BACKGROUND: The critical nephron mass needed to meet the metabolic demands of an individual depends on the body-weight. This study evaluated the effect of the kidney transplant ultrasonographic size to recipient body-weight ratio (Tx/W) on the outcome of kidney transplantation. METHODS: A consecutive series of 104 cadaveric renal transplants was studied. Transplant cross-sectional area (TXSA) was measured ultrasonographically in the first week after transplantation as an index of renal size. A 'nephron dose' index (Tx/W) was calculated by dividing TXSA by recipient weight and was used to define three groups of patients, with high (more than 0.45), medium (0.3-0.45) or low (less than 0.3) Tx/W ratios. Isotope glomerular filtration rate (GFR) measurements were made at 1, 6 and 12 months after transplantation. RESULTS: The serum creatinine level was significantly lower in the first 5 years after transplantation in patients with a high Tx/W ratio than in those with a medium or low ratio. GFR measurements were marginally higher in the groups with a high and medium Tx/W ratio compared with the low Tx/W group. A statistically significant association between Tx/W ratio and graft survival was not found. CONCLUSION: The renal transplant size to recipient weight ratio was an important determinant of long-term renal allograft function in this study. Extreme mismatching between allograft and recipient size should be avoided where possible, but the findings presented require confirmation in larger studies before clear recommendations can be made about size matching and kidney allocation.

Adult↗

PubMed2000

Long-term results of arteriovenous fistulas using transposed autologous basilic vein.

BACKGROUND: The transposed autologous basilic vein to brachial artery arteriovenous fistula provides vascular access in the absence of adequate superficial vein. The long-term patency and complication rates of this conduit are largely unreported. PATIENTS AND METHODS: Seventy-four brachiobasilic fistulas were performed in 65 patients. This was a secondary or tertiary access procedure in 84 per cent of patients. RESULTS: Of the 74 fistulas performed, 50 were successfully used for dialysis (68 per cent) and 24 (32 per cent) were never used, including 13 fistulas that failed without being used for dialysis. Of the 74 fistulas, 46 per cent failed (n = 34), 10 patients died with a functioning fistula (n = 10) and five were transplanted. The 30-day secondary patency was 73 per cent at 1 year, 53 per cent at 2 years and 43 per cent at 3 years rate was 96 per cent. Cumulative secondary patency was 73 per cent at 1 year, 53 per cent at 2 years and 43 per cent at 3 years. Nineteen (26 per cent) fistulas underwent a further 19 operative procedures. Fifty-one (69 per cent) fistulas developed complications. The most common complications were arm oedema (24 per cent), thrombosis (22 per cent) and bleeding (18 per cent). CONCLUSION: In high-risk patients the autologous transposed brachiobasilic fistula has equivalent patency and lower complication rates than those reported for polytetrafluoroethylene interposition grafts.

Adult↗

PubMed2000

Molecular changes in extracellular matrix turnover after renal ischaemia-reperfusion injury.

BACKGROUND: Renal ischaemia-reperfusion (IR) injury is an inevitable consequence of transplantation and contributes to later graft fibrosis. This study aimed to elucidate the possible mechanisms by studying the expression of genes associated with extracellular matrix (ECM) turnover. METHODS: Male Wistar rats underwent laparotomy, clamping of the right renal pedicle for 45 min, and left nephrectomy. Control animals underwent left nephrectomy only, or had no operation. Animals were killed at 8, 16 and 24 weeks and messenger RNA was extracted from renal tissue. Genes of interest were amplified and then quantified in an enzyme-linked immunosorbent assay system with levels expressed as a ratio to a known housekeeping gene (GAPDH). RESULTS: Experimental animals developed progressive proteinuria from 16 weeks onwards. At 8 weeks after IR injury, gene levels of matrix metalloproteinase (MMP) 2, an ECM-degrading enzyme, were significantly increased. Levels then fell progressively. This was associated with increasing expression of tissue inhibitor of metalloproteinases (TIMP) 1, an inhibitor of MMP-2, and of transforming growth factor (TGF) beta, a profibrotic cytokine, by 24 weeks following injury. CONCLUSION: These results suggest that, after an initial phase of increased ECM turnover following IR injury, the balance turns towards one of reduced degradation. This is likely to be an important mechanism in the subsequent development of fibrosis.

Animals↗

PubMed2000

Tacrolimus has less fibrogenic potential than cyclosporin A in a model of renal ischaemia-reperfusion injury.

BACKGROUND: Cyclosporin is associated with significant chronic nephrotoxicity, manifest in the long term mainly as renal fibrosis. There have been claims that tacrolimus is a less fibrotic drug than cyclosporin, and this study was designed to determine the effect of the two drugs on the expression of fibrosis-associated genes. METHODS: Male Wistar rats underwent clamping of the right renal pedicle for 45 min together with left nephrectomy; this model has previously been shown to be associated with upregulation of fibrosis-associated genes. Experimental groups (six animals per group) received cyclosporin A 10 mg/kg daily, tacrolimus 0.2 mg/kg daily or no treatment. Animals were killed at 16 weeks, and the renal cortical expression of fibrosis-associated genes was studied by means of quantitative reverse transcriptase-polymerase chain reaction. RESULTS: Tacrolimus-treated animals developed significantly less proteinuria and had lower serum creatinine levels than those receiving cyclosporin. Tacrolimus administration also significantly reduced the expression of transforming growth factor beta and tissue inhibitor of metalloproteinases 1, both the products of genes associated with fibrosis. Although cyclosporin treatment reduced levels of the matrix-degrading enzymes, matrix metalloproteinase (MMP) 2 and MMP-9, this was not statistically significant. CONCLUSION: Tacrolimus has less nephrotoxicity than cyclosporin in this model. It also appears to have less fibrogenic potential, and this may have implications for the choice of long-term immunosuppressant in renal transplantation.

Animals↗

PubMed2000

Differential effects of cyclosporin and tacrolimus on the expression of fibrosis-associated genes in isolated glomeruli from renal transplants.

BACKGROUND: Chronic allograft nephropathy is characterized by an excessive accumulation of extracellular matrix proteins leading to glomerular and interstitial fibrosis. The aim of this study was to determine the effects of two different immunosuppressive agents (cyclosporin and tacrolimus) on the expression of the genes controlling extracellular matrix deposition in renal transplant glomeruli. METHODS: Fifty-one renal transplant recipients were randomized to receive immunosuppression with either microemulsion cyclosporin or tacrolimus. Isolated glomeruli were plucked from protocol transplant biopsies performed 1 week, 3 months and 6 months after transplantation. Expression of the genes for collagen IValpha2, collagen III, matrix metalloproteinase 2, tissue inhibitor of metalloproteinases (TIMP) 1 and TIMP-2, tenascin and transforming growth factor (TGF) beta1 was studied by quantitative reverse transcriptase-polymerase chain reaction. RESULTS: The expression of messenger RNA (mRNA) for collagen III and TIMP-1 was significantly higher in patients receiving cyclosporin therapy than in those having tacrolimus (P < 0.01); this finding was accounted for by differences in the biopsy material at 1 week. A significant difference in collagen III, TIMP-1 and TIMP-2 mRNA expression was also detected between patients depending on the source of renal donor (cadaveric or living). There were no significant differences in the level of glomerular TGF-beta1. CONCLUSION: The data provide new in vivo evidence that tacrolimus may exert a less fibrogenic influence on transplant glomeruli than cyclosporin.

Adult↗

PubMed2000

Vascular access for haemodialysis.

BACKGROUND: The recent expansion of renal replacement therapy programmes has been associated with an increase in the number and complexity of patients requiring permanent vascular access. The introduction of strategies designed to maximize secondary access patency is, therefore, increasingly important as a means of prolonging patient survival on dialysis, reducing morbidity and reducing the escalating cost of such programmes. METHODS: A review of the current literature on the planning of vascular access, access surveillance methods and treatment of the most common complications was performed. RESULTS: Multidisciplinary vascular access planning, increased use of preoperative imaging and the preferential use of autogeneous vein are essential to obtain the best long-term results. While vascular access surveillance, in particular protocols involving direct measurement of access flow, enables the prospective detection and treatment of venous stenosis, the precise indications for treating venous stenosis remain unclear. Surgical revision remains the gold standard for the treatment of failing arteriovenous fistulas, but recent advances in interventional radiological techniques along with the suitability of arteriovenous fistulas for percutaneous intervention may offer an effective alternative. The effect of both these interventions on access patency requires comparison in a randomized trial. CONCLUSION: The introduction of strategies to improve access patency rates will change vascular access surgical practice away from the construction of new fistulas towards an increase in outpatient percutaneous intervention and surgical revisional procedures. The role of surgical interventions requires clearer definition.

Arteriovenous Shunt, Surgical↗

PubMed2000

A prospective randomized trial of three different sizes of core-cutting needle for renal transplant biopsy.

BACKGROUND: Needle-core biopsy remains one of the most important investigations in cases of renal allograft dysfunction. The size and quality of the biopsy material are likely to be important factors in achieving an accurate diagnosis. The aim of this study was to compare the success and complication rates of renal transplant biopsy procedures using three differently sized needles. METHODS: One hundred renal allograft recipients undergoing transplant biopsy using an automated needle core method were randomized to a 14, 16, or 18 gauge (G) needle. The size of each biopsy core was measured, and the presence or absence of renal cortical and medullary tissue and the number of glomeruli were recorded. Assessments of the ease with which the procedure was performed, the diagnostic usefulness of the biopsy material, and the discomfort associated with the procedure were made using verbal response and linear analog scales. RESULTS: Fourteen G biopsy cores (N = 33) were larger than both 16G (N = 33) and 18G (N = 34) cores and contained more gomeruli (mean number for 14G, 16G, and 18G = 15, 11 and 9, respectively). There were no differences in the ease of use of the three needle types, but scores for diagnostic usefulness were higher for 14G versus 18G and 16G versus 18G. The 14G needle was associated with significantly more pain than the two smaller needles when this was assessed using a linear analog score. Macroscopic hematuria occurred in eight patients, but there were no differences in complications rates between the three groups. CONCLUSIONS: All three needle sizes are safe for use in renal allograft biopsy using a semiautomated biopsy gun. The larger needles provide more tissue and glomeruli and, thus, are more diagnostically useful. Use of a 14G needle may be associated with more pain, and the 16G needle appears to offer the best compromise between diagnostic usefulness and patient acceptability.

Acute Kidney Injury↗

PubMed2000

A comparison of the results of renal transplantation from non-heart-beating, conventional cadaveric, and living donors.

BACKGROUND: In an attempt to address the shortage of conventional kidney donors, a non-heart-beating donor (NHBD) organ retrieval program has been established. We compared the results of kidney transplants from NHBDs (N = 77) with those from heart-beating cadaveric (HBD; N = 224) and living donors (LD; N = 49), performed in the same eight-year period. METHODS: Patients dying after failed attempts at resuscitation in the accident department or after intracerebral hemorrhage/anoxia were considered as potential NHBDs. After death, in situ kidney perfusion and cooling were achieved using an intra-aortic catheter inserted via a femoral artery cut down. Kidney retrieval and transplant operations were performed using standard techniques. RESULTS: The median (range) warm ischemic time for NHBD kidneys was 25 minutes (5 to 53 min). The initial function rates for NHBD, HBD, and LD transplants were 6.5, 76.3, and 93%, respectively. Primary nonfunction occurred in 5 of 75 evaluable NHBD transplants (7%) compared with only 6 out of 224 (2.7%) HBD and 1 out of 49 (2%) LD transplants (P = NS). Eighty-four percent of NHBD kidney recipients required postoperative dialysis for a median of 19 days. The mean (SD) serum creatinine at 12 months was 179 (73) micromol/L in NHBD kidneys compared with 152 (57) micromol/L for HBD kidneys and 138 (44) micromol/L for LD kidneys. The actuarial five-year graft survival rates for NHBD, HBD, and LD transplants were 79, 75, and 78%, respectively. During the period under study, NHBD organs accounted for 22% of the total renal transplant program. CONCLUSIONS: Despite being associated with poor initial graft function, the long-term allograft survival of NHBD kidneys does not differ significantly from the results of HBD and LD transplants.

Adult↗

PubMed2000

Paraganglioma-an unusual solitary nodule of the thyroid.

Explore the source record for details and available documents.

Female↗

PubMed2000

Pulmonary nitric oxide metabolism following infrarenal aortic cross-clamp-induced ischaemia-reperfusion injury.

OBJECTIVES: to investigate endogenous pulmonary nitric oxide metabolism following infrarenal aortic cross-clamp-induced ischaemia-reperfusion injury. METHODS: groups of male Wistar rats (n=6) were subjected to 60 minutes of infrarenal aortic cross-clamping under general anaesthesia. Rats were culled after 0, 60 and 120 minutes>> reperfusion, following release of the aortic clamp. A sham-operated control group was also studied. Acute lung injury (ALI) was quantified by measuring the protein concentration in lung bronchoalveolar lavage (BAL) fluid. Pulmonary myeloperoxidase activity (MPO) was measured as an index of neutrophil infiltration and degranulation in the lung. Plasma tumour-necrosis factor-alpha (TNF-alpha) was measured as an index of the pro-inflammatory cytokine response and pulmonary nitric oxide synthase (NOS) activity was determined by measuring conversion of(3)H L-arginine to(3)H L-citrulline in tissue homogenates. RESULTS: these data show significant ALI with increased pulmonary microvascular permeability and MPO activity in animals subject to 60 minutes>> ischaemia and 60 minutes or 120 minutes of reperfusion compared to control animals (p<0.01). Plasma TNF-alpha levels were significantly increased following 60 minutes of ischaemia compared to controls (p<0.01) and remained significantly increased in animals subject to reperfusion (p<0.01). Pulmonary NOS activity was significantly increased in animals subject to reperfusion (p<0.01). CONCLUSIONS: the reperfusion phase of infrarenal aortic cross-clamping provokes a significant increase in pulmonary NOS metabolism. The increase in plasma TNF-alpha and MPO activity suggests that this response may be secondary to inducible NOS expression. Manipulation of this response may benefit patients at risk of acute injury following infrarenal aortic reconstruction.

Animals↗

PubMed2000

Prevention of renal impairment following aortic cross-clamping by manipulation of the endogenous renal nitric oxide response.

OBJECTIVE: Infrarenal aortic cross-clamp-induced lower torso ischaemia-reperfusion injury is associated with impairment of glomerular filtration rate and upregulation of endogenous renal nitric oxide production. The aim of this study was to investigate whether manipulation of the endogenous renal nitric oxide response can ameliorate subsequent renal injury. METHODS: Groups of male Wistar rats (n = 6) were treated with one of the following agents before being subjected to 60 min of infrarenal aortic cross-clamping: saline (control), L-NMMA (a pan nitric oxide synthase inhibitor), 1400W (a highly selective iNOS inhibitor), hydrocortisone (an inhibitor of the systemic inflammatory response), L-arginine (the substrate for nitric oxide synthase) and NOC-18 (a nitric oxide donor). Animals were recovered after a left nephrectomy. The glomerular filtration rate (GFR) of the remaining kidney was measured on the second and seventh postoperative day using a 99Tc DPTA clearance technique as an index of renal injury. RESULTS: Animals treated with L-NMMA prior to aortic cross-clamping had a significantly impaired GFR compared to controls on the second (p<0. 01, Mann-Whitney U -test) and seventh (p<0.05, Mann-Whitney U -test) postoperative day. Hydrocortisone and 1400W had no significant effect on GFR on the second or seventh postoperative day. L-arginine and NOC-18 had no influence on GFR on the second postoperative day but significantly improved GFR on the seventh postoperative day. CONCLUSIONS: These results show that the endogenous nitric oxide response protects the kidneys from ischaemia-reperfusion injury. Manipulation of the renal nitric oxide response may have therapeutic benefits to patients undergoing aortic aneurysm repair by preventing acute renal failure.

Animals↗