Loin pain-hematuria syndrome associated with thin glomerular basement membrane disease and hemorrhage into renal tubules

Loin pain-hematuria syndrome associated with thin glomerular basement membrane disease and hemorrhage into renal tubules. Loin painhematuria (LPH) syndrome is a poorly understood disorder in which the patients, mainly young women, experience unexplained severe chronic unilateral or bilateral flank pain associated with gross and/or microscopic hematuria. By contrast, thin glomerular basement membrane (GBM) disease is generally thought to be a benign disorder, affecting males and females equally, in which the major manifestation is asymptomatic microscopic hematuria. Herein we describe seven patients (6 females, 1 male) in whom thin GBM appeared to be the cause of the LPH syndrome. The gross hematuria in these patients could be attributed to thin GBM disease because the renal biopsy demonstrated red cells in renal tubules (indicating glomerular hematuria) and the only glomerular abnormality present was thin GBM. In addition, the other causes of gross hematuria were excluded by appropriate testing. The flank pain in these patients might also have been the result of their thin GBM disease. This is suggested by renal biopsy findings of multiple renal tubules filled with red cells, apparently occluding the tubules. We suggest that occlusion of a relatively small fraction of renal tubules could cause renal pain if back-leak of glomerular filtrate occurred that was of sufficient magnitude to expand renal parenchymal volume and stretch the renal capsule. Preliminary observations suggest that treatment with the angiotensin converting enzyme (ACE) inhibitor enalapril importantly reduces the frequency and severity of the episodes of gross hematuria and flank pain in most patients. ACE inhibition might decrease glomerular hemorrhage in patients with thin GBM by decreasing glomerular hydrostatic pressure. We conclude that (1) Thin GBM disease can be the cause of gross hematuria, apparently as a result of rupture of thin GBM. (2) Rupture of thin GBM resulting in hemorrhage into renal tubules may be the cause of the flank pain and gross hematuria in some patients with the LPH syndrome

Association of thin glomerular basement membrane with other glomerulopathies

Association of thin glomerular basement membrane with other glomerulopathies. In the present study we assessed the prevalence of thin glomerular basement membrane (TGBM) in a large group of native kidney biopsies done for evaluation of renal disease. TGBM was present in 54 of 1078 biopsies (5%). In 12 of 54 biopsies (24%), TGBM was the only abnormality present. In the remaining biopsies TGBM was associated with other pathologic diagnoses. The overall prevalence of TGBM in this series is comparable to previous population studies. TGBM is significantly more common in patients with IgA nephropathy and mesangial proliferative glomerulonephritis. Compared to control patients, individuals with TGBM were more likely to have a history of familial hematuria (14% vs. 43%, P = 0.02). Furthermore, examination of urinary sediments in first degree relatives of patients with TGBM demonstrated microscopic hematuria in 92% of families and, in those families, hematuria was present in 47 ± 6% of relatives. In contrast, hematuria was discovered in 38% of families of control patients, affecting 25 ± 5% of relatives. In conclusion, the presence of TGBM in a kidney biopsy is highly predictable for the presence of familial microscopic hematuria, even in patients in whom TGBM is associated with another glomerulopathy. The present data also indicate that patients with TGBM nephropathy often have concomitant IgA nephropathy and mesangial proliferative glomerulonephritis

Lipopolysaccharide, Tumor Necrosis Factor Alpha, or Interleukin-1β Triggers Reactivation of Latent Cytomegalovirus in Immunocompetent Mice

We have previously shown that cytomegalovirus (CMV) can reactivate in lungs of nonimmunosuppressed patients during critical illness. Our recent work has shown that polymicrobial bacterial sepsis can trigger reactivation of latent murine CMV (MCMV). We hypothesize that MCMV reactivation following bacterial sepsis may be caused by inflammatory mediators. To test this hypothesis, BALB/c mice latently infected with Smith strain MCMV received sublethal intraperitoneal doses of lipopolysaccharide (LPS), tumor necrosis factor alpha (TNF-α), interleukin-1β (IL-1β), or saline. Lung tissue homogenates were evaluated for viral reactivation 3 weeks after mediator injection. Because LPS is known to signal via Toll-like receptor 4 (TLR-4) in mice, further studies blocking this signaling mechanism were performed using monoclonal MTS510. Finally, mice were tested with intravenous TNF-α to determine whether this would cause reactivation. All mice receiving sublethal intraperitoneal doses of LPS, TNF-α, or IL-1β had pulmonary reactivation of latent MCMV 3 weeks following injection, and LPS caused MCMV reactivation with kinetics similar to those for sepsis. When TLR-4 signaling was blocked, exogenous LPS did not reactivate latent MCMV. Intravenous TNF-α administration at near-lethal doses did not reactivate MCMV. Exogenous intraperitoneal LPS, TNF-α, and IL-1β are all capable of reactivating CMV from latency in lungs of previously healthy mice. LPS reactivation of MCMV appears dependent on TLR-4 signaling. Interestingly, intravenous TNF-α did not trigger reactivation, suggesting possible mechanistic differences that are discussed. We conclude that inflammatory disease states besides sepsis may be capable of reactivating CMV from latency

The association of prior cytomegalovirus infection with neovascular age-related macular degeneration

To determine if prior exposure to pathogens associated with vascular disease, cytomegalovirus, Chlamydia pneumoniae, and Helicobacter pylori correlates with neovascular age-related macular degeneration (AMD). An experimental study. Setting Institutional. Bascom Palmer Eye Institute, October 2001 to December 2002. Patient population 150 patients (47 neovascular amd, 36 dry amd, and 67 non-amd controls) were included in the study. exclusion criteria included hiv infection, malignancy, recent acute illness requiring hospitalization within 6 months, or immunosuppressive illness. Procedure Serum samples were obtained for analysis of cytomegalovirus, chlamydia pneumoniae, and helicobacter pylori igg antibody titers by elisa. Main outcome measure Comparison of the distribution of igg titers between patients with wet amd, dry amd, and controls. Results The average cytomegalovirus IgG titer was higher in patients with wet AMD versus controls (p = 0.02, Student t-test, two-tailed) and patients with dry AMD (p = 0.06). Twenty-six (55%) of 47 subjects with wet AMD had high cytomegalovirus IgG titers compared with 14 (39%) of 36 patients with dry AMD (odds ratio [OR] = 2.23, 95% confidence interval [CI] = 0.77 to 6.44) and 23 (34%) of 67 control patients (OR = 2.49, 95% CI = 0.98 to 6.33). There was no major difference in the distribution of titers for Chlamydia pneumoniae IgG and Helicobacter pylori IgG in wet and dry AMD patients. Five of 47 patients with wet AMD (11%) had high antibody titers to all three pathogens, compared with only 1 of 36 patients with dry AMD (3%) (OR = 4.17, 95% CI = 0.46 to 37.36). Conclusions There was a significant association of high cytomegalovirus IgG titer with neovascular AMD compared with dry AMD and control patients. Chronic infection with cytomegalovirus may be a novel risk factor for the progression from dry to neovascular AMD