Early monitoring of infliximab serum trough levels predicts long-term therapy failure in patients with axial spondyloarthritis.

OBJECTIVE: To evaluate whether serum infliximab trough levels (ITL) during the early stages of treatment are predictive of long-term clinical failure in patients with axial spondyloarthritis (axSpA). METHODS: Longitudinal observational study involving 81 patients with axSpA monitored during infliximab therapy. Serum ITL were measured before starting infliximab treatment and at weeks 2 (W2), W6 and W12 of treatment. Disease activity was assessed by Ankylosing Spondylitis Disease Activity Score (ASDAS) at baseline, W24 and W52, and every 6 months thereafter until treatment discontinuation, regardless of the reason. Non-clinically important improvement was defined by ΔASDAS<1.1. The association between serum levels during the early stages and clinical outcomes (non-clinically important improvement at W52, drug survival and drop-out due to secondary inefficacy) was investigated through logistic regression models and Kaplan Meier curves. Receiver operating characteristic (ROC) curves were employed to determine the best cut-off for serum ITL. RESULTS: Out of the 81 patients, 45 (56%) did not achieve clinical improvement at W52. These patients had lower serum ITL at W12 compared to those who improved: ITL [median (IQR)]: 4.1(0.9-8.3) µg/mL vs 7.1 (4.3-11.3) µg/mL, respectively;p = 0.007). ITL<6.7 µg/mL at W12 was significantly associated with: i) not achieving clinical improvement at W52 (OR: 2.3; 95%CI: 1.3-3.9); ii) shorter drug survival (5.0 years (95% CI 3.8-6.2) vs 7.0 years (95% CI 4.8-6.9; p = 0.04), and iii) higher drop-out rates due to secondary inefficacy (OR: 3.5; 95% CI: 1.2-10.2). CONCLUSION: Low serum ITL at W12 were associated with long-term clinical failure in patients with axSpA, due to secondary inefficacy.

Should Asymptomatic Bacteriuria Be Systematically Treated in Kidney Transplant Recipients? Results From a Randomized Controlled Trial.

The indication for antimicrobial treatment of asymptomatic bacteriuria (AB) after kidney transplantation (KT) remains controversial. Between January 2011 and December 2013, 112 KT recipients that developed one episode or more of AB beyond the second month after transplantation were included in this open-label trial. Participants were randomized (1:1 ratio) to the treatment group (systematic antimicrobial therapy for all episodes of AB occurring ≤24 mo after transplantation [53 patients]) or control group (no antimicrobial therapy [59 patients]). Systematic screening for AB was performed similarly in both groups. The primary outcome was the occurrence of acute pyelonephritis at 24-mo follow-up. Secondary outcomes included lower urinary tract infection, acute rejection, Clostridium difficile infection, colonization or infection by multidrug-resistant bacteria, graft function and all-cause mortality. There were no differences in the primary outcome in the intention-to-treat population (7.5% [4 of 53] in the treatment group vs. 8.4% [5 of 59] in the control group; odds ratio [OR] 0.88, 95% confidence interval [CI] 0.22-3.47) or the per-protocol population (3.8% [1 of 26] in the treatment group vs. 8.0% [4 of 50] in the control group; OR 0.46, 95% CI 0.05-4.34). Moreover, we found no differences in any of the secondary outcomes. In conclusion, systematic screening and treatment of AB beyond the second month after transplantation provided no apparent benefit among KT recipients (NCT02373085).

Mycophenolate as maintenance therapy for lupus nephritis with impaired renal function.

BACKGROUND: Mycophenolate (MF) is effective as a maintenance therapy after induction therapy in patients with lupus nephritis (LN). However, little is known about its role in patients with impaired renal function. The purpose of this study was to evaluate the efficacy and safety of MF as a maintenance therapy for LN and its association with renal function. METHODS: Data were obtained for 56 Spanish patients who were receiving MF as a maintenance therapy for LN. Patients were classified into two groups according to renal function at the initiation of MF treatment: group 1 [estimated glomerular filtration rate (eGFR) ≥60 ml/min/1.73 m(2)] and group 2 (eGFR <60 ml/min/1.73 m(2)). The primary endpoints of the study were the rates of renal relapse and responses, and their relationship with baseline renal function. Secondary outcomes were the appearance of side effects during treatment. RESULTS: At initiation of MF treatment, the only differences between the groups were for age, hemoglobin levels, anti-DNA antibody titer, proteinuria, and renal function. In group 1 (n = 38), the eGFR was 98 ± 34 ml/min/1.73 m(2) and in group 2 (n = 18) the eGFR was 43 ± 14 ml/min/1.73 m(2). Only 3 cases had an eGFR <30 ml/min/1.73 m(2). No significant differences were observed in the rate of relapse at 6 months (group 1: 20%; group 2: 23%) or at 12 months (group 1: 25%; group 2: 17%). Response rates were also similar in both groups. Side effects were unremarkable. CONCLUSIONS: MF is effective and safe as a maintenance therapy for LN both in patients with normal renal function and in those with renal impairment.

Mycophenolate as induction therapy in lupus nephritis with renal function impairment.

BACKGROUND: Mycophenolate (MF) is effective as induction therapy for lupus nephritis (LN) in patients with normal renal function; however, little is known about its role in patients with impaired renal failure. The purpose of this study was to evaluate the response to MF in LN and its association with baseline renal function. METHODS: Data were obtained for 90 patients from 12 Spanish renal units who were receiving MF as induction therapy for LN. Patients were classified into 2 groups: group 1 (estimated glomerular filtration rate [eGFR] ≥60 ml/min/1.73 m(2)) and group 2 (eGFR <60 ml/min/ 1.73 m(2)). The primary outcome measure was the percentage of patients who achieved any response and its relationship with initial eGFR. The secondary outcome measures were the percentage of patients who achieved a complete response (CR) or partial response (PR) and the appearance of relapses during treatment and side effects. RESULTS: At initiation of MF treatment, there were no differences in the main parameters between group 1 (n = 63; eGFR 87 ± 23 ml/min/ 1.73 m(2)) and group 2 (n = 27; eGFR 44 ± 12 ml/min/1.73 m(2)). Exposure to prednisone and MF was similar. The percentages of patients who achieved a response in groups 1 and 2 were, respectively, 69.2 and 43.8% at 6 months and 81.3 and 73.7% at 12 months. CR was more frequent in group 1, whereas PR was similar in both groups. Four patients relapsed and side effects were unremarkable. CONCLUSIONS: MF is effective and safe as induction therapy for LN, and response is even achieved in patients with baseline renal impairment.

Renal transplantation in emigrants from Africa in Spain: similar results but different infectious profile compared with Spanish people.

The number of renal transplantation of emigrants from Africa in Europe is increasing. However, there is little information about the results. The aim of this study was to compare the results of renal transplantation among this African emigrant population compared with a matched group of Spanish patients. From 1996-2006, 27 African emigrants (from Morocco, Guinea, and Nigeria) received renal transplants in Madrid. We compared their results with a matched cohort, including 69% who received a kidney from the same donors to 49 Caucasian Spanish patients. Demographic data were similar except that retransplantation was more frequent (32% vs 0%; P = .02) among Spanish patients and hepatitis B was more frequent among the African group (22% vs 2%; P = .004). For both groups the most frequent regimen was steroids, tacrolimus, and mycophenolate mofetil. Acute rejection incidence was similar (Africans 26% vs Spanish 22%), but rejection as a cause of graft loss was numerically more frequent in Africans (4 of 6). Patient and graft survival rates were identical in both groups (96% and 80%, respectively) at a mean follow-up of 76 months in Africans versus 68 months in Spanish people. Characteristically African patients required higher dose of tacrolimus to maintain the same levels; and notably, they suffered rare opportunistic infections, such as Phonopsis longicolla and visceral Leishmania. In summary, renal transplantation in African emigrant patients in Spain showed excellent results similar to those obtained with a Spanish population. However, these patients needed higher doses of Tacrolimus and experienced more rare opportunistic infections.

[Glomerulopathies associated to HIV infection: a Spanish perspective]. / Glomerulopatías asociadas a la infección por VIH una perspectiva española.

UNLABELLED: HIV nephropathy (HIVAN) is the most frequent cause of chronic renal failure in HIV-infected black patients. However, the prevalence of other glomerulopathies mediated by immunocomplexes has increased in the last years. We report on the glomerular diseases observed in HIV patients in our Hospital. METHODS: A retrospective study of all patients with HIV infection and glomerular diseases diagnosed by renal biopsy. RESULTS: We found 27 patients with the following glomerular diseases: membranoproliferative glomerulonephritis (MPGN) in 8 patients, non-collapsing focal segmental glomerulosclerosis (FSGS) in 7, IgA nephropaty (IgA N) in 6, collapsing glomerulosclerosis in 4 (HIVAN, and membranous nephropaty (MN) in 2. Most of patients were young white men. A high prevalence of coinfection with hepatitis C virus (HCV) (77.8%) and hepatitis B virus (HBV) (37%) was found. At diagnosis, most of patients (90%) had proteinuria, with nephrotic syndrome in 52% of them; 59% presented with acute renal failure. Nine patients (33%) showed malignant hypertension at diagnosis: this complication was particularly common among IgA N patients (4/6, 66%). CONCLUSION: In our Hospital, immunocomplex-mediated glomerulonephritis were more frequent than HIVAN among HIV-infected patients. HCV-associated MPGN was the most frequently detected glomerular disease. A high prevalence of malignant hypertension was observed at diagnosis, particularly among patients with IgAN.

GLP-1(7-36)amide binding in skeletal muscle membranes from streptozotocin diabetic rats.

A higher specific binding of GLP-1(7-36)amide is found in skeletal muscle plasma membranes from adult streptozotocin (STZ)-treated rats (insulin-dependent diabetes mellitus model) and from neonatal STZ-treated rats (non insulin-dependent diabetes mellitus model), as compared to that in normal controls; no apparent change in the affinity was observed, that indicating the presence in both diabetic models of an increased number of high affinity binding sites for the peptide. The maximal specific GLP-1(7-16)amide binding in the non insulin-dependent diabetes mellitus model was found to be significantly higher than that in the insulin-dependent diabetes mellitus model. As GLP-1(7-36)amide exerts a glycogenic effect in the rat skeletal muscle, the present data suggest that the action of the peptide in the muscle glucose metabolism may be increased in states of insulin deficiency accompanied or not by insulin resistance.

Presence of glucagon and glucagon-like peptide-1-(7-36)amide receptors in solubilized membranes of human adipose tissue.

Specific receptors for glucagon and for glucagon-like peptide-1 (GLP-1) (7-36)amide have been found in solubilized human adipose membranes. The 50% inhibition dose of the corresponding unlabeled peptide was near to their physiological levels [ID50, 0.5 nmol/L for glucagon and 1.0 nmol/L for GLP-1(7-36)amide;]. In both cases, the presence of high affinity receptors was evident [Kd, 0.5 and 0.7 nmol/L for glucagon and GLP-1(7-36)amide, respectively]; the high affinity maximal binding capacity for GLP-1(7-36)amide was higher than that for glucagon (893 and 117 fmol/mg solubilized fat membranes, respectively). Glucagon at 10(-6) mol/L did not compete with the [125I]GLP-1(7-36)amide binding, nor did GLP-1(7-36)amide (10(-6) mol/L) compete with that of [125I]glucagon. The relative abundance of GLP-1(7-36)amide receptors in human adipose tissue is further support for a direct and probably important action of this peptide in the metabolism of the fat cell.

Presence and characterization of glucagon-like peptide-1(7-36) amide receptors in solubilized membranes of rat adipose tissue.

Specific binding of [125I]glucagon-like peptide-1(7-36)amide ([125I]GLP-1(7-36)amide) to solubilized rat adipose tissue membranes was found to be dependent on temperature, time, and membrane protein concentration and readily dissociated. GLP-1(1-36)amide, GLP-2, or glucagon (10(-6) M) did not compete with [125I]GLP-1(7-36)amide binding. Half-maximal binding was achieved with 8 x 10(-10) M unlabeled GLP-1(7-36)amide, and the Scatchard plot revealed the presence of high and low affinity binding sites with Kd values of approximately 0.6 and 20 nM, respectively. The binding capacity of [125I]GLP-1(7-36)amide was about 3 times higher than that of [125I]glucagon, while the high affinity Kd and the half-maximal binding of the two peptides were similar. The presence and abundance of GLP-1(7-36)amide receptors in fat tissue together with the previous findings that the peptide stimulates glycerol and cAMP production in rat adipocytes and stimulates fatty acid synthesis in explants of rat adipose tissue open the possibility that this insulinotropic intestinal peptide may also be involved in the regulation of lipid metabolism in health and disease.

Lipolytic action of glucagon-like peptides in isolated rat adipocytes.

The lipolytic effect of GLP-1(1-36)-amide, GLP-1(7-36) amide and GLP-2 [proglucagon(126-159)] has been studied in isolated rat adipocytes. Glycerol release and cyclic AMP content were measured after incubation of adipocytes with GLPs and results have been compared with those obtained in the presence of glucagon. GLP-1(7-36)-amide and GLP-1(1-36)-amide at 10(-8), 10(-7) and 10(-6) M concentrations activated glycerol release, the truncated peptide having a more potent effect. On the other hand, GLP-2 had no effect on glycerol release. Also, it has been found that 10(-6) M GLP-1(7-36)-amide increases cyclic AMP content in adipocytes and does not compete with glucagon binding. These results demonstrate that GLP-1(7-36)-amide has a lipolytic effect on isolated rat adipocytes through different receptors than glucagon.