Eculizumab in pregnancy: a narrative overview.

Pregnancy can be a dangerous trigger for patients with paroxysmal nocturnal hemoglobinuria (PNH), atypical hemolytic uremic syndrome (aHUS), or hemolysis, elevated liver enzymes and low platelet (HELLP) syndrome. Due to the possibility of several serious complications, pregnancy is somewhat discouraged in the presence of the above diseases. Eculizumab is a humanized antibody that may dramatically change the clinical course of PNH, aHUS and HELLP syndrome. However, data on the safety of eculizumab in pregnancy are scarce. In this narrative overview, we summarize current evidence on the use of eculizumab during pregnancy in women with PNH, aHUS and HELLP syndrome. Eculizumab is not present in breast milk, and the levels observed in umbilical cord blood samples are not sufficient to affect the concentrations of complement in newborns. Therefore, eculizumab may be regarded as safe in pregnancy. Nonetheless, given that data on eculizumab in pregnancy are limited, it is not possible to completely exclude risks for both mother and fetus in treating PNH, aHUS and HELLP syndrome.

Coronary artery calcification in patients with CRF not undergoing dialysis.

BACKGROUND: Coronary artery calcification (CAC) correlates with the extent of coronary atherosclerosis and, consequently, with an increased risk for cardiovascular events. CAC is more frequent in uremic patients than in the general population. Nearly all data about CAC relate to patients on dialysis therapy. This study evaluates the prevalence and extent of CAC in patients with chronic renal failure (CRF) not yet on dialysis therapy. METHODS: Consecutive outpatients with CRF not on dialysis therapy were enrolled and compared with controls (ie, healthy volunteers and patients with essential hypertension with normal renal function). Patients and controls were asymptomatic and had no previous history of myocardial infarction, coronary bypass surgery, or angioplasty. Patients with diabetes were excluded. Clinical characteristics, biochemical test results (included homocysteinemia and C-reactive protein level), and serum concentrations of calcium, phosphorus, and intact parathyroid hormone (iPTH) were evaluated in patients and controls. CACs were searched for and scored by means of spiral computed tomography (CT). To assess the CAC progression rate, spiral CT was repeated in some patients. RESULTS: Eighty-five patients and 55 controls were studied. Patients were aged 52 +/- 13 years and had a CRF duration of 6.3 +/- 5.6 years, glomerular filtration rate of 33.0 +/- 16.0 mL/min (0.55 +/- 0.27 mL/s), serum calcium level of 9.5 +/- 0.5 mg/dL (2.37 +/- 0.12 mmol/L), serum phosphorus level of 4.1 +/- 0.9 mg/dL (1.32 +/- 0.29 mmol/L), and serum iPTH level of 143 +/- 121 pg/mL (ng/L). CAC was found in 40% of patients and 13% of controls; calcification scores were 422 +/- 634 in patients and 43.9 +/- 33 in controls. Only age ( P < 0.001) was a predictor of CAC. In patients with a repeated score performed (after a mean of 7.9 months), calcification scores increased (from 383 +/- 627 to 682 +/- 890) in 8 of 10 patients. CONCLUSION: CAC is already present in the early phase of CRF; the prevalence is greater in patients with CRF than in controls, but less than that reported in dialysis patients. Serum concentrations of calcium, phosphorus, iPTH, and inflammation markers do not predict the appearance or progression of CAC.

Maximal suppression of renin-angiotensin system in nonproliferative glomerulonephritis.

BACKGROUND: Elimination of residual proteinuria is the novel target in renoprotection; nevertheless, whether a greater suppression of renin-angiotensin system (RAS) effectively improves the antiproteinuric response in patients with moderate proteinuria remains ill-defined. METHODS: We evaluated the effects of maximizing RAS suppression on quantitative and qualitative proteinuria in ten patients with stable nonnephrotic proteinuria (2.55 +/- 0.94 g/24 hours) due to primary nonproliferative glomerulonephritis (NPGN), and normal values of creatinine clearance (103 +/- 17 mL/min). The study was divided in three consecutive phases: (1) four subsequent 1-month periods of ramipril at the dose of 2.5, 5.0, 10, and 20 mg/day; (2) 2 months of ramipril 20 mg/day + irbesartan 300 mg/day; and (3) 2 months of irbesartan 300 mg/day alone. RESULTS: Maximizing RAS suppression was not coupled with any major effect on renal function and blood pressure; conversely, a significant decrement in hemoglobin levels, of 0.8 g/dL on average, was observed during up-titration of ramipril dose. The 2.5 mg dose of ramipril significantly decreased proteinuria by 29%. Similar changes were detected after irbesartan alone (-28%). The antiproteinuric effect was not improved either by the higher ramipril doses (-30% after the 20 mg dose) or after combined treatment (-33%). The reduction of proteinuria led to amelioration of the markers of tubular damage, as testified by the significant decrement of alpha 1 microglobulin (alpha 1m) excretion and of the tubular component of proteinuria at sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). CONCLUSION: In nonnephrotic NPGN patients, standard doses of either ramipril or irbesartan lead to significant reduction of residual proteinuria and amelioration of the qualitative features suggestive of tubular damage. The enhancement of RAS suppression up to the maximal degree does not improve the antiproteinuric response and is coupled with a decrement of hemoglobin levels.

Changes of serum albumin and C-reactive protein are related to changes of interleukin-6 release by peripheral blood mononuclear cells in hemodialysis patients treated with different membranes.

Protein malnutrition, a condition associated with an albumin concentration less than 3.5 g/dL, has been shown to be a major risk factor for increased mortality in hemodialysis patients. The aim of this cross-over study was to evaluate the relationship between the type of membrane adopted and serum albumin changes by measuring peripheral blood mononuclear cells (PBMC) interleukin-6 (IL-6) release, serum albumin, and plasma concentrations of C-reactive protein (CRP) in 18 patients dialyzed with different membranes. During the study, all patients were dialyzed with cuprophan (CU), synthetically modified cellulosic (SMC) membrane (a new cellulosic membrane with lesser complement activation), and cellulose diacetate (CD) membrane, and have served as their own controls. IL-6 spontaneous release by PBMC resulted after 3 months of SMC (436.2 +/- 47.4 pg/mL) significantly (P < 0.05) reduced as compared with CU (569.3 +/- 24.5 pg/mL). This effect was more evident after 6 months of dialysis with SMC (220 +/- 35.3 pg/mL, P < 0.01 versus CU and versus 3 months of SMC). The passage to CD membrane was followed by a progressive new increase in the IL-6 PBMC release (332.3 +/- 30.7 after 3 months, and 351.2 +/- 35.8 pg/mL after 6 months, respectively) that, however, remained significantly (P < 0.05) lower than CU. The behavior of CRP plasma levels resembled that of IL-6 PBMC release (23.3 +/- 4.7 in CU, 11.0 +/- 2.1 after 3 months in SMC, and 7.9 +/- 1.5 after 6 months in SMC, respectively). IL-6 release values were positively correlated with circulating levels of CRP (r = 0.3264, P < 0.002). Serum albumin increased after 6 months of dialysis with SMC membranes (3.25 +/- 0.09 g/dL in CU and 3.64 +/- 0.07 g/dL in SMC, P < 0.05). When the patients were switched to CD, serum albumin showed a slight, though not statistically significant, decrease. Serum albumin concentrations negatively correlated with both IL-6 release values (r = -0.247, P < 0.05) and CRP plasma levels (r = -0.433, P < 0.001). In conclusion, our data clearly show that a significant relationship exists between biocompatibility of the membranes and serum albumin changes; serum albumin levels, in fact, are negatively correlated with the PBMC spontaneous IL-6 release values and CRP circulating levels.