Severity of tubulointerstitial inflammation and prognosis in immunoglobulin A nephropathy.

Many risk factors for progression in immunoglobulin A nephropathy (IgAN) have been found. We focused on renal leukocyte infiltrations and cytokines in IgAN. The subjects were 204 IgAN patients. Renal histopathological changes were semiquantitatively graded. Expression of tubulointerstitial Leukocyte common antigen (LCA), CD3, CD68, interleukin (IL)-1beta, and IL-10 was evaluated by immunohistochemistry. These parameters were correlated with progression of IgAN. The significance of these correlations was tested by a multivariate analysis. Glomerulosclerosis, tubular atrophy, interstitial inflammation, and hyaline arteriolosclerosis correlated with progression in all patients and also in patients with initially normal serum creatinine. Tubulointerstitial LCA, CD3, CD68, and IL-1beta expression correlated with progression. CD3 had the strongest correlation. In the multivariate analysis, tubulointerstitial CD3, hypertriglyceridemia, elevated serum creatinine concentration, and interstitial fibrosis were independently associated with progressive disease in all patients, and tubulointerstitial CD3 expression and hyaline arteriolosclerosis in patients with initially normal serum creatinine. We found parameters reflecting tubulointerstitial inflammation to predict deterioration of renal function in IgAN. This was also seen in patients whose serum creatinine was normal at the time of renal biopsy. Our findings show that, an immunohistochemical evaluation of tubulointerstitial inflammation seems to be a useful tool in determining the prognosis in IgAN.

Ten-year prognosis of Puumala hantavirus-induced acute interstitial nephritis.

Nephropathia epidemica (NE) is a hemorrhagic fever with renal syndrome caused by Puumala hantavirus. Its long-term prognosis is considered favorable. There are, however, some reports about subsequent hypertension, glomerular hyperfiltration, and proteinuria after previous hantavirus infection. Therefore, we studied 36 patients 5 and 10 years after acute NE, with 29 seronegative controls. Office blood pressure, ambulatory 24-h blood pressure (ABP), glomerular filtration rate (GFR), and proteinuria were examined. Hypertensive subjects were defined as those patients having increased ambulatory or office blood pressure, or receiving antihypertensive therapy. Office blood pressure was used to define hypertension only if ABP was not determined. At 5 years, the prevalence of hypertension was higher among NE patients than in controls (50 vs 21%, P=0.020). At 10 years, the difference between the groups was no more significant (39 vs 17%, P=0.098). Five years after NE, patients showed higher GFR (121+/-19 vs 109+/-16 ml/min/1.73 m(2), P=0.012) and urinary protein excretion (0.19 g/day, range 0.12-0.38 vs 0.14 g/day, range 0.09-0.24, P=<0.001) than controls. At 10 years, there were no more differences in GFR or protein excretion between the groups (GFR: 113+/-20 vs 108+/-17 ml/min/1.73 m(2), P=0.370; proteinuria: 0.14 g/day, range 0.07-0.24 vs 0.13 g/day, range 0.06-0.31, P=0.610). In conclusion, the 10-year prognosis of NE is favorable, as glomerular hyperfiltration and slight proteinuria detected at 5 years disappeared during the longer follow-up. However, the possibility exists that NE may predispose some patients to the development of hypertension.

Natriuretic peptide and echocardiography after operation of atrial septal defect.

Patients benefit from surgical seclusion of atrial septal defect but have excessive cardiovascular morbidity after the operation. We evaluated haemodynamics and looked for abnormalities of cardiac structures and function late after surgical seclusion of the defect. Serum N-terminal natriuretic peptide measurement and transthoracic and transoesophageal echocardiography were performed in 61 patients aged 43+/-15 years (mean+/-standard deviation) 21+/-5 years after surgery. The findings were compared with 67 control subjects. The patients had higher serum N-terminal atrial natriuretic peptide concentration than the control subjects (0.40+/-0.32 vs. 0.24+/-0.12 nmol/l, P=0.0001). Peptide levels correlated with current age (P=0.0001) and age at operation (P=0.0014), but not with age in the control subjects. In the patients, echocardiography measurements of cardiac dimensions correlated with hormone levels (atrial natriuretic peptide concentration with left atrial end-systolic diameter (P=0.042), left ventricular end-diastolic (P=0.021) and end-systolic diameter (P=0.042). There were only 10 patients (16%) without any abnormality in echocardiography. Their peptide concentration was 0.25+/-0.18 nmol/l (P=not significant compared to the control subjects). The association between increasing N-terminal atrial peptide levels and operation age together with echocardiography findings support the clinical consensus of treating atrial septal defect patients in their childhood and adolescence.

Time course of serum prolactin and sex hormones following successful renal transplantation.

BACKGROUND: Chronic renal failure is commonly associated with disturbances in hypothalamic-pituitary-gonadal function. METHODS: The gonadotrophins, prolactin and estradiol or testosterone levels were measured immediately before renal transplantation, at discharge from the transplantation unit (19 +/- 8 days after Tx) and 6 months after transplantation in 21 patients, 7 females and 14 males, age range 21-60 years. RESULTS: The mean prolactin level was high during uremia and decreased rapidly after transplantation, from 441 to 167 mU/l in males and from 1,057 to 521 mU/l in females. Hypergonadotrophism was seen in most uremic patients, with the mean LH and FSH levels of 14.2 and 6.0 U/l in males and 14.7 and 4.0 U/l in females, respectively. A temporary change to hypogonadotrophic hypogonadism took place 2-3 weeks after transplantation and was followed by normalization of the hypothalamic-gonadal function. The levels of circulating sex steroids were suppressed when the patients were discharged from the transplantation unit but returned to the normal range at 6 months. CONCLUSIONS: We conclude that renal transplantation corrects the hyperprolactinemia induced by uremia and is followed by rapid onset of restoration of the hypothalamic-pituitary-gonadal axis.

Thyroid hormone substitution therapy rapidly enhances left-ventricular diastolic function in hypothyroid patients.

OBJECTIVE: Alterations in thyroid status may lead to changes in both systolic and diastolic function of the heart. Pulsed Doppler echocardiography is a reliable non-invasive means of assessing left-ventricular (LV) diastolic function. The aim of the present study was to evaluate LV diastolic function in patients with primary hypothyroidism receiving thyroxine therapy. METHODS: Twelve patients (all females, mean age 47 +/- 17, range 16-69 years) with primary hypothyroidism were studied by pulsed Doppler echocardiography. The first examination was made before the start of thyroxine substitution and the second at 37-68 (mean 53 +/- 10) days after commencing thyroxine treatment (mean dose 136 +/- 22 microg/day). RESULTS: During thyroxine substitution therapy, the hypothyroid patients became clinically euthyroid and serum T4 increased from 51 +/- 21 to 119 +/- 24 nmol/l; TSH decreased from 50.4 +/- 55.3 to 1.2 +/- 1.5 mU/l. During therapy, heart rate increased from 61 +/- 8 to 68 +/- 10 (p = 0.05). The LV posterior wall (7.8 +/- 1.0 mm) and interventricular septum thickness (8.0 +/- 1.4 mm) were significantly greater in hypothyroid patients than in the control subjects (6.4 +/- 1.0 mm, p = 0.007 and 6.8 +/- 1.0 mm, p = 0.04, respectively). There was no significant change in LV dimensions and wall thickness during follow-up. E/A(max) increased significantly during treatment (from 1.679 +/- 0.432 to 1.947 +/- 0.335, p = 0.006). The isovolumic relaxation time shortened significantly (from 88 +/- 23 ms to 75 +/- 24 ms, p = 0.005). CONCLUSIONS: The present study shows that LV diastolic function as assessed by pulsed Doppler echocardiography in hypothyroid patients is enhanced by thyroxine therapy during a rather short follow-up period.

Constant, but not pulsed calcitriol suppresses hemodialysis patients' antigen-induced lymphocyte proliferation.

BACKGROUND/AIMS: In vitro constant calcitriol [1,25-(OH)(2)D(3)] inhibits healthy individuals' T lymphocyte proliferation at supraphysiological concentrations. In contrast, among hemodialysis patients, intravenous 1,25-(OH)(2)D(3) pulse therapy of secondary hyperparathyroidism has been shown to be even immunostimulatory. We studied the effect of in vitro constant and intermittent 1, 25-(OH)(2)D(3) on lymphocyte antigen response of hemodialysis patients. METHODS: Twelve hemodialysis patients' peripheral blood mononuclear cells were stimulated with purified protein derivative of tuberculin (12.5, 25 and 50 mg/l) or tetanus toxoid (TT; 1,000, 5, 000 and 10,000 Lf/l, limit of flocculation) for 7 days. Constant 1, 25-(OH)(2)D(3) was added to all cultures at concentrations of 0, 10(-10) or 0.25 x 10(-9) mol/l (0, 42 and 105 ng/l) and to half of the cultures additionally as a 0.75 x 10(-9) mmol/l (315-ng/l) pulse on the 5th culture day. RESULTS: TT-induced lymphocyte proliferation was statistically related to a constant 1,25-(OH)(2)D(3) concentration (p = 0.001, analysis of variance). With constant 1, 25-(OH)(2)D(3) concentrations of 0, 42 and 105 ng/l, the TT-induced responses were 1.53, 1.44 and 1.40 log cpm, respectively (mean of TT concentrations). The responses of the (additionally) pulse-treated cells [1.65, 1.50 and 1.40 log cpm; concentrations of constant 1, 25-(OH)(2)D(3) as above] were similar to those of the nonpulsed cells. Thus constant, but not pulsed 1,25-(OH)(2)D(3) decreased the TT responses. On the purified protein derivative of tuberculin response, neither constant nor pulsed 1,25-(OH)(2)D(3) had any significant effect. CONCLUSIONS: The decline of TT response with constant 1,25-(OH)(2)D(3) corresponds with findings on immunosuppressive action of 1,25-(OH)(2)D(3) in previous studies done on normal subjects' cells. This was not seen with intermittently applied 1,25-(OH)(2)D(3). These results support the previous concept that intermittent 1,25(OH)(2)D(3) therapy is not immunosuppressive in hemodialysis patients.

Adequate seroresponse to influenza vaccination in dialysis patients.

BACKGROUND: Hemodialysis (HD) patients are immunocompromised, and they have been shown to react suboptimally to recommended vaccinations. Advances in dialysis therapy and other supportive measures may theoretically result in better immune system functions. Clinical evidence supporting this theory has, however, not been presented. With influenza vaccination response, we tried to address this question. METHODS: 42 HD and 15 continuous ambulatory peritoneal dialysis (CAPD) patients were vaccinated with a trivalent influenza vaccine, and the seroresponses at 5 weeks were measured. The results were compared with those of similarly vaccinated 20 nephrology outpatient clinic patients with varying degrees of renal insufficiency and those of 31 cardiac patients with normal renal function. RESULTS: The dialysis patients had higher prevaccination titers of hemagglutination-inhibiting (HI) antibodies to all three vaccine virus antigens than the other groups due to more frequent previous vaccinations. The dialysis patients exhibited lower antibody increases, but an almost comparable proportion of them reached a protective antibody level (HI titers > or =40) 5 weeks after vaccination [A/H3N2: 61% (cardiac patients), 35% (nephrology outpatient clinic patients), 67% (CAPD), and 36% (HD); A/H1N1: 71, 70, 80 and 60; B: 97, 90, 80, and 76%, respectively]. Among the HD group, all patients receiving parenteral calcitriol except 1 (83%), but only 50% of the other HD patients produced protective antibody titers at least to two out of three vaccine virus antigens. No other patient- or HD treatment-associated parameter was significantly related to the vaccination-induced antibody response. CONCLUSIONS: We conclude that influenza vaccination of dialysis patients according to current recommendations may be effective. Additionally, our results suggest that parenteral calcitriol treatment may augment the immune response of HD patients even in a clinically relevant way, an effect so far shown only in in vitro studies.

QTc dispersion increases during hemodialysis with low-calcium dialysate.

BACKGROUND: The risk of ventricular arrhythmias is known to increase during hemodialysis (HD) treatment, but the cause of this phenomenon has remained unidentified. QT dispersion (= QTmax - QTmin) reflects heterogeneity of cardiac repolarization, and increased dispersion is known to predispose the heart to ventricular arrhythmias and sudden cardiac death. METHODS: We studied the effect of dialysate calcium concentration on cardiac electrical stability during HD treatment in 23 end-stage renal disease patients. Three HD treatments were applied with dialysate Ca++ concentrations of 1.25 mmol/L (dCa++1.25), 1.5 mmol/L (dCa++1.5), and 1.75 mmol/L (dCa++1.75). The QTc interval and QTc dispersion were measured before and after the three sessions. RESULTS: With the dCa++1.5 and dCa++1.75 dialyses, serum Ca++ increased and the QTc interval remained stable (dCa++1.5) or decreased (dCa++1.75), but no significant change was noted in QTc dispersion. With dCa++1.25 HD, serum Ca++ decreased (1.24 +/- 0.11 vs. 1.20 +/- 0.09 mmol/L, P < 0. 05), and both the QTc interval (403 +/- 27 vs. 419 +/- 33 ms, P < 0. 05) and QTc dispersion increased (38 +/- 19 vs. 49 +/- 18 ms, P < 0. 05). The change in the QTc interval correlated inversely with the change in serum Ca++ (r = -0.68, P < 0.0001). Except for serum Ca++ and plasma intact parathyroid hormone, predialysis and postdialysis values in other blood chemistry, blood pressure, heart rate, body weight, and total ultrafiltration were equal in the three dialysis sessions. CONCLUSION: This study is the first, to our knowledge, to demonstrate that HD increases QTc dispersion if a low-calcium (dCa++1.25) dialysate is used. This indicates that the use of low-calcium dialysate may predispose HD patients to ventricular arrhythmias and that perhaps it should be avoided, at least when treating patients with pre-existing cardiac disease.

High peritoneal permeability predisposes to hepatic steatosis in diabetic continuous ambulatory peritoneal dialysis patients receiving intraperitoneal insulin.

OBJECTIVE: To evaluate hepatic fat accumulation in diabetic patients taking intraperitoneal or subcutaneous insulin treatment during continuous ambulatory peritoneal dialysis (CAPD). DESIGN: Cross-sectional study. SETTING: Tertiary-care university hospital. PATIENTS: We studied 16 patients with diabetic end-stage renal disease currently treated with CAPD. Median age was 42 years (range: 34-70 years), duration of diabetes was 27.5 years (range: 17-39 years), and duration of CAPD was 16.5 months (range: 2-59 months). OUTCOME MEASURES: Ultrasound measures of liver steatotic area and thickness, peritoneal equilibration test (PET), weekly Kt/V urea, protein catabolic rate (PCR), hemoglobin A1c (HbA1c), lipoproteins, alanine aminotransferase, alkaline phosphatase, insulin dose, and dialysate glucose load. RESULTS: Focal hepatic fat accumulation was found. The location of steatosis was subcapsular; a negligible amount was periportal. Hepatic subcapsular steatosis was present in 7 of 8 patients taking insulin intraperitoneally and in 0 of 8 patients taking insulin subcutaneously. The maximal thickness of subcapsular steatosis correlated directly with peritoneal transport rate (2-hour dialysate-to-plasma creatinine ratio in PET, r = 0.80, p < 0.05) and inversely with PCR (r = -0.82, p < 0.05). The area of the lesions correlated directly with body weight (r = 0.80, p < 0.05) and inversely with weekly Kt/V urea (r = -0.90, p < 0.01). CONCLUSIONS: Intraperitoneal insulin, together with glucose-based peritoneal dialysate, induces hepatic subcapsular steatosis. The amount of hepatic subcapsular steatosis increases when peritoneal transfer rate and body weight are high.

Evaluation of plasma cystatin C as a marker for glomerular filtration rate in patients with type 2 diabetes.

AIM: To evaluate plasma cystatin C as a marker of the glomerular filtration rate in patients with type 2 diabetes and their age and sex-matched controls. MATERIALS AND METHODS: Forty-seven patients with one decade of type 2 diabetes and 51 non-diabetic control subjects were studied. Plasma cystatin C was measured by particle-enhanced turbidimetric immunoassay in a new application for the Hitachi 704 analyzer. For comparison, plasma creatinine and creatinine clearance were measured. The plasma clearance of 51Cr-EDTA by the single injection method was utilized as reference. RESULTS: In patients with type 2 diabetes the correlation coefficient between plasma cystatin C and the plasma clearance of 51Cr-EDTA was 0.774 (Spearman's coefficient) and that between plasma creatinine and the plasma clearance of 51Cr-EDTA was 0.556 (p = 0.001 for the difference). The correlation between creatinine clearance and the plasma clearance of 51Cr-EDTA was 0.411. In receiver operating characteristic (ROC) curve analysis the diagnostic accuracy of plasma cystatin C was significantly better than that of plasma creatinine (p = 0.047) or creatinine clearance (p = 0.001). The best diagnostic efficiency (98%) for cystatin C was obtained when the cut-off limit was set at 1.32 mg/l. In the control group the correlation coefficients were: between cystatin C and the plasma clearance of 51Cr-EDTA 0.627, between creatinine and the plasma clearance of 51Cr-EDTA 0.466 and between creatinine clearance and the plasma clearance of 51Cr-EDTA 0.416. The area under the ROC plot curve of cystatin C was also greatest in the control group, but the diagnostic accuracy of cystatin C was marginally better than that of either plasma creatinine (p = 0.05) or creatinine clearance (p = 0.08). Among the control subjects various non-renal causes may have interfered with cystatin C concentrations reducing the correlations. CONCLUSIONS: Cystatin C measurement is a more sensitive and specific test for GFR in patients with type 2 diabetes than plasma creatinine or its clearance, when GFR is normal or only slightly reduced. If an elevated cystatin C concentration is found, non-renal factors have to be excluded. The turbidimetric application described here can easily be applied for most clinical chemistry analyzers and is therefore useful in daily clinical practice.

Urinary albumin excretion rate is independently related to autonomic neuropathy in type 2 diabetes mellitus.

OBJECTIVE: To evaluate if urinary albumin excretion rate (UAER) is independently related to subclinical autonomic neuropathy in type 2 diabetes. DESIGN: A controlled cross-sectional study. SETTING: Primary health care centre. SUBJECTS: Consecutive recently diagnosed (< 1 year) type 2 diabetic patients (group A, n = 150) and patients with long-standing (median 11 years) type 2 diabetes (group B, n = 146) chosen at random. A nondiabetic control group (group C, n = 150) matched for age and gender to group A. MAIN OUTCOME MEASURES: Neuropathy by cardiovascular reflex tests and UAER by nephelometry. METHODS: Univariate statistics in group A + B (t-test chi 2- or McNemars test) with Valsalva and breathing ratios as categorical grouping variables and the independent variables gender, smoking, systolic and diastolic blood pressure, fasting serum cholesterol, HDL cholesterol, triglycerides, haemoglobin A1c, glucagon stimulated C-peptide, fasting and postload 1 and 2 h blood glucose and serum insulin, UAER, coronary heart disease and congestive heart failure. Logistic regression analyses in group A + B with Valsalva and breathing ratios as dependent categorical variables and age, systolic blood pressure, congestive heart failure, coronary heart disease, fasting blood glucose, serum triglycerides and UAER as independent variables. RESULTS: Compared to nondiabetic subjects the diabetic patients of both groups were at increased risk of neuropathy as judged by the Valsalva ratio (P < 0.01). In known diabetic patients with a UAER > or = 30 mg 24-1 h neuropathy was more common than amongst their normoalbuminuric counterparts (Valsalva test P = 0.007, breathing test P = 0.02). In logistic regression analysis UAER independently explained abnormal Valsalva (P = 0.015) and breathing tests (P = 0.04) in the group A + B. CONCLUSIONS: UAER is independently related to subclinical autonomic neuropathy in type 2 diabetes.

Adverse drug reactions in Sjögren's syndrome. Frequent allergic reactions and a specific trimethoprim-associated systemic reaction.

Trimethoprim-associated systemic reactions, including aseptic meningitis, have been reported to be very rare adverse drug reactions. Patients with Sjögren's syndrome have been overrepresented, but no epidemiological surveys of the reaction have been conducted. To study the overall frequency of adverse drug reactions, and especially trimethoprim-associated reactions, we interviewed 85 primary Sjögren's syndrome patients and compared the results with those of 45 similarly interviewed osteoarthritis patients. Antimicrobial allergy was more common among Sjögren's syndrome patients than in osteoarthritis patients (46% vs. 27%). Eleven Sjögren's syndrome patients (13%), but no osteoarthritis patient, had experienced at least a partial, non-allergic systemic reaction with trimethoprim. Of them five (6%) had had a full-blown systemic reaction including both chills/fever and headache/backache and at least one of the following: malaise, vomiting, dizziness, confusion or meningeal irritation. Our findings confirm that allergic reactions to antimicrobials are frequent in Sjögren's syndrome. In addition to allergic reactions Sjögren's syndrome patients are prone to a specific trimethoprim-associated systemic reaction. This should be remembered when prescribing antimicrobials.

Hemodialysis with high-calcium dialysate impairs cardiac relaxation.

BACKGROUND: During hemodialysis (HD), serum ionized calcium is directly related to the dialysate calcium concentration. We have recently shown an acute induction of hypercalcemia to impair left ventricular (LV) relaxation. In the current study we sought to establish whether changes in serum Ca++ also affect LV function during HD. METHODS: We echocardiographically examined the LV relaxation and systolic function of 12 patients with end-stage renal disease before and after three HD treatments with dialysate Ca++ concentrations of 1.25 mmol/liter (dCa++1.25), 1.5 mmol/liter (dCa++1.50), and 1.75 mmol/liter (dCa++1.75), respectively. Age- and sex-matched healthy controls were also examined echocardiographically. RESULTS: The LV posterior wall thickness and the interventricular septum thickness, and the LV end-diastolic dimension and the end-systolic dimensions were significantly greater in the patients when compared with the controls, and the LV fractional shortening, the ratio of peak early to peak late diastolic velocities (E/Amax), and the isovolumic relaxation time (IVRT) showed impairment of LV relaxation and systolic function in the patients. Serum ionized calcium increased significantly during the dCa++1.5 HD (1.24 +/- 0.10 vs. 1.34 +/- 0.06 mmol/liter, P = 0. 004) and dCa++1.75 HD (1.19 +/- 0.10 vs. 1.47 +/- 0.06 mmol/liter, P = 0.002), and plasma intact parathyroid hormone decreased significantly during the dCa++1.75 HD (medians 8.2 vs. 2.7 pmol/liter, P = 0.002). LV systolic function was not altered during any of the treatments. The changes in E/Amax and IVRT suggested impairment of relaxation during all sessions, but only during the dCa++1.75 HD was the impairment statistically significant (E/Amax 1. 153 +/- 0.437 vs. 0.943 +/- 0.352, P < 0.05; IVRT 147 +/- 29 vs. 175 +/- 50 msecond, P < 0.05). CONCLUSION: HD with high-calcium (dCa++1. 75 mmol/liter) dialysate impairs LV relaxation when compared with lower calcium dialysate (dCa++1.25 and dCa++1.5 mmol/liter) treatments.

Pharmacokinetics of clodronate in peritoneal dialysis patients.

OBJECTIVE: To study the pharmacokinetics of clodronate in patients on continuous ambulatory peritoneal dialysis (CAPD). DESIGN: A single intravenous dose pharmacokinetic study. SETTING: University hospital. PATIENTS: Ten CAPD patients (3 female, 7 male, age 39-79 year, median 55). METHODS: Clodronate disodium in serum, urine, and dialysate was collected for 24 hours and analyzed by capillary gas chromatography with mass-selective detection. RESULTS: Only 7% of the infused dose of clodronate was eliminated through peritoneal dialysis during 24 hours. Clearance via CAPD (CL[CAPD]) was 2.4 +/- 0.6 mL/min, which was less than 10% of the total serum clearance (CL(tot), 26.0 +/- 19.3 mL/min). Even the kidneys were a more important route of elimination than CAPD in those patients with residual diuresis of more than 500 mL/24 hr. However, in all patients most of the clodronate serum clearance (77% +/- 13%) took place via routes other than peritoneal dialysis or kidneys, that is, via nonrenal-non-CAPD clearance (CL[NRD]). CL(NRD) most likely represents the part of the drug deposited in the skeleton. There was a positive correlation between CL(NRD) and the plasma intact parathyroid hormone concentration. CONCLUSIONS: CAPD removed clodronate poorly from the circulation. Most clearance took place via routes other than CAPD or kidneys. This CL(NRD) most likely represents the skeletal deposition of the drug, and this is related to the severity of hyperparathyroidism. When treating CAPD patients with hyperparathyroid bone disease, the administration of clodronate should be adjusted as in those subjects with severe renal failure.

Calcium infusion and left ventricular diastolic function in patients with chronic renal failure.

BACKGROUND: Left ventricular (LV) function is sensitive to disorders in calcium metabolism. Most previous reports have focused on the effects of calcium on systolic performance. We studied the acute effect of calcium infusion on LV diastolic function in patients with moderate to severe chronic renal failure (CRF) and secondary hyperparathyroidism (SHP). METHODS: We infused calcium gluconate at a constant rate of 45 mumol/kg/h to 14 patients with severe to moderate CRF and SHP. Our aim was to reach slightly supranormal levels of serum ionized calcium (1.35-1.45 mmol/l). LV diastolic function was assessed by pulsed Doppler echocardiography before and after the calcium infusion. The echocardiographic indices were compared to those of 14 age- and sex-matched healthy controls. RESULTS: Before calcium infusion the patients had significantly greater LV dimensions than the controls, but there was no differences in the diastolic indices. During calcium infusion, serum ionized calcium increased from 1.18 +/- 0.03 to 1.40 +/- 0.03 mmol/l (P < 0.0001) and plasma intact PTH decreased from 38.6 +/- 5.6 to 9.0 +/- 2.2 pmol/l (P < 0.0001). Calcium infusion did not affect the LV dimensions or fractional shortening. The peak early diastolic velocity (Emax) decreased and peak late diastolic velocity (Amax) increased, and their relationship decreased significantly (1.552 +/- 0.586 vs 1.414 +/- 0.535 m/s, P = 0.03). These changes reflect impairment of LV diastolic function. CONCLUSIONS: Induction of acute hypercalcaemia by calcium infusion impairs LV diastolic function in patients with CRF and SHP.

Measurement of serum ionized magnesium in CAPD patients.

OBJECTIVE: To evaluate the magnesium status of continuous ambulatory peritoneal dialysis (CAPD) patients using a new method for assessing the level of the ionized fraction of serum magnesium. DESIGN: Serum ionized magnesium was measured in CAPD patients using the ion-selective electrode for Mg2+. SETTING: The Dialysis Unit of Tampere University Hospital. PATIENTS: Twenty-six patients on CAPD (age: 21-81 years, mean 54 +/- 16 years; duration of CAPD: 3-52 months, mean 13 months), and 26 sex- and age-matched healthy controls. RESULTS: Both serum ionized magnesium (0.73 +/- 0.11 mmol/L vs 0.56 +/- 0.07 mmol/L, p < 0.001) and total magnesium (1.11 +/- 0.22 vs 0.81 +/- 0.08 mmol/L, p < 0.01) were higher in CAPD patients than in sex- and age-matched controls. The ionized magnesium fraction of total magnesium was slightly lower in dialysis patients in spite of the fact that 16/26 patients had serum albumin less than 36 g/L. Hypermagnesemia (mean serum ionized magnesium 0.78 +/- 0.10 mmol/L) was observed in the 13 of 26 patients with 0.75 mmol/L Mg2+ dialysate; those with lower magnesium dialysate (Mg2+ 0.50 mmol/L in 10/26 and Mg2+ 0.25 mmol/L in 3/26) had mean serum ionized magnesium at the upper normal margin (0.69 +/- 0.10 mmol/L). CONCLUSION: In CAPD patients with Mg2+ 0.5-0.75 mmol/L in their dialysis fluid, both serum ionized and total magnesium concentrations were higher but the ionized/total magnesium ratio was lower than in healthy control subjects. Use of ion-selective electrodes to measure ionized magnesium may be a more useful methodology than measuring total magnesium in the evaluation of magnesium status of CAPD patients, because it is not influenced by hypoalbuminemia or increased complexed fraction of magnesium often present in dialysis patients.

Serum C-reactive protein concentration in acute myocardial infarction and its relationship to mortality during 24 months of follow-up in patients under thrombolytic treatment.

OBJECTIVES: We studied the relationship between serum C-reactive protein and mortality in acute myocardial infarction. BACKGROUND: Early recanalization of an infarct-related coronary artery is considered to be an essential prerequisite for reducing mortality by thrombolytic treatment in acute myocardial infarction. It also reduces the inflammatory reaction caused by acute myocardial infarction and is measurable by determination of serum C-reactive protein concentrations. We therefore studied the prognostic value of determining serum C-reactive protein in acute myocardial infarction. METHODS: We measured serum C-reactive protein concentrations daily for 6 days and creatine kinase, as well as its MB isoenzyme concentrations twice a day, for 3 days after a myocardial infarct, in 188 consecutive patients selected for thrombolytic therapy and treated in the same University Hospital Coronary Care Unit. The highest serum concentrations were related to total mortality as well as to the causes of death 3, 3-6, 6-12 and 12-24 months after the onset of the myocardial infarction. RESULTS: The highest serum concentrations of serum C-reactive protein were observed 2 to 4 days after the onset of myocardial infarction. The mean value of the highest serum concentration of C-reactive protein in patients who survived the whole 24-month study period was 65 mg. 1(-1), with the 95% confidence intervals for the mean ranging from 58 to 71. The corresponding values in those who died within 3, 3-6, 6-12 and 12-24 months were 166 (139-194), 136 (88-184), 85 (52-119) and 74 (38-111) mg.1(-1), respectively. The values in those who died within 3 and 3-6 months of the infarction differed statistically significantly from the values in those who survived the whole period (P < 0.001 and P < 0.05, respectively). In patients who died due to congestive heart failure the mean highest serum C-reactive protein concentration was 226 (189-265) mg.1(-1). In those who suffered sudden cardiac death and those who died from a new myocardial infarction or non-cardiac causes, the respective values were 167 (138-196), 64 (38-89) and 48 (10-86) mg. 1(-1). The values in those who died due to congestive heart failure and those suffering sudden cardiac death differed statistically significantly (P < 0.001) from the values of those who survived or died due to other causes. The highest serum concentrations of creatine kinase or its MB isoenzyme were not associated with mortality in this study. CONCLUSIONS: High serum C-reactive protein concentrations in acute myocardial infarction patients treated with thrombolytic drugs predict increased mortality up to 6 months following the infarction. Accordingly, reduction of inflammatory reaction by successful thrombolytic treatment may make an important contribution to the survival benefit of thrombolytic treatment of acute myocardial infarction.

Urinary albumin excretion rate and its determinants after 6 years in non-insulin-dependent diabetic patients.

BACKGROUND: The present study was undertaken to clarify the progression of urinary albumin excretion rate (UAER) in non-insulin-dependent diabetic (NIDD) patients 6 years after diagnosis, and to elucidate the risk factors of nephropathy. METHODS: This is a population-based controlled (baseline) cohort study. The prospective evaluation utilized the diabetic patients as internal controls. The setting was an urban primary health care centre. Main outcome measures were the UAER-24 h and fractional urinary albumin excretion rate (FAC) and their relation to mean blood pressure, haemoglobin Alc, fasting serum insulin and cholesterol and renal size. RESULTS: UAER (mg/24 h) was increased (geometric mean, quartile 1 and 3) in the diabetic patients at baseline, compared to the non-diabetic control subjects; 21 (10 and 33) versus 12 (8 and 15), P = 0.0001 (Wilcoxon's rank test). The UAER-24 h was not increased in diabetic subjects at follow-up; 24 (7 and 49) P = 0.3791 versus diabetic subjects at baseline. Eighteen per cent of normoalbuminuric (UAER < 30mg/24 h) patients developed microalbuminuria (UAER = 30-300 mg/24 h) and 3% clinical nephropathy (UAER > 300 mg/24 h). Of the microalbuminuric subjects 19% progressed to clinical nephropathy, 46% remained microalbuminuric and 35% remitted to normoalbuminuria. Serum insulin concentration, after assessment of confounding factors, measured at the baseline predicted the UAER for all diabetic subjects at follow-up in multiple linear regression analysis in an independent and significant way (P = 0.01). Serum insulin concentration (P = 0.034) and diuretic therapy (P = 0.050) at baseline independently predicted the outcome of the categorical variable progressor/nonprogressor (n = 22/86) based on the UAER-24 h at baseline and at follow-up. CONCLUSIONS: Progression of the UAER during the first 6 years is found among approximately every fifth NIDD subject who develops either microalbuminuria (from normoalbuminuria) or clinical nephropathy (from microalbuminuria). The role of serum insulin (insulin resistance) or some factor associated with it, is suggestive in the genesis of kidney disease.

Occurrence of late specific complications in type II (non-insulin-dependent) diabetes mellitus.

The objective of the present study was to determine the occurrence of late specific complications, i.e., nephropathy, retinopathy, and autonomic neuropathy, in type II (non-insulin-dependent) diabetic subjects with a recent onset and with a disease duration of at least 5 years. The study design comprised of a population-based controlled cross-sectional survey of middle-aged type II diabetic subjects in the City of Tampere, Southwest Finland. The mean (SD) albumin excretion rate per 24 h was found to have increased in recently diagnosed diabetic subjects, i.e., 54 (111) mg (p < 0.0001), and in long-term diabetic subjects, 134 (479) mg (p < 0.0001), compared to nondiabetic controls, 16 (19) mg. Microalbuminuria (30 mg/24 h < or = albumin excretion rate < or = 300 mg/24 h) was detected in 8% of nondiabetic subjects and in 29% of recently diagnosed subjects and 27% of long-term diabetic subjects. The prevalence of clinical nephropathy (albumin excretion rate > 300 mg/24 h) was 7% in long-term and 4% in recently diagnosed diabetic subjects and zero in nondiabetic subjects. The differences between diabetic and nondiabetic subjects tested for microalbuminuria and clinical nephropathy were significant (p = 0.02-0.0001) exempting the difference between recently diagnosed female diabetic subjects and nondiabetic female subjects tested for clinical nephropathy. Seventy-five percent of biopsied diabetic subjects with an albumin excretion rate exceeding 100 mg/24 h were found to have diabetic glomerulosclerosis, while the rest had a normal finding. In long-term diabetic subjects the prevalence of nonspecific, background and proliferative retinopathies were present in 40%, 31%, and 8%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)