[Idiopathic systemic capillary leak syndrome (Clarkson disease) : A rare cause of recurrent life-threatening edema]. / Idiopathisches systemisches Capillary-leak-Syndrom (Clarkson-Syndrom) : Eine seltene Ursache rezidivierender, vital bedrohlicher Ödeme.

This case report describes the episodic occurrence of severe generalized edema in a young female patient, who developed hypertension with a massive hemoconcentration (hematocrit >0.5, hemoglobin >20g/dl) and hypoalbuminemia during the course of these acute disease phases. After the first two disease exacerbations were overcome, there was a complete regression of symptoms. After a long symptom-free interval, a new exacerbation occurred as a result of which critical organ ischemia occurred due to the severe hypotension and massive edema. Despite all treatment measures a severe compartment syndrome of the lower extemities with subsequent rhabdomyelosis developed. The patient ultimately died as a result of treatment-refractory cardiovascular failure. The idiopathic systemic capillary leak syndrome (SCLS, also known as Clarkson disease) is a rare and potentially life-threatening disease with a high mortality. Since the first description of the disease only approximately 500 cases have been published worldwide. The pathophysiology of this disease remains unclear despite all previous attempts at clarification. Regulation processes of endothelial permeability seem to be essentially disturbed. Affected patients have a monoclonal gammopathy of undetermined signficance conspicuously often; however, the knowledge of the limited treatment options is of fundamental importance for the prognosis and overall survival of patients.

Different time courses of nephrogenic systemic fibrosis: Is there a role for pharmacokinetic aspects in explaining a new clinical entity?

OBJECTIVE: To report 3 cases of nephrogenic systemic fibrosis (NSF) focussing on the time course of clinical symptoms after exposure to gadolinium based contrast agents (GBCA) and to discuss pharmacokinetic aspects of commercially available GBCA. PATIENTS' DETAILS: All 3 patients (2 men, 1 woman, aged 51 - 54 years) suffered from end-stage renal disease (ESRD) and were on long-term dialysis. Linear GBCA compounds were given to all patients and NSF symptoms started 6 months, 1 and 4 years after the last GBCA exposure. In 2 patients, GBCA was administered after the occurrence of (unrecognized) NSF symptoms leading to worsening of clinical courses. 1 of the patients received multiple therapies (e.g. UV-A1 treatment, physical therapy) without significant improvement, 2 patients died from cardiac complications shortly after the diagnosis of NSF. CONCLUSION: NSF may develop after a longer period of time than generally reported and GBCA administration may aggravate or accelerate chronic, subclinical NSF symptoms.

Effect of mycophenolate mofetil on kidney graft function and body weight in patients with chronic allograft nephropathy.

BACKGROUND: Chronic allograft nephropathy (CAN) is the most common cause of late graft loss. A beneficial effect of mycophenolate mofetil (MMF) on CAN was observed, although, due to the loss of body weight (BW) under MMF, serum creatinine (sCr) and reciprocal sCr may be unsuitable markers of graft function. METHODS: In 17 kidney transplant patients with CAN, azathioprine (Aza) was replaced by MMF. The remaining therapy was not changed; specifically, the cyclosporine (CsA) dose was not decreased. The mean values and regression coefficients of reciprocal sCr, CCr, urinary creatinine excretion (uCr x V), proteinuria, BW, blood pressure (BP), serum cholesterol (sChol), and serum triglycerides (sTG) versus time were analyzed 12 months before and after institution of MMF by a paired-comparison t test. RESULTS: The mean regression coefficient of reciprocal sCr differed significantly before and after conversion to MMF (mean -0.01 +/- 0.01 vs +0.012 +/- 0.029 mg/dL per month), suggesting improved graft function. However, the mean values of BW (74 +/- 15 vs 71 +/- 15 kg, P <.001) and uCr x V (1152 +/- 321 vs 1065 +/- 266 mg per 24 hours, P=.0897) decreased, making the increase in CCr less significant (mean -1.16 +/- 2.69 vs 0.40 +/- 1.79 mL/min per month, P <.05). BP, sChol, sTG, and proteinuria before and after conversion did not differ significantly. Among patients with long-term stable graft function at 36.5 +/- 16.9 months after conversion to MMF there was an almost significant improvement in renal protein excretion. CONCLUSIONS: MMF improved graft function, although this effect was overestimated using reciprocal sCr. Other risk factors, such as BP, sChol, and sTG, showed no significant differences, suggesting that MMF accounted for the improvement in CAN. The course of proteinuria under MMF seems to be of prognostic significance.

Immune monitoring in organ transplantation using neopterin.

Transplantation has become an established and successful therapy. Rejections and infections are the principal immune-related complications in the post-transplant course. A reliable and early diagnosis is necessary to prevent graft failure and patient morbidity. Despite the immunologic nature of these complications the diagnostic procedures still rely on functional tests and organ biopsies. Non-invasive monitoring remains to be one of the major goals in transplant medicine. Neopterin is a sensitive marker of the cellular immune response. It reflects the activation of macrophages and can be easily measured in serum, plasma, urine or other body fluids. This review summarises studies on the diagnostic value of neopterin in transplant medicine. Based on these results key factors for immune monitoring in regard to neopterin are evaluated. In particular the unspecificity of diagnostic immune markers, the kinetics of the immune response, the importance of adjustment of neopterin to kidney function, and quantitative differences in immune pathways against viruses and allografts are discussed. Reflecting these points a concept to use neopterin for non-invasive immune monitoring in the clinical routine is presented. This approach calculates probabilities for specific post-transplant complications based on daily measurements of neopterin, a combination with the acute phase reactant amyloid A, and a modification of the likelihood ratio concept.

Assessment of cytomegalovirus infections using neopterin and a new immunoblot.

Human cytomegalovirus (HCMV) infections are a major cause of morbidity and mortality in immunocompromised patients despite advances in diagnostic tests and antiviral therapies. The underlying study investigates the diagnostic value of the immune marker neopterin and a recently developed HCMV-specific western blot to detect HCMV infections and to differentiate them into either syndromes or diseases. The mean period of observation was 1428 days. Thirteen HCMV diseases and nine syndromes were diagnosed retrospectively. The first appearance of clinical signs or symptoms was always associated with a marked increase of serum and urine neopterin. The HCMV-specific IgM response followed in the mean 9 days later. Median values and the course of the neopterin levels were significantly higher during the HCMV diseases. In addition, the strength of the humoral immune response was related to the severity of the HCMV infection. Patients with HCMV diseases developed antibodies against a higher number of epitopes. The anti-HCMV IgM response persisted in more than 80% of the patients for longer than 3 years. In conclusion, combining the HCMV-specific western blot and neopterin permit detection of the immune response against HCMV, reflect the severity of the infection and might guide the anti-viral therapy.

Immediate and long-term results of ATG induction therapy for delayed graft function compared to conventional therapy for immediate graft function.

The use of polyclonal antibodies for delayed graft function (DGF) was tested in 83 renal allograft recipients. Conventional immunosuppression (CI) was given to 52 patients with immediate graft function (IGF) while 31 patients with DGF received the polyclonal antibody ATG. Administration of OKT3 was restricted to steroid-resistant acute rejections in both groups. The incidence and severity of acute rejections, graft survival rate, CMV infections, and lymphocyte subsets were examined. ATG patients experienced a total of 0.6 acute rejections per patient, whereas CI patients had 0.9 on the average (P < 0.05). Second and third acute rejections occurred less frequently and later in the ATG group than in the CI group (P < 0.01). Steroid-resistant acute rejections occurred in 20 of the CI patients (38 %) but in only 7 of ATG patients (23 %). One-year graft survival in the CI and ATG groups was 98.1% and 93.2%, respectively. A decreased CD4 + to CD8 + T-lymphocyte ratio of about 0.5 was still detectable 5 years after the initial ATG administration. Hence, patients with DGF appear to benefit from induction therapy with ATG.

Persistent long-term changes in lymphocyte subsets induced by polyclonal antibodies.

BACKGROUND: Clinicians are well aware of the short-term effects of immunosuppression by mono- or polyclonal antibodies. Little is known about long-term changes induced by these therapies. METHODS: Forty-three renal allograft recipients were selected according to their initial postoperative immunosuppression: (1) BI group=basic immunosuppression with steroids and cyclosporine, n=16; (2) ATG group=basic immunosuppression plus polyclonal antibody antithymocyte globulin (ATG), n=11; and (3) OKT3 group=basic immunosuppression plus monoclonal antibody OKT3, n=16 patients. At intervals of 6 months, the following parameters were measured prospectively: lymphocyte surface antigens (HLA-DR, CD3, CD4, CD8, CD16, CD19, CD56, and CD57); serum and urine neopterin; serum amyloid A; and indirect and direct tests for herpes viruses. RESULTS: The mean period of observation was 58.4 months. The most significant differences between the groups occurred for CD4+ and CD8+ T cells. The ratios of CD4+ to CD8+ cells (n=278 measurements) were significantly and persistently lower in the ATG group (P<0.001, Brown-Mood test). Five years after transplantation, the ATG group had a CD4+ to CD8+ cell ratio of x=0.6 versus x=1.7 in the OKT3 group and x=2.0 in the BI group. This inversion was due to a persistent depletion of the CD4+ cells and an increased regeneration of the CD8+ cells, in particular of the CD8+brightCD57+ subpopulation. Extent and duration of CD4+ depletion correlated with the cumulative ATG dose (r=0.7, P<0.05, Spearman rank correlation test). CONCLUSION: Therapy with polyclonal antibody ATG induces dose-dependent long-term changes in T-cell lymphocyte subsets, which persist over a period of years.