Hope for better treatment in participating clinical drug trials.

An informed consent is a prerequisite for participating in medical trials, whereby the person asked to take part in the trial shall understand what he is committing himself to, and that the consent is given voluntarily. Voluntariness can be undermined by so-called therapeutic optimism, i.e. belief in personal benefit brought about by the trial, as well as the difficulty of understanding how conventional treatment and the trial differ from each other, i.e. the so-called therapeutic misconception. The investigator, especially if he is also the attending physician, may influence the development of therapeutic misconception, because the participant may assume that the physician works as an investigator for the best benefit of the patients. It is important to recognize unrealistic optimism and therapeutic misconception of the trial, because for the participant they may result in disappointment and loss of confidence during the trial.

[Under study or treatment?]. / Tutkimuksessa vai hoidossa?

Persons taking part in a clinical study are patients in the need of treatment. Although the values of the study and the treatment are largely consistent with each other, their goals, methods and ethics differ. Randomized studies in particular involve features that are strange to conventional treatments, such as blinding and placebo medication. Anyone participating in a study should understand that instead of obtaining a health benefit for an individual participant, its primary goal is generalizable knowledge. Any misunderstanding of the therapeutic meaning of the study may lead to disappointment of the participant.

Physicians' Ethics Forum: a Web-based ethics consultation service.

To meet all physicians' needs for ethics consultation in Finland, a novel form of service, the Physicians' Ethics Forum, was founded in 2003. The Forum is a cost-efficient service based on electronic communication. In this paper, experiences throughout its first 6 years are described.

Novel carbonic anhydrase autoantibodies and renal manifestations in patients with primary Sjogren's syndrome.

OBJECTIVE: Anti-carbonic anhydrase II (anti-CA II) antibodies have been related to renal manifestations of primary SS (pSS), and animal studies have even suggested a pathogenic role for them. However, not all pSS patients with renal tubular acidosis (RTA) present with anti-CA II antibodies. Recently, several novel CA isoenzymes have been recognized and we aimed to investigate whether antibodies to these are associated with renal manifestations of pSS. METHODS: We examined anti-CA II antibodies as well as anti-CA I, VI, VII and XIII antibodies by ELISA tests in 74 pSS patients on whom detailed nephrological examinations had been performed and, as controls, in 56 subjects with sicca symptoms, but no pSS. RESULTS: The levels of anti-CA I, II, VI and VII antibodies were significantly higher in patients with pSS compared with subjects with sicca symptoms but no pSS. None of the anti-CA antibodies was associated with the presence of complete or incomplete RTA or proteinuria or urinary α1m excretion in patients with pSS. However, levels of anti-CA II, VI and XIII antibodies correlated significantly with urinary pH, and inversely with serum sodium concentrations. The degree of 24-h urinary protein excretion correlated weakly with levels of anti-CA VII antibodies. CONCLUSION: Not only antibodies to CA II, but also anti-CA VI and XIII antibodies seem to be associated with renal acidification capacity in patients with pSS.

The severity of acute Puumala hantavirus infection does not predict the long-term outcome of patients.

BACKGROUND/AIMS: We have found greater urinary protein excretion and higher glomerular filtration rate (GFR) and blood pressure in patients 6 years after acute nephropathia epidemica (NE) compared with seronegative controls. The present aim was to establish whether the long-term outcome is determined by the severity of acute illness. METHODS: Serial plasma interleukin-6 (IL-6), tumour necrosis factor-α (TNF-α), creatinine, C-reactive protein, blood cell count as well as 24-hour urinary protein and overnight α(1)-microglobulin and albumin excretions were measured in 37 patients with acute NE. Human leucocyte antigen (HLA)-B, HLA-DRB1, TNF-α(-308) and IL-6(-174) alleles were also analyzed. After 6 years, GFR, blood pressure and urinary protein excretion were examined. RESULTS: There were no associations between the clinical severity of acute NE or the genetic factors determined and the increased GFR, hypertension or 24-hour urinary protein excretion observed 6 years later. The degree of inflammation during the acute phase was higher in patients who had increased urinary excretion of α(1)-microglobulin 6 years later compared with those with no α(1)-microglobulin excretion. CONCLUSION: Neither the severity of acute NE nor the host genetic factors determined the predicted renal function, blood pressure or 24-hour urinary protein excretion 6 years later.

Amount of external CME in groups of specialties: a nation-wide survey among Finnish doctors.

BACKGROUND: Continuing medical education (CME) is an integral part of continuing professional development and a prerequisite for good quality in health care. We aimed to describe and analyse the number of days spent in formal CME outside the workplace by specialty among Finnish doctors of working age. FINDINGS: The number of days in formal CME outside the workplace in 2005 reported by specialists was obtained from an annual postal survey, conducted by the Finnish Medical Association in March 2006, of all working-age doctors. Those who had attained their specialist degree before 2005 were included in the study. The 49 specialties were re-categorised into 15 groups. The mean reported number of days and 95% confidence intervals were calculated. Differences were analysed by Poisson regression adjusted for relevant covariates. The response rate to the question about CME was 70.2% (7,374) among specialists. The median age (interquartile range) of the respondents was 49 years (from 44 to 55 years), and 51.7% (3,810) were female. The mean reported number of days in CME was 8.8 (95% CI 8.7-9.0). Neurologists and surgery specialists participated in CME the most frequently (10.3 and 10.4 days) and ophthalmologists the least (7.6 days). In comparison with anaesthesiology and intensive care specialists, most specialists reported having significantly more formal CME, and no group reported having less. CONCLUSIONS: Significant variation was observed, and we therefore suggest studies seeking to account for this variation. The results have originally been published in Finnish in the Finnish Medical Journal.

[Competence in the medical profession: a need for a wider perspective?]. / Lääkärin ammatillisen osaamisen laajentaminen.

Working as a physician requires versatile competence, which has been dissected by using various models. Most of these include medical knowledge, patient work, interactive skills, multiprofessional collaboration, management of operational processes within medical and health care, and information technology skills. Without feedback, the ability of physicians to evaluate their developmental needs is poor, whereby the development of competence should be tied on the basis of needs to on-the-job learning and functionality. Different perspectives should be used in its planning and evaluation. After the evaluation, a development plan should be devised and resources created for its implementation.

IgA immune responses against acetaldehyde adducts and biomarkers of alcohol consumption in patients with IgA glomerulonephritis.

BACKGROUND: The pathogenesis of IgA glomerulonephritis (IgAGN) involves intense deposition of IgAs within the glomerulus. Although previous studies have shown that heavy drinking frequently leads to the generation of IgA antibodies against neo-antigens induced by ethanol metabolites and tissue deposition of IgAs, the associations between alcohol consumption, IgA immune responses, and kidney disease have not been examined. METHODS: A total of 158 IgAGN patients (96 men, 62 women) were classified as abstainers (n = 38), moderate drinkers (n = 114), and heavy drinkers (n = 6) based on self-reported alcohol consumption. The reference population included 143 individuals (99 men, 44 women) who were either apparently healthy abstainers (n = 31), moderate drinkers (n = 43), or heavy drinkers devoid of liver disease (n = 69). The assessments included various biomarkers of alcohol consumption: carbohydrate-deficient transferrin (CDT), glutamyl transferase, gamma-CDT (combination of GGR and CDT), mean corpuscular volume (MCV), tests for liver and kidney function, serum immunoglobulin A (IgA), and specific IgA antibodies against acetaldehyde-protein adducts. RESULTS: In male IgAGN patients, drinking status was significantly associated with MCV, p < 0.001; CDT, p < 0.01; and gamma -CDT, p < 0.05. In the reference population, all biomarkers and anti-adduct IgA levels were found to vary according to drinking status. In IgAGN patients, anti-adduct IgA levels were elevated in 63% of the cases but the titers did not associate with self-reported ethanol intake. CONCLUSIONS: These data indicate high levels of IgA antibodies against acetaldehyde-derived antigens in IgAGN patients, which may hamper the use of the immune responses as markers of alcohol consumption among such patients. Future studies on the pathogenic and prognostic significance of anti-adduct immune responses in IgAGN patients are warranted.

Alcohol consumption and kidney function in IgA glomerulonephritis.

BACKGROUND: IgA glomerulonephritis (IgAGN) is a kidney disease with variable prognosis. Several known risk factors exist for a more progressive course. Some population studies indicate that moderate alcohol consumption might protect kidney function, but the relationship between alcohol intake and IgAGN has not previously been examined. METHODS: We examined 158 (95 men) IgAGN patients (37 abstainers, 80 light drinkers, 25 moderate drinkers and 16 heavy drinkers) in a cross-sectional study. The definition of alcohol consumption was based on interviews on the amounts of alcohol intake combined with measurements of serum carbohydrate-deficient transferrin, a specific biomarker of alcohol abuse. Longitudinal data on renal function were available from 117 patients (76 men) in whom an analysis with respect to progression was also performed. RESULTS: Moderate drinkers showed the best kidney function. When adjusted by hypertension and 24-hour protein excretion, moderate alcohol consumption in a cross-sectional multivariate analysis, and both light and moderate alcohol consumption in a longitudinal multivariate analysis were significant factors of better kidney function. When the study population was divided by gender, the best kidney function was among light drinkers in women and among moderate drinkers in men. CONCLUSIONS: Moderate alcohol consumption might have a favorable impact on the progression of IgAGN. Light alcohol consumption in women and moderate consumption in men are associated with improved indices of the glomerular filtration estimates in patients with IgAGN.

Tubular proteinuria and glomerular filtration 6 years after puumala hantavirus-induced acute interstitial nephritis.

BACKGROUND/AIMS: We previously found increased urinary protein excretion, glomerular filtration rate (GFR) and blood pressure in a retrospective analysis of patients with previous nephropathia epidemica (NE). Here, we evaluated the long-term outcome after NE in a prospectively recruited patient group. METHODS: Proteinuria, GFR and ambulatory 24-hour blood pressure were assessed 4-7 years (mean 6) after acute NE in 37 patients, and these values were compared to those from 38 seronegative controls. RESULTS: Six years after NE, the prevalence of elevated urinary alpha(1)-microglobulin excretion was higher in the patients than controls (9/35 vs. 1/38; p = 0.005). The patients also had higher urinary protein excretion (0.17 +/- 0.05 vs. 0.14 +/- 0.04 g/day; p = 0.006), GFR (119 +/- 19 vs. 109 +/- 14 ml/min/1.73 m(2); p = 0.016) and mean systolic (123 +/- 11 vs. 117 +/- 9 mm Hg; p = 0.012), nighttime systolic (109 +/- 11 vs. 100 +/- 9 mm Hg; p = 0.001) and nighttime diastolic blood pressure (70 +/- 7 vs. 66 +/- 7 mm Hg; p = 0.035) than the controls. CONCLUSIONS: These results confirm our previous findings of a higher prevalence of tubular proteinuria and increased urinary protein excretion, GFR and systolic blood pressure 6 years after acute NE.

Incidence of biopsy-proven glomerulonephritis.

BACKGROUND: The reported biopsy-proven glomerulonephritis incidence varies according to population characteristics, the unknown true glomerulonephritis incidence and biopsy rate. Reported glomerulonephritis incidence should be evaluated against the biopsy rate. METHODS: We report here the glomerulonephritis incidence in our University Hospital (UH) consecutive biopsy material. It is compared to those from surrounding central hospitals (CH), previous single-centre studies and European biopsy registries (EBR). Biopsy rate, when reported, has been considered. RESULTS: The annual biopsy rate/10(5), median (min-max), at the UHs was 25.4 (15.6-35.1). At the CHs it was 8.7 (5.1-12.6). In previous single-centre studies it has been 18.7-21.5. In the EBRs it has been between 1.0 and 6.9 when reported. The annual incidences (median, min-max) per 10(5) (1980-2000) at the UH were as follows: proliferative glomerulonephritis (9.5, 6.8-18.1), non-proliferative glomerulonephritis (6.7, 3.4-12.6), the four major glomerulonephritis groups MesGN (7.7, 4.4-15.9), ECGN/FPGN-complex (1.4, 0.5-3.2), MCGP/FSGS-complex (0.9, 0.2-2.7) and MGN (1.4, 0.5-2.4) these which findings were compatible with the single-centre studies and higher than those of the CHs and in the EBRs. Biopsy rate had a major impact on the annual glomerulonephritis incidences explaining 60% of the variation. The relative frequency of MesGN was the highest by all observers, followed by the ECGN/FPGN-complex, MGN and MCGP/FSGS-complex whose frequencies did not differ much. For every patient commencing renal replacement therapy (Finnish Renal Replacement Registry Data) due to glomerulonephritis there were about 11 subjects with biopsy-proven glomerulonephritis, a relationship compatible with previous reports. CONCLUSIONS: The incidence of any glomerulonephritis of 17.6 per 10(5) population was comparable to those from the single-centre studies, but higher than in European biopsy registries, a fact largely explained by biopsy rates.

Inflammatory markers and the progression of IgA glomerulonephritis.

BACKGROUND: IgA glomerulonephritis (IgAGN) composes a variable prognosis with 15-40% of the patients eventually progressing to end-stage renal failure. Known risk factors for progressive course of IgAGN include hypertension, proteinuria and renal insufficiency. Although markers of inflammation such as serum or urinary interleukin-6 (IL-6) and serum albumin have predicted progression in some studies, sensitive CRP (hs-CRP) has not been directly linked to the progression of IgAGN. METHODS: A total of 174 (70 females) patients were invited for two visits 11 and 16 years (medians) after IgAGN was diagnosed in renal biopsy. All patients had been diagnosed at least 5 years before the first visit. Progressive disease was defined as cystatin-C exceeding normal limits and showing over 20% elevation between the visits, or kidney transplantation or start of dialysis. Cystatin-C and creatinine clearance, serum hs-CRP, s-albumin, s-IL-6 and white blood cell count (WBC) were available for analysis from 118 patients. RESULTS: IgAGN was progressive in 19.5% of the patients on the second visit. Hs-CRP, s-albumin and WBC of the first visit were significantly associated with the progression of IgAGN (P = 0.014; P = 0.0001; P = 0.023, respectively). S-IL-6 was not associated with the progression. All inflammatory variables correlated significantly with the concurrent level of kidney function. Possible study limitations are the relatively low number of outcomes in the study groups, and the lack of generally accepted definitions for disease progression. CONCLUSIONS: Our results suggest that inflammatory markers hs-CRP, s-albumin and WBC are associated with the progression of IgAGN.

Alternative strategies to evaluate the cost-effectiveness of peritoneal dialysis and hemodialysis.

BACKGROUND: Dialysis treatment requires considerable resources and it is important to improve the efficiency of care. METHODS: Files of all adult end-stage renal disease (ESRD) patients who entered dialysis therapy between 1991 and 1996, were studied and all use of health care resources was recorded. A total of 138 patients started with in-center hemodialysis (HD) and 76 patients with continuous ambulatory peritoneal dialysis (CAPD). Four alternative perspectives were applied to assess effectiveness. An additional analysis of 68 matched CAPD-HD pairs with similar characteristics was completed. RESULTS: Cost-effectiveness ratios (CER; cost per life-year gained) were different in alternative observation strategies. If modality changes and cadaveric transplantations were ignored, annual first three years' CERs varied between $41220-61465 on CAPD and $44540-85688 on HD. If CAPD-failure was considered as death, CERs were $34466-81197 on CAPD. When follow-up censored at transplantation but dialysis modality changes were ignored, CERs were $59409-95858 on CAPD and $70042-85546 on HD. If observation censored at any change of primarily selected modality, figures were $57731-66710 on CAPD and $74671-91942 on HD. There was a trend of lower costs and better survival on CAPD, the only exception was the strategy in which technical failure of modality was considered as death. Figures of the matched CAPD-HD pairs were very close to the figures of the entire study population. CONCLUSIONS: Compared to HD, CERs were slightly lower on CAPD.

Implications of levels of serum mineral metabolism markers, albumin and C-reactive protein for treatment costs of patients on maintenance dialysis.

BACKGROUND: Secondary hyperparathyroidism, malnutrition and inflammation have been reported to associate with adverse outcomes in dialysis patients. However, little is known about the implications of these conditions for treatment costs. METHODS: The cost data of all adult patients who had entered dialysis therapy at Tampere University Hospital between 1991 and 1996 and had remained on dialysis for at least 1 year were collected. results of measurements of parathyroid hormone (PTH), calcium, phosphorus, albumin and C-reactive protein (CRP) were obtained from the database of the hospital. RESULTS: Patients (n = 109), aged 57.0 +/- 14.9 years, included 57% men and 37% diabetics; 62% started on hemodialysis and 38% on peritoneal dialysis. Average daily costs were USD 161 (range 95-360). After controlling for patients' age, body mass index, gender, dialysis modality and primary renal disease, there was a positive correlation between average CRP and average costs and a negative correlation between albumin and costs. Correlations between mineral metabolism markers and costs were not found, but there was a trend towards lower cost among patients who achieved the Kidney Disease Outcomes Quality Initiative targets of calcium, phosphorus and PTH (USD 145 +/- 31) compared with those with nonoptimal levels (USD 165 +/- 48; p = 0.095). Costs of patients with at least one in-target PTH measurement were lower than costs of patients with constantly low PTH (USD 148 +/- 31 vs. 170 +/- 48; p = 0.01). CONCLUSION: Serum levels of albumin and CRP correlated with dialysis patients' treatment costs. Achieving the Kidney Disease Outcomes Quality Initiative targets may be associated with lower costs.

Insulin resistance and the progression of IgA glomerulonephritis.

BACKGROUND: IgA glomerulonephritis (IgAGN) has a highly variable prognosis with 15-40% of patients progressing to end-stage renal disease. Hypertension, proteinuria and renal insufficiency are risk factors associated with poor prognosis. The role of insulin resistance is unclear in IgAGN. METHODS: From a retrospective cohort of IgAGN patients, a total of 174 patients (104 males) were invited for two visits at the clinic, 11 and 16 years (median times) after IgAGN was diagnosed in renal biopsy. Of all the patients, 63% had been diagnosed at least 10 years before the first visit. Progressive disease was defined as cystatin-C exceeding normal limits and showing over 20% elevation between the first and second visits, or kidney transplantation or start of dialysis. Plasma insulin, homeostasis model assessment of insulin resistance (HOMA-IR) index and cystatin-C were obtained for analysis from 118 patients. RESULTS: IgAGN was progressive in 19.5% of the patients on the second visit. Insulin level and HOMA-IR of the first visit showed significant association with the progression of IgAGN (P = 0.019 and 0.005, respectively). CONCLUSIONS: Our results show that in addition to the known risk factors age, hypertension, proteinuria and hyperuricaemia, plasma insulin level and calculated HOMA-IR are associated with the progression of IgAGN.

Mortality in patients with rheumatoid arthritis treated with low-dose oral glucocorticoids. A population-based cohort study.

OBJECTIVE: To evaluate mortality and causes of death in patients with rheumatoid arthritis (RA) treated with low-dose oral glucocorticoids. METHODS: Mortality was analyzed in population-based data of 604 patients with RA. In the original study in 1988, state of general health, severity of RA, and treatment including the use of oral glucocorticoids were recorded. In 1999 vital status and causes of death were evaluated. Mortality in patients with RA who had not received glucocorticoids (Group A, n = 209) was compared to that in patients treated with glucocorticoids for less than 10 years (Group B, n = 276) or for more than 10 years (Group C, n = 119). RESULTS: From onset of RA to 1999, 395 (65%) patients had been treated with oral glucocorticoids. In 1999 a total of 160 (26%) patients had died, 23% of patients in Group A, 21% in Group B, and 45% in Group C. In multivariate Cox regression analysis, male sex (hazard ratio 2.50; 95% CI 1.74-3.59), impaired functional capacity by Health Assessment Questionnaire (HR 2.11; 95% CI 1.65-2.96), heart failure (HR 1.96; 95% CI 1.36-2.84), and diabetes (HR 1.87; 95% CI 1.17-3.01) predicted increased mortality. In the same analysis glucocorticoid treatment for 1 year increased the mortality risk by 14% (HR 1.14; 95% CI 0.98-1.27, p = 0.057) and treatment over 10 years by 69% (HR 1.69; 95% CI 1.12-2.56, p = 0.011) compared to RA patients without treatment. The major cause of death was cardiovascular disease in all groups, but infections and intestinal perforations due to amyloidosis were more frequent in patients with long-lasting glucocorticoid therapy. Lymphomas were more frequent in all patients treated with glucocorticoids (Groups B and C) than in those not receiving glucocorticoids. CONCLUSION: Patients with RA treated with low-dose oral glucocorticoids for more than 10 years had increased mortality compared to those who did not receive glucocorticoids or whose duration of treatment was less than 10 years. The increased mortality was related mainly to infections and complications caused by systemic amyloidosis.

Effects of erythropoietin treatment on cell-mediated immune responses in predialysis patients.

OBJECTIVE: The effects of erythropoietin (EPO) treatment on the immune functions of dialysis patients have been shown to be controversial and there are only limited data concerning predialysis patients. MATERIAL AND METHODS: Twenty-four predialysis patients with renal anemia were assigned to subcutaneous EPO treatment, and those in need (n=19) were additionally treated with i.v. iron every other week. We analyzed the effect of the start of EPO treatment on (i) lymphocyte and lymphocyte subclass counts, (ii) lymphocyte stimulation functions and (iii) persisting IgG-class antibody levels to the viral antigens of Epstein-Barr virus and cytomegalovirus. RESULTS: Our main findings were a decrease in the absolute lymphocyte count, combined with decreases in all the main lymphocyte subclass counts. The absolute number of cells with activation and memory markers remained constant, and therefore their proportion slightly increased. The proliferation responses to phytohemagglutinin, tuberculin and tetanus declined significantly, while the amount of IgG-class viral antibodies remained unchanged, meaning that the humoral side of immunity was not affected by the start of the EPO treatment. Similarly, the proliferation response to pokeweed mitogen, a B-cell mitogen, was unchanged. CONCLUSIONS: EPO treatment has a suppressive effect on cellular immune functions of predialysis patients. This suppression does not correlate with erythropoiesis, kidney function or iron status.

Vascular diseases and their risk factors in IgA nephropathy.

BACKGROUND: Many studies have focused on risk factors for renal insufficiency in IgA nephropathy (IgAN). We recently found metabolic factors, especially uric acid, to predict progression and marked histopathological lesions in IgAN. Since vascular diseases (VDs), in addition to renal insufficiency, affect the overall survival of IgAN patients, we studied the occurrence of and risk factors underlying VDs in IgAN. METHODS: In this study, VDs here comprised the presence of coronary heart disease (CHD) and/or cerebrovascular disease (CeVD). We correlated clinical, metabolic and histopathological findings with the occurrence of VDs in 221 adult patients with IgAN. Seven histopathological parameters were semiquantitatively graded. Logistic regression analysis was used to evaluate independent predictors of VDs in these patients. The occurrence of VDs in IgAN patients > or = 30 years of age was studied and compared with that in the general population drawn from the same area. RESULTS: VDs were notably common in IgAN patients. Patients with IgAN had significantly more frequent VDs, CHD and CeVD than the general population (P < 0.01 to < 0.001). Of > or = 30 years of age IgAN patients, 25% had some VD at the end of follow-up, while only 9% of the general population had VDs [odds ratio, OR 4.6 (2.2-9.4)]. Old age, male gender, hypertension, proteinuria, renal insufficiency, hyperuricaemia, hypertriglyceridaemia, diabetes, smoking and high body mass index correlated with the occurrence of VDs in univariate analysis. In all patients initial renal insufficiency and smoking were independently associated with some VD, male gender with CHD and hypertension with CeVD. In the multivariate analysis model including patients with initially normal renal function, male gender was independently associated with some VD, and hypertriglyceridaemia with CHD. CONCLUSION: VDs, especially CeVD, would seem to be particularly common in patients with IgAN. Patients with progressive renal disease run a significantly elevated risk of developing VD. Many previously known risk factors for VD were also associated with the occurrence of some VD in the present study. Vascular changes seen in renal biopsy in patients with IgAN signify an elevated risk of VDs.

High serum C3 predicts poor outcome in IgM nephropathy.

BACKGROUND: IgM nephropathy (IgMN) is an idiopathic glomerulonephritis with mesangial IgM deposition. The etiology of the depositions and possible association of serum and mesangial immunoglobulins and complement findings with renal outcome in IgMN remain unknown. Here we brought out data supplementary to our previous findings by reporting associations of immunological parameters with the outcome of IgMN. METHODS: Serum IgA, IgG, IgM, C3 and C4 were measured in 110 IgMN patients by single radial immunodiffusion or nephelometry. Mesangial IgA, IgG, IgM, C1q and C3 assessed in immunofluorescent study were graded as +/-. Seven histopathological parameters were semiquantitatively graded into three classes. The relationship of serum and mesangial immunoglobulin and complement findings with the clinical outcome and prognosis of IgMN was examined. RESULTS: We found significantly lower serum IgG and higher serum C3 levels in patients with nephrotic syndrome. Serum C3 correlated with the severity of glomerular histopathological changes. Of immunological parameters evaluated a low serum IgG/C3 ratio correlated best with the progression of renal disease. However, serum C3 was associated independently with progression in the case of patients without nephrotic syndrome. CONCLUSIONS: In addition to previously reported factors, immunological parameters may also be helpful in determining the prognosis in IgMN. High serum C3 predicts poor outcome in IgMN, being associated with high-grade proteinuria, severe histopathological changes and progression.