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.

Adult↗

PubMed2005

Posttransplantation chronic renal damage in nonrenal transplant recipients.

BACKGROUND: The growing problem of relentless deterioration of renal function in patients who undergo transplantation of nonrenal solid organs is bound to have an increasingly important impact as it may not only worsen patient morbidity and mortality but also increase transplantation costs. METHODS: We reviewed the literature in order to provide a sum of the most important data on the incidence, clinical picture, renal pathology pattern, damage mechanisms, and risk factors, along with strategies for prevention and treatment of chronic renal damage following nonrenal solid organ transplantation. RESULTS: Literature data report that 10% to 80% of transplanted patients have some degree of renal dysfunction and that they share a common clinical picture characterized by relentless asymptomatic progression, frequent hypertension, mild urinary abnormalities, and pathology features of vascular, glomerular, tubular, and interstitial involvement. These changes are very similar to those reported for chronic nephrotoxicity from calcineurin inhibitors. The occurrence of end-stage renal disease (ESRD) requiring chronic dialysis has been reported in up to 20% of nonrenal transplant recipients. Although there are some organ-specific differences, a group of common risk factors has been recognized, including the use of calcineurin inhibitors as immunosuppressive agents, age, pretransplantation renal function, intraoperative/perioperative factors, concomitant use of other nephrotoxic drugs, infections, and posttransplantation acute renal failure. CONCLUSION: Calcineurin inhibitor-induced nephrotoxicity is a growing problem and, as the age of recipients of nonrenal organs is increasing, this problem is destined to increase. It would therefore be advisable for nephrologists to share their experiences in immunomodulation with other specialties, so as to favor the cautious extension of calcineurin inhibitor-sparing protocols to the area of life-saving transplants.

Humans↗

PubMed2005

Protective effect of vitamin C supplementation in dialysis patients: not all that glitters...

Explore the source record for details and available documents.

Ascorbic Acid↗

PubMed2005

Blast from the past: the aluminum's ghost on the lanthanum salts.

Hyperphosphatemia is a common serious complication of chronic renal diseases, which needs appropriate continuous treatment in order to avoid ominous side effects. Therefore, oral chelating agents able to avoid phosphate absorption by the gut are mandatory. In the past, Aluminium salts, and more recently Calcium and Magnesium salts, and a synthetic resin polyallylamine hydrochloride have been employed, but Aluminium was later abandoned, because it has been a silent killer of many uremic patients, due to subtle absorption eventually leading to toxicity on Central Nervous System and bone, with allucinations, seizures, dementia, and osteomalacia, bone pain, fracturing osteodystrophy, and death. Recently, a new chelating agent able to bind dietary phosphate, namely Lanthanum carbonate has been introduced, with a proven efficacy profile for short-term treatment. However, after careful examination of the very few scientific papers available to date, we strongly advise caution before adopting, at present, lanthanum carbonate as a phosphate binder in uremic patients. In fact, notwithstanding minimized, some data are worrying: first, Lanthanum ions are absorbed, though at a minimal extent, by human gut; 2) pharmacokinetic evaluations show a greater exposure to Lanthanum in uremic patients;3) Lanthanum concentration is increased tenfold in blood and fivefold in bone after short-term supplementation in uremic patients; 4) there is no proofs that Lanthanum cannot cross the blood brain barrier in uremic patients; 5)Lanthanum has many biological effects and is potentially highly toxic. The Aluminum story should serve as cautionary tale when considering the use of new metal ions.

Area Under Curve↗

PubMed2004

Low-dose continuous iron therapy leads to a positive iron balance and decreased serum transferrin levels in chronic haemodialysis patients.

BACKGROUND: Iron balance is critical for adequate erythropoiesis, but its optimal therapeutic regimen remains to be defined. Continuous maintenance therapy with iron has been proposed for dialysis patients on recombinant human erythropoietin (rHuEpo) in the hope that the regimen is adequate and safe. METHODS: We determined serum ferritin, transferrin, transferrin saturation (TSAT), serum transferrin receptors, albumin and C-reactive protein (CRP) in a 3-year prospective study in 30 chronic haemodialysis patients on dialysis treatment for 132+/-111 months (18 males, 12 females; mean age 56+/-14 years). Beginning in the year 2000, they regularly received low-dose maintenance iron supplementation (i.v. iron gluconate 31.25 mg/week) for 12 months (Period 1 or first treatment phase), followed by a 6-month withdrawal (Period 2 or stop phase) and then by continuous maintenance iron therapy (i.v. iron gluconate 31.25 mg/week) for another 9 months (Period 3 or re-challenge phase). RESULTS: A significant increase in serum ferritin and TSAT was observed, with values exceeding 500 ng/ml and 50% in 10/30 (33%) and 7/30 (23%) of subjects, respectively, in Period 1, and in 11 and 5% in Period 3. A significant decrease in serum transferrin was documented during Period 1, followed by an increase in Period 2 and a decrease in Period 3. Serum albumin remained stable. Serum transferrin was always negatively correlated with ferritin (r = -0.41, P<0.001) and weakly correlated with serum transferrin receptors (r = 0.178, P<0.05), but was not correlated with serum albumin or CRP. Regression equations based on pre-treatment serum ferritin values were developed for predicting the value of serum ferritin at any time following the beginning of continuous iron supplementation. They fitted a linear relationship for males (y = 81 + 21.5 x time) and for females (y = 65 + 22 x time). Percentile charts for quantitative tracking of serum ferritin increases and decreases in patients have also been developed from values measured at different times. These charts show box-plot distributions of expected ferritin against time. CONCLUSIONS: Even continuous low-dose maintenance iron therapy, with only 31.25 mg weekly over 1 year, cannot prevent the risk of iron overload in patients with moderate anaemia. Furthermore, this treatment is responsible for decreases in serum transferrin, unrelated to changes in serum albumin, possibly of concern for hypo-transferrinaemia as an independent risk factor for iron toxicity.

Aged↗

PubMed2004

Interaction between gene polymorphisms of nitric oxide synthase and renin-angiotensin system in the progression of membranous glomerulonephritis.

BACKGROUND: The renin-angiotensin system (RAS) and nitric oxide synthase (NOS) play a key role in the progression of primary glomerulonephritis (GN). Although previous studies have examined genetic risk associated with single gene variations, experiments assessing risk conferred by multiple gene variations are still scanty. METHODS: The effect of combination of variant alleles of four genes encoding for three components of the RAS [angiotensin converting enzyme insertion/deletion (ACE I/D), angiotensin II receptor 1 (AT1R 1166A/C), angiotensinogen (AGT M235T)] and for NOS (ecNOS4b/a) on the development and progression of membranous GN (MGN) were evaluated in a longitudinal study comparing 117 patients with serum creatinine (s-Cr) <1.5 mg/dl at renal biopsy and follow-up > or = 5 years (Kaplan-Meier and Cox multivariate analysis). The control group consisted of DNA from 171 organ donors. RESULTS: We found no relationship between single or combined variations of the four gene polymorphisms and development of MGN. Among single gene variations, there were no independent genetic risk factors for the progression of renal disease, after adjustment for age, sex, hypertension, proteinuria, s-Cr, chronicity and activity index. However, double variation coincidences such as the combination of the allele a of ecNOS4b/a and both the allele D of ACE I/D (chi(2) =4.80, P = 0.028; HR = 1.97, 95% CI 0.98-3.96) and the allele T of AGT (M235T) (chi(2) = 5.09, P = 0.024; HR = 2.84, 95% CI 1.39-5.82) exerted an additional effect that was higher than that of the single gene variations. CONCLUSION: This study is the first to demonstrate a role for an interaction between simultaneous variations of genes encoding for NOS and components of RAS in the progression of MGN. Interactions between various polymorphisms may explain conflicting results obtained in previous studies that examined single gene variations, since the effect of a single locus variation may be influenced by the simultaneous presence of other variant alleles in polygenic diseases such as primary GN. However, the small sample sizes and possible multiple interactions limited the interpretation of the current findings, which may represent true biological interaction or simply statistical interactions or spurious results due to the small sample sizes.

Adult↗

PubMed2004

Validation of serum ferritin values by magnetic susceptometry in predicting iron overload in dialysis patients.

BACKGROUND: Guidelines for treating anemia in dialysis patients accept, as high-end range of serum ferritin useful to optimize erythropoietin therapy, values high as 500 to 900 microg/L, on the hypothesis that ferritin might be not representative of iron overload. METHODS: A superconducting quantum interference device (SQUID) was used to make direct noninvasive magnetic measurements of nonheme hepatic iron content in 40 dialysis patients treated with intravenous iron, and liver iron content was compared with biochemical markers of iron status. RESULTS: Only 12/40 (30%) patients showed normal hepatic iron content (SQUID <400 microg/g), while 32.5% had mild (400 to 1000 microg/g) and 37.5% severe (>1000 microg/g) iron overload, although 28/40 patients (70%) had serum ferritin below 500 microg/L. Among many parameters, hepatic iron content was only correlated with ferritin (r= 0.324, P= 0.04). The receiver operating characteristic (ROC) analysis showed the best specificity/sensitivity ratio to identify iron overload for ferritin >340 microg/L (W = 0.716). Multivariate logistic regression analysis demonstrated that an increase in serum ferritin of 100 microg/L and female gender were independent variables associated with moderate to severe hepatic iron overload: OR 1.71 (95% CI 1.10 to 2.67) and OR 10.68 (95% CI 1.81 to 63.15), respectively. CONCLUSION: Hepatic iron overload is frequent in dialysis patients with ferritin below currently proposed high-end ranges, and the diagnostic power of ferritin in indicating true iron stores is better than presumed. Safety concerns should prompt a reevaluation of acceptable iron parameters, focusing on potential gender-specific differences, to avoid potentially harmful iron overload in a majority of dialysis patients, mainly females.

Adult↗

PubMed2004