Process of care events in transplantation: effects on the cost of hospitalization.

Deviations in the processes of healthcare delivery that affect patient outcomes are recognized to have an impact on the cost of hospitalization. Whether deviations that do not affect patient outcome affects cost has not been studied. We have analyzed process of care (POC) events that were reported in a large transplantation service (n = 3,012) in 2005, delineating whether or not there was a health consequence of the event and assessing the impact on hospital resource utilization. Propensity score matching was used to adjust for patient differences. The rate of POC events varied by transplanted organ: from 10.8 per 1000 patient days (kidney) to 17.3 (liver). The probability of a POC event increased with severity of illness. The majority (81.5%) of the POC events had no apparent effect on patients' health (63.6% no effect and 17.9% unknown). POC events were associated with longer length of stay (LOS) and higher costs independent of whether there was a patient health impact. Multiple events during the same hospitalization were associated with the highest impact on LOS and cost. POC events in transplantation occur frequently, more often in sicker patients and, although the majority of POC events do not harm the patient, their effect on resource utilization is significant.

Renal and extrarenal regulation of potassium.

The ISN Forefronts in Nephrology Symposium took place 8-11 September 2005 in Kartause Ittingen, Switzerland. It was dedicated to the memory of Robert W. Berliner, who died at age 86 on 5 February 2002. Dr Berliner contributed in a major way to our understanding of potassium transport in the kidney. Starting in the late 1940s, without knowledge of how potassium was transported across specific nephron segments and depending only on renal clearance methods, he and his able associates provided a still-valid blueprint of the basic transport properties of potassium handling by the kidney. They firmly established that potassium was simultaneously reabsorbed and secreted along the nephron; that variations in secretion in the distal nephron segments play a major role in regulating potassium excretion; and that such secretion is modulated by sodium, acid-base factors, hormones, and diuretics. These conclusions were presented in a memorable Harvey Lecture some forty years ago, and they have remained valid ever since. The concepts have also provided the foundation and stimulation for later work on single nephrons, tubule cells, and transport proteins involved in potassium transport.

Metabolic and endocrine effects of metabolic acidosis in humans.

Metabolic acidosis is an important acid-base disturbance in humans. It is characterised by a primary decrease in body bicarbonate stores and is known to induce multiple endocrine and metabolic alterations. Metabolic acidosis induces nitrogen wasting and, in humans, depresses protein metabolism. The acidosis-induced alterations in various endocrine systems include decreases in IGF-1 levels due to peripheral growth hormone insensitivity, a mild form of primary hypothyroidism and hyperglucocorticoidism. Metabolic acidosis induces a negative calcium balance (resorption from bone) with hypercalciuria and a propensity to develop kidney stones. Metabolic acidosis also results in hypophosphataemia due to renal phosphate wasting. Negative calcium balance and phosphate depletion combine to induce a metabolic bone disease that exhibits features of both osteoporosis and osteomalacia. In humans at least, 1,25-(OH)2 vitamin D levels increase, probably through phosphate depletion-induced stimulation of 1-alpha hydroxylase. The production rate of 1,25-(OH)2 vitamin D is thus stimulated, and parathyroid hormone decreases secondarily. There is experimental evidence to support the notion that even mild degrees of acidosis, such as that occurring by ingestion of a high animal protein diet, induces some of these metabolic and endocrine effects. The possible role of diet-induced acid loads in nephrolithiasis, age-related loss of lean body mass and osteoporosis is discussed.

Acid-base and endocrine effects of aldosterone and angiotensin II inhibition in metabolic acidosis in human patients.

Chronic metabolic acidosis (CMA) in human beings is characterized by increased renin-angiotensin-aldosterone (RAA) activity and cortisol secretion as well as nitrogen wasting. The purpose of this study was to examine whether and to what extent increased RAA activity (i.e., angiotensin II or aldosterone) regulates acid-base equilibrium in CMA and thus might co-determine the severity of acidosis. CMA was induced in 8 normal subjects by oral NH4Cl administration (2.1 mmol/kg body weight per day) for 7 days, followed by a 7-day period of spironolactone (100 mg, 4 times a day by mouth), followed by a 4-day period of spironolactone and losartan (100 mg, every day by mouth). NH4Cl feeding was continued during all study periods. Spironolactone resulted in exacerbation of acidosis ((HCO3)p decreased from 19.8+/-0.4 mmol/L to 17.7+/-0.6 mmol/L, P<.005) because of a large increase in endogenous acid production, as evidenced by significant increases in net acid excretion (116 to 185 mmol/day, P<.005), urinary anion gap (+31 mEq/day, P<.05), and sulfate excretion (+32 mEq/day, P<.05). Plasma potassium increased from 4.2 to 4.6 mmol/L (P<.05) because of decreased urinary potassium excretion (from 108 to 92 mmol/day, P<.05). Plasma angiotensin II, cortisol, aldosterone, urinary aldosterone, urinary tetrahydrocortisol, free cortisol, and nitrogen excretion increased significantly. The subsequent addition of losartan to spironolactone administration resulted in further exacerbation of acidosis ((HCO3)p decreased to 15.7+/-0.4 mmol/L, P<.05) and hyperkalemia (5.0 mmol/L, P<.05) with no change in plasma anion gap. Renal potassium excretion decreased from 92 to 73 mmol/day (P<.05) on day 1. Exacerbation of acidosis was accounted for by a renal mechanism, as evidenced by the significant decrease in net acid excretion and unchanged urinary unmeasured anion and nitrogen excretion. We conclude the following: (1) AT-1 blockade by losartan exacerbates acidosis by inducing a distal-tubular acidification defect. Angiotensin II is an important modulator of the renal acid excretory response to CMA in human beings. (2) Inhibition of aldosterone action by spironolactone in CMA results in an increase in endogenous acid production and exacerbates acidosis by a non-renal mechanism that is mediated, at least in part, by exacerbated hyperglucocorticoidism.

Molecular cloning of the critical region for glomerulopathy with fibronectin deposits (GFND) and evaluation of candidate genes.

Glomerulopathy with fibronectin deposits (GFND, MIM 601894) is an autosomal dominant kidney disease that leads to terminal renal failure at a median age of 47 years. It represents a distinct entity of membranoproliferative glomerulonephritis (MPGN) type III and is characterized by the unique feature of massive glomerular deposits of fibronectin. We have recently localized a gene locus for GFND to human chromosome 1q32 by total genome linkage analysis in a large kindred, within a 4.1-cM critical interval between markers D1S2872 and D1S2891. This interval contains a cluster of genes for "regulators of complement activation" (RCA), which represent strong candidates for GFND. To identify positional candidate genes for GFND within the critical genetic interval, we here report the cloning of the entire critical GFND region in a complete YAC and partial PAC contig. We constructed a high-resolution transcriptional map, thereby defining positional and functional candidate genes for the disease. To evaluate their role in GFND, we performed functional studies on RCA proteins in GFND patients from the large kindred, as well as mutational analysis of the genes for complement receptor-2 (CR2), membrane cofactor protein (MCP), and decay accelerating factor (DAF). Although no loss-of-function mutation has been identified as yet, these data provide a basis for the examination of candidate genes for GFND and other genes for MPGN, which localize to the vicinity of the GFND region.

[Standard bicarbonate and base excess--obsolete parameters!]. / Standardbikarbonat und base excess--obsolete Grössen!

The various techniques of interpretation of acid-base disorders are reviewed with special reference to the in vitro generated parameters 'standard bicarbonate' and 'base excess' on one hand and to the application of in vivo physiological data on the different acid-base disturbances on the other hand. The pivotal assumption that in vitro titration of PCO2 in whole blood (needed for estimation of standard bicarbonate and base excess) is representative for the in vivo behavior of the intact organism lacks any supportive evidence. The more serious pitfalls of interpretating acid-base problems by use of standard bicarbonate and base excess can be: 1. Inaccurate identification of the severity of an underlying acid-base disturbance, 2. Inadequate estimation of the time course of adaptation to an acid-base disorder (acute versus chronic) and 3. Failure to identify mixed acid-base disorders. Therefore, it is strongly recommended to use the traditional parameters (pH, PCO2, bicarbonate) in the light of the wealth of physiological in vivo data that form a sound basis for accurate clinical diagnosis.

On the mechanism of growth hormone-induced stimulation of renal acidification in humans: effect of dietary NaCl.

Sustained administration of growth hormone (GH) to human subjects with NH(4)Cl-induced chronic metabolic acidosis (CMA) results in a large (4.5+/-0.5 mmol/l) increase in the plasma HCO(3-) concentration, as mediated by a large increase in renal net acid excretion. The renal mechanism(s) responsible for the potent stimulation of renal hydrogen ion secretion by GH remain to be elucidated. Accordingly, we have assessed the Na(+) dependence of prolonged GH-stimulated renal acidification in four normal NaCl-restricted subjects (Na(+) intake 0.3 mmol x kg(-1) x day(-1)) during CMA (4.2 mmol of NH(4)Cl x kg(-1) x day(-1) for 7 days), CMA plus GH (0.1 unit/kg every 12 h for 5 days) and then CMA plus GH plus NaCl (1.7 mmol x kg(-1) x day(-1) for 6 days). During CMA, urine Na(+) excretion averaged 22.4+/-4.1 mmol/24 h. In response to GH administration, urinary net acid excretion was essentially unchanged, and the accumulated increment over 5 days of GH treatment was not different from zero (14+/-12 mmol; not significant). The plasma HCO(3)(-) concentration increased only slightly, from 14.2+/-0.8 to 15.0+/-1.1 mmol/l (P<0.05). Despite the constraint on net acid excretion imposed by NaCl restriction, renal ammonia production increased, as suggested by increases in urine pH from 5.58+/-0.05 to 5.82+/-0.04 (P<0.005) and unchanged NH(4)(+) excretion (202+/-17 to 211+/-19 mmol/24 h; not significant). In response to dietary NaCl, urine pH decreased to 5.27+/-0.1 (P<0.001) and a large increment in net acid excretion accumulated (233+/-20 mmol; P<0.05), in association with an increase in plasma HCO(3-) to 18.7+/-1.3 mmol/l (P<0.001), a plasma HCO(3-) value similar to that reported previously in salt-replete, NH(4)Cl- fed subjects. These results demonstrate for the first time in any species that the acid excretory effect of GH administration is critically dependent on the availability of a surfeit of Na(+) for tubular reabsorption. GH and/or insulin-like growth factor-1 affect renal acid excretion proximally (by stimulation of NH(3) production) and by a Na(+)-transport-dependent mechanism in the collecting duct (voltage-driven acidification) in humans. The present results indicate that an isolated increase in renal NH(3) production is insufficient to obligate an increase in net acid excretion.

[Kidney function and kidney diseases in the elderly]. / Nierenfunktion und Nierenerkrankungen beim älteren Menschen.

The significance of age-induced alterations in renal function is described in order to explain clinically important entities in older people, such as hypo- and hypervolaemia, hyper- and hyponatraemia, hyperkalaemia and metabolic acidosis. A sound knowledge of the age-dependent changes in renal function enables the physician to effectively prevent many of these metabolic disturbances. Renovascular disease, nephrotic syndrome, renal cysts and acute renal failure are renal diseases which typically have a higher incidence in older people and require special consideration when evaluating renal disease in the elderly.

Characteristics and prognosis of myocardial infarction in patients with normal coronary arteries.

STUDY OBJECTIVES: Myocardial infarction with angiographically normal coronary arteries (MINC) is a life-threatening event with many open questions for physicians and patients. There are little data concerning the prognosis for patients with MINC. DESIGN: Retrospective follow-up study. SETTING: Tertiary referral center. PATIENTS: Patients with MINC were investigated and compared to age- and sex-matched control subjects with myocardial infarction due to coronary artery disease (CAD). The patients were examined clinically using stress exercise and hyperventilation tests. Migraine and Raynaud's symptoms were determined by means of a standardized questionnaire. Serum lipoproteins; the seroprevalence of cytomegalovirus, Helicobacter pylori, and Chlamydia pneumoniae infections; and the most frequent causes of thrombophilia were assessed. MEASUREMENTS AND RESULTS: From > 4,300 angiographies that were performed between 1989 and 1996, 21 patients with MINC were identified. The mean +/- SD patient age at the time of myocardial infarction was 42 +/- 7.5 years. When compared to control subjects (n = 21), patients with MINC had fewer risk factors for CAD. In contrast, MINC patients had more frequent febrile reactions prior to myocardial infarction (six patients vs zero patients; p < 0.05), and the migraine score was significantly higher (7.1 +/- 6.3 vs 2.2 +/- 4.1; p < 0.01). The seroprevalence of antibodies against cytomegalovirus, C pneumoniae, and H pylori tended to be higher in patients with MINC and CAD as compared to matched healthy control subjects. Three patients with MINC vs none with CAD had coagulopathy. During follow-up (53 +/- 37 months), no major cardiac event occurred in the MINC group; no patients with MINC vs nine with CAD (p = 0.0001) underwent repeated angiography. CONCLUSION: High migraine score and prior febrile infection together with a lower cardiovascular risk profile are compatible with an inflammatory and a vasomotor component in the pathophysiology of the acute coronary event in MINC patients. The prognosis for these patients is excellent.

Growth hormone corrects acidosis-induced renal nitrogen wasting and renal phosphate depletion and attenuates renal magnesium wasting in humans.

We have shown previously that chronic hyperchloremic metabolic acidosis (CMA) induces severe negative nitrogen balance and renal phosphate depletion and decreases serum insulin-like growth factor-1 (IGF-1) in association with growth hormone (GH) insensitivity in humans. The present study investigated whether acidosis-induced renal nitrogen wasting and renal phosphate depletion are mediated by GH insensitivity/low IGF-1 and thereby responsive to GH treatment. The effects of GH on acidosis-induced changes in divalent cation metabolism and acidosis-induced hypothyroidism were also investigated. CMA (delta[HCO3], -10.5 mmol/L) was induced in six healthy male subjects ingesting 4.2 mmol NH4Cl/kg body weight [BW]/d for 7 days. Recombinant human GH (0.1 U/kg BW/12 h subcutaneously) was administered for 7 days while acid feeding was continued. GH increased serum IGF-1 from 22.1 +/- 1.4 to 87 +/- 8.4 nmol/L (control level, 36.4 +/- 2.2). GH decreased urinary nitrogen excretion, resulting in a cumulative nitrogen retention of 2,404 mmol, thereby correcting the acidosis-induced cumulative increase in nitrogen excretion (2,506 mmol) despite continued acid feeding. GH attenuated the acidosis-induced hyperphosphaturia (cumulative phosphate retention, 91 mmol) and corrected the hypophosphatemia. GH did not affect acidosis-induced ionized hypercalcemia, but further exacerbated acidosis-induced hypercalciuria (cumulative loss, 27.3 mmol). GH significantly further increased serum 1,25-dihydroxyvitamin D (1,25(OH)2D) and further decreased intact PTH (from 10 +/- 1 to 6 +/- 1 pg/mL). Acidosis also induced hypomagnesemia and hypermagnesuria (cumulative loss, 9.4 mmol, ie, renal magnesium wasting), a novel finding, which was significantly attenuated by GH (cumulative retention, 5.0 mmol). In conclusion, GH corrected acidosis-induced renal nitrogen wasting, which may be caused, at least in part, by decreased IGF-1 levels. GH further increased serum 1,25(OH)2D and the systemic calcium load, which account for the suppression of parathyroid hormone (PTH) despite renal PO4 retention and correction of hypophosphatemia. GH attenuated acidosis-induced renal magnesium wasting.

Type II Na-Pi cotransport is regulated transcriptionally by ambient bicarbonate/carbon dioxide tension in OK cells.

The purpose of the present study was to determine whether isohydric changes in HCO3 concentration and PCO2 directly affect apical Na-dependent Pi (Na-Pi) cotransport in OK cells (opossum kidney cell line). Cells were kept at either 44 mM NaHCO3/10% CO2, pH 7.4 (high-HCO3/CO2 condition), or 22 mM NaHCO3/5% CO2, pH 7.4 (low-HCO3/CO2 condition) (for 14-24 h). Incubation in lower HCO3/CO2 concentrations increased Na-Pi cotransport 1.5-fold. The increased Na-Pi cotransport was paralleled by a two- to threefold increased expression of the NaPi-4 transporter protein and a two- to threefold increase in NaPi-4 mRNA abundance. The increase in NaPi-4 mRNA could be completely prevented by incubation in the presence of a transcriptional inhibitor, suggesting that the increase in NaPi-4 mRNA results from an increased NaPi-4 mRNA transcription. In agreement, the NaPi-4 promoter activity was stimulated by 50% at lower HCO3/CO2 concentrations. In conclusion, our data demonstrate that isohydric changes in HCO3 concentration and PCO2 exert a significant, direct cellular effect on Na-Pi cotransport and NaPi-4 protein expression in OK cells by affecting NaPi-4 mRNA transcription.

The gene for human fibronectin glomerulopathy maps to 1q32, in the region of the regulation of complement activation gene cluster.

Fibronectin glomerulopathy (GFND) is a newly recognized autosomal dominant disease of the kidney that results in albuminuria, microscopic hematuria, hypertension, renal tubular acidosis type IV, and end-stage renal disease in the 2d to 6th decade of life. The disease is characterized histologically by massive deposits of fibronectin (Fn) present in the subendothelial spaces of renal glomerular capillaries. The cause of human GFND is unknown. In order to localize a candidate gene for GFND, we performed linkage analysis of a large, 193-member pedigree containing 13 affected individuals. Since we had previously excluded the genes for Fn and uteroglobin as candidate genes for GFND, a total-genome search for linkage was performed. Examination of 306 microsatellite markers resulted in a maximum two-point LOD score of 4.17 at a recombination fraction of. 00 for marker D1S249, and a maximum multipoint LOD score of 4.41 for neighboring marker D1S2782. By detection of recombination events, a critical genetic interval of 4.1 cM was identified, which was flanked by markers D1S2872 and D1S2891. These findings confirm that GFND is a distinct disease entity among the fibrillary glomerulopathies. Gene identification will provide insights into the molecular interactions of Fn in GFND, as well as in genetically unaltered conditions.

IGF-I and vanadate stimulate Na/Pi-cotransport in OK cells by increasing type II Na/Pi-cotransporter protein stability.

Insulin-like growth factor (IGF)-I and vanadate increase Na-dependent phosphate (Na/Pi) cotransport in opossum kidney (OK) cells. To gain more information about the mechanisms by which IGF-I and vanadate stimulate Na/Pi-cotransport, we measured type II Na/Pi-cotransporter (NaPi-4) protein abundance by Western blot analysis and investigated the effects of protein synthesis and tyrosine kinase inhibitors. The key findings in the present studies are as follows. First, incubation in IGF-I (10(-8) M) and/or vanadate (10(-3) M) for 3 h led to a non-additive 1.4-fold increase in Na/Pi-cotransport activity which was paralleled by a 1.5- to 2-fold increase in NaPi-4 protein. Second, actinomycin D did not abolish the increase in Na/Pi-cotransport and cycloheximide did not prevent the IGF-I-induced increase in Na/Pi-cotransport and NaPi-4 protein. Third, among the protein kinase inhibitors tested, only staurosporine substantially reduced the stimulation of Na/Pi-cotransport. In conclusion, the stimulatory effect of IGF-I on Na/Pi-cotransport is paralleled by an increased expression of NaPi-4 protein that is independent of protein synthesis and therefore results from increased protein stability. The observation that IGF-I and/or vanadate lead to similar increases in Na/Pi-cotransport and NaPi-4 protein abundance provides further evidence that the stimulation of Na/Pi-cotransport by IGF-I and vanadate involves protein tyrosine phosphorylation of the same signalling molecules.

[Acquired disorder of thirst perception with intact osmoregulation of vasopressin]. / Erworbene Störung des Durstempfindens bei intakter Osmoregulation des Vasopressins.

We report a 45 y old male patient with severe hypodipsia, but intact vasopressin secretion and maximal renal response to vasopressin. The patient presented during hot summer days, 18 months after a frontal lobe hemorrhage due to a ruptured aneurysm, with severe hypernatremia (171 mmol/L) and a plasma osmolality of 348 mosm/kg. He was awake and had no interest in fluid intake. After initial correction, a thirst test for 36 hours was performed. Plasma osmolality rose from 295 to 320, urine osmolality rose from 220 to 700 mosm/kg, while plasma vasopressin levels increased more than 3-fold. Throughout the test the patient did not exhibit appreciable thirst. The intact osmoregulation of vasopressin as evidenced by the plasma levels and the elicited renal response, indicates that a selective acquired disturbance of thirst is present. Whether the thirst center is destroyed or/and thirst recognition (frontal lobe affection) is disturbed primarily, can not be decided.

[Rhabdomyolysis in carnitine palmitoyltransferase II deficiency: developments in pathophysiology, diagnosis and therapy]. / Rhabdomyolyse bei Carnitin-Palmitoyltransferase-II-Mangel: aktuelle Entwicklungen in Pathophysiologie, Diagnostik und Therapie.

In hospitalized patients rhabdomyolysis is an important clinical entity, leading to myoglobinuria and acute renal failure in 8-25% of cases. When common causes of rhabdomyolysis, such as crush, trauma, infections, and drug abuse are excluded, inherited disorders of energy metabolism, in particular lipid metabolism, should be considered. Carnitine palmitoyltransferase (CPT) II deficiency is a common disorder of mitochondrial lipid oxidation. There are two distinct clinical forms: a severe and usually fatal infantile form and a benign classical muscular form. Usually, patients with CPT II deficiency present with episodic myoglobinuria, muscle cramps and weakness prompted by strenuous exercise or prolonged fasting. Liver and cardiac dysfunction are rarely seen and indicate severe disease. Most affected patients are males, although CPT II deficiency shows an autosomal recessive mode of inheritance. The human CPT II gene has been cloned, sequenced and localised to chromosome 1p32. Several mutations have been detected in the human gene which differ in the remaining enzyme activity and may explain the heterogeneity in the clinical picture of this disorder. Diagnosis is by muscle biopsy. Normally, light microscopy shows no pathological findings, and diagnosis must be established by biochemical and molecular methods. In our report on two typical cases we set out to promote knowledge of this disorder and discuss the diagnostic approach, which requires a specialised laboratory.

Effect of growth hormone on renal and systemic acid-base homeostasis in humans.

The effects of recombinant human growth hormone (GH, 0.1 U.kg body wt-1.12 h-1) on systemic and renal acid-base homeostasis were investigated in six normal subjects with preexisting sustained chronic metabolic acidosis, induced by NH4Cl administration (4.2 mmol.kg body wt-1.day-1). GH administration increased and maintained plasma bicarbonate concentration from 14.1 +/- 1.4 to 18.6 +/- 1.1 mmol/l (P < 0.001). The GH-induced increase in plasma bicarbonate concentration was the consequence of a significant increase in net acid excretion that was accounted for largely by an increase in renal NH+4 excretion sufficient in magnitude to override a decrease in urinary titratable acid excretion. During GH administration, urinary pH increased and correlated directly and significantly with urinary NH4+ concentration. Urinary net acid excretion rates were not different during the steady-state periods of acidosis and acidosis with GH administration. Glucocorticoid and mineralocorticoid activities increased significantly in response to acidosis and were suppressed (glucocorticoid) or decreased to control levels (mineralocorticoid) by GH. The partial correction of metabolic acidosis occurred despite GH-induced renal sodium retention (180 mmol; gain in weight of 1.8 +/- 0.2 kg, P < 0.005) and decreased glucocorticoid and mineralocorticoid activities. Thus GH (and/or insulin-like growth factor I) increased plasma bicarbonate concentration and partially corrected metabolic acidosis. This effect was generated in large part by and maintained fully by a renal mechanism (i.e., increased renal NH3 production and NH+4/net acid excretion).

Plasma hypercoagulability in haemodialysis patients: impact of dialysis and anticoagulation.

BACKGROUND: Thrombotic complications are common in patients with endstage renal disease and contribute substantially to the morbidity and mortality in this population. The aim of the present study was to: i) determine the prevalence and the extent of hypercoagulability in patients undergoing dialysis treatment by measuring parameters that directly reflect thrombin concentrations; ii) assess changes in coagulation status during haemodialysis (HD); iii) quantify the relative impact of heparin, dialysis and their combined effects on coagulation status and iv) detect factors that modify coagulation haemostasis in dialysis patients. METHODS: A total of 39 patients (HD: n = 29, CAPD: n = 10) was analysed for procoagulatory and fibrinolytic activity determined by measurements of partial thromboplastin time, prothrombin fragments F1 + 2, thrombin-antithrombin complexes and D-dimer concentrations. HD patients were investigated prior to and during dialysis. A subgroup of patients was infused heparin alone without dialysis or was dialysed without heparin administration. Furthermore, subgroup and correlation analyses were performed for the type of dialysis (HD vs CAPD), dialyzer and shunt, Kt/V, underlying disease and treatment with recombinant erythropoietin (rhEPO). RESULTS: Baseline levels of all parameters-procoagulatory and fibrinolytic--were substantially elevated in all patients, but to a higher degree among those on CAPD. Moreover, haemodialysis treatment increased procoagulatory markers even further, suggesting stimulated coagulation and/or insufficient anticoagulation during dialysis. However, after 3 h of dialysis thrombin concentrations, determined by quantification of prothrombin fragments, were inversely correlated with Kt/V. Selective heparin infusion diminished procoagulatory activity only slightly and incompletely, whereas HD without heparin resulted in excess thrombin accumulation. Finally, subgroup analyses revealed more pronounced thrombin formation among patients treated with polysulfon dialyzers, whereas erythropoietin dosage was positively related with lower procoagulatory activity. CONCLUSION: A majority of patients on dialysis are in a hypercoagulable state, which is further aggravated by the haemodialysis procedure itself and may not be sufficiently controlled with current anticoagulation regimens. Intensified heparin treatment and the use of rhEPO are likely to improve coagulation haemostasis, whereas the type of dialyzer should be considered as a relevant procoagulatory factor.

Acid-induced stimulation of Na-Pi cotransport in OK cells: molecular characterization and effect of dexamethasone.

Alterations in systemic acid/base balance affect renal Pi excretion. In the present study, the effects of an acidic pH on apical Na-dependent Pi (Na-Pi) cotransport were analyzed using OK cells (opossum kidney cell line). Cells were maintained at either pH 7.4 or 7.1 (altered HCO3- concentration at constant PCO2). Incubation in acidic medium led to an increase in Na-Pi cotransport activity, which was characterized by a transient, initial response (2-4 h, 25% increase) followed by a sustained response (24 h, 75% increase). Increased Na-Pi cotransport activity (24 h) was sensitive to inhibition by parathyroid hormone. Actinomycin D did not abolish the acid-induced increases (initial and sustained responses). Cycloheximide abolished the increase in Na-Pi cotransport observed after 24 h. The increase in Na-Pi cotransport (24 h) was prevented by dexamethasone (2 x 10(-6) M). Western blots showed a twofold (3 h) and two- to threefold (24 h) increase in NaPi-4 protein after acid exposure. Cycloheximide prevented the late increase in NaPi-4 protein abundance. Also dexamethasone reduced the increase in specific protein content. In conclusion, the exposure of OK cells to an acidic medium causes a stimulation of the NaPi-4 cotransporter that is prevented by dexamethasone.