Dosing lutetium Lu 177-dotatate for a hemodialysis patient.

Lu177-dotatate (Lutathera™) is a radioactive drug approved for the treatment of adults with gastro-entero-pancreatic neuroendocrine tumors and is predominantly renally excreted. Currently all patients receive 7400 MBq (200 mCi), and there are no guidelines for treating hemodialysis patients. We measured radioactivity prior to and post administration of two cycles of Lu177-dotatate in a hemodialysis patient, and radiation exposure to staff. We reduced the standard 7400 MBq by 33% for the first cycle and patient radioactivity fell by 40% following postdilution hemodiafiltration started 6 h post dosing, and by 45% for the second cycle and radioactivity fell by 47% with postdilution hemodiafiltration started 5 h post administration. By reducing the initial administered radioactivity, coupled with early dialysis, and choosing postdilution hemodiafiltration we were able to achieve radioactivity retention curves similar to those from patients with normal renal function receiving the standard administration of 7400 MBq.

Measurement of innate immune response biomarkers in peritoneal dialysis effluent using a rapid diagnostic point-of-care device as a diagnostic indicator of peritonitis.

Peritonitis is the commonest complication of peritoneal dialysis and a major reason for treatment failure. Current diagnosis is based on clinical symptoms, cloudy effluent and a dialysate white cell count (over 100 cells/µl). A rapid point-of-care diagnostic test would accelerate diagnosis and potentially improve outcomes from infection. Here, in a clinical audit project, we used PERiPLEX®, a point-of-care device which detects when levels of matrix metalloproteinase-8 and interleukin-6 are elevated above a threshold within minutes in dialysis effluent, to assess whether it could confirm or exclude peritonitis in 107 patients undergoing peritoneal dialysis. Mean patient age was 64.6 years with a median duration of peritoneal dialysis of 13.3 months (interquartile range 6.3 - 33.5 months). Presence of peritonitis was confirmed by clinical criteria. There were 49 positive tests of which 41 patients had peritonitis, three had other causes of intra-peritoneal inflammation, three had severe urosepsis and two patients required no treatment. Fifty-eight tests were negative with one patient having a false negative result. The positive predictive value of the test was 83.7% (95% confidence interval 72.8 - 90.8) and the negative predictive value was 98.3% (89.1 - 99.8). Sensitivity and specificity were 97.6% (87.4 - 99.9) and 87.7% (77.2 - 94.5) respectively. Thus, PERiPLEX® could be used as a rapid point-of-care test that can aid the diagnosis or exclusion of peritonitis with a high negative predictive value.

Impact of Diabetes on Extracellular Volume Status in Patients Initiating Peritoneal Dialysis.

BACKGROUND: Recent reports have highlighted that diabetic patients with kidney failure are at increased risk of technique failure and transfer to haemodialysis within 90 days of initiating peritoneal dialysis (PD). We wished to determine whether there were differences between diabetic and non-diabetic patients within the first 3 months of starting PD. METHODS: We reviewed results of corresponding bioimpedance and the 1st test of peritoneal membrane function (PET) in consecutive patients, 6-10 weeks after initiating PD electively. RESULTS: Adult patients numbering 386 - 230 males (59.6%), 152 (39.4%) diabetic, 188 (48.7%) white, mean age 57.3 ±16.9 years - were studied. Although weight, residual renal function and peritoneal clearances were not different, diabetic patients had greater extracellular water to total body water (ECW/TBW; 40.4 ± 1.1 vs. 39.2 ± 1.4) and % ECW excess (9.6 [6.3-12.3] vs. 4.9 [0.7-8.9]), lower serum albumin (35.2 ± 4.7 vs. 37.8 ± 4.9 g/L), greater fat mass index (9.5 ± 4.2 vs. 7.7 ± 4.2), and although mean arterial blood pressure was similar, arterial pulse pressure was greater (66.9 ± 10.8 vs. 54.3 ± 17.3 mm Hg, all p < 0.001). On multivariate analysis, glycated haemoglobin was associated with pulse pressure (standardised ß 0.24, p < 0.001), N terminal brain natriuretic peptide (ß 0.24, p < 0.001), ECW/TBW (ß 0.19, p = 0.012) and negatively with serum albumin (ß -0.14, p = 0.033) and creatinine (ß -0.18, p = 0.02). CONCLUSION: Diabetic patients electively starting PD were found to have greater ECW/TBW ratios and ECW excess 6-10 weeks after starting PD compared to non-diabetics, despite similar PET. Increased ECW could predispose diabetic patients to be at greater risk of volume overload.

Dialysate cytokine levels do not predict encapsulating peritoneal sclerosis.

BACKGROUND: Encapsulating peritoneal sclerosis (EPS) is a rare but devastating complication of long-term peritoneal dialysis (PD). There is no well-validated method for predicting which patients will develop the condition, although known risk factors include long duration of PD, high glucose exposure and lack of residual renal function. We have investigated whether dialysate cytokines (MCP-1 (monocyte chemotactic protein-1), CCL18 (pulmonary and activation-regulated cytokine, PARC), IL-6 (interleukin-6), CCL15 (leukotactin) and angiogenin) could be used to predict the onset of EPS more effectively than known clinical risk factors. METHODS: Samples of dialysate and clinical data were prospectively collected from 151 patients at the West London Renal center between 2003 and 2010. Dialysate cytokine levels were measured using the enzyme-linked immunoabsorbant assay (ELISA) technique. Encapsulating peritoneal sclerosis subsequently developed in 17 patients during a follow-up period of 27 - 113 months. Cytokines found at higher levels in dialysate of pre-EPS patients were investigated as candidate predictors of EPS using logistic regression analysis. RESULTS: Dialysate IL-6, MCP-1 and CCL15 were significantly higher in patients who subsequently developed EPS; however, a logistic regression model using dialysate cytokines to predict EPS was no better than a model using well-recognized clinical markers (length of time on PD and membrane transport status). CONCLUSIONS: Although MCP-1, IL-6 and CCL15 were found at higher levels in the dialysate of patients who subsequently developed EPS, dialysate levels of these cytokines do not improve prediction of future EPS above a model using known clinical risk factors.

The role of peritoneal dialysis in modern renal replacement therapy.

Most patients starting dialysis can choose between peritoneal dialysis and haemodialysis. There is little evidence proving that one form of dialysis is better than the other; although there may be an early advantage to peritoneal dialysis (PD) in young patients with residual function this effect is short-lived. Technique failure develops after years on PD so dialysis modality will often change during a long dialysis career. Quality of life studies, which must be interpreted carefully, indicate that patients require information about the impact of dialysis on their lifestyle as well as health-related outcomes so that they can choose the most suitable dialysis modality. Increasing numbers of frail elderly patients are starting dialysis; support in the home by nursing staff may facilitate the use of PD in this group. In the UK guidelines prioritise the patient's choice of dialysis modality (where feasible) based on good quality predialysis education. Cost of treatment is generally lower on PD, which is particularly recommended for patients with residual renal function and few comorbidities.

Encapsulating peritoneal sclerosis: what have we learned?

Encapsulating peritoneal sclerosis (EPS) is a rare complication of peritoneal dialysis (PD), but carries significant morbidity and mortality. We review the clinical features and radiologic and histologic changes found at diagnosis of EPS. Although EPS is strongly associated with the duration of PD, the pathogenesis remains only partly understood. We discuss the mechanisms thought to underlie the abnormally thickened, sclerotic peritoneal membrane seen in long-term PD patients including epithelial to mesenchymal transition and the molecular mediators of fibrosis and angiogenesis. We review how exposure to high-glucose, nonphysiological dialysis fluids, peritonitis, and uremia may be responsible for these changes. Much remains to be learned about optimal management of EPS, both medical and surgical, because the literature lacks controlled studies. Future research challenges include defining the role of surgery, immunosuppression, and antifibrotic agents in the management of EPS. We also need to understand why some patients progress from asymptomatic peritoneal sclerosis to the extreme levels of fibrin deposition and bowel encapsulation seen in EPS. Screening PD patients for potential future EPS remains difficult, and we need strategies for monitoring patients on longer-term PD that enable us to better quantify the risk of EPS for the individual patient.

Screening for encapsulating peritoneal sclerosis in patients on peritoneal dialysis: role of CT scanning.

BACKGROUND: We previously validated a scoring system for abdominal/pelvic CT scans in patients with symptomatic encapsulating peritoneal sclerosis (EPS). CT scans of patients with symptomatic EPS were significantly different from control peritoneal dialysis (PD) or haemodialysis patient scans; scans performed before EPS was clinically evident were near normal in 9 of 13 patients. We have now investigated CT scanning as a screening modality in a larger group of patients on long-term PD. METHODS: Pre-diagnostic CT scans performed in 20 patients for routine screening or other indications at least 3 months before EPS developed, and later diagnostic scans when EPS was clinically evident, were scored by three radiologists. The control group included CT scans of 20 PD patients who had not developed EPS (median follow-up 2.25 years). Analysis was by non-parametric tests. CT scores ranged from 0 to 22; > 2.5 was considered abnormal. RESULTS: Clinical EPS only developed after transplantation or transfer to HD. Diagnostic scans scored significantly higher than pre-diagnostic or control scans (median scores 9, 2 and 1; P < 0.001), confirming previous work. The pre-EPS diagnosis of 12 asymptomatic patients had a median CT score = 1.75, similar to the control group. Eight patients had had a limited episode of abdominal symptoms (seven required hospitalization), but did not have the clinical picture of EPS; their median CT score was 4.5 (P = 0.0016 cf control group). The time from pre-diagnostic scan to clinical EPS (median 0.82 years) and duration of PD at time of pre-diagnostic scan (median 7.1 years) did not differ significantly between the symptomatic and asymptomatic groups. CONCLUSIONS: CT screening of asymptomatic PD patients is not indicated; EPS may occur within a year or less of a normal CT scan. Abdominal symptoms in long-term PD patients can be associated with CT scan abnormalities; these patients are at increased risk of EPS after stopping PD.