[Goodpasture's syndrome with neurologic involvement and negative ANCA]. / Síndrome de Goodpasture asociado con vasculitiscerebral ANCA negativa.

Goodpasture's syndrome is a rare autoimmune disorder characterized by rapidly progressive glomerulonephritis (RPGN) and alveolar hemorrhage in the presence of antiglomerular basement membrane (anti-GBM) antibodies. Central nervous system involvement is highly unusual in the absence of anti-neutrophil cytoplasmic antibodies. We report the case of a 20-year-old man with RPGN accompanied by bloody sputum, tonic-clonic seizure and high titers of anti-GBM antibody. After treatment with immunosuppressants and plasmapheresis, the patient showed reduced anti-GBM antibody titers and improved neurologic and respiratory symptoms, but renal failure persisted, requiring hemodialysis. Twenty months later, with the disease in remission, he underwent deceased-donor renal transplantation.

[Induction treatment by combining immunoglobulins, plasmapheresis and rituximab in hypersensitive patients receiving cadaveric renal allograft]. / Tratamiento de inducción combinando inmunoglobulinas, plasmaféresis y rituximab en pacientes hipersensibilizados que reciben trasplante renal de cadáver.

In our Universitary Hospital of Canarias we iniciated in May 2008 a induction therapy protocol for sensitized patients receiving cadaveric renal graft using intravenous immunoglobulins, plasmapheresis and rituximab plus immunosuppression with prednisone, tacrolimus and mycophenolate mofetil. We present the results of four patients. Everyone had anti-HLA antibodies rate (PRA by CDC) more than 75%, were on a waiting list during 4 to 17 years and follow-up time was 10-14 months after transplantation. Patient and graft survival in this period was 100%. Only one patient suffered a humoral acute rejection and another one cellular rejection, in both cases reversible with treatment. During the first year, no evidence of de novo donor-specific antibodies was detected. All patients had significantly reduced the CD19+ cells percentage after infusion of rituximab. Neurological symptoms suggestive of progressive multifocal leukoencephalopathy or serious viral infections after transplantation have not been observed. Additionally, no immediate side effects were observed after administration of medication. In summary, induction therapy by combining immunoglobulin, plasmapheresis and rituximab in hypersensitive patients allows the realization of deceased kidney transplantation with good results in the short and medium-term without serious side effects. It remains to know whether this success will continue in the long term.

Hemophagocytic lymphohistiocytosis in a pancreas-kidney transplant recipient: response to dexamethasone and cyclosporine.

We describe a severe case of hemophagocytic lymphohistiocytosis (HLH), secondary to a candida glabrata retroperitoneal abscess in a 41-year-old simultaneous pancreas-kidney transplantation (SPKT) recipient. Despite percutaneous abscess drainage and antifungal therapy, general status deteriorated with persistent fever, severe pancytopenia and liver dysfunction. Presence of hypertriglyceridemia, very high serum levels of ferritin and hemophagocytosis in a bone-marrow aspirate gave the diagnosis of HLH. Of note, change from tacrolimus to cyclosporine together with dexamethasone produced rapid response with status improvement. We concluded that HLH, a rare but often fatal condition characterized by excessive activation of lymphocytes and macrophages, is a diagnostic and therapeutic challenge in solid-organ transplanted patients and must be suspected in the presence of fever, blood cytopenia and liver dysfunction. Specific antiinfectious therapy together with cyclosporine and dexamethasone may be a therapeutic approach.

[A successful pregnancy in female after simultaneous kidney-pancreas transplantation]. / Embarazo a término en receptora de trasplante simultáneo de riñón y páncreas.

The effects of pregnancy on kidney transplant recipients have been widely described, although its impact on the mother, the fetus and the graft is still debated. Experience in simultaneous kidney-pancreas transplantation is limited, with few reported cases, which increases uncertainty about guidelines to follow in this situation. We describe a case of successful pregnancy in a 35 year-old patient who underwent simultaneous pancreas-kidney transplantation 34 months before delivery. After modifications in immunosuppressive therapy (with tacrolimus and mycophenolate, the latter being switched to azathioprine), pregnancy evolved favourably. Delivery was by caesarean section due to fetal distress at 38 weeks of gestational age. Five months after delivery the child shows normal development while both pancreas and kidney grafts show normal function.

[Improved short-term cardiovascular profile after simultaneous pancreas-kidney transplantation]. / Evolución a corto plazo de los factores de riesgo cardiovascular tras el trasplante reno-pancreático.

The prognosis of type 1 diabetes mellitus (T1DM) patients with chronic renal failure (CRF) improves after simultaneous pancreas-kidney (SPK) transplantation. In order to evaluate the changes in cardio-vascular risk (CVR) factors after SKP, we studied nine recipients before and 6 months after SPK. There were five females and four males, with a mean age of 37 +/- 8 years, duration of diabetes of 24 +/- 5 years, three of them before starting dialysis, and six on dialysis (hemodialysis = 5; peritoneal dialysis = 1). Before SPK, all patients received anti-hypertensive therapy (1-4 drugs; mean 2.2 +/- 0.9) and eight received statins. At 6 months after SPK, all patients were under triple immunosuppressive therapy (steroids + tacrolimus + MMF) without statins. They had normal renal function (Plasma Creatinine = 1.2 +/- 0.3 mg/dl) and pancreatic endocrine function (glycemia = 80 +/- 8 mg/dl). HbA1c decreased significantly (8.4 +/- 1.2 vs 4.7 +/- 0.6%; p < 0.007) with a value > 7% in seven patients before SPK and in none 6 months after SKP transplantation (p < 0.001). Although Body Mass Index increased (23 +/- 2 vs 25 +/- 3 kg/m2; p < 0.05), plasma triglycerides decreased (130 +/- 51 vs 88 +/- 33 mg/dl; p < 0.05), and total cholesterol, LDL-cholesterol and HDL-cholesterol were similar. Systolic and diastolic blood pressure (BP) decreased (156 +/- 7 vs 133 +/- 15; p < 0.01 and 96 +/- 7 vs 79 +/- 9; p < 0.007) with only two patients on anti-hypertensive therapy (1 drug). Likewise, before transplantation all patients were hypertensive (six grade 1 and three grade 2) while this was observed in only two at the end of follow-up (both grade 1) (p < 0.001). In conclusion, SPK transplantation with good renal and pancreatic function is associated with a short-term improvement in CVR profile.

Cardiovascular risk profile in nondiabetic renal transplant patients: cyclosporine versus tacrolimus.

Calcineurin inhibitors (CIs) contribute to cardiovascular risk (CR) in renal transplant (RT) patients. However, the CR profile in RT patients without preexistent diabetes is not well known. We compared CR factors in 191 nondiabetic RT recipients with functioning grafts beyond 1 year, receivingly either CsA (Neoral; n=100) or tacrolimus (Tac; n= 91). Clinical data and pretransplant CR profiles were similar in both groups. There were no differences in acute rejection episodes and graft survival rates during follow-up. The overall proportions of posttransplant diabetes (9% versus 6%), and of hypertension (73% vs 63%) were similar in both groups. Hyperlipidemia was more frequent in the CsA group (58% vs 31%; P=.0001). The cholesterol levels in the CsA group showed at 3 months (232+/-47 vs 202+/-42 m/dL; P=.0001), 6 months (232+/-49 vs 205+/-41 mg/dL; P=.0001), and 12 months (217+/-50 vs 202+/-40 mg/dL; P=.028), despite receiving a greater proportion of lipid-lowering drugs (49% vs 15%; P=.0001). Logistic regression analysis showed that CsA was an independent predictor of posttransplant hyperlipidemia (OR: 5.8, CI 95%; 3.3-10.7; P=.0001) as were age, female gender, pretransplant dyslipidemia, and body mass index (BMI). Interestingly, an interaction was observed between pretransplant BMI and CIs: Among pretransplant normal weight patients (BMI <25 kg/m2), CsA produced a greater incidence of hyperlipidemia than tacrolimus (58% vs 23%; P=.0001) while not among patients who were overweight (BMI >25 kg/m2: pretransplant 58% vs 42%; P=.341). In conclusion, CsA confers a higher risk of hyperlipidemia after RT in nondiabetic patients, particularly those with normal pretransplant weight.

Role of apolipoprotein E epsilon 4 allele on chronic allograft nephropathy after renal transplantation.

Lipid abnormalities may contribute to chronic allograft nephropathy (CAN). Apolipoprotein E (ApoE) gene polymorphism regulates lipoprotein metabolism, but little is known about an association between CAN and this polymorphism. The ApoE gene (E3/E4) polymorphism was typed by PCR assay (99 E3/E3, 28 E3/E4, 1 E4/E4) on 128 consecutive renal transplant patients with functioning grafts for more than 3 years (6.7 +/- 2.8 years). Twenty-eight patients with histological CAN were compared with 100 patients who had no clinical evidence of chronic rejection (no proteinuria and sCr < 2.5 mg%). As expected, univariate analysis revealed that patients with CAN experienced a greater acute rejection rate (78% vs 21%; P=.001), a higher serum creatinine (3.6 +/- 1.7 vs 1.4 +/- 0.5 mg%; P=.0001), and an older organ donor (43 +/- 20 vs 29 +/- 13 years; P=.0001). The lipid profiles (total cholesterol and triglycerides levels) were similar in both groups with 60% in each group receiving anti-lipemic drugs. Interestingly, the ApoE epsilon 4 allele was overrepresented in the group with CAN (39% vs 17%, P=.019). Logistic regression analysis showed that the epsilon 4 allele was an independent predictor of CAN (OR: 3.4; CI 95%: 1.07 to 11; P=.040) as were donor age and acute rejection episodes. In conclusion, an interaction between risk factors and genetic factors may determine CAN in this population. This finding may help to target prophylactic interventions in these recipients.

Transplant aspirative cytology: analysis of morphological and immunocytochemical parameters in renal allograft dysfunction.

We have analyzed 245 transplant aspirative cytologies (TACs) from 96 renal allograft patients. TACs were divided in two chronological groups: Early (TACs performed during the first 3-mo posttransplantation) and late (TACs performed after the third month post-transplantation), in order to assess the effect of allograft tolerance on TAC features. Both morphological and immunocytochemical aspects were evaluated, including CD4, CD8, IL2-R, and HLA-DR immunolabeling. A final diagnosis for each case of allograft dysfunction was achieved by other independent diagnostic means. Four diagnostic groups were considered in the present study: acute rejection (AR), chronic rejection (CR), acute tubular necrosis (ATN), and Cyclosporin A toxicity (CsA-T). In addition, a control group (C) was established from patients with stable allograft function. We found that immunocytochemical analysis of TACs is particularly helpful in the diagnosis of late allograft dysfunction, a time period when the simple cytological study of renal infiltrate is not informative enough to help take therapeutic decisions.

[A study using nondecalcified bone biopsy of the incidence and presentation forms of renal osteodystrophy]. / Estudio con biopsia ósea sin descalcificar de la incidencia y formas de presentación de la osteodistrofia renal.

BACKGROUND: Renal osteodystrophy (ROD) is a common complication of chronic renal failure. Fibrous osteitis and, to a lesser extent, osteomalacia are the predominant lesions. The aim of the present study was to evaluate the prevalence of the different forms of ROD. METHODS: Nondecalcified bone biopsies were evaluated in 100 patients with end-stage renal disease (57 in pre-dialysis and 43 on hemodialysis) in whom biochemical (calcium, phosphorus, alkaline phosphatase, parathyroid hormone) and histomorphometric studies were carried out. Bone biopsies were classified in four histological groups: mild, fibrous osteitis (FO), osteomalacia (OM) and mixed type (FO + OM). RESULTS: 96% of patients had histological findings of ROD with the following distribution: 41% mild; 30% FO; 14% OM; and 11% mixed. The most advanced types of ROD were seen in interstitial renal diseases. Pre-dialysis OM was associated with metabolic acidosis, a low phosphocalcic product and relative hypophosphoremia. Chronic aluminium poisoning was uncommon (7%) and was basically associated with OM. No instance of aluminium poisoning with osteodystrophy and bone fractures was seen. CONCLUSIONS: The most severe histological forms of OM were found in hemodialysis patients with persistent hypophosphoremia and associated with osteosclerosis.

[Recovery of kidney function in a female patient with severe lupus nephropathy]. / Recuperación de la función renal en una paciente con nefropatía lúpica severa.

The evolution of Lupus Nephritis to end-stage chronic renal failure is a frequent event. We report the case of a 28 years old patient with diffuse proliferative lupus nephritis with crescents formation and rapid decline of renal function without response to steroids, immunosuppressors and plasmapheresis. After 10 weeks of continued hemodialysis, during which the patient received 30 mg of prednisone in alternate days, renal function recovered spontaneously, and after 1 year of follow-up plasma creatinine is maintained in 2.5 mg/dl.

Síndrome de Goodpasture asociado con vasculitis cerebral ANCA negativa / Goodpasture´s syndrome with neurologic involvement and negative ANCA

El síndrome de Goodpasture (SGP) es una rara entidad de base inmunológica, caracterizada por la asociación de una glomerulonefritis rápidamente progresiva (GNRP) y hemorragia alveolar en presencia de anticuerpos antimembrana basal. La afectación del sistema nervioso central (SNC) enel SGP es extremadamente infrecuente en ausencia de ANCA. Presentamos el caso de un paciente de 20 años que comenzó con una GNRP acompañada de esputos hemoptoicos y dos episodios de crisis convulsivas tónico-clónicas generalizadas, en presencia de elevados títulos de anticuerpos antimembrana basal glomerular (Ac-anti-MBG).Tras tratamiento inmunosupresor asociado con plasmaféresis, el paciente presentó descenso de los títulos de Acanti-MBG, así como mejoría de los síntomas neurológicos y respiratorios, aunque sin recuperación de la función renal, permaneciendo en programa de hemodiálisis. Veinte meses más tarde, con la enfermedad en remisión, el paciente recibió un trasplante renal de cadáver (AU)

Goodpasture's syndrome is a rare autoimmune disorder characterized by rapidly progressive glomerulonephritis (RPGN) and alveolar hemorrhage in the presence of antiglomerular basement membrane (anti-GBM) antibodies. Central nervous system involvement is highly unusual in the absence of anti-neutrophil cytoplasmic antibodies. Were port the case of a 20-year-old man with RPGN accompanied by bloody sputum, tonic-clonic seizure and high titers of anti-GBM antibody. After treatment with immune suppressants and plasmapheresis, the patient showed reduced anti-GBM antibody titers and improved neurologic and respiratory symptoms, but renal failure persisted, requiring hemodialysis. Twenty months later, with the disease in remission, he underwent deceased-donor renal transplantation (AU)