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).

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.

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.

Mycophenolate mofetil in high-risk patients with primary glomerulonephritis: results of a 1-year prospective study.

BACKGROUND/AIMS: Glucocorticoids and classic immunosuppressive drugs can improve disease activity in primary glomerulonephritis (GN). However, these drugs have serious toxicity and patients frequently experience inadequate response or relapse, so there is a need for alternative agents. This multicenter uncontrolled study analyzed the efficacy and safety of mycophenolate mofetil (MMF) in high-risk patients with primary GN. METHODS: A total of 51 patients with biopsy-proven membranous (n = 12), membranoproliferative (n = 15), mesangioproliferative (n = 10), focal segmental glomerulosclerosis (n = 13) and minimal change disease (n = 1) received MMF with low-dose corticosteroids for 1 year. The primary outcome included the number of patients with complete/partial remission. RESULTS: Proteinuria significantly decreased, from its median value of 4.9 g/day (IQR 2.9-8.4) to 1.28 g/day (IQR 0.5-2.9), p < 0.001. The urine protein/creatinine ratio significantly improved, from a median of 3.72 (IQR 2.13-6.48) to 0.84 (IQR 0.42-2.01), p < 0.001. The mean area under the curve for proteinuria significantly decreased, from 4.99 +/- 3.46 to 2.16 +/- 2.46, between the first (visits 1-2) and last (vists 4-5) treatment periods (p < 0.001). The change was similar for every type of GN, without difference between groups. eGFR slightly increased (62.1 +/- 31.8 to 65.3 +/- 31.8 ml/min, p = n.s.) and ESR, total proteins, albumins, total- and HDL-cholesterol parameters improved significantly. Systolic, diastolic and mean blood pressure decreased (p < 0.02 for systolic blood pressure). The age of patients was the only independent predictor of complete or partial remission. CONCLUSION: MMF proved to be efficient in 70% of high-risk patients with primary GN, who reached either complete or partial remission without safety concern after 12 months of treatment. Favorable effects of MMF therapy have to be confirmed in the long term and particularly after discontinuation of the drug.

[Lupus nephritis: retrospective analysis of the course of the disease]. / Lupusni nefritis: retrospektivna analiza toka bolesti.

INTRODUCTION: Systemic lupus erythematosus is a multisystemic autoimmune disease characterized by various clinical manifestations, as well as unpredictable course and therapy response. Lupus nephritis is a severe manifestation of the disease, significantly influencing its prognosis. Since the pathogenesis of lupus nephritis has not been elucidated, optimal therapeutic approach is still subject of numerous studies. AIM: A retrospective study was undertaken with the aim to analyze clinical features of different types of lupus nephritis, their therapy response as well as their course and outcome. PATIENTS AND METHODS: The retrospective study included 67 patients who were regularly followed-up for 36-188 months after renal biopsy at the Department of Nephrology, Clinical Centre of Serbia or at the Department of Nephrology, Clinical Centre of Montenegro. Systemic lupus erythematosus was diagnosed according to the ARA criteria, while pathomorphological classification was based on WHO recommendations. RESULTS: The studied group was mostly composed of patients with proliferative lupus nephritis (21 with diffuse and 9 with focal) followed by 20 patients with membranous, 14 with mesangioproliferative (type IIb) and only one patient with type I, IIa and VI lupus nephritis each. Age distribution of the patients and incidence of extrarenal complications was equal in patient groups with different types of lupus nephritis. Only four patients were males. Choice of therapy depended on the morphological characteristics of lupus nephritis, presence and severity of extrarenal complications and renal function. At the time of analysis, 10/14 patients with lupus nephritis type IIb were in remission, as well as 14/30 type III/IV patients and 15/20 patients with type V lupus nephritis. The outcome was the worst in patients with proliferative lupus nephritis, and thus, at the time of analysis four of 30 patients had chronic renal failure, 7 were on regular haemodialysis, while 3 patients decreased. With respect to the renal function, the most favorable outcome was recorded in IIb patients, while mortality was not dependent on lupus nephritis type but on extrarenal manifestations of systemic lupus and associated diseases. Five- and ten-year patients' survival rates were 100% and 86%, respectively. Cardiovascular and cerebrovascular diseases were the most frequent causes of death. CONCLUSION: Persistent and controlled treatment using a combination of different immunosuppressive drugs along with close follow-up of patients and possibility of dialysis treatment have significantly improved prognosis of patients with lupus nephritis, even in those with diffuse proliferative changes.