Diagnosis of thoracic outlet syndrome in the emergency department

Gadodiamide at a dose of 0.1 mmol/kg was administered intravenously to 10 renal transplanted patients with stable, impaired, or slowly deteriorating renal function (serum creatinine 194-362 mumol/l). The patients were referred for contrast medium enhanced magnetic resonance imaging to rule out possible graft circulation abnormalities. The excretion of gadodiamide in urine was prolonged as compared with healthy controls. After 120 h 92% of the injected dose was excreted in urine and only 0.4% in faeces. The plasma clearance of gadodiamide was 28.6 +/- (SD) 5.5 ml/min (n = 10), and the renal clearance (0-72 h) was 26.3 ml/min. The renal clearance of 125I-iothalamate for the same time period was 27.9 +/- 5.3 ml/min. Thus, gadodiamide is eliminated by glomerular filtration also in renal transplant patients with moderately to severe impaired renal function, and gadodiamide clearance may serve as an alternative marker for the determination of the glomerular filtration rate. Serum values of creatinine and beta(2)-microglobulin and creatinine clearance were unchanged by gadodiamide and neither was the urinary enzyme excretion significantly changed. These results suggest that the renal tolerance to gadodiamide is good also in renal transplant patients with impaired renal function.     

Renal reserve is normal in adults born with unilateral renal agenesis and is not related to hyperfiltration or renal failure

This study was carried out to examine the renal hemodynamic response in adult patients with single kidneys born with unilateral renal agenesis. A group of 21 patients with unilateral renal agenesis were divided into three groups according to their glomerular filtration rate (GFR): 112 +/- 3 ml/min x 1.73 m2 in group A, 68 +/- 3.2 ml/min x 1.73 m2 in group B, and 40.7 +/- 3.3 ml/min x 1.73 m2 in group C. Mean arterial blood pressure was significantly higher in the patients of group C who were also proteinuric. The renal hemodynamic response to an oral protein load (2 g/kg of protein as beefsteak) was normal in all groups and unrelated to hyperfiltration or to renal failure and proteinuria. The study indicates that in patients with renal agenesis, the hemodynamic response to a protein challenge is similar to that of kidney donors, renal transplant recipients and uninephrectomized patients. The paper also demonstrates that the renal response to a protein challenge is inadequate to identify patients with renal agenesis who are at risk of developing renal disease. Finally, in renal agenesis with renal disease, creatinine clearance overestimated the GFR by an average of 32.7%.     

The course of kidney function in type 2 (non-insulin-dependent) diabetic patients with diabetic nephropathy

We evaluated the impact of some putative progression promoters on kidney function in albuminuric Type 2 (non-insulin-dependent) diabetic patients with biopsy-proven diabetic glomerulosclerosis. Twenty-six patients (1 female) with a mean age of 52 (standard error 2) years and a known mean duration of diabetes of 9 (1) years were followed-up prospectively for a mean of 5.2 (range 1.0-7.0) years. Twenty-one patients received antihypertensive treatment. During the observation period the glomerular filtration rate decreased from 83 (24-146) to 58 (2-145) ml.min-1 x 1.73 m-2 (mean (range)) (p < 0.001). The mean rate of decline in glomerular filtration rate was 5.7 (-3.5 to 22.0) ml/min per year. Albuminuria increased from 1.2 (0.3-7.2) to 2.3 (0.4-8.0) g/24 h (geometric mean (range)) (p < 0.001). Arterial blood pressure remained unchanged: 162/93 (SE 4/3) and 161/89 (4/2) mm Hg. Univariate analysis showed the rate of decline in glomerular filtration rate to correlate with systolic blood pressure (r = 0.71, p < 0.001), mean blood pressure (r = 0.56, p < 0.005), albuminuria (r = 0.58, p < 0.005) and the initial glomerular filtration rate (r = -0.49, p < 0.02). The rate of decline in glomerular filtration rate did not correlate significantly with dietary protein intake, total cholesterol, high-density lipoprotein cholesterol or HbA1c. Three patients died from uraemia and four patients died from cardiovascular disease. Two patients required renal replacement therapy at the end of the observation period. Our prospective observational study revealed that one-fifth of the patients developed end-stage renal failure during the 5-year observation period.(ABSTRACT TRUNCATED AT 250 WORDS)     

Significance of the karyopyknotic index in the course control of hormone-treated prostatic carcinoma

Renal function was evaluated in 40 patients with fulminant hepatic failure, They were divided into two groups on the basis of glomerular filtration rates greater than 40 ml/min or less than 25 ml/min. A number of patients in group 1 had markedly abnormal renal retention of sodium together with a reduced free water clearance and low potassium excretion which could be explained by increased proximal tubular reabsorption of sodium. The patients in group 2 had evidence that renal tubular integrity was maintained when the glomerular filtration rate was greater than or equal ml/min (functional renal failure), but evidence of tubular damage was present when this was less than 3 ml/min (acute tubular necrosis).     

Long-term improvement in renal function after cyclosporine reduction in renal transplant recipients with histologically proven chronic cyclosporine nephropathy

BACKGROUND: Chronic cyclosporine (CsA) nephropathy, which has been unequivocally documented in recipients of heart, heart-lung, liver, or bone marrow transplants, as well as in nontransplant situations, usually results in a progressive deterioration of renal function. In this study, we assessed the potential reversibility of chronic CsA nephropathy in renal transplant recipients. PATIENTS AND METHODS: Twenty-three renal transplant patients with biopsy-proven CsA nephropathy associated with long-term CsA administration (27+/-4 months) were followed up for more than 2 years after CsA reduction (18/23 patients) or withdrawal (5/23 patients) and addition of azathioprine. Changes in effective renal plasma flow and glomerular filtration rate were assessed before and 2 years after CsA reduction, whereas serum creatinine, proteinuria, blood pressure, and CsA concentrations were monitored up to 5 years. RESULTS: At 2-year follow-up, glomerular filtration rate increased from 40+/-3 to 47+/-4 (P<0.05) and effective renal plasma flow from 217+/-23 to 244+/-24 ml/min/1.73 m2 (NS). Mean arterial pressure significantly decreased from 98.7+/-2.9 to 93.1+/-2.7 mmHg (P<0.05). There was no significant change in renal vascular resistance, filtration fraction, or albumin excretion. A significant decrease in serum creatinine was also observed during the whole follow-up (73+/-6.5 months). CsA reduction was followed by only one episode of acute reversible rejection; chronic rejection developed in three patients 2 years or later after CsA reduction. CONCLUSIONS: These data suggest that CsA nephropathy participates in graft dysfunction in a small group of renal transplant recipients. In addition, graft dysfunction may be reversible when CsA dosage is reduced early after diagnosis of chronic CsA nephropathy.     

Improved method for serological testing in celiac disease--IgA anti-endomysium antibody test: a comparison between monkey oesophagus and human umbilical cord as substrate in indirect immunofluorescence test

To clarify the importance of the duration from the onset of a urinary abnormality until a biopsy is actually performed (UA-Bx time) in making a renal prognosis, we investigated 496 patients with IgA nephropathy (male/female: 222/274, mean age: 33.0 +/- 13.7 yrs, mean follow-up period: 10.8 +/- 4.3 yrs). All patients were found to have a urinary abnormality, including both hematuria and proteinuria, at clinical onset while demonstrating a normal renal function, and showing a serum creatinine level of < or = 1.2 mg/dl or a creatinine clearance level of > or = 80 ml/min. The UA-Bx time was divided into 3 groups: < 1 yrs (S-G), 1 < or = < 3 yrs (M-G), > or = 3 yrs (L-G). The severity of glomerular damage was divided into 5 groups based on the occupational rate of segmental sclerotic glomeruli. Based on a multivariate analysis of independent prognostic factors relating to renal death, the severity of glomerular damage was the most independent factor, while the UA-Bx time showed no risk for renal death. However, based on a multivariate analysis of the UA-Bx time regarding the timing of a renal biopsy, patients in L-G, which had the most glomerular damage, showed twice the hazard ratio as those in S-G or M-G and the difference was significant. These results thus indicate that because the glomerular damage is able to progress for 3 yrs or longer after the clinical onset of renal disease, a renal biopsy should therefore be performed within 3 yrs from the clinical onset in patients demonstrating both hematuria and proteinuria when such patients are also suspected of having IgA nephropathy.     

The localisations in liposomal membranes of the tetrahydrofuran ring moieties of the annonaceous acetogenins, annonacin and sylvaticin, as determined by 1H NMR spectroscopy

We studied 34 apparently healthy children and 2 propositi from kindreds with familial juvenile hyperuricaemic nephropathy (FJHN) - a disorder characterised by early onset, hyperuricaemia, gout, familial renal disease and a similarly low urate clearance relative to glomerular filtration rate (GFR) [fractional excretion of uric acid (FEur) 5.1+/-1.6%] in young men and women. In addition to the propositi, 17 asymptomatic children were hyperuricaemic -- mean plasma urate (368+/-30 micromol/l), twice that of controls (154+/-41 micromol/l). Eight of them had a normal GFR ( > 80 ml/min per 1.73 m2), and 11 renal dysfunction, which was severe in 5. The FEur in the 14 hyperuricaemic children with a GFR > 50 ml/min was 5.0+/-0.5% and in the 5 with a GFR < or =50 ml/min was still low (11.5+/-0.2%) compared with controls (18.4+/-5.1%). The 17 normouricaemic children (185+/-37 micromol/l) had a normal GFR (>80 ml/min) and FEur (14.0+/-5.3%). The results highlight the dominant inheritance, absence of the usual child/adult difference in FEur in FJHN and presence of hyperuricaemia without renal disease in 42% of affected children, but not vice versa. Since early allopurinol treatment may retard progression to end-stage renal failure, screening of all relatives in FJHN kindreds is essential.     

Donor age and graft function

We evaluated survival and renal function of cadaveric donor grafts according to donor age. The median age of the pediatric donors was 7.0 (0.7-16) years in 46 patients [median age 11.8 years (range) 3-16.8 years]. The median age of the adult donors was 34.4 (19-54) years in 59 patients [median age 12.1 years (range) 7-17.3 years]. Thirty patients were treated with azathioprine and prednisolone and 75 with cyclosporine A and prednisolone. The glomerular filtration rate (GFR) and the effective renal plasma flow (ERPF) were determined by the clearances of 51chromium-EDTA and 125iodine-hippurate 1-48 months after kidney transplantation. There was no difference in graft survival between pediatric and adult grafts. There were also no differences in GFR in patients receiving grafts from pediatric or adult donors; 2-3 months after transplantation the GFR in recipients of pediatric grafts was 62 +/- 20 ml/min per 1.73 m2 compared with 61 +/- 21 in those receiving adult grafts. The ERPF in recipients of adult grafts was significantly higher in the 1st month after transplantation: 486 +/- 239 versus 362 +/- 158 ml/min per 1.73 m2. From the 4th to the 6th month after transplantation this difference disappeared: the ERPF of grafts from pediatric donors was 279 +/- 131 ml/min per 1.73 m2 compared with 273 +/- 123 ml/min per 1.73 m2 in grafts from adult donors. Using the single-kidney GFR and ERPF on an age-matched group of probands with minor diseases as references, 2-3 months after transplant the mean GFR of grafts from pediatric donors increased to 118% +/- 51%, whereas the GFR of adult donor grafts fell to 60% +/- 22% over the same period. After 4-6 months the ERPF in pediatric grafts was 96% +/- 55% compared with 50% +/- 22% in adult grafts. We conclude that graft survival and function in children with either a pediatric or an adult graft may not differ because graft function adapts to the requirement of the recipient.     

Effect of three types of half-limb casts on in vitro bone strain recorded from the third metacarpal bone and proximal phalanx in equine cadaver limbs

This open-label, non-randomized, parallel-group trial investigated the pharmacokinetics of raltitrexed (Tomudex, formerly ZD1694) after a single intravenous dose of 3.0 mg m(-2), comparing eight cancer patients with mild to moderate renal impairment (creatinine clearance 25-65 ml min(-1)) with eight cancer patients with normal renal function (creatinine clearance >65 ml min(-1)). The primary end points were area under the plasma raltitrexed concentration-time curve from the start of the infusion to the last determined concentration (AUC(0-tldc)) and AUC to infinity (AUC(0-infinity)); secondary end points were peak concentrations of raltitrexed (Cmax) and elimination half-life (t(1/2gamma)). The groups were compared statistically using analysis of covariance. The AUCs were greater for patients with renal impairment than for patients with normal renal function (2452.2 compared with 1247.3 ng h ml(-1) for AUC(0-tldc) (ratio 1.97; 95% CI 1.36-2.84); 2961.5 compared with 1457.0 ng h ml(-1) for AUC(0-infinity) (ratio 2.03; 1.25-3.29). These differences were statistically significant (P = 0.002 and P = 0.008 for AUC(0-tldc) and AUC(0-infinity) respectively. Terminal half-life was longer for the renally impaired patients (271.2 compared with 143.3; P = 0.030). There was no significant statistical difference between the groups for Cmax (652.9 compared with 564.7 ng ml(-1) for patients with impaired and normal renal function respectively: ratio 1.16; 0.91-1.46; P = 0.204). There was a clear relationship between raltitrexed clearance and creatinine clearance. Adverse events, severe (WHO grade 3 or 4) toxicity and hospitalization due to adverse events were more frequent in the group with renal impairment. Therefore, a reduction in raltitrexed dose and increased interval between doses is recommended for patients with mild to moderate renal impairment.     

Renal function in noninsulin-dependent diabetes mellitus patients treated with angiotensin-converting enzyme inhibitors and calcium channel blockers

BACKGROUND: Data have not shown consistent effects with calcium channel blockers on the course of renal function in patients with noninsulin-dependent diabetes mellitus (NIDDM) who have hypertension alone or in association with renal damage. The differences between the antiproteinuric effects of subclasses or formulations of calcium channel blockers and the heterogeneity of renal lesions may contribute to the discrepancy in these data. Clinical studies conducted by the authors and other recent data that describe the course of renal dysfunction in hypertensive NIDDM patients treated with antihypertensive agents are reviewed. Renal structural changes were also evaluated. RESULTS: Most available data indicate that angiotensin-converting enzyme inhibitors and dihydropyridine and nondihydropyridine calcium channel blockers produce similar effects on glomerular filtration rate. In one study of patients achieving intensified, strict control of blood pressure (target<140/85 mmHg) with either cilazapril or amlodipine, glomerular filtration rate declined by 2.03+/-0.66 ml/ min/1.73 m2 per year and 2.01+/-0.71 ml/min/1.73 m2 per year, respectively, in the subgroup with normoalbuminuria and by 2.15+/-0.69 ml/min/1.73 m2 per year and 2.33+/-0.83 ml/min/ 1.73 m2 per year, respectively, in the subgroup with microalbuminuria. Renal lesions in NIDDM patients were found to be structurally heterogeneous and glomerular filtration rate appeared to decline only in patients with renal structural changes typical of NIDDM. CONCLUSIONS: The extent of blood pressure control, rather than the method by which this is accomplished, is the most important factor in determining the evolution of incipient nephropathy in hypertensive NIDDM. The kidneys of microalbuminuric NIDDM patients are structurally heterogeneous with less than one-third of patients having 'typical' diabetic nephropathology.     

Long-term nephrotoxicity of cisplatin, ifosfamide, and methotrexate in osteosarcoma

The acute renal effects of chemotherapy are known, but long-term nephrotoxicity has rarely been investigated. The aim of the present study was to assess long-term renal function in children and adolescents who received at-risk chemotherapy, including cisplatin, ifosfamide, and methotrexate, to treat an osteosarcoma. Renal function tests [creatinine clearance, microalbuminuria, and renal excretion of sodium, potassium, chloride, calcium, magnesium (Mg), phosphorus (P), and uric acid] were prospectively performed 5.4+/-2.2 (+/-SD) years after chemotherapy (total cumulative dose: methotrexate 41+/-31 g/m2, ifosfamide 39+/-14 g/m2, cisplatin 674+/-188 mg/m2) in 18 children and adolescents. The results were compared with 13 normal volunteers matched for age and sex. Creatinine clearance, which was greater than 80 ml/min per 1.73 m2 in all patients, correlated with the total dose of ifosfamide (r=0.55, P<0.05) and cisplatin (r=0.48, P<0.05). Microalbuminuria was noted in 4 patients. Hypomagnesemia was present in 4 and hypercalciuria in 3 patients; renal excretion of P, Mg, and uric acid was higher in patients than in controls. Glomerular function was not significantly altered and only mild tubular dysfunction was present. Since renal excretion of P and Mg were increased in patients compared with normal volunteers and hypercalciuria was occasionally seen, divalent ion disorders are the most-likely potential complications.     

Circadian rhythm of glomerular filtration rate in patients after kidney transplantation

Within 6 months of a kidney transplantation the graft can be regarded as an organ deprived of its innervation. We analysed whether the transplanted kidney has a diurnal rhythm of its glomerular filtration rate (GFR) similar to the GFR rhythm that has been demonstrated in normal individuals and in patients with nephrotic syndrome. GFR was measured by inulin clearances every 3 h during 1 day of bed-rest and identical food and fluid intake per 3 h in seven patients, 4-7 months after a successful kidney transplantation, and in 10 healthy volunteers. Similar to these healthy subjects, a normal circadian rhythm of GFR was detected in all but one patient with a maximum of 57 (range 45-82) ml/min in daytime, a minimum of 47 (range 36-70) ml/min during the night and a relative amplitude of 21 (range 10-41)%. The circadian rhythm of GFR was absent in the patient with the lowest value of GFR (39 ml/min). In conclusion, GFR has a circadian rhythm in patients studied within 6 months of a kidney transplantation, despite the absence of renal innervation.     

Pharmacokinetics of lamivudine in human immunodeficiency virus-infected patients with renal dysfunction

The purpose of this study was to determine the safety and pharmacokinetics of lamivudine (3TC), a nucleoside analog that has shown potent in vitro and recent in vivo activity against human immunodeficiency virus. Sixteen human immunodeficiency virus-infected patients, six with normal renal function (creatinine clearance [CLCR], > or = 60 ml/min), four with moderate renal impairment (CLCR, 10 to 40 ml/min), and six with severe renal impairment (CLCR, < 10 ml/min), were enrolled in the study. After an overnight fast, patients were administered 300 mg of 3TC orally. Blood was obtained before 3TC administration and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 32, 40, and 48 h afterward. Timed urine collections were performed for patients able to produce urine. Serum and urine were assayed for 3TC by reverse-phase high-performance liquid chromatography with UV detection. Pharmacokinetic parameters were calculated by using standard noncompartmental techniques. The peak concentration of 3TC increased with decreasing renal function; geometric means were 2,524, 3,538, and 5,684 ng/ml for patients with normal renal function, moderate renal impairment, and severe renal impairment, respectively. The terminal half-life also increased with decreasing renal function; geometric means were 11.5, 14.1, and 20.7 h for patients with normal renal function, moderate renal impairment, and severe renal impairment, respectively. Both oral and renal clearances were linearly correlated with CLCR. A 300-mg dose of 3TC was well tolerated by all three patient groups. The pharmacokinetics of 3TC is profoundly affected by impaired renal function. Dosage adjustment, by either dose reduction or lengthening of the dosing interval, is warranted.     

Growth and pubertal development in nephropathic cystinosis

In a retrospective investigation growth and pubertal development were evaluated in 30 patients with nephropathic cystinosis. Growth was investigated during the stage of chronic renal insufficiency as well as after successful kidney transplantation and growth rates were related to kidney function. Pubertal development was evaluated in 17 patients between 12 and 25 years of age. Prepubertal growth rates were stable in a range between -2 and -3 height velocity SDS as long as glomerular filtration rate was above 20ml/min per 1.73m2. A decrease in glomerular filtration rate below this threshold was followed by further decrease in height velocity. After kidney transplantation a significant catch-up growth was seen if immunosuppression was performed with cyclosporine A and low dose prednisolone. This did not occur if conventional therapy with azathioprine and high-dose prednisolone was used. Onset of puberty was delayed in all patients. Gonadotropin and oestradiol levels in female patients showed normal fluctuations according to ovulatory cycles. In male patients after puberty there was an increase in gonadotropin levels above the normal range for adult men while testosterone levels remained in the low normal range. These results indicate that adult men with nephropathic cystinosis may develop hypergonadotropic hypogonadism.     

Converting-enzyme inhibitor versus calcium antagonist in cyclosporine-treated renal transplants

The influence of antihypertensive treatment on the long-term evolution of arterial pressure and renal function was studied in a prospective controlled trial conducted in renal transplant recipients treated by cyclosporine. Within six months after transplantation, patients were randomly allocated to treatment by the angiotensin-converting enzyme inhibitor, lisinopril (ACEI, alone or associated with frusemide; N = 14), or the calcium antagonist, nifedipine (CA, alone or associated with atenolol; N = 11). Glomerular filtration rate (TcDTPA clearance) and effective renal plasma flow (hippuran clearance) as well as 24-hour urinary excretion of electrolytes and albumin were estimated at about 1 and 2.5 years of follow-up. Before initiation of antihypertensive therapy, the two groups were similar with regards to mean arterial pressure (119 +/- 2 vs. 120 +/- 4 mm Hg), effective renal plasma flow (285 +/- 26 vs. 248 +/- 33 ml/min/1.73 m2) and glomerular filtration rate (59 +/- 4 vs. 61 +/- 8 ml/min/1.73 m2 in the ACEI and CA groups, respectively). Both ACEI and CA treatments were associated with no change in renal function, a similar change in mean arterial pressure (ACEI -18 +/- 3; CA -13 +/- 5 mm Hg) and identical trough blood levels of cyclosporine. Urinary albumin excretion did not change significantly in any groups. Of interest, only in the ACEI group did filtration fraction significantly decrease (from 0.22 +/- 0.01% to 0.19 +/- 0.01% at final studies). These results indicate that in cyclosporine-treated transplant recipients, a satisfactory control of hypertension is obtained by chronic ACEI, which is as effective on arterial pressure as a combination of CA and atenolol.(ABSTRACT TRUNCATED AT 250 WORDS)     

Renal effects of aspirin and low dose methotrexate in rheumatoid arthritis

OBJECTIVES: The aim of this investigation was to study the glomerular and tubular effects of low doses (15 mg) of methotrexate in patients with rheumatoid arthritis with and without combined treatment with aspirin (2 g single dose). METHODS: Renal function was measured by the plasma clearance of EDTA labelled with chromium-51 (51Cr-EDTA) and mercaptoacetyltriglycine labelled with technetium-99m (99mTc-MAG-3). RESULTS: Clearance of 51Cr-EDTA was reduced from 98 (6) to 87 (5) ml/min (mean (SEM)) for patients receiving methotrexate only and further reduced to 76 (5) ml/min for patients receiving methotrexate and aspirin. This effect was reversible as 51Cr-EDTA increased to 85 (6) ml/min during continued treatment with methotrexate alone. Clearance of 99mTc-MAG-3 also decreased from 366 (18) to 315 (17) ml/min in patients receiving methotrexate alone and further to 295 (17) ml/min during treatment with aspirin and methotrexate. Continued treatment with methotrexate alone resulted in a further decrease in the 99mTc-MAG-3 clearance to 253 (17) ml/min. CONCLUSIONS: The study shows that treatment with low doses of methotrexate particularly when combined with aspirin affects glomerular and tubular function. These effects may be of clinical importance and renal function should therefore be monitored with more sensitive methods than serum creatinine as this may not reflect these changes.     

Glucose-induced changes in renal haemodynamics in proteinuric type 1 (insulin-dependent) diabetic patients: inhibition by acetylsalicilic acid infusion

The effect of hyperglycaemia on renal function in diabetic nephropathy remains poorly understood. We investigated the renal haemodynamic response to an acute plasma glucose rise from sustained euglycaemia to sustained hyperglycaemia in eight persistently proteinuric Type 1 (insulin-dependent) diabetic patients. Studies were performed in a double-blind cross-over manner after i.v. injection of 450 mg lysine acetylsalicilate (equivalent to 250 mg acetylsalicilic acid) or equal volume of 0.9% NaCl (isotonic saline). In the isotonic saline experiments hyperglycaemia produced a significant rise, by approximately 35%, in glomerular filtration rate in all patients from 41.5 +/- 5.2 to 55 +/- 6 ml.min-1.1.73 m-2 (p < 0.005) and an increase in sodium paraminohippurate clearance from 178 +/- 22.7 to 220 +/- 20.0 ml.min-1.1.73 m-2 (p < 0.05). These changes took place within the first 30 min of glucose infusion and were maintained for a 90 min hyperglycaemic period. Filtration fraction did not change significantly. Infusion of lysine acetylsalicilate lowered baseline glomerular filtration rate (isotonic saline vs lysine acetylsalicilate 41.5 +/- 5.2 vs 30.0 +/- 5.7 ml.min-1.1.73 m-2; p < 0.05) and significantly blunted the rise in glomerular filtration rate during hyperglycaemia (glomerular filtration rate increment: saline vs lysine acetylsalicilate: 13.6 +/- 2.8 vs 5.3 +/- 1.8 ml.min-1.1.73 m-2; p < 0.005). The effects on renal plasma flow were similarly blunted. In five additional patients, time- and volume-controlled isotonic saline experiments during sustained euglycaemia showed no significant changes in glomerular filtration rate and sodium paraminohippurate clearance.(ABSTRACT TRUNCATED AT 250 WORDS)     

Function of the C-terminal domain of the alpha subunit of Escherichia coli RNA polymerase in basal expression and integration host factor-mediated activation of the early promoter of bacteriophage Mu

Crescentic glomerulonephritis (GN) demonstrates immunopathological features of a T helper (Th)1-directed delayed-type hypersensitivity (DTH) response. The capacity of Th2 cytokines to attenuate crescentic glomerular injury in this disease was examined by administering interleukin (IL)-4 and IL-10, singly and in combination. GN was induced by i.v. administration of sheep anti-mouse glomerular basement membrane (GBM) globulin to mice sensitized to sheep globulin 10 days earlier. Treatment (2.5 microg, i.p.) with IL-4, IL-10, or both IL-4 and IL-10 (IL-4 + 10), was started 1 h before sensitization and continued daily until the end of the study (10 days after administration of anti-GBM globulin). Control mice treated with PBS developed GN with glomerular accumulation of T cells and macrophages, crescents in 42.5 +/- 4.5 % of glomeruli (normal 0 %), proteinuria (8.3 +/- 0.9 mg/24 h, normal 0.74 +/- 0.08 mg/24 h, p <0.001) and renal impairment (creatinine clearance [cr/cl]: 93 +/- 12 microl/min, normal 193 +/- 10 microl/min, p < 0.001). Treatment with either IL-4, IL-10, or IL-4 + 10 prevented crescent formation (crescentic glomeruli: 0.8 +/- 0.5, 1.2 +/- 0.9, and 1.4 +/- 1.0 %, respectively, all p < 0.01 compared to control) and attenuated proteinuria (3.6 +/- 1.0, 2.2 +/- 0.5, and 2.9 +/- 0.5 mg/24 h, respectively, all p < 0.01 compared to control). IL-4 + 10 prevented development of renal impairment (cr/cl: 183 +/- 22 microl/min); IL-10 given alone limited the decline in renal function (cr/cl: 150 +/- 20 microl/min), but IL-4 alone did not provide any significant protection (cr/cl: 121 +/- 17 microl/min). All treatments markedly diminished glomerular T cell and macrophage accumulation, reduced interferon-gamma production by splenic T cells, prevented cutaneous DTH to the disease-initiating antigen and reduced antigen-specific immunoglobulin of the IgG2a and IgG3 isotypes. These data demonstrate that crescentic GN and renal impairment can be prevented by administration of Th2 cytokines and that this effect is associated with attenuation of the Th1 response to the disease-initiating antigen.     

Urinary endothelin-like immunoreactivity in patients with cirrhosis

BACKGROUND/AIMS: To investigate a possible relationship between the renal production of endothelin and the presence of renal dysfunction and activation of vasoactive systems in cirrhosis, the urinary excretion and the circulating plasma levels of immunoreactive endothelin (irET) and the plasma levels of vasoactive hormones were measured in 19 healthy subjects, 12 cirrhotic patients without ascites and 39 patients with ascites and different degrees of renal dysfunction. METHODS: The urinary excretion and the circulating levels of irET were assessed after 5 days on a 40 mEq sodium diet and off diuretics. Renal function parameters and the plasma levels of vasoactive hormones were also measured. RESULTS: Patients with and without ascites had similar values of urinary irET as compared with healthy subjects (30+/-3, 31+/-3 and 29+/-2 ng/day, respectively, p>0.10). By contrast, patients with ascites had higher circulating levels of irET (15+/-1.2 pg/ml) than patients without ascites and healthy subjects (11+/-1.6 and 5+/-0.4 pg/ml, p<0.01). In patients with cirrhosis, no correlation was found between urinary irET and circulating irET. Moreover, urinary irET did not correlate with liver tests, serum and urine sodium, glomerular filtration rate or vasoactive substances. Patients with hepatorenal syndrome had similar urinary irET to patients with ascites without hepatorenal syndrome. CONCLUSIONS: Urinary excretion of irET is not increased in cirrhotic patients with ascites and does not correlate with abnormalities in renal function.     

The effect of angiotensin-converting enzyme inhibitors on proteinuria in chronic glomerulonephritis

The effect of two angiotensin-converting enzyme (ACE) inhibitors, lisinopril and captopril, on proteinuria and renal haemodynamics was investigated in 11 hypertensives (9 men, 2 women; mean age 46 +/- 16 years) with proteinuria (> 1.5 g/24 h) due to chronic glomerulonephritis and impaired renal function (glomerular filtration rate < 75 ml/min). In a randomized and double-blind cross-over trial the patients received, each time for six weeks, either lisinopril (5 mg/d, sometimes increased to 10 mg/d after 3 weeks) or captopril (twice daily 12.5 mg, sometimes increased to twice 25 mg after 3 weeks). Initially and between the individual treatment phases they were on a placebo phase for 4 weeks. The following were measured: protein excretion, including fractional clearance of albumin and IgG, plasma-renin activity and renal haemodynamics. Protein excretion was not significantly reduced by either drug (placebo: 7.1 +/- 4.0 g/d; lisinopril: 5.1 +/- 2.8 g/d; captopril: 5.4 +/- 3.0 g/d). Albumin excretion and fractional albumin clearance were significantly decreased only by lisinopril (P < 0.05), not by captopril. Plasma-renin activity was increased more by lisinopril than captopril (Placebo: 1.0 +/- 0.9 ng/ml.h; lisinopril: 5.2 +/- 2.8 ng/ml.h [P < 0.05]; captopril: 1.8 +/- 1.3 ng/ml.h [P < 0.05]). The renal haemodynamics was only slightly influenced by either drug, but captopril significantly decreased the filtration fraction in the presence of chronic glomerulonephritis and renal failure. - Resulting from their influence on the renin-angiotensin-aldosterone system, ACE inhibitors have, in addition to their known action on renal haemodynamics, an independent effect on the loading barrier of the basal membrane of the kidney.