Scleritis and sclerokeratitis associated with IgA vasculitis: A case series.

PURPOSE: To describe a case series of scleritis associated with IgA vasculitis (IgAV) at a tertiary referral center. OBSERVATIONS: Three men with scleritis associated with IgAV were identified: one with anterior scleritis alone, one with anterior scleritis and peripheral ulcerative keratitis (sclerokeratitis), and one with anterior and posterior scleritis. Visual acuity was preserved except from the patient who developed posterior scleritis. Ocular pain was the main symptom at presentation. All patients had a previous history of palpable purpura, but only one was aware of his underlying IgAV. Laboratory results revealed microhematuria and proteinuria with normal urinary ß2 microglobulin levels and negative serum ANCAs. Skin or kidney biopsy demonstrated leukocytoclastic vasculitis or glomerulonephritis with dominant IgA immune deposits. CONCLUSIONS AND IMPORTANCE: Although uncommon, IgAV should be included in the differential diagnosis of anterior scleritis alone or associated with peripheral ulcerative keratitis or posterior scleritis, even in systemically asymptomatic patients. Urinalysis should not be underestimated in assessment of scleritis to detect early stages of glomerular disease. Scleritis may be the first manifestation whose study may lead to the diagnosis of IgAV. Multidisciplinary approach is necessary to prevent irreversible organ damage such as renal failure.

Acute tubulointerstitial nephritis associated with atezolizumab, an anti-programmed death-ligand 1 (pd-l1) antibody therapy.

Direct stimulation of the antitumor activity of immune system through checkpoint inhibitors (ICIs) has demonstrated efficacy in the treatment of different cancer types. The activity of these antibodies takes place in the immunological synapse blocking the binding of the negative immunoregulatory proteins, thus leading to the finalization of the immune response. Despite having a favorable toxicity profile, its mechanism of action impedes the negative regulation of the immune activity which can potentially favor autoimmune attacks to normal tissues. Renal toxicity has been described in several ICI but not with atezolizumab, an IgG1 monoclonal antibody targeting PD-L1 (programmed death ligand 1), approved by FDA as a second-line therapy for advanced urothelial carcinoma. Here we present a patient with a single kidney and metastatic renal cell carcinoma treated with atezolizumab and bevacizumab combination, with biopsy-proven acute interstitial nephritis, who had a complete resolution of renal dysfunction after steroid therapy.

Determinants of renal and patient outcomes in a Spanish cohort of patients with ANCA-associated vasculitis and renal involvement.

The classification of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) remains controversial. The main objective of this study was to define the respective values of ANCA serotype-based classification, clinicopathological classification, and histopathological classification in predicting patient and renal outcomes in a Spanish cohort of patients with ANCA with specificity for myeloperoxidase, MPO-ANCA, versus ANCA with specificity for proteinase 3, PR3-ANCA. Two hundred and forty-five patients with ANCA-AAV and biopsy-proven renal involvement diagnosed between 2000 and 2104 were recruited in 12 nephrology services. Clinical and histologic data, renal outcomes, and mortality were analyzed. We applied the Chapel Hill Consensus Conference definition with categories for granulomatosis with the polyangiitis (GPA) and microscopic polyangiitis (MPA), the classification based on ANCA specificity, and the histopathological classification proposed in 2010. Eighty-two percent were MPO-ANCA positive and 18.0% PR3-ANCA positive. Altogether, 82.9% had MPA and 17.1% GPA. The median follow-up was 43.2 months (0.1-169.3). Neither ANCA-based serological nor clinical classification was predictive of renal outcomes or patient survival on bivariate or multivariate Cox regression analysis. Histopathological classification was found to predict development of end-stage renal disease (p = 0.005) in Kaplan-Meier analysis. ANCA specificity was more predictive of relapse than clinicopathological classification in multivariate analysis (HR 2.086; 95% CI 1.046-4.158; p = 0.037). In our Spanish cohort, a majority of patients had an MPO-ANCA-AAV. A classification based on ANCA specificity has a higher predictive value for relapse occurrence and could be used for decision-making with respect to induction treatment and maintenance therapies.

Mixed cryoglobulinaemia not related to hepatitis C virus, mesangiocapillary glomerulonephritis and lymphoplasmocytic lymphoma.

Kidney involvement associated to lymphoma is a known phenomenon but frequently not characterized due to the low frequency with which biopsies are realized in these patients. Several histological patterns can co-exist and happen unnoticed without a biopsy. Parenchyma infiltration in kidney for lymphoma has been found in 34% (post-mortem) and 14% (pre-mortem) and have low incident of clinical manifestations. Other patterns of renal injury are associated to lymphoma and minimal changes disease is especially related with Hodgkin's lymphoma. Renal lesions associated to paraprotein in lymphoplasmacytic lymphoma are an exceptional association, in spite of in 20% of them, appear cryoglobulinemia. There are a few cases reported in the literature with different histological patterns: light-chain disease, amyloidosis, and immunotactoid glomerulopathy related with kidney injury in patients with lymphoma. A 39-year-old male presented an association among paraproteinemia, membrano-proliferative glomerulonephritis no hepatitis C virus related and lymphoplasmacytic lymphoma with renal infiltration. This case emphasized the variety of renal lesions that lymphomas could trigger and the value of the nephropathology in the diagnosis and outcome of the hematologic diseases with paraproteinemia.

[Baclofen-associated encephalopathy in a hemodialysis patient with hiccups]. / Encefalopatía asociada a baclofeno como tratamiento del hipo refractario en un paciente en hemodiálisis.

Baclofen is a centrally acting gamma-ammino butyric acid agonist that is used like muscular relaxant in disorders with spasticity and intractable hiccups. Although encouraging and safe results were provided 5 mg/day in hemodialysis patients, his pharmacokinetic and pharmacodinamic properties are not well known in end stage renal disease. We present here the case of a hemodialysis patient with intractable hiccups who developed baclofen-associated encephalopathy with this recommended dose.

A coding polymorphism in the 12-lipoxygenase gene is associated to essential hypertension and urinary 12(S)-HETE.

The arachidonic acid-derived metabolite 12-(S)hydroxyeicosatetraenoic acid (12(S)-HETE), catalyzed by 12-lipoxygenase (12-LOX, ALOX12), exhibits a variety of biological activities with implications in cardiovascular disease. Previous studies have shown higher urinary excretion of this metabolite in essential hypertension. The aim of this study was to analyze the association of polymorphisms in ALOX12 with hypertension and urinary levels of 12(S)-HETE. We studied 200 patients with essential hypertension (aged 56+/-1 years, mean+/-s.e.m., 97 males) and 166 matched controls (aged 54+/-1 years, 91 males). Out of six polymorphisms in the coding region of ALOX12, only R261Q determined a nonconservative amino-acid change and was evaluated by polymerase chain reaction and restriction digestion. Urinary 12(S)-HETE was measured in Sep-Pack-extracted samples using specific enzyme-linked immunosorbent assay. The distribution of genotypes of the R261Q polymorphism was significantly different between patients and controls: patients 92 (0.46) GG, 84 (0.42) GA, 24 (0.12) AA vs controls 56 (0.34) GG, 78 (0.47) GA, 32 (0.19) AA (P=0.030). On the contrary, no association was observed for two intronic polymorphisms. The urinary excretion of 12(S)-HETE (ng/mg creatinine) was significantly higher in GG homozygous patients (13.0+/-1.5) than in GA (8.2+/-1.8) or in AA (8+/-1.5) patients (P=0.018). These results indicate that a nonsynonymous polymorphism in ALOX12 is associated to essential hypertension and to urinary levels of 12(S)-HETE, thus suggesting a role for this gene in this disease.

[Recurrent vascular access trombosis associated with the prothrombin mutation G20210A in a adult patient in haemodialysis]. / Trombosis recurrente del acceso vascular asociada a la mutación G202 10A del gen de la protrombina en un paciente adulto en hemodiálisis.

Vascular access-related complications are a frequent cause of morbidity in haemodialysis patients and generate high costs. We present the case of an adult patient with end-stage renal disease and recurrent vascular access thrombosis associated with the prothrombin mutation G20210A and renal graft intolerance. The clinical expression of this heterozygous gene mutation may have been favoured by inflammatory state, frequent in dialysis patients. In this patient, the inflammatory response associated with the renal graft intolerance would have favored the development of recurrent vascular access thrombosis in a adult heterozygous for prothrombin mutation G20210A. In the case of early dysfunction of haemodialysis vascular access and after ruling out technical problems, it is convenient to carry out a screening for thrombophilia.

[Cytomegalovirus esophagitis in a patient on peritoneal dyalisis]. / Esofagitis por citomegalovirus en un paciente en diálisis peritoneal.

Symptomatic cytomegalovirus (CMV) infection usually affects immunocompromised patients, such as transplant recipients. From that point of view, the patient with endstage renal disease under maintenance dialysis is considered as immunocompetent. Thus, opportunistic infections, such as CMV infection, is not systematicaly searched in these patients, despite that an impaired cellular immunity has been reported in dialysis patients. We report a case of CMV esophagitis, clinically symptomatic, in a patient endstage renal disease under peritoneal dialysis, without other known immunosuppressive factors and with a good clinical response to gancyclovir treatment.

[Evolution of left colon anastomosis after focal peritonitis induction in rats]. / Evolução de anastomoses do cólon esquerdo após a indução de peritonite focal, em ratos.

In order to know the left colon anastomosis evolution with perforation and focus peritonitis, 40 male rats, Wistar-TECPAR, 135 days old and weighing 345 g in average were divided in two groups of 20 animals each. Group A was the control group and group B the experimental group. Submitted to a laparotomy, the B rats had a left colon wound 0.3 cm in diameter, 1.5 cm in distance from the peritoneal reflection. The A rats had only a intestinal handling. All rats had a new laparotomy after 24 hours; a resection and end-to-end anastomosis. An analysis was made on third and seventh days of the macro and microscopic evolution and bursting pressure. On the second laparotomy, in the B rats, peritonitis was absent and only local reaction was present. Dehiscence, fistula or peritonitis were absent at the observation on the third and seventh days. The anastomosis evolution was similar in the two groups. It was concluded that the focus peritonitis was not sufficient to modify the healing process of the left colon anastomosis in rats during the period studied.