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- Assink, Karin, et al.
(författare)
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Mutation analysis and clinical implications of von Willebrand factor-cleaving protease deficiency.
- 2003
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Ingår i: Kidney International. - : Elsevier BV. - 1523-1755 .- 0085-2538. ; 63:6, s. 1995-1999
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Tidskriftsartikel (refereegranskat)abstract
- Background. The pentad of thrombocytopenia, hemolytic anemia, mild renal dysfunction, neurologic signs, and fever, classically characterizes the syndrome of thrombotic thrombocytopenic purpura (TTP). TTP usually occurs in adults as an acquired form but a congenital form in children has also been described. In the latter case, the initial presentation is often with neonatal jaundice and thrombocytopenia. The disorder may subsequently take a relapsing course. Deficiency of a recently identified novel metalloprotease, the von Willebrand factor (vWF)-cleaving protease, originating from mutations in the ADAMTS13 gene plays a major role in the development of TTP. Methods. Blood for DNA analysis was collected from six unrelated TTP families, consisting of nine patients from four different countries, and was screened for mutations in the ADAMTS 13 gene. This gene spans 29 exons encompassing ~37 kb. Conventional techniques of DNA extraction, polymerase chain reaction (PCR), and direct cycle sequencing were used. Results. Eight novel ADAMTS 13 mutations are presented. Half of the total number of mutant ADAMTS13 alleles are amino acid substitutions. The disease-causing mutations are spread over the gene. The pathogenicity of the individual mutations is based upon their predicted effect on the ADAMTS13 protein and segregation in family members. Although most of the patients (seven out of nine) had symptoms during the neonatal period, they were in a remarkably good condition. Only one of the nine patients had a decreased glomerular filtration rate (GFR) with proteinuria and hematuria. Another patient had epileptic seizures. Conclusion. We confirm that deficiency of ADAMTS13 is a molecular mechanism responsible for familial TTP. An early diagnosis allows prophylactic treatment with fresh plasma infusions.
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- 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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- 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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- Bergstrom, A, et al.
(författare)
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Birth weight and risk of renal cell cancer
- 2001
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Ingår i: Kidney international. - : Elsevier BV. - 0085-2538 .- 1523-1755. ; 59:3, s. 1110-1113
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Tidskriftsartikel (refereegranskat)
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- Bergström, A., et al.
(författare)
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Birth weight and risk of renal cell cancer
- 2001
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Ingår i: Kidney International. - Malden, USA : Blackwell Publishing. - 0085-2538 .- 1523-1755. ; 59:3, s. 1110-1113
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Tidskriftsartikel (refereegranskat)abstract
- Background: The prenatal period has been suggested to be important for future cancer risk. Conditions in utero are also important for the development of the kidney, and birth weight, a marker of fetal nutrition and growth, is linearly correlated with the number of nephrons and the structural and functional unit of the kidney. An association between birth weight and renal cell cancer, the major form of kidney cancer, is biologically plausible, but has never been studied.Methods: We conducted a population-based, case-controlled study in Sweden of men and women aged 20 to 79 years. We collected self-reported information on categories of birth weight from 648 patients with newly diagnosed renal cell cancer and from 900 frequency-matched control subjects. We used unconditional logistic regression to calculate odds ratios (ORs) and 95% confidence intervals (CIs) as estimates of the relative risks.Results: An increased risk of renal cell cancer was observed among men with a birth weight of > or =3500 g (adjusted OR = 1.3, 95% CI, 1.0 to 1.8) compared with men with a birth weight between 3000 and 3499 g, especially in the subgroup without hypertension or diabetes (adjusted OR = 1.8, 95% CI, 1.2 to 2.6). No clear association among men with a birth weight <3000 g or among women was found.Conclusions: Our study shows that conditions in utero, reflected by birth weight, might affect the risk of renal cell cancer in adulthood. It is unclear why no association was found among women. Further studies, based on weight from birth certificates, are needed to clarify this relationship.
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