Interleukin-6 and neopterin in renal transplant recipients: a longitudinal study

Serum and urine interleukin-6 (IL-6) levels and serum neopterin/creatinine ratios were longitudinally studied in 86 renal transplant recipients until 4 months after transplantation. During acute rejection and acute tubular necrosis (ATN), serum and urine IL-6 levels were elevated compared to during stable transplant function (P<0.001). During acute rejection, serum IL-6 levels increased at least 2 days before plasma creatinine started to rise (P<0.05), indicating its early involvement in the rejection process. During cytomegalovirus (CMV) disease, serum, but not urine, IL-6 levels were higher (P<0.01), and serum neopterin/creatinine values were higher than during stable transplant function, ATN, or acute rejection (P<0.01). No significant differences with stable transplant function occurred during cyclosporin A toxicity. Measurement of serum IL-6 provided a sensitivity of 84% and a specificity of 85% for the diagnosis of acute rejection episodes not coinciding with ATN. All cases of CMV disease could be diagnosed by measurement of serum neopterin/creatinine, which provided a specificity of 73%.     

Withdrawal of cyclosporine in renal transplant recipients with acute tubular necrosis improves renal function

Abstract In this study, patients with acute tubular necrosis (ATN) after renal transplantation were prospectively randomized to either conventional immunosuppression or withdrawal of cyclosporine and replacement with anti‐thymocyte globulin (ATG). The patients treated with cyclosporine withdrawal and ATG had a significantly shorter duration of ATN (8.9 ± 1.5 vs 10.8 ± 1.4 days; P < 0.05) and better renal function (mean serum creatinine on day 5 postoperatively: 740 ± 49 vs 918 ± 73 μmol/l; P < 0.05). The incidence of acute rejection was lower in the patients with cyclosporine withdrawal and ATG. In conclusion, cyclosporine is toxic to the renal allograft with ATN, and withdrawal of cyclosporine shortens the duration of ATN and improves renal function.     

Dietary supplementation with fish oil modifies renal reserve filtration capacity in postoperative,cyclosporin A-treated renal transplant recipients

The effect of a daily supplementation of 6 g fish oil (30% C20:5 omega-3=EPA and 20% C22:6 omega-3=DHA) for 1 month on renal function variables was investigated in a placebo-controlled (6 g coconut oil), prospective, randomized, double-blind study in acute postoperative cyclosporin A (CyA)-treated renal transplant recipients. Seventeen patients ingested placebo capsules (EPA-) and 14 patients fish oil (EPA+). Renal function tests were performed using the simultaneous determination of 125 I-iothalamate and 131 I-hippuran clearances for glomerular filtration rate (GFR) and effective renal plasma flow (ERPF), respectively. Renal reserve filtration capacity was assessed by dopamine infusion, amino acid infusion, and a combination of both stimuli. After 1 month there were no significant differences in rejection episodes, CyA dose, or CyA levels. In contrast to our earlier observations, serum creatinine, creatinine clearance, GFR, and ERPF did not differ between the EPA- and EPA+ groups. Filtration fraction (FF) differed significantly, being 0.21 in the EPA- group versus 0.26 in the EPA+ group. To exclude the possible influence of a rejection episode, the nonrejecting patients were analyzed separately, creating the subgroups EPA+ re- and EPA-re-. These two groups were comparable in age, donor age, and GFR. The EPA+ re-group had a significantly lower ERPF (164 ml/min per 1.73 m²) than the EPA-re- group (262 ml/min per 1.73 m²). FF was significantly higher in the EPA+re-group (0.26) than in the EPA-re- group (0.21). Following dopamine, no significant differences in the percentage increase of GFR and ERPF between both groups were observed, while FF fell to the same extent in both groups. Following amino acids, the fish oil-treated patients had a significantly better response on GFR (EPA+re- 15.3 versus EPA-re- 10.6%; P<0.05). The near-normal FF and the better response on amino acid infusion strongly suggest that at 1 month postoperatively, the CyA- and fish oil-treated patients have more balanced renal hemodynamics than the CyA- and coconut oil-treated patients.     

Feasibility of diagnosing renal allograft dysfunction by oligonucleotide array: Gene expression profile correlates with histopathology

BackgroundEffective non-invasive monitoring method to tell histopathology is a big challenge in renal transplantation.MethodsWe used 70-mer long oligonucleotide array with 449 immune related genes to determine gene expression profiles of peripheral blood mononuclear cells (PBMCs) under different immune status including stable renal function (TX), acute tubular necrosis (ATN), biopsy conformed acute rejection (AR), clinical rejection with pathology of borderline changes (BL), clinical rejection without biopsy proven/presumed rejection (PR) and renal dysfunction without rejection (NR).ResultsDistinct molecular expression signatures in each group were found to correlate with histopathology. And we concluded that B cell chemokine CXCL13 and mast cell may play a role in renal allograft rejection through significant difference analysis and functional pathway analysis.ConclusionsIt provides a potential non-invasive method for monitoring renal allograft function and immune status of renal transplant recipients.     

Dietary supplementation with lish oil modifies renal reserve filtration capacity in postoperative, cyclosporin A-treated renal transplant recipients

Abstract. The effect of a daily supplementation of 6 g fish oil (30% C20:5 omega-3 = EPA and 20% C22:6 omega-3 = DHA) for 1 month on renal function variables was investigated in a placebo-controlled (6 g coconut oil), prospective, randomized, double-blind study in acute postoperative cyclosporin A (CyA)-treated renal transplant recipients. Seventeen patients ingested placebo capsules (EPA-) and 14 patients fish oil (EPA +). Renal function tests were performed using the simultaneous determination of 1251-iothalamate and 1311-hippuran clearances for glomerular filtration rate (GFR) and effective renal plasma flow (ERPF), respectively. Renal reserve filtration capacity was assessed by dopamine infusion, amino acid infusion, and a combination of both stimuli. After 1 month there were no significant differences in rejection episodes, CyA dose, or CyA levels. In contrast to our earlier observations, serum creatinine, creatinine clearance, GFR, and ERPF did not differ between the EPA-and EPA + groups. Filtration fraction (FF) differed significantly, being 0. 21 in the EPA-group versus 0. 26 in the EPA+ group. To exclude the possible influence of a rejection episode, the nonrejecting patients were analyzed separately, creating the subgroups EPA + re-and EPA-re-. These two groups were comparable in age, donor age, and GFR. The EPA + regroup had a significantly lower ERPF (164 ml/min per 1. 73 nr) than the EPA-re-group (262 ml/min per 1. 73 m²). FF was significantly higher in the EPA + re-group (0. 26) than in the EPA-re-group (0. 21). Following dopamine, no significant differences in the percentage increase of GFR and ERPF between both groups were observed, while FF fell to the same extent in both groups. Following amino acids, the fish oil-treated patients had a significantly better response on GFR (EPA + re-15. 3 versus EPA-re-10. 6%; P < 0. 05). The near-normal FF and the better response on amino acid infusion strongly suggest that at 1 month postoperatively, the CyA-and fish oil-treated patients have more balanced renal hemodynamics than the CyA-and coconut oil-treated patients.     

Dopamine increases renal oxygenation: a clinical study in post‐cardiac surgery patients

Background: Imbalance of the renal medullary oxygen supply/demand relationship can cause ischaemic acute renal failure (ARF). The use of dopamine for prevention/treatment of ischaemic ARF has been questioned. It has been suggested that dopamine may increase renal oxygen consumption (RVO₂) due to increased solute delivery to tubular cells, which may jeopardise renal oxygenation. Information on the effects of dopamine on renal perfusion, filtration and oxygenation in man is, however, lacking. We evaluated the effects of dopamine on renal blood flow (RBF), glomerular filtration rate (GFR), RVO₂ and renal O₂ demand/supply relationship, i.e. renal oxygen extraction (RO₂Ex). Methods: Twelve uncomplicated, mechanically ventilated and sedated post‐cardiac surgery patients with pre‐operatively normal renal function were studied. Dopamine was sequentially infused at 2 and 4 ug/kg/min. Systemic haemodynamics were evaluated by a pulmonary artery catheter. Absolute RBF was measured using two independent techniques: by the renal vein thermodilution technique and by infusion clearance of paraaminohippuric acid (PAH), with a correction for renal extraction of PAH. The filtration fraction (FF) was measured by the renal extraction of ⁵¹Cr‐EDTA. Results: Neither GFR, tubular sodium reabsorption nor RVO₂ was affected by dopamine, which increased RBF (45–55%) with both methods, decreased renal vascular resistance (30–35%), FF (21–26%) and RO₂Ex (28–34%). The RBF/CI ratio increased with dopamine. Dopamine decreased renal PAH extraction, suggestive of a flow distribution to the medulla. Conclusions: In post‐cardiac surgery patients, dopamine increases the renal oxygenation by a pronounced renal pre‐and post‐glomerular vasodilation with no increases in GFR, tubular sodium reabsorption or renal oxygen consumption.     

Loss of corticomedullary demarcation on magnetic resonance imaging: an index of biopsy-proven acute renal transplant dysfunction

A prospective study of 19 cadaveric renal allograft recipients with suspected graft rejection was undertaken to compare the histological findings of the renal transplant biopsy with the results of magnetic resonance imaging (MRI). All 19 patients underwent a biopsy of the transplant allograft. Biopsy results included acute cellular rejection, acute vascular rejection, chronic vascular rejection (CVR), and acute tubular necrosis (ATN). Recipients of cadaveric renal allografts with normal function served as controls. The control showed distinct corticomedullary demarcation (CMD) on T1-weighted imaging. In contrast, CMD was absent or diminished in all the patients with suspected allograft rejection. Unfortunately, the loss of CMD did not correlate with a specific biopsy diagnosis. Patients with biopsy evidence of acute and chronic rejection or ATN demonstrated loss of CMD with similar image patterns. In conclusion, MRI is capable of detecting renal allograft dysfunction, but does not permit the determination of a specific cause.     

Poly(ADP-ribose) polymerase expression in kidney transplantation: from alfa (alpha) to Omega (Omega)

INTRODUCTION: Overactivation of the enzyme poly(ADP-ribose) polymerase (PARP-1) can be induced by ischemia-reperfusion and involved in the renal injury subsequent to kidney transplant. The poly(ADP-ribosy)lation mechanism alters free radical-induced DNA damage, which is repair by PARP-1 polymer. However, PARP-1 overexpression induces cellular necrosis. Our aim was to study the immunohistochemical PARP-1 expression in kidney transplant biopsies associated with various events. MATERIALS AND METHODS: We studied the nuclear expression of PARP-1 in kidney tubule cells by immunohistochemistry using the monoclonal antibody PAR01 in donor biopsies without acute tubular necrosis (ATN) (n = 60; controls), allografts that suffer ATN (n = 90) or an episode of acute humoral rejection (n = 12) or acute tubulointerstitial rejection (n = 25), or chronic allograft nephropathy (n = 25). Furthermore, we also studied protocol biopsies with subclinical rejection (n = 60). Renal lesions in transplant biopsies were graded blindly using 1997 Banff criteria without any clinical information. RESULTS: Biopsies without morphological features of ATN, namely acute tubulointerstitial rejection, borderline or subclinical rejection, showed lesser PARP-1 expression compared with biopsies with ATN or with ischemic mechanism of acute humoral rejection or chronic allograft nephropathys. We observed an inverse relation between PARP-1 expression and renal function (P < .001). Overall, renal biopsies showing ATN revealed greater expression of PARP-1 (r = 0.785, Pearson test). A significant relationship with PARP-1 expression was demonstrated with renal function (effective diuresis, serum creatinine levels) and pretransplant cold ischemia time (P < .001). CONCLUSION: Kidney transplant events including ischemia were associated with the highest PARP-1 expression and worse allograft renal function.     

Acute renal failure in hemorrhagic hypotension: cellular energetics and renal function

In male Wistar rats, renal adenosine triphosphate (ATP), inorganic phosphate (Pi) and intracellular pH were measured by 31phosphorus nuclear magnetic resonance (31P NMR) and correlated with renal function before, during, and for one hour after a period of 30 to 40 minutes hemorrhagic hypotension. In animals which suffered no change in these metabolites during hypotension, retransfusion immediately restored normal renal function. When metabolite changes were observed during hypotension, they occurred suddenly with severe ATP depletion, Pi accumulation, and intracellular acidosis occurring almost concurrently. Metabolic changes of this magnitude were always associated with renal dysfunction in the post-hypotensive period, which occurred even when the period of biochemical change was only 10 to 15 minutes. The abnormalities in post-hypotensive renal function resemble the pattern of change seen in human acute tubular necrosis (ATN): depressed glomerular filtration rate (GFR), urine output varying from polyuria to oliguria, decreased urine to plasma inulin ratio, increased urinary sodium concentration, increased fractional excretion of sodium, and increased fractional excretion of potassium. It is postulated that changes in renal cellular energy status during hemorrhagic hypotension distinguish pre-renal failure from early or incipient ATN.     

Disturbances of kidney graft perfusion as indicators of acute renal vein thrombosis in contrast-enhanced ultrasonography

Introduction

The aim of this study was to evaluate the usefulness of contrast-enhanced ultrasound (US-CE) to diagnose acute renal vein thrombosis (ARVT), acute rejection episodes (ARE), or acute tubular necrosis (ATN) in kidney grafts.

Materials and methods

We analyzed 171 US-CE among kidney transplantation patients in the early postoperative period. Patients underwent US-CE following a standard diagnostic protocol including real-time ultrasound (B-mode) and color Doppler ultrasound with spectral flow analysis. Tissue perfusion was analyzed based upon time-intensity curves for two regions: the renal cortex and the renal pyramids.

Results

Of 14 patients, in whom standard ultrasound showed high resistance parameters in the renal artery, three showed ARVT and 11 had ATN or ARE, which were confirmed by biopsy. Among patients with ARVT, the US-CE showed a lack of contrast perfusion into the cortex and renal pyramids. Patients with ARE/ATN showed slower contrast inflow into the parenchyma with reduced but still present perfusion. The differences in mean signal intensity values were significant for both the cortex and the renal pyramids: cortex: −53.8 ± 5.4 dB versus −35.0 ± 3.5 dB (P < .05) and pyramids: −54.8 ± 5.4 dB versus −37.0 ± 3.5 dB (P < .05).

Conclusion

US-CE is a noninvasive method that provides easy, reliable differentiation of ARVT from ARE/ATN.     

Detection of renal allograft dysfunction with characteristic protein fingerprint by serum proteomic analysis

This study aimed to diagnose renal allograft dysfunction with specific biomarkers by serum proteomic analysis. Surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS) and bioinformatics (support vector machine and leave-one cross validation) were used to analyze serum proteome. Enrolled patients included 38 biopsy-proved acute rejection (BPAR), 10 acute tubular necrosis (ATN), 24 subclinical rejection (SCR) and 29 stable control recipients verified by protocol biopsy. A characteristic protein profile can be detected in each renal allograft dysfunction group. BPAR patients were differentiated from stable patients with markers of 9710.1, 4971, 6675.5, 8563.8, 6709.2, 9319 and 4476.7 Da with high sensitivity and specificity. ATN can be clearly distinguished from BPAR and stable control. Subclinical rejection differentiated from stable control with markers of 9193.1, 2759.1, 8464.6 Da. The independent blind test yielded with high specificity and sensitivity for each group. Serum proteome analysis by SELDI-TOF MS combined with bioinformatics in renal allograft dysfunction is valuable and promising. Specific markers were detected in each group. Identification of these proteins may prove useful as diagnostic markers for allograft dysfunction and better to elucidate the mechanism of acute rejection.     

Prediction of chronic allograft damage index of renal allografts using serum level of plasminogen activator inhibitor‐1

Abstract: Background: Plasminogen activator inhibitor‐1 (PAI‐1) plays an important role in renal fibrosis. We conducted this study to examine whether serum PAI‐1 has a role in predicting chronic allograft nephropathy (CAN). Methods: Fifty kidney transplant recipients receiving graft biopsies were enrolled. The pathologic diagnoses were acute tubular necrosis (ATN; n = 12), borderline rejection (BR; n = 7), acute rejection (ACR; n = 12), CAN (n = 11), polyomavirus nephropathy (PVN; n = 3) and others (n = 5; glomerulopathy, n = 4; calcineurin inhibitor nephropathy, n = 1). The serum level of PAI‐1 and chronic allograft damage index (CADI) score of each patient were determined. Results: The CADI score of all patients was 4 (0–10) (median and range) and in each group was ATN 0.5 (0–4), BR 2.0 (1–4), ACR 4.0 (2–8), CAN 5.0 (4–10), PVN 7 (4–8) and others 2 (0–8). The serum PAI‐1 level of each group was ATN 9.38 (2.35–14.52) ng/mL, BR 10.09 (0.61–18.06) ng/mL, ACR 11.08 (2.32–20.68) ng/mL, CAN 14.51 (3.66–21.12), PVN 14.79 (13.94–21.94) and others 16.35 (4.05–21.01) ng/mL. CADI score is associated with serum PAI‐1 activity (r = 0.405, p = 0.003) and is inversely associated with serum creatinine (r = ?0.348, p = 0.011), but not with estimated glomerular filtration rate (p = 0.124). Conclusion: Serum PAI‐1 level has the potential to be a marker to predict CADI score, the quantitative score of CAN.     

肾移植术后肝细胞生长因子的动态监测及临床意义

目的:探讨肝细胞生长因子(HGF)在急性排斥反应的早期诊断、鉴别诊断中的意义。方法:采用双抗体夹心酶联免疫吸附法,对50例肾移植受者血清HGF水平在手术前后进行动态监测。观察肾移植术后发生急性排斥反应(AR)、急性肾小管坏死(ATN)、环孢素(CsA)中毒时血清HGF的变化。结果:术前组HGF水平与对照组相比有统计学意义(P<0.05)。稳定组术后前3天HGF下降明显,2周左右降至对照组水平。AR组在典型症状出现及血Cr升高前1~3d,HGF即有升高,且峰值出现在抗排斥治疗的当天。经甲基泼尼松龙冲击后AR逆转者HGF迅速下降。ATN组HGF升高,与AR组相比有统计学意义(P<0.05)。CsA中毒组HGF水平升高,与AR相比有统计学意义(P<0.05),但与ATN组相比无统计学意义(P>0.05)。结论:动态监测HGF可能作为急性排斥反应的早期诊断敏感指标,并且对ATN、CsA中毒的鉴别诊断也具有一定临床应用价值。     

Plasma cell densities and glomerular filtration rates predict renal allograft outcomes following acute rejection

The contribution of T cells and graft‐reactive antibodies to acute allograft rejection is widely accepted, but the role of graft‐infiltrating B and plasma cells is controversial. We examined 56 consecutive human renal transplant biopsies classified by Banff schema into T‐cell‐mediated (N = 21), antibody‐mediated (N = 18), and mixed (N = 17) acute rejection, using standard immunohistochemistry for CD3, CD20, CD138, and CD45. In a predominantly African‐American population (75%), neither Banff classification nor C4d deposition predicted the return to dialysis. Immunohistochemical analysis revealed CD3⁺ T cells as the dominant cell type, followed by CD20⁺ B cells and CD138⁺ plasma cells in all acute rejection types. Using univariate Cox Proportional Hazard analysis, plasma cell density significantly predicted graft failure while B‐cell density trended toward significance. Surprisingly T‐cell density did not predict graft failure. The estimated glomerular filtration rate (eGFR) at diagnosis of acute rejection also predicted graft failure, while baseline eGFR ≥6 months prior to biopsy did not. Using multivariate analysis, a model including eGFR at biopsy and plasma cell density was most predictive of graft loss. These observations suggest that plasma cells may be a critical mediator and/or an independently sensitive marker of steroid‐resistant acute rejection.     

Interstitial alterations in renal cortex in acute tubular necrosis (ATN) post-renal transplantation and in patients with ATN not related to renal transplant

BACKGROUND: Abnormalities of renal function with long-term implications can persist after acute tubular necrosis (ATN), probably because of permanent loss of nephrons. Residual areas of fibrosis are also observed in the renal cortex post-ATN. In this study, we investigate the interstitial alterations post-ATN using histological and immunohistochemical methods. METHODS: We studied 11 patients with ATN of different etiologies and 19 patients with ATN post-renal transplantation. Eleven patients with ATN post-renal transplantation and one with ATN not related to renal transplantation were submitted to more than one biopsy because of delayed renal function recovery. The immunohistochemical studies were performed using alpha-smooth muscle-actin (alpha-SM-actin), endothelin, nuclear factor-kappaB (NF-kappaB), Jun-N-terminal kinase (p-JNK) and fibronectin antibodies. We also analyzed the urinary content of transforming growth factor-beta (TGF-beta) during the acute phase of ATN. RESULTS: The immunohistochemical studies showed increased alpha-SM-actin, fibronectin, endothelin, p-JNK and NF-kappaB staining in the tubulointerstitium area from the renal cortex of all patients when compared with controls (p < 0.001), and these increase persisted in the patients submitted to sequential biopsies. One of the patients with ATN without renal transplant and six patients with ATN post-renal transplant developed chronic renal failure. There was a significant increase of TGF-beta excretion in the urine of patients with acute renal failure (p < 0.01) compared with control. CONCLUSIONS: Our data show that the enhancement of renal TGF-beta production and the persistent increase of myofibroblasts, fibronectin, endothelin, p-JNK and NF-kappaB in renal cortex tubulointerstitium post-ATN may explain the impaired recovery of renal function observed in patients post-ATN frequently observed in patients with ATN post-renal transplant.     

Immunohistochemical staining for proliferation antigen as a predictor of chronic graft dysfunction and renal graft loss

BACKGROUND: Assessment of proliferation rate (PR%) using monoclonal antibody for Ki-67 antigen has recently been found to have prognostic importance in lung and cardiac allografts. We ascertained whether the same might be true for renal allografts. METHODS: Newly cut sections from 20 archival paraffin blocks of renal allograft biopsy material showing acute cellular rejection and/or acute tubular necrosis (ATN) and absence of other pathology were stained using MIB-1 antibody and were further double-stained with anti-CD3, anti-CD20 or anti-CD68 antibodies. Counts of staining of mononuclear interstitial cells were correlated with clinical and pathological data. RESULTS: Mean PR% was significantly greater than that in control renal allografts (13.23 +/- 1.94 vs. 2.84 +/- 1.66, p < 0.01). PR% of cases with ATN and no or borderline rejection was significantly lower than that of the remaining cases with acute rejection pathology (6.68 +/- 1.15 vs. 14.31 +/- 1.62, p < 0.05). However, PR% was neither correlated to histological rejection grade nor to long-term graft outcome. Double labelling failed to identify the cell type of most infiltrating MIB-1 positive cells. CONCLUSIONS: Positive MIB-1 staining helps to identify the presence of rejection but does not appear to predict prognosis or correlate with the Banff classification of rejection pathology.     

Diagnostic value of urinary enzyme determination in renal transplantation

Abstract  The measurement of enzyme activity in urine provides a sensitive assessment for renal tubular cell damage. The present study was undertaken to evaluate the clinical value of the determination of tubular brush-border-associated enzymes, alkaline phosphatase (AP), gamma-glutamyl transferase (GGT), leucine aminopeptidase (LAP), and dipeptidyl peptidase IV (DPP), of patients with normal graft function (NOR, n = 20), with acute tubular necrosis (ATN, n = ll), with an acute rejection episode ( ARE, n = 17) after transplantation, and of healthy persons ( n =20). The second urine of the morning was collected daily during the patients' stay in hospital. The enzyme activities were measured at 25 °C and were expressed as U/mmol creatinine. The enzymuria in NOR is higher than in healthy controls, but is still in the normal range. By 5 days after transplantation the initial increased excretion declines as the graft function improves. Elevated enzymuria (DPP 0.69 ± 0.56, AP 3.06 ± 3.24, GGT 4.16 ± 4.13, and LAP 1.39 ± 1.27) was observed during the rejection episodes. Two days before clinical diagnosis of rejection, the release of DPP-IV and GGT increases to double, and the AP and LAP increases to 3 times the value on the fourth day before rejection. Successful treatment of rejection coincided with a quick return by the third day of the rejection period to the previous enzyme distribution. In ATN no decrease of enzymuria occurs and the excretion is much higher than in ARE. Our method with the every day monitoring of kidney graft function offers the possibility for the early diagnosis of acute rejection.     

Improved diagnosis of early kidney allograft dysfunction by ultrasound with echo enhancer--a new method for the diagnosis of renal perfusion.

BACKGROUND: Conventional ultrasound parameters such as the resistance index (RI) are only of limited use in the diagnosis of early allograft dysfunction. We, therefore, performed a prospective study to compare the value of ultrasound contrast media (USCM) with conventional US in the diagnosis of early allograft dysfunction. METHODS: A total of 48 consecutive kidney recipients underwent US examination after USCM administration 4-10 days after transplantation. Arterial inflow was determined in the interlobar artery and renal cortex using time-intensity curve (TIC) software. The difference in time-to-peak intensity between these two vascular territories was determined, and a perfusion quotient (PQ) was defined as the ratio of TIC increase of interlobar artery to renal cortex. Three patients with segmental loss of renal perfusion demonstrated by Doppler US were excluded. RESULTS: Nineteen patients had an uneventful clinical course (control group); PQ was 1.2 +/- 0.4. Seven patients with a large perirenal haematoma, without rejection had an increased PQ (P < 0.05) and a prolonged time difference (P < 0.05). Based on clinical and histological criteria, the remaining patients were classified as acute tubular necrosis (ATN) (n = 7), non-vascular rejection (n = 7) or vascular rejection (n = 5). RI determination could not discriminate these groups. Patients with ATN (PQ = 1.6 +/- 0.7) or non-vascular rejection (PQ = 1.1 +/- 0.6) had a lower PQ than patients with vascular rejection (PQ = 2.2 +/- 0.8, P < 0.05). The time difference in all three subgroups was longer compared with controls. CONCLUSIONS: USCM might be superior in the diagnosis of early kidney allograft dysfunction compared with conventional US by means of RI determination. Perirenal haematoma, ATN and vascular rejection are associated with characteristic changes of the TIC.     

Effects of prostaglandin E1 on renal hemodynamics

The glomerular filtration rate (GFR), renal plasma flow (RPF), renal blood flow (RBF), filtration fraction (FF), and the ratio of mean arterial pressure (MAP) to RBF (MAP/RBF), reflecting renal vascular resistance (RVR) were determined to investigate the effects of intravenously administered prostaglandin E₁ (PGE₁) on renal hemodynamics in humans. PGE₁ produced no significant changes in GFR, but did cause significant increases in RPF and RBF and significant decreases in FF and MAP/RBF. The relationships between MAP and GFR, MAP and RBF, and MAP and MAP/RBF were investigated. PGE₁ suppressed the increase of MAP/RBF along with the increase of MAP, increased the RBF along with the increase of MAP, and kept the GFR constant, regardless of MAP. Also, the effects of PGE₁ on renal pericapillary vessels were simulated. According to this simulation, PGE₁ had a vasodilator action on both preglomerular and postglomerular capillaries.     

Reversible acute tubular necrosis following severe acute renal rejection

The clinical observation of 6 out of 250 renal transplant patients showed that acute renal rejection may lead to reversible acute tubular necrosis (ATN) necessitating intermittent haemodialysis treatment. Despite missing early response to high-dose (methyl-) prednisolone therapy (during a mean period of 4.7 days) all 6 patients developed spontaneous diuresis 14.5 days on average after onset of rejection while on maintenance immunosuppressive therapy. From the clinical course the conclusion was drawn that in severe cases of renal rejection with arteriographic and histological findings consistent with acute tubular necrosis, prolonged therapy with high doses of (methyl-) prednisolone is not desirable, since after reversal of immunological rejection the onset of spontaneous diuresis will be determined mainly by the duration of the healing and recovery phase of acute tubular necrosis.