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- Köhler, Jan, et al.
(författare)
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Long-term effects of reflux nephropathy on blood pressure and renal function in adults.
- 2003
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Ingår i: Nephron Clinical Practice. - : S. Karger AG. - 1660-2110. ; 93:1, s. 35-46
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Tidskriftsartikel (refereegranskat)abstract
- <i>Aims:</i> We investigated whether the grade of renal damage assessed by urography in adult patients with vesicoureteral reflux can be used to identify patients at risk of developing hypertension and/or deterioration of renal function. In addition, maternal and fetal outcome of pregnancy was studied. <i>Methods:</i> Vesicoureteral reflux was diagnosed at a median age of 27 years (range 16–60) in 115 patients (98 women). Excluding patients subjected to nephrectomy or heminephrectomy after inclusion (n = 12), 88 patients had renal damage at inclusion urography and a median follow-up time of 16 years. The median follow-up time was 18 years in 15 patients without renal damage. Grading of renal damage was performed and blood pressure, serum creatinine concentration and albuminuria were measured. Hypertension was considered to be present if the systolic blood pressure was ≧140 mm Hg and/or the diastolic blood pressure was ≧90 mm Hg. It was classified as mild (<180 mm Hg systolic and <105 mm Hg diastolic), or moderate to severe (≧180 mm Hg systolic and/or ≧105 mm Hg diastolic). Renal function was classified as stable or deteriorating. <i>Results:</i> There was no significant difference in the frequency of hypertension among those with (52%) or without (33%) renal damage, but moderate to severe hypertension (16 patients) was only seen in patients with renal damage. Median systolic and diastolic blood pressure were higher in patients with than in those without renal damage. Malignant hypertension developed in 4 patients, all had extensive renal damage. Deterioration of renal function occurred in 25 patients, 1 with unilateral and 24 with extensive renal damage (bilateral or in a solitary kidney). This was associated with a high frequency of hypertension (92%) and albuminuria (88%). Sixteen patients developed end-stage renal disease. A total of 242 pregnancies occurred in 89 of the 98 women. Preeclampsia occurred in 16 (18%) women. <i>Conclusion:</i> Hypertension in adult patients with reflux nephropathy occurs with any grade of renal damage, whereas deterioration of renal function was strongly associated with extensive bilateral renal damage or damage in a solitary kidney.
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| 2. |
- Bakoush, Omran, et al.
(författare)
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High proteinuria selectivity index based upon IgM is a strong predictor of poor renal survival in glomerular diseases
- 2001
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Ingår i: Nephrology Dialysis Transplantation. - : Oxford University Press (OUP). - 1460-2385 .- 0931-0509. ; 16:7, s. 1357-1363
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The transport of large proteins across the glomerular capillary wall (GCW) may increase several fold in glomerular diseases. The occurrence of IgM in urine is a consequence of the presence of large defects or shunts in the GCW, whereas albuminuria is probably a result of an altered charge- and size-selectivity of the GCW. In order to examine whether patho-morphological differences influence the renal outcome in proteinuric glomerulopathies, we examined urinary excretion of IgM and albumin as prognostic markers of glomerular disease. METHODS: An observational study over a median of 41 (+/-3) months was conducted in 84 patients with biopsy-verified glomerular disease. The patients were subdivided into groups with low (< or =0.002) and high (>0.002) proteinuria selectivity index based upon IgM (IgM-SI), and into groups with low (< or =200 mg/mmol) and high (>200 mg/mmol) albumin creatinine index (ACI). RESULTS: In the high IgM-SI group, the median creatinine clearance (Ccr) decreased by 26%, and 62% of the patients decreased in Ccr by >5 ml/ min/year during the follow-up time. In comparison, the median Ccr decreased by 8% in the low IgM-SI group (P<0.001) and only 18% of the patients in this group deteriorated by >5 ml/min/year in the Ccr. Eleven (21%) of the 51 patients in the high IgM-SI group developed end-stage renal failure compared with none of the 33 patients in the low IgM-SI group. All the patients that progressed to uraemia had decreased Ccr (<60 ml/min) at entry into the study. However, among all these patients, only those with high IgM-SI, and none with low IgM-SI, developed end stage renal failure. The fall in Ccr did not differ significantly between the patients in high (12%) and low (16%) ACI groups. CONCLUSION: The results of this study indicate that an increased IgM-SI value is a stronger predictor of clinical outcome in proteinuric glomerulopathies than baseline albuminuria. This finding may reflect different patho-histological mechanisms influencing renal survival in glomerular diseases.
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| 3. |
- Bakoush, Omran, et al.
(författare)
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Higher urinary IgM excretion in type 2 diabetic nephropathy compared to type 1 diabetic nephropathy.
- 2002
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Ingår i: Kidney International. - : Elsevier BV. - 1523-1755 .- 0085-2538. ; 61:1, s. 203-208
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 5. |
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| 6. |
- Bakoush, Omran, et al.
(författare)
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Urine excretion of protein HC in proteinuric glomerular diseases correlates to urine IgG but not to albuminuria
- 2001
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Ingår i: Kidney International. - : Elsevier BV. - 1523-1755 .- 0085-2538. ; 60:5, s. 1904-1909
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Proteinuric glomerular diseases often are associated with tubulointerstitial injury, which imposes on the progression of renal failure. Tubular damage is partly referable to toxic effects on the tubular epithelial cells induced by filtered plasma proteins. Patients with nonselective proteinuria, that is, increased urine excretion of high-molecular-weight plasma proteins such as IgG in comparison to albumin, often have poor renal outcome. The present observational study examined correlations between the degree of tubular damage, measured by urine concentration of protein HC, and the levels of urine IgG and albuminuria. METHODS: Measurements of urine concentrations of IgG, albumin, and protein HC were performed in 56 proteinuric patients (33 males and 23 females) with nondiabetic glomerular diseases at the time of the diagnostic renal biopsy and at a mean of 49 follow-up months. RESULTS: A highly significant correlation between the urine IgG excretion and the urine protein HC concentration was found both at the start and at the end of the observational time (r = 0.74 and 0.65, respectively, P < 0.001). Furthermore, alterations in the urinary excretion of the two proteins in single patients correlated significantly to each other (r = 0.84, P < 0.001). The correlation between the degree of albuminuria and the protein HC excretion was significant at the time of kidney biopsy, but ceased to exist during the follow-up time. Stepwise linear regression analysis showed that in comparison with the creatinine clearance and albuminuria, only the changes in urinary IgG excretion were related to the corresponding changes in urinary protein HC excretion (r = 0.84 and r2 = 0.7, P < 0.001). CONCLUSION: The findings of the study suggest that the urinary protein HC concentration correlates to the degree of IgG-uria but not to the degree of albuminuria during the course of proteinuric glomerular disease. Whether this correlation is to be explained by an intrinsic toxic effect on tubular cells executed by IgG or perhaps by some other high molecular weight proteins, needs to be investigated further. However, the results contribute to the understanding of the poor renal survival in patients with glomerular diseases and nonselective proteinuria.
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| 8. |
- Ohlsson, Sophie, et al.
(författare)
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Monocyte chemoattractant protein 1 is a prognostic marker in ANCA-associated small vessel vasculitis.
- 2009
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Ingår i: Mediators of Inflammation. - New York, NY, USA : Hindawi Limited. - 0962-9351 .- 1466-1861. ; 2009:Jul 5
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 9. |
- Tencer, Jan, et al.
(författare)
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Diagnostic and prognostic significance of proteinuria selectivity index in glomerular diseases
- 2000
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Ingår i: Clinica Chimica Acta. - 0009-8981. ; 297:1-2, s. 73-83
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Tidskriftsartikel (refereegranskat)abstract
- 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 (
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| 10. |
- Tencer, Jan
(författare)
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Endogenous proteins as markers of glomerular function and dysfunction
- 1997
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- 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.
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