Comparison of two iron gluconate treatment modalities in chronic hemodialysis patients: results of a randomized trial.

BACKGROUND: Iron supplementation in chronic hemodialyzed patients is not yet completely defined concerning the dosing regimen. This study aimed to evaluate the effects of the same iron load administered in different regimens on anemia, iron status and the reticulocyte (Ret) subpopulation patterns in stable patients on chronic hemodialysis (HD). PATIENTS AND METHODS: Seventeen patients undergoing thrice-weekly chronic HD and receiving stable alphaerythropoietin therapy with absolute iron deficiency (transferrin saturation (TSAT) <20%, ferritin (Frt) <100 ng/mL) were randomly divided into two groups: group A (n=9) received 20.8 mg of sodium iron gluconate at the end of each dialysis session; group B (n=8) 62.5 mg only at the end of the 1st dialysis session of the week. The treatment period lasted 3 months (period 1) and was followed by 3 months of observation (period 2). RESULTS: Both treatments increased hemoglobin (Hb) levels by an average of 0.90 g/dL in period 1, with a progressive decline in period 2 (p=ns between groups), peaking at 11.2 g/dL in group A and 10.8 g/dL in group B. The effects on mean red blood cell volume and Hb concentrations were similar. Frt levels more than doubled during period 1 and early in period 2 in both groups (172 microg/L in group A; 149 microg/L in group B, and progressively decreased in period 2 (p=ns between groups). The TSAT index increased progressively peaking to 28.7% in group A and 24.3% in group B. Hypochromic red blood cells (hypocRBC) decreased early from 5.6-2.2% in group A, and from 5.5-2.1% in group B, and persisted in period 2; the between-period differences for the combined groups were statistically significant (p=0.0051). High fluorescence reticulocytes (HFR) increased from period 1 to period 2 only in group B (from 0.8-1.7%, p=0.012). CONCLUSIONS: Both regimens replenished iron stores and improved anemia. The HFR increase in group B could be due to soluble transferring receptor (STnfR) gene upregulation; alternatively it could indicate the prevalence of immature Ret release from bone marrow.

Blood volume controlled hemodialysis in hypotension-prone patients: a randomized, multicenter controlled trial.

BACKGROUND: Recently we have devised and tested a biofeedback system for controlling blood volume (BV) changes during hemodialysis (HD) along an ideal trajectory (blood volume tracking, BVT), continuously modifying the weight loss rate and dialysate conductivity. This multicenter, prospective, randomized, crossover study aimed to clarify whether BVT (treatment B) can improve hypotension-prone patients' treatment tolerance, compared with conventional hemodialysis (treatment A). METHODS: Thirty-six hypotension-prone patients enrolled from 10 hemodialysis (HD) centers were randomly assigned to either of the study sequences ABAB or BABA, each lasting four months. RESULTS: A 30% reduction in intradialytic hypotension (IDH) events was observed in treatment B as compared with A (23.5% vs. 33.5%, P = 0.004). The reduction was related to the number of IDH in treatment A (y = 0.54x + 5; r = 0.4; P < 0.001): the more IDH episodes in treatment A, the better the response in treatment B. The best responders to treatment B showed pre-dialysis systolic blood pressure values higher than the poor responders (P = 0.04). A 10% overall reduction in inter-dialysis symptoms was obtained also in treatment B compared to A (P < 0.001). Body weight gain, pre-dialysis blood pressure, intradialytic weight loss as well as Kt/V did not differ between the two treatments. CONCLUSIONS: An overall improvement in the treatment tolerance was observed with BVT, particularly intradialytic cardiovascular stability. Patients with the highest incidence of IDH during conventional HD and free from chronic pre-dialysis hypotension seem to respond better. Inter-dialysis symptoms also seem to improve with control of BV.

Epithelial-mesenchymal transition of tubular epithelial cells in human renal biopsies.

BACKGROUND: In recent studies performed on cultured cells and experimental nephropathies, it has been hypothesized that tubular epithelial cells (TEC), via epithelial-mesenchymal transformation (EMT), can become collagen-producing cells. According to this theory, they should proceed through several activating steps, such as proliferation and phenotype changes, to eventually synthesize extracellular matrix (ECM). METHODS: To evaluate whether EMT operates in human TECs, 133 renal biopsies of different renal diseases were studied, analyzing by immunohistochemistry and in situ hybridization the possible expression of markers of proliferation (PCNA, Mib-1), cellular phenotype (vimentin, alpha-SMA, cytokeratin, ZO-1) and ECM production (prolyl 4-hydroxylase, HSP47, interstitial collagens). RESULTS: Independently of histological diagnosis, variable degrees of TEC positivity for PCNA (2.7 +/- 2.4 cells/field) and Mib-1 (1.9 +/- 2.3) were present. TECs expressing vimentin (1.4 +/- 4.7) and alpha-smooth muscle actin (alpha-SMA; 0.04 +/- 0.4) also were detected. It was possible to observe loss of epithelial antigens from 8 to 10% of the tubular cross sections. Moreover, TECs were stained by prolyl 4-hydroxylase (3.6 +/- 4.3), heat shock protein-47 (HSP47; 2.9 +/- 5.4), collagen type I (0.2 +/- 2.7) and type III (0.3 +/- 2.0). Collagen types I and III mRNAs were found in 0.8 to 1.4 cells/field. The number of TEC with EMT features were associated with serum creatinine and the degree of interstitial damage (P< or = 0.03), and even considering the 45 cases with mild interstitial lesions, the tubular expression of all markers remained strictly associated with renal function (P< or = 0.01). CONCLUSIONS: Our results suggest that, via transition to a mesenchymal phenotype, TEC can produce ECM proteins in human disease and directly intervene in the fibrotic processes. Moreover, the association of EMT features with serum creatinine supports the value of these markers in the assessment of disease severity.

Anti-GBM nephritis complicating diabetic nephropathy.

There are several reports of glomerulonephritis (GN) in diabetics or patients with diabetic glomerulosclerosis. Cases of rapidly progressive GN where crescentic histologic changes are superimposed on diabetic glomerulosclerosis are very unusual. We report the case of a patient with type I diabetes mellitus, who developed rapidly progressive renal insufficiency. Renal biopsy disclosed anti-glomerular basement membrane nephritis superimposed on classical diabetic glomerulosclerosis.