Dialysis Patients Respond Adequately to Influenza Vaccination Irrespective of Dialysis Modality and Chronic Inflammation.

(1) Background: Chronic inflammation and suboptimal immune responses to vaccinations are considered to be aspects of immune dysregulation in patients that are undergoing dialysis. The present study aimed to evaluate immune responses in hemodialysis (HD) and online hemodiafiltration (OL-HDF) patients to a seasonal inactivated quadrivalent influenza vaccine (IQIV). (2) Methods: We enrolled 172 chronic dialysis patients (87 on HD and 85 on OL-HDF) and 18 control subjects without chronic kidney disease in a prospective, cross-sectional cohort study. Participants were vaccinated with a seasonal IQIV, and antibody titers using the hemagglutination inhibition (HI) assay were determined before vaccination (month 0) and 1, 3, and 6 months thereafter. Demographics and inflammatory markers (CRP, IL-6, IL-1ß) were recorded at month 0. The primary endpoints were the rates of seroresponse (SR), defined as a four-fold increase in the HI titer, and seroprotection (SP), defined as HI titer ≥ 1/40 throughout the study period. Statistical analyses were conducted in R (version 3.6.3) statistical software. The differences between groups were analyzed using chi-square and t-test analyses for dichotomous and continuous variables, respectively. To identify independent determinants of SR and SP, generalized linear models were built with response or protection per virus strain as the dependent variable and group, age, sex, time (month 0, 1, 3, 6), diabetes, IL-6, dialysis vintage, HD access, and HDF volume as independent explanatory variables. (3) Results: SR and SP rates were similar between control subjects, and dialysis patients were not affected by dialysis modality. SP rates were high (> 70%) at the beginning of the study and practically reached 100% after vaccination in all study groups. These results applied to all four virus strains that were included in the IQIV. IL-6 levels significantly differed between study groups, with HD patients displaying the highest values, but this did not affect SP rates. (4) Conclusions: Dialysis patients respond to influenza immunization adequately and similarly to the general population. Thus, annual vaccination policies should be encouraged in dialysis units. OL-HDF reduces chronic inflammation; however, this has no impact on SR rates.

Glomerular expression of matrix metalloproteinases in systemic lupus erythematosus in association with activity index and renal function.

PURPOSE: The aim of this study was to examine the expression of matrix metalloproteinases (MMPs) MMP-1, MMP-2, MMP-3, MMP-9, and their specific tissue inhibitor TIMP-1 in kidney biopsies of patients with lupus nephritis (LN) and to investigate the relationship between MMPs, activity index, and renal function at the time of kidney biopsy. METHODS: We performed immunohistochemistry with monoclonal antibodies against MMP-1, MMP-2, MMP-3, MMP-9, and TIMP-1 in 58 kidney-biopsy specimens with LN (according to the 2004 ISN/RPS classification) and eight specimens from normal kidney tissue. We used clinical data of 36 patients at the time of kidney biopsy to evaluate the association between MMPs expression and renal function. RESULTS: We found increased MMP-1, MMP-2, and MMP-3 expression in LN glomeruli and a significant correlation with the activity features, with higher activity index score and worse renal function (p < .001). In particular, we have noticed a significant correlation of MMP-1 with leukocyte influx (OR:16.5 95%CI 4.3-62.5 p < .001), and MMP-3 with glomerular hypercellularity (OR:18.6 95%CI 4.8-72.8 p < .001). Moreover, we found a strong correlation of MMP-2 expression with fibrinoid necrosis and cellular crescents formation (OR:17.1 95%CI 4.3-67.7 p < .001). CONCLUSIONS: MMP expression in renal biopsy of patients with LN is increased and directly related to a highly active inflammatory response. Moreover, stronger MMP expression is associated with higher activity index and a more profound renal dysfunction.

Glomerular expression of matrix metalloproteinases in AL-amyloidosis and association with renal function at the time of kidney biopsy.

BACKGROUND: Matrix metalloproteinases (MMPs) have been implicated in the pathophysiology of various renal diseases, however, there are limited data regarding their role in renal AL-amyloidosis. In the present study, we evaluated the glomerular expression of MMPs in renal-biopsy specimens containing AL-amyloid deposits. We also examined the association of MMPs with renal function at the time of diagnostic renal biopsy. METHODS: We performed immunohistochemistry with monoclonal antibodies against MMP-1, MMP-2, MMP-3, MMP-9, and TIMP-1 in 19 kidney-biopsy specimens with AL-amyloidosis and 8 specimens from normal kidney tissue. We used clinical data of the patients at the time of kidney biopsy to evaluate the association between MMP expression and renal function. RESULTS: We found increased MMP-1 and MMP-3 expression within the amyloid deposits and adjacent tissues in > 50% of the amyloid-positive biopsies, whereas MMP-1 and MMP-3 were negative in control samples. In contrast, we found no significant glomerular MMP-2 and TIMP-1 expression in amyloid-containing or normal kidneys. MMP-9 expression was found in the glomerular basement membrane equally in AL-amyloidosis and control specimens. The presence of MMP-1 and MMP-3 in the glomeruli of patients with AL-amyloidosis correlated with worse renal function at the time of kidney biopsy. CONCLUSION: The findings of this study show increased glomerular expression of MMP-1 and MMP-3 in patients with AL-amyloidosis which is associated with worse renal function at the time of the kidney biopsy. Our results suggest an important role for MMP-1 and MMP-3 in the pathogenesis of renal damage in AL-amyloidosis.

Progression of coronary artery calcification after kidney transplantation.

Calcification of coronary vessels progresses rapidly in hemodialysis (HD) patients and comprises a strong predictor of cardiovascular events. The aim of this prospective study was to evaluate the coronary artery calcification (CAC) in patients with end stage renal disease undergoing regular HD and to determine the effect of renal transplantation (RT) in the progression of CAC, using the Agatston technique for calcium scoring. The study included 20 patients with end-stage renal disease undergoing a regular HD treatment (16 males, 4 females) 54.1 ± 9.5 years old who had just received a renal transplant and 16 more HD patients (11 males, 5 females) 54.4 ± 13.8 years old as control group. The baseline evaluation showed a very high prevalence of CAC in both groups, which was positively correlated with age (p < 0.001) and CRP (p = 0.03). The second (follow-up) evaluation showed a significant slower progression of calcification after RT. In both groups, high calcium score values in the follow-up evaluation had a strong positive correlation with baseline calcium score (p < 0.001).

Primary renal MALT lymphoma presenting with cryoglobulinaemia.

Primary renal lymphoma is a rare clinicopathologic entity that typically presents as renal mass or renal impairment with enlarged kidneys. We describe the case of a 66-year-old woman who presented with type II mixed cryoglobulinaemic vasculitis as the first manifestation of underlying low-grade primary renal lymphoma.

Sclerosing peritonitis presenting 2 years after renal transplantation in a former CAPD patient.

Sclerosing peritonitis (SP) is a rare but serious complication of peritoneal dialysis (PD), characterized by a fibrous peritoneal thickening. The etiology of this condition remains unknown but is likely to be multifactorial. Patients with SP almost invariably develop ultrafiltration and clearance failure. Although a number of pharmacologic drug treatment options have been tried with various results, surgical treatment and cessation of PD are almost always necessary and transfer to hemodialysis is the only practical option. Despite some evidence supporting the recovery of gastrointestinal function after renal transplantation in such patients, SP may very rarely appear much later after the cessation of PD and even after renal transplantation. We report an interesting case of a former PD patient who 2 years after renal transplantation presented with abdominal discomfort, vomiting, and malnutrition due to SP. Despite the initial conservative treatment, the symptoms persisted and a surgical treatment was decided upon. After that the patient recovered with no further complications. Although the appearance of SP after renal transplantation is extremely rare, it must be included in the differential diagnosis of every case of unexplained malnutrition and abdominal obstruction in a patient with a PD history.

Splenic marginal lymphoma and glomerulonephritis: case report and review of the literature.

Malignant lymphomas can affect kidneys in several ways. They may precipitate acute renal failure by causing ureteral or renal vascular obstruction, or by direct renal parenchymal infiltration. Furthermore, they may insult renal function via paraneoplastic mechanisms such as hypercalcemia. Lymphomas only rarely can cause glomerulonephritis (GN). We report a case of a 72-year-old male who presented with mild renal function impairment, proteinuria, and microscopic hematuria, suggesting active glomerulonephritis, and pancytopenia of immune origin. A bone marrow biopsy led to a diagnosis of splenic marginal zone lymphoma. Although a kidney biopsy was not performed, glomerulonephritis was attributed to the lymphoma and splenic marginal zone lymphoma-related glomerulonephritis was the final diagnosis. The course of splenic marginal zone lymphoma is extremely indolent. The first manifestation in some patients can be immune cytopenia or other autoimmune phenomena. These patients may respond well to corticosteroids. Therefore, our patient was started on prednisolone resulting in a good hematologic response. Renal function also improved and proteinuria and hematuria disappeared, suggesting a lymphoma-related origin of the GN. Two years after full steroids withdrawal, the patient remained stable with a good renal function and daily protein excretion less than 300 mg. Lymphomas rarely are the cause of secondary glomerulonephritis; however, with a lack of an apparent cause, the clinician should be aware of them, particularly in the elderly with autoimmune manifestations.

Discussion of the paper "Cost effective policies for alternative distributions of stochastic water pollution" by Gren, Destouni and Tempone.

This discussion addresses some aspects of a recent paper appearing in this journal which investigates cost effective coastal water management based on different assumptions of the probability distributions (normal and log-normal) of pollutant transport. We also suggest an alternative approach to overcome the technical problems of using the theoretical correct distribution for characterising environmental data (log-normal) within a probabilistic programming framework.

Role of adrenoceptor-linked signaling pathways in the regulation of CYP1A1 gene expression.

Alpha2-adrenoceptor agents as well as stress affect the activity of several hepatic monoxygenases including those related to CYP1A enzymes. This study was therefore designed to assess the role of central and/or peripheral catecholamines and, in particular, of adrenoceptors in the regulation of B(alpha)P-induced cytochrome CYP1A1 expression. In order to discriminate the role of central from that of peripheral catecholamines in the regulation of CYP1A1 induction, the effect of central and peripheral catecholamine depletion using reserpine versus only peripheral catecholamine depletion using guanethidine was assessed. By using selected agonists and antagonists, the role of alpha and beta-adrenoceptors in the regulation of CYP1A1 induction was evaluated. The results showed that the central catecholaminergic system has a negative regulatory effect on 7-ethoxyresorufin O-deethylase (EROD) inducibility by benzo(alpha)pyrene (B(alpha)P), and that this may be mediated via alpha1-, alpha2- and beta-adrenoceptors. Specifically, stimulation of alpha2-adrenoceptors with dexmedetomidine and blockade of alpha1- or beta-adrenoceptors with prazosin or propranolol respectively, resulted in a further increase of EROD inducibility. Adrenoceptors were found to be involved in the regulation of the CYP1A1 gene at mRNA level. Both, reduced noradrenaline release in central nervous system induced with dexmedetomidine and central catecholamine depletion, as well as blockade of central alpha1-adrenoceptors induced with prazosin, all were associated with up-regulation of CYP1A1 expression. In contrast, stimulation of central beta-adrenoceptors with isoprenaline resulted in a down-regulation of CYP1A1 expression. Our observations indicate that drugs, which stimulate or block adrenoceptors and catecholamine release may lead to complications in drug therapy and modulate the toxicity or carcinogenicity of drugs that are substrates for the CYP1A1.