Thrombinuria in glomerulonephritis and its diagnostic accuracy for crescentic glomerulonephritis (CresGN) and its relation to plasma thrombin-antithrombin complex (TAT), urinary TAT, and hemoglobinuria.

<p>(<b>A</b>) Occurrence of urinary thrombin detected (>0.2 U/L) in each group; fractions over the columns indicate the number of samples with thrombin activity per the total number of samples. (<b>B</b>) Thrombin excretion level for each type of glomerulonephritis, as shown by box plots that indicate the median-25th and 75th-median percentiles. Bars with asterisks (*) show only significant differences between two groups. MPGN, membranoproliferative glomerulonephritis; IgAN, IgA nephropathy; non-IgA mesPGN, non-IgA mesangial proliferative glomerulonephritis; AGN, acute glomerulonephritis; MCNS, minimal change glomerulopathy; MN, membranous nephropathy; FSGS, focal segmental glomerulosclerosis; and TIN, tubulointerstitial nephritis. gCr indicates gram of urinary creatinine. (<b>C</b>) The receiver operating characteristic (ROC) curve for diagnosis of CresGN in patients with hematuria and proteinuria. The asterisk indicates the diagnostic accuracy at the cutoff value of 0.6 U/gCr. CI indicates confidence interval. (<b>D</b>) Relation of thrombin excretion to plasma TAT. Circles indicate patients with ANCA-associated CresGN (16 measurements in 9 patients). gCr indicates gram of creatinine. (<b>E</b>) Relation of urinary thrombin to urinary TAT. (<b>F</b>) Relation of urinary thrombin to hemoglobinuria. In (<b>E</b>) and (<b>F</b>), each circle represents an individual patient with glomerulonephritis.</p

Characteristics of the patients.

<p>*The ages of patients with healed CresGN, CresGN, MN, or nephrosclerosis were significantly higher than those of the other groups (<i>P</i><0.01) except for the patients with TIN. The ages of patients with healed CresGN and CresGN were significantly higher than those of patients with with TIN at <i>P</i><0.05. The age of patients with IgAN was significantly lower than that of patients with non-IgA mesPGN, FSGS, or TIN and that of healthy volunteers at <i>P</i><0.01 and was significantly lower than that of patients with MPGN and MCNS at <i>P</i><0.05.</p><p>†Patients with MCNS and MN had significantly heavier proteinuria compared with patients with IgAN, non-IgA mesPGN, AGN, nephrosclerosis, or TIN at <i>P</i><0.01 and patients with MPGN or CresGN at <i>P</i><0.05. Patients with FSGS manifested heavier proteinuria than patients with IgAN at <i>P</i><0.01 and patients with non-IgA mesPGN, nephrosclerosis, or TIN at <i>P</i><0.05. gCr indicates gram of urinary creatinine.</p><p>‡For the estimated glomerular filtration rate (eGFR), patients with CresGN had a significantly lower eGFR than did patients with healed CresGN (<i>P</i><0.05) and the other patients (<i>P</i><0.01) except those with TIN. Patients with TIN had a significantly lower eGFR than did the other groups except patients with CresGN or healed CresGN. Patients with healed CresGN had a significanty lower eGFR than the other patients except those with CresGN, nephrosclerosis, or TIN. Healthy volunteers had significantly higher eGFR values than the other groups except patients with IgAN, non-IgA mesPGN, AGN, MCNS, or MN. Patients with FSGS and MPGN had significantly lower values than did healthy volunteers, and patients with FSGS had a significantly lower value than did patients with IgAN at <i>P</i><0.05.</p><p>§Negative proteinuria results were obtained via the test tape method.</p><p>Characteristics of the patients.</p

Characteristics of patients with crescentic glomerulonephritis.

<p>*Cases from Sendai Shakaihoken Hospital and Kumamoto Chuo Hospital are shown by s and k, respectively.</p><p>†eGFR indicates estimated glomerular filtration rate; gCr, gram of urinary creatinine.</p><p>‡Cases 2 and 7 were associated with rheumatoid arthritis and IgA nephropathy, respectively.</p><p>**Activities less than 0.6 U/gCr were regarded as zero.</p><p>Characteristics of patients with crescentic glomerulonephritis.</p

Glomerular tissue factor expression in biopsy tissues.

<p>(<b>A</b>) Representative tissue factor expression patterns of renal biopsy tissues as shown by immunostaining. All patients, except those with acute glomerulonephritis (AGN), had thrombinuria. (<b>a</b>) Crescentic glomerulonephritis (CresGN); (<b>b</b>) control staining of CresGN with normal mouse IgG; (<b>c</b>) membranoproliferative glomerulonephritis; (<b>d</b>) IgA nephropathy; (<b>e</b>) AGN; (<b>f</b>) minimal change glomerulopathy; (<b>g</b>) focal segmental glomerulosclerosis; and (<b>h</b>) membranous nephropathy. Mφ indicates monocytes/macrophages; Epithelial, epithelial cells; and Mesangium, mesangial areas. The broken line in (<b>a</b>) outlines a cellular crescent. (<b>B</b>) Double-staining pattern of CD68 (macrophages) and tissue factor in the CresGN glomerulus.</p

Thrombinuria and fibrin deposition in glomerular tissues in glomerulonephritis.

<p>*Thr and Fib indicate thrombinuria and fibrin deposition, respectively. Fibrin deposition was determined via immunofluorescence microscopy, and thrombin activities > and below the detection limit (0.2 U/L) were regarded as positive (+) and negative (-) thrombinuria, respectively.</p><p>CresGN indicates crescentic glomerulonephritis; IgAN, IgA nephropathy; Non-IgA mesPGN, non-IgA mesangial proliferative glomerulonephritis; MPGN, membranoproliferative glomerulonephritis; MCNS, minimal change glomerulopathy; FSGS, focal segmental glomerulosclerosis; and MN, membranous glomerulopathy.</p><p>Thrombinuria and fibrin deposition in glomerular tissues in glomerulonephritis.</p

Glucocorticoid effect on thrombinuria and proteinuria and thrombinuria vs. proteinuria or estimated glomerular filtration rate.

<p>(<b>A</b>) Thrombinuria (left panel) and proteinuria and hematuria (right panel) before (pre) and after (post) steroid pulse treatment in 6 patients with crescentic glomerulonephritis (CresGN) (#1 to #6) with thrombinuria. Three days of pulse therapy with intravenous methylprednisolone at 0.5–1 g/day was followed by oral prednisolone at 20–30 mg/day. gCr indicates gram of urinary creatinine. (<b>B</b>) Relation between urinary thrombin and urinary protein levels for various types of glomerulonephritis. Each circle represents an individual patient. (<b>C</b>) Relation between excretion level of thrombin and estimated glomerular filtration rate (eGFR) for various types of glomerulonephritis. Each circle represents an individual patient. IgAN, IgA nephropathy; MPGN, membranoproliferative glomerulonephritis; MCNS, minimal change glomerulopathy; FSGS, focal segmental glomerulosclerosis; and MN, membranous glomerulopathy. In (<b>B</b>) and (<b>C</b>), asterisks (*) and solid lines indicate statistically significant associations and correlation lines, respectively.</p