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- Abedini, Sadollah, et al.
(författare)
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Inflammation in renal transplantation
- 2009
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Ingår i: Journal of the American Society of Nephrology. - 1046-6673 .- 1533-3450. ; 4:7, s. 1246-1254
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND OBJECTIVES: Renal transplant recipients experience premature cardiovascular disease and death. The association of inflammation, all-cause mortality, and cardiovascular events in renal transplant recipients has not been examined in a large prospective controlled trial. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: ALERT was a randomized, double-blind, placebo-controlled study of the effect of fluvastatin on cardiovascular and renal outcomes in 2102 renal transplant recipients. Patients initially randomized to fluvastatin or placebo in the 5- to 6-yr trial were offered open-label fluvastatin in a 2-yr extension to the original study. The association between inflammation markers, high-sensitivity C-reactive protein (hsCRP), and IL-6 on cardiovascular events and all-cause mortality was investigated. RESULTS: The baseline IL-6 value was 2.9 +/- 1.9 pg/ml (n = 1751) and that of hsCRP was 3.8 +/- 6.7 mg/L (n = 1910). After adjustment for baseline values for established risk factors, the hazard ratios for a major cardiac event and all-cause mortality for IL-6 were 1.08 [95% confidence interval (CI), 1.01 to 1.15, P = 0.018] and 1.11 (95% CI, 1.05 to 1.18, P < 0.001), respectively. The adjusted hazard ratio for hsCRP for a cardiovascular event was 1.10 (95% CI, 1.01 to 1.20, P = 0.027) and for all-cause mortality was 1.15 (95% CI, 1.06 to 1.1.25, P = 0.049). CONCLUSIONS: The inflammation markers IL-6 and hsCRP are independently associated with major cardiovascular events and all-cause mortality in renal transplant recipients.
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| 2. |
- Campistol, Josep M., et al.
(författare)
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Sirolimus therapy after early cyclosporine withdrawal reduces the risk for cancer in adult renal transplantation
- 2006
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Ingår i: Journal of the American Society of Nephrology. - 1046-6673 .- 1533-3450. ; 17:2, s. 581-589
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Tidskriftsartikel (refereegranskat)abstract
- Sirolimus (SRL) is a mammalian target of rapamycin inhibitor that, in contrast to cyclosporine (CsA), has been shown to inhibit rather than promote cancers in experimental models. At 3 mo +/- 2 wk after renal transplantation, 430 of 525 enrolled patients were randomly assigned to remain on SRL-CsA-steroids (ST) or to have CsA withdrawn and SRL troughs increased two-fold (SRL-ST). Median times to first skin and nonskin malignancies were compared between treatments using a survival analysis. Mean annualized rates of skin malignancy were calculated, and the relative risk was determined using a Poisson model. Malignancy-free survival rates for nonskin malignancies were compared using Kaplan-Meier estimates and the log-rank test. At 5 yr, the median time to a first skin carcinoma was delayed (491 versus 1126 d; log-rank test, P = 0.007), and the risk for an event was significantly lower with SRL-ST therapy (relative risk SRL-ST to SRL-CsA-ST 0.346; 95% confidence interval 0.227 to 0.526; P < 0.001, intention-to-treat analysis). The relative risks for both basal and squamous cell carcinomas were significantly reduced. Kaplan-Meier estimates of nonskin cancer were 9.6 versus 4.0% (SRL-CsA-ST versus SRL-ST; P = 0.032, intention-to-treat analysis). Nonskin cancers included those of the lung, larynx, oropharynx, kidney, gastrointestinal tract, prostate, breast, thyroid, and cervix as well as glioma, liposarcoma, astrocytoma, leukemia, lymphoma, and Kaposi's sarcoma. Patients who received SRL-based, calcineurin inhibitor-free therapy after CsA withdrawal at month 3 had a reduced incidence of both skin and nonskin malignancies at 5 yr after renal transplantation compared with those who received SRL therapy combined with CsA. Longer follow-up and additional trials are needed to confirm these promising results.
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| 3. |
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| 4. |
- Chen, Yuqing, et al.
(författare)
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Chromogranin A regulates renal function by triggering Weibel-Palade body exocytosis
- 2009
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Ingår i: Journal of the American Society of Nephrology. - 1046-6673 .- 1533-3450. ; 20:7, s. 1623-1632
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Tidskriftsartikel (refereegranskat)abstract
- Chromogranin A (CHGA), a protein released from secretory granules of chromaffin cells and sympathetic nerves, triggers endothelin-1 release from endothelial cells. CHGA polymorphisms associate with an increased risk for ESRD, but whether altered CHGA-endothelium interactions may explain this association is unknown. Here, CHGA led to the release of endothelin-1 and Weibel-Palade body exocytosis in cultured human umbilical vein endothelial cells. In addition, CHGA triggered secretion of endothelin-1 from glomerular endothelial cells and TGF-beta1 from mesangial cells cocultured with glomerular endothelial cells. In humans, plasma CHGA correlated positively with endothelin-1 and negatively with GFR. GFR was highly heritable in twin pairs, and common promoter haplotypes of CHGA predicted GFR. In patients with progressive hypertensive renal disease, a CHGA haplotype predicted rate of GFR decline. In conclusion, these data suggest that CHGA acts through the glomerular endothelium to regulate renal function.
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| 5. |
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| 6. |
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| 7. |
- Ejerblad, Elisabeth, et al.
(författare)
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Obesity and risk for chronic renal failure
- 2006
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Ingår i: Journal of the American Society of Nephrology. - Philadelphia, USA : Lippincott Williams & Wilkins. - 1046-6673 .- 1533-3450. ; 17:6, s. 1695-1702
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Tidskriftsartikel (refereegranskat)abstract
- Few large-scale epidemiologic studies have quantified the possible link between obesity and chronic renal failure (CRF). This study analyzed anthropometric data from a nationwide, population-based, case-control study of incident, moderately severe CRF. Eligible as cases were all native Swedes who were aged 18 to 74 yr and had CRF and whose serum creatinine for the first time and permanently exceeded 3.4 mg/dl (men) or 2.8 mg/dl (women) during the study period. A total of 926 case patients and 998 control subjects, randomly drawn from the study base, were enrolled. Face-to-face interviews, supplemented with self-administered questionnaires, provided information about anthropometric measures and other lifestyle factors. Logistic regression models with adjustments for several co-factors estimated the relative risk for CRF in relation to body mass index (BMI). Overweight (BMI>or=25 kg/m2) at age 20 was associated with a significant three-fold excess risk for CRF, relative to BMI<25. Obesity (BMI>or=30) among men and morbid obesity (BMI>or=35) among women anytime during lifetime was linked to three- to four-fold increases in risk. The strongest association was with diabetic nephropathy, but two- to three-fold risk elevations were observed for all major subtypes of CRF. Analyses that were confined to strata without hypertension or diabetes revealed a three-fold increased risk among patients who were overweight at age 20, whereas the two-fold observed risk elevation among those who had a highest lifetime BMI of >35 was statistically nonsignificant. Obesity seems to be an important-and potentially preventable-risk factor for CRF. Although hypertension and type 2 diabetes are important mediators, additional pathways also may exist.
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| 8. |
- He, Liqun, et al.
(författare)
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The glomerular transcriptome and a predicted protein-protein interaction network
- 2008
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Ingår i: Journal of the American Society of Nephrology. - 1046-6673 .- 1533-3450. ; 19:2, s. 260-268
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Tidskriftsartikel (refereegranskat)abstract
- To increase our understanding of the molecular composition of the kidney glomerulus, we performed a meta-analysis of available glomerular transcriptional profiles made from mouse and man using five different methodologies. We generated a combined catalogue of glomerulus-enriched genes that emerged from these different sources and then used this to construct a predicted protein-protein interaction network in the glomerulus (GlomNet). The combined glomerulus-enriched gene catalogue provides the most comprehensive picture of the molecular composition of the glomerulus currently available, and GlomNet contributes an integrative systems biology approach to the understanding of glomerular signaling networks that operate during development, function, and disease.
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| 9. |
- Jeansson, Marie, 1971, et al.
(författare)
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Adriamycin Alters Glomerular Endothelium to Induce Proteinuria
- 2009
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Ingår i: J Am Soc Nephrol. - 1533-3450 .- 1046-6673. ; 20:1, s. 114-22
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Tidskriftsartikel (refereegranskat)abstract
- The pathophysiology underlying the nephrotic syndrome is becoming clear for several inherited podocytopathies; the mechanisms of injury that lead to the acquired forms of this disease are not well understood. We explored these mechanisms using the mouse model of adriamycin-induced proteinuria. We estimated the fractional clearances for FITC-Ficolls, albumin, and neutral albumin in cooled, isolated, perfused kidneys (cIPK) in situ. Treatment with adriamycin led to a significant increase in the fractional clearance of albumin and of Ficoll with radii larger than 20 A. Neutral albumin (33.4 A) and similarly sized Ficoll behaved similarly to each other. In addition, adriamycin led to a significant loss of charge density and size selectivity of the glomerular barrier. The thickness of the glomerular endothelial surface layer (i.e., or the glycocalyx) in adriamycin-treated animals was only 20% of that in normal animals. Finally, several proteoglycans were downregulated in isolated glomeruli. In summary, adriamycin thins the glomerular glycocalyx, perhaps by downregulating proteoglycan synthesis, and alters glomerular charge- and size selectivity. These data suggest that the glomerular endothelium may play a role in the pathogenesis of proteinuric renal diseases.
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| 10. |
- Ji, Jianguang, et al.
(författare)
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Survival in bladder and renal cell cancers is familial
- 2008
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Ingår i: Journal of the American Society of Nephrology. - : American Society of Nephrology. - 1046-6673 .- 1533-3450. ; 19:5, s. 985-991
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Tidskriftsartikel (refereegranskat)abstract
- Having family members with cancer has been associated with increased risk for bladder and renal cell cancers, but its association with survival has not been examined. This study was an analysis of the nationwide Swedish Family-Cancer Database and revealed that survival for bladder and renal cell cancers was similar whether the cancer was familial or sporadic; however, when survival in offspring was analyzed according to the affected parents' length of survival, prognosis was concordant. Cox proportional hazard regression models revealed that for bladder cancer, the risk for death among offspring whose parents survived > or =5 yr was approximately one third that of offspring whose parents survived <5 yr, after adjustment for gender, age at diagnosis, time period of diagnosis, socioeconomic status, and geographic region (adjusted hazard ratio 0.34; 95% confidence interval 0.15 to 0.80, for overall mortality). A risk of similar magnitude was found for renal cell cancer (adjusted hazard ratio 0.38; 95% confidence interval 0.16 to 0.87, for overall mortality). These population-level findings suggest heritability of prognosis for bladder and renal cell cancers. Genetic factors likely contribute to the mechanism underlying this observation.
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