How to manage catheter-related right atrial thrombosis: Our conservative approach.

BACKGROUND: Catheter-related right atrial thrombosis is an underestimated, severe, and life-threatening complication of any type of central venous catheters. No clear-cut epidemiological data are available. Catheter-related right atrial thrombosis is often asymptomatic; however, it can lead to serious complications and death. CASE SERIES: We report seven catheter-related right atrial thrombosis events occurred in five hemodialysis patients; two recurrences following primary treatment are included in the report, all of them managed with a conservative approach without catheter removal. Systemic anticoagulation (vitamin K antagonists), having a well-defined target of International Normalized Ratio of 2.5-3.0, combined with urokinase as a locking solution at the end of each hemodialysis session were the therapeutic strategy used in all patients. After the first month, the anticoagulation target was reduced to an International Normalized Ratio value of 1.5-2.0 and urokinase to a weekly administration. After sixth months, when no thrombus was identified at transthoracic echocardiographic examinations, the treatment was stopped. No bleeding complications were reported. CONCLUSION: The combination therapy here described is safe, quick, and effective, achieving the goal of not removing catheters.

[Membranoproliferative glomerulonephritis with relapsing episodes of acute kidney injury in the Schnitzler syndrome].

The Schnitzler syndrome (SS) is a rare and underdiagnosed entity that associates a chronic urticarial rash, monoclonal IgM (or sometimes IgG) gammopathy and signs and symptoms of systemic inflammation. During the past 45 years the SS has evolved from an elusive, little-known disorder to the paradigm of a late-onset auto-inflammatory acquired syndrome. Though there is no definite proof of its precise pathogenesis, it should be considered as an acquired disease involving abnormal stimulation of the innate immune system, which can be reversed by the interleukin 1 (IL-1) receptor antagonist anakinra. Here we describe the case of a 56-year-old male Caucasian patient affected by SS and hospitalized several times in our unit because of relapsing episodes of acute kidney injury. He underwent an ultrasound-guided percutaneous kidney biopsy in September 2012, which showed the histologic picture of type I membranoproliferative glomerulonephritis. He has undergone conventional therapies, including nonsteroidal anti-inflammatory drugs, steroids and immunosuppressive drugs; more recently, the IL-1 receptor antagonist anakinra has been prescribed, with striking clinical improvement. Although the literature regarding kidney involvement in the SS is lacking, it can however be so severe, as in the case reported here, to lead us to recommend the systematic search of nephropathy markers in the SS.

Is the removal of a central venous catheter always necessary in the context of catheter-related right atrial thrombosis?

Catheter-related right atrial thrombosis is a severe and life-threatening complication of central venous catheters in both adult and young patients. Catheter-related right atrial thrombosis can occur with any type of central venous catheters, utilized either for hemodialysis or infusion. Up to 30% of patients with central venous catheter are estimated to be affected by catheter-related right atrial thrombosis; however, neither precise epidemiological data nor guidelines regarding medical or surgical treatment are available. This complication seems to be closely associated with positioning of the catheter tip in the atrium, whereas it is unlikely with a tip located within superior vena cava. Herein, we report the case of a patient affected by catheter-related right atrial thrombosis, who showed a quick resolution of thrombosis with a new therapeutic scheme combining loco-regional thrombolytic therapy (urokinase as a locking solution) and systemic anticoagulation therapy (vitamin K antagonists), thus avoiding catheter removal. Neither complications of the combination therapy were reported, nor recurrence of catheter-related right atrial thrombosis occurred. In conclusion, the combination therapy here described was safe, quick and effective, achieving the goal of not removing the catheter.

Kidney involvement in the Schnitzler syndrome, a rare disease.

The Schnitzler syndrome (SS) is a rare and underdiagnosed entity that associates a chronic urticarial rash, monoclonal IgM (or sometimes IgG) gammopathy and signs and symptoms of systemic inflammation. During the past 45 years, the SS has evolved from an elusive little-known disorder to the paradigm of a late-onset acquired auto-inflammatory syndrome. Though there is no definite proof of its precise pathogenesis, it should be considered as an acquired disease involving abnormal stimulation of the innate immune system, which can be reversed by the interleukin-1 receptor antagonist anakinra. It clearly expands our view of this group of rare genetic diseases and makes the concept of auto-inflammation relevant in polygenic acquired diseases as well. Increasing numbers of dermatologists, rheumatologists, allergologists, haematologists and, more recently, nephrologists, recognize the SS. The aim of this review is to focus on kidney involvement in the SS. Although the literature regarding kidney involvement in the SS is very poor it can be severe, as in our own case here reported, leading us to recommend the systematic search for nephropathy markers in the SS.

Ranking of factors determining potassium mass balance in bicarbonate haemodialysis.

BACKGROUND: One of the most important pathogenetic factors involved in the onset of intradialysis arrhytmias is the alteration in electrolyte concentration, particularly potassium (K(+)). METHODS: Two studies were performed: Study A was designed to investigate above all the isolated effect of the factor time t on intradialysis K(+) mass balance (K(+)MB): 11 stable prevalent Caucasian anuric patients underwent one standard (∼4 h) and one long-hour (∼8 h) bicarbonate haemodialysis (HD) session. The latter were pair-matched as far as the dialysate and blood volume processed (90 L) and volume of ultrafiltration are concerned. Study B was designed to identify and rank the other factors determining intradialysis K(+)MB: 63 stable prevalent Caucasian anuric patients underwent one 4-h standard bicarbonate HD session. Dialysate K(+) concentration was 2.0 mmol/L in both studies. Blood samples were obtained from the inlet blood tubing immediately before the onset of dialysis and at t60, t120, t180 min and at end of the 4- and 8-h sessions for the measurement of plasma K(+), blood bicarbonates and blood pH. Additional blood samples were obtained at t360 min for the 8 h sessions. Direct dialysate quantification was utilized for K(+)MBs. Direct potentiometry with an ion-selective electrode was used for K(+) measurements. RESULTS: Study A: mean K(+)MBs were significantly higher in the 8-h sessions (4 h: -88.4 ± 23.2 SD mmol versus 8 h: -101.9 ± 32.2 mmol; P = 0.02). Bivariate linear regression analyses showed that only mean plasma K(+), area under the curve (AUC) of the hourly inlet dialyser diffusion concentration gradient of K(+) (hcgAUCK(+)) and AUC of blood bicarbonates and mean blood bicarbonates were significantly related to K(+)MB in both 4- and 8-h sessions. A multiple linear regression output with K(+)MB as dependent variable showed that only mean plasma K(+), hcgAUCK(+) and duration of HD sessions per se remained statistically significant. Study B: mean K(+)MBs were -86.7 ± 22.6 mmol. Bivariate linear regression analyses showed that only mean plasma K(+), hcgAUCK(+) and mean blood bicarbonates were significantly related to K(+)MB. Again, only mean plasma K(+) and hcgAUCK(+) predicted K(+)MB at the multiple linear regression analysis. CONCLUSIONS: Our studies enabled to establish the ranking of factors determining intradialysis K(+)MB: plasma K(+) → dialysate K(+) gradient is the main determinant; acid-base balance plays a much less important role. The duration of HD session per se is an independent determinant of K(+)MB.

Sodium setpoint and gradient in bicarbonate hemodialysis.

BACKGROUND: The demonstration of an individual osmolar setpoint in hemodialysis (HD) is crucial to individualize dialysate sodium concentrations. Furthermore, the diffusive gradient between plasma and dialysate sodium is important in the "fine tuning" of the intradialytic sodium mass balance (MB). METHODS: The design of this study included part A: a retrospective analysis of predialysis plasma sodium concentrations extracted from a 6-year database in our HD population (147 prevalent white anuric patients); and part B: study of intradialytic sodium kinetics in 48 patients undergoing one 4-hour bicarbonate HD session. Direct potentiometry with an ion-selective electrode was used for sodium measurements. RESULTS: Study part A: the mean number of plasma sodium measurements per patient was 16.06 ± 14.03 over a mean follow-up of 3.55 ± 1.76 years. The mean of the averaged plasma sodium concentrations was 136.7 ± 2.1 mmol/L, with a low mean intraindividual coefficient of variation (1.39 ± 0.4). Study part B: mean predialysis and postdialysis plasma sodium concentrations were 135.8 ± 0.9 and 138.0 ± 0.9 mmol/L (p<0.001). Mean inlet dialyzer sodium concentration was 138.7 ± 1.1 mmol/L; the hourly diffusion concentration gradients showed a statistically significant transfer from dialysate to plasma (Wilks ? <0.0001). A statistically significant relationship was found between sodium MB and diffusion gradient (p<0.02), and between sodium MB and ultrafiltration volume (p<0.01). CONCLUSIONS: A relatively "fixed" and individual osmolar setpoint in HD patients was shown for the first time in a long-term follow-up. A dialysate sodium concentration of 140 mmol/L determined a dialysate to plasma sodium gradient.

Effect of dialysate calcium concentrations on parathyroid hormone and calcium balance during a single dialysis session using bicarbonate hemodialysis: a crossover clinical trial.

BACKGROUND: In bicarbonate-based hemodialysis, dialysate total calcium (tCa) concentration may have effects on mineral metabolism. STUDY DESIGN: Randomized crossover trial of 3 dialysate tCa concentrations (2.5, 2.75, and 3.0 mEq/L). SETTING & PARTICIPANTS: 22 stable anuric uremic patients underwent three 4-hour bicarbonate hemodialysis sessions with the 3 different dialysate tCa concentrations using a single-pass batch dialysis system. OUTCOMES: Hourly measurements of plasma water ionized calcium (iCa) and plasma parathyroid hormone (PTH) concentrations. tCa mass balances were measured from the dialysate side. RESULTS: Hourly plasma water iCa concentrations were higher with a dialysate tCa concentration of 3.0 compared with 2.75 and 2.5 mEq/L (P < 0.05), as were iCa concentrations at the end of dialysis sessions (2.66 ± 0.1, 2.56 ± 0.12, and 2.4 ± 0.08 mEq/L, respectively; P < 0.001). Mean tCa mass balance values (diffusion gradient from the dialysate to the patient) were positive with all dialysate tCa concentrations and increased progressively with dialysate tCa concentration (75 ± 122, 182 ± 125, and 293 ± 228 mg, respectively; P < 0.001). Plasma PTH levels increased during dialysis using dialysate tCa concentration of 2.5 mEq/L (mean increase, 225 ± 312 pg/mL) and decreased with dialysate tCa concentrations of 2.75 and 3.0 mEq/L (mean decreases, 68 ± 325 and 99 ± 432 pg/mL, respectively). LIMITATIONS: Small sample size and lack of measurement of total-body calcium mass balances. CONCLUSIONS: A dialysate tCa concentration of 2.75 mEq/L might be preferable to 2.5 or 3.0 mEq/L because it is associated with mildly positive tCa mass balance values, plasma water iCa levels in the reference range, and stable PTH levels during dialysis.

The systemic capillary leak syndrome: a scarcely known nephrological entity.

The idiopathic systemic capillary leak syndrome (SCLS) is a rare life-threatening disorder characterized by periodic episodes of hypovolemic shock, due to plasma leakage from the intravascular to the interstitial space, as reflected by accompanying hypoalbuminemia, hemoconcentration and edema. Here we report the case of a 65-year-old woman affected by SCLS who required aggressive resuscitation with norepinephrine, steroids, albumin and crystalloids. Then, a long-term prophylaxis with a ß(2)-adrenergic receptor agonist and theophylline was started. In conclusion, though SCLS is a rare entity, the associated morbidity and mortality require the physician's awareness to provide timely therapy. Underrecognition in the medical community and rarity of this syndrome have precluded analysis by rational clinical trial designs that are necessary to determine more targeted and adequate therapy. This report is meant to enhance awareness of SCLS in the nephrology community.

Effects of different dialysate calcium concentrations on intradialysis hemodynamic stability.

BACKGROUND: The interplay of correct solute mass balances, such as those of sodium (Na+), potassium (K+) and total calcium (tCa) (Na+MB, K+MB and tCaMB, respectively) with adequate ultrafiltration volumes (VUF) is crucial to achieving hemodynamic stability during hemodialysis (HD). METHODS: Twenty-two stable anuric uremic patients underwent three 4-hour bicarbonate HD sessions, each with a different dialysate tCa concentration (1.25, 1.375 and 1.50 mmol/L). The GENIUS dialysis system (Fresenius Medical Care, Germany) was used. Volumes of blood and dialysate processed, VUF and dialysate Na+ and K+ concentrations were prescribed to be the same. Hourly measurements of plasma water ionized Ca (Ca++), Na+ and K+ were made, and their trends analyzed. tCaMBs, Na+MBs and K+MBs were determined. Systolic (SBP), diastolic (DBP) blood pressure, mean arterial pressure (MAP) and heart rate (HR) trends during dialysis were analyzed. RESULTS: Mean hourly plasma water Ca++ concentrations were statistically significantly higher with a dialysate tCa concentration of 1.50 mmol/L. Mean tCaMBs were positive (diffusion gradient from the dialysate to the patient), increasing with increasing dialysate tCa concentrations (+75 ± 122 mg, +182 ± 125 mg, +293 ± 228 mg, respectively). Their difference was statistically significant (p<0.0005). Mean Na+MBs and K+MBs were not statistically significantly different. SBP, DBP, MAP and HR were not statistically significantly different among the 3 treatments. CONCLUSIONS: These highly controlled experiments showed that hemodynamic stability does not appear to be statistically significantly influenced by any specific dialysate tCa concentration in this peculiar subset of patients.

Bioimpedance and the duration of the hemodialysis session.

Bioelectrical impedance analysis (BIA) is composed of resistance (R) and reactance (Xc). The aim of this study was to investigate whether BIA may be influenced by the duration of hemodialysis (HD) sessions. Eleven uremic patients underwent one 4-hour and one 8-hour bicarbonate HD session. Volume of blood and dialysate processed, volume of ultrafiltration (V(UF)), and dialysate electrolyte concentrations were prescribed to be the same. R and Xc were determined at the start and the end of each session, injecting 800 µA at 50 kHz alternating sinusoidal current (BIA 101; Akern, Italy). Mean pre- and postdialysis body weights and V(UF) were not significantly different in the 4-hour and 8-hour treatments. Postdialysis R, ΔR (the difference between post- and predialysis R values), and percent increase of R values were significantly higher in the 8-hour sessions, when compared with the corresponding values of the 4-hour sessions (p < 0.0001, 0.02, and 0.02, respectively). In conclusion, this study shows that 8-hour HD sessions were associated with postdialysis R, ΔR, and percent increase of R values significantly higher than the corresponding ones of 4-hour sessions. If higher R values may represent a proxy of a correct dry body weight, it remains a matter of future research.

Calcium mass balances during standard bicarbonate hemodialysis and long-hour slow-flow bicarbonate hemodialysis.

BACKGROUND: Dialysate calcium (Ca) concentration should be viewed as part of the integrated therapeutic regimen to control renal osteodystrophy and maintain normal mineral metabolism. Thus, a correct ionized calcium mass balance (Ca++MB) during hemodialysis (HD) is crucial in the treatment of renal osteodystrophy. The GENIUS single-pass batch dialysis system (Fresenius Medical Care, Germany) consists of a closed dialysate tank of 90 L; it offers the opportunity of effecting mass balances of any solute in a very precise way. METHODS: The present study has a crossover design: 11 stable anuric HD patients underwent 2 bicarbonate HD sessions, 1 of 4 hours (4h) and the other of 8 hours (8h) in a random sequence, always at the same interdialytic interval, at least 1 week apart. The GENIUS system and high-flux FX80 dialyzers (Fresenius Medical Care, Germany) were used. The volume of blood and dialysate processed, volume of ultrafiltration and dialysate Ca concentrations (1.50 mmol/L) were prescribed to be the same. Trends of plasma Ca++, blood pH and bicarbonates during dialysis, as well as Ca++MBs were determined. Plasma parathyroid hormone (PTH) levels at the start and end of the 2 treatments were measured. RESULTS: Ca++MBs (mean ± SD) were +284.6 ± 137.4 mg and +297.7 ± 131.6 mg (p=0.307) in the 4h and 8h treatments, respectively. No single session out of the 22 had a negative Ca++MB for the patient. Mean plasma Ca++, blood pH and bicarbonate levels were not statistically significantly different when comparing the start and end of the sessions of the 2 treatments. Mean plasma Ca++, blood pH and bicarbonate levels increased significantly along the time points in both 4h and 8h HD sessions (repeated measures ANOVA: p<0.0001). Mean plasma PTH levels were not statistically significantly different when comparing the start and end of the sessions of the 2 treatments. The differences between predialysis and postdialysis plasma PTH levels were not statistically significantly different either in 4h or 8h sessions (Wilcoxon's test: p=NS), even though a trend toward lower postdialysis plasma PTH levels was observed in both 4h and 8h treatments. CONCLUSIONS: Our data show incontrovertibly that, when dialyzing with a dialysate Ca concentration of 1.50 mmol/L, 4h standard bicarbonate HD and 8h slow-flow bicarbonate HD always achieve a quite similar positive Ca++MB for the patients.

Removal of uraemic retention solutes in standard bicarbonate haemodialysis and long-hour slow-flow bicarbonate haemodialysis.

BACKGROUND: Several studies already stressed the importance of haemodialysis (HD) time in the removal of uraemic toxins. In those studies, however, also the amount of dialysate and/or processed blood was altered. The present study aimed to investigate the isolated effect of the factor time t (by processing the same total blood and dialysate volume in two different time schedules) on the removal and kinetic behaviour of some small, middle and protein-bound molecules. METHODS: The present study had a crossover design: 11 stable anuric HD patients underwent two bicarbonate HD sessions (~ 4 and ~ 8 h) in a random sequence, at least 1 week apart. The GENIUS single-pass batch dialysis system and the high-flux FX80 dialysers (Fresenius Medical Care, Bad Homburg, Germany) were used. The volume of blood and dialysate processed, volume of ultrafiltration, and dialysate composition were prescribed to be the same. For each patient, blood was sampled from the arterial line at 0, 60, 120, 180 and 240 min (all sessions), and at 360 and 480 min (8-h sessions). Dialysate was sampled at the end of HD from the dialysate tank. The following solutes were investigated: (i) small molecules: urea, creatinine, phosphorus and uric acid; (ii) middle molecule: ß(2)M; and (iii) protein-bound molecules: homocysteine, hippuric acid, indole-3-acetic acid and indoxyl sulphate. Total solute removals (solute concentration in the spent dialysate of each analyte × 90 L - the volume of dialysate) (TSR), clearances (TSR of a solute/area under the plasma water concentration time curve of the solute) (K), total cleared volumes (K × dialysis time) (TCV), and dialyser extraction ratios (K/blood flow rate) (ER) were determined. The percent differences of TSR, K, TCV and ER between 4- and 8-h dialyses were calculated. Single-pool Kt/Vurea, and post-dialysis percent rebounds of urea, creatinine and ß(2)M were computed. RESULTS: TSR, TCV and ER were statistically significantly larger during prolonged HD for all small and middle molecules (at least, P < 0.01). Specifically, the percent increases of TSR (8 h vs 4 h) were: for urea 22.6.0% (P < 0.003), for creatinine 24.8% (P < 0.002), for phosphorus 26.6% (P < 0.001), and for ß(2)M 39.2% (P < 0.005). No statistically significant difference was observed for protein-bound solutes in any of the parameters being studied. Single-pool Kt/Vurea was 1.41 ± 0.19 for the 4-h dialysis sessions and 1.80 ± 0.29 for the 8-h ones. The difference was statistically significant (P < 0.0001). Post-dialysis percent rebounds of urea, creatinine and ß(2)M were statistically significantly greater in the 4-h dialysis sessions (at least, P < 0.0002). CONCLUSIONS: The present controlled study using a crossover design indicates that small and middle molecules are removed more adequately from the deeper compartments when performing a prolonged HD, even if blood and dialysate volumes are kept constant. Hence, factor time t is very important for these retention solutes. The kinetic behaviour of protein-bound solutes is completely different from that of small and middle molecules, mainly because of the strength of their protein binding.

Is there a link between the late occurrence of a brachial artery aneurysm and the ligation of an arteriovenous fistula?

Arteriomegaly and aneurysms proximal to long-standing posttraumatic arteriovenous fistulas (AVF) have been described. Much fewer are the reports of the late occurrence of brachial artery aneurysms following the closure of a hemodialysis AVF. Here, we report the case of a 55-year-old male patient. He had received a cadaver donor kidney transplant in 1996; his distal radiocephalic (RC) wrist AVF in the left arm had been ligated in 2001; he developed an aneurysm of the left brachial artery 9 years after the ligation of the AVF (2009). He underwent the surgical intervention of aneurysmectomy at the level of the left brachial artery with construction of a bypass with autologous saphenous vein. In conclusion, the development of a RC wrist AVF is an intrinsically dynamic process characterized by the increase in both blood flow rate and internal diameter of the brachial artery; the latter might be associated with enhanced fracture of the elastic fibers with the consequent risk of the development of an aneurysm. Thus, arteriomegaly and aneurysm of the brachial artery proximal to long-standing AVFs might be seen as a "continuum" of these morphologic modifications.

Haemodynamic stability in standard bicarbonate haemodialysis and long-hour slow-flow bicarbonate haemodialysis.

BACKGROUND: The interplay of correct solute mass balances, such as that of sodium (Na+) and potassium (K+) (respectively, Na+MB and K+MB) with adequate ultrafiltration volumes (V(UF)), is crucial in order to achieve haemodynamic stability during haemodialysis (HD). The GENIUS single-pass batch dialysis system (Fresenius Medical Care, Germany) consists of a closed dialysate tank of 90 L; it offers the unique opportunity of effecting mass balances of any solute in a very precise way. METHODS: The present study has a crossover design: 11 stable anuric HD patients underwent two bicarbonate HD sessions, one of 4 h and the other of 8 h in a random sequence, always at the same interdialytic interval, at least 1 week apart. The GENIUS system and high-flux FX80 dialysers (Fresenius Medical Care, Germany) were used. The volume of blood and dialysate processed, V(UF) and dialysate Na+ and K+ concentrations were prescribed to be the same. Plasma water Na+ and K+ trends during dialysis as well as Na+MBs and K+MBs were determined. At the same time, systolic blood pressure (SBP) and diastolic blood pressure (DBP), mean arterial pressure (MAP) and heart rate trends during dialysis were analysed. Plasma volume (PV) changes were computed from plasma total protein concentrations and their trends analysed. RESULTS: Plasma water Na+ and K+ levels were not significantly different when comparing the start and the end of the sessions of the two treatments. Both the increase of plasma water Na+ levels and the decrease of plasma water K+ levels in the first 4 h were significantly slower during the 8-h sessions when compared with the 4-h ones (P < 0.048 and P < 0.006, respectively). Dialysis sessions were uneventful. SBP decreased significantly during the 4-h sessions, whereas it remained stable during the 8-h ones (P < 0.0001 and P = NS, respectively). Statistically significantly lower intradialysis decreases of SBP (-4.5 ± 16.2 vs -20.0 ± 15.0 mmHg, P < 0.02) and MAP (-1.4 ± 11.7 vs -8.6 ± 11.0 mmHg, P < 0.04) were achieved in the 8-h sessions with respect to the 4-h sessions, in spite of no significant difference for mean V(UF) (2.9 ± 0.9 vs 2.9 ± 0.8 L; P = NS) and mean Na+MBs (-298.1 ± 142.2 vs -286.2 ± 150.7 mmol; P = NS). The decrease of PV levels in the first 4 h was significantly slower during the 8-h sessions when compared with the 4-h ones (P < 0.0001). PV decrease was significantly higher at the end of the 4-h HD sessions than at the end of the 8-h HD sessions (P < 0.043). CONCLUSIONS: The present highly controlled experiments using a crossover design and precise Na+MB and K+MB controls showed that better haemodynamic stability was achieved in the 8-h sessions with respect to the 4-h sessions, in spite of no difference for mean V(UF) and Na+MBs. Thus, other pathophysiological mechanisms, namely, a better PV preservation, must be advocated in order to explain the better haemodynamic stability peculiar to long-hour slow-flow nocturnal HD treatments.

[Uremic toxins: the case of protein-bound compounds]. / Tossine uremiche: il caso dei "protein-bound compounds".

Uremic retention solutes, if biologically or biochemically active, are called ''uremic toxins''. The retention of these solutes has a negative impact on many functions of the organism, particularly the cardiovascular system. The classification which is applied today is based on the kinetic behavior of the uremic retention solutes during dialysis: 1) small water-soluble molecules (< 500 Daltons); 2) middle molecules (> 500 Daltons); 3) protein-bound compounds. The latter are the object of the present review. The most important among them are p-cresol, p-cresyl sulfate, homocysteine, phenols, and indoles. No interventional studies are currently available that show the effect of an improvement in the removal of protein-bound compounds on patient outcomes, simply because most of the alternative dialysis strategies proposed so far are not superior to standard dialysis in removing protein-bound compounds. The question as to how to improve the removal of these solutes therefore remains unanswered. Alternative strategies might include adsorption therapies, either administered orally or during the extracorporeal treatment. In conclusion, the uremic syndrome is a complex clinical entity which involves a large number of retention solutes, many more than the small water-soluble molecules. Dialysis strategies should therefore aim to remove not only urea but also retention solutes, mainly because middle and protein-bound molecules appear to be correlated more frequently with deleterious biological, biochemical and clinical effects.

[A case of drug-induced syndrome of inappropriate secretion of antidiuretic hormone]. / Un caso di sindrome da inappropriata secrezione di ormone antidiuretico indotta da farmaci.

The syndrome of inappropriate secretion of antidiuretic hormone (SIADH) is characterized by hyponatremia, plasma hypo-osmolality, a urine sodium concentration >30-40 mmol/L, normal acid-base balance, a normal plasma potassium concentration and, frequently, hypouricemia. There are different types of SIADH: idiopathic, iatrogenic, and forms caused by central nervous system or lung disorders, neoplasia and major surgical interventions. Drug-induced SIADH is becoming the most frequent cause of hyponatremia encountered in clinical practice. Here we report the case of a 60-year-old man in a coma (I-II) and with very severe hyponatremia (99 mmol/L) due to SIADH induced by fluphenazine and amitriptyline, which he had been taking since many years as antidepressant drugs. SIADH became very quickly more severe due to the recent administration of cisplatin. There was rapid improvement of the clinical symptoms after withdrawal of the drugs involved and correction of hyponatremia. In conclusion, in rare cases like the present one hyponatremia related to SIADH may be so severe as to represent a true clinical emergency. The administration of drugs known to cause hyponatremia should be avoided, if possible; otherwise, very careful monitoring of the plasma sodium concentration is mandatory to avoid severe neurological complications which may lead to the death of the patient.

Serum parathyroid hormone and phosphate influence the levels of circulating CD34+ cells in uremia.

BACKGROUND: Parathyroid hormone (PTH) is an active stimulator of bone marrow osteoblasts; it is involved in the niche organization, ie the bone marrow microenvironment which controls the turnover and the fate of endothelial progenitor cells (EPCs). PTH stimulates EPC production; this action can be measured by counting the number of circulating CD34+ cells. METHODS: This observational cross-sectional study aimed to verify this effect in 3 groups of hemodialysis patients with different serum PTH levels. The first group consisted of 11 patients affected by secondary hyperparathyroidism (SHPTH group, serum PTH levels >500 pg/ml); the second group consisted of 10 patients with serum PTH levels between 150 and 500 pg/ml (TargetPTH group); the third group consisted of 10 patients with serum PTH levels below the treatment target after parathyroidectomy (PTx group, serum PTH levels <150 pg/ml). Serum PTH, calcium (Ca), phosphorus (P), alkaline phosphatases (ALP), urea nitrogen, albumin and hemoglobin were measured. Flow cytofluorimetry with CD45+ sequential gating was effected; therefore, CD34+ cells could be analyzed. RESULTS: The SHPTH group showed significantly higher values of serum PTH, P and ALP (respectively, p<0.0001, p<0.033 and p<0.0001), and significantly lower values of circulating CD34+ cells (both in absolute and percent terms) in the SHPTH and in the TargetPTH groups (for both, p<0.0001). Two models of multiple regression analysis built with circulating CD34+ cells (expressed as percentage in the first one and as absolute values in the second one) as dependent variables showed that only serum PTH and P values were inversely associated with both. CONCLUSIONS: Our data suggest that an inverse relationship exists in uremic patients among circulating CD34+ cells and serum P and PTH levels. The count of circulating CD34+ cells might represent a novel biomarker for the assessment of the cardiovascular risk for dialysis patients.

Vitamin D treatment in hemodialysis patients with low serum levels of parathyroid hormone: which is the best choice?

BACKGROUND: This short-term prospective study aimed to assess the effects of treatment with calcidiol (25-hydroxycholecalciferol) or calcitriol in the subset of hemodialysis patients characterized by stable low serum levels of parathyroid hormone (PTH) or affected by hypoparathyroidism after total parathyroidectomy (PTx). METHODS: Two groups were created according to baseline serum levels of 25-hydroxyvitamin D (25(OH)D): group A (12 patients): <15 ng/mL; group B (12 patients): >15 ng/mL. They underwent a 6-month treatment with oral calcidiol (group A) or oral calcitriol (group B). RESULTS: Group A showed a statistically significant increase in the serum levels of calcium corrected for serum albumin (cCa), phosphorus (P), total alkaline phosphatases (ALP), PTH and 25(OH)D. Group B showed a statistically significant increase in serum levels of cCa and P. A statistically significant decrease in serum levels of ALP and 25(OH)D was observed. Baseline serum 25(OH)D levels were 12.6 + 3.8 ng/mL in group A and 23.0 + 5.0 ng/mL in group B (p<0.0001). After 6 months, they increased to 38.3 + 21.0 ng/mL in group A (p<0.01) and decreased to 16.9 + 5.8 ng/mL in group B (p<0.01). CONCLUSIONS: Treatment with oral calcitriol was associated with a decrease in the serum levels of ALP and 25(OH)D; treatment with oral calcidiol was associated with more physiological serum levels of 25(OH)D and with an increase in the serum levels of ALP and PTH: whether the statistically significant differences in the biochemical parameters achieved with the 2 treatments have a clinical relevance, remains a matter of debate.

Simvastatin-induced myoglobinuric acute kidney injury following ciclosporin treatment for alopecia universalis.

Alopecia areata can affect the entire scalp (alopecia totalis) or cause loss of all body hair (alopecia universalis). Ciclosporin (CsA) has been suggested for its treatment, with controversial results. Concomitant use of statins and CsA may increase the risk of rhabdomyolysis due to drug-drug interactions. Here we report the case of a 45-year-old woman treated with CsA for alopecia universalis, who presented a severe myoglobinuric acute kidney injury following the concomitant use of simvastatin. Upon admission to our unit, she was oligo-anuric. Her serum creatinine level was 13.8 mg/dl. CsA and simvastatin therapy were stopped, and haemodialysis treatment was started (eight daily dialysis sessions) until sufficient kidney function was regained. After 1 month, her serum creatinine level was 3.5 mg/dl; after 2 months and onwards (follow-up of 4 months), her serum creatinine level was 1.4 mg/dl and creatinine clearance was 43.2 ml/min. In conclusion, physicians should be aware of the potential risks of the combined use of CsA and statins. Patients should be advised to report any muscle symptoms when they are on statins and CsA. The laboratory follow-up should include the monitoring of serum creatinine and muscle enzyme levels, blood CsA levels and liver function tests.