The influence of coenzyme Q(10) on total serum calcium concentration in two patients with Kearns-Sayre Syndrome and hypoparathyroidism

Two patients with Kearns-Sayre Syndrome and hypoparathyroidism were treated with alfacalcidol (1a-OH D-3) and total serum calcium concentration remained within normal range for a long period. After two months of combined therapy with Coenzyme Q(10) (CoQ(10)), hypercalcemia was noticed and as a result, 1a-OHD3 was gradually discontinued. Normal total serum calcium concentration was obtained with CoQ(10) monotherapy while the replacement of CoQ(10) with placebo led to hypocalcemia. The mechanism of action of CoQ(10) is difficult to explain. Since the parathormone level remained unchanged during CoQ(10) or placebo therapy, we speculate that the capacity of producing an active form of vitamin D in mitochondria of proximal tubules was restored by CoQ(10) therapy

Membranous glomerulonephritis: A morphometric study

Archival material from 45 renal biopsies with a diagnosis of idiopathic membranous glomerulonephritis (MGN) were studied by computer-aided image analysis in order to evaluate the prognostic significance of glomerular and interstitial morphometry in MGN. The control group consisted of thirty seven normal renal biopsy specimens. The surface area, the perimeter, the major axis length and the shape factor of renal glomeruli as well as the percentage of the interstitial fibrosis were measured. All the morphometric parameters related to the size of glomeruli had significantly higher values in the patient group (p = 0.000 for all the parameters). However, no significant difference of the glomerular size between different stages of MGN was observed. In contrast, the percentage of interstitial fibrosis increased as the MGN stage rose (median values: 10.3% in stage 1, 14.2% in stage II, 26.9% in stage III, 28.9% in stage IV and 34.2% in stage V, Kruskal-Wallis ANOVA H = 37.645, p = 0.000). In the multivariate analysis the percentage of interstitial fibrosis was the only independent prognostic factor (p = 0.013). Our findings suggest that, in membraneous glomerulonephritis, the interstitial fibrosis increases as the MGN stage progresses, while the size of renal glomeruli has increased at a very early stage of the disease. This fact may indicate that interstitial fibrosis, not glomerular lesions, is mainly responsible for the reduction of renal function

Effect of intravenous calcium infusion on indices of activity of the parathyroid glands and on urinary calcium and sodium excretion in normotensive and hypertensive subjects

The effect of an intravenous calcium gluconate load (10 mg/kg over 5 min) on plasma ionized calcium concentration, parathyroid hormone (PTH), and the rate of urinary excretion of calcium, sodium, and nephrogenous cyclic adenosine monophosphate (NcAMP) was examined in 26 patients with essential hypertension and 27 age- and sex-matched normotensive subjects. Prior to calcium administration hypertensives had lower plasma ionized calcium concentration (P < .01) and higher PTH levels (P < .001) and excreted more calcium (P < .05) and NcAMP (P < .001) in the urine compared to normotensives. Following calcium infusion, plasma ionized calcium did not differ significantly between the two groups, but PTH levels remained higher in the hypertensive subjects at both 60 min (P < .001), and at 120 min (P = .02) post-load. Post-load values for both urinary calcium excretion and urinary sodium excretion were significantly higher in the hypertensive subjects than in the control group. Both before and after calcium infusion, urinary calcium excretion was positively correlated with urinary sodium excretion in each of the two groups, but for the same level of sodium excretion, hypertensives excreted more calcium in the urine, compared to normotensives, both before (P < .05) and after calcium infusion (P < .001). A positive correlation between basal plasma renin activity (PRA) values and plasma ionized calcium values obtained before (r = 0.42, P = .03) or at 60 min (r = 0.41, P = .03) and 120 min (r = 0.42, P = .03) after calcium infusion existed only in the hypertensive subject group. Postload urinary sodium excretion values were negatively correlated to basal PRA values in both groups (r = -0.55, P < .01 and r = -0.58, P < .01 for hypertensives and normotensives, respectively), but a similar negative correlation between post-load urinary calcium excretion values and basal PRA values existed only in the hypertensive subject group (r = -0.50, P < .01). The above results suggest that in essential hypertension increased overactivity of parathyroid glands may be secondary to renal calcium losses, which may be related to sodium and volume homeostasis, but also to a primary defect in renal calcium handling. © 1993

EFFECT OF AN ACUTE ORAL PROTEIN LOAD ON MICROALBUMINURIA IN UNINEPHRECTOMIZED PATIENTS IN RELATION TO THE TIME SINCE NEPHRECTOMY

To evaluate the effect of an acute oral protein lend (OPL) on urinary albumin excretion (UAE) in uninephrectomized subjects with a negative Albustix test, in relation to the time since nephrectomy. the UAE was determined by a double-antibody I-125 radioimmunoassay in 3-hour urine collections before and after 150 g OPL under conditions of moderate physical activity in 18 subjects who underwent unilateral nephrectomy more than 10 years (346.5+/-178.60 months) before evaluation and had a mean basal creatinine clearance (C-Cr) of 45.3+/-14 ml/min (group 1), in 21 subjects who under went unilateral nephrectomy less than 10 years (31.5+/-28 months) before evaluation and had a mean basal C-Cr of 76.0+/-22 ml/min (group 2), and in 16 normal volunteers (controls) with a mean basal C-Cr of 103.1+/-12 ml/min. The UAE was higher in group 1 as compared with either group 2 or controls at both basal state (90.8+/-65, 19.6+/-17, and 11.0+/-5 mu g/min/100 C-Cr for groups 1 and 2 and controls, respectively; p<0.001) and after OPL (92.0+/-65, 43.6+/-24, and 12.0+/-5 mu/min/100 C-Cr for groups 1 and 2 and controls, respectively; p<0.001). However, the increase in UAE following OPL was significant (p<0.001) only in group 2 patients. In all patients, the basal UAE was negatively correlated with basal C-Cr (r=0.63; p<0.001) and positively correlated with the time since nephrectomy (r=0.73; p<0.001) and with both systolic (r=0.57; p<0.001) and diastolic blood pressures (r=0.69; p<0.001). Ca calculated using 3-hour urine collections increased more in controls (11.2+/-44.2%) than in patient groups 1 (1.6+/-0.89) and 3 (7.7+/-3.7%; p<0.001). Basal C-Cr calculated using 24-hour urine collections the day before the test was negatively correlated with the time since nephrectomy in group 1 (r=-0.69; p<0.001) and positively correlated with the time since nephrectomy in group 2 (r=0.89; p<0.001). Multiple regression analysis revealed that the relationship between C-Cr and duration of uninephric state was independent of age or systolic and diastolic blood pressures in both patient groups. These results suggest that UAE increase significantly after an OPL in subjects who have been nephrectomized less than 10 years before the study and have basal C-Cr values higher than 50% of normal. They also suggest that the risk of developing renal insufficiency increases with time in subjects with a solitary kidney for more than 10 years; this increase in risk seems to follow a progressive compensatory increase in glomerular filtration rate of the remnant kidney during the early years following uninephrectomy

Erythropoietic response to oral iron in patients with nondialysis-dependent chronic kidney disease in the FIND-CKD trial

Aims: To evaluate erythropoietic response rates to oral iron over time in iron-deficient anemic patients with nondialysis- dependent chronic kidney disease (NDCKD). Materials and methods: FIND-CKD was a 1-year, randomized, multicenter trial of iron therapy in patients with ND-CKD, anemia, and iron deficiency, without erythropoiesis- stimulating agent (ESA) therapy. Patients with active infection or C-reactive protein > 20 mg/L were excluded. In this post-hoc analysis, response was defined as 65 1 g/dL increase in hemoglobin (Hb) from baseline, before initiation of alternative anemia therapy (i.e., ESA, transfusion, or intravenous iron). Results: 308 patients received oral iron (200 mg elemental iron/day). Mean (SD) Hb at baseline was 10.4 (0.7) g/dL. At week 4, Hb data were available from 292 patients without alternative anemia therapy: 63/292 (21.6%) showed a response. Among the 229 nonresponders at week 4, 48.8% showed a cumulative response on 651 occasion by week 52 (11.1%, 19.9%, 25.9%, and 28.7% had a response at weeks 8, 12, 24, and 52, respectively), and 27.9% had received alternative iron therapy by week 52. Baseline levels of Hb, ferritin, and transferrin saturation were lower in responders than in nonresponders. Neither concomitant medication nor adherence (as assessed by medication count) was substantially different between early responders and nonresponders. Conclusion: Four weeks after starting oral iron therapy, only 21.6% of anemic patients with ND-CKD and iron deficiency showed an Hb increase of at least 1 g/dL. Among early nonresponders, < 30% responded at any subsequent time point. Earlier consideration of alternative therapy could improve anemia management in this population