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B J Nankivell

Publications and source records attributed to B J Nankivell.

At least 19 recordsLinked to original sources
PubMed2006

The significance of subclinical rejection and the value of protocol biopsies.

Subclinical rejection (SCR) is diagnosed by protocol histology with a maximal prevalence occurring early after transplantation, falling to low levels by 1 year. Needle-core biopsy is safe, and the histology obtained fairly reflects subclinical immune activity. Several studies have consistently shown that SCR is associated with chronic tubulointerstitial damage, subsequent renal dysfunction and reduced graft survival. SCR is effectively treated by pulse corticosteroid therapy, although increased baseline immunosuppression may be necessary. A single randomized clinical trial of biopsy and corticosteroid therapy demonstrated significantly improved early structural and functional outcomes, and a (nonsignificant) 17% risk reduction in 4-year graft survival. Three possible approaches include: no protocol biopsies (usually accompanied by powerful immunosuppression); biopsies only in high-risk recipients (who may be difficult to reliably predict) or universal screening protocol biopsy (comprehensive but limited by cost and resource utilization). The appropriate screening methodology for a transplant unit is both a clinical and an economic decision; influenced by the SCR prevalence and potential gains of treatment, against costs and resource utilization. Further trials to quantify the cost-benefit balance in a typical, heterogeneous recipient population using modern immunosuppression are required.

Biopsy, Needle↗
PubMed2001

Effect of histological damage on long-term kidney transplant outcome.

BACKGROUND: Chronic renal allograft failure remains a major challenge to overcome. Factors such as donor quality, delayed graft function (DGF), acute rejection, and immunosuppression are known to affect long-term outcome, but their relationship to histological damage to graft outcome is unclear. METHODS: Protocol kidney biopsies (n=112) obtained at 3 months after transplantation yielded 102 with adequate tissue. Histology was scored by the Banff schema, and compared with implantation biopsies (n=91), repeat 12-month histology (n=39), decline in serum creatinine and serial isotopic glomerular filtration rate, onset of chronic allograft nephropathy (CAN), and actuarial graft survival censored for death with a functioning graft. RESULTS: At a median follow-up of 9.3 years, 20 patients had graft failure and 26 died with a functioning graft. Banff chronic nephropathy was present in 24% of 3-month biopsies, and was predicted by microvascular disease in the donor, cold ischemia, DGF, and acute vascular rejection (P<0.001). Acute glomerulitis at 3 months correlated with segmental glomerulosclerosis at 12 months, subsequent recurrent glomerulonephritis, and graft failure (P<0.01). Subclinical rejection at 3 months occurred in 29% of biopsies, correlated with prior acute rejection and HLA mismatch, and led to chronic histological damage by 12 months (r=0.25-0.67, P<0.05-0.001). Subclinical rejection, arteriolar hyalinosis, and tubulitis present at 3 months had resolved by 12 months. The 10-year survival rates for Banff chronic nephropathy were 90.4% for grade 0, 81.0% grade 1, and 57.9% for grades 2 or greater (P<0.01). Early tubulointerstitial damage at 3 months profoundly influenced graft survival beyond 10 years. CAN was predicted by kidney ischemia, 3-month chronic intimal vascular thickening, tubular injury, proteinuria, and late rejection. Chronic fibrointimal thickening of the small arteries and chronic interstitial fibrosis at 3 months independently predicted graft loss and decline in renal function (P<0.05-0.001). CONCLUSIONS: Early transplant damage occurs in the tubulointerstitial compartment from preexisting donor kidney injury and discrete events such as vascular rejection and DGF. Subsequent chronic damage and graft failure reflect accumulated previous injury and chronic interstitial fibrosis, vascular impairment, subclinical rejection, and injury from late rejection. CAN may be conceptualized as the sequelae of incremental and cumulative damage to the transplanted kidney. The duration of graft survival is dependent and predicted by the quality of the transplanted donor kidney combined with the intensity, frequency, and irreversibility of these damaging insults.

Adult↗
PubMed2001

Diagnosis of kidney transplant obstruction using Mag3 diuretic renography.

Kidney transplant obstruction (KTO) following renal transplantation remains an important reversible cause of allograft dysfunction, requiring prompt diagnosis to prevent long-term graft damage. Although ultrasound can accurately diagnose renal transplant hydronephrosis, it cannot be used to assess its functional significance. We prospectively assessed the utility of technetium-99m mercaptoacetyltriglycine (Tc99m MAG3) diuretic renography for the diagnosis of allograft KTO, using standard visual and quantitative parameters, as well as calculated renal output efficiency (OE), which has been postulated to improve diagnostic yield. From a cohort of 45 renal transplant patients, two subgroups were formed. The first group of transplant recipients (n = 21) with stable function and no obstruction was used to derive normal values for Tc99m MAG3 scans. A second group of transplant recipients with acute renal dysfunction in whom KTO was clinically suspected was used to test the diagnostic utility of these derived values (n = 43 scans). KTO was diagnosed independently of the MAG3 scans by a fall in the serum creatinine in response to renal pelvis urinary drainage. OE in 12 renal allografts with KTO was significantly reduced compared with 31 Tc99m MAG3 scans without KTO (59.6 +/- 18.9 vs. 81.6 +/- 5.4%, p < 0.001). In KTO, the mean time of isotope appearance in the bladder (time to bladder [TTB]) was extended compared with unobstructed allografts (7.9 +/- 4.1 vs. 3.6 +/- 1.5 min, p < 0.001). Measurement of OE significantly improved the accuracy of diuretic MAG3 renography in the diagnosis of renal allograft KTO, especially when supplemented by the TTB, parenchymal transit time and shape of the renogram curve. Ureteric obstruction of the kidney transplant can be diagnosed with an OE reduced to < 75% (sensitivity 92%, specificity 87%) and confirmed by isotope hold-up in the pelvicalyceal system. A normal or slowly declining renogram curve effectively excluded KTO (sensitivity of 96%, negative predictive value of 84%). A parenchymal transit time of > 5 min and a TTB of > 7 min both yielded a sensitvity of 92% and a specificity of 81%. In conclusion, MAG3 renography is a clinically useful investigation for the diagnosis of KTO.

Adult↗
PubMed2000

Posttransplant cataract: lessons from kidney-pancreas transplantation.

INTRODUCTION: Cataract is a major cause of visual disturbance after transplantation. Although corticosteroid therapy has been linked with posterior subcapsular cataract, its natural history in the cyclosporine era is not well understood. METHODS: Baseline and regular postoperative slit-lamp biomicroscopy and ophthalmic examinations (n=432) were performed in 108 eyes of simultaneous kidney/pancreas (SPK) recipients (n=54) for up to 10 years after transplantation. Triple therapy immunosuppression of cyclosporine, azathioprine, and prednisolone was used. RESULTS: Cataract was present in 40% of eyes at simultaneous kidney/pancreas associated with duration of diabetes, lower insulin dose, and the use of pretransplant hemodialysis (P<0.05-0.01). Cataract became increasing more common 2 years after simultaneous kidney/pancreas, and lens abnormalities were virtually universal at 6-10 years by slit lamp biomicrosopy. The instantaneous hazard rate for new cataract formation was highest within the first 2 years and remained abnormal for the study duration. Nuclear and posterior subcapsular cataract increased significantly after transplantation (P<0.05) and were the predominant types of cataract presenting late. Risk factors for posttransplant cataract formation included older age and high-dose pulse methylprednisolone dose. Visual acuity was reduced by severity of cataract grade, presence of combined nuclear and subcapsular cataract, retinal hemorrhage and underlying diabetic retinopathy (P<0.05-0.001). Cataract formation imposed significant additional impairment of visual acuity above that of diabetic retinopathy. Cataract surgery was undertaken in 14% of eyes, improving visual acuity from mean decimalized score of 0.28 to 0.43, P<0.01 but did not normalize it to the noncataract level of 0.72. CONCLUSION: Transplantation substantially increases all types of cataract, and is highly prevalent by slit lamp examination. High-risk patients are older and diabetic, and received hemodialysis and pulse corticosteroid therapy. In contrast to older studies using high-dose corticosteroid and azathioprine, the pattern of cataract in the cyclosporine era is different with broader cataract types, a weaker association with corticosteroids and a progressive course. Regular screening of visual acuity and appropriate surgery for posterior subcapsular or severe cataract are recommended.

Adult↗
PubMed2000

Progression of macrovascular disease after transplantation.

INTRODUCTION: Cardiovascular and cerebrovascular disease are major causes of morbidity and mortality after kidney transplantation. The aim of this longitudinal study was to examine the natural history of carotid plaque and to determine risk factors for the progression of vascular disease in uremic, type 1 diabetic patients who received a combined kidney and pancreas transplant. METHODS: Carotid artery (n=765) and lower limb vascular duplex scanning (n=656) were prospectively undertaken in 82 recipients before transplantation, at 6 months, and then at annual intervals for up to 10 years. Plaque in the internal carotid artery (ICA), external carotid artery, and common carotid artery was classified by type, location, extent, and degree of functional obstruction, and evaluated using multivariate analysis. RESULTS: Carotid plaque was present in 22.5% of patients at initial scanning, but increased to 56.6% by 7-10 years after transplantation, especially in the ICA and common carotid artery. Both the severity and extent of plaque increased, and plaque became more complex and heterogeneous with time after transplantation (P<0.001). Carotid plaque was associated with older age, current cigarette smoking, hyperphosphatemia, hypoalbuminemia, duration of pretransplantation dialysis, and presence of lower limb plaque (P<0.05-0.001). The severity of carotid plaque increased in older, hypertensive recipients and was associated with metabolic acidosis and hyperphosphatemia (all P<0.05). Severity of ICA disease correlated with disease in the contralateral ICA (r=0.57, P<0.001) and femoral arteries (r=0.42, P<0.001). Paradoxically, each carotid artery progressed independently of the other. ICA disease severity progressed when heterogenous, calcified, or new plaque was present on scanning, and with reduced renal transplant function (P<0.01-0.001). The mean ICA blood flow remained stable with time but was progressively impaired by hypertension, fasting hyperglycemia, and a lower prednisolone dose (P<0.05). Cerebrovascular events occurred in only four patients and were unrelated to carotid disease, implying relative plaque stability. CONCLUSION: Extensive carotid vascular wall abnormalities increased significantly despite kidney and pancreas transplantation. Initiation of plaque was associated with systemic factors, whereas progression of established plaque was largely influenced by local factors within the arterial wall.

Adult↗
PubMed1999

Predictors of renal transplant histology at three months.

BACKGROUND: The quality of a damaged kidney, the complexity of the surgery, and the events in the first weeks after transplantation, such as delayed graft function (DGF) and acute rejection, may influence its histological appearance and long-term survival. The aim of this study was to evaluate the importance of these factors in predicting renal allograft histology at 3 months. METHODS: Prospective, protocol kidney biopsy specimens (n=112), obtained 3 months after transplantation, were scored for chronic damage by the Banff schema and evaluated by multivariate analysis against donor factors, implantation histology, prior recipient sensitization, ischemia, perioperative factors, and subsequent clinical events, such as DGF and acute rejection. RESULTS: Adequate samples were obtained in 102 of 112 biopsies and classified as chronic Banff grade 0 (n=22), grade I (n=56), grade II (n=23), or grade III (n=1). Acute Banff scores were minimal. DGF occurred in 49% and was the strongest predictor of tubulointerstitial damage at 3 months. DGF correlated with acute tubular necrosis on the implantation biopsy specimen and with the number of acute rejection episodes; DGF also correlated with the Banff grades of chronic glomerulitis, chronic interstitial fibrosis, and tubular atrophy scores (P<0.05-0.001) in the 3-month biopsy specimen. By multivariate analysis, chronic tubular atrophy was independently predicted by the presence of vascular disease in the donor biopsy specimen, DGF, and vascular rejection occurring within the first 3 months (P<0.05-0.001). Chronic interstitial fibrosis was unrelated to fibrosis in the donor biopsy specimen but was independently predicted by DGF, donor age, and vascular rejection (P<0.05-0.001). Vascular disease in the donor biopsy specimen correlated with chronic intimal thickening (r=0.36, P<0.01) and arteriolar hyalinosis score (r=0.54, P<0.001) on the 3-month biopsy specimen. Banff chronic intimal vascular thickening was independently predicted by donor biopsy specimen vascular grade, prior vascular rejection episodes, and renal cold ischemia time (P<0.05-0.01). There were no correlates with the mean cyclosporine (CsA) dose, blood levels, diagnosis of CsA toxicity, or cellular rejection within the first 3 months. CONCLUSIONS: This study has demonstrated that the quality of the donor organ at implantation was strongly predictive of subsequent renal histology in grafts functioning at 3 months. Vascular rejection and DGF had a significant long-term effect on graft damage, but cellular rejection and simple measures of CsA exposure did not.

Acute Disease↗
PubMed1999

Successful obstetric outcome after simultaneous pancreas and kidney transplantation.

A 34-year-old woman became pregnant two years after having a simultaneous pancreas and kidney (SPK) transplantation, necessitated by type 1 diabetes and end-stage renal disease. The pregnancy was uneventful until 30 weeks' gestation, when she developed pancreatitis and a worsening of mild hypertension. A healthy 1700 g boy was delivered by caesarean section at 34 weeks' gestation. This is the first report of a successful pregnancy after SPK transplantation in Australia.

Adult↗
PubMed1999

Mercaptoacetyltriglycine diuretic renography and output efficiency measurement in renal transplant patients.

Suspected urinary tract obstruction following renal transplantation presents a diagnostic dilemma. The purposes of this study were: (1) to establish a normal range of measurement of output efficiency (OE) in the renal transplant population, and (2) to assess prospectively the usefulness of OE in the setting of allograft obstruction. Twenty-two renal transplant patients with stable renal function and no evidence of hydronephrosis on serial ultrasound examination had a diuretic mercaptoacetyltriglycine scan with calculation of OE. Three renal transplant patients with confirmed graft obstruction were also studied. Standard qualitative and quantitative parameters as well as OE were calculated. The mean OE for the 22 normal renal transplant patients was 86.3%+/-3.7% (range: 77%-91%). OE values in the three obstructed patients were 59%, 68% and 75% respectively. It is concluded that OE should normally exceed 77% in renal graft recipients. OE is a promising means of diagnosing functional obstruction in these patients.

Adult↗
PubMed1999

Diabetic retinopathy after combined kidney-pancreas transplantation.

Diabetic retinopathy (DR) is amenable to good diabetic control; however, only successful pancreas transplantation can achieve sustained normoglycaemia. The aim of this long-term study was to examine the course of DR in insulin-dependent diabetic recipients of a simultaneous kidney and pancreas transplant (SPK). Successful SPK recipients (n = 46) and failed pancreas transplant with a functioning kidney transplant (n = 8) were assessed by baseline and regular post-transplant ophthalmic examinations (n = 432) for up to 10 yr after SPK. At the time of SPK (n = 108 eyes), the mean duration of diabetes was 25 +/- 7 yr, ten eyes were blind, and 79% of eyes had advanced DR that had panretinal laser (panretinal photocoagulation, PRP. Successful SPK recipients had normal glucose control with a mean HBA1C of 5.2 +/- 0.6%. DR remained stable in 75% of both the study and control groups, with no difference between groups. The DR mostly evolved towards inactive proliferative DR. After SPK, 14% of non-blind eyes showed improvement of DR, 76% remained stable and 10% progressed. Early vitreous haemorrhage occurred in 6.1% of eyes, and was related to established DR. Cataract of all types increased after transplantation (p < 0.01), which reduced visual acuity (VA) in affected eyes. The mean overall VA remained unchanged for the study duration. In summary, uremic patients from diabetic nephropathy had a high prevalence of severe proliferative DR and blindness at the time of presentation for SPK. This was subsequently stabilised to inactive proliferative DR by appropriate laser therapy followed by metabolic control achieved by SPK.

Cataract↗
PubMed1999

Low-dose dopamine after kidney transplantation: assessment by Doppler ultrasound.

Low-dose dopamine (LDD) is commonly used after kidney transplantation as a renoprotective agent, although the benefits of dopamine (DA) in this setting are controversial. LDD increases renal blood flow, decreases resistive index (RI) and causes diuresis in normal kidneys. We hypothesised that the vasculature of a denervated renal transplant may not respond to DA in the same way as healthy native kidneys. In a prospective, controlled study, renal blood flow velocity and vascular resistance were measured by Doppler ultrasound in recent kidney transplants (n = 20) over a range of DA doses (0-5 microg/kg/min). Main renal artery velocity was lower in kidneys with acute renal dysfunction than in those with normal function (0.60 +/- 0.31 vs. 0.81 +/- 0.24, respectively, p < 0.05). There was no demonstrable haemodynamic effect of LDD on either RI or main renal artery velocity as measured by Doppler ultrasound. Interestingly, the only significant correlation with mean RI was trough cyclosporin A level (r = 0.57, p < 0.001). Technical or timing factors cannot be used to explain the absence of DA effect, with equivalent doses capable of producing vasodilatation and reduced RI in studies of normal kidneys. In summary, these findings contrast the DA response of healthy native kidneys and may explain studies showing no clinical benefit of LDD in the early post-transplant period. These data suggest an insensitivity of recently implanted kidneys to the vasodilatory effects of LDD, that other factors such as cyclosporin A vasoconstriction may also be important, and question the rationale for routine LDD after kidney transplantation.

Adult↗
PubMed1999

Acute renal impairment after immersion and near-drowning.

Acute renal impairment (ARI) secondary to immersion and near-drowning is rarely described and poorly understood. A retrospective case-control study was performed: (1) to determine the incidence of ARI associated with near-drowning or immersion and (2) to define the clinical syndrome and to assess clinical predictors of ARI. Of 30 patients presenting after immersion or near-drowning, 50% were identified with ARI, with a mean admission serum creatinine of 0.24 +/- 0.33 mmol/L (2.7 +/- 3.7 mg/dl). These patients were a heterogeneous group: Eight had mild reversible ARI, three had ARI related to shock and multisystem failure, two had rhabdomyolysis-related ARI, and two had severe isolated ARI. Two patients required supportive hemodialysis and two died. Patients with ARI experienced more marked acidosis than control patients, as measured by serum bicarbonate (P < 0.001), pH (P < 0.001), and base excess (P < 0.001). There was also a higher admission lymphocyte count in the ARI group (P = 0.056). Dipstick hematuria on admission was significantly more common in patients with ARI (P = 0.016), and patients with 2 to 3+ of admission dipstick proteinuria had a higher peak serum creatinine than patients with less proteinuria (P < 0.05). Admission predictors of ARI by univariate logistic regression analysis included reduced serum bicarbonate (P = 0.002), pH (P = 0.001), and base excess (P < 0.001). The best predictor of ARI on multivariate analysis was a negative base excess (P = 0.01). In summary, acute renal impairment commonly occurs after immersion and near-drowning and is a heterogeneous condition. Although mild reversible renal impairment (serum creatinine < 0.30 mmol/L) (3.4 mg/dl) is usual, severe acute renal failure requiring dialysis can occur. It is recommended that any patient who presents after near-drowning or immersion should be assessed for potential ARI by serial estimations of serum creatinine, particularly when there is an increase in the initial serum creatinine, marked metabolic acidosis, an abnormal urinalysis, or a significant lymphocytosis.

Acute Disease↗
PubMed1998

Maintenance therapy with oral ganciclovir after treatment of cytomegalovirus infection.

While oral ganciclovir (OGCV) has been used as primary prophylaxis in patients at high risk for cytomegalovirus (CMV) infection after solid organ transplantation, its value in secondary prophylaxis is unknown. We have examined the use of OGCV as maintenance therapy following confirmed CMV infection on 16 occasions in 15 patients, in kidney (n = 4), kidney-pancreas (n = 3) lung (n = 6) and heart-lung (n = 1) recipients. OGCV was used in two distinct clinical situations. One group (n = 7) received OGCV as consolidation therapy (mean duration of 21 +/- 5 d) following i.v. ganciclovir induction therapy (mean duration of 16 +/- 5 d) for acute CMV infection, and sustained remission was achieved in 6/7 patients for a median follow-up of 300 d. In the second scenario, OGCV suppressed clinical disease in all patients with relapsing CMV infection (n = 9), with minimal or absent toxicity with a median follow-up of 152 d. OGCV reduced morbidity by allowing removal of central lines used for long-term i.v. therapy in patients with poor peripheral access. Hence, this study demonstrates the safe and effective use of OGCV as consolidation therapy after standard induction treatment with i.v. ganciclovir, and as long-term suppressive therapy in transplant recipients with recurrent CMV infection.

Administration, Oral↗
PubMed1998

Glucose homeostasis standards for pancreas transplantation.

Simultaneous pancreas and kidney transplantation (SPK) is capable of achieving normoglycemia, as assessed by oral glucose tolerance tests (OGTT), in the majority of diabetic recipients with end-stage renal disease. Despite its success over the last decade, standard ranges for OGTT after SPK are not available for comparison between studies and techniques. We examined 327 prospectively performed OGTT, undertaken in insulin-free bladder-drained SPK recipients, between 1 month and 10 yr after transplantation. Ranges of values for glucose, insulin and C-peptide were derived and areas under the time concentration curves calculated. The normal range of 2-h glucose values from SPK recipients was comparable to WHO criteria for the diagnosis of diabetes mellitus in a normal population; however, the fasting glucose fell below these levels. Fasting and area-under-the-curve (AUC) glucose were remarkably stable with time after SPK, although insulin fell with time after pancreas transplantation. These ranges may allow clinical evaluation of the endocrine function in individual SPK recipients, provide standards for comparison between different centers and techniques, and provide targets for islet transplantation.

Adult↗
PubMed1997

Diabetic neuropathy after pancreas transplantation: determinants of recovery.

Although simultaneous pancreas and kidney transplantation (SPK) achieves normoglycemia and correction of uremia in type I diabetic patients with renal failure, little data are available on long-term outcome and clinical determinants of recovery of peripheral neuropathy. In this prospective study, 219 electrophysiological studies using a standardized protocol were performed before and up to 8 years after SPK in 44 patients. Nine control diabetic recipients with functioning kidney but nonfunctioning pancreas transplants were studied on 35 occasions. Patients were 38.5+/-7.9 years old (mean+/-SD) with pretransplant diabetes present for 25.2+/-7.6 years. Significant polyneuropathy (total nerve conduction scores [NCS] <-1.0) was present in 89% before transplantation, which correlated with body weight (r=0.628, P<0.001). Two distinct patterns of neurological recovery were observed after SPK. Conduction velocity (CV) improved in a biphasic pattern, with a rapid initial recovery followed by subsequent stabilization. In contrast, the recovery of nerve amplitude was monophasic, and continued to improve for up to 8 years. Initial improvement in NCS was primarily due to an increase in CV (P=0.002 vs. baseline), and was best in shorter and younger patients. Recovery of total NCS at 6 months after SPK, assessed by multivariate analysis, was least in obese recipients and when performed in patients who had started dialysis before SPK, and was associated with lower transplant kidney isotopic glomerular filtration rate and HLA mismatch (P<0.05 to 0.001). Subsequent improvement was associated with less severe initial neuropathy, smaller body weight, and longer duration of diabetes (P<0.01 to 0.001). Fasting hyperinsulinemia was associated with impairment of initial recovery and subsequent NCS after SPK, but was worse in the control group. Recovery of nerve action potential amplitudes was predicted by better initial amplitudes and HLA mismatch, lower body weight, and the use of nifedipine (P<0.05 to 0.001). Nifedipine was used for hypertension in 33% of SPK and was associated with better CV and amplitudes, particularly in the upper limbs, where there was less neuropathy. The use of angiotensin-converting enzyme inhibitors also appeared beneficial, but this was confined to the lower limbs. SPK resulted in a gradual, sustained, and late improvement in nerve action potential amplitudes, consistent with axonal regeneration and partial reversal of diabetic neuropathy. These data suggest that early transplantation of uremic diabetic patients before onset of severe neuropathy, minimizing obesity and optimizing renal transplant function, maximizes neurological recovery after SPK. Furthermore, the preliminary data support randomized clinical trials for evaluation of nifedipine and angiotensin-converting enzyme inhibitors in diabetic neuropathy.

Adult↗
PubMed1997

The mechanism of cyclosporine toxicity induced by clarithromycin.

AIMS: Recently a number of case reports have described the interaction of clarithromycin with cyclosporine A, resulting in cyclosporine toxicity. This interaction is presumed to take place via the hepatic cytochrome P450 enzyme system. METHODS: Following a case of cyclosporine toxicity and acute renal failure in a transplant patient started on clarithromycin, we investigated the effect of oral clarithromycin on the hepatic P450 system in five healthy normal male volunteers, by means of the erythromycin breath test. RESULTS: Cytochrome P4503A (CYP3A) activity was reduced in all subjects by a mean level of 26% following clarithromycin treatment. This would result in a significant reduction in cyclosporine clearance in patients receiving clarithromycin. CONCLUSIONS: As clarithromycin was shown to inhibit CYP3A activity in all subjects tested, we recommend that a high degree of caution be exercised when clarithromycin is administered to patients receiving cyclosporine therapy or other drugs known to be eliminated by CYP3A-mediated metabolism.

Anti-Bacterial Agents↗
PubMed1996

Clinical determinants of glucose homeostasis after pancreas transplantation.

Although successful simultaneous pancreas and kidney transplantation (SPK) achieves normoglycemia in the majority of diabetic recipients with end-stage renal disease, little is known about the factors that influence long-term endocrine function. In this prospective study of 48 bladder-drained SPK patients, 209 oral glucose tolerance tests were performed between 3 months and 6 years after transplantation. Normal fasting glucose levels and systemic hyperinsulinemia were stable for up to 6 years after SPK. Multivariate analysis revealed that increased area-under-curve (AUC) levels of C-peptide 3 months after transplantation were predicted by short surgical pancreas anastomosis time, greater recipient body weight, and total HLA mismatch score. Episodes of acute pancreas rejection were not associated with reduced allograft insulin output in the long term. Insulin output, stimulated by oral glucose tolerance tests and assessed by the ratio of AUC insulin to AUC glucose, fell gradually after transplantation and was decreased by an elevated serum calcium level and high cyclosporine dose. The ratio of fasting insulin to glucose, which acts as a marker of peripheral insulin resistance, fell with time after transplantation and was increased by greater body weight, higher prednisolone dose, and lower cyclosporine dose. The inhibitory effect of cyclosporine on both fasting and postprandial insulin output was, however, minor when quantified by multivariate analysis. Endocrine function of the transplanted pancreas was not correlated with its exocrine function measured by urinary amylase excretion, nor was there a correlation with change in renal function measured by isotopic glomerular filtration rate. In summary, simultaneous pancreas and kidney transplantation leads to excellent long-term glucose homeostasis maintained at the expense of systemic hyperinsulinemia. The key factors adversely affecting peripheral resistance in SPK were corticosteroid therapy, body weight, and time after transplantation. The susceptibility of islets to ischemia-reperfusion injury, as quantitated by surgical anastomosis time, may have implications for islet transplantation programs, as may the relative resistance of islets to allograft rejection. Glucose homeostasis after SPK, while remaining abnormal, may be used as the standard against which islet transplantation must be measured.

Adult↗
PubMed1996

Australian multicentre evaluation of a new polyurethane vascular access graft.

BACKGROUND: A new three-layered cast polyurethane vascular access graft (Thoratec VAG) is the most recent addition to the list of materials used in the search for the perfect prosthetic graft material for haemodialysis vascular access. Despite its use in 23 countries, a clinical assessment has not been published. METHODS: An independent retrospective evaluation by questionnaire was obtained for 145 implantation procedures performed by 30 surgeons. RESULTS: Ninety-two per cent of procedures were performed for an acute need for vascular access and 73% had prior failed vascular access surgery. Patients were hospitalized for a median of 4 days and the graft was initially used at a median of 3 days. Median follow-up was 306 days. Thoratec VAG had a problem-free (primary) patency of 44.9% and a functional (secondary) patency 64.5% at 1 year. Major causes of graft loss were thrombosis (17%) and infection (11%). Intra-operative thrombosis was the only significant risk factor for subsequent thrombosis (P = 0.013). Infection was less in patients with antibiotic prophylaxis that included vancomycin (P = 0.02). CONCLUSION: The ability to use the graft soon after surgery is a major advance for patients who urgently need reliable medium to long-term haemodialysis access.

Arteriovenous Fistula↗