Anna V. Oláh

Cystatin C is a suitable marker of glomerular function in children with cancer

Antineoplastic chemotherapy is associated with nephrotoxic side effects. Data on nephrotoxicity in childhood cancer are scanty, in part because of the difficulties in obtaining reliable markers of glomerular function. We used serum cystatin C (cysC) to assess glomerular function. CysC was compared with serum creatinine concentration (SCr), the endogenous creatinine clearence ( C Cr), and the calculated Counahan formula ( C Counahan) in children with leukemia and solid tumors. CysC was measured by particle-enhanced immunoturbidimetric assay. Serum and urinary creatinine concentrations were determined by the Jaffé method. Samples were obtained from 258 children, including 92 receiving anticancer chemotherapy, 108 long-term survivors, 40 children without any renal disease, and 18 patients with chronic renal insufficiency. CysC of patients on current chemotherapy was assessed both before and after treatment. Significant correlations were found between cysC and SCr and between 1/cysC and C Counahan. CysC increased significantly after cisplatin, methotrexate, cyclophosphamide, ifosfamide, and multimodality treatment. Our results suggest that cysC measurement can be used to characterize glomerular function in children with cancer.

Late effects on renal glomerular and tubular function in childhood cancer survivors

Late nephrotoxicity among childhood cancer survivors is poorly documented.

The influence of intraoperative complications on adhesion formation during laparoscopic and conventional cholecystectomy in an animal model

BackgroundThe aim of this study was to evaluate the extent of postoperative adhesion formation after laparoscopic and open cholecystectomy.Materials and methodsQualified surgeons performed 60 experimental laparoscopic cholecystectomies (LC) in dogs with the aim to acquire the laparoscopic technique. To assess the relation between the complications during the operation (bleeding, laceration of the liver bed, or gallbladder perforation) and the formation of adhesions, surviving animals were divided into four groups according to the type of complication occurred. Assessment of the results was made by second-look laparoscopy 4 weeks after LC using the adhesion index (AI; score range, 0–4). The animals then were killed so the extent of adhesion formation could be measured. As a control, open cholecystectomy was performed in 15 dogs without intraoperative complications. The Mann-Whitney rank-sum test and Dunn’s method were used for statistical analysis.ResultsNo adhesion formation or intraoperative complications were registered in the laparoscopic group I. In all the cases wherein bleeding or laceration of the liver bed occurred and was managed with electrocoagulation, adhesions formed. Adhesion formation in these groups was significantly higher than in “ideal LC” or cases of gallbladder perforation alone (p<0.01). All the animals in the control group developed significantly more adhesions than those in the experimental group (p<0.05).ConclusionsIt seems that LC has a lower rate of adhesion formation than the conventional open technique. Complications such as bleeding or laceration of the liver bed during LC can enhance adhesion formation. No adhesion formation can be mentioned in relation to gallbladder perforation during LC.

Rosuvastatin improves impaired endothelial function, lowers high sensitivity CRP, complement and immuncomplex production in patients with systemic sclerosis - a prospective case-series study

IntroductionWe studied the effect of rosuvastatin on endothelial and macrovascular function, cardiovascular risk factors and the complement pathway in patients with systemic sclerosis (SSc).MethodsAltogether 28 patients with SSc underwent laboratory and complex vascular assessments before and after six months of 20 mg rosuvastatin treatment. Flow-mediated dilation (FMD) of the brachial artery, as well as carotid artery intima-media thickness (ccIMT), carotid-femoral and aorto-femoral pulse wave-velocity (PWV) were analyzed by ECG-synchronized ultrasound. Ankle-brachial index (ABI) was determined by Doppler, and forearm skin microcirculation was assessed by Laser Doppler perfusion monitoring.ResultsBrachial artery FMD significantly improved upon rosuvastatin therapy (2.2% ± 3.3% before versus 5.7% ± 3.9% after treatment, P = 0.0002). With regard to patient subsets, FMD significantly improved in the 21 lcSSc patients (from 2.1% to 5.6%, P = 0.001). In the seven dcSSc patients, we observed a tendency of improvement in FMD (from 3% to 6%, P = 0.25). Changes in PWV, ccIMT and ABI were not significant. Mean triglyceride (1.7 ± 0.97 versus 1.3 ± 0.46 mmol/l, P = 0.0004), total cholesterol (5.3 ± 1.6 mmol/l versus 4.2 ± 1.3 mmol/l, P = 0.0003), low density lipoprotein cholesterol (3.0 ± 1.3 versus 2.2 ± 1.0 mmol/l, P = 0.005) and C-reactive protein levels (CRP) (5.1 ± 5.2 versus 3.4 ± 2.7, P = 0.01) levels significantly decreased after rosuvastatin treatment. Mean C3, C4 and IC levels also decreased significantly as compared to pretreatment values.ConclusionsSix-month rosuvastatin therapy improves endothelial function and lowers CRP, C3, C4 and IC levels indicating possible favourable effects of this statin on the cardiovascular and immune system in SSc.

Anthracycline antibiotics induce acute renal tubular toxicity in children with cancer

Experimental evidence suggests that anthracyclines, widely used in cancer chemotherapy, may impair kidney function. We assessed kidney function by serum creatinine, urinary N-acetyl-β-D-glucosaminidase activity indices (NAGi) and microalbuminuria (MA) in 160 serum and urine samples obtained from 66 children with cancer. The effect of dexrazoxane was analyzed in 6 children on dexrazoxane supportive therapy in conjunction with daunorubicin (DNR) treatment, as compared with 6 children not receiving this agent. NAG; was significantly (p<0.05) elevated after treatment by DNR, doxorubicin, epirubicin (EPI) and idarubicin (IDA). MA proved to be a less sensitive indicator of kidney damage than NAGL DNR resulted in a progressive deterioration of proximal tubular function as determined by linear regression analysis. The mean NAG1 in the dexrazoxanetreated group was significantly (p<0.005) lower than in children not receiving dexrazoxane prior to DNR treatment. In conclusion, our study demonstrated that DNR, EPI and IDA induced an acute renal tubular damage similar to known tubulotoxic agents as cisplatin, carboplatin, cyclophosphamide and ifosfamide. The damage was clinically mild and only a minor proportion of patients can be expected to develop long-lasting tubulopathy with negative impact on the quality of life.

Urinary N-acetyl-β-d-glucosaminidase in epileptic children treated with antiepileptic drugs

AIM To investigate the effect of prolonged use of antiepileptic drugs on renal function in children. METHODS Prospective study of 72 children (aged 3–18 years) with epilepsy, on either monotherapy (n = 44) or combined therapy (n = 28). The length of treatment varied from 1 to 13 years. Drugs used were valproic acid, carbamazepine, ethosuximide, clonazepam, clobazepam, and vigabatrin. RESULTS In 65 patients plasma concentrations of the drugs were in the therapeutic range. In the remaining seven, plasma concentrations were slightly high. In 33 patients urinary N-acetyl-β-d-glucosaminidase (NAG) activity was raised. The incidence of pathological NAG indices was significantly higher in the combined therapy group than in the monotherapy group. There were also significant differences in the NAG indices of patients depending on the duration of therapy. CONCLUSIONS Results suggest that chronic use of some antiepileptic drugs—in spite of normal blood concentrations—may alter tubular function, and the dysfunction may result in clinical symptoms. Therefore, we recommend screening of tubular function in these patients.

Mutational Spectrum of Smith-Lemli-Opitz Syndrome Patients in Hungary

Smith-Lemli-Opitz (SLO) syndrome is an autosomal recessive disorder characterized by multiple congenital abnormalities and mental retardation. The condition is caused by the deficiency of 7-dehydrocholesterol reductase (DHCR7) which catalyzes the final step in cholesterol biosynthesis. Biochemical diagnosis is based on increased concentration of 7-dehydrocholesterol (7-DHC) in the patient serum. Both life expectancy and quality of life are severely affected by the disease. The estimated prevalence of SLO syndrome ranges between 1:20,000 and 1:40,000 among Caucasians. Although the mutational spectrum of the disease is wide, approximately 10 mutations are responsible for more than 80% of the cases. These mutations show a large interethnic variability. There are no mutation distribution data from Hungary to date. Thirteen patients were diagnosed with SLO syndrome in our laboratory. As first-line tests, serum 7-DHC and total cholesterol were measured and, in positive cases, molecular genetic analysis of the DHCR7 gene was performed. Complete genetic background of the disease could be identified in 12 cases. In 1 case only 1 mutation was detected in a heterozygote form. One patient was homozygous for the common splice site mutation c.964–1G>C, while all other patients were compound heterozygotes. One novel missense mutation, c.374A>G (p.Tyr125Cys) was identified.

Urinary Homogentisic Acid in Alkaptonuric and Healthy Children

Abstract To detect and follow-up the metabolic status of patients with alkaptonuria (AKU), urinary homogentisic acid (HGA) was measured by gas chromatography. These results were close to values we obtained by colorimetric method (linearity: up to 700 mg/l, detection limit: 1 mg/l, within-run imprecision (CV): 1.2% at 100 mg/l HGA, 4.9% at 10 mg/l, between-run CV: 6.8% at 100 mg/l). To determine urinary reference ranges of HGA, 84 healthy children (age: 2months–18 years) were divided into five age groups. HGA and creatinine were measured in their morning urine. Statistical analysis proved that urinary HGA/creatinine ratio is age-dependent. The ratio is relatively high between 1 and 6 years of age, with large scatter (upper limit of reference ranges given as mean + 2 SD: 5.5–7.2 mg/mmol = 0.03–0.04 mmol/mmol creatinine), and it decreases with age. Approximately at the age of 7 years, HGA/creatinine ratio becomes constant, and later it is similar to the adult value (upper limit: 2.8 mg/mmol = 0.017 mmol/mmol creatinine). We monitored a patient during her 1–5th year of life, and her urinary HGA was 80–200 times higher than the upper limit of the age-matched reference ranges. The measurement of HGA supports the decision for starting restricted protein diet and is useful for the evaluation of the effectiveness of therapy.

The epidemic of chronic kidney disease requires the estimation of glomerular filtration rate

Nowadays chronic kidney disease has become a major public health problem due to the great increase in atherogenic nephropathies. In the absence of classic renal symptoms, chronic kidney disease is mostly diagnosed when renal failure is already advanced, although it can be revealed by laboratory tests in the earlier stages. When diagnosis is late, the progression to end-stage renal failure is unavoidable and renal replacement therapy is needed. Even early-moderate renal failure significantly increases the risks for atherosclerosis, thereby leading to the deaths of patients from cardiovascular disease before initiation of dialysis. Therefore screening for asymptomatic chronic kidney disease is urgently needed. Estimated glomerular filtration rate has the greatest importance in the screening and in the timely intervention to slow down the progression of renal failure and cardiovascular disease. In 2005, the Hungarian Society of Nephrologists and the Hungarian Society of Laboratory Medicine suggested the automatic estimation and reporting of glomerular filtration rate, each time serum creatinine measurements were made. This practice is used more frequently by laboratories in Hungary. This article aims to help facilitate the utilization and evaluation of estimated glomerular filtration rate.

Identification of sulfhemoglobinemia after surgical polypectomy

Sulfhemoglobinemia (SHb) is an uncommon cause of cyanosis that is predominantly drug-induced in adults. We report an unusual case of sodium sulfate-induced sulfhemoglobinemia in a 61-year-old woman after surgical polypectomy. Fractional hemoglobin derivates were assayed by spectrophotometry and high-performance liquid chromatography. The SHb ratio was 8.6% in the first sample and 3.77% a month later measured by spectrophotometry. In the blood hemolysate, a new peak was identified as SHb with high-performance liquid chromatography (HPLC). HPLC showed the presence of 9.37% SHb in the first sample and 4.88% a month later. After removing the suspected toxic agent the cyanosis decreased significantly. The findings underline the importance of routine SHb detection in cyanosis of unknown origin especially in emergency cases.