The present study concerned two primary forms of glomerulonephritis, IgA nephropathy (IgAN) and IgM nephropathy (IgMN). The etiology and pathogenesis of both diseases are still unresolved. A traditional manifestation of IgAN is macroscopic hematuria associated with respiratory tract infection. However, in IgAN as also in IgMN the initial symptoms may be only microscopic hematuria or on the other hand nephrotic range proteinuria. Hypertension is particularly common at the time of diagnosis of IgAN and IgMN and becomes even more so during the course of disease. The incidence of terminal renal insufficiency in IgAN or IgMN cannot be strictly determined due to variation in patient populations in different studies. It would seem that in 10-20% of patients end-stage renal disease (ESRD) develops during 10-20 years of follow-up. There are many studies concerning risk factors for progression in IgAN. Certain clinical and histopathological parameters (e.g. high-grade proteinuria, ele! vated serum creatinine, hypertension, glomerulosclerosis or tubulointerstitial changes) are commonly recognized as independently inducing the development of renal insufficiency in IgAN. Recently new risk factors have been reported, for example hyperurichemia, obesity and hyperlipidemia, their role in the pathogenesis of renal damage remaining however obscure. Likewise the importance of active inflammation seen in renal biopsy remains undefined. Previous studies have shed little light on risk factors in IgMN.
Patients with marked renal insufficiency have a clearly elevated risk of vascular diseases (VDs). It appears that minor renal dysfunction also affects metabolic changes which may constitute a risk of develop VDs. However, it is not clear whether patients with some renal disease without renal insufficiency as evaluated by traditional methods carry a higher risk of VDs compared to the general population.
The present study was undertaken to further clarify the clinical picture and prognostic factors in IgAN and in IgMN. Immunological parameters were also under investigation, one focus being on role of newer parameters, especially hyperurichemia, in inducing renal histopathological changes in IgAN. The significance of intrarenal inflammatory cell infiltrations in the natural course of IgAN was established. An assessment of the prevalence and risk factors of VDs in IgAN was one of the main aims.
In the present work 223 IgAN patients and 110 IgMN patients were studied. Almost all IgAN patients were adults, whereas about one third of the original IgMN population was children. A cohort comprising 203 persons ≥30 years of age collected from the same residential area served as a control group representing the general population in studying the prevalence of VDs in IgAN. The mean follow-up time was eight years in IgMN and ten in IgAN. Renal biopsies from were examined by light-microscopy and immunohistochemical methods. Clinical data, such as biochemical parameters, blood pressure measurements and data on VDs were collected. Data on the control group were collected from the Health 2000 Survey organized by the National Public Health Institute of Finland.
Of renal histopathological changes, serum uric acid correlated most strongly with tubulointerstitial changes and blood pressure with vascular changes in IgAN. Also a level of serum triglycerides appeared to be associated with renal morphological changes. Further studies are needed to evaluate the effect of uric acid-lowering therapy on the prognosis of IgAN. Tubulointerstitial inflammation, especially CD3+ T-lymphocyte infiltrations and IL-1β expression, constitutes a poor prognosis in IgAN. In future evaluation the level of intrarenal inflammation may direct prevailing therapy practices.
Vascular diseases are clearly more common in IgAN patients than in the general population. Male gender, hypertension, renal insufficiency, smoking and high serum triglyceride concentration were independently associated with some manifestation of VDs. Progressive renal disease is associated with the development of VDs in IgAN, renal vascular changes signify an elevated risk of VDs in this form of the disease.
The present findings showed renal insufficiency to have developed in about one third and hypertension in half of IgMN patients. Some IgMN patients develop FSGS, which is closely associated with ESRD. IgMN patients with only hematuria (HU) appeared to be mainly female and to have a lower progression rate. Elevation of serum C3 correlated with clinical and histopathological factors in IgMN indicating severe renal disease. Serum C3 was associated with progressive renal disease in IgMN patients.
In conclusion, all significant clinical risk factors for the progression of IgAN correlated with morphological changes in renal tissue. Of these, serum uric acid correlated most strongly with tubulointerstitial changes, which has been proved to be the most potent histopathological risk factor for progression. Inflammation of tubulointerstitial tissue clearly carries a poor prognosis in IgAN. Vascular diseases are more common in IgAN patients than in the general population regardless of renal function, but risk factor profiles for VDs are similar. IgMN is a more severe disease than has previously been suggested. It may be divided into two distinct subgroups with similar renal histology but different sex distribution and clinical outcome. Serum and intrarenal immunoglobulin and complement measurements may be of prognostic significance in IgMN.
