Basal levels of [Ca2+]i are elevated in diabetes mellitus. Such an abnormality is most likely due to both increased calcium influx into cells and decreased efflux of this ion out of the cells. The present study examined the cellular pathways that are responsible for hyperglycemia-induced acute rise in polymorphonuclear leukocytes (PMNL), and explored whether such a rise is due to increased calcium entry into PMNL and/or to calcium release from their intracellular stores. There were dose dependent and time dependent rises in the [Ca2+]i of PMNL exposed to high concentrations of glucose. Similar effects were observed when the PMNL were exposed to high concentrations of choline chloride or mannitol. A substantial part of the rise in [Ca2+]i was inhibited when the media contained verapamil or nifedipine or when the PMNL were placed in calcium free media, and the rise in [Ca2+]i was completely abolished when the PMNL were placed in calcium free media containing ryanodine. GDP beta S or pertussis toxin almost completely prevented the glucose-induced rise in [Ca2+]i of PMNL. Rp-cAMP, H-89 or staurosporine produced significant inhibition of the rise in [Ca2+]i. High concentrations of glucose produced a dose dependent shrinkage of PMNL volume over a period of two hours. The volume of PMNL, however, was normal after 24 hours in vitro incubation studies as well as after 1, 2 and 12 days of streptozotocin-induced hyperglycemia in rats. The results are consistent with the formulation that the osmotic activity (cell shrinkage) of the high glucose concentrations activates G protein(s) which then stimulates the adenylate-cAMP-protein kinase A pathway, phospholipase C system and calcium channels. The stimulation of these cellular pathways permits both calcium influx into the PMNL as well as mobilization of calcium from their intracellular stores. Both of these events contribute to the acute rise in their [Ca2+]i. It is possible that the rise in [Ca2+]i is critical for the stimulation of the events that lead to the generation and accumulation of inorganic osmolytes to restore cell volume to normal.

The results show that (i) [Ca2+]i of PMNL increases and phagocytosis decreases rapidly after the induction of diabetes; (ii) treatment of diabetic rats with amlodipine normalizes [Ca2+]i of PMNL and markedly improves their phagocytosis, despite hyperglycemia; (iii) high [Ca2+]i is responsible, in major part, for the impaired phagocytosis but other factors are also operative; and (iv) calcium channel blockers could prove useful in the treatment of the metabolic and functional derangements of PMNL in patients with poorly controlled diabetes.

Dialysis patients with troponin-I levels above the cut-off value diagnostic for acute myocardial event (AME) are sometimes labeled as having "renal cause" of elevated troponin-I. Patients with troponin-I levels above 0.0 ng/mL, but below the cut-off level for an AME, are reported to have increased risk for coronary heart disease and mortality. Single pre-dialysis blood samples were taken from 150 asymptomatic dialysis patients (on hemo- or peritoneal dialysis) for troponin-I, cardiac enzymes, C-reactive protein (CRP) and lipid parameters. Troponin-I was measured by a chemiluminescent microparticle immunoassay (CMIA), of which the cut-off value for AME was set at ≥0.4 ng/mL. Patients with troponin-I levels of 0.0 ng/mL, and those with levels between 0.1 and 0.3 ng/mL, were compared regarding their cardiovascular risk profile. None of the patients had troponin-I concentrations above the cut-off level diagnostic for an AME, with 85.3% of the patients having levels of 0.0 ng/mL. While there was no difference in the "traditional" risk factors such as age, body mass index, prevalence of diabetes mellitus, hypertension, total cholesterol and low-density lipoprotein cholesterol between patients with troponin-I levels of 0.1-0.3 ng/mL and those with levels of 0.0 ng/mL, CRP concentrations were higher in the former. In peritoneal dialysis patients, the weekly Kt/V was lower in the patients with troponin levels between 0.1 and 0.3 ng/mL. The findings should add strong support in settling the debate of whether or not in patients on dialysis, falsely elevated levels of troponin-I "commonly" occur. An increased level of CRP and lower Kt/V might add to the cardiovascular risk in patients with troponin-levels between 0.1 and 0.3 ng/mL.

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Hemodiafiltration (HDF) is not associated with lower mortality risk compared to standard hemodialysis (HD). However, there are many critical clinical outcomes in dialysis patients in addition to mortality; the impact of HDF on these other outcomes is not clear. This retrospective study included all patients referred to DaVita Clinics in the Kingdom of Saudi Arabia. High‐flux HD was the initial modality in all patients. Those who did not achieve adequacy targets or those with poorly controlled phosphorus were switched to postdilution HDF using 18 to 23 L exchange per treatment. Patients dialyzing with a central venous catheter, patients who dialyzed less than 90 days at DaVita, and those with interrupted HDF were excluded. Of the 1115 patients, 215 (19%) were on HDF and 900 on high‐flux HD; the median follow‐up was 6 months for all patients. The HDF group showed a significant reduction in serum phosphate (P < .001), a significant increase in serum calcium (P < .012) and a significant improvement in Kt/V (P < .0001). The HDF group had significantly higher hemoglobin levels than the HD group (P = .024), with a significant reduction in weekly erythropoiesis‐stimulating agent dose after starting HDF (P < .001). A modified protocol that included prolonged dialysis duration, larger‐sized dialyzer, faster blood flow rates, and adding hemofiltration fluid may be helpful in achieving the recommended targets. Thus, HDF can enable the achievement of adequate dialysis care in some patients. Randomized‐controlled clinical trials are necessary to confirm these findings.