Nephrectomy in impaired renal function

Nephrectomy was performed in 2 elderly patients despite a significant reduction in over-all renal function. Both exhibited a surprising degree of increase in function in the remaining kidney, as measured by serial clearance studies. These findings may be important in considering ablative renal surgery in patients with preexisting diminution of renal function.     

Targeting vascular endothelial growth factor (VEGF)-receptor-signaling in renal cell carcinoma

Metastatic renal cell carcinoma (RCC) is resistant to conventional chemotherapy. Combined data for a variety of immunotherapies resulted in an overall chance of partial (PR) or complete remission (CR) of only 12.9%. There is a clear need for novel, more effective therapies to prevent relapse, control metastases and improve overall survival. Improved understanding of RCC disease biology has led to the introduction of molecularly targeted treatment strategies in these cancers. Von Hippel-Lindau (VHL) gene inactivation is observed in most clear cell renal carcinoma, resulting in vascular endothelial growth factor (VEGF) over-expression and driving the malignant phenotype. This review discusses the efficacy of novel therapies targeting the VEGF receptor (VEGFR) (e.g. anti-VEGF antibodies, VEGFR tyrosine kinase inhibitors, mTOR inhibitors), some of which were recently approved by the Food and Drug Administration/European Medicines Evaluation Agency (FDA/EMEA) and represent the new treatment standards in RCC patients.     

Mechanisms of impaired renal function with PEEP

Deterioration in renal function associated with positive end-expiratory pressure (PEEP) has been attributed to renal hypoperfusion from the fall in cardiac output and mean arterial blood pressure. Using a canine in vivo model, renal function was measured during control, zero end-expiratory pressure (ZEEP), and PEEP (5, 10, and 15 cm H2O) ventilatory cycles, while renal blood flow was maintained constant with a pump. High PEEP (15 cm H2O) led to a rise in renal vein pressure (RVP) and a fall in mean arterial pressure (MAP). PEEP resulted in no change in glomerular filtration rate (GFR) or solute exertion; however, free-water clearance (FWC) became less negative in the 15-cm H2O PEEP group. Intrarenal autoregulation maintains GFR during ventilation with PEEP when renal blood flow is constant, supporting the view that altered filtration and solute excretion clinically is secondary to changes in aortic pressure and renal perfusion.     

First-year renal function predicts long-term renal allograft loss

Purpose

We performed a retrospective study to examine the impact on long-term graft survival of first-year posttransplantation renal function, as evaluated by serum creatinine.

Patients and Methods

We analyzed data from 1,273 adult kidney transplants performed between 1983 and 2008. All recipients >18 years old were included if their grafts had survived beyond 1 year, excluding patients simultaneously transplanted with other organs. Cox proportional hazards multivariable analysis was used to examine the relationship between first-year posttransplantation renal function and death-censored graft loss, adjusted for other variables. Renal function in the first year was expressed as serum creatinine levels at 1, 6, and 12 months as well as the change in creatinine between those 3 periods.

Results

Posttransplantation 1-month serum creatinine levels and change between 1 and 6 months were independent predictors of long-term graft loss. Multivariable analysis also identified donor age (increasing), acute rejection episode occurrence, recipient age at transplantation (decreasing), and gender (female) as independently predictive of graft failure, adjusting for other factors usually associated with graft loss, namely, pretransplantation time on dialysis, HLA mismatches, and delayed graft function. The predictive effect of creatininemia was sustained at 6 and 12 months, after adjusting for these covariates.

Conclusions

Posttransplantation serum creatinine levels at 1, 6, and 12 months were independent predictors of graft survival, suggesting that they could be considered as surrogate endpoints for long-term death-censored graft loss.     

Corneal endothelial cell loss following trephination

The amount of endothelial cell loss that occurs to the donor cornea during the trephination process was evaluated in 40 porcine eyes. A vital staining technique (alizarin red S and acid violet 19) was used to quantify the extent of endothelial damage and removal. Two types of corneal punches (Weck and H&I0 were used for trephination. The average amount of endothelial loss from the peripheral cornea was 7.9%, accounting for only a 3% loss of endothelial cells over the total surface area of the corneal button. a comparison of the Weck and H&I corneal punches showed no significant difference (P greater than 0.1) by Student's test for both endothelial cell damage and removal.     

Kidney graft function determines endothelial progenitor cell number in renal transplant recipients

BACKGROUND: Circulating bone marrow-derived endothelial progenitor cells (EPCs) promote vascular repair, and their number correlates with endothelial function and cardiovascular risk in humans. In uremic patients, the number of functionally active EPCs is reduced. Thus, we assessed EPCs in stable patients 6 months or more after renal transplantation. METHODS: We analyzed circulating CD34+ hematopoietic progenitor cells (HPCs) using flow cytometry and EPCs (in vitro assay) in 74 renal transplant patients (51.6+/-11.5 years; 46 males), 74 age-matched healthy subjects, and 29 patients with preterminal renal failure. RESULTS: EPC numbers were similar in renal transplant recipients and controls (232+/-92 vs. 250+/-103/high power field; n.s.), but were significantly higher than in uremic patients (160+/-97/high power field; P=0.004). In addition, transplant recipients had more HPCs than controls (2.71+/-1.65 vs. 1.99+/-1.12 /microl; P=0.004) and uremic patients (1.64+/-0.96/microl; P=0.001). EPCs in renal transplant recipients correlated significantly with graft function(that is, Cockcroft-Gault clearance [r=0.294; P=0.012]), but not with age or HPCs. Moreover, in the multiple regression analysis, graft function (r=0.332; P=0.01) and diastolic blood pressure (r=-0.278; P=0.03) were independent predictors of EPCs. In vitro, sera from renal transplant recipients with poor graft function significantly inhibited EPC differentiation compared with sera from patients with a clearance above 50 mL/min (151+/-54 vs. 274+/-94 EPCs/high power field; P=0.02). CONCLUSIONS: EPC numbers in stable renal transplant recipients are comparable to those found in healthy subjects. In addition, graft function is a significant determinant of EPCs. Prospective studies should explore whether improvement of EPCs influences cardiovascular risk in renal transplant recipients.     

Antimicrobial therapy in patients with impaired renal function

In order to formulate a thoughtful and rational approach to drug dosing in renal failure, the nephrologist must consider several features that influence drug disposition in uremia. Drug bioavailability is generally adversely influenced in patients with renal disease. Drug distribution is frequently altered to an unpredictable degree. Drug protein binding is affected not only by changes in the amount of circulating binding protein but also by the accumulation of endogenous toxins. Renal failure frequently affects drug biotransformation. Drug-dosing tables and nomograms are important; however, they are not a substitute for an encompassing clinical approach and sound clinical judgment.     

Anaesthesia for the patient with impaired renal function

Patients with renal disease are at risk of further deterioration of renal function and acute tubular necrosis when subjected to anaesthesia and surgery. Optimal fluid loading and careful selection of anaesthetic techniques and agents, appropriate monitoring and the use of mannitol and dopamine assist in the maintenance of renal blood flow and help preserve renal function in these patients. In association with renal failure, physiological changes in other systems result in reduced oxygen supply to the tissues, metabolic disturbances, impairment of the coagulation and immune defence mechanisms and an increased risk of cardiac and cerebrovascular catastrophe. Although many anaesthetic techniques including regional analgesia may be used successfully in these patients caution with most drugs, especially pethidine, phenoperidine, suxamethonium and all non-depolarising neuromuscular relaxants is recommended. Of the volatile anaesthetics currently available, halothane is the agent of choice. Oxygen therapy and close monitoring of cardiorespiratory function are necessary postoperatively.     

Outcome of renal transplants with impaired renal function at 6 months

At 6 months after kidney transplantation 59 adults with impaired renal function were divided into three groups according to their serum creatinine level: group I 150-199 mumol/l; group II 200-299 mumol/l; and group III greater than or equal to 300 mumol/l. These patients were followed up for 5 years or to graft loss when it became apparent that the eventual outcome was related to the degree of renal impairment at 6 months. Age of donor and age of recipient did not have a bearing on the eventual outcome nor did the frequency of acute tubular necrosis or rejection episodes. Patients with severely impaired renal function with serum creatinine levels greater than or equal to 300 mumol/l have a poor outlook but there are no particular prognostic features on which to base a forecast for the individual patient.     

Tumour vascular endothelial growth factor (VEGF) mRNA in relation to serum VEGF protein levels and tumour progression in human renal cell carcinoma

Angiogenesis is gaining interest because of its importance in tumour growth and metastasis. Renal cell carcinoma (RCC) is known to be a well-vascularized tumour. The aim of this study was to evaluate the expression of VEGF mRNA and receptor flt-1 mRNA (VEGF R1) in a clinical material of RCCs compared with clinicopathological variables and serum VEGF levels. Total RNA was extracted from snap-frozen tumour tissue obtained from 61 patients. Expression of mRNA for VEGF₁₂₁, VEGF₁₆₅ and flt-1 were analysed using quantitative RT-PCR. Relative VEGF mRNA levels, corrected for corresponding cyclophilin value, were related to stage, grade, RCC type and survival time. Serum VEGF₁₆₅ protein was analysed using a quantitative ELISA. Papillary RCC had significantly lower VEGF₁₂₁ and flt-1 mRNA levels compared with conventional RCC (p=0.001). VEGF₁₂₁ mRNA levels were significantly lower in locally advanced tumours in relation to tumours limited to the kidney and those with metastatic disease (p=0.047 and p=0.036). This statistical difference disappeared when only conventional RCCs were evaluated. No association was found between VEGF mRNA levels and nuclear grade. Patients with lower VEGF₁₂₁ mRNA levels had significantly longer survival time compared with those with higher levels (when adjusted to stage, p=0.0097, log rank test). There was an inverse relation between VEGF₁₆₅ mRNA and serum VEGF₁₆₅ levels. The trend to lower VEGF₁₂₁ mRNA levels in locally advanced RCC indicate that angiogenic activity and degradation might be up-regulated in tumours with a high ability to invade. The association with tumour progression shows that VEGF is a promising angiogenic factor especially important in conventional RCCs. VEGF expression might possibly be of help to identify RCCs susceptible for anti-angiogenic therapies.     

Ovariectomy enhances renal cortical expression and function of cyclooxygenase-2

BACKGROUND: Cyclooxygenase-2 (COX-2) inhibitors are used as analgesics in postmenopausal women, who develop edema and require a salt-restricted diet. This study was performed to determine the renal expression of COX-2 and on COX-2-dependent regulation of renal blood flow (RBF) in ovariectomized rats. METHODS: Sprague-Dawley rats were divided into 4 groups: sham-operated rats fed a normal-salt diet (Sh+NS) or a low-salt diet (Sh+LS), and bilaterally ovariectomized rats fed a normal-salt diet (Ox+NS) or a low-salt diet (Ox+LS) (N= 6 in each group). Estrogen replacement therapy was performed on other ovariectomized rats. A renal clearance study was performed in anesthetized animals. RESULTS: Ovariectomy increased renal cortical COX-2 expression independently of dietary salt intake (Sh+NS 相似文献   

Fractional oxalate clearance in subjects with normal and impaired renal function

The 14C-oxalate clearance was determined in 13 healthy subjects and 22 patients with various diseases and varying degrees of renal function impairment, including 5 patients with primary hyperoxaluria (PH). The clearances of oxalate (Cox) and creatinine (Ccr) were correlated (r = 0.95). The regression line intersects the ordinate at the origin, while the regression coefficient is 2.0. This implies that the fractional Cox is constant, irrespective of the underlying disease and the degree of renal failure. Plasma oxalate (Pox), as calculated from the urinary oxalate excretion (Uox) and Cox, was elevated in patients with severely impaired kidney function and those with PH. Plasma creatinine (Pcr) and Pox were correlated as well (r = 0.83). Pox values of patients with PH were above the 95% confidence limits of the regression line. It is of practical importance that Pox can be estimated from Uox and Ccr when a 14C-oxalate clearance test cannot be performed. The reasons for the constancy of the Cox/Ccr ratio are discussed, and it is suggested that the effective renal plasma flow (ERPF) is the regulating factor for the tubular secretion of oxalate.