Heikki Saha

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.

Diagnostic Accuracies of Plasma Creatinine, Cystatin C, and Glomerular Filtration Rate Calculated by the Cockcroft–Gault and Levey (MDRD) Formulas

Estimation of the glomerular filtration rate (GFR) is the most widely used test of renal function, reflecting the relative mass of functional renal tissue and thus the number of functioning nephrons. Methods based on measurement of exogenous substances such as inulin, 51Cr-EDTA, 99mTc-diethylenetriaminepentaacetic acid, and iohexol are accurate but too complex and laborious for routine clinical use; thus, measurement of endogenous blood substances is common practice. Plasma or serum creatinine and its renal clearance are the approaches most commonly used despite their acknowledged unreliability. Cystatin C, a small basic protein, has been proposed as a better marker than creatinine. Recently, the value of cystatin C was thoroughly reviewed in this Journal (1), and according to this review and a new metaanalysis (2), most studies have concluded that cystatin C is superior to plasma creatinine, whereas several authors have concluded that cystatin C provides no advantage. One purpose of the present study was to clarify possible reasons for the earlier, partly conflicting results. A recently published guideline from the National Kidney Foundation (3) recommended that GFR be estimated from prediction equations taking into account the serum creatinine concentration and some or all of the following variables: age, gender, race, and body size. We therefore also compared cystatin C with GFRs calculated by the Cockcroft–Gault (4) and the MDRD(5) formulas. We studied 112 patients (55 men and 57 women) for whom 51Cr-EDTA clearance had been requested. The mean age of the patients was 57.0 years (range, 17–89 years). Body mass index (BMI) was 15.2–42.4 kg/m2, and 51 …

Bone mass and structure in adolescents with type 1 diabetes compared to healthy peers

SummaryWe measured bone mass and structure using pQCT and DXA in adolescents with Type 1 diabetes and compared the results with those of healthy peers. Our results showed that diabetes is associated with reduced bone mass and smaller bones. The diabetes-associated deficits seemed to concern male adolescents more than females.IntroductionThe aim of this study was to compare bone mass and structure between adolescents with type 1 diabetes and their healthy peers.MethodsPeripheral quantitative computed tomography (pQCT) at radius and tibia, and dual-energy X-ray absorptiometry (DXA) at lumbar spine and proximal femur were performed for 48 adolescents, 26 girls and 22 boys, with type 1 diabetes, and for healthy peers matched for age, sex, body height and weight, and pubertal maturity.ResultsDiabetes was associated with reduced bone mineral content (BMC) and smaller bone cross-sectional size. Diabetic boys seemed to be more affected than diabetic girls. Among the boys, the mean deficit in BMC of all measured skeletal sites was more than 10%, while among the girls it was less than 5%.ConclusionIn conclusion, type 1 diabetes is associated with reduced BMC and appears to affect bone cross-sectional size and cortical rigidity. The diabetes-related skeletal deficits seemed to concern male adolescents more than females. Whether diabetes-related deficits would contribute to an increased risk of fractures in adulthood or later in life remains to be confirmed.

Effect of Intravenous Calcitriol on Cardiac Systolic and Diastolic Function in Patients on Hemodialysis

The systolic and diastolic function of the heart of hemodialysis (HD) patients and the effect of intravenous vitamin D therapy on cardiac function was studied by Doppler and digitized M-mode echocardiography in 10 HD patients before and after 3–4.5 months of calcitriol therapy. Calcitriol was administered intravenously 1–3 times a week at a dose of 1–2 µg after the dialysis sessions. Ten age- and sex-matched healthy controls were also examined echocardiographically. Before calcitriol therapy cardiac wall thicknesses (interventricular septum, posterior wall) and left ventricle (LV) dimensions (end diastolic, end systolic) were greater, and LV diastolic (peak late diastolic velocity, peak early diastolic velocity/peak late diastolic velocity ratio, isovolumic relaxation time) and systolic (fractional shortening) function was impaired in HD patients as compared to controls. The LV posterior wall thickness was related to plasma parathyroid hormone (PTH; r = 0.70, p = 0.01) in the patients. Calcitriol therapy raised serum ionized Ca from 1.23±0.04 to 1.33 ± 0.04 mmol/l and reduced PTH from 41.1±10.7 to 34.2±11.7 pmol/l (29±11%). Calcitriol therapy did not cause any significant changes in cardiac function in the whole patient group. However, in a subgroup of 5 patients with severe but controllable hyperparathyroidism (PTH >3 times upper normal margin) the LV dimensions and systolic function improved (LV end systolic dimension from 39.0 ± 4.0 to 31.3 ± 2.9 mm, p = 0.03; LV end diastolic dimension from 57.7 ± 3.1 to 53.4 ± 3.0 mm, p = 0.06; fractional shortening from 33 ± 4 to 42 ± 3%, p = 0.03). The diastolic indices improved also, but not significantly. In conclusion, left ventricle hypertrophy and systolic and diastolic dysfunction was observed in HD patients. Intravenous calcitriol therapy improved cardiac function in patients with severe secondary hyperparathyroidism.

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 ≧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.

Left Ventricular Structure and Function in Primary Hyperparathyroidism before and after Parathyroidectomy

Objective: Our aim was to study the effect of primary hyperparathyroidism (PHPT) and parathyroidectomy (PTX) on left ventricular (LV) wall thicknesses and systolic and diastolic function. Methods: Fifteen patients with untreated PHPT were evaluated by applying Doppler and digitized M-mode echocardiography before and 2–3 months after PTX. Fifteen age- and sex-matched healthy controls were also examined echocardiographically. Results: Prior to PTX, interventricular septal thickness (IVST), LV mass (LVM), aortic root dimension and left atrium dimension were greater and LV fractional shortening was slightly decreased in patients as compared to controls. Significantly increased LV peak late diastolic velocity (Amax) and isovolumic relaxation time, and a slightly decreased ratio of peak early to peak late diastolic velocities (E/Amax) in the patients indicated impairment of LV diastolic function in hyperparathyroidism. PTX reduced serum total Ca from 2.79 ± 0.13 to 2.39 ± 0.09 mmol/l (p < 0.001) and tended to reduce IVST [10.6 ± 2.1 vs. 10.4 ± 2.0 mm; not significant (n.s.)], LV posterior wall thickness (9.6 ± 2.0 vs. 9.2 ± 1.0 mm, n.s.) and LVM (250 ± 102 vs. 213 ± 42 g; n.s.). Before PTX, there was a significant correlation between serum total Ca and LVM (r = 0.63, p < 0.05), and the PTX-induced change in serum total calcium correlated with the change in LVM (r = 0.59, p < 0.05). PTX induced no significant changes in LV systolic or diastolic function during the follow-up of 2–3 months. Conclusions: The present findings indicate that PHPT induces LV hypertrophy, slight impairment of LV systolic function and significant impairment of LV diastolic function, which are not substantially improved after TX and 2–3 months of normocalcemia.

Clinical Follow-Up of 54 Patients with IgM-Nephropathy

The clinical course of mesangial glomerulopathy with IgM deposits (IgM-nephropathy) was studied in 54 patients. The initial manifestations of the disease were nephrotic syndrome in 18, proteinuria in 21, proteinuria together with hematuria in 4 and isolated hematuria in 11 patients. The nephrotic syndrome was steroid-responsive in 60% of cases and of these 80% were steroid-dependent. During a 5-year postbiopsy follow-up 3 patients went into terminal uremia and in 6 more patients a milder renal insufficiency was observed. Three patients were rebiopsied and in 2 of these the second biopsy specimen disclosed typical focal and segmental glomerulosclerosis. Hematuria was a favorable sign, as no patient with hematuria showed progressive impairment of renal function. The prevalence of hypertension in the whole material was 37%. At close of follow-up 35% of all patients were in clinical remission. It is suggested that IgM-nephropathy associated with abundant proteinuria or the nephrotic syndrome represents a distinct disorder from that associated with hematuria. While the nephrotic type often manifested itself with a morphologic change and a tendency to develop renal insufficiency, the hematuric type showed female predominance, a high tendency to spontaneous clinical remission and a favorable clinical course.

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 µg/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/Amax 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.

Potassium channel-mediated vasorelaxation is impaired in experimental renal failure

Chronic renal failure is associated with increased cardiovascular morbidity and abnormal arterial tone, but the underlying pathophysiological mechanisms are poorly understood. Therefore, we studied the responses of isolated mesenteric arterial rings from Wistar-Kyoto rats in standard organ chambers 6 wk after subtotal (5/6) nephrectomy or sham operation. Subtotal nephrectomy resulted in a 1.7-fold elevation of plasma urea nitrogen, whereas blood pressure was not significantly affected. Endothelium-mediated relaxations of norepinephrine-precontracted rings to ACh were impaired in renal failure rats. The nitric oxide (NO) synthase inhibitor N(G)-nitro-L-arginine methyl ester inhibited relaxations to ACh more effectively in the renal failure group, whereas the cyclooxygenase inhibitor diclofenac did not significantly affect the response in either group. Inhibition of Ca(2+)-activated K(+) channels by charybdotoxin and apamin attenuated NO synthase- and cyclooxygenase-resistant relaxations to ACh in control but not renal failure rats and abolished the difference between these groups. Endothelium-independent relaxations to isoproterenol and cromakalim, vasodilators acting via beta-adrenoceptors and ATP-sensitive K(+) channels, respectively, were impaired in the renal failure group, whereas relaxations to the NO donor nitroprusside were similar in both groups. In conclusion, endothelium-mediated relaxation in renal failure rats was impaired in the absence and presence of NO synthase and cyclooxygenase inhibition but not with prevented smooth muscle hyperpolarization. Endothelium-independent relaxations to isoproterenol and cromakalim were also attenuated after 5/6 nephrectomy. These results suggest that impaired vasodilatation in experimental renal failure could be attributed to reduced relaxation via arterial K(+) channels.Chronic renal failure is associated with increased cardiovascular morbidity and abnormal arterial tone, but the underlying pathophysiological mechanisms are poorly understood. Therefore, we studied the responses of isolated mesenteric arterial rings from Wistar-Kyoto rats in standard organ chambers 6 wk after subtotal (5/6) nephrectomy or sham operation. Subtotal nephrectomy resulted in a 1.7-fold elevation of plasma urea nitrogen, whereas blood pressure was not significantly affected. Endothelium-mediated relaxations of norepinephrine-precontracted rings to ACh were impaired in renal failure rats. The nitric oxide (NO) synthase inhibitor N G-nitro-l-arginine methyl ester inhibited relaxations to ACh more effectively in the renal failure group, whereas the cyclooxygenase inhibitor diclofenac did not significantly affect the response in either group. Inhibition of Ca2+-activated K+ channels by charybdotoxin and apamin attenuated NO synthase- and cyclooxygenase-resistant relaxations to ACh in control but not renal failure rats and abolished the difference between these groups. Endothelium-independent relaxations to isoproterenol and cromakalim, vasodilators acting via β-adrenoceptors and ATP-sensitive K+ channels, respectively, were impaired in the renal failure group, whereas relaxations to the NO donor nitroprusside were similar in both groups. In conclusion, endothelium-mediated relaxation in renal failure rats was impaired in the absence and presence of NO synthase and cyclooxygenase inhibition but not with prevented smooth muscle hyperpolarization. Endothelium-independent relaxations to isoproterenol and cromakalim were also attenuated after 5/6 nephrectomy. These results suggest that impaired vasodilatation in experimental renal failure could be attributed to reduced relaxation via arterial K+ channels.

Serum ionized versus total magnesium in patients with intestinal or liver disease

Abstract In serum, magnesium exists in three fractions: protein-bound, complex-bound and free ionized form. Only the free ionized fraction is biologically active. Until recently, only the measurement of serum total magnesium has been in clinical use. Now, commercially available instruments using new ion-selective electrodes for Mg++ have made possible the reliable measurement of serum ionized magnesium in clinical practice. For the measurement of serum ionized magnesium we used a magnesium-selective electrode installed in a six-channel electrolyte analyzer. We compared the use of ionized versus total magnesium measurement in 52 patients with intestinal disease, 54 with liver disease, and in 75 healthy control subjects. In the patients with alcoholic liver disease both serum ionized and total magnesium were lower, and in those with inflammatory bowel disease slightly higher than in control subjects. The correlation coefficient between serum ionized and total magnesium was r=0.87 (p<0.001) in the patients, and r=0.75 (p<0.001) in the controls. In the patient group the fraction of ionized magnesium in the total was negatively related to the serum albumin level (r=−0.41, p<0.001). Serum total magnesium was below the reference range in 30 out of 150 measurements, serum ionized magnesium in only 9 out of 150 measurements, respectively. Thus, 21 cases with low total but normal ionized magnesium (two thirds of hypomagnesemia according to serum total magnesium) were false positive. Total magnesium measurement may overestimate the incidence of hypomagnesemia when significant hypoalbuminemia is present. Measurement of serum ionized magnesium instead of total magnesium may therefore be of advantage in evaluating patients with hypoalbuminemia and when hypomagnesemia is expected.