Solid Organ Cancer and Melanoma in Kidney Transplant Recipients: TumorTx Base Preliminary Results.

BACKGROUND: Incidence of malignancy in transplant recipients is higher than in the general population. Malignancy is a major cause of mortality following solid organ transplantation and a major barrier to long-term survival for the kidney. The aim of this study was to estimate the incidence of solid organ malignancy (SOM) and melanoma in renal transplant recipients (RTR) transplanted at 2 representative transplant centers in Poland based on data from the Polish Tumor Registry. MATERIAL AND METHODS: We analyzed the medical data of 3069 patients who underwent kidney transplantation (KTx) between 1995 and 2015. RESULTS: In our study 112 SOM (3.6%) were diagnosed. The majority of patients were male (n = 71; 63.4%; P < .01). The mean age at KTx was 48.0 ± 13.1 years and the mean age at the time of cancer diagnosis was 55.9 ± 12.7 years. The average time of malignancy occurrence was 5.9 ± 5.0 years after KTx. SOM was the cause of death in 60 patients (53%). The most common were malignancies of gastrointestinal tract (25%), urinary tract tumors (23.2%), lung cancer (n = 18; 16%), and lymphoma (13.4%). We found an increase in the percentage of chronic glomerular nephropathy in the group of SOM (n = 56; 50%) compared with renal insufficiency of other etiologies. CONCLUSIONS: RTR in Poland are at a significant risk of malignancy development in a variety of organs, primarily urinary tract tumors and lymphoma. Cancers most frequently occurring in the general population such as lung and colorectal cancer are common in our RTR. On this basis an appropriate tumor screening schedule can be developed in individual countries.

Gastrointestinal Pathologies in Patients After Successful Renal Transplantation-A Pilot Study.

BACKGROUND: The beneficial effect of kidney transplantation in patients requiring continuous renal replacement therapy owing to chronic kidney disease is well known and accepted. Kidney transplantation protects the patient from complications that may develop during chronic dialysis. Unfortunately, there is also evidence that kidney transplant patients are more prone to developing cancer than healthy persons. The aim of this study was to evaluate the prevalence of gastrointestinal pathologies in patients after kidney transplantation. METHODS: Adult patients after kidney transplantation, who are under the care of the Outpatient Department of Nephrology in Gdansk, received alarm symptom questionnaires and referral for testing for the presence of fecal occult blood. Then, in 45 selected patients (29 men and 16 women) endoscopic examination was performed. Mean age was 57.6 ± 10.1 (range, 35-83) years. RESULTS: Out of ∼940 patients after kidney transplantation, resting under supervision of outpatient department, 181 patients completed the questionnaire and 100 gave a stool sample for testing: 32 results were positive. After analyzing the questionnaires and stool results, 88 patients were qualified for further investigation. The endoscopic examination had been performed so far in 45 patients and revealed gastritis and/or duodenitis in 33 patients, diverticular colon disease in 18, esophagitis in 8, colon polyps in 14, stomach polyps in 3, inflammatory bowel disease in 7, and cancers in 3. CONCLUSIONS: The preliminary results indicate that patients after kidney transplantation have significant risk of gastrointestinal pathologies and require detailed diagnostic endoscopy.

Pregnancy after kidney transplantation: a single-center experience and review of the literature.

After kidney transplantation (KT), pregnancy is possible, although the risk of maternal and fetal complications is much higher than in the general population. Outcome of 22 pregnancies in 17 patients transplanted in the Gdansk center in the period 1980-2012 was studied. Mean maternal age at pregnancy was 30 ± 5 (range, 23-39) years, interval between transplantation and conception 3.4 ± 2.5 (range, 0.6-11) years. Mean creatinine concentration before conception was 1.29 ± 0.36 (range, 0.8-2.45) mg/dL and was stable during 1 year preceding pregnancy (mean increase, 0.01 mg/dL). Nine of the 17 patients received 1 and 4 received ≥2 antihypertensive drugs, and 1 had proteinuria. Twelve of the 17 patients were primagravidas, 1 was pregnant 3 times, and 14 times. At the time of conception, 20 patients received CNI (14 cyclosporine, 6 tacrolimus), 15 antimetabolites (3 mycophenolate mofetil [MMF], 12 azathioprine), 1 mammalian target of rapamycin inhibitor (mTORi; sirolimus), and all prednisone. MMF and mTORi were discontinued before or during the 1st weeks of pregnancy. Maternal outcome: all survived the pregnancy. None experienced rejection or graft loss as a direct result of pregnancy. Maternal complications included edema (5/17), worsening of blood pressure control (5/17), and worsening (1/17) or new onset of proteinuria (2/17). Mean creatinine decrease during pregnancy was 0.06 mg/dL. Mean creatinine 1 year after pregnancy was 1.49 ± 0.53 mg/dL. There were 12 cesarean sections. Fetal outcomes: 17 live births (2 with serious congenital defects), 2 spontaneous and 1 induced abortion, 2 stillbirths. Mean pregnancy age and neonate birth weights were 35 ± 4 (range, 23-39) weeks and 2,552 ± 629 (range, 1,480-3,420) g, respectively. During mean 8.5 (range, 1-25) years of follow-up after pregnancy, 4/17 patients lost grafts. Grafts were lost in the 3rd to 7th years after pregnancy. We conclude that pregnancy does not exert a direct negative influence on patient and graft survivals; 68% of all pregnancies resulted in delivering healthy neonates.

Sebaceous carcinoma in patients receiving long-term immunosuppresive treatment: case report and literature review.

BACKGROUND: Sebaceous carcinoma (SC) is a very rare and aggressive malignant skin cancer that appears to occur with a greater frequency in the clinical setting of chronic immunosuppression; however, it is not reported in the literature as frequently as is squamous cell carcinoma (SCC). We report 2 cases of SC in organ transplant patients from clinical and histopathological points of view. METHODS: A 48-year-old patient after 3 renal transplantations (1986, 1986, and 1998) was presented to the Dermatology Department in 1999 because of a papillomatous lesion along her right upper eyelid. The lesion was excised. Histopathologically, it was diagnosed as a SC. There was no lymphovascular invasion and no metastasis; therefore no other treatment was included. No symptoms of recurrent disease were present 14 years since diagnosis. An 87-year-old patient after a renal transplantation in 1989 was referred to dermatologist in 1993 because of the lesion on his right temple. The lesion was excised; histopathologically, it was diagnosed as SC. Because of metastatic disease, he had a course of radiotherapy to the right side of the neck. The immunosuppressive drugs azathioprine and cyclosporine A were reduced. The patient died of metastatic disease 1 year later (3 years since diagnosis). Both patients had very high cumulative UV exposition during their lifetimes, and many skin cancers were diagnosed, especially SCC. RESULTS: It is necessary to realize that this cancer occurs more frequently in organ transplant patients, and its correct diagnosis is an essential issue because it has significantly more aggressive behavior than does SCC. In the 2 presented patients, we observed very rapid progression of disease. Despite aggressive treatment and reduction of immunosuppressive drugs, the second patient died 3 years after diagnosis. CONCLUSIONS: Regular dermatological follow-up is required in the population of organ transplant patients to identify all skin tumors in the early stage.

Oxidative stress, inflammation and nutritional status during darbepoetin alpha treatment in peritoneal dialysis patients.

UNLABELLED: Recombinant human erythropoetin beta; (rHuEPO) has not only an erythropoietic effect but also appears to affect production of cytokines and may improve nutritional status of dialysis patients. Darbepoetin alpha; is a new erythropoiesis-stimulating protein with a threefold longer serum half-life when compared with rHuEPO. The objective of this prospective study was to assess oxidative stress, inflammation, nutrition and hematological response in peritoneal dialysis (PD) patients who were switched from rHuEPO beta to darbepoetin alpha. 12 stable PD patients (6 M, 6 F; mean age 56.2 +/- 15.1 yr.) were evaluated during this study together with 22 healthy volunteers serving as a control group. All patients had been receiving erythropoetin beta subcutaneously once a week before they were reassigned to darbepoetin. The new drug was administered every other week for 6 months, in a dose equivalent to a weekly dose of previously taken rHuEPO. Hematology, iron status and biochemical profiles were evaluated monthly. Markers of oxidative stress: malondialdehyde/ 4-hydroxynoneal (MDA/4HNE), carbonyl groups (CG), oxyLDL and AGEs and markers of inflammation: CRP, TNF alpha, IL-6 were measured on rHuEPO beta before the switch to darbepoetin, and after 1st and 6th month of darbepoetin treatment. The assessment of nutritional status was determined by body mass index (BMI), serum albumin concentration and Subjective Global Assessment (SGA). RESULTS: Mean levels of Hb and Hct were stable during 6 months of observation and not significantly different from the data observed for on rHuEPO. Nutritional status was good in 9 patients, 3 patients were malnourished at the beginning of this study as assessed by SGA and this status persisted to the end of observation. The levels of markers of oxidative stress and inflammation were statistically higher than in the control group (p < 0.05). CONCLUSION: Darbepoetin alpha given subcutaneously once every 2 weeks is effective for the treatment of anemia in PD patients. Less frequent administration of darbepoetin has a biological response similar to weekly administration of rHuEPO.

Renal transplantation in dialysis patients with the history of coronary artery bypass grafting and cardiac valve replacement.

Death with a functioning kidney is the most frequent cause of graft failure. Cardiovascular disease is the most frequent cause of death after renal transplantation. Therefore, prior to grafting, it is mandatory to diagnose and treat coronary artery disease and heart valve impairment. Transplantation is the best option for renal replacement therapy as far as the quality of life and life expectancy are concerned, although patients with such comorbidities may experience a higher short-term mortality risk. The objective for this study was to analyze both short- and long-term results of patients after coronary artery bypass grafting (CABG) or cardiac valve replacement (CVR). The cardiac surgery recipient group (CSR) included 16 patients (15 men, 1 woman) aged from 44 to 73 (mean 54.9 +/- 7.8) years. CABG was performed in 13/16 patients, and CVR in 3/16. The rest of our patients were treated as a comparative noncardiac surgery recipient (non-CSR) group. It consisted of 422 patients (264 men, 158 women) aged from 14 to 68 years (mean 43.2 +/- 12.9). The comparison revealed that graft function estimated at 1 year after transplantation was not different: serum creatinine concentrations of 1.7 +/- 0.2 and 1.6 +/- 0.5 mg/dL in CSR and non-CSR, respectively. One-year patient survival in the CVR group of 93.8% was slightly worse than that in the non-CSR group (97.9%), but death-censored 1-year graft survivals were comparable in both groups (93.8% vs 92%). Urinary tract and cytomegalovirus infections were the most common complications in the CSR group. One patient lost his graft in month 3(rd) due to many serious infectious complications. One patient died at the end of 12 months as a result of a cardiovascular event (1/16). Our single-center results confirm that transplantation in patients after CABG or CVR is a safe procedure; therefore, such patients should be referred into the waiting list.

Influence of spontaneous platelet aggregation on progression of glomerular disease.

UNLABELLED: Platelet secretion products may play an important role in the pathogenesis and progression of the kidney disease. Amongst the parameters describing platelet hyperactivity the measurement of spontaneous platelet aggregation (SPA) seems particularly useful. In this study SPA as well as mean platelet volume (MPV), modal platelet volume (PLT Mode) and platelet count (PLT) were investigated in 60 patients with biopsy proven primary glomerulonephritis. SPA was measured using the turbidimetric method according to Born with no enhancers added. Serum creatinine concentration (Cr), reciprocal serum creatinine concentration (1/Cr) and endogenous creatinine clearance (Cl(Cr)) were used for the renal function estimation. Protein and lipid profiles as well as coagulo-fibrinolytic balance were measured in parallel. The investigated group consisted of 30 non-nephrotic patients (CGN) - in 9, SPA was found (CGN-B) while 21 had SPA <10% (CGN-A), and 30 nephrotic patients (CGN+NS) - 19 with SPA (CGN+NS-B) and 11 without (CGN+NS-A). SPA was found to be a constant platelet feature in patients with chronic glomerulopathy. The group remained under observation for 36 months. 41 patients were included in the 3-year prospective study which revealed the significant influence of the blood platelet hyperaggregability on the renal disease progression. A significantly increased serum creatinine concentration, decreased 1/Cr parameter and decreased glomerular filtration rate (Cl(Cr)) were noted in subgroups showing SPA. A significant correlation between SPA and (Delta)Cr/month (r = 0.41), (Delta)1/Cr/month (r = 0.38) as well as (Delta)Cl(Cr)/month (r = 0.52) was found. The platelet activity and thus SPA can be altered by various factors: albumin and fibrinogen plasma concentrations, thrombosis activation and possibly lipoprotein metabolism disturbances. A characteristic feature of spontaneously aggregating platelet is their increased volume (MPV). CONCLUSION: Platelet hyperaggregation in one of nonimmunological factors stimulates the progression of glomerulonephritis.

[The concentration of adenine nucleotides in platelets of patients with primary chronic glomerulonephritis]. / Stezenie nukleotydów adeninowych w plytkach krwi chorych z pierwotnymi klebuszkowymi zapaleniami nerek.

UNLABELLED: Nephrotic syndrome (n.s.) is associated with numerous blood coagulation abnormalities and a marked predisposition to thromboembolism. Increased aggregation and activation of platelets in patients with glomerulonephritis (g.l.n. p.t.s.) may partly explain this status. The aim of this study was to measure the platelets adenine nucleotides concentration. The study was performed in 57 patients with a renal biopsy confirmed primary glomerulonephritis and 24 sex and age matched healthy volunteers which served as a control group. The patients were divided into two subgroups: subgroup I/A--36 patients with the symptoms of the nephrotic syndrome and subgroup I/B--21 patients with chronic glomerulonephritis and proteinuria but without the symptoms of nephrotic syndrome. Concentration of adenine nucleotides in platelets was measured using HPLC. In the subgroup I/A significantly lower levels of ATP, ADP and AMP concentrations in platelets were observed comparing to control subjects. Simultaneously significant correlation between both ATP and ADP concentration and plasma levels of albumin, total cholesterol, LDL-cholesterol, triglycerides and fibrinogen were found in g.l.n. p.t.s. SUMMARY AND CONCLUSIONS: 1. Significantly lower concentrations of adenine nucleotides in platelets of gln pts with the nephrotic syndrome may result from their activation. 2. Protein and lipid metabolism as well as fibrinogen seem to influence ATP and ADP concentrations in platelets of g.l.n. p.t.s.

The influence of recombinant human erythropoietin on tumor necrosis factor alpha and interleukin-10 production by whole blood cell cultures in hemodialysis patients.

Impaired immunological response in hemodialysis (HD) patients, which leads to inappropriate cytokine production, is partially caused by the hyperstimulation of both T lymphocytes and monocytes/macrophages. Recent data suggest that human recombinant erythropoietin (rhEPO) may have an immunological action. The goal of our study was to estimate the influence of rhEPO treatment on the production of the inflammatory cytokine tumor necrosis factor alpha (TNFalpha) and antiinflammatory cytokin interleukin-10 (IL-10) in 10 HD patients receiving rhEPO for 6 months. The levels of cytokines were measured in the in vitro cultures of whole blood. The level of IL-10 increased in all treated patients during the therapy, and it was accompanied by a transitory decrease of TNFalpha. The results of our studies suggest that rhEPO may reduce the inflammatory process by decreasing production of TNFalpha and increasing production of IL-10.