agents and inhibition of the renin-angiotensin system have been implicated in its aetiology. The evaluation of erythropoietin (EPO) levels may contribute to understanding the relative contributions of these factors. METHODS: Two-hundred and seven renal transplant recipients attending the Belfast City Hospital were studied. Clinical and laboratory data were extracted from the medical records and laboratory systems. RESULTS: Of the 207 patients (126 male), 47 (22.7%) were found to be anaemic (males, haemoglobin (Hb)<12 g/dl, females Hb<11 g/dl). The anaemic group had a significantly higher mean serum creatinine level (162.8 micromol/l vs 131.0 micromol/l, P<0.001) and lower mean estimated glomerular filtration rate (eGFR) (41.5 ml/min vs 54.9 ml/min, P<0.001) than the non-anaemic group. Individual immunosuppressive regimens were comparable between those with and those without anaemia. Angiotensin converting enzyme inhibitor (ACE-I) or angiotensin receptor blocker (ARB) administration was not more prevalent in those with anaemia compared with those without (36.2 vs 38.8%, P=0.88). There was a significant inverse correlation between Hb levels and serum EPO levels (R=-0.29, P<0.001), but not between EPO levels and eGFR (R=0.02, P=0.74). Higher EPO levels were predictive of anaemia, independent of eGFR in multivariate analysis. CONCLUSION: Anaemia is common in post-renal transplant patients. The levels of renal function and serum EPO and not immunosuppressive regimens or ACE-I/ARB use, are strong and independent predictors of anaemia.

Does angiotensin blockade influence graft outcome in renal transplant recipients with IgA nephropathy?

BACKGROUND: IgA nephropathy (IgAN) is a frequent cause of end-stage renal disease (ESRD) and recurrent disease causes deterioration and graft loss in transplant recipients. No definitive management is known to reduce the risk or severity of recurrent IgAN, and the evidence to support the use of renin-angiotensin system blockade in such patients is limited. METHODS: All 1137 renal transplants performed at the Belfast City Hospital over a 27-year period were reviewed. A total of 75 patients with ESRD due to biopsy-proven IgAN were identified; 39 of them had been prescribed an angiotensin-converting enzyme inhibitor (ACEi) or angiotensin-II type I receptor blocker (ARB). RESULTS: The two groups were well-matched in terms of demographic details, immunosuppressive regimens and duration of follow-up (median 65 months, range 18-261 months). The 5- and 10-year graft survivals were higher in those prescribed ACEi/ARB therapy compared with those who were not, although these differences did not reach statistical significance (92.9 vs 86.5%; P = 0.34 and 81.6 vs 72.7%; P = 0.32, respectively). These results were similar when censored for death with a functioning graft. In the group where an ACEi/ARB was not prescribed, all four with biopsy-proven recurrent IgAN progressed to ESRD, compared with three out of nine in the group treated with an ACEi/ARB. CONCLUSIONS: In transplant recipients with ESRD due to biopsy-proven IgAN, a trend towards improved 5-year and 10-year graft survival was seen in those prescribed ACEi/ARBs. All with recurrent IgAN in their grafts who were not treated with ACEi/ARB therapy progressed again to ESRD.

Is screening for factor V Leiden and prothrombin G20210A mutations in renal transplantation worthwhile? Results of a large single-center U.K. study.

This single center study is the largest series of renal transplant recipients and donors screened for the commonest prothrombotic genotypes. A total of 562 transplant recipients and 457 kidney donors were genotyped for the factor V Leiden and prothrombin G20210A mutations. The prevalence of heterozygous factor V Leiden was 3.4% and 2.6% and prothrombin G20210A was 2.0% and 1.1% in recipients and donors, respectively, similar frequencies to that of the general U.K. population. The 30-day and 1-year graft survival rates in recipients with thrombophilic mutations were 93% and 93%, compared with 88% and 82% in patients without these mutations (log-rank P=0.34). Thrombophilia in recipients (odds ratio 0.55; confidence interval 0.06-2.29; P=0.56) or in donors (odds ratio 1.53; confidence interval 0.27-5.74; P=0.46) did not correlate with graft loss at 30 days after transplantation. In contrast to recent reports, this study did not demonstrate an association between thrombophilia and renal allograft loss, and routine screening is not recommended.