Shunt Nephritis: A Case of Mistaken Identity.

BACKGROUND: Membranoproliferative glomerulonephritis is a histological pattern of glomerular injury due to the deposition of immune complexes and complement factors. It is associated with bacterial and viral infections, auto-immune diseases such as systemic lupus erythematosus and Sjögren's syndrome, monoclonal gammopathy, and complement disorders (dense deposit disease and C3 glomerulopathy).  Case presentation: This is the report of a 25-year-old male with membranoproliferative glomerulonephritis who was initially treated for systemic lupus erythematosus, but who was later diagnosed with nephritis due to a chronic infection of a central nervous system shunt, last revised at the age of 3 years old. DISCUSSION: We highlight the challenges in making an early diagnosis of shunt nephritis, and succinctly discuss the clinical, biochemical, histopathological findings, and differential diagnosis of this type of infection-related glomerulonephritis.

Risk prediction models for acute kidney injury in adults: An overview of systematic reviews.

BACKGROUND: The incidence of Acute Kidney Injury (AKI) and its human and economic cost is increasing steadily. One way to reduce the burden associated with AKI is to prevent the event altogether. An important step in prevention lies in AKI risk prediction. Due to the increasing number of available risk prediction models (RPMs) clinicians need to be able to rely on systematic reviews (SRs) to provide an objective assessment on which RPM can be used in a specific setting. Our aim was to assess the quality of SRs of RPMs in AKI. METHODS: The protocol for this overview was registered in PROSPERO. MEDLINE and Embase were searched for SRs of RPMs of AKI in any setting from 2003 till August 2020. We used the ROBIS tool to assess the methodological quality of the retrieved SRs. RESULTS: Eight SRs were retrieved. All studies were assessed as being at high risk for bias using the ROBIS tool. Eight reviews had a high risk of bias in study eligibility criteria (domain 1), five for study identification and selection (domain 2), seven for data collection and appraisal (domain 3) and seven for synthesis and findings (domain 4). Five reviews were scored at high risk of bias across all four domains. Risk of bias assessment with a formal risk of bias tool was only performed in five reviews. Primary studies were heterogeneous and used a wide range of AKI definitions. Only 19 unique RPM were externally validated, of which 11 had only 1 external validation report. CONCLUSION: The methodological quality of SRs of RPMs of AKI is inconsistent. Most SRs lack a formal risk of bias assessment. SRs ought to adhere to certain standard quality criteria so that clinicians can rely on them to select a RPM for use in an individual patient. TRIAL REGISTRATION: PROSPERO registration number is CRD 42020204236, available at https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=204236.

Angiosarcoma in an arteriovenous fistula after kidney transplantation: Case report and review of treatment options.

We present a patient with an angiosarcoma in an arteriovenous fistula and we reviewed current treatments for angiosarcomas. We extended the systematic review by Oskrochi et al. on this topic in 2015, using the same search query. We searched systematically OVID, EMBASE and PubMed from April 2015 until January 2020 with the aim to update the state of the art in managing this rare but serious condition. We retrieved 12 new case reports about 11 unique patients. Mean age was 61.5 ± 11 years. Six arteriovenous fistulas had failed spontaneously. Two fistulas were operatively closed post-transplant. Nine patients (81.8%) were receiving ongoing immunosuppressive therapy. Pain and growing lesions, mass or swelling were the most frequent symptoms. Angiosarcoma mostly presents with a nonspecific clinical picture of pain, growing lesions and swelling of a previously normal arteriovenous fistula. Amputation of the limb was most frequently conducted as treatment in localized disease. Treatment of systemic disease included supportive care, chemotherapy, especially with paclitaxel and change of immunosuppressive regimen. Metastasized angiosarcoma has a very poor prognosis. Classical chemotherapy has rather low response rates. There is limited data supporting treatment of angiosarcomas with tyrosine kinase inhibitors or immunotherapy. Further comparative research is needed.

External Validation of a risk stratification model to assist shared decision making for patients starting renal replacement therapy.

BACKGROUND: Shared decision making is nowadays acknowledged as an essential step when deciding on starting renal replacement therapy. Valid risk stratification of prognosis is, besides discussing quality of life, crucial in this regard. We intended to validate a recently published risk stratification model in a large cohort of incident patients starting renal replacement therapy in Flanders. METHODS: During 3 years (2001-2003), the data set collected for the Nederlandstalige Belgische Vereniging voor Nefrologie (NBVN) registry was expanded with parameters of comorbidity. For all incident patients, the abbreviated REIN score(aREIN), being the REIN score without the parameter "mobility", was calculated, and prognostication of mortality at 3, 6 and 12 month after start of renal replacement therapy (RRT) was evaluated. RESULTS: Three thousand four hundred seventy-two patients started RRT in Flanders during the observation period (mean age 67.6 ± 14.3, 56.7 % men, 33.6 % diabetes). The mean aREIN score was 4.1 ± 2.8, and 56.8, 23.1, 12.6 and 7.4 % of patients had a score of ≤4, 5-6, 7-8 or ≥9 respectively. Mortality at 3, 6 and 12 months was 8.6, 14.1 and 19.6 % in the overall and 13.2, 21.5 and 31.9 % in the group with age >75 respectively. In RoC analysis, the aREIN score had an AUC of 0.74 for prediction of survival at 3, 6 and 12 months. There was an incremental increase in mortality with the aREIN score from 5.6 to 45.8 % mortality at 6 months for those with a score ≤4 or ≥9 respectively. CONCLUSION: The aREIN score is a useful tool to predict short term prognosis of patients starting renal replacement therapy as based on comorbidity and age, and delivers meaningful discrimination between low and high risk populations. As such, it can be a useful instrument to be incorporated in shared decision making on whether or not start of dialysis is worthwhile.

Prevention and conservative management of acute kidney injury.

The incidence of acute kidney injury (AKI) is increasing steadily. This can be attributed to a growing prevalence of risk factors for AKI, such as aging, diabetes, underlying cardiovascular disease and the escalating application of more complex procedures. Currently, there is no treatment for established AKI, except for renal replacement therapy in case of life-threatening conditions. The focus should thus be shifted towards AKI prevention rather than treatment. Several promising pharmacological and non-pharmacological interventions for prevention of AKI in animal models did not fulfill the expectations when applied in humans. There are multiple reasons why these interventions prove to be disappointing. The pathophysiology of AKI in different settings has not been fully elucidated, the underlying cause of AKI in the clinical setting is often multifactorial, and animal AKI models often do not mimic human AKI very well. Ischemia-reperfusion models are representative for human AKI in the setting of aortic clamping or in case of delayed graft function after kidney transplantation, but are not suited to study AKI in many other conditions such as sepsis. Moreover, several drugs for AKI prevention are associated with deleterious adverse events in humans as they lack selectivity. In this review, an overview of the strategies that can be used in the clinical setting for AKI prevention will be presented. Potential preventive strategies in certain specific clinical conditions will also be reviewed.

Protecting the peritoneal membrane: factors beyond peritoneal dialysis solutions.

Functional deterioration of the peritoneal membrane in patients on peritoneal dialysis has been described as being the result of a combination of neoangiogenesis and fibrosis. Glucose, glucose degradation products, and the unphysiological pH of the dialysate solution contribute to these changes. Although newer solutions clearly perform better in terms of their biocompatibility in an in vitro setting and in animal models, the benefit of such solutions over older solutions in the clinical setting is so far unproven. The difficulties in showing a benefit of the newer, more biocompatible solutions in the clinical setting can be explained by the fact that other factors also affect the properties of the peritoneal membrane. These factors are often neglected in clinical studies, which results in unnoticed differences in case-mix and blurs the potential impact of the novel solutions. However, many of these factors are modifiable, and attention should be paid to them in clinical practice to maintain the integrity of the peritoneal membrane. This Review focuses on factors that potentially influence the integrity of the peritoneal membrane, other than those associated with the peritoneal dialysis fluid itself.

Dialysis water and fluid purity: more than endotoxin.

The evolution of extracorporeal treatment of end-stage renal failure has enforced focus on the purity of dialysis fluid. A major challenge of high-flux haemodialysis (HD) and haemodiafiltration relates to the necessity for ultrapure dialysis fluid and for sterile non-pyrogenic substitution fluid. The present review focuses especially on the possible microbial contamination including, next to intact micro-organisms, a variety of microbial derivatives. It is pointed out that there are conditions (e.g. contamination by non-culturable micro-organisms or bacterial derivatives other than lipopolysaccharides) where the detection of biologically relevant contaminants can be missed when applying the recommended standard detection methods such as bacterial culture and limulus amoebocyte lysate test. Possible approaches for action upon positive sampling results, exceeding the levels recommended in the latest ISO 11663:2009, are described in detail and illustrated with flow charts. The issue of purity of dialysis fluids is highly relevant, since the chronic exposure of HD patients to low levels of cytokine-inducing microbial components can significantly contribute to the micro-inflammatory status of these patients.

The fate of older diabetic patients on peritoneal dialysis: myths and mysteries and suggestions for further research.

The outcome of older and especially of female diabetic patients appears to be worse on peritoneal dialysis (PD) than on hemodialysis (HD). This opinion is based mostly on data coming from the USA, whereas data from other regions seem to give a more balanced picture. The questions arise whether indeed outcome is worse in this patient group, and what might be the underlying reasons for this; further research to unravel this phenomenon is warranted. This review proposes several suggestions for further exploration. The observed differences in outcome might be attributable to differences in treatment practices and experience with PD versus HD. As cardiovascular mortality is a major killer in end-stage renal disease patients, differences in fluid homeostasis and how it is achieved are potential explanations. Fluid balance is potentially more difficult to obtain in PD patients, especially as in the past it was spuriously suggested that fluid restriction was less important in PD patients. PD and HD might also have different impacts on factors related to inflammation, insulin resistance, and hormone balance. The adipocytokine network is of special interest in this respect. It is also possible that bias introduced by the way we measure body composition might have a more negative impact on PD than on HD patients. Finally, it still is not fully established that if diabetic patients are treated appropriately, their outcome on PD is worse than that on HD; further observational trials in this respect are needed. All these topics require further clarification and investigation.

Clamping of the dialysate outlet line in the Genius dialysis system does not alter dialysate flow or clearances.

BACKGROUND: The Genius dialysis system is advocated as a tool to perform slow extended daily dialysis (SLEDD) in patients with acute renal failure at the intensive care unit. At low blood flows however, it is sometimes problematic to maintain sufficient systemic pressure in the dialysate circuit, a problem that can be overcome by clamping the dialysate outflow line. This intervention can however decrease the flow in the dialysate circuit, and can thus potentially decrease the clearance. This article analyses the impact of this intervention on the blood and dialysate flows and on the removal of retention products. METHODS: The study was done in 20 stable chronic dialysis patients to avoid additional bias caused by changing comorbidities in ICU patients. Patients were treated by Genius, once with clamping and once without clamping, cross-over in a randomized fashion, and with 1 week interval. Flows in the dialysate and blood circuit were measured with a transsonic flow probe. Urea, creatinine, Beta 2 microglobulin and phosphate were measured in the dialysate, and in the serum before and after dialysis. RESULTS: There was no clinically significant difference in blood or dialysate flows, nor in clearance or removal of retention products during the sessions with or without clamping. CONCLUSIONS: The technique of using clamping of the dialysate outflow line in the Genius system to increase systemic pressure, when the system is used in SLEDD, is a safe technique which does not alter the clearances.

The importance of standardization of creatinine in the implementation of guidelines and recommendations for CKD: implications for CKD management programmes.

BACKGROUND: In an attempt to reduce late referral and to improve the care of patients with chronic kidney disease (CKD), different organizations have issued guidelines on when to refer patients to the nephrologist. Most suggest referral of patients with a GFR below 60 ml/min/1.73 m2, and demand referral if the GFR is below 30 ml/min/1.73 m2. It is recommended to use the abbreviated MDRD equation to estimate GFR. This formula is, however, sensitive to the creatinine assay methodology. In addition, the impact of the implementation of such guidelines on the nephrology practice has never been evaluated. This study (i) identifies the true burden of CKD in a population and simulates the effects of a 100% implementation of the guidelines on the nephrology work load, and (ii) evaluates the validity of the estimated GFR using the abbreviated MDRD formula when routinely provided. METHODS: Different laboratories (both hospital and private) in our region were asked to report on all the serum creatinine values performed during the first week of December 2004. If patients had more than one determination, only the lowest serum creatinine value was retained. Patients already known to a nephrology unit were not included. GFR was calculated using the abbreviated MDRD, using the serum creatinine as reported by these laboratories, or after correction to the MDRD-standard using different published equations. RESULTS: 20,108 patients, with a mean age of 53.4+/-16.2 years, 48% females, had at least one serum creatinine determination in the observation period. According to the K/DOQI CKD classification, 20.2, 1.6 and 0.8% of females and 13.3, 1.6 and 0.6% of males were in stage 3, 4 and 5, respectively, when the abbreviated MDRD formula was used with the serum creatinine value as reported by the laboratories. Important differences in classifications were obtained when the different correction formulae for creatinine were applied. According to the current recommendations, this would lead to a mandatory referral of 1650-2400 CKD stage 4 patients per 100 000 inhabitants and a suggested referral of another 4100-15 360 CKD stage 3 patients per 100,000 inhabitants to a nephrology unit. CONCLUSION: Implementation of the current guidelines for referral of CKD patients to nephrologists would lead to an overload of the nephrology care capacities. Large differences in estimated GFRs with different corrections for serum creatinine are observed, resulting in important CKD classification differences. Standardization of serum creatinine assays is mandatory before guidelines, and especially the routine provision of the estimated GFR by the abbreviated MDRD formula, can be implemented in clinical practice.

The personal dialysis capacity test is superior to the peritoneal equilibration test to discriminate inflammation as the cause of fast transport status in peritoneal dialysis patients.

This study evaluated the potential of the Personal Dialysis Capacity (PDC) test to discriminate fast transport status (FTS) as a consequence of inflammation versus FTS because of other causes. This distinction is important because new therapeutic options such as icodextrin and automated peritoneal dialysis can abolish the negative impact on outcome of FTS if fast transport is not caused by inflammation. A PDC test and a Peritoneal Equilibration Test (PET) were performed in 135 incident PD patients. Membrane characteristics were related with baseline biochemical parameters and C-reactive protein. After correction for other covariates, only large pore flux (J(v)L) but not surface area over diffusion distance (A0/dX) or dialysate over plasma concentration was related to C-reactive protein. Using the PDC test for detection of inflammation, positive and negative predictive values were 16/36 and 80/99, respectively, whereas with PET, positive predictive value was 5/20 and negative predictive value 92/115 (chi2 = 0.009). In a Cox regression for patient survival with correction for age, a J(v)L higher than expected by the surface area over diffusion distance, predicted outcome (P = 0.04). Patients with inflammation had a higher J(v)L (0.21 +/- 0.12 versus 0.17 +/- 0.09; P = 0.06) and a lower ultrafiltration (89 +/- 631 versus 386 +/- 601 ml/d; P = 0.06) and urine output (878.45 +/- 533.55 versus 1322 +/- 822 ml/d; P = 0.023) than patients without inflammation. There was no difference for surface area over diffusion distance (A0/dX) or dialysate over plasma concentration. A PDC test yields far more information about the peritoneal membrane characteristics than a PET. A J(v)L higher than expected by the A0/dX is an indicator of inflammation and is related to an increased mortality. The PET is not able to discriminate between FTS because of inflammation versus because of anatomic reasons, whereas the PDC test does.

Improving salt balance in peritoneal dialysis patients.

Volume homeostasis is an important predictor of outcome in peritoneal dialysis. Because volume retention is driven by salt retention, maintenance of salt balance should be a concern to all nephrologists. An important factor in this is dietary salt restriction. This has long been neglected in peritoneal dialysis patients, where it was considered that the continuous nature of the therapy and residual renal function would be sufficient to remove any extra salt load. In patients with preserved renal function, diuresis and salt excretion can be enhanced by the application of high doses of loop diuretics. This practice seems not to have an impact on the further deterioration of renal function. Peritoneal salt removal can be enhanced using polyglucose. Also, the use of low sodium-containing dialysate can be efficient. These solutions are, however, not commercially available, and they need higher concentrations of glucose to obtain an efficient osmolarity. It should always be considered that, due to sodium sieving over the ultrasmall pores, fluid and salt removal are not always concordant.

Efficacy of erythropoietin administration in the treatment of anemia immediately after renal transplantation.

Anemia negatively impacts cardiovascular comorbidity and hospitalization. In animals, recombinant erythropoietin (RhuEPO) leads to faster recovery after acute tubular necrosis. This study evaluates the effect of RhuEPO (Recormon, Hoffman-La Roche, Basel, Switzerland) on the correction of anemia and kidney function after renal transplantation. Patients receiving a renal transplant were randomized to receive or not receive RhuEPO 100 U/kg three times per week if the hemoglobin (Hb) level was less than 12.5 g/dL. The time to reach an Hb level greater than 12.5 g/dL was 66.5+/-14.5 days versus 52.6+/-23.7 days in the non-EPO and EPO groups, respectively (P=0.05). After 3 months, Hb levels were not different between the non-EPO and EPO groups (12.6+/-1.5 g/dL vs. 12.0+/-1.5 g/dL, respectively), although there was a higher increase in the EPO group (4.1+/-1.1 g/dL vs. 3.2+/-1.1 g/dL, P=0.02). In a Cox regression analysis, EPO use (relative risk 7.2, P=0.004) and dose (relative risk=0.63, P=0.04) were retained as independent variables predicting the time to reach an Hb level greater than 12.5 g/dL. In the EPO group, 14 of 22 patients reached the target Hb level of more than 12.5 g/dL versus 12 of 18 patients in the non-EPO group (P=not significant). Serum creatinine levels were not different between groups. RhuEPO in the immediate posttransplantation period seems to have no relevant clinical impact on the correction of anemia. There was no difference in the evolution of serum creatinine levels. In view of the cost, the use of RhuEpo in the posttransplantation period should be limited to high-risk patients.

The role of APD in the improvement of outcomes in an ESRD program.

We review the role of automated peritoneal dialysis (APD) in improving outcomes of an end-stage renal disease (ESRD) program. As the "integrated care approach" becomes accepted as the preferred strategy for treatment of ESRD patients, we looked for the potential place of APD in such an approach. APD has probably the same advantages as CAPD as a first-line renal replacement modality in suitable patients willing to perform PD. There is currently no hard evidence that residual renal function (RRF) should decline more rapidly in APD than in CAPD, at least if a dry abdomen during the day is avoided. The detection of peritonitis is probably more delayed in APD, but the frequency of peritonitis is lower, and there is no hard evidence pointing to a poorer outcome of peritonitis in APD as compared to CAPD. Quality of life is at least as good in APD, which is mostly related to the increased possibilities for adapting the exchange pattern to employment-related time frames. APD also has the potential to prolong technique success in patients failing CAPD rather than transferring them to hemodialysis. Nevertheless, APD remains more expensive and technically complicated, thereby missing the beauty of CAPD's simplicity. Therefore we believe that APD has its role in an integrated approach and that all patients should be informed of its potential. It would, however, not be correct to present APD as the preferred PD method for all patients, as it also has some drawbacks that make it less suitable for some categories of patients. In all cases, patients should have a free and informed choice.

Peritoneal dialysis in anuric patients: concerns and cautions.

Most recent studies have found an equivalent survival for patients on peritoneal dialysis (PD) and hemodialysis (HD); evidence even suggests that PD might be the preferred modality during the first 3-4 years of renal replacement therapy. This is probably related to the continuous and minimally invasive character of PD as compared to HD, resulting in better preservation of residual renal function (RRF) and less cardiovascular strain. On the other hand, blood pressure control, fluid balance, and adequacy targets may be difficult to obtain in long-term PD patients. The question arises whether PD is a feasible option in anuric patients. It is clear that the answer depends on the body size and the peritoneal membrane transport characteristics of the patient, so that PD will be feasible in some anuric patients, whereas in others it will not be. Evaluation of the peritoneal transport characteristics and adaptation of the PD prescription is warranted. A constant evaluation of the fluid balance, nutritional, and cardiovascular status is needed. This article reviews the physiologic insights and clinical evidence necessary for a good PD prescription in anuric patients.