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T Törnroth

Publications and source records attributed to T Törnroth.

At least 19 recordsLinked to original sources
PubMed2003

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↗
PubMed2002

Henoch-Schoenlein nephritis in adults-clinical features and outcomes in Finnish patients.

BACKGROUND: Henoch-Schoenlein purpura (HSP) is a small vessel vasculitis that often involves the kidneys. It affects many more children than adults. Few studies on HSP nephritis (HSN) in adult patients have been reported. One aim of the study described here was to determine clinical features in adults diagnosed at a single center as suffering from HSN. Other aims were to record outcomes of the disease and factors associated with its progression. METHODS: Between 1980 and 1995, 42 adults attending our clinic were diagnosed consecutively, by means of renal biopsy, as suffering from HSN. Data on 38 patients with a follow-up period of at least a year were subsequently analyzed to determine whether any clinical, laboratory or histopathological variable was associated with the progression of HSN. RESULTS: The mean age of the patients on biopsy was 42.0 years (SD 16.5). Eighteen of the 38 patients were male. Eleven of the 38 patients had isolated hematuria as an indication for renal biopsy and 25 had Ccr > or = 85 ml/min on diagnosis. Eight patients exhibited progression of HSN, 3 to end-stage renal failure (ESRF), during a mean follow-up time of 6.1 years (SD 4.3). Renal survival 10 years after renal biopsy was 91%. No histopathological findings were associated with poor outcome. The only factor statistically significantly related to the progression of HSN was a level of proteinuria greater than 1.0 g/24 h (p < 0.05). Hypertension and level of renal function were not significant prognostic factors either, except in a subgroup of 25 patients with initially normal renal function on diagnosis (p < 0.05 in both). In this subgroup, lower serum albumin levels were also found to be predictive for the progression of HSN. CONCLUSIONS: HSN is rare in adults and outcomes are unpredictable. However, any adult with purpura and persistent urinary abnormalities should undergo renal biopsy to determine a diagnosis: all patients suffering from HSN should be carefully monitored to determine whether the condition progresses. Attention should be paid especially to the degree of proteinuria, and also to hypertension in early stages of the disease.

Adult↗
PubMed2002

Factors associated with progression of IgA nephropathy are related to renal function--a model for estimating risk of progression in mild disease.

BACKGROUND: A number of factors are linked to the outcome of IgA nephropathy (IgAN). However, it has been difficult to compare results of studies since patient populations have varied greatly. There were 3 aims in the study reported here, namely to compare factors associated with renal outcome in IgAN patients with different levels of renal function on diagnosis; to determine factors which were independently associated with progression of renal disease in initially mild IgAN; and to create a model for the estimation of the risk of progression in individual IgAN patients with normal renal function on diagnosis. METHODS: Two hundred and fifty-nine IgAN patients who had been followed on average for 9.1 (SD 4.5) after diagnosis were divided into 2 groups on the basis of renal function on diagnosis. In group 1 (98 patients), Ccr (creatinine clearance, estimated by the Cockcroft-Gault formula) was < 85 ml/min, in group 2 (161 patients) > or = 85 ml/min. Univariate analyses were used to find significant differences between progressors and non-progressors in both groups. Logistic regression analysis was used to determine factors independently associated with progression in group 2. RESULTS: Several factors were found to be associated with outcome in both groups, such as hypertension, level of Ccr, serum cholesterol, proteinuria, and also histopathological changes. Factors associated with progression in patients with initially decreased renal function (group 1), were predictable, such as male sex, absence of episodes of macroscopic hematuria, serum urate level and degree of tubular atrophy. Surprisingly, in patients with initially normal renal function (group 2), numbers of urinary erythrocytes were associated with outcome. The factors independently associated with progression in this group were number of urinary erythrocytes, existence of hypertension and in histopathology arteriolosclerosis and the level of glomerular score. A model for estimating risk of progression on the basis of various combinations of factors found to be independently associated with outcome is presented. CONCLUSIONS: We concluded that association between variable and outcome in IgAN depends partly on renal function at the time of assessment of the factor. Since there are factors which are independently associated with the outcome of early and apparently mild disease, early diagnosis of IgAN is desirable: outcome in mild IgAN can be predicted reliably on the basis of factors found to be independently associated with outcome.

Adrenal Cortex Hormones↗
PubMed2000

Expression of the cytomegalovirus genome in kidney allografts during active and latent infection.

Cytomegalovirus (CMV) infection is suggested to be a risk factor for chronic rejection. Here we investigated whether CMV can persist in renal allografts, and in which structures the viral genome is found during an acute infection and a latent period after an active infection. CMV infection was diagnosed in 72/157 patients by CMV antigenemia tests and by viral cultures. CMV antigens were demonstrated in 38 available biopsies by immunohistochemistry, and CMV genome by DNA hybridization in situ. Standard histology was also performed. CMV antigens were detected in 7/15 biopsies obtained during acute infection, in three with acute rejection, and chronic changes in the other biopsies. CMV genome was located in inflammatory cells, in tubuli and in the capillary endothelium. During a latent period without a positive finding in blood or urine, CMV antigens were still found in 6/31 biopsies. CMV DNA was found in inflammatory cells, tubular and glomerular structures and in the endothelium of the arterioles. During the latent period with persistent CMV in the graft, in most cases (10/12) mild to moderate chronic changes were recorded.

Antigens, Viral↗
PubMed2000

Danish type gelsolin related amyloidosis: 654G-T mutation is associated with a disease pathogenetically and clinically similar to that caused by the 654G-A mutation (familial amyloidosis of the Finnish type).

BACKGROUND: Familial amyloidosis of the Finnish type (FAF, Finnish hereditary amyloidosis) is caused by a 654G-A mutation in the gelsolin gene on chromosome 9 resulting in the expression of mutant Asn-187 gelsolin which is abnormally proteolytically processed generating amyloidogenic fragments that polymerize into amyloid fibrils. We have recently shown that in a Danish and a Czech family with a clinical syndrome similar to FAF, including corneal lattice dystrophy, cranial neuropathy and skin changes, the disease is caused by another mutation at the same position, namely 654G-T predicting a Try-for-Asp substitution at 187 in secreted gelsolin. AIM: To undertake a closer examination of the Danish subtype of FAF and report immunohistochemical and biochemical findings. RESULTS: Immunostaining of plasma gelsolin isolated from heterozygous FAF of the Danish subtype revealed a pattern similar to that found in FAF-Asn 187. The > 60 kDa gelsolin species contain an epitope characteristic of the amyloid forming region as revealed by an amyloid specific antibody, whereas the approximately 50 kDa fragments are devoid of it. Compared with the wild-type gelsolin peptide (Asp-187), the corresponding mutant peptide (Tyr-187) showed dramatically increased fibrillogenicity as revealed by quantitative thioflavine-T based fluorimetry; ultrastructurally, amyloid-like fibrils were formed by the mutant peptide. Immunohistochemistry showed that antibodies directed against residues 231-242 of secreted gelsolin, representing the carboxy terminus of the sequence forming the amyloid protein (residues 173-243) laid down in the tissues in a fibrillar form in FAF, specifically labelled the amyloid deposited in rectum and skin in the Danish (654G-T) subtype. CONCLUSIONS: The 654G-T mutation in the gelsolin gene gives rise to an amyloid disease clinically and pathogenetically similar to that caused by the 654G-A mutation.

Amyloid↗
PubMed1999

Renoprotective effects of captopril in hypertension induced by nitric oxide synthase inhibition in experimental nephritis.

OBJECTIVE: To investigate effects of angiotensin I converting enzyme (ACE) inhibition in experimental nephritis during chronic inhibition of nitric oxide (NO) synthase. METHODS: Rats with and without autoimmune Heymann nephritis were treated with a NO synthase inhibitor L-NAME (50 mg/100 ml) and/or an ACE inhibitor captopril (20 mg/100 ml) in drinking water for 12 weeks. Urinary cGMP excretion was used as an indirect measure of NO activity. Blood pressure, urinary albumin, nitrite and nitrate levels, plasma ANP, and plasma renin activity were measured. Kidneys were examined with light microscopy and immunohistochemical methods. RESULTS: Captopril treatment protected rats receiving L-NAME and none of the captopril-treated rats died. Mortality was greatest in the nephritis-L-NAME (57%) and L-NAME (43%) groups. Captopril normalized cGMP excretion, blood pressure, and prevented partly the appearance of albuminuria. Peritubular infiltration of mononuclear cells was clearly enhanced in the nephritis-L-NAME group (found in 80% of the rats) as compared with the nephritis (20%), L-NAME (40%), and control (0%) groups. The peritubular cell infiltration caused by L-NAME was prevented by captopril treatment. L-NAME-induced hypertension was associated with cardiac hypertrophy and this was prevented by captopril. CONCLUSIONS: NO may play an important renoprotective role in disease progression of chronic membranous glomerulonephritis. Captopril prevents L-NAME-induced hypertension, improves survival, and ameliorates renal damage in this type of nephritis. Dysfunction of renal NO pathways may be an important factor causing progressive renal damage in chronic nephritis. Our results suggest that the dysfunctional renal NO system may be beneficially activated by ACE inhibitors.

Albuminuria↗
PubMed1998

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↗
PubMed1997

Urinary transforming growth factor-beta 1 in membranous glomerulonephritis.

BACKGROUND: Human idiopathic membranous glomerulonephritis (MGN) has a highly variable clinical course and factors determining its outcome are poorly known. Since transforming growth factor-beta 1 (TGF-beta 1) has an essential role in renal fibrogenesis, we studied the possibility to use urinary excretion of TGF-beta 1 in the assessment of progression of the disease in patients with MGN. METHODS: Urinary TGF-beta 1 was determined in 41 patients with MGN, 25 healthy subjects, six non-proteinuric renal transplant patients, 10 patients with IgA glomerulonephritis, and seven proteinuric patients (with non-progressive diseases) using a novel, double antibody enzyme immunoassay. The results were compared with renal morphology and clinical indices of activity of MGN over 12 months. RESULTS: The median urinary TGF-beta 1 excretion (pg/mg creatinine) was significantly higher (1730; range 60-16,970) in MGN patients than in the healthy controls (300; 30-1330; P < 0.0001). In renal allograft recipients the excretion was 840 (250-3440; P < 0.0001 vs healthy controls), in IgA GN it was 1130 (30-4910; P = 0.039), and in proteinuric patients it was 39 (29-165; P = NS). In MGN but not in the proteinuric controls or renal allograft recipients, urinary TGF-beta 1 correlated with urinary albumin excretion (r = 0.86, P < 0.0001) but no correlation with renal function or the duration of the disease was found. Urinary TGF-beta 1 at renal biopsy correlated with interstitial cellular inflammation and its excretion 1 year before the biopsy correlated with indices of sclerosis/fibrosis. Immunosuppressive therapy significantly decreased urinary TGF-beta 1 from 2800 (1610-16,960) to 840 (170-1600) pg/mg creatinine (P = 0.028). Patients with persistent nephrotic syndrome and/or declining renal function had a higher initial TGF-beta 1 excretion (median 3680; 1830-7420 pg/mg creatinine) than those entering partial or complete remission (1060; 60-1960; P = 0.003) within 12 months from sampling.

Adult↗
PubMed1996

Chronic inhibition of nitric oxide synthase in Heymann nephritis.

Effects of nitric oxide (NO) synthase inhibition on blood pressure and on the course of Heymann nephritis was examined in rats. L-NG-nitroarginine-methylester (L-NAME, 10 mg/100 ml in the drinking water for 12 weeks) was used as an inhibitor of NO synthase. Urinary excretion of guanosine 3',5'-cyclic monophosphate (cGMP), a second messenger of NO, was used as an indirect estimate of NO activity. Rats were divided into the following groups: control, nephritis, L-NAME, and nephritis-L-NAME. Urinary cGMP excretion was lower in the nephritis group (p < 0.05) and in the nephritis-L-NAME group (p < 0.005) compared with controls. Plasma atrial natriuretic peptide (ANP) levels were elevated in the nephritis (p < 0.001) and in the nephritis-L-NAME groups (p < 0.05. L-NAME treatment alone did not have any effect on plasma ANP levels. Blood pressure rose progressively in all L-NAME-treated rats. Most marked albuminuria developed in the nephritis-L-NAME group. No differences in the immunohistological findings were observed between the nephritis and the nephritis-L-NAME groups. NO synthase inhibition causes hypertension and aggravates albuminuria in chronic nephritis. Moreover, nephritis itself may decrease then production of cGMP either as a consequence of blunted NO activity or, in addition, because of ANP resistance. It appears that NO synthase inhibition does not change the immunological course of Heymann nephritis but rather the increased hemodynamic load makes the course of nephritis worse.

Albuminuria↗
PubMed1995

Increased renal expression of cytokines and growth factors induced by DOCA-NaCl treatment in Heymann nephritis.

DOCA-NaCl treatment causes hypertension, accelerates development of proteinuria, and leads to glomerulosclerosis in rats with autoimmune Heymann nephritis. To study the mechanisms of kidney injury induced by renal haemodynamic load in chronic nephritis, we studied by immunohistochemistry the local expression of various cytokines, growth factors and adhesion molecules in the kidneys of Heymann nephritic rats with or without DOCA-NaCl-induced hypertension. The DOCA-NaCl-nephritis group developed hypertension and marked renal enlargement as compared with the nephritis group, the DOCA-NaCl group, and the controls. Albuminuria appeared earlier and was heavier in the DOCA-NaCl-nephritis group compared with the nephritic rats without DOCA-NaCl. Expression of IL-6, TNF-alpha, GM-CSF, b-FGF, NGF, TGF-beta, and ICAM-1 was enhanced in the kidneys of the DOCA-NaCl-nephritis group as compared with other groups, localized mainly in the glomerular mesangium (IL-6, GM-CSF, TGF-beta), glomerular and peritubular endothelium (ICAM-1), and collecting ducts (TNF-alpha, b-FGF, NGF, TGF-beta), possibly associated with the observed tubulointerstitial mononuclear cellular infiltration. Thus in autoimmune Heymann nephritis, DOCA-NaCl treatment causes hypertension and increased renal mass together with upregulation of local cytokine and growth factor production, which may further aggravate hypertension and accelerate progression of renal damage.

Animals↗
PubMed1994

Long-term survival in idiopathic membranous glomerulonephritis: can the course be clinically predicted?

72 adult patients with idiopathic membranous glomerulonephritis (iMGN), 92% having proteinuria 3 g/24 h or more, were studied for the clinical evolution of the disease and factors which might be involved in the development of chronic renal insufficiency (CRI). At 10 years, 46% were in complete or partial remission, 4% had the nephrotic syndrome (NS), 26% had some degree of CRI, and 24% were dead or started on dialysis. The actuarial patient and kidney survival rates were 80% and 64%, respectively at 10 years. Patient survival rate was not affected by gender, age (after adjustment for age- and sex-matched population) or the severity of NS at diagnosis. 20 patients showed CRI and apart from the more frequent (p < 0.05) presence of CRI at diagnosis, no clinical features discriminated them from those having intact renal function. Furthermore, no clinical factors at diagnosis predicted the final renal function among the 72 patients. However, it appeared that the evolution of clinical status of iMGN was rapid CRI appearing 1.4 (median, range from 0 to 15.1) years after the diagnosis. At one and two years, renal function correlated significantly (r = 0.54, p < 0.0001 at two years) with the final renal function. What is more, the type of the evolution of proteinuria over the first two years gave valuable information on the eventual deterioration of renal function. Patients having stable non-nephrotic grade proteinuria and those in whom NS disappeared, had excellent renal outcome while those in particular showing an increased severity of NS had poor prognosis in terms of renal survival.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗