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 beta2-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.     

Nephrotoxicity of high- and low-osmolality contrast media

Nephrotoxicity of radio-opaque contrast media (CM) is generally believed to involve toxic injury of proximal tubular cells. Measurement of urinary tubular enzyme excretion has been advocated as a sensitive marker of such toxic injury. It has been claimed that the new low-osmolality or nonionic CM reduce the incidence of nephrotoxicity but this remains uncertain. We studied 23 patients with normal renal function undergoing coronary angiography; patients were randomized into three groups receiving either diatrizoate (1,800 mmol/kg H2O), ioxaglate (600 mmol/kg H2O) or iohexol (850 mmol/kg H2O). Urinary excretion of a panel of enzymes increased significantly in all groups by 20 h (p less than 0.05 to less than 0.005). Alanine aminopeptidase excretion at 20 h was greater after the administration of high osmolality ionic CM than with the others but all three CM produced a similar pattern of enzyme excretion. No significant change in glomerular filtration rate was found in any group so the significance of the enzymuria remains uncertain.     

Nephrotoxic effects of ionic and nonionic contrast media on rat and human renal cortical slices

Background. Nephrotoxicity is a well-known adverse effect of radiographic contrast medium (CM). Recently, several kinds of low- osmolality nonionic CM have been developed. However, the nephrotoxic effects of nonionic CM compared with those of ionic CM have not been well evaluated. Methods. To compare the direct nephrotoxic effects of ionic and nonionic CM on renal epithelial cells, rat and human renal cortical slices were incubated with CM at 37°C for 120 min. Diatrizoate and iothalamate were employed as ionic CM. Iopamidol, iohexol, iomeprol, ioversol, iopromide, and ioxilan were employed as nonionic CM. Direct toxicity of CM was evaluated by the activities of N-acetyl-β-D-glucosaminidase (NAG) and γ-glutamyl-transferase (GGT) released from the renal slices into the incubation buffer. Results. In the experiment with rat renal slices, NAG and GGT activities in buffer solutions were increased dose-dependently by 30, 60, and 90 mg I/ml of CM. There was no significant difference in NAG or GGT release between ionic and nonionic CM at the concentration of 60 mg I/ml. In the experiment with human renal slices, incubation with 60 mg I/ml of diatrizoate, iothalamate, iomeprol, and iopromide did not affect NAG levels. Significantly greater increases in NAG levels, compared with the control, were observed after incubation with iopamidol, iohexol, ioxilan and ioversol. Nevertheless, the increases in NAG caused by some of the nonionic CM were very slight. GGT release from human renal slices was significantly greater than that of the control in all experimental groups. Again, there was no significant difference in renal toxicity between ionic and nonionic CM. Conclusions. Newly developed nonionic CM had almost the same degree of nephrotoxicity against rat and human renal epithelial cells as conventional ionic CM, when direct renal toxicity was evaluated by enzyme release in an in-vitro experimental system using renal cortical slices. Received: November 22, 2000 / Accepted: March 6, 2001     

Gadolinium-based contrast media compared with iodinated media for digital subtraction angiography in azotaemic patients.

BACKGROUND: To determine whether gadolinium-based contrast media (CM) could be used safely for angiographies in patients with renal dysfunction we investigated renal function after gadobutrol exposure and compared the results with standard iodinated CM (iohexol) in a randomized clinical study. METHODS: Twenty-one patients (aged 67+/-11 years, nine female and 12 male) with severely impaired renal function [mean serum creatinine 3.2+/-1.3 mg/dl, mean glomerular filtration rate (GFR) 31+/-16 ml/min/1.73 m(2)] who needed to have angiography because of severe peripheral vascular disease, renal artery stenosis or aortic aneurysms were randomized to receive in a blinded manner either gadobutrol (Gadovist 1.0 mmol/ml) or iohexol (Omnipaque 350) as contrast agents. GFR was measured by CM clearance (Renalyzer) at baseline and 48 h after CM administration. The primary end point was the mean change of GFR from baseline at 48 h, the secondary one the incidence of CM-induced acute renal failure, defined as a decrease in GFR of >50% from baseline within 48 h of CM administration. RESULTS: In the gadobutrol group (n = 10) we observed a statistically significant decrease in GFR of 10.6+/-13.8 ml/min/1.73 m(2) within 48 h after CM administration (P<0.05, paired t test). The incidence of CM-induced ARF amounted to 50%. In comparison, the iohexol group (n = 11) also showed a statistically significant GFR reduction of 8.7+/-8.8 ml/min/1.73 m(2) (P<0.05, paired t test), and of ARF by 45%. The percentile of differences of GFR decreases between the two groups was not significant (P = 0.70). No patient demonstrated other adverse effects of gadobutrol or iohexol administration, apart from GFR reduction. Despite the decline in GFR, no patient required haemodialysis in the 10 following days. CONCLUSIONS: In our study, gadolinium-based angiography showed no benefit over iohexol angiography with respect to preventing GFR reduction in patients with severely impaired renal function.     

Glomerular and Tubular Effects of Contrast Media Diatrizoate and Iopromide

The aim of this study is to evaluate the nephrotoxicity of two contrast media (CM), with different physicochemical characteristics: diatrizoate (ionic high-osmolar), iopromide (nonionic low-osmolar). Intravenous urography was performed in 34 patients: 17 were examined with diatrizoate and 17 with iopromide, randomly assigned. Different parameters of glomerular and tubular function were measured before and at 6, 24, and 48 h after urography. Both contrast media induced a reversible increase of urine enzymes, which was significantly higher after diatrizoate. In particular, diatrizoate determined a relevant increase of brush border enzymes -γ-glutamyltransferase (GGT) and alkaline phosphatase (ALP) and of cytosolic enzyme lactate dehydrogenase (LDH), while, after iopromide increases of urinary enzymes were less evident and were significant only for GGT and ALP. In addition, diatrizoate affected other tubular functions (clearances of phosphorus and uric acid) and slightly decreased glomerular function in a few patients. In no case did these glomerular and tubular effects have a clinical relevance. In conclusion, the nonionic low-osmolar contrast medium iopromide appeared less nephrotoxic than diatrizoate. The cost-benefit ratio needs further examination.     

A comparative study of the renal damage produced after the extracorporeal shock wave lithotripsy according to the lithiasis location

IntroductionThe Extracorporeal shock waves lithotripsy (ESWL) is fundamental in the treatment of lithiasis. However, there are evidences that it can produce renal damage. The objective of our study is to determine the degree of affectation of the glomerular and tubular function after LEOC, and the influence of the lithiasis location on the type of renal damage.Material and methodsA prospective longitudinal study was carried out in 14 patients with normal renal function subjected to ESWL. We determined the basal level, and the levels at the 24 hours, at the 4th and the 10th day post ESWL of: microalbuminuria (MA) (that values the glomerular function), and N-acetil glucosamide (NAG) and alanine aminopeptidase (AAP), (that value the tubular function).ResultsThe basal levels of of MA, NAG and AAP didn’t show significant differences in connection with the localization of the stones. A significant increase was observed of the three parameters only 24 hours post ESWL No significant differences were observed between the variation of the microalbuminuria levels, AAP and NAG and the treatment in relation to the localization of the stones.ConclusionsIt exists a glomerular and tubular damage after ESWL. This damage is not related with the pelvic or calicial location of the stones. In patient with previous normal renal function, the renal damage recovers at the 4º day post ESWL.     

Inhibition of gluconeogenesis and <Emphasis Type="Italic">p</Emphasis>-aminohipuric acid accumulation in rat renal cortical slices by ionic and nonionic contrast media

Background. Renal dysfunction is a well-recognized complication induced by contrast media (CM). Nonionic CM have been introduced into clinical use to replace conventional ionic CM in an effort to reduce toxicity. However, the nephrotoxic effects of nonionic CM have not been fully evaluated. We previously determined the activities of N-acetyl--d-glucosaminidase and -glutamyltransferase released from rat and human renal slices incubated with contrast media. Dose-dependent enzyme release from renal slices was observed, but there was no statistical difference in the increase of enzyme activities between ionic and nonionic CM. The present experiment was conducted to compare the effects of ionic and nonionic CM on the metabolic function of rat renal slices.Methods. Rat renal cortical slices were incubated with ionic CM (diatrizoate, iothalamate) and nonionic CM (iopamidol, iohexol) at 37°C for 90min. To examine the dose–response effects of CM on gluconeogenesis and p-aminohipuric acid (PAH) accumulation in the rat renal slices, slices were incubated with 30, 60, and 90mgI/ml of CM. The inhibitory effects of nonionic CM on gluconeogenesis and PAH accumulation were compared with those of ionic CM in an independent experiment, in which slices were incubated with CM at a concentration of 60mgI/ml. In addition, rat renal slices were incubated with mannitol instead of CM to investigate the effects of osmotic pressure on gluconeogenesis and PAH accumulation.Results. A dose-dependent reduction of gluconeogenesis in rat renal slices was demonstrated by both ionic CM and nonionic CM. The inhibition of PAH accumulation was dose-dependent with nonionic CM, but not with ionic CM. Gluconeogenesis and PAH accumulation within the renal slices were both inhibited according to the increase in osmotic pressure produced by mannitol. The reduction in gluconeogenesis and PAH accumulation within the rat renal slices incubated with 60mgI/ml of nonionic CM were significantly less than those resulting from the same concentration of ionic CM.Conclusions. Nonionic CM is less nephrotoxic than ionic CM with regard to gluconeogenesis and PAH accumulation in rat renal slices. These differences in nephrotoxic effect between ionic and nonionic CM may in part be attributable to differences in osmotic pressure.     

Xuezhikang ameliorates contrast media-induced nephropathy in rats via suppression of oxidative stress,inflammatory responses and apoptosis

Background: The aim of this study was to assess the preventive effect of xuezhikang (XZK) to replace atorvastatin on the contrast media-induced acute kidney injury (CI-AKI).

Methods: The male Sprague–Dawley rats were divided into five groups: group 1 (sham), injected with normal saline; group 2 (XZK), treated with XZK; group 3 contrast media (CM), injected with CM; group 4 (CM?+?ATO), injected with CM?+?pretreatment with atorvastatin; group 5 (CM?+?XZK), injected with CM?+?pretreatment with XZK. Twenty-four hours after injection with normal saline or CM, the blood sample and the kidneys were collected for the measurement of biochemical parameters, oxidative stress markers, nitric oxide production, inflammatory parameters, as well as renal histopathology and apoptosis detection.

Results: Our results indicated that XZK restored the renal function by reducing serum blood urea nitrogen (BUN) and serum creatinine (Scr), depressing renal malondialdehyde (MDA), increasing renal NO production, decreasing TNF-ɑ and IL-6 expression, attenuating renal pathological changes and inhibiting the apoptosis of renal tubular cells.

Conclusion: XZK’s therapeutic effect is similar, or even better than atorvastatin at the same effectual dose in some parts.     

Nephrotoxicity of ionic and nonionic contrast media in selective renovasography

Nephrotoxic effect of ionic and non-ionic contrast media was examined in a doubleblind study by evaluation of serum creatinine, blood urea nitrogen, urine volume, urinary protein excretion and erythrocyturia before and after selective renovasography. In 19 of 22 patients reliable results were obtained. With optimal hydration before and after renovasography no significant differences between both administered contrast media (Rayvist 300 and Omnipaque 300) could be found by evaluation of the aforementioned parameters. In 3 patients with preexistent proteinuria (greater than 200 mg/l) urine protein excretion remained at the same or a lower level after application of the non-ionic contrast medium Omnipaque 300. Three patients with proteinuria tended to increase the proteinuria after administration of the ionic contrast medium (Rayvist 300) up to 48 h after angiography indicating a higher nephrotoxic potential of ionic contrast media in patients with preexistent renal disease. The constant values of urine volume and serum creatinine indicate an absence of clinically relevant nephrotoxicity of both contrast media in this study when administered in well-hydrated patients. This emphasizes the importance of sufficient hydration in prophylaxis of nephrotoxic effects, especially in patients with risk factors.     

Assessment of renal function in the early stages of nephrotoxicity induced by iodinated contrast media.

To determine whether there are early renal function parameters (RFP) which can be monitored to rapidly detect nephrotoxicity induced by contrast media (CM), we observed RFP in 16 patients with normal renal function before and after administration of CM. Forty-eight hours after diatrizoate meglumine administration, blood urea nitrogen (BUN) and serum creatinine (SCr) increased (p < 0.05). In all patients, acute tubular damage was revealed by early urinary RFP. Increases in levels of serum angiotensin-I-converting enzyme (ACE), beta(2)-microglobulin (beta(2)M) and urinary albumin (Alb) were associated with alterations in glomerular function. The changes in early RFP occurred earlier than those of BUN and SCr. The present study demonstrates that serum ACE, beta(2)M, urinary Alb, gamma-glutamyl-transpeptidase and N-acetyl-beta-D-glucosidase are sensitive parameters for the early assessment of subclinical nephrotoxicity induced by CM.     

Study on urinary splitting enzymes and proteins. III. Effect of non-ionic contrast medium on renal function

Renal toxicity of non-ionic contrast medium (iohexol) for drip infused pyelography (DIP) was studied in a randomized trial of nine patients with normal renal function. Urine samples were collected before and immediately after DIP, and analyzed for albumin, an index of glomerular permeability; gamma-glutamyl transpeptidase (gamma-GTP), a brush-border enzyme; N-acetyl-beta-glucosaminidase (NAG), a lysosomal enzyme; alpha 1 microglobulin (alpha 1MG) and beta 2 microglobulin (beta 2MG), an index to tubular proteinuria; and creatinine. The urinary excretion of enzymes and proteins was compared with urinary creatinine. Urinary excretion of gamma-GTP and NAG increased significantly (P less than 0.001, 0.02) after DIP. Urinary alpha 1 MG and beta 2-MG did not change significantly. The change of urinary albumin was mild. Our data suggest that non-ionic, low osmolal radiocontrast medium ioheol shows a lower renal tubular toxicity, and the brush-border enzyme gamma-GTP and lysosomal enzyme NAG are considered as a good index for renal tubular damage.     

Exacerbation of radiocontrast nephrotoxicity by endothelin receptor antagonism

BACKGROUND: Endothelin is a potent vasoconstrictor that has been implicated in the pathogenesis of radiocontrast nephrotoxicity. Endothelin antagonists may reduce the renal hemodynamic abnormalities following radiocontrast administration. METHODS: One hundred fifty-eight patients with chronic renal insufficiency [mean serum creatinine +/- SD = 2.7 +/- 1.0 mg/dL (242. 3 to +/- 92.8 micromol/L)] and undergoing cardiac angiography were randomized to receive either a mixed endothelin A and B receptor antagonist, SB 290670, or placebo. All patients received intravenous hydration with 0.45% saline before and after radiocontrast administration. Serum creatinine concentrations were measured at baseline, 24 hours, 48 hours, and 3 to 5 days after radiocontrast administration. The primary end point was the mean change in serum creatinine concentration from baseline at 48 hours; the secondary end point was the incidence of radiocontrast nephrotoxicity, defined as an increase in serum creatinine of > or =0.5 mg/dL (44 micromol/L) or > or = 25% from baseline within 48 hours of radiocontrast administration. RESULTS: The mean increase in serum creatinine 48 hours after angiography was higher in the SB 209670 group [0.7 +/- 0. 7 mg/dL (63.5 +/- 58.6 micromol/L)] than in the placebo group [0.4 +/- 0.6 mg/dL (33.6 +/- 55.1 micromol/L), P = 0.002]. The incidence of radiocontrast nephrotoxicity was also higher in the SB 209670 group (56%) compared with placebo (29%, P = 0.002). This negative effect of SB 209670 was apparent in both diabetic and nondiabetic patients. Adverse effects, especially hypotension or decreased blood pressure, were more common in the SB 209670 group. CONCLUSIONS: In patients with chronic renal insufficiency who were undergoing cardiac angiography, endothelin receptor antagonism with SB 209670 and intravenous hydration exacerbate radiocontrast nephrotoxicity compared with hydration alone.     

Renal tubulointerstitial injury from ureteral obstruction in the neonatal rat is attenuated by IGF-1

BACKGROUND: The administration of insulin-like growth factor-1 (IGF-1) has been shown to ameliorate the renal injury resulting from ischemic acute renal failure. As there are a number of similarities between acute renal failure and obstructive nephropathy, we examined the effects of IGF-1 on the renal cellular response to unilateral ureteral obstruction (UUO) in the neonatal rat. METHODS: Forty-five rats were subjected to UUO or sham operation within the first 48 hours of life and received IGF-1 (2 mg/kg/day) or saline for the following three or seven days, after which kidneys were removed for study by morphometry and immunohistochemistry. To determine the effects of UUO on endogenous expression of IGF-1 and its receptor, six additional rats were subjected to UUO or sham operation, and mRNA was measured by solution hybridization. RESULTS: There was no effect of seven days of UUO on the renal expression of endogenous IGF-1 or its receptor. Moreover, seven days of exogenous IGF-1 did not improve the suppression of nephrogenesis, the delay in glomerular maturation, or the reduction in tubular proliferation induced by ipsilateral UUO. However, in the obstructed kidney, IGF-1 reduced tubular expression of vimentin, apoptosis, and tubular atrophy by 38 to 50% (P < 0.05). In addition, IGF-1 also decreased renal interstitial collagen deposition in the obstructed kidney by 44% (P < 0.05). Following three days of UUO, the administration of IGF-1 also reduced tubular apoptosis (P < 0.05), but did not alter tubular proliferation. CONCLUSIONS: IGF-1 has a profound salutary effect on the tubular and interstitial response to UUO in early development, without affecting glomerular injury or development. These results suggest that IGF-1 may have therapeutic potential in the management of congenital obstructive nephropathy.     

Use of interventional radiology as initial hemorrhage control to improve outcomes for potentially lethal multiple blunt injuries

IntroductionRecently, trauma management has been markedly improved with interventional radiology (IVR) and damage-control strategies. However, the indications for its use in hemodynamically unstable patients with severe trauma remains unclear. In some cases, IVR may be more effective than surgery for damage-control hemostasis; however, performing IVR in life-threatening trauma settings is challenging. To address this, we practiced and evaluated a trauma-management system with emergency physicians who trained for both severe trauma management, and techniques of surgery and IVR.Materials and methodsAmong the 1822 patients with severe trauma admitted between October 2014 and December 2016, 201 underwent emergency surgery or IVR. Among these, 16 patients whose systolic blood pressure was ≤90 mmHg, without improvement following primary resuscitation, and whose first intervention was IVR, were analyzed. We retrospectively evaluated the admission characteristics, IVR-related characteristics, and prognoses, and compared several parameters before and after IVR.ResultsThis study included 10 men and 6 women (median age: 46 years). IVR was performed for 10 pelvic fractures; five liver-, one splenic-, and one renal injury; and one transection each of the external carotid-, vertebral-, axillosubclavian-, intercostal-, and lumbar arteries. The mean times from the patient arrival, and diagnosis to the start of IVR were 56.3 ± 26.6 and 15.1 ± 3.8 min, respectively. The mean time spent in the angiography suite was 50 min. The systolic blood pressure, pulse rate, base excess/deficit, serum-lactate levels, and D-dimer values were significantly improved after IVR. Although two patients needed additional treatment for morbidities following IVR intervention, all achieved complete recovery. The mortality rate was 25.0%, and no preventable deaths were noted. Eight patients showed unexpected survival.ConclusionsIn some cases, IVR may be the best first measure for resuscitative hemostasis in potentially lethal multiple injuries, given efficient diagnoses/actions and the ability to deal with complications.     

Effects of an acute dose of L-arginine during coronary angiography in patients with chronic renal failure: a randomized,parallel, double-blind clinical trial

BACKGROUND: Contrast media (CM) are nephrotoxic and might further worsen renal function in patients with chronic renal failure. L-Arginine, the substrate of nitric oxide, protects kidney function and may improve endothelial function in patients with coronary artery disease. HYPOTHESIS: Acute administration of L-arginine in a subset of patients with combined coronary artery disease and impaired kidney function during coronary angiography might prevent superimposed acute renal failure. METHODS: A double-blind study of patients with mild/moderate chronic renal failure (Cr >1.7 mg/dl) undergoing coronary angiography (meglumine ioxaglate) was conducted. Patients received either L-arginine (300 mg/kg) or placebo and were followed for 48 h. Cardiac hemodynamic parameters, renal function and nitric oxide production were sequentially recorded. RESULTS--PRIMARY AND SECONDARY: Both groups experienced a decrease of creatinine clearance 48 h following the procedure (p < 0.05). Creatinine levels slightly increased following the administration of L-arginine (p < 0.05) but not in the placebo treated group. No changes of systemic and cardiac pressures, total peripheral resistance or cardiac output were recorded within and between the treatment and placebo groups. CONCLUSION: CM injection causes an impairment of renal function. Addition of intravenous L-arginine during cardiac catheterizations in patients with chronic renal failure does not prevent CM-induced nephrotoxicity and does not affect endothelial dysfunction in the particular population studied by the authors, i.e. patients with coronary artery disease (CAD) of various degrees, or suspicion of CAD and chronic mild renal failure.     

Effect of Post-Transplant Cardiac Angiographic Procedures on Post-Transplant Renal Function

BackgroundCardiac interventions often are performed before and after renal transplant for coronary artery disease. The aim of this study was to investigate whether post-transplant cardiac coronary procedures affect post-transplant renal function.MethodWe retrospectively included renal transplant recipients who underwent renal transplant procedures at Baskent University between April 28, 1997 and January 20, 2020. We analyzed the effect of cardiac catheterization in renal transplant recipients between 6 and 12 months post-transplant with post-transplant renal function assessed by glomerular filtration rate (GFR). We compared the effect of the type of coronary intervention on GFR change in group 1, whereby group 1 was divided into 2 subgroups (coronary artery bypass grafting [CABG] and stenting). Group 1 included patients who underwent cardiac intervention, whereas group 2 included those who had not undergone cardiac intervention.ResultsIn all, 108 patients underwent coronary angiography; 45 (41.7%) had normal coronaries or minimal coronary artery disease (CAD); 37 (34.3%) underwent stent implantation; 26 (24.1%) underwent CABG. The mean post- transplantation GFR of all patients after cardiac catheterization was 84.26+25.91 (mL/min/1.73 m²). The final, after 12 months mean GFR of all patients was 69.55+27.05. The final GFR was significantly lower than the initial post-renal GFR value in patients who underwent cardiac intervention but not in non-intervened patients.ConclusionInvasive cardiac revascularization procedures showed a negative effect on post-transplant renal function in renal transplant recipients. All renal transplant recipients who underwent cardiac intervention survived the intervention, and there was no mortality. The reason for this outcome was assumed to be because of the short follow-up period.     

Hyperplasia precedes increased glomerular filtration rate in rat remnant kidney

Using 3H-thymidine (3H-T), we examined DNA synthesis in rats subjected to either uninephrectomy (UNI), five-sixths nephrectomy (R) or sham (S) surgery. Twenty-four, 48, or 72 hours later, animals were infused with 14C-inulin, PAH and 3H-T and clearances obtained. Prior to sacrifice, India ink was injected for glomerular counting. By 24 hours, glomerular filtration rate per nephron was significantly increased in UNI. However, in R, glomerular filtration rate per nephron was significantly lower than S until 72 hours. Total micrograms DNA per nephron was unchanged in UNI but significantly increased in R compared to S at all times. 3H-T incorporation into DNA was twice as great in UNI as in S was over five-fold greater at 24 hours in R than in S; this marked increase persisted in R at 48 and 72 hours. Autoradiographs confirmed that DNA was synthesized predominantly by renal tubular cells and not infiltrating cells. These results indicate that hyperplasia in compensatory renal growth is related to the quantity of tissue removed and that, in the remnant kidney, DNA synthesis precedes the compensatory increase in glomerular filtration rate per nephron.     

Lymphokine (MIF) production by glomerular T-lymphocytes in experimental glomerulonephritis

Glomerular T-lymphocyte infiltration has recently been demonstrated to precede glomerular macrophage influx in a pre-immunized model of anti-glomerular basement-membrane antibody-induced glomerulonephritis (antiGBM-GN). In the current study, the functional role of these glomerular T-lymphocytes in directing macrophage localization was sought by measuring their production of macrophage migration inhibition factor (MIF). MIF activity in supernatants from cultured isolated glomeruli was measured in a conventional capillary tube bioassay. Glomerular T-lymphocytes (OX19 positive cells) were maximal (1.95 +/- 0.19 cells/glomerular cross section, c/gcs) 24 hours after injection of antiGBM antibody into sensitized animals. Seventy-two hours after antibody injection, T-lymphocyte numbers were reduced (1.02 +/- 0.14 c/gcs) while macrophage accumulation was maximal (at 24 hrs 4.2 +/- 1.3 macrophages/glomerulus (m/g), at 72 hrs 19.8 +/- 3.7 m/g). MIF activity was only detected in supernatants from T-lymphocyte infiltrated glomeruli (12 hrs 40.81 +/- 4.32% migration inhibition, 24 hrs 45.11 +/- 4.11% migration inhibition, 48 hrs 38.24 +/- 3.53% migration inhibition, 72 hrs 20.86 +/- 3.85% migration inhibition, all P less than 0.05). Control glomeruli from normal animals, pre-immunized animals given normal sheep globulin, pre-immunized animals given anti-GBM antibody and Cyclosporin A, and non-pre-immunized animals given antiGBM antibody did not contain glomerular T-lymphocytes, and their supernatants contained no MIF activity. This data indicates that the glomerular T-lymphocytes in pre-immunized antiGBM-GN are sensitized cells which release MIF and thus may direct glomerular macrophage localization in this model of antibody-induced glomerulonephritis.     

Time course of serial cystatin C levels in comparison with serum creatinine after application of radiocontrast media

BACKGROUND: The delayed increase of creatinine after radiocontrast application is a potential reason for overlooking radiocontrast nephrotoxicity. Cystatin C may be more useful to rapidly assess a decrease in glomerular filtration rate (GFR). We compared cystatin C and creatinine to examine their kinetics after application of radiocontrast media. PATIENTS AND METHODS: Forty-one patients (60.8 +/- 8.8 years, 68% males) with normal to subnormal GFR scheduled for coronary angiography (27% with angioplasty), were studied for serum cystatin C and creatinine levels before, 5 h, 24 h and 48 h after angiography. Furthermore, alpha1-microglobulin was checked for evidence of tubular damage. RESULTS: At 5 hours after angiography, there was no significant change compared to baseline in either serum creatinine nor cystatin C. In comparison with the value immediately before coronary angiography, the increase of cystatin C achieved a maximum at 24 h after the application of the contrast agent (+7.2%). Within 48 h, cystatin C decreased to the level before angiography. Serum creatinine increased at 24 h (+7.7%) and continued to increase at 48 h (+11.3%). CONCLUSION: Cystatin C increases earlier after radiocontrast application compared with creatinine. Therefore, cystatin C needs to be investigated as a potential early marker for nephrotoxicity, especially in the upcoming setting of short-time hospitalizations for coronary angiographies and interventions. Thus, further studies in patients with renal failure undergoing radiocontrast application are warranted to assess the usefulness of cystatin C in respect of an earlier detection of radiocontrast nephrotoxicity.     

Electron beam computerized tomography assessment of in vivo single kidney glomerular filtration rate and tubular dynamics during chronic partial unilateral ureteral obstruction in the pig.

PURPOSE: The assessment of hydronephrosis due to chronic partial ureteral obstruction is controversial. We determined whether a new radiographic technique for assessing kidney function, electron beam computerized tomography (CT), can detect altered renal physiology due to chronic partial ureteral obstruction. We also compared and contrasted electron beam CT with standard well tempered diuretic mercaptoacetyltriglycine (MAG-3) urography. MATERIALS ANDS METHODS: Six pigs underwent creation of unilateral partial ureteral occlusion or sham operation. Three weeks after surgery diuretic enhanced MAG-3 renal scan was done and 48 hours later contrast enhanced electron beam CT was performed. RESULTS: Mean differential function plus or minus standard error of mean of the obstructed kidney was 5.6% +/- 2.4% on MAG-3 renography. In contrast, electron beam CT revealed significantly preserved mean renal function at 24.5% +/- 2.7% (p <0.01). Electron beam CT analysis of tubular function revealed persistent glomerular filtration and filtrate flow through the proximal tubules and loop of Henle with a selective decrease in distal tubular flow, which were findings suggestive of proximal tubular sparing that were not demonstrated by nuclear renography. CONCLUSIONS: Renal function on MAG-3 renography is primarily determined by measuring kidney perfusion and tubular secretion of the isotope. In contrast, electron beam CT determines renal function via quantifying the in vivo single kidney glomerular filtration rate and by assessing renal tubular function. This study documents that electron beam CT of differential renal function is significantly different from that of MAG-3 renography. To our knowledge which of these 2 radiographic studies is most clinically applicable is unknown to date.