The impact of coronary angiography on renal transplant function.

INTRODUCTION: There may be reluctance to perform coronary angiography in kidney transplant patients due to perceived risk of iodinated contrast, despite an increased risk of cardiovascular disease compared with the general population. AIM: We sought to determine if renal transplant function was adversely affected within 7, 30 and 180 days of coronary angiography. DESIGN AND METHODS: Renal transplant recipients undergoing coronary angiography in a single centre (01/2006-02/2018) were identified retrospectively. Baseline and highest SCr within 7, 30 and 180 days of coronary angiography were extracted from the electronic patient record. Rise in creatinine >26 micromol/l was considered significant [equivalent to Acute Kidney Injury (AKI) Network criteria stage 1 AKI] and case note review performed to determine circumstance of renal decline. RESULTS: There were 127 coronary angiographies conducted in 90 patients: 67.7% were male and mean age was 58.0 (±10.1) years. There was AKI within 7 days in 18.9% cases, but SCr returned to baseline within 7 days or there was an alternative explanation for AKI in 83.3% of these. In the remaining four cases, there was progressive decline in renal transplant function. In the absence of critical illness, no patient required dialysis or extended hospital stay for contrast-associated AKI. CONCLUSIONS: In this cohort of renal transplant recipients undergoing coronary angiography, AKI occurred in a minority of cases, and in more than 95% of such cases this effect was transient, with progressive renal decline a rare and predictable event. Renal transplant should not be regarded as a contraindication to coronary angiography.

Acute tubulointerstitial nephritis in Scotland.

BACKGROUND AND AIMS: Acute tubulointerstitial nephritis (ATIN) is a potentially reversible cause of acute kidney injury with the majority of cases drug related. Our aims were to examine the incidence profile of patients with ATIN in Scotland and to assess the impact of corticosteroid treatment. DESIGN AND METHODS: All adult patients with biopsy-proven ATIN, diagnosed between 2000 and 2012, presenting to renal units serving 1.9 of Scotland's 5 million population were included. Patient demographics, presenting, aetiologic and pathologic features, treatment given and outcome were extracted from patient records. RESULTS: In total, 171 cases representing 4.7% of native renal biopsies were identified. Median serum creatinine (sCr) was 327 µmol/l at biopsy (106 µmol/l at baseline). Eosinophilia, fever or rash was present in 57% with all 3 in only 1.1%. Active urinary sediment was found in 68%. Aetiology appeared drug induced in 73%. Proton pump inhibitors (PPIs) were likely causative in almost as many cases as antibiotics (35% each) and were more frequently implicated than non-steroidal anti-inflammatory drugs (20%). Number of PPI-related cases paralleled the rising prescription of these drugs. Corticosteroids were prescribed in 59% of drug-induced ATIN (median sCr at biopsy: 356 µmol/l vs. 280 µmol/l in those managed conservatively). There was no difference in sCr at 1, 6 and 12 months, with similar proportions of both groups experiencing complete renal recovery (48% vs. 41%) and becoming dialysis dependent (10% in both). CONCLUSIONS: Incidence of biopsy-proven ATIN in Scotland has been rising over the past decade with the majority of cases drug induced. Evidence supporting corticosteroid treatment is lacking.

Seed train development for the fermentation of bagasse from sweet sorghum and sugarcane using a simplified fermentation process.

A process was developed for seed culture expansion (3.6 million-fold) using 5% of the hemicellulose hydrolysate from dilute acid pretreatment as the sole organic nutrient and source of sugar. Hydrolysate used for seed growth was neutralized with ammonia and combined with 1.0mM sodium metabisulfite immediately before inoculation. This seed protocol was tested with phosphoric acid pretreated sugarcane and sweet sorghum bagasse using a simplified process with co-fermentation of fiber, pentoses, and hexoses in a single vessel (SScF). A 6h liquefaction (L) step improved mixing prior to inoculation. Fermentations (L+SScF process) were completed in 72 h with high yields (>80 gal/US ton). Ethanol titers for this L+SScF process ranged from 24 g/L to 32 g/L, and were limited by the bagasse concentration (10% dry matter).

Skin tumours in the West of Scotland renal transplant population.

BACKGROUND: Organ transplant recipients have an increased risk of skin cancers. A specialist dermatology clinic for renal transplant recipients (RTRs) was established in 2005. OBJECTIVES: To analyse the type and incidence of skin cancers in prevalent patients in the West of Scotland after renal transplant, and to analyse the impact of the time since transplant and the immunosuppression regimen. METHODS: Skin cancer data for RTRs attending the transplant dermatology clinic over a 38-month period were collected and recorded in the West of Scotland electronic renal patient record. Skin cancer data were intrinsically linked to each individual's transplant and immunosuppression data. RESULTS: Overall, 610 patients attended. The median follow-up time from the date of first transplant was 10 years. Ninety-three patients (15.2%) had experienced a total of 368 skin cancers since transplant, and the prevalence increased with time since transplant. Basal cell carcinomas (BCCs) occurred in 74 patients (12.1%) and squamous cell carcinomas (SCCs) in 42 patients (6.9%). Three patients (0.5%) had experienced a melanoma. The SCC:BCC ratio was 0.7. Survival analysis showed significant reduction in the time to develop skin cancer in patients transplanted from 1995 onwards (P < 0.0001) and in patients who had been on triple immunosuppressant therapy at 1 year after transplant, compared with dual therapy (P < 0.0001). CONCLUSIONS: This is the first study of skin cancer in prevalent Scottish RTRs. The incidence of skin cancer is high and appears to have a direct relationship to the overall burden of immunosuppression. The SCC:BCC ratio, which is lower than reports from other centres, deserves further scrutiny.

Injection of air into the headspace improves fermentation of phosphoric acid pretreated sugarcane bagasse by Escherichia coli MM170.

Microaeration (injecting air into the headspace) improved the fermentation of hemicellulose hydrolysates obtained from the phosphoric acid pretreatment of sugarcane bagasse at 170°C for 10 min. In addition, with 10% slurries of phosphoric acid pretreated bagasse (180°C, 10 min), air injection into the headspace promoted xylose utilization and increased ethanol yields from 0.16 to 0.20 g ethanol/g bagasse dry weight using a liquefaction plus simultaneous saccharification and co-fermentation process (L+SScF). This process was scaled up to 80 L using slurries of acid pretreated bagasse (96 h incubation; 0.6L of air/min into the headspace) with ethanol yields of 312-347 L (82-92 gal) per tone (dry matter), corresponding to 0.25 and 0.27 g/g bagasse (dry weight). Injection of small amounts of air into the headspace may provide a convenient alternative to subsurface sparging that avoids problems of foaming, sparger hygiene, flotation of particulates, and phase separation.

BK viremia surveillance after kidney transplant: single-center experience during a change from cyclosporine-to lower-dose tacrolimus-based primary immunosuppression regimen.

BACKGROUND: The aim was to report our experience of BK viremia surveillance after kidney transplant during a period of change from cyclosporine (CyA)-to lower-dose tacrolimus (Tac)-based primary immunosuppression regimens. METHODS: In a prospective single-center observational cohort study, 68 consecutive patients received renal transplant during the period when we used a CyA-based primary immunosuppression regimen and 66 after we changed to a lower-dose Tac-based regimen. Testing for BK viremia by quantitative polymerase chain reaction assay was performed at least monthly for a minimum of 1 year. RESULTS: Thirty-nine (29.1%) patients developed BK viremia and 2 (1.5%) developed BK nephropathy. The actuarial time to BK viremia was shorter in patients receiving CyA/mycophenolate mofetil (MMF)/prednisolone (Pred) compared with Tac/MMF/Pred (P=0.04) and primary immunosuppression with CyA/MMF/Pred was the only independent predictor of BK viremia (hazard ratio 1.95; P=0.047). Comparing patients who experienced BK viremia and those who did not, there was no difference in incidence of acute rejection (20.5% vs. 25.3%; P=0.56) or estimated glomerular filtration rate at 12 months (48.8 vs. 49.9 mL/min/1.73 m(2)), but the incidence of ureteric stenosis was higher (10.3% vs. 1.1%; P=0.01). CONCLUSIONS: Our data demonstrate a lower incidence of BK viremia in patients on lower-dose Tac compared with CyA-based primary immunosuppression in contrast to previous studies, and provide further support for the association between BK virus and ureteric complications.

Effect of reduced sulfur compounds on the fermentation of phosphoric acid pretreated sugarcane bagasse by ethanologenic Escherichia coli.

The addition of reduced sulfur compounds (thiosulfate, cysteine, sodium hydrosulfite, and sodium metabisulfite) increased growth and fermentation of dilute acid hydrolysate of sugarcane bagasse by ethanologenic Escherichia coli (strains LY180, EMFR9, and MM160). With sodium metabisulfite (0.5mM), toxicity was sufficiently reduced that slurries of pretreated biomass (10% dry weight including fiber and solubles) could be fermented by E. coli strain MM160 without solid-liquid separation or cleanup of sugars. A 6-h liquefaction step was added to improve mixing. Sodium metabisulfite also caused spectral changes at wavelengths corresponding to furfural and soluble products from lignin. Glucose and cellobiose were rapidly metabolized. Xylose utilization was improved by sodium metabisulfite but remained incomplete after 144 h. The overall ethanol yield for this liquefaction plus simultaneous saccharification and co-fermentation process was 0.20 g ethanol/g bagasse dry weight, 250 L/tonne (61 gal/US ton).

Serum phosphate and outcome at one year after deceased donor renal transplantation.

Traditional risk factors do not adequately explain the increased prevalence of cardiovascular disease in renal patients. This study considered a "non-traditional" risk factor, serum phosphate and outcome in renal transplant recipients. Data from 377 patients who received a first deceased donor renal transplant between January 1, 1999, and December 31, 2008, were recorded; 10% (n=38) had diabetes, 16.7% (n=63) were smokers, and 18.8% (n=71) had a history of vascular disease. Three hundred and thirty-three patients were alive at the time of the analysis. Survivors were significantly younger, less likely to be smokers or diabetic, and had a higher estimated glomerular filtration rate at one yr post-transplantation. Serum phosphate was significantly lower in these patients (0.95 ± 0.23 vs. 1.04 ± 0.26, p = 0.031). Analysis of recipient survival, stratified by serum phosphate at one yr post-transplant, revealed that serum phosphate > 1.11 mMol/L was a significant predictor of all-cause mortality (p=0.006). Serum phosphate between 0.9 and 1.11 mMol/L afforded the best outcome. In multivariate analysis, serum phosphate remained a significant predictor of mortality (p=0.016). Serum phosphate at one yr after transplant seems to have a J-shaped relationship with mortality, and this effect is independent of traditional cardiovascular risk factors.

Simplified process for ethanol production from sugarcane bagasse using hydrolysate-resistant Escherichia coli strain MM160.

Hexose and pentose sugars from phosphoric acid pretreated sugarcane bagasse were co-fermented to ethanol in a single vessel (SScF), eliminating process steps for solid-liquid separation and sugar cleanup. An initial liquefaction step (L) with cellulase was included to improve mixing and saccharification (L+SScF), analogous to a corn ethanol process. Fermentation was enabled by the development of a hydrolysate-resistant mutant of Escherichia coli LY180, designated MM160. Strain MM160 was more resistant than the parent to inhibitors (furfural, 5-hydroxymethylfurfural, and acetate) formed during pretreatment. Bagasse slurries containing 10% and 14% dry weight (fiber plus solubles) were tested using pretreatment temperatures of 160-190°C (1% phosphoric acid, 10 min). Enzymatic saccharification and inhibitor production both increased with pretreatment temperature. The highest titer (30 g/L ethanol) and yield (0.21 g ethanol/g bagasse dry weight) were obtained after incubation for 122 h using 14% dry weight slurries of pretreated bagasse (180°C).

Optimizing the saccharification of sugar cane bagasse using dilute phosphoric acid followed by fungal cellulases.

A low level of phosphoric acid (1% w/w on dry bagasse basis, 160 degrees C and above, 10 min) was shown to effectively hydrolyze the hemicellulose in sugar cane bagasse into monomers with minimal side reactions and to serve as an effective pre-treatment for the enzymatic hydrolysis of cellulose. Up to 45% of the remaining water-insoluble solids (WIS) was digested to sugar monomers by a low concentration of Biocellulase W (0.5 filter paper unit/gWIS) supplemented with beta-glucosidase, although much higher levels of cellulase (100-fold) were required for complete hydrolysis. After neutralization and nutrient addition, phosphoric acid syrups of hemicellulose sugars were fermented by ethanologenic Escherichia coli LY160 without further purification. Fermentation of these syrups was preceded by a lag that increased with increased pre-treatment temperature. Further improvements in organisms and optimization of steam treatments may allow the co-fermentation of sugars derived from hemicellulose and cellulose, eliminating need for liquid-solid separation, sugar purification, and separate fermentations.

Discharging patients from the nephrology clinic to primary care--will they get appropriate monitoring of renal function?

BACKGROUND: Chronic kidney disease (CKD) guidelines have been produced to allow affected individuals to be identified early and managed more effectively, thereby reducing cardiovascular risk and slowing the progression of CKD. The guidelines allow patients with stable early CKD, who were previously followed in nephrology clinics, to be discharged back to primary care for monitoring of their CKD. AIM: To determine if patients discharged from the nephrology clinic have appropriate monitoring of renal function in primary care according to the UK CKD guidelines, and if patients are being referred back to the clinic appropriately. METHODS: All patients discharged from a weekly satellite unit general nephrology clinic over a 2-year period were identified (n = 160). Clinic letters, the local laboratory system and direct contact with the general practice were used to determine if the timing of tests of renal function were consistent with the UK CKD guidelines. RESULTS: Most subjects (88%) had CKD Stages 1-3 at the time of discharge (i.e. eGFR > 30 ml/min). After exclusion of patients with an incomplete management plan or insufficient time since discharge (n = 50), 85% of eligible patients (n = 110) had at least one measure of eGFR after discharge. In 65% (n = 84) of these patients, measurement occurred within 1 month of the correct timing according to the guidelines. Four patients were re-referred appropriately. There were no other patients who should have been re-referred due to deteriorating renal function. CONCLUSION: Patients with stable early CKD get appropriate monitoring of renal function after discharge from the nephrology clinic to primary care and are also referred back to the renal clinic appropriately.

Multiple myeloma in chronic kidney disease. Utility of discretionary screening using serum electrophoresis.

INTRODUCTION: The incidence of multiple myeloma (MM) has increased in Scotland over the last 20 years. Approximately 25% of cases present directly to renal services. Serum electrophoresis is commonly included in the diagnostic screening tests performed in patients with chronic kidney disease (CKD). We examined the utility of serum electrophoresis in the population presenting to renal outpatient services in Glasgow. METHODS: All new patient attendances at general nephrology clinics in the Glasgow renal units between 1/08/2004 and 31/07/2006, along with clinical data, were retrieved from the electronic patient records. Patients with acute kidney injury were excluded. All serum and urine electrophoresis requests and results for the same period were identified from Biochemistry and Immunology Laboratory Services. RESULTS: A total of 2,544 new patients attended a renal clinic for the first time in the inception period, of whom 1,608 (63.2%) had serum electrophoresis tested. One patient with MM was identified, but the diagnosis was clinically apparent before the serum electrophoresis result was requested. A further 40 subjects had abnormal serum electrophoresis with mean paraprotein of 8.3 g/l (SD 6.1); none of these patients have subsequently developed MM, and the renal abnormalities are felt to be unrelated. This prevalence of monoclonal gammopathy of uncertain significance in 2.5% of the cohort is consistent with the expected prevalence in the general population. CONCLUSION: Our data demonstrate that serum electrophoresis in patients with CKD is not a useful screening test to identify MM.

The early impact of the United Kingdom Chronic Kidney Disease (CKD) guidelines on the number of new attendances at renal clinics.

INTRODUCTION: In April 2006 the United Kingdom (UK) Chronic Kidney Disease (CKD) guidelines and laboratory estimated glomerular filtration rate (eGFR) reporting were introduced to encourage identification and appropriate management of patients with CKD. The aim of this study was to assess the early impact of the implementation of the UK CKD guidelines on new patient attendances at nephrology clinics in our unit. METHODS: The number of adult new patients, sex, mean age and number in each CKD stage were analysed in consecutive 6 month blocks from 2000 to 2006. RESULTS: The number of new attendances gradually rose 2000 to 2006 until an abrupt 48% rise from 333 to 492 patients in the 6 months before and after June 2006. Between the second 6 months of 2005 and second 6 months of 2006 the proportion of females (43.4% to 56.3%; p<0.0001) and mean age (61.3 v 66.4 years; p<0.0001) rose abruptly. The increase was mainly in patients with stage 3B (eGFR 30-44.9ml/min/1.73m2) and stage 4 CKD (15-29.9ml/min/1.73m2). DISCUSSION: The data demonstrate that substantial changes in practice can be implemented rapidly within both primary and secondary care. Further studies will determine if this is going to improve outcome in patients with CKD.

Vascular access in haemodialysis patients: a modifiable risk factor for bacteraemia and death.

BACKGROUND: Bacteraemia and the development of sepsis syndrome is second only to cardiovascular disease as the leading cause of death in patients on renal replacement therapy. AIM: To determine the contributions of laboratory and clinical variables to the risk of bacteraemia and death in haemodialysis patients. DESIGN: Retrospective analysis. METHODS: We analysed all patients receiving haemodialysis in our renal unit at the beginning of January 2004 (n=263), recording clinical and laboratory variables for each patient at study entry. Bacteraemia and mortality were recorded for the subsequent 18-month period. Multivariate analysis using a Cox proportional hazards model was used to test for independent associations between variables and outcomes. RESULTS: During the study period, 45 patients (17.1%) developed bacteraemia and 65 (24.7%) died. Under multivariate analysis, use of dialysis catheters at study entry was a major factor in the development of bacteraemia and death with hazard ratios (HR) of 5.4 (p<0.001) and 2.8 (p=0.012), respectively, for tunnelled central venous catheters vs. arteriovenous fistulas (AVFs) and 3.1 (p=0.01) and 3.4 (p=0.001), respectively, for non-tunnelled central venous catheters vs. AVFs. Elevated CRP at study entry was independently associated with bacteraemia (HR 1.5 per unit log-CRP, p=0.006). Low serum albumin (HR 0.92, p=0.005) was independently associated with death. DISCUSSION: Use of synthetic vascular access catheters and heightened inflammatory state both have strong independent associations with subsequent bacteraemia and death. Bacteraemia surveillance strategies should be developed, with consideration of vascular access type and baseline inflammatory state as key components.

The relationship between serum creatinine and estimated glomerular filtration rate: implications for clinical practice.

INTRODUCTION: A new classification of chronic kidney disease (CKD) has been widely adopted that stratifies patients into 5 'stages' according to estimated glomerular filtration rate (eGFR). In adults the most commonly used formulae to calculate eGFR are the Cockcroft and Gault (C and G) and Modification of Diet in Renal Disease (MDRD) formulae. The UK Renal Association has recommended calculation of MDRD eGFR to screen for reduced kidney function in primary and secondary care. AIM: The aim of this study was to explore the implication of using these predictive formulae. METHODS: We searched for patients currently attending a renal clinic who have ever had a serum creatinine (SCr) of exactly 100 micromol/L, 150 micromol/L or 200 micromol/L. The C and G and MDRD eGFRs corresponding to that SCr were calculated. The proportion of patients in each stage of the CKD classification was determined. RESULTS: For a SCr of 100 micromol/L mean eGFR was 86.5 ml/min (range 31.0 - 192.8) by C and G and 63.8 ml/min (range 39.7 - 99.9) by MDRD (p < 0.0001; t-test of mean). For SCr 150 micromol/L mean eGFR was 51.7 ml/min (18.0 - 110.4) by C and G and 38.0 ml/min (20.7 - 54.8) by MDRD (p < 0.0001). For SCr of 200 micromol/L mean eGFR was 34.4 ml/min (12.6 - 89.5) by C and G and 27.3 ml/min (16.7 - 41.3) by MDRD (p < 0.0001). Using MDRD eGFR 46.5% patients with a SCr of 100 micromol/L have stage 3 CKD (GFR 30-60 ml/min) and all patients with a SCr of 150 micromol/L or 200 micromol/L have CKD 3 or worse. 8.6% of males with SCr 100 micromol/L had stage 3 CKD or worse compared with 86.8% females. 70.2% patients > 65 years old with SCr 100 micromol/L had stage 3 CKD. CONCLUSIONS: Targeted screening of patients at-risk for CKD will identify a large number of patients who require management of CKD and potential referral to nephrology services even at levels of SCr regarded as 'normal' or mildly.

Assessing the utility of the stop dialysate flow method in patients receiving haemodiafiltration.

BACKGROUND: The stop dialysate flow (SDF) method of post-dialysis urea sampling is the most commonly used method in the UK. It can also be used with a published formula to predict 30 min equilibrated urea accurately. The method has not been validated in patients undergoing haemodiafiltration (HDF). Given the increased use of HDF across Europe, we felt it prudent to assess the utility of the SDF method and prediction equation in this modality. METHODS: Fourteen patients from two renal units were studied. Blood samples were taken at 1 min intervals from the arterial side of the dialysis circuit in the first 5 min after HDF had ceased whilst blood circulation continued. A peripheral sample was taken from the contralateral arm immediately after HDF had ceased and a 30 min sample was taken from the arterial needle. These samples were used to assess the utility of 5 min arterial blood urea and the 30 min prediction formula, respectively. RESULTS: Blood urea measured from the arterial circuit at 5 min correlated closely with the contralateral sample taken immediately post-HDF, with no significant difference (6.45+/-2.11 vs 6.52+/-2.19 mmol/l, P = 0.39). The use of 5 min arterial blood urea and prediction formula allowed an accurate prediction of 30 min urea (R2 = 0.96). CONCLUSIONS: The use of the SDF method with a 5 min post-HDF arterial sample is valid in patients receiving HDF. The previously published prediction formula for estimating 30 min urea is also valid using the 5 min post-HDF sample.

Hypertension, antihypertensive agents and outcomes following renal transplantation.

UNLABELLED: Hypertension is common following renal transplantation and adversely affects graft and patient survival. However, strategies for antihypertensive drug therapy and target blood pressure have not been clearly defined. AIM: To assess the influence of achieved blood pressure and antihypertension drug therapy on graft and patient survival with the aim of identifying targets and event rates for future intervention studies. METHODS: We undertook a longitudinal follow up study of 634 renal transplant patients. Patients were surveyed in December 1994 and followed up after 102 months. Blood pressure (BP) was determined from the mean of three clinic readings and antihypertensive drug therapy recorded. RESULTS: Complete follow up data were available for analysis on 622 patients (57.2% male; mean age: 45.2 +/- 13.0 yr. There were 158 (25.4%) deaths and 115 (18.5%) death-censored graft failures. Lower systolic and diastolic blood pressure were associated with better graft survival in the Kaplan-Meier analysis. Univariate analysis showed serum creatinine (HR 1.012, p < 0.001), duration of renal replacement therapy (HR 0.946, p = 0.012), age (HR 0.979, p = 0.014) and pulse pressure (HR 1.017, p = 0.044) to be predictors of graft survival with serum creatinine and duration of renal replacement therapy as the only significant factors in the multivariate analysis. Lower systolic and pulse pressure were associated with better patient survival in the Kaplan-Meier analysis. Age (HR) 1.062, p < 0.0001), serum creatinine (HR 1.002, p = 0.021), diabetes (HR 3.371, p < 0.0001), and pulse pressure (HR 1.013, p = 0.036) were significant predictors of patient survival in the univariate and multivariate analysis. Patient survival was reduced with increasing number of antihypertensives (p < 0.05), as was graft survival (p < 0.05). Reduced patient and graft survival were seen in patients prescribed calcium channel antagonists (p < 0.01). There was no increased patient mortality in those patients on beta-blockers or angiotensin converting enzyme (ACE) inhibitors. CONCLUSION: Hypertension is a risk factor, which remains despite the use of anti-hypertensives, for reduced patient and graft survival. The risk was not significant when blood pressure was entered together with serum creatinine in the multivariate analysis. Beta-blockers may have a beneficial effect on cardiovascular mortality, and ACE inhibitors a beneficial effect on both patient and graft survival. There is a pressing need for interventional studies to assess the impact of blood pressure targets on patient and graft survival and the effect of individual agents on these outcomes.

Cyclosporine in renal transplantation: a Scottish experience.

The renal transplant unit in Glasgow has performed over 1500 renal transplants since the introduction of cyclosporine (CyA) in 1984. We extracted data on all renal transplants from cadaveric donors, where the recipient received primary immunosuppression with CyA, between 1984 and 2002. A total of 1262 transplants were analyzed in four eras (1984-1988, 1989-1992, 1993-1996, 1997-2002). Over this time period we observed progressive improvement in graft and patient survival, with the clearest improvements coinciding with the introduction of the Neoral formulation of CyA.