Calcium-PTH relationship in dialysis patients: the pitfalls of using a constant dialysate calcium concentration during the dynamic tests.

The calcium-PTH relationship in uremic patients has been often studied during dialysis sessions with high or low dialysate calcium concentration (CaD). This method has been used because it is less complex and invasive than i.v. infusion of calcium salts and calcium chelating agents. However, the constancy of CaD during the tests does not allow for the control of the serum calcium profile and, given that the blood calcium concentration is only one factor of a more complex calcium-related mechanism of the PTH release, the calcium-PTH curve may become dependent on the unpredictable rate at which the ionized calcium changes. Dynamic testing of the parathyroid gland was performed in 9 dialysis patients comparing constant CaD of 1.0 and 2.0 mmol/l (A) with a linear change in CaD (B). The rate of serum calcium change remained constant over time only in experiment B. The total decrease in calcemia (0-0.38 +/- 0.03 vs -0.14 +/- 0.1 mmol/l) and PTHmax (748.25 +/- 124.76 vs 374.89 +/- 53.03 pg/ml) were significantly higher in B, whereas the total increase in calcemia (+0.26 +/- 0.03 vs +0.28 +/- 0.02 mmol/l) and the minimum value of PTH (59.15 +/- 9.53 vs 55.64 +/- 9.08 pg/ml) were similar in both experiments. The calcium-PTH curves were clearly different in A and B. The setpoint and the slope were significantly higher in A (1.196 +/- 0.01 vs 1.142 +/- 0.02 mmol/l; 840.54 +/- 96.85 vs 542.43 +/- 112.26%/mmol). For similar serum calcium values (1.084 +/- 0.01 vs 1.059 +/- 0.02 in the stimulation test and 1.325 +/- 0.02 vs 1.336 +/- 0.02 mmol/l in the inhibition test) the PTH secretion was significantly different (335.86 +/- 44.36 vs 647.65 +/- 104.09 in the stimulation test and 76.35 +/- 12.57 vs 105.03 +/- 20.59 pg/ml in the inhibition test). In conclusion, the way of inducing serum calcium change affected the calcium-PTH curve and the value of the set point and the slope was a function of the way in which the blood calcium changes were achieved. The modulated CaD dialysis was shown to be a more correct method of studying the calcium-PTH relationship in dialysis patients, as well as an alternative to the more complex and invasive infusional methodology.

Beta-2 microglobulin in patients on peritoneal dialysis and hemodialysis.

Serum beta 2 microglobulin (beta 2 mu) levels were determined in 62 patients on chronic dialysis, divided according to the type of dialysis--cuprophane hemodialysis, chronic ambulatory peritoneal dialysis (CAPD), or CAPD started after 76 +/- 47 months on cuprophane hemodialysis--and to residual urine output greater than 400 mL/day or less than 10 mL/day. In addition, for patients on CAPD, peritoneal excretion, peritoneal clearance, and urinary excretion of the protein were determined. In anuric patients serum beta 2 mu levels were significantly higher in HD than in CAPD. In patients with residual urine output, serum concentrations of the microprotein were similar in HD and in CAPD. Significant differences were observed in beta 2 mu serum levels and peritoneal clearances in patients switched to CAPD from hemodialysis as compared to those starting with CAPD. Peritoneal clearances of the microprotein was slightly and non-significantly greater in patients with urine output than in anuric patients.

Short-term effects of low-calcium dialysis solutions on calcium mass transfer, ionized calcium, and parathyroid hormone in CAPD patients.

Patients on CAPD using calcium carbonate (CaCO3) as phosphate binder might benefit from low-calcium (Ca) concentration dialysis solutions; however, no data are available for the effects of this regimen on Ca metabolism. We studied 10 patients on stable CAPD regimens with standard dialysis solutions (Ca 7 mg/dL) who were taking CaCO3 to control hyperphosphatemia (mean daily doses 4.5 +/- 2.4 g). Hypercalcemic episodes had been recorded in 6 patients. Standard dialysis solutions were replaced with solutions containing 5 mg/dL of Ca. Calcium and phosphate peritoneal mass transfer (MT), serum concentrations of total Ca, ionized Ca (Ca++), phosphate, intact PTH, and mid-molecular PTH, were evaluated before and 48 hours after change of dialysate. The switch to low-Ca solutions was accompanied by significant changes in calcium mass transfer (Ca MT) (+9.84 +/- 48.22 versus -96.74 +/- 48.32 mg/day, p less than .001). Ca MT was significantly (p less than .05) correlated with the serum/dialysate Ca gradient. There was no difference in phosphate MT. Serum Ca++ significantly (p less than .05) decreased from 5.20 +/- 0.32 to 4.88 +/- 0.36 mg/dL, and intact PTH significantly increased (81.5 +/- 139 versus 112.4 +/- 168 pg/mL, p less than .05). It is concluded that dialysis solutions with Ca 5 mg/dL result in a negative peritoneal Ca MT and can be useful to prevent and treat hypercalcemia in CAPD patients taking CaCO3 as phosphate binder. A careful monitoring of ionized calcium, PTH, and phosphate is suggested when an extensive and long-term use of this solution is considered.

The sigmoidal parathyroid hormone-ionized calcium curve and the set point of calcium in hemodialysis and continuous ambulatory peritoneal dialysis.

A high incidence of adynamic bone disease not related to aluminum intoxication has been reported in continuous ambulatory peritoneal dialysis (CAPD). Since reduced parathyroid hormone (PTH) secretion may predispose to adynamic bone, we investigated whether parathyroid gland sensitivity may be depressed in CAPD in comparison with hemodialysis (HD). Thus we determined parathyroid function by the evaluation of the PTH-ionized calcium (ICa) relationship, which was obtained inducing hypocalcemia and hypercalcemia in 19 CAPD and 18 HD patients with biochemical and histological evidence of mild (MILD) or severe (OF) hyperparathyroidism, but negative stainable bone aluminum. Either CAPD or HD patients with OF showed a shift to the right of the sigmoidal PTH-ICa curve in comparison with patients with MILD, greater set point of calcium, and maximal PTH stimulation and inhibition. The PTH-ICa curve and the other parathyroid function parameters were not different in CAPD and HD patients within the same bone histological group. In conclusion, our data document that parathyroid gland activity is stimulated either in CAPD and HD patients with OF, but is not depressed in CAPD patients in comparison with HD patients.

Effects of the infusion mode on bicarbonate balance in on-line hemodiafiltration.

BACKGROUND: Electrolyte and acid-base balance may be differently affected by the infusion mode in on-line hemodiafiltration (HDF). We studied the effects of the different infusion modes on bicarbonate transport across the dialyzer membrane, and thus on the final bicarbonate balance of the HDF sessions. METHODS: Instantaneous HCO3- transfer across the dialyzer membrane, blood bicarbonate profile and the total balance of the sessions were studied in six dialysis patients under the same operating conditions over 36 HDF sessions, in order to compare the effects of predilution HDF (pre-HDF), postdilution HDF (post-HDF), and mixed HDF on the final bicarbonate balance. RESULTS: The final HCO3- balance was more positive in post-HDF vs pre-HDF (142 +/- 36 vs 99 +/- 41 mmol/session, p<0.05), with a final blood HCO3- concentration of 26.6 +/- 1.0 vs 25.4 +/- 1.1 mmol/L, (p<0.05). Mixed HDF yielded intermediate results (balance: 119 +/- 42 mmol/session, final HCO3- 26.2 (1.2 mmol/L). These differences were seen to result from the increased HCO3- concentration of blood entering the filter in predilution, due to the infused HCO3-, enhancing convective loss and reducing the driving force for diffusive HCO3- gain. CONCLUSIONS: Bicarbonate concentration in dialysate-reinfusate is critical in order to obtain an adequate end of session HCO3- balance in on-line HDF. The predilution method produced the lowest cumulative net HCO3- gain between the three studied infusion modes. Our data suggest that, under the same operating conditions and excluding the effect of ultrafiltration, dialysate HCO3- should be increased by about 2 mmol/L in pre-HDF, and 1 mmol/L in mixed HDF, to yield the same final balance as in post-HDF.

[Natural history of hepatitis B virus infection in dialysis patients: prospective study by quantitative analysis of HBV viremia]. / Storia naturale dell'infezione da virus dell'epatite B in dialisi: studio prospettico mediante analisi quantitativa della viremia HBV.

BACKGROUND: The natural history of hepatitis B virus (HBV) infection in patients undergoing maintenance dialysis is still unclear. The aim of this study was to measure the HBV viral load (HBV DNA) in a cohort (n=20) of HBsAg positive chronic dialysis patients over a 12-month observation period. METHODS; HBV DNA was measured by the Amplicor HBV MonitorTM Test Kit, an in vitro test that utilizes Polymerase Chain Reaction (PCR) nucleic acid amplification and DNA hybridisation for the quantitative measurement of hepatitis B viral DNA in human serum. Amplicor HBV MonitorTM Test Kit amplifies a sequence in the pre-Core/Core region of the HBV genome with biotinylated and non-biotinylated oligonucleotide primers. RESULTS: There was no significant difference between the median HBV load at the start and the end of the study, 1.85 x 104 HBV copies/ml (percentile 16.84; 6.35 x 102 - 3.5 x 106 HBV copies/ ml) and 8.5 x 103 HBV copies/ml (percentile 16.84; 5.5 x 102 - 6.38 x 105 HBV copies/ml), respectively. These serum HBV DNA levels were lower than those measured by the same test in patients with chronic hepatitis B and normal renal function (Hepatology 2000; 32: 116-23). In the group of HBsAg positive carriers on dialysis, we identified three patterns of HBV viremia over time: 1) patients (n=6) with persistent HBV DNA, 2) those (n=2) with undetectable HBV DNA and 3) those (n=12) with intermittent HBV DNA. Patients with persistent HBV DNA (median, 3.3 x 104 HBV copies/ml; percentile 16.84; 3.5 x 103 - 2.3 x 106 HBV copies/ml) had higher viral HBV load than those with intermittent HBV viremia (median, 1.2 x 103 HBV copies/ml; percentile 16.84; 3.5 x 102 - 2.3 x 104 HBV copies/ml) (p=0.0001). Patients with persistent HBV DNA had higher frequency of serum hepatitis B e antigen (HBeAg) positivity than those showing intermittent and negative HBV DNA, 50% (3/6) vs. 0% (p=0.04). The frequency of serum IgM antibody against hepatitis B core antigen (IgM anti-HBc) was higher in patients with persistent HBV DNA than those having intermittent or negative HBV DNA, 100% (6/6) vs. 33% (4/12), p=0.03. We detected no difference in aminotransferase activity between patients with persistent HBV DNA and those showing intermittent or negative HBV DNA. In the group with persistent HBV DNA, the mean difference between maximum and minimum values of HBV DNA observed in each individual patient was 6.13+/-1.25 decimal logarithm (Log10) and in patients with intermittent HBV DNA 3.87+/-1.49 Log10 (p=0.006). In the entire group, the fluctuations in HBV DNA values over time between and within individuals were not significant. CONCLUSIONS: The viremic HBV load was low and relatively stable over a 12-month follow-up period; three patterns of HBV viremia over time were observed; 30% of the viremic patients had persistent HBV viremia, and those patients had larger viral load and higher frequency of HBeAg and anti-HBc IgM than did patients with intermittent or negative HBV DNA. Prospective studies with longer observation periods are in progress to fully understand the natural history of HBV in these immunosuppressed patients.

Pregnancy in women with chronic renal failure.

We describe 19 pregnancies in 18 women with chronic renal disease and plasma creatinine greater than or equal to 1.6 mg/dl before pregnancy. There were 2 spontaneous abortions (11th and 21st week), 2 therapeutic abortions (18th and 19th week), 1 stillbirth (30th week), 1 neonatal death (31st week) and 13 live births, 7 of them were preterm. Nine cesarean sections were done. Serial determinations of plasma creatinine during pregnancy showed a trend to decrease during the first half and to increase during the second half of pregnancy. The effect of pregnancy on the progression of renal failure was evaluated in 14 patients by comparing the linear regression lines of reciprocal plasma creatinine versus time before and after pregnancy. In 5 patients the rate of progression worsened after pregnancy. Our data indicate that women with chronic renal failure may have a successful pregnancy, but one third of them will have an accelerated rate of progression of the disease.

Acquired immunodeficiency syndrome transmitted by transplanted kidney: clinical course during maintenance haemodialysis.

We describe the clinical course of a 39-year-old man who developed AIDS during maintenance haemodialysis. The infection had been transmitted by cadaveric kidney transplantation from a donor with a history of i.v. drug abuse. Fever, splenomegaly, hypergammaglobulinaemia and thrombocytopenia were the first signs, and appeared when haemodialysis was resumed 26 months after transplantation. Twenty-eight months later the patient developed a cerebral abscess due to toxoplasma infection. A striking improvement was obtained with cotrimoxazole, but the treatment had to be stopped because of severe leukopenia. The patient died due to relapse of the cerebral abscess. End-stage renal failure does not seem to have modified the clinical course of AIDS in our patient.

Molecular epidemiology of hepatitis C virus infection in dialysis patients.

There are very few data on the molecular biology of hepatitis C virus (HCV) infection in dialysis patients. 101 patients undergoing dialysis treatment in 4 units in the Lombardy, northern Italy, were analyzed by RT-PCR for HCV viremia, by line probe assay technology for HCV genotyping and by a serological analysis for detecting type-specific antibodies. 61 of 101 (60%) patients showed detectable HCV RNA in serum; HCV genotype 2a was dominant (30/53 = 57%), followed by HCV genotype 1b (20/53 = 37%). There was no relationship between HCV genotyping and the clinical or demographic features of the patients. The antibody response toward the c33-c, c100-3, and 5-1-1 antigens was more frequent in HCV genotype 1b compared with genotype 2a (p = 0.046, p = 0.001 and p = 0.0001, respectively). The antibody levels to NS-3 and NS-4 HCV proteins were significantly higher in patients with-HCV genotype 1b in comparison with HCV 2a-infected individuals (p = 0.0001). There was a high level (82%) of agreement between HCV genotyping by RT-PCR and the assessment of type-specific antibodies by serological analysis; further, it was possible to detect type-specific antibodies in 6 of 22 (27%) patients in whom PCR amplification was unsuccessful. In conclusion, HCV subtype 2a was dominant in our population of HCV-infected dialysis patients, dialysis patients infected by different genotypes showed similar demographic and clinical characteristics, the antibody response toward the NS-3- and NS-4-related antigen of HCV was genotype dependent. There was a high level of agreement between HCV genotyping by RT-PCR and the detection of type-specific antibodies by serological analysis. As significant biological differences may exist among HCV strains, the assessment of HCV types may be very useful in the routine clinical activity of nephrologists in dialysis units.

Mixed predilution and postdilution online hemodiafiltration compared with the traditional infusion modes.

BACKGROUND: On postdilution hemodiafiltration (post-HDF), convective removal of medium-high molecular weight solutes is, at the highest ultrafiltration rates, limited by high blood viscosity and protein concentration. Prefilter reinfusion (pre-HDF) may overcome this problem, but plasma dilution may affect the overall efficiency of the technique. In this study, an experimental system of online HDF with combined prefilter and postfilter infusion (mixed HDF) was evaluated and compared with the traditional predilution and postdilution modes. METHODS: Removal of urea (U), creatinine (Cr), phosphate (Phos), and beta(2)-microglobulin (beta(2)m), ultrafiltration coefficients of the dialyzer (K(UF)), and rheologic conditions of the blood circuit were evaluated during the three infusion modes (a total of 36 runs lasting 180 min), performed with a polysulfone hemofilter 1.8 m(2), blood flow (Q(b)) 400 mL/min, dialysate flow (Q(d)) 700 mL/min, and infusion rate 120 mL/min (pre-HDF and post-HDF), or 60 + 60 mL/min (mixed HDF). RESULTS: The mean effective U and Cr clearances and urea index of dialysis dose (eKt/V) were significantly higher on post-HDF than on pre-HDF (K(WB) (U) 210 vs. 193 mL/min, K(DQ) (Cr) 152 vs. 142 mL/min, eKt/V 1.41 vs. 1.30), while mixed HDF did not show significant differences versus post-HDF (K(WB) (U) 201 mL/min, K(DQ) (Cr) 149 mL/min). K(DQ) for Phos and beta(2)m were higher on post-HDF in only absolute values. Similar differences were found for instantaneous dialyzer clearances (K(I)) at 60, 120, and 180 minutes of the sessions, with a common trend to decrease with time. K(UF) and the apparent beta(2)m sieving coefficient showed their lowest values toward the end of post-HDF sessions. Increasing filtration fractions (FFs) were associated with increasing transmembrane pressure (TMP) and solute clearances up to FF values of 0.45. These were values achieved in only post-HDF, at which point the curve of the relationship between TMP and FF assumed its steepest exponential trend. CONCLUSIONS: Mixed HDF, by better preserving the characteristics of water and solute transport of the membrane, ensured safer operating conditions than post-HDF, while achieving similar removal of small- and large-size solutes. Optimizing the ratio of prefilter/postfilter infusion and the total infusion according to the relationships found in our study between solute clearances, FF, and TMP, convective flux and transport may avoid excessive hemoconcentration and dangerous pressure gradients.

Influence of hepatitis C virus (HCV) viraemia upon serum aminotransferase activity in chronic dialysis patients.

BACKGROUND: There are many reports concerning HCV in dialysis patients and most of them conclude that the clinical and biochemical features of hepatitis C are often silent in chronic dialysis patients. Elevated levels of serum alanine aminotransferase activity are a sensitive measure of hepatocellular injury, but so far the relationship between anti-HCV and ALT among chronic dialysis patients has been considered imperfect. To our knowledge, however, such an issue has not been adequately addressed. METHODS: Demographic, biochemical, and virological data from 506 patients undergoing chronic dialysis treatment in four dialysis units in Lombardy, northern Italy were collected in order to assess the influence of virological and host factors on serum aminotransferase values. RESULTS: Analysis of covariance showed that positivity for anti-HCV antibody was significantly associated with raised serum AST (P = 0.0001) and ALT (P = 0.0001) levels in the dialysis patients of the whole study group. Logistic regression analysis performed in the subset of patients tested for HCV viraemia and genotype showed that detectable HCV RNA in serum is a strong predictor of raised AST (P = 0.0001) and ALT (P = 0.000001) values. Gender showed an independent weak influence on AST levels (P = 0.055), serum levels of ferritin were significantly (P = 0.042) associated with AST values, the coexistence of HBsAg infection and positivity for anti-HCV antibody was independently associated with raised ALT levels (P = 0.016). The other factors (including positivity for anti-HCV) showed no independent effect on serum aminotransferase levels when they were matched with HCV viraemia in our multivariate analysis. HCV RNA positive patients showed serum AST (P < 0.008) and ALT levels (P < 0.0001) higher than HCV RNA negative patients. There was no relationship between HCV genotypes and liver enzymes. CONCLUSIONS: Our data show that detectable HCV RNA in serum is a strong independent predictor of raised aminotransferase values in chronic dialysis patients; the relationship between serum aminotransferase values and anti-HCV antibody was exclusively related to the association between raised aminotransferase values and HCV viraemia; HCV RNA positive patients show higher hepatic enzyme levels than dialysis patients with no detectable HCV RNA; no association between HCV genotype and serum aminotransferase activity was apparent.