The most common indications for measuring metanephrine and normetanephrine in plasma - a rational approach.

Aim To determine the most common indications for measuring metanephrine and normetanephrine in plasma by gender and age and to compare the concentrations of metanephrine and normetanephrine by indication, gender and age. Methods The study was conducted on 224 patients whose plasma metanephrine and normetanephrine concentrations were measured at the Clinical Institute for Laboratory Diagnostics at the University Hospital Centre Osijek for one year, until 1st January 2020. Results The most frequent indications for biochemical testing were adrenal incidentaloma, 138 (6.6 %), and symptoms of pheochromocytoma, 41 (18.3%). Metanephrine concentration was lower in females (p=0.009). No significant correlation was found between age and metanephrine concentration, while age and normetanephrine concentration were positively correlated (p=0.01). Of the 224 patients, only one patient was diagnosed with pheochromocytoma, whose indication for measurement of metanephrine and normetanephrine was adrenal incidentaloma. Conclusion Adrenal incidentalomas and symptoms suggestive of pheochromocytoma are very common in the general population, while the incidence of pheochromocytoma is extremely low. Clear guidelines for the referral of patients for biochemical testing are needed to avoid unnecessary costs and to identify the correct diagnosis promptly.

Hospitalization and death after recovery from acute COVID-19 among renal transplant recipients.

INTRODUCTION: Data on post-COVID-19 in renal transplant recipients (RTR) is scarce. We investigated the rate of hospitalizations, reasons for hospital admission, and mortality rate among RTR who survived acute COVID-19. METHODS: A multi-center retrospective observational cohort study measured hospital admission and death to 180 days after acute SARS-CoV-2 infection in 308 adult patients. RESULTS: The median age was 57 years, 64.9% were male. All patients had at least one comorbidity, and 26.3% had diabetes. Data on post-COVID-19 course was available for 267 patients, and 49 of them (15.9%) required hospital treatment after recovery from the acute infection. The most common indications included pneumonia (24.5%) and renal allograft dysfunction (22.4%), 7 (14.3%) had sepsis and 5 (10.2%) had thrombotic events. A median duration of the hospital stay was 12 days. Six patients (2.2%) died due to multiorgan failure, respiratory insufficiency or urosepsis. The strongest predictor for hospitalization after acute COVID-19 was hospitalization for acute SARS-CoV-2 infection, while better allograft function decreased the probability of hospitalization. CONCLUSION: Delayed consequences of acute COVID-19 are highly prevalent and the health care systems should be prepared to respond to the needs of RTR suffering from post-COVID-19 complications.

Angiotensin II type 1 receptor is involved in flow-induced vasomotor responses of isolated middle cerebral arteries: role of oxidative stress.

This study aimed to determine the mechanosensing role of angiotensin II type 1 receptor (AT1R) in flow-induced dilation (FID) and oxidative stress production in middle cerebral arteries (MCA) of Sprague-Dawley rats. Eleven-week old, healthy male Sprague-Dawley rats on a standard diet were given the AT1R blocker losartan (1 mg/mL) in drinking water (losartan group) or tap water (control group) ad libitum for 7 days. Blockade of AT1R attenuated FID and acetylcholine-induced dilation was compared with control group. Nitric oxide (NO) synthase inhibitor Nω-nitro-l-arginine methyl ester (l-NAME) and cyclooxygenase inhibitor indomethacin (Indo) significantly reduced FID in control group. The attenuated FID in losartan group was further reduced by Indo only at Δ100 mmHg, whereas l-NAME had no effect. In losartan group, Tempol (a superoxide scavenger) restored dilatation, whereas Tempol + l-NAME together significantly reduced FID compared with restored dilatation with Tempol alone. Direct fluorescence measurements of NO and reactive oxygen species (ROS) production in MCA, in no-flow conditions revealed significantly reduced vascular NO levels with AT1R blockade compared with control group, whereas in flow condition increased the NO and ROS production in losartan group and had no effect in the control group. In losartan group, Tempol decreased ROS production in both no-flow and flow conditions. AT1R blockade elicited increased serum concentrations of ANG II, 8-iso-PGF2α, and TBARS, and decreased antioxidant enzyme activity (SOD and CAT). These results suggest that in small isolated cerebral arteries: 1) AT1 receptor maintains dilations in physiological conditions; 2) AT1R blockade leads to increased vascular and systemic oxidative stress, which underlies impaired FID.NEW & NOTEWORTHY The AT1R blockade impaired the endothelium-dependent, both flow- and acetylcholine-induced dilations of MCA by decreasing vascular NO production and increasing the level of vascular and systemic oxidative stress, whereas it mildly influenced the vascular wall inflammatory phenotype, but had no effect on the systemic inflammatory response. Our data provide functional and molecular evidence for an important role of AT1 receptor activation in physiological conditions, suggesting that AT1 receptors have multiple biological functions.

PERIODONTAL DISEASE IN DIFFERENT STAGES OF CHRONIC KIDNEY DISEASE.

Periodontal disease is a chronic multifactorial disease the worldwide incidence of which is higher than the incidence of caries and represents one of the leading problems in dental medicine. It is manifested by the loss of the attachment apparatus of the tooth and leads to the loss of teeth. Numerous studies have shown the association of periodontal disease and various chronic systemic diseases such as diabetes mellitus and cardiovascular disease. It is believed that low-grade level of chronic inflammation and release of bacterial toxins and inflammatory mediators in the bloodstream aggravate a chronic systemic disease. The purpose of our research was to investigate the possible association of periodontal disease and chronic kidney disease via the inflammatory cytokines path. In this cross-sectional study, we surveyed a total of 80 subjects divided into two groups. First group included subjects with chronic renal disease stages III and IV, and the second group included patients with chronic renal disease stage V that were on hemodialysis. We compared periodontal status, as well as serum levels of different cytokines, interleukin 6, interleukin 17A and tumor necrosis factor α between the two groups. The results showed no significant between-group differences in periodontal status, but interleukin 6 levels were significantly higher in the hemodialysis group of patients and were also associated with a poorer periodontal status.

Bone fragility fractures in hemodialysis patients: Croatian surveys.

Disturbances of bone mineral metabolism are common complications of chronic kidney disease with bone fractures as one of the most important consequences. The aim of this study was to estimate prevalence of bone fractures among Croatian hemodialysis patients and to determine the possible fracture risk. The study was carried out in 767 hemodialysis patients from nine Croatian hemodialysis centers. Demographic, laboratory and bone fracture data were collected from medical records as well as therapy with vitamin D analogs. Fragility fractures were defined according to the World Health Organization definition. In 31 patient a total of 36 fractures were recorded. The prevalence of patients with bone fractures was 4.0%. The mean age of patients with fractures was 68.6 years. There were 9 male and 22 female patients with frac- tures. The mean hemodialysis duration was 63.3 months. Among all fractures the most common were hip fractures (39%) followed by forearm fractures (22%). This is the first study regarding epidemiology of bone fractures in Croatian hemodialysis patients. The prevalence of patients with bone fractures in our group of hemodialysis patients is high. Fractures were more frequent among women and older patients, patients who have been longer on dialysis and in patients with higher concentration of PTH.

[Cystine urolithiasis: recommendations for diagnosis, treatment and recurrence prevention]. / Cistinska urolitijaza: preporuke za dijagnostiku, lijecenje i prevenciju recidiva.

Cystine lithiasis is a diagnostic and therapeutic challenge. This consensus document has outgrown of discussion of experts in nephrology and urology. It is our hope that this document will be of use for all physicians who are facing this disturbing type of urolithiasis. So far, in our national literature there have been no comprehensive documents dealing with this entity and we believe that not only nephrologists and urologists will benefit, but also specialists in internal medicine and general practitioners.

[Malignant disease in potential renal transplant recipients--diagnostic and therapeutic chalenge]. / Zlocudna bolest u potencijalnog primatelja bubrega--dijagnosticki i terapijski izazov.

Renal transplantation is the treatment of choice for many patients with end-stage renal disease. There are a few generally accepted contraindications to transplantation: active infection, malignancy, substance abuse or non-adherence to therapy, chronic illness with life expectancy of less than one year, and poorly controlled psychosis. Potential renal transplant candidates must undergo thorough screening for exclusion of malignant diseases, with an individual approach to each patient. Patients with a history of malignancy might be placed on the waiting list for renal transplantation after a waiting period, which depends on the type of tumor and individual patient characteristics, and there are no signs of tumor. This group of patients require careful surveillance during the waiting time, as well as after transplantation.

Sensorineural hearing loss in hemodialysis patients.

Chronic renal failure affects all organ systems. Senses are not exception and hearing impairment is common, particularly sensorineural hearing loss (SNHL). The term SNOS of unknown origin or uremic deafness is related to only a smaller part of the cases with unclear etiology of the impairment. The study searched for SNOS in 66 chronic hemodialysis (HD) patients, mean age 51.50 +/- 12.70 years. They were treated by HD for 69.70 +/- 53.80 months. The relation between the severity of the impairment and the patients' age, duration of HD treatment (months) and a set of laboratory parameters typical for chronic HD patients was examined. The aim of the study was to detect potential causes of the impairment. The increased hearing threshold (HT) of above 20 dB for all frequencies was found in 42 patients (mean HT 26 +/- 10.50 dB), for speaking area frequencies in 22 patients (mean HT 19.70 +/- 8.80 dB), and in 56 patients for high frequencies (mean HT 41.70 +/- 19.70 dB). The significant positive correlation of HT was found only with the patients' age (r = 0.49, p < 0.01). The patients older than 45 years had higher mean HT than those younger, and those older than 65 also had higher HT than the younger ones. Patients with pathological value of HT were significantly more common among the older subgroup of patients, when divided according to the age at both cutoff values of 45 and of 60 years. Mean HT did not differ significantly according to the duration of HD treatment (subgroups A- no longer than 60 months, B- from 61 to 120 months, and C- longer than 120 months). The patients with pathological HT did not differ significantly in frequency among those subgroups, and the subgroups were not different according to the mean age (A--50.30 +/- 13.20 years; B--51.40 +/- 12.75 years; C--55.80 +/- 10.55 years). In conclusion, our results along with other authors'published data report on SNHL as very frequent finding among chronic HD patients and suggest multifactorial etiology. Accurate proportion of those with SNHL of unknown origin is not possible to determine. Those cases are probably not caused by uremic polyneuropathy and/or preterm vascular aging only, although those factors are likely to play crucial roles.

Are lipoprotein disturbances in chronic hemodialyzed patients only renal failure related?

Chronically hemodialyzed (HD) patients frequently suffer from quantitative and even more often qualitative serum lipids disorders. Mostly they have increased triglycerides and VLDL-cholesterol, slightly increased or normal total and LDL-cholesterol and decreased HDL-cholesterol concentrations. The study compared lipid profile between two groups of chronic HD patients coming from regionally distinct areas, the continental and the maritime one. The aim was to examine the hypothetic influence of their different dietary habits on lipid profile. The study included 72 patients from continental region (39 men) and 50 from maritime part of the country (30 men). Patients suffering from diabetes mellitus, hypothyroidism, liver disease, alcoholics as well as sevelamer treated patients were not included. Prior to a HD session the patients were determined fasting total cholesterol, triglycerides, HDL- and LDL-cholesterol, total proteins, albumins and C-reactive protein serum concentrations. All patients were undergoing bicarbonate hemodialysis with polysulphone dialysers of low permeability. The continental group of patients were somewhat older, undergoing HD for longer period of time, of lower height, greater weight, greater body mass index, higher total (4.70 +/- 0.91:4.42 +/- 1.02 mmol/L), and LDL-cholesterol (2.78 +/- 0.74:2.66 +/- 0.75 mmol/L) concentrations, while lower triglycerides (1.72 +/- 0.84:1.81 +/- 0.83 mmol/L) and HDL-cholesterol (1.13 +/- 0.42:1.16 +/- 0.54 mmol/L). However all the differences were without statistical significance. Chi-square test showed that the continental group of patients consumed more often pork, bacon, smoked and cured meats, margarine, butter, walnuts, almonds, garlic, cream and full-fat cheese than fish. They prepare food more often with lard and sunflower oil. Almost every fourth continental patient received statins, while only every 25th in the maritime group of patients. There were not any statistically significant Chi-square values for differences in frequencies of patients with total cholesterol greater than 5.2 mmol/L, triglycerides above 1.6 mmol/L, HDL-cholesterol less than 1.1 mmol/L, LDL-cholesterol greater than 2.6 mmol/L, obesity and malnutrition between the two groups. Based on the results of this study we have concluded that diet has significant influence on lipid profile of HD patients. Even though the continental and the maritime groups of patients differed significantly in diet, they were similar in plasmatic lipoprotein concentrations. However, this similarity was ascribed only to statin treatment, which was more frequent in the continental group of patients. The influence of ESRD and HD as a method of renal replacement therapy on lipid profile was not more dominant than diet.

[Diabetic nephropathy and prevention of diabetic nephropathy caused chronic renal insufficiency]. / Dijabeticka nefropatija i prevencija kronicnog bubreznog zatajenja uzrokovanog dijabetickom nefropatijom.

There is an ongoing trend of a rapid increment in the frequency of diabetes mellitus, expecially the non-insulin dependent form. By the end of the 2nd millenium 150 million cases were recorded worldwide, while the estimations predicted doubling the number by the year 2030. Numerous chronic complications accompany the disease, among them micro-, as well as macrovascular prevail, affecting small and large blood vessels. This paper provides a literature review on the topic of diabetic nephropathy, the main microvascular complication of diabetic disease. Microalbuminuria is the earliest sign of the diabetic renal involvement, with more than 30 mg and less than 300 mg of albumins in 24 h urine sample. The reduction of renal function begins with albuminuria leaving microalbuminuria level and entering the pathologic proteinuria range. Renal failure advances through the 5 stages, the final fifth occurring fortunately only in a minor proportion of the patients. The final stage ensues in 232 of 100 000 diabetic patients, according to the US data. However, in many developed countries there are 30-40% of new patients entering chronic dialysis treatment for diabetic nephropathy. Pathogenesis of diabetic nephropathy is based on hyperglycemia and distinct hemodynamic changes, glomerular hyperfiltration and high intraglomerular pressure. The important role have oxidative stress, advanced glycation end products, some cytokines, growth factors and sorbitol pathway. Nevertheless, genetic influence is considered by far the most important risk factor for diabetic nephropathy. Heritage determines the susceptibility in one and the protection in another diabetic patient. At the moment of pathologic proteinuria occurrence, glomerular filtration rate begins to decline for 1.2 ml/min/monthly in some patients, making the annual reduction of 7-14 ml/min/1.73 m2 of body surface area. Improving glycemia, blood pressure control, renal anemia correction with rHu-Epo, dyslipidemia control, reduction in protein intake, i.e. management of the nongenetic factors, could slower the renal function loss in some of the patients. Hence, these measures could reduce the proportion of the patients reaching end-stage renal disease, having in mind that morphological and functional changes are reversible only within certain limits. Therefore, the success of kidney protection is better if commenced earlier.

[Correlation between children's weight and height at medical examination on enrolling in 1st class of primary school and birth growth parameters with parental heights]. / Korelacije tjelesne visine i tezine djece pri upisu u 1. razred Osnovne skole i pokazatelja rasta djece pri rodenju s tjelesnom visinom roditelja.

Physical growth is permanently influenced by genetic and environmental factors. Their impacts are overlapping, and therefore it is difficult to separate the contribution particularly ascribable to one or another kind of the factors. The study investigated the relation between body weight and height in 397 children (195 girls and 202 boys) enrolling primary school and their birth growth features on the one side, and their parents' heights on the other. The correlations between children's weight and height on enrolling primary school and their birth growth features were also studied. The aim was to examine the proportion of genetic determinacy of children's growth. Mean birth weight and length were 3440 +/- 413 g and 50.50 +/- 2.00 cm, respectively, and mean head circumference was 34.50 +/- 1.20 cm. On entering the primary school, the children were 6.70 +/- 0.30 years of age in average, and had mean body weight and height of 24.60 +/- 5.00 kg and 122.70 +/- 6.15 cm, respectively. Majority of children had both parents with middle or low education level, 285 (71.79%) of them. Majority of children also had both parents employed. 266 (67.00%) of them. Children's height on enrolling the school was in significant positive correlation with birth weight, length and head circumference, and with parents' heights. The correlation coefficient was the highest with father's height (r=0.473, p<0.01), and the lowest with birth weight (r=0.158, p<0.05). Children's weight on enrolling the school significantly positively correlated with the three birth growth features and with father's height, but not with mother's height (r=0.091, p>0.05). The correlation coefficient was the highest for father's height (r=0.288, p<0.01) again. All the birth parameters correlated stronger with mother's than with father's height. In the subgroup of children whose mothers were of equal or greater height than fathers (n=28), correlation coefficient between children's and fathers' heights (r=0.295, p<0.01) was lower than between children's and mothers' heights (r=0.474, p<0.01). In conclusion, children's weight and height at the time of enrolling primary school significantly positively correlates with their parents' heights. The correlations are stronger with father's height. Though, it is not the matter of gender, but of the higher parent. The birth growth parameters are only in part related to parents' heights (all three with mother's and only one with father's height). It is obvious that mothers' influence is dominant for children's growth at that time. There was no significant difference in any examined parameter between subgroups of children divided according to their parents education level and employment status.

[The impact of glucose absorbed from dialysis solution on body weight gain in peritoneal dialysis treated patients]. / Utjecaj glukoze apsorbirane iz dijalizata na tjelesnu tezinu peritonejskom dijali lijecenih bolesnika.

A proportion of peritoneal dialysis (PD) patients experience substantial body weight (BW) gain with time. It is caused by fat tissue accumulation or fluid retention. It is believed that fat tissue accumulates due to caloric contribution of glucose absorbed from dialysis solution or to the mitochondrial fat regulatory uncoupling protein (UCP) gene polymorphism. This study examined BW fluctuations in 40 patients (24 females, 16 males), treated by PD at least 36 months (initial mean age 54.50+/-9.00 years, mean BW 68.00+/-8.50 kg and mean height 164.00+/-8.50 cm), relation of the BW fluctuation and caloric contribution of glucose absorbed from dialysis solution and characteristics of the patients with BW gain. Initial BW increased after 6, 12, 24 and 36 months by 5.90+/-3.50 kg, 7.90+/-4.90 kg, 9.50+/-5.00 and 11.00+/-5.00 kg, or for 8.68, 11.62, 13.97 and 16.18% of the initial value, respectively. After the first 6 and 12 months 38 patients gained weight, 39 after 24 and all 40 patients after 36 months. There was not significant correlation between BW gain and caloric contribution of glucose absorbed from dialysis solution. Female patients had initially lower BW, but for the first 12 months period significantly increased BW more than males, and not for the other observed periods. High transporters (patients with higher transport, higher transmission of glucose from peritoneal solution into the blood, and urea and creatinine in the opposite direction, with rapid decrement of osmolality gradient between dialysate and blood that is necessary for excessive fluid elimination), had lower initial BW and, although without statistical significance, only within the first period increased BW more than low transporters. In conclusion, with time BW gain was found in all the PD dialysis patients, it was not related to caloric contribution of glucose absorbed from dialysis solution, and women and high transporters increased BW weight more than men and low transporters in the first year of treatment. The BW gain is at least in part caused by fluid retention.

[How much body water volume affects evaluation of urea clearance in patients treated with peritoneal dialysis?]. / Koliko volumen tjelesne vode utjece na procjenu klirensa ureje u bolesnika koji su lijeceni peritonejskom dijalizom?

AIM OF THE STUDY: Peritoneal dialysis adequacy is usually estimated using the ratio of total weekly urea clearance (Kt) and urea distribution volume (V), the later being identical to total body water volume. It is observed that even patients with acceptable Kt/V values sometimes show signs and symptoms of dialysis inadequacy. A question arose whether the discrepancy came from a falsely assessed urea distribution volume, because the less the urea distribution volume measured the higher the Kt/V gained. PATIENTS: The survey included 32 patients (15 women, 17 men) in whom 62 total weekly urea clearances were calculated during a 2-year period. Each Kt was used in 4 different equations (A-Watson's method, B-Hume's method, C-58% of body mass for urea distribution volume, D-for urea distribution volume: 58% of body mass reduced by 2 kg, and then augmented by 2 kg added for dialysate volume assumed). It resulted in 4 different Kt/V for each Kt, i.e. a total of 248 Kt/V values. RESULTS AND DISCUSSION: At the moment of the examination the patients were aged 57.66 +/- 8.66 years, weighted 75.54 +/- 11.04 kg (with dialysate intraperitoneally), and were treated with peritoneal dialysis for a mean of 23.28 +/- 27.55 months. Their mean total weekly urea clearance was 79.94 +/- 12.53 L. Depending on the method used, the mean urea distribution volumes were as follows: A = 37.24 +/- 5.27 L, B = 37.89 +/- 5.22 L, C = 43.81 +/- 6.40 L and D = 44.65 +/- 6.47 L, and mean Kt/V 2.15 +/- 0.32 (A), 2.11 +/- 0.32 (B), 1.82 +/- 0.33 (C) and 1.79 +/- 0.34 (D). The highest mean urea distribution volume (D) was higher than the lowest value (A) by 19.90%, and the difference between those values was statistically significant (tV D: A = 6.99, p < 0.01). The highest mean total weekly Kt/V (A) was higher than the lowest value (D) by 20.11%, and the difference was also significant ((tKt/V A: D = 6.08, p < 0.01). CONCLUSION: The estimation of urea distribution volume has a direct impact on calculation results of total weekly Kt/V in peritoneal dialysis patients. Urea distribution volumes as assessed by the anthropometrical methods or by a certain percentage of body mass were approximate values. We suggest replacing "nondeuterial methods" by deuterial, in order to get more comparable results.

Effects of rHuEPO treatment on red blood cell osmotic resistance.

Red blood cell osmotic resistance (RBCOR) is defined as resistance to osmotic changes in cell integrity after their exposure to hypotonic saline solution. The investigation examined the effect of rHuEPO on RBCOR in hemodialysed patients. The study included 58 patients aged 49 +/- 14 years, treated by hemodialysis for 59 +/- 43 months on average. Half of the patients received rHuEPO for anemia correction. RBCOR was determined in all patients as 3 values: hemolysis start point (HSP), hemolysis end point (HEP) and middle osmotic resistance (MOR). The patients underwent laboratory checkup for parameters characteristically changed in the uremic syndrome. In the control group of healthy subjects (n = 16) RBCOR was only determined. No differences were found in the average values of HSP, HEP and MOR between the rHuEPO treated group of patinets and the untreated group. Compared to healthy individuals, the hemodialysed patients displayed significantly higher values of HSP, HEP and MOR. The only one significant correlation of RBCOR and routine laboratory features was found between MOR and predialytic serum concentrations of calcium (r = 0.28, p < 0.05) and hydrogen ions (r = 0.37, p < 0.05). Our results suggest that the administration of rHuEPO does not affect RBCOR in hemodialysed patients, that RBCOR is not always reduced in this population and that it correlates with a small number of laboratory parameters characteristic for the uremic syndrome.

[Prevalence of gallstones in patients on hemodialysis]. / Prevalencija zucnih kamenaca u hemodijaliziranih bolesnika.

End-stage renal disease affects all organ systems. Nevertheless, frequency of some pathologic conditions does not differ in end-stage renal disease patients in comparison with their age- and sex-matched controls recruited from general population. The paper presents the results of the survey on the prevalence of gallstones in a relatively big group of hemodialysis patients (n = 114; 49 females, 65 males). The goal of the study was to examine whether the genesis of gallstones could be explained by renal failure itself. Gallstones have been found in 24 of 114 hemodialysis patients (21.05%), predominantly females (n = 14). Gallstones have been found in 28.75% of female patients, and in only 15.38% of male patients. The frequency of gallstones correlated significantly with age of the patients (r = 0.26, p < 0.05), number of pregnancies (r = 0.20, p < 0.005) and deliveries (r = 0.22, p < 0.05). Patients suffering from gallstones were significantly older (60.58 +/- 11.99:51.72 +/- 14.01 years, t = 3.10, p < 0.01), with every third older than 54 affected. The results observed do not differ from the results of other authors that report the morbidity in general population. In conclusion, gallstones in hemodialysis patients show same frequency as in general population and probably result from the same pathophysiologic mechanisms.