Excretion Rate Of Tamm-Horsfall Protein Research Articles

Urinary Excretion Rate of Tamm-Horsfall Protein Is Related to Salt Intake in Humans

Background/Aims: Increased salt intake and enhanced salt sensitivity are implicated in the pathogenesis of hypertension. The aim of the present study was to investigate whether the urinary excretion rate of Tamm-Horsfall protein (THP) is dependent on salt intake in healthy, genetically hypertension-prone individuals. Methods: Thirty unrelated subjects (13 men and 17 women, mean age 48.1 ± 6.7 years) with at least one first-degree relative with primary hypertension were studied. After a baseline investigation, the study subjects were put on a low-salt diet (10 mmol of sodium and 70 mmol of potassium per day) for 1 week. During the second week, sodium chloride capsules (230 mmol/day) were added to the diet to achieve a high-salt intake of 240 mmol/day. Urine samples (24-hour and overnight collections) were collected before the baseline investigation and at the end of the high- and low-salt diet weeks. The salt sensitivity was calculated as the difference between the blood pressure during high salt intake and the blood pressure during low salt intake. Results: A low salt intake induced a decrease in the urinary excretion rate of THP during the night (11.7 µg/min) compared with baseline (19.5 µg/min; p < 0.05) and high salt intake (23.1 µg/min; p < 0.01). Furthermore, a greater response in blood pressure to a high salt intake, i.e. high salt sensitivity, was associated with increased excretion of THP in urine during the change to high salt intake (r = 0.38, p < 0.05). Conclusion: We were able to confirm that urinary excretion of THP is dependent on sodium intake. Patients with a high salt sensitivity, i.e. an exaggerated blood pressure response to high salt intake, responded to the high salt intake with an even greater increase in the urinary excretion rate of THP. The mechanism underlying this response is still unknown, but it might indicate that distal nephron function in healthy, genetically hypertension-prone individuals is altered.

Urinary sulphated glycosaminoglycans and Tamm-Horsfall protein in type 1 diabetic patients.

In diabetic nephropathy there is a decrease in glycosaminoglycans (GAG) in basement membranes and in Tamm-Horsfall protein (THP) in the distal tubules of the kidneys. Since GAG is present in both glomerular and tubular basement membranes, and the synthesis of both GAG and THP involves glycosylation, this study was carried out in order to investigate whether urinary excretion of these substances is interrelated. 24-h urinary collections were analysed. A total of 94 diabetic patients were grouped in accordance with the urinary albumin excretion rate as normo- (<20 microg/min) (n = 35), micro- (20-200 microg/min) (n = 30) and macroalbuminuria (>200 microg/min) (n = 29). In comparison with 26 control subjects, the excretion rate of GAG was decreased in patients with micro- and macroalbuminuria and excretion of Tamm-Horsfall protein in patients with macroalbuminuria. The excretion rates of GAG and THP were associated (r = 0.64, p < 0.001) and correlated with creatinine clearance (r= 0.46 and r= 0.53, p < 0.001; respectively) but not with levels of HbA1c. In conclusion, albuminuria was associated with decreased urinary excretion of sulphated GAGs, which was associated with the excretion rate of Tamm-Horsfall protein, indicating that excretion of GAG was associated with distal tubular dysfunction in diabetic patients.

Urinary Excretion of Tamm-Horsfall Protein and Epidermal Growth Factor in Chronic Nephropathy

Tamm-Horsfall protein (THP) and epidermal growth factor (EGF) are both synthesized by tubular cells in the distal part of the nephron and excreted with the urine. The present study examines the urinary excretion rates of the two peptides in relation to functional tubular markers in patients with chronic nephropathy. Four groups of patients with moderate to severely reduced renal function were studied: glomerulonephritis (n = 10), diabetic nephropathy (n = 11), tubulointerstitial nephropathy (n = 13), and polycystic kidney disease (n = 8). The renal function was evaluated by glomerular filtration rate (GFR) as an indicator for the general renal function, lithium clearance (C_Li) as an indicator for proximal tubular function, and absolute distal reabsorption of sodium (ADR_Na) as an indicator for distal tubular function. The excretion rate of EGF was rather closely correlated with GFR, C_Li and ADR_Na (Spearman coefficients of variation 0.88, 0.69, and 0.74, respectively). The correlations between the excretion rate of THP and GFR, C_Li and ADR_Na were weaker (Spearman coefficients of variation 0.68, 0.42, and 0.44). When the effect of GFR had been accounted for by multiple variance analyses, the excretion rates of the two peptides were still associated with ADR_Na but not with C_Li. In conclusion, the urinary excretion rates of especially EGF but also those of THP were correlated with renal function and distal tubular reabsorption of sodium in patients with chronic nephropathy.

Urinary excretion of Tamm-Horsfall protein in normotensive, normo-albuminuric type 1 diabetic patients.

The excretion rate of a marker of distal tubular function, Tamm-Horsfall protein (THP), has been measured in urine (micrograms/min) overnight, during orthostasis and during a glycaemic clamp (blood glucose concentration 7.0 mmol/l) with stable diuresis in 41 normotensive, normo-albuminuric type 1 diabetic patients. Eleven healthy subjects who were not clamped served as controls. A further 4 normo-albuminuric type 1 diabetic patients were rendered euglycaemic without a waterload. The excretion rate of THP overnight was similar in type 1 diabetic patients and normal subjects (26.1 vs. 23.5 micrograms/ml, p = NS). During the waterloaded euglycaemic clamp, THP increased significantly both in type 1 diabetic patients and control subjects (p < 0.001), but the increase was slightly greater in type 1 diabetic patients (67.2 vs. 38.4 micrograms/min, p = 0.05). Orthostasis did not increase the excretion rate of THP in either type 1 diabetic patients or in control subjects. In the 4 type 1 diabetic patients who were only clamped, the THP excretion rate increased less compared to the clamp plus waterload experiment (means: overnight 11.3 micrograms/min; clamp 22.5 micrograms/min). In Type 1 diabetes, overnight THP excretion was inversely correlated both with fasting blood glucose, HbA1 and sodium-lithium counter-transport activity (SLC). A direct relationship was present between urinary flow and the excretion rate of THP. In conclusion, this study shows that normotensive, normo-albuminuric type 1 diabetic patients present similar overnight excretion rates of THP compared to healthy controls and that the excretion rate of THP is unaffected by posture and increased during acute euglycaemia and waterload. The association between SLC and THP might suggest some relation between this putative marker of nephropathy and distal tubular function, but this finding needs confirmation and further study.

Urinary tamm-horsfall protein increased after potassium citrate therapy in calcium stone formers

Objectives To evaluate the effect of oral potassium citrate therapy on urinary excretion rates of citrate, Tamm-Horsfall protein (THP), and on calcium oxalate monohydrate crystal agglomeration inhibition [tm], in patients with recurrent calcium stone formation. Methods To evaluate the effect of oral therapy with potassium citrate on urinary citrate, THP, and [tm], 24-hour urine samples were collected before and at least 2 months after initiation of oral potassium citrate therapy in 33 calcium stone-forming patients who had no dietary restrictions. The citrate concentration was measured by an adaptation of a citrate lyase method. Urinary disaggregated THP concentration was determined with a quantitative enzyme-linked immunosorbent assay. The [tm] was determined by observing the effects of patients' urine, before and after oral potassium citrate therapy, on the uptake of 45Ca 2+ onto the surfaces of added preformed calcium oxalate crystals in a supersaturated solution of calcium oxalate, using the in vitro kinetic method described by other investigators. Results We observed an increased urinary excretion rate of citrate from a mean of 1.9 mmol/24 h prealkali to 2.6 mmol/24 h postalkali ( P < 0.0004) and of THP from a mean of 94.0 mg/24 h prealkali to 199.3 mg/24 h postalkali ( P <0.0016). A corresponding increase in [tm] from a mean of 177.1 minutes prealkali to 221.0 minutes postalkali ( P < 0.024) was also observed. Conclusions To our knowledge this is the first report correlating increased urinary citrate with THP excretion rate following oral alkalinization with potassium citrate in calcium stone formers. Of clinical importance is the corresponding increase in [tm], which was previously shown to be inversely related to stone-forming activity. Moreover, urinary citrate and THP are known to have a synergistic effect on [tm]. Our data suggest that the effectiveness of potassium citrate therapy in calcium stone-forming patients may, at least in part, be due to increased levels of THP.

Urinary excretion rate of NC1 and Tamm-Horsfall protein in the microalbuminuric type I diabetic patient

Fifty-six type I diabetic patients with microalbuminuria (albumin excretion rate 20–200 μg/min) were characterized as to sex, age, duration of diabetes, smoking habits, blood pressure, glomerular filtration rate, urinary NC1 (the carboxy-terminal domain of collagen IV), and Tamm-Horsfall protein excretion rate. Albumin excretion rate was considered a sign of glomerular damage, NC1 excretion rate a measure of renal basement membrane turnover, and Tamm-Horsfall protein excretion rate a marker for distal tubular function. There were no differences between males and females and between smokers and nonsmokers with respect to blood pressure, body-mass index, albumin excretion rate, glomerular filtration rate, excretion rate of NC1, and Tamm-Horsfall protein. As a group, the patients with microalbuminuria had normal glomerular filtration rate, excretion rate of NC1, and Tamm-Horsfall protein. The latter was influenced by glycosylated hemoglobin (HbA 1c) levels, especially so in patients with an albumin excretion rate less than the median value of 53.0 μg/min ( r = −0.61, p < 0.01). Furthermore, both excretion rate of NC1 and Tamm-Horsfall protein were increased in patients with high glomerular filtration rate ≥130 mL min −1 1.73 m −2). There was no association between glomerular filtration rate and HbA 1c levels. As glomerular filtration rate is related to kidney size, these observations suggest that patients with a high glomerular filtration rate have an increased mass and turnover of tubular basement membrane. Because high glomerular filtration rate has been suggested to be a predictor for the development of clinical nephropathy it may be suggested that changes in excretion rate of NC1 and/or Tamm-Horsfall protein may reflect important pathogenic mechanisms for the development of nephropathy. Furthermore, a low Tamm-Horsfall protein excretion rate in patients with poor metabolic control and with an albumin excretion rate in the lower range of microalbuminuria may indicate an early and potentially reversible tubular dysfunction.

Tubular Secretion of Tamm-Horsfall Protein Is Decreased in Type 1 (Insulin-Dependent) Diabetic Patients with Diabetic Nephropathy

Signs of glomerular, proximal and distal tubular dysfunction as well as metabolic control were studied in type 1 diabetes mellitus. To that end, the urinary excretion rates of albumin, sodium, phosphate and Tamm-Horsfall protein as well as HbA1c levels were measured in 20 patients with different degrees of diabetic nephropathy (positive Albustix for several years). Eight diabetic patients with short duration of diabetes and without any diabetic complications and 10 apparently healthy subjects were studied for comparison. The HbA1c levels in the three groups were 8.6 +/- 1.2, 5.9 +/- 2.2 and 4.1 +/- 0.4%, respectively (mean +/- SD). Duration of diabetes in the two diabetic groups were 27 +/- 7 and 3 +/- 1 years, respectively. The urinary protein levels were measured by enzyme-linked immunoassays. The fractional clearance of sodium (1.9 +/- 1.9%; p < 0.001) and phosphate (27 +/- 11%; p < 0.01) were increased in patients with diabetic nephropathy compared to diabetic patients without nephropathy (0.6 +/- 0.2 and 16 +/- 4%) and healthy control subjects (0.6 +/- 0.1 and 16 +/- 4%, respectively). Tamm-Horsfall protein excretion rate was decreased in both diabetic groups (15.0x/3.1 and 37.9x/1.9 micrograms/min, geometric mean x/tolerance factor, p < 0.001 and p < 0.05, respectively) compared to the healthy subjects (63.8x/1.3 micrograms/min). Furthermore, patients with diabetic nephropathy had a lower excretion rate of Tamm-Horsfall protein (15.0x/3.1 micrograms/min) compared to patients without signs of nephropathy (37.9x/1.9 micrograms/min, p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Tubular secretion of Tamm-Horsfall protein in type 1 (insulin-dependent) diabetes mellitus using a simplified enzyme linked immunoassay

The relationship between glomerular and tubular dysfunction and metabolic control in type 1 diabetes was studied. To that end the urinary excretion rates of albumin and Tamm-Horsfall protein as well as HbA1c levels were measured in 58 patients with different degrees of diabetic nephropathy and in 76 apparently healthy subjects matched for sex and age. The urinary Tamm-Horsfall protein levels were measured by a simplified enzyme linked immunoassay. The intra- and interassay variations were 8.9% and 13.6%, respectively. The intraindividual variation was 41% and the sensitivity of the assay was 4 micrograms/l. The Tamm-Horsfall protein excretion rate was 42.1 x/2.0 micrograms/min (geometric mean x/tolerance factor) in the diabetic patients compared to 34 x/1.9 micrograms/min in the control subjects (NS). The diabetic patients had higher albumin excretion rate (38.5 x/7.3 micrograms/min) than the control subjects (4.7 x/2.3 micrograms/min; P less than 0.001). By using multivariate analysis of variance, HbA1c level was found to be the only independent variable associated with Tamm-Horsfall protein excretion rate in diabetic patients (r = -0.28; P = 0.04), while no relationship was found between Tamm-Horsfall protein excretion rate and age, age at onset and duration of diabetes, gender, serum creatinine, diuresis, urinary albumin excretion rate, systolic and diastolic blood pressure levels and antihypertensive treatment. The urinary albumin excretion rate was associated with diastolic blood pressure (r = 0.34; P = 0.02) but not with HbA1c levels when testing the above variables by multivariate analysis of variance. In conclusion, these results may indicate a lack of relationship between glomerular and tubular dysfunction. The former was influenced only by diastolic blood pressure levels and the latter only by the degree of metabolic control. However, the correlations were weak and do not provide any insight into what is actually responsible for glomerular and tubular dysfunction.

Tamm-Horsfall protein in Balkan endemic nephropathy.

It is suggested that Tamm-Horsfall protein, a specific renal glycoprotein, may be involved in the pathogenesis of some renal diseases. In cadmium nephropathy and Fanconi syndrome (primary tubular diseases of the kidney) an increased excretion rate of Tamm-Horsfall protein has been observed. Balkan endemic nephropathy is a chronic tubulointerstitial disease of unknown etiology, most probably a primary disease of the kidney tubules with secondary reaction of the interstitial tissue. Investigation of Tamm-Horsfall proteinuria in Balkan endemic nephropathy has shown that subjects living in the area where this condition is prevalent have a significantly higher Tamm-Horsfall protein /creatinine ratio than those living in the control area where the condition has not been observed. Differences in this ratio among diseased, suspect and subjects "at risk" were not observed, despite differences in their glomerular filtration rates. But excretion of Tamm-Horsfall protein per litre of glomerular filtrate was significantly different among diseased, suspect and subjects "at risk" and significantly higher compared to control subjects. a relatively significant correlation was obtained between Tamm-Horsfall protein excretion rate and glomerular filtration rate as measured by creatinine clearance in both control and subjects living in the area of Balkan endemic nephropathy. Determination of Tamm-Horsfall protein in urine together with determination of proteinuria by electrophoresis on cellulose acetate membranes as a screening procedure, and by SDS -electrophoresis in polyacrylamide gell may be useful laboratory tests in detecting this nephropathy.