Effects of sodium-glucose co-transporter 2 inhibitors on ultrafiltration in patients with peritoneal dialysis: a protocol for a randomized, double-blind, placebo-controlled, crossover trial (EMPOWERED).

BACKGROUND: Volume overload is common and associated with high mortality in patients on peritoneal dialysis (PD). Traditional strategies including diuretics, water/salt restriction, and icodextrin-based solutions cannot always fully correct this condition, necessitating novel alternative strategies. Recent studies confirmed the expression of sodium-glucose cotransporter 2 (SGLT2) in the human peritoneum. Experimental data suggest that SGLT2 inhibitors decrease glucose absorption from the PD solution, thereby increasing the ultrafiltration volume. This trial aims to assess whether SGLT2 inhibitors increase the ultrafiltration volume in patients on PD. METHODS: The EMPOWERED trial (trial registration: jRCTs051230081) is a multicenter, randomized, double-blind, placebo-controlled, crossover trial. Patients with clinically diagnosed chronic heart failure are eligible regardless of the presence of diabetes if they use at least 3 L/day glucose-based PD solutions. Participants will be randomly assigned (1:1) to receive empagliflozin 10 mg once daily and then placebo or vice versa. Each treatment period will last 8 weeks with a 4-week washout period. This study will recruit at least 36 randomized participants. The primary endpoint is the change in the daily ultrafiltration volume from baseline to week 8 in each intervention period. The key secondary endpoints include changes in the biomarkers of drained PD solutions, renal residual function, and anemia-related parameters. CONCLUSIONS: This trial aims to assess the benefit of SGLT2 inhibitors in fluid management with a novel mechanism of action in patients on PD. It will also provide insights into the effects of SGLT2 inhibitors on solute transport across the peritoneal membrane and residual renal function.

Retroperitoneal Hemorrhage in Patients with COVID-19 Undergoing Hemodialysis: Three Case Reports.

A 73-year-old man receiving hemodialysis and antiplatelets was admitted with a mild case of COVID-19. Heparin was added, and iliopsoas hemorrhage developed. He was successfully treated by interventional radiology. A 76-year-old man receiving hemodialysis and antiplatelets was admitted with mild COVID-19. Heparin was added, and iliacus hemorrhage developed. Despite heparin discontinuation, he died of worsening pneumonia. A 74-year-old man undergoing hemodialysis was admitted with severe COVID-19. Gastrointestinal bleeding developed during continuous hemodiafiltration with heparin. Upon switching to nafamostat and increasing the dose, iliopsoas hemorrhage developed. Despite interventional radiology, he died of infectious complications. Attention to hemorrhagic complications is therefore needed in patients with COVID-19.

Axillary arterial angiosarcoma in a nonfunctioning arteriovenous fistula limb of a patient undergoing hemodialysis: case report with literature review.

A 54-year-old man was admitted to our hospital with a painful left axillary mass. He had a 27-year history of hemodialysis for end-stage kidney disease because of chronic glomerulonephritis. He had a right radial artery-cephalic vein arteriovenous fistula and left nonfunctioning arteriovenous fistula. Computed tomography imaging showed a left axillary arterial mass with peripheral hematoma and multiple lung tumors. On hospital day 3, he showed disturbances in consciousness as well as enlargement of the axillary mass and hematoma. We performed emergency surgery to resect the left axillary tumor. The patient was diagnosed with angiosarcoma upon histopathological examination of the resected specimen on hospital day 15. Because his condition was extremely poor, we provided supportive care to him, not chemotherapy. He expired on hospital day 25. Angiosarcoma remains a rare disease; however, this case highlights the importance of including angiosarcoma in the differential diagnosis for upper extremity pain in patients undergoing hemodialysis.

Lidocaine-Propitocain Cream, a Eutectic Mixture of Local Anesthetics, Effectively Relieves Pain Associated With Vascular Access Intervention Therapy in Patients Undergoing Hemodialysis: A Placebo-Controlled, Double-Blind, Crossover Study.

Vascular access intervention therapy (VAIVT) is necessary to maintain vascular access in patients undergoing hemodialysis. VAIVT-associated vasodilatation is painful. However, few reports have focused on effective pain relief at the time of VAIVT. The present study was performed to determine whether lidocaine-propitocain cream, a eutectic mixture of local anesthetics (EMLA), effectively reduces VAIVT-associated pain in patients undergoing hemodialysis. This placebo-controlled, double-blind, crossover study was conducted in a single center. Among 210 patients who underwent a total of 437 VAIVT procedures from August 2017 to June 2018, 30 patients were randomly allocated to either the EMLA-placebo arm or placebo-EMLA arm at the time of VAIVT. EMLA application significantly reduced the visual analog scale score compared with placebo (47.0 ± 21.1 vs. 68.6 ± 20.7 mm, respectively; P < 0.05). EMLA is a safe and effective treatment for relief of VAIVT-associated pain in patients undergoing hemodialysis.

Severe Hypocalcemia and Resulting Seizure Caused by Vitamin D Deficiency in an Older Patient Receiving Phenytoin: Eldecalcitol and Maxacalcitol Ointment as Potential Therapeutic Options for Hypocalcemia.

An 82-year-old man treated with phenytoin for the prevention of symptomatic epilepsy was hospitalized to treat consciousness disturbance, seizure, and hypocalcemia (serum calcium: 4.6 mg/dL). Serum 25-hydroxyvitamin D level was very low (5.4 ng/mL), whereas serum calcitriol level was normal (27 pg/mL) and serum intact parathyroid hormone level was increased (369 pg/mL). He was finally diagnosed with vitamin D deficiency associated with low sunlight exposure and long-term phenytoin use for symptomatic epilepsy: phenytoin is shown to accelerate catabolism of 25-hydroxyvitamin D. Combination treatment with eldecalcitol and maxacalcitol ointments successfully normalized corrected serum calcium level: both eldecalcitol and maxacalcitol are vitamin D receptor activators used for osteoporosis and psoriasis, respectively. Our case illustrates the importance of periodic serum calcium level monitoring in patients receiving anti-epileptic drugs and the usefulness of eldecalcitol and maxacalcitol ointment as a therapeutic option for hypocalcemia, especially in countries where native vitamin D and 25-hydroxyvitamin D are not available.

Hypercalcemia and acute kidney injury induced by eldecalcitol in patients with osteoporosis: a case series of 32 patients at a single facility.

BACKGROUND: Eldecalcitol (ELD) is an active vitamin D3 analog that is widely used in Japan for the treatment of osteoporosis. The most common adverse drug reaction of ELD is hypercalcemia. However, few reports have focused on acute kidney injury (AKI) associated with ELD-induced hypercalcemia. MATERIALS AND METHODS: We retrospectively reviewed the medical records at our hospital for cases of hypercalcemia-induced AKI between April 2013 and February 2018. Among them, we focused on patients who developed AKI secondary to ELD-induced hypercalcemia. RESULTS: Among 69 patients who developed hypercalcemia-induced AKI, 32 patients (46.4%) developed AKI associated with ELD-induced hypercalcemia. Their mean age was 82 ± 5 years, 97% of them were female, mean corrected serum calcium level was 12.2 ± 1.5 mg/dL, serum creatinine level was 2.5 ± 2.2 mg/dL, and estimated glomerular filtration rate was 23.9 ± 14.4 ml/min/1.73 m2 on admission. ELD administration was discontinued in all patients and some of them were treated with hydration with or without calcitonin, which was followed by a normalization of serum calcium level. Corrected serum calcium level on admission was significantly higher (p < .05) in patients treated with magnesium oxide. Although there were no significant differences, serum calcium and creatine levels on admission tended to be higher in patients who were treated with other drugs that affect renal hemodynamics and renal calcium metabolism than those not taking these drugs. CONCLUSIONS: Prescribers of ELD should regularly monitor serum calcium levels and kidney function to prevent hypercalcemia and AKI associated with ELD and pay more attention to concomitant drugs especially magnesium oxide.

Early postoperative change in serum creatinine predicts acute kidney injury after cardiothoracic surgery: a retrospective cohort study.

BACKGROUND: Acute kidney injury (AKI) is one of the most severe complications after cardiothoracic surgery (CTS). However, diagnosis of AKI by elevation of serum creatinine (SCr) misses a critical time period for prevention and treatment of AKI. We have observed that patients who develop AKI show a smaller SCr decrease after CTS than those without AKI. Hence, we hypothesized that the magnitude of the SCr change (ΔSCr) measured early after CTS can predict subsequent AKI. METHODS: We conducted a retrospective analysis from January 2014 to December 2016 to examine the association of ΔSCr with AKI. ΔSCr was calculated as follows: (early postoperative SCr on intensive care unit [ICU] admission) - (preoperative SCr). Established risk factors and demographics were included in the multivariate-adjusted logistic regression model. AKI was defined by SCr criteria of the Kidney Disease: Improving Global Outcomes group. RESULTS: Among 252 patients who underwent CTS, 69 developed AKI. The median ΔSCr was - 0.14 mg/dL (range - 0.96-0.45). Patients were divided into three groups based on ΔSCr: Group 1, ≤ - 0.2 mg/dL (n = 84); Group 2, > - 0.2 to < - 0.1 mg/dL (n = 76); and Group 3, ≥ - 0.1 mg/dL (n = 92). In the multivariate analysis, Group 3 had a significantly higher incidence of AKI than Group 1 (odds ratio, 7.34; 95% confidence interval 2.55-23.3). ΔSCr was an independent risk factor for AKI (odds ratio for every 0.1-mg/dL increase in ΔSCr, 1.55; 95% confidence interval 1.23-1.97). CONCLUSIONS: A minor change in the SCr level early after CTS can predict subsequent AKI just after ICU admission.

Better Oral Hygiene Habits Are Associated With a Lower Incidence of Peritoneal Dialysis-Related Peritonitis.

Some peritoneal dialysis (PD)-related peritonitis cases are thought to be caused by the pathogens in the oral cavity; however, the relationship between peritonitis and oral hygiene habits is unclear. In this study, we retrospectively examined the relationship between oral hygiene habits and peritonitis in patients who agreed to a questionnaire survey. Of the 75 patients, 37 patients developed PD-related peritonitis during the observation period. Peritonitis-free survival was significantly higher in patients who spent more time on oral hygiene daily and in patients who replaced their toothbrush more frequently (P < 0.05). According to multivariable analysis, increased daily oral hygiene duration and more frequent toothbrush replacement were associated with a significantly (P < 0.01) lower risk for peritonitis (hazard ratio [HR] 0.37 [95% CI, 0.18-0.77] and HR 0.35 [95% CI, 0.17-0.70], respectively). In conclusion, PD patients with superior oral hygiene habits showed a lower risk for PD-related peritonitis.

A case of congenital left ventricular diverticulum in a patient with autosomal dominant polycystic kidney disease: possible mechanistic link between polycystin and ventricular diverticulum.

A 40-year-old woman had been followed as an outpatient to manage chronic kidney disease secondary to autosomal dominant polycystic kidney disease (ADPKD). Atrial premature contraction was found incidentally on an electrocardiogram during her regular follow-up examination. Subsequent transthoracic echocardiography detected an abnormal structure located very close to the left ventricular outflow tract (23 mm long × 15 mm wide in diastole). The structure was finally diagnosed as congenital left ventricular diverticulum (CLVD) using transesophageal echocardiography, contrast-enhanced computed tomography, and magnetic resonance imaging. Although CLVD occasionally causes intraventricular coagulation, lethal arrhythmia, and congestive heart failure, the size and location of her diverticulum remained unchanged over time and a 24-h Holter electrocardiogram showed no lethal arrhythmias. Accordingly, neither anticoagulation therapy nor surgical resection of the diverticulum was performed. To the best of our knowledge, ours is the first case of CLVD in a patient with ADPKD. Because gene abnormalities in polycystin coding are mechanistically related to the development of colonic diverticulum and abnormal cyst formation in ADPKD patients, we suspected that CLVD and abnormal cyst formation were related to the same gene abnormality in ADPKD. More case reports, case series studies, and basic research are required to determine whether CLVD in ADPKD is mechanistically associated with abnormal polycystin or just a coincidence.

Cholesterol Crystal Embolism Induced by Direct Factor Xa Inhibitor: A First Case Report.

An 80-year-old man presented at our hospital with renal failure. He had been treated with edoxaban, an oral direct factor Xa inhibitor, for deep vein thrombosis for 10 months prior to admission. Although the pulses in his bilateral pedal arteries were palpable, cyanosis was present in the bilateral toes. Laboratory data indicated azotemia and eosinophilia. A skin biopsy confirmed a diagnosis of cholesterol crystal embolism (CCE). Because no invasive vascular procedure was performed, we assumed that CCE was related to edoxaban. To the best of our knowledge, this is the first case report suggesting CCE induced by an Xa inhibitor.

Modified Simple Peritoneal Wall Anchor Technique (PWAT) in Peritoneal Dialysis.

♦ BACKGROUND: Outflow obstruction, a common complication in patients with peritoneal dialysis (PD), usually results in unnecessary catheter removal or replacement. This study describes a modified simple method of anchoring a PD catheter on the anterior peritoneal wall without using a laparoscopic system (peritoneal wall anchor technique, PWAT). ♦ METHODS: We performed a retrospective cohort study of consecutive PD catheter insertions, and compared the catheter survival rate between the traditional method and the modified simple PWAT. The traditional method was used in 54 cases and the modified simple PWAT was used in 17 cases. The primary endpoint was the occurrence of surgical catheter repair because of outflow obstruction by day 365. The secondary endpoint was the occurrence of catheter migration with obstruction requiring any interventions, including the alpha-replacement method by day 365. Catheter survival was analyzed by Kaplan-Meier survival curves. ♦ RESULTS: Migration-free catheter survival was significantly (p = 0.02) higher in the PWAT group (100%, 17/17) than in the traditional group (72.2%, 39/54). Catheter survival without surgical repair or cessation of PD was also significantly (p = 0.04) higher in the PWAT group (100%, 17/17) than in the traditional group (77.8%, 42/54). Similarly, migration-free and surgery-free catheter survival rates in cases with a straight-type catheter in the PWAT group were significantly higher than those in cases with a straight-type catheter in the traditional group. ♦ CONCLUSIONS: Our results suggest that the modified simple PWAT provides a better catheter survival rate than the traditional method by preventing catheter migration with obstruction in PD.

Autoimmune autonomic ganglionopathy manifesting as acute-onset orthostatic hypotension in a patient undergoing peritoneal dialysis.

Orthostatic hypotension is an important complication in the management of patients receiving dialysis therapy. As for the orthostatic hypotension caused by decreased peripheral artery resistance, diabetic neuropathy and amyloidosis are the two main causes of hypotension in dialysis patients. However, some patients develop orthostatic hypotension that is caused by dysfunction of the autonomic nervous system, not by diabetic or amyloidosis-related neuropathy. We herein present a case of a 56-year-old man with a 17-year history of peritoneal dialysis therapy, who developed acute-onset orthostatic hypotension accompanied by hypohidrosis and erectile dysfunction. Because serum autoantibodies to ganglionic nicotinic acetylcholine receptor were detected, he was diagnosed with autoimmune autonomic ganglionopathy (AAG). He was treated with high-dose immunoglobulin therapy (0.6 g per kg of body weight per day) for 5 consecutive days, which resulted in a gradual improvement in dizziness. Two months after the onset of AAG, he could discontinue vasopressors (fludrocortisone acetate and midodrine hydrochloride) and continued maintenance dialysis therapy without the use of vasopressors. This case indicates that physicians should consider autonomic neuropathy including AAG as a differential diagnosis when they encounter dialysis patients with orthostatic hypotension.

Prognostic significance of left ventricular hypertrophy observed at dialysis initiation depends on the pre-dialysis use of erythropoiesis-stimulating agents.

BACKGROUND: Recent experimental studies suggest that erythropoietin promotes beneficial myocardial remodeling during left ventricular hypertrophy (LVH); however, such compensatory capacity may be limited due to insufficient erythropoietin production in chronic kidney disease patients. Thus, this study aimed to explore the effect of pre-dialysis erythropoiesis-stimulating agent (ESA) use on the prognostic significance of LVH in dialyzed patients. METHODS: This retrospective study included 404 consecutive patients who started dialysis between 2001 and 2009. The interaction of ESA with the association between left ventricular mass index (LVMI) observed at dialysis initiation and all-cause and cardiovascular mortality was analyzed at the end of 2010 using the Cox model. RESULTS: During a median follow-up of 36.5 months, 164 patients died, 31 of them from heart failure. The frequency of pre-dialysis ESA use was 58.7 % and median LVMI was 160.3 g/m(2). Of interest, patients with the lowest tertile of LVMI had worse survival compared with those with each subsequent tertile. LVMI was inversely associated with all-cause mortality [hazard ratio (HR) 0.991, 95 % confidence interval (CI) 0.988-0.995, P = 0.000] after extensive adjustment including ejection fraction, whereas the prognostic value of LVMI for cardiovascular mortality was dependent on pre-dialysis ESA use [adjusted HR 1.010, 95 % CI 0.999-1.020, P = 0.065 for pre-dialysis ESA(+) and 0.978, 95 % CI 0.967-0.989, P = 0.000 for pre-dialysis ESA(-), respectively]. CONCLUSIONS: Our results suggest that reverse epidemiology may exist between LVH and mortality and that pre-dialysis ESA use may modify the prognostic significance of LVH observed at dialysis initiation for cardiovascular mortality in dialyzed patients.

[Ratio of serum levels of 1,25-dihydroxyvitamin D3 and parathyroid hormone for the diagnosis and treatment of tuberculous peritonitis in a chronic kidney disease patient: a case report].

An 80-year-old man was admitted to our hospital because of exacerbation of preexisting chronic kidney disease (CKD). On admission, he showed elevated levels of serum creatinine (6.37 mg/dL) and corrected calcium (13.7 mg/dL). Although the serum levels of intact parathyroid hormone (I-PTH) and parathyroid hormone-related peptide(PTITH-rP)were low, the serum 1,25-dihydroxyvitamin D3 (1,25 (OH)2D3)levels were high. Computed tomography (CT) revealed ascites, and the ascitic fluid was exudative and serous with predominance of lymphocytes. The levels of adenosine deaminase (ADA) in the ascitic fluid were also elevated, and the results of QuantiFERON-TB2G (QFT-2G)assay were positive, indicating tuberculous peritonitits. Ascites resolved rapidly after initiation of the antituberculosis therapy. The elevated levels of serum calcium and 1,25 (OH) 2D3 returned to below-normal levels; however, serum i-PTH levels increased from 8.9 pg/ mL to 432 pg/mL. Diagnosis of extrapulmonary tuberculosis is often difficult in CKD patients. CKD patients show abnormal vitamin D activation, so these patients usually have low levels of serum 1,25(OH)2D3. On the other hand, in our patient, 1,25(OH)2D3 was extrarenally produced from tuberculous granuloma and therefore, he showed high levels of serum 1,25(OH)2D3 and correspondingly, low levels of serum i-PTH. We observed that the ratio of 1,25 (OH) 2D3:i-PTH decreased due to antituberculosis therapy. This ratio facilitated the diagnosis and evaluation of treatment for this condition.

Long-term outcomes of idiopathic membranous nephropathy in Japanese patients treated with low-dose cyclophosphamide and prednisolone.

BACKGROUND: Treatment with cyclophosphamide and steroids for idiopathic membranous nephropathy (IMN) is effective in Caucasian patients, but the cumulative cyclophosphamide dosage exceeds 10 g and includes steroid pulse therapy. Adverse effects and difficulties with repeating treatment are major limitations. We studied the long-term outcomes of low-dose cyclophosphamide and prednisolone therapy in Japanese patients, who were thought to have relatively benign IMN compared with Caucasian patients. METHODS: This is a prospective cohort study of 103 consecutive Japanese patients with IMN and nephrotic syndrome. Patients were treated with cyclophosphamide (50 mg/day for the first 3 months and 25 mg/day for the next 3 months) and prednisolone (30 mg/day for the first week and the dosage was gradually tapered to withdraw by 2 years). Additional therapies were allowed for initial treatment failure or relapse. RESULTS: With a mean observation period of 8.5 years, 90 patients (87.4%) achieved proteinuria of <1 g/day and 78 (75.7%) achieved complete remission. A total of 27 patients did not respond to initial treatment and 30 patients had relapses after remission. Of these patients, 39 received additional therapies. At the last observation, 12 patients had developed renal insufficiency (S-Cr >1.5 mg/dL) but only 2 patients had reached renal death. Multivariate analysis revealed that the duration without remission was the strongest risk factor for renal prognosis. There were 14 deaths, and 8 patients developed cancers during the observation period. CONCLUSION: Treating nephrotic IMN in Japanese patients with low-dose cyclophosphamide and prednisolone is beneficial for long-term renal prognosis with relatively few adverse effects.