scholarly journals Cgnz1 allele confers kidney resistance to damage preventing progression of immune complex–mediated acute lupus glomerulonephritis

2013 ◽  
Vol 210 (11) ◽  
pp. 2387-2401 ◽  
Author(s):  
Yan Ge ◽  
Chao Jiang ◽  
Sun-Sang J. Sung ◽  
Harini Bagavant ◽  
Chao Dai ◽  
...  
Keyword(s):  
Immune Complex ◽  
Organ Damage ◽  
Distal Region ◽  
Chromosome 1 ◽  
Chronic Glomerulonephritis ◽  
Female Mice ◽  
Inflammatory Parameters ◽  
Stage Renal Disease ◽  
End Stage ◽  
Lupus Glomerulonephritis

Cgnz1 and Agnz1 on the distal region of mouse chromosome 1 are associated with chronic glomerulonephritis (cGN) and acute GN (aGN). NZM2328.Lc1R27 (R27) was generated by introgressing a C57L/J region where Cgnz1 is located to NZM2328. R27 female mice developed aGN mediated by immune complex (IC) deposition and complement activation without progression to cGN with severe proteinuria. End stage renal disease (ESRD) was not seen in R27 mice as old as 15 mo. Thus, aGN and cGN are under separate genetic control, and IC-mediated proliferative GN need not progress to cGN and ESRD. NZM2328 and R27 female mice have comparable immune and inflammatory parameters. In contrast to NZM2328, R27 mice were resistant to sheep anti–mouse GBM serum-induced nephritis, supporting the hypothesis that aGN is mediated by autoimmunity and resistance to the development of cGN is mediated by end organ resistance to damage. Thus, autoimmunity should be considered distinct from end organ damage. The Cgnz1 region has been mapped to a 1.34 MB region with 45 genes. Nine candidate genes were identified. Clinical relevance of these observations is supported by case studies. Clinical implications and the significance to human lupus and other diseases are presented.

scholarly journals The Association Between Inflammatory Markers and Hypertension. A Call for Anti-Inflammatory Strategies?

2006 ◽  
Vol 6 ◽  
pp. 1262-1273
Author(s):  
Néstor H. García ◽  
Luis I. Juncos
Keyword(s):  
Blood Pressure ◽  
Endothelial Dysfunction ◽  
Beta Blockers ◽  
Organ Damage ◽  
Left Ventricular ◽  
Cardiovascular Damage ◽  
Inflammatory State ◽  
Anti Inflammatory ◽  
Stage Renal Disease ◽  
End Stage

The most important goal of antihypertensive therapy is to prevent the complications associated with hypertension (stroke, myocardial infarction, end-stage renal disease, etc). For this, secondary targets such as left ventricular hypertrophy, proteinuria, dementia, and other signs of hypertension-induced organ damage help the physician to assess risks and monitor treatment efficacy. New treatment targets may be arising, however. One such target may be endothelial dysfunction. In effect, endothelial dysfunction not only may precede the elevation of blood pressure, but may also pave the way to conditions often associated with hypertension, such as diabetes, arteriosclerosis, microalbuminuria, congestive heart failure, and tissue hypertrophy. Because inflammation often accompanies endothelial dysfunction, approaches to counteract inflammation are now being evaluated. For this, antagonists of the renin-angiotensin-aldosterone system, statins, and beta blockers are all being tested. All of these agents seem to prevent or delay the induction of proinflammatory molecules aside from, and in addition to, their specific effects on blood pressure. The focus of this review is to update some of the animal and human research showing that hypertension sets off an inflammatory state and also to consider some of the anti-inflammatory approaches that may prevent the development of endothelial dysfunction, and the subsequent renal and cardiovascular damage.

scholarly journals Breaking Tolerance to Double Stranded DNA, Nucleosome, and Other Nuclear Antigens Is Not Required for the Pathogenesis of Lupus Glomerulonephritis

2004 ◽  
Vol 199 (2) ◽  
pp. 255-264 ◽  
Author(s):  
Samuel T. Waters ◽  
Marcia McDuffie ◽  
Harini Bagavant ◽  
Umesh S. Deshmukh ◽  
Felicia Gaskin ◽  
...  
Keyword(s):  
Lupus Erythematosus ◽  
Antinuclear Antibody ◽  
Early Mortality ◽  
Chromosome 1 ◽  
Chronic Glomerulonephritis ◽  
Chromosome 4 ◽  
Double Stranded Dna ◽  
Nuclear Antigens ◽  
Dsdna Antibody ◽  
Lupus Glomerulonephritis

In lupus-prone NZM2328 mice, a locus Cgnz1 on chromosome 1 was linked to chronic glomerulonephritis, severe proteinuria, and early mortality in females. A locus Adnz1 on chromosome 4 was linked to antinuclear antibody (ANA) and anti–double stranded DNA (dsDNA) antibody (Ab) production. In this investigation, two congenic strains, NZM2328.C57L/Jc1 (NZM.C57Lc1) and NZM2328.C57L/Jc4 (NZM.C57Lc4), were generated by replacing the respective genetic intervals containing either Cgnz1 or Adnz1 with those from C57L/J, a nonlupus-prone strain. The NZM.C57Lc1 females had markedly reduced incidence of chronic glomerulonephritis and severe proteinuria. NZM.C57Lc4 females had chronic glomerulonephritis and severe proteinuria without circulating ANA, anti-dsDNA, and antinucleosome Ab. These data confirm the linkage analysis. Unexpectedly, NZM.C57Lc1 females had little anti-dsDNA and related Ab, suggesting the presence of a second locus Adnz2 on chromosome 1. The diseased NZM.C57Lc4 kidneys had immune complexes by immunofluorescence and electron microscopy. The eluates from these kidneys did not contain ANA, anti-dsDNA, and antinucleosome Ab, indicative of the presence of non–anti-dsDNA nephritogenic Ab. Thus, breaking tolerance to dsDNA and chromatin is not required for the pathogenesis of lupus nephritis. These results reaffirm that anti-dsDNA and related Ab production and chronic glomerulonephritis are under independent genetic control. These findings have significant implications in the pathogenesis of systemic lupus erythematosus.

scholarly journals Multicenter study of the causes of the end stage renal disease in patients on chronic hemodialysis in Minsk

2020 ◽  
Vol 17 (1) ◽  
pp. 49-54
Author(s):  
К. S. Komissarov
Keyword(s):  
Diabetes Mellitus ◽  
Renal Disease ◽  
End Stage Renal Disease ◽  
Systemic Vasculitis ◽  
Chronic Hemodialysis ◽  
Kidney Damage ◽  
Chronic Glomerulonephritis ◽  
Cross Sectional ◽  
Stage Renal Disease ◽  
End Stage

The cross-sectional study of the patients receiving hemodialysis (HD) treatment in the dialysis departments in Minsk at the beginning of the year 2017 was made. The aim of the study was to define the main cause of the end stage renal disease (ESRD) among HD patients in the dialysis departments in Minsk. According to the inclusion and exclusion criteria, 289 patients were selected for further analysis. The median of the age was 57 (45; 66) years, for men it was 174 (60.2 %) years. The median of therapy duration was 26 (8; 66) months. The main cause of the end stage renal disease was chronic glomerulonephritis in 35.3 % of patients, the second was diabetes mellitus in 15.9 % of patients, and the third was the polycystic disease in 13.5 % of patients. Kidney damage in the frame of ANCA-vasculitis was revealed in 4 (1.4 %) patients, which is less than in Eastern European Centers where systemic vasculitis is the cause of ESRD in 6.7 % of cases. Histological verification of the diagnosis was conducted in 25 (8.7 %) patients while the most frequent diagnosis was IgA-nephropathy tht was defined in 44 % of biopsied persons. The results of our analysis point to an insufficient rate of histopathology that proved the diagnosis among of the HD patients in Minsk. It does not allow us to conduct a complete differential diagnosis between kidney damage due to the primary diffuse kidney disease or arterial hypertension, diabetes mellitus and systemic vacuities.

Icodextrin and Intraperitoneal Inflammation

2008 ◽  
Vol 28 (3_suppl) ◽  
pp. 96-100 ◽  
Author(s):  
Misaki Moriishi ◽  
Hideki Kawanishi
Keyword(s):  
Peritoneal Dialysis ◽  
Degradation Products ◽  
Chronic Glomerulonephritis ◽  
Inflammatory Reactions ◽  
Markers Of Inflammation ◽  
Peritoneal Dialysis Fluid ◽  
Peritoneal Permeability ◽  
Equilibrium Test ◽  
Stage Renal Disease ◽  
End Stage

⋄ Background The peritoneum is impaired by exposure to biocompatible dialysis solutions. Because icodextrin peritoneal dialysis fluid (PDF) is made from cornstarch, a possibility that it induces intraperitoneal inflammation has been reported. In the present study, patients on glucose PDF were switched to icodextrin PDF and then switched back to glucose PDF. Icodextrin PDF-induced intraperitoneal inflammation was investigated based on changes in peritoneal permeability and inflammatory reactions. ⋄ Patients and Methods The subjects were 7 stable peritoneal dialysis patients (4 men, 3 women), with a mean age of 59.1 ± 3.8 years (range: 55.2 - 64.6 years). The mean duration of peritoneal dialysis was 58.3 ± 27.4 months (range: 34.3 - 97.7 months), and the cause of end-stage renal disease was chronic glomerulonephritis in all patients. For the overnight dwell, glucose PDF was changed to icodextrin PDF, and the patients returned to glucose PDF 30 months later. To evaluate peritoneal permeability, a peritoneal equilibrium test (PET) was performed, and dialysate-to-plasma (D/P) ratios of creatinine (Cr), β2-microglobulin (β2M), albumin, immunoglobulin G (IgG), and α2-macroglobulin (α2M) were measured in the overnight dialysate and serum. As markers of inflammation and fibrinolysis or coagulation, interleukin-6 (IL-6) and fibrinogen degradation products (FDPs) were measured in overnight effluent. The evaluations were made every 6 months for 36 months. ⋄ Results A significant elevation in FDP levels was detected in overnight effluent 6 months after the switch to icodextrin PDF, and IL-6 levels tended to increase. The D/P ratios of Cr, β2M, and albumin were also significantly increased, and the D/P ratios of IgG and α2M tended to increase. The D/P ratio of Cr as measured by PET was slightly increased, but the elevation was not significant. In 5 patients, after icodextrin PDF was switched back to glucose PDF at 30 months, the D/P ratios of Cr, β2M, albumin, IgG, and α2M in overnight effluent were significantly reduced. The FDP levels decreased slightly in those patients. In the remaining 2 patients, the D/P ratios of Cr on PET and of Cr, β2M, albumin, IgG, and α2M in overnight effluent, and the FDP and IL-6 levels in overnight effluent were markedly elevated after the switching from glucose to icodextrin PDF, and they remained high after the switch back to glucose PDF. One of these 2 patients developed pre-EPS and was treated with prednisolone and concomitant hemodialysis. The other was switched from peritoneal dialysis to hemodialysis. ⋄ Conclusions Icodextrin dialysis solution may induce an inflammatory reaction in the peritoneum. Further investigation is necessary for the long-term use of icodextrin PDF.

scholarly journals Hemodilution Impacts Assessment of Thyroid Status before and after Hemodialysis in Patients with End-Stage Renal Disease

2020 ◽  
pp. 988-994
Author(s):  
Toru Sanai ◽  
Ken Okamura ◽  
Tomoaki Onoue ◽  
Takashi Ono ◽  
Kenichi Motomura ◽  
...  
Keyword(s):  
Renal Disease ◽  
End Stage Renal Disease ◽  
Thyroid Stimulating Hormone ◽  
Chronic Glomerulonephritis ◽  
Thyroid Status ◽  
Before And After ◽  
Stage Renal Disease ◽  
End Stage ◽  
Esrd Patients

<b><i>Background:</i></b> To elucidate the role of hemodilution in the alteration of thyroid hormone levels in end-stage renal disease (ESRD), we compared thyroid function before and after hemodialysis (HD). <b><i>Methods:</i></b> Twenty-three male ESRD patients (age &#x3c;65 years) with either chronic glomerulonephritis (CGN) or diabetic nephropathy (DN), who were enrolled between June 2019 and August 2019, were included in the study. The free thyroxine (fT<sub>4</sub>), free tri-iodothyronine (fT<sub>3</sub>), and thyroid-stimulating hormone (TSH), thyroxine-binding globulin (TBG), and thyroglobulin (Tg), measured before and after HD in 12 patients with CGN (48.7 ± 11.8 years [mean ± standard deviation]) and 11 patients with DN (57.6 ± 6.5 years), were compared with 45 healthy controls (52.5 ± 11.9 years). <b><i>Results:</i></b> The fT<sub>4</sub>, fT<sub>3</sub>, and TBG were significantly low before HD and increased in parallel with an increase in hematocrit and albumin after HD in both ESRD subgroups. The TSH was high before HD and decreased significantly after HD, while Tg remained almost unchanged. In DN, the fT<sub>4</sub> levels were nearly identical, while fT<sub>3</sub> was lower with slightly higher TSH, compared with CGN. The TSH/fT<sub>4</sub> ratios before HD were significantly higher in both subgroups, and the fT<sub>3</sub>/fT<sub>4</sub> ratios after HD were significantly lower in DN than the control. <b><i>Conclusions:</i></b> Our findings suggest that the low fT<sub>4</sub> and fT<sub>3</sub> levels found in ESRD are due to hemodilution before HD, resulting in a slightly higher TSH level but almost unchanged Tg level, and that DN is associated with decreased T<sub>4</sub>-to-T<sub>3</sub> conversion.

scholarly journals End stage renal disease patients on haemodialysis profiled epidemiologically at medical college of sub-Himalayan region of India

2019 ◽  
Vol 7 (5) ◽  
pp. 1594
Author(s):  
Pankaj Kumar Gupta ◽  
Dinesh Kumar
Keyword(s):  
Diabetes Mellitus ◽  
Renal Disease ◽  
End Stage Renal Disease ◽  
Organ Damage ◽  
Common Complication ◽  
Common Cause ◽  
Heart Damage ◽  
Medical College ◽  
Stage Renal Disease ◽  
End Stage

Background: Mostly, end organ damage becomes the reason for morbidity and mortality among patients with non-communicable diseases (NCDs) due their chronicity. Derangement of renal function along with brain and heart damage are considered to be a significant problem of NCDs. The objectives of this study were on this background of end stage renal disease (ESRD) as a common complication for common NCDs, present study was planned to study the distribution of responsible NCDs.Methods: Over three-year period, all the cases reported GFR <15ml/min/1.73m2 were studied.Results: Total 100 patients (male:65) were studied with mean age of 51.0±13.0 years. Diabetes mellitus (38.0%), hypertension (28.0%), and glomerulonephritis (16.0%) were three leading cause for ESRD. Idiopathic cause was observed among 12.0% patients. Fifteen percent patients could not survive.Conclusions: NCDs mainly diabetes mellitus and hypertension observed to be most common cause for ESRD.

scholarly journals The effect of hemodialys on endothelial dysfunction in patients with end-stage renal disease

2017 ◽  
Vol 95 (10) ◽  
pp. 935-939
Author(s):  
Aleksandr B. Susla ◽  
I. R. Mysula ◽  
A. I. Gozhenko
Keyword(s):  
Endothelial Dysfunction ◽  
Renal Disease ◽  
End Stage Renal Disease ◽  
Platelet Rich Plasma ◽  
Circulating Endothelial Cells ◽  
Chronic Glomerulonephritis ◽  
Nitrate Anion ◽  
Sh Groups ◽  
Stage Renal Disease ◽  
End Stage

Purpose. To study the effect of a single hemodialysis (HD) session on the endothelial structure and function by analyzing the contents of nitric oxide (NO) stable metabolites and circulating endothelial cells (CECs) number, and to establish the interrelation between the oxidative stress (OS) marker malondialdehyde (MDA) and endothelial dysfunction indices in patients with end-stage renal disease (ESRD). Material and methods. The study included 20 chronic HD patients (9 men aged 41,0±3,0 years; HD duration, (40,4±4,8) months). Patients with chronic glomerulonephritis (65%) dominated. Plasma content of MDA, the activity of superoxide dismutase (SOD) and catalase (CT) in erythrocytes, blood content of SH-groups were measured before and after the HD session by standard methods. Plasma content of nitrite-( NO2-) and nitrate anion (NO3-) was estimated by the spectrophotometric method, and CEC amount in platelet-rich plasma ss described by Hladovec J. et al., 1978 in our modification. Results. After the HD session NO2- content decreased by 18,4% (p<0,001), NO3- by 13,4% (p=0,007), while CEC number did not significantly change (p=0,478). Due to HD the content of MDA increased by 10,5% (p=0,007), the activity of SOD, CT increased by 8,9% (p=0,005) and 16,2% (p=0,016) respectively, and the concentration of SH-groups decreased by 20,8% (p<0,001). Significant correlation between the content of MDA and NO2- (Rs=-0,56, p=0,010), CECs amount (Rs=0,52, p=0,018) was established; the CEC number was in turn related to the level of NO2- (Rs=-0,58, p=0,007). Conclusions. The HD session is associated with the development of OS, lack of NO and possibly endothelial damage which confirms practicability of endothelial protection, in particular modulation of the L-arginine-NO system, during HD session in patients with ESRD.

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