Benefit of acetylcysteine for prevention of contrast-induced nephropathy after primary angioplasty.
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Comment↗
Biomedical subjects
Bernhard K Krämer
Publications and source records attributed to Bernhard K Krämer.
Effect of MTHFR C677T genotype on survival in type 2 diabetes patients with end-stage diabetic nephropathy.
BACKGROUND: The MTHFR C677T single nucleotide polymorphism TT genotype is associated with increased levels of plasma homocysteine and possibly an effect on cardiovascular mortality. We evaluated the effect of C677T genotype on mortality in a large end-stage renal disease (ESRD) cohort. METHODS: C677T genotype was determined in 439 Caucasians with end-stage diabetic nephropathy (DNP) (cases) recruited from 30 dialysis centres in Southern Germany. A total of 482 type 2 diabetes patients without DNP (no microalbuminuria) at inclusion served as a genotype control collective. Patients were prospectively followed for 4 years. Primary endpoint was all-cause mortality. RESULTS: In contrast to controls, the genotype distribution in cases was not in Hardy-Weinberg equilibrium (HWE, P = 0.003), due to a less than expected number of patients with the TT genotype. The requirements of HWE were met in cases with < 2 years dialysis therapy prior to study inclusion (n = 219). TT genotype was associated with a decreased body mass index (P = 0.002) and long diabetes duration in dialysis patients (P = 0.03). However, TT genotype was not associated with an increased risk of all-cause or cardiac mortality in the total dialysis collective or the subgroup. Also, we observed no association of MTHFR genotype with cardiovascular morbidity in cases or controls (P > 0.05), or with an increased rate of progression to novel microalbuminuria. CONCLUSION: MTHFR 677TT genotype was significantly underrepresented in patients with ESRD in our study, but was not associated with premature mortality in these patients. We found no evidence for survival bias due to C677T genotype in the ESRD cohort, or bias due to genetically determined accelerated progression to novel microalbuminuria in the controls. However, we cannot exclude that the TT genotype protects from progression from microalbuminuria to more advanced stages of DNP, or that TT genotype is associated with premature mortality before a patient progresses to ESRD.
Cohort Studies↗
Expression of the chemokine receptor CXCR3 in human renal allografts--a prospective study.
BACKGROUND: Mechanisms involved in the recruitment and activation of inflammatory cells during renal allograft injury are still incompletely understood. Since chemokines play pivotal roles in this process, our prospective study was performed to evaluate further the role of the chemokine receptor CXCR3. METHODS: A total of 138 biopsies were included from patients without rejection and unaltered morphology (according to Banff 97 classification grade 1, n = 49), with acute interstitial rejection (Banff grade 4 type I, n = 8), with acute vascular rejection (Banff grade 4 type II, n = 23), with chronic allograft nephropathy (Banff grade 5, n = 16), without rejection but with various other lesions (Banff grade 6, n = 36) and from pre-transplant kidneys (n = 6). The expression of CXCR3-, CD4- and CD8-positive cells was localized by immunohistochemistry and quantified by image analysis. RESULTS: CXCR3 was expressed by infiltrating inflammatory cells, but not by intrinsic renal structures. CXCR3-positive cells were found to be involved in tubulitis and vascular rejection. The area of CXCR3-positive staining was significantly larger in biopsies with acute interstitial rejection (P<0.001) and acute vascular rejection (P<0.001) as compared with normal renal graft biopsies. There was a strong morphological and numerical correlation between CXCR3 and both CD4- and CD8-positive T cells, respectively. CONCLUSIONS: A significant part of both CD4- and CD8-positive T cells express the chemokine receptor CXCR3. During renal allograft rejection, the number of these cells increases significantly at the site of injury and might be targeted by CXCR3 blocking agents.
Biomarkers↗
Expression of cyclooxygenase-1 and cyclooxygenase-2 in human renal allograft rejection-- a prospective study.
Cyclooxygenases (COX) are known to be involved in inflammatory kidney diseases. However, there are no data available about the expression of COX-1 and only preliminary reports about the expression of COX-2 in biopsies of patients undergoing acute renal allograft rejection. We conducted this prospective study to analyze the expression, distribution, and cellular localization of COX-1 and -2 and thus to elucidate the role of COX in human kidney transplantation. One hundred forty-four biopsies were included from patients without rejection and unaltered morphology (n = 60), with acute interstitial rejection (n = 7), with acute vascular rejection (n = 21), with chronic allograft nephropathy (n = 16), without rejection but with various other lesions (n = 40). COX-1 and -2 expression was localized in each biopsy by immunohistochemistry. We found a highly significant up-regulation of COX-1 in vessels and in infiltrating interstitial cells of patients with acute allograft rejection compared with biopsies with well-preserved tissue. Also, COX-2 expression was significantly elevated in infiltrating interstitial cells of biopsies with acute rejection. This is the first prospective study demonstrating a significant induction of both COX-1 and -2 in human allograft biopsies with acute rejection after renal transplantation.
Adult↗
Two corticosteroid-free regimens-tacrolimus monotherapy after basiliximab administration and tacrolimus/mycophenolate mofetil-in comparison with a standard triple regimen in renal transplantation: results of the Atlas study.
BACKGROUND: The side effects associated with corticosteroids have led to efforts to minimize their use in renal transplant patients. In this study we compared two corticosteroid-free tacrolimus-based regimens with a standard triple therapy. METHODS: This was a 6-month, phase III, open-label, parallel-group, multicenter study. The total analysis set comprised 451 patients, randomized (1:1:1) to receive tacrolimus (Tac) monotherapy following basiliximab (Bas) administration (n=153), Tac/mycophenolate mofetil (MMF) (n=151), or, Tac/MMF/corticosteroids triple therapy as a control (n=147). RESULTS: The study was completed by 91.2% (triple therapy), 94.7% (Tac/MMF), and 82.4% (Bas/Tac) of patients. Patient baseline characteristics were similar in all groups. The incidences of biopsy-proven acute rejection were 8.2% (triple therapy), 30.5% (Tac/MMF), and 26.1% (Bas/Tac), p<0.001 (multiple test for comparison with triple therapy); Bas/Tac vs. Tac/MMF, p=ns. The incidences of corticosteroid-resistant acute rejection were 2.0%, 4.0%, and 5.2%, p=ns. Graft survival (95.9%, 96.7%, and 94.7%, p=ns) and patient survival (100%, 99.3%, and 99.3%, p=ns) were similar in all groups. Median serum creatinine at month 6 was 123.0 micromol/L (triple therapy), 134.7 micromol/L (Tac/MMF) and 135.8 micromol/L (Bas/Tac). The overall safety profiles were similar; differences (p<0.05) were reported for anaemia (24.5% vs. 12.6% vs. 14.5%), diarrhoea (12.9% vs. 17.9% vs. 5.9%), and leukopenia (7.5% vs. 18.5% vs. 5.9%) for the triple therapy, Tac/MMF, and Bas/Tac group, respectively. The incidences of new-onset diabetes mellitus were 4.6%, 7.1%, and 1.4%, respectively. CONCLUSION: Corticosteroid-free immunosuppression was feasible with the Bas/Tac and the Tac/MMF regimens. Both corticosteroid-free regimens were equally effective in preventing acute rejection, with the Bas/Tac therapy offering some safety benefits.
Adrenal Cortex Hormones↗
Calcium inhibits renin gene expression by transcriptional and posttranscriptional mechanisms.
The aim of this study was to investigate the role of cytosolic calcium for renin gene expression in juxtaglomerular cells. For this purpose, we used the immortalized juxtaglomerular mouse cell line As4.1. To increase cytosolic calcium concentration, we treated the cells with thapsigargin and cyclopiazonic acid, inhibitors of the endoplasmatic reticulum Ca- ATPase. Thapsigargin and cyclopiazonic acid inhibited renin gene expression in a characteristic time and concentration-dependent manner. This effect was concentration-dependently blocked by BAPTA-AM, an intracellular Ca2+ chelator. Pharmacological blocking of protein kinase C activity by calphostin, Gö6976, and Gö6983 did not change the effect of thapsigargin on renin gene expression. Experiments with renin1C-promoter-reporter constructs revealed that thapsigargin inhibited renin gene transcription. Analysis of deletion constructs of the renin1C promoter indicated that regulatory elements involved in the calcium-mediated inhibition of renin gene transcription are located in the enhancer region of the renin gene and that > or =3 transcription factor-binding sites are involved in this process. In addition, thapsigargin reduced the renin mRNA half-life from 10 hours (control conditions) to 4 hours. Knockdown studies with small interfering RNA directed to dynamin-1 mRNA revealed that dynamin-1 is likely to be involved in the calcium-mediated destabilization of renin mRNA. These data suggest that calcium inhibits renin gene expression in juxtaglomerular cells via a concerted action of inhibition of renin gene transcription and destabilization of renin mRNA.
Animals↗
Gene expression of 5-, 12-, and 15-lipoxygenases and leukotriene receptors along the rat nephron.
The arachidonate signaling pathways comprise prostanoids formed by cyclooxygenases, EETs, and HETEs formed by cytochrome P-450 (CYP) enzymes and HETEs and leukotrienes generated by lipoxygenases. Whereas the intrarenal localization of cyclooxygenases and of some CYP enzymes along the nephron has already been determined, the localization of lipoxygenases and leukotriene-forming enzymes together with leukotriene receptors in the kidney is less clear. This study therefore aimed to determine the expression of 5-, 12-, and 15-lipoxygenases as well as the leukotriene receptors along the rat nephron. The kidneys were dissected into cortex and outer and inner medulla, and the microdissected nephron segments were collected after a collagenase digestion. mRNA abundance was determined by RT-PCR and real-time PCR. 15-LOX mRNA showed a characteristic expression pattern along the distal nephron. 12-LOX mRNA was only found in the glomerulus. Similarly, 5-LOX mRNAs together with 5-LOX-activating protein mRNAs were expressed in the glomerulus and also in the vasa recta. The leukotriene A4 hydrolase was found in all nephron segments, whereas leukotriene C4 synthase mRNA could not be found in any nephron segment. The leukotriene receptor B4 and the cysteinyl leukotriene receptor type 1 were selectively expressed in the glomerulus, whereas cysteinyl receptor type 2 was not found in any nephron segment. Our data suggest that the glomerulus is a major source and target for 5- and 12-HETE and for leukotrienes. The collecting duct system, on the other hand, appears to be a major source of 15-HETE.
Animals↗
Efficacy and safety of tacrolimus compared with cyclosporin A microemulsion in renal transplantation: 2 year follow-up results.
BACKGROUND: Comparison studies of calcineurin inhibitors as cornerstone immunosuppressants in renal transplantation have demonstrated that tacrolimus consistently reduces acute rejection rates and, in some studies, also improves long-term renal outcome in comparison to cyclosporin A (CsA). The aim of the present 2 year follow-up of the European Tacrolimus vs Cyclosporin A Microemulsion Renal Transplantation Study was to investigate long-term clinical outcome in terms of rate of acute rejection, graft and patient survival and graft function. METHODS: The European Tacrolimus vs Cyclosporin A Microemulsion Renal Transplantation Study was a randomized, comparative 6 month trial of the calcineurin inhibitors tacrolimus and CsA in combination with both azathioprine and steroids. The intent-to-treat population (ITT) consisted of 286 patients in the tacrolimus arm and 271 in the CsA microemulsion (CsA-ME) arm. Whereas whole blood level targets were 10-20 and 5-15 ng/ml for tacrolimus and 100-400 and 100-200 ng/ml for CsA during months 0-3 and 4-6, respectively, during the investigator-driven follow-up after termination of the main study (months 7-24) no specific calcineurin inhibitor target levels were required. Follow-up data were collected at 2 years post-transplantation from 237 (82.9% of the ITT population) patients who received tacrolimus and 222 (81.9% of the ITT population) patients who received CsA-ME. RESULTS: Calculated on ITT populations, mortality (2.0% vs 3.3%; P<0.05 in Kaplan-Meier analysis) was lower, but rate of graft loss (9.3% vs 11.2%; P = 0.12 in Kaplan-Meier analysis) was not significantly different after 2 years with tacrolimus- vs CsA-ME-based immunosuppression. Biopsy-proven acute rejection was significantly lower (19.6%) with tacrolimus than with CsA-ME (37.3%) during months 0-6 (P<0.0001), but was not significantly different during months 7-12 and 13-24 of follow-up (1.7% and 0.8% with tacrolimus and 4.7% and 0.9% with CsA-ME, respectively). A composite endpoint consisting of graft loss, patient death and biopsy-proven acute rejection occurred significantly more frequently in CsA-ME patients than in tacrolimus patients (42.8% vs 25.9%; P<0.001) during 24 months follow-up. Renal function 2 years post-transplant, measured by serum creatinine concentrations, was significantly better in tacrolimus-based compared with CsA-ME-based immunosuppression (136.9 vs 161.6 micromol/l; P<0.01). Cornerstone immunosuppression remained unchanged in 82.5% and 66.2% of patients treated with tacrolimus and CsA-ME, respectively. At 2 years, more patients in the tacrolimus arm were off steroids and received calcineurin inhibitor monotherapy, and fewer tacrolimus patients remained on a triple immunosuppressive regimen. The cardiovascular risk profile was affected favourably in the tacrolimus arm, with lower cholesterol and triglyceride concentrations (despite less use of cholesterol-lowering drugs); no significant difference in requirement for antidiabetic medication was noted. CONCLUSIONS: The 2 year study results confirm that tacrolimus is a highly efficacious cornerstone immunosuppressant in kidney transplantation. Tacrolimus-based immunosuppression may induce long-term benefits with regard to graft function and graft survival. The overall side-effect profile is considered to be favourable.
Adolescent↗
RANTES gene polymorphisms predict all-cause and cardiac mortality in type 2 diabetes mellitus hemodialysis patients.
INTRODUCTION: Patients with type 2 diabetes (DM2) and end stage renal disease (ESRD) have a dismal survival prognosis, mainly due to cardiovascular events. There is sparse data on genetic predictors. Chemokines and their receptors are important in regulating leukocyte influx and activation in atherosclerosis, and functional polymorphisms in the respective genes are associated with cardiovascular disease risk. METHODS: We enrolled 225 prevalent Caucasian DM2 patients receiving maintenance hemodialysis in 30 centres in Southern Germany (time from dialysis initiation <2.0 years) from August 1999 to January 2000 for prospective study until December 2003. The CX3CR1 T280M, and MCP-1 -2518 and RANTES -403 and -28 promoter and intronic In1.1T/C polymorphisms were assessed by real-time PCR. Primary end point was all-cause mortality (ACM). RESULTS: Patients carrying the RANTES -403A or In1.1C allele had a significantly higher ACM risk (multivariate hazard ratio for -403A, dominant model=1.81 [95% CI: 1.22-2.67], p=0.003), mainly due to cardiac events. Similar data were obtained by haplotype analysis. The other SNPs showed no effect on survival. DISCUSSION: In DM2 patients with ESRD, ACM due to cardiac events is associated with RANTES gene variants that are known to alter the expression of this chemokine important in atherosclerosis. Further study of the role of chemokine and chemokine receptor gene variation in determining vascular end points is needed.
Aged↗
Everolimus treatment downregulates renocortical cyclooxygenase-2 expression in the rat kidney.
Based on recent evidence that renal cyclooxygenase-2 (COX-2) gene expression is suppressed by immunosuppressive agents such as cyclosporin A (CsA), tacrolimus and dexamethasone, this study aimed to characterize the effect of the new immunosuppressant everolimus on COX-2 expression in the rat kidney. Oral application of everolimus (3 mg kg(-1) day(-1)) to male Sprague-Dawley rats (175-200 g; n=8) for 7 days lowered COX-2 expression in the rat renal cortex and outer medulla, while COX-2 expression in the inner medulla as well as COX-1 expression remained unaltered. Furthermore, everolimus decreased renocortical prostaglandin (PG) E(2) concentration. Everolimus also attenuated the stimulation of renocortical COX-2 expression by furosemide (12 mg day(-1) for 7 days; s.c. via osmotic minipumps), by low salt intake (0.02% NaCl, wt wt(-1)) or by a combination of low salt intake with the AT(1)-receptor antagonist valsartan (30 mg kg(-1) day(-1); oral). In line with these findings, everolimus decreased renocortical PGE(2) concentration during these treatment maneuvers. Everolimus moderately increased natriuresis and diuresis, while the urinary excretion of PGE(2), 6-keto PGF(1alpha) and thromboxane B(2) was decreased. These findings suggest that everolimus inhibits basal and also stimulated expression of renocortical COX-2 and of tissue prostanoid formation. Since inhibition of renal prostanoid formation by everolimus was associated by an increased rather than decreased natriuresis and diuresis, it appears as if everolimus also inhibits tubular salt and water resorption.
Animals↗
The chemokine receptor 5 Delta32 mutation is associated with increased renal survival in patients with IgA nephropathy.
BACKGROUND: Chemokine receptor 5 (CCR5) plays an important role in the recruitment of monocytes and T cells in inflammation and experimental studies suggest that CCR5 might be involved in the pathogenesis of IgA nephropathy. A mutation in the CCR5 gene (CCR5 Delta32), leading to a nonfunctional receptor, was recently described. We therefore evaluated the potential role of this mutation on renal survival in patients with IgA nephropathy. METHODS: The distribution of the CCR5 Delta32 genotype was determined by polymerase chain reaction (PCR) analysis in 228 patients with biopsy-proven IgA nephropathy. In 190 patients with available demographic and clinical follow-up data, the effect of the mutation on the clinical outcome was analyzed using the Log-rank test and the Cox proportional hazard model. In vitro, the influence of the CCR5 Delta32 genotype on the chemotactic response of monocytes was assessed. RESULTS: Of the 190 patients, 158 (83.2%) had a CCR5 wild-type genotype, 29 (15.3%) were heterozygous, and three patients had a homozygous CCR5 Delta32 genotype (1.6%). Renal survival was significantly longer in patients with the CCR5 Delta32 genotype than in the wild-type group (Log-rank P < 0.001). Using the multivariate Cox proportional hazard model, the CCR5 Delta32 genotype was identified as an independent factor associated with a lower risk to develop end-stage renal disease (ESRD) [hazard ratio (HR) 0.23, 95% CI 0.09 to 0.57, P= 0.002]. In vitro analysis of monocytes from CCR5 Delta32 carriers showed a reduced chemotactic response to CCR5 ligands in vitro. CONCLUSION: Our study demonstrates an independent role of the CCR5 Delta32 genotype for the clinical outcome in IgA nephropathy. In vitro experiments revealed a reduced chemotactic response of monocytes from CCR5 Delta32 carriers, thus pointing out a possible pathophysiologic explanation for the beneficial effect of the CCR5 Delta32 genotype.
Alleles↗
C-reactive protein as predictor of death in end-stage diabetic nephropathy: role of peripheral arterial disease.
BACKGROUND: Patients with diabetes type 2 receiving dialysis therapy have a poor survival prognosis, mainly due to cardiovascular events. Increased C-reactive protein (CRP) levels, important in atherosclerosis, are associated with an increased risk for cardiovascular events. However, to date no study has shown the predictive value of CRP in relation to peripheral arterial disease stage. METHODS: We enrolled all 445 prevalent patients with diabetic nephropathy receiving maintenance hemodialysis in 30 centers in Southern Germany from August 1999 to January 2000 for prospective study until December 2003. At inclusion, CRP and a complete clinical phenotype, including peripheral arterial disease Fontaine Stage were determined. The primary end point was all-cause mortality. RESULTS: A total of 305 (68.5%) patients died. An increased log CRP at study inclusion was significantly associated with an increase in hazard ratio (HR) by multivariate Cox regression for all-cause (HR = 1.5, P= 0.002) and cardiac death (HR = 1.76, P= 0.02) in the entire collective. This result was applicable only to patients with peripheral arterial disease Fontaine stage IV (N= 190, multivariate HR = 1.75 for all-cause mortality, P= 0.006). Possibly due to inadequate power, we observed only an insignificant trend for CRP as predictor of all-cause death in patients without peripheral arterial disease or with less severe forms of peripheral arterial disease (HR = 1.36, P= 0.08). CONCLUSION: In contrast to patients with peripheral arterial disease stage IV, patients with less severe atherosclerosis and elevated CRP are, if any, at less risk for cardiovascular mortality, possibly due to the difference in extent of affected vasculature and thus activated platelets and coagulation. Before judging the predictive value of CRP for mortality, peripheral vessel status should be determined.
Aged↗
N-acetylcysteine in the prevention of radiocontrast-induced nephropathy: clinical trials and end points.
N-acetylcysteine (NAC) has been suggested to prevent radiocontrast-induced nephropathy (RCIN) in patients with a reduced renal function. However, clinical studies have not been demonstrating this effect consistently. Also, reviews and meta-analyses dealing with the question of prevention of RCIN by NAC have been controversial. Nearly all investigators used serum creatinine as surrogate end point of their trials, and changes in serum creatinine concentrations are thought to reflect the extent of renal injury as primary outcome. In a recent study, an effect of NAC on creatinine values and estimated glomerular filtration rate without any effect on cystatin C levels has been shown in volunteers with a normal renal function. Therefore, before renal protective effects of NAC in RCIN are proposed, any direct effects of NAC on creatinine, urea, and estimated glomerular filtration rate should be addressed. In future trials, the glomerular filtration rate should preferentially be measured directly, or at least additional markers of the renal function (e.g., serum cystatin C) have to be assessed. Furthermore, additional 'hard' end points, i.e., hospital morbidity, mortality, or dialysis dependency, should be considered in the design of future studies of RCIN.
Acetylcysteine↗
Steroid-free organ transplantation.
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Adrenal Cortex Hormones↗
Cyclosporine A and chlorambucil in the treatment of idiopathic focal segmental glomerulosclerosis.
BACKGROUND: The therapy of nephrotic syndrome in focal segmental glomerulosclerosis (FSGS) is still a matter of controversy. METHODS: We performed a prospective randomized study of the treatment of nephrotic syndrome due to FSGS. We compared 2 specific treatment protocols to assess the effect of treatment on proteinuria and renal function. Fifty-seven patients were randomly assigned to 2 groups: group 1 (n = 34) received steroids and cyclosporine, and group 2 (n = 23) received steroids and chlorambucil for 6 months. When treatment was refractory to chlorambucil, the patients in this group were treated with cyclosporine. Creatinine, blood urea nitrogen, proteinuria, lipids, and arterial hypertension were monitored at regular intervals. RESULTS: Patients showed a mean serum creatinine of 1.5 +/- 0.2 mg/dL (132.6 +/- 17.7 micromol/L) and proteinuria of 4.8 +/- 2.8 g/24 h with no differences between the groups. At the end of the chlorambucil therapy, patients in group 2 had creatinine levels of 1.8 +/- 0.6 mg/dL (159.1 +/- 53 micromol/L) and proteinuria levels of 3.4 +/- 1 g/24 h. All patients in this group were given cyclosporine. After 4 years the mean creatinine level in group 1 was 1.7 +/- 0.4 mg/dL (150.3 +/- 35.4 micromol/L) and the proteinuria level was 2.5 +/- 1 g/24 h. In group 2, the mean creatinine level was 1.9 +/- 0.6 mg/dL (168 +/- 53 micromol/L) (not significant [NS]) and the mean proteinuria level was 2.3 +/- 1.1 g/24 h (NS). Full remission occurred in 23% of the patients in group 1 (n = 8) and 17% of the patients in group 2 (n = 4; NS). Partial remission was observed in 38% of the patients in group 1 (n = 13) and 48% in group 2 (n = 11; NS). The number of patients who developed end-stage renal disease was comparable in both groups: 4 of 34 patients in group 1 after 2.5 +/- 0.8 years, and 5 of 23 patients in group 2 (NS). CONCLUSION: Additional treatment with chlorambucil was found to be ineffective in FSGS. Patients responded to treatment with steroids or cyclosporine, but additional treatment with chlorambucil did not improve the patient's outcome. Future studies must focus on the long-term prognosis of these patients.
Adult↗
The value of N-acetylcysteine in the prevention of radiocontrast agent-induced nephropathy seems questionable.
Prevention of contrast agent-induced nephropathy is of crucial importance for a number of diagnostic studies. N-Acetylcysteine (NAC) was recently reported to decrease serum creatinine levels in this setting, and its administration before radiocontrast medium administration has been widely recommended. The objective of this prospective study was to investigate whether there are effects of NAC on serum creatinine levels that are independent of alterations in GFR. Volunteers with normal renal function who did not receive radiocontrast medium were studied. Fifty healthy volunteers completed the study protocol. NAC was administered orally at a dose of 600 mg every 12 h, for a total of four doses. Surrogate markers of renal function, such as serum creatinine, urea, albumin, and cystatin C levels, were measured and estimated GFR (eGFR) was assessed immediately before the administration of NAC and 4 and 48 h after the last dose. There was a significant decrease in the mean serum creatinine concentration (P < 0.05) and a significant increase in the eGFR (P < 0.02) 4 h after the last dose of NAC. The cystatin C concentrations did not change significantly. In several studies, a protective effect of NAC on renal function after radiocontrast medium administration has been postulated. This is the first study to demonstrate an effect of NAC on creatinine levels and eGFR, surrogate markers of renal injury, without any effect on cystatin C levels. Before renoprotective effects of NAC against contrast agent-induced nephropathy are considered, the direct effects of NAC on creatinine levels, urea levels, and eGFR should be assessed.
Acetylcysteine↗
Gene expression of adenosine receptors along the nephron.
BACKGROUND: In view of the multiple effects of adenosine on kidney function, this study aimed to determine the expression of adenosine receptors (AR) along the rat and mouse nephron. METHODS: For this purpose, we semiquantified mRNA abundance for adenosine A1-, A2A-, A2B-, and A3 receptors by RNAse protection and by reverse transcription-polymerase chain reaction (RT-PCR) in the kidney zones and in the different nephron segments of mice and rats. RESULTS: We found very similar expression patterns for rat and mice. For the kidney zones A1-AR mRNA and A2A-AR mRNA abundance displayed a marked difference, with an increase from cortex to the inner medulla. This was not seen for A2B receptors, which showed in general a rather weak expression. Along the nephron, A1-AR was strongly expressed in the thin limbs of Henle and in the collecting duct system and to a lesser extent in the medullary thick ascending limb. A2A-AR mRNA was clearly detected in glomeruli but not in other nephron segments. A2B-AR mRNA was strongly expressed in the cortical thick ascending limb of Henle and in the distal convoluted tubule. A3-AR mRNA was not found in any nephron segment. CONCLUSION: Our data demonstrate a distinct mutual expression of the AR subtypes along the nephron. A1 receptors are expressed in medullary tubular structures, while A2B receptors are predominant in cortical tubular structures. A2A receptor expression in the kidney appears to be restricted to vascular cells.
Animals↗