Joanna Matuszkiewicz-Rowińska

State of the art paper Urinary tract infections in pregnancy: old and new unresolved diagnostic and therapeutic problems

Urinary tract infections (UTIs) are common in pregnant women and pose a great therapeutic challenge, since the risk of serious complications in both the mother and her child is high. Pregnancy is a state associated with physiological, structural and functional urinary tract changes which promote ascending infections from the urethra. Unlike the general population, all pregnant women should be screened for bacteriuria with urine culture, and asymptomatic bacteriuria must be treated in every case that is diagnosed, as it is an important risk factor for pyelonephritis in this population. The antibiotic chosen should have a good maternal and fetal safety profile. In this paper, current principles of diagnosis and management of UTI in pregnancy are reviewed, and the main problems and controversies are identified and discussed.

Pseudotumour orbitae as the initial manifestation in Wegener's granulomatosis in a 7-year-old girl

Wegener’s granulomatosis (WG) is a systemic granulomatous vasculitis that typically affects the upper airways, lungs and kidneys. This form of vasculitis is extremely rare in children, the most common form of paediatric systemic vasculitis being Henoch–Schönlein purpura (HSP). Children with systemic vasculitis look ill and have multiple constitutional complaints, often with prolonged fever [1]. As in adults, WG in children is a multisystem disease. There are no precise statistical data concerning ocular involvement in Wegener’s granulomatosis in children. Ocular disease occurs in 50%–60% adult patients with WG and may be an extension of the sinus inflammation or an orbital pseudotumour independent of the sinus disease (15%–50%) [2, 3]; sometimes it presents as an ocular myositis. The most common presenting sign of orbital disease is ptosis and anterior displacement of the eye, pain, blurred vision, eyelid swelling and reduction of eye motility. Here we present the case of a 7-year-old girl with WG whose initial manifestation was pseudotumour orbitae. This patient was negative for an initial c-ANCA test. Biopsy specimens obtained from the lacrimal gland and kidney demonstrated granulomatous vasculitis. Treatment with glucocorticoids and cyclophosphamide led to complete, long-lasting remission.

Homeostatic model assessment indices in evaluation of insulin resistance and secretion in hemodialysis patients.

Background Some previous observations suggest that insulin resistance and glucose metabolism disturbances are frequent complications of chronic kidney disease. However, there are no conclusive studies on other indices of the effectiveness of insulin action in end-stage renal disease (ESRD) patients, including chronically hemodialysed (HD) ones. Material/Methods The groups comprised 33 non-diabetic ESRD hemodialysed patients and 33 healthy controls matched for age, sex, and body mass index (BMI). In both groups, HOMA-%B, HOMA-%S, HOMA-IR indices, and DI were calculated using HOMA1 and HOMA2 as measures of insulin resistance. The indices were also assessed in subgroups divided according to BMI. Results Mean fasting plasma glucose concentrations were lower in ESRD patients than in healthy persons (82.4±10.4 vs. 93.9±11.6, p=0.001). Fasting serum insulin concentrations were similar in both groups (median 6.8 vs. 6.0 mU/l, p=0.698). HOMA1-%B values were higher in ESRD patients than controls (median 137.1 vs. 81.6, p=0.002). HOMA1-%S (median 75.6 vs. 71.5) and HOMA1-IR (median 1.3 vs. 1.4) values were not significantly different (p=0.264 and p=0.189, respectively). DI1 levels were higher for HD patients than for healthy subjects (median 1.16 vs. 0.53, p<0.001). In subgroup analysis, all statistically significant differences were restricted mainly to persons with BMI <25 kg/m2. Similar results as for the HOMA1 model were obtained for HOMA2. Conclusions 1. HOMA beta-cell function is strongly correlated with HOMA insulin resistance in HD patients. 2. In non-diabetic ESRD hemodialysed patients, the HOMA indices and DI may be useful and important models in interpretation of glucose metabolism disturbances.

FGF23 and Klotho in Relation to Markers of Endothelial Dysfunction in Kidney Transplant Recipients

BACKGROUND Fibroblast growth factor (FGF) 23 is a newly discovered member of the FGF family. Klotho is a cofactor of FGF23. Activation of the FGF23-Klotho system is responsible for negative phosphate balance. In addition, FGF23 appears to be a risk factor for cardiovascular complications. The aim of this study was to assess levels of FGF23 and Klotho in stable kidney transplant recipients on triple immunosuppressive therapy in relation to comorbidities and markers endothelial dysfunction. Healthy volunteers served as a control group. METHODS Hemoglobin, urea, and creatinine were studied with the use of standard laboratory methods in the hospital central laboratory. We assessed FGF23 and Klotho, markers of endothelial function/injury von Willebrand factor (vWF), intercellular adhesion molecule (ICAM), vascular cell adhesion molecule (VCAM), and interleukin (IL) 6, N-terminal pro-B-type natriuretic peptide (NT-proBNP) and copeptin with the use of commercially available assays. RESULTS FGF23 was significantly higher and Klotho significantly lower in kidney transplant recipients compared with healthy volunteers. FGF23 correlated with copeptin (r = 0.28; P < .05), IL-6 (r = 0.39; P < .01), VCAM (r = 0.36; P < .01), time after transplantation (r = 0.31; P < .05), platelet count (r = 0.31; P < .05), mean corpuscular volume (r = -0.40; P < .01), and phosphate (r = 0.31; P < .05). Klotho correlated with NT-proBNP (r = 0.38; P < .01), vWF (r = -0.26; P < .05), calcium (r = -0.39; P < .01), and age (r = 0.45; P < .001). FGF23 was significantly higher and Klotho significantly lower in patients with estimated glomerular filtration rate (eGFR) >60 mL/min compared with patients with eGFR <60 mL/min. CONCLUSIONS Disturbances in the FGF23-Klotho system appeared to be related to the endothelial cell injury. Thus they are involved not only in pathogenesis of the metabolic bone disease but also in cardiovascular complications, particularly in kidney disease.

Iron metabolism in hemodialyzed patients - a story half told?

Introduction All living organisms have evolved sophisticated mechanisms to maintain appropriate iron levels in their cells and within their body. Recently our understanding of iron metabolism has dramatically increased. Overt labile plasma iron (LPI) represents a component of non-transferrin bound iron (NTBI) that is both redox active and chelatable, capable of permeating into organs and inducing tissue iron overload. The LPI measures the iron-specific capacity of a given sample to produce reactive oxygen species. We studied for the first time NTBI correlations with markers of iron status and inflammation in prevalent hemodialyzed patients. Material and methods Complete blood count, urea, serum lipids, fasting glucose, creatinine, ferritin, serum iron, total iron binding capacity (TIBC) were studied by standard laboratory method. The NTBI was assessed commercially available kits from Aferrix Ltd in Tel Aviv, Israel. A test result of 0.6 units of LPI or more indicates a potential for iron-mediated production of reactive oxygen species in the sample. Results Patients with LPI units ≥ 0.6 had higher serum iron, erythropoiesis stimulating agents (ESA) dose, ferritin, high-sensitivity C-reactive protein (hsCRP), hepcidin and lower hemojuvelin. In hemodialyzed patients NTBI correlated with hsCRP (r = 0.37, p < 0.01), ferritin (r = 0.41, p < 0.001), IL-6 (r = 0.43, p < 0.001). In multivariate analysis predictors of NTBI were hemoglobin and alkaline phosphatase, explaining 58% of the variability Conclusions Elevated NTBI in HD may be due to disturbed iron metabolism. Anemia and liver function might also contribute to the presence of NTBI in this population.

Long-term cholecalciferol administration in hemodialysis patients: a single-center randomized pilot study.

Background Data on the potent pleiotropic extraskeletal effects of vitamin D have renewed interest in its use in selected populations, including patients with chronic kidney disease, but the available data are still insufficient to make recommendations. This study assessed the long-term effect of small cholecalciferol doses on serum vitamin D, parathormone (PTH), and bone mineral density (BMD) in hemodialysis patients. Material/Methods Nineteen patients with serum 25(OH)D <20 ng/mL were randomized into cholecalciferol (2000 IU 3×/week) and no-treatment groups, then observed for 1 year. Patients with hypercalcemia, hyperphosphatemia, and receiving vitamin D/calcimimetics were excluded. Serum 25(OH)D, 1,25(OH)2D, PTH, and alkaline phosphatase activity were examined every 2 months and BMD was measured before and after the study. Results We observed normalization of serum 25(OH)D with an increase in medians from 11.3 to 44.9 ng/mL (P=0.02) in the cholecalciferol group and no change in the controls (P<0.001). Simultaneously, median serum 1,25(OH)2D increased from 18.2 to 43.1 pmol/L (P=0.02) in the cholecalciferol group and from 10.6 to 21.2 pmol/L (P=0.02) in controls (P=0.013). The treatment was associated with a small increase in serum calcium, but serum phosphate, PTH, alkaline phosphatase, and BMD remained unchanged in both groups. Conclusions Oral cholecalciferol at a dose of 2000 IU/3×/week is an effective and safe way to treat vitamin D deficiency in hemodialysis patients, leading to a significant increase in serum 1,25(OH)2D. However, it was insufficient to suppress the activity of parathyroid glands or to significantly change BMD.

Netrin-1 and Semaphorin 3A Predict the Development of Acute Kidney Injury in Liver Transplant Patients

Acute kidney injury (AKI) is a serious complication after liver transplantation. Currently there are no validated biomarkers available for early diagnosis of AKI. The current study was carried out to determine the usefulness of the recently identified biomarkers netrin-1 and semaphorin 3A in predicting AKI in liver transplant patients. A total of 63 patients’ samples were collected and analyzed. AKI was detected at 48 hours after liver transplantation using serum creatinine as a marker. In contrast, urine netrin-1 (897.8±112.4 pg/mg creatinine), semaphorin 3A (847.9±93.3 pg/mg creatinine) and NGAL (2172.2±378.1 ng/mg creatinine) levels were increased significantly and peaked at 2 hours after liver transplantation but were no longer significantly elevated at 6 hours after transplantation. The predictive power of netrin-1, as demonstrated by the area under the receiver-operating characteristic curve for diagnosis of AKI at 2, 6, and 24 hours after liver transplantation was 0.66, 0.57 and 0.59, respectively. The area under the curve for diagnosis of AKI was 0.63 and 0.65 for semaphorin 3A and NGAL at 2 hr respectively. Combined analysis of two or more biomarkers for simultaneous occurrence in urine did not improve the AUC for the prediction of AKI whereas the AUC was improved significantly (0.732) only when at least 1 of the 3 biomarkers in urine was positive for predicting AKI. Adjusting for BMI, all three biomarkers at 2 hours remained independent predictors of AKI with an odds ratio of 1.003 (95% confidence interval: 1.000 to 1.006; P = 0.0364). These studies demonstrate that semaphorin 3A and netrin-1 can be useful early diagnostic biomarkers of AKI after liver transplantation.

Renal Support During Liver Transplantation: When to Consider It?

Patients undergoing orthotopic liver transplantation constitute a difficult-to-treat population. They often have multiorgan dysfunction: acute kidney injury, severe water-electrolyte and acid-base imbalances, systemic inflammatory responses, thrombocytopenia, as well as abnormalities of coagulation and fibrinolysis. All of these disorders may be further exacerbated by the surgical procedure, which is lengthy and technically complex, requiring massive blood product and other fluid infusions with a high risk to develop severe lactic acidosis, hyperkalemia, or cerebral edema. These considerations provide a rationale to institute intraoperative renal replacement therapy (ioRRT), at least for the most critically ill, namely, patients with kidney dysfunction, or those in whom one anticipates intraoperative clinical and technical problems. This article discusses the most common indications and strategies for ioRRT, examining their advantages and disadvantages as well as current experiences.

Biomedical monitoring of phosphate removal by hemodialysis.

A compact flow analysis system for non-invasive, dialysate-side monitoring of phosphate removal in the course of clinical hemodialysis treatment is presented. The monitor is based on solenoid operated micro-pumps and extremely cheap optoelectronic flow-through detector allowing photometric determination of phosphate in spent dialysate using a molybdenum blue method. The monitor can operate in both, discrete and continuous modes of measurement. The analytical utility of monitor has been tested with samples of spent dialysate produced by artificial kidney in the course of real hemodialysis sessions. The results of monitoring are comparable with those obtained using reference off-line method recommended for clinical analysis. Additionally, the possibility of two-side (dialysate and blood) monitoring of hemodialysis treatments with optoelectronic flow-through detectors has been announced.

The growth of acute kidney injury: Eastern European perspective.

To the Editor: We read with much interest an excellent and thorough review published in the January issue of Kidney International by Siew and Davenport on an alarming increase in incidence of acute kidney injury (AKI) in North America and Western Europe.1 The question asked by the Authors, namely whether these changes reflect the real rise or are rather driven by better diagnostics, reimbursement issues, and a more liberal use of dialysis, seems to be crucial and should prompt future well-designed studies. Therefore, we would like to share our experience. Recently, we retrospectively analyzed the data obtained from individual hospital records of 774 consecutive patients with AKI, as defined by KDIGO criteria,2 requiring dialysis (AKI-D) in our single university hospital between Jan 2005 and Dec 2009. A subgroup of 126 patients, residents of three identifiable districts of Warsaw covered by the hospital with an estimated adult population of 149,687, were isolated to count the incidence.