[Bioimpedance vector analysis as a tool for the determination and adjustment of dry weight in patients undergoing hemodialysis]. / VECTORES DE IMPEDANCIA BIOELÉCTRICA COMO HERRAMIENTA PARA LA DETERMINACIÓN Y AJUSTE DEL PESO SECO EN PACIENTES SOMETIDOS A HEMODIÁLISIS.

BACKGROUND AND OBJECTIVE: Overhydration in hemodialysis patients is associated with cardiovascular mortality. Adequate removal of liquids and achievement of dry weight is one of the main goals of therapy. So far there are no clinical or laboratory parameters that are reliable, simple and affordable for its determination. The bioelectrical impedance vector analysis (BIVE) is a tool that allows identifying and monitoring hydration status, so the aim of this study was to use BIVE to adjust the intensity of ultrafiltration and achieve dry weight in hemodialysis patients. METHODS: We studied 26 patients on hemodialysis, which were performed monthly measurements of bioelectrical impedance for four months. Corresponding vectors were plotted to know in an individual way the state of hydration, according to which the dry weight was adjusted when necessary. RESULTS: Dry weight adjustment was performed in 13 patients, 7 of which required increase and 6 decrease of dry weight. The displacement of vectors on the ellipses corresponded to the type of intervention made. Dry weight was reached in 84.6% of patients at the end of the study with a significant decrease in mean arterial blood pressure and an increase in phase angle in the group of decrease of dry weight. CONCLUSIONS: Bioelectrical impedance vector analysis is an useful tool for adjusting the dry weight in patients undergoing hemodialysis.

Antecedentes y objetivo: La sobrehidratación en los pacientes en hemodiálisis se asocia con mortalidad cardiovascular, por lo que la adecuada remoción de líquidos y el logro del peso seco es uno de los principales objetivos de la terapia. Hasta el momento no hay parámetros clínicos ni de laboratorio que sean confiables, sencillos y accesibles para su determinación. El análisis de vectores de impedancia (VIBE) es una herramienta que permite identificar y monitorizar el estado de hidratación, por lo que el objetivo de este estudio fue usar el VIBE para ajustar la intensidad del ultrafiltrado y alcanzar el peso seco en pacientes en hemodiálisis. Material y método: Se estudiaron 26 pacientes en hemodiálisis a los cuales se les realizaron medidas mensuales de impedancia bioeléctrica durante cuatro meses. Se graficaron los vectores correspondientes para conocer de manera individual el estado de hidratación, de acuerdo con lo cual se ajustó el peso seco en los casos necesarios. Resultados: Se realizó ajuste de peso seco en 13 pacientes, 7 de ellos necesitaron aumento de peso y 6 disminución del mismo. El desplazamiento de los vectores sobre las elipses correspondió al tipo de intervención realizada. Se logró alcanzar el peso seco en el 84.6% de los pacientes al final del estudio, con una disminución significativa de la presión arterial media y aumento del ángulo de fase en el grupo de disminución de peso seco. Conclusiones: El análisis de vectores de impedancia es útil para el ajuste del peso seco en los pacientes sometidos a hemodiálisis.

Long-term outcomes of IgA nephropathy presenting with minimal or no proteinuria.

The long-term outcome of patients with IgA nephropathy who present with normal renal function, microscopic hematuria, and minimal or no proteinuria is not well described. Here, we studied 141 Caucasian patients with biopsy-proven IgA nephropathy who had minor abnormalities at presentation and a median follow-up of 108 months. None of the patients received corticosteroids or immunosuppressants. We reviewed renal biopsies using the Oxford classification criteria. In this sample, 46 (32%) patients had mesangial proliferation, whereas endocapillary proliferation, focal glomerulosclerosis, and tubulointerstitial abnormalities were uncommon. Serum creatinine increases >50% and >100% were observed in five (3.5%) patients and one (0.7%) patient, respectively; no patients developed ESRD. After 10, 15, and 20 years, 96.7%, 91.9%, and 91.9% of patients maintained serum creatinine values less than a 50% increase, respectively. Using Cox proportional hazards regression, the presence of segmental glomerulosclerosis was the only factor that significantly associated with a >50% increase in serum creatinine. Clinical remission occurred in 53 (37.5%) patients after a median of 48 months. Proteinuria>0.5 and >1.0 g/24 h developed in 21 (14.9%) and 6 (4.2%) patients, respectively. Median proteinuria at the end of follow-up was 0.1 g/24 h, with 41 (29.1%) patients having no proteinuria. At presentation, 23 (16.3%) patients were hypertensive compared with 30 (21.3%) patients at the end of follow-up; 59 (41.8%) patients were treated with renin-angiotensin blockers because of hypertension or increasing proteinuria. In summary, the long-term prognosis for Caucasian patients with IgA nephropathy who present with minor urinary abnormalities and normal renal function is excellent.

Enhanced phosphoinositide 3-kinase δ activity is a frequent event in systemic lupus erythematosus that confers resistance to activation-induced T cell death.

Systemic lupus erythematosus (SLE) is a human chronic inflammatory disease caused by the action of autoreactive T and B cells. Class I phosphoinositide-3-kinases (PI3K) are enzymes that trigger formation of 3-poly-phosphoinositides that induce cell survival. Enhanced PI3K activation is a frequent event in human cancer. Nonetheless, in a genetic model with enhanced activation of class I(A) PI3K in T cells, mice show a greater tumor index but die of a lupus-like disease. In this study, we studied the potential PI3K involvement in human SLE. The PI3K pathway was frequently activated in SLE patient PBMC and T cells (∼70% of cases), more markedly in active disease phases. We examined the mechanism for PI3K pathway activation and found enhanced activation of PI3Kδ in SLE peripheral blood T cells. The magnitude of PI3K pathway activation in patients paralleled activated/memory T cell accumulation. We examined potential tolerance mechanisms affected by increased PI3K activity; SLE patients showed reduced activation-induced cell death of activated/memory T cells. Moreover, the defective activation-induced cell death in SLE T cells was corrected after reduction of PI3Kδ activity, suggesting that PI3Kδ contributes to induction of enhanced SLE memory T cell survival. These observations point to PI3Kδ as a target of clinical interest for SLE.

Nephrotic syndrome and idiopathic membranous nephropathy associated with autosomal-dominant polycystic kidney disease.

We report the case of a 38-year-old male with autosomal-dominant polycystic kidney disease (ADPKD) and concomitant nephrotic syndrome secondary to membranous nephropathy (MN). A 3-month course of prednisone 60 mg daily and losartan 100 mg daily resulted in resistance. Treatment with chlorambucil 0.2 mg/kg daily, low-dose prednisone, plus an angiotensin-converting enzyme inhibitor (ACEI) and an angiotensin II receptor blocker (ARB) for 6 weeks resulted in partial remission of his nephrotic syndrome for a duration of 10 months. After relapse of the nephrotic syndrome, a 13-month course of mycophenolate mofetil (MFM) 2 g daily and low-dose prednisone produced complete remission for 44 months. After a new relapse, a second 24-month course of MFM and low-dose prednisone produced partial to complete remission of proteinuria with preservation of renal function. Thirty-six months after MFM withdrawal, complete remission of nephrotic-range proteinuria was maintained and renal function was preserved. This case supports the idea that renal biopsy is needed for ADPKD patients with nephrotic-range proteinuria in order to exclude coexisting glomerular disease and for appropriate treatment/prevention of renal function deterioration. To the best of our knowledge, this is the first reported case of nephrotic syndrome due to MN in a patient with ADPKD treated with MFM, with remission of proteinuria and preservation of renal function after more than 10 years. Findings in this patient also suggest that MFM might reduce cystic cell proliferation and fibrosis, preventing progressive renal scarring with preservation of renal function.

Inhibition of tyrosine kinases by sunitinib associated with focal segmental glomerulosclerosis lesion in addition to thrombotic microangiopathy.

Sunitinib is an orally administered inhibitor of tyrosine kinases and has become the standard of care for many patients with metastatic renal cell carcinoma. Its use has been associated with renal toxicity in some patients. We report a patient with a metastatic clear-cell renal carcinoma who showed arterial hypertension, nephrotic syndrome and azotaemia 10 months after treatment with sunitinib. The renal biopsy revealed focal segmental glomerulosclerosis (FSGS) in addition to thrombotic microangiopathy (TMA), and the complete syndrome disappeared 6 months after sunitinib withdrawal. To our knowledge, this is the first case of FSGS associated to TMA secondary to sunitinib treatment. We discuss the possible glomerular pathomechanism.

Effects of cinacalcet on gastrointestinal hormone release in patients with secondary hyperparathyroidism undergoing dialysis.

UNLABELLED: Objective. Our aim has been evaluating the influence of an acute dose of cinacalcet on the gastrointestinal hormonal responses to a test meal in uraemic patients with secondary hyperparathyroidism undergoing peritoneal dialysis (PD) or haemodialysis (HD). METHODS: Twenty patients (11 PD, 9 HD) on cinacalcet treatment (30-120 mg/day) were studied. Twelve patients (1 PD, 11 HD) who never received cinacalcet were studied as control group. Each patient received a test meal with blood samples at 0, 2 and 4 h. At 0 time, patients in the cinacalcet group received their usual oral dose of this calcimimetic. Plasma concentrations of intact parathyroid hormone (PTH), vasoactive intestinal peptide (VIP), ghrelin, substance P, serotonin, cholecystokinin (CCK) and gastrin were quantified at 0, 2 and 4 h. RESULTS: No significant differences in baseline concentrations of serum VIP, ghrelin, substance P, serotonine, CCK and gastrin were found between controls and cinacalcet-treated patients. In comparison with the control group, cinacalcet administration was followed by a significant decrease in VIP concentration at 4 h and a significant increase in substance P at 4 h. However, the areas under the curves of all studied gut hormones were similar in both groups. CONCLUSION: An acute dose of cinacalcet exerts minimal influence on gut hormone responses to a mixed meal in dialysis patients on chronic therapy with this drug. The small but significant differences between control subjects and patients on cinacalcet in VIP and substance P levels at 4 h should be investigated in symptomatic patients.

Focal segmental glomerulosclerosis due to a relapsing non-Hodgkin's lymphoma diagnosed by positron emission tomography.

Glomerulonephritis rarely appears associated with Hodgkin's disease or non-Hodgkin's lymphoma (NHL). We present a patient with a relapse of a non-Hodgkin's lymphoma which first presented as nephrotic syndrome due to focal segmental glomerulosclerosis (FSGS). This case report discusses the unusual association of non-Hodgkin's lymphoma and focal segmental glomerulosclerosis, as well as the crucial role of positron emission tomography in detecting the relapsing lymphoma.

High prevalence of anti-C1q antibodies in biopsy-proven active lupus nephritis.

BACKGROUND: Anti-C1q antibodies (anti-C1q) have been shown to correlate positively with systemic lupus erythematosus (SLE) nephritis. Several clinical studies indicated a high negative predictive value, suggesting that active lupus nephritis is rarely seen in patients with no anti-C1q. However, the true prevalence of anti-C1q at the time of active lupus nephritis has not been well established. The aim of this study was to determine prospectively the prevalence of anti-C1q in proven active lupus nephritis at the time of the renal biopsy. METHODS: In this prospective multi-centre study, we investigated adult SLE patients undergoing renal biopsy for suspected active lupus nephritis. Serum samples were taken at the time of the biopsy and analysed for the presence of anti-C1q in a standardized way. The activity of lupus nephritis was classified according to the renal histology. Biopsies were also analysed for the presence of glomerular IgG, C1q and C3 deposition. RESULTS: A total of 38 patients fulfilling at least 4/11 American College of Rheumatology (ACR) criteria for the diagnosis of SLE were included. Out of this, 36 patients had proliferative (class II, III or IV) and two had class V lupus nephritis. All but one patient with proliferative lupus nephritis were positive for anti-C1q (97.2%) compared with the 35% of control SLE patients with inactive lupus nephritis and 25% of SLE patients without lupus nephritis ever. All patients were positive for glomerular C1q (36/36) and 37/38 patients had glomerular IgG deposits. Anti-C1q strongly decreased during successful treatment. CONCLUSIONS: Anti-C1q have a very high prevalence in biopsy-proven active lupus nephritis, thus a negative test result almost excludes active nephritis. The data support the hypothesis of a pathogenic role of anti-C1q in lupus nephritis.

Renal cell carcinoma co-existent with other renal disease: clinico-pathological features in pre-dialysis patients and those receiving dialysis or renal transplantation.

BACKGROUND: Patients on chronic dialysis are prone to developing acquired cystic kidney disease (ACKD), which may lead to the development of renal cell carcinoma (RCC). The risk factors for the development of RCC so far have not been determined in pre-dialysis patients with co-existent renal disease. The aim of this study was to evaluate the clinico-pathological features of RCC in pre-dialysis patients with associated renal diseases or in those undergoing chronic dialysis and renal transplantation. METHODS: We studied 32 kidneys from 31 patients with RCC and associated renal diseases. Of those, 18 kidneys were from 17 patients not on renal replacement therapy (RRT) when diagnosed with RCC; 14 patients received dialysis or dialysis followed by renal transplantation. Several clinico-pathological features were analysed and compared between the two groups. RESULTS: Overall, there was a preponderance of males (75%); nephrosclerosis was the predominant co-existent disease (31%). The median intervals from renal disease to RCC in the dialysis and transplanted groups were significantly longer than in the pre-dialysis group (15.8+/-1.1 vs 2.4+/-0.7 years, P<0.0001). In contrast to pre-dialysis RCC, the dialysis and transplant RCC groups had greater frequency of ACKD (100 vs 28%, P<0.0001), papillary type RCC (43 vs 11%, P<0.05) and multifocal tumours (43 vs 5%, P<0.05). At the end of the study, 71% of dialysis and transplanted patients and 72% of pre-dialysis patients were alive. CONCLUSIONS: ACKD develops in dialysis patients, as it does in those with renal disease prior to RRT. The duration of renal disease, rather than the dialysis procedure itself, appears to be the main determinant of ACKD and RCC. The RCC occurring in patients with ACKD and prolonged RRT is more frequently of the papillary type and multifocal than the RCC occurring in patients with no or few acquired cysts and a short history of renal disease. Long-term outcomes did not differ between the two groups.