Wojciech Zaluska

The mortality risk of overhydration in haemodialysis patients

Background. While cardiovascular events remain the primary form of mortality in haemodialysis (HD) patients, few centres are aware of the impact of the hydration status (HS). The aim of this study was to investigate how the magnitude of the prevailing overhydration influences long-term survival. Methods. We measured the hydration status in 269 prevalent HD patients (28% diabetics, dialysis vintage = 41.2 ± 70 months) in three European centres with a body composition monitor (BCM) that enables quantitative assessment of hydration status and body composition. The survival of these patients was ascertained after a follow-up period of 3.5 years. The cut off threshold for the definition of hyperhydration was set to 15% relative to the extracellular water (ECW), which represents an excess of ECW of ∼2.5 l. Cox-proportional hazard models were used to compare survival according to the baseline hydration status for a set of demographic data, comorbid conditions and other predictors. Results. The median hydration state (HS) before the HD treatment (ΔHSpre) for all patients was 8.6 ± 8.9%. The unadjusted gross annual mortality of all patients was 8.5%. The hyperhydrated subgroup (n = 58) presented ΔHSpre = 19.9 ± 5.3% and a gross mortality of 14.7%. The Cox adjusted hazard ratios (HRs) revealed that age (HRage = 1.05, 1/year; P < 0.001), systolic blood pressure (BPsys) (HRBPsys = 0.986 1/mmHg; P = 0.014), diabetes (HRDia = 2.766; P < 0.001), peripheral vascular disease (PVD) (HRPVD = 1.68; P = 0.045) and relative hydration status (ΔHSpre) (HRΔHSpre = 2.102 P = 0.003) were the only significant predictors of mortality in our patient population. Conclusion. The results of our study indicate that the hydration state is an important and independent predictor of mortality in chronic HD patients secondary only to the presence of diabetes. We believe that it is essential to measure the hydration status objectively and quantitatively in order to obtain a more clearly defined assessment of the prognosis of haemodialysis patients.

Towards improved cardiovascular management: the necessity of combining blood pressure and fluid overload

BACKGROUND Hypertension and fluid overload (FO) are well-recognized problems in the chronic kidney disease (CKD) population. While the prevalence of hypertension is well documented, little is known about the severity of FO in this population. METHODS A new bioimpedance spectroscopy device (BCM-Body Composition Monitor) was selected that allows quantitative determination of the deviation in hydration status from normal ranges (DeltaHS). Pre-dialysis systolic blood pressure (BPsys) and DeltaHS was analysed in 500 haemodialysis patients from eight dialysis centres. A graphical tool (HRP-hydration reference plot) was devised allowing DeltaHS to be combined with measurements of BPsys enabling comparison with a matched healthy population (n = 1244). RESULTS Nineteen percent of patients (n = 95) were found to have normal BPsys and DeltaHS in the normal range. Approximately one-third of patients (n = 133) exhibited reasonable control of BPsys and fluids (BPsys <150 mmHg and DeltaHS <2.5 L). In only 15% of patients (n = 74) was hypertension observed (BPsys >150 mmHg) with a concomitant DeltaHS >2.5 L (possible volume-dependent hypertension). In contrast, 13% of patients (n = 69) were hypertensive with DeltaHS <1.1 L (possible essential hypertension). In 10% of patients (n = 52), BPsys <140 mmHg was recorded despite DeltaHS exceeding 2.5 L. CONCLUSION Our study illustrated the wide variability in BPsys regardless of the degree of DeltaHS. The HRP provides an invaluable tool for classifying patients in terms of BPsys and DeltaHS and the proximity of these parameters to reference ranges. This represents an important step towards more objective choice of strategies for the optimal treatment of hypertension and FO. Further studies are required to assess the prognostic and therapeutic role of the HRP.

International Differences in Dialysis Mortality Reflect Background General Population Atherosclerotic Cardiovascular Mortality

Existing national, racial, and ethnic differences in dialysis patient mortality rates largely are unexplained. This study aimed to test the hypothesis that mortality rates related to atherosclerotic cardiovascular disease (ASCVD) in dialysis populations (DP) and in the background general populations (GP) are correlated. In a cross-sectional, multinational study, all-cause and ASCVD mortality rates were compared between GP and DP using the most recent data from the World Health Organization mortality database (67 countries; 1,571,852,000 population) and from national renal registries (26 countries; 623,900 population). Across GP of 67 countries (14,082,146 deaths), all-cause mortality rates (median 8.88 per 1000 population; range 1.93 to 15.40) were strongly related to ASCVD mortality rates (median 3.21; range 0.53 to 8.69), with Eastern European countries clustering in the upper and Southeast and East Asian countries in the lower rate ranges. Across DP (103,432 deaths), mortality rates from all causes (median 166.20; range 54.47 to 268.80) and from ASCVD (median 63.39 per 1000 population; range 21.52 to 162.40) were higher and strongly correlated. ASCVD mortality rates in DP and in the GP were significantly correlated; the relationship became even stronger after adjustment for age (R(2) = 0.56, P < 0.0001). A substantial portion of the variability in mortality rates that were observed across DP worldwide is attributable to the variability in background ASCVD mortality rates in the respective GP. Genetic and environmental factors may underlie these differences.

Angiotensin II Type 1 Receptor Gene Polymorphism in End-Stage Renal Disease

The genes of the renin-angiotensin system (RAS) are involved in progression of renal failure. We examined the A1166C polymorphism at the angiotensin II type 1 (AT1R) locus in patients with end-stage renal disease (ESRD). The distribution of genotype and allele frequencies was compared in 430 dialysis patients and 260 healthy controls. DNA samples were amplified by the polymerase chain reaction (PCR) and amplification products were digested with BsuRI restriction enzyme. In the presence of cytosine (C) there is a restriction site for this enzyme, giving a fragment of 231 bp (C allele), whereas undigested 255 bp fragment indicates the presence of the A allele. The higher frequency of combined AC and CC genotypes was observed in the patient group than in controls (48.6 vs. 39.5%, p < 0.05). The average time from the onset of renal disease to ESRD in patients with C allele was significantly shorter than in those with AA genotype (6.3 vs. 13 years, p < 0.01). Positive family history of renal disease in patients with AC/CC genotype seems to increase this effect. Our results indicate that the presence of C allele of the AT1R locus polymorphism might be associated with faster deterioration of renal function.

Relative underestimation of fluid removal during hemodialysis hypotension measured by whole body bioimpedance.

Whole body bioimpedance is considered helpful in monitoring the removal of excess body water by ultrafiltration in hemodialysis patients. In this study, the cumulative, estimated decrease in extracellular volume (Vest) modeled from whole body bioimpedance data was compared with measured volume (Vmeas) removed by ultrafiltration (UFR = 1.01 ± 0.31 L/hr) in 12 patients during 36 high efficiency hemodialysis treatments. In the mean, estimated (Vest=3.0 ± 1.4 L) and measured volumes (Vmeas=3.4 ± 1.1 L) correlated linearly: Vest = 1.05 x Vmeas − 0.60, r2 = 0.68. Patients developed hypotension in half the treatments. Except for a larger decrease in systolic blood pressures in hypotensive (34 ± 24 mmHg) vs. stable (14 ± 15 mmHg) treatments, patient and treatment characteristics were not different between groups. However, at the end of hemodialysis, the difference Vest − Vmeas was − 0.8 ± 0.9 L in hypotensive, and only 0.1 ± 0.4 L in stable patients (p < 0.05). The difference between Vest and Vmeas can be explained by a predominant removal of excess body water from central body compartments such as the trunk and the central blood volume during hypotension. These compartments are not adequately measured by whole body bioimpedance techniques. However, this information could be helpful in identifying patients with delayed peripheral fluid removal that may occur when either target weight is too low or UFR rates are too high.

Clinical management of atypical carcinoid and large-cell neuroendocrine carcinoma: a multicentre study on behalf of the European Association of Thoracic Surgeons (ESTS) Neuroendocrine Tumours of the Lung Working Group †

OBJECTIVES In 2012, the European Society of Thoracic Surgeons (ESTS) created the Lung Neuroendocrine Tumors Working Group (NETs-WG) with the aim to develop scientific knowledge on clinical management of such rare neoplasms. This paper outlines the outcome and prognostic factors of two aggressive NETs: atypical carcinoids (ACs) and large-cell neuroendocrine carcinomas (LCNCs). METHODS Using the ESTS NETs-WG database, we retrospectively collected data on 261 patients in seven institutions in Europe, between 1994 and 2011. We used a Cox regression model to evaluate variables affecting patient survival and disease-free survival. Univariate and multivariate analysis were also carried out. RESULTS Five-year overall survival rates for ACs and LCNCs were 77 vs 28% (P < 0.001), respectively. We found that for ACs, age (P < 0.001), tumour size (P = 0.015) and sub-lobar surgical resection (P = 0.005) were independent negative prognostic factors; for LCNCs, only pTNM stage III tumours (P = 0.016) negatively affected outcome in the multivariate analysis. Local recurrences and distant metastases developed in 93 patients and were statistically more frequent in LCNCs (P = 0.02). CONCLUSIONS The biological aggressiveness of ACs and LCNCs has been demonstrated with this study. Our aim is to confirm these results with enhanced data collection through the ESTS NETs database.

Phosphate, urea and creatinine clearances: haemodialysis adequacy assessed by weekly monitoring

BACKGROUND The specific distribution of phosphate and the control mechanisms for its plasma level makes phosphate kinetics during haemodialysis (HD) considerably different from those of urea and creatinine and makes the quantitative evaluation of adequacy of phosphate removal difficult. We propose the application of equivalent continuous clearance (ECC) as a phosphate adequacy parameter and compare it with ECC for creatinine and urea. METHODS Three consecutive dialysis sessions were evaluated for 25 patients on maintenance HD. Concentrations of phosphate, urea and creatinine in plasma were measured every 1h during the treatment and 45 min after, and every 30 min in dialysate. ECC was calculated using the removed solute mass assessed in dialysate and weekly solute profile in plasma. Similar calculations were performed also for the midweek dialysis session only. Different versions of the reference concentration for ECC were applied. RESULTS ECC with peak average reference concentration was 5.4 ± 1.0 for phosphate, 7.0 ± 1.0 for urea and 4.7 ± 1.0 mL/min for creatinine. ECC for urea and creatinine were well correlated in contrast to the correlations of ECC for phosphate versus urea and creatinine. Midweek ECC were higher than weekly ECC, but they were well correlated for urea and creatinine, but only weakly for phosphate. CONCLUSIONS HD adequacy monitoring for phosphate may be performed using ECC, but it is less predictable than similar indices for urea and creatinine. The values of ECC for phosphate are within the range expected for its molecular size compared with those for urea and creatinine.

Polymorphism in microRNA-196a2 contributes to the risk of cardiovascular disease in type 2 diabetes patients

AIMS To investigate the effect of the microRNA-196a2 gene polymorphism (rs11614913) on risk of cardiovascular disease in type 2 diabetes patients. METHODS We examined 920 patients with diabetes and 834 healthy controls. All subjects were genotyped for the miRNA-196a2 SNP by polymerase chain reaction (PCR) and restriction analysis. RESULTS The genotype distribution among controls and patients was in Hardy-Weinberg equilibrium (p=0.227 and 0.308, respectively). The frequency of the T allele was lower in patients than in controls (p=0.044). The odds ratio 0.66 (95% CI 0.54-0.79) suggests an association of the T allele with decreased risk of T2DM. For the main purpose of the study, T2DM patients were stratified into patients with CVD and those without it. The T allele and TT genotype were significantly more frequent in patients with CVD compared to those without CVD (p=0.013, p<0.001, respectively). The odds ratio for the T allele in the CVD+subgroup vs. CVD- was 1.76 (1.35-2.30), p<0.0001, mostly due to the overrepresentation of TT homozygotes. The highest risk of development of CVD was observed in the additive model for TT homozygotes (OR 3.33, 95% CI 2.05-5.42, p<0.0001). CONCLUSION Our findings suggest that miRNA-196a2 T/C polymorphism (rs11614913) is associated with an increased risk of CVD in type 2 diabetes patients. This provides further insights on pathogenesis of cardiovascular disease in type 2 diabetes patients.

Effect of Haemodialysis on Regional and Transmural Inhomogeneities of the Ventricular Repolarisation Phase

Recent studies have indicated increased ventricular repolarisation dispersion in haemodialysis (HD) patients. The purpose of this study was to estimate the effect of the HD process on parameters of regional and transmyocardial repolarisation inhomogeneities. Thirty-two selected HD patients (without relevant diseases and medication known to affect the QT interval) were included. Dispersion of the QT corrected interval (QT-c-D) and the corrected interval between the peak and the end of the T wave (Tpe-c-D) were evaluated before and after HD, and in controls. Blood chemistry and extracellular body water (ECW) were evaluated before and after HD. Predialysis QT-c-D and Tpe-c-D were higher in patients (53.40 ± 17.39 and 47.50 ± 13.68 ms, respectively) than in controls (34.91 ± 17.70 ms, p < 0.001 and 31.9 ± 16.76 ms, p < 0.001, respectively). HD induced an increase in the QT-c-D (67.59 ± 19.40 ms; p < 0.001) and Tpe-c-D (62.89 ± 14.33 ms; p < 0.001). Stepwise multiple regression identified the independent risk factors of QT-c-D (the differences between pre- and postdialysis phosphorus, potassium and calcium levels and ECW values) and Tpe-c-D (the differences between pre- and postdialysis phosphorus levels, calcium levels and ECW values) increases, induced by the HD process. The HD process increases regional and transmyocardial repolarisation phase inhomogeneities in HD patients. Changes of phosphorus, calcium and potassium levels plus ECW values seem to be important predisposing factors as far as the increase in ventricular inhomogeneities in HD patients is concerned.

Continuous veno-venous hemofiltration to adjust fluid volume excess in septic shock patients reduces intra-abdominal pressure.

OBJECTIVE To analyze the effect and the time course of continuous veno-venous hemofiltration (CVVH) with net ultrafiltration (UF) on intra-abdominal pressure (IAP) body fluid volumes in septic shock patients with acute kidney injury (AKI). METHODS Patients were studied at baseline and after 6, 12, 24, 48, 72, and 96 hours of CVVH treatment. IAP was measured via the bladder, and abdominal perfusion pressure (APP) was calculated as mean arterial pressure minus IAP. Fluid volume excess (VE), total body water (TBW), extracellular body water (ECW), and intracellular body water (ICW) were derived from wholebody bioimpedance analysis (BIA). RESULTS 30 patients entered final analysis, of which 6 died during CVVH (non-survivors). Fluid VE, TBW, ECW, ICW, and IAP significantly decreased in 24 survivors, whereas these variables remained essentially unchangedin non-survivors. APP slowly increased in survivors, while it did not change in nonsurvivors. IAP strongly correlated with VEin survivors: The lower the IAP, the lower the fluid volume excess. CONCLUSION CVVH with net UF successfully reduced IAP, TBW, ECW, and ICW in critically ill patients who survived 96 h of CVVH. Failure to increase APP was associated with fatal outcome, and, finally, IAP correlated with fluid volume excess. BIA could be helpful to monitor fluid status in patients with AKI.