Renal failure in multiple myeloma: presenting features and predictors of outcome in 94 patients from a single institution.

BACKGROUND: Twenty percent of patients with multiple myeloma (MM) have renal failure. OBJECTIVE: To analyze the presenting features, the response to therapy, and the factors associated with renal function recovery and survival in 94 patients with MM and renal failure. PATIENTS AND METHODS: Medical records of patients from our institution with MM and renal failure diagnosed between January 1969 and December 1994 were reviewed. The statistical methods consisted of Kaplan-Meier survival curves, the log-rank test, logistic regression analysis, and the Cox proportional hazards model for survival analysis. RESULTS: Renal failure was observed in 94 (22.2%) of 423 patients. Patients with renal failure had more advanced disease than the others. Patients with renal failure had a lower response rate to chemotherapy than those with normal renal function (39% vs 56%; P<.001). However, when patients dying within the first 2 months of treatment were excluded, no significant differences in the response rate were found between patients with renal failure and those with normal renal function. Renal function recovery was observed in 26% of patients. Serum creatinine level (<354 micromol/L [<4 mg/dL]), serum calcium level (> or =2.88 mmol/L [> or = 11.5 mg/dL]), and amount of proteinuria (< 1 g/24 h) were associated with renal function recovery. Patients who recovered renal function had a median survival of 28 months vs 4 months for those with nonreversible renal failure (P<.001). In the multivariate analysis, only serum creatinine level (P=.003) and response to chemotherapy (P<.001) were correlated with survival. CONCLUSIONS: Renal failure was present in almost one fourth of patients with MM. Patients with reversible renal failure had longer survival than those not recovering renal function. When patients dying within the first 2 months of treatment were excluded, the response rate was not affected by renal function. Factors associated with renal function recovery were degree of renal failure, presence of hypercalcemia, and amount of proteinuria. Response to chemotherapy and severity of renal failure were the only independent factors associated with survival.

Association between vitamin D receptor gene polymorphism and relative hypoparathyroidism in patients with chronic renal failure.

To study the influence of vitamin D receptor (VDR) gene polymorphism on parathyroid cell function in chronic renal failure, 85 patients who had serum PTH levels <12 pmol/L (the low intact PTH [iPTH] group) and 46 patients who had serum iPTH levels >60 pmol/L (the high iPTH group) were selected out of a total dialysis population of 170 individuals. As a result of subsequent exclusions based on several criteria in both groups (diabetic patients, serum aluminum levels, serum calcium levels, and time on dialysis), the final low iPTH group consisted of 34 patients and the final high iPTH included 32 patients. A healthy control population (n = 120) and 162 of the 170-patient dialysis population served as control groups. VDR gene polymorphism was determined by digestion with the BsmI enzyme and single-strand conformation polymorphism analysis of PCR amplified fragments. Serum iPTH levels were lower in patients with the BB genotype than in those with the Bb or bb genotype, both in the total dialysis population and when the various exclusion criteria were applied. No differences in genotypic and allelic frequencies were found between the healthy control population and the high iPTH group. However, the genotypic distribution was significantly different in the low iPTH group of patients before and after applying all exclusion criteria (P = 0.037 and P = 0.018, respectively). In the final selected population, the bb genotype was less frequent in the low iPTH group than in the total dialysis population (14.7% versus 36.4%; odds ratio, 0.3; confidence interval, 0.11 to 0.82; P = 0.01). Conversely, the BB genotype was over-represented in the low iPTH group (23.3% versus 19.7%; odds ratio, 1.9; confidence interval, 0.85 to 4.3; P = 0.1). In addition, the bb genotype and the b allele frequencies were lower in the low iPTH group than in the high iPTH group (14.7% versus 34.4%, P = 0.06, and 41.2% versus 60.9%, P = 0.02, respectively), and the BB genotype and the B allele were significantly more frequent in the low PTH group than in the high iPTH group (32.3% versus 12.5%, P = 0.05, and 58.8% versus 39.1%, P = 0.02, respectively). Thus, VDR gene polymorphism influences parathyroid function in chronic renal failure.

Response to the hepatitis B virus vaccine in haemodialysis patients: influence of malnutrition and its importance as a risk factor for morbidity and mortality.

OBJECTIVE: To assess if malnutrition influences the response to the hepatitis B virus vaccine in haemodialysis patients and whether this correlates with morbidity and mortality in these patients. DESIGN: A 4-year prospective open study. SETTING: Haemodialysis unit of a 434-bed University Hospital. PATIENTS: Sixty-four patients with end-stage chronic renal failure on maintenance haemodialysis. INTERVENTIONS: Three-dose vaccination series with recombinant hepatitis B virus vaccine. MEASUREMENTS: Antibody formation against the vaccine, predialysis serum urea, serum albumin and prealbumin, dialysis efficacy (Kt/V), protein catabolic rate (PCR), arm muscle circumference, triceps skinfold, serum parathyroid hormone concentration, mortality and morbidity (hospital days per year of dialysis). RESULTS: Increase in age negatively influences the formation of antibodies (P = 0.01), whereas serum albumin (P = 0.008) and predialysis blood urea concentration (P = 0.004) are positively correlated with the formation of antibodies. Responders had significantly higher levels of serum albumin and prealbumin and predialysis blood urea than non-responders. The percentage of non-responders was higher (70%) in the group with predialysis blood urea concentration between 90 and 125 mg/dl than in those with predialysis blood urea concentrations between 176 and 225 mg/dl (14.2%). Patients with serum albumin levels between 3 and 3.5 g/dl were non-responders in a higher percentage (87.5%) than those with serum albumin levels between 4.5 and 5 g/dl (18.8%). After a 4-year follow-up, survival was 20% higher in the responder group (P < 0.05). Morbidity, expressed as hospital days per year of haemodialysis, was markedly lower in the responder group (10.4 +/- 2 versus 32 +/- 14 days, P = 0.03). CONCLUSIONS: Malnutrition negatively influences the response to the hepatitis B virus vaccine in haemodialysis patients. Non-responders have higher morbidity and mortality than responders, and therefore the absence of response to the hepatitis B vaccine can be considered as a risk factor in the haemodialysis population.

Low-calcium dialysate stimulates parathormone secretion and its long-term use worsens secondary hyperparathyroidism.

The long-term clinical effects of the use of a low calcium concentration in the dialysate are largely unknown. For this reason, the influence of low-calcium dialysate on parathyroid hormone (PTH) secretion in hemodialysis patients and its long-term effect on the severity of secondary hyperparathyroidism were studied. In 35 hemodialysis patients, the dialysate calcium concentration was lowered from 1.75 to 1.25 mmol/L. Twelve months later, serum iPTH levels increased significantly from 18.6 to 33.2 pmol/L and so did alkaline phosphatase levels, from 210 to 330 IU/L, without significant changes in serum calcium or phosphorus levels. Hemodialysis with low-calcium dialysate (1.25 mmol/L) induced a net calcium loss in 10 patients, without modifications in ionized serum calcium levels. In addition, mean serum iPTH increased 20% over baseline levels, reaching the maximal level at 30 min after the start of hemodialysis with low-calcium dialysate. In contrast, mean serum iPTH levels drop dramatically at 30 min of hemodialysis with high-calcium dialysate (1.75 mmol/L). It was concluded that low-calcium dialysate worsens secondary hyperparathyroidism in hemodialysis patients, probably by inducing a negative calcium balance and causing repetitive stimulation of PTH secretion in each dialysis. The maintenance of normal serum calcium levels could be due to PTH-induced calcium mobilization from bone.

Peritoneal transport evaluation in peritonitis: comparison between methods.

Peritoneal dialysis patients may need solute permeability transport evaluation during acute peritonitis. The aim of this study was to assess if the simplified mass transfer coefficient (MTCS) or the peritoneal equilibration test (PET) was equivalent to the complex MTC (MTCX) in solute transport evaluation during acute peritonitis in continuous ambulatory peritoneal dialysis (CAPD) patients. We studied 15 episodes of peritonitis (PTIS). Results were compared to a baseline patient study (PRE) and a control study done 30 days after diagnosis of peritonitis (POST). All peritoneal evaluation methods showed a significant increase in solute transport during acute peritonitis compared to baseline and control studies. There was an acceptable correlation between MTCX and simplified methods including the PET in the baseline and control studies. However, correlation between MTCX and simplified methods decreased during acute peritonitis. Likewise, the PET showed a better correlation with MTCX than MTCS. We conclude that the PET has an acceptable agreement with MTCX even during acute peritonitis, so the PET can be a useful tool in evaluating peritonitis-induced peritoneal permeability changes.

Level-dependent inhibitory effect of hyperaluminaemia on parathyroid hormone secretion in patients with end-stage renal failure.

OBJECTIVES: Serum aluminium and parathyroid hormone levels were measured in chronic dialysis patients at discovery of accidental exposure to high dialysate aluminium levels and followed after adequate water purification. PATIENTS AND METHODS: Twenty-nine patients with chronic renal failure on maintenance haemodialysis were accidently exposed to dialysate aluminium levels of 65 micrograms/L (recommended Food and Drug Administration values less than 10 micrograms/L) for 18 months. At discovery, oral aluminium was withdrawn and dialysate aluminium levels were corrected to less than 5 micrograms/L. Serum aluminium, parathyroid hormone, calcium, phosphorus and alkaline phosphatase levels were determined at discovery and two months and one year after the corrective measures. RESULTS: Mean serum aluminium level was 167.6 +/- 15 micrograms/L at discovery and simultaneous serum parathyroid levels were 7.9 +/- 2.2 pmol/L (normal values 1.1 to 4.6 pmol/L). Two months after discontinuation of oral aluminium and correction of dialysate aluminium levels to less than 5 micrograms/L, the patients' mean serum aluminium dropped to 49.6 +/- 4.3 micrograms/L and simultaneous serum parathyroid hormone levels rose to 14.6 +/- 3.2-pmol/L (p < 0.001). Similar levels were maintained at one year. Serum calcium did not change significantly. There was a significant correlation between the drop in serum aluminium and the increase in parathyroid hormone. CONCLUSION: These results confirm animal experiments and show convincingly that aluminium inhibits parathyroid secretion also in humans.

Pharmacokinetics of vancomycin in patients undergoing hemodialysis with polyacrylonitrile.

The pharmacokinetics of vancomycin in patients undergoing dialysis with cuprophane membranes are well known, however little has been reported of the use of polyacrylonitrile membranes in dialysis. We studied, in a crossover design, eight dialysis patients (7 men, 1 woman) aged 30 to 66 years who prospectively received 1 gram of vancomycin i.v. before first dialysis and were subsequently hemodialyzed with cuprophane every second day for a total of three times. A month later trial was repeated using polyacrylonitrile. A mono-compartment model was used to calculated pharmacokinetic parameters. Mean +/- standard deviation of vancomycin clearance varied from 5.2 +/- 2.1 ml/min in the interdialysis period to 9.7 +/- 2.7 ml/min during dialysis with cuprophane and to 58.4 +/- 15.6 ml/min during dialysis with polyacrylonitrile (p less than 0.001). Vancomycin half-life varied from 71.5 +/- 23.0 to 35.9 +/- 9.8 and to 6.1 +/- 1.4 hours, respectively (p less than 0.001). Fractional removal of vancomycin increased from 4% using the cuprophane dialyzer to 34% using the polyacrylonitrile dialyzer (p less than 0.001). Serum vancomycin levels at 100 and 168 hours were higher with cuprophane than with polyacrylonitrile (7.0 +/- 2.2 vs 3.9 +/- 1.2 micrograms/ml) (p less than 0.001). Moreover, the mean levels at 100 hours were suboptimal on polyacrylonitrile. Approximately 208 +/- 53 mg of vancomycin were removed during one polyacrylonitrile dialysis. Thus, those patients who undergo dialysis with polyacrylonitrile and are treated with vancomycin may need supplementary doses post dialysis or to lessen dosage intervals than those traditionally used for dialysis patients since clearance of the drug is significantly higher than with cuprophane dialyzers. Continuous monitoring of vancomycin levels is also recommended.