Search

Background: Chronic kidney disease (CKD) patients affected by mineral bone disorders (MBD) have higher rates of all-cause and cardiovascular-related mortality. Approximately, one-third of dialysis patients have low serum parathyroid hormone (PTH) levels (≤ 150 pg/mL). However, the reason why these patients have higher mortality compared to patients with normal PTH levels has not yet been fully elucidated., Methods: The FARO study was performed on 2453 Italian patients followed prospectively from 28 dialysis centres over a 2-year period. Data were collected every 6 months and end points included time-to-death cumulative probability in patients with serum intact PTH (iPTH) ≤ 150 pg/mL and the effect of vitamin D receptor activation (VDRA) therapy. Kaplan-Meier curves and proportional hazards regression models stratified by PTH levels (i.e. ≤ 150 and >150 pg/mL) were used to determine cumulative probability of time-to-death and adjusted hazard ratios (HRs) for demographic, clinical and CKD-MBD treatment characteristics., Results: The cumulative probability of death was higher (P < 0.01) for patients with serum iPTH levels ≤ 150 pg/mL [25.1%, 95% confidence interval (CI): 22.1-28.5 at 18 months] versus those with serum iPTH levels within the normal range (18.0%, 95% CI: 16.1-20.1). In a model with time-dependent covariates restricted to time periods when patients had iPTH levels ≤ 150 pg/mL, lower mortality was observed in patients treated with VDRA [i.e. HR = 0.62, 95% CI: 0.42-0.92 for oral or intravenous (IV) calcitriol; HR = 0.18, 95% CI: 0.04-0.8 for IV paricalcitol] versus those not receiving any VDRA (P < 0.01) independently of other variables. Patients who received IV paricalcitol, compared with either oral or IV calcitriol, showed reduced mortality, but this was not statistically significant (HR = 0.3, 95% CI: 0.07-1.31, P = 0.11)., Conclusion: Results from this observational study suggest that VDRA therapy was associated with improved survival in dialysis patients, even with low serum iPTH levels.

The percentage of patients on dialysis who do not adhere to their dietary and therapeutic regimens ranges from 25% to 86%. These data are relevant because nonadherence to the prescribed diet affects the mortality and morbidity of these patients. The aim of this study was to evaluate some indicators of nonadherence to drug therapy and diet. Patients showing serum potassium levels >6 mEq/L, serum phosphate levels >5.5 mg/dL, or interdialysis weight gain >5.7% of their body weight were considered as nonadherent. Behaviors, habits and adherence to prescribed therapies were investigated by administering a drug and diet questionnaire to the patients. The percentages of values exceeding the nonadherence threshold were 16.4% for potassium, 30.2% for phosphate, and 7.5% for weight gain. The weight gain index was significantly related to both potassium (p<0.01) and phosphate (p<0.05) indexes. Age was inversely correlated with non -adherence indexes of both phosphate (p<0.05) and weight gain (p<0.05). Residual diuresis was associated with better adherence to potassium (p<0.01). Factor analysis of the questionnaire suggested a 4-factor solution. None of these subscales were correlated with nonadherence indexes. ''Continuity in the intake of drugs'' showed a correlation with the ''trust in the drugs'' factor (p<0.01). Measurements of nonadherence remain a crucial step for understanding the impact on patients' quality of life.

Background: Ascorbate supplementation for patients on regular dialysis treatment (RDT) is advised to obviate deficiency and improve epoetin response in those with functional iron deficiency. However, clear-cut safety concerns regarding hyperoxalemia are still poorly understood. This study tries to establish safety/efficacy profiles of ascorbate and oxalate during long-term intravenous ascorbate supplementation., Methods: A prospective study was performed in 30 patients on RDT showing ascorbate deficiency (plasma ascorbate < 2.6 mg/L [<15 micromol/L]): 18 patients were administered intravenous ascorbate during 18 months (250 mg/wk, subsequently increased to 500 mg), and 12 patients were taken as reference untreated cases. Plasma ascorbate and oxalate assays and dialytic balance determinations were performed (ion chromatography and reverse-phase high-performance liquid chromatography, respectively) at baseline, during treatment, and 12 months after withdrawal., Results: Plasma ascorbate levels increased dose dependently with supplementation (1.6 +/- 0.8 mg/L [9.1 +/- 4.6 mumol/L] at baseline, 2.8 +/- 1.8 mg/L [15.9 +/- 10.1 micromol/L]) with 250 mg of ascorbate, and 6.6 +/- 2.8 mg/L [37.5 +/- 16.0 micromol/L] with 500 mg/wk of ascorbate), but only normalized with greater dosages for several months in 94% of patients. Baseline plasma oxalate levels increased from 3.2 +/- 0.8 mg/L (35.8 +/- 8.8 micromol/L) to 3.6 +/- 0.8 mg/L (39.5 +/- 9.1 micromol/L) and 4.5 +/- 0.9 mg/L (50.3 +/- 10.4 micromol/L) with 250 and 500 mg, respectively ( P < 0.001). The calcium oxalate saturation threshold was exceeded by 7 of 18 patients (40%) during 6 months therapy with 500 mg/wk. Ascorbate dialysis removal increased from 37.8 +/- 23.2 mg (215 +/- 132 micromol) to 99.6 +/- 51.7 mg (566 +/- 294 micromol) during supplementation (P < 0.001), with corresponding increases in oxalate removal from 82.5 +/- 33.2 mg (917 +/- 369 micromol) to 111.2 +/- 32.6 mg/L (1,236 +/- 362 micromol; P < 0.01). Withdrawal reverted plasma levels and dialysis removal to initial values. Values for untreated patients did not change during 1 year of follow-up., Conclusion: Patients on RDT may resolve ascorbate deficiency with intravenous supplementation of 500 mg/wk, but this implies a significant risk for oxalate supersaturation. Oxalate measurements are strongly recommended during long-term ascorbate therapy.

Background: QT interval prolongation increases the risk of ventricular arrhythmias and sudden death in diabetic autonomic neuropathy and ischemic heart disease. In end-stage renal disease (ESRD), the effects of hemodialysis on QT interval are diverse and the influence of autonomic neuropathy has yet to be clearly defined., Methods: Sixty-nine ERSD patients (age 64 +/- 14) were studied. Prior to the dialysis session, patients underwent four standard autonomic cardiovascular tests; before and after the dialysis session, a 12-lead ECG was recorded. Corrected QT intervals (QTc) were measured and QT dispersion (QTd) was calculated. Twelve subjects (age 59 +/- 6) with normal renal function served as control group., Results: Compared to controls, ESRD patients showed a longer QTc (434 +/- 26 vs 414 +/- 28 ms; p = 0.016) and a similar QTd (35 +/- 13 vs 37 +/- 14 ms; p = 0.54).QTc was > 440 ms in 33.3% of the patients. No difference in the prevalence or score of autonomic neuropathy was observed between the subgroups with and without a prolonged QTc. After the hemodialysis session, QTc increased in 56% and decreased in 43% of the patients, and QTd increased in 45 % and decreased in 55% of the patients. QTc and QTd changes were not related to the presence of autonomic neuropathy., Conclusions: A large variability in QTc and QTd response was observed after hemodialysis. Autonomic neuropathy did not contribute to QTc and QTd length, nor to QTc and QTd change after dialysis.

Background: We implemented a program for continuous renal replacement therapies (CRRT) in intensive care units (ICU) based on the cooperative work of dialysis and ICU personnel. Our aim was to report the main details of this program and compare its cost with that of intermittent hemodiafiltration (IHDF)., Methods: The study referred to 181 ICU patients with renal failure. We considered the costs of both technical devices and assisting personnel. CRRT was performed as continuous veno-venous hemodiafiltration (CVVHDF) (24 hr daily); dialysis and ICU nurses shared surveillance. Only dialysis nurses performed IHDF (as acetate-free biofiltration, 4 hr daily) in the ICU., Results: The daily cost of CRRT was Euro 276.70; of which 79% was for devices and 21% was for human resources. Nurse surveillance required 141 min per day, ICU nurses supplied 55% (77 min) and dialysis nurses 45% (64 min). On average, CRRT surveillance required less than 1 min/nurse/hr for both dialysis and ICU nurses. The daily cost of 4-hr IHDF sessions of was Euro 247.83, of which 44% was for technical devices and 56% was for human resources., Conclusions: The cooperation between dialysis and ICUs improved the use of human resources and allowed us to supply CRRT to all critically ill patients with acute renal failure. The expenditure for CRRT was 12% higher than that for IHDF, due to the cost of technical devices.

Primary hyperoxaluria (PH) type 1 and type 2 are autosomal recessive defects of oxalate metabolism resulting from glyoxylate accumulation which occurs by two distinct pathways. PH1 is associated to glycolic aciduria; PH2 to L-glyceric aciduria. Because hyperoxaluria leads to nephrolithiasis or nephrocalcinosis in both, they can be differentiated only through detection of the associated acidurias. However, glycolate and L-glycerate assays are not widely available and, in the setting of ESRF, diagnosis is hampered by a number of misleading events. At any stage of the disease diagnosis is crucial because there are differences between the two forms in clinical behaviour, long-term prognosis, and treatment. In this paper we outline diagnostic criteria for identification of PH2 in two patients, one with maintained renal function and one with ESRF on CPD, based on the use of a novel HPLC assay of L-glycerate in different body fluids. With the routine application of this procedure PH2 has been identified in two of 23 patients fulfilling criteria for diagnosis of PH. This suggests that the type 2 variant of PH may occur more frequently than so far suspected, and should be tested for even in the setting of ESRF.

We assessed plasma levels and removal rates of oxalate in 24 patients on chronic peritoneal dialysis (CPD) for oxalosis-unrelated renal failure. The ion-chromatographic (IC) measurements of oxalate in plasma, dialysate, and urine (in seven patients with residual renal function) were used to calculate peritoneal and renal clearances of oxalate. The serum state of saturation with calcium oxalate was calculated by means of a computer-based model system. Patient data were compared with those from 19 healthy individuals. Peritoneal clearance of oxalate was 6.3 +/- 4.7 mL/min, ie, 8% of the normal renal clearance. As a result, both plasma oxalate and calcium oxalate saturation were higher than in controls and did not overlap. Plasma was supersaturated with calcium oxalate in only two of 24 patients (8%). Removal of oxalate by dialysis was related to the amount of fluid infused. Overall removal of oxalate (dialysate plus urine) was similar to 24-hour excretion of normal subjects and was taken as a measure of its generation. Oxalate generation rate was dependent on protein (whole and animal) intake, but not on caloric intake or pyridoxine status. Pyridoxine supplementation, 75 and 300 mg daily for 1 months, was not effective in reducing plasma levels or generation rates of oxalate. Residual renal function had a minor influence on oxalate patterns. We conclude that current programs are adequate to maintain oxalate balance in patients on CPD under basic conditions.

Regular dialysis treatment (RDT) does not obviate hyperoxalemia of chronic renal failure (CRF). However, there is emerging evidence suggesting that current dialysis prescription is not always associated to progressive oxalate accumulation. In view of the controversy still concerning this issue, we have investigated on plasma profiles and dialysis kinetics of oxalate in patients on RDT. Oxalate was determined by ion chromatography on serum ultrafiltrates and on the whole dialyzate in 23 stable patients on RDT for end-stage renal failure unrelated to primary hyperoxaluria. Nine patients were on traditional hemodialysis (HD) and 14 on soft hemodiafiltration (HDF). Dialysis prescription was set so as to obtain similar KT/V of urea. Mean dialyzer clearance of oxalate (KdOx) was calculated by standard procedures and was compared to urea (KdUrea) and creatinine (KdCr) clearances. Oxalate removal was measured on the whole spent dialyzate. Distribution volume of oxalate (VOx) was estimated by assuming a single-pool model and was used to estimate the oxalate appearance rate (OxAR). Plasma profiles showed that dialysis patients were virtually always hyperoxalemic. However, the threshold of supersaturation for calcium oxalate was exceeded in only 13 of 138 (9.4%) assayed ultrafiltrates, 13% on HD and 7.1% on HDF. Dialysis reduced plasma oxalate by more than 60%. There was a postdialysis oxalate rebound averaging 9.6% at 30 min from the end of dialysis. Plasma oxalate predialysis was independent of sex, age and time on dialysis. KdOx was mildly higher on HDF than on HD, and was lower than both KdUrea and KdCr, irrespective of the dialysis technique.(ABSTRACT TRUNCATED AT 250 WORDS)

Regular dialysis treatment (RDT) does not obviate hyperoxalemia of chronic renal failure (CRF). However, there is emerging evidence suggesting that current dialysis prescription is not always associated with progressive oxalate accumulation. In view of the controversy still concerning this issue we have investigated on plasma profiles and dialysis kinetics of oxalate in patients on RDT. Oxalate was determined by ion chromatography on serum ultrafiltrates and on the whole dialysate in 23 stable patients on RDT for end-stage renal failure unrelated to primary hyperoxaluria. Nine patients were on traditional hemodialysis (HD) and 14 on soft hemodiafiltration (HDF). Plasma profiles showed that dialysis patients were virtually always hyperoxalemic. Dialysis reduced plasma oxalate by more than 60%. There was a post-dialysis oxalate rebound averaging 9.6% at 30 minutes from the end of dialysis. Oxalate dialyzer clearances were mildly higher on HDF than on HD, and were lower than both urea and creatinine clearances, irrespective of the dialysis technique. Distribution space of oxalate was 21.5 1, that is 37.3% of dry body weight, and was quite similar to estimates obtained in normal subjects and in patients with CRF by alternative isotope dilution methods. Oxalate appearance rate averaged 337 +/- 69 mumol/24 h and was not different from the daily oxalate excretion assessed in 40 healthy subjects. Oxalate appearance was significantly related to urea generation and protein catabolic rates. From our results we conclude that, unless metabolic generation of oxalate is increased, current dialysis programs should prevent progressive oxalate accumulation in the majority of the patients.

Citrate is a relevant component of the inhibitory potential of the urine environment. Its excretion and renal handling have been widely studied in subjects with normal renal function, but little is known about changes induced by chronic renal insufficiency. We have investigated renal handling of citrate in 50 patients with different degrees of renal insufficiency as compared to 30 healthy subjects with normal renal function. Among patients 34 were defined as having mild renal insufficiency based on a GFR of 80 through 40 ml/min/1.73 m2 BSA, while 16 had moderate-to-severe renal failure, defined by a GFR ranging from 40 to 20 ml/min/1.73 m2 BSA. Serum citrate increased in mild renal insufficiency, while it tended to be restored to normal values at more advanced renal failure. There was a stepwise decrease in the filtered load of citrate as GFR decreased, while its renal clearance was significantly reduced only at higher degrees of renal failure. This behavior was due to an increase in the fractional excretion of citrate which was inversely related to the decrease in GFR (p = 0.015). These data suggest that serum citrate levels and excretion are governed by renal mechanisms at mild degrees of renal insufficiency; in these conditions citrate is shown to behave conformly to other poorly reabsorbable anions such as sulfate. At more advanced renal failure the ensuing metabolic acidosis plays a crucial role as a regulatory factor of both serum concentration and renal handling of citrate, by increasing cellular uptake and metabolism as well as tubular reabsorption of this anion.(ABSTRACT TRUNCATED AT 250 WORDS)

An ion chromatographic procedure for the determination of plasma oxalate is proposed, in which the ultrafiltered sample is injected into an ion-chromatographic system. Sample processing appears effective in avoiding spontaneous oxalogenesis. Sensitivity (down to 1.0 mumol/l) allows determinations in normal and pathological samples; recoveries from plasma ultrafiltration are 94.6 +/- 11.7%. Protein binding was investigated and precautions to improve recoveries from plasma ultrafiltration are proposed. The technique is simple to perform from healthy controls averaged 6.75 +/- 2.62 mumols/l (mean +/- S.D. n = 18); samples from patients with primary hyperoxaluria and chronic renal failure undergoing regular dialysis were also analysed and some of the data obtained are reported and discussed.

The occurrence of chronic renal insufficiency was investigated in 171 patients with severe idiopathic calcium stone disease. Ninety healthy subjects matched for age and sex were used as controls. The patients were thereafter subclassified into two subgroups, assuming a GFR of 80 ml/min/1.73 m2 body surface area as a cut-off value: the normal GFR, 141 patients, and the impaired GFR, 30 patients. The normal GFR group included more males and the patients were younger both at onset and at presentation. In the impaired GFR group the disease lasted longer, but the overall stones and the stone recurrence rate were as high as those of the normal GFR patients. The single stone episodes were more severe in the former group as suggested by the occurrence of more surgery and complications. The GFR level was in part predicted by the age of patients; however, stone disease was shown to induce a clear-cut influence in accelerating the natural worsening of GFR with age. The onset of renal insufficiency causes multiple changes in renal pathophysiology, which result in a sharp decrease in the urine saturation with respect to calcium salts. These changes account for the decrease in the stone recurrence rate in the impaired GFR group. Thus, unless factors independent of or complicating the calcium stone disease supervene, the renal insufficiency of treated patients remains mild and relently progressive.