Peter Schollmeyer

Treatment of Ostial Renal-Artery Stenoses with Vascular Endoprostheses after Unsuccessful Balloon Angioplasty

BACKGROUND Percutaneous transluminal renal angioplasty is a safe and effective treatment for nonostial stenoses of the renal arteries, but it has proved to be disappointing for ostial stenoses. Therefore, we prospectively studied the use of intravascular stents for the treatment of critical ostial stenoses after unsuccessful balloon angioplasty. METHODS Stainless-steel endoprostheses were placed across 74 renal-artery stenoses located within 5 mm of the aortic lumen in 68 patients with hypertension. Twenty patients had mild or severe renal dysfunction. The indications for stent placement were elastic recoil (63 arteries) or dissection (1 artery) of the vessel after angioplasty, or restenosis after initially successful balloon angioplasty (10 arteries). Patients were followed for a mean of 27 months with measurements of blood pressure and serum creatinine, duplex sonography, and intraarterial angiography. RESULTS Initial technical success was achieved in all patients. Minor complications (local hematomas) occurred in only three patients; there were no major complications. Eighty-four percent of the patients were free of primary occlusion 60 months after the procedure. Restenosis of more than 50 percent of the vessel diameter occurred in 8 of 74 arteries (11 percent). Reintervention resulted in a secondary patency rate of 92 percent. Long-term normalization of blood pressure was achieved in 11 patients (16 percent). Serum creatinine levels did not change significantly after successful stent implantation in patients with previously impaired renal function. CONCLUSIONS Accurate placement of renal-artery stents is technically feasible without major complications. The favorable early and long-term results suggest that primary stent placement is an effective treatment for renal-artery stenosis involving the ostium.

BONE FRACTURE AND OSTEODENSITOMETRY WITH DUAL ENERGY X-RAY ABSORPTIOMETRY IN KIDNEY TRANSPLANT RECIPIENTS

Kidney transplant recipients have multiple factors leading to osteoporosis. The purpose of this study was to determine the fracture rate after kidney transplantation and the significance of osteodensitometry with dual energy x-ray absorptiometry (DXA) in identifying the risk patients. Bone mineral density (BMD) was measured with DXA in 100 graft recipients (mean interval 63 +/- 53 months after transplantation) and correlated with the incidence of fractures. Fracture rate of peripheral bones increased from 0.009 before transplantation and 0.012 on hemodialysis to 0.032 fractures per patient and year after transplantation. Seventeen fractures of peripheral bones occurred in 11% of the patients within a mean of 103 +/- 59 months after transplantation. Three additional patients had fractures of the lumbar spine. Patients with fractures were characterized by low or low-normal BMD (0.93 +/- 0.23 versus 1.04 +/- 0.17 g/cm2 at lumbar spine), a frequent history of parathyroidectomy (21% versus 6%), and a longer transplant interval (103 +/- 59 versus 57 +/- 49 months). Fractures occurred in patients with low and normal BMD. DXA at the femoral neck proved to be of no value to define patients at risk of fractures. DXA at the lumbar spine also proved to be of limited value for this question. Therefore, alternatively, more sensitive methods of BMD and of bone architecture measurements are necessary for identifying the kidney transplant recipients at risk of fracture.

Pancreatic lesions in the von Hippel-Lindau syndrome

Common manifestations of the von Hippel-Lindau syndrome, an autosomally dominant inherited cancer-prone disorder, include retinal angiomatosis, hemangioblastoma of the central nervous system, renal cysts, renal cancer, pheochromocytoma, and epididymal cystadenoma. Multiple cysts and microcystic (serous) cystadenomas of the pancreas have also been reported occasionally in patients afflicted with this syndrome. In the large Freiburg study of the von Hippel-Lindau syndrome composed of 66 affected individuals, pancreatic lesions were systematically studied. Fifty-five living individuals were examined by abdominal ultrasound imaging. Abnormal findings were confirmed by computed tomographic scan and/or magnetic resonance imaging. For an additional 11 decreased patients autopsy data were available. Cystic lesions of the pancreas were found in 10 patients (15%). One of these patients presented with multiple pancreatic cysts as the only manifestation of the syndrome. In one patient, a malignant islet-cell tumor was found at autopsy. Because multiple pancreatic cysts did not cause major clinical symptoms and because follow-up examinations over an average period of 5 years did not show significant progression of the lesions, it is concluded that these patients usually do not require surgical treatment. Abdominal ultrasound screening is recommended for patients at risk as a tool to identify potential von Hippel-Lindau syndrome gene carriers with pancreatic manifestations. In all patients with multiple pancreatic cysts, the von Hippel-Lindau syndrome should be included in the differential diagnosis.

Bone mineral density after kidney transplantation : a cross-sectional study in 190 graft recipients up to 20 years after transplantation

Kidney transplant recipients are exposed to multiple factors that lead to osteoporosis after kidney transplantation. Recent short-term longitudinal studies revealed a strong decline of bone mineral density (BMD) within 1 year after transplantation. The long-term course of BMD after transplantation is still unknown. Therefore, we performed a cross-sectional study to determine BMD in 190 renal graft recipients (mean age 44 years, range 20-71 years) by dual-energy x-ray absorptiometry at various time intervals up to 20 years after transplantation (range 0-237 months). Mean BMD of graft recipients was lower than BMD values of an age- and sex-matched European reference collective at every time of measurement after renal transplantation (P < 0.01). Lowest mean BMD values were measured 12-24 months after transplantation. No loss of BMD occurred after the second posttransplant year beyond the normal age- and sex-dependent decline of BMD. Mean daily prednisone dosage was significantly higher within the first 2 posttransplant years compared with the later posttransplant period (13.1 +/- 6.2 vs. 6.7 +/- 3.4 mg/day). Other drugs or metabolic causes, including daily dosage of CsA, AZA, parathormone level, and graft function, did not show additional important differences before and after the second posttransplant year. Interpreting the results of a cross-sectional study in light of a time-dependent process, we suggest that the preexisting low BMD of kidney transplant recipients at the time of transplantation is further strongly reduced within the initial 2 posttransplant years, probably due mainly to the effect of prednisone therapy. After that time, when prednisone dosage is below a threshold of 7.5 mg/day, only a moderate, normal loss of BMD is apparent, even in patients up to 20 years after transplantation.

Impairment of Endothelium-Dependent Dilation in Rabbit Renal Arteries by Oxidized Lipoprotein(a) Role of Oxygen-Derived Radicals

BACKGROUND Hyperlipoproteinemia is associated with impairment of nitric oxide (NO)-mediated, endothelium-dependent dilation in renal arteries. In the present study, we assessed and compared the effects of human lipoprotein(a) and LDL on endothelium-dependent and -independent dilation in vitro. METHODS AND RESULTS Dilator responses were detected in isolated, saline-perfused, preconstricted arterial segments by a photoelectric device. Acetylcholine-induced, endothelium-dependent dilator responses of rabbit renal arteries were not significantly attenuated after 150 minutes of incubation with native lipoprotein(a) (30 and 100 micrograms/mL). However, exposure to in vitro oxidized lipoprotein(a) (150 minutes, 30 and 100 micrograms/mL) suppressed acetylcholine-induced dilator responses in a dose-dependent manner. At similar concentrations, native and oxidized LDL had no effect. Endothelium-independent dilations induced by the NO-donor sodium nitroprusside were also impaired by oxidized lipoprotein(a), whereas forskolin-induced dilator responses were unaffected, indicating that smooth muscle dilator capacity was not impaired. Attenuation of dilator responses by oxidized lipoprotein(a) was potentiated in the presence of superoxide dismutase (SOD). The SOD effect was completely blunted by coincubation with catalase (100 U/mL) or deferoxamine. In the absence of SOD, catalase or deferoxamine had no effect on dilator responses. Using a chemiluminescence assay, we could detect increased O2- production by arteries pretreated with oxidized lipoprotein(a), which suggested that enhanced NO inactivation by O2- could be the underlying mechanism for impairment of endothelium-dependent dilations. CONCLUSIONS These data indicate that oxidized lipoprotein(a) impairs endothelium-dependent dilation and is more potent than oxidized LDL in this effect. The mechanism of the impairment may involve formation of O2- and inactivation of NO.

Treatment of osteopenia and osteoporosis after kidney transplantation.

BACKGROUND Osteopenia and osteoporosis are frequent complications after kidney transplantation. Data for the treatment of low bone mass after kidney transplantation are not available. METHODS To test the efficacy of antiresorptive treatment, 46 patients with osteopenia or osteoporosis after kidney transplantation (bone mineral density < or =1.5 SD below normal) were randomly assigned to three groups cyclically treated as follows: group 1 with daily oral clodronate (800 mg) and group 2 with daily intranasal calcitonin (200 IU) for 2 weeks every 3 months. These two groups were compared with a control group (group 3). Every patient was supplemented with 500 mg of calcium per day. Bone mineral density (BMD) was measured by dual energy x-ray absorptiometry (DEXA) at the lumbar spine and femoral neck before and after the 12-month treatment period. RESULTS BMD at the lumbar spine was increased by 4.6% in the clodronate group (n=15, P=0.005), by 3.2% in the calcitonin group (n=16, P=0.034), and by 1.8% in the control group (n=15, P=0.265). However, the differences in BMD changes among the groups were not statistically significant. During therapy, serum calcium decreased slightly in all groups by 4.6%; however, parathyroid hormone values increased significantly in the treatment groups by 116%. Therapy was well tolerated without impact on graft function. CONCLUSIONS Cyclical therapy with clodronate or calcitonin appears to induce a gain in BMD at the lumbar spine in patients with low bone mass after kidney transplantation. This treatment had no adverse impact on graft function but may aggravate preexisting secondary hyperparathyroidism.

Influence of hepatic cirrhosis and end-stage renal disease on pharmacokinetics and pharmacodynamics of furosemide

SummaryAfter rapid intravenous injection of furosemide 40 mg (Fu), plasma levels were determined in 7 healthy volunteers, 8 patients with liver cirrhosis with ascites and 7 patients with end-stage renal disease (ESRD). The diuretic response was evaluated by measuring the urinary excretion of sodium and potassium and the urine volume. The mean elimination half life (tF1/2+) of Fu averaged 51±7.7 (±SD) min in healthy subjects, 52±7.7 min in cirrhosis and 200±57 min in ESRD. The non-renal clearance (Clnr) in healthy subjects (56±28 ml/min) corresponds to the total plasma clearance in functionally anephric patients (54±18 ml/min). In cirrhosis there was no significant change in the disposition parameters of Fu in comparison to the healthy volunteers, but there was a significant reduction in urine sodium and volume, whereas potassium excretion remained unchanged. Fu “excretion rate — response” curves showed diminished tubular sensitivity to Fu in cirrhosis.

Oxidized lipoproteins inhibit endothelium-dependent vasodilation. Effects of pressure and high-density lipoprotein.

Hypertension and atherogenic low-density lipoproteins cause attenuation of endothelium-dependent dilations in vivo. We investigated a potential interference of high transmural pressure with the effects of low-density lipoproteins on endothelium-dependent dilation in vitro. Furthermore, we determined whether high-density lipoproteins preserve endothelial function. Endothelium-intact rabbit renal arteries were isolated, placed in an organ bath, perfused intraluminally with Tyrodes solution, and exposed to different degrees of transmural pressure and native or oxidized low-density lipoproteins. In preconstricted arteries perfused under low-pressure conditions (30 mm Hg), acetylcholine dose dependently elicited endothelium-dependent dilations that were not altered by increasing the perfusion pressure to 100 mm Hg for 90 minutes (high-pressure conditions). Incubation of the arteries with native or oxidized low-density lipoproteins (0.2 and 1 mg/mL for 60 minutes, respectively) under low-pressure conditions did not attenuate acetylcholine-induced dilations. However, under high-pressure conditions dilations were dose dependently attenuated by oxidized but not by native low-density lipoproteins. Endothelium-independent dilations to glyceroltrinitrate (0.001 to 3 mumol/L) were not affected. Preincubation of the segments with high-density lipoproteins (0.5 mg/mL, 30 minutes) prevented attenuation of dilator responses. The attenuation of endothelium-dependent dilations by oxidized low-density lipoproteins under high-pressure conditions was accompanied by a transmural, dose-dependent infiltration of the vessel wall with lipoprotein, as detected by light microscopy of cryostat sections stained with Sudan III. This infiltration was prevented by high-density lipoprotein. Under low-pressure conditions no lipoprotein infiltration was visible. In segments incubated with native low-density lipoprotein, no lipoprotein infiltration was detectable.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of extracellular ATP on contraction, cytosolic calcium activity, membrane voltage and ion currents of rat mesangial cells in primary culture.

1 The effects of extracellular ATP on contraction, membrane voltage (Vm), ion currents and intracellular calcium activity [Ca2+]i were studied in rat mesangial cells (MC) in primary culture. 2 Addition of extracellular ATP (10−5 and 10−4 m) to MC led to a cell contraction which was independent of extracellular calcium. 3 Membrane voltage (Vm) and ion currents were measured with the nystatin patch clamp technique. ATP induced a concentration‐dependent transient depolarization of Vm (ED50: 2 × 10−6 m). During the transient depolarization ion currents were monitored simultaneously and showed an increase of the inward‐ and outward current. 4 In a buffer with a reduced extracellular chloride concentration (from 145 to 30 mm) ATP induced a depolarization augmented to −4 ± 4 mV. 5 ATP‐γ‐S and 2‐methylthio‐ATP depolarized Vm to the same extent as ATP, whereas α,β‐methylene‐ATP (all 10−5 m) had no effect on Vm. 6 The Ca2+ ionophore, A23187, depolarized Vm transiently from −51 ± 2 to −28 ± 4 mV and caused an increase of the inward current. 7 The intracellular calcium activity [Ca2+]i was measured with the fura‐2 technique. ATP stimulated a concentration‐dependent increase of [Ca2+]i (ED50: 5 × 10−6 m). The increase of [Ca2+]i was biphasic with an initial peak followed by a sustained plateau. 8 The [Ca2+]i peak was still present in an extracellular Ca2+‐free buffer, whereas the plateau was abolished. Verapamil (10−4 m) did not inhibit the [Ca2+]i increase induced by ATP. 9 The data indicate that extracellular ATP contracts MC and is able to increase [Ca2+]i by the release of Ca2+ from intracellular stores and recruitment from the extracellular space. In addition ATP depolarizes Vm of MC by activating a Cl− conductance. The ATP‐induced depolarization is mediated by a P2y receptor.

Treatment of retroperitoneal fibrosis by mycophenolate mofetil and corticosteroids

Retroperitoneal fibrosis is an idiopathic disorder that leads to compression of the uterer, vena cava, and aorta by retroperitoneal mass. Findings strongly suggest an autoimmune aetiology. Beside surgery, immunosuppression with corticosteroids, azathioprine, and tamoxifen has been reported. Immunosuppressive therapy was, however, successful only in early stages of disease. Once anuric renal failure due to retroperitoneal fibrosis had occurred, conventional immunosuppressive therapy failed in every patient in a series of 60. The new immunosuppressive drug mycophenolate mofetil, a selective inhibitor of T and B lymphocytes, blocks various autoimmune processes. Mycophenolate mofetil also decreases the rate of rejection after renal transplantation and has been successfully used to treat systemic vasculitis, IgA nephropathy, and bullous pemphigoid. We tried mycophenolate mofetil in a man aged 38 years with advanced retroperitoneal fibrosis. On admission he was completely anuric, potassium concentration was 7·6 mmol/L, serum creatinine 2060 mol/L, and C-reactive protein 131 mg/L. Antinuclear antibodies, antineutrophilic cytoplasmic antibodies, and rheumatoid factor were negative. Computed tomography of the abdomen showed a large retroperitoneal mass (figure) with a craniocaudal extension of 8 cm, which caused bilateral ureteral obstruction, hydronephrosis, and compression of the vena cava and aorta. Retrograde pyelogram revealed medial deviation of both ureters, with a 12 cm stenosis on the left side and a 3 cm stenosis on the right side. A computed-tomography-guided biopsy of the retroperitoneal mass showed chronic inflammation with fibrosis and an infiltration of lymphocytes, plasma cells, and eosinophils. Aetiology of retroperitoneal fibrosis was idiopathic since evidence for drug-induced origin or associates diseases could not be detected. The patient underwent one haemodialysis session. After endoscopic insertion of two double J catheters in both uterers, immunosuppressive therapy was started with mycophenolate mofetil 2 g/daily and prednisone (250 mg on 3 days, followed by 50 mg/day). Prednisone was decreased every week by 10 mg. After 10 weeks, the retroperitoneal mass had regressed and the double J catheters were removed. 8 months after immunosuppressive therapy was started, there was an almost complete remission of the retroperitoneal mass. Serum creatinine concentration was 88·4 mol/L. Prednisone (5 mg) was stopped after 12 months. Mycophenolate mofetil was continued for a further 6 months and relapse did not occur. Despite the advanced stage of disease, combined mycophenolate mofetil and prednisone led to remission of retroperitoneal fibrosis, which made surgery unnecessary.