Urinary Excretion Of Tamm-Horsfall Protein Research Articles

A study of urinary Tamm-Horsfall protein excretion in adult type 2 diabetes mellitus .

To study the excretion of urinary Tamm-Horsfall protein (THP) with a wide range of urinary albumin creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR) in a population with type 2 diabetes mellitus (T2DM). A retrospective investigation was performed in 3,599 adult inpatients with T2DM in Anhui Provincial Hospital of China. Demographic information, urinary THP data, and other lab reports were obtained from the Electronic Patient Record (EPR). (1) In T2DM, average HbA1c was 8.6%, and 55.2% of the patients had an HbA1c > 9%. The percentages with normal excretion, decreased excretion, and increased excretion of urinary THP were 49.8%, 41.7%, and 8.5%, respectively. Serum creatinine (Scr), blood urea nitrogen (BUN), and UACR levels were highest, and eGFR was lowest, in the decreased urinary THP group. (2) The proportion of decreased urinary THP excretion rose, and the level of urinary THP declined when UACR increased or eGFR decreased. (3) Urinary THP showed a negative correlation to Scr, BUN, triglyceride (TG), and UACR (rs = -0.173, -0.228, -0.060 and -0.237, respectively), but a positive correlation with eGFR and high-density lipoprotein cholesterol (HDL-C) (rs =0.128 and 0.040, respectively). (4) Logistical regression analysis showed that Scr, BUN, TG, UACR, and eGFR were independent risk factors for decreased urinary THP (OR=3.477, 1.461, 1.160, 2.124, and 2.087, respectively). Increased albuminuria and decreased GFR are predictors of decreased urinary THP excretion. Distal convoluted tubule lesion may precede glomerular damage in a portion of T2DM patients. .

Relationship between urinary Tamm–Horsfall protein excretion and renal function in dogs with naturally occurring renal disease

Tamm-Horsfall protein (THP) is physiologically excreted in urine, but little is known about the role of THP in the diagnosis of renal disease in dogs. The aim of this study was to evaluate to which extent naturally occurring renal disease affects the urinary excretion of THP. Dogs were divided into 5 groups according to plasma creatinine concentration, urinary protein-to-creatinine ratio (UP/UC), and exogenous plasma creatinine clearance (P-ClCr ) rates: Group A (healthy control dogs; n = 8), nonazotemic and nonproteinuric dogs, with P-ClCr rates > 90 mL/min/m(2) ; group B (n = 25), nonazotemic and nonproteinuric dogs with reduced P-ClCr rates (51-89 mL/min/m(2) ); group C (n = 7), nonazotemic but proteinuric dogs with P-ClCr rates 53-98 mL/min/m(2) ; group D (n = 8), azotemic and borderline proteinuric dogs (P-ClCr rates: 22-45 mL/min/m(2) ); and group E (n = 15), azotemic and proteinuric dogs (not tested for P-ClCr ). THP was measured by quantitative Western blot analysis, and the ratio of THP-to-urinary creatinine (THP/UC) was calculated. The THP/UC concentrations were not different among dogs of groups A-D, but were reduced in dogs of group E (P < .001). THP/UC correlated negatively with serum creatinine (P < .01) and UP/UC (P < .01), but was not significantly associated with P-ClCr . Decreased levels of THP/UC were present in moderately to severely azotemic and proteinuric dogs. This suggests tubular injury in these dogs and that THP might be useful as urinary marker to study the pathogenesis of renal disease.

Tubular function in diabetic children assessed by Tamm-Horsfall protein and glutathione S-transferase

In a previous study, we found urinary excretion of Tamm-Horsfall protein (THP) to be persistently decreased in 25% of patients during the first year after diagnosis of diabetes mellitus. We thus wanted to study another marker for distal tubular function, pi glutathione S-transferase (pi-GST) and compare this and THP with proximal tubular function evaluated with alpha-GST and alpha-1-microglobulin (HC) in patients with longer duration of diabetes. One hundred and eighty-four diabetic and 16 control children were studied with timed overnight urine collections. Median age was 14 years, and median age at diagnosis was 8 years. The urinary excretion of alpha- and pi-GST was significant lower in diabetic than control children. There were no differences in the excretion of HC and THP. Diabetic children with decreased alpha-GST had higher albumin excretion, HbA 1c levels, and longer diabetes duration but decreased THP excretion and cystatin-C clearance compared with those with normal excretion. In contrast, a decreased pi-GST or THP excretion was not associated with such differences. Diabetic children with increased HC excretion had increased HbA 1c levels. Diabetic children, before the stage of microalbuminuria, may have signs of both proximal and distal tubular dysfunction, which is related to diabetes duration and poor metabolic control. Alpha-GST and pi-GST seem to be more sensitive than other parameters studied.

Early changes in glomerular size selectivity in young adults with type 1 diabetes and retinopathy. Results from the Diabetes Incidence Study in Sweden

Objective To investigate the relationship between early-onset retinopathy and urinary markers of renal dysfunction. Research Design and Methods The Diabetes Incidence Study in Sweden (DISS) aims to register all new cases of diabetes in young adults (15–34 years). In 1987–1988, 806 patients were reported and later invited to participate in a follow-up study focusing on microvascular complications after ∼10 years of diabetes. In the present study, 149 patients with type 1 diabetes, completed eye examination, and urine sampling were included. Results The patients with retinopathy ( n=58, 39%) had higher HbA 1c ( P<.001) and urinary IgG2/creatinine ( P<.05) and IgG2/IgG4 ratios ( P<.05). Patients with maculopathy had the highest levels. No significant differences in urinary albumin/creatinine, glycosaminoglycans (GAGs)/creatinine, Tamm–Horsfall protein (THP)/creatinine, and IgG4/creatinine ratios were found. Women had higher urinary albumin/creatinine ( P<.01) and urinary IgG2/creatinine ratios ( P<.01) than men. Conclusions Young adults with type 1 diabetes and early-onset retinopathy had higher IgG2/creatinine and IgG2/IgG4 ratios than patients without retinopathy indicating that retinopathy is associated with a change in glomerular size selectivity. This was found in association with normal urinary albumin and THP excretion and may be suspected to reflect early general vascular changes.

Tamm-Horsfall protein in recurrent calcium kidney stone formers with positive family history: abnormalities in urinary excretion, molecular structure and function

Tamm-Horsfall protein (THP) powerfully inhibits calcium oxalate crystal aggregation, but structurally abnormal THPs from recurrent calcium stone formers may promote crystal aggregation. Therefore, increased urinary excretion of abnormal THP might be of relevance in nephrolithiasis. We studied 44 recurrent idiopathic calcium stone formers with a positive family history of stone disease (RCSF(fam)) and 34 age- and sex-matched healthy controls (C). Twenty-four-hour urinary THP excretion was measured by enzyme linked immunosorbent assay. Structural properties of individually purified THPs were obtained from analysis of elution patterns from a Sepharose 4B column. Sialic acid (SA) contents of native whole 24-h urines, crude salt precipitates of native urines and individually purified THPs were measured. THP function was studied by measuring inhibition of CaOx crystal aggregation in vitro (pH 5.7, 200 mM sodium chloride). Twenty-four-hour urine excretion of THP was higher in RCSF(fam) (44.0 +/- 4.0 mg/day) than in C (30.9 +/- 2.2 mg/day, P = 0.015). Upon salt precipitation and lyophilization, elution from a Sepharose 4B column revealed one major peak (peak A, cross-reacting with polyclonal anti-THP antibody) and a second minor peak (peak B, not cross-reacting). THPs from RCSF(fam) eluted later than those from C (P = 0.021), and maximum width of THP peaks was higher in RCSF(fam )than in C (P = 0.024). SA content was higher in specimens from RCSF(fam) than from C, in native 24-h urines (207.5 +/- 20.4 mg vs. 135.2 +/- 16.1 mg, P = 0.013) as well as in crude salt precipitates of 24-h urines (10.4 +/- 0.5 mg vs. 7.4 +/- 0.9 mg, P = 0.002) and in purified THPs (75.3 +/- 9.3 microg/mg vs. 48.8 +/- 9.8 microg/mg THP, P = 0.043). Finally, inhibition of calcium oxalate monohydrate crystal aggregation by 40 mg/L of THP was lower in RCSF(fam) (6.1 +/- 5.5%, range -62.0 to +84.2%) than in C (24.9 +/- 6.0%, range -39.8 to +82.7%), P = 0.022, and only 25 out of 44 (57%) THPs from RCSF(fam )were inhibitory (positive inhibition value) vs. 25 out of 34 (74%) THPs from C, P < 0.05. In conclusion, severely recurrent calcium stone formers with a positive family history excrete more THP than healthy controls, and their THP molecules elute later from an analytical column and contain more SA. Such increasingly aggregated THP molecules predispose to exaggerated calcium oxalate crystal aggregation, an important prerequisite for urinary stone formation.

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.

Selectively reduced expression of thick ascending limb Tamm-Horsfall protein in hypothyroid kidneys.

Hypothyroidism causes major changes in the kidney by affecting its growth, structure, function, and biosynthesis of its specific gene products. As a consequence, the nephron shows a selective hypotrophy in the medullary portion of the thick ascending limb (TAL). Contrastingly, we have shown earlier that the abundance of the major ion transporter of the TAL, the furosemide-sensitive Na-K-2Cl cotransporter (NKCC2) was increased when related to kidney function in the hypothyroid organism. Synthesis of Tamm-Horsfall protein (THP), the most abundant urinary protein produced in the TAL, has been suggested to interfere with TAL function. We therefore studied the localization and synthesis rate of THP in the hypothyroid kidney. We used rats chronically treated with methimazole. Kidneys were processed for western blotting and histochemical evaluation. Morphologically the hypothyroid TAL displayed a selectively reduced epithelial cell height of its medullary portion. This was paralleled by decreased THP immunostaining and mRNA abundance. Western blotting indicated a 40% reduction in renal THP content ( P<0.005), and daily urinary THP excretion was 68% lower than in controls ( P<0.05). T3 substitution restored these parameters. To further confirm that changes were specific for THP and not merely the consequence of reduced kidney growth, the abundance of barttin, another distal tubular protein related to chloride transport, was tested as well. Barttin was increased by 43% in the hypothyroid rats. Together with our previous results showing increased NKCC2 expression in hypothyroidism, these results demonstrate a selective decrease in medullary THP synthesis. We suggest a potential involvement of THP in the renal functional changes associated with hypothyroidism.

Role of urinary inhibitors of crystallization in uric acid nephrolithiasis: Dalmatian dog model

ObjectivesTo study the role of urinary inhibitors on crystallization—nephrocalcin, Tamm-Horsfall protein (THP), and glycosaminoglycans (GAGs)—in hyperuricosuric nephrolithiasis using Dalmatian dogs, a breed well-known for high levels of uric acid excretion, in an in vivo model. MethodsUrine samples were collected from 10 stone-forming Dalmatian dogs and from 5 age-matched Dalmatians without kidney stones. Purine derivatives present in urine were studied by high-performance liquid chromatography. THP, GAGs, and nephrocalcin were isolated and measured. ResultsAs expected, the Dalmatians excreted a large amount of uric acid in urine, but without differences between the two groups (0.42 ± 0.08 mg/mg creatinine versus 0.48 ± 0.11 mg/mg creatinine for stone-forming and healthy Dalmatians, respectively, P = 0.64). No other metabolites were derived from purine in their urine. Stone-forming Dalmatians showed significantly lower urinary excretion of THP than did normal Dalmatians (0.09 ± 0.03 mg/mg creatinine versus 0.21 ± 0.03 mg/mg creatinine, P <0.03). The urinary excretion of GAGs was lower in the stone-forming Dalmatians, although the difference was not statistically significant. Inhibition of calcium oxalate monohydrate crystal growth caused by nephrocalcin isoforms from healthy and stone-forming dogs were in the same order of ∼10−7 M, as calculated from a Langmuir isotherm type plot. ConclusionsThe urinary excretion of THP and GAGs was decreased in stone-forming Dalmatians compared with healthy ones. Our results support the suitability of Dalmatian dogs as an in vivo model to investigate the interrelationship of urine inhibitors of crystallization and hyperuricosuria.

Early urinary changes in Tamm-Horsfall protein and epidermal growth factor in diabetic children.

Both glomerular and tubular markers have been used to follow diabetic nephropathy. However, neither albumin nor proximal tubular markers have proven useful in prepubertal diabetes. Hence we studied two markers derived from the distal tubular cells, Tamm-Horsfall protein (THP) and epidermal growth factor (EGF). The urinary excretion of THP and EGF was examined in samples obtained during the first 20 days and 1 year after diagnosis of diabetes in children aged 4-15 years. Fourteen children without and 18 with ketonuria were examined, and 17 age-matched healthy children participated as controls. The excretion rate of EGF was increased at diagnosis, while that of THP was not. After 20 days of treatment the excretion of EGF had normalized, while the excretion of THP was decreased. Similar results were obtained after 1 year. In conclusion, in spite of good metabolic control a reduced excretion of THP persisted for at least 1 year after the diagnosis of diabetes. Whether the finding of reduced excretion of THP has any biological significance awaits further study.

Determinants of urinary excretion of Tamm–Horsfall protein in non‐selected kidney stone formers and healthy subjects

The aim of the study was to measure urinary excretion of Tamm-Horsfall protein (THP), an important inhibitor of crystallization, and to identify possible determinants of urinary THP excretion in non-selected kidney stone formers (SF) and healthy subjects (C). By means of a commercially available ELISA (Pharmacia and Upjohn/Elias, Germany), we measured THP in 24-h urines of 104 SF (74 males/30 females, age 16-74 years) who had formed 8.7+/-2.4 stones (range 1-240), and of 71 C (41 males/30 females, age 22-62 years). Types of stones formed by SF were 88 calcium, eight uric acid, six infection, and two cystine. All values are means+/-SE. The normal range (5th to 95th percentile) of U(THP)xV was 9.3-35.0 mg/day in males and 9.0-36.3 mg/day in females respectively. Mean U(THP)xV was 21.3+/-1.2 mg/day (range 3. 4-51.6) in male and 15.2+/-1.6 mg/day (range 1.8-32.3) in female SF (P=0.008 vs male SF). Since U(THP)xV was positively correlated with C(Crea) (r=0.312, P=0.001) in SF as well as with U(Crea)xV (r=0.346, P=0.0001) and with body surface (r=0.271, P=0.0003) in all study subjects, mean THP/Crea (mg/mmol) was used for all further calculations. Overall, THP/Crea was lower in SF (1.42+/-0.07 vs 1. 68+/-0.08, P:=0.015), mainly due to increased THP/Crea in female C (2.08+/-0.11, P=0.0036 vs female SF, P=0.0001 vs male C and vs male calcium SF), which also explains decreased THP/Crea values in calcium SF (1.46+/-0.08, P=0.041 vs C). In addition, THP/Crea was reduced in uric acid SF (1.11+/-0.21, P=0.049 vs C). Whereas THP/Crea was not related to age, urine volume, intake of dairy calcium, or urinary markers of protein intake, either in C or in SF, it correlated significantly with urinary Citrate/Crea, both in C (r=0.523, P=0.0001) and in SF (r=0.221, P=0.025). In C only, but not in SF, THP/Crea was correlated with urinary Calcium/Crea (r=0. 572, P=0.0001) and with Oxalate/Crea (r=0.274, P=0.022). Both in C and SF, urinary THP excretion is related to body size, renal function and urinary citrate excretion, whereas dietary habits apparently do not affect THP excretion. Uric acid and calcium stone formation predict reduced THP excretion in comparison with C, whereas female gender goes along with increased urinary THP excretion in C. Possibly most relevant to kidney stone formation is the fact that THP excretion rises only in C in response to increasing urinary calcium and oxalate concentrations, whereas this self-protective mechanism appears to be missing in SF.

Urinary excretion of epidermal growth factor and Tamm–Horsfall protein in three rat models with increased renal excretion of urine

Epidermal growth factor (EGF) and Tamm–Horsfall protein (THP) are synthesized in the kidneys by the distal tubular cells and excreted into urine. The urinary excretion of these peptides has been suggested as a potential index for distal tubular function. The urinary excretion rates of EGF and THP were examined in three groups of rats with increased renal excretion of urine: uninephrectomy, non-osmotic polyuria and diabetic osmotic polyuria. Twenty-four hour urine samples were obtained after 7, 14 and 21 days. The urinary volume per kidney was doubled in uninephrectomy when compared to controls. There was a seven-fold increase in urinary volume in rats with non-osmotic polyuria and diabetic osmotic polyuria, as compared to controls. Uninephrectomy, non-osmotic polyuria and diabetes all affected the urinary excretion of EGF and THP differently. The EGF excretion in uninephrectomized rats was 60–80% of that of the controls, whereas THP excretion was unchanged, indicating that EGF excretion varied with renal tissue mass. Non-osmotic polyuria caused a five-fold increase in THP excretion but no change in EGF excretion. THP excretion in the diabetic rats was increased three-fold after 21 days when compared to controls, whereas EGF excretion was decreased when expressed per kidney weight. Immunohistochemistry demonstrated that EGF and THP were colocalized in the thick ascending limbs of Henle's loops and distal tubules in all five groups of rats. In conclusion, the EGF excretion appears to follow renal tissue mass and seems independent of urinary volume, whereas THP excretion is dependent mainly on urinary volume. This has implications for the use of EGF and/or THP excretion rates as an indicator for distal tubular function.

Biochemical and quantitative analysis of Tamm Horsfall protein in rats

The involvement of Tamm Horsfall protein (THP) in nephrolithiasis is currently under investigation in several laboratories. Although rat is a commonly used species as an in vivo model for such studies, there is only limited information available about the biochemical properties and excretion profile of THP in normal rats. In order to characterize rat THP, we purified and analyzed normal male rat THP, and compared it with normal human male urinary THP by gel electrophoresis. Both THPs migrated at approximately 90 KDa, and stained similarly for protein (Coomassie blue) as well as carbohydrates (periodic acid Schiff reagent). Compositional analysis revealed that rat THP was largely similar to human THP in amino acid and carbohydrate contents but showed differences in the individual sugar components from other mammals. There was considerable variation in the day-to-day urinary excretion of THP in normal rats, with values ranging from 552.96 micrograms to 2865.60 micrograms and a mean value of 1679.54 micrograms per 24 h. It was concluded from this study that rat THP did not contain any unusual biochemical components and was primarily similar to human THP in composition and mean urinary concentration.

Abnormal function of renal tubules in patients with simple renal cysts.

The present study aimed to assess the function of proximal and distal tubules in patients with simple renal cysts. Thirty-one patients with simple renal cysts and 10 healthy subjects were examined. Based on the cyst fluid/plasma sodium ratio, 25 cysts were found to be of proximal origin and 6 of undetermined origin. In all patients cyst fluid and plasma concentrations of beta-2-microglobulin (beta-2-MG), sodium, potassium, calcium, phosphorus and total protein were assessed. Urinary excretions of sodium, potassium, calcium, phosphorus, beta-2-MG and Tamm-Horsfall protein (THP) were also estimated. Fractional excretion of beta-2-MG was calculated. The concentrations of beta-2-MG in fluid obtained from cysts of proximal origin were significantly higher than in fluid from cysts of undetermined origin (2.26 +/- 0 36 vs. 0.65 +/- 0.13 mg/l, p = 0.0004). Concentrations of THP (6.85 +/- 1.21 vs. 3.14 +/- 1.06 micrograms/ml, p < 0.05), and potassium (4.39 +/- 0.07 vs. 3.13 +/- 0.44 mmol/l, p < 0.05) were also higher in fluid from proximal cysts than in fluid from cysts of undetermined origin. Plasma beta-2-MG concentration was significantly higher in patients with proximal and undetermined cysts than in the control group (4.35 +/- 0.34 and 4.11 +/- 0.74 vs. 1.89 +/- 0.1 mg/l, p < 0.001). Urinary beta-2-MG excretion was also significantly higher in both groups of patients than in healthy subjects (474.8 +/- 165.9 and 346 +/- 94 vs. 100.2 +/- 19.6 micrograms/24 h, p < 0.05). Urinary THP excretion was significantly higher in patients with proximal cysts than in healthy subjects (31.0 +/- 5.1 vs. 16.3 +/- 2.5 mg/24 h, p < 0.05). From the results obtained in this study it seems that patients with simple renal cysts of proximal origin are characterized by abnormal tubular handling of beta-2-MG, and calcium and THP excretion. Thus, in patients with proximal cysts presence of a latent renal tubulopathy seems to be likely.

Urinary Tamm-Horsfall protein as a marker of renal transplant function.

In a total of 428 urine samples collected from 15 patients aged between 23 and 60 years after cadaveric kidney transplantation during a postoperative hospital stay, Tamm-Horsfall protein (THP) was quantitatively determined using the ELIAS SYNELISA-THP immunoassay. All patients were treated with azathioprine, cyclosporine, prednisolone, given an intraoperative high-dose single antilymphocyte globulin bolus and discharged with functioning grafts. In clinically uncomplicated courses, even after immediate transplant function, the recovery of graft function took on average 7 days. Thereafter the urinary THP excretion was relatively stable and amounted, on average, to 14.5 +/- 4.9 mg/24 h (i.e. was at the lower limit of normal urinary THP excretion). In cases of delayed onset of graft function of undetermined origin accompanied by extremely reduced urinary THP excretion, the functional recovery, whether spontaneous or brought about by treatment, was characterized by a continuous increase in urinary THP excretion. In connection with interstitial rejections urinary THP excretion seems not to be a recommendable diagnostic parameter. Daily measurement of urinary THP is, however, suitable for monitoring the functional state of transplanted kidneys.

Urinary Excretion of Tamm-Horsfall Protein in Women with Recurrent Urinary Tract Infections

Since MS-fimbriated bacteria adhere to Tamm-Horsfall protein, it has been suggested that Tamm-Horsfall protein may trap urinary pathogens and prevent them from colonizing the mucosal surfaces of the urinary tract. To test the hypothesis that low urinary Tamm-Horsfall protein excretion rates predispose to urinary tract infection we obtained serial urine samples from 17 women with and 18 without a history of recurrent urinary tract infection. None of the women had known structural abnormalities of the urinary tract. Concentrations of Tamm-Horsfall protein in urine were measured with a sensitive enzyme-linked immunosorbent assay method. On the average, 3 urine samples per person collected within 3 to 6 months were analyzed. The mean Tamm-Horsfall protein excretion of women with recurrent urinary tract infection was 57.0mg./l. and that of controls was 66.3mg./l.; this difference was not statistically significant. The mean coefficient of variation was 44.2 and 62.1%, respectively. We conclude that urinary Tamm-Horsfall protein concentration is not significantly decreased in women with recurrent urinary tract infection compared with controls, and that excretion varies widely in repeat samples obtained from the same individual. (J. Urol., 144: 1185–1187, 1990)

Oxygen free radical involvement in urinary Tamm-Horsfall protein excretion after intrarenal injection of contrast medium.

To discover whether the increase in urinary excretion of Tamm-Horsfall protein (THP) is mediated by oxygen free radicals generated after injection of contrast medium, the authors tested the hypothesis that inhibition of oxygen free radical production after injection of sodium methylglucamine diatrizoate or iothalamate sodium diminishes urinary THP excretion. In three groups of dogs, kidneys received continuous infusions of either superoxide dismutase (SOD) and normal saline (six dogs), heat-inactivated SOD and normal saline (six dogs), or normal saline alone (four dogs). Urinary THP excretion, glomerular filtration rate, renal blood flow, mean arterial pressure, and renal venous malondialdehyde concentrations were measured before and after administration of contrast medium to each kidney. During the postcontrast period, SOD significantly attenuated the increase in urinary THP excretion, accompanied by an attenuated increase in renal venous malondialdehyde concentration. Heat-inactivated SOD did not attenuate renal hemodynamics or urinary THP excretion. The use of another contrast medium, iothalamate sodium, similarly increased urinary THP excretion. These results show that intrarenal administration of contrast medium induces a transient increase in urinary THP mediated in part by oxygen free radical damage to the kidney. Thus, THP may be a marker of renal tubular injury after injection of contrast medium.