Echocardiographic evolution of pulmonary artery pressure after acute pulmonary embolism. Results from IPER registry.

AIMS: The aim of the study is to describe the course of the echocardiographically measured pulmonary artery systolic pressure (PAsP) in a series of patients included in the Italian Pulmonary Embolism Registry (IPER). METHODS: Patients with confirmed PE received an echo-Doppler evaluation within 24 hours from hospital admission and after one year. Pulmonary hypertension (PH) was considered "likely" , "possible" or "unlikely" with a right ventricular-right atrial (RV-RA) pressure gradient>45 mm Hg, between 32 and 45 mm Hg and ≤31 mm Hg and no additional echocardiographic variables suggestive of PH, respectively. RESULTS: We studied 286 patients (169 females and 117 males, mean age 67 ± 15; mean follow-up 387 ± 45 days): 240 had a baseline tricuspid regurgitation (TR) and a RV-RA gradient of variable degree. PH was considered likely, unlikely and possible in 97, 93 and 50 patients respectively. At FU echocardiography, 6 patients (2.1%) had a likely PH and all of them were part of the group of 97 patients with a baseline likely PH; 24 patients (8.4%) had a possible PH, and 67% of them had an initial likely PH. No patients with a baseline unlikely PH or without TR developed a follow-up PH (both likely or possible). The probability to show a likely PH at FU echocardiography for patients with a baseline RV-RA gradient>45 mm Hg was 6.2%, while the probability not to have a likely PH for patients with a baseline RV-RA gradient ≤ 45 mm Hg was 100%. CONCLUSION: In our study population of patients with acute PE, we observed that those presenting with a baseline echocardiographic RV-RA pressure gradient ≤ 45 mm Hg were completely free from a likely PH after 1-year.

Anti-C1q autoantibodies in lupus nephritis: prevalence and clinical significance.

Recently, anti-C1q autoantibodies have been proposed as a useful marker in systemic lupus erythematosus (SLE) since their occurrence correlates with renal involvement and, possibly, with nephritic activity. We aimed to evaluate the prevalence of anti-C1q antibodies in patients with SLE, with and without renal involvement, and to correlate these markers' presence and levels with the activity of the disease and nephropathy. We studied 61 patients with SLE, 40 of whom had biopsy-proven lupus nephritis; 35 patients with other connective tissue diseases; and 54 healthy controls. In addition, 18 lupus nephritis patients were followed up during the disease time course. Anti-C1q antibodies were measured using "homemade" ELISA with high salt concentration (1 M sodium chloride). High anti-C1q antibody titers (> 55 AU) were present in 27 of 61 (44%) SLE patients and in 4% and 0% of normal blood donors and pathologic controls, respectively. Anti-C1q antibodies were found in 60% of patients with lupus nephritis compared with only 14% of SLE patients without nephropathy (P < 0.05). Moreover, patients who were positive for anti-C1q antibodies had a higher European Consensus Lupus Activity Measurement (ECLAM) score (4.35 vs. 2.2); 89% of patients with active lupus nephritis showed high titers of anti-C1q antibodies compared with 0% of patients with inactive nephritis. Anti-C1q and anti-dsDNA antibodies agreed in 79% of cases. Our results confirm that anti-C1q antibodies are present in a significant percentage of SLE patients, and that their presence and levels correlate with disease activity-in particular, during renal flare-ups.

Comparison of two iron gluconate treatment modalities in chronic hemodialysis patients: results of a randomized trial.

BACKGROUND: Iron supplementation in chronic hemodialyzed patients is not yet completely defined concerning the dosing regimen. This study aimed to evaluate the effects of the same iron load administered in different regimens on anemia, iron status and the reticulocyte (Ret) subpopulation patterns in stable patients on chronic hemodialysis (HD). PATIENTS AND METHODS: Seventeen patients undergoing thrice-weekly chronic HD and receiving stable alphaerythropoietin therapy with absolute iron deficiency (transferrin saturation (TSAT) <20%, ferritin (Frt) <100 ng/mL) were randomly divided into two groups: group A (n=9) received 20.8 mg of sodium iron gluconate at the end of each dialysis session; group B (n=8) 62.5 mg only at the end of the 1st dialysis session of the week. The treatment period lasted 3 months (period 1) and was followed by 3 months of observation (period 2). RESULTS: Both treatments increased hemoglobin (Hb) levels by an average of 0.90 g/dL in period 1, with a progressive decline in period 2 (p=ns between groups), peaking at 11.2 g/dL in group A and 10.8 g/dL in group B. The effects on mean red blood cell volume and Hb concentrations were similar. Frt levels more than doubled during period 1 and early in period 2 in both groups (172 microg/L in group A; 149 microg/L in group B, and progressively decreased in period 2 (p=ns between groups). The TSAT index increased progressively peaking to 28.7% in group A and 24.3% in group B. Hypochromic red blood cells (hypocRBC) decreased early from 5.6-2.2% in group A, and from 5.5-2.1% in group B, and persisted in period 2; the between-period differences for the combined groups were statistically significant (p=0.0051). High fluorescence reticulocytes (HFR) increased from period 1 to period 2 only in group B (from 0.8-1.7%, p=0.012). CONCLUSIONS: Both regimens replenished iron stores and improved anemia. The HFR increase in group B could be due to soluble transferring receptor (STnfR) gene upregulation; alternatively it could indicate the prevalence of immature Ret release from bone marrow.

Fractional excretion of IgG predicts renal outcome and response to therapy in primary focal segmental glomerulosclerosis: a pilot study.

BACKGROUND: Prolonged treatment with steroids and/or cyclophosphamide improves the prognosis of primary focal segmental glomerulosclerosis (FSGS). In nephrotic patients, no clinical or histological feature predicts responsiveness to therapy. METHODS: In 50 patients with FSGS, fractional excretion (FE) of immunoglobulin G (IgG), albumin, transferrin, and alpha(1)-microglobulin (alpha(1)m) was calculated. The aim of the study is to assess whether FE IgG and FE alpha(1)m: (1) correlate with histological lesions, (2) predict outcome, and (3) may be useful to guide therapy. RESULTS: The association of FE IgG with percentage of glomeruli with segmental sclerosis was at the limit of significance (P = 0.01). FE alpha(1)m was associated with extent of tubulointerstitial damage (P = 0.008). By multiple regression analysis, FE alpha(1)m was dependent on FE IgG (R(2) = 0.76; P = 0.000). The predictive value of proteinuric variables on outcome was evaluated in 29 patients with nephrotic syndrome and baseline normal renal function (serum creatinine level, 1.04 +/- 0.22 mg/dL [92 +/- 19 micromol/L]; follow-up, 50 +/- 33 months); remission rates were 91% and 0% in patients with FE IgG less than versus greater than 0.140 (P = 0.0009). By multiple logistic regression analysis, only FE IgG was associated with remission (P = 0.043). Proteinuria less than versus greater than 7.5 g/d of protein predicted end-stage renal failure (0% versus 36%; P = 0.004); the predictive value of FE IgG less than versus greater than 0.140 was higher (0% versus 71%; P = 0.0000). Patients with FE IgG less than 0.025 were responsive to steroids alone (70%) or steroids and cyclophosphamide (20%); patients with FE IgG greater than 0.025 and less than 0.140 were responsive to steroids alone (20%) or steroids and cyclophosphamide (80%); and 100% of patients with FE IgG greater than 0.140 were unresponsive to therapy (P = 0.000). CONCLUSION: In FSGS, FE IgG is at the limit of statistically significant association with segmental sclerosis, and FE alpha(1)m is associated with extent of tubulointerstitial damage. FE IgG shows the best predictive value for remission, progression, and response to therapy and may be useful to guide treatment. Am J Kidney Dis 41:328-335.

Urinary N-acetyl-beta-glucosaminidase excretion is a marker of tubular cell dysfunction and a predictor of outcome in primary glomerulonephritis.

BACKGROUND: The urinary excretion of N-acetyl-beta-glucosamynidase (NAG) is increased in subjects exposed to substances toxic for renal tubular cells. In experimental and human glomerular diseases, its increased excretion is probably due to the dysfunction of tubular epithelial cells induced by increased traffic of proteins in the tubular lumen. The first aim of this study was to evaluate whether NAG excretion is correlated not only with the amount of proteinuria but also with some proteinuric components which reflect both glomerular capillary wall damage (IgG) and an impairment of tubular reabsorption of microproteins (alpha(1) microglobulin). The second aim was to assess whether NAG excretion has a predictive value on functional outcome and response to therapy. METHODS: In 136 patients with primary glomerulonephritis [74 with idiopathic membranous nephropathy (IMN), 44 with primary focal segmental glomerulosclerosis (FSGS) and 18 with minimal change disease (MCD)] urinary NAG excretion was measured by a colorimetric method and expressed in units per gram of urinary creatinine. RESULTS: Using univariate linear regression analysis NAG excretion in all 136 patients was significantly dependent on IgG excretion, 24-h proteinuria, fractional excretion of alpha(1) microglobulin (FE alpha(1)m) and diagnosis. Using multiple linear regression analysis, NAG excretion was significantly dependent only on IgG excretion and 24-h proteinuria. Limiting the analysis to 67 patients with nephrotic syndrome (NS) and baseline normal renal function, by multiple linear regression, NAG excretion was significantly dependent on IgG excretion (P=0.0004), 24-h proteinuria (P=0.0067) and FE alpha(1)-m (P=0.0032) (R(2)=0.63). In 66 patients with NS and normal baseline renal function (MCD 10 patients; FSGS 20 patients; IMN 36 patients), according to values below or above defined cut-offs (IMN, 18 U/g urinary Cr; FSGS and MCD, 24 U/g urinary Cr), NAG excretion predicted remission in 86 vs 27% of IMN patients (P=0.0002) and 77 vs 14% of FSGS patients (P=0.005). Progression to chronic renal failure (CRF) was 0 vs 47% in IMN patients (P=0.001) and 8 vs 57% in FSGS patients (P=0.03). Using Cox model, in IMN patients only NAG excretion (P=0.01, RR 5.8), but not 24-h proteinuria, predicted progression to CRF. All MCD patients had NAG excretion values below the chosen cut-off, and 90% of them developed remission. Response to immunosuppressive therapy was significantly different in patients with NAG excretion values below or above the cut-offs. CONCLUSION: Urinary NAG excretion can be considered as a reliable marker of the tubulo-toxicity of proteinuria in the early stage of IMN, FSGS and MCD; the excretion values show a significant relationship with 24-h proteinuria, IgG excretion and FE alpha(1)m. Its determination may be a non-invasive, useful test for the early identification of patients who will subsequently develop CRF or clinical remission and responsiveness to therapy.