Heart Rate Variability as Early Biomarker for the Evaluation of Diabetes Mellitus Progress.

According to the American Diabetes Association (ADA), the side effects of diabetes mellitus have recently increased the global health expenditure each year. Of these, the early diagnostic can contribute to the decrease on renal, cardiovascular, and nervous systems complications. However, the diagnostic criteria, which are commonly used, do not suggest the diabetes progress in the patient. In this study, the streptozotocin model in mice (cDM) was used as early diagnostic criterion to reduce the side effects related to the illness. The results showed some clinical signs similarly to five-year diabetes progress without renal injury, neuropathies, and cardiac neuropathy autonomic in the cDM-model. On the other hand, the electrocardiogram was used to determine alterations in heart rate and heart rate variability (HRV), using the Poincaré plot to quantify the HRV decrease in the cDM-model. Additionally, the SD1/SD2 ratio and ventricular arrhythmias showed increase without side effects of diabetes. Therefore, the use of HRV as an early biomarker contributes to evaluating diabetes mellitus complications from the diagnostic.

Influencia de la infección de vías urinarias no complicada en la frecuencia de exacerbaciones en pacientes con nefritis proliferativa difusa lúpica / Influence of non-complicated urinary tract infection on renal relapses in proliferative lupus nephritis

Objetivo: Determinar si la infección de vías urinarias (IVU) es un indicador de retraso en el tratamiento inmunodepresor y de recaída renal en pacientes con nefritis lúpica. Pacientes y metodos: Se analizó a pacientes con nefritis lúpica proliferativa difusa que recibieron tratamiento con ciclofosfamida intravenosa durante, al menos, 6 meses. Al cabo de ese tiempo se realizó un seguimiento prospectivo asignando a los pacientes a uno de 2 grupos: grupo I (pacientes que durante el seguimiento desarrollaron IVU), y grupo II (grupo control, pacientes sin infección). Se evaluaron bimestralmente la función renal y el número de recaídas durante un año de seguimiento. Para el análisis estadístico, se emplearon la prueba de la t de Student, la prueba de la 2 , el test de Fisher (cuando se requiera) y el análisis bivariado. Resultados: Se incluyó a 50 pacientes, 25 en cada grupo. Los casos del grupo I correspondieron a IVU no complicada. La edad promedio fue de 30,07 ± 8,15, y el 82% eran mujeres. El uropatógeno descrito con más frecuencia fue Escherichia coli (73%). La presencia de IVU determinó la interrupción temporal del tratamiento en 19 casos (76%), mientras que en el grupo sin IVU esto ocurrió sólo en 3 pacientes (12%), por otras causas, como leucopenia grave, hipersensibilidad y síntomas gastrointestinales graves (odds ratio = 23,22; intervalo de confianza del 95%, 5,26-105,1; p = 0,001). Durante el año de seguimiento, en el grupo I, el 90,9% alcanzó la remisión parcial en los primeros 3 meses de seguimiento y el 35% logró la remisión completa después de un año; en el grupo II, los porcentajes de remisión fueron del 85 y el 63%, respectivamente. En el grupo I se observó un incremento en la albuminuria (p < 0,05), persistencia de hipocomplementemia y títulos elevados de anticuerpos anti-ADN. En este grupo se encontraron 18 exacerbaciones y en el grupo control, 9. Conclusiones: En pacientes con nefritis lúpica proliferativa difusa, la presencia de IVU no complicada se asocia a un retraso en el tratamiento inmunodepresor y a un incremento en las recaídas renales (AU)

Objective: In patients with proliferative lupus nephritis treated with IV cyclophosphamide, analyze urinary tract infection (UTI) as a cause of treatment delay and renal relapses, compared with lupus nephritis patients without infection. Patients and methods: We studied SLE patients (ACR criteria) with renal biopsy showing nephritis class IV. All patients received monthly intravenous cyclophosphamide (CYC) treatment during 6 months. Thereafter patients were assigned to 2 groups: patients who developed UTI, and those who did not; renal function tests, UTI and renal relapses were bimonthly evaluated during one year (follow-up period). To analyze data, t student test, 2 , Fisher exact (when appropiate), and bivariate analysis, were performed. Results: We studied 50 patients, 25 with UTI (Group I) and 25 without UTI (G-II).The mean age was 30.07 ± 8.15 years, 82% were female. E. coli was the pathogen most frequently isolated (73%). UTI (G-I) was the cause for treatment delay in 19 cases (76%), compared with 3 patients (12%) in G-II whose treatment was delayed because of some other causes (severe leucopenya, hypersensibility and gastrointestinal side effects) (OR 23.22, 95% CI, 5.26-105.1; P=001). During the follow up, 90.9% of patients in G-I reached partial or complete renal remission within 3 months, but only 35% maintained remission after the year of follow up. Meanwhile, patients in G-II had complete and partial renal remission of 85% and 63%, respectively. In the first group we observed persistent albuminuria (P <05), low complement levels and highab-dsDNA titers. Renal flares were present in 18patients in G-I and 9 in G-II. Conclusions: UTI in lupus nephritis patients has a negative impact. It leads to delayed CYC therapy and to a higher renal flare rate (AU)

Influencia de la infección de vías urinarias no complicada en la frecuencia de exacerbaciones en pacientes con nefritis proliferativa difusa lúpica / Influence of non-complicated urinary tract infection on renal relapses in proliferative lupus nephritis

Objetivo: Determinar si la infección de vías urinarias (IVU) es un indicador de retraso en el tratamiento inmunodepresor y de recaída renal en pacientes con nefritis lúpica. Pacientes y métodos: Se analizó a pacientes con nefritis lúpica proliferativa difusa que recibieron tratamiento con ciclofosfamida intravenosa durante, al menos, 6 meses. Al cabo de ese tiempo se realizó un seguimiento prospective asignando a los pacientes a uno de 2 grupos: grupo I (pacientes que durante el seguimiento desarrollaron IVU), y grupo II (grupo control, pacientes sin infección). Se evaluaron bimestralmente la función renal y el número de recaídas durante un año de seguimiento. Para el análisis estadístico, se emplearon la prueba de la t de Student, la prueba de la χ2, el test de Fisher (cuando se requiera) y el análisis bivariado. Resultados: Se incluyó a 50 pacientes, 25 en cada grupo. Los casos del grupo I correspondieron a IVU no complicada. La edad promedio fue de 30,07±8,15, y el 82% eran mujeres. El uropatógeno descrito con más frecuencia fue Escherichia coli (73%). La presencia de IVU determinó la interrupción temporal del tratamiento en 19 casos (76%), mientras que en el grupo sin IVU esto ocurrió sólo en 3 pacientes (12%), por otras causas, como leucopenia grave, hipersensibilidad y síntomas gastrointestinales graves (odds ratio=23,22; intervalo de confianza del 95%, 5,26-105,1; p=0,001). Durante el año de seguimiento, en el grupo I, el 90,9% alcanzó la remisión parcial en los primeros 3 meses de seguimiento y el 35% logró la remisión completa después de un año; en el grupo II, los porcentajes de remisión fueron del 85 y el 63%, respectivamente. En el grupo I se observó un incremento en la albuminuria (p<0,05), persistencia de hipocomplementemia y títulos elevados de anticuerpos anti-ADN. En este grupo se encontraron 18 exacerbaciones y en el grupo control, 9. Conclusiones: En pacientes con nefritis lúpica proliferativa difusa, la presencia de IVU no complicada se asocia a un retraso en el tratamiento inmunodepresor y a un incremento en las recaídas renales (AU)

Objective: In patients with proliferative lupus nephritis treated with IV cyclophosphamide, analyze urinary tract infection (UTI) as a cause of treatment delay and renal relapses, compared with lupus nephritis patients without infection. Patients and methods: We studied SLE patients (ACR criteria) with renal biopsy showing nephritis class IV. All patients received monthly intravenous cyclophosphamide (CYC) treatment during 6 months. Thereafter patients were assigned to 2 groups: patients who developed UTI, and those who did not; renal function tests, UTI and renal relapses were bimonthly evaluated during one year (follow-up period). To analyze data, t student test, χ2, Fisher exact (when appropiate), and bivariate analysis, were performed. Results: We studied 50 patients, 25 with UTI (Group I) and 25 without UTI (G-II).The mean age was 30.07 ± 8.15 years, 82% were female. E. coli was the pathogen most frequently isolated (73%). UTI (G-I) was the cause for treatment delay in 19 cases (76%), compared with 3 patients (12%) in G-II whose treatment was delayed because of some other causes (severe leucopenya, hypersensibility and gastrointestinal side effects) (OR 23.22, 95% CI, 5.26-105.1; P=001). During the follow up, 90.9% of patients in G-I reached partial or complete renal remission within 3 months, but only 35% mantained remission after the year of follow up. Meanwhile, patients in G-II had complet and partial renal remission of 85% and 63%, respectively. In the first group we observed persistent albuminuria (P<05), low complement levels and high ab-dsDNA titers. Renal flares were present in 18 patients in G-I and 9 in G-II. Conclusiones: UTI in lupus nephritis patients has a negative impact. It leads to delayed CYC therapy and to a higher renal flare rate (AU)

[Influence of non-complicated urinary tract infection on renal relapses in proliferative lupus nephritis]. / Influencia de la infección de vías urinarias no complicada en la frecuencia de exacerbaciones en pacientes con nefritis proliferativa difusa lúpica.

OBJECTIVE: In patients with proliferative lupus nephritis treated with IV cyclophosphamide, analyze urinary tract infection (UTI) as a cause of treatment delay and renal relapses, compared with lupus nephritis patients without infection. PATIENTS AND METHODS: We studied SLE patients (ACR criteria) with renal biopsy showing nephritis class IV. All patients received monthly intravenous cyclophosphamide (CYC) treatment during 6 months. Thereafter patients were assigned to 2 groups: patients who developed UTI, and those who did not; renal function tests, UTI and renal relapses were bimonthly evaluated during one year (follow-up period). To analyze data, t student test, χ(2), Fisher exact (when appropiate), and bivariate analysis, were performed. RESULTS: We studied 50 patients, 25 with UTI (Group I) and 25 without UTI (G-II).The mean age was 30.07 ± 8.15 years, 82% were female. E. coli was the pathogen most frequently isolated (73%). UTI (G-I) was the cause for treatment delay in 19 cases (76%), compared with 3 patients (12%) in G-II whose treatment was delayed because of some other causes (severe leucopenya, hypersensibility and gastrointestinal side effects) (OR 23.22, 95% CI, 5.26-105.1; P=001). During the follow up, 90.9% of patients in G-I reached partial or complete renal remission within 3 months, but only 35% mantained remission after the year of follow up. Meanwhile, patients in G-II had complet and partial renal remission of 85% and 63%, respectively. In the first group we observed persistent albuminuria (P<05), low complement levels and high ab-dsDNA titers. Renal flares were present in 18 patients in G-I and 9 in G-II. CONCLUSIONS: UTI in lupus nephritis patients has a negative impact. It leads to delayed CYC therapy and to a higher renal flare rate.

Tratamiento inmunosupresor en pacientes con glomerulonefritis lúpica. Revisión de eventos adversos / Immunosuppresive treatment in patients with lupus glomerulonephritis. Review of adverse events

El pronóstico de la nefritis lúpica ha mejorado notablemente en las últimas décadas, debido al mejor conocimiento de la patogenia e historial natural de la enfermedad, mejores esquemas terapéuticos y a la disponibilidad de nuevos fármacos para las enfermedades intercurrentes. La ciclofosfamida (CFM) se considera aún la mejor alternativa terapéutica inicial para la nefritis proliferativa, si bien aún existe controversia en relación al mejor esquema de dosificación, duración del tratamiento y terapia de mantenimiento después de la inducción. Sin embargo, para el médico y el paciente son motivo de gran preocupación la presencia de eventos adversos tales como las infecciones graves, neoplasias o amenorrea permanente. Para los casos resistentes al tratamiento, se pueden considerar nuevos inmunosupresores y agentes inmunoablativos, análogos de nucleósidos y terapia biológica. En todos estos casos, sin embargo, será necesario contar con estudios a largo plazo que verifiquen que estos nuevos tratamientos, con satisfactoria respuesta inicial, mantengan la respuesta y con menores efectos secundarios(AU)

The prognosis of lupus nephritis has improved significantly over the past few decades. This has been partly contributed to by a better understanding of the natural history of the disease, improved treatment regimens, and the use of adjunctive treatments. Despite the development of new modalities, cyclophosphamide (CYC) remains the preferred initial treatment for severe proliferative lupus nephritis. Controversies continue about the best route, dosage, and duration of CYC treatment. However, adverse events as major infections, neoplasia and permanent amenorrhea, remain as a great concern for physicians and patients. For recalcitrant disease, new immunosuppresive and immunomodulating agents, nucleoside analogues and the biological response modifiers can be considered. New treatments directed against more specific targets may theoretically be associated with higher efficacy and lower toxicity. Longterm studies are needed with new treatments to verify this assumed lower toxicity(AU)

[Immunosuppresive treatment in patients with lupus glomerulonephritis. Review of adverse events]. / Tratamiento inmunosupresor en pacientes con glomerulonefritis lúpica. Revisión de eventos adversos.

The prognosis of lupus nephritis has improved significantly over the past few decades. This has been partly contributed to by a better understanding of the natural history of the disease, improved treatment regimens, and the use of adjunctive treatments. Despite the development of new modalities, cyclophosphamide (CYC) remains the preferred initial treatment for severe proliferative lupus nephritis. Controversies continue about the best route, dosage, and duration of CYC treatment. However, adverse events as major infections, neoplasia and permanent amenorrhea, remain as a great concern for physicians and patients. For recalcitrant disease, new immunosuppresive and immunomodulating agents, nucleoside analogues and the biological response modifiers can be considered. New treatments directed against more specific targets may theoretically be associated with higher efficacy and lower toxicity. Longterm studies are needed with new treatments to verify this assumed lower toxicity.