Pathogenetic aspects of IgA nephropathy.
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Antigen-Antibody Complex↗
Biomedical subjects
J Syrjänen
Publications and source records attributed to J Syrjänen.
Hypertriglyceridaemia and hyperuricaemia are risk factors for progression of IgA nephropathy.
BACKGROUND: The prognosis of IgA nephropathy (IgAN) is variable and about 10-20% of patients progress to end-stage renal disease (ESRD) in 10 years. Hypertension, proteinuria and renal insufficiency at the time of diagnosis are risk factors associated with poor prognosis. Lipid abnormalities may have a role in the progression of glomerulonephritides, and glomerulosclerosis and atherosclerosis may have similar pathophysiological mechanisms. We therefore evaluated factors associated with cardiovascular diseases, especially hypercholesterolaemia, hypertriglyceridaemia, and hyperuricaemia, as predictors of the progression of IgAN. METHODS: A total of 223 patients with IgAN (141 men, 82 women; median age 41 years, range 8-78 years) were studied. The following parameters were recorded at the time of renal biopsy: presence of hypertension or diabetes, smoking habits, body mass index (BMI), serum creatinine, total and HDL-cholesterol, triglycerides, and urate and 24-h urinary protein excretion. The patients were followed up for 0.2-17 years (median 10 years) with respect to progression of renal disease defined as elevation of serum creatinine above 125 micromol/l in men or 105 micromol/l in women, and over 20% elevation from baseline. RESULTS: Forty-one patients (18%) showed progression. Hypertriglyceridaemia and hyperuricaemia were significantly more common at the time of renal biopsy in patients with progressive than in those with stable disease. In patients with normal renal function at the time of diagnosis initial hypertriglyceridaemia, hyperuricaemia, hypertension and proteinuria were independent risk factors for progression of IgAN in the Cox regression hazard model. CONCLUSIONS: Our results show that hypertriglyceridaemia and hyperuricaemia at the time of diagnosis are important, previously underestimated predictors of poor outcome in IgAN, although causality between these factors and progression cannot be inferred from the present study.
Adolescent↗
Angiotensin-converting enzyme insertion/deletion polymorphism and prognosis of IgA nephropathy.
BACKGROUND/AIM: Well-known factors for a poor prognosis in IgA nephropathy (IgAN) are hypertension, proteinuria, and renal insufficiency at the time of diagnosis. Also hypertriglyceridemia and hyperuricemia seem to play a role in the progression of IgAN. Angiotensin-converting enzyme (ACE) gene I/D polymorphism has been associated with cardiovascular diseases and with progression of IgAN. We, therefore, investigated the contribution of ACE gene I/D polymorphism in the prognosis of IgAN and its association with the other risk factors affecting the prognosis. METHODS: A total of 168 patients with IgAN were followed up for 6-17 (median 11) years from renal biopsy with respect to progression of renal disease defined as elevation of serum creatinine above 125 microM (1.4 mg/dl) in men or 105 microM (1.2 mg/dl) in women and over 20% from the baseline level. In addition to serum creatinine, the urinary protein excretion was evaluated at the time of renal biopsy and at the assessment visit at the end of the follow-up period. RESULTS: During the follow-up period, 26 (15%) patients showed progression of renal disease. Patients with ACE genotype II had a more favorable course than those with genotypes ID or DD. Although there were no significant differences among the ACE genotypes with respect to proteinuria > or =1 g/24 h at the time of renal biopsy, proteinuria > or =1 g/24 h was more frequent in patients with genotypes ID or DD than in those with genotype II at the end of the follow-up period. No associations were found between hypertension, serum lipids or serum urate, and ACE genotypes. CONCLUSIONS: Our results show that patients with ACE genotype II have a more favorable prognosis than those with genotypes ID/DD. Secondly, proteinuria (> or =1 g/24 h) found in patients with genotype II at diagnosis may improve, while in patients with genotypes ID/DD it is a more constant feature.
Adolescent↗
Infection as a risk factor for cerebral infarction.
Cerebral infarction is a common complication in severe bacteraemic infections, such as endocarditis and meningitis, but it also occurs in other more common, milder infections. Febrile infections, mostly of the respiratory tract, and of probable bacterial origin, have been found as a risk factor for cerebral infarction. There are many mechanisms that could link a preceding infection to cerebral infarction, including septic emboli, arteritis, activation of the coagulation system and changes in blood rheology.
Adult↗
Thrombo-embolic complications in bacteraemic infections.
Thrombo-embolic complications including stroke and myocardial infarction are common in bacteraemic patients with and without endocarditis: about 20% of patients with infective endocarditis will develop stroke during their disease. Small miliary type myocardial infarctions are found in about 80-90% of autopsied endocarditis patients, but large myocardial infarctions are much more infrequent and acute myocardial infarctions are seldom diagnosed in the lifetime of these patients. About 10% of bacteraemic patients without endocarditis will develop stroke within one month of the onset of bacteraemia, and about 4% of bacteraemic patients will develop myocardial infarction. The risk of cerebral or myocardial infarction is very high in bacteraemic patients compared with the corresponding risk in the general population of the same age, and it has been estimated that about 10% of all strokes are associated with bacteraemic infections. The mechanisms which could cause thrombo-embolic complications in septic patients are numerous, but activation of the coagulation system is probably the most important. Currently, appropriate antimicrobial therapy is the best way to reduce mortality and also probably thrombo-embolic complications in bacteraemic patients who are not routinely using any anticoagulant therapy.
Bacteremia↗
Pneumococcal bacteraemia during a recent decade.
We retrospectively reviewed 159 episodes of bacteraemic pneumococcal infection in 157 adult patients at the Helsinki University Central Hospital during two periods between 1976 and 1979 and 1986 and 1989. We looked especially at changes in underlying diseases and prognostic factors. The overall case fatality rate was 21% and there was a small diminishing trend in that rate from 28% (16/58) in the late 1970s to 17% (17/101) in the late 1980s. The patients who died in the late 1980s were younger than those who died in the earlier period. The most common underlying factors were alcohol abuse, cardiovascular diseases and chronic obstructive pulmonary diseases. Old age was neither a predisposing factor nor did it predict the outcome. No significant changes in underlying diseases or prognostic factors were noted during the two periods studied except a small decrease in connective tissue diseases as underlying conditions. The factors related to increased fatality included hepatic cirrhosis, a combination of pneumonia and meningitis, complications such as shock, respiratory insufficiency, central nervous system disorders and circulatory acidosis, and laboratory findings such as thrombocytopenia, absence of leucocytosis and increased amounts of serum creatinine, aspartate aminotransferase and alanine aminotransferase on admission to the hospital. Previous splenectomy and malignant diseases were not associated with higher mortality. The thrombocytopenia at the time of positive blood culture and the circulatory acidosis as a complication seemed to be independently the most useful predictive factors for a fatal outcome using multivariate logistical regression analysis after adjustment to classic risk factors.
Adolescent↗
Clinical presentation and outcome of listeriosis in patients with and without immunosuppressive therapy.
Seventy-four cases of systemic listeriosis occurring from 1971 to 1989 in the greater Helsinki area in Finland are reviewed with a special interest in the effect of preceding immunosuppressive therapy on the clinical presentation. Of these patients, 66% had an underlying disease, most commonly malignancy, diabetes mellitus, or renal transplantation, and 43% had received immunosuppressive therapy within 1 week before onset of listeriosis. Bacteremia and central nervous system infections (both in 43% of cases) were the most common clinical entities. The percentage of patients with meningitis was not greater among immunosuppressed patients (13/32, 41%) than among patients with underlying diseases not treated with immunosuppressive agents (9/16, 56%) or among previously healthy nonpregnant hosts (7/11, 64%). Immunosuppressed patients did not die more frequently than did those with underlying diseases not treated with immunosuppressive therapy (case fatality rate, 29% vs. 38%, respectively). However, all previously healthy non-neonatal patients survived, whereas 32% (15/47) of those with any kind of underlying disease succumbed.
Adolescent↗
Vascular diseases and oral infections.
Vascular diseases are multifactorial, and several risk factors, such as increasing age, male sex, hypertension, diabetes, dyslipidemias and smoking, are well-known. In recent studies, associations have also been found between preceding infections and development of myocardial or cerebral infarction. Preceding acute respiratory infections are reported to be more common in patients with myocardial or cerebral infarction. Cerebral infarction may follow infective endocarditis, bacterial meningitis or any other bacteremic infection. Oral infections are common chronic bacterial infections. Although oral infections are local, they may lead to systemic infectious complications via stransient bacteremias, and there may also be other systemic effects, for instance, via immunologic or toxic mechanisms. Association between oral infections and vascular diseases has been studied in 2 Finnish case-control studies concerning myocardial and cerebral infarction. In these case-control studies, it was found that oral infections were more common in patients with myocardial or cerebral infarction than in their age- and sex-matched community controls. There are many factors, such as diabetes, smoking and alcohol abuse, which may predispose to both development of infarction and oral infections. Therefore, the observed association between oral infections and vascular diseases may result from these common predisposing factors, and causality between them cannot be inferred. There are, however, several possible links between oral infections and infarction. Although causality between oral infections and infarction cannot be proven, patients who have poor oral health need health education, paying attention to those common risk factors of oral infections and vascular diseases. Furthermore, their oral infections should be treated, because they may predispose to infectious complications, which may lead to infarction.
Bacterial Infections↗
[Oral infections and blood vessel diseases].
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Blood Vessels↗
Dental infections in association with cerebral infarction in young and middle-aged men.
The association between dental infections and cerebral infarction was investigated in a case-control study involving 40 patients with ischaemic cerebral infarction under the age of 50, and 40 randomly selected community controls matched for sex and age. Poor oral health, as assessed by two indices measuring the severity of infections of teeth and periodontium, or by the presence of subgingival calculus or the presence of suppuration in the gingival pockets, were more common in male patients than in male controls, but no difference was observed in females. If severe dental infections were combined with other probable bacterial infections there were altogether 16 patients (40%) but only two controls (5%) who had suffered from a probable bacterial infection within 1 month or at the time of the stroke or when examined as a control (P less than 0.01). Our results suggest an association between bacterial infection and ischaemic cerebrovascular disease in patients under 50 years of age. Severe chronic dental infection seems to be an important type of infection associated with cerebral infarction in males.
Adolescent↗
Acute phase response in cerebral infarction.
The serum concentrations of the acute phase proteins, C-reactive protein, serum amyloid A protein, and alpha-1-antichymotrypsin were determined in 50 young and middle aged patients with cerebral infarction and in sex and age matched community controls. Of 46 case control pairs, 11 cases but only one control had raised acute phase protein concentrations simultaneously (p less than 0.01); four case control pairs were excluded because of an infectious complication following infarction and an acute phase response. Seven of the 11 patients (64%) with raised acute phase protein concentrations had a history of bacterial infection in the preceding month but of the remaining 35 patients without raised concentrations only four (11%) had such a history (p less than 0.01). In general, the acute phase response was less pronounced and occurred less often than has been reported in patients after acute myocardial infarction. The results suggest that a positive acute phase response is associated with a preceding bacterial infection or with an infectious complication after cerebral infarction. Measurement of acute phase proteins, therefore, could be used to evaluate the possible role of preceding bacterial infection in the development of cerebral infarction and also in the management of these patients as an early indicator of possible infectious complications.
Acute-Phase Reaction↗
Central nervous system complications in patients with bacteremia.
The occurrence of central nervous system (CNS) complications was studied retrospectively in 150 patients with bacteremia caused by Staphylococcus aureus, Streptococcus pneumoniae, beta-hemolytic streptococci or Escherichia coli. The incidence and clinical manifestations of different CNS complications were noted during 1 month after the bacteremia. Special attention was paid to vascular complications (infarction or hemorrhage), infections (meningitis or brain abscess) and mental changes when they were the only signs of CNS origin (lowered level of consciousness, confusion or delirium). The risk of cerebral infarction was elevated in the patients with bacteremia during the first month after the positive blood culture as compared with the overall risk of stroke in the general population. 10/150 patients (7%) developed cerebral infarction during that month. Two of these cases were associated with bacterial meningitis and 1 with endocarditis. Mental changes as a main symptom of CNS origin occurred in 27% of patients with bacteremia. Increasing patient age predisposed to this complication. Mental changes were not associated with any bacterial species studied. Altogether 40% of the patients developed CNS complications, which were a significant risk factor for death during the first month after the bacteremia.
Adolescent↗
Preceding infection as an important risk factor for ischaemic brain infarction in young and middle aged patients.
The role of preceding infection as a risk factor for ischaemic stroke was investigated in a case-control study of 54 consecutive patients under 50 years of age with brain infarction and 54 randomly selected controls from the community matched for sex and age. Information about previous illnesses, smoking, consumption of alcohol, and use of drugs was taken. A blood sample was analysed for standard biochemical variables and serum cholesterol, high density lipoprotein cholesterol, triglyceride, and fasting blood glucose concentrations determined. Titres of antimicrobial antibodies against various bacteria, including Staphylococcus, Streptococcus, Yersinia, and Salmonella and several viruses were determined. Febrile infection was found in patients during the month before the brain infarction significantly more often than in controls one month before their examination (19 patients v three controls; estimated relative risk 9.0 (95% confidence interval 2.2 to 80.0)). The most common preceding febrile infection was respiratory infection (80%). Infections preceding brain infarction were mostly of bacterial origin based on cultural, serological, and clinical data. In conditional logistic regression analysis for matched pairs the effect of preceding febrile infection remained significant (estimated relative risk 14.5 (95% confidence interval 1.9 to 112.3)) when tested with triglyceride concentration, hypertension, smoking, and preceding intoxication with alcohol. Although causality cannot be inferred from these data and plausible underlying mechanisms remain undetermined, preceding febrile infection may play an important part in the development of brain infarction in young and middle aged patients.
Adolescent↗
Anticardiolipin response and its association with infections in young and middle-aged patients with cerebral infarction.
Antibodies binding to solid-phase cardiolipin (anticardiolipin antibodies, ACA), which are closely associated with lupus anticoagulant activity, have been found in patients with thrombosis. ACA are often seen also in patients after acute infections. To study further our recent observation on the association between infection and cerebral infarction in young and middle-aged patients we measured anticardiolipin response (IgG, IgM, IgA) in paired sera from 54 consecutive patients with cerebral infarction under 50 years of age and in 54 community controls matched for sex and age. An elevated IgG-class ACA level or a significant change in level as observed in 2 serial samples occurred in 15 (28%) patients, but in only 4 (7%) controls (P less than 0.02). These ACA levels were only slightly elevated, and there were no patients with levels approaching values commonly seen in lupus anticoagulant-positive patients. Neither were there any patients with systemic lupus erythematosus (SLE) as an underlying disease. The combination of IgG-class ACA positivity and preceding probable bacterial infection (based on clinical, cultural or serologic data) was found in 10 patients (18%) but in only 2 controls (4%) (P less than 0.05). There were no significant differences in IgM- or IgA-class ACA between the patients and their controls. These results suggest that IgG-class ACA response associated with preceding probable bacterial infection is more common in patients with cerebral infarction than in their community controls. However, slightly elevated ACA are probably only indirect indicators of preceding infection and not directly involved in the pathogenesis of thrombosis itself.
Adolescent↗
Is there a link between infection and infarction?
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Bacterial Infections↗
Increased bacterial antibody titres and IgA deficiency in epileptic patients.
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Adolescent↗
Association between cerebral infarction and increased serum bacterial antibody levels in young adults.
Increased antibody levels against several bacteria were found in 15 of the 34 stroke patients (44%) under the age of 45 years, but in only six of the 68 controls (9%) (p less than 0.001). Based on the serologic data, the most common preceding infections were streptococcal, staphylococcal, and enterobacterial. There was no relationship between viral antibodies and cerebral infarction. When the clinical history of the patients was also taken into consideration, stroke was found to be associated with a recent infection in 68% of the patients, as compared with 26% for the second most common risk factor, ethanol intoxication. The results suggest an association between cerebral infarction and bacterial infections in young adults.
Adult↗
Three different pathogenic mechanisms for paraparesis in association with bacterial infections.
Three different pathogenic mechanisms are apparent for paraparesis in association with a bacterial infection: a spinal cord compression caused by either an epidural abscess or a vertebral collapse due to spondylitis, an ischaemic spinal cord lesion as a result of septic thromboembolus in abdominal aorta, and a nonspecific, probably immunological, cause in association with reactive polyarthritis. An example of each of these mechanisms is described by means of case histories.
Adult↗