Evaluation of Tc-99m-DTPA for renal clearance studies in the pig

Summary Conventional creatinine clearance studies in the pig are complicated by difficulties with catheterisation, infection, accurate collection and active creatinine renal tubular reabsorption. We compared a single injection, ^99mTc-DTPA elimination method with creatinine clearance. Nineteen pairs of GFR estimations were performed in 10 pigs: 7 in normal pigs and 12 following bile duct ligation and/or nephrectomy. Red cell and plasma protein binding of the isotope and its hepatobiliary excretion was assessed. Absolute and weight normalised endogenous creatinine clearances correlated significantly with ^99mTc-DTPA elimination. ^99mTc-DTPA red cell binding and hepatobiliary excretion were negligible. Thus, ^99mTc-DTPA elimination is a valid indicator of changes in renal function in grouped porcine studies, particularly in the biliary obstruction model. However, isotope plasma protein binding was high in the 2 normal pigs assessed. Individual accuracy would be improved by routine protein binding correction, unless consistently low for a particular preparation.     

Creatinine excretion rates for evaluation of kidney function in children

A protein load protocol for evaluation of kidney function was tested in normal children and pediatric renal patients. An overnight, timed urine collection was used for calculation of the baseline cretinine clearance and creatinine excretion rate. One hour following ingestion of a standardized protein meal (baked chicken), a 2–3 h urine collection was begun. The post-protein meal changes in creatinine clearance showed considerable variation in both the normal children and those with renal disorders. In contrast, the rate of excretion of creatinine was consistently increased in the normal children following the protein meal (73.4±18%; range 48.2%–122.4%). Of 33 renal patients, 14 showed less than a 48% increase in creatinine excretion rate, even though 9 of these children had baseline creatinine clearances within the normal range. These 9 patients have evidence of less than normal quantities of functioning renal tissue. Serial studies over a year on 2 children who presented with acute renal failure showed a progressive increase in creatinine clearance with scant increases in creatinine excretion rate. These studies provide indirect evidence that a less than normal enhancement of the rate of creatinine excretion following a protein load reflects the presence of adaptive glomerular hyperfiltration and hyperperfusion.     

353例小儿肾小球疾病的病理及临床分布特点

目的 了解小儿肾小球疾病病理与临床分布特点。方法 收集353例肾活检患儿资料进行回顾性分析。结果 353例患儿中诊断为紫癜性肾炎117例(33.1%),孤立性血尿94例(26.6%),原发性肾病综合征87例(24.6%),急性肾炎综合征23例(6.5%),其次还有乙肝相关性肾炎、狼疮性肾炎、孤立性蛋白尿、慢性肾炎等。肾小球疾病中以原发性肾小球疾病最为常见(206例,占58.4%),病理改变主要为:系膜增生性肾小球肾炎(MsPGN)66例,占32.0%; IgA肾病(IgA N)54例,占26.2%;轻微病变37例,占18.0%;其他还包括微小病变(MCD)、膜增生性肾小球肾炎(MPGN)、膜性肾病(MN)、毛细血管增生性肾小球肾炎等。继发性肾小球疾病以紫癜性肾炎最常见。结论 肾小球疾病以原发性肾小球疾病为主,临床诊断以孤立性血尿最常见,继发性肾炎以紫癜性肾炎最常见。     

白细胞介素13抑制肾小球系膜细胞增殖及白细胞介素6表达

目的:探讨白细胞介素13(IL-13)对体外培养的大鼠系膜细胞的增殖及其产生白细胞介素6(IL-6)的影响。方法:用四甲基偶氮唑(MTT)法测定系膜细胞增殖,用逆转录聚合酶链反应(RT-PCR)及酶联免疫吸附法(ELISA)测定系膜细胞IL-6mRNA表达及其蛋白水平。结果:IL-13在1、10、100μg/L浓度范围呈剂量依赖性地抑制系膜细胞的增殖;5%FCSRPMI1640培养条件下系膜细胞IL-6mRNA表达及IL-6分泌水平较低,脂多糖(LPS)可刺激系膜细胞IL-6mRNA的表达及提高IL-6分泌水平,而IL-13可抑制LPS诱导的系膜细胞IL-6分泌及其mRNA表达。结论:IL-13抑制体外培养的系膜细胞增殖及LPS诱导的系膜细胞IL-6的产生,IL-13可能对于肾小球肾炎的系膜细胞炎症反应具有拮抗作用。     

Role of glycosaminoglycans in diabetic nephropathy

A number of abnormalities of glycosaminoglycan metabolism have been reported in diabetes mellitus. These include anomalous synthesis, catabolism and sulphation. In this review glycosaminoglycan metabolism in diabetes mellitus is discussed with reference to its possible impact on glomerular basement membrane permeability, and on the physiology and metabolism of glomerular resident cells, specifically of the mesangium. Experimental results demonstrating favourable therapeutic activities of some glycosaminoglycans in mesangioproliferative glomerulitis and diabetic nephropathy are reported. These pharmacological actions do not depend on the well-known anticoagulative activity of glycosaminoglycans, but most probably on their antiproliferative effect. A more complex role of glycosaminoglycans in the pathogenesis of diabetic nephropathy is suggested.     

A Simplified Method for Measuring the Thickness of Glomerular Basement Membranes

Measurement of the thickness of glomerular basement membranes is required for the diagnosis of thin membrane nephropathy. Over the years various morphometric methods have been used but some are laborious so there is a need for establishing a simplified method for measuring thickness. In the present study 20 renal biopsies were used to carry out a comparative morphometric analysis between 2 methods. The first method was based on measuring thickness at the maximum number of available points, whereas for the second method, thickness was measured at only 5 points per loop. Since both methods gave mean values that are not statistically different in each patient, the authors recommend that the simplified method be used routinely for diagnosis.     

Alport Disease: A Review of the Diagnostic Difficulties

In patients with familial hematuria, ultrastructural study of the renal biopsy has been the gold standard for the diagnosis of Alport disease, based on characteristic findings of glomerular basement membrane thickening due to reduplication of the lamina densa. But the diagnosis has difficulties as not all biopsies from Alport disease patients have these structural changes. In adult female patients or in children, extensive thinning of the basement membrane can be the major abnormality by electron microscopy. Until the genetic mutation of collagen IV responsible for Alport disease can be demonstrated in all patients, the diagnosis will continue to be a challenge at the clinical and at the ultrastructural levels.     

Comparison of Cystatin C,Creatinine and Creatinine Clearance vs. GFR for Detection of Renal Failure in Renal Transplant Patients

Background: Serum cystatin C (Scyst) has been suggested as an alternative index of glomerular filtration rate (GFR) and could be useful in renal transplant patients. Methods: In a 60‐subject cohort (40 ± 12 years old), we compared the simultaneous measurements of Scyst, serum creatinine (Screat), creatinine clearance (Ccreat), Cockcroft and Gault's estimated clearance (Ccg) and GFR measured using inulin clearance (Cin). Receiver operating characteristic (ROC) analysis was performed using two Cin cut‐off (60 and 90 mL/min/1.73 m²). Results: A significant correlation was found among Cin on one hand and 1/Scyst, Ccreat, 1/Screat and Ccg on the other hand. Best fits (sensitivity/specificity) at 90 mL/min/1.73 m² were 1.18 mg/L (0.72/0.80) for Scyst, 1.32 mg/dL (0.67/0.90) for Screat, 77 mL/min (0.80/0.70) for Ccg and 104 mL/min (0.88/0.80) for Ccreat. The areas under the ROC curves were not significantly different. Conclusions: This study provides cut‐off values for Screat and Ccg for detection of renal failure in renal transplant patients. However, the results also suggest that Scyst is not a more sensitive marker than Screat or Ccg for detecting renal failure in renal transplant patients.     

RENAL EFFECTS OF CARDIAC ANGIOGRAPHY WITH DIFFERENT LOW-OSMOLAR CONTRAST MEDIA

The aim of this study was to evaluate the renal effects of cardiac angiography performed with three low-osmolar contrast media (CM): iopromide (IPR), ioversol (IVR) and ioxaglate (IOX). IPR and IVR are non-ionic CM, IOX is an ionic CM. Different parameters of renal function were determined before and 6, 24, 48, 72 hrs after angiography in 45 patients: 15 patients were examined with IPR, 15 with IVR and 15 with IOX. Glomerular effects – Plasma creatinine increased slightly at the 24th hour after IVR and IOX and at 48 hours after IOP. A significant increase in plasma β2-microglobulin was observed, at the same time, only after IOX. A significant decrease in creatinine clearance was found at 6 hours after IOX. No significant variations in glomerular filtration rate (GFR) and in effective renal plasma flow were found at 48 hours after cardiac angiography; while filtration fraction was significantly reduced after IOP and IOX. Tubular effects – A marked decrease in sodium clearance and a relevant increase of urinary activities of different tubular enzymes were found after cardiac angiography with all CM, but were more evident after the ionic CM IOX, than after the two non-ionic agents. These tubular effects reached the maximum between 6 and 24 hours and returned to baseline within 72 hrs after cardiac angiography. In conclusion, slight glomerular effects were observed mainly after IOX. A reversible tubular malfunction was found with the three low-osmolar CM and was more evident after ionic CM IOX, thus suggesting that other mechanisms, besides osmolarity, play a role in tubular toxicity due to CM. In no patient did the glomerular and tubular effects of CM have a clinical relevance.     

The Effects of Acute Renal Failure on Long-Term Renal Function

The relationship between acute renal failure (ARF) and long-term renal function remains unknown. We therefore undertook a study of patients at the Baltimore VA Hospital to examine the effects of a bout of acute renal injury on long-term renal function. We retrospectively reviewed the relationship between serum creatinine and time of observation for 6058 individuals who had values greater than 1.4 mg/dL in any two consecutive years. Individuals were stratified according to total years of observation with a minimum of two years. Severity of acute renal injury was divided into mild, moderate, and severe with elevations in baseline creatinine of <50%, 50–300% and >300% respectively. Sporadic elevations in creatinine were evident in 8–15% of the population. There were a total of 1328 episodes of acute renal failure in 916 patients that were suitable for analysis. Mild ARF on a substrate of normal or mildly abnormal renal function resolved without long-term sequelae. Moderate and severe ARF occurred more frequently on a background of reduced renal function but baseline function was retained in at least 60% of patients. We conclude that ARF is more frequent in patients with chronic kidney disease but it is not invariably associated with an accelerated course to end-stage renal disease or death. Overall, the majority of ARF events resolved without adverse long-term effects suggesting appropriate management in the majority of instances.