Coxsackie B viruses and the kidney--a neglected topic

Coxsackie B viruses types 1-6 (CVB1-6) occur worldwide and cause a broad spectrum of diseases, including myocarditis and aseptic meningitis. Although renal damage due to CVB has been suspected since the 1950s, these agents are only rarely searched for in today's clinical nephrological practice. Nevertheless, CVB can infect mesangial cells. Furthermore, infections with these viruses lead to a histological picture resembling mesangioproliferative glomerulonephritis and IgA-nephropathy in mice. In the present article, we provide an overview of this largely neglected topic, and of the slowly and steadily increasing evidence suggesting a link between coxsackieviral infections and kidney diseases.

A mixed epithelial and stromal tumor of the kidney in a ringtail lemur (Lemur catta)

Primary renal tumors are rare neoplasms in nonhuman primates. This report describes a mixed epithelial and stromal tumor of the kidney (MESTK) in a 14.5-year-old female ringtail lemur. The well-demarcated, solid, and cystic mass was located in the pelvis of the left kidney and consisted histologically of both epithelial and mesenchymal components. The mesenchymal cells were arranged in fascicles around cysts lined by a well-differentiated epithelium. Neither the mesenchymal nor the epithelial parts showed significant nuclear atypia or mitotic figures. To our knowledge, only 1 similar case, classified as adenoleiomyofibromatous hamartoma, has been reported in a ringtail lemur. In humans this tumor affects predominantly perimenopausal women and can express estrogen and progesterone receptors. However, neither estrogen nor progesterone receptors could be identified by immunohistochemistry in the tumor of the present ringtail lemur. Therefore, a hormonal mechanism could not be demonstrated in this case.

Diagnostic criteria for hematopoietic stem cell transplant-associated microangiopathy: results of a consensus process by an International Working Group

BACKGROUND AND OBJECTIVES: There are no widely accepted criteria for the definition of hematopoietic stem cell transplant -associated microangiopathy (TAM). An International Working Group was formed to develop a consensus formulation of criteria for diagnosing clinically significant TAM. DESIGN AND METHODS: The participants proposed a list of candidate criteria, selected those considered necessary, and ranked those considered optional to identify a core set of criteria. Three obligatory criteria and four optional criteria that ranked highest formed a core set. In an appropriateness panel process, the participants scored the diagnosis of 16 patient profiles as appropriate or not appropriate for TAM. Using the experts' ratings on the patient profiles as a gold standard, the sensitivity and specificity of 24 candidate definitions of the disorder developed from the core set of criteria were evaluated. A nominal group technique was used to facilitate consensus formation. The definition of TAM with the highest score formed the final PROPOSAL. RESULTS: The Working Group proposes that the diagnosis of TAM requires fulfilment of all of the following criteria: (i) >4% schistocytes in blood; (ii) de novo, prolonged or progressive thrombocytopenia (platelet count <50 x 109/L or 50% or greater reduction from previous counts); (iii) sudden and persistent increase in lactate dehydrogenase concentration; (iv) decrease in hemoglobin concentration or increased transfusion requirement; and (v) decrease in serum haptoglobin. The sensitivity and specificity of this definition exceed 80%. INTERPRETATION AND CONCLUSIONS: The Working Group recommends that the presented criteria of TAM be adopted in clinical use, especially in scientific trials.

Effect of cinacalcet cessation in renal transplant recipients with persistent hyperparathyroidism

BACKGROUND: Persistent hyperparathyroidism after renal transplantation affects bone and allografts. Cinacalcet, a calcimimetic, reduces serum calcium and PTH in renal transplant recipients with persistent hyperparathyroidism. Here, we address the question whether this effect of cinacalcet persists after withdrawal. METHODS: Therefore, cinacalcet was stopped after 12 months treatment in 10 stable renal transplant patients. Serum calcium, phosphate, PTH, creatinine and cystatin C were monitored for 3 months. RESULTS: Serum calcium, normalized in nine patients before cessation of cinacalcet (2.32 +/- 0.05mmol/l, mean +/- SEM), increased after 3 months of discontinuation by 0.17 +/- 0.04mmol/l, P < 0.05, but remained within the normal range in eight patients. Compared with the time point of cessation, PTH remained unchanged or decreased further after 3 months without therapy in six patients. Measurements of cystatin C suggested an improvement of the glomerular filtration rate after cessation in 9 out of 10 patients (1.55 +/- 0.09 vs 1.33 +/- 0.12 mg/l, P < 0.01). CONCLUSION: First, a beneficial effect of cinacalcet beyond the duration of a 12-month therapy appears to be present in some patients and second, the previously suspected influence of cinacalcet therapy on renal function is reversible. Thus, it is reasonable to consider a trial of cinacalcet cessation to identify these patients. The optimal time point for such a discontinuation is unknown. The present observations are preliminary. They clearly require a prospective randomized trial for definitive confirmation.

[Hypophyseal incidentaloma in a patient with autosomal dominant polycystic kidney disease]

The prevalence of incidentally discovered lesions within the pituitary (pituitary incidentalomas) is about 10%. The most common form of sellar mass are clinically nonfunctioning adenomas (less than 10 mm); functioning adenomas, however, are rare. Incidentally discovered pituitary microadenomas causing growth hormone hypersecretion are uncommon. In addition, the association of autosomal dominant polycystic kidney disease with acromegaly is exceptional and has not yet been reported to our knowledge.

Blood concentration curve of cyclosporine: impact of itraconazole in lung transplant recipients

Although the influence of cytochrome P450 inhibitory drugs on the area under the curve (AUC) of cyclosporine (CsA) has been described, data concerning the impact of these substances on the shape of the blood concentration curve are scarce. By assessment of CsA blood levels before and 1, 2, and 4 hr after oral intake (C0, C1, C2, and C4, respectively) CsA profiling examinations were performed in 20 lung transplant recipients taking 400 mg, 200 mg, and no itraconazole, respectively. The three groups showed comparable results for C0, C2, and AUC(0-12). Greater values were found for Cmax, Cmax-C0, peak-trough fluctuation and rise to Cmax in favor of the non-itraconazole group. Additionally, tmax was shorter in the non-itraconazole group. Comedication with the metabolic inhibitor itraconazole is associated with a flattening of the CsA blood concentration profile in lung transplant recipients. These changes cannot be assessed by isolated C0, C2, or AUC(0-12) values alone.

Prevalence of cholecystolithiasis and its management among kidney/pancreas-transplanted type 1 (insulin-dependent) diabetic patients

BACKGROUND: Simultaneous pancreas/kidney transplantation (SPK) should be the procedure of choice for (pre)uremic patients with type 1 diabetes. All standard immunosuppressive protocols for SPK include a calcineurin-inhibitor. Both calcineurin inhibitors, cyclosporine (CyA) and probably tacrolimus (FK506) too, are associated with the occurrence of cholelithiasis due to their metabolic side effects. PATIENTS AND METHODS: We evaluated the prevalence of cholelithiasis in 83 kidney/pancreas transplanted type I-diabetic patients (46 males, 37 females, mean age 42.8 +/- 7.5 years) by conventional B-mode ultrasound 5 years after transplantation. 56 patients received CyA (group 1) and 27 received tacrolimus (group 2) as first-line-immunosuppressive drug. Additional immunosuppression consisted of steroids, azathioprine or mycophenolate mofetil. Additionally, laboratory analyses of cholestasis parameters (gamma-GT and alcalic phosphatasis) were performed. RESULTS: In total, 23 patients (28%) revealed gallstones and 52 patients (62%) revealed a completely normal gallbladder. In eight patients (10%) a cholecystectomy was performed before or during transplantation because of already known gallstones. No concrements in the biliary ducts (choledocholithiasis) could be detected. In group 2 the number of patients with gallstones was slightly lower (22%) compared with group 1 patients (30%), but without statistical significance. - Cholestasis parameters were not increased and HbA1c values were normal in both groups of patients. CONCLUSION: The prevalence of biliary disease in kidney/pancreas transplanted type I-diabetic patients with 28% is increased in comparison to the general population (10-15%). Lithogenicity under tacrolimus seems to be lower as under cyclosporine based immunosuppressive drug treatment. We recommend regular sonographical examinations to detect an acute or chronic cholecystis as early as possible, which may develop occultly in these patients.

Solid organ transplantation: are there predictors for posttransplant noncompliance? A literature overview

BACKGROUND: Many studies confirm that noncompliance or poor compliance is one of the great problems in health care as it results in waste of resources and funds. METHODS: This overview includes literature on heart, liver, and kidney transplants with emphasis on heart transplantation in adult and pediatric transplant patients and addresses the following variables as potential predictors of postoperative compliance problems: demographic variables (age, marital status, gender) psychological variables (anxiety, denial) psychiatric disorders (major depression, anxiety, and personality disorders), poor social support, pretransplant noncompliance, obesity, substance abuse, and health-related variables (distance from transplant center, indication for transplantation, required pretransplant assist device). Relevant studies on these topics that were conducted up to 1999 are included and discussed in this overview. The most important results are presented in tables. RESULTS: Unfortunately, there has not been any systematic and comprehensive review of the literature on predictors of noncompliance in organ transplant patients so far. With organ transplantation noncompliance impairs both life quality and life span as it is a major risk factor for graft rejection episodes and is responsible for up to 25% of deaths after the initial recovery period. Therefore, it might be assumed that well-informed transplant patients are a highly motivated group whose compliance is just as high. This is not the case. However, even when graft loss means loss of life as in heart or liver transplantation, noncompliance occurs. To best select potential organ recipients, it would be ideal if patients who are very likely to show noncompliant behavior could be identified already before being transplanted. CONCLUSION: The literature overview shows the necessity of preoperative psychosocial screening regarding predictors for posttransplant noncompliance.

[Noncompliance in organ transplantation: a review]

The effectiveness of medical treatment depends not only on the appropriateness of the treatment modality but also on the patient's compliance with the intended regimen. The consequences of failing to comply can be damaging and devastating for the individual patient and his/her family. Noncompliance also leads to waste in two areas: first, a reduction of the potential benefits of therapy, and second, the additional cost of treating the avoidable consequent morbidity. A dramatic example of the consequences of noncompliance with the treatment regimen concerns patients who have had organ transplants: life-long immunosuppression is a pre-requisite for good graft function, and noncompliance is often associated with the occurrence of late acute rejection episodes, graft loss, and death. Here it might be assumed that these patients constitute a highly motivated group, and that compliance would be high. Unfortunately, this is not the case: overall noncompliance rates vary from 20 to 50%. There is no systematic and comprehensive review of the literature on noncompliance and its consequences in organ transplant patients to date. This overview includes literature on heart, liver and kidney transplants in adult and paediatric transplant patients and addresses the following issues: preoperative behaviour patterns as predictors of postoperative compliance problems, compliance behaviour after transplantation, noncompliance and its relationship to organ loss and death, retransplantation outcome after graft loss due to noncompliance, reasons for postoperative noncompliance, and ways to promote compliance.

A feasibility study on model-based evaluation of kidney perfusion measured by means of FAIR prepared true-FISP arterial spin labeling (ASL) on a 3-T MR scanner

RATIONALE AND OBJECTIVES: A feasibility study on measuring kidney perfusion by a contrast-free magnetic resonance (MR) imaging technique is presented. MATERIALS AND METHODS: A flow-sensitive alternating inversion recovery (FAIR) prepared true fast imaging with steady-state precession (TrueFISP) arterial spin labeling sequence was used on a 3.0-T MR-scanner. The basis for quantification is a two-compartment exchange model proposed by Parkes that corrects for diverse assumptions in single-compartment standard models. RESULTS: Eleven healthy volunteers (mean age, 42.3 years; range 24-55) were examined. The calculated mean renal blood flow values for the exchange model (109 +/- 5 [medulla] and 245 +/- 11 [cortex] ml/min - 100 g) are in good agreement with the literature. Most important, the two-compartment exchange model exhibits a stabilizing effect on the evaluation of perfusion values if the finite permeability of the vessel wall and the venous outflow (fast solution) are considered: the values for the one-compartment standard model were 93 +/- 18 (medulla) and 208 +/- 37 (cortex) ml/min - 100 g. CONCLUSION: This improvement will increase the accuracy of contrast-free imaging of kidney perfusion in treatment renovascular disease.