Effects of the glutamate carboxypeptidase II (GCP2 1561C>T) and reduced folate carrier (RFC1 80G>A) allelic variants on folate and total homocysteine levels in kidney transplant patients

Effects of the glutamate carboxypeptidase II (GCP2 1561C>T) and reduced folate carrier (RFC1 80G>A) allelic variants on folate and total homocysteine levels in kidney transplant patients.BackgroundThe effect of the glutamate carboxypeptidase II GCP2 1561C>T and the reduced folate carrier 1 RFC1 80G>A polymorphisms on folate and total homocysteine (tHcy) plasma levels of kidney transplant patients are unknown.MethodsIn a cross-sectional study of 730 kidney allograft recipients, GCP2 1561C>T, RFC1 80G>A, folate, and tHcy plasma levels were analyzed using linear regression models that allowed dependent covariates to follow a gamma distribution for univariate and multivariate analyses.ResultsThe allele frequency for GCP2 1561C>T was 0.05, and 0.43 for RFC1 80G>A. Heterozygosity or homozygosity for GCP2 1561C>T was associated with higher folate plasma levels compared to patients without mutation (P < 0.0001), while RFC1 80G>A showed no influence. Multiple testing, also including MTHFR 677C>T and MTHFR 1298A>C, revealed no interaction between the different genotypes and the folate plasma concentration. Neither GCP2 1561C>T nor RFC1 80G>A showed an association with tHcy plasma levels.ConclusionWe conclude that GCP2 1561C>T is associated with elevated folate levels. GCP2 1561C>T and RFC1 80G>A are no major determinants of tHcy plasma levels in kidney transplant patients

Agalsidase Alfa Slows the Decline in Renal Function in Patients with Fabry Disease

The aim of this study was to determine the effects of enzyme replacement therapy with agalsidase α on renal function in patients with Fabry nephropathy. Serum creatinine data were collected from 165 adult patients during 3 years of treatment. Serum creatinine increased in all men whereas it was stable in women, except in stage II renal disease (Kidney Disease Outcomes Quality Initiative). The estimated glomerular filtration rate (eGFR) declined in males with stage I and II (from 115.0 ± 22.2 to 98.3 ± 27.3 and from 76.5 ± 8.1 to 66.3 ±21.6 ml/min/1.73 m2, respectively; both p 2; p = 0.01). The 24-hour proteinuria was <1 g in all patients, and most patients (96%) were treated with angiotensin receptor blockers (ARBs) or angiotensin-converting enzyme (ACE) inhibitors. Agalsidase α in combination with ACE inhibitors/ARB may be effective in slowing the deterioration in renal function in Fabry nephropathy

Effects of TCN2 776C>G on vitamin B12, folate, and total homocysteine levels in kidney transplant patients

Effects of TCN2 776C>G on vitamin B12, folate, and total homocysteine levels in kidney transplant patients.BackgroundControversy exists regarding the possible associations between a single nucleotide polymorphism of the transcobalamin II encoding gene (TCN2 776C>G) and plasma levels of vitamin B12, folate, or total homocysteine.MethodsIn a cross-sectional study of 732 kidney allograft recipients, patients were categorized by TCN2 776C>G genotype. In univariate and multivariate linear regression models that allowed the outcome variables vitamin B12, folate, and total homocysteine plasma levels to follow a gamma distribution, we tested for possible associations of allelic variants of the TCN2 776C>G gene and these three dependent variables.ResultsThe allele frequency for TCN2 776C>G was 0.46. Heterozygosity or homozygosity for TCN2 776C>G was not associated with plasma levels of vitamin B12 (776CG, P = 0.22; 776GG, P = 0.89), folate (776CG, P = 0.91; 776GG, P = 0.84), or total homocysteine (776CG, P = 0.11; 776GG, P = 0.33) even after adjustment for several possible confounders.ConclusionWe conclude from this largest study on the subject thus far that there are no associations between allelic variants of TCN2 776C>G and plasma vitamin B12, folate, or total homocysteine plasma levels in kidney transplant patients

GBV-C/HGV in hemodialysis patients: Anti-E2 antibodies and GBV-C/HGV-RNA in serum and peripheral blood: mononuclear cells

GBV-C/HGV in hemodialysis patients: Anti-E2 antibodies and GBV-C/HGV-RNA in serum and peripheral blood mononuclear cells. Hepatitis G virus (GBV-C/HGV), a recently identified RNA virus adds to the risk of parenteral transmitted viral infections in hemodialysis patients. We studied the prevalence of GBV-C/HGV-RNA in serum and peripheral blood mononuclear cells (PMNC) by reverse transcription-polymerase chain reaction (RT-PCR) and determined antibodies against the envelope protein E2 of GBV-C/HGV by ELISA. A total of 119 dialysis patients were studied. GBV-C/HGV-RNA was found in 16 of 119 patients (13%) as compared with 2% of healthy controls (P = 0.014). Two of the 16 GBV-C/HGV-RNA+ patients were co-infected with HCV, and none was positive for HBV-DNA. In 38% of serum GBV-C/HGV-RNA+ patients GBV-C/HGV-RNA was also detected in PMNC. In addition, GBV-C/HGV-RNA was identified in PMNC of 2 patients negative for GBV-C/HGV-RNA in serum. Twenty-four patients had anti-E2 antibodies in serum (20%), but were GBV-C/HGV-RNA-. In addition, two of the 16 GBV-C/HGV-RNA+ patients were concomitantly positive for anti-E2 antibodies. Only one of the 16 GBV-C/HGV infected patients had elevated aminotransferases; this patient was co-infected with hepatitis C virus. GBV-C/HGV-RNA positivity was independent on duration of hemodialysis, but GBV-C/HGV-RNA+ patients had received more units of blood in the past. Combined data of past contact, as assessed by anti-E2 antibodies, and present infection, documented by GBV-C/HGV-RNA, indicate a high overall exposure to GBV-C/HGV in dialysis patients

HBV and HCV genome in peripheral blood mononuclear cells in patients undergoing chronic hemodialysis

HBV and HCV genome in peripheral blood mononuclear cells in patients undergoing chronic hemodialysis. Patients undergoing chronic hemodialysis are at risk for infection with hepatitis B virus (HBV) and hepatitis C virus (HCV). As peripheral blood mononuclear cells (PMNC) are known to be susceptible to infection of both HBV and HCV, assessment of viral genomes in those cells could uncover occult infections not detected by serologic methods or virus determination in serum. We investigated all 67 patients undergoing chronic hemodialysis at a single dialysis unit by PCR for the presence of HBV or HCV genomes in serum as well as in PMNC. None of the 67 patients was HBsAg positive or showed HBV-DNA in serum, but in 5 patients HBV-DNA in PMNC was detected as the only marker of HBV-infection; those patients were also anti-HBc negative. In 9 patients HCV-RNA was positive in serum; in 5 of those patients it was also found in PMNC. Three of these infected patients were negative for anti-HCV. One other patient had no anti-HCV or HCV-RNA in serum, but was positive for HCV-RNA in PMNC. Thus, in 6 patients (8.9%) undergoing chronic hemodialysis we found evidence of infection with HBV or HCV by detecting viral genomes in PMNC without the presence of viremia, antigenemia or specific viral antibodies in serum. The detection of viral genomes in PMNC could be useful in the positive identification of additional potentially infectious patients

Epidemiology of Uromodulin-Associated Kidney Disease – Results from a Nation-Wide Survey

BACKGROUND/AIMS: Uromodulin-associated kidney disease (UAKD) is caused by uromodulin mutations and leads to end-stage renal disease. Our objective was to examine the epidemiology of UAKD. METHODS: Data from all UAKD families in Austria were collected. Patients included in the Austrian Dialysis and Transplantation Registry (OEDTR) with unclear diagnoses or genetic diseases were asked whether they had (1) a family history of kidney disease or (2) had suffered from gout. Patients with gout and autosomal dominant renal disease underwent mutational analysis. Kaplan-Meier and Cox analysis was employed to estimate time to renal failure. RESULTS: Of the 6,210 patients in the OEDTR, 541 were approached with a questionnaire; 353 patients answered the questionnaire. Nineteen of them gave two affirmative answers. In 7 patients, an autosomal dominant renal disease was found; in 1 patient a UMOD mutation was identified. One family was diagnosed through increased awareness as a consequence of the study. At present, 14 UAKD patients from 5 families are living in Austria (1.67 cases per million), and 6 of them require renal replacement therapy (0.73 per 1,000 patients). Progression to renal failure was significantly associated with UMOD genotype. CONCLUSION: UAKD patients can be identified by a simple questionnaire. UMOD genotype may affect disease progression

Associations between MTHFR 1793G>A and plasma total homocysteine, folate, and vitamin B12 in kidney transplant recipients

Associations between MTHFR 1793G>A and plasma total homocysteine, folate, and vitamin B12 in kidney transplant recipients.BackgroundCurrently, no evidence is available on the putative associations between a novel single nucleotide polymorphism of the 5,10-methylenetetrahydrofolate reductase gene MTHFR 1793G>A and plasma levels of vitamin B12, folate, or total homocysteine (tHcy).MethodsIn a cross-sectional study of 730 kidney allograft recipients, patients were categorized by MTHFR 1793G>A genotype. In univariate and multivariate linear regression models that allowed the outcome variables vitamin B12, folate, and tHcy plasma levels to follow a gamma distribution, we tested for possible associations of allelic variants of MTHFR 1793G>A and these three dependent variables. As hypothesized in previous work, we specifically evaluated possible effect modification between the MTHFR 1793G>A and 1298A>C mutations on these outcomes.ResultsThe allele frequency for MTHFR 1793G>A was 0.052. Heterozygosity (N = 72) or homozygosity (N = 2) for MTHFR 1793G>A was not independently associated with plasma levels of vitamin B12 (P = 0.33) or tHcy (P = 0.70), but a borderline association with higher folate concentrations was detected (Δfolate = 1.91 nmol/L) (95% CI -0.03 to 3.86 nmol/L) (P = 0.05). Further, we found strong and significant positive interactions between the MTHFR 1793G>A and 1298A>C mutations on vitamin B12 concentrations.ConclusionHigher folate concentrations in kidney transplant recipients with MTHFR 1793GA or 1793AA and markedly higher concentrations of vitamin B12 in patients with combined MTHFR 1793G>A and 1298A>C mutations may contribute to the survival advantage that has been postulated for such patients showing these genotypes

Oral Sodium Bicarbonate Supplementation Does Not Affect Serum Calcification Propensity in Patients with Chronic Kidney Disease and Chronic Metabolic Acidosis

Background: Cardiovascular disease is the leading cause of death in patients with chronic kidney disease (CKD) and metabolic acidosis might accelerate vascular calcification. The T50 calcification inhibition test (T50-test) is a global functional test analyzing the overall propensity of calcification in serum, and low T50-time is associated with progressive aortic stiffening and with all-cause mortality in non-dialysis CKD, dialysis, and transplant patients. Low serum bicarbonate is associated with a short T50-time and alkali supplementation could be a simple modifier of calcification propensity. The aim of this study was to investigate the short-term effect of oral sodium bicarbonate supplementation on T50-time in CKD patients. Material and Methods: The SoBic-study is an ongoing randomized-controlled trial in CKD-G3 and G4 patients with chronic metabolic acidosis (serum HCO3– ≤21 mmol/L), in which patients are randomized to either achieve serum HCO3– levels of 24 ± 1 mmol/L (intervention group) or 20 ± 1 mmol/L (rescue group). The effect of bicarbonate treatment on T50-time was assessed. Results: The study cohort consisted of 35 (14 female) patients aged 57 (±15) years, and 18 were randomized to the intervention group. The mean T50-time was 275 (± 64) min. After 4 weeks, the mean change of T50-time was 4 (±69) min in the intervention group and 18 min (±56) in the rescue group (β = –25; 95% CI: –71 to 22; p = 0.298). Moreover, change of serum bicarbonate in individual patients was not associated with change in T50-time, analyzed by regression analysis. Change of serum phosphate had a significant impact on change of T50-time (β = –145; 95% CI: –237 to –52). Conclusion: Oral sodium bicarbonate supplementation showed no effect on T50-time in acidotic CKD patients

Dose-dependent effect of parenteral iron therapy on bleomycin-detectable iron in immune apheresis patients

Dose-dependent effect of parenteral iron therapy on bleomycin-detectable iron in immune apheresis patients.BackgroundIron deficiency and anemia are commonly encountered in patients with autoimmune diseases undergoing immune apheresis. This makes erythropoietin and iron substitution necessary in most patients. However, intravenous iron therapy may result in an increase of potentially toxic nontransferrin-bound iron.MethodsWe examined the effect of 50 mg or 100 mg of iron (III) sucrose on bleomycin-detectable iron (BDI) in immune apheresis patients. Six patients with autoimmune disorders and normal kidney function were enrolled. Before and after the injection of 50 mg or 100 mg of iron (III) sucrose, BDI was measured in serum samples at five different time points.ResultsThere was no BDI traceable before injection of iron (III) sucrose. BDI was present in serum of all patients after the administration of 100 mg of iron (III) sucrose in concentrations up to 0.49 μmol/L. In contrast, only one patient showed BDI at a concentration of 0.16 μmol/L after the administration of 50 mg of iron (III) sucrose.ConclusionWe conclude that if parenteral iron is administered after apheresis treatment, despite the equal tolerability, use of 50 mg of iron (III) sucrose is superior to 100 mg of iron (III) sucrose in avoiding the formation of potentially toxic nontransferrin-bound iron