Search

The aim of the present study was to investigate the role of the endogenous nitric oxide synthase inhibitor asymmetric dimethylarginine (ADMA) and its degrading enzyme dimethylarginine dimethylaminohydrolase (DDAH) in angiotensin II (ANG II)-induced hypertension and target organ damage in mice. Mice tyansgenic for the human DDAH1 gene (TG) and wild-type (WT) mice (each, n = 28) were treated with 1.0 [micro]g*[kg.sup.-1]* [min.sup.-1] ANG II, 3.0 [micro]g*[kg.sup.-1]*[min.sup.-1] ANG II, or phosphate-buffered saline over 4 wk via osmotic minipumps. Blood pressure, as measured by tail cuff, was elevated to the same degree in TG and WT mice. Plasma levels of ADMA were lower in TG than WT mice and were not affected after 4 wk by either dose of ANG II in both TG and WT animals. Oxidative stress within the wall of the aorta, measured by fluorescence microscopy using the dye dihydroethidium, was significantly reduced in TG mice. ANG II-induced glomerulosclerosis was similar between WT and TG mice, whereas renal interstitial fibrosis was significantly reduced in TG compared with WT animals. Renal mRNA expression of protein arginine methyltransferase (PRMT)I and DDAH2 increased during the infusion of ANG II, whereas PRMT3 and endogenous mouse DDAH1 expression remained unaltered. Chronic infusion of ANG II in mice has no effect on the plasma levels of ADMA after 4 wk. However, an overexpression of DDAH1 al|eviates ANG II-induced renal interstitial fibrosis and vascular oxidative stress, suggesting a blood pressure-independent effect of ADMA on ANG II-induced target organ damage. dimethylarginine dimethylaminohydrolase; hypertension; transgenic

Abstract Background Microdeletions on chromosome 17q12 cause of diverse spectrum of disorders and have only recently been identified as a rare cause of Mayer-Rokitansky-Kuester-Hauser-Syndrome (MRKH), which is characterized by uterus aplasia ± partial/complete vaginal aplasia in females with a regular karyotype. For the first time we report about a patient with a 17q12 microdeletion who is affected by MRKH in combination with a vascular and soft tissue disorder. Repeatedly she suffered from kidney transplant failure caused by consuming membranous nephropathy. Case presentation A 38-year-old female patient had been diagnosed with right kidney aplasia, left kidney dysplasia and significantly impaired renal function during infancy. Aged 16 she had to start hemodialysis. Three years later she received her first kidney transplant. Only then she was diagnosed with MRKH. The kidney transplant was lost due to consuming nephrotic syndrome caused by de novo membranous nephropathy, as was a second kidney transplant years later. In addition, a hyperelasticity syndrome affects the patient with congenital joint laxity, kyphoscoliosis, bilateral hip dysplasia, persistent hypermobility of both elbows, knees and hips. Her clinical picture resembles a combination of traits of a hypermobile and a vascular form of Ehlers-Danlos-Syndrome, but no mutations in the COL3A1 gene was underlying. Instead, array-based comparative genomic hybridisation (CGH) detected a heterozygous 1.43 Mb deletion on chromosome 17q12 encompassing the two renal developmental genes HNF1β and LHX1. Conclusions Deletions of HNF1β have recently drawn significant attention in pediatric nephrology as an important cause of prenatally hyperechogenic kidneys, renal aplasia and renal hypodysplasia. In contrast, membranous nephropathy represents an often-unaccounted cause of nephrotic syndrome in the adult population. A causative connection between theses two conditions has never been postulated, but is suggestive enough in this case to hypothesize it.

Abstract Background Chyluria is a medical condition with presence of chyle in the urine. The disease is most prevalent in endemic regions of Africa and the Indian subcontinent where it is mostly caused by parasitic infections, particularly lymphatic filariasis due to wucheria bancrofti. Non-parasitic chyluria, however, is a very rare finding. Case Presentation We report the case of a 48 year old woman who developed a lymphorenal fistula with chyluria following ureterrenoscopy with biopsies taken for urological work-up of persistent macrohematuria. Renal biopsy confirmed the diagnosis of benign familial hematuria due to thin basement nephropathy, a condition frequently associated with episodes of macrohematuria. Conclusions This case highlights a rare case of non-parasitic chyluria as a complication of urological work-up for macrohematuria of benign nature.

Abstract Background Diarrhea is common in patients with Crohn's disease and may be accompanied by acid base disorders, most commonly metabolic acidosis due to intestinal loss of bicarbonate. Case Presentation Here, we present a case of severe metabolic alkalosis in a young patient suffering from M. Crohn. The patient had undergone multiple resections of the intestine and suffered from chronic kidney disease. He was now referred to our clinic for recurrent acute kidney injury, the nature of which was pre-renal due to profound volume depletion. Renal failure was associated with marked hypochloremic metabolic alkalosis which only responded to high volume repletion and high dose blockade of gastric hypersecretion. Intestinal failure with stomal fluid losses of up to 5.7 litres per day required port implantation to commence parenteral nutrition. Fluid and electrolyte replacement rapidly improved renal function and acid base homeostasis. Conclusions This case highlights the important role of gastrointestinal function to maintain acid base status in patients with Crohn's disease.

Background. Randomized trials have shown that early adoption of everolimus-based immunosuppressive regimens without a calcineurin inhibitor (CNI) improves long-term kidney graft function, but the optimal strategy for CNI minimization remains uncertain.Methods. In a prospective, randomized, multicentre, 12-month trial, 499 de novo kidney transplant patients were randomized at Month 3 to (i) remain on standard CNI (cyclosporine) therapy with mycophenolic acid, (ii) convert to everolimus with mycophenolic acid or (iii) start everolimus with reduced CNI and no mycophenolic acid (clinical trials registry: ClinicalTrials.gov-NCT00514514). Results. The primary endpoint, change in estimated glomerular filtration rate (eGFR) (Nankivell) from randomization to Month 12, was significantly greater in the CNI-free arm versus standard CNI therapy: mean difference 5.6 mL/min/1.73 m2 [95% confidence interval (CI) 2.8–8.3 mL/min/1.73 m2, P < 0.001]. The improvement in eGFR in the CNI-free arm was also higher than in the low-CNI group (mean difference 5.5 mL/min/1.73 m2, 95% CI 2.8–8.2 mL/min/1.73 m2, P < 0.001), while results were similar in the low-CNI and standard CNI arms. The post-randomization incidence of biopsy-proven acute rejection was 11.7%, 8.1% and 7.9% in the CNI-free, low-CNI and standard CNI groups, respectively (CNI-free versus standard CNI, P = 0.27; low-CNI versus standard CNI, P = 1.00). Adverse events led to study drug discontinuation in 28.7%, 15.5% and 15.2% of CNI-free, low-CNI and standard CNI patients, respectively. Conclusions. Everolimus initiation with CNI withdrawal at Month 3 after kidney transplantation achieves a significant improvement in renal function at 12 months, with a similar rate of acute rejection. [ABSTRACT FROM AUTHOR]