Ex Vivo Repair and Renal Autotransplantation for Complex Renal Artery Aneurysms in a Solitary Kidney

Renal artery aneurysm (RAA) is a rare clinical entity with an incidence of 0.015-1%. Indications for interventional or surgical repair of RAAs are expanding aneurysms, diameter >2.5 cm, intractable renovascular hypertension, dissecting RAA, hematuria, and renal infarction after distal embolization. Interventional insertion of a stent graft as well as aortorenal bypass implantation are both low-risk procedures in simple aneurysms of the proximal renal artery. However, complex distal renal aneurysms involving several renal artery branches require not only an excellent result of vascular reconstruction, but also a surgical technique offering maximal protection for the kidney during the ischemic period. Here, we present a case of a solitary kidney with two consecutive RAAs of segmental renal artery branches (type 2 RAA). A surgical strategy including renal explantation, ex vivo renal preservation, ex vivo reconstruction of the renal artery, and renal heterotopic autotransplantation was successfully applied. The technique of ex vivo repair is a safe and effective surgical procedure in this clinical setting.     

The effects of exogenous epidermal growth factor on the developing urinary tract in rats: a stereological description

Systemic treatment with epidermal growth factor (EGF) induces growth of all wall layers of the urinary tract in pigs and rats. In this study, we describe the time-dependent growth of the ureter and bladder. Forty-eight female Wistar rats were allocated into five groups receiving EGF treatment (150 μg/kg per day) for 0 (controls), 1, 2, 3 or 4 weeks before being killed. The 24-h urine excretion was increased only in the group treated for 4 weeks with EGF. Measured by a simple infusion device, EGF significantly increased the bladder capacity by more than 50% in all the EGF-treated groups. The volumes of the wall layers of the ureter and bladder were quantified using stereology. After 4 weeks of treatment with EGF, the total volumes of the ureter and bladder were 1.8- and 2.1-fold larger than in the control group (the urothelium was 2.8- and 3.5-fold larger and the muscular coat 1.6- and 1.6-fold larger in the ureter and bladder, respectively). In conclusion, the EGF-induced growth of the urinary tract is characterized by increased bladder capacity, and increased volume of all wall layers – most prominently the urothelium. Received: 5 February 1997 / Accepted: 29 October 1997     

Rat cytomegalovirus and Listeria monocytogenes infection enhance chronic rejection after allogenic rat lung transplantation

The role of infection in the pathomechanism of obliterative bronchiolitis (OB) after human lung transplantation is controversial. In a rat lung transplantation model, we analyzed the effect of viral [rat cytomegalovirus (RCMV)] and bacterial infection [Listeria monocytogenes (LM)] on the development of chronic allograft rejection. Fisher rats underwent single left lung transplantation with allografts from Lewis rats. Postoperatively, animals were infected with either RCMV or LM, or served as noninfected controls. Animals were killed on day 120 and both lungs were evaluated histopathologically for chronic airway and chronic vascular rejection. Infection with RCMV produced a significant increase in the incidence of chronic airway rejection (66.7% vs. 20%), compared with noninfected long-term surviving animals. In rats with bacterial infection (LM) a similar increase of chronic airway changes as in viral infection (50% vs. 20%) was observed. Chronic rejection of allografts infected with either RCMV or LM was associated with significantly enhanced expression of intercellular adhesion molecule-1 (ICAM-1) on the endothelium. More infiltrating leukocytes (CD18, CD11a, CD44) and ED1-positive macrophages were found in allografts of infected animals. In this experimental model of chronic airway rejection in long-term surviving rats, not only viral but also bacterial infection resulted in enhanced development of chronic airway and vascular rejection. These results support our hypothesis that infectious complications have a substantial influence on the development of OB in human lung allografts.     

Complete remission of post-transplant FSGS recurrence by long-term plasmapheresis

Focal segmental glomerulosclerosis (FSGS) is known to recur in approximately 30% of renal allografts with graft loss in about half of these cases. The exact etiology remains unclear, though a putative circulating permeability factor or loss of inhibitory substances is being discussed. Different therapeutic approaches have been used. We report on a 10-year-old Arabian boy with a recurrence of FSGS immediately after transplantation. In addition to intensifying immunosuppressive therapy with high-dose cyclosporin A and cyclophosphamide, plasmapheresis was initiated and remission was achieved after 8 months. Three weeks after cessation of plasmapheresis a relapse occurred. Plasmapheresis was resumed and remission was achieved again after four additional sessions. The interval between plasmapheresis treatments was then gradually increased and fourteen months after transplantation plasmapheresis was stopped again. Since then (1.5 years after cessation of treatment) the patient has been in complete remission without any further episode of proteinuria. In conclusion, complete and sustained remission with stable renal function was achieved in our patient by long-term plasmapheresis in combination with intensified immunosuppression. Therefore, continuation of plasmapheresis treatment should be considered even in the situation of initial non-response.     

Blood pressure, antihypertensive treatment, and graft survival in kidney transplant patients

Whether the use of angiotensin-converting enzyme inhibitor or angiotensin receptor blocker inhibitor (ACEI/ARB) is beneficial in renal transplant recipients remains controversial. In this retrospective study on 505 renal transplant recipients, we analyzed blood pressure and graft survival according to antihypertensive treatment with ACE-I/ARB and/or calcium channel blockers (CCB) over a period of 10 years. Patients were stratified according to their blood pressure 1 year after transplantation [controlled (≤130/80 mmHg; CTR, 181 patients) and noncontrolled (>130/80 mmHg; non-CTR, 324 patients)] and according to antihypertensive treatment (ACE-I/ARB and/or CCB taken for at least 2 years). One year after transplantation, 88.4% of CTR and 96.6% of non-CTR received antihypertensive treatment ( P  < 0.05). Graft survival was longer in CTR than in non-CTR ( P  < 0.05). Importantly, graft survival was longer in patients who received long-term treatment with ACEI/ARB, CCB, or a combination of ACEI/ARB and CCB ( P  < 0.001). The beneficial effect of ACEI/ARB therapy was more pronounced in non-CTR compared with that of CTR. We conclude that blood pressure control is a key target for long-term graft survival in renal transplant patients. Long-term ACEI/ARB and CCB therapy is beneficial for graft survival, especially in patients with diabetes and/or albuminuria.     

Does positron emission tomography data acquisition impact simultaneous diffusion-weighted imaging in a whole-body PET/MRI system?

Objectives

The purpose of this study was to test whether the acquisition of positron emission tomography (PET) does interfere with simultaneous diffusion weighted imaging (DWI) in an integrated whole-body PET/MRI system.

Material and methods

Fourteen consecutive oncological patients (9 men, 5 women; age 54 ± 13 years ([mean ± standard deviation]) scheduled for routine [¹⁸F]-FDG PET/CT were prospectively enrolled. For DWI, an echo planar imaging (EPI) sequence (b = 0–500–1000 s/mm²) was acquired twice on an integrated whole-body 3 T PET/MRI system in each patient; first with simultaneous PET acquisition and a second time with the PET component switched off. The apparent diffusion coefficient (ADC) and the signal-to-noise ratio at b = 1000 s/mm² (SNR) of the myocardium, paraspinal muscle, liver, spleen, renal cortex and tumor tissue (if present) were measured. In addition, the coefficient of variation (CV) of ADC values was calculated. Student's t-test for paired samples was performed to test for differences of the mean ADC, ADC CV and SNR between DWI with and without simultaneous PET acquisition.

Results

There were no significant differences of the ADC [(mean ± standard deviation)] between the DWI acquisitions with and without simultaneous PET acquisition for the myocardium (2572 ± 441 × 10⁻⁶ mm²/s and 2586 ± 376 × 10⁻⁶ mm²/s, respectively) (P = 0.817), paraspinal muscle (1279 ± 254 × 10⁻⁶ mm²/s vs. 1219 ± 181 × 10⁻⁶ mm²/s) (P = 0.318), liver (1245 ± 158 × 10⁻⁶ mm²/s vs. 1254 ± 171 × 10⁻⁶ mm²/s) (P = 0.848), spleen (980 ± 122 × 10⁻⁶ mm²/s vs. 1000 ± 187 × 10⁻⁶ mm²/s) (P = 0.676) and renal cortex (1951 ± 226 × 10⁻⁶ mm²/s vs. 1930 ± 273 × 10⁻⁶ mm²/s) (P = 0.730). Mean ADC of lymph node metastases (n = 6) did not differ between with PET acquisition (853 ± 174 × 10⁻⁶ mm²/s) and without simultaneous PET (865 ± 170 × 10⁻⁶ mm²/s) (P = 0.675). There were no significant differences between the CV of ADC values or the SNR values measured in DWI datasets that were acquired with or without simultaneous PET for any evaluated organ site.

Conclusion

The simultaneous acquisition of DWI and PET on an integrated PET/MRI system does not impact ADC quantification of normal and tumor tissue and does not alter SNR. This knowledge provides a basis for the use of simultaneous multiparametric PET/MRI comprising DWI in diagnostic imaging and quantitative tumor therapy monitoring using repeated ADC measurements.     

Involvement of cyclic nucleotides in renal artery smooth muscle relaxation

The elevation of vascular smooth muscle tone in the renal arteries during kidney transplantation and nephron-sparing surgery plays a major role in postsurgical organ dysfunction. Therefore, a better understanding of the intracellular mechanisms of contraction and relaxation is of fundamental interest to improve urological treatment. The present study was designed to investigate the complex intracellular system of cyclic nucleotides involved in the regulation of smooth muscle relaxation by using swine renal artery rings in the Schuler organ bath. Phenylephrine (PE) induced dose-dependent and fully reversible isometric contractions with a threshold concentration of 10 nM and an EC(50) of 804 nM. The receptor was identified as alpha(1A)-subtype by the selective antagonist WB4101. Increasing the intracellular concentration of cyclic 3':5'-adenosine monophosphate (cAMP) by dibutyryl-cAMP (5 mM) and forskolin (5 micro M) resulted in a decreased contractiltity of 48.0% and 76.3%, respectively. Elevation of the cytosolic content of cyclic 3':5'-guanosine monophosphate (cGMP) using dibutyryl-cGMP (1 mM), sodium nitroprusside (100 micro M) and SIN-1 (100 micro M) decreased the average PE-induced contraction by 16.4%, 41.9% and 62.4%, respectively. The unselective phosphodiesterase inhibitors theophylline (1 mM), papaverine (100 micro M) and IBMX (5 mM) reduced the PE-induced contraction by 37.3%, 93.1% and 95.5%, respectively. Furthermore, selective inhibition of phosphodiesterases by milrinone (PDE(3)-selective) resulted in a decreased contractility by 1.3% (50 micro M), 29.5% (100 micro M) and 93.5% (5 mM), and using rolipram (PDE(4) selective), the PE-induced contraction was inhibited by 57.9% (50 micro M) and 81.9% (100 micro M). The results suggest the involvement of cAMP and cGMP in the relaxation of renal artery smooth muscle cells. Moreover, phosphodiesterases, especially PDE(3) and PDE(4), seem to play a critical role in the regulation of renal artery smooth muscle tone.     

Cellular mechanisms of ischemia-reperfusion injury

As of yet, only a few strategies to prevent myocardial reperfusion injury have been tested clinically. In the first minutes of reperfusion, the myocardium can be damaged by contracture development, causing mechanical stiffness, tissue necrosis, and the "stone heart" phenomenon. Reperfusion-induced contracture can have two different causes, namely, Ca2+overload-induced contracture or rigor-type contracture. Ca2+ contracture results from rapid re-energization of contractile cells with a persistent Ca2+ overload. Strategies to prevent this type of injury are directed at cytosolic Ca2+ control or myofibrillar Ca2+ sensitivity. Rigor-contracture occurs when re-energization proceeds very slowly. It does not depend on Ca2+ overload. It may be prevented by strategies improving early mitochondrial reactivation