血清胱抑素C对高血压和糖尿病早期肾功能损伤的诊断价值

目的探讨血清胱抑素C(Cys-C)水平对高血压、糖尿病早期肾功能损害的临床价值。方法收集22例高血压患者、28例糖尿病患者及44例肾病患者的血清标本,用酶法测定血清肌酐、尿素氮,用颗粒增强免疫比浊法测定血清Cys-C,放射免疫法测定β2-微球蛋白。结果血清Cys-C和β2-微球蛋白的异常检出率显著高于血清肌酐、尿素氮;高血压及糖尿病两组患者血清Cys-C水平均较正常对照组明显升高(P<0.01);肾病组各项检测指标均显著高于高血压组、糖尿病组和正常对照组。结论对早期肾功能损害的诊断价值,血清Cys-C测定敏感性稍次于β2-微球蛋白,但其特异性优于血清β2-微球蛋白,综合比较,血清Cys-C可作为高血压及糖尿病早期肾功能损害的辅助诊断指标之一。     

兴趣区设置对Gates法测定肾小球滤过率的影响

目的:探讨肾脏及本底兴趣区ROI的勾画方式对Gates法测定肾小球滤过率(GFR)的影响.方法:对41例患者行肾动态显像,并按不同ROI勾画法计算GFR.改变本底ROI位置、大小、本底与肾脏ROI距离及肾脏ROI大小、局部偏离,观察GFR变化;将各GFR与标准Gates法GFR比较,观察结果偏离程度及导致结果偏离的因素.结果:①logistic多因素分析表明,本底ROI位置、大小、本底与肾脏ROI间距离以及"肾脏ROI大小、局部偏离"均是影响GFR的重要因素(χ2分别为250.9,73.9,53.5,215.8,P=0.000);②本底位于肾脏正下方较大范围内或肾脏ROI在外下方局部外偏时GFR与标准Gates法十分接近;本底ROI、肾脏ROI的其它各种改变均可对GFR产生较大程度的影响.结论:①Gates法GFR测定时,ROI勾画须注意多种影响因素的作用.②本底ROI设置于肾脏正下方(20～160)象素大小、(0～16)象素距离范围内可减少本底大小、距离对GFR影响.     

Renal interstitial pressure and tubuloglomerular feedback control in rats during infusion of atrial natriuretic peptide (ANP)

Atrial natriuretic peptide (ANP), injected at physiological concentrations, is known to induce both natriuresis and diuresis. It has been suggested by some investigators that these changes result from an increasing glomerular filtration rate (GFR), but others have been unable to demonstrate an increased GFR. The tubuloglomerular feedback (TGF) mechanism is an important regulator of GFR, and the sensitivity of TGF is decreased during ANP administration. Furthermore, resetting of TGF is, in most instances, related to changes in renal interstitial hydrostatic and oncotic pressures. It is also known that ANP may increase capillary permeability which may change renal interstitial pressure. The present study was performed to examine renal interstitial pressures and the TGF mechanism during ANP infusion. In accordance with previous studies, TGF sensitivity was found to be decreased. The tubular flow rate which elicited half the maximal drop in stop-flow pressure (P_sf) was increased from 18.5 to 25.7 nl min^-1. In contrast, ANP infusion resulted in a decreased interstitial hydrostatic pressure and an increased interstitial oncotic pressure. From previous experiments, such changes in interstitial pressures would be expected to increase TGF sensitivity. The changes in interstitial pressure cannot, therefore, directly explain the resetting of the feedback mechanism. In conclusion, the present paper shows a decreased renal net interstial pressure after intravenous administration of ANP.     

Three-year outcomes from the CRADLE study in de novo pediatric kidney transplant recipients receiving everolimus with reduced tacrolimus and early steroid withdrawal

CRADLE was a 36-month multicenter study in pediatric (≥1 to <18 years) kidney transplant recipients randomized at 4 to 6 weeks posttransplant to receive everolimus + reduced-exposure tacrolimus (EVR + rTAC; n = 52) with corticosteroid withdrawal at 6-month posttransplant or continue mycophenolate mofetil + standard-exposure TAC (MMF + sTAC; n = 54) with corticosteroids. The incidence of composite efficacy failure (biopsy-proven acute rejection [BPAR], graft loss, or death) at month 36 was 9.8% vs 9.6% (difference: 0.2%; 80% confidence interval: −7.3 to 7.7) for EVR + rTAC and MMF + sTAC, respectively, which was driven by BPARs. Graft loss was low (2.1% vs 3.8%) with no deaths. Mean estimated glomerular filtration rate at month 36 was comparable between groups (68.1 vs 67.3 mL/min/1.73 m²). Mean changes (z-score) in height (0.72 vs 0.39; P = .158) and weight (0.61 vs 0.82; P = .453) from randomization to month 36 were comparable, whereas growth in prepubertal patients on EVR + rTAC was better (P = .050) vs MMF + sTAC. The overall incidence of adverse events (AEs) and serious AEs was comparable between groups. Rejection was the leading AE for study drug discontinuation in the EVR + rTAC group. In conclusion, though AE-related study drug discontinuation was higher, an EVR + rTAC regimen represents an alternative treatment option that enables withdrawal of steroids as well as reduction of CNIs for pediatric kidney transplant recipients. ClinicalTrials.gov: NCT01544491.     

Effects of mTOR inhibitor–related proteinuria on progression of cardiac allograft vasculopathy and outcomes among heart transplant recipients

We have previously described the use of sirolimus (SRL) as primary immunosuppression following heart transplantation (HT). The advantages of this approach include attenuation of cardiac allograft vasculopathy (CAV), improvement in glomerular filtration rate (GFR), and reduced malignancy. However, in some patients SRL may cause significant proteinuria. We sought to investigate the prognostic value of proteinuria after conversion to SRL. CAV progression and adverse clinical events were studied. CAV progression was assessed by measuring the Δ change in plaque volume (PV) and plaque index (PI) per year using coronary intravascular ultrasound. Proteinuria was defined as Δ urine protein ≥300 mg/24 h at 1 year after conversion to SRL. Overall, 137 patients were analyzed (26% with proteinuria). Patients with proteinuria had significantly lower GFR (P = .005) but similar GFR during follow-up. Delta PV (P < .001) and Δ PI (P = .001) were significantly higher among patients with proteinuria after adjustment for baseline characteristics. Multivariate Cox regression analysis showed higher all-cause mortality (hazard ratio 3.8; P = .01) with proteinuria but similar risk of CAV-related events (P = .61). Our results indicate that proteinuria is a marker of baseline renal dysfunction, and that HT recipients who develop proteinuria after conversion to SRL have less attenuation of CAV progression and higher mortality risk.     

Renal response to amino acid infusion in rats: effect of dopamine receptor antagonists and benserazide

Previously, we have found that feeding is a dominant factor controlling urinary dopamine excretion (U_DA) in conscious rats (Mühlbauer and Osswald 1992). Since the renal response to feeding is also characterized by an increase in glomerular filtration rate (GFR), we wanted to investigate in a first step whether the feeding-induced elevations of GFR and U_DA could be causally related phenomena. Therefore, we studied the influence of dopamine synthesis and dopamine receptor blockade on the renal response to amino acid infusion (AA) in thiopental anesthetized rats. AA infusion (n = 7) increased GFR by 33±7% (P<0.001) and U_DA by 87±19% (P<0.001). In the presence of benserazide (BZD, n = 5), an inhibitor of dopamine synthesis, infused i.v. at a dose of 30 g/min/kg, U_DA was suppressed to values below detection limit and the AA-induced GFR increase was abolished. Continuous intravenous infusion of the DA₁ receptor antagonist SCH 23390 (SCH, n = 7) in a dose of 4.0 g/kg/min did not prevent the AA-induced increase in GFR (33±3%, P<0.001) and U_DA (97±12%, P< 0.001). In contrast, S-sulpiride (SUL), a specific DA₂ receptor antagonist, infused continuously i.v. in a dose of 5 g/kg/min, completely abolished the AA-induced GFR increase, while U_DA was increased 1.6-fold (P<0.01). Like BZD, both dopamine receptor antagonists did not affect renal sodium excretion substantially.Our results suggest, that endogenous dopamine could act as a mediator in the renal response to amino acid infusion in the rat, most likely by activation of DA₂ receptors. Correspondence to:B. Mühlbauer at the above address     

Tc-99m diethylenetriamine pentaacetic acid (DTPA): Is it reliable for assessment of methotrexate-induced cumulative effect on renal filtration in rheumatoid arthritis patients?

Methotrexate[MTX] is commonly employed as the initial DMARD used for treatment of Rheumatoid arthritis[RA]. We aimed to contribute to the safety profile of MTX by assessing its cumulative effect on renal filtration. Fifty two RA adult females with normal base-line serum creatinine and GFR at the initial diagnosis of the disease were included. Group-1[G1] included 30 patients[mean age 40.4 ± 4.4 years] on MTX and NSAIDS, while 22 RA patients[mean age 38.5 ± 8.2 years] who received NSAIDs only served as the control group[G2]. Renal function was assessed by GFR-measurement using Technetium diethylenetriamine-pentaacetic acid[Tc-99 m-DTPA] at the point of the study time corresponding to disease duration. 21/30[70%] in G1 showed reduced GFR compared to 6/22[27.3%] in G2[P0.007] with 3.3 ± 0.5% annual reduction of GFR. Reduced GFR in G1 showed significant negative correlation with age[r = ?0.396, P = 0.005], MTX-cumulative dose[r = ?0.263, P = 0.049], MTX-intake duration[r = ?0.293, P = 0.031] and NSAID-intake duration[r = ?0.344, P = 0.014]. Low dose MTX has a slow cumulative effect on renal filtration manifested by GFR reduction over time that could be monitored by Tc-99 m DTPA.     

Routine Determination of GFR in Renal Transplant Recipients by HPLC Quantification of Plasma Iohexol Concentrations and Comparison With Estimated GFR

Estimated glomerular filtration rate (eGFR) methods are not sufficiently reliable in renal transplant recipients (RTR) and should be replaced by iohexol plasma clearance measurement. However, this method has poor availability in health centers. The aim of our study was to develop a high‐performance liquid chromatography (HPLC) method for plasma iohexol measurement in routine practice and to evaluate its plasma clearance as a reference of GFR. We developed an HPLC method using UV detection. We evaluated sample storage conditions to provide recommendations for routine practice. Then, we compared GFRbased on plasma iohexol clearance (GFR‐iohexol) to eGFR using modification of diet in renal disease, Cockcroft and Gault, and CDK‐EPIequations in 40 RTR. The method was validated over a concentration range of 15–300 μg/l. Excellent linearity (r > 0.998), inter‐ and intraday precision (CV < 3.3%), and accuracy (>96.8%) were complied with ICH guidelines. We also demonstrated excellent samples stability (9 days). Although eGFR methods are not references in RTR, we found a correct concordance between eGFR and GFR‐iohexol in our population. To conclude, our method is simple, rapid, accurate, and reliable for routine clinical and research use especially in RTR. J. Clin. Lab. Anal. 26:376‐383, 2012. © 2012 Wiley Periodicals, Inc.     

Advances in Percutaneous Coronary Interventions for Elderly Patients

Coronary heart disease (CHD) is one of the leading causes of morbidity and the most common cause of death in older adults. Paradoxically, elderly patients tend to be systematically excluded from randomized-controlled cardiovascular trials, which complicates decision-making in this population. Management of CHD in the elderly is frequently more difficult in virtue of chronic comorbid conditions and aging-intrinsic dynamics. Despite these challenges, the number of elderly and very elderly patients undergoing percutaneous coronary interventions (PCI) is increasing. Elderly patients in many registries and large clinical series exhibit even a greater benefit from interventional procedures than younger patients, but they have a higher rate of overall complications. We present an overview of the current available evidence of PCI in older adults with stable and unstable CHD, including comparisons between drug-eluting and bare-metal stents, transfemoral and transradial access, and methods of revascularization. Adjuvant antiplatelet and antithrombotic therapies are also discussed.