Phosphorus metabolism in peritoneal dialysis- and haemodialysis-treated patients.

BACKGROUND: Phosphorus control is generally considered to be better in peritoneal dialysis (PD) patients as compared with haemodialysis (HD) patients. Predialysis phosphorus concentrations are misleading as a measure of phosphorus exposure in HD, as these neglect significant dialysis-related fluctuations. METHODS: Parameters of mineral metabolism, including parathyroid hormone (PTH) and fibroblast growth factor-23 (FGF-23), were determined in 79 HD and 61 PD patients. In PD, phosphorus levels were determined mid-morning. In HD, time-averaged phosphorus concentrations were modelled from measurements before and after the mid-week dialysis session. Weekly renal, dialytic and total phosphorus clearances as well as total mass removal were calculated from urine and dialysate collections. RESULTS: Time-averaged serum phosphorus concentrations in HD (3.5 ± 1.0 mg/dL) were significantly lower than the mid-morning concentrations in PD (5.0 ± 1.4 mg/dL, P < 0.0001). In contrast, predialysis phosphorus concentrations (4.6 ± 1.4 mg/dL) were not different from PD. PTH and FGF-23 levels were significantly higher in PD. Despite higher residual renal function, total phosphorus clearance was significantly lower in PD (P < 0.0001). Total phosphorus mass removal, conversely, was significantly higher in PD (P < 0.05). CONCLUSIONS: Our data suggest that the time-averaged phosphorus concentrations in patients treated with PD are higher as compared with patients treated with HD. Despite a better preserved renal function, total phosphorus clearance is lower in patients treated with PD. Additional studies are needed to confirm these findings in a population with a different demographic profile and dietary background and to define clinical implications.

Prevalence and determinants of anemia in the immediate postkidney transplant period.

At the time of renal transplantation, erythropoiesis-stimulating agents and iron supplementation are routinely discontinued in the prospect of recovery of renal function. This recovery, however, is often delayed and suboptimal. In addition, blood loss because of frequent diagnostic phlebotomies may be substantial. Renal transplant recipients may thus be considered at high risk of anemia in the immediate post-transplant period. We performed a single-center observational study, including 391 recipients of a single kidney. Hemoglobin levels and parameters of iron metabolism were monitored during the immediate post-transplant period, i.e., the first 3 months after transplantation. Hemoglobin levels decreased by 3.8 ± 1.5 g/dl to reach a nadir of 9.1 ± 1.2 g/dl at day 7. Transient severe anemia was observed in 91.3% of the patients. Donor age, gender, renal diagnosis of polycystic disease, pretransplant hemoglobin and ferritin level, estimated glomerular filtration rate at month 3, and duration of initial hospitalization were observed to be independently associated with the hemoglobin level at month 3. Transient severe anemia is an almost universal observation in incident renal transplant recipients. Poor graft function, high donor age, and low iron stores are independently associated with low hemoglobin levels at month 3.

Fibroblast growth factor-23 in early chronic kidney disease: additional support in favor of a phosphate-centric paradigm for the pathogenesis of secondary hyperparathyroidism.

BACKGROUND AND OBJECTIVES: The discovery of fibroblast growth factor-23 (FGF-23) and the elucidation of its function as a phosphaturic and 1,25(OH)2VitD counter-regulatory hormone provides a new conceptual framework for the understanding of the pathogenesis of secondary hyperparathyroidism. This study aims to elucidate the complex associations between FGF-23, parathyroid hormone (PTH), 1,25(OH)2D, and phosphate in patients with early-stage chronic kidney disease (CKD) and to provide clinical evidence in favor of the new phosphate-centric paradigm for the pathogenesis of secondary hyperparathyroidism. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Serum biointact PTH and FGF-23, 25(OH)D, 1,25(OH)2D, calcium, phosphate, 24-hour urine excretion of phosphate and calcium, and urinary fractional excretion of phosphate were determined in a cross-sectional study including 125 patients with CKD stages 1 to 3. RESULTS: Serum phosphate levels showed an inverse association with estimated GFR (eGFR), but were within the normal range in all but one patient. FGF-23 and PTH were inversely associated with eGFR, even in the subgroup of patients with CKD stages 1 and 2. High FGF-23 levels were significantly more prevalent than high PTH levels. The urinary fractional excretion of phosphate was highest in patients with both a high serum FGF-23 and PTH level. Increased FGF-23 and phosphate and decreased 25(OH)D were independently associated with decreased 1,25(OH)2D. CONCLUSIONS: Our data are in favor of the new paradigm for the pathogenesis of secondary hyperparathyroidism according to which a reduced phosphate excretion capacity is the principal abnormality that initiates secondary hyperparathyroidism.

Immunogenicity of a standard trivalent influenza vaccine in patients on long-term hemodialysis: an open-label trial.

BACKGROUND: Disturbances in acquired immunity are considered to be responsible, at least in part, for the high infection rate and inadequate response to vaccinations observed in hemodialysis (HD) patients. The present prospective trial aimed to: (1) evaluate the immunogenicity of a standard influenza vaccine in HD patients, and (2) identify determinants of the immune response. STUDY DESIGN: Prospective interventional open-label study. SETTING & PARTICIPANTS: 201 long-term HD patients and 41 healthy volunteers. INTERVENTION: Vaccination with a standard trivalent inactivated influenza vaccine. OUTCOMES: The primary outcome was seroprotection rate, defined as percentage of participants with an antibody titer of 40 or greater 1 month after vaccination. MEASUREMENTS: All antibody titers were determined in duplicate by using the hemagglutination inhibition assay. Regression analyses were performed to investigate the association between demographics, uremic retention solutes (including p-cresol), inflammation, nutrition, iron status, trace elements, and immune response in HD patients. RESULTS: More than 80% of HD patients showed seroprotection after vaccination. The immune response of HD patients was similar to that of healthy volunteers. Booster vaccination did not improve the immune response. High serum ferritin level was the only parameter independently associated with a better vaccination-induced antibody response in HD patients. LIMITATIONS: A high seroprotection rate at baseline undermined the power to identify clinical determinants of the immune response. CONCLUSIONS: Influenza vaccination is as efficacious in HD patients as in healthy volunteers. With the exception of serum ferritin, none of the investigated parameters of nutrition, inflammation, and dialysis adequacy had a significant impact on the immune response. Our data support annual vaccination of HD patients and question the clinical relevance of disturbances in acquired immunity in contemporary HD patients.

Calcium metabolism in the early posttransplantation period.

BACKGROUND AND OBJECTIVES: Information on the time course of serum calcium levels after renal transplantation is scanty, especially in the early posttransplantation period. Both the abrupt cessation of calcium-containing phosphorus binders and vitamin D (analogs) at the time of surgery and the recovery of renal function may be hypothesized to affect serum calcium levels in this period. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In this prospective observational study, biointact parathyroid hormone, calcidiol, calcitriol, calcium, and phosphorus levels were monitored in 201 renal transplant recipients at the time of transplantation and 3 mo thereafter. In addition, the serum calcium nadir and peak in each individual patient within this time frame were identified and the urinary fractional calcium excretion was determined at month 3. RESULTS: Serum calcium levels followed a biphasic pattern with a significant decline during the first postoperative week, followed by a significant increase. High pretransplantation parathyroid hormone levels protect against hypocalcemia within the first postoperative week but put patients at risk for hypercalcemia later. These complications, occurring in 41 and 14% of the patients, respectively, most probably reflect inappropriate calcium release from the skeleton, rather than inappropriate renal calcium handling. CONCLUSIONS: Our data indicate that both hypo- and hypercalcemia are prevalent in the early posttransplantation period. Pretransplantation parathyroid function is an important predictor of posttransplantation calcium levels.

Recovery of hyperphosphatoninism and renal phosphorus wasting one year after successful renal transplantation.

BACKGROUND AND OBJECTIVES: In the first months after successful kidney transplantation, hypophosphatemia and renal phosphorus wasting are common and related to inappropriately high parathyroid hormone (PTH) and fibroblast growth factor-23 (FGF-23) levels. Little is known about the long-term natural history of renal phosphorus homeostasis in renal transplant recipients. DESIGN, SETTING, PARTICIPANTS: We prospectively followed parameters of mineral metabolism (including full-length PTH and FGF-23) in 50 renal transplant recipients at the time of transplantation (Tx), at month 3 (M3) and at month 12 (M12). Transplant recipients were (1:1) matched for estimated GFR with chronic kidney disease (CKD) patients. RESULTS: FGF-23 levels (Tx: 2816 [641 to 10665] versus M3: 73 [43 to 111] versus M12: 56 [34 to 78] ng/L, median [interquartile range]) and fractional phosphorus excretion (FE(phos); M3: 45 +/- 19% versus M12: 37 +/- 13%) significantly declined over time after renal transplantation. Levels 1 yr after transplantation were similar to those in CKD patients (FGF-23: 47 [34 to 77] ng/L; FE(phos) 35 +/- 16%). Calcium (9.1 +/- 0.5 versus 8.9 +/- 0.3 mg/dl) and PTH (27.2 [17.0 to 46.0] versus 17.5 [11.7 to 24.4] ng/L) levels were significantly higher, whereas phosphorus (3.0 +/- 0.6 versus 3.3 +/- 0.6 mg/dl) levels were significantly lower 1 yr after renal transplantation as compared with CKD patients. CONCLUSIONS: Data indicate that hyperphosphatoninism and renal phosphorus wasting regress by 1 yr after successful renal transplantation.

Calcium requirements after parathyroidectomy in patients with refractory secondary hyperparathyroidism.

BACKGROUND/AIMS: Calcium supplements are often required following successful parathyroidectomy (PTX) in order to prevent overt hypocalcemia. The current study aims to quantify these calcium needs and to identify predictors of a high calcium need present at the time of surgery. METHODS: Charts of 42 patients with chronic kidney disease stage 5D, who underwent a successful subtotal PTX, were reviewed in detail. Biochemical indices of mineral metabolism available within a time frame of 4 weeks before and 6 weeks after the surgery were registered. Details concerning active vitamin D (1-alpha-calcidiol and calcitriol) and calcium supplementation were recorded as well. RESULTS: Serum calcium, phosphorus and PTH levels declined whereas total alkaline phosphatase levels increased significantly in the early post-PTX period. Transient hypocalcemia was observed in 83% of the patients. The median daily postoperative elemental calcium requirements amounted to 3.2 g during week 1, and declined to 2.4 g during week 6. A high preoperative PTH level and a low serum calcium level were identified as independent predictors of a high postoperative calcium need. CONCLUSION: Substantial amounts of elemental calcium are required following successful subtotal PTX in order to avoid frank hypocalcemia, especially in patients with a high PTH level and a low calcium level before surgery.

AA amyloidosis due to chronic oxalate arthritis and vasculitis in a patient with secondary oxalosis after jejunoileal bypass surgery.

We report a case of a woman with secondary oxalosis after jejunoileal bypass surgery for obesity, who presented with oxalate stone disease and renal insufficiency requiring dialysis. Thirty years after surgery, longstanding osteoarticular symptoms were recognized as oxalate arthritis. Eventually, she also developed oxalate vasculitis, which improved with corticoid treatment and intensification of dialysis. Work-up for kidney transplantation revealed AA amyloidosis on gastric and colonic biopsies. Since no other cause of chronic inflammation could be identified, it was concluded that the amyloidosis was secondary to oxalate arthritis and vasculitis. To our knowledge, this is the first report on this association.

The influence of inulin on the absorption of nitrogen and the production of metabolites of protein fermentation in the colon.

In the present study, the production and fate of bacterial metabolites in the colon were investigated in a direct way using two substrates labelled with stable isotopes: lactose [(15)N,(15)N]ureide as a source of labelled ammonia and egg proteins intrinsically labelled with [(2)H4]tyrosine as a precursor of [(2)H4]p-cresol. Both ammonia and phenolic compounds are believed to be carcinogenic. Stimulation of carbohydrate fermentation in order to prevent accumulation of these toxic metabolites was induced by inclusion of inulin in a test meal or by addition of inulin to the daily diet, allowing us to distinguish between changes induced by the actual presence of a fermentable carbohydrate and effects caused by a long-term dietary intervention. When a single dose of inulin was administered together with the labelled substrates, a significant increase in faecal (15)N excretion, accompanied by a proportional decrease in urinary (15)N excretion was observed, probably reflecting an enhanced uptake of ammonia for bacterial biosynthesis, since an increased concentration of labelled N in bacterial pellets was found. A statistically significant reduction of urinary [(2)H4]p-cresol excretion was also noted. Upon supplementation of inulin to the daily diet during 4 weeks, however, only a tendency towards decreased urinary excretion of both labelled and unlabelled p-cresol was noted. Further studies are warranted to confirm these results in a larger cohort.