The urinary sediment beyond light microscopical examination.
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Humans↗
Biomedical subjects
F P Schena
Publications and source records attributed to F P Schena.
Confocal laser scanning microscope study of terminal villi vessels in normal term and pre-eclamptic placentas.
The aim of this study was to compare immunocytochemical confocal scanning laser microscopy measures of villus capillarization in control placentas with pre-eclamptic ones. Accordingly, placentas from normal term pregnancies (n=3) and cases of late-onset pre-eclampsia without intrauterine growth retardation (IUGR) featuring normal uterine artery Doppler (n=3) were analyzed by confocal scanning laser microscopy (CSLM), which is a powerful technique for obtaining three-dimensional reconstructions of any kind of blood vessels (arteries, veins, capillaries). A laser light beam is used in order to detect CD34 antibody-related immunofluorescence, which is a marker of endothelial cells. Villus capillarization was assessed by estimating the following parameters: number of pixels, mean, maximum and minimum immunofluorescence amplitude. Our results show a significant hyper-ramification of the capillary loop in pre-eclamptic placentas, featuring irregular profile and narrow lumina. Such findings support the hypothesis that several agents causing angiogenesis and vasoconstriction affect villus vessels in pre-eclamptic placentas, thus promoting a lasting condition of fetal hypoxia by decreasing endothelial surface and materno-fetal exchanges.
Adult↗
A randomized trial of steroid avoidance in renal transplant patients treated with everolimus and cyclosporine.
In this randomized trial renal transplant recipients were treated with basiliximab, everolimus 3 mg/day, low-dose CsA. At transplantation, patients were randomized to stop steroids at the seventh day (group A) or to continue oral steroids in low doses (group B). Of the 113 patients enrolled, 65 were randomized to group A and 68 to group B. All patients were followed for 2 years. During the study 28 (43%) group A patients required reintroduced corticosteroids. One patient died, in group B. The Graft survival rate was 97% in group A and 90% in group B. There were more biopsy-proven rejections in group A (32% vs 16%; P = .044). The mean creatinine clearance was 54 +/- 21 mL/min in group A vs 56 +/- 22 mL/min in group B. Mean levels of serum cholesterol tended to be lower in group A, but the difference was of borderline significance (191 +/- 91 vs 251 +/- 188 mg/dL; P = .07). Vascular thrombosis (0 vs 5) and pneumonia requiring hospitalization (2 vs 7) tended to be more frequent in group B. Only three cases of CMV infection (1 vs 2) occurred. An immunosuppressive therapy with everolimus and low-dose CsA allows one to obtain excellent renal graft survival and stable graft function at 2 years. Early interruption of steroids in patients treated with this regimen may increase the risk of acute rejection, but neither affects graft survival nor graft function, while possibly reducing the risk of hyperlipemia and vascular thrombosis. About 60% of patients given everolimus and low-dose CsA can definitively stop steroids after 1 week.
Adolescent↗
Sirolimus-based therapy with or without cyclosporine: long-term follow-up in renal transplant patients.
This open-label, phase 3b, extension trial in renal transplant recipients (Sirolimus Study 311) assessed the long-term safety of sirolimus (SRL) administered with cyclosporine (CsA) (SRL + CsA group, n = 98) or without CsA (SRL group, n = 69). Renal transplant recipients who had either completed one of seven previous SRL studies sponsored by Wyeth Research or had participated for > or =3 months and reached a protocol-designated endpoint were eligible for enrollment. Data were available for 167 patients, all of whom initially received steroids. Mean total SRL exposure was 1526 days, including previous study participation. After enrollment in the extension study, there were significantly more acute rejections in the SRL + CsA group (6.1% vs 0%, P < .05). Differences in rates of graft loss (3.1% vs 1.4%) and death (6.1% vs 1.4%) were not significantly different between SRL + CsA and SRL groups, respectively. At 48 months after transplantation, calculated GFR (53.4 vs 70.9 mL/min) and hemoglobin (124.9 vs 136.6 g/L) were significantly better in the SRL group. Lipid values were not significantly different between groups at 48 months. The incidence of treatment-emergent increased creatinine, anemia, hypertension, headache, epistaxis, abnormal kidney function, and upper respiratory infection were significantly higher in the SRL + CsA group, whereas no adverse events were significantly higher in the SRL group. Malignancies were reported more frequently (11.2% vs 0%) with SRL + CsA. Results from this extension study indicate that SRL-based therapy without CsA is a safe alternative to combination therapy with CsA, offering long-term improvement in renal function with no increased risk of late acute rejection.
Adult↗
Hepatitis C virus RNA and core protein in kidney glomerular and tubular structures isolated with laser capture microdissection.
The role of hepatitis C virus (HCV) in the production of renal injury has been extensively investigated, though with conflicting results. Laser capture microdissection (LCM) was performed to isolate and collect glomeruli and tubules from 20 consecutive chronically HCV-infected patients, namely 6 with membranoproliferative glomerulonephritis, 4 with membranous glomerulonephritis, 7 with focal segmental glomerulosclerosis and 3 with IgA-nephropathy. RNA for amplification of specific viral sequences was provided by terminal continuation methodology and compared with the expression profile of HCV core protein. For each case two glomeruli and two tubular structures were microdissected and processed. HCV RNA sequences were demonstrated in 26 (65%) of 40 glomeruli, but in only 4 (10%) of the tubules (P < 0.05). HCV core protein was concomitant with viral sequences in the glomeruli and present in 31 of the 40 tubules. HCV RNA and/or HCV core protein was found in all four disease types. The immunohistochemical picture of HCV core protein was compared with the LCM-based immunoassays of the adjacent tissue sections. Immune deposits were detected in 7 (44%) of 16 biopsy samples shown to be positive by extraction methods. The present study indicates that LCM is a reliable method for measuring both HCV RNA genomic sequences and HCV core protein in kidney functional structures from chronically HCV-infected patients with different glomerulopathies and provides a useful baseline estimate to define the role of HCV in the production of renal injury. The different distribution of HCV RNA and HCV-related proteins may reflect a peculiar 'affinity' of kidney microenvironments for HCV and point to distinct pathways of HCV-related damage in glomeruli and tubules.
Adult↗
Antimicrobial agents for preventing peritonitis in peritoneal dialysis patients.
BACKGROUND: Peritoneal dialysis (PD) is used as substitutive treatment of renal function in a large proportion (15-50%) of the end-stage kidney disease (ESRD) population. The major limitation is peritonitis which leads to technique failure, hospitalisation and increased mortality. Oral, nasal, topical antibiotic prophylaxis, exit-site disinfectants and other antimicrobial interventions are used to prevent peritonitis. OBJECTIVES: The objective of this systematic review of randomised controlled trials (RCTs) was to evaluate what evidence supports the use of different antimicrobial approaches to prevent peritonitis in PD. SEARCH STRATEGY: The Cochrane CENTRAL Registry (issue 1, 2004), MEDLINE (1966-May 2003), EMBASE (1988-May 2003) and reference lists were searched for RCTs of antimicrobial agents in PD. SELECTION CRITERIA: Trials of the following agents were included: antibiotics by any route (oral, nasal, topical), exit-site disinfectants (chlorhexidine, povidone iodine, soap and water), vaccines, and ultraviolet germicidal devices. DATA COLLECTION AND ANALYSIS: Two reviewers extracted data on the number of patients with one or more episodes and rates of peritonitis and exit-site/tunnel infection, catheter removal, catheter replacement, technique failure, toxicity of antibiotic treatments, all-cause mortality. Statistical analyses were performed using the random effects model and the results expressed as relative risk (RR) with 95% confidence intervals (CI). MAIN RESULTS: Nineteen trials, enrolling 1949 patients met our inclusion criteria. Nasal mupirocin compared with placebo significantly reduced the exit-site and tunnel infection rate (one trial, 2716 patient months, RR 0.58, 95% CI 0.40 to 0.85) but not peritonitis rate (one trial, 2716 patient months, RR 0.84, 95% CI 0.44 to 1.60). Perioperative intravenous antibiotics compared with no treatment significantly reduced the risk of early peritonitis (four trials, 335 patients, RR 0.35, 95% CI 0.15 to 0.80) but not exit site and tunnel infection (three trials, 114 patients, RR 0.32, 95% CI 0.02 to 4.81). No intervention reduced the risk of catheter removal or replacement. REVIEWERS' CONCLUSIONS: This review demonstrates that nasal mupirocin reduces exit-site/tunnel infection but not peritonitis. Preoperative intravenous prophylaxis reduces early peritonitis but not exit-site/tunnel infection. No other antimicrobial interventions have proven efficacy. Given the large number of patients on PD and the importance of peritonitis, the lack of adequately powered RCTs to inform decision making about strategies to prevent peritonitis is striking.
Anti-Bacterial Agents↗
Catheter type, placement and insertion techniques for preventing peritonitis in peritoneal dialysis patients.
BACKGROUND: As many as 15-50% of end-stage kidney disease patients are on peritoneal dialysis (PD), but peritonitis limits its more widespread use. Several PD catheter-related interventions have been purported to reduce the risk of peritonitis in PD. OBJECTIVES: To evaluate the use of catheter-related interventions for the prevention of peritonitis in PD. SEARCH STRATEGY: The Cochrane Renal Group's specialised register (June 2004), The Cochrane CENTRAL Register of Controlled Trials (The Cochrane Library Issue 2 2004), MEDLINE (1966-April 2004), EMBASE (1988-April 2004) and reference lists were searched without language restriction SELECTION CRITERIA: Trials comparing different catheter insertion techniques, catheter types, use of immobilisation techniques or different break in periods were included. Trials of different PD sets were excluded. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial quality and extracted data. Statistical analyses were performed using a random effects model and the results expressed as relative risk (RR) with 95% confidence intervals (CI). MAIN RESULTS: Seventeen eligible trials (1089 patients) were identified, eight of surgical strategies of catheter insertion, eight of straight versus coiled catheters, one of single cuff versus double cuff catheters and one of an immobiliser device. The methodological quality was suboptimal. There were no significant differences with laparoscopy compared with laparotomy for peritonitis, the peritonitis rate, exit-site/tunnel infection or catheter removal/replacement. Standard insertion with resting but no subcutaneous burying of the catheter versus implantation and subcutaneous burying was not associated with a significant reduction in peritonitis rate, exit-site/tunnel infection rate or all-cause mortality. Midline compared to lateral insertion showed no significant difference in the risk of peritonitis or exit-site/tunnel infection. There was no significant difference in the risk of peritonitis, peritonitis rate, exit-site/tunnel infection, exit-site/tunnel infection rate or catheter removal/replacement between straight versus coiled intraperitoneal portion catheters. One trial compared single versus double cuffed catheters and showed no significant difference in the risk of peritonitis, exit-site/tunnel infection or catheter removal/replacement. One trial compared immobilisation versus no immobilisation of the PD catheter and showed no significant difference in the risk of peritonitis and exit-site/tunnel infection. No trials of different break-in periods were identified. REVIEWERS' CONCLUSIONS: No major advantages from any of the catheter-related interventions which have been purported to reduce the risk of PD peritonitis could be demonstrated in this review. The frequency and quality of available trials are suboptimal.
Catheterization↗
Experience with cyclosporine: approaching the therapeutic window for C2 levels in maintenance kidney transplant recipients.
This study was aimed to evaluate the clinical benefit of C2 monitoring in 191 stable renal transplant patients previously monitored by C0. All patients had been transplanted for at least 1 year and received cyclosporine (CsA)-based immunosuppression since the start. At the inceptions C0 levels were significantly correlated with C2 values (P<.0001). Patients with starting C2 levels >1000 ng/mL showed significantly higher levels of serum creatinine (sCr) both at inception (1.66 +/- 0.50 vs 1.44 +/- 0.41 mg/dL; P=.0021) and at the end of a 2-year follow-up (1.84 +/- 0.80 vs 1.46 +/- 0.51 mg/dL; P=.005). C2 monitoring revealed that a high percentage of patients were overexposed to CsA, mainly in the subgroup with most recent renal engraftments (12 to 24 months). The switch to C2 monitoring was associated with a slower deterioration of graft function (P=.02). Further, the mean values of C2 over a 2-year follow-up were inversely correlated with sCr at the end of follow-up (P=.0005). Finally, patients with mean threshold C2 levels above 720 ng/mL, roughly corresponding to the median value of C2, showed significantly lower levels of sCr at the end of follow-up (P=.0004). In conclusion, C2 monitoring of maintenance renal transplant patients allows one to identify a significant percentage of overexposed subjects, possibly limiting the rate of progression of chronic graft dysfunction. Target range values between 700 and 900 ng/mL appear to be associated with better long-term kidney graft function.
Creatinine↗
Medical and surgical complications after kidney transplantation from "suboptimal donors": one centre's experience.
To overcome the organ shortage, the pool of donors can be expanded to include aged donors (>55 years old) or patients with diabetes and long-standing hypertension, the so-called "suboptimal donors." Our experience on medical and surgical complications in kidney recipients from such donors and their impact on the graft and patient survival rates is reported. From January 1998 to April 2003, 276 kidney transplantation were performed: 107 from suboptimal donors (group A) and 169 from optimal ones (group B). After a mean follow-up of 26.8 months (range, 1-63 months), the 1-year graft survival rate was 89.3% and 97% for groups A and B, respectively. Medical complications were observed in 18.8% of group A and 6% of group B and surgical complications in 34.5% and 20%, respectively. In conclusion, even if the complication rate is higher among the suboptimal donor group, the patient and graft survival rates appear to be only slightly affected, therefore, validating the use of marginal donors.
Cadaver↗
Stem cells and kidney diseases.
The role of the stem cell (SC) in physiology and physiopathology has recently attracted much interest. SCs may originate from embryos, aborted fetuses, umbilical cord blood, and adult organs and tissues. In the adult, SCs were first defined in tissues with a high cell turnover, like skin and gut. Today, SCs have also been identified in tissues with no or low regenerative potential and turnover. However, the SC concept is changing rapidly: adult SCs not only reside locally in specific niches, but may also be recruited from the circulation to actively participate in the regeneration of various tissues. Furthermore, reverse differentiation has been demonstrated. In the kidney, both glomerular and tubular cells may differentiate into a range of phenotypes during the remodelling process in response to injury. The glomerular and tubulointerstitial scarring processes involve primarily interactions between infiltrating inflammatory cells and resident renal cells that culminate in loss of renal cells and their replacement by extracellular collagenous matrix. Reverse embryogenesis is a key step in renal healing and scarring: intrinsic renal cells regress to primitive/embryonic mesenchymal phenotype. In addition, it is clear that renal remodelling in health and disease involves the migration of hematopoietic SCs into the kidneys. These cells assume various glomerular and tubular epithelial phenotypes. Therefore, a better understanding of some of these key events in renal remodelling may open the way to new interventions based on their manipulations. Cell-based therapy may be a more successful strategy by providing a dynamic and individualized therapeutic approach that responds to the physiopathological condition of the patient. In fact, SCs may provide innovative methods for drug delivery, immunotherapy, tissue regenerative or replacement engineering.
Acute Kidney Injury↗
Immunosuppressive agents for treating IgA nephropathy.
BACKGROUND: IgA nephropathy (IgAN) is a world-wide disease and the cause of end-stage renal failure (ESRF) in 15 to 20% of patients within 10 years and in 30 to 40% of individuals within 20 years from the apparent onset of disease. No specific treatment has yet been established but many approaches have been investigated. OBJECTIVES: To assess the benefits and harms of immunosuppressive treatment for IgAN. SEARCH STRATEGY: We searched The Cochrane Renal Group's specialized register (May 2003), Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 3, 2002) MEDLINE (1966 - September 2002), EMBASE (1988 - September 2002) and handsearched reference lists of retrieved articles and conference proceedings. SELECTION CRITERIA: Randomized controlled trials (RCTs) and quasi-RCTs comparing treatment of IgAN with immunosuppressive agents against placebo, no treatment, other immunosuppressive or non-immunosuppressive agents. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial quality and extracted data. Statistical analyses were performed using the random effects model and the results expressed as relative risk (RR) for dichotomous outcomes and weighted mean difference (WMD) for continuous outcomes, with 95% confidence intervals (CI). MAIN RESULTS: Thirteen eligible RCTs involving 623 patients were identified. All identified RCTs had a placebo, no treatment or warfarin/dipyridamole control group. Seven trials used steroids, three used alkylating agents/cyclosporin and three used combinations of steroids and alkylating agents/cyclosporin. No trial directly compared steroids versus alkylating agents/cyclosporin. Quality was sub-optimal. Steroids were associated with a lower risk of progression to ESRF (RR 0.44, 95% CI 0.25 to 0.80) and lower urinary protein excretion (WMD -0.49 g/24h, 95% CI -0.72 to -0.12). Urinary protein excretion was lower for patients treated with alkylating agents/cyclosporin compared to placebo/no treatment (WMD -0.94 g/24h, 95% CI -1.43 to -0.46). There was no significant reduction of urinary protein excretion with combination treatment of steroids and alkylating agents compared with placebo/no treatment. REVIEWER'S CONCLUSIONS: The optimal management of IgAN remains uncertain. The RCTs identified were small, of sub-optimal methodological quality and tended to only report favorable and surrogate outcomes without a thorough reporting of treatment harms. All outcomes favor the use of immunosuppressive interventions, with steroids appearing to be the most promising. Further study, in the form of RCTs, is necessary to ascertain which patients would benefit from these interventions, whether they are the ones with early signs of renal dysfunction or those with more advanced renal impairment.
Glomerulonephritis, IGA↗
Haemoglobin and haematocrit targets for the anaemia of chronic renal disease.
BACKGROUND: Anaemia affects 60-80% of patients with renal impairment, reduces quality of life and is a risk factor for early death. Treatment options are blood transfusion, erythropoietin (EPO) alpha or beta and darbepoetin alfa. Recently higher haemoglobin (Hb) and haematocrit targets have been widely advocated because of positive data from observational studies. However, higher targets may lead to access thrombosis and hypertension and are costly. OBJECTIVES: This review assesses the benefits and harms of low (Hb </= 100 g/L or HCT </= 30%) and high (Hb > 100 g/L or HCT > 30%) targets in pre- and post-dialysis patients receiving any treatment for anaemia. SEARCH STRATEGY: We searched The Cochrane Renal Group specialised register (September 2002), Cochrane Controlled Trials Register (The Cochrane Library, Issue 3, 2002) MEDLINE (1966 - September 2002), EMBASE (1988 - September 2002) and reference lists of retrieved articles. SELECTION CRITERIA: Randomised controlled trials (RCTs) and quasi-RCTs comparing low Hb/HCT targets (Hb</- 100 g/L) with high Hb/HCT targets (Hb > 100 g/dL) in patients with anaemia of chronic renal disease. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial quality and extracted data. Statistical analyses were performed using the random effects model and the results expressed as relative risk (RR) for dichotomous outcomes and weighted mean difference (WMD) for continuous outcomes, with 95% confidence intervals (95% CI). MAIN RESULTS: Fifteen trials were identified in which 2096 patients were included. Twelve trials (673 patients) compared placebo with EPO and three trials (1423 patients) compared two doses of EPO. Hb values of 100 g/L (obtained with low EPO doses) were associated with lower mortality compared to Hb values of 140 g/L or more (obtained with high EPO doses) in the population with chronic renal disease and cardiovascular impairment (two trials, 1379 patients: RR 0.82; 95% CI 0.68 to 0.99). Lower targets obtained with a placebo resulted in an increased risk for seizures (four trials, 219 patients: RR 5.25; 95% CI 1.13 to 24.34) as compared to higher targets reached with EPO treatment. Finally, there was a reduced risk for hypertensive episodes with lower Hb targets reached with a placebo as compared to higher targets reached with EPO (six trials, 387 patients: RR 0.50; 95% CI 0.33 to 0.76). Quality of life was not adequately evaluated in the studies. REVIEWER'S CONCLUSIONS: Lower Hb targets of 100 g/L were associated with a lower risk of death in the population with cardiovascular impairment and chronic renal disease as compared to Hb 140 g/L. Lower Hb targets (Hb < 100 g/L) were also significantly associated with an increased risk for seizures and a reduced risk of hypertension compared to Hb > 100 g/L. There is a need of more adequately powered, well-designed and reported trials in this area. In particular, randomised controlled trials comparing the benefits and harms of low (Hb < 100 g/L) versus intermediate (Hb 130 g/L) and high (Hb 140 g/L) targets in the pre-dialysis population with chronic renal disease are necessary. In fact, there is a large deficiency of trials in the pre-dialysis population. The new trials should focus on hard outcomes and also look at outcomes which were previously not studied adequately, such as seizures and quality of life, which is to be assessed with validated measures.
Anemia↗
For further investigations in IgA nephropathy the approach from phenotype to genotype is welcome.
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Genetic Predisposition to Disease↗
Protease-activated receptor 1 and plasminogen activator inhibitor 1 expression in chronic allograft nephropathy: the role of coagulation and fibrinolysis in renal graft fibrosis.
BACKGROUND: Chronic allograft nephropathy (CAN), the major cause of renal graft failure, frequently displays extensive interstitial fibrin deposition. Little is known in regard to the cause of the altered coagulation/fibrinolysis balance and its relevance in the pathogenesis of CAN. Thrombin, present within the fibrin clots, can interact with a specific receptor, protease-activated receptor 1 (PAR-1), and modulate a variety of cell functions. On the other hand, the derangement of the fibrinolytic system may directly affect extracellular matrix (ECM) degradation. METHODS: In the present study, we investigated, by in situ hybridization, PAR-1 gene expression and the mRNA levels for tissue factor and plasminogen activator inhibitor 1 (PAI-1), two key regulatory molecules of coagulation and fibrinolysis, in 16 CAN biopsies and in 10 normal human kidney grafts. The thrombin-induced transforming growth factor beta (TGF-beta) gene and protein expression in proximal tubular cells (PTC) was investigated by Northern blotting and ELISA, respectively. RESULTS: Fibrin deposits, absent in normal grafts, were observed in the interstitial space and arterial wall of CAN. Tissue factor gene expression was not increased either at the vascular or at the interstitial level in CAN. On the contrary, PAI-1 gene expression, barely detectable in control tissue, was strikingly increased in CAN, with a distribution resembling the pattern of fibrin deposition. Note that PAI-1 gene expression was directly correlated with the degree of interstitial fibrosis. In addition, fibrin deposits were strictly associated with a marked increase of PAR-1 gene expression in endothelial cells and PTC. The tubular expression of PAR-1 was significantly higher in Banff grade II-III than in grade I. In vitro, incubation of PTC with thrombin caused a significant up-regulation of TGF-beta gene expression, followed by an increased TGF-beta release into the supernatant. Interestingly, urine from CAN patients contained significantly higher levels of TGF-beta. CONCLUSIONS: Fibrin deposits in CAN may result from the increased expression of PAI-1 and the subsequent inhibition of fibrinolysis. The reduced fibrinolysis may cause, in turn, a decreased ECM turnover. Finally, thrombin, preserved in the active form within the fibrin clots, may interact with PAR-1 highly expressed on PTC and induce an up-regulation of ECM deposition in a TGF-beta-dependent manner.
Chronic Disease↗
Immunoglobulin a nephropathy with mild renal lesions: a call in the forest for physicians and nephrologists.
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Glomerulonephritis, IGA↗
ACE gene polymorphism and IgA nephropathy: an ethnically homogeneous study and a meta-analysis.
BACKGROUND: Conflicting results have implicated the angiotensin-converting enzyme (ACE) D allele in the progression of renal damage in patients with IgA nephropathy (IgAN). Most of these findings have been obtained by heterogeneous studies. METHODS: We investigated the ACE insertion/deletion (I/D) gene polymorphism by polymerase chain reaction (PCR) amplification of genomic DNA in an ethnically homogeneous sample size of IgAN patients from Southern Italy. The association between ACE I/D gene polymorphism and the development of the disease was examined in 247 biopsy-proven IgAN patients and 205 healthy subjects. The association with the progression of renal damage was evaluated in 136 patients with a follow-up of > or =3 years according to the slope of the creatinine clearance against time, and in 221 patients with a follow-up of > or =1 year assessing by univariate and multivariate analyses of renal survival. These associations were further estimated in a meta-analysis of seven studies retrieved in the Medline database. The meta-analysis was performed according to the Mantel-Haenszel-Peto method when homogeneity of the studies was established using the chi(2) test by Breslow-Day. RESULTS: No difference in the ACE I/D gene distribution between patients and controls and between patients with stable and those with deteriorating renal function was found in our study. A meta-analysis performed separately for Caucasian and Asian studies showed that the ACE I/D gene polymorphism did not contribute to the genetic susceptibility of the development of IgAN (total OR 0.93, 95% CI, 0.71 to 1.23; and 0.95, 95% CI, 0.64 to 1.42, respectively) or the progression of the renal damage (total OR 1.12, 95% CI, 0.67 to 1.88; and 2.26, 95% CI, 0.75 to 6.79, respectively) in both groups. CONCLUSIONS: Our study and meta-analysis suggest caution in the interpretation of results from association studies enrolling heterogeneous populations. Further studies using new tests, which are free of the bias due to population stratification and ethnicity, are warranted.
Adolescent↗
Angiotensin IV and renal diseases.
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Angiotensin II↗
Immunologic evaluation during the first year of life of infants born to cyclosporine-treated female kidney transplant recipients: analysis of lymphocyte subpopulations and immunoglobulin serum levels.
BACKGROUND: In rodents, CsA has been shown to affect T-cell development, giving rise to an abnormal production of mature T cells and the absence of many T-cell subsets as well as to autoimmunity. Surprisingly, only a few studies investigated the effect of the immunosuppressive drug on the immune system of the human fetus. METHODS: We examined six infants born to female kidney transplant recipients who had received cyclosporine and methylprednisolone throughout their pregnancies. Peripheral blood was obtained 1 day and 2, 4, 6, and 12 months after birth, and two-color flow cytometric immunophenotyping of lymphocytes was performed. RESULTS: Total T cells, as well as CD4+ and CD8+ T cells, were low at birth, but normalized thereafter. Among T-cell activation markers, the expression of CD25, the alpha chain of the interleukin-2 receptor, was below the normal range or low range throughout the study period, and HLA-DR expression was extremely low at birth and failed to increase up to 12 months. The number of total B cells was lower than normal at birth, but steeply increased over time. In contrast, B-cell subset bearing CD5 antigen was severely depleted throughout the first year of life. Total IgG concentration was significantly lower than in controls at 2 months, mainly because of subnormal levels of IgG1 and IgG3 subclasses, which remained in the low range up to 6 months. Finally, infants showed normal numbers of true natural killer (NK) cells (CD3-CD16+CD56+), whereas the expression of CD57 antigen, defining non-MHC-restricted cytotoxic lymphocytes, was barely detectable at birth and failed to increase over time, in both CD8+ and CD8- subsets. Of note, none of the infants had clinical evidence of an immunodeficient state. CONCLUSIONS: continuous exposure to CsA in utero seemingly impairs T-, B-, and NK-cell development and/or maturation, and most of its effects are still apparent at 1 year, which might suggest that conventional vaccinations should be delayed in these infants.
Antigens, CD↗