Clearing the clouds: Case-report and review of the literature.

In peritoneal dialysis (PD), a cloudy dialysate is an alarming finding. Bacterial peritonitis is the most common cause, however, atypical infections and non-infectious causes must be considered. A 46-year-old man presented with asthenia, paraesthesia, foamy urine and hypertension. Laboratory testing revealed severe azotaemia, anaemia, hyperkalaemia and nephrotic-range proteinuria. Haemodialysis was started through a central venous catheter. Later, due to patient preference, a Tenckhoff catheter was inserted. Conversion to PD occurred 3 weeks later, during hospitalization for a presumed central line infection. A month later, the patient was hospitalized for neutropenic fever. He was diagnosed an acute parvovirus infection and was discharged under isoniazid for latent tuberculosis. Four months later, the patient presented with fever and a cloudy effluent. Peritoneal fluid (PF) cytology was suggestive of infectious peritonitis, but the symptoms persisted despite antibiotic therapy. Bacterial and mycological cultures were negative. No neoplastic cells were detected. Mycobacterium tuberculosis eventually grew in PF cultures, despite previous negative molecular tests. Directed therapy was then initiated with excellent response. Thus, facing a cloudy effluent, one must consider multiple aetiologies. Diagnosis of peritoneal tuberculosis is hampered by the lack of highly sensitive and specific exams. Here, diagnosis was only possible due to positive mycobacterial cultures.

Arteriolar C4d in IgA Nephropathy: A Cohort Study.

RATIONALE & OBJECTIVE: Glomerular C4d (C4dG) as an indicator of the lectin pathway of complement activation in immunoglobulin A nephropathy (IgAN) has been associated with more severe kidney damage. Recent studies have suggested that vascular lesions in IgAN biopsy specimens with complement deposition are also associated with disease progression. We aimed to study the clinical significance of arteriolar C4d (C4dA) in IgAN kidney biopsy tissue. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: Kidney biopsy specimens from 126 adults with IgAN diagnosed by Oxford classification criteria were stained using immunohistochemistry and classified according to C4dG and C4dA deposition. Additionally, vascular lesions including acute and chronic microangiopathy, arteriolar hyalinosis, and arterial intima fibrosis were characterized. PREDICTOR: C4dA. OUTCOME: Progressive kidney disease, defined as a decline in estimated glomerular filtration rate by≥50% or occurrence of kidney failure. ANALYTICAL APPROACH: The association of C4dA and C4dG with baseline clinical and histologic characteristics, as well as progressive kidney disease, were assessed with survival analysis using multivariable Cox regression analysis. RESULTS: C4dA was identified in 21 (17%) patients and was associated with mean arterial pressure, arterial intima fibrosis, and chronic microangiopathy. C4dA was also significantly associated with C4dG and both were associated with progressive kidney disease. In regression analysis, C4dA remained significantly associated with progressive kidney disease after adjusting for other significant predictors, including baseline estimated glomerular filtration rate, mean arterial pressure, and the presence of crescents. LIMITATIONS: Findings based on the retrospective evaluation of a single center's experience, limited number of events, a small number of patients with a broad range of kidney disease stages, and use of immunohistochemistry rather than immunofluorescence to detect C4d. CONCLUSIONS: C4dA is a potential biomarker for disease progression in IgAN. It should be further investigated in larger cohorts to determine the value of C4dA in improving prediction of IgAN disease progression.

The microbiome in chronic kidney disease patients undergoing hemodialysis and peritoneal dialysis.

Chronic kidney disease (CKD) is associated with an imbalanced human microbiome due not only to CKD-associated factors such as uremia, increased inflammation and immunosuppression, but also to pharmacological therapies and dietary restrictions. End-stage renal disease patients require renal replacement therapies commonly in the form of hemodialysis (HD) or peritoneal dialysis (PD). HD implies the existence of a vascular access, such as an arteriovenous fistula/graft or a venous catheter, whereas PD implies a long-term peritoneal catheter and the constant inflow of peritoneal dialysate. Also, dietary adaptations are mandatory in both therapies. This revision explores the impact of HD or PD therapies on human microbiome. HD and PD appear to be associated with different changes in the gut microbiome, for example a decrease in Proteobacteria relative abundance in HD patients and increase in PD patients. Both therapies may also have an impact on the human microbiome beyond the gut, leading to increased relative abundance of specific bacteria in the blood microbiome of HD patients and increased relative abundance of other bacteria in the peritoneal microbiome of PD patients. HD and PD catheter biofilms may also play an important role in the changes observed in these microbiomes. A more interdisciplinary approach is needed to further clarify the role of microbial groups other than bacteria in all body habitats to allow the complete understanding of the impact of HD or PD on the microbiome of CKD patients. Moreover, strategies that promote a healthy balance of the human microbiome on these patients should be explored.

Oral Colonization of Staphylococcus Species in a Peritoneal Dialysis Population: A Possible Reservoir for PD-Related Infections?

Peritoneal dialysis-related infections are important morbidity/mortality causes, being staphylococci the most prevalent agents. Since Staphylococcus aureus nasopharynx carriage is a known risk factor for PD infections and the oral cavity is a starting point for systemic diseases development, we aimed at comparing the oral staphylococci colonization between PD patients and controls and studying the association with PD-related infections. Saliva samples were plated in Mannitol salt, and isolates were identified by DnaJ gene sequencing. Staphylococci PD-related infections were recorded throughout the 4-year period following sample collection. Staphylococcus colonization was present in >90% of the samples from both groups (a total of nine species identified). PD patients presented less diversity and less prevalence of multispecies Staphylococcus colonization. Although all patients presenting Staphylococcus epidermidis PD-related infections were also colonized in the oral cavity by the same agent, only 1 out of 7 patients with ESI caused by S. aureus presented S. aureus oral colonization. Staphylococci are highly prevalent in the oral cavity of both groups, although PD patients presented less species diversity. The association between oral Staphylococcus carriage and PD-related infections was present for S. epidermidis but was almost inexistent for S. aureus, so, further studies are still necessary to evaluate the infectious potential of oral Staphylococcus carriage in PD.

Oral Yeast Colonization and Fungal Infections in Peritoneal Dialysis Patients: A Pilot Study.

Peritonitis and exit-site infections are important complications in peritoneal dialysis (PD) patients that are occasionally caused by opportunistic fungi inhabiting distant body sites. In this study, the oral yeast colonization of PD patients and the antifungal susceptibility profile of the isolated yeasts were accessed and correlated with fungal infection episodes in the following 4 years. Saliva yeast colonization was accessed in 21 PD patients and 27 healthy controls by growth in CHROMagar-Candida® and 18S rRNA/ITS sequencing. PD patients presented a lower oral yeast prevalence when compared to controls, namely, Candida albicans. Other species were also isolated, Candida glabrata and Candida carpophila. The antifungal susceptibility profiles of these isolates revealed resistance to itraconazole, variable susceptibility to caspofungin, and higher MIC values of posaconazole compared to previous reports. The 4-year longitudinal evaluation of these patients revealed Candida parapsilosis and Candida zeylanoides as PD-related exit-site infectious agents, but no correlation was found with oral yeast colonization. This pilot study suggests that oral yeast colonization may represent a limited risk for fungal infection development in PD patients. Oral yeast isolates presented a variable antifungal susceptibility profile, which may suggest resistance to some second-line drugs, highlighting the importance of antifungal susceptibility assessment in the clinical practice.

Fibroblast growth factor 23 is associated with left ventricular hypertrophy, not with uremic vasculopathy in peritoneal dialysis patients.

AIMS: Cardiovascular (CV) events are the leading cause of morbidity and mortality in patients with chronic kidney disease (CKD), including those patients on peritoneal dialysis (PD). Fibroblast growth factor 23 (FGF23) has been associated with left ventricular hypertrophy (LVH) and mortality in patients with CKD. However, the role of FGF23 in uremic vasculopathy remains unclear. In this study, we aimed to assess the relationship between FGF23 and LVH, endothelial dysfunction, vascular calcification, and arterial stiffness in 48 stable PD patients. METHODS: Left ventricular mass index (LVMI) was assessed using 2-D echocardiography. Intact FGF23 blood levels were evaluated using an ELISA kit (Immutopics, Inc., San Clemente, CA, USA). Reactive hyperemia index (RHI) is a surrogate marker of endothelial dysfunction and the augmentation index (AI) is a surrogate marker of arterial stiffness. Both were assessed using peripheral arterial tonometry (EndoPAT 2000). Vascular calcification (VC) was assessed using the Adragão score. RESULTS: In unadjusted analysis; FGF23 was positively correlated with serum Pi (r = 0.487, p < 0.001), serum urea (r = 0.351, p = 0.015), serum creatinine (r = 0.535, p < 0.001), dialysis vintage (r = 0.309, p = 0.033), and LVMI (r = 0.369, p = 0.027) and was negatively correlated with age (r = -0.343, p = 0.017), residual renal function (r = -0.359, p < 0.012), and AI (r = -0.304, p = 0.038). In multivariate adjusted analysis, FGF23 was associated with LVMI (ß = 0.298, p = 0.041), serum Pi (ß = 0.345, p = 0.018), and age (ß = -0.372, p = 0.007) independent of dialysis vintage, gender, residual renal function (RRF), albumin, C-reactive protein and systolic blood pressure. There were no associations found between FGF23 and RHI, AI, or VC in multivariable- adjusted models. CONCLUSIONS: Our results show that FGF23 is associated with LVH but not with endothelial dysfunction, arterial stiffness, or vascular calcification in PD patients.

Renalase regulates peripheral and central dopaminergic activities.

Renalase is a recently identified FAD/NADH-dependent amine oxidase mainly expressed in kidney that is secreted into blood and urine where it was suggested to metabolize catecholamines. The present study evaluated central and peripheral dopaminergic activities in the renalase knockout (KO) mouse model and examined the changes induced by recombinant renalase (RR) administration on plasma and urine catecholamine levels. Compared with wild-type (WT) mice, KO mice presented increased plasma levels of epinephrine (Epi), norepinephrine (NE), and dopamine (DA) that were accompanied by increases in the urinary excretion of Epi, NE, DA. In addition, the KO mice presented an increase in urinary DA-to-l-3,4-dihydroxyphenylalanine (l-DOPA) ratios without changes in renal tubular aromatic-l-amino acid decarboxylase (AADC) activity. By contrast, the in vivo administration of RR (1.5 mg/kg sc) to KO mice was accompanied by significant decreases in plasma levels of Epi, DA, and l-DOPA as well as in urinary excretion of Epi, DA, and DA-to-l-DOPA ratios notwithstanding the accompanied increase in renal AADC activity. In addition, the increase in renal DA output observed in renalase KO mice was accompanied by an increase in the expression of the L-type amino acid transporter like (LAT) 1 that is reversed by the administration of RR in these animals. These results suggest that the overexpression of LAT1 in the renal cortex of the renalase KO mice might contribute to the enhanced l-DOPA availability/uptake and consequently to the activation of the renal dopaminergic system in the presence of renalase deficiency.

The urogenital microbiome in chronic kidney disease patients on peritoneal dialysis.

INTRODUCTION AND OBJECTIVES: Diabetes, dyslipidemia, older age, gender, urinary tract infections, and recent antibiotic intake have been associated with a decrease in the urobiome richness and other fluctuations in this microbiome. Gut and blood microbiome have been reported to be altered in patients with chronic kidney disease (CKD), and specifically in peritoneal dialysis (PD) patients. Still, there are currently no studies describing the urogenital microbiome in CKD-PD patients. In this study we characterized the urobiome profile in 46 PD patients and analyzed its clinical and inflammatory parameters. MATERIALS AND METHODS: Mid-stream urine, fecal and blood samples were collected from 46 patients undergoing PD at Centro Hospitalar Universitário de São João (CHUSJ) in Porto, Portugal. Exclusion criteria were age under 18 years old, inability to give informed consent, history of infection in the last three months, and antibiotic intake in the last three months. The microbiome communities were analyzed by amplification and sequencing of the V3-V4 region of the bacterial 16S rRNA gene. Correlations with the patients' clinical data and inflammatory profile were performed. RESULTS: CKD-PD patients presented a unique urobiome profile dominated by Bacillota, Actinomycetota and Pseudomonadota and characterized by a lower Shannon diversity than fecal and blood microbiome. The taxonomic profiles of urogenital samples were organized in multiple subtypes dominated by populations of Lactobacillus, Staphylococcus, Streptococcus, Gardnerella, Prevotella, Escherichia-Shigella, being similar to other non-PD-CKD patients. Gender, sCD14, residual diuresis and history of peritonitis were significantly associated to variations in the urobiome. Although not reaching statistical significance, diabetes and the time on PD also showed association with particular taxonomic groups. Depletion of Gardnerella, Staphylococcus, Corynebacterium, Lactobacillus or Dermabacter populations correlated with CKD-PD patients with history of diabetes, history of peritonitis and altered levels of sCD14. CONCLUSIONS: Our results highlight urogenital microbiome as a potential partner and/or marker in the overall health state of CKD-PD patients.

Systemic and local complement activation in peritoneal dialysis patients via conceivably distinct pathways.

BACKGROUND: Despite several advantages compared to haemodialysis (HD), peritoneal dialysis (PD) remains an underused dialysis technique due to its high technique failure rate related to membrane fibrosis and peritonitis events. Previous work has suggested a harmful role for the complement system in these processes, highlighting the need for a more comprehensive examination in PD. METHODS: Plasma levels of C1q, mannose-binding lectin (MBL), Properdin, Factor D, C3d/C3-ratio and soluble membrane attack complex (sC5b-9) were determined in PD patients (n = 55), HD patients (n = 41), non-dialysis chronic kidney disease (CKD) patients (n = 15) and healthy controls (n = 14). Additionally, C1q, MBL, Properdin, Factor D and sC5b-9 levels were assessed in the peritoneal dialysis fluid (PDF). In a subgroup, interleukin-6, matrix metalloproteinase-2 (MMP-2), myeloperoxidase (MPO) and elastase were measured in the PDF. RESULTS: PD patients had significantly higher systemic levels of sC5b-9 compared to healthy controls, CKD and HD patients (p < 0.001). Plasma levels of C1q and C3d/C3-ratios were significantly associated with systemic sC5b-9 levels (p < 0.001). Locally, sC5b-9 was detected in the PDF of all PD patients, and levels were approximately 33% of those in matched plasma, but they did not correlate. In the PDF, only Properdin levels remained significantly associated with PDF sC5b-9 levels in multivariate analysis (p < 0.001). Additionally, PDF levels of sC5b-9 positively correlated with elastase, MPO and MMP-2 levels in the PDF (p < 0.01). CONCLUSIONS: Our data reveal both systemic and local complement activation in PD patients. Furthermore, these two processes seem independent considering the involvement of different pathways and the lack of correlation.

Renalase regulates renal dopamine and phosphate metabolism.

Renalase is a kidney-secreted catecholamines-degrading enzyme whose expression and activity are downregulated by increased dietary phosphate. A renalase knockout (KO) mouse model was used to explore the mechanisms mediating renalase's effect on phosphate excretion. Compared with wild-type (WT) mice maintained on a regular diet, KO mice show decreased serum PO4(-) (KO = 5.3 ± 0.2 vs. WT = 6.0 ± 0.1, n = 6; P < 0.04) and increased urinary PO4(-) excretion (urine PO4(-)/creatinine: KO = 7.7 ± 0.3 vs. WT = 6.1 ± 0.3, n = 6; P < 0.02). However, both WT and KO mice respond similarly to PO4(-) restriction by increasing renal COMT-1 activity and markedly decreasing PO4(-) excretion, which excludes an intrinsic renal defect in the KO. Renal sodium-phosphate cotransporter Npt2a, sodium proton exchanger NHE3 expression, and MAO-A and B activity did not differ between WT and KO. Only catechol-O-methyl transferase (COMT) expression and activity were significantly increased in KO mice. Despite that, urinary dopamine increased by twofold, whereas urinary l-DOPA excretion decreased by twofold in the KO mouse, indicating an upregulation of renal dopamine (DA) synthesis. These data indicate that renalase deficiency is associated with increased renal DA synthesis, stimulated PO4(-) excretion, and moderately severe hypophosphatemia. The signal to increase renal DA synthesis is strong since it overcomes a compensatory increase in COMT activity.

Blood, Gut, and Oral Microbiome in Kidney Transplant Recipients.

Background and Objective: Recent reports describe the existence of a blood microbiome profile not associated with an infection state. Given the high impact that the dysbiotic human microbiome appears to have in chronic kidney disease and, in particular, in the outcome of kidney transplant recipients (KTRs), we aimed to explore the variations and correlations of the gut, oral, and blood microbiome of recipients, 3 months after kidney transplantation. Materials and Methods: We conducted a cross-sectional study where the microbiome of stool, saliva, and blood collected from recipients 3 months after kidney transplantation (N = 6) was analyzed by polymerase chain reaction (PCR) amplification and sequencing of the V3-V4 hypervariable regions of the 16S rRNA gene using MiSeq Illumina® technology. Results: Blood of KTRs harbors a distinct low-abundance microbiome dominated by Proteobacteria and Firmicutes. Gut and oral microbiome of KTRs also present distinct profiles. The existence of a proportion of shared operational taxonomic units among the different body sites is reported, mainly classified as Proteobacteria and Firmicutes. Conclusions: This study provides evidence of existence a blood microbiome in KTRs, different from the gut and the oral microbiome profiles, with a small number of operational taxonomic units representing a shared microbiome. The clinical relevance of this observation should be further explored in these patients.

Lessons from Four Decades of Systemic Amyloidosis with Renal Involvement.

BACKGROUND: Apart from ATTR amyloidosis, the epidemiology and outcomes of the most common subtypes of systemic amyloidosis in Portugal remain primarily unknown. METHODS: This retrospective cohort study evaluated patients with renal biopsy-proven amyloidosis, diagnosed from January 1978 to December 2019. Follow-up started at kidney disease presentation and ended at death or August 2020. Clinical presentation, survival, and prognostic factors were analysed. RESULTS: Of 123 patients with amyloid nephropathy, 111 had definite amyloid typing and were analysed. AA amyloidosis was the most frequent type (56.1%) and was related mainly to chronic infection (47.8%) and chronic inflammatory arthritis (29.0%). AL amyloidosis was present in 25.2% of patients and hereditary forms in 6.5% (4.1% AFibE526V, 2.4% ATTRV30M). During follow-up, 73.9% of AA and 54.8% of AL patients progressed to end-stage renal disease, and 79.7% of AA and 77.4% of AL died; median overall survival was 66.0 (95% CI, 33.0-99.0) and 18.0 (95% CI, 9.3-26.7) months (p = 0.025), respectively. There were no significant differences in renal outcome and survival on dialysis between these two types. In multivariate analysis, cardiac involvement at presentation (HR 6.26 [95% CI, 2.89-13.56]) and estimated glomerular filtration rate <30 mL/min/1.73 m2 (HR 2.05 [95% CI, 1.06-3.99]) independently influenced AA and AL amyloidosis survival. Cardiac involvement at presentation was an independent predictor of death (HR 9.65 [95% CI, 2.91-31.95]) and early mortality in AL amyloidosis. CONCLUSIONS: In Portugal, AA amyloidosis and related chronic infections are still relevant. Regarding AL amyloidosis, the low incidence and advanced disease at presentation result from missed and erroneous diagnoses, leading to delayed referrals and poor outcomes in these patients.

Physical examination of dysfunctional arteriovenous fistulae by non-interventionalists: a skill worth teaching.

BACKGROUND: Physical examination (PE) of arteriovenous fistulae (AVF) has recently emerged as an important element in the detection of stenotic lesions. This study examines the accuracy of PE in the assessment of AVF dysfunction by non-interventionalists in comparison with angiography. METHODS: A total of 177 consecutive patients who had AVF dysfunction and were referred to our centre by general nephrologists for angioplasty between November 2009 and July 2010 were included in this analysis. Eleven referring general nephrologists completed a form reporting the PE findings regarding their patients' AVFs. Before angiography examination was carried out, a trained nephrology resident performed a PE in all the cases. Angiography of the AVFs was then performed by an interventionalist. Cohen's κ value was used as the measurement of the level of agreement beyond chance between the diagnosis made on PE and angiography. RESULTS: There was a moderate agreement beyond chance between the general nephrologists' PE and angiography in the detection of AVF inflow stenosis (κ = 0.49), outflow stenosis (κ = 0.58) and thrombosis (κ = 0.52). On the other hand, PE performed by the trained nephrology resident strongly agreed with angiography in the detection of AVF inflow stenosis (κ = 0.84), outflow stenosis (κ = 0.92) and thrombosis (κ = 0.98). The agreement between PE and angiography in the detection of co-existing AVF inflow-outflow stenosis was poor for the general nephrologists and moderate for the trained nephrology resident (κ = 0.14 versus κ = 0.55, respectively). CONCLUSION: PE may provide an accurate means of diagnosis of AVF dysfunction. Theoretical and hands-on training in PE of dysfunctional AVFs should be provided for nephrologists in-training and for the dialysis staff.

Effects of starting hemodialysis with an arteriovenous fistula or central venous catheter compared with peritoneal dialysis: a retrospective cohort study.

BACKGROUND: Although several studies have demonstrated early survival advantages with peritoneal dialysis (PD) over hemodialysis (HD), the reason for the excess mortality observed among incident HD patients remains to be established, to our knowledge. This study explores the relationship between mortality and dialysis modality, focusing on the role of HD vascular access type at the time of dialysis initiation. METHODS: A retrospective cohort study was performed among local adult chronic kidney disease patients who consecutively initiated PD and HD with a tunneled cuffed venous catheter (HD-TCC) or a functional arteriovenous fistula (HD-AVF) in our institution in the year 2008. A total of 152 patients were included in the final analysis (HD-AVF, n = 59; HD-TCC, n = 51; PD, n = 42). All cause and dialysis access-related morbidity/mortality were evaluated at one year. Univariate and multivariate analysis were used to compare the survival of PD patients with those who initiated HD with an AVF or with a TCC. RESULTS: Compared with PD patients, both HD-AVF and HD-TCC patients were more likely to be older (p<0.001) and to have a higher frequency of diabetes mellitus (p = 0.017) and cardiovascular disease (p = 0.020). Overall, HD-TCC patients were more likely to have clinical visits (p = 0.069), emergency room visits (p<0.001) and hospital admissions (p<0.001). At the end of follow-up, HD-TCC patients had a higher rate of dialysis access-related complications (1.53 vs. 0.93 vs. 0.64, per patient-year; p<0.001) and hospitalizations (0.47 vs. 0.07 vs. 0.14, per patient-year; p = 0.034) than HD-AVF and PD patients, respectively. The survival rates at one year were 96.6%, 74.5% and 97.6% for HD-AVF, HD-TCC and PD groups, respectively (p<0.001). In multivariate analysis, HD-TCC use at the time of dialysis initiation was the important factor associated with death (HR 16.128, 95%CI [1.431-181.778], p = 0.024). CONCLUSION: Our results suggest that HD vascular access type at the time of renal replacement therapy initiation is an important modifier of the relationship between dialysis modality and survival among incident dialysis patients.

Gut Microbiome and Organ Fibrosis.

Fibrosis is a pathological process associated with most chronic inflammatory diseases. It is defined by an excessive deposition of extracellular matrix proteins and can affect nearly every tissue and organ system in the body. Fibroproliferative diseases, such as intestinal fibrosis, liver cirrhosis, progressive kidney disease and cardiovascular disease, often lead to severe organ damage and are a leading cause of morbidity and mortality worldwide, for which there are currently no effective therapies available. In the past decade, a growing body of evidence has highlighted the gut microbiome as a major player in the regulation of the innate and adaptive immune system, with severe implications in the pathogenesis of multiple immune-mediated disorders. Gut microbiota dysbiosis has been associated with the development and progression of fibrotic processes in various organs and is predicted to be a potential therapeutic target for fibrosis management. In this review we summarize the state of the art concerning the crosstalk between intestinal microbiota and organ fibrosis, address the relevance of diet in different fibrotic diseases and discuss gut microbiome-targeted therapeutic approaches that are current being explored.

Renalase deficiency aggravates ischemic myocardial damage.

Chronic kidney disease (CKD) leads to an 18-fold increase in cardiovascular complications not fully explained by traditional risk factors. Levels of renalase, a recently discovered oxidase that metabolizes catecholamines, are decreased in CKD. Here we show that renalase deficiency in a mouse knockout model causes increased plasma catecholamine levels and hypertension. Plasma blood urea nitrogen, creatinine, and aldosterone were unaffected. However, knockout mice had normal systolic function and mild ventricular hypertrophy but tolerated cardiac ischemia poorly and developed myocardial necrosis threefold more severe than that found in wild-type mice. Treatment with recombinant renalase completely rescued the cardiac phenotype. To gain insight into the mechanisms mediating this cardioprotective effect, we tested if gene deletion affected nitrate and glutathione metabolism, but found no differences between hearts of knockout and wild-type mice. The ratio of oxidized (NAD) to reduced (NADH) nicotinamide adenine dinucleotide in cardiac tissue, however, was significantly decreased in the hearts of renalase knockout mice, as was plasma NADH oxidase activity. In vitro studies confirmed that renalase metabolizes NADH and catecholamines. Thus, renalase plays an important role in cardiovascular pathology and its replacement may reduce cardiac complications in renalase-deficient states such as CKD.

Endovascular treatment of thrombosed dialysis fistulae: a cumulative cost analysis.

OBJECTIVES: In the present study, we determined the cumulative costs and outcomes of endovascular treatment of thrombosed autogenous arteriovenous fistulae (AVF) at our medical center. BACKGROUND: Previous studies examining the salvage procedures of thrombosed AVFs have focused exclusively on clinical outcomes, and, in the absence of costing data, current guidelines do not take into consideration economic issues. METHODS: A retrospective cohort study was performed among local hemodialysis patients with completely thrombosed AVFs receiving endovascular treatment in our institution between January 1 and December 31, 2008. Forty-four patients were enrolled and followed-up for 1 year. Success and complications were recorded according to consensus definitions, and a comprehensive measurement of total vascular access care-related costs was obtained. Costs are reported in 2010 in U.S. dollars. RESULTS: Clinical success was achieved in 95% of cases. The primary and secondary patency rates were 63 and 78% at 1 year, respectively. Primary patency rate at 12 months was significantly better for radiocephalic AVFs (70% vs. 43%; P = 0.047). The mean cumulative cost of all vascular access care during year 1 was $2,504 (median $1,484; range, $1,362-$18,279; Table V) per patient-year at risk. The mean cumulative cost for maintaining radiocephalic and brachiocephalic AVFs was $1,624 (median $1,381; range, $1,130-$3,116) and $3,578 (median $2,092; range, $1,470-$18,279) per patient-year at risk, respectively (P = 0.022). CONCLUSION: The cost of maintenance of a thrombosed AVF by endovascular intervention is high, with patients with clotted radiocephalic fistulae incurring the lowest costs and achieving higher survival times.

Conversion from sirolimus to everolimus in kidney transplant recipients receiving a calcineurin-free regimen.

BACKGROUND: Everolimus (EVL) and sirolimus (SRL) were introduced into immunosuppressive regimens, in an attempt to replace or reduce the dose of the nephrotoxic calcineurin inhibitors (CNI). In our institution, due to an administrative decision, conversion from SRL to EVL, was carried out, providing us the opportunity to investigate the effectiveness and safety profile of both drugs and to review the practical conversion dose between them. METHODS: We retrospectively analyzed the medical records of 51 maintenance kidney transplant recipients receiving an SRL-based CNI-free regimen, who were switched to EVL. SRL dose was concentration controlled to a through level of 4-8 ng/mL. Patients were converted to a variable dose of EVL that was adjusted to achieve a trough concentration of 3-8 ng/mL. RESULTS: SRL mean dose at time of conversion was 2.0 ± 0.9 mg/d. Initial EVL mean dose was 1.3 ± 0.5 mg/d. Six months after conversion, mean EVL trough level was 6.2 ± 2.8 ng/mL. EVL dose at this point was 2.0 ± 0.9 mg/d, which was not statistically different from SRL dose at the time of conversion (p = 0.575), suggesting a conversion factor of 1:1. During this six month period post conversion, no significant changes were observed in serum creatinine, hematocrit level, platelet count, proteinuria or lipid levels. No patient experienced an acute rejection episode. CONCLUSIONS: Conversion from SRL to EVL in renal transplant recipients receiving a CNI-free immunosuppressive regimen can be performed safely with a low trough level range of EVL. We report for the first time a conversion factor between SRL and EVL.

Circulating Renalase as Predictor of Renal and Cardiovascular Outcomes in Pre-Dialysis CKD Patients: A 5-Year Prospective Cohort Study.

Chronic kidney disease (CKD) is an independent risk factor for adverse cardiovascular and cerebrovascular events (MACCEs), and mortality since the earlier stages. Therefore, it is critical to identify the link between CKD and cardiovascular risk (CVR) through early and reliable biomarkers. Acknowledging that CKD and CKD progression are associated with increased sympathetic tone, which is implicated in CVR, and that renalase metabolizes catecholamines, we aimed to evaluate the relationship between renalase serum levels (RNLS) and cardiovascular and renal outcomes. The study included 40 pre-dialysis CKD patients (19F:21M) with median age of 61 (IQ 45-66) years. At baseline, we measured RNLS as well as routine biomarkers of renal and cardiovascular risk. A prospective analysis was performed to determine whether RNLS are associated with CKD progression, MACCEs, hospitalizations and all-cause mortality. At baseline, the median level of RNLS and median estimated glomerular filtration rate (eGFR) were 63.5 (IQ 48.4-82.7) µg/mL and 47 (IQ 13-119) mL/min/1.73 m2, respectively. In univariate analysis, RNLS were strongly associated with eGFR, age and Charlson Index. Over the course of a mean follow-up of 65 (47 to 70) months, 3 (7.5%) deaths, 2 (5%) fatal MACCEs, 17 (42.5%) hospital admissions occurred, and 16 (40%) patients experienced CKD progression. In univariate analysis, RNLS were associated with CKD progression (p = 0.001), hospitalizations (p = 0.001) and all-cause mortality (p = 0.022) but not with MACCEs (p = 0.094). In adjusted analysis, RNLS predicted CKD progression and hospitalizations regardless of age, Charlson comorbidity index, cardiovascular disease, hypertension, diabetes and dyslipidemia. Our results suggest that RNLS, closely related with renal function, might have a potential role as predictor of renal outcomes, hospitalizations, and mortality in pre-dialysis CKD patients.