Allo-Hemodialysis, a Novel Dialytic Treatment Option for Patients with Kidney Failure: Outcomes of Mathematical Modelling, Prototyping, and Ex Vivo Testing.

It has been estimated that in 2010, over two million patients with end-stage kidney disease may have faced premature death due to a lack of access to affordable renal replacement therapy, mostly dialysis. To address this shortfall in dialytic kidney replacement therapy, we propose a novel, cost-effective, and low-complexity hemodialysis method called allo-hemodialysis (alloHD). With alloHD, instead of conventional hemodialysis, the blood of a patient with kidney failure flows through the dialyzer's dialysate compartment counter-currently to the blood of a healthy subject (referred to as a "buddy") flowing through the blood compartment. Along the concentration and hydrostatic pressure gradients, uremic solutes and excess fluid are transferred from the patient to the buddy and subsequently excreted by the healthy kidneys of the buddy. We developed a mathematical model of alloHD to systematically explore dialysis adequacy in terms of weekly standard urea Kt/V. We showed that in the case of an anuric child (20 kg), four 4 h alloHD sessions are sufficient to attain a weekly standard Kt/V of >2.0. In the case of an anuric adult patient (70 kg), six 4 h alloHD sessions are necessary. As a next step, we designed and built an alloHD machine prototype that comprises off-the-shelf components. We then used this prototype to perform ex vivo experiments to investigate the transport of solutes, including urea, creatinine, and protein-bound uremic retention products, and to quantitate the accuracy and precision of the machine's ultrafiltration control. These experiments showed that alloHD performed as expected, encouraging future in vivo studies in animals with and without kidney failure.

Sodium removal per ultrafiltration volume in automated peritoneal dialysis in pediatric patients.

BACKGROUND: The standard rate of sodium removal in adult anuric patients on continuous ambulatory peritoneal dialysis (CAPD) is 7.5 g/L of ultrafiltration volume (UFV). Although automated PD (APD) is widely used in pediatric patients, no attempt has yet been made to estimate sodium removal in APD. METHODS: The present, retrospective cohort study included pediatric patients with APD who were managed at Tokyo Metropolitan Children's Medical Center between July 2010 and November 2017. The patients underwent a peritoneal equilibrium test (PET) at our hospital. Sodium removal per UFV was calculated by peritoneal function and dwell time using samples from patients on APD with 1- and 2-h dwell effluent within three months of PET and 4- and 10-h dwell effluent at PET. RESULTS: In total, 217 samples from 18 patients were included, with 63, 81, and 73 of the samples corresponding to the High [H], High-average [HA], and Low-average [LA] PET category, respectively. Sodium removal per UFV (g/L in salt equivalent) for dwell times of one, two, four, and ten hours was 5.2, 8.8, 8.0, and 11.5 for PET [H], 5.3, 5.8, 5.6, and 8.1 for PET [HA], and 4.6, 5.1, 5.1, and 7.1 for PET [LA], respectively. CONCLUSIONS: Sodium removal per UFV in pediatric APD was less than the standard adult CAPD and tended to be lower with shorter dwell times, leading to sodium accumulation. Therefore, salt intake should be restricted in combination with one or more long daytime dwells, especially in anuric patients.

Novel Algorithm for the Differential Diagnosis of Hyponatraemia in Anuric Patients Undergoing Maintenance Haemodialysis.

INTRODUCTION: Hyponatraemia is associated with increased mortality in patients undergoing maintenance haemodialysis. In anuric patients, hyponatraemia development depends on the water-sodium ratio in retained fluid within the interdialysis interval (IDI). OBJECTIVE: This study aimed to calculate the retained sodium-retained water ratio in patients on maintenance haemodialysis and make a differential diagnosis of hyponatraemia according to these data. METHODS: The amount of retained water was determined as body weight gain (ΔBW) within the IDI. Sodium retention was calculated using our formula: eRNa+ = ΔBW × (SNa+)t2 - total body water (TBW)t1 × ([SNa+]t1 - [SNa+]t2), where TBW represents the calculated volume of the total body water and (SNa+)t1 and (SNa+)t2 represent the sodium concentration at the beginning and at the end of the IDI, respectively. We performed 89 measurements in 32 anuric patients on maintenance haemodialysis. RESULTS: Hyponatraemia was detected in 13 measurements at the end of the IDI. The ΔBW had no statistically significant difference between normonatraemic and hyponatraemic patients. Hyponatraemic patients had significantly lower levels of retained sodium. The retained water--retained sodium ratio facilitated in differentiating dilution hyponatraemia, nutritional hyponatraemia, depletion hyponatraemia, and dilution hyponatraemia associated with sodium wasting or malnutrition. CONCLUSION: The composition of retained fluid during the IDI may be hypotonic, hypertonic, or isotonic in relation to the extracellular fluid. Most of the hyponatraemic patients had hypotonic fluid retained during the IDI because of dilution as well as gastrointestinal sodium loss and/or malnutrition.

Successful High-dose Chemotherapy in Combination With Autologous Peripheral Blood Stem Cell Transplantation in an Anuric Child With Neuroblastoma.

No reports describe high-dose chemotherapy (HDCT) with autologous peripheral blood stem cell transplantation (auto-PBSCT) in pediatric patients with neuroblastoma and end-stage renal disease. Here, we report the case of a patient with high-risk neuroblastoma who developed anuria during treatment. HDCT with auto-PBSCT under hemodialysis, with strict attention to the ultrafiltration volume and dose modification of alkylating agents, was performed. Although the first auto-PBSCT led to engraftment failure, the second auto-PBSCT resulted in successful myeloid engraftment 8 months after anuria. This case demonstrated that HDCT with auto-PBSCT can be safely performed in children with renal failure under hemodialysis.

Reflex Anuria Following Retrograde Pyelography: A Case Report and Literature Review.

A case of acute kidney injury due to reflex anuria that was caused by retrograde pyelography and required temporary hemodialysis is reported. An 83-year-old Japanese woman presented with anuria 2 days after undergoing bilateral retrograde pyelography for the investigation of gross hematuria. Retrograde pyelography showed no apparent abnormality, such as malignancy or urolithiasis, but pyelorenal extravasation of contrast medium was remarkable. Her anuria improved promptly after hemodialysis, allowing her treatment to conclude with only one hemodialysis session, and a normal renal function was restored with no sequelae. The details of this case and a review of the relevant literature are presented.

Bilateral retrograde pyelography leading to anuria.

Retrograde pyelography (RGP) is done to evaluate the collecting system when intravenous contrast studies are contraindicated due to renal insufficiency or prior adverse reactions. We report a patient who developed acute renal shutdown following bilateral RGP in the same sitting done for evaluation of positive malignant cytology of urine. A 65-year-old man on treatment for left stroke and hypertension, with a baseline serum creatinine of 1.9 mg/dl presented with painless haematuria for 2 months. Plain computed tomogram revealed a small papillary growth on the posterior wall of the urinary bladder. Transurethral resection revealed inflammatory atypia. As the patient continued to have haematuria, he was taken up for bilateral ureteric washings for cytology and bilateral RGP. A 5-Fr universal ureteral catheter was used to cannulate the ureters, urine was aspirated for cytology and 6 ml of 76% meglumine diatrizoate (1:2) was injected, and sufficient opacification with no abnormality or pyelosinus/venous or lymphatic reflux was noted. In the immediate postoperative period, he developed anuria and the serum creatinine rose to 3.6 mg/dl on postoperative day 1 and to 7.5 mg/dl on day 5. He needed three sessions of haemodialysis. Ultrasonography showed no hydroureteronephrosis. Urine output improved and his serum creatinine stabilized at the preoperative level of 1.8 mg/dl. The patient is doing well with stable renal function at 12 months. Although RGP is useful, it needs to be done with caution if a bilateral procedure is contemplated. This entity is seldom reported, and routine double-J stenting following unilateral/bilateral RGP also needs evaluation.

Uremic encephalopathy in patients undergoing assisted peritoneal dialysis: a case series and literature review.

We sometimes hesitate to switch renal replacement therapy from peritoneal dialysis (PD) particularly in elderly patients due to their physical tolerance levels and lifestyles. Here, we describe the cases of three patients treated with PD alone despite an anuric status who subsequently developed uremic encephalopathy, which was successfully treated with hemodialysis (HD). The first patient was a 75-year-old woman who developed uremic encephalopathy with an anuric status and inadequate PD after 7 months of treatment. HD immediately improved her condition; encephalopathy did not recur with combined therapy of PD and HD. The second patient was a 69-year-old woman who developed anuria and was treated with combined therapy. Her arteriovenous fistula was obstructed; therefore, she was treated with PD alone. Total weekly Kt/V was sufficiently high at 1.95; however, she developed uremic encephalopathy the following month, which was successfully treated with HD. The third patient was an 84-year-old woman who developed anuria, but was treated with PD alone with adequate total weekly Kt/V of 2.2. PD could not be performed for 2 days because of myocardial infarction intervention; subsequently, she developed uremic encephalopathy, which was successfully treated with HD. These cases are the first of their kinds, wherein patients undergoing PD, developed uremic encephalopathy without any obvious triggers, including drugs, and illustrate the necessity of initiating combined therapy for such patients considering the risk of developing severe uremia leading to uremic encephalopathy, in spite of it being less preferable for elderly patients due to their physical conditions and lifestyles.

Amnioinfusions to Treat Early Onset Anhydramnios Caused by Renal Anomalies: Background and Rationale for the Renal Anhydramnios Fetal Therapy Trial.

Anhydramnios caused by early anuria is thought to be universally fatal due to pulmonary hypoplasia. Bilateral renal agenesis and early fetal renal failure leading to anhydramnios constitute early pregnancy renal anhydramnios (EPRA). There have been successful reports of amnioinfusions to promote lung growth in the setting of EPRA. Some of these successfully treated EPRA fetuses have survived the neonatal period, undergone successful dialysis, and subsequently received a kidney transplant. Conversely, there are no reports of untreated EPRA survivors. This early success of amnioinfusions to treat EPRA justifies a rigorous prospective trial. The objective of this study is to provide a review of what is known about fetal therapy for EPRA and describe the Renal Anhydramnios Fetal Therapy trial. We review the epidemiology, pathophysiology, and genetics of EPRA. Furthermore, we have performed systematic review of case reports of treated EPRA. We describe the ethical framework, logistical challenges, and rationale for the current single center (NCT03101891) and planned multicenter trial.

Emphysematous pyelonephritis and cystitis in a patient with uremia and anuria: A case report and literature review.

INTRODUCTION: Emphysematous pyelonephritis (EPN) or cystitis (EC) is a severe infection of the urinary tract with high mortality. EPN is uncommon among the patients of end stage of renal failure (ESRD) CASE PRESENTATION:: A 38-year-old male with uremia and anuria who was on hemodialysis was found to have gas formation in the bilateral pelvis, ureters, and urinary bladder by CT scan. The diagnosis was emphysematous pyelonephritis and cystitis. And Foley catheter was placed and bladder irrigation was performed. Escherichia coli infection was identified in urine culture and antibiotic was prescribed accordingly. Gas disappeared completely and the patient recovered uneventfully. CONCLUSION: This is the first case report of asymptomatic EPN and EC in uremic patient, and conservative management was optimistic in this condition. More attention should be paid to EPN and EC happening to ESRD patients.

Recovery of renal function in a heart transplantation recipient with over 300 days of iatrogenic anuria: A case report.

RATIONALE: Anuria is a severe symptom indicating severe kidney damage. Patient recovery from prolonged anuria is rarely reported. PATIENT CONCERNS: A 15-year-old boy received gender- and weight-mismatch heart transplantation (HT) due to dilated cardiomyopathy. He developed severe hypotension, and heart failure 24 hours after surgery, which were relieved by preload reduction treatments. Although, routine examinations did not show any abnormalities in renal function before surgery, anuria occurred 4 days after preload reduction treatments (24-hour urine volume was 23 mL). DIAGNOSIS: The patient was diagnosed with acute kidney injury (AKI). INTERVENTIONS: He was admitted to continuous renal replacement therapy (CRRT) or hemodialysis. OUTCOMES: Surprisingly, his urine volume was gradually, and miraculously, restored to more than 1000 mL/24 hours after over 300 days of anuria. Hemodialysis was not needed in the twentieth month after surgery. Moreover, he partially, recovered renal function. LESSONS: This case indicates the likelihood of recovery from long-term anuria.

Influenza-associated thrombotic microangiopathies.

Thrombotic microangiopathy (TMA) refers to phenotypically similar disorders, including hemolytic uremic syndromes (HUS) and thrombotic thrombocytopenic purpura (TTP). This review explores the role of the influenza virus as trigger of HUS or TTP. We conducted a literature survey in PubMed and Google Scholar using HUS, TTP, TMA, and influenza as keywords, and extracted and analyzed reported epidemiological and clinical data. We identified 25 cases of influenza-associated TMA. Five additional cases were linked to influenza vaccination and analyzed separately. Influenza A was found in 83%, 10 out of 25 during the 2009 A(H1N1) pandemic. Two patients had bona fide TTP with ADAMTS13 activity <10%. Median age was 15 years (range 0.5-68 years), two thirds were male. Oligoanuria was documented in 81% and neurological involvement in 40% of patients. Serum C3 was reduced in 5 out of 14 patients (36%); Coombs test was negative in 7 out of 7 and elevated fibrin/fibrinogen degradation products were documented in 6 out of 8 patients. Pathogenic complement gene mutations were found in 7 out of 8 patients tested (C3, MCP, or MCP combined with CFB or clusterin). Twenty out of 24 patients recovered completely, but 3 died (12%). Ten of the surviving patients underwent plasma exchange (PLEX) therapy, 5 plasma infusions. Influenza-mediated HUS or TTP is rare. A sizable proportion of tested patients demonstrated mutations associated with alternative pathway of complement dysregulation that was uncovered by this infection. Further research is warranted targeting the roles of viral neuraminidase, enhanced virus-induced complement activation and/or ADAMTS13 antibodies, and rational treatment approaches.

Acute Stylet Peritoneal Dialysis in Acute Kidney Injury: The Soul Never Dies.

BACKGROUND: Acute Kidney Injury (AKI) has a significant mortality rate. In developing countries, mortality due to AKI is high due to lack of access to dialysis facilities and related cost. The main goal of International Society of Nephrology (ISN) 0 by 25 initiative is to eliminate deaths due to AKI. Peritoneal dialysis is an underutilized modality in such a scenario. The aim of this study was to look into effectiveness of starting Acute stylet Peritoneal Dialysis (PD) in a resource constraint settings. METHODS: In this prospective study conducted over a year, patients with AKI due to various aetiologies were subjected to Acute stylet PD. The clinical Outcome, demographic, biochemical and treatment data was assessed. Descriptive statistics was used to analyze the data. RESULTS: A total of 79 (41 anuric, 33 oliguric and 5 nonoliguric) patients were included in the study. Sepsis was the predominant cause of AKI. Recovery was seen in 34% of patients. Patients with relatively preserved urine output recovered with PD in comparison to the anuric patients (p value <0.01). 58% of patients, majority of whom were anuric needed Hemodialysis (HD) in due course (7 ± 3 days) of time. The mortality in our study was 7.5%. CONCLUSIONS: Acute stylet PD can be considered as a modality of Renal Replacement Therapy (RRT) to treat a selected (oliguric, nonoliguric) group of AKI patients and as a bridge therapy for HD in those AKI patients in anuria.

Renin-angiotensin system blockers and residual kidney function loss in patients initiating peritoneal dialysis: an observational cohort study.

BACKGROUND: Although angiotensin-converting enzyme inhibitors (ACEI) and angiotensin-II receptor blockers (ARB) have been shown to preserve residual kidney function in a select group of Asian patients undergoing continuous ambulatory peritoneal dialysis (PD) in two small randomized clinical trials, the effectiveness of these drugs has yet to be demonstrated in a more diverse population of patients with multiple comorbid conditions. We investigated the association between ACEI/ARB use and development of recorded anuria in a cohort of patients initiating PD in the U.S. METHODS: We conducted a retrospective observational cohort study using the US Renal Data System and electronic health records data from a large national dialysis provider. We identified adult patients who initiated PD from 2007 to 2011. Only patients who participated in the federal prescription drug benefit program, Medicare Part D, for the first 90 days of dialysis were included. Patients who filled a prescription for an ACEI or ARB during those 90 days were considered users. We applied Cox proportional hazards models to an inverse probability of treatment-weighted (IPTW) cohort to estimate the hazard ratio (HR) for anuria (24-h urine volume < 200 ml) in ACEI/ARB users vs. non-users. RESULTS: Among 886 patients, 389 (44%) used an ACEI/ARB. Almost a third of these patients were black or Hispanic, and more than a quarter had comorbidities that would have excluded them from the randomized clinical trials of ACEI/ARB. Two hundred eighty patients reached anuria over 840 person-years of follow-up, for a composite event rate of 33 events per 100 person-years. We found no clear association between ACEI/ARB use and progression to anuria [HR: 0.86, 95% CI: 0.73-1.02]. CONCLUSIONS: ACEI/ARB use is common in patients initiating PD in the U.S. but was not associated with a lower risk of anuria. Residual confounding by unmeasured variables is an important limitation of this observational study. Still, these findings suggest that pragmatic clinical trials are warranted to test the effectiveness of ACEI/ARB in slowing the decline of residual kidney function in a diverse population of peritoneal dialysis patients with multiple comorbid conditions.

[Renal decapsulation for the treatment of anuria : A "forgotten" treatment from the early 20th century]. / Die Dekapsulierung der Niere als Therapie der Anurie : Ein "vergessenes" Therapieverfahren aus dem frühen 20. Jahrhundert.

In the early 20th century, Harrison first performed renal decapsulation in anuric children with scarlet fever and observed improvement in renal function postoperatively. The pathophysiological explanation was seen in intraparenchymal renal pressure due to edema which was improved by surgical decapsulation. The technique of decapsulation was simple excision after incision and blunt dissection of the renal parenchyma. Renal decapsulation then became a procedure commonly used for many indications in inflammatory renal conditions; indications were renal angioneurosis, hydronephrosis, toxic, bacterial and chronic nephritis, renal abscess and even eclampsia. With the beginning of the antibiotic era, renal decapsulation became obsolete and has disappeared from the urological spectrum completely.

Three Versus 4 Daily Exchanges and Residual Kidney Function Decline in Incident CAPD Patients: A Randomized Controlled Trial.

BACKGROUND: Incident patients treated with continuous ambulatory peritoneal dialysis (CAPD) are often prescribed either 3 or 4 exchanges per day. However, the effects on residual kidney function and clinical outcomes of 3 versus 4 exchanges are not known. STUDY DESIGN: Prospective, randomized, controlled, open-label study. SETTING & PARTICIPANTS: Incident CAPD patients aged 18 to 80 years with glomerular filtration rates (GFRs; mean of renal urea and creatinine clearance from a 24-hour urine collection) ≥ 2mL/min and urine volume ≥ 500mL/d. Exclusion criteria included refusal for informed consent, history of maintenance hemodialysis therapy or transplantation, or limited life expectancy. INTERVENTION: 24-month intervention with 3- or 4-exchange CAPD using glucose-based peritoneal dialysis fluids. OUTCOMES: Primary outcomes were GFR, urine volume, and anuria-free survival. Secondary outcomes included peritonitis, patient survival, and technique survival. RESULTS: The study recruited 139 patients, 70 in the 3-exchange group and 69 in the 4-exchange group. Baseline body mass indexes were 21.4±3.0 and 21.9±3.2kg/m2 for the 3- and 4-exchange groups, respectively (P=0.4). After 24 months, for 3 versus 4 exchanges, GFR (1.6±2.0 vs 1.7±1.9mL/min; P=0.8), urine volume (505±522 vs 474±442mL/d; P=0.8), and anuria-free survival (log-rank test statistic = 0.055; P=0.8) did not differ between groups, but Kt/V (1.95±0.39 vs 2.19±0.48; P=0.03) and ultrafiltration (404±499 vs 742±512mL/d; P=0.004) were lower in the 3-exchange group. The 3-exchange group had nominally longer peritonitis-free survival time (log-rank test statistic = 3.811; P=0.05), and nominally fewer patients had peritonitis in this group, though this was not statistically significant (13% vs 26%; P=0.06). Patient survival (log-rank test statistic = 0.978; P=0.3) and technique survival (log-rank test statistic = 0.347; P=0.6) were similar between groups. LIMITATIONS: Single-center design; no formal sample-size calculations. CONCLUSIONS: In this small trial, CAPD regimens with 3 and 4 exchanges had similar effects on residual GFR, urine volume, and time to anuria. Incremental peritoneal dialysis starts appear safe when patients are monitored.

Comparative Study on Trace Element Excretions between Nonanuric and Anuric Patients Undergoing Continuous Ambulatory Peritoneal Dialysis.

Few studies have been reported on alterations of trace elements (TE) in peritoneal dialysis patients. Our objective was to investigate and assess the characteristics of daily TE excretions in continuous ambulatory peritoneal dialysis (CAPD) patients. This cross-sectional study included 61 CAPD patients (nonanuric/anuric: 45/16) and 11 healthy subjects in Wuhan, China between 2013 and 2014. The dialysate and urine of patients and urine of healthy subjects were collected. The concentrations of copper (Cu), zinc (Zn), selenium (Se), molybdenum (Mo), and arsenic (As) in dialysate and urine were determined using inductively coupled plasma mass spectrometer (ICP-MS). Various clinical variables were obtained from automatic biochemical analyzer. Daily Cu, Zn, Se, and Mo excretions in nonanuric patients were higher than healthy subjects, while arsenic excretion in anuric patients was lower. A strong and positive correlation was observed between Se and Mo excretion in both dialysate (ß = 0.869, p < 0.010) and urine (ß = 0.968, p < 0.010). Furthermore, the clinical variables associated with Se excretion were found to be correlated with Mo excretion. Our findings indicated that nonanuric CAPD patients may suffer from deficiency of some essential TEs, while anuric patients are at risk of arsenic accumulation. A close association between Se and Mo excretion was also found.