High-osmolality and low-osmolality contrast agents.
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Canada↗
Biomedical subjects
P S Parfrey
Publications and source records attributed to P S Parfrey.
Autosomal dominant polycystic kidney disease: new information for genetic counselling.
We evaluated the accuracy of ultrasonographic diagnosis of autosomal dominant polycystic kidney disease (ADPKD) and factors influencing its prognosis in members of 17 Newfoundland families originally described in 1984. In 10 families showing genetic linkage between ADPKD and markers for the PKD1 locus, rates of false negative ultrasonographic diagnosis are estimated as 36% below the age of 10 years and 8% or less thereafter, comparable with findings of genetic linkage studies of a subset of family members. At ages above 30 years, false negative ultrasonographic diagnosis of PKD1 disease is unlikely. In 2 families in which ADPKD is not co-inherited with PKD1 markers, only 11% of members aged less than 30 years had kidney cysts. The mean (SE) age of onset of ESRD is 56.3 (1.8) years for persons with the PKD1 form of ADPKD, and 68.7 (1.7) years for affected members of families in which ADPKD is not co-inherited with PKD1 markers (P = 0.01). In the PKD1 families, age of onset of end stage renal disease (ESRD) was unrelated to the sex of the affected individual but was earlier in persons inheriting the disease from their mothers than from their fathers (50.5 vs. 64.8 years, P = 0.004), consistent with an influence of genetic imprinting on disease progression. In females with a PKD1 mutation, onset of ESRD was not influenced by parity. In PKD1 families, resemblance in age of onset of ESRD was apparent; variation was less within than between families (F = 13.0, P less than 0.0001), and risk of false negative ultrasonographic diagnosis appears largely restricted to families in which ESRD occurs relatively late.
Adolescent↗
A comparison of nonionic, low-osmolality radiocontrast agents with ionic, high-osmolality agents during cardiac catheterization.
BACKGROUND: Nonionic, low-osmolality radiocontrast agents are used frequently because they are believed to be safer than ionic, high-osmolality agents, but they are also more expensive. We conducted a randomized trial to compare the incidence of adverse events after the administration of ionic, high-osmolality and of non-ionic, low-osmolality radiocontrast agents during cardiac angiography. METHODS: We compared the need to treat patients for adverse reactions and the frequency and severity of specific hemodynamic, systemic, and symptomatic side effects in two groups of patients randomly assigned to receive either ionic, high-osmolality or nonionic, low-osmolality radiocontrast material, and also in 366 patients who could not be randomized. RESULTS: Treatment for adverse events was required in 213 of 737 patients who received high-osmolality contrast agents (29 percent) but in only 69 of 753 patients who received nonionic agents (9 percent) (95 percent confidence interval for the percent difference, 15.9 to 23.6 percent). Hemodynamic deterioration and symptoms also occurred more often in the high-osmolality group, as did severe or prolonged reactions (2.9 percent, as compared with 0.8 percent in the nonionic group; P = 0.035). The severe reactions were largely confined to patients with severe cardiac disease. Multivariate analysis showed that the presence of severe coronary disease and unstable angina were predictors of clinically important adverse reactions. If all the patients in our randomized trial had been given nonionic contrast material, the incremental cost per procedure would have been $89. CONCLUSIONS: Nonionic, low-osmolality contrast material is better tolerated during cardiac angiography than ionic, high-osmolality contrast material. Since cost constraints may prevent the universal use of nonionic contrast material, its selective use in patients with severe cardiac disease could be considered.
Contrast Media↗
Contrast nephropathy in patients with impaired renal function: high versus low osmolar media.
Prescription of low osmolar contrast to prevent nephrotoxicity in subjects with pre-existing renal impairment is costly and has not been clearly shown to be effective. We entered 249 subjects with a pre-contrast serum creatinine greater than 120 mumol/liter (1.35 mg/dl) having cardiac catheterization or intravenous contrast into a randomized controlled trial comparing high and low osmolar contrast. The outcome assessed was a rise in serum creatinine repeated 48 to 72 hours after contrast. A further 117 patients entered the non-randomized prospective arm of the study. In the randomized study the serum creatinine rose by at least 25% after contrast in 8 of 117 (6.8%) given high and in 5 of 132 (3.8%) given low osmolar contrast (P greater than 0.05, one-tailed 95% confidence interval for the difference 3 to 7.8%). More severe renal failure (greater than 50% increase in serum creatinine) after contrast was uncommon (3.4% with high and 1.5% with low osmolar contrast). A rise in serum creatinine after contrast was significantly associated with the severity of the pre-contrast renal impairment and the presence of diabetes mellitus, but not with type of contrast. Diabetics with a serum creatinine greater than 200 mumol/liter (2.25 mg/dl) pre-contrast had a highest risk of deterioration in renal function after contrast. We conclude that in patients with pre-existing renal impairment the incidence of contrast nephropathy was not significantly different comparing high osmolar and nonionic contrast. The potential benefit of nonionic contrast in moderate renal impairment is likely to be small, but trials in diabetics with severe renal impairment should be undertaken urgently.
Aged↗
Nonionic low-osmolality versus ionic high-osmolality contrast material for intravenous use in patients perceived to be at high risk: randomized trial.
To determine the cost-effectiveness of selective use of nonionic low-osmolality contrast material, the authors randomly assigned 955 patients to receive high-osmolality and 1,158 to receive low-osmolality intravenous contrast material. All patients had one or more of the following perceived risk factors for adverse reactions: prior reaction to contrast material, allergies, asthma, diabetes, cardiac or renal disease, anxiety, severe illness, and age greater than 50 years. The occurrence of any adverse event, need for therapy, or subjective symptoms was assessed in a double-blind fashion. An adverse reaction necessitating the attention of a physician occurred in 3.9% (n = 37) of patients in the high-osmolality and 0.9% (n = 10) of patients in the low-osmolality groups (P less than .000005). Therapy was administered to 1.4% (n = 13) and 0.5% (n = 6), respectively (P = .035). The difference was due to a reduction in urticaria and other mild anaphylactoid reactions. In a multivariate analysis, only prior reactions and allergy were independent risk factors. Selective use of intravenous nonionic contrast material is best justified in those with prior reactions, allergy, or asthma; at least 67% of reactions would be prevented.
Contrast Media↗
Comparison of patients with idiopathic calcium phosphate and calcium oxalate stones.
Our primary objective was to test the hypothesis that a defect in acidification is more common in patients who have idiopathic calcium phosphate kidney stones than in those whose stones are formed mainly of calcium oxalate. Additionally, other risk factors might differ for these 2 stone types. Urine pH was measured serially over 24 hours, and along with ammonium and titratable acid, it was measured before and serially after ingestion of ammonium chloride in 3 groups of subjects: 24 patients with predominantly calcium phosphate stones, 30 patients with calcium oxalate stones, and 15 health non-stone-formers. Twenty-six parameters potentially related to stone formation and acidification were assayed on urines collected over 24 hours, and 15 parameters on blood. The data base was a computerized list of 5900 analyses of stones from patients living in Newfoundland. Patients not known by their physician to have had urinary tract infection, anatomical abnormality, hyperparathyroidism, or renal tubular acidosis were asked to participate in the study. Differences between means were considered significant if p values were less than 0.05 for F by analysis of variance and also less than 0.01 by t-test. In all patients with calcium oxalate stones and all non-stone-formers, urine acidified to pH less than 5.25, but in 8 of the 23 phosphate stone formers who completed the ammonium chloride study urine failed to acidify to pH less than 5.25. As all 8 had normal values for venous pH, total CO2, and chloride, they were considered to have incomplete renal tubular acidosis (IRTA). The 8 phosphate stone formers with IRTA had greater mean values for urine pH on all 9 specimens collected serially over 24 hours (all means greater than 6.2), and after administration of ammonium chloride (p less than 0.01), as well as lower mean values for urine titratable acid excretion (p less than 0.01), both after administration of ammonium chloride and in 24-hour urine samples, compared with the remaining phosphate stone formers whose urine acidified and the oxalate and non-stone-forming control groups. Nearly all the phosphate stone formers had 1 or more risk factors for stone formation, but with frequencies not significantly higher than those found in the oxalate group. Hypercalciuria and hypocitruria were the commonest, but increased oxalate or urate also occurred. Thus, idiopathic calcium phosphate stone formation can be associated with 1 or more of several risk factors, and, with the possible exception of those with IRTA, treatment should be similar to that given to patients with calcium oxalate stones.
Acidosis, Renal Tubular↗
The natural history of myocardial disease in dialysis patients.
Among dialysis patients, only 23% have a normal echocardiogram, about 10% have recurrent or chronic congestive heart failure, and 17% have asymptomatic ischemic heart disease. The predisposing factors for congestive heart failure are dilated cardiomyopathy, hypertrophic hyperkinetic disease, and ischemic heart disease. Dilated cardiomyopathy, a disorder of systolic function, includes among its risk factors age, hyperparathyroidism, and smoking. Hypertrophic disease results in diastolic dysfunction, and its predictors include age, hypertension, aluminum accumulation, anemia, and, perhaps, hyperparathyroidism. Ischemic heart disease is due to the presence of coronary artery disease and also to nonatherosclerotic disease caused by the reduction in coronary vasodilator reserve and altered myocardial oxygen delivery and use. The clinical outcome of congestive heart failure is comparable to that of nonrenal patients with medically refractory heart failure. Left ventricular hypertrophy is an important independent determinant of survival. A subset have hyperkinetic disease with severe hypertrophy and have a bad survival, as low as 43% have a 2-yr survival after the first admission to hospital with cardiac failure. The prognosis for those with dilated cardiomyopathy is less severe but is worse than those with normal echocardiogram. The survival of patients with symptomatic ischemic heart disease was little different from that of patients without symptoms, suggesting that the underlying cardiomyopathies had an adverse impact on survival independent of ischemic disease. Much research needs to be undertaken on the risk factors, natural history, and therapy of the various types of cardiac disease prevalent in dialysis patients.
Cardiomegaly↗
The diagnosis and prognosis of autosomal dominant polycystic kidney disease.
BACKGROUND: Autosomal dominant polycystic kidney disease is usually caused by a mutant gene at the PKD1 locus on the short arm of chromosome 16, but in about 4 percent of families with the disorder it is caused by unknown mutations elsewhere in the genome. The natural course of the disease in both genetic forms is not well characterized. METHODS: We studied 17 families with autosomal dominant polycystic kidney disease to compare presymptomatic diagnosis by ultrasonography with diagnosis by genetic-linkage studies and to relate clinical variation of the disease to whether the PKD1 mutation was implicated. RESULTS: In 10 families the disorder was found to cosegregate with polymorphic DNA markers flanking the PKD1 locus, in 2 families it did not, and in 5 families linkage could not be determined. In the 10 families with the PKD1 mutation, 46 percent of the members less than 30 years old who had a 50 percent risk of inheriting a mutation had renal cysts, as compared with 11 percent of the members of the two families without linkage (P less than 0.001). In the PKD1 families, all 67 diagnoses made by ultrasonography were confirmed by determination of the genotype as inferred from linkage. Forty of 48 members (83 percent) less than 30 years old who inherited the PKD1 mutation had renal cysts. All 27 members 30 years old or older who inherited the mutation had renal cysts, suggesting that the probability of a false negative diagnosis did not exceed 0.13 in this age group (P less than 0.05). The mean (+/- SE) age at the onset of end-stage renal disease among members of the PKD1 families was 56.7 +/- 1.9 years, as compared with 69.4 +/- 1.7 years among members with cysts in the families without linkage (P = 0.0025). Hypertension and renal impairment were less frequent and occurred later in the families without the PKD1 mutation. CONCLUSIONS: At present, in most persons with a 50 percent risk of autosomal dominant polycystic kidney disease, imaging techniques are the only mode of reaching a diagnosis before symptoms appear. In such persons a negative ultrasonographic study during early adult life indicates that the likelihood of inheriting a PKD1 mutation is small. In the few who inherit a non-PKD1 mutation for polycystic kidney disease, renal failure is likely to occur relatively late in life.
Adult↗
Outcome of congestive heart failure, dilated cardiomyopathy, hypertrophic hyperkinetic disease, and ischemic heart disease in dialysis patients.
Congestive heart failure in dialysis patients is associated with dilated cardiomyopathy, hypertrophic hyperkinetic disease and ischemic heart disease. To determine the natural history of these four diseases, 150 dialysis patients were prospectively followed for 3-5 years. The 2-year cumulative survival rate was 33% in those with recurrent or persistent congestive heart failure vs. 80% in dialysis patients without. Survival was significantly worse in patients with an echocardiographic diagnosis of dilated cardiomyopathy compared to patients with normal echo-cardiogram (2-year survival rate 67 vs. 90%). In hypertrophic hyperkinetic disease the 2-year survival rate was 30% after entry into the study, and 43% after first admission with congestive heart failure. Symptomatic ischemic heart disease did not have an adverse impact on mortality when compared to those without ischemic heart disease. We conclude that congestive heart failure in dialysis patients has a bad prognosis. Its associated disorders include dilated cardiomyopathy and hypertrophic hyperkinetic disease, the latter being associated with a high mortality. As the prognosis for patients with overt ischemic heart disease was not different from patients without, it is likely that the underlying cardiomyopathy directly influenced survival.
Cardiomegaly↗
Clinical and psychological correlates of somatic symptoms in patients on dialysis.
Somatic symptoms are common in patients on dialysis. Their causes are largely unknown and their therapy is unsatisfactory. To examine the relationship of psychological and clinical factors to these symptoms, 191 interviews were done in patients on hemo- and peritoneal dialysis. The severity of 8 somatic symptoms (tiredness, sleep disturbance, cramps, pruritus, headache, nausea, dyspnea, joint pain) of importance in dialysis patients was measured using previously validated scales. Indices of affect and quality of life were obtained, as was demographic, clinical and laboratory information. The severity of each symptom was significantly related to the indices of affect and quality of life. Using multiple logistic regression, poor affect score was the strongest correlate of each of the following somatic symptoms, tiredness, pruritus, sleep disturbance and cramps. It was ahead of any clinical or demographic variable and was also significantly correlated with the severity of the other symptoms. Indices of hyperparathyroidism were significantly associated with headache, joint pain, dyspnea and nausea. We conclude that the strongest correlate of common somatic symptoms in dialysis patients is affect disturbance, and that therapy aimed at improving the affect may improve the symptoms.
Affect↗
The clinical course of left ventricular hypertrophy in dialysis patients.
To determine the clinical and echocardiographic outcome of left ventricular hypertrophy a prospective study was undertaken of 104 nondiabetic dialysis patients without dilated cardiomyopathy, who were followed for 3-5 years. 33% of patients had normal echocardiogram, 41% mild and 27% severe hypertrophy (left ventricular wall thickness greater than or equal to 1.4 cm in diastole). In the first 2 groups 16% progressed to severe hypertrophy, 23% were admitted with congestive heart failure after starting dialysis therapy, and 2-year cumulative survivals were 97 and 85%. In the group with severe hypertrophy 88% already had severe hypertrophy on starting dialysis therapy, it was persistent in 87%, 50% were admitted at least once with congestive heart failure, and the 2-year cumulative survival was 53%. 71% of those who died in the severe group died from cardiac or cerebrovascular causes compared to none of those with normal echocardiogram, which accounted for the significantly worse (p = 0.001) survival. We conclude that severe left ventricular hypertrophy occurs frequently in dialysis patients, is often present at the start of end-stage renal disease therapy, is persistent, may predispose to congestive heart failure, and is associated with a high mortality.
Cardiomegaly↗
The cardinal manifestations of Bardet-Biedl syndrome, a form of Laurence-Moon-Biedl syndrome.
To determine the interfamilial and intrafamilial variation in the expression of the Bardet-Biedl syndrome (a form of Laurence-Moon-Biedl syndrome), we looked for the five recognized features of the disorder (retinal dystrophy, obesity, polydactyly, mental retardation, and hypogonadism), plus possible renal manifestations, in some or all of 32 patients with this disorder. All 28 patients examined had severe retinal dystrophy, but only 2 had typical retinitis pigmentosa. Polydactyly was present in 18 of 31 patients, but syndactyly, brachydactyly, or both were present in all. Obesity was present in all but 1 of 25 patients. Only 13 of 32 patients were considered mentally retarded. Scores on verbal subtests of intelligence were usually lower than scores on performance tasks. Seven of eight men had small testes and genitalia, which was not due to hypogonadotropism. All 12 women studied had menstrual irregularities, and 3 had low serum estrogen levels (1 of these had hypogonadotropism, and 2 had primary gonadal failure). The remaining women who were of reproductive age had endocrinologic evidence of reproductive dysfunction. Diabetes mellitus was present in 9 of 20 patients. Renal structural or functional abnormalities were universal (n = 21), and three patients had end-stage renal failure. We conclude that the characteristic features of Bardet-Biedl syndrome are severe retinal dystrophy, dysmorphic extremities, obesity, renal abnormalities, and (in male patients only) hypogenitalism. Mental retardation, polydactyly, and hypogonadism in female patients are not necessarily present.
Female↗
Contrast material-induced renal failure in patients with diabetes mellitus, renal insufficiency, or both. A prospective controlled study.
To determine the risk of nephrotoxicity induced by the infusion of radiographic contrast material, we undertook a prospective study of consecutive patients undergoing radiographic procedures with intravascular contrast material. There were three study groups: patients with diabetes mellitus and normal renal function (n = 85), patients with preexisting renal insufficiency (serum creatinine level, greater than or equal to 150 mumol per liter) without diabetes (n = 101), and patients with both diabetes and renal insufficiency (n = 34). The control group consisted of patients undergoing CT scanning or abdominal imaging procedures without the infusion of contrast material who had diabetes mellitus (n = 59), preexisting renal insufficiency (n = 145), or both (n = 64). Clinically important acute renal failure (defined as an increase of greater than 50 percent in the serum creatinine level) attributable to the contrast material did not occur in nondiabetic patients with preexisting renal insufficiency or in diabetics with normal renal function. The incidence of clinically important contrast-induced renal failure among the diabetic patients with preexisting renal insufficiency was 8.8 percent (95 percent confidence interval, 1.9 to 23.7 percent), as compared with 1.6 percent for the controls. The incidence of acute renal insufficiency, more broadly defined as an increase of greater than 25 percent in the serum creatinine level after the infusion of contrast material, was 11.8 percent among all patients with preexisting renal insufficiency. After the exclusion of patients whose acute renal insufficiency could be attributed to other causes, the incidence was 7.0 percent (95 percent confidence interval, 3.2 to 12.8 percent), as compared with 1.5 percent in the control group. The risk of acute renal insufficiency attributable to the contrast material was therefore 5.5 percent, and the relative risk associated with the infusion of contrast material was 4.7. These rates were similar whether the osmolarity of the contrast material was high or low. We conclude that there is little risk of clinically important nephrotoxicity attributable to contrast material for patients with diabetes and normal renal function or for nondiabetic patients with preexisting renal insufficiency. The risk for those with both diabetes and preexisting renal insufficiency is about 9 percent, which is lower than previously reported.
Clinical Trials as Topic↗
Development of a health questionnaire specific for end-stage renal disease.
To compare the efficacy of various end-stage renal disease (ESRD) therapies valid and reproducible probes which measure well-being and are specific for ESRD are necessary. Four studies were undertaken to provide and test these probes. (1) 107 dialysis and 119 transplant recipients were interviewed to determine the prevalence of 24 physical symptoms. (2) A questionnaire was devised using 2 new indexes (a symptom scale derived from the first study using 12 symptoms and an affect scale comprising 12 emotions) and 6 indexes previously used in other chronic illnesses. Interobserver and intraobserver reproducibility was satisfactory. (3) Construct validity for the questionnaire was shown by interviewing 97 dialysis and 82 transplant patients in whom we hypothesized that physical well-being would be better in transplant patients. After age matching the transplant group was more active, with a higher objective quality of life and fewer physical symptoms than the dialysis group. (4) 63 stable dialysis, 67 stable transplant, 15 dialysis patients successfully transplanted in the intervening year and 5 failed transplanted patients were reinterviewed 1 year later to assess the responsiveness of the questionnaire. In the group who had recently been successfully transplanted both physical, affect and quality of life scores showed a major improvement following transplant. We conclude that this questionnaire is specific for ESRD, examines physical, psychological, and social well-being, is brief, easily administered, reproducible, has construct validity and is responsive to changes in therapy.
Adult↗
The relationship of affect to physical symptoms in renal transplant recipients.
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Adult↗
Sonographic and urographic correlation in Bardet-Biedl syndrome (formerly Laurence-Moon-Biedl syndrome).
To determine the spectrum of urologic disease and the value of ultrasound as a screening mechanism, renal imaging was performed on 23 patients with Bardet-Biedl syndrome. On intravenous urography (IVU), abnormal calices were present in 22 patients, with communicating cortical cysts/diverticula in 17. Ultrasound detected caliceal or cystic changes in 70%. On IVU, 21 patients had fetal-type lobular outlines that were detected on sonography in 95%. Renal structural abnormalities are characteristic of the Bardet-Biedl syndrome, and are still best imaged by urography.
Adolescent↗
Left ventricular hypertrophy in end-stage renal disease.
To determine the prevalence of left ventricular hypertrophy (LVH; left ventricular wall thickness greater than or equal to 1-2 cm in diastole) among end-stage renal disease (ESRD) patients and the most important risk factors that independently relate to LVH, 189 non-diabetic ESRD patients without dilated cardiomyopathy in two centres had echocardiography and full clinical review. 104 of 189 (55%) patients had LVH consisting of 52 of 83 (65%) patients on haemodialysis, 18 of 20 (90%) peritoneal dialysis patients and 34 of 86 (40%) transplanted patients. Using multiple logistic regression, the most important factors which independently related to LVH, in all patients studied, were dialysis as current ESRD treatment (p less than 0.001), followed by age (p = 0.008), hypertension as defined by number of blood pressure medications (p = 0.007), followed by high serum alkaline phosphatase which probably reflects hyperparathyroidism (p = 0.03). In a subset of patients with severe LVH (left ventricular wall thickness greater than or equal to 1.4 cm), a high serum alkaline phosphatase level was the best predictor of LVH (p less than 0.001), followed by high diastolic blood pressure (p = 0.004) and age (p = 0.02). In dialysis patients, the most important variable were age (p = 0.009) and high serum alkaline phosphatase (p = 0.03). In the transplant group, patients with LVH were taking significantly more antihypertensive medications than those without LVH (p = 0.002). This variable was the only predictor of LVH in the transplant group.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Clinical features and severity of nonspecific symptoms in dialysis patients.
Nonspecific symptoms are common in dialysis patients but few methods are available to measure their severity and their response to alteration in dialysis therapy. To determine the clinical features and measure the severity of the most important symptoms in end-stage renal disease (ESRD) patients, 97 dialysis patients were interviewed, 63 of whom were reinterviewed 1 year later. For comparison 82 transplant recipients were also interviewed. The six most important symptoms in dialysis patients (using the product of the patient's perception of severity and prevalence) were tiredness, cramps, pruritus, dyspnea, headaches and joint pain. The symptoms were long-standing, occurred frequently, with little difference in prevalence between hemo- and peritoneal dialysis patients, and were often unrelated to a hemodialysis session. For each symptom, several dimensions of severity were assessed including frequency, duration, effect on sleep, daily living, activity, subjective quality of life and necessity for drug therapy. Often these dimensions did not correlate with patient's perception of severity. For each symptom these items were combined to give an aggregate score with a range 0-10. Interobserver reproducibility for each symptom score was greater than or equal to 0.7 but intraobserver reproducibility was poor for 3 symptoms, because of the fluctuating nature of the symptoms. Construct validity was demonstrated by finding a significantly worse distribution of aggregate scores for tiredness, cramps, pruritus, dyspnea and nausea/vomiting in dialysis compared to transplant patients. Aggregate scores changed little after 1 year's follow-up in stable dialysis patients but significant improvement in the aggregate scores for tiredness, dyspnea and nausea/vomiting were observed in 14 patients after successful transplantation.(ABSTRACT TRUNCATED AT 250 WORDS)
Attitude to Health↗