Total dialysate calcium effects on calcium balance during dialysis.

INTRODUCTION: Total dialysate calcium concentration has an important influence on calcium metabolism in bicarbonate high-flux dialysis. The aim of the study is to investigate the influence of different dialysate calcium concentrations on serum concentration of ionised calcium and on the balance of total dialysate calcium. MATERIALS AND METHODS: A total of 20 stable aneuric patients on chronic bicarbonate high-flux haemodialysis with a frequency of 4 hours, 3 times per week with two different concentrations of total dialysate calcium (tdCa) were included in the study. Dialysis in the first session was performed with total dialysate calcium of 1.25 mmol/L, and at the next session with dialysate calcium of 1.5 mmol/L. The serum concentrations of total and ionized calcium were determined before and after each dialysis session. The balance of total dialysate calcium was measured on the dialysate side. RESULTS: Serum concentration of total calcium before and after haemodialysis did not show any significant difference in HD with a total dialysate calcium of 1.25 mmol/L (2.40 ± 0.19 mmol/L before HD and 2.46 ± 0.15 mmol/L after HD). Serum ionized calcium in HD with tdCa 1.25 significantly decreased after HD (1.16 ± 0.09 mmol/L before HD to 1.08 ± 0.04 mmol/after HD, p < 0.05). The total serum calcium significantly increased after HD in comparison to HD with tdCa of 1.5 mmol/L (2.40 ± 0.15 mmol/L to 2.65 ± 0.16 mmol/L, p < 0.05). The concentration of serum ionized calcium did not increase significantly in HD with tdCa 1.50 mmol/L (1.16 ± 0.08 mmol/L to 1.20 ± 0.05 mmol/L). Average values of total dialysate calcium balance (gradient of diffusion between dialysate and patient) were negative in tdCa 1.25 (1.38 ± 0.08 mmol/L versus 1.48 ± 0.43 mmol/L), but in HD with tdCa 1.5 were slightly positive (1.56 ± 0.07 mmol/L versus 1.52 ± 0.07). CONCLUSION: The use of total dialysate calcium of 1.5 mmol/L is beneficial because balance values of total dialysate calcium are slightly positive, but serum concentration of ionized calcium stays in the normal range.

The Oxford classification of IgA nephropathy: single centre experience.

The Oxford classification for the pathological classification of a glomerular disease in IgA nephropathy was established and published in 2009. Four of the pathological variables: 1) mesangial hypercellularity score, 2) segmental glomerulosclerosis, 3) endocapillary hypercellularity and 4) tubular atrophy/interstital fibrosis were presented as having value in predicting renal outcome in this glomerular disease. These features were recommended to be taken into account for predicting the outcome. In our study, we correlated these four variables with the outcome of the disease in 40 adult patients with IgA nephropathy. Standard histopathologic procedure was used to determine four variables as 0/1. The results were compared with renal outcome, clinical data were obtained from the out-patient files of the patients. The whole follow-up period was 3-27 years. The average survival of the whole group was 10.8±7.47 years (M±SD). Mesangial hypercellularity was confirmed to be associated with the renal outcome (p=0.047), as well as glomerular sclerosis (p=0.009), endocapillary hypercellularity (p=0.001) and tubular atrophy/interstitial fibrosis (p=0.045). When we analysed only patients with a severe form of the disease (nephrotic syndrome; patients treated with immunosuppression), the survival of the patients was associated only with the degree of tubulointerstitial changes (p=0.018). Analysing separately patients with mild clinical form, we found only a predictive value of segmental glomerulosclerosis on renal survival.

Mesenchymal stem cells prevent progressive experimental renal failure but maldifferentiate into glomerular adipocytes.

Glomerulonephritis (GN) is a major cause of renal failure. This study sought to determine whether intrarenal injection of rat mesenchymal stem cells (MSC) can preserve renal function in a progressive rat model of GN. Early in GN (day 10), fluorescently labeled rat MSC localized to more than 70% of glomeruli, ameliorated acute renal failure, and reduced glomerular adhesions. Fifty days later, proteinuria had progressed in controls to 40 +/- 25 mg/d but stayed low in MSC-treated rats (13 +/- 4 mg/d; P < 0.01). Renal function on day 60 in the MSC group was better than in medium controls. Kidneys of the MSC group as compared with controls on day 60 contained 11% more glomeruli per 1-mm(2) section of cortex but also significantly more collagen types I, III, and IV and alpha-smooth muscle actin. Approximately 20% of the glomeruli of MSC-treated rats contained single or clusters of large adipocytes with pronounced surrounding fibrosis. Adipocytes exhibited fluorescence in their cytoplasm and/or intracellular lipid droplets. Lipid composition in these adipocytes in vivo mirrored that of MSC that underwent adipogenic differentiation in vitro. Thus, in this GN model, the early beneficial effect of MSC of preserving damaged glomeruli and maintaining renal function was offset by a long-term partial maldifferentiation of intraglomerular MSC into adipocytes accompanied by glomerular sclerosis. These data suggest that MSC treatment can be a valuable therapeutic approach only if adipogenic maldifferentiation is prevented.

R-roscovitine (CYC202) alleviates renal cell proliferation in nephritis without aggravating podocyte injury.

BACKGROUND: Cyclin-dependent kinase (CDK) inhibition is a new therapeutic approach to proliferative glomerulonephritides. CDK2 is required for G(1)/S transition and DNA synthesis and is inhibited by CYC202 (R-roscovitine). Since podocytes express CDK2 in nephritis and since loss of podocytes contributes to glomerulosclerosis, the rationale of the present study was to test whether CDK2 inhibition is safe in instances of podocyte injury. METHODS: Rats with passive Heymann nephritis, a model of membranous glomerulonephritis, were treated (day 3 to 30) with vehicle, low (25 mg/kg/day), or high (50 mg/kg/day) doses of CYC202. RESULTS: On day 27, blood pressure was normal in nephritic controls and was dose-dependently reduced by CYC202. Urinary albumin excretion did not differ between the groups on days 9, 16, 23, and 30. To investigate podocyte injury, we assessed the glomerular de novo expression of desmin, which was markedly up-regulated in almost all passive Heymann nephritis glomeruli but was not significantly different between the three groups. No tubulointerstitial de novo expression of desmin or alpha-smooth muscle actin (alpha-SMA), or tubulointerstitial monocyte/macrophage infiltration was noted in any group. Biologic activity of CYC202 was evident in the form of a dose-dependent decrease in the number of glomerular and tubulointerstitial mitotic figures as compared to vehicle alone. Glomerular immunostaining for cyclin D1, a marker for G(0) to G(1) transition, was significantly decreased in CYC202 treated groups at day 9. CONCLUSION: Whereas inhibition of CDKs by CYC202 reduced intrarenal cell proliferation in passive Heymann nephritis it did not aggravate podocyte damage, suggesting that this novel therapeutic approach is safe in renal diseases characterized by podocyte injury.