Histology and Immunohistochemistry of Radial Arteries Are Suggestive of an Interaction between Calcification and Early Atherosclerotic Lesions in Chronic Kidney Disease.

Background and Objectives: recent studies suggest an implication of immune mechanisms in atherosclerotic disease. In this paper, the interaction between inflammation, calcification, and atherosclerosis on the vessel walls of patients with chronic kidney disease (CKD) is described and evaluated. Materials and Methods: patients with stage V CKD, either on pre-dialysis (group A) or on hemodialysis (HD) for at least 2 years (group B), in whom a radiocephalic arteriovenous fistula (RCAVF) was created, were included in the study. The control group included healthy volunteers who received radial artery surgery after an accident. The expressions of inflammatory cells, myofibroblasts, and vascular calcification regulators on the vascular wall were estimated, and, moreover, morphometric analysis was performed. Results: the expressions of CD68(+) cells, matrix carboxyglutamic acid proteins (MGPs), the receptor activator of nuclear factor-kB (RANK) and RANK ligand (RANKL), and osteoprotegerin (OPG), were significantly increased in CKD patients compared to the controls p = 0.02; p = 0.006; p = 0.01; and p = 0.006, respectively. In morphometric analysis, the I/M and L/I ratios had significant differences between CKD patients and the controls 0.3534 ± 0.20 vs. 0.1520 ± 0.865, p = 0.003, and 2.1709 ± 1.568 vs. 4.9958 ± 3.2975, p = 0.03, respectively. The independent variables correlated with the degree of vascular calcification were the intensity of CD34(+), aSMA(+) cells, and OPG, R2 = 0.76, p < 0.0001, and, with intima-media thickness (IMT), the severity of RANKL expression R2 = 0.3, p < 0.0001. Conclusion: atherosclerosis and vascular calcification in CKD seem to be strongly regulated by an immunological and inflammatory activation on the vascular wall.

Fibroblast Growth Factor 23 and α-Klotho Protein Are Associated with Adverse Clinical Outcomes in Non-Dialysis CKD Patients.

BACKGROUND: Fibroblast growth factor 23 (FGF-23) and α-Klotho protein appear to have an important role in the pathogenesis of CKD-mineral and bone disorders. The aim of this study was to investigate the association of FGF-23 and α-Klotho levels with adverse clinical outcomes in patients with non-dialysis CKD. MATERIALS AND METHODS: We conducted a prospective cohort study, enrolling participants with non-dialysis CKD from a single center in Greece. At enrollment, glomerular filtration rate (GFR) was measured (mGFR) and plasma levels of carboxyl terminal FGF-23 (cFGF-23) and soluble α-Klotho (sKlotho) were determined by enzyme-linked immunoassay. Participants were followed for up to 5 years or until the occurrence of the primary endpoint of initiation of renal replacement therapy or death. Multivariate regression tree analysis was used to identify informative baseline parameters in order to categorize participants. Also, using median values of cFGF-23 and sKlotho, participants were categorized into 4 groups, in whom survival was compared using Kaplan-Meier and Cox regression analysis. RESULTS: 128 participants were enrolled with a median mGFR of 41.5 mL/min/1.73 m2 (IQR = 28.2). Baseline mGFR correlated with cFGF-23 and sKlotho (r = -0.54 and r = 0.49, respectively; p < 0.0001 for both). cFGF-23 and sKlotho levels correlated negatively (r = -0.24, p = 0.006). Multivariate regression tree analysis resulted in 3 groups defined by cutoff values of mGFR (60.9 mL/min/1.73 m2) and phosphate (3.7 mg/dL). These groups correlated with CKD stage, cFGF-23, and sKlotho (p < 0.0001 for all). During a median follow-up of 36 months (IQR = 22), 40 (31.2%) participants reached the primary endpoint (31 initiated renal replacement therapy, 9 died). Survival to primary endpoint differed among the 4 groups formed using median values of both biomarkers, with the low FGF-23/high Klotho and high FGF-23/low Klotho having the longest and shortest survival, respectively. High FGF-23/low Klotho group, compared to the opposite one, had a significantly elevated risk of the primary outcome (HR, 6.8; 95% CI, 2.3-19.6; p = 0.0004). CONCLUSIONS: In patients with CKD stages 1-5, the combination of higher cFGF-23 and lower sKlotho levels along with mGFR and serum phosphate was associated with adverse clinical outcomes. The utility of combinations of traditional and novel biomarkers to predict outcomes warrants further study.

The effect of dry-weight reduction guided by lung ultrasound on ambulatory blood pressure in hemodialysis patients: a randomized controlled trial.

Approximately 85% of hemodialysis patients are hypertensive, but less than 30% achieve adequate blood pressure (BP) control. Reduction of volume overload is fundamental for BP control, but clinical criteria to estimate dry-weight are inaccurate. In the present study we examined the effect of dry-weight reduction with a lung-ultrasound-guided strategy on ambulatory BP in 71 clinically euvolemic hemodialysis patients with hypertension. Patients were equally randomized into an active group, following a strategy for dry-weight reduction guided by pre-hemodialysis lung ultrasound, and a control group with standard-of-care treatment. All patients underwent 48-hour ambulatory BP monitoring (ABPM) at baseline and after eight weeks. Overall, more patients in the active than in the control group had dry weight reduction, 54.3% compared to 13.9%, respectively. The ultrasonographic-B line change during follow-up was significantly different (-5.3±12.5 in active versus +2.2±7.6 in control group), which corresponded to significant differences in dry weight changes between the groups. The magnitude of reductions in 48-hour systolic BP (-6.61±9.57 vs. -0.67±13.07) and diastolic BP (-3.85±6.34 vs. -0.55±8.28) was significantly greater in the active group. Similarly, intradialytic BP, 44-hour BP, and daytime or night-time systolic/diastolic BP during both days of the interdialytic interval were significantly reduced in the active group but remained unchanged in the control group. The percentage of patients experiencing one or more intradialytic hypotensive episodes was marginally lower in the active group (34.3% vs. 55.6%). Thus, a lung-ultrasound-guided strategy for dry-weight reduction can effectively and safely reduce ambulatory BP levels in hemodialysis patients. Clinical implementation of this simple technique can help increase BP control in this population.

A nephrology trainee can define the fluid status through lung ultrasonography and inferior vena cava measurements in hemodialysis patients: an observational study in a single center.

AIMS: The determination of ideal weight in hemodialysis patients remains a common problem. The use of Lung Ultrasound (LUS) is an emerging method of assessing the hydric status of hemodialysis patients. LUS combined with Inferior Vena Cava (IVC) ultrasonography can define the fluid status in hemodialysis patients. METHODS: This study included 68 hemodialysis patients from the Dialysis Unit of Papageorgiou General Hospital in Thessaloniki. The patients underwent lung and IVC ultrasound 30 min before and after the end of the dialysis session by a nephrology trainee. Patients' ideal weight was modified based on daily clinical practice rather than ultrasound findings. The presence of B lines and ultrasound findings of the IVC were evaluated. RESULTS: The average B line score was 11.53 ± 5.02 before dialysis and became 5.57 ± 3.14 after the session. The average diameter of the IVC was 14.266 ± 0.846 mm before dialysis and 12.328 ± 0.879 mm after the session. The patients were categorized based on the magnitude of overhydration and the findings were evaluated. In addition, findings after the session showed a statistically significant correlation between the b line score and the diameter of the IVC adjusted for the body surface area. (p = 0.009 < 0.05). CONCLUSIONS: A high rate of hyperhydration was detected before the dialysis session (25%). While it is the first study conducted by a nephrology trainee highlighting that it is a feasible technique. Intervention studies should be carried out in the future to draw more precise conclusions.

Lung ultrasound-guided dry-weight reduction and echocardiographic changes in clinically euvolemic hypertensive hemodialysis patients: 12-month results of a randomized controlled trial.

OBJECTIVE: Left ventricular hypertrophy (LVH) and dysfunction are highly prevalent in hemodialysis patients and are independently associated with adverse outcomes. This study examines the long-term effects of dry-weight reduction with a standardized lung ultrasound (LUS)-guided strategy on echocardiographic indexes of left ventricular (LV) mass and function in hemodialysis patients. METHODS: Seventy-one clinically euvolemic hemodialysis patients with hypertension were randomized to dry-weight reduction guided by pre-hemodialysis LUS (n = 35) or standard-of-care treatment (n = 36) and were followed-up for 12 months. Two-dimensional and tissue-Doppler echocardiographies (TDI) were performed at the baseline and 12-month evaluations. RESULTS: During follow-up, dry-weight reduction took place in more patients in the active arm than in the control arm of the trial (71.4% vs 22.2%; p < 0.001). Left atrial (LA) surface (-1.37 ± 4.50 vs 1.28 ± 5.00 cm2; P = 0.006) and LA volume index (-3.22 ± 11.82 vs 4.76 ± 12.83 ml/m2; P = 0.009) decreased in the active and increased in the control group. LV end-diastolic volume (-0.94 ± 11.45 vs 6.58 ± 13.92 ml/m2; P = 0.015) decreased only in the active group. The LV mass index was unchanged in the active (134.21 ± 44.75 vs 133.57 ± 45.51; P = 0.844) and marginally increased in the control group (134.21 ± 40.96 vs 143.77 ± 50.04 g/m2; P = 0.089). The LV E/e' wave ratio was unchanged in the active (12.45 ± 4.69 vs 12.56 ± 4.89; P = 0.521) and increased in the usual-care group (10.91 ± 4.97 vs12.36 ± 6.43; P = 0.003). LV systolic function did not differ between the two study arms across the trial. CONCLUSION: Over 12 months, LUS-guided dry-weight reduction is associated with reverse LV and LA remodeling, myocardial hypertrophy regression, and improved LV diastolic filling properties.

Novel and Founder Pathogenic Variants in X-Linked Alport Syndrome Families in Greece.

Alport syndrome (AS) is the most frequent monogenic inherited glomerulopathy and is also genetically and clinically heterogeneous. It is caused by semi-dominant pathogenic variants in the X-linked COL4A5 (NM_000495.5) gene or recessive variants in the COL4A3/COL4A4 (NM_000091.4/NM_000092.4) genes. The disease manifests in early childhood with persistent microhematuria and can progress to proteinuria and kidney failure in adolescence or early adulthood if left untreated. On biopsy, pathognomonic features include alternate thinning, thickening and lamellation of the glomerular basement membrane (GBM), in the presence of podocyte foot process effacement. Although previous studies indicate a prevalence of AS of about 1/50,000, a recent publication reported a predicted rate of pathogenic COL4A5 variants of 1/2320. We herewith present 98 patients (40 M/58 F) from 26 Greek families. We are selectively presenting the families segregating the X-linked form of AS with pathogenic variants in the COL4A5 gene. We found 21 different pathogenic variants, 12 novel: eight glycine and one proline substitutions in the collagenous domain, one cysteine substitution in the NC1 domain, two premature termination of translation codons, three splicing variants, one 5-bp insertion/frameshift variant, one indel-frameshift variant and four gross deletions. Notably, patients in six families we describe here and three families we reported previously, carried the COL4A5-p.G624D substitution, a founder defect encountered all over Europe which is hypomorphic with mostly milder symptomatology. Importantly, on several occasions, the correct genetic diagnosis reclassified patients as patients with AS, leading to termination of previous immunosuppressive/cyclosporine A therapy and a switch to angiotensin converting enzyme inhibitors (ACEi). With the understanding that all 98 patients span a wide range of ages from infancy to late adulthood, 15 patients (11 M/4 F) reached kidney failure and 11 (10 M/1 F) received a transplant. The prospects of avoiding lengthy diagnostic investigations and erroneous medications, and the advantage of delaying kidney failure with very early administration of renin-angiotensin-aldosterone system (RAAS) blockade, highlights the importance of timely documentation of AS by genetic diagnosis.

Impact of C-reactive protein on absolute reticulocyte count in haemodialysis patients: the role of iron status.

BACKGROUND: The exact mechanisms by which the effects of inflammation on erythropoiesis occur are still to be determined. We aimed to examine the relation between C-reactive protein (CRP) and erythropoiesis as quantified by the absolute reticulocyte count (RTC) and the possible effect of iron status on this relationship. METHODS: As part of a study that follows the changes of haematologic parameters after the intravenous (IV) administration of iron in 93 stable haemodialysis (HD) patients, we made a cross-sectional analysis of baseline measurements and an analysis of changes in RTC 1 week after baseline measurements and iron administration. RESULTS: Multiple linear regression analysis revealed that RTC had a positive correlation with CRP; RTC had a negative correlation with reticulocyte haemoglobin content (CHr). An interaction was also found between CRP and CHr in that CRP had a significant relation to RTC only in those patients whose CHr was more than 31.2 pg. At lower values of CHr, the correlation between CRP and RTC was not significant. Five days after the IV administration of 200 mg iron sucrose, a significant increase of RTC was observed, only in those patients with elevated baseline CRP levels who also showed an increase in CHr levels from ≤ 31.2 pg at baseline to ≥ 31.2 pg post-administration, supporting the presence of an independent positive correlation between CRP and RTC when iron is adequate. CONCLUSIONS: It is indicated that, in HD patients, elevated CRP values are associated with increased erythroid production only when CHr is quite satisfactory.

Effect of cyclosporine therapy with low doses of corticosteroids on idiopathic nephrotic syndrome.

Cyclosporine (CyA) has an immunosuppressive effect that might suggest a therapeutic role in idiopathic glomerular conditions. We focused on the optimization of CyA treatment control in patients with idiopathic nephrotic syndrome by using trough-level CyA measurements (C0) and the 2-h postdose levels (C2). Twenty-two patients (14 male, 8 female) with idiopathic nephrotic syndrome and the mean age of 51 +/- 18 months (mean [M] +/- standard deviation [SD]) were enrolled in our study during a period of 10 months (range: 3-18 months). All of the patients received CyA (2-3 mg/kg) in combination with methylprednisolone. In the present study protocol CyA concentrations (C0, C2), renal function, lipid profile, and degree of proteinuria were determined. The mean proteinuria of our patients before treatment was 11 972 +/- 7953 mg/24 H (+/-SD) and the mean creatinine level (Cr) was 0.99 +/- 0.37 mg/dL (+/-SD). Proteinuria decreased significantly already from the first month of therapy with CyA to 3578 +/- 2470 mg/24 H (M+/- SD), and during the whole study period this reduction was significant (0.56 +/- 0.37 gr/24 H (M +/- SD), P < 0.05). At the same time renal function preserved, 1.09 +/- 0.48 mg/dL (M +/- SD). The blood levels of C0 were 135.10 +/- 97.36 ng/mL (M +/- SD) and the blood levels of C2 were 725 +/- 256 ng/mL (M +/- SD) at the first month of therapy. At the same time renal function preserved, 1.09 +/- 0.48 mg/dL (M +/- SD). Total cholesterol levels reduced significantly during study period (276.89 +/- 45.57 to 200.67 +/- 40.27 mg/dL [M +/- SD]). The mean number of antihypertensive medication remained the same. The whole therapeutic protocol did not provoke any kind of side effects and CyA was quite tolerated by our patients. Treatment of idiopathic nephrotic syndrome with low doses of CyA with methylprednisolone leads to remission of proteinuria without deterioration of renal function. Blood levels of C0 for monitoring and treatment of nephrotic syndrome agrees with recent literature, while our study focus on establishing the proper levels of C2 for the treatment of nephrotic syndrome. The efficacy of CyA is combined with safety and tolerance.

Ambulatory blood pressure profile and blood pressure variability in peritoneal dialysis compared with hemodialysis and chronic kidney disease patients.

Hypertension in end-stage renal disease patients is highly prevalent and poorly controlled. Data on the ambulatory blood pressure (BP) profile and BP variability (BPV) in peritoneal dialysis (PD) patients are absent. This study examined the BP profile and BPV of patients undergoing PD in comparison with hemodialysis (HD) and predialysis chronic kidney disease CKD patients. Thirty-eight PD patients were matched for age, sex, and dialysis vintage with 76 HD patients and for age and sex with 38 patients with CKD stage 2-4. Patients under PD or HD underwent 48-h and CKD patients 24-h ambulatory BP monitoring. BP levels and BPV indices were compared for the 48-h, first and second 24 h, daytime and nighttime periods. Two-way mixed ANOVA for repeated measurements was used to evaluate the effects of dialysis modality and time on ambulatory BP in PD and HD. During all periods studied, SBP and DBP were numerically higher but not significantly different in PD than in HD patients. Systolic BP was significantly higher in PD or HD than in predialysis CKD (PD: 138.38 ± 20.97 mmHg; HD: 133.75 ± 15.5 mmHg; CKD: 125.52 ± 13.4 mmHg, p = 0.003), a difference evident also during daytime and nighttime periods. Repeated-measurements ANOVA showed no effect of dialysis modality on ambulatory BP during any period studied. All BPV indices studied were similar between PD and HD patients, in whom they were higher than in CKD individuals (first 24-h systolic-ARV: PD: 11.86 ± 3.19 mmHg; HD: 11.23 ± 3.45 mmHg; CKD: 9.81 ± 2.49 mmHg, p = 0.016). Average BP levels and BPV indices are similar between PD and HD patients, in whom they are higher than in their CKD counterparts. The dialysis modality has no effect on the ambulatory BP profile. These results suggest that PD is no better than HD with regard to overall BP control or BP fluctuations over time.

Normal white blood cell counts predict long-term mortality of hemodialysis patients.

PURPOSE: It is unclear whether normal white blood cell (WBC) counts are predictive of subsequent mortality in hemodialysis patients. METHODS: All patients aged 17 years or more, who initiated hemodialysis at a tertiary Hospital from January 2000 to August 2017 with a dialysis vintage of greater than 90 days and normal median WBC count of their first dialysis year were included in the study. They were followed until they died, transferred to other dialysis facilities, switched to peritoneal dialysis, received a renal transplant or reached the end of the study (August 31, 2018). Cox regression was used to estimate hazard ratios for mortality of tertiles of WBC counts, adjusting for baseline demographic, clinical and laboratory variables. RESULTS: 611 patients [median (interquartile range) age 65.2 (53.3-72.6) years, 62.4% male] were studied. During a median follow-up of 3.9 (1.6-7.2) years, 270 participants died. Patients in the mid- (6.25-7.73 × 103/µL, n = 203) and top-tertile (7.73-10.50 × 103/µL, n = 203) of normal WBC counts had significantly higher mortality than patients in the bottom-tertile (3.50-6.25 × 103/µL, n = 205). The adjusted hazard ratio for mortality relative to the bottom-tertile was 1.54, 95% confidence interval (CI) 1.05-2.25 and 2.20, 95% CI 1.46-3.32, for the mid- and top-tertiles, respectively. CONCLUSIONS: In hemodialysis patients, higher WBC count within the normal range is associated with increased long-term mortality. This finding is described for the first time and provides further insight into the clinical significance of a "normal" WBC count result in dialysis patients.

Efficacy and safety of a low monthly dose of intravenous iron sucrose in peritoneal dialysis patients.

PURPOSE: Scientific data regarding intravenous iron supplementation in peritoneal dialysis (PD) patients are scarce. In attempting to administer the minimum monthly IV iron dose that could improve erythropoiesis, we wanted to assess the safety and efficacy of monthly maintenance intravenous administration of 100 mg iron sucrose in PD patients. METHODS: In a 9-month prospective study, all clinically stable PD patients received intravenously 200 mg of iron sucrose as a loading dose, followed by monthly doses of 100 mg for five consecutive months. Levels of hemoglobin (Hb), ferritin, transferrin saturation (TSAT), reticulocyte hemoglobin content (CHr) and C-reactive protein (CRP) were measured before each administration and 3 months after the last iron infusion. Also, doses of concurrent erythropoietin administration were recorded. RESULTS: Eighteen patients were eligible for the study. Mean levels of Hb and ferritin increased significantly (from 10.0 to 10.9 mg/dL, p = 0.01 and from 143 to 260 ng/mL, p = 0.005), as well as the increase in TSAT levels approached borderline significance (from 26.2 to 33.1%, p = 0.07). During the 6 months of iron administration, the erythropoietin dose was reduced in five patients and discontinued in one. During the 3 months following the last iron infusion, three of them again raised the erythropoietin dose to previous levels. None of the patients experienced any side effects related to IV iron administration. CONCLUSIONS: A monthly maintenance intravenous dose of 100 mg iron sucrose may be a practical, effective, and safe in the short term, treatment of anemia in PD patients resulting in improved hemoglobin levels, iron indices, and erythropoietin response.

Effects of mineralocorticoid receptor antagonists in proteinuric kidney disease: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Reductions in albuminuria of more than 30% are considered a strong marker of delay of chronic kidney disease (CKD) progression. Single renin-angiotensin system (RAS) blockade represents the cornerstone of CKD treatment. However, as CKD progression still occurs, other nephroprotective options were explored; mineralocorticoid receptor antagonists (MRA) were tested with generally positive results. METHODS: We conducted a systematic review and meta-analysis on the effects of MRAs on albuminuria/proteinuria, and adverse events, such as change in renal function and hyperkalemia incidence. A detailed search in electronic databases, clinical trial registries and grey literature was performed to retrieve randomized controlled trials (RCTs) in which administration of an MRA alone or on-top of ACEi/ARB was compared with placebo or active treatment. RESULTS: Of the 45 initially identified reports, 31, with 2767 participants, were included in analysis of the primary outcome. The use of MRAs (alone or on top of RAS blockade) compared with placebo decreased urine albumin-to-creatinine ratio (UACR) by -24.55% (95% CI -29.57 to -19.53%), urine protein-to-creatinine ratio (UPCR) by -53.93% (95% CI -79% to -28.86%) and 24 h albumin excretion by -32.47% (95% CI -41.1 to -23.85%). MRAs also reduced UACR by -22.48% (95% CI -24.51 to -20.44%) compared with calcium-channel-blockers (CCBs), whereas no differences were found compared with a second ACEi/ARB or nonpotassium-sparing diuretics. Addition of an MRA was associated with change in estimated glomerular filtration rate (eGFR) of -2.38 ml/min per 1.73 m (95% CI -3.51 to -1.25), rise in potassium by 0.22 mEq/l (95% CI 0.16-0.28 mEq/l) and a 2.6-fold increase in hyperkalemia risk (RR 2.63, 95% CI 1.69-4.08) compared with placebo/active control. CONCLUSION: Use of MRAs alone or on top of RAS blockade confers important antiproteinuric effects in patients with CKD, with a slight increase in mean potassium levels.

Lung Ultrasound-Guided Dry-Weight Reduction in Hemodialysis Patients Does Not Affect Short-Term Blood Pressure Variability.

BACKGROUND: Increased short-term blood pressure (BP) variability (BPV) in hemodialysis is associated with increased cardiovascular and all-cause mortality. Studies on the impact of BP-lowering interventions on BPV are scarce. This study examined the effect of dry-weight reduction with a lung ultrasound-guided strategy on short-term BPV in hemodialysis patients with hypertension. METHODS: This is a prespecified analysis of a randomized clinical trial in 71 hemodialysis patients with hypertension, assigned in a 1:1 ratio in the active group, following a strategy for dry-weight reduction guided by pre-hemodialysis lung ultrasound and the control group following standard-of-care treatment. All patients underwent 48-hour ambulatory BP monitoring at baseline and after 8 weeks. BPV was calculated with validated formulas for the 48-hour interval and the 2 daytime and nighttime periods. RESULTS: Dry-weight changes were -0.71 ± 1.39 in active vs. +0.51 ± 0.98 kg in the control group (P < 0.001), generating a between-group difference of 5.9/3.5 mm Hg (P < 0.05) in 48-hour BP at study end. All brachial BPV indices [SD, weighted SD, coefficient of variation, and average real variability (ARV)] did not change significantly from baseline to study end in the active [systolic blood pressure (SBP)-ARV: 12.58 ± 3.37 vs. 11.91 ± 3.13, P = 0.117; diastolic blood pressure (DBP)-ARV: 9.14 ± 1.47 vs. 8.80 ± 1.96, P = 0.190] or control (SBP-ARV: 11.33 ± 2.76 vs. 11.07 ± 2.51, P = 0.544; DBP-ARV: 8.38 ± 1.50 vs. 8.15 ± 1.49, P = 0.295) group (between-group comparison P = 0.211/0.117). Aortic BPV indices followed a similar pattern. Likewise, no significant changes in BPV indices for the daytime and nighttime periods were noted in both groups during follow-up. CONCLUSIONS: This study is the first to evaluate the effects of a nonpharmacological intervention on short-term BPV in hemodialysis, showing no effect of dry-weight reduction on BPV, despite BP decrease.

Immunosuppressive regimens based on Cyclophospamide or Calcineurin inhibitors: Comparison of their effect in the long term outcome of Primary Membranous Nephropathy.

INTRODUCTION: Management of the Primary Membranous Nephropathy (PMN) usually involves administration of immunosuppressives. Cyclophosphamide (Cyclo) and Calcineurin Inhibitors (CNIs) are both widely used but only limited data exist to compare their efficacy in long term follow-up. AIM: The aim of the present study was to estimate and compare long term effects of Cyclo and CNIs in patients with PMN. PATIENTS-METHODS: Clinical data, histologic findings and long term outcome were retrospectively studied. The response to treatment and rate of relapse was compared between patients treated with CNIs or Cyclo based immunosuppressive regimens. RESULTS: Twenty three centers participated in the study, with 752 PMN patients (Mean age 53.4(14-87) yrs, M/F 467/285), followed for 10.1±5.7 years. All patients were initially treated with Renin Angiotensin Aldosterone System inhibitors (RAASi) for at least 6 months. Based on their response and tolerance to initial treatment, patients were divided into 3 groups, group I with spontaneous remission, who had no further treatment, group II, continued on RAASi only, and group III on RAASi+immunosuppression. Immunosuppressive regimes were mainly based on CNIs or Cyclo. Frequent relapses and failure to treatment were more common between patients who had started on CNIs (n = 381) compared to those initially treated with Cyclo (n = 110), relapse rate: 25.2% vs. 6.4%, p<0.0001, and no response rate: 22.5% vs. 13.6%, p = 0.04, respectively. CONCLUSIONS: Long term follow up showed that administration of Cyclo in PMN is followed by better preservation of renal function, increased response rate and less frequent relapses, compared to CNIs.

Comparative analysis of immunophenotypic abnormalities in cellular immunity of uremic patients undergoing either hemodialysis or continuous ambulatory peritoneal dialysis.

AIM: To investigate the abnormalities of cellular immune responses in patients on hemodialysis (HD) and in those on continuous ambulatory peritoneal dialysis (CAPD). PATIENTS AND METHODS: Forty-five (45) healthy volunteers, 34 patients on HD therapy, and 37 patients on CAPD were recruited for the present study. Lymphocyte subpopulations (CD2+, CD3+, CD3+/CD4+, CD3+/CD8+, CD3-/16+56+, CD19, and CD4/CD8) were determined by flow cytometry. RESULTS: Lymphopenia, decreased absolute counts, and altered percentage values of CD3+, CD3+/ 4+, and CD19+ subpopulations were found in both patient groups. The HD and CAPD patients showed increased percentages of natural killer cells (CD3-/16+56+) compared to controls but CD4+/CD8+ ratio showed no significant changes among uremic patients and controls. CONCLUSIONS: Replacement therapy may contribute to the quantitative alterations of immune subsets found in HD and CAPD patients compared to normal subjects. We speculate that these changes account, at least in part, for the immune dysregulation observed in patients with chronic renal failure. Analysis of lymphocyte subsets will help the research and the evaluation of the possible causes of immunodeficiency in uremic patients undergoing replacement therapy and will probably contribute to more efficient and preventive strategies.

Therapeutic apheresis of immune diseases in nephrology department.

OBJECTIVE: The clinical efficacy of therapeutic apheresis is still controversial. We undertook a retrospective review of apheresis treatment to ascertain its safety and efficacy. METHODS: We reviewed 31 patients (13 male, 18 female). Plasmapheresis was performed on 7 patients with hematologic disorders, 5 patients with neurologic disorders, 6 patients with systemic diseases, and 3 patients with Lyell syndrome. Immunoadsorption onto protein A sepharose was evaluated as rescue therapy in 7 patients. Low-density lipoprotein (LDL) apheresis was performed on 3 patients. RESULTS: There were five mortalities due to serious complications of their primary disease. Most complications were mild such as hypotension and hypocalcemia. Two patients who received LDL apheresis had severe anaphylactic reactions. Apheresis was effective in the remaining 24 patients. CONCLUSIONS: The therapeutic apheresis consists of a continuously improving therapeutic method for diseases with high mortality and morbidity, especially in cases with poor outcome by using current medications.