Sacubitril/Valsartan in Dialysis Patients: Update on Current Perspectives.

Sacubitril/Valsartan is a combination of neprilysin inhibitor and angiotensin II receptor blocker that proved its own efficacy and safety in heart failure patients to ameliorate cardiovascular morbidity and mortality compared to angiotensin II-converting enzyme inhibitors alone. However, end-stage renal disease patients have not been included in the randomized controlled trials, so the beneficial effects as well as the risk profile of this association remain still undefined in these patients. Only observational studies on this drug association have been carried out in end-stage renal disease patients investigating mostly biohumoral or echocardiographic markers. Therefore, its application is still controversial and not free of complications due to the potential risk of hypotension and hyperkaliemia. The efficacy to improve biohumoral markers and cardiac function in dialysis patients and the potential application especially in those patients with severe and resistant hypertension and/or left ventricular dysfunction could be crucial in end-stage renal disease patients. Ongoing long-term randomized controlled trials should thoroughly define the effective benefits and/or adverse effects in patients on substitutive treatment.

Ultrasonographic Assessment of Atherosclerotic Renal Artery Stenosis in Elderly Patients with Chronic Kidney Disease: An Italian Cohort Study.

Although atherosclerotic renal artery stenosis (ARAS) is strictly associated with high cardiovascular risk and mortality, it often may remain unrecognized being clinically silent and frequently masked by co-morbidities especially in elderly patients with coexisting chronic kidney disease (CKD). The present observational study was conducted in elderly CKD-patients with atherosclerosis on other arterial beds. The aims were assessment of (1) ARAS prevalence; (2) best predictor(s) of ARAS, using duplex ultrasound; and (3) cardiovascular and renal outcomes at one-year follow-up. The cohort was represented by 607 consecutive in-patients. Inclusion criteria were age ≥65 years; CKD stages 2−5 not on dialysis; single or multiple atherosclerotic plaque on epiaortic vessels, abdominal aorta, aortic arch, coronary arteries, peripheral arteries that had been previously ascertained by one or more procedures. Duplex ultrasound was used to detect ARAS. Multiple regression analysis and ROS curve were performed to identify the predictors of ARAS. ARAS was found in 53 (44%) out of 120 patients who met the inclusion criteria. In univariate analysis, GFR (b = −0.021; p = 0.02); hemoglobin (b = −0.233; p = 0.02); BMI (b = 0.134; p = 0.036) and atherosclerosis of abdominal aorta and/or peripheral vessels (b = 1.025; p < 0.001) were associated with ARAS. In multivariable analysis, abdominal aorta and/or peripheral atherosclerosis was a significant (p = 0.002) predictor of ARAS. The area under the ROC curve was 0.655 (C.I. = 0.532−0.777; p = 0.019). ARAS is common in older CKD patients with extra-renal atherosclerosis, with the highest prevalence in those with aortic and peripheral atherosclerosis. ARAS may pass by unnoticed in everyday clinical practice.

Contrast-enhanced ultrasound in peritoneal dialysis: when and how to perform it.

In the field of peritoneal dialysis contrast enhanced ultrasound (CEUS) is a new add-on examination to B-mode ultrasound, but until recently it has never been systematically studied. Based on the experience of the Project Group "Integrated Imaging and Interventional Nephrology" of the Italian Society of Nephrology, CEUS is helpful for evaluating catheter malfunction, peritoneal-pleural communication, leakage, and herniation, and in particular it facilitates dynamic functional imaging of the catheter and its complications. The use of CEUS in peritoneal dialysis is simple, repeatable, safe, radiation-free, and appears to be less time-consuming and more cost-effective than other radiological imaging techniques such as peritoneography, computed tomography, magnetic resonance or peritoneal scintigraphy.

The Underrated Role of Ultrasound in Peritoneal Dialysis.

Ultrasound is very effective in performing procedures and assessment of complications in peritoneal dialysis. The ultrasound examination can be applied for preoperative assessment, during the peritoneal catheter placement, for the detection and monitoring of infection, as well as for the evaluation of the catheter malfunction. Despite being not only a cost- and time-saving technique but also a bedside procedure, ultrasonography remains an underrated clinical tool in the field of peritoneal dialysis. This publication wants to explain and reinforce the clinical utility of US in PD and to expand the diagnostic equipment for the clinician.

Role of Contrast-Enhanced Ultrasound (CEUS) in Native Kidney Pathology: Limits and Fields of Action.

Gray scale ultrasound has an important diagnostic role in native kidney disease. Low cost, absence of ionizing radiation and nephrotoxicity, short performance time, and repeatability even at the bedside, are the major advantages of this technique. The introduction of contrast enhancement ultrasound (CEUS) in daily clinical practice has significantly reduced the use of contrast enhancement computed tomography (CECT) and contrast enhancement magnetic resonance (CEMR), especially in patients with renal disease. Although there are many situations in which CECT and CEMRI are primarily indicated, their use may be limited by the administration of the contrast medium, which may involve a risk of renal function impairment, especially in the elderly, and in patients with acute kidney injury (AKI) and moderate to severe chronic kidney disease (CKD). In these cases, CEUS can be a valid diagnostic choice. To date, numerous publications have highlighted the role of CEUS in the study of parenchymal micro-vascularization and renal pathology by full integration with second level imaging methods (CECT and CEMRI) both in patients with normal renal function and with diseased kidneys. The aim of this review is to offer an updated overview of the limitations and potential applications of CEUS in native kidney disease.

Diagnostic capability of ultrasound in peritoneal catheter malfunction compared to videolaparoscopy.

BACKGROUND: The approach to peritoneal catheter malfunction consists usually in a diagnostic and therapeutic sequence of laxative prescription, abdominal radiography, brushing of the catheter, guide-wire manipulation or fluoroscopy and in the end of a videolaparoscopy (VLS) rescue intervention. Ultrasound (US) is able to find out major causes of peritoneal catheter malfunction, however without a clearly defined diagnostic value. The aim of the study was to validate the diagnostic capability of US in catheter malfunction compared to the diagnostic reference of VLS. METHODS: US scans of the subcutaneous and intraperitoneal segment of the catheter were performed prior to a VLS intervention in 40 adult patients presenting persistent catheter malfunction within a prospective multicentre study. Laxative prescription and brushing of the catheter lumen were undertaken prior to US scan. US diagnosis was compared to the corresponding at VLS, kappa coefficient calculated and the causes of mismatch analysed. RESULTS: In US, causes of persistent malfunction were catheter dislocation combined with omental wrapping in 21 cases, omental wrapping without dislocation in 11 cases, dislocation only in 4 cases, adherences to non-omental structures in 3 cases and entrapment in the lateral inguinal fossa in 1 case. The US diagnosis corresponded to the respective at VLS in 36 of 40 cases, resulting in a kappa coefficient of 0.89 (95% CI: 0.78-1.00). The discrepancies were due to improper visualization of the catheter between omentum and intestinal loops, resulting in an erroneous US diagnosis of omental wrapping. CONCLUSIONS: This study suggests that US might have a pivotal role in the diagnostic approach to peritoneal catheter dysfunction.

Use of ultrasounds in PD catheter-related infections: indications and clinical implications / Utilizzo degli ultrasuoni nelle infezioni da catetere peritoneale: indicazioni e risvolti clinici

Peritoneal dialysis (PD) related infections continue to be a major cause of morbidity and mortality in patients undertaking renal replacement therapy with PD. Nevertheless, despite the great effort invested in the prevention of PD infective episodes, almost one third of technical failures are still caused by peritonitis. Recent studies support the idea that there is a direct role of exit-site (ESIs) and tunnel infections (TIs) in causing peritonitis. Hence, both the prompt ESI/TI diagnosis and correct prognostic hypothesis would allow the timely start of an appropriate antibiotic therapy decreasing the associated complications and preserving the PD technique. The ultrasound exam (US) is a simple, rapid, non-invasive and widely available procedure for the tunnel evaluation in PD catheter-related infections. In case of ESI, the US possesses a greater sensibility in diagnosing a simultaneous TI compared to the clinical criterions. This peculiarity allows to distinguish the ESI episodes which will be healed with antibiotic therapy from those refractories to medical therapy. In case of TI, the US permits to localize the catheter portion involved in the infectious process obtaining significant prognostic information; while the US repetition after two weeks of antibiotic allows to monitor the patient responsiveness to the therapy. There is no evidence of the US usefulness as screening tool aimed to the precocious diagnosis of TI in asymptomatic PD patients.

Peritoneal Dialysis Catheter Position Evaluated by Ultrasound: Can it Replace Abdomen X-Ray in Patients Presenting Catheter Misplacement?

Background Malfunction of the peritoneal dialysis catheter is frequently caused by dislocation. The diagnostic approach is classically based on abdomen X-ray together with detailed case history and physical examination. Despite being rarely applied in clinical practice to evaluate catheter misplacement, ultrasound is a noninvasive, radiation-free technique that is potentially useful also to explore reasons for catheter malfunction. Consequently, we aimed to evaluate the diagnostic accuracy of ultrasound to identify peritoneal catheter misplacement. Methods In a multicenter observational blinded study, we compared ultrasound to abdomen X-ray for catheter localization in 93 consecutive peritoneal dialysis patients with dialysate outflow problems enrolled in two nephrology and dialysis units. The position of the catheter was annotated on a standard scheme of nine abdominopelvic regions. The sensitivity, specificity, positive and negative predictive value and Kappa coefficient were calculated. Results Dislocation out of the inferior abdominopelvic regions was present in 19 patients (20 %) at X-ray and 23 patients (25 %) at ultrasound. Correct determination of the position of the catheter in the lower abdomen by ultrasound had a sensitivity of 93 % (95 % CI 84 - 97 %), specificity of 95 % (95 % CI 72 - 100 %), positive predictive value of 99 % (95 % CI 91 - 100 %), negative predictive value of 78 % (95 %CI 56 - 92 %) and Kappa coefficient of 0.82 (95 % CI 0.67 - 0.96). In 10 out of 93 patients (11 %), there was a position mismatch between X-ray and ultrasound in an adjacent abdominopelvic region. Conclusion Our results suggest that abdomen X-ray for the evaluation of peritoneal catheter position can be replaced by ultrasound in experienced hands. This bedside diagnostic procedure might reduce costs, the time necessary for diagnosis and lifetime radiation exposure.

A load volume suitable for reaching dialysis adequacy targets in anuric patients on 4-exchange CAPD.

INTRODUCTION: Continuous ambulatory peritoneal dialysis (CAPD) depuration indexes are targeted to get a minimum total weekly peritoneal urea clearance (Kt/V) of 1.70 and creatinine clearance/1.73 m(2) (pCrCL) of 50 l. In anuric patients these targets are difficult to achieve. Since dialysis volumes (load, VOL(in); drain, VOL(out)) are the main determinants of peritoneal clearances (pCLs), we aimed to estimate the minimum volumes required to fulfill these targets in anuric patients. METHODS: Sixty-nine CAPD anuric patients from eight dialysis units were observed retrospectively. Demographic data, dialysis schedule, VOLs and depuration indexes were recorded. The relationship between normalized VOLs and pCLs was estimated by linear regression analysis as a whole (95 % confidence interval of the fit) and stratified by tertiles of body weight (BW) and surface area (BSA). RESULTS: Mean weekly pKt/V was 1.89 ± 0.29, pCrCL 52.9 ± 8.0, VOL(in) 32.9 ± 5.3 ml/kg and VOL(out) 37.4 ± 6.7 ml/kg exchange. VOL(in) and VOL(out) correlated with depuration indexes only if normalized. A VOL(in) of 28.5 ml/kg exchange (27.0-30.0) was associated with a pKt/V of 1.70, and a VOL(in) of 29.5 (26.5-31.5) with a pCrCL of 50 l, with a VOL(out) of 31.7 ml/kg (29.5-33.5) and 32.4 (27.2-35.5), respectively. Smaller patients needed a lower normalized VOL(in)/exchange to obtain pKt/V = 1.70 (1st vs. 2nd vs. 3rd BW tertiles: 28.3 vs. 28.9 vs. 29.0 ml/kg; BSA tertiles: 1,696 vs. 1,935 vs. 2,086 ml/1.73). CONCLUSIONS: In CAPD anuric patients VOL(in) prescription could be tailored to body mass to reach the minimum depuration target. Normalized VOL(in) might be prescribed in slightly higher doses (from 27 to 30 ml/kg exchange) for patients with higher body mass.

The peritoneal dialysis catheter.

The results obtained from the positioning and management of the catheter for peritoneal dialysis depend on the techniques used, but also and above all, on the experience of the practitioners. A comparison between practitioners may help to change their convictions, as well as to further improve results, in the interests of patient welfare. This is the aim of these Best Practice Guidelines..

Peritoneal dialysis access: open versus laparoscopic surgical techniques.

AIM: To outline pros and cons with the open and laparoscopic techniques when placing peritoneal dialysis (PD) catheters. BACKGROUND: Controversy exists regarding which technique, the open and laparoscopic, if any, is superior to the other. In addition, there is the question of which approach is best in rescuing malfunctioning PD catheters. RESULTS: Rather than promoting one doctrine fits all, philosophically, doing the right thing for the patient by specific criteria is ethically the better model. These specific selection criteria include patient characteristics, the team's skills and knowledge and institutional resources and commitment. Also, the sophistication of a PD unit for training and monitoring of patients is crucial for successful outcomes. Open paramedian and two laparoscopic approaches are described in detail, outlining advantages and disadvantages of each, with suggestions when one method is preferred. CONCLUSIONS: In general, the laparoscopic technique is associated with longer operative times, higher costs and the need to utilize general anesthesia. It is, however, the preferred method when rescuing malfunctioning catheters and may increase the PD patient population in patients with previous abdominal surgeries. The dialysis access surgeon should be familiar with both open and laparoscopic techniques and appropriately choose the ideal method based upon the individual patient and institutional resources.

Videolaparoscopic catheter placement reduces contraindications to peritoneal dialysis.

BACKGROUND: Videolaparoscopy is considered the reference method for peritoneal catheter placement in patients with previous abdominal surgery. The placement procedure is usually performed with at least two access sites: one for the catheter and the second for the laparoscope. Here, we describe a new one-port laparoscopic procedure that uses only one abdominal access site in patients not eligible for laparotomic catheter placement. METHOD: We carried out one-port laparoscopic placement in 21 patients presenting contraindications to blind surgical procedures because of prior abdominal surgery. This technique consists in the creation of a single mini-laparotomy access through which laparoscopic procedures and placement are performed. The catheter, rectified by an introducer, is inserted inside the port. Subsequently, the port is removed, leaving the catheter in pelvic position. The port is reintroduced laterally to the catheter, confirming or correcting its position. Laparotomic placement was performed in a contemporary group of 32 patients without contraindications to blind placement. Complications and long-term catheter outcome in the two groups were evaluated. RESULTS: Additional interventions during placement were necessary in 12 patients of the laparoscopy group compared with 5 patients of the laparotomy group (p = 0.002). Laparoscopy documented adhesions in 13 patients, with need for adhesiolysis in 6 patients. Each group had 1 intraoperative complication: leakage in the laparoscopy group, and intestinal perforation in the laparotomy group. During the 2-year follow-up period, laparoscopic revisions had to be performed in 6 patients of the laparoscopy group and in 5 patients of the laparotomy group (p = 0.26). The 1-year catheter survival was similar in both groups. Laparoscopy increased by 40% the number of patients eligible to receive peritoneal dialysis. CONCLUSIONS: Videolaparoscopy placement in patients not eligible for blind surgical procedures seems to be equivalent to laparotomic placement with regard to complications and long-term catheter outcome. The number of patients able to receive peritoneal dialysis is substantially increased.

Sonographic subclinical entheseal involvement in dialysis patients.

Long-term dialysis treatment can be associated with several musculoskeletal complications. Entheseal involvement in dialysis patients remains rarely studied as its prevalence is underestimated due to its often asymptomatic presentation. The aims of the study were to determine the prevalence of subclinical enthesopathy in haemodialysis and peritoneal dialysis patients at the lower limb level, to investigate the inter-observer reliability of ultrasound assessment and to analyse the influence of biometric and biochemical parameters. Ultrasound examination was conducted at the entheses of the lower limbs level in 33 asymptomatic dialysis patients and 33 healthy adopting the Glasgow Ultrasound Enthesitis Scoring System (GUESS). The inter-observer reliability was calculated in 15 dialysis patients. Ultrasound found at least one sign of enthesopathy in 165 out of 330 (50%) entheses of dialysis patients. In healthy subjects, signs of enthesopathy were present in 54 out of 330 (16.3%) entheses (p < 0.0001). No power Doppler signal was detected in healthy controls, in contrast to four of 330 entheses of dialysis patients. No US signs of soft tissue amyloid deposits were found. The GUESS score was significantly higher in dialysis patients than in controls (p < 0.0001). There was no difference in terms of enthesopathy between haemodialysis and peritoneal dialysis. Dialysis duration resulted to be the most important predictor for enthesopathy (p = 0.0004), followed by patient age (p = 0.02) and body mass index (p = 0.035). Parathormone, calcium, phosphorus, C-reactive protein, cholesterol and triglycerides apparently did not play a relevant role in favour of enthesopathy. The inter-observer reliability showed an excellent agreement between sonographers with different degree of experience. Our results demonstrated a higher prevalence of subclinical enthesopathy in both haemodialysis and peritoneal dialysis patients than in healthy subjects. Follow-up will provide further information with respect to the predictive value of US findings for the development of symptomatic dialysis-related arthropathy.

Giant mesenteric cyst of mesothelial origin in a haemodialysis patient with previous peritoneal dialysis therapy.

A 55-year-old female haemodialysis patient presented progressive abdominal liquid formation after having been excluded from peritoneal dialysis therapy because of recurrent peritonitis. Ultrasound was suspicious for ascites secondary to sclerosing peritonitis. Computed tomography revealed a thin-walled mesenteric cyst extending from the epigastric to the pelvic region. The cyst was excised incompletely as extensive adhesions were present. Histology was consistent with a mesothelial cyst of inflammatory origin. Three months after surgery, ultrasound detected a local recurrence at the descending colon. This case emphasizes the relation between mesenteric cyst, persistent inflammatory status and preceding peritoneal dialysis complicated by peritonitis.

Videolaparoscopy as rescue therapy and placement of peritoneal dialysis catheters: a thirty-two case single centre experience.

BACKGROUND: Malfunction of the peritoneal catheter is a frequent complication in peritoneal dialysis (PD). Videolaparoscopy is a minimal invasive technique that allows rescue therapy of malfunctioning catheters and consecutive immediate resumption of PD. Furthermore, Tenckhoff catheters can be safely positioned in patients with previous abdominal surgery. We analysed the clinical diagnosis, videolaparoscopic treatment and the outcome of PD patients on whom videolaparoscopic interventions had been performed at our centre. METHODS: Thirty-two cases of videolaparoscopic interventions were performed for salvage of malfunctioning peritoneal catheters, implantation and abdominal surgical interventions in 25 PD patients. The videolaparoscope was inserted through a mini-laparotomy site of 15 mm diameter which was closed with purse-string sutures at the end of the intervention. RESULTS: Videolaparoscopy was used in 21 cases of catheter malfunction mostly due to omental wrapping (12 cases) and dislocation (five cases). In eight patients with previous surgical abdominal interventions, laparoscopic placement of the PD catheter was performed. In two cases the gall bladder was removed. One case of intestinal occlusion was evaluated laparoscopically in an attempt to minimize invasive surgery. Leakage of the peritoneal fluid presented the only complication caused by insufficient closure of one mini-laparotomy site. Minimal follow-up time of rescued catheters was 5 months. Videolaparoscopy prolonged PD catheter function by a median of 163 days (range 5-1469 days). CONCLUSIONS: Videolaparoscopy prolongs peritoneal catheter survival by treating directly the causes of malfunction. In patients with preceding abdominal interventions, the PD catheter can be placed safely even in cases necessitating surgical preparation like adhesiolysis.

Detection of the complement degradation product C4d in renal allografts: diagnostic and therapeutic implications.

The immunohistochemical detection of the complement degradation product C4d, a component of the classical complement pathway, offers a new and currently poorly defined tool in the evaluation of renal allograft biopsies. Our retrospective study aims at determining the diagnostic and clinical significance of C4d accumulation in kidney transplants, employing immunofluorescence microscopy. We analyzed 398 diagnostic allograft biopsies (n = 265 patients with 1 to 5 biopsies obtained 7 to 7165 d posttransplantation [tx]) and correlated the detection of C4d with 18 histologic changes, panel-reactive antibody titers, response to treatment, and outcome. One hundred twenty-five native kidney and baseline tx biopsies served as controls. Linear deposition of C4d along peritubular capillaries was only found in a subgroup (30%) of allografts post-tx, mainly during the early time-course (median, 38 d post-tx; range, 7 to 5646 d). There was no significant association with infections. C4d staining could change from negative to positive and vice versa within days to weeks. The accumulation of C4d was most tightly linked to a morphologic subtype of rejection, transplant glomerulitis (P < 0.0001). In addition, tubular MHC class II expression was correlated with C4d deposition (P < 0.0001). Both features are signs of "acute active rejection." In comparison with C4d-negative controls, 43% of C4d-positive patients showed increased (>10%) panel-reactive antibody titers (versus 19% in the negative group; P = 0.001). C4d positivity was frequently associated with higher serum creatinine levels at time of biopsy (compared with C4d-negative group; P < 0.01). More C4d-positive patients were treated with polyclonal antithymocyte globulins (ATG) or monoclonal anti-CD3 antibodies (OKT3) (P < 0.0001). Outcome did not significantly differ between C4d-positive and C4d-negative groups. In conclusion, the detection of C4d identifies a humoral alloresponse in a subgroup of kidney transplants, which is often associated with signs of cellular rejection, i.e. tx glomerulitis. Allograft dysfunction in C4d-positive rejection episodes is often more pronounced. We provide first evidence that C4d-positive rejection might benefit from intensive therapy, potentially preventing the previously reported high graft failure rate. In addition, we show that a subgroup of C4d-positive cases may not require any immediate therapeutic intervention. The presence of C4d is clinically relevant and should be reported in the histologic diagnosis.