The Lipid lowering and Onset of Renal Disease (LORD) Trial: A randomized double blind placebo controlled trial assessing the effect of atorvastatin on the progression of kidney disease

Background: There is evidence that dyslipidemia is associated with chronic kidney disease (CKD). Experimental studies have established that lipids are damaging to the kidney and animal intervention studies show statins attenuate this damage. Small clinical trials, meta-analyses, observational studies and post-hoc analyses of cardiovascular intervention studies all support the concept that statins can reduce kidney damage in humans. Based on this background, a double blind randomized placebo controlled trial was designed to assess the effectiveness of atorvastatin 10 mg on slowing the progression of kidney disease in a population of patients with CKD

Reoperations after first lumbar disc herniation surgery; a special interest on residives during a 5-year follow-up

BACKGROUND: The overall rate of operations after recurrent lumbar disc herniation has been shown to be 3–11%. However, little is known about the rate of residives. Thus the aim of this study was to explore the cumulative rates of re-operations and especially residive disc herniations at the same side and level as the primary disc herniation after first lumbar disc herniation surgery and the factors that influence the risk of re-operations over a five year follow-up study. METHODS: 166 virgin lumbar disc herniation patients (mean age 42 years, 57% males) were studied. Data on patients' initial disc operations and type and timing of re-operations during the follow-up were collected from patient files. Back and leg pain on visual analog scale and employment status were collected by questionnaires. RESULTS: The cumulative rate of re-operations for lumbar disc herniation was 10.2% (95% Cl 6.0 to 15.1). The rate of residives at initial site was 7.4% (95% Cl 3.7 to 11.3) and rate of lumbar disc herniations at other sites was 3.1% (95% Cl 0.6 to 6.2). The occurrence of residive lumbar disc herniations was evenly distributed across the 5 years. Neither age, gender, preoperative symptoms, physical activity nor employment had effect on the probability of re-operation. CONCLUSION: Seven percent of the lumbar disc patients had a residive lumbar disc operation within five years of their first operation. No specific factors influencing the risk for re-operation were found

Monocyte/mesangial cell interactions in high-glucose co-coltures

BACKGROUND: Monocytes bind to human mesangial cells (HMC) in a co-culture model of leukocyte/ glomerular cell interactions. Since monocytic infiltration has been demonstrated in the early stages of diabetic glomerulopathy, we examined whether co-culture with myelomonocytes of the U937 cell line in media mimicking the diabetic microenvironment modulated phenotype, growth, and extracellular matrix production patterns of HMC. METHODS: HMC monolayers grown for 5 days in 5.5 mmol/l (NG) or 30 mmol/l (HG) glucose media were examined 3, 24 and 48 h after addition of U937 cells by computer-assisted image analysis/fluorescence microscopy following fixation, staining for cell adhesion, and TUNEL/propidium iodide labelling for apoptosis. As matrix components may be relevant to both phenotype of cultured HMC and monocyte adhesion, reverse transcription-polymerase chain reaction, zymography, and ELISA were used to detect urokinase-plasminogen activator (uPa), collagen type IV (COL IV), transforming growth factor beta1 (TGF-beta1), matrix metalloproteinases (MMP), and relative inhibitors (tissue inhibitor of MMP (TIMP)) expression in co-cultures in NG/HG. RESULTS: U937 adhesion at 1-3 h was increased in HG (from 54.9+/-6.6 to 87.1+/-5.8% U937/HMC). Control HMC proliferating in NG supplemented with 10% fetal bovine serum had an average cross-sectional area of 9993+/-505 micro(2) with 1.2+/-0.1 hillocks/high-power field, which increased to 13 651+/- 1114 micro(2) with 0.5+/-0.2 hillocks/high-power field in HG (P<0.05). TUNEL+HMC were nearly identical (4.9+/-1.7 vs 4.2+/-0.4% in HG, P=NS). Enhanced transcription and secretion of urokinase (uPA, +656%), COL IV (+137%), TGF-beta1 (+590%) were observed in co-cultures in HG. COL IV and TGF-beta1, but not uPA, were also increased in HMC alone, exposed to HG for 5 days. MMP-2/TIMP-2 ratio was decreased while MMP-1/TIMP-1 was increased in HG co-cultures. In both NG and HG, U937 adhesion reduced HMC number and hillocks at 24 h, with constant apoptosis. The effects of U937 were no longer detectable at 48 h, when apoptosis was 2.1+/-0.6 vs 4.0+/-0.4% in HG, and cell counts returned above basal, possibly due to a delayed proliferative response. CONCLUSIONS: High glucose medium increases U937 cell adhesion to HMC. In turn, monocytes modulate number and spatial distribution of HMC, which are also markedly affected by ambient glucose levels. These interactions may be relevant to leukocyte infiltration, mesangial expansion, and glomerulosclerosis in diabetes

1-Alpha-OH-cholecalciferol (1-alpha-OHD3) and low phosphate diet in predialysis chronic renal failure: Effects on renal function and on secondary hyperparathyroidism

The effect of 1-alpha-OHD3 on the rate of decline of renal function was studied in 18 patients with predialytic chronic renal failure. 9 patients with serum creatinine 4.19 ± 1.63 mg/dl, were treated with 1-alpha-OHD3 0.4 ± 0.11 μg/day and a low phosphate diet and 9 patients with serum creatinine 3.69 ± 1.24 mg/dl, received the low phosphate diet alone. In the first group retrospectively in 8 patients up to 3-44 months and prospectively in all patients reciprocal values of serum creatinine levels fell linearly with time. Comparison of the slopes of the regression lines before and following the start of treatment did not show statistical differences in 6 cases, in 1 case the decline of renal function improved significantly and in 1 case it became positive. Serum calcium increased significantly (p &lt; 0.025), alkaline phosphatase decreased (p &lt; 0.005) and serum iPTH decreased in 6 of 8 cases. In the low phosphate diet group, serum calcium and alkaline phosphatase did not change while iPTH increased in 8 of 9 cases. The rate of decline of renal function before treatment in 3 cases did not improve after the institution of the diet. In conclusion improvement or prevention of secondary hyperparathyroidism in predialytic chronic renal failure can be achieved with daily doses of ≤ 0.5 μg 1-alphaOHD3 and a low phosphate diet. The small increment in serum calcium levels induced by the treatment did not accelerate the deterioration of renal function while showing a better control of alkaline phosphatase and serum iPTH than the low phosphate diet alone

Bone GLA protein in predialysis chronic renal failure. Effects of 1,25(OH)2D3 administration in a long-term follow-up.

Bone GLA protein in predialysis chronic renal failure. Effects of 1,25(OH)2D3 administration in a long-term follow-up. Serum bone GLA protein (BGP) was measured by radioimmunoassay in 42 patients (age, 47.5 ± 16.6 years; serum creatinine, 4.32 ± 1.9 mg/dl) with predialysis chronic renal failure (CRF). Nineteen patients were studied within a short period of time, while 23 were followed with repeated measurements of serum BGP, creatinine, iPTH, and alkaline phosphatase (AP) for a mean period of 17.1 ± 8.1 months. Eleven of these patients were treated with 1,25(OH)2D3 for a mean of 16.8 ± 6.4 months. In 23 patients at various stages of CRF, a transiliac bone biopsy was performed for histomorphometric evaluation. In the untreated patients, serum BGP was higher than normal and showed a positive correlation with creatinine levels (P < 0.001). Serum BGP was also positively correlated with iPTH, AP, serum phosphate, active resorption surface, active osteoblastic surface, osteoid surface, and volume. EHiring treatment with 1,25(OH)2D3, BGP, iPTH, and AP were significantly lower than in the untreated patients. The reduction in iPTH and BGP was proportional, while BGP and AP no longer correlated. Repeated measurements of BGP during the long-term follow-up showed a progressive rise in the untreated patients and a downward course of BGP levels during treatment. In conclusion, serum BGP increases progressively in CRF, rising with advancing renal damage in close correlation with iPTH, AP, and the severity of renal osteodystrophy. Treatment with 1,25(OH)2D3 causes a parallel decline in BGP and iPTH levels and dissociation between BGP and AP can be observed. Compared to AP, BGP seems to be a more reliable index of secondary hyperparathyroidism and potentially more useful in the long-term monitoring of treatment with 1,25(OH)2D3.