Monitoring of renal allografts by duplex ultrasound

Abstract. Deterioration of renal transplant function due to rejection is accompanied by changes in renal blood flow that can be measured by duplex ultrasound (DU). In the present study, 60 transplanted patients were followed up. A total of 233 duplex examinations, 68 percutaneous biopsies, 44 renal scintigraphies, and 6 transplant nephrectomies were performed on these patients. Diagnoses were made on the basis of clinical and histological data. Renal perfusion was calculated by means of DU. In addition, the arterial Doppler signals were quantified using a pulsatility index (PI). Mean perfusion of normal renal allografts was 0. 47 1/min. A decrease in blood flow could be found in acute vascular and chronic rejection but not in acute cellular rejection. A lack of renal perfusion due to acute vascular rejection was observed in four patients. Mean PI, used as a parameter of DU, rose significantly in all forms of rejection, which could be diagnosed with a sensitivity of 93% and a specificity of 86%. Cyclosporin overdosage did not alter the Doppler flow shape.     

Monitoring of renal allografts by duplex ultrasound

Deterioration of renal transplant function due to rejection is accompanied by changes in renal blood flow that can be measured by duplex ultrasound (DU). In the present study, 60 transplanted patients were followed up. A total of 233 duplex examinations, 68 percutaneous biopsies, 44 renal scintigraphies, and 6 transplant nephrectomies were performed on these patients. Diagnoses were made on the basis of clinical and histological data. Renal perfusion was calculated by means of DU. In addition, the arterial Doppler signals were quantified using a pulsatility index (PI). Mean perfusion of normal renal allografts was 0.47 l/min. A decrease in blood flow could be found in acute vascular and chronic rejection but not in acute cellular rejection. A lack of renal perfusion due to acute vascular rejection was observed in four patients. Mean PI, used as a parameter of DU, rose significantly in all forms of rejection, which could be diagnosed with a sensitivity of 93% and a specificity of 86%. Cyclosporin overdosage did not alter the Doppler flow shape.     

Acute Page Kidney Following Renal Allograft Biopsy: A Complication Requiring Early Recognition and Treatment

The acute Page kidney phenomenon occurs as a consequence of external compression of the renal parenchyma leading to renal ischemia and hypertension. Between January 2000 and September 2007, 550 kidney transplants and 518 ultrasound-guided kidney biopsies were performed. During that time, four recipients developed acute oligo-anuria following ultrasound-guided allograft biopsy. Emergent doppler-ultrasounds were performed demonstrating absence of diastolic flow as well as a sub-capsular hematoma of the kidney. Prompt surgical exploration with allograft capsulotomy was performed in all cases. Immediately after capsulotomy, intraoperative Doppler study demonstrated robust return of diastolic flow. Three patients maintained good graft function, and one kidney was lost due to acute antibody-mediated rejection. We conclude that postbiopsy anuria associated with a subcapsular hematoma and acute absence of diastolic flow on doppler ultrasound should be considered pathognomonic of APK. All renal transplant specialists should be able to recognize this complication, because immediate surgical decompression can salvage the allograft.     

Evaluation of renal transplant dysfunction by duplex Doppler sonography: a prospective study and review of the literature

A disconcertingly wide variation exists in the literature as to the accuracy of duplex Doppler sonography in the detection of acute renal transplant rejection. Sensitivities range from 9% to 76%. In an attempt to explain the disparity of results, we undertook a double-blind prospective study of the accuracy of duplex Doppler ultrasound in the detection of acute rejection in renal transplants. We scanned 49 consecutive patients with a total of 65 biopsies; 46 biopsies in 33 consecutive patients were included in our study. In our population, the prevalence of acute rejection was 61% (28/46). Using a resistive index (RI) cutoff of greater than 0.90 based on the main renal artery flow pattern, the sensitivity of our test was 43%, with a 67% specificity. The positive predictive value was 67%. Our results are contrasted and compared with the published data from other groups in a critical survey of the literature. We conclude that duplex Doppler sonography alone is inadequate to evaluate acute rejection in renal transplants.     

Evaluation of canine renal transplants with pulsed Doppler duplex sonography

Preliminary studies of human renal transplants suggested that pulsed Doppler sonography may complement other studies of renal transplant dysfunction. To further evaluate the Doppler technique, 11 dogs who received renal transplants were examined a total of 50 times. No antirejection chemotherapy was used, and following rejection the kidneys were removed and examined histologically. The canine transplants underwent accelerated acute or hyperacute rejection. A pulsed Doppler index (PDI) was derived to quantitate patterns of renal blood flow and peripheral vascular resistance. Arterial Doppler signals were obtained from renal transplant branch vessels in vivo and the PDI consistently fell as rejection occurred. No arterial signals were obtained from one kidney which was subsequently proven to have arterial thrombosis. Pulsed Doppler analysis provides new information about renal transplant blood flow patterns and may demonstrate evidence of rejection and renal arterial occlusion.     

The evaluation of paediatric renal transplants using resistive index and renal blood flow

Six children (aged 1.3–6.9 years) were examined with serial duplex Doppler sonography and diethylenetriaminepenta-acetic acid (DTPA) isotope renography in the post-renal transplant period. The resistive index (RI) was derived from sonographic studies and the renal blood flow (RBF) calculated from the isotope scans. The clinical status of the child and the corresponding plasma creatinine level were assessed together with these two parameters. The RIs ranged from 40% to 100% and the RBF from 0% to 16.8%. There were six rejection episodes in four patients. A significant fall in RBF mirrored a rise in plasma creatinine on each occasion, but there was no significant change in RI recorded. There were two graft losses, both associated with renal venous thrombosis. In both cases no significant RBF could be detected on DTPA renography. In one patient, the RBF remained low throughout a period of primary non-function associated with acute tubular necrosis, and increased as primary function was established and the plasma creatinine fell. Throughout this period there was no significant change in the RI. From our preliminary data RBF reflects graft dysfunction more accurately than does the RI.     

Plasma fibronectin levels in patients with chronic uremia

Plasma fibronectin (FN) concentration was measured in patients with idiopathic glomerulonephritis (GN) with or without impaired renal function, in uremic patients undergoing periodic hemodialysis and in renal transplant patients before and after an acute rejection crisis. Results show normal FN levels in idiopathic GN and in renal transplant patients with normal renal function, while significantly lower levels were found in GN with severe renal damage, in uremia before and after dialysis, and in renal transplant patients during acute and chronic graft rejection. Significant correlations between high serum creatinine values and low plasma FN levels were found in renal transplant patients. These findings suggest that the kidney may influence FN levels in the blood since acute (rejection crisis) and chronic renal failure (uremia) cause low concentrations of this protein, while levels tend to return to normal values in patients with uremia after renal transplantation. We hypothesize that the normal kidney removes or perhaps degrades some substances or hormones that may control the release or synthesis of FN. These substances are not dialyzed by cellophane membranes since low plasma FN levels persist after periodic hemodialysis. Only the renal graft provokes an increase of FN in the blood stream.     

Evaluation of renal allograft function by Doppler spectrum analysis

A decreased renal function is rather common after renal transplantation. The causes of this decreased function are diverse and difficult to differentiate. Yet, duplex examination, and especially quantitative Doppler spectrum analysis of the blood velocities in the renal artery, may be an effective method for differentiating between some of these causes. Forty-five renal transplant recipients were included in this preliminary study. Doppler spectra were recorded from the renal artery to the allograft. Parameters were derived from every Doppler spectrum in order to characterize each spectrum. Renal allograft function was evaluated on the basis of a number of clinical parameters. A significant correlation was found between the clinical parameters and the Doppler spectrum parameters indicative for changes in the peripheral resistance. Patients with a normal renal allograft function showed Doppler spectra with a high diastolic flow, typical of a vascular bed with a low peripheral resistance. Patients with a decreased renal allograft function caused by a stenosis in the renal artery could be distinguished by a low peak velocity and a low pulsatility index. A decreased allograft function caused by allograft rejection or cyclosporin nephrotoxicity also led to characteristic arterial flow disturbances. In these cases, the peripheral resistance was increased, and this was primarily reflected in a decrease in the diastolic blood velocity. We conclude that quantitative analysis of the blood velocities in the renal artery by Doppler spectrum analysis seems to be a useful, noninvasive diagnostic tool that discriminates between some of the causes of a decreased renal allograft function.     

Graft failure due to hemolytic uremic syndrome recurrence

The hemolytic uremic syndrome (HUS) is a severe disease characterized by microangiopathic hemolytic anemia, thrombocytopenia, and acute renal failure. We herein report our experience with a 43-year-old female patient who underwent a second cadaveric kidney transplantation in February 2005, for adult-onset HUS. The first renal transplantation, which was performed in 1996, required removal after 3 weeks for probable recurrence of HUS. The immunosuppressive regimen for the second transplant included basiliximab, tacrolimus, mycophenolate mofetil, and steroids. On postoperative day (POD) 7, she received steroid treatment for an acute rejection episode with improved renal function. On POD 19 due to worsening renal function, a graft biopsy showed HUS recurrence, thus we instituted hemodialysis and then plasmapheresis treatments. At two months after transplantation, the patient continued under plasmapheresis treatment due to clinical evidence of HUS. On POD 80, cytomegalovirus infection was diagnosed and intravenous gancyclovir treatment started for 3 weeks. After 110 days from transplant, a deterioration in renal function was evident: the graft was swollen and painful with Doppler ultrasound showing patency of both the renal artery and vein but, low blood flow. After 2 weeks of hemodialysis, the patient underwent transplantectomy. In adult-onset HUS the recurrence rate reduces graft survival, particularly among patients undergoing second transplantation.     

Analysis of urinary donor-derived DNA in renal transplant recipients with acute rejection

Abstract: In renal transplantation we usually diagnose an acute rejection by based on the results of a needle biopsy; however, this takes time and findings in some cases are not definite. We analysed the urine of renal recipients for the presence of donor DNA in an attempt to establish a diagnostic means of acute rejection. Sixty-four renal transplant recipients were examined. Thirty-seven patients had no trouble after transplantation and 22 patients developed acute rejection, diagnosed based on serum creatinine levels and/or needle biopsy findings of the graft. Five patients had drug-induced renal dysfunction. In female recipients with a male graft we examined urine for the presence of Y-chromosome (SRY and DYZ-1) and in recipients receiving a HLA mismatched graft we investigated the HLA-DR gene (DRB1) by the polymerase chain reaction (PCR) method. Among female recipients with a male graft there were 14 patients with stable renal function and SRY and DYZ-1 on Y-chromosome were negative in 13 (93%) and positive in one, whereas SRY and DYZ-1 of urine were positive in the four female patients with acute rejection and these DNA fragments disappeared in three after rejection therapy. One patient was subjected to haemodialysis. Among 23 recipients of a graft from HLA mismatched donors with stable renal function, DRB1 was negative in 21(91%). Among 18 patients with acute rejection DRB1 was positive in 16 (93%) and negative in two. These DNA fragments disappeared in 13 patients after rejection therapy. In all patients with drug-induced renal dysfunction donor-derived DNA was negative. Presence of donor-specific DNA in the urine of the recipient is associated strongly with acute rejection and analysis of DNA derived from donor cells in urine might be an effective and accurate method for the diagnosis of acute rejection of a renal transplant.     

Clinical impact of complement deposition findings on biopsies in acute rejection episodes of pediatric renal transplant patients

IntroductionRejection is the most important problem for renal graft function and survival. Complement system plays a key role in immune responses from host to graft. It was demonstrated that complement system activation is related with renal fibrosis. We evaluate clinical impact of complement deposition findings on biopsies in acute rejection episodes of pediatric renal transplant patients.MethodDemographics of the patients, graft functions, acute rejection episodes and graft loss were recorded from data files of 165 pediatric renal transplant patients. Findings of 98 renal biopsies were retrospectively evaluated.ResultsThirty three patients with kidney transplant had 44 acute rejection episodes (32 pure cellular acute rejection episodes / 1 pure humoral acute rejection episode / 11 combined acute cellular and acute humoral rejection episodes) proven by biopsy. C1q staining was positive in 7 biopsies, C3 staining in 15 biopsies and, C4d staining in 15 biopsies. 26 patients had graft fibrosis. All patients with a rejection history had a significant decrease in GFR value during follow-up. Patients who did not have fibrotic changes in first biopsy had same level of deterioration of GFR when compared with patients who had fibrotic changes in first biopsy.ConclusionWe could not demonstrate a significant relation between complement deposition and renal fibrosis, and between complement deposition and GFR values. Our data demonstrated that graft outcomes and graft loss after acute rejection episodes cannot be predicted only with complement deposition on graft or only with graft fibrosis.     

Impaired renal artery blood flow at transplantation is correlated to delayed onset of graft function

The aim of this prospective study was to evaluate a transit time flowmeter (Transonic, USA) in renal transplantation with respect to feasibility and estimation of graft circulation. Subsequently, the measurements were evaluated for their ability to predict delayed onset of function, occurrence of acute rejection or graft loss within 3 months after transplantation. Renal artery blood flow was measured and resistance calculated in 100 transplants-62 cadaveric donor (CD) and 38 living donor (LD)-immediately after restoration of graft circulation and before wound closure. Low blood flow(<250 ml/min) and high resistance (>392 mPRU) correlated positively with a long cold ischemia time and delayed onset of graft function, including the need for post-transplant dialysis. No correlation with rejection or graft loss was found. Blood flow measurements with the transit time flowmeter were easy to perform and immediate estimation of transplant circulation was achieved. Transplants at risk for delayed onset of function were identified.     

The value of pulsed Doppler for the follow-up of the transplanted kidney in the first 3 months of transplantation

This prospective study was conducted in 34 consecutive renal transplant patients. Pulsed doppler was used to evaluate the peripheral resistance (PR) in the transplant vessels. Under normal conditions, the PR of the graft is low, resulting in a continuous diastolic blood flow. The intensity of this blood flow was evaluated by means of a resistance index (RI), Pourcelot's index, calculated as follows: RI = systolic peak - end-diastolic peak/systolic peak This study demonstrated values for RI of 0.71 +/- 0.087 in 14 totally asymptomatic patients. In 10 cases of acute rejection, the RI increased to 0.91 +/- 0.12. The 7 patients with acute tubular necrosis had an RI equal to 1. In patients with cytomegalovirus infection of suffering from cyclosporin overdose, the RI was not modified in relation to asymptomatic subjects. This study demonstrates the existence of a rise in the PR in cases of acute rejection and acute tubular necrosis with a sensitivity of 90% and 100% respectively for these two diagnoses. However, this method cannot be used to distinguish between acute rejection and acute tubular necrosis.     

Enzyme Linked Immunosorbent Spot (ELISPOT) Assay for Interferon-Gamma Independently Predicts Renal Function in Kidney Transplant Recipients

Post-transplant monitoring of cellular immunity might be useful in predicting long-term outcomes of kidney transplant recipients. We used an enzyme linked immunoabsorbent spot (ELISPOT) assay to serially measure the frequency of peripheral blood lymphocytes producing interferon-gamma in response to stimulator cells from donors or third parties in 55 primary kidney transplant recipients. Mean frequencies measured during the first 6 months after transplantation correlated significantly with the serum creatinine concentration at both 6 and 12 months following transplantation. The mean frequencies were higher in patients with acute rejection than in those without acute rejection. Multiple regression analyses indicated that the correlations between the early ELISPOT measurements of interferon-gamma and serum creatinine were independent of acute rejection, delayed graft function, or the presence of panel reactive antibodies before transplantation. Patients with low mean frequencies of interferon-producing cells in the early post-transplant period were generally free from acute rejection and exhibited excellent renal function at 6 and 12 months post-transplant. In conclusion, using the ELISPOT assay, we show an independent correlation between early cellular alloreactivity and long-term renal function. Increased levels of early alloreactivity measured with this assay may serve as a surrogate for chronic allograft dysfunction.     

Contribution of color and power Doppler sonography to the differential diagnosis of acute and chronic rejection, and tacrolimus nephrotoxicity in renal allografts

The aim of the present study was to differentiate acute rejection, chronic rejection, and tacrolimus nephrotoxicity with color and power Doppler imaging of renal transplants. One hundred examinations were obtained from 45 patients. Pulsatility and resistive indices were calculated from color Doppler images. The grade of renal vascularization was quantified using computer-assisted pixel analysis in a rectangular region-of-interest. The percentage of vessel-covered renal parenchyma (POV) was calculated using a histogram that discriminated renal vessels from renal parenchyma via power Doppler images. Furthermore, the distance from the most peripherally located vessels to the renal capsule (PVD) was measured. A reduced POV K 55 % proved to be the best discriminator when chronic rejection was suspected (sensitivity 79 %, specificity 87 %). Tacrolimus nephrotoxicity showed not only a moderate elevation of the Doppler signal but also an increased PVD L 3.9 mm and a normal POV. We conclude that the evaluation of renal vessels by power Doppler images improves diagnostic accuracy for patients with renal allografts. Received: 22 June 1998 Received after revision: 29 September 1998 Accepted: 12 October 1998     

Careful clinical monitoring in comparison to sequential Doppler sonography for the detection of acute rejection in the early phase after renal transplantation

Abstract Acute rejection is the most frequent cause of early graft failure. There is unanimity that Doppler sonography is a helpful method for the detection of complications after kidney transplantation. In the past, the indication for renal biopsy relied mainly on clinical assessment, although this assessment has not been standardised. Therefore, we conducted this prospective study to compare the value of sequential Doppler measurements with a standardised clinical rejection score, based on renal function, weight gain, graft swelling and tenderness. Fifty‐eight patients (37 males, 21 females, mean age 46 ± 12 years) after kidney transplantation were consecutively enrolled into the study. Doppler investigations were obtained within the first 24 h after transplantation, followed by an interval of 48‐72 h. At the same time, a clinical examination was scored by a transplant physician blinded to the Doppler results. Clinical score and Doppler results, both were referred to the histological results of renal biopsy. In 24 out of 58 patients 25 acute rejections occurred. In seven patients, acute rejection was superimposed on primary graft failure. The cut‐off levels for rejection were set at RI ≥ 0.80 and PI ≥ 1.70 based on receiver‐operator curves using data from 663 Doppler examinations. Sensitivity and specificity was 72 % for RI, and 72 % and 74 % for PI, respectively. The calculation of the intraindividual increase (ΔRI ≥ 3 %, ΔPI ≥ 10 %) did not improve these values. The clinical score revealed a sensitivity and specificity of 82% and 87 %, respectively. The combined analysis of Doppler indices and clinical score showed a sensitivity of 96 % with a specificity of 66%. Careful clinical monitoring alone using a clinical score is an appropriate procedure with which to decide about renal biopsy. Our data show that Doppler sonography should be performed within the first 24 h after transplantation to evaluate graft perfusion and baseline values. Afterwards, it should be used when clinical signs of rejection occur to underline the decision for renal biopsy even in borderline cases.     

Similar impact of slow and delayed graft function on renal allograft outcome and function

Kidney transplant patients can be divided into three groups, according to the initial graft function. First-week dialyzed patients form the delayed graft function (DGF) group. Nondialyzed patients are divided into slow graft function (SGF) or immediate graft function (IGF) according to whether the day 5 serum creatinine was higher versus lower than 3 mg/dL, respectively. SGF patients showed worse graft survival, above higher incidence of acute rejection and lower renal function than IGF patients, although few reports have analyzed outcomes in these groups. We analyzed the impact of SGF on graft survival, first-year renal function, and incidence of acute rejection in 291 renal transplant patients. Creatinine was significantly worse at 12 months for SGF and DGF than for IGF patients (1.9 +/- 0.8 mg/dL, 1.8 +/- 0.7 mg/dL, 1.5 +/- 0.5 mg/dL, respectively; P < .05). There was no difference in first-year renal function between SGF and DGF. The acute rejection rate was higher among the SGF than the IGF group (45% vs 21%, P < .05), but not different from DGF patients (42%, P < .05). Graft survival was better among IGF than SGF or DGF patients, with no significant difference between the last two groups (3-year graft survival, 82%, 71%, 70%, respectively; log-rank test, P < .05). Kidney transplant recipients who develop SGF have a worse outcome than patients with IGF, similar to DGF patients. SGF patients show worse graft survival, worse renal function, and higher acute rejection rates than IGF patients, despite not needing dialysis.     

Transplant Renal Artery Stenosis: A Case Report of Functional Recovery Six Months After Angioplasty

Transplant renal artery stenosis (TRAS) is a common vascular complication after kidney transplantation, leading to worsening or refractory hypertension, deterioration in renal function, and possible cause of graft loss. Early diagnosis and an appropriate treatment are crucial for organ preservation. Endovascular treatment, including percutaneous transluminal angioplasty and stent implantation, is considered the first-line therapy for TRAS. Here we report the case of a 69-year-old woman with end-stage renal disease for chronic kidney disease not biopsy proven, who underwent a kidney transplant from expanded criteria donors on December 2018. Postoperative course was characterized by delayed graft function. Doppler ultrasonography (US) showed an increase of peak systolic velocity at the origin of the renal artery, and parvus-tardus waveform in periferic graft arteries and an abdominal computed tomography scan confirmed a stenosis at the origin of the main renal artery (TRAS). The patient underwent a percutaneous transluminal angioplasty. It was not possible to place a stent at the particular location of the stenosis at the anastomosis. Despite the improvement of the graft's perfusion, monitored with Doppler US, the patient showed a very poor improvement in renal function and remained on hemodialysis for months. A percutaneous needle biopsy reported a normal renal parenchyma and excluded acute rejection. During this period, the patient received immunosuppressive therapy. About 6 months after the transplant, the patient had an unexpected and slow renal function recovery until she was weaned completely from hemodialysis.     

CD69 expression on peripheral CD8 T cells correlates with acute rejection in renal transplant recipients

BACKGROUND: The development of a noninvasive method to diagnose renal allograft rejection could prevent the complications associated with graft biopsy and allow more accurate surveillance of allograft function. The present study determines whether expression of CD69 on peripheral T lymphocytes of renal allograft recipients correlates with the presence of acute graft rejection. METHODS: Peripheral blood T lymphocytes from healthy volunteers, renal allograft recipients with elevated creatinine but no evidence of rejection on biopsy, and renal allograft recipients with biopsy-proven rejection were analyzed by flow cytometry for the expression of CD69 and various intracellular cytokines (interleukin-2, interferon-gamma). Results were then compared with the degree of rejection on biopsy. RESULTS: CD69 expression on CD3+, CD4+, and CD8+ T-cell subsets was low in controls and transplant recipients without allograft rejection. In contrast, patients with renal allograft rejection showed significantly elevated percentages of CD69+ cells in the CD3+ (P<0.01) and CD8+ subsets (P<0.01). The fraction of CD69+ and CD8+ T cells was found to be a more clinically useful test based on receiver-operator characteristics. CD69 expression on CD4+ T cells did not correlate with rejection. Significant intracellular cytokine levels were not detected in unstimulated T cells from any of the groups; stimulation with mitogens increased expression equally among the three groups. CONCLUSIONS: We demonstrate that expression of CD69 on CD3+ and CD8+ peripheral blood T cells correlates closely with the presence of acute graft rejection in renal allograft recipients. Measurement of this surface marker may provide a rapid, noninvasive, and accurate means by which graft rejection can be identified.     

Arteriovenous fistula after biopsy of renal transplant kidney: diagnosis and treatment

An 11-year-old renal transplant recipient was noted to have a bruit over her transplant graft 26 months post transplant and 17 months following percutaneous renal biopsy during an episode of rejection. Diagnosis of an arteriovenous (AV) fistula was made by ultrasound examination with Doppler flow and was confirmed with arteriography. The AV fistula was occluded by transcatheter embolotherapy with placement of a steel coil into the fistula from the renal vein approach. This procedure allowed nonsurgical closure of the AV shunt without significant change in renal function.