Renal allograft rupture caused by acute tubular necrosis

Renal allograft rupture is a rare but potentially lethal complication of kidney transplantation. A renal allograft recipient receiving quadruple immunosuppressive therapy developed a spontaneous allograft rupture 13 days after kidney transplantation. Warm ischaemia time during the transplant was 80 minutes. The ruptured kidney graft could not be salvaged because of the patient's haemodynamic instability. The histopathological examination showed interstitial oedema with severe acute tubular necrosis with no signs of acute rejection. The most common causes of renal graft rupture are acute rejection and vein thrombosis, while acute tubular necrosis may only rarely be responsible for this complication. Renal graft rupture may be the result of interstitial damage attributed both to the prolonged warm ischaemia time during the transplant and to post-transplant acute tubular necrosis in the absence of graft rejection. In those patients whose haemodynamic status cannot be stabilized by appropriate aggressive haemodynamic support therapy, graft nephrectomy should be considered the only definitive treatment.     

Successful Management of Eviscerated Renal Allograft with Preservation of Function

Although most wound complications after renal transplantation are minor, the renal allograft, in its superficial and extraperitoneal location, is vulnerable to exposure if there is wound breakdown resulting in loss of overlying tissue. We describe a 66-year-old man who received a renal allograft from a deceased donor for end-stage renal disease (ESRD) secondary to polycystic kidney disease. His immediate posttransplant course was complicated by delayed graft function from acute tubular necrosis, reexploration for perigraft hematoma and subsequent wound dehiscence. After unsuccessful conservative wound care, the renal allograft became completely eviscerated due to fascial retraction of the dehisced wound. While the allograft was initially covered with a pedicled rectus femoris muscle flap, several local tissue rearrangements were required for definitive coverage. The allograft function was recovered after initial flap coverage and was subsequently maintained; follow-up more than 2 years after transplantation has demonstrated not only continued stable graft function but also complete healing of the dehiscent wound.     

The Impact of Living Donor Nephrectomy With Multiple Renal Arteries on Graft Function and Complications in Renal Transplantation

BackgroundThe aim of this study was to investigate the early outcome of living donor kidney transplantation using allografts with a single artery and multiple arteries.MethodsFrom February 2018 to December 2019, a total of 62 patients underwent living donor nephrectomy at our institution: 20 multiple artery donor nephrectomies (MADNs) and 42 single artery donor nephrectomies (SADNs). All operations were performed by the same surgeon as the laparoscopic procedure. The MADN and SADN groups were compared regarding donor and recipient hospital stay, operative time, warm ischemia time, and postoperative complications with Clavien-Dindo classification. Graft function was evaluated considering episodes of acute tubular necrosis during the first week, delayed graft function, serum creatinine (SCr), and glomerular filtration rate for 6 months after transplantation.ResultsSixty-two patients were included in this study. There was no difference in terms of age, sex, body mass index, nephrectomy side, smoking status, preoperative SCr, or preoperative glomerular filtration rate between the 2 groups. Warm ischemia time and operation time were statistically significantly higher in the MADN group (P < .001 and P < .001). Regarding graft function, the prevalence of acute tubular necrosis did not differ between groups. There was also no significant difference in the acute rejection or mortality rates after transplantation. Although SCr levels were lower in multiple renal artery recipients, there was no statistical difference during the 6 months of follow-up. Recipient morbidity and mortality were not different between the 2 groups.ConclusionsRenal allograft transplantation with multiple renal arteries can be performed with reasonable complications and acceptable results.     

Spontaneous kidney allograft rupture

Spontaneous renal allograft rupture is one of the most dangerous complications of kidney transplantation, which can result in graft loss. This condition needs immediate surgical intervention. Conservative management has dismal results. Its prevalence varies from 0.3% to 3%. Rupture occurs in first few weeks after transplantation. Predisposing factors for graft rupture are acute rejection, acute tubular necrosis, and renal vein thrombosis. There are growing reports about successful results of repairing these ruptured kidneys. In this study, we reviewed the medical records of 1682 patients who received kidney allografts from living donors from 1986 through 2003. There were six (0.35%) cases of renal allograft rupture. All were preceded by acute graft rejection. They were treated with antirejection medications. In first three cases, the kidney allografts were removed because the procedure of choice in this situation is graft nephrectomy; but in three next cases we repaired the ruptured grafts with good results in two of them. In conclusion, the procedure of choice for kidney allograft rupture is graft repair.     

Renal Contrast‐Enhanced Sonography Findings in a Model of Acute Cellular Allograft Rejection

Noninvasive methods to diagnose and differentiate acute cellular rejection from acute tubular necrosis or acute calcineurin inhibitor toxicity are still missing. Because T lymphocytes play a decisive role in early states of rejection, we investigated the suitability and feasibility of antibody‐mediated contrast‐enhanced ultrasound by using microbubbles targeted to CD3⁺, CD4⁺, or CD8⁺ T cells in different models of renal disease. In an established rat renal transplantation model, CD3‐mediated ultrasound allows the detection of acute rejection as early as on postoperative day 2. Ultrasound signal intensities increased with the severity of inflammation. Further, an early response to therapy could be monitored by using contrast‐enhanced sonography. Notably, acute tubular necrosis occurring after ischemia–reperfusion injury as well as acute calcineurin inhibitor toxicity could easily be differentiated. Finally, the quantified ultrasound signal correlated significantly with the number of infiltrating T cells obtained by histology and with CD3 mRNA levels, as well as with chemokine CXCL9, CXCL11, and CCL19 mRNA but not with KIM‐1 mRNA expression, thereby representing the severity of graft inflammation but not the degree of kidney injury. In summary, we demonstrate that antibody‐mediated contrast‐enhanced ultrasound targeting T lymphocytes could be a promising tool for an easy and reproducible assessment of acute rejection after renal transplantation.     

Recurrent 2,8‐Dihydroxyadenine Nephropathy: A Rare but Preventable Cause of Renal Allograft Failure

Adenine phosphoribosyltransferase (APRT) deficiency is a rare autosomal recessive enzyme defect of purine metabolism that usually manifests as 2,8‐dihydroxyadenine (2,8‐DHA) nephrolithiasis and more rarely chronic kidney disease. The disease is most often misdiagnosed and can recur in the renal allograft. We analyzed nine patients with recurrent 2,8‐DHA crystalline nephropathy, in all of whom the diagnosis had been missed prior to renal transplantation. The diagnosis was established at a median of 5 (range 1.5–312) weeks following the transplant procedure. Patients had delayed graft function (n = 2), acute‐on‐chronic (n = 5) or acute (n = 1) allograft dysfunction, whereas one patient had normal graft function at the time of diagnosis. Analysis of allograft biopsies showed birefringent 2,8‐DHA crystals in renal tubular lumens, within tubular epithelial cells and interstitium. Fourier transformed infrared microscopy confirmed the diagnosis in all cases, which was further supported by 2,8‐DHA crystalluria, undetectable erythrocyte APRT enzyme activity, and genetic testing. With allopurinol therapy, the allograft function improved (n = 7), remained stable (n = 1) or worsened (n = 1). At last follow‐up, two patients had experienced allograft loss and five had persistent chronic allograft dysfunction. 2,8‐DHA nephropathy is a rare but underdiagnosed and preventable disorder that can recur in the renal allograft and may lead to allograft loss.     

Delayed Graft Function in Renal Transplantation: Etiology, Management and Long-term Significance

Purpose

In cadaveric renal transplantation a period of delayed graft function postoperatively is not uncommon and often associated with a poor outcome. We reviewed the biology of reperfusion injury and delayed graft function in renal transplantation, as well as its prevention, management and long-term effects.

Materials and Methods

The medical literature covering acute tubular necrosis, delayed graft function in renal transplantation and immunology of ischemia reperfusion injury was reviewed.

Results

Delayed graft function is clearly associated with poor allograft survival, and is caused by an interaction of ischemic and immunological factors. Technical and pharmacological maneuvers can improve early function rates. The response to ischemic injury is complex, and may increase graft immunogenicity and promote the chronic proliferative changes seen in chronic allograft nephropathy.

Conclusions

Improvement in early renal function should be a primary goal in renal transplantation to enhance early and long-term results. Basic research into the injury response may yield insights into renal pathophysiology.     

The prognostic value of frozen section preimplantation graft biopsy in the outcome of renal transplantation

Introduction: Preimplantation biopsy provides a window on the state of the renal allograft. In this study, the prognostic value of frozen section preimplantation graft biopsy was estimated and compared to regularly processed formalin-fixed biopsy. Materials and Methods: Seventy-four renal allograft recipients were studied. The degree of glomerulosclerosis, acute tubular necrosis, interstitial fibrosis, arteriosclerosis, and arteriolosclerosis was rapidly estimated in frozen sections and correlated to the renal function in the immediate posttransplantation period and 3 months thereafter. The histological changes were also examined in paraffin-embedded sections. Results: The histological changes observed in rapidly processed frozen sections were comparable to those observed on regularly processed sections and their differences did not reach statistical significance. Glomerulosclerosis and arteriolosclerosis were underestimated, whereas acute tubular necrosis and interstitial fibrosis were overestimated, in the frozen sections compared to permanent ones, but those differences were not statistically significant. Immediate graft function was observed in 45 patients (61%). Delayed graft function was more frequently observed among recipients with donor age above 60 years (57% vs. 32%). Serum creatinine 3 months after transplantation was above 2 mg/dL in 33 recipients (44.5%) and was positively correlated to the degree of tubular necrosis (p = 0.04) and donor age (p = 0.03). Donor age was correlated to the degree of arteriolosclerosis (p < 0.01). Conclusions: Frozen section preimplantation biopsy gives reliable information for the situation of the graft that is related to the outcome of renal transplantation.     

Cholesterol crystal embolic disease in renal allografts

Cholesterol embolic disease in the renal allograft is not recognized as an important cause of graft dysfunction. We describe here two renal transplant patients with cholesterol embolization in their allograft biopsies. The first, a 48-year-old patient, received a renal transplant from a 62-year-old donor with a history of hypertension and tobacco use. On account of initial non-function, a renal biopsy was taken, which showed acute tubular necrosis and cholesterol emboli. The second, a 55-year-old man, presented chronic allograft failure six years after transplantation; ultrasonography showed a solid renal mass. Nephrectomy specimens revealed renal carcinoma and a combination of chronic rejection and multiple cholesterol emboli. Cholesterol embolic disease is probably an under-reported cause of renal graft dysfunction. The source of the emboli may be either the donor or the recipient's vessels. Since the current tendency is to accept older donors and recipients with more advanced atherosclerotic disease, this condition is likely to become more frequent in the future. Particular care must be taken at the time of organ procurement and during the evaluation of organ donors, in order to reduce the risk of embolization.     

The role of C-reactive protein in graft dysfunction after renal transplantation

PURPOSE: We investigated whether serial daily measurements of serum C-reactive protein could help differentiate episodes of transplant dysfunction due to rejection, infection, cyclosporin A nephrotoxicity or acute tubular necrosis in renal allograft recipients. MATERIALS AND METHODS: Morning serum was obtained daily from 134 patients during the first 30 days after renal transplantation. All episodes of graft dysfunction were recorded and compared to transplant biopsies. C-reactive protein concentrations were correlated with postoperative graft function and the various causes of graft dysfunction. RESULTS: All patients demonstrated an increase in C-reactive protein in response to surgery and a maximum level was reached on day 2 after transplantation. Mean C-reactive protein concentration was significantly increased for delayed (61.50 microg./ml.) compared to primary (mean 38.01) graft function (p = 0.001, Mann-Whitney U test). There were significant increases in C-reactive protein for bacterial infections other than asymptomatic bacteriuria (33.98 microg./ml), interstitial graft rejection (16.43) and acute tubular necrosis (30.50) compared to uneventful courses. C-reactive protein was unchanged for viral infections or cyclosporin A toxicity. CONCLUSIONS: Serial C-reactive protein measurements help to identify renal transplant dysfunction of different origins. However, rejection, infection and acute tubular necrosis show similar patterns of C-reactive protein increase. Thus, C-reactive protein is unable to discriminate the causes of renal graft dysfunction. Biopsy remains the gold standard for the differential diagnosis of renal allograft dysfunction.     

Early Presence of Calcium Oxalate Deposition in Kidney Graft Biopsies is Associated with Poor Long-Term Graft Survival

Accumulated oxalate will be excreted after renal transplantation, creating an increased risk of tubular precipitation, especially in the presence of allograft dysfunction. We evaluated calcium oxalate (CaOx) deposition in renal allograft biopsies with early dysfunction, its association with acute tubular necrosis (ATN) and graft survival. We studied 97 renal transplant patients, submitted to a graft biopsy within 3 months post-transplant, and reanalyzed them after 10 years. We analyzed renal tissue under polarized light and quantified CaOx deposits. CaOx deposits were detected in 52.6% of the patients; 26.8% were of mild and 25.8% of moderate intensity. The deposits were more frequent in biopsies performed within 3 weeks post-transplant (82.4 vs. 63.0%, p < 0.05) and in allografts with more severe renal dysfunction (creatinine 5.6 mg/dL vs. 3.4 mg/dL, p < 0.001). ATN incidence was also higher in patients with CaOx deposits (47% vs. 24%, p < 0.001). Twelve-year graft survival was strikingly worse in patients with CaOx deposits compared to those free of deposits (49.7 vs. 74.1%, p = 0.013). Our study shows a high incidence of CaOx deposits in kidney allografts with early dysfunction, implying an additional risk for acute tubular injury, with a negative impact on graft survival.     

Histopathologic evaluation of pretransplant biopsy as a factor influencing graft function after kidney transplantation: a 1-year observation

INTRODUCTION: Many factors affect long-term results in kidney transplantation including histologic damage as a independent predictor, such as chronic allograft/nephropathy in protocol biopsies and age-dependent lesions. Histopathologic findings correlate with the incidence of delayed graft function, renal function, and allograft survival, allowing a rather precise prediction of graft outcome. MATERIALS AND METHODS: We analyzed 92 renal thick needle preimplantation and 29 postexplantation biopsies. Biopsies were preserved in 4% formalin and immersed in paraffin. Optimal biopsies contained at least 10 glomeruli and at least 2 cross-sections of arteries. We analyzed tubulitis, intensity of acute tubular necrosis, inflammatory infiltration, glomerulonephritis, arterial hyalinization, arteritis, fibrosis, tubular atrophy, arterial intimal fibrosis, increase of mesangial matrix, and percentage of glomerulosclerosis. During the postoperative course we analyzed patients condition, exigency of postoperative dialysis, urine output, as well as serum concentrations of creatinine, urea, uric acid, and ions. During a 1-year observation period, we analyzed living recipients, graft loss, death with a functioning graft, incidence of nephropathy (CAN), and acute rejection episodes (ARE). RESULTS: We observed a significant correlation between immediate graft function (IGF) and lack of ATN in the pre-0 biopsy. We observed no correlation between renal function and arterial hyalinization and fibrosis, inflammatory infiltration, tubular atrophy. In the postoperative period, we observed a significant correlation between IGF and lack of interstitial fibrosis with significantly lower levels of creatinine, urea, and potassium and higher urine output early after transplantation. IGF and better function of the right kidney was correlated with shorter time to reach a creatinine level of 2 mg%. In the postoperative periods, we also observed a difference between renal function depending on gender. The presence of acute tubular necrosis, arterial fibrosis, lack of inflammatory infiltration in the pre-0 biopsy correlated with worse late renal function. Among explantation biopsies 65.5% showed signs of CAN, and 37.93%, histologic marks of ARE.     

Clinical management of the living donor kidney transplant recipient

To analyze the clinical management of the renal transplant recipient from a kidney living donor. The renal transplantation (RT) from a living donor without surgical complications has a very low frequency of acute tubular necrosis (ATN) that facilitates enormously the clinical control. The scheme of follow-up after-RT must include: (1) Hemodynamic monitoring; (2) Clinical management; (3) Renal allograft monitoring: renal function, diuresis, radionuclide imaging and ultrasound-Doppler; (4) Pharmacological treatment: analgesia, gastric protection, antibiotic prevention; (5) Monitoring of the immunosuppressive therapy; (6) Digestive monitoring; (7) Control of the cardiovascular risk; (8) Preventions infectious; (9) Osteodistrophia control. In living donor RT a rapid normalization of the renal function and a time of hospitalization reduced are observed. The presence of a long ATN or a renal dysfunction of the graft must force to realize an early renal allograft biopsy.     

Delayed presentation of arteriovenous fistula and pseudoaneurysms in a renal transplant patient 10 years after percutaneous allograft biopsy

A 51-year-old man was admitted with microscopic hematuria at 10 years after living donor renal transplantation. In order to distinguish between acute tubular necrosis and acute rejection, a graft biopsy was performed under ultrasound guidance at 1 month posttransplantation. Doppler sonography revealed 3 pulsatile cystic masses and an arteriovenous fistula (AVF) in the lower kidney pole. Selective transplant renal angiography revealed 3 pseudoaneurysms with an AVF supplied by a lobular artery in the lower pole. The diagnosis was AVF with pseudoaneurysm, which developed secondary to percutaneous renal allograft biopsy. Interventional treatment was performed because of the high risk for pseudoaneurysm rupture. The AVF and pseudoaneurysms were treated successfully by percutaneous transluminal embolization; renal function remained stable after embolization.     

Diagnostic significance of semiquantitative and quantitative parameters of Tc99m-Ethylenedicystine renal allograft scintigraphy

OBJECTIVES: No objective parameters for renal allograft evaluation have yet been described for Tc99m-Ethylenedicystine. This study evaluates the diagnostic significance of different quantitative and semi-quantitative parameters of renal allograft scintigraphy using Tc99m-Ethylenedicystine. METHODS: A total of 72 renal dynamic scintigraphic studies were performed within 2-weeks of renal transplantation in 42 patients. The graft perfusion, kidney/aorta ratio, washout index and retention index were derived from all studies. All these parameters were evaluated for their ability to distinguish between a normal graft, a graft with acute rejection (AR), and a graft with acute tubular necrosis (ATN). Histopathological verification of diagnosis was obtained in all cases. RESULTS: Studies were subdivided into 3 groups according to histopathological findings: acute rejection (n = 42), normal (n = 18) and acute tubular necrosis (n = 12). Normal allografts were visualized with in 2.66 +/- 0.59 seconds of visualization of abdominal aorta. The K/A ratio, wash out index and retention index was 15.22 +/- 6.86, 1.67 +/- 0.45, and 5.48 +/- 0.98 respectively. Allografts with ATN were visualized with in 3.36 +/- 0.80 seconds of visualization of abdominal aorta. The K/A ratio, wash out index and retention index was 12.73 +/- 6.74, 0.60 +/- 0.14, and 9.18 +/- 1.48 respectively. In AR, allografts were visualized 15.18 +/- 9.48 seconds after visualization of abdominal aorta. The K/A ratio, wash out index and retention index was 7.07 +/- 2.15, 0.63 +/- 0.11, and 2.26 +/- 1.28 respectively. CONCLUSIONS: Retention index can separate all the three condition of normal, acute rejection and acute tubular necrosis from each other. Retention index of < 4 suggests acute rejection, a value between 4 and 7 suggests normal allograft and a value of > or = 7 is suggestive of acute tubular necrosis. However, perfusion, K/A ratio and washout index can not segregate all the three groups.     

The Basics of Renal Allograft Pathology

Renal allograft biopsy provides critical information in the management of renal transplant patients, and must be analyzed in close collaboration with the clinical team. The histologic correlates of acute T-cell mediated rejection are interstitial inflammation, tubulitis, and endothelialitis; polyomavirus nephropathy is a potential mimic. Evidence of antibody-mediated rejection includes C4d deposition; morphologic acute tissue injury; and donor specific antibodies. Acute tubular injury/necrosis is a reversible cause of impaired graft function, especially in the immediate post-transplant period. Drug toxicity, recurrent disease, chronic injury, and other entities affecting both native and transplant kidneys must also be evaluated.     

Renal Allograft Fibrosis: Biology and Therapeutic Targets

Renal tubulointerstitial fibrosis is the final common pathway of progressive renal diseases. In allografts, it is assessed with tubular atrophy as interstitial fibrosis/tubular atrophy (IF/TA). IF/TA occurs in about 40% of kidney allografts at 3–6 months after transplantation, increasing to 65% at 2 years. The origin of renal fibrosis in the allograft is complex and includes donor‐related factors, in particular in case of expanded criteria donors, ischemia‐reperfusion injury, immune‐mediated damage, recurrence of underlying diseases, hypertensive damage, nephrotoxicity of immunosuppressants, recurrent graft infections, postrenal obstruction, etc. Based largely on studies in the non‐transplant setting, there is a large body of literature on the role of different cell types, be it intrinsic to the kidney or bone marrow derived, in mediating renal fibrosis, and the number of mediator systems contributing to fibrotic changes is growing steadily. Here we review the most important cellular processes and mediators involved in the progress of renal fibrosis, with a focus on the allograft situation, and discuss some of the challenges in translating experimental insights into clinical trials, in particular fibrosis biomarkers or imaging modalities.     

Renal functional recovery 47 days after renal artery occlusion

A patient with a single kidney and oliguric renal failure for 47 days experienced dramatic restoration of glomerular filtration and renal function following graft bypass of an occluded renal artery. There was very little evidence of acute tubular necrosis. The case emphasizes the importance of the renal collateral circulation in the maintenance of tissue viability, even when the hydrostatic pressure of collateral flow is inadequate for glomerular ultrafiltrate formation. The differentiation of oliguric renal failure due to renal arterial occlusion from that due to acute tubular necrosis following arterial injection of radiocontrast material is imperative because of the dramatic response to reconstructive vascular surgery.     

Legionella infection with acute renal failure and thrombocytopenia mimicking allograft rejection

A patient is described who developed cavitary Legionella pneumonia 2 weeks after kidney transplantation. The initial pulmonary symptoms were followed by severe thrombocytopenia and acute renal failure. Although acute irreversible graft rejection was suspected, this was not supported by the pathology findings in the resected kidney, which were compatible with tubular damage. We presume that the extrapulmonary symptoms were caused by Legionellosis.     

Renal vein reconstruction with interposition allografts in cadaveric renal transplantation

The short or injured renal vein in cadaveric transplantation is a surgical challenge. Over a 2-year period, we have performed ex vivo renal vein lengthening with an interposition vascular allograft in 17 recipients of cadaveric kidneys. Indications for renal vein extension allografts were a short right renal vein (N=12), procurement injury to the vein (N=4), and double renal vein (N=1). In six cases (35.3%), ex vivo renal artery reconstruction was performed in combination with the venous repair. Our preferred approach is to employ allograft material in ex vivo reconstruction under cold storage conditions. Bench surgery ranged from 10 to 30 min, and the mean in situ anastomosis time was 20 min. The mean length of renal vein prior to reconstruction was 12 mm, and the mean length of venous interposition allograft after revascularization was 27 mm. There were no episodes of vascular thrombosis or primary nonfunction. Three patients (17.6%) required postoperative hemodialysis for acute tubular necrosis, which was subsequently resolved. The mean serum creatinine at 1 month post-transplant was 1.7 mg/dl. These preliminary results suggest that ex vivo renal vein reconstruction with an interposition allograft is a safe and effective modality which should be added to the transplant surgeon's armamentarium in select cases.