Peritoneal Microbiome in End-Stage Renal Disease Patients and the Impact of Peritoneal Dialysis Therapy.

Factors influencing the occurrence of peritoneal dialysis (PD)-related infections are still far from fully understood. Recent studies described the existence of specific microbiomes in body sites previously considered microbiome-free, unravelling new microbial pathways in the human body. In the present study, we analyzed the peritoneum of end-stage kidney disease (ESKD) patients to determine if they harbored a specific microbiome and if it is altered in patients on PD therapy. We conducted a cross-sectional study where the peritoneal microbiomes from ESKD patients with intact peritoneal cavities (ESKD non-PD, n = 11) and ESKD patients undergoing PD therapy (ESKD PD, n = 9) were analyzed with a 16S rRNA approach. Peritoneal tissue of ESKD patients contained characteristically low-abundance microbiomes dominated by Proteobacteria, Firmicutes, Actinobacteria, and Bacteroidetes. Patients undergoing PD therapy presented lower species richness, with dominance by the Pseudomonadaceae and Prevotelaceae families. This study provides the first characterization of the peritoneal microbiome in ESKD patients, bringing new insight to the human microbiome. Additionally, PD therapy may induce changes in this unique microbiome. The clinical relevance of these observations should be further explored to uncover the role of the peritoneal microbiome as a key element in the onset or aggravation of infection in ESKD patients, especially those undergoing PD.

Influence of dialysis therapies on oral health: a pilot study.

OBJECTIVES: Chronic kidney disease (CKD) is a public health problem worldwide. Currently, the link between oral health status, dialysis modality, and dialysis vintage is still not clear. The aim of this study was to evaluate periodontal disease, dental caries, and Candida colonization among patients under hemodialysis (HD) therapy, peritoneal dialysis (PD) therapy, and PD with previous history of HD (HD/PD). METHOD AND MATERIALS: The clinical history, smoking, and oral hygiene habits were recorded. Decayed, missing, or filled teeth (DMFT) index, Visible Plaque Index (VPI), clinical attachment level (CAL), bleeding on probing, saliva flow rate, saliva pH, and oral yeast colonization were assessed. RESULTS: HD/PD patients were generally submitted to longer periods of dialysis therapy than the other groups. The number of decayed and filled teeth did not differ between groups; HD patients presented a higher number of teeth, but poor periodontal status. Among the three groups, HD patients presented higher VPI, CAL, and oral Candida colonization, independently of the time under dialysis therapy. Candida albicans (HD and PD), Candida krusei (HD), and Candida carpophila (PD) were isolated in these patients. CONCLUSION: HD presented a more adverse impact on oral health than PD, particularly periodontal disease and oral Candida colonization; however, this impact on oral health appears to be reduced or ameliorated when patients change from HD to PD therapy.

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.

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 yeast colonization throughout pregnancy

BACKGROUND: Recent studies suggest that placenta may harbour a unique microbiome that may have origin in maternal oral microbiome. Although the major physiological and hormonal adjustments observed in pregnant women lead to biochemical and microbiological modifications of the oral environment, very few studies evaluated the changes suffered by the oral microbiota throughout pregnancy. So, the aim of our study was to evaluate oral yeast colonization throughout pregnancy and to compare it with non-pregnant women. MATERIAL AND METHODS: The oral yeast colonization was assessed in saliva of 30 pregnant and non-pregnant women longitudinally over a 6-months period. Demographic information was collected, a non-invasive intra-oral examination was performed and saliva flow and pH were determined. RESULTS: Pregnant and non-pregnant groups were similar regarding age and level of education. Saliva flow rate did not differ, but saliva pH was lower in pregnant than in non-pregnant women. Oral yeast prevalence was higher in pregnant than in non-pregnant women, either in the first or in the third trimester, but did not attain statistical significance. In individuals colonized with yeast, the total yeast quantification (Log10CFU/mL) increase from the 1st to the 3rd trimester in pregnant women, but not in non-pregnant women. CONCLUSIONS: Pregnancy may favour oral yeast growth that may be associated with an acidic oral environment

Phase Angle Predicts Arterial Stiffness and Vascular Calcification in Peritoneal Dialysis Patients.

OBJECTIVES: Fluid overload (FO) is frequently present in peritoneal dialysis (PD) patients and is associated with markers of malnutrition, inflammation, and atherosclerosis/calcification (MIAC) syndrome. We examined the relationships in stable PD patients between phase angle (PhA) and the spectrum of uremic vasculopathy including vascular calcification and arterial stiffness and between PhA and changes in serum fetuin-A levels. METHODS: Sixty-one stable adult PD patients were evaluated in a cross-sectional study (ST1). Phase angle was measured by multifrequency bioimpedance analysis (InbodyS10, Biospace, Korea) at 50 kHz. Augmentation index (AI), a surrogate marker of arterial stiffness, was assessed by digital pulse amplitude tonometry (Endo PAT, Itamar Medical, Caesarea, Israel). Vascular calcification was assessed by simplified calcification score (SCS). Serum fetuin-A levels were measured by ELISA (Thermo scientific; Waltham, MA, USA). Serum albumin was used as a nutritional marker, and serum C-reactive protein (CRP) was used as an inflammatory marker. The same assessments were carried out longitudinally (ST2) in the first 33 patients who completed 1 year of evaluation in ST1. RESULTS: In ST1, patients with PhA < 6° had higher CRP levels, AI, and SCS and lower serum albumin and fetuin-A levels, in comparison with patients with PhA ≥ 6°. In addition, PhA was a predictor of both AI (ß = -0.351, p = 0.023) and SCS ≥ 3 (EXP (B) = 0.243, p = 0.005). In ST2, the increase of PhA over time was associated with decreases in both AI (r = -0.378, p = 0.042) and CRP levels (r = -0.426, p = 0.021), as well as with the increase in serum fetuin-A levels (r = 0.411, p = 0.030). CONCLUSIONS: Phase angle predicts both arterial stiffness and vascular calcification in stable PD patients.

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.

Asymptomatic Effluent Protozoa Colonization in Peritoneal Dialysis Patients.

Currently, chronic kidney disease (CKD) is a global health problem. Considering the impaired immunity of CKD patients, the relevance of infection in peritoneal dialysis (PD), and the increased prevalence of parasites in CKD patients, protozoa colonization was evaluated in PD effluent from CKD patients undergoing PD. Overnight PD effluent was obtained from 49 asymptomatic stable PD patients. Protozoa analysis was performed microscopically by searching cysts and trophozoites in direct wet mount of PD effluent and after staining smears. Protozoa were found in PD effluent of 10.2% of evaluated PD patients, namely Blastocystis hominis, in 2 patients, and Entamoeba sp., Giardia sp., and Endolimax nana in the other 3 patients, respectively. None of these patients presented clinical signs or symptoms of peritonitis at the time of protozoa screening. Our results demonstrate that PD effluent may be susceptible to asymptomatic protozoa colonization. The clinical impact of this finding should be further investigated.

Low prevalence of oral protozoa colonization in Portuguese healthy and end-stage renal disease patients undergoing peritoneal dialysis / Baja prevalencia de la colonización oral de protozoos en Portugueses saludables y o pacientes renales del último estadio de enfermedad y que necesitan de diálisis del peritoneo

Infections are a major complication in end-stage renal disease (ESRD) patients undergoing peritoneal dialysis (PD). Because the oral cavity may act as a source of systemic pathogens, some authors advocated specific measures when these patients are submitted to oral interventions, such as the administration of prophylactic antibiotics. Oral protozoa colonization may vary significantly with geographic distribution and to our knowledge no studies were performed in Portugal. The aim of the present study was to evaluate protozoa colonization in the saliva of ESRD patients undergoing PD and of their family members, living in the north of Portugal. Saliva was collected from 39 PD patients with a mean time on PD therapy of 12.7 - 15.9 months, and from 18 healthy volunteers (ESRD family members) for microscopic evaluation of protozoa by Lugols’ direct smear and specific staining techniques (Giemsa, Trichrome and Kinyoun). After the analysis of 456 smears obtained from 57 participants, only one PD patient (2.6%) presented an amoeba trophozoite in saliva. In conclusion, very low oral protozoa colonization was found, both on PD patients and family controls, suggesting that the oral protozoa colonization of Portuguese population is low and not significantly modified by the presence of end-stage chronic kidney disease. Further studies are required to address this issue.

Las infecciones son la principal complicación en pacientes renales del último estadio (ESRD) y que necesitan de diálisis del peritoneo (PD). Como la cavidad oral puede funcionar como una fuente de patógenos sistémicos, algunos autores indican medidas específicas cuando esos pacientes son sometidos a intervenciones orales, como la administración de antibióticos profilácticos. La colonización oral puede variar significativamente con la distribución geográfica. Según nuestros conocimientos, no han sido realizados estudios similares en Portugal. El principal objetivo fue evaluar la colonización de protozoos en saliva de pacientes ESRD del Norte de Portugal que hacían PD y, también, de sus familiares. Muestras de saliva fueron recogidas de 39 pacientes PD, con tiempo medio de terapia de PD de 12,7-15,9 meses y, también de 18 voluntarios saludables (familiares de ESRD). Las mismas utilizadas para evaluación microscópica de protozoos en laminas con lugol y tinciones especificas (Giemsa, Trichrome and Kinyoun). Después del análisis de 456 laminas, obtenidas de los 57 participantes, solamente en un paciente PD (2.6%) se observó un trofozoíto del ameba. En conclusión, se encontró una baja prevalencia de colonización oral de protozoos en el grupo estudiado. Así, la colonización oral de la población Portuguesa por protozoos es baja y no se cambia con la evolución de la enfermedad. Para mejor analizar esta situación, futuros estudios son necesarios.

Evolution of bone disease after kidney transplantation: A prospective histomorphometric analysis of trabecular and cortical bone.

AIM: Post-transplant bone disease results from multiple factors, including previous bone and mineral metabolism disturbances and effects from transplant-related medications. Bone biopsy remains the gold-standard diagnostic tool. METHODS: We aimed to prospectively evaluate trabecular and cortical bone by histomorphometry after kidney transplantation. Seven patients, willing to perform follow-up bone biopsy, were included in the study. Dual-X-ray absorptiometry and trans-iliac bone biopsy were performed within the first 2 months after renal transplantation and repeated after 2-5 years of follow-up. RESULTS: Follow-up biopsy revealed a significant decrease in osteoblast surface/bone surface (0.91 ± 0.81 to 0.47 ± 0.12%, P = 0.036), osteoblasts number/bone surface (0.45 (0.23, 0.94) to 0.00/mm(2) , P = 0.018) and erosion surface/bone surface (3.75 ± 2.02 to 2.22 ± 1.38%, P = 0.044). A decrease in trabecular number (3.55 (1.81, 2.89) to 1.55/mm (1.24, 2.06), P = 0.018) and increase in trabecular separation (351.65 ± 135.04 to 541.79 ± 151.91 µm, P = 0.024) in follow-up biopsy suggest loss in bone quantity. We found no significant differences in cortical analysis, except a reduction in external cortical osteonal eroded surface (5.76 (2.94, 13.97) to 3.29% (0.00, 6.67), P = 0.043). Correlations between bone histomorphometric and dual-X-ray absorptiometry parameters gave inconsistent results. CONCLUSIONS: The results show a reduction in bone activity, suggesting increased risk of adynamic bone and loss of bone volume. Cortical bone seems less affected by post-transplant biological changes in the first years after kidney transplantation.

The biochemistry of saliva throughout pregnancy / O efeito da gravidez sobre a bioquímica salivar

BACKGROUND & OBJECTIVE: Sialometric and sialochemical analyses during pregnancy are not consistent, and frequently contradictory in terms of salivary flow rate, pH, and concentration of calcium, phosphorous, sodium, potassium, chloride, glucose and α-amylase. We, therefore, measured the evolution of these parameters throughout pregnancy. METHOD: A cross-sectional study compared sialometric and sialochemical analyses of 30 pregnant women vs. 30 age-matched non-pregnant women, and a longitudinal study evaluated the pregnant women in the first and third trimester of pregnancy. RESULTS: Pregnant women presented acidic non-stimulated saliva, but neutral stimulated saliva pH, and no relevant changes in salivary flow rate. Scialochemical analysis showed decreased calcium levels, increased phosphate levels, and a progressive decrease in glucose levels throughout pregnancy. CONCLUSION: Pregnancy significantly changes the oral biochemical milieu, creating a favorable environment for the development of oral pathology, in particular, dental caries.

OBJETIVO: Os achados relativos às análises sialométricas e sialoquímicas durante a gravidez não são consistentes, e por vezes são mesmo contraditórias. Assim, fizemos uma revisão da literatura e comparamos os níveis salivares de cálcio, fósforo, sódio, potássio, cloreto, glucose, α-amilase, pH e a taxa de fluxo salivar entre mulheres grávidas e não grávidas, bem como, avaliamos a evolução desses parâmetros ao longo da gravidez. MÉTODO: Realizamos um estudo transversal comparando a bioquímica salivar de um grupo inicial de 30 mulheres grávidas com um grupo inicial de 30 mulheres não gestantes da mesma idade seguido de um estudo longitudinal avaliando as mulheres grávidas no primeiro e terceiro trimestre de gravidez. RESULTADO: As mulheres grávidas apresentaram um pH da saliva não estimulada ácido, mas um pH da saliva estimulada neutro, assim como diminuição dos níveis salivares de cálcio, aumento dos níveis salivares de fosfato, e uma diminuição progressiva nos níveis de glicose na saliva ao longo da gravidez. CONCLUSÃO: A gravidez muda significativamente o ambiente bioquímico oral, criando condições favoráveis para o desenvolvimento de patologia oral, em particular da cárie dentária.

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.

Plasma and urine renalase levels and activity during the recovery of renal function in kidney transplant recipients.

Renalase is a recently described enzyme secreted by the kidney into both plasma and urine, where it was suggested to degrade catecholamines contributing to blood pressure control. While there is a controversy regarding the relationship between renal function and plasma renalase levels, there is virtually no data in humans on plasma renalase activity as well as on both urine renalase levels and activity. We prospectively examined the time course of plasma and urine renalase levels and activity in 26 end-stage renal disease (ESRD) patients receiving a cadaver kidney transplant (cadaver kidney recipients [CKR]) before surgery and during the recovery of renal function up to day 90 post transplant. The relationship with sympathetic and renal dopaminergic activities was also evaluated. The recovery of renal function in CKR closely predicted decreases in plasma renalase levels (r = 0.88; P < 0.0001), urine renalase levels (r = 0.75; P < 0.0001) and urine renalase activity (r = 0.56; P < 0.03), but did not predict changes in plasma renalase activity (r = -0.02; NS). Plasma norepinephrine levels positively correlated with plasma renalase levels (r = 0.64, P < 0.002) as well as with urine renalase levels and activity (r = 0.47 P < 0.02; r = 0.71, P < 0.0005, respectively) and negatively correlated with plasma renalase activity (r = -0.57, P < 0.002). By contrast, plasma epinephrine levels positively correlated with plasma renalase activity (r = 0.67, P < 0.0001) and negatively correlated with plasma renalase levels (r = -0.62, P < 0.003). A significant negative relationship was observed between urine dopamine output and urine renalase levels (r = -0.48; P < 0.03) but not with urine renalase activity (r = -0.33, NS). We conclude that plasma and urine renalase levels closely depend on renal function and sympathetic nervous system activity. It is suggested that epinephrine-mediated activation of circulating renalase may occur in renal transplant recipients with good recovery of renal function. The increase in plasma renalase activity observed in ESRD patients and renal transplant recipients can be explained on the basis of reduced inhibition of the circulating enzyme.

Concerted action of ANP and dopamine D1-receptor to regulate sodium homeostasis in nephrotic syndrome.

The edema formation in nephrotic syndrome (NS) is associated with a blunted response to atrial natriuretic peptide (ANP). The natriuretic effects of ANP have been related to renal dopamine D1-receptors (D1R). We examined the interaction between ANP and renal D1R in rats with puromycin aminonucleoside-induced NS (PAN-NS). Urinary sodium, cyclic guanosine monophosphate (cGMP) excretion, and D1R protein expression and localization in renal tubules were evaluated in PAN-NS and control rats before and during volume expansion (VE). The effects of zaprinast (phosphodiesterase type 5 inhibitor), alone or in combination with Sch-23390 (D1R antagonist), were examined in both groups. The increased natriuresis and urinary cGMP excretion evoked by acute VE were blunted in PAN-NS despite increased levels of circulating ANP. This was accompanied in PAN-NS by a marked decrease of D1R expression in the renal tubules. Infusion of zaprinast in PAN-NS resulted in increased urinary excretion of cGMP and sodium to similar levels of control rats and increased expression of D1R in the plasma membrane of renal tubular cells. Combined administration of Sch-23390 and zaprinast prevented natriuresis and increased cGMP excretion induced by zaprinast alone. We conclude that D1R may play a major role in the ANP resistance observed in PAN-NS.

Intestinal and renal guanylin peptides system in hypertensive obese mice.

Guanylin (GN), uroguanylin (UGN) and the GC-C receptor have been associated with two endocrine axes: the salt and water homeostasis regulating enterorenal axis and the recently described appetite-regulating UGN/GC-C extraintestinal axis. The present work assessed the mRNA expression levels of GN peptides system (GPS) in a model of diet-induced obesity. Male C57BL/6J mice were submitted to either a high-fat high-simple carbohydrate diet (obese) or a normal diet (control). The renal and intestinal GN, UGN and GC-C receptor mRNA expression were evaluated by reverse transcriptase quantitative polymerase chain reaction in both groups, during normo-saline (NS) and high-saline (HS) diet. The diet-induced obesity was accompanied by glucose intolerance and insulin resistance as well as by a significant increase in blood pressure. During NS diet, obese mice presented reduced mRNA expression of GN in ileum and colon, UGN in duodenum, ileum and colon and GC-C in duodenum, jejunum, ileum and colon. This was accompanied by increased UGN mRNA expression in renal cortex. During HS diet, obese mice presented reduced mRNA expression of GN in jejunum as well as reduced mRNA expression of UGN and GC-C in duodenum, jejunum and colon. The data obtained suggest that, in a mouse model of diet-induced obesity, a down-regulation of intestinal mRNA expression of GN, UGN and its GC-C receptor is accompanied by a compensatory increase of renal UGN mRNA expression. We hypothesize that the decrease in gene expression levels of intestinal GPS may contribute to the development of hypertension and obesity during hypercaloric diet intake.

Sodium-dependent modulation of systemic and urinary renalase expression and activity in the rat remnant kidney.

OBJECTIVE: The present study examined the influence of high-sodium intake on systemic and urinary renalase levels and activity in 3/4 nephrectomized (3/4nx) and Sham rats. RESULTS: The reduced circulating renalase levels in 3/4nx rats during normal-sodium intake were accompanied by increased plasma renalase activity. The sodium-induced increase of blood pressure in 3/4nx rats was accompanied by significant decreases in circulating renalase levels and activity as well as by a significant decrease in cardiac renalase levels in 3/4nx rats but not in Sham rats. During normal-sodium intake, no significant differences were observed in either urine renalase levels or activity between 3/4nx and Sham rats, not withstanding the ∼75% decrease in daily urine dopamine output observed in the rat remnant kidney. During high-sodium intake, urinary renalase levels increased in both 3/4nx and Sham groups by three-fold whereas urinary renalase activity increased in 3/4nx and Sham rats by greater than twelve-fold and greater than four-fold, respectively. This was accompanied by sodium-induced increases in daily urinary dopamine output in both 3/4nx and Sham rats by ∼2.3-fold and ∼1.6-fold, respectively. CONCLUSION: The reduced circulating renalase levels in 3/4nx rats are accompanied by increased plasma renalase activity, which appears to be related with decreased inhibition of the circulating enzyme. Differences in systemic and urinary renalase levels and activity between 3/4nx and Sham rats during high-sodium intake may contribute to activation of the sympathetic nervous system, hypertension and enhanced cardiovascular risk in CKD but do not appear to account for the decrease in renal dopaminergic activity in the rat remnant kidney.