Malnutrition inflammation score (MIS) is stronger predictor of mortality in hemodialysis patients than waist-to-hip ratio (WHR)-4-year follow-up.

PURPOSE: The main purpose of this study is to correlate the significance of the malnutrition inflammation score (MIS) and the waist-to-hip ratio (WHR) in the prediction of mortality in hemodialysis patients. METHODS: The study was conducted from March 2016 to April 2020, covering 100 hemodialysis patients. Anthropometric measures (Waist circumference (WC), Hip circumference (HC), Waist-to-hip ratio (WHR), Caliper and BMI) and biomarkers of inflammation (IL6, hsCRP) and nutrition (Transfferin, Albumin) were determined and for the above-mentioned biomarkers, we monitored all-cause mortality for 4 years. The hemodialysis patients were divided in three groups based on their MIS score. RESULTS: In this prospective, longitudinal study, we enrolled 100 patients (54 males and 46 females) with a median age of 58 (51-65) years. All patients were divided into three groups according to MIS score values. We performed univariate Cox regression survival analysis for a period of 4 years, and then included for multivariate survival Cox regression analysis well-defined nutritional markers: BMI, mid-arm circumference, WHR and MIS score. The MIS score was demonstrated to be the best independent predictor of 4-year mortality in our study (p < 0.001). CONCLUSION: The results of our study have shown that there is no significance of WHR in the prediction of mortality in hemodialysis patients, but that the MIS score is a strong, independent predictor of all-cause 4-year mortality.

Small Intestine Posttransplant Lymphoproliferative Disorder in a Kidney Transplant Recipient: A Case Report.

Posttransplant lymphoproliferative disorder is a serious, life-threatening complication in organ transplant patients receiving immunosuppressive therapy. Isolated posttransplant lymphoproliferative disorder of the gastrointestinal tract is rare. Posttransplant lymphoproliferative disorder encompasses a spectrum of clinical manifestations, in addition to a wide range of histopathological findings, from B-cell hyperplasia to lymphoma. Renal transplant patients with small intestinal posttransplant lymphoproliferative disorder are more likely to be of younger age, but less frequently represent Hodgkin and Hodgkin-like lesions. They also have better patient survival compared with transplant recipients with posttransplant lymphoproliferative disorder in other locations. We report on the treatment of a kidney transplant recipient with confirmed isolated posttransplant lymphoproliferative disorder in the small intestine. The patient presented with acute abdomen and small intestine perforation, 17 years after kidney transplant, despite being without calcineurin inhibitor in immunosuppressive therapy, to mitigate previous ductal breast carcinoma. Pathological examinations revealed isolated EpsteinBarr virus-positive diffuse large B-cell non-Hodgkin lymphoma of small intestine, clinical stage IV A E. The patient was treated with reduction of immunosuppression, rituximab, and the CHOP regimen (ie, cyclophosphamide, doxorubicin, vincristine, and prednisone). A complete remission was achieved. Kidney allograft function was stable throughout the follow-up period. Physicians should consider isolated gastrointestinal posttransplant lymphoproliferative disorder as a possible etiology in posttransplant, immunocompromised patients who present with different gastrointestinal symptoms. Given good clinical response to treatment, early identification of posttransplant lymphoproliferative disorder has a key role in monitoring and treatment.

Decreased insulin-like growth factor-1 (IGF-1) concentration correlates with reduced left-ventricle ejection fraction (LVEF) in hemodialysis patients.

PURPOSE: The main purpose of this study is to determine the correlation between the serum IGF-1 concentration and certain cardiac indexes in hemodialysis patients. METHODS: The study was conducted at the Clinical Center of Montenegro and three regional hemodialysis centers. The echocardiographic studies were performed the day after the hemodialysis sessions. Blood samples were taken before dialysis for the measurement of IGF1 and PTH. RESULTS: A total of 102 patients were divided into two groups according to their left-ventricular ejection fraction (EF). Patients in the group with the higher EF had higher IGF-1 concentration (p = 0.024). IGF-1 was positively correlated with EF (ρ = 0.251, p = 0.012), and negatively correlated with LVMI (ρ = - 0.621, p < 0.001), SW (ρ = - 0.632, p < 0.001), and LW (ρ = - 0.632, p < 0.001). Multiple linear regression analysis was performed to determine the possible independent association between the EF and IGF-1 and the clinical data. The age of patients, their gender, and smoking habits did not have any combined influence on EF, but IGF-1 had a strong influence and was independently associated with the ejection fraction. CONCLUSION: Our results may indicate the possible protective role of IGF-1 in the maintenance of heart structure and function in hemodialysis patients.

First case of drug-induced liver injury associated with the use of tocilizumab in a patient with COVID-19.

BACKGROUND AND AIMS: Tocilizumab (TCZ; interleukine-6 receptor antagonist) has been proposed to treat severe forms of Coronavirus disease-19 (COVID-19) because interleukine-6 plays an important role in COVID-19-induced cytokine storm. Several clinical studies have shown very good effects of TCZ in patients with COVID-19, with a few minor side effects reported. Only eight serious liver injuries caused by TCZ were reported before being used in the treatment of patients with COVID-19. Considering the significantly increased use of TCZ for the treatment of COVID-19, we would like to warn of its rare but possible serious hepatotoxicity, especially when used together with other hepatotoxic drugs. METHODS: We describe a patient with COVID-19-induced cytokine storm who developed drug-induced liver injury associated with the use of TCZ. RESULTS: One day after TCZ administration, serum transaminase levels increased 40-fold. Nevertheless, TCZ had a positive effect on clinical and laboratory parameters in cytokine storm, with transaminases values normalizing in 10 days. CONCLUSIONS: This is the first reported case of DILI caused by TCZ in a COVID-19 patient. Intensive liver function monitoring is imperative in COVID-19 patients, because of frequent polypharmacy with potentially hepatotoxic drugs.

Cutaneous Manifestations of Tuberous Sclerosis.

Dear Editor, Tuberous sclerosis (TS) is an autosomal dominant multisystem disease, which occurs due to genetically determined hyperplasia of ectodermal and mesodermal cells. Clinical manifestations present on the skin and in the nervous system, kidneys, heart, and other organs. Recent studies estimate the incidence of TS at 1/6000 to 1/10,000 live births, and a prevalence in the general population of approximately 1 in 20,000 (1). There are two different genetic loci responsible for TS: 9q34 (TSC1-hamartin) and 16p13.3 (TSC2-tuberin) (2). Cutaneous manifestations occur in about 96% of patients (3). Neurological disorders occur in 50% of patients in the form of seizures and motor and psychomotor symptomatology (4). A 19-year-old male patient was hospitalized for clinical and diagnostic evaluation in February 2016 year in Clinic for Nephrology, Clinical Center of Montenegro, Podgorica, Montenegro. Polycystic kidney changes were verified by ultrasound when the patient was three years old, with the presence of several calcified nodules in lateral ventricles and supraventricularly in the brain as well as the existence of several hypopigmented maculae on the skin. During the last hospitalization in February 2016, the following tests were performed: cranial magnet resonance imaging (MRI) findings showed the existence of visible changes in the signal in the form of ectopic tuber tissue in the region of the cortex and subcortical white matter of the brain, but without neurological and psychomotor abnormalities; ultrasound of the urinary tract showed that both kidneys were enlarged with multiple cysts, with dominant cysts at the lower pole of the right kidney with a size of 55 mm and at the upper pole of the left kidney, approximately 40 mm. Reduced functional capacity of kidneys was found on dynamic scintigraphy, slightly more in the left kidney (41%) compared with the right (59%). Electroencephalography, X-ray of the lungs and heart, and echocardiography were also performed, but without any pathological findings. Dermatological examination found numerous fibroma up to 0.5 cm in diameter, the largest located nasolabially, periorally, and on the chin skin (Figure 1) at the age of seven, whereas a fibroma and several white maculae were present from birth on the skin of the forehead. They were now also present on the skin of the trunk and on the upper and lower extremities (Figure 2), accompanied by surrounding minor changes in the form of confetti-like maculae. A subungual fibroma was present on the third finger of the right hand. Collagen nevus (shagreen patch) (5), i.e. a subepidermal fibrosis as a mildly elevated, palm-sized area is also characteristic of TS, which is described in literature, in most cases in the lumbosacral region. In our case, such a fibrosis about 3 cm in diameter, and with the consistency of an orange peel, was discovered on the right shoulder. Subungual fibromas (Koenen tumors) (6), which can develop in adolescence, were present in our patient on the third finger of the right hand. The diagnosis of TS was established based on genetic testing, physical examination, ultrasound-verified polycystic kidney disease and reduced global renal functions, intracranial MRI, many hypomelanotic changes, and angiofibromas found with dermatological examination (7). There is no specific therapeutic approach for TS, and the treatment is symptomatic. Angiofibromas of the skin can be removed by dermabrasion or laser. Recent data show a good therapeutic effect of applying 0.1% rapamycin (8), which leads to a reduction of angiofibromas in patients with TS. On dermatological follow up after five weeks of application of tacrolimus, angiofibromas of the face were in regression. Some studies suggest the simultaneous topical applications of both of those drugs (9). In adolescents and adults of reproductive age, genetic counseling is recommended (10).

Renal aspergillosis in a liver transplant patient: A case report and review of literature.

BACKGROUND: Aspergillosis is a frequent invasive fungal infection in liver recipients (affecting 1%-9.2% of all patients), second only to candidiasis. Significant risk factors for invasive aspergillosis in liver recipients include corticosteroid therapy, neutropenia, T-cell dysfunction, renal failure and requirement for renal replacement therapy. Aspergillus infection usually affects the lungs of liver recipients, with hematogenous dissemination occurring in 50%-60% of cases. Renal involvement is rare and is considered to occur in 0.4% of all cases of invasive aspergillosis. CASE SUMMARY: This paper describes a case of a liver recipient presenting with a newly formed renal mass a year after liver transplantation. The patient underwent liver transplantation due to alcoholic liver cirrhosis, with preoperative corticosteroid therapy and postoperative immunosuppressants (tacrolimus and mycophenolate mofetil). His 1-year follow-up was uneventful, with a satisfying graft function and lack of any symptoms. During a routine follow-up abdominal ultrasound, he was diagnosed with a renal tumor. The renal imaging findings were inconclusive (with a differential diagnosis to renal cell carcinoma), while the computed tomography (CT) of the chest showed scar tissue in the lungs suggestive of previous inflammation. The patient underwent radical nephrectomy, with histopathological analysis showing renal aspergilloma, yielding postoperative treatment with voriconazole. His follow up was uneventful, and the chest CT did not show any change in pulmonary lesions. This case illustrates the possibility of aspergillosis affecting the lungs of liver recipients, subsequently affecting the kidney and forming an aspergilloma. CONCLUSION: Clinicians should be aware of aspergilloma mimicking solid organ tumors in organ recipients.

Increased Serum Level of IGF-1 Correlates With Better Cognitive Status in End-Stage Renal Disease Patients Undergoing Hemodialysis.

Prevalence of cognitive function decline in end stage renal disease (ESRD) patients undergoing hemodialysis is higher than in the general population. We analyzed risk factors for cognitive function decline in those patients. This study included 93 ESRD patients undergoing hemodialysis two or three times a week in three centers for hemodialysis in Montenegro. The cognitive status of patients was assessed using the mini mental score examination (MMSE) test. All 93 patients have been divided into three groups according to the results of MMSE. Patients in the first group had severe cognitive impairment and MMSE score below 17 (26.88%), patients in the second group with MMSE score 18-23 had moderate cognitive impairment (40.86%) and third group of patients have MMSE >24 and no cognitive impairment (32.26%). There were no significant differences between groups for gender, smoking habits and level of parathyroid hormone. Level of schooling was significantly different between groups of patients (P < 0.001). Laboratory markers observed in this study with significant differences between groups were: IGF 1, IGFBP 3, erythrocytes and hemoglobin (P < 0.001, P = 0.004, P < 0.001, P = 0.002, respectively). IGF 1 proved to be of great importance for evaluating cognitive status in our study. This marker was statistically different between groups (P < 0.001) and Tukey post hoc analysis showed significant differences between all three groups (first and second group P = 0.045, second and third group P = 0.015, first and third group P < 0.001). Our data suggest that IGF 1 can be considered as novel biomarker for assessment of cognitive functioning in CKD patients, which can be of huge clinical importance.

The European Renal Association - European Dialysis and Transplant Association Registry Annual Report 2014: a summary.

Background: This article summarizes the European Renal Association - European Dialysis and Transplant Association Registry's 2014 annual report. It describes the epidemiology of renal replacement therapy (RRT) for end-stage renal disease (ESRD) in 2014 within 35 countries. Methods: In 2016, the ERA-EDTA Registry received data on patients who in 2014 where undergoing RRT for ESRD, from 51 national or regional renal registries. Thirty-two registries provided individual patient level data and 19 provided aggregated patient level data. The incidence, prevalence and survival probabilities of these patients were determined. Results: In 2014, 70 953 individuals commenced RRT for ESRD, equating to an overall unadjusted incidence rate of 133 per million population (pmp). The incidence ranged by 10-fold; from 23 pmp in the Ukraine to 237 pmp in Portugal. Of the patients commencing RRT, almost two-thirds were men, over half were aged ≥65 years and a quarter had diabetes mellitus as their primary renal diagnosis. By day 91 of commencing RRT, 81% of patients were receiving haemodialysis. On 31 December 2014, 490 743 individuals were receiving RRT for ESRD, equating to an unadjusted prevalence of 924 pmp. This ranged throughout Europe by more than 10-fold, from 157 pmp in the Ukraine to 1794 pmp in Portugal. In 2014, 19 406 kidney transplantations were performed, equating to an overall unadjusted transplant rate of 36 pmp. Again this varied considerably throughout Europe. For patients commencing RRT during 2005-09, the 5-year-adjusted patient survival probabilities on all RRT modalities was 63.3% (95% confidence interval 63.0-63.6). The expected remaining lifetime of a 20- to 24-year-old patient with ESRD receiving dialysis or living with a kidney transplant was 21.9 and 44.0 years, respectively. This was substantially lower than the 61.8 years of expected remaining lifetime of a 20-year-old patient without ESRD.

Prooxidant-antioxidant balance, hsTnI and hsCRP: mortality prediction in haemodialysis patients, two-year follow-up.

Oxidative stress and inflammation are highly intertwined pathophysiological processes. We analyzed the markers of these processes and high-sensitive troponin I (hsTnI) for mortality prediction in patients on haemodialysis. This study enrolled a total of 62 patients on regular haemodialysis. The patients were monitored for two years, and the observed outcomes were all-cause and cardiovascular mortality. Blood samples were taken before one dialysis session for analysis of the baseline concentrations of prooxidant-antioxidant balance (PAB), total antioxidant status (TAS), total oxidative status (TOS), hsTnI, hsCRP and resistin. The overall all-cause mortality was 37.1% and CVD mortality 16.1%. By univariate and multivariate logistic regression, our findings suggest that good predictors of all-cause mortality include hsCRP and PAB (p < .05) and of CVD mortality hsCRP (p < .05) and hsTnI (p < .001). To evaluate the relationship between the combined parameter measurements and all-cause/CVD mortality risk, patients were divided into three groups according to their PAB, hsCRP and hsTnI concentrations. The cutoffs for hsCRP and hsTnI and the median for PAB were used. Kaplan-Meier survival curves pointed out that the highest mortality risk of all-cause mortality was in the group with hsCRP levels above the cutoff and PAB levels above the median (p < .001). The highest risk of CVD mortality was found in the group with hsCRP and hsTnI levels above the cutoff levels (p = .001). Our data suggest that hsCRP and PAB are very good predictors of all-cause mortality. For CVD complications and mortality prediction in HD patients, the most sensitive parameters appear to be hsTnI and hsCRP.

[[GUIDELINES FOR THE PREVENTION, MONITORING AND THERAPY OF CHRONIC KIDNEY DISEASE-METABOLIC BONE DISEASE IN PATIENTS WITH CHRONIC KIDNEY DISEASE].]

Chronic kidney disease (CKD) is a systemic disease with numerous complications associated with increased morbidity and mortality. Chronic kidney disease-metabolic bone disease (CKD-MBD) starts at early stages of CKD with phosphorus accumulation and consequent initiation of numerous events that result with the development of secondary hyperparathyroidism with changes on bones and extraskeletal tissues. The most important and clinically most relevant consequences of CKD-MBD are vascular calcifications which contribute to cardiovascular mortality. Patients with the increased risk for the development of CKD-MBD should be recognized and treated. Prevention is the most important therapeutic option. The first step should be nutritional counseling with vitamin supplementation if necessary and correction of mineral status. Progression of CKD requires more intensive medicamentous treatment with the additional correction of metabolic acidosis and anemia. Renal replacement therapy should be timely initiated, with the adequate dose of dislaysis. Ideally, preemptive renal transplantion should be offered in individuals without contraindication for immunosuppressive therapy.

Renal replacement therapy in Europe: a summary of the 2012 ERA-EDTA Registry Annual Report.

BACKGROUND: This article summarizes the 2012 European Renal Association-European Dialysis and Transplant Association Registry Annual Report (available at www.era-edta-reg.org) with a specific focus on older patients (defined as ≥65 years). METHODS: Data provided by 45 national or regional renal registries in 30 countries in Europe and bordering the Mediterranean Sea were used. Individual patient level data were received from 31 renal registries, whereas 14 renal registries contributed data in an aggregated form. The incidence, prevalence and survival probabilities of patients with end-stage renal disease (ESRD) receiving renal replacement therapy (RRT) and renal transplantation rates for 2012 are presented. RESULTS: In 2012, the overall unadjusted incidence rate of patients with ESRD receiving RRT was 109.6 per million population (pmp) (n = 69 035), ranging from 219.9 pmp in Portugal to 24.2 pmp in Montenegro. The proportion of incident patients ≥75 years varied from 15 to 44% between countries. The overall unadjusted prevalence on 31 December 2012 was 716.7 pmp (n = 451 270), ranging from 1670.2 pmp in Portugal to 146.7 pmp in the Ukraine. The proportion of prevalent patients ≥75 years varied from 11 to 32% between countries. The overall renal transplantation rate in 2012 was 28.3 pmp (n = 15 673), with the highest rate seen in the Spanish region of Catalonia. The proportion of patients ≥65 years receiving a transplant ranged from 0 to 35%. Five-year adjusted survival for all RRT patients was 59.7% (95% confidence interval, CI: 59.3-60.0) which fell to 39.3% (95% CI: 38.7-39.9) in patients 65-74 years and 21.3% (95% CI: 20.8-21.9) in patients ≥75 years.

[Disseminated intravascular coagulation and acute kidney injury requiring renal replacement therapy after diagnostic amniocentesis]. / Diseminirana intravaskularna koagulacija i akutno zatajenje bubrega nakon amniocenteze.

Disseminated intravascular coagulation (DIC) is a very rare complication of amniocentesis. We present a case of a 33-year-old patient who developed DIC with acute respiratory distress syndrome and acute kidney injury after diagnostic amniocentesis. The patient required replacement of renal function for 59 days with continuous venovenous hemodiafiltration and later with hemodialysis. She was treated with heparin, fresh frozen plasma, platelets and cryoprecipitate. Her condition was further complicated with the development of intracranial hematoma. After 67 days of hospitalization, she was discharged from the hospital with serum creatinine 337 µmol/L. Three years later, her serum creatinine was 102 µmol/L, and she is currently in the 7th month of pregnancy.

[Kidney function in a patient with thrombotic thrombocytopenic purpura]. / Bubrezna funkcija bolesnika s trombotickom trombocitopenicnom purpurom.

Thrombotic thrombocytopenic purpura is a systemic disorder with high mortality rate if not treated with plasma exchange. We present a case of severe thrombotic thrombocytopenic purpura diagnosed and treated at Montenegro Clinical Center, with spe- cial reference to the follow-up of renal function.

Renal replacement therapy in Europe: a summary of the 2011 ERA-EDTA Registry Annual Report.

BACKGROUND: This article provides a summary of the 2011 ERA-EDTA Registry Annual Report (available at www.era-edta-reg.org). METHODS: Data on renal replacement therapy (RRT) for end-stage renal disease (ESRD) from national and regional renal registries in 30 countries in Europe and bordering the Mediterranean Sea were used. From 27 registries, individual patient data were received, whereas 17 registries contributed data in aggregated form. We present the incidence and prevalence of RRT, and renal transplant rates in 2011. In addition, survival probabilities and expected remaining lifetimes were calculated for those registries providing individual patient data. RESULTS: The overall unadjusted incidence rate of RRT in 2011 among all registries reporting to the ERA-EDTA Registry was 117 per million population (pmp) (n = 71.631). Incidence rates varied from 24 pmp in Ukraine to 238 pmp in Turkey. The overall unadjusted prevalence of RRT for ESRD on 31 December 2011 was 692 pmp (n = 425 824). The highest prevalence was reported by Portugal (1662 pmp) and the lowest by Ukraine (131 pmp). Among all registries, a total of 22 814 renal transplantations were performed (37 pmp). The highest overall transplant rate was reported from Spain, Cantabria (81 pmp), whereas the highest rate of living donor transplants was reported from Turkey (39 pmp). For patients who started RRT between 2002 and 2006, the unadjusted 5-year patient survival on RRT was 46.8% [95% confidence interval (CI) 46.6-47.0], and on dialysis 39.3% (95% CI 39.2-39.4). The unadjusted 5-year patient survival after the first renal transplantation performed between 2002 and 2006 was 86.7% (95% CI 86.2-87.2) for kidneys from deceased donors and 94.3% (95% CI 93.6-95.0) for kidneys from living donors.

Thrombosis of the great cerebral vein in a hemodialysis patient.

Cerebral venous thrombosis is a rare condition with various clinical presentations which may delay diagnosis. It is frequently associated with severe consequences. We present the first documented case of thrombosis of the great cerebral vein in a hemodialysis patient. A 29-year-old female patient with end-stage renal disease of unknown etiology was admitted to a hospital with altered consciousness and nausea. Severe headache in the right parietal area had started 2 days before. On examination, she was in the poor overall condition, dysartric, with a severe nystagmus. Urgent brain multislice computerized tomography and magnetic resonance imaging revealed thrombosis of the great cerebral vein with hypodense zones in hypothalamus, thalamus and basal ganglia. She was treated with heparin bolus of 25000 IU with a favorable outcome. Detailed examination demonstrated increased lupus anticoagulant (LA) 1 and LA2 and increased LA1/LA2. Control magnetic resonance imaging performed 1 year later revealed multiple vascular lesions within the brain. Acetylsalicylate was introduced in therapy. Thrombosis of the cerebral veins should be suspected in patients with end-stage renal disease, altered neurological status and signs of increased intracranial pressure.

High uric acid and low superoxide dismutase as possible predictors of all-cause and cardiovascular mortality in hemodialysis patients.

PURPOSE: We investigated the role of serum uric acid (sUA) and superoxide dismutase (SOD) as predictive factors for mortality in hemodialysis (HD) patients. METHODS: SOD, butyrylcholinesterase, and malondialdehyde were estimated spectrophotometrically and the other parameters by standard procedures. High-sensitive C-reactive protein was assayed by a sandwich ELISA method. RESULTS: sUA among survivors (112.1 ± 13.82 µmol/L) was significantly lower than in deceased (160.8 ± 16.81 µmol/L, p < 0.001), while SOD was higher in survivors (31.8 ± 6.61 kU/L) than among deceased (20.2 ± 3.03, p < 0.05). Kaplan-Meier survival curves showed the greatest mortality risk in the highest tertile of basal sUA concentration (≥ 127.11 µmol/L, p < 0.001), and for SOD in the lowest tertile (≤ 23.83 kU/L, p < 0.05). CONCLUSION: Our results suggest that high sUA and low SOD may predict all-cause and cardiovascular mortality in HD patients.