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BACKGROUND Apparent treatment–resistant hypertension (aTRH) is defined as failure to achieve adequate blood pressure (BP) control despite taking ≥3 antihypertensive medications from different categories or when taking ≥4 antihypertensives regardless of BP levels. METHODS In this cross-sectional study, we estimated the prevalence of aTRH in 140 patients receiving long-term peritoneal dialysis (PD) in four centers of Northern Greece, using the “gold-standard” method of ambulatory BP monitoring for the assessment of BP control status. The presence of subclinical overhydration was evaluated with the method of bioimpedance spectroscopy (BIS). RESULTS Incorporating the diagnostic threshold of 130/80 mmHg for 24-hour ambulatory BP, the prevalence of aTRH in the overall study population was 30%. Compared to patients without aTRH, those with aTRH tended to be older in age, had higher PD vintage, had higher dialysate-to-plasma creatinine ratio, had more commonly history of diabetes mellitus, and were more commonly current smokers. With respect to the volume status, the overhydration index in BIS was higher in those with versus without aTRH (2.0 ± 1.9 L vs. 1.1 ± 2.0 L, P 2.5 L, was also higher in the subgroup of patients with aTRH (38.1% vs. 18.4, P = 0.01). CONCLUSION The present study showed that among patients on PD, the prevalence of aTRH was 30%. However, 38% of PD patients with aTRH had subclinical overhydration in BIS, suggesting that the achievement of adequate volume control may be a therapeutic opportunity to improve the management of hypertension in this high-risk patient population. The present study showed that among patients on PD, the prevalence of aTRH was 30%. However, 38% of PD patients with aTRH had subclinical overhydration in BIS, suggesting that the achievement of adequate volume control may be a therapeutic opportunity to improve the management of hypertension in this high-risk patient population. CLINICAL TRIALS REGISTRATION Trial Number NCT03607747

Introduction: Prior studies conducted in peritoneal dialysis (PD) patients in the late 1990s provided considerably variable estimates of the prevalence and control of hypertension. The present study aimed to investigate the current state of hypertension management in this high-risk population. Methods: In 140 stable PD patients, we performed standardized automated office blood pressure (BP) measurements and 24-h ambulatory BP monitoring (ABPM) using the Mobil-O-Graph device (IEM, Germany). Office and ambulatory hypertension was diagnosed in patients with office BP ≥140/90 mm Hg and 24-h BP ≥130/80 mm Hg, respectively. Patients treated with ≥1 BP-lowering medications were also classified as hypertensives. Results: The prevalence of office and ambulatory hypertension was 92.9% and 95%, respectively. In all, 92.1% of patients were being treated with an average of 2.4 BP-lowering medications daily. Adequate BP control was achieved in 52.3% and 38.3% of hypertensives by office BP and ABPM, respectively. The agreement between these 2 techniques in the identification of patients with BP levels above the diagnostic thresholds of hypertension was moderate (k-statistic: 0.524). In all, 5% of patients were normotensives with both techniques, 31.4% had controlled hypertension, 5% had white-coat hypertension, 19.3% had masked hypertension, and 39.3% had sustained hypertension. Isolated nocturnal hypertension was detected in 23.6% of patients, whereas no patient had isolated daytime hypertension. Conclusion: Among PD patients, hypertension is highly prevalent and remains often inadequately controlled. The use of ABPM enables the better classification of severity of hypertension and identification of isolated nocturnal hypertension, which is a common BP phenotype in the PD population.

INTRODUCTION Assessment of dry-weight among patients on dialysis is challenging in the absence of reliable markers to define fluid overload (FO). This study aimed to explore the value of two simple clinical signs, pedal edema, and crackles at pulmonary auscultation, in diagnosing hypervolemia, using bioimpendence spectroscopy (BIS) as reference standard. METHODS In a cohort of 107 asymptomatic dialysis patients, FO was assessed with physical examination and BIS shortly before the mid-week dialysis session. Patients were also asked to perform home blood pressure (BP) monitoring with a validated, automatic device (HEM-705, Omron, Healthcare) for 1 week in order to determine their BP outside of dialysis. FINDINGS Patients within the high tertile of predialysis FO had longer dialysis vintage, lower serum albumin and higher home systolic BP, despite the more aggressive treatment with a higher average number of antihypertensives daily. In receiver-operating-characteristic (ROC) curve analysis, pedal edema (area under curve [AUC]: 0.534; 95% confidence interval [CI]: 0.416-0.651) and pulmonary crackles (AUC: 0.551; 95% CI: 0.432-0.671) had limited accuracy in detecting excess predialysis FO > 2.2 L. The agreement of pedal edema (k-coefficient: 0.065) and pulmonary crackles (k-coefficient: 0.122) with BIS-derived FO was poor. In multivariate linear regression analysis, longer dialysis vintage (β: 0.306, p

Background and Aims Earlier studies provided considerably variable estimates on the prevalence and control rates of hypertension in hemodialysis because of their heterogeneity in definitions and blood pressure (BP) measurement techniques applied to detect hypertension. Method In the present study, 116 clinically stable hemodialysis patients from 3 dialysis centers of Northern Greece underwent home BP monitoring for 1 week with the validated automatic device HEM-705 (Omron, Healthcare). Routine BP recordings taken before and after dialysis over 6 consecutive sessions were also prospectively collected and averaged. Hypertension was defined as: (i) 1-week averaged home BP ≥135/85 mmHg; (ii) 2-week averaged predialysis BP ≥140/90 mmHg; (iii) 2-week averaged postdialysis BP ≥130/80 mmHg. Participants on treatment with ≥1 antihypertensives were also classified as hypertensives. Results The prevalence of hypertension was 88.8% by home, 86.2% by predialysis and 91.4% by postdialysis BP recordings. In all, 96 participants (82.7%) were being treated with an average of 1.7 antihypertensive medications. Among drug-treated participants, 32.6% were controlled by home, 50.5% by predialysis and 45.3% by postdialysis BP recordings. In multivariate logistic regression analysis, greater use of antihypertensive medications and postdialysis overhydration, assessed with bioimpendence spectroscopy, were both independently associated with higher odds of inadequate home BP control. Conclusion This study shows that epidemiology of hypertension in hemodialysis differs considerably between routine dialysis-unit and home BP recordings. Since greater antihypertensive drug use and postdialysis overhydration appeared to be the major determinants of inadequate home BP control, then management of hypertension should be initially relied on strategies targeting to control volume overload.

BACKGROUND: Evidence suggests that the anti-aging protein a-Klotho is a central modulator of mineral homeostasis. Circulating a-Klotho exerts endocrine activity and has been implicated in the process of vascular calcification, which is accelerated in patients with chronic kidney disease (CKD) and portends an unfavorable overall prognosis. However, the role of a-Klotho in this process remains unclear. The purpose of this study was to investigate the possible interaction between a-Klotho and the calcification of the aortic valve and coronary arteries in patients with CKD. METHODS: In this study we enrolled a total of 60 adult patients with CKD. Group 1 included 30 participants with CKD stage V and group 2 included 30 participants with CKD stage III. RESULTS: Participants in group 1 had lower levels of circulating a-Klotho compared to group 2 (390; 280–590 vs. 722; 501–897 pg/mL; P=0.001), were of younger age (55.5; 45–63 vs. 69; 62–74 years; P

In the era of newly introduced hypertension guidelines recommending lower blood pressure (BP) targets for drug-treated hypertensives, the necessity for optimized management of hypertension becomes even more urgent. The concept of home BP-guided antihypertensive therapy is for long suggested as a simple and feasible approach to improve BP control rates and optimize the management of hypertension. Home BP-guided antihypertensive therapy is particularly applicable to hypertensives with chronic kidney disease (CKD) for several reasons including the following: (1) difficult-to-control BP and high BP variability in the CKD setting; (2) poor accuracy of office BP in determining hypertension control status and detecting "white-coat" and "masked" hypertension; (3) poor value of routine office BP recordings in predicting the longitudinal progression of target-organ damage; and (4) superiority of home BP over office BP recordings in prognosticating the risk of incident end-stage renal disease or death. The concept of home BP-guided antihypertensive therapy is even more relevant for those on hemodialysis, given the high intradialytic and interdialytic BP variability and poor value of conventional peridialytic BP recordings in estimating the actual BP load recorded outside of dialysis with the use of home or ambulatory BP monitoring. Randomized trials comparing home BP-guided antihypertensive therapy versus usual care are warranted to prove the feasibility and effectiveness of this therapeutic approach and convince clinicians for using home BP monitoring as the standard of care when managing hypertension, particularly in people with CKD or end-stage renal disease.

Background: Endothelial dysfunction leading to unbalanced vasoconstriction and ischemia of renal parenchyma is increasingly proposed as an alternative pathway of renal damage in autosomal dominant polycystic kidney disease (ADPKD). However, human studies investigating the evolution of such phenomena are limited. This study investigated the levels of emerging biomarkers of endothelial function, angiogenesis and hypoxia, in ADPKD patients with different renal function. Methods: The study population consisted of three groups: 26 ADPKD patients with impaired renal function (Group A; estimated glomerular filtration rate [eGFR] 45–70 mL/min/1.73 m2), 26 ADPKD patients with preserved renal function (Group B; eGFR >70 mL/min/1.73 m2), and 26 age- and sex-matched controls with no history of renal disease. Circulating levels of endocan (endothelial cell-specific molecule-1) angiopoietin-2, and hypoxia-inducible factor-1a (HIF-1a) were determined by enzyme-linked immunosorbent assay techniques. Results: Patients in Group A had significantly higher levels of endocan (7.17 ± 0.43 ng/mL), angiopoietin-2 (5,595.43 ± 3,390), and HIF-1a (163.68 ± 37.84 pg/mL) compared to patients in Group B (6.86 ± 0.59 ng/mL, p = 0.017, 3,854.41 ± 3,014.30, p = 0.018, 136.84 ± 42.10 pg/mL, p = 0.019 respectively) or controls (4.83 ± 0.69 ng/mL, 1,069 ± 427.88 pg/mL, 70.20 ± 17.49 pg/mL, p < 0.001 for all comparisons). Of note, patients in Group B had also higher levels of all markers compared to controls (p < 0.001) despite having similar renal function. In correlation analyses within ADPKD patients, we noted strong correlations of all studied markers with asymmetric dimethylarginine (ADMA; endocan r = 0.908, p < 0.001, angiopoietin-2 r = 0.983, p < 0.001 and HIF-1a r = 0.998, p < 0.001), and only weak or modest correlations with eGFR. Conclusions: This study suggests that endothelial dysfunction causing microcirculatory changes, linked to angiogenesis and hypoxia, may come early in the course of ADPKD and could be a key regulator of renal injury progression.

Background/Aims: The pathophysiology of renal disease progression in autosomal dominant polycystic disease (ADPKD) is largely unknown. Recent evidence suggests microvascular dysfunction leading to renal ischemia, as an additional pathway for renal function decline. This study examined the levels of serum Fas ligand (FasL), serum myostatin and urine transforming growth factor-beta 1 (TGF-β1) and their association with markers of endothelial dysfunction, in ADPKD patients with preserved or impaired renal function. Methods: Seventy-eight participants were enrolled in the study, divided in three groups: Group A consisted of 26 ADPKD patients with impaired renal function (eGFR 45-70 ml/min/1.73m2), Group B of 26 ADPKD patients with preserved renal function (eGFR > 70 ml/min/1.73m2), and Group C of 26 age- and sex- matched controls with no history of renal disease. Serum FasL, myostatin and urine levels of TGF-β1 were measured as biomarkers of vascular dysfunction, apoptosis and fibrosis with ELISA techniques. Results: Group A patients had significantly higher levels of FasL (13.12±1.69 ng/mL), myostatin (4.62±0.59 ng/mL) and urine logTGF-β1 (3.56±0.49 ng/24h) compared to Group B (9.6±1.28 ng/mL, 3.06±0.35, and 2.09±0.37, respectively, p< 0.001 for all comparisons) or controls (6.59±1.17 ng/mL, 2.18±0.45 ng/ml, and 1.58±0.21, respectively, p< 0.001 for all comparisons). Patients in Group B had also higher levels of all markers compared to controls (p< 0.001), despite having similar renal function. In ADKPD patients negative associations of eGFR with FasL (r=-0.799, p< 0.001), myostatin (r=-0.856, p< 0.001) and TGF-β1 (r=-0.476, p< 0.001) but positive correlations of these markers with asymmetric dimethylarginine (ADMA) (r=0.825; r=0.749; and r=0.599, respectively p< 0.001) were noted. Multivariate analysis demonstrated that FasL was independently associated with high urine TGF-β1 (OR 3.774, 95%CI 1.180-12.072, p=0.025). Conclusions: ADPKD patients with moderately preserved renal function have higher levels of FasL, myostatin and urine TGF-β1 than controls. These results indicate that an interplay between endothelial dysfunction and renal ischemia with mechanisms linked to apoptosis and fibrosis may be present even in early stages of ADPKD.

BACKGROUND Earlier studies provided considerably variable estimates on the prevalence and control rates of hypertension in haemodialysis because of their heterogeneity in definitions and blood pressure (BP) measurement techniques applied to detect hypertension. MATERIALS AND METHODS In this cross-sectional study, 116 clinically stable haemodialysis patients from 3 dialysis centres of Northern Greece underwent home BP monitoring for 1 week with the validated automatic device HEM-705 (Omron, Healthcare). Routine BP recordings taken before and after dialysis over 6 consecutive sessions were also prospectively collected and averaged. Hypertension was defined as: (a) 1-week averaged home BP ≥ 135/85 mm Hg; (b) 2-week averaged predialysis BP ≥ 140/90 mm Hg; and (c) 2-week averaged postdialysis BP ≥ 130/80 mm Hg. Participants on treatment with ≥1 antihypertensives were also classified as hypertensives. RESULTS The prevalence of hypertension was 88.8% by home, 86.2% by predialysis and 91.4% by postdialysis BP recordings. In all, 96 participants (82.7%) were being treated with an average of 2.0 ± 1.1 antihypertensive medications. Among drug-treated participants, 32.6% were controlled by home, 50.5% by predialysis and 45.3% by postdialysis BP recordings. In multivariate logistic regression analysis, greater use of antihypertensive medications and postdialysis overhydration, assessed with bioimpedance spectroscopy, were both independently associated with higher odds of inadequate home BP control. CONCLUSIONS This study shows that the prevalence, but mainly the control rates of hypertension in patients on haemodialysis, differs between peridialytic and interdialytic BP recordings. Therefore, the wider use of home BP monitoring may improve the determination of BP control status in this high-risk population.

Immune-checkpoint-inhibitors (ICPIs) represent a novel class of immunotherapy against several malignancies. These agents are associated with several “immune-mediated” adverse effects, but the reported renal toxicity of ICPIs is less well defined. We present the case of a 60-year-old man with a history of non-small cell lung cancer, who developed acute kidney injury (AKI) approximately 3.5 months after initiation of immunotherapy with nivolumab. Urinalysis revealed sterile pyuria, without microscopic hematuria or proteinuria. Immunological examination was negative. A renal biopsy showed severe interstitial inflammatory infiltration of T-cells, monocytes, and eosinophils without interstitial granulomas and normal appearance of glomeruli, indicating acute interstitial nephritis (AIN) as the cause of AKI. After a short-term course of corticosteroids and permanent nivolumab discontinuation, partial recovery of renal function was noted. AIN is a rare adverse effect of ICPIs that mandates the close monitoring of renal function in patients under immunotherapy with these agents.

Increased blood pressure (BP) variability (BPV) is associated with high cardiovascular risk in hemodialysis. Studies on the effects of antihypertensive drugs on BPV in hemodialysis are scarce. This study examines the effects of nebivolol and irbesartan on short-term BPV in patients with intradialytic hypertension. This randomized-cross-over study included 38 patients (age: 60.4 ± 11.1 years, male: 65.8%) with intradialytic hypertension (intradialytic-SBP increase ≥ 10 mmHg at ≥4 over 6 consecutive sessions). After the baseline evaluation, participants were randomized to nebivolol 5 mg and subsequently irbesartan 150 mg, or vice versa, with a two-week wash-out period before initiation of the second drug. Patients underwent three respective 24 h-ABPM sessions starting before a midweek-session. We calculated the standard deviation (SD), weighted SD (wSD), coefficient of variation (CV), and average real variability (ARV) of BP with validated formulas. The post-hemodialysis and 24 h-SBP and DBP levels were significantly lower after treatment with both drugs. The systolic-BPV indices were marginally lower after nebivolol but not after irbesartan compared to baseline (SD: baseline 15.70 ± 4.69; nebivolol 14.45 ± 3.37, p = 0.090; irbesartan 15.39 ± 3.85, p = 0.706; wSD: 14.62 ± 4.36 vs 13.40 ± 3.07, p = 0.053 vs 14.36 ± 3.47, p = 0.805, respectively). The diastolic-BPV indices decreased with nebivolol and increased with irbesartan, resulting in significant differences between the two drugs (SD: baseline 10.56 ± 2.50; nebivolol 9.75 ± 2.12; irbesartan 10.84 ± 1.98, between-drug p = 0.014; wSD: baseline 9.86 ± 2.12; nebivolol 9.34 ± 2.01; irbesartan 10.25 ± 2.01, between-drug p = 0.029). The diastolic-BPV during intradialytic and day-time periods was marginally lower with nebivolol than with irbesartan. During nighttime, the BPV indices were unchanged with either drug. The short-term BPV was reduced after nebivolol but not after irbesartan treatment in patients with intradialytic hypertension. These findings suggest that sympathetic-overdrive may be a major factor that affects BPV in intradialytic hypertension patients.

In hemodialysis patients, the intradialytic rise in blood pressure (BP) is associated with increased mortality risk. However, the mechanisms of this adverse effect are not yet elucidated. This study examined whether intradialytic rise in BP is associated with increased arterial stiffness and wave reflections, which are powerful cardiovascular risk predictors in hemodialysis. The pattern of intradialytic hemodynamic response was evaluated in 70 prevalent hemodialysis patients, by measuring seated brachial BP before and after the mid-week dialysis session. All patients had pre- and post-dialysis determination of aortic pulse wave velocity (PWV) and heart rate-adjusted augmentation index [AIx(75)], as measures of arterial stiffness and wave reflections, with the Sphygmocor device. Intradialytic rise in brachial systolic BP (SBP) was evident in 17 patients, whereas intradialytic change in SBP (ΔSBP) of −10 to 0 mmHg was observed in 23 and ΔSBP greater than −10 mmHg in 30 patients. Participants with intradialytic SBP rise had significantly higher pre-dialysis aortic PWV (10.4 ± 1.6 vs 8.3 ± 1.9 vs 9.4 ± 2.4 m/s, P

Arterial stiffness is an important risk factor for cardiovascular morbidity and mortality in patients with end-stage renal disease (ESRD). Arterial stiffness aggravates cardiovascular risk via multiple pathways, such as augmentation of aortic systolic pressure, subendocardial hypoperfusion, and excess pulsatile energy transmission from macro- to microcirculation. Pathogenesis of the arteriosclerotic process in ESRD is complex and not yet fully understood. Several factors unique to ESRD, such as mineral metabolism disturbances, vascular calcifications, formation of advanced glycation end-products, and acute and chronic volume overload, are proposed to play a particular role in the progression of arteriosclerosis in ESRD. As these and other mechanistic pathways of arterial stiffening in ESRD are elucidated, there is hope that this knowledge will be translated into novel therapeutic interventions targeting arterial stiffness. In the meantime, blood pressure (BP) lowering via strict volume control and appropriate use of antihypertensive drugs is a fundamental step in reversing accelerated arterial stiffening and modifying the cardiovascular risk profile of ESRD patients. In this article, we review the pathogenesis, clinical epidemiology, and therapies targeting arterial stiffness in ESRD, discussing recent advances and high-priority goals of future research in these important areas.

Sodium polystyrene sulfonate (SPS) is a cation-exchanging resin that has been widely used for several decades as first-line therapy of mild chronic hyperkalemia in patients with chronic kidney disease (CKD). However, evidence to prove the long-term tolerability and efficacy of SPS for the treatment of this condition is still missing. In this retrospective, observational study, we enrolled 26 outpatients with stages 3–4 CKD who received oral therapy with low-dose SPS for mild chronic hyperkalemia in the Outpatient Nephrology clinic of our Department during 2010–2016. We obtained medical records on side effects potentially attributable to SPS use, and we analyzed the changes in serum electrolytes before and after the initiation of SPS therapy. Serum potassium levels fell from 5.9 ± 0.4 to 4.8 ± 0.5 mmol/l (P

ObjectiveLipid abnormalities are common in patients on continuous ambulatory peritoneal dialysis (CAPD) and they are risk factors for atherosclerosis. In this prospective uncontrolled study, the aim was to evaluate the efficacy and safety of atorvastatin, a new statin, in hypercholesterolemic CAPD patients with or without hypertriglyceridemia who failed to respond to diet control.MethodsFollowing a hypolipidemic diet for 2 months, atorvastatin was administered at a dose of 10 mg/day once daily in 24 patients (14 males, 10 females). Mean age was 59.9 years (range, 19-74 years) and average time on CAPD was 16.6 months (range, 4-52 months). The results were evaluated at 0, 1, 3, 6, 12, 18, 24, 30, 36, 42, and 48 months. A total of three patients received atorvastatin for longer than 48 months, eight patients received it for longer than 42 months, 10 patients for longer than 36 months, 17 patients for longer than 24 months, 20 patients for longer than 18 months, and all (24) patients for longer than 12 months.ResultsHighly significant decreases were noted in total cholesterol (from 282 ± 28 to 178 ± 22 mg/dL, 20-50%, mean, 34%; p < 0.001), low-density lipoprotein cholesterol (from 198 ± 25 to 112 ± 20 mg/dL, 21-53%, mean, 37%; p < 0.001), and triglycerides (from 256 ± 116 to 177 ± 40 mg/dL, 12-45%, mean, 28%, p < 0.01) from the sixth month. High-density lipoprotein cholesterol was significantly increased from the sixth month (from 40 ± 9 to 48 ± 9 mg/dL, 11-28%, mean, 19.4%; p < 0.01). These changes remained steady during the study. No liver function abnormalities were observed and serum creatinine kinase levels remained within normal limits during treatment. No complications or other side effects were detected.ConclusionsOur data indicate that atorvastatin, even at a low dose of 10 mg/day, is an effective, safe, and well-tolerated drug for the long-term treatment of hyperlipidemia in CAPD patients. [Hong Kong J Nephrol 2003;5(2):78-83]

The purpose of this study was to determine if Kt/V urea in continuous ambulatory peritoneal dialysis (CAPD) could be estimated by a multivariate model based upon simple clinical observations. The study included 439 clearance studies in 301 CAPD patients followed in 8 dialysis centers. Weekly urea clearance, 24 h urine volume and 24 h drain volume were normalized to body water by the formulae of Watson (Kt/V, UV/V, and DV/V respectively). Adequate dialysis was defined as Kt/V ≥2.0 weekly. Subjects at 2 units were used to derive the models, while others were used for model validation. Stepwise multiple linear regression was performed on the derivation set (DS) to identify the clinical variables that correlated with Kt/V. The model was then used to estimate Kt/V for the validation set (VS). In the DS, 110 clearance studies were performed in subjects with residual renal function. Multiple linear regression showed that weekly Kt/V was defined by the expression: Kt/V = 1.48 + 24.1 (UV/V) + 2.92(DV/V) - 0.049 (serum creatinine) (r=0.750, p2.3 weekly (7.9%, 54.7% and 79.7%, respectively; p2.3 weekly (8.1%, 68.8%, and 100%, respectively; p

Objective To study whether or not continuous peritoneal dialysis (CPD) can provide acceptable levels of normalized urea and creatinine clearance in heavyweight individuals. Design Retrospective analysis of urea and creatinine clearance studies. Setting CPD patients followed in four dialysis units in Albuquerque, two dialysis units in Thessaloniki, and two dialysis units in Athens. Participants One hundred and ninety-nine patients on CPD with 266 clearance determinations between 1991 and 1995. Interventions The heavyweight group consisted of 22 patients (24 clearance studies) weighing 100 kg or more (109.0±8.7 kg) at the time of the clearance study. All subjects were obese. The reference group consisted of 177 CPD subjects (242 clearance studies)ofnormal weight (68.7±12.2 kg). Urea fractional clearance (KT/V) and normalized creatinine clearance (Ccr) were compared between the heavyweight and the reference groups. Main Outcome Measures The lowest acceptable weekly levels were set at 1.70 for KT/V and 54.4 L/1. 73 m2 for Ccr. Results Weekly KT/V was 1.75±0.41 in the heavyweight group and 1.94±0.52 in the reference group (p = 0.047). Corresponding weekly Ccr levels were 64.0±24.3 and 77.6±40.3 L/1.73 m2, respectively (p = 0.021). In the heavyweight group, 13 studies (54.2%) had acceptable KT/V values compared to 160 studies (66.1 %) in the reference group (NS). Corresponding values for acceptable Ccr were 17 (70.8%) and 165 (68.2%), respectively (NS). Drain volume was 12.96±4.40 L/24 hours in the heavyweight group and 9.63±2.58 L/24 hours in the reference group (p = 0.001). High daily exchange volume was delivered by a combination of daily continuous ambulatory peritoneal dialysis (CAPD) and nocturnal automated peritoneal dialysis (APD) in 13116 heavyweight studies. This combination was tolerated better than any other method of delivering a large daily exchange volume. Conclusion Although normalized urea and creatinine clearances are lower in obese, heavyweight individuals than in lean CPD subjects with lower weight, approximately equal percentages of these two groups achieve acceptable clearance levels. However, heavyweight individuals require larger-than-usual daily exchange volumes. The preferred way to deliver these large dialysate volumes is a combination of daily CAPD and nocturnal APD.

ObjectiveTo compare estimates of urea volume (V) and KT/V obtained by the Watson and Hume anthropometric formulas, and to identify the similarities and differences between these estimates.DesignTheoretical analysis applying wide variations in the determinants of anthropometric V (age, height, weight) in hypothetical women and men. Analysis of urea kinetic studies performed in patients on continuous peritoneal dialysis (CPD).SettingFour dialysis units in Albuquerque, two in Athens, and two in Thessaloniki.ParticipantsThree hundred and two CPD patients who had 440 urea kinetic studies.InterventionStandard urea clearance was performed by 24-hour collections of urine and drained dialysate followed by blood sampling. V was estimated by both the Watson and Hume formulas.Main Outcome MeasuresEstimates of V and KT/V were compared separately in women and men by Student's t-test, linear regression, and limits of agreement (mean difference±2 SD). The agreement of the KT/V estimates was also tested by the kappa ratio using a value of 1.70 weekly as the lowest acceptable KT/V.ResultsThe theoretical analysis indicated important disagreement only in extreme variations from the ordinary in height and, to a lesser extent, weight. Differences due to height variation were pronounced only in hypothetical women. CPD patient findings were as follows: in women, Watson V and weekly KT/V were 30.4±4.4 L and 2.10±0.61, respectively. Corresponding Hume estimates were 30.3±5.4 L and 2.12±0.66, respectively. Corresponding estimates for men were 40.5±5.7 L and 1.92±0.57 (Watson) plus 41.4±5.6 L and 1.88±0.57 (Hume), respectively. By linear regression, KT/VHume = -0.083 + 1.052 (KT/Vw8tson), r = 0.961 (women); and KT/VHume = -0.026 + 0.992 (KT/Vwatson), r = 0.985 (men). Limits of agreement were -1.41 L and 2.10 L for V, and -0.15 and 0.14 weekly for KT/V. In 94.3% of the cases, KT/Vw8tson and KT/VHume agreed (both >1.70 or both ConclusionThe Watson and Hume formulas provide similar estimates of V and KT/V in CPD patients. Differences may be noted only if women's height or, to a lesser extent, both sexes’ weight is at a great variance with the ordinary values.

Objective To study how the presence of osmotic solutes in medium affects growth of the peritoneal mesothelial cells and fibroblasts and how osmotic solutes influence the production of factors regulating growth of these cells. Design The proliferation of mesothelial cells and fibroblasts was evaluated by measuring the incorporation of 3H-thymidine into the cells. Cells were exposed to osmotic solutes; the concentration of the latter in the medium was continuously lowered over the time of the experiment to simulate changes of their concentration in the dialysate. The synthesis of factors influencing the proliferation of the mesothelial cells or fibroblasts, by mesothelial cells or fibroblasts themselves, or by peritoneal leukocytes, was tested by the characteristics of the “conditioned” medium. The conditioned medium was produced by exposing standard medium to mesothelial or fibroblasts monolayer or to peritoneal leukocytes over 24 hours; following filtration it was applied to growing test cells for the study of growth factors. Results The effect of osmotic solutes on the growth of mesothelial cells is less inhibitory when their concentration is gradually lowered over the time of the study, compared to previous findings with a constant concentration. Peritoneal leukocytes produce growth factors for mesothelial cells and fibroblasts. Glucose and amino acids inhibit production of peritonealleukocyte-derived growth factors for mesothelial cells, while glycerol increases synthesis of such growth factors for fibroblasts. Mesothelial cells produce factors stimulating the proliferation of mesothelial cells and fibroblasts. In the presence of glycerol or amino acids synthesis of mesothelium derived growth factors for fibroblasts is augmented. Finally, fibroblasts produce factors that inhibit the proliferation of the mesothelial cells, and this effect is potentiated in the presence of amino acids. Conclusions Cytotoxicity of the osmotic solutes measured by the inhibition of growth of the mesothelial cells or their increased damage is significantly reduced during in vitro kinetic study when the concentration of these solutes is gradually lowered. Presence of osmotic solutes in the medium affects synthesis of growth factors derived from mesothelium, fibroblasts, or peritoneal leukocytes, which affect the proliferation of mesothelial cells or fibroblasts.

Uremic xerosis is a bothersome condition that is poorly responsive to moisturizing and emollient therapy.A randomized, double-blind, intraindividual (left versus right comparison), multicentric clinical study was performed on 100 patients with moderate to severe uremic xerosis for 7 days, during which the patients applied twice daily an emulsion combining glycerol and paraffin (test product) on one allocated lower leg, and the emulsion alone (comparator) on the other lower leg. This was followed by an open-labeled use of the test product on all of the xerotic areas for 49 days. The main efficacy parameter was treatment response on each lower leg, as defined by a reduction from baseline of at least two grades in a five-point clinical score on day 7.Among the 99 patients analyzed, the test product was highly effective with a treatment response in 72 patients (73%), whereas 44 patients (44%) responded to the comparator (P0.0001, intergroup analysis). This was associated with an objective reduction in the density and thickness of the scales on day 7 (P0.0001 compared with the comparator) and a substantial improvement of the uremic pruritus (75%) and quality of life of the patients at study end (P0.001, intragroup analysis). The test product was very well tolerated, with product-related local intolerance (exacerbated pruritus, local burning, or erythema) occurring in only five patients (5%).Uremic xerosis can be managed successfully when an appropriate emollient therapy is used.

We studied the effect of Intraperitoneal Infusion of various volumes and concentrations of dextrose (D) and amino acid (AA) solutions, In a variety of peritoneal dialysis schedules on food Intake and biochemical profile in normal and uremic rabbits.Following omentectomy, a peritoneal catheter was implanted. Animals had free access to food, and consumption was measured daily by weight of the remaining food in the cage.We studied the effect of volume (30-50-100 mL/kg), dextrose concentration (0.5-1.5-2.5-4.25-6.6 g/dL) and AA (Travasol based) (2% in Dianeal or glucose-free solution).Dialysis schedules Included once/day, twice/day, or four-daily exchanges similar to CAPD.The durations of the exchanges were 4–6 weeks and in certain groups, amino acid exchanges for a week alternated with dextrose exchanges.Our results Indicate the following: omentectomy and catheter implantation significantly decrease food Intake. There is a significant decrease In food Intake after initiation of dialysis that returns to baseline after 2–4 weeks while dialysis continues. Higher volumes (100 mL/kg) decrease food Intake significantly, especially with hypertonic solution of either D or AA. There was no difference in food Intake between D and AA Infusion In any amount of infused volumes.Amino acids do not seem to have a suppressing effect on appetite. However, large volumes and hypertonicity reduce food Intake.

We Investigated the psychiatric and psychosocial status of 31 elderly (age >65 years) end-stage renal disease patients undergoing hemodialysis (HO) (17 patients) and continuous ambulatory peritoneal dialysis (CAPO) (14 patients). There was no difference between the two groups In terms of age (67.3:1:.2.3 and 68.5:1:.4.3 In HO and CAPO groups, respectively), duration of dialysis treatment, and biochemical profile. The psychiatric and psychosocial status of the patients was assessed using the standardized psychiatric Interview (SPI), Hamilton's depression scale (HRS-O), and a questionnaire for the evaluation of the psychosocial Impact of the method of treatment. Sixteen of 31 patients presented with psychiatric morbidity (9 mild, 5 moderate, 2 severe). However, there was no significant relationship between psychiatric morbidity and method of dialysis (HO or CAPO). The mean values of SPI (21.47:1:.16.38 and 17.14:1:.13) and HRS-O (20.91:1:.17.33 and 15.41:1:.13.13) scores for the HO and CAPO groups, respectively, did not differ significantly. The analysis of the results of the questionnaire regarding the Impact of the method of treatment on psychosocial status Indicated that the HO patients felt that their lives were more dependent on factors that they could not Influence (I.e., the dialysis equipment, etc.). Our findings suggest that the psychiatric status of elderly patients undergoing chronic dialysis treatment Is not affected by the method of treatment, a factor that should be taken Into consideration when deciding the proper dialysis treatment for these patients.

To study the prevalence and pathogenesis of uremic pruritus, CAPD and HD patients were asked to complete a questionnaire. The replies were quantitated based on numerical scales, and the results were compared with various hematological and biochemical parameters, underlying disease, and duration of dialysis. There were 113 CAPD patients (63 males and 50 females), mean age 60 (range 20–84) years, average time on CAPD 20 (range 1–163) months and 76 HD patients (44 males and 32 females) mean age 57 (range 23–81) years, mean time on HD 44 (range 2–242) months. Replies to questions were evaluated and graded by the same Investigator who did not know the patients. Pruritus was present in 70 (62%) CAPD patients (64% in females and 600/0 in males p=NS) and in 41 (54%) HD patients (69% in females and 43% in males, p=0.025). Before starting dialysis pruritus was present in 30% CAPD patients and 28% HD patients. Pruritus was graded as mild, moderate and severe; the distribution was 58.6%, 34.3%, and 7.1% (CAPD) and 43.90/0, 41.5%, and 14.6% (HD), respectively. Dry skin was reported by 73% CAPD patients and 72% HD patients. This xerodermia was correlated with the severity of pruritus and was also present In 65% CAPD and 48.5% HD patients without pruritus. Patients with pruritus were older than those without pruritus both for CAPD (63 vs 54 years, p=0.004) and HD (61 vs 51 years, p=0.003). A significant correlation was observed only between pruritus score and age for CAPD patients. There were no other correlations between pruritus and the other parameters studied. We conclude that pruritus Is a frequent symptom In dialysis patients, but It Is severe only In a small proportion. Its prevalence, as also that of dry skin, Increases after start of dialysis and Is higher In females on HD. Patients with pruritus are older, and the severity of pruritus correlates with age in the CAPD patients. Presence of dry skin correlates with severity of pruritus, and Its prevalence Is high even among patients without pruritus.

This study reports our experience with permanent peritoneal catheters. From July 1983 until December 1997, 225 catheters were implanted surgically in 207 patients (120 males, 87 females) with mean age of 58 ± 16 years (range: 2 -82 years), and a mean duration of continuous peritoneal dialysis (CAPD) of 21.9 ± 21.3 months (range: 1 145 months). Two hundred and seventeen catheters were used in 199 patients suffering from end-stage renal disease (ESRD), and 8 catheters in 8 patients with end-stage heart failure resistant to medical therapy. One patient used 3 catheters and 16 patients used 2 catheters. The catheters used were: Tenckhoff, 2; Oreopoulos Zellerman-1 (OZ-1), 10; OZ-2, 205; and OZ-pediatric, 8. All catheters were implanted by the same surgical team, through a paramedian incision under local anesthesia. By life table analysis, the actuarial survival rates at 1 year, 2 years, 3 years, and 5 years were 97%, 92%, 87%, and 82% respectively for all catheters. The catheter-related complications were: 5 obstructions, 2 dislodgments, 13 dialysate leaks (6 early; 7 late), 90 exit-site/tunnel infections (in 56 patients), 2 cuff extrusions, and 37 hernias (in 31 patients). Eighteen catheters were replaced for persistent peritonitis (15 cases), dislodgment (1 case), obstruction (1 case), and accidental shortening (1 case). The total observation period was 4526 patient-months. The overall incidence of peritonitis was one episode per 15 patient-months, and of exit-site/tunnel infections was one episode per 50 patient-months, with a significant improvement during the last years. We conclude that OZ catheters implanted surgically through a paramedian incision have a very high survival rate and a low complication rate.

Pruritus is a common, unpleasant symptom of uremic patients. Serotonin and histamine have been reported as possible mediators of uremic pruritus, and ondansetron is a potent and selective inhibitor of 5-HT3 receptors. The aims of our study were (1) to evaluate the effect of ondansetron on uremic pruritus in continuous ambulatory peritoneal dialysis (CAPD) patients and its safety and (2) to investigate the role of histamine and serotonin in uremic pruritus. To study the prevalence and pathogenesis of uremic pruritus, CAPD and hemodialysis (HD) patients were asked to complete a pruritus questionnaire. The replies were scored based on numerical scales, and the results were evaluated by the same investigator who did not know the patients. Pruritus was graded, according to the total points for each patient, as mild, moderate, or severe. Of 54 patients on HD, 29 (53.7%) had pruritus, and of 43 patients on CAPD, pruritus was present in 21 (48.8%). In HD patients, pruritus was mild in 14 (48.3%), moderate in 12 (41.4%), and severe in 3 (10.3%) patients; the distribution in CAPD patients was 9 (42.9%), 10 (47.6%), and 2 (9.5%), respectively. There was no correlation between the presence and severity of pruritus and age, sex, primary renal disease, duration of dialysis, dialysis solutions used, and hematological and biochemical parameters except for serum histamine and serotonin levels and their product. Plasma histamine levels in CAPD patients were 13.1 ± 1.1 ng/ml in pruritic and 11.0 ± 3.9 ng/ml in nonpruritic patients (p = 0.06), serum serotonin levels were 115.6 ± 43.3 ng/ml and 64 ± 42.3 ng/ml (p < 0.05), respectively, and the histamine × serotonin product was 1,461 ± 576 and 646 ± 545 (p < 0.01), respectively. Eleven CAPD patients (6 males, 5 females) with a mean age of 66 (range 33–83) years and an average time on CAPD of 18 (range 3–31) months with moderate to severe pruritus were treated with ondansetron (4 mg twice daily p.o.) for a mean period of 3 (range 1–5) months. All patients responded to the treatment. There was a significant reduction of the severity of pruritus from the start of treatment, and on the 3rd day the pruritic score (mean value) was 10 (range 5–19) points, while at time 0 (before treatment) it was 26 (range 19–37) points (p < 0.0001). Pruritus disappeared in 7 patients at the end of the 1st week and in all patients at the end of the 2nd week of treatment. This effect was maintained during the study. Plasma histamine levels decreased significantly during the treatment from 12.9 ± 1.2 to 6.7 ± 5.9 ng/ml (p < 0.05). Also, serum serotonin levels were reduced from 125.1 ± 47.8 to 59.3 ± 27.5 ng/ml (p < 0.05) at the end of the 1st month of treatment, and the histamine × serotonin product showed a more significant reduction: from 1,544 ± 656 to 454 ± 436 (p < 0.01). Three patients reported an improvement in their nausea and vomiting during the treatment. Weekly clinical and laboratory examinations showed no side effects, adverse reactions, or other complications. Our data indicate that ondansetron is an effective, safe, and well-tolerated drug for the treatment of uremic pruritus in CAPD patients and that histamine and serotonin may have a crucial role in the appearance or perception of the uremic pruritus.

A logistic regression model developed and validated in Albuquerque identified 24 hr urine volume (UV) and 24 hr drain volume/(body water) (DV/V) as predictors of fractional urea clearance (KT/V) in continuous peritoneal dialysis (CPD). Solution of this model provided DV/V values consistent with KT/V at least equal to a target KT/V for a given UV. The predictive accuracy of these unique DV/V values was tested in urea kinetic studies performed in 108 CPD patients in Thessaloniki and Athens with UV varying between 0 and 2 L/24 h. Two target weekly KT/V values, 1.70 and 1.90, were investigated. The equation DV/V = (5.2811-3.6996 UV)/ 17.554, derived by solving the logistic regression model, detected weekly KT/V1.70 (69/108, or 63.9% of the studies) with a sensitivity of 87.3% and a specificity of 60.4%. According to the same equation, the maximal UV consistent with weekly KT/Vor = 1.70 is 1.427 L/24 hr. The equation DV/V = (5.4994-2.6007 UV)/17.007 detected weekly KT/V1.90 (44/108, or 40.7% of the studies) with a sensitivity of 90.3% and a specificity of 79.2%. According to this equation, the maximal UV consistent with weekly KT/Vor = 1.90 is 2.115 L/24 hr. Determination of the lowest daily DV consistent with a target KT/V at any daily UV (within a wide range) is feasible in CPD.

The effects of volume disturbances on the KT/V were investigated prospectively in 133 consecutive urea clearance studies on patients on continuous ambulatory peritoneal dialysis (CAPD). Four subjects (group A) had fluid loss (actual weightdry weight), 57 (group B) were studied on the basis of their dry weight, 58 (group C) had moderate fluid excess (0.5% of dry weight), and 14 patients (group D) had severe fluid excess (5% of dry weight). The KT/V was calculated on the basis of dry weight and actual weight with V obtained from the Watson anthropometric formulae which were applied either uncorrected or with a correction for changes in body water from dry weight conditions. The groups compared by variance analysis. The following weekly KT/V estimates were obtained: (1) using dry weight V: group A 1.81 +/- 0.17, group B 2.0 +/- 0.59, group C 1.79 +/- 0.46, group D 1.85 +/- 0.37 (no difference between groups); (2) using uncorrected actual weight V: group A 1.85 +/- 0.15, group B 2.05 +/- 0.59, group C 1.77 +/- 0.45, group D 1.78 +/- 0.37 (group B had a higher KT/V than group C, p0.05), and (3) using corrected actual weight V: group A 1.93 +/- 0.14, group B 2.05 +/- 0.59, group C 1.70 +/- 0.43, group D 1.63 +/- 0.36, (group B had a higher KT/V than either group C or group D, both at p0.01). In CAPD, fluid deficit is rare and causes a small increase in KT/V, whereas fluid retention is frequent and causes a decrease in KT/V. This decrease is pronounced in patients with severe fluid excess. The uncorrected Watson formulae underestimate V and, consequently, overestimate KT/V in CAPD patients with fluid excess.

The pharmacokinetics of Aztreonam (AZT) administered i.p. in six stable patients undergoing continuous ambulatory peritoneal dialysis (CAPD) for end-stage renal disease (ESRD) were studied. One gram of AZT was added into a 2 L bag of dialysate (Medital-Bieffe®) just prior to infusion into the peritoneal cavity. The dwell time was 8 h. The serum maximum concentration of AZT was 42.5 ± 12.4 mg/L (x ± SD), achieved in 4.6 ± 1.0 h. The elimination half-life was 2.4 ± 0.8 h, almost equal to that found in normal subjects (1.7–2 h). The pharmacokinetic parameters of elimination, as elimination rate constant and clearance of AZT from peritoneal cavity were found 0.305 ± 0.101 h-1 and 10.05 ± 3.7 mL/min, respectively, while the bioavailability via the peritoneal mem brane was 90.8 ± 3.05% of administered dose. It is concluded that AZT is eliminated from dialysate at a high rate after i.p. administration and its dialysate and serum levels exceed the MIC for the majority of sensitive organisms including Pseudomonas species. Aztreonam appears to be a potentially useful antibiotic for CAPD peritonitis.