The Density of Renal Lymphatics Correlates With Clinical Outcomes in IgA Nephropathy.

Introduction: IgA nephropathy (IgAN) is the most common primary glomerulonephritis (GN) worldwide. The disease course fluctuates, and the most important challenge is the considerable variation in the time lag between diagnosis and the development of a hard clinical end point, such as end-stage kidney disease (ESKD). The reaction of renal tissue to damage resembles the common wound-healing response. One part of this repair in IgAN is the expansion of lymphatic vessels known as lymphangiogenesis. The aim of this work was to establish the prognostic value of the density of lymphatic vessels in the renal biopsy at the time of diagnosis, for predicting the risk of ESKD in a Spanish cohort of patients with IgAN. Methods: We performed a retrospective multicenter study of 76 patients with IgAN. The end point of the study was progression to ESKD. The morphometric analysis of lymphatic vessels was performed on tissue sections stained with antipodoplanin antibody. Results: Density of lymphatic vessels was significantly higher in patients with IgAN with mesangial hypercellularity >50%, segmental sclerosis, higher degrees of interstitial fibrosis, and tubular atrophy. Patients with more lymphatic vessels had significantly higher values of proteinuria and lower estimated glomerular filtration rate (eGFR). A density of lymphatic vessels ≥8 per mm2 was associated with a significantly higher rate of progression to ESKD at 3 years from biopsy. After adjustment for the International IgAN prediction score, at the multivariate logistic regression, high density of lymphatic vessels (≥8 per mm2) remained significantly associated with a higher rate of early progression to ESKD. Conclusion: This study contributes to the understanding of the natural history of the progression to ESKD in patients with IgAN revealing the density of lymphatics vessels may optimize the prognostic value of the International IgA predicting tool to calculate the risk of ESKD, favoring the evaluation of new targeted therapies.

Efectos de la rotigotina sobre la sintomatología, calidad de vida e higiene de sueño en el síndrome de piernas inquietas en hemodiálisis / Effects of rotigotine on clinical symptoms, quality of life and sleep hygiene adequacy in haemodialysis-associated restless legs syndrome

Introducción: El síndrome de piernas inquietas (SPI) es un trastorno neurológico caracterizado por una molesta sintomatología, asociado a deterioro de calidad de vida e higiene de sueño. Rotigotina constituye una novedosa alternativa terapéutica, si bien existen escasos estudios publicados sobre rotigotina en pacientes en hemodiálisis (HD) con SPI. Objetivos: 1.- Establecer la prevalencia de SPI en nuestra unidad de HD. 2.- Evaluar la eficacia y el perfil de seguridad asociado a rotigotina así como su efecto sobre la sintomatología, calidad de vida e higiene del sueño en nuestra población en HD con SPI. Material y métodos: Estudio unicéntrico, prospectivo de 12 semanas de duración. Dos fases (6 semanas): fase 1 (no tratamiento) y fase 2 (rotigotina). Analizamos: 1.- Datos demográficos, bioquímicos, parámetros de adecuación de HD y tratamiento médico relacionado con SPI. 2.- Cuestionario sobre síntomas en extremidades inferiores (QS). 3.- Escala de gravedad de los síntomas (GRLS). 4.- Calidad de vida SPI: John Hopkins RLS-QoL (JH-QoL). 5.- Higiene del sueño: Escala SCOPA. Resultados: Se incluyó a 66 pacientes en HD. De ellos, 14 con SPI; el 44,4% eran hombres, con 70,2±9,9 años y 111,1±160,8 meses en HD. El 22,9%, con SPI. Únicamente en la fase 2 observamos una mejoría significativa para QS (10±2,4 vs. 5,7±1,0), GRLS (21±4 vs. 5,7±4,6), JH-QoL (22,1±4,4 vs. 4,3±4,0) y SCOPA (16±5,3 vs. 6,7±1,9). Un 77,7 y un 11,1% presentaron remisión parcial (>20%) y completa (>80%), respectivamente. Un 55,5% alcanzó sintomatología «cero». Un único paciente presentó intolerancia digestiva y ninguno, augmentation efect. No observamos cambios en datos bioquímicos, adecuación dialítica ni tratamiento médico. El análisis intergrupos mostró una mejoría significativa en la fase 2 con relación a QS, GRLSS, JH-QoL y SCOPA. Conclusiones: En nuestro estudio, el SPI urémico presentó una prevalencia considerable. Rotigotina mejoró la sintomatología clínica, la calidad de vida y la higiene de sueño en los pacientes con SPI en HD, por lo que resulta ser un fármaco seguro, con mínimos efectos adversos y con cumplimento terapéutico completo. No obstante, serían necesarios futuros estudios para confirmar el beneficio de rotigotina en la población en HD con SPI (AU)

Background: Restless legs syndrome (RLS) is a neurological disorder characterised by bothersome symptoms associated with impaired quality of life and sleep hygiene. Rotigotine is a novel therapeutic alternative, although few studies have been published in patients on haemodialysis (HD) with RLS treated with rotigotine. Objectives: 1.- To establish the prevalence of RLS in our HD unit. 2.- To evaluate the efficacy and safety profile of rotigotine and its effect on symptoms, quality of life and sleep hygiene in our HD population with RLS. Material and methods: A single-centre, 12-week prospective study. Two stages (6 weeks): stage 1 (no treatment) and stage 2 (rotigotine). We analysed: 1.- Demographic data, biochemistry data, HD suitability parameters and RLS medical treatment data. 2.- Lower extremity symptoms questionnaire (QS). 3.- RLS severity symptoms scale (SRLSS). 4.- RLS Quality of life: John Hopkins RLS-QoL (JH-QoL). 5.- Sleep hygiene: SCOPA Scale. Results: We included 66 HD patients, 14 with RLS; 44.4% male, 70.2±9.9 years and 111.1±160.8 months on HD. And 22.9% RLS. Exclusively in stage 2, a significant improvement for QS (10±2.4 vs. 5.7±1.0), SRLSS (21±4 vs. 5.7±4.6), JH-QoL (22.1±4.4 vs. 4.3±4.0) and SCOPA (16±5.3 vs. 6.7±1.9) were observed. A 77.7 and 11.1%, showed partial (> 20%) and complete (> 80%) remission, respectively, while 55.5% achieved «zero» symptoms. Only one patient had gastrointestinal intolerance and none experienced augmentation effect. No changes in biochemical data, suitability for dialysis or medical treatment were found. The inter-group analysis showed a significant improvement in relation to QS, SRLSS, JH-QoL and SCOPA in stage 2. Conclusions: RLS showed a considerable prevalence in our HD unit. Rotigotine improved clinical symptoms, quality of life and sleep hygiene in RLS patients on HD and was found to be a safe drug with minimal side effects and total therapeutic compliance. Nevertheless, future studies should be performed to confirm the benefits of rotigotine in RLS patients on haemodialysis (AU)

Effects of rotigotine on clinical symptoms, quality of life and sleep hygiene adequacy in haemodialysis-associated restless legs syndrome. / Efectos de la rotigotina sobre la sintomatología, calidad de vida e higiene de sueño en el síndrome de piernas inquietas en hemodiálisis.

BACKGROUND: Restless legs syndrome (RLS) is a neurological disorder characterised by bothersome symptoms associated with impaired quality of life and sleep hygiene. Rotigotine is a novel therapeutic alternative, although few studies have been published in patients on haemodialysis (HD) with RLS treated with rotigotine. OBJECTIVES: 1.- To establish the prevalence of RLS in our HD unit. 2.- To evaluate the efficacy and safety profile of rotigotine and its effect on symptoms, quality of life and sleep hygiene in our HD population with RLS. MATERIAL AND METHODS: A single-centre, 12-week prospective study. Two stages (6 weeks): stage 1 (no treatment) and stage 2 (rotigotine). We analysed: 1.- Demographic data, biochemistry data, HD suitability parameters and RLS medical treatment data. 2.- Lower extremity symptoms questionnaire (QS). 3.- RLS severity symptoms scale (SRLSS). 4.- RLS Quality of life: John Hopkins RLS-QoL (JH-QoL). 5.- Sleep hygiene: SCOPA Scale. RESULTS: We included 66 HD patients, 14 with RLS; 44.4% male, 70.2±9.9 years and 111.1±160.8 months on HD. And 22.9% RLS. Exclusively in stage 2, a significant improvement for QS (10±2.4 vs. 5.7±1.0), SRLSS (21±4 vs. 5.7±4.6), JH-QoL (22.1±4.4 vs. 4.3±4.0) and SCOPA (16±5.3 vs. 6.7±1.9) were observed. A 77.7 and 11.1%, showed partial (> 20%) and complete (> 80%) remission, respectively, while 55.5% achieved «zero¼ symptoms. Only one patient had gastrointestinal intolerance and none experienced augmentation effect. No changes in biochemical data, suitability for dialysis or medical treatment were found. The inter-group analysis showed a significant improvement in relation to QS, SRLSS, JH-QoL and SCOPA in stage 2. CONCLUSIONS: RLS showed a considerable prevalence in our HD unit. Rotigotine improved clinical symptoms, quality of life and sleep hygiene in RLS patients on HD and was found to be a safe drug with minimal side effects and total therapeutic compliance. Nevertheless, future studies should be performed to confirm the benefits of rotigotine in RLS patients on haemodialysis.

Efficacy of mycophenolate treatment in adults with steroid-dependent/frequently relapsing idiopathic nephrotic syndrome.

BACKGROUND: This study assessed the efficacy of therapy with mycophenolate (MF) and reduced doses of steroids in adults with steroid-dependent/frequently relapsing idiopathic nephrotic syndrome (SD/FR-INS). METHODS: Twenty-nine nephrotic patients (including 16 males and 13 females; mean age: 40 years, range: 18-74) were treated. Starting doses of MF were 2000 mg/day for mofetil MF (1500 mg/day in one patient) or 1440 mg/day for sodium MF. The initial prednisone (PDN) dose was 10 mg/day in 14 patients, 5 mg/day in two patients and no steroids in one patient. In the remaining 12 patients, moderate initial doses of PDN were administered (mean: 23.7 mg/day, range: 15-40), tapering to 10 mg/day after 1 month. RESULTS: Nephrotic syndrome remission was achieved in 27/29 cases (93.1%) (25 complete, 2 partial). Two patients showed resistance to the prescribed schedule. The first cycle of MF therapy was concluded in 20 patients after a mean (range) of 16.9 months (12-49). Maintenance of remission was observed in 11 of these 20 cases (55%) after a mean follow-up of 32.8 months (12-108). In nine patients with nephrotic syndrome relapse after tapering of MF (MF dependency), the same MF-PDN schedule was restarted, leading again to remission in all nine. The remaining seven MF-sensitive patients are still receiving their first therapeutic cycle. To date, the mean time under therapy in the 27 MF-sensitive patients is 38 months (4-216). Regarding complications, only minor digestive disorders and a slight decrease in blood haemoglobin levels were observed in a few patients. CONCLUSIONS: MF plus reduced doses of PDN is an effective and well-tolerated therapy for adult SD/FR-INS. Though MF dependence is observed, its low toxicity could allow long periods of therapy if it is required to maintain nephrotic syndrome remission.

Efecto de la electroestimulación neuromuscular sobre la fuerza muscular, capacidad funcional y composición corporal en los pacientes en hemodiálisis / The effect of neuromuscular electrical stimulation on muscle strength, functional capacity and body composition in haemodialysis patients

Introducción: Los pacientes en hemodiálisis (HD) se caracterizan por una gran pérdida muscular. Recientemente, la electroestimulación neuromuscular (EENM) constituye una nueva alternativa terapéutica para mejorar la condición física de estos pacientes. No existen estudios acerca de la EENM sobre la composición corporal en HD. Objetivo: Analizar el efecto de la EENM sobre la fuerza muscular, capacidad funcional y composición corporal en nuestros pacientes en HD. Material y métodos: Estudio prospectivo unicéntrico (12 semanas). Los pacientes fueron asignados a grupo electroestimulación (EM) o control (CO). El grupo EM incluía un programa de electroestimulación cuadricipital intradiálisis (Compex® Theta 500i). El grupo C recibió cuidado habitual en HD. Analizamos: 1) parámetros nutricionales; 2) composición muscular del cuádriceps; 3) fuerza de extensión máxima del cuádriceps (FEMQ) y handgrip (HG); 4) sit to stand to sit (STS10), six-minutes walking test (6MWT) y 5) composición corporal (bioimpedancia eléctrica). Resultados: De un total de 20 pacientes, el 55% fueron hombres. Edad media: 67,7 años, con 30,3 meses en HD. Principal etiología: DM (35%). Hubo 13 pacientes en EM y 7 en el grupo CO. Al final del estudio, únicamente EM presentó mejoría en (*p<0,05): FEMQ* (11,7±7,1 vs. 13,4±7,4kg), STS10 (39,3±15,5 vs. 35,8±13,7s) y 6MWT* (9,9%; 293,2 vs. 325,2m). Igualmente, el grupo EM incrementó el área muscular (AMQ*: 128,6±30,2 vs. 144,6±22,4cm2) y disminuyó el área grasa cuadricipital (AGQ*: 76,5±26,9 vs. 62,1±20,1cm2). No se observaron cambios relevantes en el resto de la composición corporal, parámetros nutricionales ni adecuación dialítica. Conclusiones: 1) La EENM mejoró la fuerza muscular, la capacidad funcional y la composición muscular del cuádriceps de nuestros pacientes. 2) Con los resultados obtenidos, la EENM podría ser una nueva alternativa terapéutica para evitar la atrofia muscular y el deterioro progresivo de la condición física de estos pacientes. 3) No obstante, serían necesarios futuros estudios para establecer los potenciales efectos beneficiosos de la EENM en los pacientes en HD (AU)

Introduction: Haemodialysis (HD) patients are characterised by significant muscle loss. Recently, neuromuscular electrical stimulation (NMES) has emerged as a new therapeutic alternative to improve these patients’ physical condition. To date, no studies on the effects of NMES on body composition in HD patients have been published. Objective: To analyse the effect of NMES on muscle strength, functional capacity and body composition in our HD patients. Material and methods: A 12-week, single-centre, prospective study. The patients were assigned to an electrical stimulation (ES) or control (CO) group. The ES group was subjected to intradialytic electrical stimulation of the quadriceps (Compex® Theta 500i), while the CO group received standard HD care. We analysed the following: 1) nutritional parameters; 2) muscle composition of the quadriceps; 3) maximum quadriceps extension strength (mes) and hand-grip (HG); 4) «sit to stand to sit» (STS10) and «six-minute walking test» (6MWT); 5) body composition (bioelectrical impedance analysis). Results: Of 20 patients, 55% were men. Mean age 67.7 years, 30.3 months in HD. Main aetiology: DM (35%). In the ES group were 13 patients, and 7 in the CO group. At the end of the study, an improvement was only observed in the ES group (*P<.05): MES* (11.7±7.1 vs. 13.4±7.4kg), STS10 (39.3±15.5 vs. 35.8±13.7s) and 6MWT* (9.9%, 293.2 vs. 325.2m). Furthermore, increased quadriceps muscle area (QMA*: 128.6±30.2 vs. 144.6±22.4cm2) and lowered quadriceps fat area (QFA*: 76.5±26.9 vs. 62.1±20.1cm2) were observed. No relevant changes in body composition, nutritional parameters and dialysis adequacy were found. Conclusions: 1) NMES improved muscle strength, functional capacity and quadriceps muscle composition in our patients. 2) Based on the results obtained, NMES could be a new therapeutic alternative to prevent muscle atrophy and progressive physical deterioration. 3) However, future studies are necessary to establish the potential beneficial effects of NMES in HD patients (AU)

The effect of neuromuscular electrical stimulation on muscle strength, functional capacity and body composition in haemodialysis patients. / Efecto de la electroestimulación neuromuscular sobre la fuerza muscular, capacidad funcional y composición corporal en los pacientes en hemodiálisis.

INTRODUCTION: Haemodialysis (HD) patients are characterised by significant muscle loss. Recently, neuromuscular electrical stimulation (NMES) has emerged as a new therapeutic alternative to improve these patients' physical condition. To date, no studies on the effects of NMES on body composition in HD patients have been published. OBJECTIVE: To analyse the effect of NMES on muscle strength, functional capacity and body composition in our HD patients. MATERIAL AND METHODS: A 12-week, single-centre, prospective study. The patients were assigned to an electrical stimulation (ES) or control (CO) group. The ES group was subjected to intradialytic electrical stimulation of the quadriceps (Compex® Theta 500i), while the CO group received standard HD care. We analysed the following: 1) nutritional parameters; 2) muscle composition of the quadriceps; 3) maximum quadriceps extension strength (mes) and hand-grip (HG); 4) «sit to stand to sit¼ (STS10) and «six-minute walking test¼ (6MWT); 5) body composition (bioelectrical impedance analysis). RESULTS: Of 20 patients, 55% were men. Mean age 67.7 years, 30.3 months in HD. Main aetiology: DM (35%). In the ES group were 13 patients, and 7 in the CO group. At the end of the study, an improvement was only observed in the ES group (*P<.05): MES* (11.7±7.1 vs. 13.4±7.4kg), STS10 (39.3±15.5 vs. 35.8±13.7s) and 6MWT* (9.9%, 293.2 vs. 325.2m). Furthermore, increased quadriceps muscle area (QMA*: 128.6±30.2 vs. 144.6±22.4cm2) and lowered quadriceps fat area (QFA*: 76.5±26.9 vs. 62.1±20.1cm2) were observed. No relevant changes in body composition, nutritional parameters and dialysis adequacy were found. CONCLUSIONS: 1) NMES improved muscle strength, functional capacity and quadriceps muscle composition in our patients. 2) Based on the results obtained, NMES could be a new therapeutic alternative to prevent muscle atrophy and progressive physical deterioration. 3) However, future studies are necessary to establish the potential beneficial effects of NMES in HD patients.

Complete low-intensity endurance training programme in haemodialysis patients: improving the care of renal patients.

BACKGROUND: Patients on haemodialysis (HD) have a decreased physical and functional capacity. Several studies have reported the beneficial effects of exercise on the physical, functional and psychological functioning of HD patients. Despite these results, exercise programmes on HD are not commonplace. OBJECTIVE: To analyse the effect of an intradialysis endurance training programme on muscular strength and functional capacity in our HD patients. MATERIAL AND METHODS: A 6-month single-centre prospective study. HD patients were non-randomly assigned to an exercise group (group E) or a control group (group C). Exercise training included complete endurance training using balls, weights and elastic bands in the first 2 h of an HD session; group C received standard HD care. Analysed data: (1) biochemical parameters; (2) biceps and quadriceps muscle tone, maximum quadriceps length strength (MQLS) and dominant hand grip (HG); (3) functional capacity tests: sit-to-stand-to-sit (STS10) and 6-min walking test (6MWT). RESULTS: Forty patients were included, 55% were men; their mean age was 68.4 years; the patients were 61.6 months on HD; 16 patients were in group E and 24 in group C. In group E, muscular strength showed a significant improvement in MQLS (15.6 ± 10.7 vs. 17.7 ± 12.5 kg, p < 0.05) and HG (22.1 ± 13.2 vs. 24.1 ± 15.8 kg, p < 0.05) at the end of the programme, while a global decrease was reported in group C (MQLS 20.9 ± 9.3 vs. 16.2 ± 8.4 kg, p < 0.05; HG 25.1 ± 10.3 vs. 24.1 ± 11.1 kg). 6MWT significantly improved in group E (20%, 293.1 vs. 368 m, p < 0.001) and decreased in group C (10%, 350 vs. 315 m, p < 0.004). At the end of the programme, STS10 time was reduced in group E (2.1 ± 18.5 vs. 28.7 ± 20.6 s), while it rose in group C (31.5 ± 17.9 vs. 36.4 ± 19.8 s), though significant differences were not found. CONCLUSIONS: (1) The intradialysis training programme improved muscular strength and functional capacity in our HD patients. (2) These results support the benefits of exercise training for HD patients. (3) Nephrologists should consider exercise training as a standard practice for the care of HD patients.

Conversion from calcineurin inhibitors to sirolimus in chronic allograft dysfunction: changes in glomerular haemodynamics and proteinuria.

BACKGROUND: The study was conducted in order to describe possible intraglomerular haemodynamic changes inducing proteinuria after 14 patients with chronic allograft dysfunction were converted from calcineurin inhibitors (CIs) to sirolimus without changing concomitant immunosuppression or antihypertensive treatment. METHODS: Creatinine, glomerular filtration rate (GFR), proteinuria, renal functional reserve (RFR) and effective renal plasma flow (ERPF) were determined before and 8 months after conversion. Intraglomerular pressure (P(G)), afferent arteriolar resistance (AAR) and efferent arteriolar resistance (EAR) were calculated using Gomez's formula. RESULTS: Creatinine (1.97 vs 2.075 mg/dl; P = 0.270) and GFR (40 vs 43 ml/min; P = 0.505) remained unchanged, proteinuria increased (338 vs 1146 mg/24 h; P = 0.006), RFR decreased (34.84 vs 13.47%; P = 0.019), ERPF (248 vs 310.6 ml/min; P = 0.0625) and P(G) (42.72 vs 46.17 mmHg; P = 0.0625) tendentially increased and AAR tendentially decreased (14.12 vs 10.28 dyne/s/cm(5); P = 0.0625). CONCLUSION: After conversion, P(G) shows a tendency to increase and RFR decreases significantly-characteristics of hyperfiltration, which could possibly partially explain the increase of proteinuria. Therefore, the application of angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers seems promising. To avoid hyperfiltration, conversion should be performed early when renal insufficiency is still moderate.

Acute renal failure secondary to imatinib mesylate treatment in chronic myeloid leukemia.

A 58-year-old woman with chronic myeloid leukemia (CML), and previous intolerance to interferon was treated with the BCR-ABL tyrosine kinase protein inhibitor imatinib mesylate. Coincidentally, with the start of treatment, the patient developed acute renal failure, with acute tubular necrosis being observed on histopathology. Imatinib was stopped and three hemodialysis sessions were performed, which was followed by a progressive improvement of the renal function and normalization of the urine output. One year later the patient still has mild chronic renal failure and remains in chronic phase of CML on hydroxyurea treatment.