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Biomedical subjects

E Honkanen

Publications and source records attributed to E Honkanen.

At least 19 recordsLinked to original sources

Complications of gallstone disease in kidney transplantation patients.

BACKGROUND: We studied the complications of gallstone disease in kidney transplantation patients and evaluated whether the screening and treatment of gallstones before acceptance to the kidney waiting list is relevant. METHODS: Complications of gallstone disease were evaluated in 1608 kidney transplantation patients on cyclosporine and long-term steroid treatment with median age 45.5 years, transplanted between 1990 and 2000. To evaluate the prevalence of cholecystolithiasis after kidney transplantation an abdominal ultrasound examination was cross-sectionally performed to a subgroup of 304 patients and the results were correlated to their serum lipid values, changes in BMI and use of statins. RESULTS: Pre-transplant cholecystectomy due to cholecystolithiasis (prerequisite for acceptance to kidney waiting list) had been performed on 71 (4%) of the patients. Thirty (15%) patients with diagnosed post-transplant gallstones and four without gallstones developed biliary complications. There were 25 cases of cholecystitis of which three resulted in gallbladder perforations. Seventeen patients (50%) with biliary complications required urgent surgery and one (3%) patient died of post-operative complications. In the subgroup of ultrasound examination patients (median 7 years post-transplant follow-up) 81% of the patients had no gallstones and 9% of the patients had gallstones had developed after transplantation. Patients with pre-transplant gallstones were older (P < 0.01) and patients with post-transplant gallstones gained the most weight during the follow-up. No differences in lipid values were found. CONCLUSION: In transplantation patients, the complications of gallstone disease may be severe. Screening and treatment of pre- and post-transplantation gallstone disease are recommended.

Adolescent↗

Measurement of the abdominal circumference for the detection of intra-abdominal hemorrhage has no diagnostic value.

BACKGROUND: Measuring the circumference of the abdomen is still commonly used when treating a patient with suspicion of intra-abdominal bleeding. In the present study the usefulness of this method for a diagnostic purpose is questioned because of the assumed method-related interindividual variation. METHODS: The study group consisted of 34 end-stage renal failure (ERSF) patients treated with peritoneal dialysis. Each patient was measured by the same nurse at the level of the umbilicus and the level of the iliac crest both before and after an infusion of 2000 ml of peritoneal dialysis fluid into the peritoneal cavity. One healthy female served as a control. Her abdominal circumference was measured at the level of the umbilicus by 10 different emergency medical technicians (EMTs), each of whom performed the measurement three times. The measuring tape was blank and the place of the first measurement was marked as performed in clinical practice. RESULTS: The mean abdominal circumference at the level of the umbilicus before an infusion of peritoneal fluid was 93.2 +/- 9.5 cm (SD), and after filling the peritoneal cavity 96.3 +/- 9.5 cm (difference 3.1 +/- 1.7 cm). These figures at the level of the iliac crest were 96 +/- 8.3 and 97.2 +/- 8.4 cm (difference 1.2 +/- 1.4 cm) (P < 0.0001), respectively. The mean value between the smallest and largest values when measuring the circumference of a healthy control person was 1.85 +/- 1.11 (P < 0.0005). The mean difference in circumference in the peritoneal dialysis patients was smaller than the largest difference among the three measurements taken by the same EMT. CONCLUSION: Measuring the abdominal circumference should not be used as a diagnostic tool when intra-abdominal bleeding is suspected.

Abdomen↗

Elevated serum C-reactive protein associates with deterioration of renal function in transplant recipients.

AIM: Since t he elevated concentration of serum C-reactive protein (CRP) is a sensitive indicator of underlying inflammation, we investigated the association between serum CRP during the initial 6 post-transplantation months and histopathological changes in the 6-month protocol biopsies in 79 patients. We stained the biopsies for CRP and C3 to elucidate a possible role of CRP in renal injuries. RESULTS: Forty patients showed no or minimal (Grade 0-1) tubular atrophy or interstitial fibrosis and 39 patients mild to moderate (Grade > or = 2) chronic histopathological changes. The latter group had had higher concentration of CRP during the first 6 post-transplant months. Because the histopathological changes predict poor long-term prognosis, we followed--from 6th month onwards--40 patients who had no or minimal histopathologic changes, and analyzed the association between CRP elevation and development of chronic allograft dysfunction. During this follow-up period (mean 51, range 14-72 months), 23 of 40 patients retained normal CRP level (Group A, mean CRP 1.12 mg/l), and 17 patients had elevated CRP concentrations (Group B, mean CRP 4.16 mg/l); 24-hour creatinine clearance improved or remained the same in all Group A patients, whereas it decreased in 7 of 17 (41%) of Group B patients (p < 0.001). In Group B patients, the annual change of creatinine clearance correlated inversely with the mean CRP concentration (r = -0.682, p < 0.01). CONCLUSION: Our results show that histological changes in 6-month biopsies were more prominent in patients with more transplantation-associated complications, infections and frequently higher CRP levels during the initial 6 post-transplant months than in those with lower CRP levels. During post-biopsy follow-up, we found low-grade systemic inflammation--measured as elevated CRP--to associate with impairment of graft function in patients with no or minimal histological findings in 6-month biopsies, and permanently low CRP to rule out chronic allograft dysfunction.

Adult↗

Soluble intercellular adhesion molecule-1 (sICAM-1) after kidney transplantation: the origin and role of urinary sICAM-1?

BACKGROUND: Intercellular adhesion molecule-1 (ICAM-1) binds to leukocyte adhesion receptors LFA-1 and MAC-1, and mediates leukocyte adhesion to target structures. During acute rejection there is increased expression of ICAM-1 in vascular and tubulointestial cells, and consequently accumulation of inflammatory leukocytes. Soluble ICAM-1 (sICAM-1) is released from ICAM-1 expressing cells and excreted into the surrounding fluid. Increased serum sICAM-1 levels are found in patients with acute rejections of various allografts, and high urinary levels in steroid resistant acute kidney allograft rejection. METHODS: Urinary excretion of sICAM-1 was measured by EIA in 136 kidney allograft recipients during the first 1-6 post transplant weeks: 30 patients developed acute rejection, and 106 patients had stable graft function. The molecular weight, binding to hyaluronan, and the origin of urinary sICAM-1 were studied. RESULTS: We show that urinary sICAM-1 circulates as a monomer with a molecular weight between 50 and 100 kD. It binds to immobilized, but not to circulating hyaluronan. About one week after transplantation the mean sICAM-1/creatinine ratio (306 ng/mmol) in transplanted patients was higher than in the healthy controls (167 ng/mmol, P<0.01), and remained basically unchanged during the follow-up in patients with stable graft function, whereas it increased in patients developing rejection, being about 2.5-fold above the initial level a few days before rejection (P<0.01). Urinary sICAM-1 did not correlate with the urinary albumin, whereas in patients developing rejection it correlated with urinary IL-2R (r=0.5146, P<0.001), a marker of lymphocyte activation. In the urinary sediment of rejecting patients ICAM-1 was demonstrated in the tubular epithelial cells, and in the macrophages. CONCLUSIONS: Increased urinary excretion of sICAM-1 was demonstrated in kidney transplanted patients a few days before acute rejection. It seems to originate from activated macrophages and/or from the tubular epithelial cells. The fact that urinary sICAM-1 is not bound to hyaluronan or to leukocytes suggests that it is not able to compete with membrane-bound ICAM-1 for these bindings, but may do so for the binding of activated macrophages.

Albuminuria↗

Should Helicobacter pylori infection be treated before kidney transplantation?

BACKGROUND: Before the introduction of modern medication for ulcer disease, gastroduodenal complications were often fatal in recipients of kidney transplants. Helicobacter pylori causes gastritis and is an important risk factor for peptic ulcer disease and gastric malignancies. The aim of this study was to evaluate whether H. pylori infection influences the outcomes of kidney transplantation. METHODS: Between 1991 and 1994, serum H. pylori antibodies were determined in samples taken just before transplantation from 500 consecutive recipients of kidney transplants. Clinical data were collected retrospectively by means of questionnaires sent to the patients and from the national kidney transplantation registry. RESULTS: The prevalence of seropositivity of H. pylori was 31% in the 500 renal transplant subjects, and the seropositivity increased with age. There were no differences in patient or graft survival between the seronegative and seropositive patients. During the first 3 months after transplantation, five seronegative and one seropositive patient had gastroduodenal ulcers, with bleeding complications in three of the seronegative ones. After 3 months, there were more ulcers in the seropositive group (6 vs 3%) and more oesophagitis in the seronegative group (9 vs 7%). During the 6-year follow-up, two cases of gastroduodenal malignancies were found in the helicobacter-positive group and none in the seronegative group. CONCLUSIONS: Helicobacter pylori infections did not result in significant postoperative gastric complications. Two of the 155 seropositive patients developed gastroduodenal malignancies.

Adolescent↗

The effect of ketorolac and sevoflurane anesthesia on renal glomerular and tubular function.

UNLABELLED: We assessed the renal effects of the combination of ketorolac and sevoflurane anesthesia by using sensitive and specific markers of renal proximal and distal tubular and glomerular function. Thirty women (ASA physical status I and II) undergoing breast surgery received either ketorolac 30 mg IM or saline at premedication, at the end, and 6 h after anesthesia maintained with sevoflurane. Peak levels of serum fluoride at 2 h after the end of anesthesia were 30.1 micromol/L (21.0-50.0 micromol/L) in the Ketorolac group and 33.3 micromol/L (13.0-38.0 micromol/L) in the Control group (mean and range, not significant). Urine alpha1-microglobulin indexed to urine creatinine was increased from 2 h after the start of anesthesia until the first postoperative day in the Ketorolac group (peak level, 0.8 +/- 0.4 mg/mmol; upper limit of normal, 0.7 mg/mmol) but did not change in the Control group. Urine glutathione-S-transferase (GST)-alpha indexed to urine creatinine (GST-alpha/creatinine) and GST-pi/creatinine were increased 2 h after anesthesia and returned to baseline values thereafter in both groups. There were no changes in serum cystatin C and urine kallikrein or urine output per hour between groups. The perioperative administration of ketorolac to healthy, well hydrated patients anesthetized with sevoflurane did not produce renal glomerular or tubular dysfunction. IMPLICATIONS: Ketorolac 90 mg IM, given in divided doses over approximately 10 h to patients anesthetized with sevoflurane with a fresh gas flow rate of 4-6 L/min, did not result in clinically significant changes in renal glomerular or tubular function.

Adolescent↗

Changes of urinary alpha1-microglobulin in the assessment of prognosis in renal transplant recipients.

BACKGROUND: After transplantation, even if the graft starts functioning immediately, there are morphological and functional changes in tubular structures. In addition, acute allograft rejection causes damage in the tubular epithelium, tubular basement membrane, and intertubular connective tissue. It also affects the functional capacity of proximal tubular cells resulting in impaired reabsorption and thus increased urinary excretion of low molecular weight proteins. METHODS: We present a double-antibody radioimmunoassay for determination of the concentration of alpha1-microglobulin (alpha1 M) in urine. It was used to measure urinary excretion of alpha1 M approximately once a week during the first 1-6 posttransplant weeks in 136 consecutive patients: 30 patients developing acute rejection (75 24-hr urine samples) and 106 patients with stable graft function (223 24-hr urine samples). The results are expressed as alpha1 M/creatinine ratios. RESULTS: Approximately 8 days after transplantation the mean (+/-SD) urinary alpha1 M/creatinine ratio of all patients was 17.0+/-14.8 mg/mmol, being about the same both in patients with uncomplicated posttransplantation course (16.3+/-14.0 mg/mmol) and in those who later developed rejection (19.3+/-15.1 mg/mmol), but about 60-fold higher than in healthy controls (0.27+/-0.15 mg/mmol). At that time, when all patients were included there was a correlation (r=0.3465, P<0.001) between alpha1 M/creatinine ratio and duration of cold ischemia. Thereafter, during the second week alpha1 M/creatinine ratio decreased in 89% of patients with stable graft function, but only in 14% of patients who later developed rejection (P<0.001). On the contrary, a significant increase (P<0.01) of alpha1 M/creatinine ratio was observed 4 to 1 day before rejection in all 15 patients, who had urines collected at that time. At the end of the follow-up period, alpha1 M/creatinine ratio in patients with rejection was 3-fold compared with the nonrejecting patients, and 100-fold compared with the healthy controls. CONCLUSION: These results show that cadaveric transplantation results in impaired low molecular weight protein reabsorption, the degree of dysfunction relating to the duration of cold ischemia, and suggest that during the posttransplant weeks decreasing alpha1 M/creatinine ratio in consecutively collected urine samples indicates improved tubular function and in most cases rules out development of acute rejection.

Adolescent↗

Does increased urinary interleukin-1 receptor antagonist/interleukin-1beta ratio indicate good prognosis in renal transplant recipients?

BACKGROUND: Interleukin-1 (IL-1) is produced by activated monocytes/macrophages; highly increased amounts of IL-1 have been found in renal tissue in acute rejection of renal grafts. The endogenous inhibitor of IL-1, interleukin-1 receptor antagonist (IL-1ra), is produced in many cells in response to the same stimulus as IL-1. There is some evidence that the balance between IL-1 and IL-1ra is important in the regulation of inflammatory responses. In many inflammatory diseases in both humans and animals, a high concentration of endogenous IL-1ra or administration of exogenous IL-1ra has been shown to relate to shorter recovery time or to reduced mortality. METHODS: We measured the urinary excretion of IL-1ra and IL-1beta during the first 3-6 posttransplant weeks in 23 patients with acute rejection (69 24-hr urine samples) and in 17 patients with stable graft function (51 24-hr urine samples) and expressed the results as cytokine/creatinine ratios. RESULTS: Within the follow-up time, patients with rejection had higher urinary IL-1beta/creatinine (ng/mmol) ratios (median 5.0 vs. 2.7; P<0.005), lower IL-1ra/creatinine (ng/mmol) ratios (median 18.1 vs. 34.2; P<0.1), and consequently lower IL-1ra/IL-1beta ratios (median 3.6 vs. 20.3, P<0.005), compared with patients without rejection. In rejecting patients, IL-1ra/creatinine was constantly low and decreased even further during acute rejection, whereas IL-1beta/creatinine ratios increased from a median prerejection value of 3.5 (range not measurable to 9.0) to a median value of 8.1 (P<0.0005) (range 1.6 to 18.3) during rejection. CONCLUSION: These results suggest that patients who produce high amounts of IL-1ra in relation to IL-1beta are less prone to acute allograft rejection than patients with low IL-1ra/IL-1beta ratios.

Adult↗

Outcome of infrainguinal bypass surgery for critical leg ischaemia in patients with chronic renal failure.

OBJECTIVE: To determine whether infrainguinal bypass surgery is worthwhile in patients with critical limb ischaemia (CLI) and chronic renal failure. DESIGN: Longitudinal observational study. MATERIALS AND METHODS: Twenty-two patients with moderate renal failure indicated by serum creatinine level above 150 mumol/l, 10 patients with end-stage renal disease requiring dialysis, and three patients with functioning kidney transplant, underwent 39 bypass procedures for critical limb ischaemia. RESULTS: Six femoropopliteal, 14 femorocrural and 19 femoropedal bypasses were performed. The immediate, 1-month, and 1-year primary patency rates were 97%, 84% and 70%, respectively. The limb salvage was 93% at 1-month and 72% at 1-year follow-up. One-year patency and leg salvage rates were 81% and 79% in non-dialysis patients, and 47% and 37% in dialysis patients. At 1-year follow-up, 55% of surviving patients had salvaged limbs. None of the patients in dialysis was alive with salvaged legs 4 months after revascularisation. Among preoperative risk factors, only serum creatinine showed a statistical significance in predicting leg salvage and survival. CONCLUSIONS: As the outcome of patients on dialysis is very poor after infrainguinal bypass grafting, revascularisation is seldom indicated. On the contrary, leg salvage can achieve good results in patients not requiring dialysis.

Adult↗

Peritoneal dialysis access: a comparison of peritoneoscopic and surgical insertion techniques.

Prospectively collected data were analysed comparing 108 consecutive peritoneoscopically (n = 65) and surgically (n = 43) placed peritoneal dialysis catheters during a three-year period. Catheter-linked mechanical complications occurred more often in the peritoneoscopical group, and pericatheteral leakage ended in catheter loss in 13.8%. Overall probability of catheter survival in the peritoneoscopic group at 12, 24 and 36 months was 73%, 56% and 24%, and in the surgical group 87%, 87% and 66%, respectively (p < 0.05). Rates of infectious complications, peritonitis and exit site infections were similar.

Case-Control Studies↗

Adhesion molecules and urinary tumor necrosis factor-alpha in idiopathic membranous glomerulonephritis.

Adhesion molecules are required in several physiological processes, but their altered function/expression is associated with the pathogenesis of inflammatory diseases. In the present study on idiopathic membranous glomerulonephritis (MGN) the expression of adhesion molecules (ICAM-1, VCAM-1, PECAM-1, E-selectin, LFA-1, Mac-1) was analyzed in different cellular compartments of the kidney using an indirect immunoperoxidase technique and monoclonal antibodies. Relationships between the expression of these molecules and the clinical and morphological activity of the disease and the urinary excretion of tumor necrosis factor alpha (TNF-alpha) were studied in 20 patients. The results were compared with the findings in ten normal kidneys and urinary TNF-alpha in 17 healthy subjects. The expression of adhesion molecules in glomeruli and tubules was unchanged apart from a diminished expression of VCAM-1 (P = 0.014) in glomerular parietal epithelial cells and PECAM-1 in glomerular endothelial cells (P < 0.01). Interstitial peritubular capillaries expressed significantly (P = 0.009) more E-selectin compared with the controls. The interstitial compartment had a highly increased number of cells expressing ICAM-1 in MGN (32.4 +/- 4.6 cells/high power field) compared with the controls (9.4 +/- 1.2; P < 0.001). Also, cells expressing VCAM-1 (10.2 +/- 1.6 vs. 2.8 +/- 1.9; P = 0.005). PECAM-1 (25.9 +/- 5.3 vs. 7.4 +/- 2.1; P = 0.006), and LFA-1 (20.4 +/- 3.6 vs. 8.3 +/- 1.5; P = 0.041) were increased in the interstitium. Proteinuria correlated particularly with the expression of E-selectin in peritubular capillaries (r = 0.63, P = 0.004). The number of LFA-1 expressing inflammatory cells in the interstitium correlated with peritubular capillary E-selectin (r = 0.8, P < 0.001) and interstitial ICAM-1 (r = 0.61, P = 0.009) expression, but histological alterations did not correlate with the expression of adhesion molecules. Tumor necrosis factor-alpha excretion was significantly increased in MGN (41 +/- 8 pg/mg creatinine) compared with the controls (13 +/- 2; P = 0.001), and in particular, it correlated with the interstitial expression of LFA-1 (r = 0.71, P = 0.002). This study suggests that active MGN leads not only to proteinuria but also to increased urinary TNF-alpha excretion. These may serve as triggers for the up-regulation of adhesion molecules in the peritubular capillaries and interstitial cells thus enhancing the development of the interstitial injury.

Adult↗

Validation of a predictive model of idiopathic membranous nephropathy: its clinical and research implications.

Although a number of factors have consistently correlated with progression to chronic renal insufficiency (CRI) in idiopathic membranous glomerulonephropathy (IMGN), they appear late, are not quantitative in nature and have not been validated. We have determined that the highest sustained six-month period of proteinuria is an important predictor of progression. Using multiple logistic modelling, the only additional prognostic variables of importance in 184 Canadian patients were the initial creatinine clearance and the rate of change in function over this six-month interval. Independent data from Italy (101 patients) and Finland (78 patients) were obtained for comparison. Sensitivity, specificity, negative and positive predictive values and overall accuracy, as well as Pearson's goodness-of-fit and Harrell's "C" statistic were used to assess the fits of the model. Accuracy of prediction was > or = 85% in all three countries. Pearson's Chi-square goodness-of-fit showed good agreement across the spectrum and Harrell's "C" statistic was > or = 90%. Therefore, a predictive, semiquantitative algorithm in IMGN has been validated. Its relevance in patient management and in clinical trials is illustrated.

Algorithms↗