BackgroundAutosomal dominant polycystic kidney disease (ADPKD) is responsible for 10% of cases of the end stage renal disease. Early diagnosis, especially of potential fast progressors would be of benefit for efficient planning of therapy. Urine excreted proteome has become a promising field of the search for marker patterns of renal diseases including ADPKD. Up to now however, only the low molecular weight fraction of ADPKD proteomic fingerprint was studied. The aim of our study was to characterize the higher molecular weight fraction of urinary proteome of ADPKD population in comparison to healthy controls as a part of a general effort aiming at exhaustive characterization of human urine proteome in health and disease, preceding establishment of clinically useful disease marker panel.ResultsWe have analyzed the protein composition of urine retentate (>10 kDa cutoff) from 30 ADPKD patients and an appropriate healthy control group by means of a gel-free relative quantitation of a set of more than 1400 proteins. We have identified an ADPKD-characteristic footprint of 155 proteins significantly up- or downrepresented in the urine of ADPKD patients. We have found changes in proteins of complement system, apolipoproteins, serpins, several growth factors in addition to known collagens and extracellular matrix components. For a subset of these proteins we have confirmed the results using an alternative analytical technique.ConclusionsObtained results provide basis for further characterization of pathomechanism underlying the observed differences and establishing the proteomic prognostic marker panel.
BACKGROUND AND PURPOSE: ADPKD correlates with an increased frequency of ICANs, but universal screening for ICANs in patients with ADPKD is not currently recommended. The aim of our study was to determine which groups might benefit from screening by determining the prevalence of ICANs in the Polish ADPKD population and identifying any subgroups with an increased risk for ICANs.
SummaryAutosomal dominant polycystic kidney disease (ADPKD) is one of the most common genetic disorders caused by a single gene mutation.The disease usually manifests itself at the age of 30–40 years and is characterized by formation of renal cysts along with the enlargement of kidneys and deterioration of their function, eventually leading to renal insufficiency.Imaging studies (sonography, computed tomography, magnetic resonance imaging) play an important role in the diagnostics of the disease, the monitoring of its progression, and the detection of complications. Imaging is also helpful in detecting extrarenal manifestations of ADPKD, most significant of which include intracranial aneurysms and cystic liver diseases.
We report a case of 30-year-old White male with sirolimus (SRL)-associated hepatotoxicity. Because of end-stage renal failure due to chronic glomerulonephritis, renal transplantation was performed at 29 years of age. Initial immunosuppression included steroids, cyclosporin A (CsA) and SRL. Because of severe steroid-resistant acute rejection, triple immunosuppressive regimen was continued over third month post-transplant. Later, simvastatin (10 mg daily) was applied as the result of moderate mixed hyperlipemia and cilazapril (0.5 mg daily) due to slight proteinuria and polyglobulia. At 16th month post-transplant, serum aminotransferases increased. The patient was asymptomatic, with no significant abnormalities on physical examination and abdominal ultrasonography. Trough levels were CsA 165 ng/dl and SRL 6.3 ng/dl. Alcohol consumption, viral hepatitis and cytomegalovirus infection were excluded. Because of suspected Epstein-Barr virus infection, the patient received acyclovir. Subsequently, as the result of suspected atypical pathogen infection, doxycyclin was applied. As a result serum aminotransferases gradually increased (maximal levels: AspAT: 368 IU/l, AlAT: 579 IU/l). Nonspecific changes were observed most probably because of drug-induced injury when liver biopsy was performed. Steatosis was definitively excluded (Fig. 1). At 24-month post-transplant, SRL was changed to mycophenolate mofetil which was followed by quick normalization of serum aminotransferases.Hepatotoxicity of SRL is underestimated, but it is not an unknown phenomenon. In clinical trials, in renal transplant recipients, elevated aminotransferases were more frequent in SRL versus CsA groups [1,2] and SRL versus SRL + CsA group [3]. SRL-associated hepatotoxicity was also reported in liver transplant recipients [4]. It is generally acknowledged that patients may benefit from synergistic actions of calcineurin inhibitor and SRL, combining effective prevention of rejection with the potential of reducing side-effects of both drugs [5,6]. There were no cases of severe SRL hepatotoxicity requiring discontinuation of SRL reported in kidney transplant recipients treated with SRL, CsA and steroids.It is unlikely that, in our case, liver enzymes elevation was caused by other drugs. Although cilazapril and simvastatin had been withdrawn, aminotransferases did not decrease. Moreover, treatment with these drugs was star- SummaryThe aim of our paper was to describe hepatotoxicity of sirolimus (SRL) in a kidney graft recipient. We report the case of a 30-year-old male after kidney transplantation, treated with steroids, cyclosporin A and SRL, with steroidresistant acute rejection in anamnesis. At 16th month after transplantation, elevation of serum aminotransfereases was observed. After exclusion of common reasons of this condition, liver biopsy was performed. Nonspecific changes were observed, with probability of drug-induced injury. SRL was changed to mycophenolate mofetil, which was followed by quick normalization of serum aminotransferase levels. Hepat...
This study assessed inhalation exposure to particulate matter (PM1)-bound mercury (Hgp) and PM1-bound polycyclic aromatic hydrocarbons (PAHs) among university students. For this purpose, simultaneous indoor (I) and outdoor (O) measurements were taken from two Polish technical universities (in Gliwice and Warsaw) located in distinct areas with respect to ambient concentrations and major sources of PM. The indoor geometric mean concentrations of Hgp were found to be 1.46 pg·m−3 and 6.38 pg·m−3 in Warsaw and Gliwice, while the corresponding outdoor concentrations were slightly lower at 1.38 pg·m−3 and 3.03 pg·m−3, respectively. A distinct pattern was found with respect to PAH concentrations with estimated I/O values of 22.2 ng·m−3/22.5 ng·m−3 in Gliwice and 10.9 ng·m−3/11.12 ng·m−3 in Warsaw. Hazard quotients (HQs) as a result of exposure to Hgp for students aged 21 ranged from 3.47 × 10−5 (Warsaw) to 1.3 × 10−4 (Gliwice) in terms of reasonable maximum exposure (RME). The non-cancer human health risk value related to Hgp exposure was thus found to be below the acceptable risk level value of 1.0 given by the US EPA. Daily exposure values for lecture hall occupants, adjusted to the benzo(a)pyrene (BaP) toxicity equivalent (BaPeq), were 2.9 and 1.02 ng·m−3 for the Gliwice and Warsaw students, respectively. The incremental lifetime cancer risk (ILCR) values with respect to exposure to PM1-bound PAHs during the students’ time of study were 5.49 × 10−8 (Warsaw) and 1.43 × 10−7 (Gliwice). Thus, students’ exposure to indoor PAHs does not lead to increased risk of lung cancer.
Background/Aims: Autosomal dominant polycystic kidney disease (ADPKD) is correlated with an increased frequency of both intracranial aneurysms (ICANs), and arterial hypertension (AH). The aim of our study was to search for the association between blood pressure (BP) and ICANs in ADPKD patients. Methods: Sixty-eight adult, pre-dialysis phase ADPKD patients underwent both screening for ICANs with magnetic resonance angiography of the brain, and ambulatory blood pressure monitoring (ABPM). Results: ICANs were diagnosed in 10 patients (ICAN(+) group), while in 58 were not (ICAN(-) group). The nighttime maximum diastolic blood pressure (DBP), maximum increase in DBP from measurement to measurement (positive delta of DBP) at night, and the standard deviation of the daytime mean arterial pressure were significantly higher in ICAN(+) compared to ICAN(-) patients. Additionally, in a subgroup of patients after 45 years-of-age, ICAN(+) patients had significantly higher maximum 24-hour and daytime systolic blood pressure, maximum 24-hour, daytime, nighttime DBP, maximum daytime and nighttime positive delta of DBP compared to ICAN(-) cases. Conclusions: Development of ICANs in hypertensive ADPKD patients is accompanied with higher values of some BP parameters measured by ABPM. Hypertensive ADPKD patients with substantial fluctuations in BP assessed by ABPM, especially those after 45 years-of-age, should become candidates for screening for ICANs.
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