Serum matrix metalloproteinase-3 in hemodialysis patients with dialysis-related amyloidosis

Background: Matrix metalloproteinase‐3 (MMP‐3) has been linked to osteoarticular destruction in rheumatic arthritis. To investigate the role of MMP‐3 in dialysis‐related amyloidosis (DRA), we determined serum MMP‐3 in long‐term hemodialysis (HD) patients with and without clinical manifestations of DRA. Methods: Thirty‐three subjects (63% female, 3% diabetic) enrolled in the study between September 2001 and June 2003. All patients underwent standard HD three times per week, using high‐flux dialyzers. Four patients had active DRA complications (DRA patients), whereas the others (n = 29) had no evidence of DRA. We determined serum concentrations of MMP‐3, C‐reactive protein (CRP), β₂‐microglobulin (β₂M), and interleukin‐6 (IL‐6). We also studied the effects of hemodiafiltration (HDF) on inflammatory measures by transferring the DRA patients from regular HD to predilution HDF. Results: The DRA group had been on dialysis significantly longer than the control group. Significant positive correlations were observed between MMP‐3 and IL‐6 (R² = 0.5143, p < 0.0001) and MMP‐3 and CRP (R² = 0.6492, p < 0.0001). IL‐6 levels increased after a single dialysis treatment, but this effect was minimal with predilution HDF (the increment of IL‐6 levels did not exceed 10 pg/mL). Serum MMP‐3 levels decreased in parallel with the decrease of IL‐6. Conclusions: MMP‐3 serum levels increase in accordance with clinical manifestations of DRA and elevated circulating levels of IL‐6. For the evaluation of the pathophysiologic state of DRA, serum MMP‐3 may be a useful predictor indicative of chronic inflammation and osteoarticular disorders in DRA patients.     

Hemodialysis‐associated soft tissue amyloidomas of the chest and abdominal wall

Amyloidoma is a highly unusual presentation of amyloidosis in tumoral or nodular form. Isolated soft tissue amyloidomas in individuals with end‐stage renal disease on chronic hemodialysis is exceedingly rare, particularly in the era of advanced dialysis technologies. We report the case of a 55‐year‐old male with end‐stage renal disease due to autosomal‐dominant polycystic kidney disease, on HD for over 30 years, who was found to have soft‐tissue, dialysis‐related (β₂‐microglobulin) amyloidomas (DRA). He presented with painful, palpable masses within the thoracic and abdominal walls. Serum β₂‐microglobulin level was only mildly elevated at 24.9 mg/L. Biopsy confirmed amyloidosis with positivity for Congo Red staining and apple‐green birefringence under polarized light. Amyloid subtyping with immunohistochemistry showed positive β₂‐microglobulin staining within the deposits. Conservative therapy involving pain management and close monitoring resulted in eventual improvement in symptoms and thus proved to be a viable option for treatment.     

Confounding factors for early death in incident end‐stage renal disease patients: Role of emergency dialysis start

Hemodialysis (HD) has been associated with higher 1‐year mortality than peritoneal dialysis (PD) after dialysis start. Confounding effects of late referral, emergency dialysis start, or start with central venous catheter on this association have never been studied concomitantly. Survival was studied among the 495 incident dialysed patients in our department from 1995 to 2006 and followed at least 1 year until December 31, 2007. Nested Cox models adjusted on patient characteristics explored factors associated with 1‐year and ≥1‐year mortality. Hemodialysis patients were 332 (67.1%), 104 (21.0%) were late referred (<6 months), 167 (33.7%) started dialysis in emergency, and 144 (29.1%) started with central venous catheter. When adjusted only on age, sex, and comorbidities, HD was associated with poor 1‐year outcome: adjusted hazard ratio (aHR) for death in HD vs. PD was 1.77, P=0.02. In fully adjusted model, among first dialysis feature variables, only emergency dialysis start was significantly associated with 1‐year mortality: aHR 1.53, P=0.02. Dialysis modality was not associated with 1‐year mortality rates in this fully adjusted model: aHR in HD vs. PD became 1.03, P=0.91. In ≥1‐year period, HD was associated with lower mortality than PD (aHR 0.61, P=0.004), whereas other first dialysis features were not associated with death. Other factors associated with death were age, type 2 diabetes, peripheral vascular disease, heart failure, and hepatic failure. Negative association between HD and 1‐year survival on dialysis was explained by confounders. Emergency dialysis start was strongly associated with early mortality on dialysis. Its prevention may improve patient survival.     

Intensive dialysis and blood pressure control: A review

The prevalence of hypertension in hemodialysis (HD) patients has increased over the years. In the early days of maintenance HD blood pressure (BP) control was achieved in most patients. As sessions were shortened, the prevalence of hypertension increased. Yet, in principle, dialysis is able to control hypertension. Today, in programs using long HD, most patients are normotensive without antihypertensive medication. The same is true for patients on daily dialysis, but not for those on short thrice‐weekly HD. In all studies reporting BP normalization, dry weight is regularly achieved. Why the poor control of hypertension now? At first sight the shortened session duration is the culprit. This is suggested by several epidemiologic observations and strongly supported by a prospective experience of changing the HD schedule (short to long HD or conversely) in the same group of patients. Recent studies, however, using strict volume control show that BP normalization can be obtained in conventional 3 x 4 hr/week dialysis with relatively low delivered Kt/V_urea. Therefore, prolonging the dialysis time and/or increasing the dialysis dose are not required to achieve BP control. Intensive dialysis most probably normalizes BP by getting the extracellular volume and the amount of sodium in the body back to normal. It acts in conjunction with a moderate dietary sodium restriction and the use of reasonably low dialysate sodium. With this approach improved BP control can be achieved in the vast majority of HD patients.     

Plasma myeloperoxidase,NT‐proBNP,and troponin‐I in patients on CAPD compared with those on regular hemodialysis

Myeloperoxidase (MPO) is a hemoprotein that is released during inflammation and may lead to irreversible protein and lipid modification, increasing levels of oxidized low density lipoprotein, and promoting athrogenesis. Recently, it has been considered as a risk factor for cardiovascular diseases. Similarly, the measurement of carotid intima‐media thickness gives an indication about the degree of atherosclerosis and prediction of clinical cardiovascular events. Elevated white blood cells counts may indicate a state of acute inflammation and follow its progression. Dialysis patients are at a high risk of developing cardiovascular disease compared with healthy subjects. The role of N‐terminal pro‐brain natriuretic peptide and increased cardiac troponin in identification and prognostication of cardiovascular diseases in end‐stage renal disease patients has been investigated. The current study aimed to evaluate plasma MPO and its possible relationship with carotid intima‐media thickness, troponin I, N‐terminal pro‐brain natriuretic peptide (NT‐proBNP), and insulin resistance as measured by homeostatic model assessment (HOMA index) in a cohort of Saudi patients who are undergoing hemodialysis (HD) vs. continuous ambulatory peritoneal dialysis for end‐stage renal disease. Plasma MPO was significantly higher in patients on continuous ambulatory peritoneal dialysis (CAPD) than in those on HD and in normal subjects (P<0.001). Conversely, NT‐proBNP plasma levels were significantly higher in patients on HD (both predialysis and postdialysis) than in those on CAPD (P<0.01) and than normal subjects. Similarly, plasma troponin‐I levels were significantly higher in patients on HD compared with those of CAPD and than normal subjects (P<0.001). Plasma troponin‐I and NT‐proBNP levels were positively correlated in the 3 groups namely those on CAPD, Pre‐HD, and post‐HD (r: 0.464 and P=0.047; r: 0.330 and P=0.013; and r: 0.452 and P=0.024), respectively. There was no correlation between the MPO level and carotid intima‐media thickness (P>0.05). However, plasma MPO level correlated positively with the white blood cell count in patients on CAPD and in those on HD (P<0.05). Our findings suggest an increased oxidative stress in CAPD patients compared with HD patients, while the reported difference in plasma NT‐proBNP and troponin‐I may be related to the rapid decline of residual renal function in HD and type of membrane used in the HD dialysis procedure itself.     

Survival with short‐daily hemodialysis: Association of time,site, and dose of dialysis

In thrice‐weekly hemodialysis, survival correlates with the length of time (t) of each dialysis and the dose (Kt/V), and deaths occur most frequently on Mondays and Tuesdays. We studied the influence of t and Kt/V on survival in 262 patients on short‐daily hemodialysis (SDHD) and also noted death rate by weekday. Contingency tables, Kaplan‐Meier analysis, regression analysis, and stepwise Cox proportional hazard analysis were used to study the associations of clinical variables with survival. Patients had been on SDHD for a mean of 2.1 (range 0.1–11) years. Mean dialysis time was 12.9 ± 2.3 h/wk and mean weekly stdKt/V was 2.7 ± 0.5. Fifty‐two of the patients died (20%) and 8‐year survival was 54 ± 5%. In an analysis of 4 groups by weekly dialysis time, 5‐year survival continuously increased from 45 ± 8% in those dialyzing <12 hours to 100% in those dialyzing >15 hours without any apparent threshold. There was no association between Kt/V and survival. In Cox proportional hazard analysis, 4 factors were independently associated with survival: age in years Hazard Ratio (HR)=1.05, weekly dialysis hours HR=0.84, home dialysis HR=0.50, and secondary renal disease HR=2.30. Unlike conventional HD, no pattern of excessive death occurred early in the week during SDHD. With SDHD, longer time and dialysis at home were independently associated with improved survival, while Kt/V was not. Homedialysis and dialysis 15+ h/wk appear to maximize survival in SDHD.     

Positive association between plasma levels of oxidized low‐density lipoprotein and myeloperoxidase after hemodialysis in patients with diabetic end‐stage renal disease

End‐stage renal disease (ESRD) patients undergoing hemodialysis (HD) have a high prevalence of cardiovascular events. Low‐density lipoprotein (LDL) in dialysis patients has been shown to be susceptible to in vitro peroxidation; therefore, oxidized‐LDL (ox‐LDL) could be generated in these patients. Moreover, myeloperoxidase (MPO) released from activated neutrophils may play a role in the induction of LDL oxidation. The purpose of this study was to investigate the relationship between plasma ox‐LDL levels, plasma MPO levels, and serum high‐sensitivity C‐reactive protein (hs‐CRP) levels during initial HD in patients with diabetic ESRD. Patients (n = 28) had serial venous blood samples drawn before and after HD at the initial, second, and third sessions. Plasma ox‐LDL levels were measured using a specific monoclonal antibody (DLH3), and plasma MPO levels were measured using an enzyme‐linked immunosorbent assay kit. Plasma ox‐LDL levels and MPO levels after a single HD session increased significantly (ox‐LDL, P < 0.005; MPO, P < 0.0001) compared with levels before that HD session. However, the increase was transient since the levels returned to pre‐HD session levels. Additionally, plasma MPO levels showed a positive correlation with plasma ox‐LDL levels during HD (R = 0.62, P = 0.0029). No significant change was observed in serum hs‐CRP levels before and after each HD session. This study demonstrates that plasma MPO levels are directly associated with plasma ox‐LDL levels in diabetic ESRD patients during initial HD. These findings suggest a pivotal role for MPO and ox‐LDL in the progression and acceleration of atherosclerosis in patients undergoing HD.     

Platelet‐to‐lymphocyte ratio better predicts inflammation than neutrophil‐to‐lymphocyte ratio in end‐stage renal disease patients

Neutrophil‐to‐lymphocyte ratio (NLR) was introduced as a potential marker to determine inflammation in end‐stage renal disease (ESRD) patients. Recently, platelet‐to‐lymphocyte ratio (PLR) and NLR were found to positively correlated with inflammatory markers including tumor necrosis factor‐α (TNF‐α) and interleukin (IL)‐6 in cardiac and noncardiac patients. Data regarding PLR and its association with inflammation are lacking in hemodialysis (HD) and peritoneal dialysis (PD) patients. Hence, we aimed to determine the relationship between PLR, NLR, and inflammation in ESRD patients. This was a cross‐sectional study involving 62 ESRD patients (29 females, 33 males; mean age, 49.6 ± 14.6 years) receiving PD or HD for ≥6 months in the Dialysis Unit of Necmettin Erbakan University. PLR, NLR, C‐reactive protein, TNF‐α, IL‐6 levels were measured. PLR, NLR, serum high sensitive C‐reactive protein, IL‐6, and TNF‐α levels were significantly higher in PD patients when compared with HD patients. ESRD patients with PLR ≥ 140 had significantly higher NLR, IL‐6, and TNF‐α levels when compared to patients with PLR < 139. In the bivariate correlation analysis, PLR was positively correlated with NLR, IL‐6, and TNF‐α in this population. When we compared the association of PLR and NLR with IL‐6 (r = 0.371, P = 0.003 vs. r = 0.263, P = 0.04, respectively) and TNF‐α (r = 0.334, P = 0.008 vs. r = 0.273, P = 0.032, respectively), PLR was found to be superior to NLR in terms of inflammation in ESRD patients. Simple calculation of PLR can predict inflammation better than NLR in ESRD patients.     

Heparin‐grafted dialysis membrane allows minimal systemic anticoagulation in regular hemodialysis patients: A prospective proof‐of‐concept study

This prospective, multicenter, proof‐of‐concept study aimed to evaluate the possibility to reduce the ordinary heparin dose and the systemic anti‐Xa activity during hemodialysis (HD) sessions using a new heparin‐grafted HD membrane. In 45 stable HD patients, the use of a heparin‐grafted membrane with the ordinary heparin dose was followed by a stepwise weekly reduction of dose. Reduction was stopped when early signs of clotting (venous pressure, quality of rinse‐back) occurred during two out of three weekly HD sessions. Heparin dose was decreased for 67% of patients resulting in the lowering of these patients' anti‐Xa activity by 50%. Dose reductions were achieved with both types of heparin (low‐molecular‐weight heparin: 64 ± 14 to 35 ± 12 IU/kg, P < 0.0001; unfractionated heparin: 82 ± 18 to 46 ± 13 IU/kg, P < 0.0001) resulting in a decrease of anti‐Xa activity at dialysis session end (low‐molecular‐weight heparin: 0.51 ± 0.25 to 0.25 ± 0.11 IU/mL, P < 0.0001; unfractionated heparin: 0.28 ± 0.23 to 0.13 ± 0.07 IU/mL, P < 0.0001). Failure to further decrease heparin dose was related to signs of clotting in blood lines (57% of sessions), in dialyzer (9%), or both (34%). Significant reduction of heparin dose and anti‐Xa activity at the end of HD sessions was possible in stable HD patients using heparin‐grafted membrane. HD patients who require low anti‐Xa activity at the end of HD sessions might benefit from a heparin‐grafted membrane to reduce bleeding risk and other heparin adverse events.     

Does hemodiafiltration improve the removal of homocysteine?

High prevalence of hyperhomocysteinemia is common in hemodialysis (HD) patients and could contribute to worsen the cardiovascular risk. Beyond vitamin B status, dialysis modality itself could influence homocysteine (Hcy) levels. The objective was compare the reduction rate (RR) of Hcy and cysteine in stable dialyzed patients treated by standard HD or hemodiafiltration (HDF). Seventy‐five patients undergoing stable dialysis through standard high‐flux HD (n = 35) or HDF (n = 40) were included. Biological parameters were determined before and after a midweek dialysis session. Urea percent reduction per session and Kt/V index (K, body urea clearance, T, time of dialysis, and V, urea distribution volume), defined as a marker of dialysis efficacy, were similar between HD and HDF groups. By contrast, higher RR of beta2 microglobulin (β2m) was observed in HDF compared with HD (78.6 vs. 72.0%, respectively; P < 0.001). Likewise, higher RR of Hcy was obtained with HDF compared to HD (46.0 vs. 41.5%, respectively; P < 0.05), whereas the RR of cysteine was similar in both groups. Interestingly, a positive correlation between Hcy RR and urea Kt/V index was observed (r = 0.29, P < 0.05) and between Hcy RR and β2m RR (r = 0.45, P < 0.001). Time‐averaged concentration (TAC) of Hcy was lower with HDF compared with HD (17.8 vs. 19.1 μmol/L, respectively), although not significant. There was no difference in median Hcy according to dialysis modality for neither pre‐ nor postdialysis levels. Significant higher removal of Hcy was observed with HDF compared with standard HD, although urea Kt/V index was similar. Enhanced removal of middle molecules, such as β2m, could be involved in Hcy RR improvement with HDF.     

Association between patient psychosocial characteristics and receipt of in‐center nocturnal hemodialysis among prevalent dialysis patients

Introduction: Compared to traditional in‐center hemodialysis (HD), in‐center nocturnal dialysis (INHD) is characterized by longer sessions and nighttime administration, which may lead to better outcomes for some patients. Given the importance of patient choice in the decision to initiate INHD, we explored associations between patients’ psychosocial characteristics and their receipt of INHD. Methods: Among hemodialysis patients at a medium‐sized dialysis organization, we identified INHD patients as those for whom ≥80% of dialysis sessions were INHD sessions—starting at 6:30 pm or later and lasting ≥5 hours—over the 3 months (≥20 sessions total) after their first INHD session. We extracted dialysis session data from electronic medical records and psychosocial data from social worker assessments. We tested associations of patients’ psychosocial characteristics—as well as demographic and clinical characteristics—with INHD receipt among all hemodialysis patients (INHD and HD) in bivariate analyses and multivariable logistic regression models. Findings: Among 759 patients with complete data, we identified 47 (6.2%) as INHD patients. On average, these patients were more likely than HD patients to be employed (full‐time 10.6% vs. 5.2%; part‐time 17.0% vs. 4.2%; P < 0.001), and they were significantly less likely to require ambulatory assistance (14.9% vs. 39.6%, P < 0.001). In multivariable regressions, we found that part‐time employment (versus being unemployed) was associated with a 7.1 percentage‐point higher likelihood of being an INHD patient (P = 0.01), and the negative association with ambulatory assistance needs approached statistical significance (P = 0.056). No other psychosocial factors included in this main regression analysis were statistically significantly associated with INHD patient status. Discussion: Researchers comparing the outcomes of patients undergoing INHD versus other treatment modalities will need to account for differences in employment status—and other factors like requiring ambulatory assistance and age which may predict the ability to work—between INHD users and comparison patients to avoid bias in estimates.     

Outcomes of patients with end‐stage renal disease (ESRD) under chronic hemodialysis requiring continuous renal replacement therapy (CRRT) and patients without ESRD in acute kidney injury requiring CRRT: A single‐center study

In most continuous renal replacement therapy (CRRT) studies, end‐stage renal disease (ESRD) patients were excluded and the outcomes of patients with ESRD treated with chronic hemodialysis (HD) were unknown. The purposes of this study were to (1) evaluate short‐term patient survival and (2) compare the survival of conventional HD patients needing CRRT with the survival of non‐ ESRD patients in acute kidney injury (AKI) requiring CRRT. We evaluated adults (>18 years) requiring CRRT who were treated in the intensive care unit (ICU) at Kosin University Gospel Hospital from January 1, 2009 to December 31, 2010. A total of 100 (24 ESRD, 76 non‐ESRD) patients underwent CRRT during the study period. Patients were divided into two major groups: patients with ESRD requiring chronic dialysis and patients without ESRD (non‐ESRD) with AKI. We compared the survival of conventional HD patients requiring CRRT with the survival of non‐ ESRD patients in AKI requiring CRRT. For non‐ESRD patients, the 90‐day survival rate was 41.6%. For ESRD patients, the 90‐day survival rate was 55.3%. Multivariate Cox proportional hazards analyses demonstrated that conventional HD was not a significant predictor of mortality (hazard ratio [HR]: 0.334, 95% confidence interval [CI]: 0.063–1.763, P = 0.196), after adjustment for age, gender, presence of sepsis, APACHE score, use of vasoactive drugs, number of organ failures, ultrafiltration rate, and arterial pH. The survival rates of non‐ESRD and ESRD patients requiring CRRT did not differ; ESRD with conventional HD patients may be not a significant predictor of mortality.     

Ultrapure dialysis fluid: Improving conventional and daily dialysis

Dialysis fluid of standard quality contains a certain amount of bacteria and endotoxin. This has been considered acceptable because the dialysis membrane was believed to be a protective barrier to blood. However, improved methods for detection of cellular activation have demonstrated that bacterial products in the dialysate may stimulate monocytes to produce cytokines with most dialysis membranes. Ultrapure dialysis fluid is practically free from bacteria and endotoxin (< 0.1 CFU/mL and < 0.03 EU/mL) and can be prepared from standard‐quality dialysis fluid using a single step of controlled ultrafiltration. The European guidelines for hemodialysis (HD) set the use of ultrapure dialysis fluid as the goal for all dialysis modalities. Several clinical studies report improved inflammatory status in HD patients when ultrapure dialysis fluid is used, compared with standard‐quality dialysate. The benefits include less frequent occurrence of carpal tunnel syndrome, lower C‐reactive protein values, reduced need for erythropoietin, better nutritional status, and even better preservation of residual renal function. For patients on daily dialysis, dialysate quality is especially important because such patients are often treated at home where quality control of incoming water may be less rigorous, and increased treatment frequency leads to exposure to larger volumes of dialysis fluid than with conventional dialysis. The use of ultrapure dialysis fluid together with low‐complement‐activating membranes maximizes the biocompatibility of a dialysis treatment, a goal of treatment, although there is a lack of evidence to date supporting a beneficial effect on mortality. From a physiologic point of view the reduced inflammatory stimulus that can be achieved with ultrapure dialysis fluid is highly desirable. In addition, achieving ultrapure dialysis fluid is realistic, because today it can be practically and economically prepared using modern equipment and applying appropriate microbiologic surveillance techniques.     

Infective spondylodiscitis in patients on high‐flux hemodialysis and on‐line hemodiafiltration

Infective spondylodiscitis (ISD) is a rare but potentially devastating condition in hemodialysis (HD) patients. Reports are limited especially in patients receiving high‐flux HD and hemodiafiltration (HDF). In a retrospective analysis, 13 patients on our maintenance high‐flux HD/HDF program were identified as having has infective spondylodiscitis over a 10‐year period (1997–2006), an incidence of approximately 1 episode every 215 patient‐years. The incidence was around 3 times higher in patients dialyzing with tunnelled central venous catheters (TCVC) than in those with arteriovenous fistulae. Affected patients were elderly (mean age 70 years) and had multiple comorbidities. Access problems, particularly TCVC infection, were common in the months preceding it's onset. Tunnelled central venous catheter removal during these episodes did not necessarily prevent it. Diagnosis was based on a history of back pain, raised C‐reactive protein, positive blood cultures, and characteristic magnetic resonance findings. Many patients were apyrexial and had normal white cell counts. In our patients on high‐flux HD/hemodiafiltration, its incidence appears comparable to that in conventional HD settings. No patients had infection with waterborne organisms. Blood cultures were positive in 77%. Gram‐positive organisms predominated, particularly Staphylococcus aureus. The major route of infection was hematogenous, with the most likely source the venous access. All received antibiotics for 6 to 12 weeks or until death. Only 2 patients underwent surgical drainage. Mortality was high (46%) and predicted by the development of complications, and by pre‐existing cardiovascular comorbidity. Prevention, using strategies to reduce the prevalence of bacteremia, including limiting the use of TCVC, should be an overriding aim.     

Acute hemodialysis complications in end‐stage renal disease patients: The burden and implications for the under‐resourced Sub‐Saharan African health systems

Little is known about the challenges of routine renal replacement therapy in Sub‐Saharan Africa. We investigated the fatal and nonfatal acute hemodialysis (HD) complications in patients with end‐stage renal disease (ESRD) in two main dialysis centers in Cameroon. 1000 consecutive HD sessions incurred over a 4‐month period by 129 patients (96 men, 74%) with ESRD, receiving two weekly HD sessions of 4 hours each, were considered. Personal and clinical profiles before, during, and within 24 hours after HD sessions were used to diagnose complications. Participants were aged 7 to 80 years (mean 46 years). In all, 452 acute complications were recorded in 411 (41%) of the 1000 HD sessions. Of the 11 types of complications, hypotension (25%), muscular cramps (22%), hypertensive crisis (14%), pruritus (10%), and fever (7%) were the most frequent. Three hundred and six complications (67.7%) occurred during understaffed nighttime. The vascular access was the main bleeding site with 64%. Being diabetic and ultrafiltration rate >1000 mL/h were associated with hypotension and muscle cramps. The shorter duration in dialysis was associated with the risk of bleeding and the disequilibrium syndrome while longer duration was associated with muscle cramps. Four deaths (three from bleeding and one from disequilibrium syndrome) occurred, all during nighttime. Nearly half of dialysis sessions in these settings are associated with acute complications, some of which are fatal. Those complications occurred mostly during understaffed periods. Urgent strategies are needed to quickly solve the human capital crisis in the health care sector.     

Kidney embolization induces prompt organ response in a 86‐year‐old patient with MGRS‐related AL‐amyloidosis

Despite substantial improvements following the introduction of novel agents and antibodies, amyloid light‐chain (AL)‐amyloidosis still carries a grim prognosis. Here, we report on the case of a severely frail 86‐year‐old patient suffering from monoclonal gammopathy of renal significance (MGRS)‐associated AL‐amyloidosis with a diuretic‐refractory nephrotic syndrome. In this patient, treatment with bortezomib–dexamethasone effectively induced a serological response, but was unfortunately poorly tolerated and failed to promote renal recovery fast enough to prevent secondary complications. Facing ongoing nephrotic syndrome, we performed unilateral kidney embolization and observed a substantial improvement of hypoalbuminemia accompanied by a significant gain in overall quality of life despite the necessity for thrice weekly dialysis. It can be concluded that systemic drugs in MGRS typically do not lead to instantaneous organ recovery but may initially rather be associated with substantial treatment‐related morbidity. In this setting, unilateral renal artery embolization is effective to treat nephrotic syndrome and its secondary complications. The risk of potentially adverse effects, including post‐embolization syndrome, can be minimized by unilateral embolization, still noting that also one‐sided renal ablation has to be balanced against the requirement for life‐long renal replacement therapy. Prospective controlled trials in a more comprehensive cohort will be needed to estimate the overall benefit of kidney embolization relative to novel agent therapies in frail patients with MGRS‐related AL‐amyloidosis.     

Tailoring dialysis and resuming low‐protein diets may favor chronic dialysis discontinuation: Report on three cases

Renal function recovery (RFR), defined as the discontinuation of dialysis after 3 months of replacement therapy, is reported in about 1% of chronic dialysis patients. The role of personalized, intensive dialysis schedules and of resuming low‐protein diets has not been studied to date. This report describes three patients with RFR who were recently treated at a new dialysis unit set up to offer intensive hemodialysis. All three patients were females, aged 73, 75, and 78 years. Kidney disease included vascular‐cholesterol emboli, diabetic nephropathy and vascular and dysmetabolic disease. At time of RFR, the patients had been dialysis‐dependent from 3 months to 1 year. Dialysis was started with different schedules and was progressively discontinued with a “decremental” policy, progressively decreasing number and duration of the sessions. A moderately restricted low‐protein diet (proteins 0.6 g/kg/day) was started immediately after dialysis discontinuation. The most recent update showed that two patients are well off dialysis for 5 and 6 months; the diabetic patient died (sudden death) 3 months after dialysis discontinuation. Within the limits of small numbers, our case series may suggest a role for personalized dialysis treatments and for including low‐protein diets in the therapy, in enhancing long‐term RFR in elderly dialysis patients.     

Removal of vancomycin administered during dialysis by a high‐flux dialyzer

Introduction: Hemodialysis patients frequently receive vancomycin for treatment of gram‐positive bacterial infections. This drug is most conveniently administered in outpatient dialysis units during the hemodialysis treatment. However, there is a paucity of data on the removal of vancomycin by high‐flux polyamide dialyzers. Methods: This is a prospective crossover study in which seven uninfected chronic hemodialysis patients at three dialysis units received vancomycin 1 gram intravenously over one hour immediately after the dialysis treatment (Phase 1), and vancomycin 1.5 grams during the last hour of dialysis treatment using a polyarylethersulfone, polyvinylpyrrolidone, polyamide high‐flux (Polyflux 24R) dialyzer (Phase 2). There was a three‐week washout period between phases. Serial serum vancomycin concentrations were used to determine the removal of vancomycin when administered during dialysis. Findings: Dialysis removed 35 ± 15% (range 18‐56%) of the vancomycin dose when administered during the last hour of dialysis. The calculated area under the curve (AUC) of vancomycin levels for 0‐44.5 hours from the start of infusion were similar between the two phases (AUC_{Phase 1} 884 ± 124 mg‐hr/L, mean ± SD; AUC_{Phase 2} 856 ± 208 mg‐hr/L; P=0.72). Serum vancomycin concentrations immediately prior to the next dialysis treatment following vancomycin administration were also similar between the two phases (13.1 ± 2.7 mg/L in Phase 1 and 12.3 ± 3.3 mg/L in Phase 2; P=0.55). Discussion: When using a polyarylethersulfone, polyvinylpyrrolidone, and polyamide high‐flux HD membrane with a 24R Polyflux dialyzer, vancomycin can be administered during the last hour of dialysis if the dose that is prescribed for intra‐dialysis dosing is empirically increased to account for intra‐dialytic drug removal.     

Comparison of serum albumin,C‐reactive protein and carotid atherosclerosis as predictors of 10‐year mortality in hemodialysis patients

Serum albumin, C‐reactive protein (CRP), and the intima‐medial thickness of the common carotid artery (CA‐IMT) are associated with clinical outcomes in hemodialysis (HD) patients. However, it remains unclear which parameters are more reliable as predictors of long‐term mortality. We measured serum albumin, CRP, and CA‐IMT in 206 HD patients younger than 80 years old, and followed them for the next 10 years. One hundred sixty‐eight patients (age: 57 ± 11 years, time on HD: 11 ± 7 years) were enrolled in the analyses. We divided all patients into three tertiles according to their albumin levels, and conducted multivariate analyses to examine the impact on 10‐year mortality. Seventy‐three (43.5%) patients had expired during the follow‐up. Serum albumin was significantly lower in the expired patients than in the surviving patients (3.8 ± 0.3 vs. 4.0 ± 0.3, P<0.01), while CRP (4.7 ± 5.0 vs. 2.8 ± 3.5 g/L, P=0.01) and CA‐IMT (0.70 ± 0.15 vs. 0.59 ± 0.11 mm, P<0.01) were significantly higher in the expired group. The multivariate analysis revealed that there was a significantly higher risk for total mortality in HD patients with serum albumin <3.8 g/dL (odds ratio 5.04 [95% CI: 1.30–19.60], P=0.02) when compared with those with albumin >4.1 g/dL. In contrast, CRP and CA‐IMT did not associate with total death. It follows from these findings that serum albumin is more superior as a mortality predictor compared with CRP and CA‐IMT in HD patients.