Hyperparathyroidism and new onset diabetes after renal transplantation.

BACKGROUND: Secondary hyperparathyroidism persists after renal transplantation in a substantial number of patients. Primary hyperparathyroidism and secondary hyperparathyroidism are both associated with abnormalities in glucose metabolism, such as insufficient insulin release and glucose intolerance. The association of hyperparathyroidism and diabetes after renal transplantation has, as far as we know, not been studied. Our aim was to investigate whether hyperparathyroidism is associated with new-onset diabetes mellitus after transplantation (NODAT) during the first year posttransplantation. STUDY DESIGN: In a retrospective study, we analyzed data on patient characteristics, treatment details, and parathyroid hormone (PTH) in 245 adult nondiabetic patients who underwent renal transplantation between January 2000 and June 2011. RESULTS: The first year cumulative incidence of NODAT was 15%. The first serum PTH value after transplantation was above normal range in 74% of the patients. In multiple logistic regression analysis, PTH levels above twice normal range (>13.80 pmol/L) were significantly associated with NODAT (odds ratio [OR], 4.25; 95% confidence interval [CI], 1.13-15.92; P = .03) compared with PTH within normal range (≤6.9 pmol/L). Age between 45 and 65 years (OR, 2.80; 95% CI, 1.07-7.36; P = .04) compared with age <45 years was also associated with NODAT. CONCLUSION: We found a strong association between hyperparathyroidism and NODAT in the first year after renal transplantation. Both conditions are common and have a negative impact on graft and patient survivals. Our results should be confirmed in prospective studies.

The importance of exercise training in predialysis patients with chronic kidney disease.

Patients with chronic renal failure show a decline in maximal exercise capacity and muscle strength as renal function decreases. Renal anemia, skeletal muscle dysfunction, tiredness and increasing inactivity are the major causes of this deterioration in predialysis patients. Exercise training improves maximal exercise capacity, muscle strength and endurance in young, middle-aged and elderly predialysis patients. It has a positive effect on muscle catabolism and counteracts weight loss and malnutrition. Moreover, exercise training has positive effects on functional capacity and health-related quality of life. However, early referral to a nephrologist and multiprofessional teamwork in the care of predialysis patients is essential in order to implement comprehensive predialysis care and exercise training successfully.

The haemodialysis machine as a lifeline: experiences of suffering from end-stage renal disease.

AIM: The aim of this study was to describe patients' experiences of suffering from end-stage renal disease (ESRD). RATIONALE: The rationale was to investigate how persons find meaning or make sense of their situation and how they experience suffering. The theoretical basis for the study was to view suffering at three levels. The first level was related to sickness and treatment. The second level was related to the care provided and the third level was related to each person's unique life experience and existence. METHOD: Data were collected by interviews focusing on questions concerning daily life, needs, and expectations for the future. A qualitative interpretative content analysis was used. Fifteen patients between the ages of 50-86 participated in the study. FINDINGS: Two main themes were identified describing these patients suffering. The first theme, 'the haemodialysis machine as a lifeline' consisted of three subthemes: 'loss of freedom', 'dependence on the caregiver', and 'disrupted marital, family and social life'. The second theme 'alleviation of suffering' consisted of two subthemes: 'gaining a sense of existential optimism' and 'achieving a sense of personal autonomy'. CONCLUSION: This study indicated that, in the lives of patients on haemodialysis, the main areas of suffering were related to loss of freedom expressed as dependence on the haemodialysis machine as a lifeline and, the caregivers. This time-consuming and tiring dependence affected marital, family and social life. Alleviation of suffering could be achieved by accepting dependence on the haemodialysis machine and maintaining autonomy by being seen as an individual by the caregivers.

Twelve weeks of exercise training increases muscle function and walking capacity in elderly predialysis patients and healthy subjects.

Muscle function declines with age and progressive uraemia. We examined whether elderly predialysis patients could improve thigh muscle function, walking capacity, and functional mobility to the same extent as elderly healthy subjects when participating in 12 weeks of individual muscle endurance exercises for the thigh as well as in a low-intensive group programme. The uraemic exercise and comparison groups comprised 16 patients (age 76 +/- 7 years, glomerular filtration rate 18 +/- 5 ml/min) and 9 patients (age 72 +/- 6 years, glomerular filtration rate 16 +/- 5 ml/min), respectively. The healthy exercise and comparison groups comprised 18 subjects (age 75 +/- 7 years) and 5 subjects (age 79 +/- 4 years), respectively. Muscular strength, dynamic endurance, walking capacity, and functional mobility increased significantly in both the uraemic and the healthy exercise groups after 12 weeks of regular muscle endurance exercise training, whereas there was no significant change in static muscle endurance and quality of life in either group. None of the values changed for the uraemic comparison group nor the healthy comparison group during the observation period. Elderly predialysis patients had lower muscle function and mobility as compared with elderly healthy subjects, but were able to improve both after 12 weeks of exercise training to the same extent as elderly healthy subjects.

Preoperative treatment of anemic women with epoetin beta.

AIM: To compare the effects of preoperative treatment with recombinant human erythropoietin (EPO) and iron with iron only on hemoglobin levels (Hb) in anemic women prior to hysterectomy. METHODS: The study was an open-labelled randomized parallel study. Fifteen women scheduled for hysterectomy due to uterine myoma were given oral iron and EPO (NeoRecormon) 4 weeks prior to surgery (group I) and 16 women were given oral iron only (group II). RESULTS: Group I showed a significantly greater increase in mean Hb during the pre-surgery study period compared with group II (p=0.007). Two weeks postoperatively, however, there was no significant difference in mean Hb between the two groups. CONCLUSION: We found that a significantly greater increase in Hb was achieved with iron in combination with EPO, although in most cases iron only seemed to be as efficacious as iron+EPO in correcting anemia in myoma patients pre-operatively.

Chronic cobalt exposure affects antioxidants and ATP production in rat myocardium.

Chronic cobalt exposure is characterized by severe cardiac insufficiency. Since the mechanisms of cobalt toxicity are not yet clear, we analysed the effects of chronic cobalt exposure on antioxidant enzyme activities and myocardial mitochondrial ATP production rate in a rat model. One group of rats was fed a conventional diet and another a cobalt supplemented diet for 24 weeks. The manganese-superoxide dismutase activity was markedly reduced in the cobalt rats (18+/-4.7 U/mg protein) compared to the control rats (100+/-22 U/mg protein; p <0.001). Activity in the respiratory chain enzymes succinate-cytochrome c reductase, NADH-cytochrome c reductase and cytochrome c oxidase was also reduced in the cobalt rats (p<0.01). Glutamate dehydrogenase activity, located in the mitochondrial matrix, was unchanged. The mitochondrial ATP production rate in relation to myocardial mass was lower in the cobalt rats for all substrates tested except palmitoyl-l-carnitine + malate. In conclusion, 24 weeks of chronic cobalt exposure induces a marked decrease in manganese-superoxide dismutase activity, a moderate decrease in mitochondrial ATP production rate and a general reduction in the capacity of the respiratory chain. The impairment in mitochondrial ATP production might be secondary to the decreased manganese-superoxide dismutase activity, causing inactivation of mitochondrial factors susceptible to superoxide radicals.

Improving the nurse-patient relationship: a multi-faceted approach.

AIM: A Corporate Education Session was held to provide concrete strategies for overcoming several specific barriers in the daily nurse-patient relationship that negatively affect the patient, nurse, or both, and to provide the latest information about best practice as it affects nurses in renal care. METHODOLOGY: The session was led by a moderator who presented three video case studies to the audience. Communication strategies for recognising and overcoming nurse-patient communication barriers were presented. The audience expressed their views about each case study using voting pads, and a panel of experts addressed the comments of the audience and discussed guidelines for best practice in renal care. The panel comprised three experienced renal nurses, a senior nephrologist, and an expert in social interaction. CONCLUSIONS: Optimal treatment of patients with renal disease should include early treatment of anaemia, adequate levels of dialysis, and a multidisciplinary approach, responding to both the medical and the social needs of the patient.

The efficacy of once weekly compared with two or three times weekly subcutaneous epoetin beta: results from a randomized controlled multicentre trial. Swedish Study Group.

BACKGROUND: Anaemia in haemodialysis patients can be effectively treated with erythropoietin. We investigated whether subcutaneous (SC) epoetin ss administered once weekly was as effective as the same weekly dosage given in two to three divided doses. METHODS: One hundred and fifty-eight patients (delivered Kt/V >1.0, where K=dialyser-renal urea clearance, t=dialysis time and V=filtration volume, obtained by urea kinetic modelling) were randomized to treatment with SC epoetin beta either once weekly (n=118), or to their original dosage two or three times weekly (control group, n=40) for 24 weeks. All patients received intravenous iron supplementation when necessary. RESULTS: Eight-eight patients in the once weekly group and 30 patients in the control group were treated for at least 16 weeks and are included in the analysis. Stable haemoglobin levels were maintained without epoetin dose increases in 73% of patients in both groups. Mean haemoglobin levels at randomization and after 16 and 24 weeks were 11.4, 11.1 and 11.1 g/dl, respectively, in the once weekly group compared with 11.2, 11.3 and 11.2 g/dl, respectively, in the control group. The mean weekly epoetin beta dosages at randomization and after 16 and 24 weeks were 102, 103 and 106 IU/kg bodyweight, respectively, in the once weekly group compared with 109, 109 and 115 IU/kg bodyweight, respectively, in the control group. No statistically significant between-group differences were apparent for changes in haemoglobin levels or epoetin beta dosages at week 24. CONCLUSIONS: Once weekly SC administration of epoetin beta is as safe and effective in maintaining haemoglobin levels in stable haemodialysis patients as two or three times weekly administration of the same total dose. By using the once weekly regimen, patients can avoid up to 104 injections per year. This would reduce clinic time for patients who do not self administer, and may also encourage self-administration and improve overall compliance.

Myocardial morphology and cardiac function in rats with renal failure.

The effects of chronic renal failure on cardiac performance and myocardial morphology were studied in rats: 17 with 5/6 nephrectomy (CRF rats) and 12 with sham operation (controls). Cardiac function was assessed 8 weeks postoperatively, using the Langendorff technique for an isolated working heart model. After the hemodynamic study the hearts were fixed for electron and light microscopy. In the CRF rats left ventricular systolic pressure was significantly higher at all preloads (10-20 cmH2O) and afterloads (70-90 cmH2O), and left ventricular stroke work was significantly increased at preload 20 cmH2O with afterloads 70 or 90 cmH2O. Light microscopy revealed fibronecrotic lesions consisting of fibroblastic proliferation with newly formed collagen interposed between or entrapping degenerative myocytes. The changes were focally distributed, with perivascular accentuation and were most frequent in the basal half of the ventricular wall. Electron microscopy of non-necrotic myocytes showed intact myocytes, with mitochondria morphometrically similar in the 2 groups, but a significantly lower incidence of mitochondrial granules in the CRF rats. Thus 8 weeks of CRF showed no cardiac dysfunction associated with the focally distributed fibronecrotic myocardial lesions and decrease in mitochondrial granules. The precise mechanism of the discrepancy between the morphological change and the cardiac function is unclear. One possible explanation may be that because the pathological changes in the myocardium were focal or mild to moderate, some compensation mechanism may be involved or it may be the turning point of functional change from acute renal failure to the chronic state.

Predialysis education helps patients choose dialysis modality and increases disease-specific knowledge.

UNLABELLED: The aims of this study were first, to evaluate the effects of a patient-education programme for a group of 28 uraemic patients (the Experimental (EG) group) with regard to their knowledge and perceived amount of information and to relate these effects to their sense of coherence and secondly, to study the patients' perception of their dialysis treatment. The results were compared with a comparison group (the Companion (CG) group, n = 28) which had received routine information only. The education programme seemed to have covered what the EG wanted to know. Significantly more patients in the EG group stated that they had acquired sufficient knowledge to enable them to participate in choosing dialysis modality compared with the CG group. The EG patients were significantly more informed in the post-educational evaluation compared with the pre-educational evaluation. In the EG, there was a significant relationship between the scores for knowledge and perceived amount of information. Men and younger patients perceived that they had received a greater amount of information than women and older patients. After having started dialysis treatment, there were no differences in the scores for knowledge and information between the EG and the CG. This indicates that other sources of knowledge and information were available to the CG patients. There was no significant correlation between the score of the Sense of Coherence (SOC) scale and the knowledge and information scores. Kidney transplantation, progression of renal failure, other patients' experiences of dialysis, dependence - independence, present and future wellbeing, how to cope with physical and psycho-social demands and continuity in their contacts with doctors and other health professionals were predominant concerns for the two groups of patients. CONCLUSION: the predialysis group education programme enabled patients to choose dialysis modality to achieve an understanding of their illness and its treatment. It also provided the possibility of informal support by fellow patients and health professionals. The study emphasizes the special needs of elderly patients and we recommend that education programmes are tailored to their requirements.

Predialysis patient education: effects on functioning and well-being in uraemic patients.

This study evaluated the effects of a predialysis patient education programme on functioning and well-being in 28 uraemic patients. The programme consisted of four group sessions with the following themes: renal disease and dietary restriction, active renal replacement therapy, physical exercise, and the impact of chronic renal failure on economy, family and social life. Three to 9 months after having started dialysis the patients were evaluated regarding symptoms, perceived health (Health Index), functional (SIP) and emotional (STAI) status. Twenty-eight patients already on dialysis treatment informed according to conventional routines constituted the comparison group. There were no significant differences between the groups regarding age, sex, educational or social background, duration of kidney disease, choice of dialysis treatment, cause of renal disease and laboratory tests except for s-urea. The patients who participated in the education programme scored significantly better mood, less mobility problems (HI), less functional disabilities (SIP) and lower levels of anxiety (STAI) compared to the comparison group. There were no significant differences between the two groups regarding symptoms and overall health. The differences between the groups prevailed during the first 6 months on dialysis treatment, after which the differences disappeared. In the comparison group age correlated significantly to anxiety and overall SIP, which was not the case in the experimental group. In conclusion, the experimental group that participated in a predialysis patient education programme, showed better functional and emotional well-being than the non-educated comparison group. The positive effects of participating in an education programme prevailed during the first 6 months of dialysis treatment. Moreover, the younger patients seemed especially to benefit from participation in a predialysis patient education programme. It is suggested that patient education should be ongoing for patients with end-stage renal failure initiated during the predialysis stage and continued after maintenance dialysis has been established.

In vitro endothelialisation of arteriovenous loop grafts for haemodialysis.

OBJECTIVES: To evaluate the feasibility in a pilot study of in vitro endothelialisation of PTFE grafts used as interposition arteriovenous fistulas in uraemic patients. METHODS: Autologous saphenous vein endothelial cells were harvested and cultured on PTFE grafts in seven patients undergoing maintenance haemodialysis. The patients had several previous failures of vascular access sites. The patients were followed with duplex ultrasound, clinical examination and in one case an explanted graft was examined. RESULTS: At the end of follow-up four of the seven patients had patent grafts. One patient occluded the graft immediately postoperatively and another after 3.5 months. The former patient received a second endothelialised graft. In two further patients revision of the outflow was performed. In two patients a functioning graft was excised, in one case because of bleeding of a venous aneurysm and in one case because of suspected infection. The former which was excised 5 weeks postoperatively revealed that 85% of the surface was covered by endothelial cells. CONCLUSIONS: This pilot study shows that in vitro endothelialisation of PTFE grafts used for haemodialysis is possible in uraemic patients. In this highly problematic patient group the results are promising with endothelial cell coverage after 5 weeks of implantation.

Well-being and functional ability in uraemic patients before and after having started dialysis treatment.

In this study perceived well-being and functioning in 28 uraemic patients (14 women and 14 men, mean age 54 years) were measured in the predialysis stage during conservative renal therapy and 3-9 months after having started maintenance dialysis treatment. The patients had participated in a patient education programme in the predialysis stage. Disease-specific symptoms, perceived health (Health Index), functional (SIP) and emotional (STAI) status were analysed. The results showed that there were no significant differences in the patients' correction of uraemia, frequency of symptoms or anxiety prior to and after having started dialysis. After having started dialysis treatment, fatigue, lack of energy and functional disability in work increased while disability in recreation and pastime decreased. Standard bicarbonate correlated significantly to the symptoms of leg cramps and itching. Serum albumin correlated significantly to eating dysfunction in the SIP. There was a large variation within the group with regard to their self-rated disturbances. Some patients reported a relatively intact quality of life, some reported a moderate influence, and some a severe decrease in quality of life irrespective of whether they were in the predialysis state or on maintenance haemodialysis or CAPD. In conclusion, dialysis treatment resulted in increased fatigue and lack of energy, while disease-specific symptoms, functional disability and anxiety did not increase during the first months on dialysis. The symptoms of itching and leg cramps correlated significantly with level of metabolic acidosis, and eating disability correlated with serum albumin levels, indicating that biochemical variables should be combined with patient assessment of health and well-being in order to optimize treatment and care. Moreover, the wide range of scores in all the research variables indicates that assessment of quality of life can be helpful in allocating support to those patients in need of it.

Quality of life in predialytic uremic patients.

This study describes and analyses how 38 predialytic uremic patients perceived their sense of well-being, functional ability, level of anxiety and sense of coherence. The patients in this study reported decreased sense of well-being, considerable functional disabilities, and a high level of anxiety when compared to a healthy reference group. These observations were independent of laboratory data with the exception of hemoglobin concentration which showed a significant negative correlation to the SIP scale work. There was a significant negative correlation between the scores of sense of coherence and anxiety. Patients with a weak sense of coherence and a high level of anxiety perceived their well-being as being worse than those with higher scores in the sense of coherence test and lower scores in the level of anxiety test. Sense of well-being in turn influenced functional ability in daily life. Social and marital status also affected the results. These results indicate that the investigated group of predialytic patients have a decrease in quality of life. The results obtained provide a useful instrument showing in which areas care should be concentrated and in what way patients' own resources need to be strengthened while preparing for dialysis treatment.

Effects of hemodialysis and long-term erythropoietin treatment on protein C, and on free and total protein S.

We studied 37 hemodialysis patients during hemodialysis in order to assess the effects of dialysis on endogenous plasma coagulation inhibitors (antithrombin III, protein C, free and total protein S). The patients were examined prior to erythropoietin (EPO) treatment, upon reaching target hemoglobin (Hb) and after 3 months at steady state Hb levels. The levels of protein C increased significantly during dialysis. However, EPO treatment did not affect the levels of any of the endogenous coagulation inhibitors, either upon reaching target Hb or after 3 months of steady state Hb. The sequence of change during dialysis of protein C, free and total protein S was constant when comparing respective patterns prior to EPO treatment to those at target Hb and steady state Hb respectively. In conclusion, hemodialysis seems to activate synthesis of endogenous coagulation while partial correction of anaemia with EPO does not affect the levels of these inhibitors.

Treatment with recombinant human erythropoietin induces a moderate rise in hematocrit and thrombin antithrombin in healthy subjects.

Recombinant human erythropoietin (EPO) therapy in uremic patients raises the hematocrit (Hct) and increases physical exercise capacity (1,2) and quality of life (1). In general, partial correction of anemia to subnormal levels in uremic patients has proven to be safe with few serious adverse effects apart from hypertension (3). Ever since the advent of EPO the prospect of abuse of the hormone by sportsmen has been subject to scrutiny. Both maximal oxygen uptake and endurance capacity are increased after EPO treatment in healthy subjects (4). Moreover, EPO treatment in healthy subjects has been found to induce an accentuated blood pressure reaction after submaximal exercise (5). Previous studies have shown that extreme physical exertion can predispose to an increased intravascular coagulation (6). Moreover there is a significantly increased risk of thrombosis in patients with myeloproliferative disorders, particularly in polycythemia vera (7). An enhanced risk of cardiovascular events may therefore arise should sportsmen abuse EPO as a blood doping agent. The aim of this study was to examine the effects of an EPO-induced increase in Hct on the coagulation system in healthy subjects.

Long-term effects of erythropoietin treatment on the coagulation system during standardized hemodialysis.

We studied 37 hemodialysis patients, treated with erythropoietin (EPO), prior to and upon reaching target Hb and after 3 months at steady state Hb levels. Our aim was to analyze the effects of EPO on markers of all stages of coagulation and anticoagulation during a standardized hemodialysis procedure upon reaching target Hb as well as long term effects of a stable Hb. The Hb rose from 82 +/- 9 to 111 +/- 12 g/L at target Hb (p < 0.0001) and was 108 +/- 15 g/L after 3 months of steady state. The heparin dose was individually titrated, using a whole blood activated coagulation time method (WBACT) and kept constant during the first phase of the study. The titrated heparin dose increased significantly at target Hb and this increase persisted after 3 months at steady state. Accordingly the increase in WBACT decreased significantly. There was a significant increase in platelets at target Hb and this increase persisted at steady state. beta-thromboglobulin increased significantly at target Hb and this increase persisted after 3 months at steady state. Platelet factor 4 was unchanged throughout the study period. Inhibitors of plasma coagulation: AT III, protein C and total and free protein S were unchanged throughout the study period. There was no changes in indicators of intravascular coagulation: TAT, fibrin monomers or FPA throughout the study period. There was no FPA generation during dialysis. The residual blood volume in the dialyzer was unaffected throughout the study period. There was a significant decrease in D-dimers at target Hb and after 3 months at steady state.(ABSTRACT TRUNCATED AT 250 WORDS)

Subcutaneous epoetin beta in renal anemia: an open multicenter dose titration study of patients on continuous peritoneal dialysis.

OBJECTIVE: To establish dose requirements (target hemoglobin > 100 g/L) and safety of subcutaneously administered epoetin beta. DESIGN: Open multicenter study. PATIENTS: Forty-five anemic patients (21 female, 24 male; mean age 55 years; range 20-79 years) who had been on continuous peritoneal dialysis for 1-157 months (mean 24 months). Thirty patients required blood transfusions during the year prior to the study. Mean hemoglobin concentration pretreatment was 75 g/L (range 57-89 g/L). INTERVENTION: After a pretreatment period of two weeks, 60 IU kg-1 week-1 divided into three weekly doses of epoetin beta was administered subcutaneously. The dose was increased by 60 IU kg-1 week-1 after ten weeks, and when necessary, every fourth week in patients with hemoglobin levels below 100 g/L. MAIN OUTCOME MEASURES: Hemoglobin concentration. Analysis of factors affecting the response to epoetin beta. Safety of epoetin beta. RESULTS: Thirty-eight of the 45 patients completed six months and 21 patients completed one year in the study. Twenty-six patients reached hemoglobin 100 g/L within six months and 8 patients did later on. The mean hemoglobin concentration after three months was 93 g/L (range 64-144 g/L) and after six months was 99 g/L (range 59-130 g/L; mean epoetin beta dose 122 IU kg-1 week-1). During the second six-month period of the study, hemoglobin levels were stable in most patients. After one year, the mean hemoglobin was 110 g/L (range 84-153 g/L) and the mean epoetin beta dose was 107 IU kg-1 week-1. Prolonged correction time and impaired response to epoetin were observed in patients with infections or hemorrhages and in patients with low hemoglobin concentration before starting epoetin treatment. Iron deficiency was controlled by iron supplementation, either orally or, in 10 patients, intravenously. Increased blood pressure, requiring intensified antihypertensive treatment, was observed in 13 patients. CONCLUSIONS: Continuous peritoneal dialysis patients with moderate anemia (Hb 75-90 g/L) and without complicating disorders can be managed with subcutaneous doses of epoetin < 120 IU kg-1 week-1. The epoetin beta dose should be adjusted after the first month of treatment since most patients required higher doses than the initial 60 IU kg-1 week-1.

The effect of erythropoietin treatment on arteriovenous haemodialysis fistula/graft: a prospective study with colour flow Doppler ultrasonography.

To determine the effect of erythropoietin (EPO) on patency the haemodynamics and morphology in haemodialysis fistula/graft were prospectively assessed using ultrasonographic two-dimensional imaging and colour flow Doppler together with pulsed Doppler, prior to and during partial correction of anaemia with EPO. Nineteen radiocephalic fistula and 11 loop grafts in 30 patients on routine maintenance haemodialysis were investigated prior to EPO treatment. A significant stenosis defined as a localised 100% increase in flow velocity was found in the arterial inflow in seven (23%) patients, in the loop graft in seven (64% of loop grafts) patients, and in the venous segments in 23 (77%) patients. Fourteen patients were rescanned after more than 200 days of EPO therapy. There was a significant increase in haemoglobin (84 +/- 14 g/l to 104 +/- 18 g/l) and haematocrit (24 +/- 4 to 31 +/- 5%) during this time. One arterial, four loop grafts and two venous stenoses appeared or increased in severity, and one venous return flow segment had occluded. Blood flow according to ultrasonography was unchanged. Of the 16 patients lost to follow-up, three underwent surgical intervention (clinical failure rate 0.20 access/year). EPO therapy may contribute to minor changes in access haemodynamics but does not seem to be detrimental to patency.