Risk of end-stage kidney disease in kidney transplant recipients versus patients with native chronic kidney disease: multicentre unmatched and propensity-score matched analyses.

BACKGROUND: In kidney transplant recipients (KTR), the end-stage kidney disease (ESKD) risk dependent on the risk factors acting in native chronic kidney disease (CKD) remains undefined. METHODS: We compared risk and determinants of ESKD between 757 adult KTR and 1940 patients with native CKD before and after propensity-score (PS) analysis matched for unmodifiable risk factors [(age, sex, diabetes, cardiovascular disease and estimated glomerular filtration rate (eGFR)]. RESULTS: In unmatched cohorts, eGFR was lower in CKD versus KTR (45.9 ± 11.3 versus 59.2 ± 13.4 mL/min/1.73 m2, P < 0.001). During a median follow-up of 5.4 years, the unadjusted cumulative incidence of ESKD was consistently lower in unmatched KTR versus CKD. Conversely, in PS-matched analysis, the risk of ESKD in KTR was 78% lower versus CKD at 1 year of follow-up while progressively increased over time resulting similar to that of native CKD patients after 5 years and 2.3-fold higher than that observed in CKD at 10 years. R2 analysis in unmatched patients showed that the proportion of the outcome variance explained by traditional ESKD determinants was smaller in KTR versus native CKD (31% versus 70%). After PS matching, the risk of ESKD [hazard ratio (HR), 95% confidence interval (95% CI)] was significantly associated with systolic blood pressure (1.02, 1.01-1.02), phosphorus (1.31, 1.05-1.64), 24-h proteinuria (1.11, 1.05-1.17) and haemoglobin (0.85, 0.78-0.93) irrespective of KTR status. Similar data were obtained after matching also for modifiable risk factors. CONCLUSIONS: In KTR, when compared with matched native CKD patients, the risk of ESKD is lower in the first 5 years and higher later on. Traditional determinants of ESKD account for one-third of the variability of time-to-graft failure.

[Ultrasonography in chronic lithium nephropathy: a case report].

Lithium has always been used as a first-choice therapy in bipolar disorders. However, its therapeutic index is restricted by placing patients at risk of potential nephrotoxic effects ranging from polyuria, to Insipid Nephrogenic Diabetes, to chronic kidney disease with a slow reduction of renal function over time. The Nephrologist has the role to diagnose chronic lithium nephropathy, monitoring its evolution and optimizing the management of risks associated with the treatment. In fact, the main objective, to be shared with the psychiatrist, is to encourage the maintenance of therapy even in the presence of nephropathy. Renal ultrasound, a safe, repeatable and low-cost technique, is essential to pursue this goal as it not only confirms the diagnosis of chronic lithium nephropathy hypothesized on the basis of the history and clinical picture, but is also helpful in monitoring its evolution. In this paper, we report a case of chronic lithium nephropathy in order to analyze the etiopathogenesis of renal damage, the clinical-laboratory and histological picture and, in particular, the fundamental role of ultrasound imaging.

Competing-Risk Analysis of Death and End Stage Kidney Disease by Hyperkalaemia Status in Non-Dialysis Chronic Kidney Disease Patients Receiving Stable Nephrology Care.

Hyperkalaemia burden in non-dialysis chronic kidney disease (CKD) under nephrology care is undefined. We prospectively followed 2443 patients with two visits (referral and control with 12-month interval) in 46 nephrology clinics. Patients were stratified in four categories of hyperkalaemia (serum potassium, sK ≥ 5.0 mEq/L) by sK at visit 1 and 2: Absent (no-no), Resolving (yes-no), New Onset (no-yes), Persistent (yes-yes). We assessed competing risks of end stage kidney disease (ESKD) and death after visit 2. Age was 65 ± 15 years, eGFR 35 ± 17 mL/min/1.73 m², proteinuria 0.40 (0.14⁻1.21) g/24 h. In the two visits sK was 4.8 ± 0.6 and levels ≥6 mEq/L were observed in 4%. Hyperkalaemia was absent in 46%, resolving 17%, new onset 15% and persistent 22%. Renin-angiotensin-system inhibitors (RASI) were prescribed in 79% patients. During 3.6-year follow-up, 567 patients reached ESKD and 349 died. Multivariable competing risk analysis (sub-hazard ratio-sHR, 95% Confidence Interval-CI) evidenced that new onset (sHR 1.34, 95% CI 1.05⁻1.72) and persistent (sHR 1.27, 95% CI 1.02⁻1.58) hyperkalaemia predicted higher ESKD risk versus absent, independently from main determinants of outcome including eGFR change. Conversely, no effect on mortality was observed. Results were confirmed by testing sK as continuous variable. Therefore, in CKD under nephrology care, mild-to-moderate hyperkalaemia status is common (37%) and predicts per se higher ESKD risk but not mortality.

[Anti-diabetics and chronic kidney disease]. / Terapia antidiabetica nel paziente con diabete tipo 2 e malattia renale cronica: "an update".

Diabetes mellitus (DM) is the most important non-communicable disease after hypertension. Prevalence of type 2 DM has progressively increased over the last decades. In Italy, 11.8% of the general adult population can be identified as diabetic. The major complication of DM is diabetic nephropathy (DM-CKD), which develops in approximately one-third of diabetics. Achieving optimal glycemic control is the first therapeutic goal in the management of DM-CKD. In recent years, new antidiabetic drugs have been marketed (GLP1 analogues, DPP-4 inhibitors, SGLT-2 inhibitors) to ameliorate glycemia in patients nave or treated by means of traditional agents, such as sulfonylureas, metformin, glinides, insulin. However, use of these drugs in DM-CKD should be evaluated carefully, mainly because of the higher risk of hypoglycemia that requires dosing adjustments. Metformin still represents an adequate choice if proper dose adjustments are made on the basis of renal function. Sulfonylureas with limited renal clearance, i.e., gliquidone, glipizide and gliclazide are an alternative to metformin and more effective than repaglinide on glycemic control. Other antidiabetic agents with potential nephroprotective effects, namely DPP-4 inhibitors, incretin analogues and SGLT-2 inhibitors, may allow nephroprotective effects independent of glycemic control. Insulin remains the cornerstone of therapy when oral therapy is no longer effective.

Phytomorphological and essential-oil characterization in situ and ex situ of wild biotypes of oregano collected in the Campania region (Southern Italy).

Oregano is an aromatic species of great interest, which spreads spontaneously over the Mediterranean area, but its genetic resources are not yet adequately developed. Moreover, the results of studies of wild strains of different origin - although quite numerous - are not always comparable, and, therefore, the influence of the environment and genotype on the variability cannot be distinguished. Hence, the plant morphology and the essential-oil composition of three wild, white-flowering biotypes of oregano collected in the Campania region (southern Italy) were characterized, and the effects of genotype and environment were assessed by comparison in situ and ex situ. This allowed deducing that the biotypes belonged to two different subspecies, i.e., Origanum vulgare ssp. virens and O. vulgare ssp. viridulum. The essential-oil yield was higher for the biotype belonging to ssp. virens, and it was significantly correlated with the glandular and stomatal density. The chemical composition of the oils obtained by hydrodistillation was found to be influenced by the genotype and the conditions of plant growth.

The effect of increasing age on the prognosis of non-dialysis patients with chronic kidney disease receiving stable nephrology care.

To define whether age modifies the prognosis of patients with chronic kidney disease (CKD) on nephrology care, we prospectively followed patients with CKD who have been receiving nephrology care in a clinic for 1 year or more. The incidence of end-stage renal disease (ESRD), defined by the occurrence of dialysis or transplant, or death without ESRD was estimated by a competing-risk approach, and interactions between age and risk factors tested in Cox models over a median follow-up period of 62.4 months. Of 1248 patients with stage III­V CKD, 481 were younger than 65, 410 were between 65 and 75, and 357 were over 75 years old. Within each age class, the mean estimated glomerular filtration rate(eGFR) was 31, 32, and 29 ml/min per 1.73 m2, respectively. There were 394 ESRD events and 353 deaths. The risk of ESRD was higher than the risk of death without ESRD for ages <60 years, and independent of eGFR. The ESRD risk diminished with aging but still prevailed for eGFRs of 25­35 in patients between 65 and 75 years and with an eGFR below 15 in those up to 85 years old. Proteinuria significantly increased the risk of ESRD with advancing age. Surprisingly, the unfavorable effects of cardiovascular disease on ESRD and of diabetes on survival significantly decreased with increasing age. Male gender, higher phosphate, lower body mass index, and hemoglobin were age-independent predictors for ESRD, while cardiovascular disease, lower hemoglobin, higher proteinuria and uric acid, and ESRD also predicted death. Thus, in older patients on nephrology care, the risk of ESRD prevailed overmortality even when eGFR was not severely impaired. Proteinuria increases ESRD risk, while the predictive role of other modifiable risk factors was unchanged compared with younger patients.

Renin-angiotensin system inhibitors reduce the progression of mesangioproliferative glomerulonephritis: 10 year follow-up.

BACKGROUND: Proteinuria is a common presentation of mesangioproliferative glomerulonephritis (MsPGN). No studies are available on the long-term effect of treatment by renin-angiotensin system (RAS) inhibitors on renal outcome in MsPGN patients. This study prospectively evaluates the effects of RAS inhibitors on renal outcome in patients with low risk MsPGN followed up for 10 years using historical patients with similar features at the time of presentation as untreated controls. ENDPOINTS: decrease of basal proteinuria>20% and loss>20% of basal glomerular filtrate rate (GFR) at the end of first year of observation. The patients were re-evaluated bimonthly during the first year and every 6 months thereafter. RESULTS: Twenty-five patients fulfilled the selection criteria. After one year follow-up 19 patients reached the endpoint of proteinuria and no patient reached the endpoint of GFR. No significant change in blood pressure levels (BP) and GFR was registered, by contrast daily proteinuria decreased significantly (p<0.001), falling by 29% at sixth month and 47% at the end of the follow-up. The historical control group consisted of 15 untreated patients seen between 1987 and 1992. The two-way analysis of variance for repeated measures showed greater values of GFR (p<0.001) and lower levels of daily proteinuria (p<0.001) in treated patients as compared to untreated controls. CONCLUSIONS: This 10-year follow-up study indicates that the early treatment with RAS inhibitors at low doses favourably influences the long-term renal outcome in proteinuric patients with MsPGN. Limitations were the small sample size and lack of randomization.

Hypertension management in chronic kidney disease: translating guidelines into daily practice.

BACKGROUND: Whether nephrology management improves over time achievement of blood pressure (BP) goal (<130/<80 mm Hg) in nondialysis CKD is still ill-defined. This historical cohort analysis evaluated the relationship between 1-year nephrology management and BP control in 275 incident CKD patients in an academic renal clinic. METHODS: Comparative analysis between referral and month-12 visit. RESULTS: Estimated glomerular filtration rate (GFR) was 42.1 ± 15.5 ml/min per 1.73 m2 and median proteinuria 0.20 g/24 hours. From baseline to month-12 visit, BP decreased from 148 ± 23 / 81 ± 12 mm Hg to 136 ± 18 / 76 ± 11 mm Hg, with BP goal prevalence increasing from 13.8% to 33.8%. We stratified patients into at-goal and not-at-goal on the basis of month-12 BP levels. Regression analysis identified diabetes (odds ratio [OR] = 1.96; 95% confidence interval [95% CI], 1.07-3.56) and basal systolic BP (OR=1.12; 95% CI, 1.03-1.21) as independent predictors of not-at-goal BP. The decrease in systolic/diastolic BP was smaller in not-at-goal versus at-goal patients (-7/3 mm Hg vs. -21/9 mm Hg); in not-at-goal reduction was, however, significant versus baseline (p<0.001) and coupled with a similar decline in proteinuria (p<0.001). CONCLUSIONS: Sustained nephrology management improves hypertension control in CKD, but achievement of BP goals remains suboptimal, with high systolic BP and diabetes being the main problems. Further studies are needed to verify the clinical significance of BP and proteinuria changes in patients whose BP remains above target levels.

Burden of resistant hypertension in hypertensive patients with non-dialysis chronic kidney disease.

BACKGROUND/AIMS: In chronic kidney disease (CKD), no data on resistant hypertension (RH) are so far available despite the high prevalence of uncontrolled hypertension. We evaluated frequency, correlates and prognosis of RH in 300 consecutive incident hypertensive CKD patients in an academic renal clinic. METHODS: RH was defined as office blood pressure (BP) ≥130/80 mm Hg despite ≥3 drugs at full dose including a diuretic, or as BP at goal with ≥4 full-dose drugs. Patients were evaluated at referral and after 6 months of nephrology management; thereafter, they were included in a renal survival analysis lasting 37.6 months. RESULTS: On referral, glomerular filtration rate was 41.3 ± 16.6 ml/min/1.73 m² and BP 148 ± 23/81 ± 12 mm Hg. After 6 months, BP decreased by 8 ± 23/3 ± 12 mm Hg. From referral to month 6, RH detection increased from 26 to 38% due to the significant increment in full-dose antihypertensive medications (from 2.0, IQR 1.0-3.0 to 2.5, IQR 2.0-3.0). Diabetes and proteinuria predicted the incidence of RH at month 6. Presence of RH at month 6 was associated with greater risk of renal death (HR, 1.85, 95% CI, 1.13-3.03), independent of main clinical features and degree of BP control. CONCLUSION: In CKD, RH is prevalent and associated with decreased renal survival, independent of BP levels.

Intra- and post-dialytic changes of haemoglobin concentrations in non-anaemic haemodialysis patients.

BACKGROUND: Non-anaemic haemodialysis (HD) patients are potentially more prone to the adverse effects of ultrafiltration-induced haemoconcentration. No study, however, has assessed the effects of dialytic session on haemoglobin (Hb) levels in these patients. METHODS: The levels of Hb and total protein before, at the end (T0) and up to 120 min (T120) after the third HD session of the week were compared in non-anaemic (Hb >13 g/dl, n = 14, NOR) and anaemic (Hb = 11-12 g/dl, n = 18, LOW) HD patients. RESULTS: The intradialytic weight loss was similar in the two groups (4.0 +/- 0.9 and 4.1 +/- 0.9% body weight). During the treatment, Hb levels increased to the same extent in both groups (from 14.4 +/- 1.2 to 16.3 +/- 1.9 g/dl in NOR, and from 11.4 +/- 0.8 to 12.7 +/- 0.9 g/dl in LOW) in the presence, presumably, of a smaller plasma volume in NOR, whereas the increment of total protein was greater in NOR (from 7.1 +/- 0.2 to 9.6 +/- 0.5 g/dl) than in LOW (from 7.3 +/- 0.6 to 8.7 +/- 0.8 g/dl) (P < 0.0001). At T120, the Hb decline in NOR was almost double that measured in LOW (-9.2 +/- 3.0 vs -4.7 +/- 2.4%, P < 0.001). Consequently, Hb concentration did not differ from the pre-dialytic value in NOR (P = 0.10), but persisted higher in LOW (P < 0.005). The extent of the post-dialytic decrement of Hb was inversely related to the total protein values at T0 (r = -0.547, P = 0.0012). CONCLUSIONS: This study indicates that in NOR: (i) the extent of intradialytic increment of Hb is limited by a greater intradialytic plasma refilling; (ii) the greater plasma refilling persists after the end of dialysis, with the restoration of pre-dialytic Hb levels within the initial 2 h; and (iii) the force driving this phenomenon resides mainly in the larger changes of total protein concentration.

Supplemented very low protein diet ameliorates responsiveness to erythropoietin in chronic renal failure.

BACKGROUND: The aim of this study was to evaluate the relationship between uremic state and erythropoiesis in patients with predialytic chronic renal failure (CRF). METHODS: We monitored for 2 years the erythropoietin (EPO) requirement in patients with advanced CRF (creatinine clearance < or =25 mL/min), randomized to either low protein diet (LPD) group (0.6 g/kg body weight/day, N = 10) or very low protein diet (VLPD) group (0.3 g/kg body weight/day, N = 10) supplemented with a mixture of ketoanalogs and essential amino acids, both kept at target hemoglobin levels. RESULTS: The achieved protein intake after 6 months was 0.79 +/- 0.02 g/kg body weight/day and 0.50 +/- 0.02 g/kg body weight/day in LPD and VLPD, respectively; such a difference was maintained up to the end of follow up. The final hemoglobin values did not differ from the basal values in either group (11.5 +/- 0.2 g/dL and 11.5 +/- 0.3 g/dL). EPO dose, that was similar at baseline (62.4 +/- 9.6 UI/kg body weight/week and 61.8 +/- 8.8 UI/kg body weight/week subcutaneously), remained unchanged in LPD but progressively decreased in VLPD down to the final value of 41.2 +/- 7.0 UI/kg body weight/week (P < 0.0001 vs. basal and LPD). VLPD was associated with a decrease of urinary excretion and serum levels of urea nitrogen and phosphate; however, EPO requirement was not correlated with the changes of these parameters. On the contrary, the variation of EPO dose directly correlated with the modification of parathyroid hormone (PTH) levels, that diminished from 229 +/- 55 pg/mL to 118 +/- 16 pg/mL (P < 0.0001) in VLPD and did not change in LPD. CONCLUSION: In patients with advanced CRF, an effective decrease of protein intake of 0.3 g/kg body weight/day induces a reduction of about 35% of the EPO dose required to maintain the target hemoglobin levels. This effect appears dependent on the correction of a moderate secondary hyperparathyroidism.

Daily nutrient intake represents a modifiable determinant of nutritional status in chronic haemodialysis patients.

BACKGROUND: In maintenance haemodialysis patients, daily food intake is changeable; however, its relationship with nutritional status is unexplored. This study aimed to evaluate the isolated, long-term effect of daily nutrient intake on nutritional status in haemodialysis patients. METHODS: We performed a prospective 1-year controlled study in 27 chronic haemodialysis patients, without recognized risk factors for malnutrition. Each day for 1 week, four times in the year, we measured protein nitrogen appearance, and assessed dietary protein (DPI) and energy (DEI) intake from dietary diaries. We compared the nutritional outcome of patients spontaneously reducing nutrient intake below the threshold of 0.8 g/kg body weight/day for DPI and 25 kcal/kg body weight/day for DEI during the week (LOW, n = 8), with controls at adequate nutrient intake (CON, n = 19). An interventional 6-month study was then carried out in LOW to verify the cause-effect relationship. RESULTS: All patients showed a day-by-day reduction of whole nutrient intake during interdialytic period, which was mostly relevant in the third interdialytic day (L3). During the 1-year study, even in the presence of adequate dialysis dose and normal inflammatory indexes, body weight (68.0 +/- 5.5 to 65.8 +/- 5.9 kg), serum albumin (3.96 +/- 0.07 to 3.66 +/- 0.06 g/dl) and creatinine (9.2 +/- 1.1 to 8.1 +/- 0.7 mg/dl) significantly decreased in LOW but not in CON. Diaries evidenced in LOW a reduced number of meals at L3 that was explained by the fear of excessive interdialytic weight gain. During the interventional study, daily DPI and DEI increased at L3; this was associated with a significant increment of body weight, and serum albumin and creatinine levels. CONCLUSIONS: In maintenance haemodialysis patients the persistent, marked reduction of daily nutrient intake, even if limited to a single day of the week, is an independent determinant of reversible impairment of nutritional status.

Maximal suppression of renin-angiotensin system in nonproliferative glomerulonephritis.

BACKGROUND: Elimination of residual proteinuria is the novel target in renoprotection; nevertheless, whether a greater suppression of renin-angiotensin system (RAS) effectively improves the antiproteinuric response in patients with moderate proteinuria remains ill-defined. METHODS: We evaluated the effects of maximizing RAS suppression on quantitative and qualitative proteinuria in ten patients with stable nonnephrotic proteinuria (2.55 +/- 0.94 g/24 hours) due to primary nonproliferative glomerulonephritis (NPGN), and normal values of creatinine clearance (103 +/- 17 mL/min). The study was divided in three consecutive phases: (1) four subsequent 1-month periods of ramipril at the dose of 2.5, 5.0, 10, and 20 mg/day; (2) 2 months of ramipril 20 mg/day + irbesartan 300 mg/day; and (3) 2 months of irbesartan 300 mg/day alone. RESULTS: Maximizing RAS suppression was not coupled with any major effect on renal function and blood pressure; conversely, a significant decrement in hemoglobin levels, of 0.8 g/dL on average, was observed during up-titration of ramipril dose. The 2.5 mg dose of ramipril significantly decreased proteinuria by 29%. Similar changes were detected after irbesartan alone (-28%). The antiproteinuric effect was not improved either by the higher ramipril doses (-30% after the 20 mg dose) or after combined treatment (-33%). The reduction of proteinuria led to amelioration of the markers of tubular damage, as testified by the significant decrement of alpha 1 microglobulin (alpha 1m) excretion and of the tubular component of proteinuria at sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). CONCLUSION: In nonnephrotic NPGN patients, standard doses of either ramipril or irbesartan lead to significant reduction of residual proteinuria and amelioration of the qualitative features suggestive of tubular damage. The enhancement of RAS suppression up to the maximal degree does not improve the antiproteinuric response and is coupled with a decrement of hemoglobin levels.

Influence of the cyclic variation of hydration status on hemoglobin levels in hemodialysis patients.

BACKGROUND: Maintenance hemodialysis (HD) patients were studied to assess the effect on hemoglobin (Hb) concentration induced by the cyclic variation in hydration status. METHODS: Forty-nine HD patients were examined in three consecutive HD sessions in a 1-week treatment period. In a subgroup of 23 patients, Hb levels also were investigated during the long interdialytic interval. RESULTS: Hb levels at the end of the long interdialytic interval were significantly lower by 0.5 to 0.6 g/dL (5 to 6 g/L) than those at the end of short intervals. Among all pre-HD and post-HD Hb values, levels measured at the end of short intervals were closest to the mean Hb value of the week, derived from calculation of the area under the curve (12.0 +/- 0.2 g/dL [120 +/- 2 g/L]). Intradialytic Hb increments were different in the three sessions (+1.6 +/- 0.1 g/dL [+16 +/- 1 g/L] after the long interval, +1.1 +/- 0.1 g/dL [+11 +/- 1 g/L] and +1.1 +/- 0.1 g/dL [+11 +/- 1 g/L] after short intervals [P < 0.001] and proportionate to weight loss [-3.4 +/- 0.1, -2.7 +/- 0.1, and -2.6 +/- 0.1 kg, respectively; P < 0.001]). Hb level increment and weight loss correlated directly (r = 0.527; P < 0.0001); each 1 L of ultrafiltration (UF) led to an increase in Hb level of approximately 0.4 g/dL (4 g/L). Plasma refilling accounted for an approximately 45% decrement in the intradialytic increase in Hb level 2 hours post-HD. CONCLUSION: This study suggests that: (1) the end of the short interdialytic period is the most appropriate timing for anemia assessment, and (2) the remarkable hemodiluting effect of post-HD plasma refilling protects against excessive increments in Hb levels induced by UF.

Postdialytic rebound of serum phosphorus: pathogenetic and clinical insights.

To gain insights into postdialytic rebound of serum phosphate (PDR-P), serum phosphate (P), calcium (Ca), and parathyroid hormone (PTH), levels were compared from the end of treatment (T0) to the subsequent 30 to 120 min and up to 68 hr in uremic patients who underwent with crossover modality a single session of two dialytic treatments characterized by different convective removal: standard hemodialysis (HD) and hemodiafiltration (HDF). In HDF, versus HD, P removal was greater (1171 +/- 90 versus 814 +/- 79 mg; P < 0.05) in the presence of similar predialytic P levels (6.0 +/- 0.2 and 5.9 +/- 0.4 mg/dl) and Kt/V (1.35 +/- 0.06 and 1.34 +/- 0.05); however, the serum P values at T0 did not differ (3.0 +/- 0.2 versus 3.3 +/- 0.2 mg/dl). In HDF, PDR-P was more rapid (30 min versus 90 min) and of a greater extent (at T120: +69 +/- 6% versus +31 +/- 4%; P < 0.0001). The higher P levels were maintained throughout the interdialytic period. Ca x P and PTH changed in parallel. Thereafter, patients were randomized to receive either HD or HDF for 3 mo. During this period, in the presence of similar Kt/V, protein intake, and dose of phospate binder, predialytic serum P levels diminished in HDF (from 5.8 +/- 0.2 to 4.4 +/- 0.3 mg/dl; P < 0.05), but they remained unchanged in HD. A similar pattern of changes was detected in Ca x P. Therefore, PDR-P is likely dependent on the mobilization of phosphate from a deep compartment induced by the intradialytic removal of this solute. Enhancement of convective removal acutely amplifies the entity of the phenomenon but allows a better control of Ca-P homeostasis in the medium term.

Effect of dialysate sodium concentration on interdialytic increase of potassium.

To evaluate the role of plasma tonicity in the postdialysis increment of plasma potassium (p[K(+)]), the outcome of two hemodiafiltration treatments that differed only in the Na(+) level in dialysate (Na(D))-143 mmol/L (high dialysate sodium concentration [H-Na(D)]) and 138 mmol/L (low dialysate sodium concentration [L-Na(D)])-were compared in the same group of uremic patients from the end of treatment (T0) to the subsequent 30 to 120 min and up to 68 h. Kt/V and intradialytic K(+) removal were comparable. At T0, plasma [Na(+)] was 145+/-1 and 137+/-1 mmol/L after H-Na(D) and L-Na(D), respectively (P<0.001). The difference in plasma tonicity persisted from T0 to T68 h. At T120, p[K(+)] was increased from the T0 value of 3.7+/-0.2 to 4.7+/-0.2 mmol/L (P<0.05) after H-Na(D), whereas it was unchanged after L-Na(D). The change of p[K(+)] was still different after 68 h (+76+/-10% and +50+/-7% in H-Na(D) and L-Na(D), respectively; P<0.05). Of note, in the first 2 h after the end of treatment, bioimpedance analysis revealed only in H-Na(D) a significant 11+/-3% decrement of phase angle that is compatible with a decrease of intracellular fluid volume at the expense of the extracellular volume. Similarly, within the same time frame, in H-Na(D), a significant reduction of mean corpuscular volume of red cells, associated with a 2 +/-1% decrease of the intracellular [K(+)], was observed. In contrast, mean corpuscular volume of red cells did not change and erythrocyte [K(+)] increased by 6+/-1% after L-Na(D) (P<0.005 versus H-Na(D)). Thus, hypertonicity significantly contributes to the increase of p[K(+)] throughout the whole interdialytic period by determining intracellular fluid volume/extracellular volume redistribution of water and K(+).