Intermittent Oral Dosing of Roxadustat in Peritoneal Dialysis Chronic Kidney Disease Patients with Anemia: A Randomized,Phase 3, Multicenter,Open‐Label Study

Roxadustat is an oral hypoxia‐inducible factor prolyl hydroxylase inhibitor developed to treat anemia in chronic kidney disease (CKD) patients. This Phase 3, randomized, open‐label, 24‐week study investigated the efficacy and safety of roxadustat in Japanese CKD patients with anemia on peritoneal dialysis (PD) who were previously treated or not treated with erythropoiesis stimulating agents (ESAs). Patients not previously receiving ESA (ESA‐Naïve group) were randomized to roxadustat at a starting dose of 50 or 70 mg three times weekly; patients previously receiving ESA (ESA‐Converted group) switched from ESA to roxadustat 70 or 100 mg three times weekly depending on the prior ESA dose. Outcomes included maintenance rate of average hemoglobin (Hb) level within 10–12 g/dL at weeks 18–24, cumulative response rate at end of treatment (Hb thresholds, 10.0 g/dL or 10.5 g/dL; Hb increase, ≥1.0 g/dL), and average Hb levels at weeks 18–24. Safety was assessed by occurrence of treatment‐emergent adverse events (TEAEs). Fifty‐six patients were enrolled (ESA‐Naïve, n = 13; ESA‐Converted, n = 43). Maintenance rates (weeks 18–24) were 92.3% (95% CI: 64.0–99.8; ESA‐Naïve) and 74.4% (95% CI: 58.8–86.5; ESA‐Converted). Cumulative response rate was 100.0% in the ESA‐Naïve group. Average Hb levels (weeks 18–24) were 11.05 g/dL (95% CI: 10.67–11.42; ESA‐Naïve) and 10.93 g/dL (95% CI: 10.73–11.13; ESA‐Converted). Common TEAEs included nasopharyngitis and back pain. Roxadustat was well tolerated and effective in maintaining target Hb levels in CKD patients on PD who were previously treated or not treated with ESA.     

Renal Transplantation in Patients with Sarcoidosis: A French Multicenter Study

Background and objectives: Sarcoidosis is a multisystem disorder of unknown etiology. The outcome of renal transplantation on patients with sarcoidosis is not well known. A few case reports have described recurrence of sarcoidosis after transplant. Here, we report for the first time results and outcome of renal transplantation in a series of patients with sarcoidosis.Design, setting, participants, & measurements: Eighteen patients with sarcoidosis who underwent renal transplantation were identified retrospectively in eight French renal transplantation departments. Patient medical charts, demographics, and the outcome of renal transplantation were reviewed.Results: Initial renal disease was related to sarcoidosis in 10 patients. At the end of the follow-up (median, 42 months), patient and death-censored graft survival were 94.4% and the mean GFR was 60 ml/min per 1.73 m². Five patients (27%) experienced recurrence of sarcoidosis including extra-renal involvement in two patients and renal involvement in three patients. Median GFR was lower in the group of patients with renal recurrence compared with that of the entire cohort: 31 ml/min per 1.73 m². Recurrence occurred shortly after transplantation (median period, 13 months). Risk factors for recurrence included primary renal disease related to sarcoidosis and a shorter delay between the last episode of sarcoidosis and renal transplantation.Conclusions: Our results indicate that renal transplantation may be carried out safely in transplant candidates with sarcoidosis. Recurrence is not rare and is likely to affect graft outcome. These results fully justify a specific clinical and histologic monitoring mainly during the early posttransplant period.Sarcoidosis is a multisystem disorder of unknown etiology that generally occurs in young adults between the ages of 20 and 39 years (1). It is characterized by the presence of noncaseating granulomas in various organs, usually involving the respiratory tract (2). The highest annual incidence reported for sarcoidosis was 40 cases per 100,000 people in northern Europe (3).Although sarcoidosis is benign in >50% of cases, it can also be severe, involving extrapulmonary sites, such as the heart, kidneys, central nervous system, liver, larynx, or eyes (4). Renal involvement in sarcoidosis is rare, but it is probably underestimated (5). The current prevalence of renal failure ranges from 0.7 to 4.3% (6–8). Renal disease is mainly related to disturbed calcium metabolism including hypercalciuria (40% of patients), hypercalcemia (11% of patients), and renal lithiasis (10% of patients). Granulomatous tubulointerstitial nephritis, a less common cause of renal impairment, is present in 7 to 27% of all patients in postmortem studies (9) and is associated with both acute and chronic renal failure. Corticosteroids remain the cornerstone of renal therapy, with a good success rate, but prolonged therapy is often necessary to preserve renal function and to delay the onset of ESRD (10–13).End-stage organ disease that is secondary to sarcoidosis is uncommon (2,14). Sarcoidosis as the initial disease accounts for only a minority of organ transplantations. Thus, only 3% of lung transplants and <1% of heart and liver transplants involve sarcoidosis as the primary disease (2). Neither the incidence of graft rejection nor patient or graft survival appears to be different from the results observed in an overall population of similar organ recipients (15–19). By contrast, sarcoidosis recurrence does not appear to be uncommon, particularly after lung transplantation, with a recurrence rate close to 50% (16,20). Although there are case reports for patients that have undergone liver and heart transplantation, the sarcoidosis recurrence rate remains undetermined (21–25).There is even less information on sarcoidosis recurrence in the field of renal transplantation. Only a few case reports describe renal sarcoidosis recurrence (26–30), and there is no available information on patient and graft outcome. Here, we describe the first series of 18 patients with sarcoidosis who underwent renal transplantation, including patient and graft outcomes, incidence, and potential risk factors of recurrence.     

Low Serum Bicarbonate Predicts Residual Renal Function Loss in Peritoneal Dialysis Patients

Low residual renal function (RRF) and serum bicarbonate are associated with adverse outcomes in peritoneal dialysis (PD) patients. However, a relationship between the 2 has not yet been determined in these patients. Therefore, this study aimed to investigate whether low serum bicarbonate has a deteriorating effect on RRF in PD patients.This prospective observational study included a total of 405 incident patients who started PD between January 2000 and December 2005. We determined risk factors for complete loss of RRF using competing risk methods and evaluated the effects of time-averaged serum bicarbonate (TA-Bic) on the decline of RRF over the first 3 years of dialysis treatment using generalized linear mixed models.During the first 3 years of dialysis, 95 (23.5%) patients became anuric. The mean time until patients became anuric was 20.8 ± 9.0 months. After adjusting for multiple potentially confounding covariates, an increase in TA-Bic level was associated with a significantly decreased risk of loss of RRF (hazard ratio per 1 mEq/L increase, 0.84; 0.75–0.93; P = 0.002), and in comparison to TA-Bic ≥ 24 mEq/L, TA-Bic < 24 mEq/L conferred a 2.62-fold higher risk of becoming anuric. Furthermore, the rate of RRF decline estimated by generalized linear mixed models was significantly greater in patients with TA-Bic < 24 mEq/L compared with those with TA-Bic ≥ 24 mEq/L (−0.16 vs −0.11 mL/min/mo/1.73 m², P < 0.001).In this study, a clear association was found between low serum bicarbonate and loss of RRF in PD patients. Nevertheless, whether correction of metabolic acidosis for this indication provides additional protection for preserving RRF in these patients is unknown. Future interventional studies should more appropriately address this question.     

Peritoneal Dialysis Therapy for Patients with Liver and Renal Failure with Ascites

Two patients with severe liver disease complicated with ascites were recently treated at our institution. Both rapidly developed renal failure. In one patient, liver disease was the result of alcohol abuse, and in the other, was due to malnutrition associated with obesity and acute weight loss. The only reasonable therapeutic approach for these patients was believed to be a course of peritoneal dialysis, along with other supportive measures. In both cases, the management was successful. Furthermore, it was possible to discontinue dialysis at the time of discharge. We conclude that peritoneal dialysis can be a life-saving procedure in patients with severe liver disease and ascites complicated by renal failure.     

Umbilical Hernia in Peritoneal Dialysis Patients: Surgical Treatment and Risk Factors

No previous reports have focused on surgical treatments and risk factors of umbilical hernia alone in peritoneal dialysis (PD) patients. Herein, we evaluated the treatments and risk factors. A total of 411 PD patients were enrolled. Of the 15 patients with umbilical hernia (3.6%), six underwent hernioplasty. There was no recurrence in five patients treated with tension‐free hernioplasty. The mean PD vintage after onset of hernia in the hernioplasty group tended to be longer than that in the non‐hernioplasty group. An incarcerated hernia occurred in one non‐hernioplasty patient. Although the incidence was significantly higher among women (P = 0.02), female sex was not a risk factor for umbilical hernia (P = 0.08). Our findings suggest that umbilical hernias should be repaired for continuing PD. Furthermore, there were no significant risk factors for umbilical hernia in PD patients. Future studies with larger sample groups are required to elucidate these risk factors.     

Periodontal Treatment Reduces Chronic Systemic Inflammation in Peritoneal Dialysis Patients

Chronic systemic inflammation, a non traditional risk factor of cardiovascular diseases, is associated with increasing mortality in chronic kidney disease, especially peritoneal dialysis patients. Periodontitis is a potential treatable source of systemic inflammation in peritoneal dialysis patients. Clinical periodontal status was evaluated in 32 stable chronic peritoneal dialysis patients by plaque index and periodontal disease index. Hematologic, blood chemical, nutritional, and dialysis‐related data as well as highly sensitive C‐reactive protein were analyzed before and after periodontal treatment. At baseline, high sensitive C‐reactive protein positively correlated with the clinical periodontal status (plaque index; r = 0.57, P < 0.01, periodontal disease index; r = 0.56, P < 0.01). After completion of periodontal therapy, clinical periodontal indexes were significantly lower and high sensitivity C‐reactive protein significantly decreased from 2.93 to 2.21 mg/L. Moreover, blood urea nitrogen increased from 47.33 to 51.8 mg/dL, reflecting nutritional status improvement. Erythropoietin dosage requirement decreased from 8000 to 6000 units/week while hemoglobin level was stable. Periodontitis is an important source of chronic systemic inflammation in peritoneal dialysis patients. Treatment of periodontal diseases can improve systemic inflammation, nutritional status and erythropoietin responsiveness in peritoneal dialysis patients.     

Acute Kidney Injury in Critically Ill Patients: A Prospective Randomized Study of Tidal Peritoneal Dialysis Versus Continuous Renal Replacement Therapy

Few studies have discussed the role of peritoneal dialysis (PD) in managing acute kidney injury (AKI) in critically ill patients. The present study compares the outcome of AKI in intensive care unit (ICU) patients randomized to treatment with tidal PD (TPD) or continuous venovenous hemodiafiltration (CVVHDF). One hundred and twenty‐five ICU patients with AKI were randomly allotted to CVVHDF, (Group A, N = 62) or TPD, (group B, N = 63). Cause and severity of renal injury were assessed at the time of initiating dialysis. The primary outcome was hospital mortality at 28 days, and secondary outcomes were time to recovery of renal function, duration of stay in the ICU, metabolic and fluid control, and improvement of sensorial and hemodynamic parameters. No statistically significant differences were observed between groups in regard to patients’ characteristics. The survival at 28 days was significantly better in the patients treated with TPD when compared to CVVHDF (69.8% vs. 46.8%, P < 0.01). Infectious complications were significantly less (P < 0.01) in the TPD group (9.5%) when compared to the CVVHDF group (17.7%). Recovery of kidney function (60.3% vs. 35.5%), median time to resolution of AKI and the median duration of ICU stay of 9 days (7–11) vs. 19 days (13–20) were all in favor of TPD (P < 0.01). This study suggests that there are better outcomes with TPD compared to CRRT in the treatment of critically ill patients with AKI.     

Effect of Peritoneal Dialysis on Gastric Myoelectrical Activity in Patients with Chronic Renal Failure

Impaired gastric myoelectrical activity has been reported in patients with chronic renal failure (CRF). The effect of peritoneal dialysis on this function has not previously been described. The aim here was to investigate the effect of peritoneal dialysis on gastric myoelectrical activity. Gastric myoelectrical activity was recorded by electrogastrography (EGG) in 23 patients with CRF (18 with dyspepsia) during peritoneal dialysis and with the peritoneal cavity empty of dialysis fluid (14 patients), and in 20 healthy controls. Two 30-min EGG recordings before and after a solid test meal were analyzed using spectral analysis methods. No significant difference in the percentage of normal 2- to 4-cpm slow waves was found in patients on peritoneal dialysis compared to those with the peritoneal cavity empty of dialysis fluid or to controls (in fasting state 83 ± 3%, 80 ± 5% and 89 ± 4%, in fed state 91 ± 3%, 86 ± 4% and 83 ± 4%, respectively). It was found that the power ratio (change in power of normal slow waves in fed state) was significantly higher in the 14 patients on peritoneal dialysis compared to the same patients with the peritoneal cavity empty of dialysis fluid (27.2 ± 10.7 vs 8.6 ± 4.8, P < 0.05). There was no significant difference in the power ratio between patients with the peritoneal cavity empty of dialysis fluid and controls (8.6 ± 4.8 vs 7.5 ± 2.2). The subgroup of patients with no dyspepsia had a significantly higher power ratio compared to those with dyspepsia both on dialysis and with the peritoneal cavity empty of dialysis fluid (39.4 ± 13.7 vs 12.4 ± 5.2 and 29.2 ± 21.5 vs 2.8 ± 0.4 respectively, P < 0.05). In conclusion, there was no significant difference in gastric myoelectrical activity between patients with the peritoneal cavity empty of dialysis fluid and controls. Dialysis fluid in the peritoneal cavity seems to enforce the gastric myoelectrical signal.     

Encapsulating Peritoneal Sclerosis in Patients on Peritoneal Dialysis in Slovenia

Encapsulating peritoneal sclerosis (EPS) is a rare complication in patients on peritoneal dialysis (PD), the prevalence of which increases with the time spent on PD. Various causative factors have been proposed, but the pathogenesis still remains unclear. The aim of our retrospective study was to analyze the basic clinical characteristics and outcomes of five patients diagnosed with EPS out of 423 patients treated with PD between January 1983 and December 2003. One patient was admitted due to ultrafiltration failure of the peritoneal membrane, and four patients were admitted for acute peritonitis. All of our patients presented with clinical symptoms suggestive of obstructive ileus. We confirmed the diagnosis of EPS with a computer tomography scan, a diagnostic laparotomy or laparoscopy, and a biopsy of the parietal peritoneum. We treated all of our patients with catheter removal, transferal to hemodialysis, antibiotics, complete parenteral nutrition, methylprednisolone, and tamoxifen for 6 months. One patient was treated with surgical enterolysis and died of septic complications, another patient died of sudden cardiac death during treatment. Three patients were doing well for 4–7 months after the treatment was started. The incidence of EPS was 1.2% and the mortality rate was 40%. EPS is a rare complication in longstanding PD patients in our institution. Despite treatment with hemodialysis, complete parenteral nutrition, steroids, tamoxifen and surgical intervention, the mortality rate is high and comparable to other reports.     

Reducing Cardiometabolic Risk in Peritoneal Dialysis Patients: Role of the Dialysis Solution

Peritoneal dialysis (PD) is a well-established form of therapy for stage 5 chronic kidney disease requiring renal replacement therapy. d-Glucose has been used successfully for several decades as the osmotic agent employed in dialysis solutions to achieve adequate fluid removal. The absorption of 100–200 grams of glucose per day has been suggested as potentially increasing cardiometabolic risk, particularly in patients with diabetes. Supporting and undermining evidence for this hypothesis is reviewed, with a focus on the role of glucose absorption in changes in body composition, dyslipidemia, and glycemic control in diabetic PD patients. Clinical strategies to optimize fluid removal while minimizing the metabolic impact of glucose absorption are also discussed.     

Dialysis patients refusing kidney transplantation: data from the Slovenian Renal Replacement Therapy Registry

Kidney transplantation is considered the best renal replacement therapy (RRT) for patients with end-stage renal disease; nevertheless, some dialysis patients refuse to be transplanted. The aim of our registry-based, cross-sectional study was to compare kidney transplant candidates to dialysis patients refusing transplantation. Data were collected from the Slovenian Renal Replacement Therapy Registry database, as of 31 December 2008. Demographic and some RRT data were compared between the groups. There were 1448 dialysis patients, of whom 1343 were treated by hemodialysis and 105 by peritoneal dialysis (PD); 132 (9%) were on the waiting list for transplantation, 208 (14%) were preparing for enrollment (altogether 340 [23%] dialysis patients were kidney transplant candidates); 200 (13.7%) patients were reported to refuse transplantation, all ≤ 65 years of age; 345 (24%) were not enrolled due to medical contraindications, 482 (33%) due to age, and 82 (6%) due to other or unknown reasons. No significant difference was found in age, gender, or presence of diabetes between kidney transplant candidates vs. patients refusing transplantation (mean age 50.5 ± 13.9 vs. 51.3 ± 9.6 years, males 61% vs. 63%, diabetics 18% vs. 17%). The proportion of patients ≤ 65 years old who were refusing transplantation was 28% (187/661) for hemodialysis and 17% (13/79) for PD patients (P = 0.03). There is a considerable group of dialysis patients in Slovenia refusing kidney transplantation. Compared to the kidney transplant candidates, they are similar in age, gender and prevalence of diabetes. Patients treated by peritoneal dialysis refuse kidney transplantation less often than hemodialysis patients.     

Relationship Between Residual Renal Function and Serum Fibroblast Growth Factor 23 in Patients on Peritoneal Dialysis

Fibroblast growth factor 23 (FGF23) levels in dialysis patients are influenced by various factors, including phosphorus load. However, the clinical parameters that determine serum FGF23 levels in patients on peritoneal dialysis (PD) remain unclear. The aim of the present study was to examine the effects of clinical factors, on serum FGF23 levels, with an emphasis on residual renal function (RRF). This cross‐sectional study included 56 outpatients undergoing PD therapy. Urine volume ≥100 mL/day or renal creatinine (Cr) clearance was used as a surrogate marker for RRF. Clinical characteristics were compared between patients with and without RRF. Linear regression analysis was conducted with serum FGF23 level as the dependent variable and renal Cr clearance as the main independent variable. The median and interquartile range of serum FGF23 levels were 5970 (1451–11 688) pg/mL. Patients with RRF showed higher urinary and total phosphate eliminations, and lower serum FGF23 and phosphate levels than patients without RRF. Multivariate linear regression analysis showed that the renal Cr clearance and serum phosphate and dialysis history were negatively associated with serum FGF23 levels, even after adjusting for potential confounders including peritoneal Cr clearance. Further, the predictabilities of serum FGF23 were comparable among renal Cr clearance, Kt/V for urea, and renal phosphate clearance. RRF determined by renal Cr clearance or residual urine volume is an independent negative determinant of serum FGF23 levels in PD patients.     

A 24‐Week Anemia Correction Study of Daprodustat in Japanese Dialysis Patients

Daprodustat is an oral hypoxia‐inducible factor prolyl hydroxylase inhibitor developed for treating anemia of chronic kidney disease. This 24‐week, phase 3, open‐label study (NCT02829320) evaluated whether daprodustat could achieve and maintain target hemoglobin levels in Japanese hemodialysis patients with anemia not receiving an erythropoiesis‐stimulating agent. Twenty‐eight patients received daprodustat 4 mg once daily for 4 weeks, after which doses were adjusted to achieve a hemoglobin target of 10.0 to 12.0 g/dL (inclusive). Baseline mean hemoglobin was 9.10 g/dL and mean change from baseline at 4 weeks was 0.79 g/dL (95% CI, 0.53 to 1.05). Mean hemoglobin levels reached the target range by week 8 and were maintained within this range through week 24. Daprodustat 4 mg once daily increased hemoglobin over the first 4 weeks. Throughout the 24‐week study, daprodustat achieved and maintained hemoglobin within the target range and no new safety concerns were identified in hemodialysis patients not receiving erythropoiesis‐stimulating agents.