Infodemiology of renal diseases: a novel opportunity to investigate public global interest.

OBJECTIVE: The aim of this study was to investigate the global community interest about renal diseases through relative search volumes (RSVs) of Google Trends (GT). MATERIALS AND METHODS: The online interest for the search terms hematuria (H), proteinuria (P), chronic kidney disease (CKD) and dialysis (D) was measured by evaluating RSVs from 2010 to 2019. All countries listed in GT were analysed and those presenting RSVs related to all search terms were considered following geographical position. RESULTS: Mean values of RSVs for D, CKD, H and P were 80±9%, 11±2%, 17±2% and 11±1%, respectively. D is the search term most frequently typed in English-speaking countries. On the other hand, in Latin Countries, the interest for P and H was higher than D. Searching for D, CKD and H are highly correlated whilst correlation coefficients between RSVs for D, CKD, and H with P are lower. Since 2010, the interest for renal diseases maintained stable. CONCLUSIONS: GT is a reliable tool in evaluating global interest for renal diseases in different geographical areas and temporal patterns. Although infodemiology represents a method for investigating the dissemination of information at a global level, our results suggest the need for increasing general population's interest for renal diseases especially, and move from simple interest to global awareness in the view of prevention strategies.

Present and future of kidney replacement therapy in Italy: the perspective from Italian Dialysis and Transplantation Registry (IDTR).

Incidence of kidney replacement therapy (KRT) stabilizes or declines both in Europe and in the US; however, it is predictable that global prevalence of KRT will double by 2030. In this paper, we focus on the patterns of incidence, mortality, and prevalence of KRT in Italy, and we compare, when possible, the findings with other countries. The Italian Dialysis and Transplantation Registry (IDTR) currently collects aggregate data from regional registries. In Italy, KRT yearly incidence is around 160 patients per million population (pmp). This incidence showed an increasing trend up until 2011 with an average annual percentage change (AAPC) of 1.8%, after which it stabilized. Older age is an important determinant for KRT incidence, and it is strongly associated with the variability between Italian regions. Incidence is very stable within patients less than 50 years old; however, it greatly differs between regions for patients over 75 years old, ranging from 400 to 900 pmp. Moreover, the incidence for patients over 50 years old declined from 366 pmp in 2011 to 285 in 2017. An age-period-cohort (APC) model showed a very strong cohort effect, which shows the decline in incidence seems mainly due to the better health conditions of people born after 1940. Mortality rate in KRT patients was 109 per 1000 patient-year (py) between 2011 and 2017 with great differences among treatment modalities: 162 per 1000 py in haemodialysis, 117 per 1000 py in peritoneal dialysis, and 16 per 1000 py in kidney transplantation. Premature death is better detected by the standard expected years of life lost (YLL). The distribution of YLL rate per age shows a sharp increase between 40 and 70 years old both in haemodialysis and peritoneal dialysis patients with an AAPC of 5.2% and 4.1% respectively. Transplanted patients experience a very low YLL rate at any age. KRT prevalence was 1118 pmp in 2017 and it should be close to 1175 pmp by 2025 with a projected increase of transplanted patients' prevalence to 500 pmp, and a decrease of dialysis patients from 714 to 680 pmp. The proportion of patients treated with one of the three modalities strictly depends on age, with a sharp increase of haemodialysis after the age of 50. All data suggests the necessity to improve the care of middle and older age patients who experience the higher incidence of disease and mortality.

Evolution of transmitted HIV-1 drug resistance and viral subtypes circulation in Italy from 2006 to 2016.

OBJECTIVES: The aim was to evaluate the evolution of transmitted HIV-1 drug resistance (TDR) prevalence in antiretroviral therapy (ART)-naïve patients from 2006 to 2016. METHODS: HIV-1 sequences were retrieved from the Antiviral Response Cohort Analysis (ARCA) database and TDR was defined as detection of at least one mutation from the World Health Organization (WHO) surveillance list. RESULTS: We included protease/reverse transcriptase sequences from 3573 patients; 455 had also integrase sequences. Overall, 68.1% of the patients were Italian, the median CD4 count was 348 cells/µL [interquartile range (IQR) 169-521 cells/µL], and the median viral load was 4.7 log10 HIV-1 RNA copies/mL (IQR 4.1-5.3 log10 copies/mL). TDR was detected in 10.3% of patients: 6% carried mutations to nucleos(t)ide reverse transcriptase inhibitors (NRTIs), 4.4% to nonnucleos(t)ide reverse transcriptase inhibitors (NNRTIs), 2.3% to protease inhibitors (PIs), 0.2% to integrase strand transfer inhibitors (INSTIs) and 2.1% to at least two drug classes. TDR declined from 14.5% in 2006 to 7.3% in 2016 (P = 0.003): TDR to NRTIs from 9.9 to 2.9% (P = 0.003) and TDR to NNRTIs from 5.1 to 3.7% (P = 0.028); PI TDR remained stable. The proportion carrying subtype B virus declined from 76.5 to 50% (P < 0.001). The prevalence of TDR was higher in subtype B vs. non-B (12.6 vs. 4.9%, respectively; P < 0.001) and declined significantly in subtype B (from 17.1 to 8.8%; P = 0.04) but not in non-B subtypes (from 6.1 to 5.8%; P = 0.44). Adjusting for country of origin, predictors of TDR were subtype B [adjusted odds ratio (AOR) for subtype B vs. non-B 2.91; 95% confidence interval (CI) 1.93-4.39; P < 0.001], lower viral load (per log10 higher: AOR 0.86; 95% CI 0.75-0.99; P = 0.03), site in northern Italy (AOR for southern Italy/island vs. northern Italy, 0.61; 95% CI 0.40-0.91; P = 0.01), and earlier calendar year (per 1 year more recent: AOR 0.95; 95% CI 0.91-0.99; P = 0.02). CONCLUSIONS: The prevalence of HIV-1 TDR has declined during the last 10 years in Italy.

Venetoclax: Bcl-2 inhibition for the treatment of chronic lymphocytic leukemia.

Venetoclax (ABT-199) is a small-molecule selective oral inhibitor of the antiapoptotic protein Bcl-2 that promotes programmed cell death of chronic lymphocytic leukemia (CLL) cells regulating the release of proapoptotic factors, such as Smac/Diablo, apoptosis-inducing factor (AIF) and cytochrome c. In April 2016, the U.S. Food and Drug Administration (FDA) granted accelerated approval to venetoclax for patients diagnosed with CLL with 17p deletion, as detected by an FDA-approved test, who have received at least one prior therapy. This review will focus on the mechanism of action, preclinical studies and clinical development of venetoclax both as a monotherapy and in combination with other drugs for CLL in the current milieu of therapy dominated by novel tyrosine kinase inhibitors such as ibrutinib and idelalisib.

Use of efavirenz or atazanavir/ritonavir is associated with better clinical outcomes of HAART compared to other protease inhibitors: routine evidence from the Italian MASTER Cohort.

Randomized trials and observational cohorts reported higher rates of virological suppression after highly active antiretroviral therapy (HAART) including efavirenz (EFV), compared with boosted protease inhibitors (PIs). Correlations with immunological and clinical outcomes are unclear. Patients of the Italian MASTER cohort who started HAART from 2000 to 2010 were selected. Outstanding outcome (composite outcome for success (COS)) was introduced. We evaluated predictors of COS (no AIDS plus CD4+ count >500/mm(3)plus HIV-RNA <500 copies/mL) and of eight single outcomes either at month 6 or at year 3. Multivariable logistic regression was conducted. There were 6259 patients selected. Patients on EFV (43%) were younger, had greater CD4+ count, presented with AIDS less frequently, and more were Italians. At year 3, 90% of patients had HIV RNA <500 copies/mL, but only 41.4% were prescribed EFV, vs. 34.1% prescribed boosted PIs achieved COS (p <0.0001). At multivariable analysis, patients on lopinavir/ritonavir had an odds ratio of 0.70 for COS at year 3 (p <0.0001). Foreign origin and positive hepatitis C virus-Ab were independently associated with worse outcome (OR 0.54, p <0.0001 and OR 0.70, p 0.01, respectively). Patients on boosted PIs developed AIDS more frequently either at month 6 (13.8% vs. 7.6%, p <0.0001) or at year 3 (17.1% vs. 13.8%, p <0.0001). At year 3, deaths of patients starting EFV were 3%, vs. 5% on boosted PIs (p 0.008). In this study, naïve patients on EFV performed better than those on boosted PIs after adjustment for imbalances at baseline. Even when virological control is achieved, COS is relatively rare. Hepatitis C virus-positive patients and those of foreign origin are at risk of not obtaining COS.

The EQUAL study: a European study in chronic kidney disease stage 4 patients.

The timing of the start of dialysis in elderly patients is driven by the desire to optimize the quantity and quality of life. Limited data exist on how the level of renal function, and uraemic signs and symptoms can be used to determine when dialysis should be initiated in elderly patients. EQUAL, an international prospective cohort study, aims to address these issues. To this end, it will enroll 3500 patients >65 years of age with CKD of various aetiologies under the care of nephrologists. These patients will be followed until death, discharge from the nephrology clinic to primary care or until the end of the observation period after 4 years of follow-up. At the time of enrollment, patients must have an estimated glomerular filtration rate (eGFR) of 20 mL/min/1.73 m(2) or lower, but should not yet be on dialysis. Standardized data collection will include demographics, lifestyle, comorbidities, uraemic signs and symptoms, nutritional status, medication and routine blood and urine biochemistry. It will also comprise quality of life data, information on decision making including patients preferences and patients satisfaction.

Waist circumference modifies the relationship between the adipose tissue cytokines leptin and adiponectin and all-cause and cardiovascular mortality in haemodialysis patients.

BACKGROUND: the relationships between the adipose tissue cytokines leptin and adiponectin (ADPN) and clinical outcomes have not been well studied in haemodialysis (HD) patients and remain highly controversial. As central obesity is an important modifier of the effect of various risk factors for clinical outcomes, we tested the hypothesis that waist circumference (WC) modifies the link between these cytokines and both overall and cardiovascular death in HD patients. METHODS: a total of 537 HD patients participated in a prospective cohort study. RESULTS: leptin and ADPN were inversely related to each other and robustly associated with WC (P < 0.001). During follow-up (average 29 months, range 1-47 months) 182 patients died, including 115 from cardiovascular causes. In analyses adjusting for potential confounders, there were strong interactions between leptin and WC in relationship to both all-cause (P < 0.001) and cardiovascular death (P = 0.002). Accordingly, a fixed excess of leptin signalled a gradually increasing risk for all-cause and cardiovascular mortality in patients with a large WC but an opposite effect in those with a relatively small WC. An interaction between ADPN and WC for all-cause (P = 0.01) and cardiovascular mortality (P = 0.01) emerged only in models excluding the leptin-WC interaction, suggesting that these adipokines share a common pathway leading to adverse clinical events in HD patients. CONCLUSIONS: the predictive value of leptin and ADPN for all-cause and cardiovascular death in HD patients appears to be critically dependent on WC. These findings support the hypothesis that disturbances in adipokine levels are involved in adverse clinical outcomes in HD patients with abdominal obesity.

[Census 2004 of the Italian renal and dialysis units. Basilicata - Calabria - Puglia]. / Censimento 2004 dei Centri di Nefrologia e Dialisi Italiani. Basilicata - Calabria - Puglia.

The Italian Society of Nephrology (SIN) sponsored in 2004 a National Census of the Italian renal and dialysis units. This paper presents the main structural, technical, organizational features, as well as the human resources and the activities of three South-East regions of Italy: Basilicata (B), Calabria (C), and Puglia (P). EPIDEMIOLOGY: incidence of dialysis patients was 149 per million population (pmp) in B, 134 pmp in C and 172 pmp in P; prevalence of dialysis patients 729, 694 and 886 pmp, respectively; prevalence of transplanted patients 188 in B, 264 in C and 249 pmp in P; gross mortality rate of dialysis patients was 12.7% (B), 12.2% (C) and 10.8% (P). TYPE OF VASCULAR ACCESS IN PREVALENT DIALYSIS PATIENTS: arteriovenous fistula: 83.9% (B), 87.7% (C) and 86.5% (P); central venous catheter: 14.2% (B), 8.4% (C) and 11.2% (P); vascular graft 1.9% (B), 3.9% (C) and 2.3% (P). STRUCTURAL RESOURCES: nephrological beds 37, 34 and 88 pmp, respectively; dialysis stations 265, 209 and 207 pmp. PERSONNEL RESOURCES: renal physicians 45 (B), 67 (C) and 64(P) pmp; renal nurses 189, 190 and 207 pmp; each nephrologist cares for 16 (B), 10 (C) and 14 (P) dialysis patients, whereas each renal nurse takes care of 3.8 (B), 3.7 (C) and 4.3 (P) dialysis patients. ACTIVITY: hospitalizations 1378, 1834 and 3439 pmp, respectively; renal biopsies 40 (B), 64 (C) and 107 (P) pmp. The main goal of this project was to create a reference for benchmarking studies. Therefore, data from the Puglia region were compared to data from other regions with similar population size (such as Piemonte and Emilia-Romagna). Moreover, a Census may became a useful qualitative tool for renal registries: this report compares data from the Census with data collected by the dialysis and transplantation registry of the Puglia region. Generally speaking, prevalence for Basilicata and Calabria is close to the Italian one, whereas incidence is inferior; things are opposite in Puglia. Furthermore, compared to Basilicata, Calabria and Italy on average, the Puglia region shows a significant higher number of in-patient beds and a lower DRG weight. Compared to Piemonte, Emilia Romagna and Italy on average, all the three South-East regions do not show differences in number/pmp of dialysis centres. More physicians (nephrologists = 80%) are reported to be active in Puglia and Calabria, compared to Piemonte and Emilia Romagna. Nurses in Puglia look after a greater number of dialysis patients than in Calabria and Basilicata. The number of renal biopsies/ pmp is similar to the Italian mean only in Puglia; it is inferior in the other two regions. These data highlight many differences among these three South-East regions, as well as among Piemonte, Emilia Romagna and Puglia. A relevant inequality in health care structures and resources has been found and discussed.

[Standardization criteria to ensure the uniformity of data collection by the Italian Registry of Dialysis and Transplantation]. / Criteri di uniformità per la raccolta dei dati del Registro Italiano di Dialisi e Trapianto.

The Italian Registry of Dialysis and Transplantation (RIDT) collects data concerning patients in renal replacement therapy (RRT) sent from Regional Registries. Until 2003, the data were sent in summary tables. From 2004, each region has been sending patient data as single non-summarized forms (i.e. one record for each patient). This paper summarizes the collection criteria and the ideal method to codify data ensuring that data sent to the RIDT are consistent. This standardization process is necessary to ensure the statistical analyzability of the data and their comparability with data from other registries. Moreover, the standardization process is the initial step in allowing the RIDT to obtain clinical data to transform the registry from an epidemiological registry to a clinical governance instrument.

[Italian Registry of Dialysis and Transplantation: 1996-2001 experience]. / Registro Italiano Dialisi e Trapianto. Esperienza 1996-2001.

The Italian Registry of Dialysis and Transplantation (RIDT) was born in 1996 under the aegis of the Italian Society of Nephrology, and it is organized as a federation of regional registries. This study aimed to completely revise the epidemiological data collected during the first 5 yrs (1996-2001) of RIDT activity to evaluate the trends of the main epidemiological features. During this period, regional registries were not always able to assure complete and exhaustive information according to RIDT requirements, owing to different levels of organization and functioning. To avoid any possible error in data analysis, information inadequately assessed was refused. The incidence of end-stage renal disease (ESRD) patients on renal replacement therapy (RRT) in Italy has increased from 114 pmp in 1996 to 139 pmp in 2001, that means an increase of 3.5%/yr, corresponding to 5718 patients during 1996 and 8000 patients during 2001. Primary renal diseases (according to the EDTA) in incident ESRD patients are vascular and diabetic nephropathy. Main dialysis modality in incident patients was hemodialysis (HD) (85%), while peritoneal dialysis (PD) was only 15%; pre-emptive transplantation was a very unusual modality. The prevalence of ESRD patients at 31 December was 693 pmp in 1996 and 827 pmp in 2001; among dialysis patients, the corresponding rates were 575 pmp and 657 pmp, respectively. Consequently, the number of dialyzed patients increased, respectively, from 28892 to 37919. The prevalent dialysis modality was bicarbonate dialysis in 74% of cases, followed by hemodiafiltration (HDF) in 15%, continuous ambulatory peritoneal dialysis (CAPD) in 7% and APD in 3%. The gross mortality rate in dialyzed patients was stable during this period, at approximately 14%, the main causes of death being cardiovascular diseases and cachexia.

[Xerostomia and Xerophthalmia in haemodialysis patients]. / Xerostomia e Xeroftalmia nei pazienti in dialisi.

BACKGROUND: A reduction in salivary and lachrymal secretion has been described in many pathologies; however, such alterations have not been described in patients with renal failure. This study was designed to estimate the frequency of alterations in salivary and lachrymal secretion in haemodialysed patients. PATIENTS ABD METHODS: We studied 63 haemodialysed patients and 23 healthy control subjects. In all of them we tested salivary secretion (Saxon test), lachrymal secretion (Shirmer test) as well as the presence of symptoms of xerostomia and xerophthalmia. In a subgroup of patients We investigated any evidence of ocular lesions and tissue damage of salivary glands (histopathology). We also tested the correlation between salivary and lachrymal secretion and autonomic nervous system function. Furthermore, we also studied the association between xerostomia and xerophthalmia and serum auto antibodies (anti nuclear, anti-Ro (SS-A), anti-La (SS-B)) and anti HCV antibodies. RESULTS: On average salivary and the lachrymal secretion was markedly reduced in uraemic patients compared with healthy controls. We found the alterations in salivary glands function to be strongly related to salivary glands fibrosis and atrophy and independent of amyloid accumulation. On the other hand, we observed that xerostomia and xerophthalmia were unrelated to autonomic dysfunction as well as to HCV infection and circulating auto antibodies. Moreover, xerophthalmia was frequently associated with evidence of corneal damage. CONCLUSIONS: Reduced salivary and lachrymal secretion is frequent in uraemic patients. Such alterations are often asymptomatic and could be an expression of the accelerated age-dependent decline in glandular function and the attendant fibrosis and atrophy.

Level of minimal residual disease after consolidation therapy predicts outcome in acute myeloid leukemia.

We used flow cytometry to quantify minimal residual disease (MRD) in 56 patients with acute myeloid leukemia (AML) expressing a leukemia-associated phenotype. Thirty-four patients aged 18 to 60 years were entered into the AML-10 protocol (induction, consolidation, and autologous stem-cell transplantation [ASCT]), whereas 22 patients older than 60 years received the AML-13 protocol (induction, consolidation, and consolidation II). After induction, the level of MRD that was best associated with treatment outcome was 4.5 x 10(-4) residual leukemic cells. However, the outcome in patients with at least 4.5 x 10(-4) cells (n = 26) was not significantly different from that in patients with fewer leukemic cells (n = 30); there were 15 (58%) relapses in the first group and 12 (40%) relapses in the second. After consolidation, the most predictive MRD cutoff value was 3.5 x 10(-4) cells: 22 patients had an MRD level of 3.5 x 10(-4) cells or higher and 17 (77%) of these patients had relapse, compared with 5 of 29 patients (17%) with lower MRD levels (P <.001). An MRD level of 3.5 x 10(-4) cells or higher after consolidation was significantly correlated with poor or intermediate-risk cytogenetic findings, a multidrug resistance 1 (MDR1) phenotype, short duration of overall survival, and short duration of relapse-free survival (P =.014,.031,.00022, and.00014, respectively). In multivariate analysis, this MRD status was significantly associated with a high frequency of relapse (P <.001) and a short duration of overall (P =.025) and relapse-free survival (P =.007). ASCT did not alter the prognostic effect of high MRD levels after consolidation: the relapse rate after transplantation was 70%. Thus, we found that an MRD level of 3.5 x 10(-4) cells or higher at the end of consolidation strongly predicts relapse and is significantly associated with an MDR1 phenotype and intermediate or unfavorable cytogenetic findings. (Blood. 2000;96:3948-3952)

Plasma adrenomedullin during acute changes in intravascular volume in hemodialysis patients.

BACKGROUND: Adrenomedullin, is a potent vasorelaxant that is highly expressed in the adrenal medulla, kidney, heart and lung. Since there is indirect evidence that hypervolemia enhances the release of this peptide, we measured plasma adrenomedullin in 9 uremic patients on chronic dialysis treatment and in 10 healthy subjects matched for age and gender. METHODS: Measurements were performed in baseline conditions, after isotonic fluid subtraction (by isolated ultrafiltration) and during a 70 degrees tilt. Tilt was performed in volume-depleted state, that is, after isolated ultrafiltration (UF). In the control experiment patients underwent sham UF (UF = 0) followed by a period of supine resting identical to the one they had spent in tilted position in the active experiment. Adrenomedullin was measured on pre-extracted plasma samples (Sep-Pak C-18 cartridges) by a specific RIA for human adrenomedullin 1-52. RESULTS: The average plasma adrenomedullin was 2.6 times higher (P < 0.01) in uremic patients (103 +/- 8 pg/ml) than in healthy subjects (39 +/- 7 pg/ml). After fluid subtraction (-2.6 +/- 0.2 liter) adrenomedullin fell to 79. +/- 8 pg/ml (P = 0.02) but remained well above the upper limit of the 95% CI in normal subjects (52 pg/ml). There was no relationship between adrenomedullin and ANF changes. In the control experiment sham UF did not modify plasma adrenomedullin. Tilt did not significantly change plasma adrenomedullin either in dialysis patients or healthy subjects. CONCLUSIONS: Plasma adrenomedullin is markedly raised in uremic patients on dialysis, which confirms that the kidney has a major role in the clearance of this peptide. However, the fall in plasma adrenomedullin after isolated UF indicates that the plasma concentration of this peptide is influenced by the body fluid volume status. Whether or not adrenomedullin participates in the counter-regulatory response to fluid subtraction in uremic patients remains to be explored by specific antagonists of this substance.

Prognostic relevance of the expression of Tdt and CD7 in 335 cases of acute myeloid leukemia.

We have analyzed the expression of Tdt and CD7 in 335 cases of unequivocal acute myeloid leukemia (AML). Tdt was expressed in 80 (25%) of 321 evaluable cases. Twenty-six of 77 (34%) Tdt+ patients assessable for response, entered complete remission (CR) vs 121 of 209 (58%) Tdt- cases (P < 0.001). CD7 was expressed in 102 of 332 (30%) evaluable cases; 37 of 93 assessable (40%) CD7+ patients attained a CR as compared to 114/204 (56%) CD7- (P = 0.013). Duration of survival was significantly shorter for patients with CD7+ or Tdt+ AML (P = 0.006 and 0.001, respectively). In a multivariate analysis, Tdt was found to significantly adverse achievement of CR (P = 0.018), while CD7 affected duration of CR (P = 0.037). Overall the expression of either Tdt or CD7 correlated with a relatively high expression of CD34 (P < 0.001), GP-170 (P = 0.003), lymphoid antigens (LyAg) (P < 0.001), t(9;22) or anomalies of chromosome 5/7 (P < 0.001). Finally, we pooled the patients into four phenotypic classes, according to the presence of Tdt, CD7 or both: [Tdt-CD7-], [Tdt+CD7-], [Tdt-CD7+] and [Tdt+CD7+]. The category [Tdt+CD7+] was characterized by a more unfavorable outcome as suggested by a lower rate of CR (P < 0.001) and a shorter duration of survival as compared to cases [Tdt-CD7-], [Tdt+CD7-] and [Tdt-CD7+] (P = 0.002). This figure is consistent with the frequent convergence in the subset [Tdt+CD7+] of GP-170 positivity (P = 0.003), translocation t(9;22), anomalies of chromosome 5 and/or 7 (P < 0.001) and signs of lineage infidelity (deviant expression of lymphoid antigens) (P < 0.001). We conclude that the expression of Tdt or CD7 is associated with an unfavorable outcome and that the combination of both defines a clinical subset with a poorer prognosis due to the significantly higher association with MDR phenotype, and 'poor prognostic' chromosomal abnormalities.

Red blood cell depletion of cord blood using hydroxyethylstarch double sedimentation: analysis of 40 cases.

Cord blood has been shown to successfully reconstitute haematopoiesis following allogeneic transplantation in a variety of disorders. A major drawback of cord blood has been the risk of transfusion reaction secondary to ABO incompatibility and reduction in the stem cell pool if cord blood is manipulated to remove red cells. We report our experience on red blood cell depletion of cord blood (CB) with hydroxyethylstarch (HES) double sedimentation. The nucleated and mononucleated cell recovery passed from 78.4% at 90 min to 92.9% at 180 min and from 85% at 90 min to 96% at 180 min, respectively. The overall recovery of CCD34+ cells and of haemopoietic progenitors (CFU-GM) was 90.5% and 83.8%, respectively. The data indicate that HES double sedimentation is a simple and effective technique for cord blood manipulation, but further studies are necessary to evaluate the clonogenic progenitor recovery after thawing.

The influence of volume depletion and central hypovolemia on the plasma concentration of parathyroid hormone in dialysis patients.

Because changes in extracellular volume during dialysis cause reflex neurohonnonal changes that may influence parathyroid hormone (PTH) release independently of calcium, the influence of isotonic volume depletion (by isolated ultrafiltration) and central hypovolemia (70 degrees tilt) on serum PTH1-84 was studied in 16 hemodialysis patients. Tilting was performed in volume depleted state, i.e., immediately after hemodialysis. In the control study, patients underwent sham ultrafiltration (UF = 0) and after dialysis maintained the supine position for the same length of time they remained in the tilt position in the active experiment. Isolated ultrafiltration (-2.3 +/- SEM 0.3 L) caused a 21% fall in mean arterial pressure (from 101 +/- 6 to 80 +/- 6 mmHg, P < 0.01), a fall that was accompanied by a marked increase in plasma catecholamine levels (norepinephrine P < 0.001, epinephrine P < 0.025), in plasma renin activity (P < 0.001) and in plasma arginine vasopressin (P < O.001). Atrial natriuretic factor showed a slight reduction, whereas the plasma endothelin-1 level did not change. Serum Ca showed the expected, hemoconcentration-dependent rise (from 4.1 +/- 0.1 to 4.4 +/- 0.1 meq/L, P < 0.01). Interestingly, UF caused a marked rise in plasma PTH1-84 concentration (from 252 +/- 62 to 335 +/- 72 pg/ml, P < 0.01). UF-induced changes in serum PTH1-84 were related to norepinephrine changes (r = 0.57) as well as to plasma renin activity (r = 0.50). After hemodialysis, tilting induced a pronounced rise in serum PTH1-84 (from 102 +/- 29 to 200 +/- 55 pg/ml), and these changes were slightly related to plasma epinephrine (r = 0.49) but independent of other parameters. In the control experiment, neither sham UF nor recumbency modified serum PTH. In hemodialysis patients, serum PTH is sensitive to changes in extracellular and central blood volume of magnitude sufficient to decrease arterial pressure. Avoiding marked volume stimuli might help to refine the interpretation of the Ca/PTH curves during hemodialysis in these patients.