[Hypertension and nutrition. Position paper of the Austrian Nutrition Society]. / Hypertonie und Ernährung. Positionspapier der Österreichischen Gesellschaft für Ernährung (ÖGE).

Arterial hypertension is one of the leading causes of overall mortality and is responsible for a high proportion of deaths due to stroke as well as coronary heart disease. It is defined as a pathological elevation of blood pressure which leads to damage of the cardiovascular system. Cut-off values for hypertension are defined as blood pressure levels higher than 140/90 mmHg (systolic/diastolic). In the pathogenesis of hypertension genetic factors, age and sex play a role, as well as body weight and lifestyle factors, such as nutrition and physical exercise. Lifestyle optimization reduces the risk of developing hypertension and contributes to the treatment in patients with established hypertension. Nutritional factors associated with hypertension are discussed in this article and recommendations regarding diet are made based on the literature. The nutritional factors with the highest impact on blood pressure are reduction of salt intake, a diet rich in potassium, weight management, the DASH (dietary approach to stop hypertension) diet and moderation of alcohol consumption. Salt restriction is essential in the prevention and treatment of hypertension. Based on the literature, in this article recommendations for nutrition and hypertension are given.

The novel immunosuppressant FK778 inhibits formation of the immunologic Synapse.

The malononitrilamide FK778 is a derivative of A77 1726, the active metabolite of the antirheumatic drug leflunomide. A77 1726 inhibits de novo pyrimidine synthesis and activity of Src-family kinases; thus, it may interfere with T-cell proliferation as well as with early T-cell signaling. Formation of a stable interaction between T cells and antigen-presenting cells (APC)--the immunologic synapse--has emerged to be of crucial importance for T-cell activation. Here in we show that FK778 inhibits formation of the immunologic synapse by blocking superantigen-stimulated relocalization of adhesion (LFA-1), and signaling molecules (CD3) to the T-cell/APC contact site. These data show that FK778 affects T-cell/APC interactions, particularly events crucial for T-cell adhesion and formation of stable conjugates underlying sustained and effective T-cell activation. Thus, in this model system close to physiologic T-cell stimulation, FK778 affects critical events in the course of T-cell-mediated immune responses earlier than T-cell proliferation, which may contribute to its immunosuppressive potential.

The malononitrilamide FK778 inhibits activation of NF-kappaB in human dendritic cells.

FK778, a derivative of the active leflunomide-metabolite, A77 1726, has been shown to be a powerful immunosuppressant in several transplantation models, particularly efficient in prevention of chronic allograft rejection. However, the cellular and molecular mechanisms underlying these effects of FK778 have not been investigated yet in detail. Because dendritic cells (DCs) are a crucial cell type in initiation of immune responses including chronic allograft rejection, we investigated whether FK778 affects this peculiar cell population. NF-kappaB is the essential transcription factor involved in DC activation and function. We found that lipopolysaccharide (LPS)-induced activation of NF-kappaB, as assessed using electromobility shift assay, is markedly inhibited by FK778 in human monocyte-derived DCs. Hence, FK778 could exert its immunosuppressive effects via inhibition of activation and thus function of the central antigen-presenting cell, ie, DC.

Mechanisms of allo-recognition. Recognition by in vivo-primed T cells of specific major histocompatibility complex polymorphisms presented as peptides by responder antigen-presenting cells.

There is evidence of two pathways of allorecognition, the direct pathway where T cells recognize intact allo-MHC molecules on the surface of target cells, and the indirect pathway where T cells recognize processed allo-MHC presented by self antigen-presenting cells. We used synthetic class II MHC allopeptides to study the cellular mechanisms of the indirect allorecognition pathway and its potential role in vascularized allograft rejection. LEW (RT1l) rat T cells--which are primed by immunization with a mixture of four 25 mer class II MHC allopeptides, representing the full length sequence of the beta chain of the hypervariable domain of the RT1.Du (WF), or by primary WF (RT1u) vascularized cardiac allografts--were capable of recognizing and proliferating to specific polymorphic class II MHC sequences when presented as peptides by responder APCs. T cells from naive LEW animals, WF animals immunized with syngeneic RT1.Du beta peptides, or LEW recipients of third-party BN (RT1n) vascularized cardiac allografts did not proliferate to the RT1.Du beta peptides, indicating the specificity of allopeptide recognition. In the strain combination used, immunogenicity of class II MHC allopeptides is determined by factors other than polymorphisms alone, since epitopic differences in 2 of the 4 RT1.Du beta allopeptides were not immunogenic. Responder T cells were CD4+, and were inhibited by monomorphic anticlass II monoclonal antibodies, and by specific anticlass II alloantibodies. These observations confirm the occurrence of self MHC-restricted recognition of processed allo-MHC in primary vascularized allograft rejection, and provide the rationale to develop novel and specific immunotherapies in organ transplantation.

The alloantibody network following intrathymic immunomodulation of sensitized rat recipients of cardiac allografts.

An intrathymic injection of allogeneic spleen cells (2 x 10(7)) prevents accelerated (< 36 hr) rejection in sensitized LEW rats, and prolongs the survival of LBNF1 cardiac allografts to about 11 days. This effect is donor-specific, x-irradiation-sensitive and thymus-dependent, and it does not require adjunctive immunosuppressive therapy. We have recently shown that following intrathymic allo-Ag injection, host cell proliferative responses in lymphoid organs are markedly depressed as compared with untreated sensitized recipients. Little is known about how intrathymic immunomodulation may affect host humoral alloreactivity. In this work, we studied the dynamic interplay between the humoral responses, both in the circulation and at the graft site of sensitized hosts. Intrathymic allo-Ag exposure triggered a profound change in the utilization pattern of alloreactive IgM, IgG, and IgG subclasses compared with recipients receiving syngeneic cells. Administration of allo-Ag into the thymus at the time of sensitization resulted in an earlier and significantly increased systemic production of IgM, as shown by flow cytometry. Subsequently, isotype switching to IgG occurred prematurely and resulted in elevated levels of IgG1 and IgG2a. Indeed, the addition of such allo-Ab enriched serum suppressed the MLR assay in a dose-dependent manner. The binding of Ig to cardiac allografts was analyzed in eluates by flow cytometry, and by immunohistochemical staining at day 1 after transplantation. Intragraft IgM and IgG levels were consistently higher in well-functioning grafts following administration of allo-Ag, as compared with controls. IgG deposits at the graft site consisted predominantly of IgG1 and IgG2a, while significant amounts of IgG2b could only be detected in control hosts undergoing accelerated graft rejection. These data document that intrathymic injection of donor-specific allo-Ag in sensitized recipients leads to profound alterations of the host humoral alloresponses, and that such elevated allo-Ab levels interfere with the Ag reactivity or alloresponsive effector cells in vitro. These results support the notion that the pattern of allo-Ab utilization is indicative of the functional status of the alloimmune response in the transplant recipient.

The indirect pathway of allorecognition. The occurrence of self-restricted T cell recognition of allo-MHC peptides early in acute renal allograft rejection and its inhibition by conventional immunosuppression.

There is evidence that T cells can "directly" recognize intact allo-MHC molecules on the surface of allogeneic stimulator or target cells, and/or "indirectly" recognize processed allo-MHC peptides presented by self antigen-presenting cells (APCs). We and others have recently demonstrated that in vivo-primed rat CD4+ T cells recognize and proliferate to specific polymorphic amino acid sequences when presented as MHC allopeptides by self APCs. Studies on the mechanisms of indirect T cell recognition of alloantigen are now reported. First, we studied the immunogenicity of 4 synthetic polymorphic class II MHC allopeptides representing full-length sequences of the hypervariable domains of RT1.Du beta (DR or I-E-like) in several responder strains: LEW (RT1(l)), ACI (RT1a), BUF (RT1b), BN (RT1n), and control syngeneic WF (RT1u) strains. Immunogenicity of the individual 25mer allopeptides varied in the different responder strains, indicating that self-restricted T cell recognition of allo-MHC peptides is determined not only by polymorphisms, but also by the responder MHC genotype. Self-restricted CD4+ T cell recognition of processed allo-MHC peptides has been shown to occur during acute skin and cardiac allograft rejection, and there is evidence that this pathway may play an important role in initiating and amplifying the immune response to allografts. T cells from LEW animals primed in vivo by WF (RT1u) vascularized renal allografts were capable of proliferating to the RT1.Du beta peptides as early as 3 days postengraftment, when presented by self APCs. We then tested the effects of various immunosuppressive drugs on self-restricted primed T cell proliferative response to an immunogenic MHC allopeptide in vitro. Methylprednisolone, cyclosporine, and FK506 inhibited the proliferative response of RT1.Du beta 2-primed LEW T cells in a dose-dependent fashion. In addition, a single injection of cyclosporine (25 mg/kg i.m.) to LEW recipients of WF renal allografts on the day of transplantation completely abolished the proliferative response of in vivo-primed T cells to RT1.Du beta 2, indicating the susceptibility of the indirect pathway of allorecognition to conventional immunosuppressive drugs.

Intrathymic injection of donor-specific X-irradiation-sensitive spleen cells abrogates accelerated rejection of cardiac allografts in sensitized rats.

LBNF1 cardiac allografts are rejected within 36 hr in Lewis (LEW) rats sensitized with Brown Norway (BN) skin grafts (acute rejection = 7.5 days). We analyzed the effects of intrathymic versus intravenous alloantigen challenge upon graft survival in this well-defined accelerated rejection model. Intrathymic injection of LBNF1 spleen cells (2 x 10(7)) at the time of skin transplantation (day -7) abrogated < 36 hr rejection, and prolonged the survival of cardiac allografts to about 11 days. This striking effect did not require concomitant immunosuppression, and was donor specific, as the transfer of syngeneic (LEW) or third-party (Wistar-Furth) splenocytes was ineffective. X-irradiation of donor spleen cells before inoculation restored accelerated rejection, whereas thymectomy at day -6 or 0 (the day of heart transplant) significantly shortened graft survival. In contrast, although intravenous administration of the same number of donor cells into sensitized recipients prolonged cardiac allograft survival to about 9 days, the effect was x-irradiation resistant and was never influenced by thymectomy. Radioactive tracer studies have revealed distinct trafficking patterns for the transferred cells, with those given intrathymically retained mostly in the thymus, and sequestered into host spleen and lymph nodes. Instead, intravenously injected splenocytes did not accumulate in the thymus, but were eventually trapped in the liver. Moreover, intrathymic immunomodulation has switched off cellular, rather than humoral, events at the graft site, and markedly depressed cell proliferative responses in host lymphoid organs, as analyzed by immunohistology and mixed lymphocyte response (MLR)* assay, respectively. In contrast, intravenous therapy did not have any significant effect on early intragraft cellular infiltration, including considerable neutrophil infiltration, and did not affect lymph node cell proliferation in vitro. These data document the importance of the thymus as a potential target organ for modulation of alloreactivity in vivo, and reinforce the role of distinct "central" and "peripheral" host immune mechanisms contributing to immunological unresponsiveness following organ transplantation.

High incidence of nephrogenic adenoma of the bladder after renal transplantation.

BACKGROUND: Tumors of the bladder termed nephrogenic adenomas in kidney allograft recipients are believed to develop as urothelial metaplastic proliferations in response to mechanical trauma, chemical noxae, irradiation, and bacterial or viral pathogens. We report on the incidence of nephrogenic adenoma of the bladder in patients who received renal transplants during a period of 7 years and 3 months at the University Hospital of Vienna. METHODS: Diagnosis was obtained by cystoscopy and histological analysis. Nephrogenic adenoma was treated by transurethral electroresection and administration of antibiotics in case of urinary tract infections. Follow-up consisted of cytological controls of urine and bladder irrigation fluid as well as of cystoscopy every 3 months. RESULTS: In 7 of 1328 renal allograft recipients, nephrogenic adenoma could be detected after 7 to 60 months following renal transplantation. In five patients, recurrence was detected 9 to 23 months after diagnosis of the initial lesion. No evidence of malignant degeneration was observed in any patient. Nephrogenic adenoma was not related to immunosuppressive therapy, cytomegalovirus disease, or gancyclovir therapy. CONCLUSIONS: We suggest that after successful transurethral electroresection of nephrogenic adenomas, cytological controls are adequate every 3 months. Only in renal transplant patients with recurrence of voiding disturbances, macrohematuria, or urinary tract infection are cystoscopy and biopsy indicated in the routine follow-up regimen.

Influence of HLA phenotypes on the inhibition of in vitro alloreactivity by cyclosporine.

Interindividual variations in the immunosuppressive effect of Cyclosporine have been observed in clinical organ transplantation. Searching for an in vitro correlate we investigated a possible relation between inhibition of alloresponsiveness by CsA and the HLA phenotypes of the responder or stimulator in mixed lymphocyte reactions. Peripheral blood mononuclear cells from 28 healthy volunteers were used as responder or stimulator cells (gamma-irradiated) and the inhibitory effect of graded amounts of CsA was determined in 130 criss-cross combinations. Sensitivity of alloresponsiveness to the drug was expressed as the dose causing 50% inhibition (ED50) and was read from the inhibition curves generated after four-parameter logistic curve fitting. ED50 ranged from 0.35 ng/ml to 33.4 ng/ml and correlated only weakly with the magnitude of the response (r = 0.12). In MLC with HLA DR4-positive responder cells, ED50 was significantly lower (Pc = 0.0035, Kruskal Wallis) when compared with MLC with responder cells of other DR haplotypes. For HLA DR5-positive responder cells ED50 was significantly higher (Pc = 0.042) when compared with DR5-negative responder cells. No significant correlation between ED50 and any particular haplotype of the stimulator cells could be observed. Sensitivity to CSA did not differ in MLC with 1 or 2 mismatches in the HLA-DR locus. In summary, we found that sensitivity of in vitro alloreactivity was different for particular HLA DR phenotypes, which may have important implications for the immunosuppressive therapy of transplanted patients with cyclosporine.

Twelve months of lamivudine treatment for chronic hepatitis B virus infection in renal transplant recipients.

BACKGROUND: Chronic hepatitis B virus (HBV) infection increases morbidity and mortality in renal transplant recipients (RTR). Lamivudine has shown promising results in patients with chronic hepatitis B, but experience with its use in RTR is limited. METHODS: In a prospective, open labeled, uncontrolled trial, 19 HBsAg(+) RTR were treated with lamivudine for 12 months. HBV-serologic analysis, HBV-DNA quantitation, and HBV genome sequence analysis were performed every 3 months. RESULTS: At baseline 16 patients were HBV DNA(+), 12 patients were HBeAg(+)/Ab (-). After 3 months HBV DNA was negative in 80% of patients. In the 3 patients with elevated liver enzymes, normal values were achieved within 12 weeks. At 12 months 4 of 8 HBeAg(+)/Ab(-) patients on treatment showed HBeAb, two of them with loss of HBeAg. Three patients developed mutations of the HBV polymerase gene associated with lamivudine resistance. CONCLUSIONS: Lamivudine is safe and effective in HB-sAg(+) RTR, the rate of HBe-seroconversion and of lamivudine-resistance is comparable to that of nonimmunosuppressed patients.

The effects of lipid-lowering agents on acute renal allograft rejection.

BACKGROUND: Preliminary results from clinical trials suggest that 3-hydroxy-3-methylglutaryl co-enzyme A reductase inhibitors may help prevent acute renal allograft rejection. However, the mechanism for this putative effect of 3-hydroxy-3-methylglutaryl co-enzyme A reductase inhibitors, and whether it is independent of lipid-lowering per SE are unknown. METHODS: Immediately after renal transplantation we randomly allocated (proportioned 2:1:2) patients to: 1) simvastatin (10 mg/day, n=53), 2) simvastatin placebo plus gemfibrozil (dose adjusted for renal function, n=36), and 3) simvastatin placebo (n=52). RESULTS: Simvastatin, but not gemfibrozil, reduced total and low density lipoprotein cholesterol during the first 90 days posttransplant. There were no major adverse effects of therapy. However, there were no effects of treatment on acute rejection. Indeed, survival free of acute rejection at 90 days was 72% in the simvastatin group, 72% in the gemfibrozil group, and 77% in the placebo control group (P=0.771). A post hoc power analysis suggested that there was only a 7.5% chance that a true effect of simvastatin on acute rejection (versus placebo) was not detected, and a 2.5% chance that an effect of gemfibrozil on acute rejection (versus placebo) was not detected in this study. CONCLUSION: Lipid-lowering agents may not reduce the incidence of acute renal allograft rejection. However, additional studies are needed to confirm this observation. In the mean time, many if not most renal transplant recipients should be treated with HMG-CoA reductase inhibitors starting early posttransplant to prevent cardiovascular disease complications. The results of this study suggest that starting lipid-lowering therapy immediately after renal transplantation is both safe and effective in lowering total and low density lipoprotein cholesterol.

The effects of nondepleting CD4 targeted therapy in presensitized rat recipients of cardiac allografts.

The immunosuppressive effects of RIB-5/2, a nondepleting anti-rat CD4 monoclonal antibody (mAb), were analyzed in a well-defined model of accelerated cardiac allograft rejection. (LEW x BN)F1 hearts are rejected within 24 hours in LEW hosts presensitized with BN skin grafts at day -7. Treatment with RIB-5/2 mAb (3.5 mg/day i.v.) at days -7 and -1, prolonged cardiac allograft survival to the median of >62 days. The long-term recipients rejected acutely third-party (Wistar-Furth) test skin grafts, without an adverse effect on the survival of the original cardiac transplants. Lymphocytes harvested from mAb-treated hosts significantly decreased proliferative responses of donor cells in mixed leukocyte reaction. The cell activation and cytokine elaboration patterns were evaluated at the mRNA and protein levels by competitive template reverse transcriptase polymerase chain reaction and immunohistochemistry, respectively. Cardiac allografts in CD4 mAb-treated rats at 24 hours displayed reduced CD3, CD25, tumor necrosis factor-alpha, interleukin (IL)-1beta, IL-2, interferon (IFN)-gamma, and IL-10 mRNA levels as compared to those in rejecting grafts. Equal amounts of IL-4 mRNA were detected throughout in both animal groups; the expression of IL-10 mRNA increased progressively in the treated hosts. In contrast, IFN-gamma was consistently depressed after mAb therapy. The mRNA levels coding for CD3, CD25, tumor necrosis factor-alpha, IL-1-beta, and IL-2 genes were comparable in long-surviving and rejecting allografts. The staining for IL-2R, IL-2, and IFN-gamma was diminished, whereas the staining for IL-4 was either unaffected or enhanced in well-functioning grafts in RIB-5/2 mAb-treated hosts. The untreated recipients elicited strong circulating IgM allo-Ab response, which peaked around the time of cardiac rejection and then switched to IgG allo-Ab 4-7 days after heart transplantation. Treatment with RIB-5/2 mAb decreased IgM and prevented the switch into the IgG allo-Ab response. In conclusion, the ability of RIB-5/2 mAb treatment to combat accelerated rejection and to produce long-term graft acceptance is unprecedented in our experience in this model. These data provide new insights into the complexities of the cellular and humoral responsiveness, contributing to the the induction of donor-specific unresponsiveness in sensitized hosts. This study, along with our previous reports, indicate that an immune deviation in which intragraft Th1-type cytokines (primarily IFN-gamma) are diminished and Th2-type cytokines (IL-4 and IL-10) are maintained represents the common effector mechanism of CD4 mAb regimens in recipients of vascularized organ allografts.

A case of continuous ambulatory peritoneal dialysis peritonitis with an uncommon organism and an atypical clinical course.

This report describes a 46-year-old patient who experienced an atypical course of peritonitis while undergoing continuous ambulatory peritoneal dialysis (CAPD). The first sign of peritonitis was progressive impairment of ultrafiltration with increasing fluid absorption. The patient came to the center after 5 days with leg edemas and 645 leukocytes/microL in the first dialysate outflow. On the same day, the dialysate cell count decreased to 208/microL. During the following days, ultrafiltration failure persisted despite spontaneous normalization of PD-fluid leukocytes. No other clinical symptoms were observed, and the serum C-reactive protein (CRP) level remained normal. Magnetic resonance peritoneography and abdominal radiograph did not show dislocation of the catheter, a dialysate leak, or other causes of ultrafiltration failure. At day 14, fever, diarrhea, and an elevated serum CRP level occurred. Dialysate cultures taken on days 8, 11, and 14 showed growth of NEISSERIA: sicca. After initiation of antibiotic therapy with levofloxacine on day 14 ultrafiltration, clinical symptoms and serum CRP normalized within 3 days. In conclusion, Neisseria sicca should be considered as a rare cause of PD peritonitis. Our case report further illustrates the importance of ultrafiltration failure as an early and main symptom of peritoneal inflammation. The frequently used peritonitis criteria may not apply to cases of mild PD peritonitis.

Role of humoral immune reactions as target for antirejection therapy in recipients of a spousal-donor kidney graft.

Excellent graft outcome has been reported for spousal-donor kidney transplantation. In husband-to-wife transplantation, however, a tendency toward inferior graft survival has been described for recipients who were previously pregnant. In our series of spousal-kidney transplantations (nine transplantations; three female recipients), actual graft survival is 100% (median observation time, 339 days). Five patients experienced early allograft rejection. In four transplant recipients, rejection was easily reversible by conventional antirejection therapy. In a multiparous recipient, however, mild interstitial allograft rejection associated with early graft dysfunction was resistant to anticellular treatment (antilymphocyte antibody, tacrolimus rescue therapy). The particular finding of polymorphonuclear neutrophils in peritubular capillaries and the finding of diffuse capillary deposits of the complement split product, C4d, in a posttransplantation biopsy specimen suggested a role of antibody-mediated graft injury. Retrospective flow cytometry cross-matching showed the presence of preformed immunoglobulin G (IgG) antibodies to HLA class I antigens that were not detectable by pretransplantation lymphocytotoxic cross-match testing or screening for panel reactive antibodies. After transplantation, however, complement-fixing antibodies, also presumably triggered by reexposure to spousal-donor HLA antigens, could be detected in the patient's serum. These findings suggested antibody-mediated allograft rejection and led to the initiation of immunoadsorption therapy (14 sessions) with staphylococcal protein A. Selective removal of recipient IgG resulted in complete reversal of graft dysfunction. Our findings suggest that in husband-to-wife transplantation, donor-specific antibodies, presumably triggered by previous pregnancies, might occasionally induce sustained allograft dysfunction. Thus, in this particular setting, a detailed immunologic and histopathologic work-up regarding antibody-mediated allograft dysfunction is warranted because immunoadsorption may be a highly effective treatment modality.

Primary peripheral T cell lymphoma in a kidney transplant under immunosuppression with cyclosporine A.

A 56-year-old patient received a cadaveric renal allograft because of primary cystic kidney disease. The donor was a 28-year-old man who died from head trauma. No other major illnesses were present at the time of transplantation. Immunosuppression was performed with cyclosporine A and steroids. After 3 months, the patient presented with fever and abdominal pain which was located in the region of the allograft. Ultrasonography demonstrated a tumor mass at the renal transplant hilus that was suspected to be an infected hematoma. Kidney biopsy from the cortex revealed only severe morphologic signs of cyclosporine A toxicity which was due to high cyclosporine A levels during the first 2 months after transplantation. The patient died from pulmonary embolism 6 months posttransplant. Histologic evaluation of the tumor specimens obtained at autopsy showed an extensive infiltration of the renal hilus and the medulla by a peripheral T cell lymphoma of the large-cell type. The T cell origin was confirmed by immunohistochemistry using the T cell-associated monoclonal antibodies UCHL-1 and MT1.

Role of magnetic resonance imaging in renal transplant recipients with acquired cystic kidney disease.

OBJECTIVES: To evaluate the impact of magnetic resonance imaging (MRI) in renal transplant recipients whose ultrasound (US) examinations of the native kidneys have met the criteria of acquired cystic kidney disease (ACKD). METHODS: The US scans of 840 renal allograft recipients were prospectively studied. In addition, 46 of 169 patients diagnosed with ACKD by US scans underwent MR examination. MRI protocols included (a) T1 and T2-weighted fast spin echo imaging, (b) T2-weighted gradient echo imaging, and (c) gadolinium-enhanced T1-weighted imaging in 7 patients with evidence of complex cysts. In the case of complex lesions, both US and MRI follow-up examinations were performed between 6 and 12 months after the prior examination. RESULTS: US examination showed ACKD in 169 of 840 patients. In addition, US revealed 8 patients with renal cell carcinomas (RCC). Of these 8 patients, 7 had evidence of ACKD. The median number of cysts depicted on US examination in native kidneys of renal transplant recipients was 3 (range 0 to 10) on both sides. MRI revealed significantly more and smaller cysts compared to US. The median number of cysts was seven on the left and nine on the right native kidneys, respectively. MRI revealed 18 complex lesions in 7 patients. Thirteen of 18 complex lesions were undetected by US. CONCLUSIONS: MRI is superior to US in depiction of simple and complex lesions of native kidneys in renal allograft recipients. MRI exhibits no overestimation of the prevalence of ACKD on the basis of the US criteria already mentioned. Advantages of MRI do not justify routine screening tests by this imaging modality. However, MRI should be used for further evaluation of complex lesions detected by US.

Basal calcitonin levels and the response to pentagastrin stimulation in patients after kidney transplantation or on chronic hemodialysis as indicators of medullary carcinoma.

Plasma concentrations of calcitonin (hCT) were determined in 150 patients with chronic renal failure on chronic hemodialysis therapy (CHD) and in 800 patients after successful kidney transplantation (KT). Basal hCT concentrations exceeded 10 pg/mL in 44 of 150 patients (29%) with CHD and in 48 of 800 (6%) in patients with KT. Among these patients with elevated basal hCT, pentagastrin-stimulated concentrations of hCT exceeded 100 pg/mL in 4 patients with CHD and in 7 with KT. Thyroidectomy was performed in 8 patients (5 with KT, 3 with CHD) revealing the presence of medullary thyroid carcinoma (MTC) (n = 2) or of C-cell hyperplasia (n = 6). Two patients with C-cell hyperplasia had the neoplastic form of this disorder. One patient with MTC and 1 with C-cell hyperplasia also presented a papillary microcarcinoma. Stimulated concentrations of hCT were only moderately elevated in the remaining 3 patients and follow-up rather than surgery was deemed appropriate due to their concomitant severe medical problems. In conclusion, basal concentrations of hCT higher than 10 pg/mL are more common in patients with CHD (29%) and after successful KT (6%) than previously described in patients with thyroid nodular disease (3%). In spite of various additional factors complicating the interpretation of elevated hCT in CHD, pentagastrin-stimulated values above 100 pg/mL must be considered to indicate the presence of C-cell hyperplasia and/or of medullary thyroid carcinoma. Although thyroidectomy would theoretically be the therapy of choice, the potential benefit of the operation must be seen in the context of the patient's general condition.

Pattern of endothelin immunostaining during rejection episodes after kidney transplantation.

A pathophysiological role for endothelin (ET), one of the most potent vasoconstrictor peptides, has been suggested in ATN and during kidney allograft rejection. As ET is known to have predominantly local effects, we investigated intrarenal ET content in 82 kidney transplant biopsies and 10 normal control kidneys. ET-immunostaining, using a polyclonal anti-ET-1 antibody was investigated in 4 intrarenal vascular beds (glomeruli, capillaries, arterioles, arteries) and in tubular epithelium. Normal kidneys showed a strong staining of endothelial cells in all vessels and of tubular epithelium. In biopsies with signs for acute vascular rejection a marked decrease in ET staining intensity was seen. In contrast, normal staining similar to control kidneys was detected in interstitial rejection and in ATN. The presence of chronic CyA toxicity, however, lead to a significant reduction of endothelial ET staining. Neither mean doses nor trough levels of CyA correlated closely with the immunostaining findings. Plasma big-ET levels were elevated during vascular rejection, but not in interstitial rejection and ATN. This study demonstrates a significant reduction of ET immunostaining in intrarenal vascular endothelium of kidney transplant biopsies showing signs of endothelial damage. In vascular allograft rejection these changes are often associated with a concomitant rise in plasma ET levels. Our findings support a postulated role of ET in vascular rejection and during CyA toxicity and show that endothelial damage, independent of its genesis, can lead to a reduction of intrarenal ET content.

Increased levels of plasma amylin in advanced renal failure.

Amylin, a 37 amino acid polypeptide, has been suggested to play a prominent role in the pathogenesis of insulin resistance in type II diabetes mellitus. Various studies have demonstrated most recently that amylin is cosecreted with insulin. No data are available on the elimination of amylin from the circulation. We therefore tested plasma levels of amylin, insulin and C-peptide in 49 non-obese, non-diabetic patients (27 male/22 female) with various degree of renal impairment (Group A: CCr less than 20 ml/min, n = 20; Group B: CCr 20-89 ml/min, n = 18; and Group C: CCr greater than 80 ml/min, n = 9). We found a significant increase of plasma amylin when kidney function, expressed by creatinine clearance fell below 20 ml/min (17.9 +/- 1.7 vs. 12.2 +/- 0.8 vs. 8.8 +/- 1.2 pg/ml; p = 0.0005). Plasma amylin correlated closely with serum C-peptide (r = .764; p = 0.0001), and to a lesser extent with insulin (r = .595; p = 0.0001) underlining its postulated cosecretion with these peptides. The data indicate that amylin might be eliminated by renal mechanisms. Our data show that besides type II diabetes mellitus, advanced renal failure is another clinical situation with enhanced plasma amylin levels. Whether amylin plays any pathogenetic role in renal patients remains to be elucidated.

[Radiologic therapy of symptomatic lymphoceles following kidney transplantation]. / Radiologische Therapie von symptomatischen Lymphozelen nach Nierentransplantation.

During a four and a half year period ending in November 1988, we performed 13 percutaneous needle aspirations and 35 percutaneous drainages on 32 patients suffering from symptomatic lymphoceles (LC) following renal transplantation. Of 13 needle aspirations, 4 were therapeutic (31%); in 9 cases recurrent lymphoceles were observed within 3 days. 35 percutaneous catheter drainages were carried out on 29 patients. 16 of these (55%) did not require any additional therapy. In 8 cases recurrent lymphoceles were treated surgically by marsupialization, another 5 underwent repeated percutaneous drainage. One patient needed 3 percutaneous interventions until his symptoms ceased. In 8 patients 5 ml. of fibrinous glue was administered before the catheter was removed; nevertheless, 3 of them developed recurrent LC. In the group of patients without any symptoms after percutaneous drainage, 5 LC were infected, in the group of repeatedly drained LC, 2 had superinfection which was treated with antibiotics. All of the infected LC could be managed successfully by percutaneous drainage. The overall rate of success was 72%.