Three Diseases Mediated by Different Immunopathologic Mechanisms—ANCA-Associated Vasculitis, Anti-Glomerular Basement Membrane Disease, and Immune Complex-Mediated Glomerulonephritis—A Common Clinical and Histopathologic Picture: Rapidly Progressive Crescentic Glomerulonephritis

Immune mechanisms play an important role in the pathogenesis of glomerulonephritis (GN), with autoimmunity being the main underlying pathogenetic process of both primary and secondary GN. We present three autoimmune diseases mediated by different autoimmune mechanisms: glomerulonephritis in vasculitis mediated by anti-neutrophil cytoplasmic antibodies (ANCAs), glomerulonephritis mediated by anti-glomerular basement membrane antibodies (anti-GBM antibodies), and immune complex-mediated glomerulonephritis. Some of these diseases represent a common clinical and histopathologic scenario, namely rapidly progressive crescentic glomerulonephritis. This is a severe illness requiring complex therapy, with the main role being played by therapy aimed at targeting immune mechanisms. In the absence of immune therapy, the crescents, the characteristic histopathologic lesions of this common presentation, progress toward fibrosis, which is accompanied by end-stage renal disease (ESRD). The fact that three diseases mediated by different immunopathologic mechanisms have a common clinical and histopathologic picture reveals the complexity of the relationship between immunopathologic mechanisms and their clinical expression. Whereas most glomerular diseases progress by a slow process of sclerosis and fibrosis, the glomerular diseases accompanied by glomerular crescent formation can progress, if untreated, in a couple of months into whole-nephron glomerulosclerosis and fibrosis. The outcome of different immune processes in a common clinical and histopathologic phenotype reveals the complexity of the relationship of the kidney with the immune system. The aim of this review is to present different immune processes that lead to a common clinical and histopathologic phenotype, such as rapidly progressive crescentic glomerulonephritis

Acute Acalculous Cholecystitis Associated with Abscesses—An Unknown Dual Pathology

(1) Introduction and Aims: Little is known about the relationship between renal pathology and gallbladder pathology, although the two organs (the gallbladder and the right kidney) are in close proximity to one another. If a renal abscess disseminates, the gallbladder would be one of the secondary organs involved. As the bile provides a favorable environment for the development of pathogenic germs, it allows for the development of acute cholecystitis, even if calculi are absent, thus resulting in the development of acute acalculous cholecystitis. The aim of our study was to analyze the association between acute acalculous cholecystitis (AAC) and renal abscesses. (2) Methods: A department-wide retrospective cohort observational study including 67 patients with renal abscesses, with a mean age of 34.5+/−16.21 years and with five males and 62 females, was conducted. All of the patients were examined by an abdominal ultrasound. The lab tests included CBC with differential liver enzymes and serum bilirubin (in order to assess alterations in the liver function which can be associated with AAC) and serum creatinine (in order to assess the renal function). Blood culture and urine culture tests were also performed. (3) Results: Of the 67 patients with renal abscesses, eight (11.94%) were associated with acute cholecystitis: four cases (5.97%) of acalculous cholecystitis and four cases (5.97%) of calculous cholecystitis, two of which presented biliary sludge (acute micro-calculous cholecystitis). All four cases of acute acalculous cholecystitis presented with sepsis, and there was one case of septic shock at onset. We did not observe an impairment in renal function in the patients presenting with acute acalculous cholecystitis, and hepatic impairment was inconstant and moderate. All of the cases had a favorable outcome after a prompt initiation of intensive antibiotic therapy; both the renal abscess and the acute acalculous cholecystitis receded without further complications. (4) Conclusions: The association of acute acalculous cholecystitis with renal abscesses could be related to the possibility of germ dissemination from the infectious focus. In the case of a renal abscess, careful clinical, lab, and imaging exams of the gallbladder are recommended in order to ensure early therapeutic intervention in the event of an association with acute acalculous cholecystitis

Renal function is similar in solitary kidneys from patients with and without diabetes

Objectives: Due to the shortage of living kidney donors and the current diabetes mellitus (DM) pandemic, studying the association of solitary kidney (SK) with DM is of paramount importance. Our aim was to assess the significance of the association between SK and DM. Materials and methods: Eighty-four patients with SK and DM (group A), with a mean age of 62.46 ± 12.72 years, of whom 36 were males and 48 were females, were enrolled in the study. The control group (group B) comprised 84 SK patients without DM of similar age and duration of existence of a SK. Mean age: 61.58 ± 8.22 years, 23 males and 61 females. Serum creatinine, GFR (CKD-EPI), glycaemia, cholesterol, triglycerides, uric acid, proteinuria/24 h, systolic blood pressure (SBP), diastolic blood pressure (DBP) and BMI were assessed. Results: The group of patients with SK and DM (group A) had a higher BMI (p = 0.0007), higher metabolic abnormalities (higher glycaemia [p < 0.001], triglycerides [p = 0.0004], uric acid [p = 0.019] and proteinuria/24 h [p = 0.006]). The study group also had a higher prevalence of hypertension (p = 0.003) and coronary artery disease (p = 0.031). Conclusions: We found a higher value of proteinuria in the study group, significant metabolic abnormalities, as well as a higher prevalence of hypertension and coronary artery disease. However, no differences with respect to GFR were found, which could have significant implications for transplantation

Vitamin D deficiency--prognostic marker or mortality risk factor in end stage renal disease patients with diabetes mellitus treated with hemodialysis--a prospective multicenter study.

End stage renal disease (ESRD) patients on renal replacement therapy (RRT) with diabetes mellitus (DM) have a higher mortality rate and an increase prevalence of vitamin D deficiency compared to those without DM. It is still debated if vitamin D deficiency is a risk factor or a prognostic marker for mortality in these patients. This study investigated the prevalence of vitamin D deficiency and its impact on all-cause mortality in HD patients with DM.Our prospective non-interventional cohort study included 600 patients on hemodialysis therapy (HD) (median aged 56, interquartile range (19) years, 332 (55.3%) males) recruited from 7 HD centers, from all main geographical regions of Romania. The prevalence of DM was 15.3%. They were then followed regarding: dialysis duration, dialysis efficiency, renal anemia, CKD-MBD, inflammatory status and comorbidities: coronary artery disease (CAD), peripheral vascular disease (PVD) and stroke. The deficiency of 25-OH vitamin D was defined as a value lower than 12 ng/mL.Patients were followed for 3 years. The overall 3 year mortality was 25.5% (153 individuals), being higher in patients with DM as compared to those without DM (33.7% vs. 24.0%; P = 0.049). The time-related prognosis was also influenced by the presence of DM, at the survival analysis resulting in a HR of 1.52 [1.03 to 2.26] 95% CI, P = 0.037, for death in dialyzed patients with DM. In DM patients, 25-OH vitamin D deficiency was significantly higher (37.0% compared to 24.0%, P = 0.009). Furthermore, in patients with DM we observed a shorter dialysis duration (2 vs. 3 years, P<0.001) and a lower intact parathyroid hormone (iPTH) (258.0 pg/ml vs. 441.9 pg/ml, P = 0.002). Regarding the presence of comorbidities at the inclusion in the study, the presence of diabetes in dialyzed patients was associated with increased prevalence of CAD (87.0% vs. 58.1%, P<0.001), PVD (67.4% vs. 17.3%, P<0.001) and history of stroke (29.3% vs. 14.0%, P<0.001). In patients with DM the presence of 25-OH vitamin D deficiency increased the probability of death (50.0% vs. 24.1%; P = 0.011). In multiple Cox proportional hazards analysis, vitamin D deficiency remained an independent predictor for mortality in dialysis patients with DM (HR = 1.71, 95% CI 1.21 to 2.43, P = 0.003). In the same time, multiple Cox proportional hazards analysis showed that age (HR = 1.02 per one year increase, P = 0.004), CAD (HR = 1.55, P = 0.046) and PVD (HR = 1.50, P = 0.029) were independent predictors for mortality in dialysis patients with DM.ESRD patients with DM treated with HD have a higher overall mortality than non-DM patients. Vitamin D deficiency is significantly more prevalent in HD patients with DM. Low 25-OH vitamin D levels were associated with increased all-cause mortality in these patients. According to our data, in HD patients with DM, screening for vitamin D deficiency (and its correction) should be mandatory for an optimal risk reduction strategy

Proximal tubule dysfunction is associated with podocyte damage biomarkers nephrin and vascular endothelial growth factor in type 2 diabetes mellitus patients: a cross-sectional study.

There is an ongoing debate as to whether early diabetic nephropathy in Type 2 diabetes mellitus may be attributed to the glomerulus or to the proximal tubule. Urinary excretion of nephrin and vascular endothelial growth factor may increase even in the normoalbuminuria stage. In the course of diabetic nephropathy, the proximal tubule may be involved in the uptake of urinary nephrin and vascular endothelial growth factor.Two groups of consecutive Type 2 diabetes mellitus outpatients (38 normo-, 32 microalbuminuric) and 21 healthy subjects were enrolled in a cross-sectional study and evaluated concerning the relation of proximal tubule dysfunction with the podocyte biomarkers excretion, assessed by ELISA methods. The impact of advanced glycation end-products on this relation was also queried.Urinary alpha1-microglobulin and kidney injury molecule-1 correlated with urinary albumin:creatinine ratio (R2 = 0.269; p < 0.001; R2 = 0.125; p < 0.001), nephrinuria (R2 = 0.529; p<0.001; R2 = 0.203; p < 0.001), urinary vascular endothelial growth factor (R2 = 0.709; p < 0.001; R2 = 0.360; p < 0.001), urinary advanced glycation end-products (R2 = 0.578; p < 0.001; R2 = 0.405; p < 0.001), serum cystatin C (R2 = 0.130; p < 0.001; R2 = 0.128; p<0.001), and glomerular filtration rate (R2 = 0.167; p < 0.001; R2 = 0.166; p < 0.001); nephrinuria and urinary vascular endothelial growth factor correlated with urinary albumin:creatinine ratio (R2 = 0.498; p < 0.001; R2 = 0.227; p<0.001), urinary advanced glycation end-products (R2 = 0.251; p < 0.001; R2 = 0.308; p < 0.001), serum cystatin C (R2 = 0.157; p < 0.001; R2 = 0.226; p < 0.001), and glomerular filtration rate (R2 = 0.087; p = 0.007; R2 = 0.218; p < 0.001).In Type 2 diabetes mellitus there is an association of proximal tubule dysfunction with podocyte damage biomarkers, even in the normoalbuminuria stage. This observation suggests a potential role of the proximal tubule in urinary nephrin and urinary vascular endothelial growth factor processing in early diabetic nephropathy, a fact which could be related to advanced glycation end-products intervention. Podocyte damage and proximal tubule dysfunction biomarkers could be validated as a practical approach to the diagnosis of early diabetic nephropathy by further studies on larger cohorts

Exploring the relation between mortality and left ventricular structure and function in stable hemodialysis treated patients, a longitudinal multicenter cohort study

Abstract Left ventricular (LV) structure and function anomalies are frequent during the CKD continuum and are associated with increased risk of mortality. Cross section and longitudinal ultrasound data are available for advanced CKD and transition to ESKD. Less information is available about LV changes during stable, long-term hemodialysis (HD) treatment. All stable HD patients from 9 HD centers (1034 patients, 671 males, age 58.71 ± 12.94 years) have been enrolled in January 2015. The cohort was followed-up for 4 years, kidney transplantation or death. Yearly, two-dimensional and M-mode continuous and Pulse Doppler echocardiography were performed. During the follow-up, the prevalence of cardiovascular comorbidities significantly increased (p  5% decrease, > 5% increase and ± 5% variations). More than 5% increase of LVEF was associated with higher mortality risk (crude 1.5-fold, adjusted 1.43-fold) compared to stationary EF (p = 0.001). Cardiovascular disease progresses during stable long-term HD therapy and increases mortality risk. HF becomes highly prevalent but only HF with decreased LVEF < 50% is associated with increased risk of mortality

Survival analysis: dialyzed patients with DM vs. without DM.

<p>Survival analysis: dialyzed patients with DM vs. without DM.</p

Cancer before and after the start of hemodialysis and association with mortality – an Eastern-European multicenter study

AbstractIntroduction East-European data on cancer in patients undergoing hemodialysis (HD) are scarce. This study aimed to assess the pattern of cancer and related mortality in patients with end-stage kidney disease (ESKD) undergoing HD.Methods Retrospectively analyzing data from 7 HD centers, this study examined 1377 incident HD patients divided into three groups: no-cancers (NoC), cancers that occurred prior to HD initiation (CPI) and de novo cancer developed after HD initiation (DNC). Mortality risk and survival trends within groups were analyzed using Cox regression and Kaplan-Meier methods.Results In the cohort, 89.46% of the patients had no cancer (NoC group), 3.63% had cancer before (CPI group), and 6.89% had cancer after HD initiation (DNC group). The mean time from HD initiation to DNC diagnosis was 1 [2.75] years. Older age was associated with a higher risk of developing DNC (p < 0.001). Chronic tubulointerstitial nephritis (CTIN) is more prevalent in cancer patients. The most common cancer sites among DNC patients were the digestive (29.47%) and urinary tracts (18.95%), while those in CPI subjects were hematologic (22%) and digestive (20%). Cancer was an independent predictor of mortality risk (HR = 6.9, 95% [CI]:4.5–10.6, p < 0.001).Conclusions East-European ESKD patients undergoing HD have a high incidence of de novo cancers whose primary cancer sites are the digestive and urinary tracts. Almost half of the HD patients with CPI have hematologic and digestive tract cancers. Age and CTIN were associated with cancer risk. Cancer is an independent risk factor for all-cause mortality in patients undergoing hemodialysis (HD)

The Survival of Roma Minority Patients on Chronic Hemodialysis Therapy - A Romanian Multicenter Survey.

OBJECTIVE:The Roma minority represents the largest ethnic group in Central and South-East European countries. Data regarding the mortality in Roma hemodialysis subjects are limited. We evaluated the 3 year mortality of ESRD Roma patients treated with hemodialysis (HD). STUDY DESIGN AND SETTING:Our prospective cohort study included 600 ESRD patients on HD therapy recruited from 7 HD centers, from the main geographical regions of Romania. The median age of the patients was 56 (19) years, 332 (55.3%) being males, 51 (8.5%) having Roma ethnicity. RESULTS:Roma ESRD patients initiate dialysis at a younger age, 47.8 years vs. 52.3 years (P = 0.017), present higher serum albumin (P = 0.013) and higher serum phosphate levels (P = 0.021). In the Roma group, the overall 3 year mortality was higher when compared to Caucasians (33.3% vs. 24.8%). The multivariate survival analysis revealed that being of Roma ethnicity is an independent risk factor for mortality (HR = 1.74; 95% CI = 1.04-2.91; P = 0.035). CONCLUSIONS:Roma patients with ESRD initiate HD therapy at a younger age as compared to Caucasians. They have a higher 3 year mortality rate and are dying at a younger age. Roma ethnicity represents an independent risk factor for mortality in our cohort

Comparison between patients with T2DM without vs. with 25-OH vitamin D deficiency.

<p>*Differences are significant</p><p>^a Distributions are not Gaussian. Data is presented as median and [interquartile range]; p was calculated with Mann-Whitney U test.</p><p>^b Data is presented as mean±S; p was calculated with t-student test.</p><p>^c Data is presented as number and (percentage of total). p was calculated using chi-square test.</p><p>Continuous variables distributions were tested for normality using Shapiro-Wilk test and for equality of variances with Levene’s test.</p><p>Comparison between patients with T2DM without vs. with 25-OH vitamin D deficiency.</p