[Experimental pancreatic islet transplant into the genito-urinary tract simultaneous to kidney transplant]. / Trasplante experimental de islotes de pancreas en el tracto genitourinario asociado al trasplante renal.

INTRODUCTION AND OBJECTIVES: Simultaneous kidney and pancreas transplant is a good treatment for both renal and pancreas insufficiency. Experimental apply of genitourinary tract for pancreas implantation is reported in this work. MATERIAL AND METHOD: Twenty animals aged as average 5.5 monts (SD 1.1) and an average weight of 53 kgr were submitted to this protocol. In the day 1 a left nephrectomy is completed and the graft is perfused with University of Wisconsin solution. A partial pancreatectomy is completed at following, isolation of pancreatic islets by colagenase enzymatic digestion. Islets are dryed with Ditizone and culptured for 24 hours at 37 degrees C and 5% CO2. Day-2 a right nephrectomy is performed and orthotopic renal autotransplant using the left kidney is completed. Pancreatic islets are transplanted in 4 different locations of the genitourinary tract: renal subcapsular space, bladder submucosae, testis parenchyma and vas deferens. Day-7, all the animals were sacrifized to complete pathological study. RESULTS AND CONCLUSIONS: Viable islets were isolated in bladder submucosae and testis after transdeferential injection.

Trasplante experimental de islotes de páncreas en el tracto genitourinario asociado al trasplante renal / Experimental pancreatic islet transplant into the genito-urinary tract simultaneous to kidney transplant

Conceptualmente el trasplante de páncreas (TP) asociado al trasplante renal (TR) puede resolver la insuficiencia renal crónica (IRC) y la diabetes (DM). Aunque el lugar de implantación más frecuentemente utilizado es la vena porta, el tracto genitourinario puede ser adecuado desde un punto de vista técnico durante el TR. 20 animales con una edad media de 5,5 (SD 1,1) meses y una mediana de peso de 53 (30,102) kg se sometieron al siguiente protocolo experimental. El primer día, se lleva a cabo la nefrectomía izquierda y el injerto es perfundido con solución de Wisconsin, lo que se sigue de una pancreatectomía distal y el aislamiento de islotes por medio de la digestión enzimática con Colagenasa. Los islotes son teñidos con el colorante vital Ditizona (DTZ) y cultivados durante 24 horas a 37º y 5% de Co2. El día 2 se realiza la nefrectomía derecha y un TR ortotópico del injerto renal izquierdo preservado. Los islotes son trasplantados en 4 localizaciones diferentes en el tracto genitourinario: el espacio subcapsular del injerto renal, en la submucosa de vejiga, en el parénquima testicular y por vía deferencial. El día 7, los animales son sacrificados para estudio histopatológico. Se demostraron islotes viables en la submucosa vesical y en el testículo tras infusión por vía deferencial

Introduction and objectives: Simultaneous kidney and pancreas transplant is a good treatment for both renal and pancreas insufficiency. Experimental apply of genitourinary tract for pancreas implantation is reported in this work. Material and method. Twenty animals aged as average 5.5 monts (SD 1.1) and an average weight of 53 kgr were submitted to this protocol. In the day 1 a left nephrectomy is completed and the graft is perfused with University of Wisconsin solution. A partial pancreatectomy is completed at following, isolation of pancreatic islets by colagenase enzymatic digestion. Islets are dryed with Ditizone and culptured for 24 hours at 37ºC and 5% CO2. Day-2 a right nephrectomy is performed and orthotopic renal autotransplant using the left kidney is completed. Pancreatic islets are transplanted in 4 different locations of the genitourinary tract: renal subcapsular space, bladder submucosae, testis parenchyma and vas deferens. Day-7, all the animals were sacrifized to complete pathological study. Results and conclusions: Viable islets were isolated in bladder submucosae and testis after transdeferential injection

Pancreas islet transplantation in the genitourinary tract associated with renal transplantation: an experimental study.

Conceptually, pancreas islet transplantation (PIT) associated with renal transplantation (RT) should resolve not only chronic renal failure but also diabetes. Although the most frequently used site for PIT is the portal vein, genitourinary locations could be technically feasible during RT. Seventeen pigs (age 3 to 4 months; mean weight 34.5 kg) underwent the following experimental steps: On day 1 a left nephrectomy was performed and the kidney was perfused with cold Wisconsin solution. This was followed by a caudal pancreatectomy and islet isolation by means of digestion with intraductal collagenase. Islets were stained with Dithizone and cultured overnight al 37 degrees C and 5% CO(2). On day 2 a right nephrectomy and orthotopic RT of the preserved left kidney were performed. The islets were transplanted into four different sites: subcapsular in the kidney graft, in the bladder submucosa, in the testis by puncture, and in the testis by infusion through the vas deferens. On day 7 the animals were sacrificed. Islet viability was determined by histological examination with insulin immunostaining and determination of insulin in the blood of the veins draining the implantation sites. The mean weight of the pancreatic specimens was 27.8 g (13 to 46). The mean number of islets was 536,000 (16,600 to 1,5000,000). Islets were shown in the bladder submucosa and the testes after vas deferens infusion. The number of viable islets in the other implantation sites was very scarce. The insulin levels of the venous effluents were: 15.1 microU/mL for bladder submucosa, 10.2 microU/mL for intradeferential injection in the testis, 7.3 microU/mL for intratesticular injection by puncture, and 2.6 microU/mL for subcapsular implantation in the graft. In conclusion, the bladder submucosa and testis via the vas deferens might represent alternative sites for PIT. The latter route may benefit from the immunoprivileged and special trophic conditions of the testis. For the first time, the feasibility of the bladder submucosa as an implantation site for pancreas islets was demonstrated.

Recurrent acute postinfectious glomerulonephritis.

Recurrent acute postinfectious glomerulonephritis is infrequent in childhood and exceptional in adults. The factors that determine recurrence are poorly understood. Selective IgA deficiency is characterized by an increased incidence of gastrointestinal and respiratory infections. The case of a 33-year-old man with a history of repetitive sinopulmonary infections and diagnosed with selective IgA deficiency is described. He suffered 2 episodes of postinfectious glomerulonephritis within a 15-year period. Selective IgA deficiency may have predisposed to the development of recurrent postinfectious glomerulonephritis

[Tubulointerstitial nephritis associated with treatment with selective Cox-2 inhibitors, celecoxib and rofecoxib]. / Nefritis tubulointersticial asociada al tratamiento con inhibidores de la Cox-2, celecoxib y rofecoxib.

The nephrotoxic effect of nonselective nonsteroidal anti-inflamatory drugs (NSAIDS) has been widely described. The main benefit of the Cox-2 inhibitors in relation to the NSAIDS is the production of a very similar analgesic effect, but with fewer gastrointestinal side effects. However, their effects on renal function are little known as yet and their long-term safety is still pending definition. The use of selective Cox-2 inhibitors as anti-inflamatory analgesic is becoming more and more common in our environment. We report two cases of tubulointersticial nephritis confirmed by renal biopsy, associated with administration of the two Cox-2 inhibitors currently available on the market, celecoxib and rofecoxib. In both cases, we were talking about elderly women, with deterioration of the general condition and acute renal failure. In the former case, renal biopsy showed an acute tubulo-intersticial nephritis (TIN) so highly "variegated" in its histologic expression. In the second case, was associated with strong indications of chronicity. Treatment with steroid was initiated in both patients and improvement of renal function was observed.

Nefritis tubulointersticial asociada al tratamiento con inhibidores de la Cox-2, celecoxib y rofecoxib / Tubulointerstitial nephritis associated with treatment with selective cox-2 inhibitors, celecoxib and rofecoxib

El efecto nefrotóxico de los inhibidores selectivos de la Cox-2 es poco conocido. Elprincipal beneficio de los inhibidores de la Cox-2 con respecto a los AINES clásicos esla producción de un efecto analgésico muy similar, pero con menos efectos secundariosa nivel gastrointestinal. Sin embargo, sus efectos sobre la función renal son pococonocidos todavía y su seguridad a largo plazo está todavía por definir. El uso de inhibidoresselectivos de la Cox-2 como analgésicos y antiinflamatorios es cada vez másfrecuente en nuestro medio. Nosotros referimos dos casos de nefritis tubulointersticialconfirmadas por biopsia renal, asociadas a la toma de los dos inhibidores de la Cox-2comercializados en la actualidad, celecoxib y rofecoxib. Ambos se presentaron enmujeres de edad avanzada, cursaron con importante afectación del estado general yfracaso renal agudo. En el primer caso, la biopsia renal mostró una nefritis tubulointersticialaguda (NTI) muy abigarrada en su expresión histológica. En el segundo, seasoció con importantes datos de cronicidad. Los dos casos se trataron con esteroidescon buena evolución de la función renal

The nephrotoxic effect of nonselective nonsteroidal anti-inflamatory drugs(NSAIDS) has been widely described. The main benefit of the Cox-2 inhibitors in relationto the NSAIDS is the production of a very similar analgesic effect, but with fewergastrointestinal side effects.However, their effects on renal function are little known asyet and their long-term safety is still pending definition. The use of selective Cox-2 inhibitorsas anti-inflamatory analgesic is becoming more and more common in our environment. We report two cases of tubulointersticial nephritis confirmed by renalbiopsy, associated with administration of the two Cox-2 inhibitors currently availableon the market, celecoxib and rofecoxib. In both cases, we were talking about elderlywomen, with deterioration of the general condition and acute renal failure. In the formercase, renal biopsy showed an acute tubulo-intersticial nephritis (TIN) so highly«variegated» in its histologic expression. In the second case, was associated withstrong indications of chronicity. Treatment with steroid was initiated in both patientsand improvement of renal function was observed

Spanish experience with cyclosporine.

Our experience with cyclosporine (CsA) in de novo renal transplantation (RT) may be systematized in four consecutive periods. From February 1986 to December 1989, patient survival was higher among 128 consecutive CsA-prednisone-treated cadaver allograft recipients than in previous patients on azathioprine. One-year graft survival was significantly higher in CsA patients, a difference that was thereafter progressively reduced: at 10 years graft survivals were 50% versus 45%, and at 15 years 37% versus 35%, respectively. The most frequent cause of graft loss was death with a functioning graft. Acute rejection caused more graft losses among Aza-treated patients than CsA-treated ones. However, chronic allograft nephropathy produced more graft losses in CsA patients. After this initial experience with CsA-based immunosuppression we developed a second phase in which better results were obtained in 209 first cadaveric RT recipients. The use of lower initial CsA doses, more rapid steroid tapering, and a better approach to CsA nephrotoxicity or chronic nephropathy by substantial reductions in CsA exposure and delayed azathioprine addition, lead to these improvements. From March 1995 through 2000, we used the new microemulsion CsA formulation (Neoral) with steroids or azathioprine in 110 first de novo RT recipients. Mean donor and recipient ages were significantly higher in this phase than in previous ones; consequently, survival and function results were slightly worse. Blood CsA concentrations measured 2 hours after administration represent a more precise predictor of exposure than trough concentrations. The last step in optimizing Neoral use in RT on our service was application of reduced-dosage with C2 monitoring instead of classical C0 testing. Acute rejection and treatment failure rates were low and renal allograft function improved with respect to previous full-dose C0 experiences. CsA use has evolved in these two decades in four consecutive phases. Short-term results have improved or been maintained from phase to phase, even with expanded-criteria donors until excellent features during last years with C2 monitoring and combination with potent drugs such as MMF or everolimus. During the coming years, new drugs and protocols will allow even more optimized use.

Retinoids as a potential treatment for experimental puromycin-induced nephrosis.

1 Puromycin aminonucleoside (PAN)-induced nephrosis is a model of human minimal change disease. In rats, PAN induces nephrotic-range proteinuria, renal epithelial cell (podocyte) damage, infiltration of mononuclear leukocytes, and apoptosis of several renal cell types. 2 Retinoic acid (RA) modulates a wide range of biological processes, such as inflammation and apoptosis. Since renal damage by PAN is characterized by inflammatory infiltration and epithelial cell death, the effect of treatment with all-trans RA (tRA) was examined in the PAN nephrosis model and in the cultured differentiated podocyte. 3 Treatment with tRA 4 days after PAN injection did not inhibit the proteinuria peak but reversed it significantly. However, treatment with tRA both before and 2 days after the injection of PAN protected the glomerular epithelial cells, diminishing the cellular edema and diffuseness of the foot process effacement. Preservation of the podocyte architecture correlated with the inhibition of proteinuria. The anti-inflammatory effect of tRA was evidenced by the inhibition of PAN-induced interstitial mononuclear cell infiltration and the decreased renal expression of two molecules involved in monocyte infiltration: fibronectin and monocyte chemoattractant protein-1. TUNEL assays showed that tRA inhibited the PAN-induced apoptosis of cultured differentiated mouse podocytes. 4 We conclude that tRA treatment may prevent proteinuria by protecting the podocytes from injury and diminishing the interstitial mononuclear infiltrate in the model of PAN nephrosis. Retinoids are a potential new treatment for kidney diseases characterized by proteinuria and mononuclear cell infiltration.

[Minimal-change disease with mesangial IgA deposits associated with Sjogren syndrome]. / Enfermedad de cambios mínimos con depósitos mesangiales de IgA asociada a síndrome de Sjögren.

Sjögren's syndrome may be accompanied by a dysregulation of IgA system implying the presence of increased serum polymeric IgA or circulating immune complexes and their consequent deposition within the kidney. In this context IgA nephropathy may only represent one of the complications brought by IgA deposition. Glomerular involvement and primary Sjögren's syndrome has been described previously only in isolated case reports, membranous nephropathy and membranoproliferative glomerulonephritis have been reported. We have not found any case of minimal change disease and glomerular IgA deposition associated with Sjögren's syndrome. In this patient nephrotic syndrome was related to serum increase of CA 19-9; this association has been reported in only three previous cases.

Glomerulonefritis membranosa en un caso de artritis reumatoide no tratada con oro ni D-penicilamina / Membranous glomerulonephritis in rheumatoid arthritis not treated with gold salts or D-penicillamine

El desarrollo de glomerulonefritis membranosa (GM) es relativamente frecuente en pacientes con artritis reumatoide (AR) tratados con fármacos antirreumáticos de acción lenta (FARAL) como las sales de oro o la D-penicilamina. Por otro lado, se han descrito casos de GM en sujetos con esta enfermedad no tratados con dichos fármacos. Estos casos son poco frecuentes según la bibliografía revisada. Describimos un caso de AR que desarrolla una GM sin haber recibido previamente tratamiento con ningún tipo de FARAL (AU)

[Acute interstitial nephritis caused by clozapine]. / Nefritis intersticial aguda inducida por clozapina.

We are reporting a case of a 69 years old man developed acute renal failure due to interstitial nephritis during treatment with the drug clozapine, and that improve after to discontinuation of this drug. The clozapine is a new antipsychotic drug that may produce severes adverses reactions, like medullary toxicity. Recently 10 cases of clozapine-induced AIN have been reported. We want to associate to the cases publicated with a new case because it is a severe adverse reaction.

Enfermedad de cambios mínimos con depósitos mesangiales de IgA asociada a síndrome de Sjögren / Minimal changes disease with mesangial deposits of IgA associated to Sjögren syndrome

El síndrome de Sjögren se acompaña de una disfunción del sistema inmune que da lugar a un aumento de la IgA polimérica y los complejos inmunes IgA circulantes, secundariamente se produce el depósito de estos a nivel mesangial y la asociación con nefropatía IgA. Otras formas de afectación glomerular en el síndrome de Sjögren primaria son muy infrecuentes, se han descrito casos aislados de glomerulonefritis membranosa (GNM) y glomerulonefritis membranoproliferativa (GNMP).Revisando la literatura, no hemos encontrado ningún caso con enfermedad de cambios mínimos y depósitos de IgA en la biopsia renal asociada a síndrome de Sjögren, lo que convierte este caso en excepcional.En este paciente, el síndrome nefrótico se acompañó de una elevación del marcador tumoral CA 19-9, sin neoplasia asociada. Se han descrito previamente tres casos de síndrome de Sjögren y elevación de CA 19-9 (AU)

Nefritis intersticial aguda inducida por clozapina / Clozapine-induced acute interstitial nephritis

Describrimos el caso de un paciente de 69 años que desarrolla un fracaso renal debido a nefritis intersticial (NIA) coincidiendo con el inicio de tratamiento con clozapina y que mejora tras la retirada de este fármaco. La clozapina es un fármaco antipsicótico nuevo con efectos secundarios graves como toxicidad medular. Recientemente se han descrito en la literatura diez casos de fallo renal agudo secundario (NIA) durante el tratamiento con clozapina. Nosotros queremos sumarnos a los ya publicados con un nuevo caso dado que se trata de un efecto secundario grave (AU)

Outcome of cadaveric renal transplant patients treated for 10 years with cyclosporine: is chronic allograft nephropathy the major cause of late graft loss?

BACKGROUND: The introduction of cyclosporine (CsA) has improved the short-term outcome of renal transplantation, but its effect on the long-term survival is not well known. METHODS: We analyzed 128 cadaveric first renal transplant recipients with CsA and prednisone as basal immunosuppression followed for at least 10 years, and we have compared them with a group of 185 historical patients treated with azathioprine (Aza) and prednisone. RESULTS: The 1-year graft survival was 83% in the CsA-treated patients and 68% in the Aza-treated patients (P<0.025), and the differences were significant for 3 years. Acute rejection accounted for the 10.9% of losses in CsA-treated patients and for 23.8% of losses in Aza-treated patients (P=0.046). Chronic allograft nephropathy was the cause of graft losses in 40.6% and 16.8% of cases (P=0.008). Patient survival at 5 years was 88% in CsA-treated patients and 79% in the Aza-treated patients (P<0.025). When analyzing the data of the 64 CsA-treated patients and the 84 Aza-treated patients with one functioning graft at 10 years, mean serum creatinine values were significantly higher in the CsA-treated patients at all time points but the increases were not significantly different. At 10 years, mean blood pressure was higher (P=0.002), and hypercholesterolemia (P=0.011) and hyperuricemia (P=0.000) were more prevalent in the CsA-treated patients. CONCLUSIONS: CsA resulted in a better short-time patient and graft survival that was not maintained in the long-term outcome. Chronic allograft nephropathy was the leading cause of graft loss in CsA-treated patients. Graft function was poorer in the CsA-treated patients, but its decline was similar in the two groups.

Tubulointerstitial nephritis and asymptomatic uveitis.

We describe a case of a 10 year-old boy who had fever, weakness, anorexia, weight loss and general malaise. No other remarkable symptoms were present. He had been treated with Aspirin and Ibuprofen. Deterioration of renal function, glucosuria, proteinuria, anemia and increased erythrocyte sedimentation rate were detected. After 7 days observation with no treatment, renal function worsened, glucosuria increased and fever persisted. A renal biopsy was performed and acute tubulointerstitial nephritis was diagnosed. The most common aetiologies of this entity were excluded. An ophthalmologic study revealed bilateral anterior uveitis, therefore the patient was diagnosed as having tubulointerstitial nephritis with uveitis. The child improved on corticosteroid therapy, but uveitis relapsed when treatment was stopped.

[Nanobacteria. An experimental neo-lithogenesis model]. / Nanobacteria. Un modelo de neo-litogénesis experimental.

OBJECTIVE: To study the phenomenon of biomineralization in an experimental model of lithogenesis by percutaneous renal punction without laparotomy and no antibiotics. METHODS/RESULTS: The study comprised 4 Brown-Norway rats. Nanobacteria inoculum (X, 2X and 4X) was administered to three rats and the remaining one was used as control. The analytical and radiological findings showing the development of obstructive pyelocaliceal lithiasis in the kidneys of rats no. 2 and 3 are presented. CONCLUSIONS: Translumbar percutaneous renal puncture has permitted performing laparotoy without antibiotic coverage, which was the main difficulty of the experimental model of lithogenesis. Nanobacteria were cultured successfully, but not without difficulty, and formation of calculi in the rat pyelocaliceal system was achieved. This experimental model will provide further insight into lithogenesis and will allow us to find the answers to some of the many questions concerning this condition that remain.