Cocaine/levamisole-induced systemic vasculitis with retiform purpura and pauci-immune glomerulonephritis

Levamisole has been increasingly used as an adulterant of cocaine in recent years, emerging as a public health challenge worldwide. Levamisole-associated toxicity manifests clinically as a systemic vasculitis, consisting of cutaneous, hematological, and renal lesions, among others. Purpura retiform, cutaneous necrosis, intravascular thrombosis, neutropenia, and less commonly crescentic nephritis have been described in association with anti-neutrophil cytoplasmic antibodies (ANCAs) and other autoantibodies. Here we report the case of a 49-year-old male who was a chronic cocaine user, and who presented spontaneous weight loss, arthralgia, and 3 weeks before admission purpuric skin lesions in the earlobes and in the anterior thighs. His laboratory tests on admission showed serum creatinine of 4.56 mg/dL, white blood count 3,800/μL, hemoglobin 7.3 g/dL, urinalysis with 51 white blood cells/μL and 960 red blood cells/μL, and urine protein-to-creatinine ratio 1.20. Serum ANCA testing was positive (>1:320), as well as serum anti-myeloperoxidase and anti-proteinase 3 antibodies. Urine toxicology screen was positive for cocaine and levamisole, with 62.8% of cocaine, 32.2% of levamisole, and 5% of an unidentified substance. Skin and renal biopsies were diagnostic for leukocytoclastic vasculitis and pauci-immune crescentic glomerulonephritis, respectively. The patient showed a good clinical response to cocaine abstinence, and use of corticosteroids and intravenous cyclophosphamide. Last serum creatinine was 1.97 mg/dL, white blood cell count 7,420/μL, and hemoglobin level 10.8 g/dL. In levamisole-induced systemic vasculitis, the early institution of cocaine abstinence, concomitant with the use of immunosuppressive drugs in severe cases, may prevent permanent end organ damage and associate with better clinical outcomes.

Exposición crónica a hidrocarburos y glomerulopatías en humanos: [revisión] / Chronic exposure to hydrocarbons and glomerular diseases in humans: [review]

Los hidrocarburos representan una gran variedad de compuestos que tienen en su estructura sólo carbono e hidrógeno y pueden ser considerados como las moléculas principales de las que derivan todos los demás compuestos orgánicos. Las exposiciones breves e incidentales pueden ser relativamente inocuas, sin embargo las exposiciones prolongadas pueden ser tóxicas. Neuquén es la provincia del país con la prevalencia más elevada de pacientes en diálisis (superior a 800 pacientes por millón de habitantes) y una alta incidencia de enfermedad renal crónica estadio 5 (mayor a 190 pacientes por millón de habitantes). Presenta además una prevalencia notablemente elevada de glomerulopatías primarias. En Neuquén se desarrolla una importante actividad hidrocarburífera, lo que nos lleva a cuestionarnos si existe asociación entre ambas condiciones. Revisamos la evidencia disponible en la literatura sobre la relación existente entre exposición crónica a hidrocarburos en el desarrollo y progresión de glomerulopatías en humanos.

Immunoglobulin M nephropathy nephropathy in adults and adolescents in India: A single-center study of natural history.

Background: Immunoglobulin M nephropathy (IgMN) is an idiopathic glomerulonephritis (GN) usually presenting clinically as steroid resistant/dependent nephrotic syndrome (NS) with pathology of mesangial proliferative GN or focal and segmental glomerulosclerosis with diffuse predominant mesangial IgM deposits. Not much information is available about its natural history. This is the first Indian study to our knowledge on IgMN in adults and adolescents. Materials and Methods: We evaluated renal biopsies performed at our center between January,'04 to September,'09. Biopsies of all adolescents and adults were evaluated for IgMN and we studied their age, gender distribution, blood pressure (BP), disease duration, steroid/immunosuppressive management and serial serum creatinine (SCr), urinary proteins, and BP values. Patients with other systemic diseases/infections and children were excluded. Results: IgMN constituted 4.3% of 2702 adult renal biopsies. No significant gender predilection was noted. Males presented at average age of 23.1 years, females at 30 years. Steroid-dependent NS was the commonest presentation noted in 75% followed by steroid-resistant NS. Hypertension was noted in 10% patients. Mesangial proliferative GN (MePGN) was commonest histopathological finding noted in 74.4%, followed by focal segmental glomerulosclerosis (FSGS) in 16.2%, and minimal change disease (MCD) in 9.4% biopsies. Sole IgM deposits were noted in 88.5%. All MCD, 35.6% MePGN reached remission, FSGS progressed to renal failure by 1 year. Hypertension, proteinuria, interstitial fibrosis, and FSGS were bad prognosticators. Conclusions: This is the first Indian study of IgMN in adults and adolescents carried out over a period of 5.8 years, which has shown that hypertension, proteinuria, and interstitial fibrosis at presentation have bad prognosis.

Desenvolvimento e patogenia da glomerulonefrite na leishmaniose visceral em camundongo / Development and pathogeny of glomerulonephritis in visceral leishmaniasis in mouse

Foi estudado desenvolvimento e patogenia da glomerulonefrite em camundongos BALB/c infectados intraperitonealmente com Leishmania (L.) chagasi. Nós observamos hipercelaridade glomerular dos 7 aos 30 dias pós-infecção (PI). Foram observados depósitos de IgG no glomérulo aos 7 dias PI. A presença de células CD11+ e F4/80+ e a expressão de caspase 3 clivada aumentou progressivamente em glomérulos dos 7 aos 15 dias PI. As células T CD4+ e CD8+ foram detectadas em glomérulos no mesmo período. Os resultados sugerem que IgG e vários elementos celulares assim como um processo apoptótico ativo contribuem na patogenia da glomerulonefrite na leishmaniose visceral em camundongo / Development and pathogenesis of glomerulonephritis in BALB/c mice infected intraperitoneally with Leishmania (L.) chagasi were studied. We observed glomerular hipercellularity from 7 through 30 days post-infection (PI). IgG deposits were observed in glomeruli at 7 days PI. Presence of CD11+ and F4/80+ cells and cleaved caspase 3 expression increased progressivelly in glomeruli from 7 through 15 days PI. CD4+ and CD8+ T cells were detected in glomeruli in the same period. The results suggest that IgG and various cellular elements besides an active apoptotic process contribute in the pathogenesis of glomerulonephrisis in murine visceral leishmaniasis...

Renal dysfunction in patients of kala azar treated with sodium antimony gluconate.

We studied 27 patients presenting with renal dysfunction after Stibamate therapy. Eighteen patients were proved cases of Kala Azar, others of PUO. Out of 10 cases in whom Kidney biopsy was done, 6 had tubular necrosis, one had mild mesangial proliferation and 3 had normal picture.

Reduction of urine volume ameliorates adriamycin-induced nephropathy

1. Adriamycin, a commonly used antineoplastic antibiotic, induces glomerular lesions in rats, resulting in persistent proteinuria and glomerulosclerosis. 2. The effect of urine volume on the progression of adriamycin-induced nephropathy was studied in 70 male Wistar rats (180-200 g) observed for 30 weeks and separated into 4 groups: healthy control group (HCG, N = 10) inoculated i.v. with 1 ml of saline, and nephrotic groups inoculated iv with a single dose of adriamycin of 3 mg/kg body weight. The nephrotic rats were separated into 3 groups (N = 20): nephrotic control group (NCG) receiving only adriamycin; dehydrated nephrotic group (DNG) water deprived for 36 h within each 48-h period, and furosemide nephrotic group (FNG) treated with 12 mg/dl furosemide, and 0.9 g/dl NaCl in the drinking water. 3. The 30-week survival rates of the DNG (100 per cent ) and HCG (100 per cent ) were significantly higher than those of the NCG (85 per cent ) and FNG (55 per cent ). 4. The proteinuria observed in the HCG (range, 7.38 +/- 0.7 to 13.6 +/- 1.27 mg/24 h) was significantly lower than that observed for all the nephrotic groups throughout the experiment. The DNG presented significantly less proteinuria (range, 42.71 +/- 6.83 to 140.10 +/- 19.22 mg/24 h) than the NCG (range, 35.32 +/- 7.64 to 250.00 +/- 25.91 mg/24 h) from week 10 on. There was no significant difference between the mean 24-h proteinuria of the NCG (range, 35.32 +/- 7.64 to 250.00 +/- 25.91 mg/24 h) and the FNG (range, 35.82 +/- 7.91 to 221.54 +/- 26.74). 5. The mean frequency of damaged glomeruli was 0.3 per cent +/- 0.3 for HCG, 42 per cent +/- 6 per cent for CNG, 40.8 per cent +/- 8 per cent for DNG, and 47 per cent +/- 14 per cent for FNG. The median value of the tubulointerstitial lesion, evaluated by a semiquantitative method, was 0 in HCG, 10 in CNG, 8.5 in DNG and 9.5 in FNG (P < 0.05 for all groups compared to HCG). 6. The data indicate that reduction of urine volume has a protective effect on adriamycin-induced nephropathy

Induction of immune complex glomerulonephropathy in rabbits exposed to formalin vapour: a condition resembling human goodpastures syndrome

Forty two rabbits were used to induce glomerulonephropathy by exposure to 10% formalin vapour. Seven groups of rabbits were exposed to formalin vapour at a rate of twenty three hours per day and one hour ventilation for eight successive months. The results showed that IgG was deposited in 50% of the glomeruli accompanied by histological changes occurred in most of the glomerular tufts. The lesions all together resembeled Goodpastures syndrome of man

Nefropatía atribuible a penicilamina en una paciente con enfermedad de Wilson / Nephropathy to D-penicillamine attributable on patients of Wilson's disease

Se presenta una mujer de 20 años de edad tratada con 2000 mg/día de DPA desde los 17 años por enfermedad de Wilson. Consultó en agosto de 1988: tenía artropatía, hematuria parda, fiebre, amenorrea, úlcera de lengua, pancitopenia, FAN y anti-DNA positivos, síndrome nefrótico y función renal alterada con antiestreptolisina O, hepatograma, coagulograma, completo y tensión arteriales normales. Al suspender DPA desaparecieron la artropatía, la úlcera de lengua y la fiebre y se negativizaron FAN y anti-DNA. En setiembre de 1988 tuvo fiebre y disnea con infiltrado parahiliar izquierdo algodonoso; se descartaron colagenopatías e infecciones, remitiendo en forma espontánea. La biopsia renal mostró alteraciones avanzadas de una glomerulonefritis necrotizante y proliferativa, moderada arteriolonefroesclerosis y ausencia de inmunodepósitos. Recibió pulsos de corticoides y ciclofosfamida sin beneficio. En los seis meses siguientes desapareció la hematuria, reapareció el período menstrual y redujo la proteinuria. Al reiniciar la DPA aumento la proteinuria, suspendiéndose la droga. En julio de 1989 la proteinuria era moderada y la creatinina normal. No se describe glomerulopatía asociada al Wilson; los síntomas y la serología de LES desaparecieron al suprimir la droga. El síndrome urinario, el síndrome pulmonar sin hemoptisis que coincidió con deterioro de la función renal al momento de la biopsia y el tipo de lesión, hallada en la paciente permitirían inscribir este cuadro entre las formas atípicas de púrpura pulmonar y nefritis, cuya incidencia fue estimada en menos del 0,5%en pacientes tratados con DPA por enfermedad de Wilson

Effect of polychlorinated biphenyl (Aroclor 1260) on histology of kidney and thyroid of rats.

Gross histological alteration in kidney and thyroid structures were observed in male Wistar rats fed polychlorinated biphenyls (PCBs; Aroclor 1260) at 50 and 100 ppm level in normal commercial diet for 120 days. While the kidney showed glomerulonephritis, degenerative changes in the proximal and distal tubules and increased cellularity of glomeruli, thyroid showed degeneration of follicles, fibrosis of follicles and lymphocytic infiltration followed by thyroiditis.

Glomerulonefritis y su posible asociación con hidrocarburos / Glomerulonephritis and its possible association with hydrocarbons

Se informa que en los últimos años diversas drogas y productos químicos han sido señalados como tóxicos o potencialmente lesivos para el riñón, la mayoría de ellos, más que afección glomerular, lo que produce es un daño tubular. Se expresa que informes recientes han llamado la atención de la posible asociación entre enfermedades glomerulares o exposición a hidrocarburos y petroderivados. Se presentan 3 ejemplos clínicos de enfermedad glomerular primaria que tenían como elemento común una larga historia de exposición crónica a los hidrocarburos. Se indica que por microscopia de luz, uno de los enfermos mostraba glomerulonefritis proliferativa mesangial; otro, una glomerulosclerosis global focal y el tercero desarrolló una glomerulonefritis proliferativa endo y extracapilar difusa, lo que se comportó como un síndrome rápidamente progresivo. Se revisan las hipótesis actuales acerca de la posible relación causal entre afección glomerular y exposición mantenida a los petroderivados. Se sugiere que se efectúen estudios ulteriores de mayor envergadura, con el fin de precisar la verdadera magnitud de esta probable concordancia patogénica