Glomerular and tubular dysfunction in children with congenital cyanotic heart disease: effect of palliative surgery

BACKGROUND: Nephropathy has long been recognized as a potential complication of congenital cyanotic heart disease (CCHD). The present study was undertaken to investigate some aspects of glomerular function by measuring urinary total protein, microalbumin, and tubular function by assessing urinary alpha-1-microglobulin. The structural integrity of the renal proximal tubules was also studied by measuring urinary activities of the brush-border enzyme leucine-aminopeptidase and the lysosomal enzyme -acetyl-beta-d-glucosaminidase. The levels of hematocrit (Hct) and oxygen saturation were also investigated as predisposing factors for renal impairment in CCHD. METHODS: These investigations were done by recruiting 86 children who were grouped as follows: the control group (G1 ) consisted of 14 children (aged 4-12 years); the other 72 children with CCHD were divided according to age (ie, duration of cyanosis) into 4 equal groups, each containing 18 patients: G2 (age <1 year), G3 (age > or = 1 year and <5 years), G4 (age > or = 5 years and <10 years), and G5 (age > or = 10 years). In addition, 10 of the 72 patients underwent a palliative surgery and were included as G6 (regardless of age: 2 from G3, 4 from G4, and 4 from G5 ) to study the effect of the palliative surgery on the above-mentioned parameters. RESULTS: Results of the present work showed that with increasing duration of cyanosis (ie, on going from G2 to G5 ) among the studied children with CCHD, there was a significant elevation in the urinary excretion of the investigated functional and structural parameters of the glomeruli and proximal tubules compared with the control children. The data also showed a significant increase in Hct, whereas oxygen saturation was significantly decreased. Results of G6 after the palliative surgery demonstrated a significant decrease in the urinary excretion of the investigated parameters of the kidney, with a significant decrease in Hct and increase in oxygen saturation levels, compared with the results of the patients of this group before the palliative surgery. CONCLUSIONS: These results suggest impairment of both glomerular and tubular functions as well as structure of the proximal tubules among children with CCHD and that the palliative surgery has significantly improved this impairment.     

Evaluation of renal glomerular and tubular functional and structural integrity in neonates

BACKGROUND: Renal cells are not fully differentiated at birth, representing a major risk in preterm infants. We evaluated glomerular and tubular functional integrity as well as structural integrity of renal tubules among healthy full-term and preterm infants as well as diseased preterm infants. METHODS: A total of 50 newborns (10 healthy full-term, 10 healthy preterm, and 30 diseased preterm, at 38.9 +/- 1.10, 34.2 +/- 0.92, and 32 +/- 2.47 weeks gestational age, respectively) were included in the present study. Glomerular function was assessed by measuring urinary levels of both microalbumin and immunoglobulin G as well as serum creatinine levels, whereas the proximal tubular function was investigated by measuring the urinary levels of both alpha1-microglobulin and beta2-microglobulin as well as retinol-binding protein. Also, distal tubular reabsorption capacity was investigated by assessing fractional excretion of sodium. Moreover, the structural integrity of renal proximal tubules was studied by measuring the urinary activities of both the brush-border membrane enzyme leucine-aminopeptidase (LAP) and the lysosomal enzyme N-acetyl-beta-D-glucosaminidase. The preceding investigations were done on both the first and third days of life of all 50 newborns. RESULTS: Glomerular and tubular function and structure was relatively impaired at birth among both healthy and diseased preterm as well as healthy full-term neonates and improved rapidly thereafter. The diseased preterm neonates showed worse renal function and structure with minimal improvement regardless of the underlying sickness. CONCLUSION: Renal insufficiency and renal immaturity could be evaluated using enzymuria and low- and high-molecular-weight proteinuria as noninvasive methods.     

Response of superficial proximal convoluted tubule to decreased and increased renal perfusion pressure. In vivo microperfusion study in rats

Although urinary sodium excretion is positively influenced by acute changes in renal perfusion pressure, micropuncture studies show highly conflicting results concerning the response of superficial proximal tubule sodium reabsorption to changes in renal perfusion pressure. In the present study, the changes of superficial proximal reabsorption to decreased and increased renal perfusion pressure were determined in rats by an in vivo microperfusion method. In vivo microperfusion was selected as the method to determine the proximal sodium reabsorption because this method made it possible to deliver a constant fluid and electrolyte load to the proximal tubule without the influence of possible changes of glomerular filtration rate. Renal perfusion pressure was decreased from normal pressure by inflating a suprarenal aortic cuff and was increased from the normal level by the occlusion of celiac and mesenteric arteries and the infrarenal aorta. Although fractional excretion of sodium (FENa) in the urine was decreased from 1.24 +/- 0.23% to 0.45 +/- 0.11% (n = 7, p less than 0.01) when renal perfusion pressure was decreased from 125 +/- 6 to 99 +/- 3 mm Hg, absolute tubular reabsorption by the superficial proximal convoluted tubules was not increased (from 4.4 +/- 0.5 to 4.2 +/- 0.3 nl/min/mm, n = 22). When the renal perfusion pressure was elevated from 126 +/- 4 to 149 +/- 4 mm Hg, tubular reabsorption by the superficial proximal tubules was decreased from 4.1 +/- 0.3 to 2.5 +/- 0.3 nl/min/mm (n = 36, p less than 0.01) with an accompanying increase in FENa (from 1.28 +/- 0.24% to 2.29 +/- 0.37%, n = 9, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Role of prostaglandins in proximal tubule sodium reabsorption: response to elevated renal interstitial hydrostatic pressure

Previous studies have shown that the elevation of renal interstitial hydrostatic pressure by the direct expansion of renal interstitial volume increases urinary sodium excretion. The objective of the present study was to investigate whether proximal tubules respond to the elevated renal interstitial hydrostatic pressure and whether the inhibition of prostaglandin synthesis would alter the effect of elevated renal interstitial hydrostatic pressure on proximal sodium reabsorption. Expansion of renal interstitial volume by injecting 100 microliters of 2.5% albumin solution through a chronically implanted matrix increased renal interstitial hydrostatic pressure similarly in control rats (n = 8) and in indomethacin (n = 8) or meclofenamate-treated (n = 7) rats. In the absence of prostaglandin synthesis inhibition, renal interstitial volume expansion significantly increased the fractional delivery of sodium at the superficial late proximal tubules from 56.5 +/- 6.1 to 67.0 +/- 6.5% (p less than 0.01) with an accompanying increase in fractional excretion of sodium from 2.1 +/- 0.5 to 3.0 +/- 0.4% (p less than 0.01). In the presence of indomethacin or meclofenamate, renal interstitial volume expansion failed to augment the fractional delivery of sodium and the fractional excretion of sodium. In summary, these studies demonstrate that the synthesis of prostaglandins plays a role in the regulation of sodium reabsorption by the proximal tubules in response to elevated renal interstitial hydrostatic pressure.     

Candesartan reduces urinary fatty acid-binding protein excretion in patients with autosomal dominant polycystic kidney disease

BACKGROUND: Free fatty acids (FFAs) bound to albumin are overloaded in renal proximal tubules and exacerbate tubulointerstitial damage. Liver-type fatty acid-binding protein (L-FABP) is an intracellular carrier protein of FFAs that is expressed in renal proximal tubules in humans. Urinary L-FABP reflects the clinical prognosis of chronic glomerulonephritis. The aim of the present study was to determine whether urinary L-FABP excretion is altered in patients with autosomal dominant polycystic kidney disease (ADPKD) and whether candesartan cilexetil, an angiotensin II receptor antagonist, affects these levels. METHODS: Subjects comprised 20 normotensive ADPKD patients (8 men and 12 women, mean age 42.6 years) and 20 age-matched healthy volunteers (8 men and 12 women, mean age 44.0 years). The 20 ADPKD patients participated in a randomized double-blind placebo-controlled study of candesartan cilexetil for 6 months. Urinary L-FABP levels were measured by a newly established ELISA method. RESULTS: Urinary L-FABP levels were significantly higher in ADPKD patients (154.5 +/- 110.6 microg/g Cr) than in healthy subjects (5.5 +/- 3.8 microg/g Cr) (P < 0.001). Candesartan cilexetil reduced urinary L-FABP levels from 168.5 +/- 104.5 microg/g Cr to 98.5 +/- 68.5 microg/g Cr after 3 months (P < 0.01) and to 44.6 +/- 30.8 microg/g Cr after 6 months (P < 0.001). Placebo had no effect on L-FABP levels (before, 140.5 +/- 100.5 microg/g Cr; at 3 months, 148.5 +/- 108.5 microg/g Cr; at 6 months, 150.5 +/- 110.8 microg/g Cr). During the 6 months, serum creatinine, blood urea nitrogen, 24-hour creatinine clearance and blood pressure showed little change in either group. CONCLUSIONS: Increased urinary L-FABP levels may be associated with the development of ADPKD, and candesartan cilexetil has a beneficial effect on reducing these levels.     

Net renal tubular reabsorption of zinc in healthy man and impaired handling in sickle cell anemia

Zinc deficiency is a significant clinical finding in sickle cell anemia (SCA) and abnormalities of zinc handling such as hyperzincuria are present. The cause of increased urinary zinc excretion in SCA is not clear. To define the renal handling of zinc in SCA and in healthy subjects, we measured zinc (total and ultrafilterable plasma zinc, urine zinc) and creatinine clearance in eight healthy and seven SCA subjects. Ultrafilterable zinc in plasma was assessed by equilibration of plasma with 65Zn followed by filtration through Amicon Cetriflo CF25 cones. While the mean filtered load of zinc was not significantly different between the two groups, the mean zinc excretion rate was approximately three-fold higher in patients (1.73 +/- 0.96 vs. 0.63 +/- 0.39 micrograms/min, P less than .05). In controls, zinc excreted was significantly less than zinc filtered (P less than .005), the fractional excretion of zinc averaging 0.49 +/- 0.31, indicating net reabsorption. This was not the case for the SCA patients. We conclude that there is impaired renal tubular handling of zinc in SCA.     

The course of incipient diabetic nephropathy: studies of albumin excretion and blood pressure

With the aim of defining the transitional phase from normal or near normal albumin excretion to overt diabetic nephropathy, 23 male diabetics of more than 7 years' duration, below 40 years of age and a baseline urinary albumin excretion above 15 micrograms/min but without clinical proteinuria (incipient diabetic nephropathy) were studied. For comparison 18 normals, 23 diabetics with normal albumin excretion and 10 patients with overt nephropathy were also examined. Diastolic blood pressure (DBP) was elevated to 88 +/- 9 mmHg (mean +/- S.D.) compared to patients with normal urinary albumin excretion: 80 +/- 7 (S.D.) (2p = 0.13%) but was below pressures in patients with overt diabetic nephropathy 109 +/- 15 (2p = 0.002%). Glomerular filtration rate (GFR) was elevated to 142 +/- 21 ml/min (mean +/- S.D.) compared to 132 +/- 9 in patients with normal urinary albumin excretion (2p = 4.3%). Renal plasma flow (RPF) was not altered. Renal vascular resistance (RVR) was increased (0.200 +/- 0.035) compared to that of patients with normal urinary albumin excretion (0.180 +/- 0.025) (2p = 3.8%). In a longitudinal study of 10 of the patients with incipient nephropathy, followed for 4.9 (Mean) years, urinary albumin excretion increased significantly during the observation period, the yearly increase rate being 19 +/- 22% (mean +/- S.D.). DBP increased from 84 +/- 9 to 93 +/- 13 (2p = 3.8%) in 6 patients followed for more than 4 years.(ABSTRACT TRUNCATED AT 250 WORDS)     

The role of the renal kallikrein-kinin system in sodium metabolism in normal and low renin essential hypertension

In order to investigate the pathophysiological role of the renal kallikrein-kinin system in renin subgroups of essential hypertension, the quantity and activity of urinary kallikrein, urinary kinin excretion, and correlations of kallikrein and kinin excretions with renal sodium handling in the renal tubules were studied in 17 normal subjects, 23 patients with normal renin and 12 patients with low renin essential hypertension. Urine samples were collected by the 2-hour clearance method in the early morning. The quantity and activity of urinary kallikrein, and the urinary excretion of kinin were significantly lower in both low and normal renin patients than in normal subjects. Comparing the normal renin and the low renin group, no significant difference was found in the quantity of urinary kallikrein, while the activity of urinary kallikrein and urinary kinin excretion were significantly lower in low renin patients than in normal renin ones. Fractional excretions of sodium (FENa) and inorganic phosphorus (FEP), which reflect renal tubular and proximal tubular sodium reabsorption, respectively, were significantly lower in the low renin patients than in the normal renin ones. A significantly positive correlation was observed between the urinary kallikrein activity or urinary kinin excretion and FENa or FEP in both normal subjects and normal renin patients, but not in low renin patients.(ABSTRACT TRUNCATED AT 250 WORDS)     

Tamm-Horsfall-Protein excretion as a marker of ascending limb transport indicates early renal tubular damage in diabetes mellitus type I

Tamm-Horsfall Protein (THP) is a 95 kD glycoprotein which is secreted in the thick ascending loop of Henle (TALH) of the kidney. After renal tubular damage the secretion of THP is reduced. In diabetes mellitus (DM), TALH has not been studied. To differentiate between glomerular (albumin), proximal tubular microglobulinuria (α₁-microglobulin), and TALH function (THP), we investigated 65 patients 4–61 years of age. In well-controlled DM, mean hemoglobin A₁ equalled 7.4% and proximal tubular parameters indicated reversible damage early after onset. THP excretion (per 24 hrs or per day) was significantly elevated in DM duration of greater than ten years, suggesting enhanced TALH ion transport (glomerular hyperfiltration). THP secretion decreased in DM duration of greater than 15 years despite normal albumin excretion. Thus, renal THP excretion indicates early medullary dysfunction (TALH) in DM type I.     

Correction of hypozincemia following liver transplantation in children is associated with reduced urinary zinc loss

Zinc deficiency is a relatively common problem in children with chronic liver disease. We have previously shown inappropriate urinary zinc excretion in children with chronic liver disease and hypozincemia. This study was designed to determine if zinc deficiency and inappropriate urinary zinc losses are corrected in children with liver disease by liver transplantation. Thirty-three patients (age 1-19 years) underwent 35 liver transplants for acute and chronic liver disease. At the time of transplant, 17 patients had low plasma zinc (hypozincemic) (plasma zinc, 45.4 +/- 1.8 microg/dL), whereas 18 had normal plasma zinc (75.7 +/- 3.8). Before transplant, patients with zinc deficiency had higher urinary zinc to creatinine ratio compared with those with normal zinc status (6.6 +/- 1.9 vs. 2.2 +/- 0.6; P =.03) and lower serum albumin concentrations (low: 2.8 +/- 0.1 vs. normal: 3.3 +/- 0.2; P =.02). After transplant, there was a significant reduction in urinary zinc losses in the hypozincemic group followed by normalization of plasma zinc levels by 7 days posttransplant. These data suggest that the abnormal renal zinc homeostasis that is present in approximately 50% of pediatric patients undergoing liver transplant is rapidly improved and biochemical zinc deficiency is reversed after liver transplantation.     

Urinary albumin and beta 2-microglobulin excretion rates in patients with systemic lupus erythematosus

The daily urinary albumin and beta 2-microglobulin excretion rates were measured with sensitive radioimmunoassays in 14 patients with systemic lupus erythematosus (SLE). The duration of SLE ranged from 0.5 to 18 years, mean 10 years. The mean age was 37 years. All patients except 5 received prednisone, 5-20 mg/day. None of the patients had proteinuria as judged by the "Albustix" test, and all had normal serum creatinine. The daily urinary albumin and beta 2-microglobulin excretion rates were nearly the same as those previously found by us in 27 adult control subjects with a mean age of 44 years. Our study shows that SLE patients without clinical proteinuria have a completely normal renal glomerular and tubular protein handling, irrespective of the duration of the disease.     

Thyroxine in unextracted urine

The aim of this work was to estimate the daily urinary excretion of free and conjugated thyroxine using a direct radioimmunoassay and enzyme hydrolysis. The renal clearance of free T4 was also determined. The mean urinary values of free and total T4 (mean +/- 1 SD) in 112 euthyroid controls were 1353 +/- 496 and 1855 +/- 651 pmol/24 h, respectively. Urinary excretion of free hormone in 13 hyperthyroid patients was 5552 +/- 4320 pmol/24 h and total T4 was 8122 +/- 7219 pmol/24 h. Urinary free T4 excretion was 223 +/- 223 pmol/24 h in hypothyroid patients and total T4 was 542 +/- 490 pmol/24 h. These results indicate that daily urinary T4 excretion is a good indicator of thyroid function. The mean renal clearance of free T4 was 52 +/- 19 ml/min (mean +/- 1 SD) in euthyroid patients, 53.7 +/- 12.3 ml/min in hyperthyroid patients, and 67.6 +/- 13.1 ml/min in hypothyroid patients. We estimated the endogenous creatinine renal clearance as a control of the renal filtration rate. The data suggest that there is T4 filtration of unbound T4 and partial tubular reabsorption. Further experimental studies will be necessary to clarify the renal handling of thyroxine as well as the fate of reabsorbed T4.     

Inhibition by prostaglandin E2 of renal effects of calcitonin in rats

To investigate the possible role of prostaglandin E2 (PGE2) in modulating the actions of PTH and calcitonin (CT) in the kidney, the effects of PGE2 were examined on the in vivo conversion of [3H]25-hydroxyvitamin D3 to [3H]1,25-dihydroxyvitamin D3 ([3H]1,25-(OH)2D3) in vitamin D-deficient thyroparathyroidectomized (T-PTX) rats and on the urinary excretion of phosphate (Pi) in vitamin D-replete T-PTX rats in the presence of either PTH or CT. Plasma accumulation of [3H] 1,25-(OH)2D3 increased from 12.2 +/- 0.6 pmol/100 ml in controls to 19.5 +/- 1.1 (P less than 0.01) by 20 micrograms/h PGE2 to 29.8 +/- 1.8 (P less than 0.001) by 7.5 U/h PTH, and to 23.3 +/- 0.7 (P less than 0.01) by 500 mU/h CT. Administration of PGE2 inhibited CT-stimulated accumulation of 1,25-(OH)2D3 to levels not different from those by PGE2 alone (17.8 +/- 1.0 pmol/100 ml). In contrast, PGE2 had no effect on PTH-stimulated 1,25-(OH)2D3 accumulation. PTH and CT caused an increase in urinary Pi excretion and a decrease in plasma Pi levels. PGE2 abolished the effects of CT, but not of PTH, on both urinary Pi excretion and plasma Pi levels. Administration of PGE2 alone caused no significant changes in plasma Pi levels and only minimal increase in urinary Pi excretion. PGE2 did not suppress urinary cAMP excretion stimulated by CT. These results demonstrate that PGE2 specifically suppresses the effects of CT to stimulate synthesis of [3H]1,25-(OH)2D3 from [3H]25-hydroxyvitamin D3 and to inhibit tubular reabsorption of Pi without affecting urinary cAMP excretion. Since CT appears to stimulate 1 alpha-hydroxylase and inhibit Pi reabsorption in proximal tubules, nephron segments devoid of CT-sensitive adenylate cyclase, these data suggest that PGE2 modulates the actions of CT, but not of PTH, on proximal tubular functions.     

Does Increased Glomerular Filtration Rate or Disturbed Tubular Function Early in the Course of Childhood Type 1 Diabetes Predict the Development of Nephropathy?

To clarify whether glomerular hyperfiltration or disturbances in renal tubular function may be early markers of the later development of nephropathy a follow-up study was performed in 34 young Type 1 diabetic patients, who had originally been investigated 12 years previously. The initial median age was 14 (range 7-18) years and median diabetes duration 7 (2-14) years. At initial examination only one of the 34 diabetic patients exhibited increased urinary albumin excretion rate. The median glomerular filtration rate was increased (136 vs 107 ml min-1 1.73 m-2; p less than 0.0001) and median threshold concentration of phosphate per litre of glomerular filtrate was decreased (1.27 vs 1.76 mmol l-1; p less than 0.0001) in the diabetic group as compared to that of 28 healthy children. At follow-up 17 patients showed increased urinary albumin excretion rate and the median glomerular filtration rate in this group was significantly lower than that of 17 patients with normal urinary albumin excretion rate (108 vs 125 ml min-1 1.73 m-2; p less than 0.05). However, no relationships were found between the increased urinary albumin excretion (incipient and/or overt diabetic nephropathy) at follow-up to either the initial glomerular filtration rate (134 vs 137 ml min-1 1.73 m-2; p greater than 0.05) or to renal tubular function assessed from urinary excretion rate of beta 2-microglobulin (0.059 vs 0.069 microgram min-1; p greater than 0.05) and the renal threshold concentration of phosphate per litre of glomerular filtrate (1.29 vs 1.22 mmol l-1; p greater than 0.05).     

Increased proximal tubular reabsorption of sodium in childhood diabetes mellitus

Type 1 diabetes mellitus is associated with an increase in total exchangeable body sodium. To delineate a site of possible altered sodium handling, proximal tubular sodium reabsorption (PTRNa) was measured in 30 diabetic children, age 12.0 (range 7-16) yr, duration of diabetes 4.5 (range 0.2-12) yr, and compared with 10 non-diabetic children, age 10.0 (range 8.6-12.5) yr. PTRNa was calculated from the fractional clearance of lithium, which was determined from a single blood sample and a random untimed urine sample, taken between 0700 and 0830 h at home, fasting, before insulin therapy. PTRNa was significantly increased in the diabetic children compared with the non-diabetic children (81.6(SE 1.0) vs 74.2(2.6)%, p = 0.014). There was no relationship of PTRNa with age, duration of diabetes, metabolic control (glycosylated haemoglobin, plasma and urinary glucose, plasma lactate), or urinary protein excretion (albumin, N-acetyl-beta-D-glucosaminidase). Elevated sodium reabsorption in the proximal renal tubule may account for the high total exchangeable body sodium found in Type 1 diabetic patients.     

Sex differences in uric acid metabolism in adults: evidence for a lack of influence of estradiol-17 beta (E2) on the renal handling of urate

The serum urate concentration of adult women, which is lower than in men of a similar age, is thought to be related to a higher renal clearance of urate in women, possibly due to their higher plasma estrogen levels. Intersexual differences in the renal handling of uric acid was assessed in 9 normal adult women and 9 normal age-matched men. Women showed a significantly lower serum urate concentration as compared to men (3.5 +/- 0.3 v 4.9 +/- 0.7 mg/dL, P less than 0.001), higher fractional excretion of urate (9.8 +/- 1.0 v 7.3 +/- 0.8%, P less than 0.001), and significantly lower tubular urate postsecretory reabsorption (67.2 +/- 1.6 v 76.6 +/- 1.4% of secreted urate, P less than 0.01). To test whether plasma E2 has a uricosuric effect we administered estradiol valerate and estradiol benzoate to either oophorectomized or adult women. Plasma E2 levels and urinary total estrogen excretion increased significantly in both groups but the treatment failed to significantly modify serum urate or the fractional excretion of uric acid. Furthermore, in 4 normal adult women, the tubular phases that modulate the renal excretion of urate were not significantly influenced by increased plasma E2 levels. We conclude that in comparison to men of a similar age, the lower tubular urate postsecretory reabsorption of adult women is in accordance with the intersexual differences in uric acid metabolism. Plasma E2 does not influence renal handling of uric acid or serum urate levels.     

Leukodepletion improves renal function in patients with renal dysfunction undergoing on-pump coronary bypass surgery: a prospective randomized study

BACKGROUND: We aimed to show the impact of leukodepletion on renal function in patients undergoing on-pump coronary revascularization. PATIENTS AND METHODS: Fifty patients awaiting elective on-pump coronary revascularization with normal preoperative cardiac functions and with plasma creatinine levels ranging between 1.5 and 2.0 mg/dL were prospectively randomized into two groups: on-pump CABG with (group A: n = 25) and without leukodepletion (group B, n = 25). Renal glomerular and tubular injury were assessed by urinary alpha glutathione s-transferase (GST), plasma creatinine, and blood urea nitrogen (BUN) levels. RESULTS: The patients consisted of 14 females and 36 males with a mean age of 57.6 +/- 5.3 years. In the leukodepletion group, the mean levels of creatinine, BUN and urinary GST were found to be decreased on the first, third and fifth postoperative days compared with the control group. There was no mortality. Three patients in the control group needed postoperative dialysis. CONCLUSION: Patients with renal dysfunction undergoing on-pump CABG surgery seem to benefit from leukodepletion as a measure to prevent tubular damage and renal impairment compared with a control group.     

Massive cerebral calcifications associated with increased renal phosphate reabsorption

Extensive bilateral cerebral cortical calcifications were demonstrated in a young patient with a history of convulsions since the age of 4 years. Initial metabolic workup showed normal serum calcium levels, hyperphosphatemia, normal renal function, low urinary calcium excretion, and normal serum immunoreactive parathyroid hormone levels. The intravenous infusion of edetate disodium (disodium EDTA) showed a normal phosphaturic and cyclic adenosine monophosphate response, ruling out the diagnosis of pseudohypoparathyroidism. The infusion of acetazolamide produced a blunted phosphaturia with almost no change in the renal phosphorus threshold, suggesting a tubular defect that allows enhanced proximal tubular reabsorption of phosphorus. Although the exact mechanisms responsible for the localized calcifications remain obscure, we suggest that an enhanced proximal tubular reabsorption of phosphorus could be involved in the pathophysiologic basis of this abnormality.     

Evaluation of silicosis in ceramic workers

This study is aimed to evaluate the incidence of silicosis and the relation of it with personal and work-related factors among workers exposed to silica in ceramic factory. Workers were evaluated by respiratory symptoms, physical examination, pulmonary function and radiological findings. Occupational and Enviromental Pulmonary Disease Evaluation Questionnaire of the Turkish Thoracic Society Enviromental and Occupational Pulmonary Diseases Working Group was used. 365 of 626 workers had exposure to silica and the rest 261 were concerned as control group. There was no difference between mean age, duration of work and smoking pack year among the groups (p> 0.05). Cough and sputum rates were higher in silicosis group FEV1 and FVC values were lower in silica group but this was not statistically significant. When the two subgroups of silica group (the workers in high dust concentration and the ones in low concentration) were compared, the high concentrated group had significantly more sputum but the other symptoms and pulmonary functional parameters were not different significantly. 24 workers had parenchymal densities adjusted with pneumoconiosis. The workers with the pneumoconistic finding, had a higher mean age and longer duration of work. As a conclusion, ceramic industry has risk for silicosis. And the risk increase by time and age.     

Proximal renal tubular acidosis in TASK2 K+ channel-deficient mice reveals a mechanism for stabilizing bicarbonate transport

The acid- and volume-sensitive TASK2 K+ channel is strongly expressed in renal proximal tubules and papillary collecting ducts. This study was aimed at investigating the role of TASK2 in renal bicarbonate reabsorption by using the task2 -/- mouse as a model. After backcross to C57BL6, task2 -/- mice showed an increased perinatal mortality and, in adulthood, a reduced body weight and arterial blood pressure. Patch-clamp experiments on proximal tubular cells indicated that TASK2 was activated during HCO3- transport. In control inulin clearance measurements, task2 -/- mice showed normal NaCl and water excretion. During i.v. NaHCO3 perfusion, however, renal Na+ and water reabsorption capacity was reduced in -/- animals. In conscious task2 -/- mice, blood pH, HCO3- concentration, and systemic base excess were reduced but urinary pH and HCO3- were increased. These data suggest that task2 -/- mice exhibit metabolic acidosis caused by renal loss of HCO3-. Both in vitro and in vivo results demonstrate the specific coupling of TASK2 activity to HCO3- transport through external alkalinization. The consequences of the task2 gene inactivation in mice are reminiscent of the clinical manifestations seen in human proximal renal tubular acidosis syndrome.