Monocyte Chemoattractant Protein 1 is a Prognostic Marker in ANCA-Associated Small Vessel Vasculitis

Background. The (anti neutrophil cytoplasmatic autoantibody ANCA), associated small vessel vasculitides (ASVV) are relapsing-remitting inflammatory disorders, involving various organs, such as the kidneys. (Monocyte chemoattractant protein 1 MCP-1) has been shown to be locally up regulated in glomerulonephritis and recent studies have pointed out MCP-1 as a promising marker of renal inflammation. Here we measure urinary cytokine levels in different phases of disease, exploring the possible prognostic value of MCP-1, together with (interleukin 6 IL-6), (interleukin 8 IL-8) and (immunoglobulin M IgM). Methods. MCP-1, IL-6 and IL-8 were measured using commercially available ELISA kits, whereas IgM in the urine was measured by an in-house ELISA. Results. The MCP-1 levels in urine were significantly higher in patients in stable phase of the disease, compared with healthy controls. Patients in stable phase, with subsequent adverse events; had significantly higher MCP-1 values than patients who did not. MCP-1 and IgM both tended to be higher in patients relapsing within three months, an observation, however, not reaching statistical significance. Urinary levels of IL-6 correlated with relapse tendency, and IL-8 was associated with disease outcome. Conclusions. Patients with ASVV have raised cytokine levels in the urine compared to healthy controls, even during remission. Raised MCP-1 levels are associated with poor prognosis and possibly also with relapse tendency. The association with poor prognosis was stronger for U-MCP-1 than for conventional markers of disease like CRP, BVAS, and ANCA, as well as compared to candidate markers like U-IgM and U-IL-8. We thus consider U-MCP-1 to have promising potential as a prognostic marker in ASVV

Magnetic survey in the process of large-scale construction sites

Archaeogeophysical prospection is necessary when planning large constructions. Motorized magnetometry systems offer an effective method to identify archaeology prior the construction. A sufficiently large area must be surveyed to estimate the archaeological potential correctly

Pliska and Veliki Preslav: non-invasive research into the urban planning of two early medieval centers

Geophysical surveys in Pliska and Veliki Preslav (Bulgaria) brought a breakthrough in our view of the appearance of early medieval centres in the Balkans. Urban planning on a scale of dozens of hectares has been documented for the first time. It has been found that wooden buildings massively accompany masonry architecture. Using a magnetic survey, we have been able to define the road network and functionally specific areas

Endogenous proteins as markers of glomerular function and dysfunction

Plasma and urine concentrations of endogenous proteins are frequently used in the diagnosis of kidney diseases and in studies of glomerular filter function. The main issues addressed in these studies were: storage of urine samples for subsequent protein analysis, use of protein concentrations in urine and in plasma in health and as markers of glomerular diseases, and the application of renal plasma-to-urine clearance of endogenous proteins in estimating the size-selectivity properties of the glomerular capillary wall. Studies of the stability of endogenous proteins in urine stored under different conditions showed certain proteins (immunoglobulin G, protein HC, and a1-antitrypsin) to deteriorate in native urine stored at -20°C, and a1-antitrypsin to be also unstable in native urine kept at room temperature or at 4°C. The addition of the preservative solution employed in these studies was shown to allow reliable measurements to be made of all the proteins investigated, and under all conditions tested, with the exception of a1-antitrypsin in frozen urine. Measurements of urine concentrations of endogenous proteins in healthy adults, using rapid, generally available methods, showed that the same upper reference limits for urinary protein excretion may be used for both genders and regardless of age or the type of urine collection. Moreover, the protein content in normal urine does not correlate to the presence of haematuria or granular casts in urinary sediment. Increased plasma concentrations of acute phase proteins, a1-antitrypsin, haptoglobin and orosomucoid, but not C-reactive protein, were detected in patients with primary chronic glomerulonephritides. The findings imply that, despite the indolent clinical picture, persistent inflammatory processes occur in chronic glomerulonephritides and that, the three first-mentioned acute phase proteins may be used as markers of these diseases. Moreover, the C-reactive protein level may be used to diagnose infections or other inflammatory conditions affecting patients with chronic glomerulonephritides. Urine excretion of glycosaminoglycans was decreased in patients with primary glomerulonephritis or renal amyloidosis. Significant differences in this variable were also observed between various kinds of glomerular diseases, urine concentrations being lower in acute glomerulonephritis compared to the chronic forms of the disease, and in amyloidosis compared to other glomerular diseases. These findings indicate that urinary glycosaminoglycans excretion can not only be used as a marker of glomerulonephritis or renal amyloidosis, but it can also be used in the differential diagnosis of the acute and chronic forms of the former disease, and in screening for amyloidosis in patients with glomerular diseases or with chronic inflammatory diseases, with or without clinical signs of renal involvement. Finally, based on findings in the study of fractional protein clearance in rats with inhibited tubular protein reabsorption, the large pore radius of the glomerular basement mem-brane could be estimated to be 110-115 Å. Thus, the existence of ‘shunt pathways’ in the glomerular basal membrane is open to question

Higher urinary IgM excretion in type 2 diabetic nephropathy compared to type 1 diabetic nephropathy.

BACKGROUND: Proteinuria, due to impairment of the charge- and/or size selectivity of the glomerular capillary wall (GCW) is the earliest clinical evidence of diabetic nephropathy (DN). To study the pathophysiological differences between patients with DN in type 1 diabetes mellitus (type 1 DN) and type 2 diabetes mellitus (type 2 DN), we compared the patterns of urinary proteins of different size and charge in the two entities of diabetic kidney disease. METHODS: Urine concentrations of albumin, IgG2, IgG4 and IgM were assessed in 22 (15 males and 7 females) patients with type 1 DN, and in 20 (18 males and 2 females) patients with type 2 DN. Comparisons with one control group of 13 (12 males and one female) patients with nephrosclerosis due to systemic hypertension and a second control group of 16 (14 males and 2 females) healthy controls were made. RESULTS: The urine excretion of IgG2 and IgM and the ratio of IgG2 to IgG4 (IgG2/IgG4), were significantly higher in type 2 DN compared to type 1 DN (P < 0.01). Patients with type 2 DN and patients with nephrosclerosis had significantly higher urine excretion of IgG and IgM compared to the age-matched healthy subjects (P < 0.001). The IgG2/IgG4 ratio was higher in type 2 DN compared to nephrosclerosis and healthy controls (P < 0.01). CONCLUSION: The increased urine excretion of IgG and IgM that accompanies albuminuria in type 2 DN suggests that the dominant pathophysiological mechanism of proteinuria in type 2 DN might be an alteration of the size selective properties of the glomerular capillary wall, including the occurrence of non-discriminatory "shunt pathways." The charge selective properties of the glomerular capillary wall seem to be intact in type 2 DN, as indicated by the high IgG2/IgG4 ratio. The mechanisms of proteinuria in type 1 DN seem to be merely a consequence of an impaired charge selectivity of the glomerular capillary wall

The response to antihypertensive therapy is dependent on renal structural changes. A 5-year prospective study of renal biopsy in type 2 diabetic patients with micro-macroalbuminuria.

A substantial fraction of patients with diabetes mellitus develop end-stage renal disease. We wanted to study the influence of renal structural changes on the response to treatment of the systemic blood pressure (BP) in type 2 diabetic patients with micro- or macroalbuminuria. METHODS: A 5-year observational prospective study of 40 type 2 diabetic patients. Renal biopsy was performed on the indication micro-macroalbuminuria. Twenty-four-hour ambulatory BP and urine sampling were performed yearly. The goal for treatment was a nightly systolic BP below 140 mmHg. Glomerular filtration rate was examined early with plasma clearance of iohexol. RESULTS: The nightly systolic BP goal <140 mmHg was achieved in 23 of 40 patients. The nightly systolic BP at start of study was correlated to the mean level of nightly systolic BP during the observation period. The glomerular basement membrane (GBM) thickness (BMT) was of prognostic significance for achieving the goal for antihypertensive treatment. Of the 12 patients with BMT below the median of 478 nm, 9 (75%) achieved the goal, while only 5 of 12 (42%) with BMT above 478 nm achieved a nightly systolic BP <140 mmHg. Also, the degree of interstitial fibrosis correlated to the nightly systolic BP. CONCLUSION: A thick basement membrane and the degree of interstitial fibrosis were associated with a lower number of patients achieving the goal of a nightly systolic BP <140 mmHg

Diagnostic and prognostic significance of proteinuria selectivity index in glomerular diseases

The proteinuria selectivity index (SI) describes changes of the glomerular permeability for macromolecules. In the present study, we examine the implications of SI as a diagnostic (199 patients) and a prognostic (49 patients) marker in glomerular diseases. Using SI based on alpha(2)-macroglobulin (alpha(2)-M-SI) or on IgM (IgM-SI) we found that minimal change nephropathy could be discriminated by low SI values and crescentic necrotizing glomerulonephritis by high SI values compared to other diseases. SI based on IgG (IgG-SI) was less useful in determining specific diagnoses. During a follow-up of 46 months creatinine clearance (Cr cl) decreased 36% in a group of patients with high IgG-SI (>0.2) and 38% in a group of patients with high IgM-SI (>1.5(-3)) compared to only 8% in patients with low IgG-SI (</=0.2) or low IgM-SI (</=1.5(-3)). Furthermore, Cr cl decreased more than 30% in 12 (92%) out of thirteen patients with high baseline levels of both IgG-SI and IgM-SI compared to three out of thirteen patients with low baseline values of both the indexes. The decline rate of Cr cl correlated significantly to the SI levels but not to the degree of albuminuria. The findings of the study indicate that urinary excretion of high-molecular-weight proteins, and not of albumin, is a potential prognostic marker in proteinuric glomerulopathies and it may also serve as valuable diagnostic aid in these disorders

Long-term Stability of Albumin, Protein HC, Immunoglobulin G, κ- and λ-chain-immunoreactivity, Orosomucoid and α1-antitrypsin in Urine Stored at -20°C

The stability of albumin, protein HC, immunoglobulin G, κ- and λ-chain immunoreactivity, orosomucoid and α1 -antitrypsin in urine stored at -20°C for up to 24 months was investigated. Significant decreases of the median concentration values for protein HC, IgG and α1-antitrypsin were observed for native urine. Addition to urine of a preservative solution containing benzamidinium chloride, EDTA, tris(hydroxymethyl)-aminomethane and azide prevented the decreases of the concentration values for protein HC and IgG but not for α1-antitrypsin. The median concentration values for albumin, orosomucoid and κ-and λ-chain immunoreactivity did not change significantly upon storage of native urine, nor for urine with the preservative solution