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Biomedical subjects

Robert C Atkins

Publications and source records attributed to Robert C Atkins.

At least 55 records · Page 3Linked to original sources
PubMed2004

Arterial function after successful renal transplantation.

BACKGROUND: Renal transplantation is increasingly the preferred method of renal replacement therapy. Cardiovascular disease is the major barrier to long-term survival for transplant recipients. The aim of this study was to determine whether the increased arterial stiffness of patients with chronic renal failure is improved after successful renal transplantation. METHODS: The study involved a group of 36 patients, aged 27 to 68 years (mean +/- SD, 46 +/- 11 years) who had cardiovascular risk assessment and measurements of carotid artery intima-media thickness (IMT), arterial pulse wave velocity [aorto-femoral (PWV a-f) and femoral-dorsalis pedis (PWV f-d)], systemic arterial compliance (SAC), and arterial wave reflection (augmentation index, AI(x)) performed before and 12 months after successful renal transplantation. B-mode ultrasound measurements were used to determine mean carotid IMT and applanation tonometry techniques to determine SAC, AI(x), PWV (a-f), PWV (f-d), and central pressures. On each occasion the following were also measured: fasting lipids, homocysteine (tHcy), red cell folate, cobalamin, and fibrinogen levels. RESULTS: One year after transplantation, mean serum creatinine was 143 +/- 47 micromol/L, and creatinine clearance 60 +/- 16 mL/min/1.74m(2) (range 25 to 104 mL/min/1.74m(2)). Total and low-density lipoprotein (LDL) cholesterol were significantly reduced. tHcy was decreased by 38% and normalized in 45%. Systolic and diastolic blood pressure and mean arterial pressure were all improved. From baseline to 12 months' post-transplantation, there was no significant change in carotid IMT (mean IMT 0.76 +/- 0.11 vs. 0.75 +/- 0.14 mm, P= 0.28) or SAC (0.45 +/- 0.23 vs. 0.46 +/- 0.22 units, P= 0.95), but PWV [PWV (a-f) 9.6 +/- 2.6 vs. 8.8 +/- 2.2 m/sec, P= 0.007; PWV (f-d) 10.7 +/- 1.8 vs. 8.4 +/- 1.7 m/sec, P < 0.001] and AI(x) (24.3 +/- 13.4 vs. 15.9 +/- 11.4%, P= 0.003) improved. After adjusting for the differences in blood pressure, the changes in PWV (a-f) were no longer significant, but the differences in PWV (f-d) persisted. The change in AI(x) remained significant after adjusting for differences in heart rate, and the fall in AI(x) was greater in patients on immunosuppression with tacrolimus compared with those on cyclosporine. CONCLUSION: One year after successful renal transplantation, improvement in cardiovascular risk factors was associated with improvement in indices of arterial stiffness.

Adult↗
PubMed2004

Prevalence of albuminuria in Australia: the AusDiab Kidney Study.

BACKGROUND: Albuminuria is an important predictor of risk of progressive renal disease, cardiovascular disease, and mortality; however, the prevalence in the general population is not well defined. We determined estimates of the population prevalence and associations of microalbuminuria and macroalbuminuria in Australian adults; 11,247 Australians aged > or = 25 years living in 42 randomly selected population clusters were tested for albuminuria (spot urine albumin:creatinine (mg/mmol): normal < 3.4, microalbuminuria 3.4 to 34, macroalbuminuria > 34). METHODS: Prevalence of micro- and macroalbuminuria were assessed with age, sex, obesity, smoking, hypertension (> or = 140/90 mm Hg or known diagnosis on treatment), glucose metabolism status (WHO criteria according to fasting glucose and oral glucose tolerance test), ischemic heart and cerebrovascular disease, and low glomerular filtration rate (calculated glomerular filtration rate < 60 mL/min/1.73m2). RESULTS: Microalbuminuria and macroalbuminuria proteinuria were present in 6.0% and 0.6% of the population, respectively. The majority of subjects with microalbuminuria (64%) and macroalbuminuria (76%) had hypertension, and approximately half of those with albuminuria had abnormal glucose metabolism. Of all participants with microalbuminuria, 25.9% had normal blood pressure and glucose metabolism, and in this group, alternative associations of microalbuminuria included obesity (13.5%), smoking (20.7%), and low glomerular filtration rate (12.3%). CONCLUSION: Albuminuria is present in a small percentage of the general adult population, but is highly prevalent in subjects with hypertension and/or abnormal glucose metabolism. The majority of cases of microalbuminuria and macroalbuminuria in the general population are among those with hypertension.

Albuminuria↗
PubMed2004

Impact of irbesartan, blood pressure control, and proteinuria on renal outcomes in the Irbesartan Diabetic Nephropathy Trial.

BACKGROUND: It is important to know the reliability of early changes in proteinuria in predicting late renal outcomes. The IDNT was a trial in which treatment assignment, baseline and follow-up blood pressure determinations, and albumin/creatinine ratios (ACR), and renal outcomes were recorded. METHODS: Risk of renal outcomes in the IDNT was assessed by proportional hazards modeling as a function of treatment assignment, and achieved systolic blood pressure (SBP) both without, and then with, inclusion of values for baseline proteinuria and early changes in proteinuria. RESULTS: In models without ACR variables, both treatment with irbesartan and achieved SBP during follow-up were significantly predictive of the risk of renal outcomes. Addition of ACR variables to the models reduced the apparent impact of assignment to irbesartan by 52% to 81%, and irbesartan was no longer a significant predictor of renal outcomes. Conversely, addition of ACR variables to the models attenuated the effect of achieved follow-up SBP by only 32% to 46%, and follow-up BP remained a highly significant predictor of renal outcomes. CONCLUSION: The ability of early changes in proteinuria to predict the impact of treatment on renal outcomes is a function of the specific treatment. One must use caution in using early changes in proteinuria as a surrogate for longer-term renal outcomes.

Antihypertensive Agents↗
PubMed2004

Albuminuria is evident in the early stages of diabetes onset: results from the Australian Diabetes, Obesity, and Lifestyle Study (AusDiab).

BACKGROUND: Albuminuria is a common complication of diabetes and a leading cause of end-stage renal disease. We determined the prevalence of and factors associated with albuminuria in an Australian population and examined the association of albuminuria with glucose tolerance. METHODS: The Australian Diabetes, Obesity, and Lifestyle Study included 11,247 adults aged 25 years and older from 42 randomly selected areas of Australia. Microalbuminuria is defined as an albumin-creatinine ratio of 22 to 220 mg/g (2.5 to 25 mg/mmol) in men and 31 to 220 mg/g (3.5 to 25 mg/mmol) in women, and macroalbuminuria is defined as an albumin-creatinine ratio of 220 mg/g or greater (> or =25.0 mg/mmol). RESULTS: Overall, 25.3% of patients with diabetes mellitus (known [KDM] and newly diagnosed [NDM], type 1 and type 2) had evidence of albuminuria (21.0%, microalbuminuria; 4.3%, macroalbuminuria). Prevalence increased with increasing glycemia (normal glucose tolerance [NGT], 5.1%; impaired fasting glucose [IFG], 9.3%; impaired glucose tolerance, 11.0%; NDM, 17.8%; and KDM, 32.6% [type 2 only]). Patients with diabetes (KDM and NDM) and IFG had an increased risk for albuminuria compared with those with NGT independent of age, sex, and other known risk factors for albuminuria. Logistic regression modeling identified age, duration of diabetes, systolic blood pressure, current smoking, body mass index, and glycated hemoglobin level as independent risk factors for albuminuria. CONCLUSION: This Australian population-based study shows that albuminuria is common among patients with established diabetes, is present before the onset of diabetes, and becomes more prevalent with worsening glucose tolerance.

Aged↗
PubMed2003

Macrophages act as effectors of tissue damage in acute renal allograft rejection.

BACKGROUND: Macrophages constitute 38% to 60% of infiltrating cells during acute renal allograft rejection. Their contribution to tissue damage during acute rejection was examined by depleting macrophages in a rat model. METHODS: Lewis rats underwent bilateral nephrectomy and then received a Dark Agouti renal allograft and liposomal-clodronate, control phosphate-buffered saline liposomes, or saline intravenously (n=7 per group) on days 1 and 3 postsurgery. Grafts were harvested on day 5. RESULTS: Liposomal-clodronate treatment resulted in a 70% reduction in blood ED1+ monocytes and 60% reduction in intragraft ED1+ macrophages (both P<0.01). Half of all remaining interstitial ED1+ cells were undergoing apoptosis (terminal deoxynucleotide transferase-mediated dUTP nick-end labeling+/ED1+), and thus functional depletion of more than 75% of macrophages was achieved. Histologic and functional parameters of acute rejection were attenuated: interstitial infiltrate, tubulitis, and glomerulitis (P<0.01); tubular cell apoptosis (P<0.001); tubular cell proliferation (P<0.001); and serum creatinine (P<0.01). Production of inducible nitric oxide synthase by infiltrating cells and urinary nitric oxide excretion was reduced by 90% (P<0.001). In contrast, no reduction in the number of other leukocytes was seen (CD3+, CD4+, CD8+, and natural killer cells). Activation of lymphocytes (CD25+) and production of lymphocyte effector molecules (granzyme B) were unaltered. CONCLUSION: This study demonstrates that macrophages contribute to tissue damage during acute rejection.

Acute Disease↗
PubMed2003

Blockade of macrophage colony-stimulating factor reduces macrophage proliferation and accumulation in renal allograft rejection.

Macrophage accumulation within an acutely rejecting allograft occurs by recruitment and local proliferation. To determine the importance of M-CSF in driving macrophage proliferation during acute rejection, we blocked the M-CSF receptor, c-fms, in a mouse model of acute renal allograft rejection. C57BL/6 mouse kidneys (allografts, n = 20) or BALB/c kidneys (isografts, n = 5) were transplanted into BALB/c mice. Anti-c-fms antibody (AFS98) or control Ig (50 mg/kg/day, i.p.) was given daily to allografts from days 0-5. All mice were killed day 6 postoperatively. Expression of the M-CSF receptor, c-fms, was restricted to infiltrating CD68+ macrophages. Blockade of c-fms reduced proliferating (CD68+/BrdU+) macrophages by 82% (1.1 v 6.2%, p < 0.001), interstitial CD68+ macrophage accumulation by 53% (595 v 1270/mm2, p < 0.001), and glomerular CD68+ macrophage accumulation by 71% (0.73 V 2.48 CD68+ cells per glomerulus, p < 0.001). Parameters of T-cell involvement (intragraft CD4+, CD8+ and CD25+ lymphocyte numbers) were not affected. The severity of tubulointerstitial rejection was reduced in the treatment group as shown by decreased tubulitis and tubular cell proliferation. Macrophage proliferation during acute allograft rejection is dependent on the interaction of M-CSF with its receptor c-fms. This pathway plays a significant and specific role in the accumulation of macrophages within a rejecting renal allograft.

Animals↗
PubMed2003

Blockade of macrophage migration inhibitory factor does not prevent acute renal allograft rejection.

Macrophage migration inhibitory factor (MIF) is a pro-inflammatory molecule involved in cell-mediated immunity and delayed-type hypersensitivity (DTH). We inhibited systemic and local MIF production to determine its contribution to acute rejection (AR). Skin DTH response and acute rejection of skin and kidney allografts were examined using MIF gene knockout (MIF -/-) and wild-type mice (MIF +/+) with anti-MIF or control antibody. MIF-Ab reduced skin DTH by 60% (p < 0.01), but absence of the MIF gene (MIF -/-) had no effect. Local absence of MIF had no effect on the survival of skin grafted onto BALB/c recipients. Similarly MIF +/+ and MIF -/- kidneys transplanted into BALB/c recipients showed a similar degree of histological rejection, graft dysfunction and cellular infiltrate suggesting that AR is not dependent on local MIF production. To investigate the influence of systemic MIF, BALB/c donor skin was grafted onto MIF +/+ and MIF -/- mice. The tempo of AR was not altered by systemic absence of MIF (MIF-Ab or MIF -/-). BALB/c kidneys transplanted into MIF +/+ (with or without MIF-Ab) and MIF -/- mice showed similar parameters of rejection. MIF blockade reduces the DTH response; however, neither local nor systemic MIF are required for the rejection of fully mismatched skin and renal allografts.

Animals↗
PubMed2003

Role of interleukin-10 in rat mesangioproliferative glomerulonephritis.

Interleukin-10 (IL-10) has been recognized as a growth factor for rat mesangial cells in vitro; however, its role in mesangioproliferative glomerulonephritis is unknown. We studied the expression of IL-10 mRNA in the rat anti-Thy-1 model of mesangioproliferative glomerulonephritis (experiment 1) and, subsequently, the effects of blocking IL-10 during anti-Thy-1 nephritis using the IL-10 inhibitor, AS101 (experiment 2). In experiment 1, PCR analysis failed to detect IL-10 mRNA in normal rat kidney, however, a clear signal for IL-10 mRNA was evident on day 6 of anti-Thy-1 nephritis. In situ hybridization showed IL-10 mRNA expression in focal glomerular areas in anti-Thy-1 nephritis. Combined in situ hybridization and immunohistochemistry showed that glomerular IL-10 mRNA was expressed by both macrophages and mesangial cells. In experiment 2, treatment with AS101 significantly downregulated renal IL-10 gene expression, as demonstrated by semiquantitative PCR. However, the induction of glomerular hypercellularity, mesangial proliferation (PCNA+ cells), mesangial cell activation (alpha-SMA expression) and macrophage accumulation (ED1+ cells) seen in saline-treated anti-Thy-1 nephritis was unaffected by AS101 treatment. In conclusion, renal IL-10 gene expression is upregulated during pathological mesangial cell proliferation in rats with anti-Thy-1 nephritis. However, the inability of IL-10 suppression with AS101 to prevent anti-Thy-1 disease suggests that IL-10 is not essential for pathological mesangial cell proliferation.

Animals↗
PubMed2003

Interferon-gamma induces macrophage migration inhibitory factor synthesis and secretion by tubular epithelial cells.

Macrophage migration inhibitory factor (MIF) promotes macrophage accumulation and leucocyte activation during inflammation. Macrophage migration inhibitory factor is upregulated in intrinsic renal cells in many types of kidney diseases, and has a pathogenic role in rat crescentic nephritis. However, little is known about the factors that regulate the production and secretion of MIF in kidney cells. In this study, we evaluated whether interferon-gamma (IFN-gamma), a cytokine implicated in the development of kidney disease and a potent inducer of MIF production in macrophages, could promote MIF synthesis and secretion from renal tubular epithelial cells. Northern blot analysis detected constitutive expression of MIF mRNA in rat tubular epithelial cells (NRK52E), which increased twofold after a 6-h stimulation with IFN-gamma. Macrophage migration inhibitory factor protein was found only in the cytoplasm of NRK52E cells. Following IFN-gamma stimulation, intracellular MIF in NRK52E cells was rapidly secreted with a maximal reduction of 50% after 20 min, which returned to normal levels after 2-4 h. Rapid secretion of MIF in response to IFN-gamma was also seen in rat mesangial cells. These findings indicate that IFN-gamma induces rapid secretion of MIF by tubular epithelial cells, and suggest that this may be an important mechanism leading to inflammatory cell accumulation and activation during kidney disease.

Animals↗
PubMed2003

Cardiovascular risk in dialysis patients: a comparison of risk factors and cardioprotective therapy between 1996 and 2001.

Cardiovascular disease (CVD) is the major cause of mortality in dialysis patients. Aspirin, beta-blockers, statins, and angiotensin-converting enzyme (ACE) inhibitors reduce CVD mortality in the general population, as may angiotensin II receptor antagonists. The prevalence of cardiovascular risk factors and usage rates of cardioprotective agents in end-stage renal failure are unknown. A retrospective, cross-sectional study of dialysis patients was performed to compare: (i) prevalence of cardiovascular risk factors (age, hypertension, hyperlipidaemia, diabetes mellitus, and smoking); (ii) use of cardioprotective agents; and (iii) prevalence of cardiovascular disease between the time-points: 1996 (n = 262) versus 2001 (n = 369). We found an increase in the risk factors of age (53.6 +/- 14.9 years in 1996 vs 58.4 +/- 14.3 in 2001; P < 0.001) and hyperlipidaemia (45 vs 51.8%; P < 0.001) between the two time-points, with a reduction in the prevalence of smoking (14.5 vs 8.1%; P = 0.016). There was no difference in the prevalence of cardiovascular disease (37.4 vs 40.7%; P = 0.44). Cardioprotective agents were underutilized, with improvement in prescribing practice between 1996 and in 2001, especially in the usage of statins (21.4 vs 38.7% in 2001; P = 0.019). In conclusion, CVD is the primary cause of mortality in our dialysis patients. Although traditional cardiovascular risk factors affect the majority of the dialysis population, underutilization of cardioprotective agents is common. Proof of efficacy of these agents in this population of enormous risk is urgently required.

Cardiotonic Agents↗
PubMed2003

Historical controlled trial of OKT3 versus basiliximab induction therapy in simultaneous pancreas-renal transplantation.

Simultaneous pancreas-kidney (SPK) transplant recipients are at high immunological risk of rejection. Antibody induction is beneficial but lymphocyte-depleting therapy is associated with a high incidence of side-effects. We performed a historical controlled trial to compare OKT3 versus anti-CD25 antibody (basiliximab) induction therapy with regard to patient, kidney and pancreas survival, as well as to examine for any differences in acute rejection, graft function, and infective complications. Twenty-eight consecutive SPK transplants were performed at the Monash Medical Centre between December 1997 and November 2001. Anti CD3 monoclonal antibody (OKT3) was used prior to March 2000 (n = 12) and basiliximab was used after (n = 16), both in combination with cyclosporin, mycophenolate, and prednisolone. A retrospective comparison of outcomes was performed. At 6 months, patient (100 vs 100%), kidney (91.7 vs 91.7%) and pancreas (75 vs 83.3%) survival were similar in the OKT3 and basiliximab groups, respectively. A minority of subjects in each group remained free from rejection (42% basiliximab vs 25% on OKT3, P = NS). Renal function was superior in the basiliximab group (mean calculated creatinine clearance 79.4 +/- 11.9 vs 54.5 +/- 15.9 mL/min for basiliximab vs OKT3, P < 0.001). The incidence of major opportunistic infection was lower in basiliximab-treated patients (9 vs 50% in the OKT3 group, P = 0.033). Basiliximab was associated with similar 6-month patient, kidney and pancreas survival, superior renal function and less opportunistic infection as compared with OKT3 induction therapy in SPK transplants. Basiliximab is at least as effective and is safer than OKT3 for induction therapy in SPK transplantation.

Adult↗
PubMed2003

Epidemiology of vascular access in the Australian hemodialysis population.

BACKGROUND: A number of demographic and comorbid factors have been demonstrated to be associated with the placement of arteriovenous grafts (AVG) and central venous catheters (CVC) as opposed to native arteriovenous fistulas (AVF). However, no data are available regarding these factors in a hemodialysis population where AVF utilization is high. METHODS: All adult patients on hemodialysis on September 30, 2001 in Australia were included in the study. Vascular access was recorded as AVF, AVG, or CVC. Patients were separated into incident (<150 days since first dialysis) and prevalent cohorts (> or =150 days). Multinomial logistic regression was used to assess factors associated with AVG and CVC use. RESULTS: Of the 4968 patients who were studied, 877(17%) were classed as incident and the remainder prevalent. AVF were present in 61% versus 77%, AVG were present in 11% versus 19%, and CVC were present in 28% versus 4% in the incident and prevalent cohorts, respectively (all P < 0.001). After adjustment for confounding factors, age and female gender were associated with an increased frequency of AVG in both cohorts. In addition, type I diabetes mellitus was associated with increased frequency of AVG use in the incident cohort, whereas body mass index (BMI) > or =30 kg/m2 and peripheral vascular and cerebrovascular disease were significant in the prevalent group. For CVC, female gender, type I and II diabetes mellitus and late referral were associated with increased frequency in the incident cohort, while females, cigarette smoking, and peripheral vascular disease were predictive in the prevalent group. Significant variations in access type were also seen depending on geographic location. CONCLUSION: Certain patient characteristics such as age and female gender, but not type II diabetes mellitus, remain significantly associated with AVG and catheter use despite the high prevalence of AVF use in Australia. However, the significant variation in risk by geographic location suggests more attention needs to be paid to physician practice patterns to increase AVF utilization rates.

Adult↗
PubMed2003

Activation and cellular localization of the p38 and JNK MAPK pathways in rat crescentic glomerulonephritis.

BACKGROUND: The p38 and c-Jun N-terminal kinase (JNK) mitogen-activated protein kinase (MAPK) are intracellular signal transduction pathways involved in the production of inflammatory mediators. Little, however, is known about the contribution of these pathways to renal inflammation, nor the cell types in which these pathways are activated within normal and inflamed kidneys. The aim of this study was therefore to delineate the pattern and cellular localization of p38 and JNK activation in normal rat kidney and rat acute and chronic inflammatory renal disease. METHODS: Normal male Sprague-Dawley rats and groups of rats given accelerated anti-glomerular basement membrane (GBM) disease were killed at 3 hours, day 1, day 7, or day 28 and examined for p38 and JNK pathway activation by Western blotting and immunolocalization of the phosphorylated p38 (p-p38) and JNK (p-JNK) kinases. RESULTS: In terms of glomerular MAPK activation, Western blotting identified the presence of both p-p38 and p-JNK in normal glomeruli, localized by immunohistochemistry to podocytes and epithelial cells of Bowman's capsule. In anti-GBM disease, Western blotting showed that p38 activation peaked at 3 hours and remained elevated above normal throughout the disease time course. JNK activation (via the 54 kD isoform) likewise increased at 3 hours of anti-GBM disease and remained elevated throughout disease. At 3 hours, p-p38, but not p-JNK, was localized to neutrophils and glomerular endothelial cells. p-JNK was localized to glomerular endothelial cells at day 7. Macrophages, lymphocytes, activated podocytes, and myofibroblasts were positive for both p-p38 and p-JNK. In terms of tubular MAPK activation, Western blotting identified p38 and JNK activation in tubules of normal kidney. Immunostaining showed that most cortical tubules contained some p-p38 and p-JNK stained cells. There was a significant increase in tubular p38 activation at 3 hours of anti-GBM disease, followed by increased JNK activation of the 54 kD isoform from day 7 onward, and the 46 kD isoform at day 28. Immunostaining of diseased tissue localized p-p38 and p-JNK to virtually all cortical tubular cells. CONCLUSION: The p38 and JNK MAPK pathways are activated in glomeruli and tubules of normal kidney. In acute anti-GBM disease, there was an increase in p38 activation within glomerular endothelial cells and within infiltrating neutrophils, suggesting an important role for p38 MAPK in acute inflammation. In progressive anti-GBM disease, p38 and JNK activation in podocytes, glomerular endothelial cells, infiltrating macrophages, T cells, and myofibroblasts suggests that both the p38 and JNK MAPK pathways are important in chronic inflammation and fibrosis. Blockade of these pathways may therefore be potentially therapeutic in the treatment of acute and chronic renal inflammation.

Animals↗
PubMed2003

Adoptive transfer studies demonstrate that macrophages can induce proteinuria and mesangial cell proliferation.

BACKGROUND: Glomerular macrophage accumulation is a feature of proliferative human and experimental glomerulonephritis. However, our understanding of the role of macrophages in the induction of renal injury is based upon indirect evidence from depletion studies, most of which lack specificity for this cell type. Therefore, an adoptive transfer approach was used to directly assess the potential of macrophages to induce renal injury. METHODS: Accelerated anti-glomerular basement membrane (anti-GBM) disease was induced in rats by immunization with sheep IgG (day -5), followed by administration of sheep anti-rat GBM serum (day 0), with animals killed on day 2. To facilitate the adoptive transfer studies, immunized animals were made leukopenic by cyclophosphamide (CyPh) given on day -2. Bone marrow-derived (BM) or NR8383 macrophages were transferred by tail vein injection 24 hours after injection of anti-GBM serum, with animals killed 3 or 24 hours after transfer. RESULTS: Pretreatment with CyPh prevented glomerular leukocyte accumulation and completely inhibited proteinuria, glomerular cell proliferation and hypercellularity in accelerated anti-GBM disease. Adoptive transfer led to significant glomerular accumulation of BM or NR8383 macrophages within 3 hours of injection, and this was still evident 24 hours later. Adoptive transfer of BM or NR8383 macrophages induced proteinuria (63 +/- 16 BM vs. 5 +/- 2 mg/24 h CyPh control; P < 0.001), glomerular cell proliferation (5.1 +/- 1.2 BM vs. 0.5 +/- 0.1 PCNA+ cells/gcs CyPh; P < 0.001) and glomerular hypercellularity (51.2 +/- 2.0 BM vs. 41.9 +/- 0.9 nuclei/gcs CyPh; P < 0.001). The degree of renal injury correlated with the number of transferred glomerular macrophages. Two-color immunostaining demonstrated that most glomerular proliferative cell nuclear antigen+ (PCNA+) proliferating cells were OX-7+ mesangial cells. CyPh treatment did not prevent up-regulation of glomerular intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule (VCAM-1) expression or an increase in urinary monocyte chemoattractant protein-1 (MCP-1) excretion. CONCLUSION: This study provides the first direct evidence that macrophages can induce renal injury in terms of proteinuria and mesangial cell proliferation.

Adoptive Transfer↗