Prevalence and Management of Lower Urinary Tract Symptoms Related to Benign Prostatic Obstruction in a Contemporary Series of Renal Transplant Recipients.

BACKGROUND: The kidney is the most frequently transplanted human organ worldwide. In patients with end-stage renal failure, renal transplantation improves both quality of life and life expectancy. The current literature indicates that the numbers of renal recipients over 60 years of age has increased in recent years. OBJECTIVES: To evaluate the prevalence and management of lower urinary tract symptoms (LUTS) related to benign prostatic obstruction (BPO) in a contemporary series of male renal transplant (RTx) recipients. MATERIALS AND METHODS: We retrospectively evaluated 150 consecutive transplant recipients at the University of Jena 12 months postoperatively for the presence and treatment of LUTS related to BPO. RESULTS: The mean age of the patients was 59 years (range 27 - 82 years). By 12 months postoperatively, 91% (n = 137/150) were off dialysis with a functioning kidney graft. Two patients died during follow up. Six patients had undergone treatment for prostate cancer prior to RTx. Of the remaining 131 patients, 47% (n = 62/131) were considered as patients with BPO 12 months after RTx. Six percent (n = 8/131) of the patients experienced urinary retention due to BPO and 6% (n = 8/131) had a transurethral resection of the prostate (TURP) during the first year after RTx. No major complications were observed in those patients. A significant increase was noted in the use of α-blocker therapy after RTx (P = 0.004). CONCLUSIONS: We observed a high prevalence of LUTS related to BPO in our cohort of patients. Due to the increasing age of transplant recipients, more attention should be paid to the evaluation and treatment of BPO prior to RTx.

FAT1 mutations cause a glomerulotubular nephropathy.

Steroid-resistant nephrotic syndrome (SRNS) causes 15% of chronic kidney disease (CKD). Here we show that recessive mutations in FAT1 cause a distinct renal disease entity in four families with a combination of SRNS, tubular ectasia, haematuria and facultative neurological involvement. Loss of FAT1 results in decreased cell adhesion and migration in fibroblasts and podocytes and the decreased migration is partially reversed by a RAC1/CDC42 activator. Podocyte-specific deletion of Fat1 in mice induces abnormal glomerular filtration barrier development, leading to podocyte foot process effacement. Knockdown of Fat1 in renal tubular cells reduces migration, decreases active RAC1 and CDC42, and induces defects in lumen formation. Knockdown of fat1 in zebrafish causes pronephric cysts, which is partially rescued by RAC1/CDC42 activators, confirming a role of the two small GTPases in the pathogenesis. These findings provide new insights into the pathogenesis of SRNS and tubulopathy, linking FAT1 and RAC1/CDC42 to podocyte and tubular cell function.

Anti-hLAMP2-antibodies and dual positivity for anti-GBM and MPO-ANCA in a patient with relapsing pulmonary-renal syndrome.

BACKGROUND: Pulmonary-renal syndrome associated with anti-glomerular basement membrane (GBM) antibodies, also known as Goodpasture's syndrome, is a rare but acute and life-threatening condition. One third of patients presenting as anti-GBM antibody positive pulmonary-renal syndrome or rapidly progressive glomerulonephritis are also tested positive for anti-neutrophil cytoplasmic antibodies (ANCA). Whilst anti-GBM disease is considered a non-relapsing condition, the long-term course of double-positive patients is less predictable. CASE PRESENTATION: We report a patient with such dual positivity, who presented with pulmonary hemorrhage, crescentic glomerulonephritis and membranous nephropathy. Plasmapheresis in combination with immunosuppressive therapy led to a rapid remission but the disease relapsed after two years. The serum of the patient was tested positive for antibodies to human lysosomal membrane protein 2 (hLAMP2), a novel autoantigen in patients with active small-vessel vasculitis (SVV). The anti-hLAMP2 antibody levels correlated positively with clinical disease activity in this patient. CONCLUSION: We hypothesize that this antibody may indicate a clinical course similar to ANCA-associated vasculitis in double-positive patients. However, this needs to be confirmed on comprehensive patient cohorts.

Pregnancy-associated plasma protein-A is an independent short-time predictor of mortality in patients on maintenance haemodialysis.

AIMS: Mortality of maintenance haemodialysis (HD) patients is very high due to polymorbidity, mostly from metabolic and cardiovascular disease. In order to identify patients with high risk for life-threatening complications, reliable prognostic markers would be helpful. Pregnancy-associated plasma protein-A (PAPP-A) has been shown to predict cardiovascular events and death in patients with stable coronary artery disease as well as in acute coronary syndrome in patients with normal renal function. It was the aim of this study to evaluate PAPP-A as a marker for death in patients on maintenance HD. METHODS AND RESULTS: PAPP-A serum levels were measured in 170 patients participating in the monitor! trial, a prospective dynamic dialysis cohort multicenter study in Switzerland. Patients were followed up for a median time of 17 months after measuring PAPP-A, and evaluated for death of any cause. Survivors and non-survivors were compared with regard to baseline PAPP-A concentrations. A multivariate logistic regression analysis for death was performed including PAPP-A, age, sex, number of comorbidities, dialysis vintage, Kt/V, IL-6, C-reactive protein, parathyroid hormone (PTH), Ca x PO(4) product, and total serum cholesterol. A cut-off value for PAPP-A was calculated for discrimination between patients with low and high mortality risk, respectively. A total of 23 deaths occurred during follow-up, equalling an incidence rate of 0.1. Baseline median PAPP-A levels were 40% higher in non-survivors vs. survivors (P = 0.023). In a multivariate analysis, only PAPP-A, age, and Ca x PO(4) product were independent predictors of mortality. A cut-off value of 24 mIU/L discriminates significantly (P = 0.015) between patients at low or high risk for death with a negative predictive value of 91%. CONCLUSION: PAPP-A is a novel and independent short-time predictor of mortality in a maintenance HD population. The pathogenetic relevance of PAPP-A, particularly in the development of cardiovascular disease, remains to be further elucidated.

High-throughput quantitative analysis by desorption electrospray ionization mass spectrometry.

A newly developed high-throughput desorption electrospray ionization (DESI) source was characterized in terms of its performance in quantitative analysis. A 96-sample array, containing pharmaceuticals in various matrices, was analyzed in a single run with a total analysis time of 3 min. These solution-phase samples were examined from a hydrophobic PTFE ink printed on glass. The quantitative accuracy, precision, and limit of detection (LOD) were characterized. Chemical background-free samples of propranolol (PRN) with PRN-d(7) as internal standard (IS) and carbamazepine (CBZ) with CBZ-d(10) as IS were examined. So were two other sample sets consisting of PRN/PRN-d(7) at varying concentration in a biological milieu of 10% urine or porcine brain total lipid extract, total lipid concentration 250 ng/microL. The background-free samples, examined in a total analysis time of 1.5 s/sample, showed good quantitative accuracy and precision, with a relative error (RE) and relative standard deviation (RSD) generally less than 3% and 5%, respectively. The samples in urine and the lipid extract required a longer analysis time (2.5 s/sample) and showed RSD values of around 10% for the samples in urine and 4% for the lipid extract samples and RE values of less than 3% for both sets. The LOD for PRN and CBZ when analyzed without chemical background was 10 and 30 fmol, respectively. The LOD of PRN increased to 400 fmol analyzed in 10% urine, and 200 fmol when analyzed in the brain lipid extract.

Time-resolved, high-resolution contrast-enhanced MR angiography of dialysis shunts using the CENTRA keyhole technique with parallel imaging.

PURPOSE: To evaluate the use of a dynamic keyhole magnetic resonance angiography (MRA) sequence combined with sensitivity encoding (SENSE) for hemodialysis shunts, because surveillance with conventional contrast-enhanced MRA (CE-MRA) is limited by its low temporal resolution, resulting in arteriovenous overlay. MATERIALS AND METHODS: A total of 12 patients with Brescia-Cimino shunts were investigated prospectively using the new technique. During the contrast passage (gadoterate, Gd-DOTA) a series of five to nine dynamic central k-space measurements (10% for upper-arm shunt, 25% for lower-arm shunt) followed by a full reference data set were acquired. The outer k-space data of the single reference scan were used to complete the dynamic data sets. RESULTS: All studies were diagnostic (17 stenoses, three aneurysms) without complications. The acquisition times for a single dynamic scan of the upper- and lower-arm shunts were 2.2 and 3.2 seconds, respectively, while the reference scan needed 13 and 22.4 seconds, respectively. The dynamic angiograms allowed the differentiation of arterial and venous filling despite a mean peak delay time of only 4.2 seconds in the shoulder region. Image quality qualified in consensus by two experienced readers was rated "good" in 19 cases and "intermediate" in five cases with high mean values for signal-to-noise ratios (SNRs) and contrast-to-noise-ratios (CNRs). CONCLUSION: We have successfully implemented a fast, dynamic, CE-MRA technique with CE timing robust angiography (CENTRA) keyhole and SENSE in clinical routine. High spatial and temporal resolution improve the diagnostics of dialysis shunts and allow the assessment of detailed, dynamic, four-dimensional (4D) information.