Kidney transplant recipients are exposed to multiple factors that lead to osteoporosis after kidney transplantation. Recent short-term longitudinal studies revealed a strong decline of bone mineral density (BMD) within 1 year after transplantation. The long-term course of BMD after transplantation is still unknown. Therefore, we performed a cross-sectional study to determine BMD in 190 renal graft recipients (mean age 44 years, range 20-71 years) by dual-energy x-ray absorptiometry at various time intervals up to 20 years after transplantation (range 0-237 months). Mean BMD of graft recipients was lower than BMD values of an age- and sex-matched European reference collective at every time of measurement after renal transplantation (P < 0.01). Lowest mean BMD values were measured 12-24 months after transplantation. No loss of BMD occurred after the second posttransplant year beyond the normal age- and sex-dependent decline of BMD. Mean daily prednisone dosage was significantly higher within the first 2 posttransplant years compared with the later posttransplant period (13.1 +/- 6.2 vs. 6.7 +/- 3.4 mg/day). Other drugs or metabolic causes, including daily dosage of CsA, AZA, parathormone level, and graft function, did not show additional important differences before and after the second posttransplant year. Interpreting the results of a cross-sectional study in light of a time-dependent process, we suggest that the preexisting low BMD of kidney transplant recipients at the time of transplantation is further strongly reduced within the initial 2 posttransplant years, probably due mainly to the effect of prednisone therapy. After that time, when prednisone dosage is below a threshold of 7.5 mg/day, only a moderate, normal loss of BMD is apparent, even in patients up to 20 years after transplantation.
The effects of prostaglandin E2 (PGE)2 and the thromboxane A2 (TxA2) receptor agonist U-46619 on noradrenaline release and pressor responses to renal nerve stimulation (RNS) at 1 Hz were investigated in isolated kidneys of spontaneously hypertensive rats (SHR; 5–7 weeks) and age-matched Wistar–Kyoto rats (WKY). After incubation with 3H-noradrenaline, the renal nerves were stimulated. The stimulation-induced (S-l) outflow of radioactivity was taken as an index of noradrenaline release. Absolute S-l outflow of radioactivity was lower in SHR than in WKY but pressor responses to RNS were greater in SHR than in WKY. Tetrodotoxin (1 µmol/l) abolished S-l outflow of radioactivity and pressor responses to RNS in both strains. PGE2 (0.06 µmol/l) inhibited S-l outflow of radioactivity in SHR but not in WKY kidneys. PGE2 (0.6 µmol/l) inhibited S-l outflow of radioactivity in both strains. In SHR, PGE2 (0.6 µmol/l) decreased pressor responses to RNS, but increased them in WKY. In WKY, but not in SHR kidneys, pressor responses to RNS were markedly reduced by the ɑ1-adrenoceptor antagonist prazosin (0.1 µmol/l). The prazosin-resistant pressor responses to RNS were blocked by ɑ,ß-methylene adenosine triphosphate (ATP; 1 µmol/l). In kidneys of SHR, pretreated with 6-OH-dopamine (50 mg/kg intravenously, 24 and 48h before isolation of the kidneys) to destroy sympathetic nerve endings, pressor responses to RNS and S-l outflow of radioactivity were almost abolished. U-46619 (0.1 µmol/l) increased perfusion pressure in SHR and WKY kidneys and this effect was blocked by the TxA2 receptor antagonist daltroban (BM 13505; 3µmol/I). U-46619 did not significantly modulate S-l outflow of radioactivity. The results suggest that activation of prejunctional PGE2 receptors in kidneys of SHR and WKY inhibits noradrenaline release. The prejunctional inhibitory PGE2 receptor mechanism on renal sympathetic nerves seems to operate more effectively in SHR than in WKY. There is no evidence for prejunctional TxA2 receptors in the kidneys of SHR or WKY. Pressor responses to RNS at 1 Hz in SHR kidneys seem to be due entirely to release of a purinergic co-transmitter from renal sympathetic nerves, and PGE2 possibly reduces pressor responses to RNS by inhibiting release of this purinergic co-transmitter.
Abstract The effect of the calcium channel blockers nifedipine (9 and 18 μ g kg ‐1 h ‐1 ), diltiazem (100 and 200 μ g kg ‐1 h ‐1 ) and verapamil (19 μ g kg ‐1 h ‐1 ) continuously infused during haemodialysis on granulocyte and complement activation was investigated. Plasma levels of lactoferrin, elastase in complex with α 1 ‐proteinase inhibitor (E‐ α 1 PI) and C3a were measured in patients dialysed with dialysers made of cuprophane, polymethylmethacrylate (PMMA) and polyacrylonitrile (PAN). Calcium channel blockers caused no change of blood pressure during haemodialysis in all patients. There was no effect of nifedipine, diltiazem or verapamil on plasma lactoferrin, E‐ α 1 PI or C3a levels in patients dialysed with cuprophane. However, plasma lactoferrin and E‐ α 1 PI values were significantly reduced by all calcium channel blockers in patients dialysed with PMMA, and also by nifedipine and verapamil in patients dialysed with PAN. Our data indicate that calcium channel blockers inhibit granulocyte activation occurring in dialysers with very little anaphylatoxin formation. These drugs, however, are ineffective in patients dialysed with cuprophane where complement activation takes place. Therefore, granulocyte activation during haemodialysis in the absence of complement activation seems to be mediated by calcium ions.
Summary. Carnitine metabolism is altered in renal insufficiency and influenced by the treatment modalities. Chronically uremic patients with end-stage renal disease under conservative therapy, hemodialysis, or peritoneal dialysis show low, normal, or elevated serum levels of TC and a distorted pattern of FC, SCAC, and LCAC. HD induces a marked depletion of FC, while predialytic elevated SCAC and LCAC are in the normal range at the end of dialysis treatment. All carnitine fractions rapidly return to predialysis levels 6 h after HD due to a transport of carnitine from muscle stores to plasma pool. Muscle carnitine content is elevated in chronic uremic patients under conservative therapy. Normal or decreased levels are observed in patients on long-term HD treatment. In addition, weekly losses of carnitine in patients undergoing HD or peritoneal dialysis do not exceed urinary carnitine excretion of CO. Supplementation with currently recommended doses (1-2 g L-carnitine i.v. at the end of each HD) is followed by a marked rise in plasma carnitine levels, suggesting limited carnitine utilization in uremia. Therefore, lower carnitine doses and modified application regimens should be considered to avoid exaggerated plasma levels of carnitine and carnitine esters. Furthermore, carnitine application has been reported to show beneficial, worsening, or no effect on the deranged lipid metabolism of the uremic patients. In patients undergoing CAPD or IPD predominantly normal serum carnitine levels have been
Intraperitoneal phagocytes play an important role in local defense in preventing continuous ambulatory peritoneal dialysis (CAPD) peritonitis. This study therefore investigates the effect of the conventional lactate-based dialysis solution-pH 5.2 (LBDS-pH 5.2) and a bicarbonate-based dialysis solution (BBDS) on various cell functions.We studied C5a-induced actin polymerization (AP) as a measure of the cytoskeletal alteration, phagocytosis of zymosan particles, and chemotaxis in neutrophils incubated in either LBDS-pH 5.2, LBDS-pH 7.4, or BBDS-pH 7.4, comparing the data with cells treated with phosphate-buffered saline-pH 7.4 (PBS-pH 7.4) as a control.Polymorphonuclear neutrophils (PMNs) were isolated from the blood of healthy donors and incubated with dialysis solution prior to the experiment.C5a-induced AP was dramatically inhibited in PMNs incubated in LBDS-pH 5.2, paralleled by a complete inhibition of phagocytosis and C5a-induced chemotaxis. In comparison, BBDS improved AP to values above the control and also nearly normalized phagocytosis. Chemotaxis markedly improved in cells treated with the low glucose-containing BBDS (Bic 20), containing high glucose concentrations (Bic 30).In comparison with conventional lactate-based dialysis solution-pH 5.2, bicarbonate-based dialysis solution at low osmolality better preserves neutrophil functions that involve the cytoskeleton.
1. Urea cycle enzymes and ornithine ketoacid transaminase were extracted from rat liver using various buffer systems and different procedures for the mechanical disintegration of the cells.Of the buffers tested, phosphate and glutathipne gave optimal results, whereas significant differences were found when other extracting media were used: activities of ornithine ketoacid transaminase and ornithine carbamyl transferase were significantly decreased in triethanolamine-and in tris-[hydroxymethyl]-amiiiomethane (tris)-buffer when compared with phosphate.Arginase activity remains unchanged in phosphate and in tris-buffer, but it decreased significantly in triethanolamine-buffer.With the exception of ornithine ketoacid transaminase, no significant increase of enzyme activities were found when livers were extracted with 0.1 % cetylammonium bromide and distilled water respectively.Carbamylphosphate synthetase from rat liver was inactive in the presence of phosphate ions as was ornithine ketoacid transaminase when glutathione (1 mmol/1 GSH) was added to the extracting medium.With the exception of Carbamylphosphate synthetase, all other enzymes tested showed significantly higher activities in liver homogenates than in 100 000 g supernatants.2. Optimal extraction of urea cycle enzymes from small specimens (e. g. liver biopsies) could be achieved by disintegrating the tissue in an micro all-glass homogenizer, followed by ultrasonic treatment.The use of cetylammonium bromide and the reextractipn of bioptic specimens could be avoided.In contrast, larger tissue samples (500 mg and more) must be reextracted for the complete elution of urea cycle enzymes.3. Urea cycle enzymes and ornithine ketoacid transaminase were differentiated according to the intracellular localisation by the method of fractional tissue extraction.It could be demonstrated that ornithine ketoacid transaminase, Carbamylphosphate synthetase and ornithine carbamyl transferase were of mitochondrial origin, whereas arginino'succinate lyase activity was found exclusively in the extramitochondrial cell compartment.Arginase activity could be measured mainly extramitochondrially, most probably bound to subcellular structures.However it could not be excluded that at least a small amount of this enzyme was of mitochondrial origin.
<b>Background/Aims:</b> Transplant renal artery stenosis usually develops in the later period after renal transplantation and is usually due to atherosclerosis and fibrosis at the anastomosis. A kinking renal artery stenosis, however, is a rare cause of early graft dysfunction. <b>Methods:</b> In a 34-year-old-man early graft failure developed within 1 week after kidney transplantation. In the presence of histologically proven ischemic damage an arterial kinking stenosis was diagnosed by color Doppler sonography. Selective arteriography confirmed the sharp kinking of the transplant renal artery; however, a significant stenosis could not be visualized by arteriography. <b>Results:</b> Due to progressive loss of renal function surgical resection of scar tissue in the kink of the transplant artery and nephropexy was performed. Immediately thereafter graft function and blood pressure significantly improved so that the successful clinical outcome of this unusual case of early graft failure confirmed the relevance of the arterial kinking stenosis. <b>Conclusions:</b> In this unusual case of early graft dysfunction relevant kinking renal artery stenosis could not be adequately visualized by arteriography, although color Doppler sonography clearly demonstrated the stenosis. Therefore, both methods should be considered if parenchymal causes of graft dysfunction are excluded by biopsy and a kinking renal artery stenosis is suspected.
In a recent issue of <i>Nephron</i> Berlot and Lucchese [1] reported their management of heparin-associated thrombocytopenia (HAT) during continuous venovenous hemofiltration. They described a case of rapid onset of severe thrombocytopenia after initiating intravenous heparin therapy and stated ‘that the diagnostic criteria for HAT have been completely fulfilled’. Despite of that, they reported a continuation of heparin therapy at lower doses without recovery of platelet counts at that stage and at last the slow return of platelet counts into the normal range more than 1 week after finishing intravenous heparin therapy. With reference to the current literature and the clinical experience in our hospital, this approach does not seem to be adequate.
