The ERA Registry Annual Report 2021: a summary.

Background: The European Renal Association (ERA) Registry collects data on kidney replacement therapy (KRT) in patients with end-stage kidney disease (ESKD). This paper is a summary of the ERA Registry Annual Report 2021, including a comparison across treatment modalities. Methods: Data was collected from 54 national and regional registries from 36 countries, of which 35 registries from 18 countries contributed individual patient data and 19 registries from 19 countries contributed aggregated data. Using this data, incidence and prevalence of KRT, kidney transplantation rates, survival probabilities and expected remaining lifetimes were calculated. Result: In 2021, 533.2 million people in the general population were covered by the ERA Registry. The incidence of KRT was 145 per million population (pmp). In incident patients, 55% were 65 years or older, 64% were male, and the most common primary renal disease (PRD) was diabetes (22%). The prevalence of KRT was 1040 pmp. In prevalent patients, 47% were 65 years or older, 62% were male, and the most common PRDs were diabetes and glomerulonephritis/sclerosis (both 16%). On 31 December 2021, 56% of patients received haemodialysis, 5% received peritoneal dialysis, and 39% were living with a functioning graft. The kidney transplantation rate in 2021 was 37 pmp, a majority coming from deceased donors (66%). For patients initiating KRT between 2012-2016, 5-year survival probability was 52%. Compared to the general population, life expectancy was 65% and 68% shorter for males and females receiving dialysis, and 40% and 43% shorter for males and females living with a functioning graft.

A comparison of the epidemiology of kidney replacement therapy between Europe and the United States: 2021 data of the ERA Registry and the USRDS.

BACKGROUND AND HYPOTHESIS: This paper compares the most recent data on the incidence and prevalence of kidney replacement therapy (KRT), kidney transplantation rates, and mortality on KRT from Europe to those from the United States (US), including comparisons of treatment modalities (haemodialysis (HD), peritoneal dialysis (PD), and kidney transplantation (KTx)). METHODS: Data were derived from the annual reports of the European Renal Association (ERA) Registry and the United States Renal Data System (USRDS). The European data include information from national and regional renal registries providing the ERA Registry with individual patient data. Additional analyses were performed to present results for all participating European countries together. RESULTS: In 2021, the KRT incidence in the US (409.7 per million population (pmp)) was almost 3-fold higher than in Europe (144.4 pmp). Despite the substantial difference in KRT incidence, approximately the same proportion of patients initiated HD (Europe: 82%, US: 84%), PD (14%; 13% respectively), or underwent pre-emptive KTx (4%; 3% respectively). The KRT prevalence in the US (2436.1 pmp) was 2-fold higher than in Europe (1187.8 pmp). Within Europe, approximately half of all prevalent patients were living with a functioning graft (47%), while in the US, this was one third (32%). The number of kidney transplantations performed was almost twice as high in the US (77.0 pmp) compared to Europe (41.6 pmp). The mortality of patients receiving KRT was 1.6-fold higher in the US (157.3 per 1000 patient years) compared to Europe (98.7 per 1000 patient years). CONCLUSIONS: The US had a much higher KRT incidence, prevalence, and mortality compared to Europe, and despite a higher kidney transplantation rate, a lower proportion of prevalent patients with a functioning graft.

Association of multiple retinal nodular hamartomas and "confetti" skin lesions with end-stage renal disease in patients with tuberous sclerosis.

PURPOSE: The main purpose of this study is to explore characteristics of patients with chronic kidney disease in tuberous sclerosis (TSC) and to underline differences in clinical characteristics between end-stage renal disease (ESRD) patients and patients in earlier stages of chronic kidney disease. METHODS: This multicentric, retrospective study included data for 48 patients from seven South-Eastern European countries (Albania, Bosnia and Herzegovina, Croatia, Greece, Montenegro, Serbia, Slovenia) in the period from February to August 2020. Researchers collected data from local and national nephrological and neurological registries and offered clinical and laboratory results from medical histories in follow-up periods. RESULTS: This study enrolled 48 patients with a median age of 32.3 years (range, 18-46 years), and predominant female gender (60.45%). The percentage of patients with chronic kidney disease (CKD) diagnosis of the total number of patients was 66.90%, with end-stage renal disease development in 39.6%. The most prevalent renal lesions leading to chronic kidney disease were angiomyolipomas (AMLs) in 76.6%, while multiple renal cysts were present in 42.6% of patients. Nephrectomy was performed in 43% of patients, while the mTOR inhibitors were used in 18 patients (37.5%). The majority of patients had cutaneous manifestations of tuberous sclerosis-83.30% had hypomelanotic cutaneous lesions, and 68.80% had angiofibromas. Multiple retinal nodular hamartomas and "confetti" skin lesions were more frequent in end-stage renal disease (ESRD) than in patients with earlier stages of chronic kidney disease (p-0.033 and 0.03, respectively). CONCLUSION: Our study has also shown that retinal hamartomas and "confetti" skin lesions are more frequent in end-stage renal diseases (ESRD) patients than in other chronic kidney disease (CKD) patients. Usage of mTOR inhibitors can also reduce the number of complications and associated with tuberous sclerosis, such as dermatological manifestations and retinal hamartoma, which are more common in the terminal stage of chronic kidney disease.

The ERA Registry Annual Report 2019: summary and age comparisons.

BACKGROUND: Data on renal replacement therapy (RRT) for end-stage renal disease were collected by the European Renal Association (ERA) Registry via national and regional renal registries in Europe and countries bordering the Mediterranean Sea. This article provides a summary of the 2019 ERA Registry Annual Report, including data from 34 countries and additional age comparisons. METHODS: Individual patient data for 2019 were provided by 35 registries and aggregated data by 17 registries. Using these data, the incidence and prevalence of RRT, the kidney transplantation activity and the survival probabilities were calculated. RESULTS: In 2019, a general population of 680.8 million people was covered by the ERA Registry. Overall, the incidence of RRT was 132 per million population (p.m.p.). Of these patients, 62% were men, 54% were ≥65 years of age and 21% had diabetes mellitus as primary renal disease (PRD), and 84% had haemodialysis (HD), 11% had peritoneal dialysis (PD) and 5% had pre-emptive kidney transplantation as an initial treatment modality. The overall prevalence of RRT on 31 December 2019 was 893 p.m.p., with 58% of patients on HD, 5% on PD and 37% living with a kidney transplant. The overall kidney transplant rate was 35 p.m.p. and 29% of the kidney grafts were from a living donor. The unadjusted 5-year survival probability was 42.3% for patients commencing dialysis, 86.6% for recipients of deceased donor grafts and 94.4% for recipients of living donor grafts in the period 2010-14. When comparing age categories, there were substantial differences in the distribution of PRD, treatment modality and kidney donor type, and in the survival probabilities.

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.

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).

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.

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.

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.

[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.