Effect of diet on creatinine clearance and excretion in young and elderly healthy subjects and in patients with renal disease.

Thirty-seven young healthy subjects with normal renal function were studied to assess the quantitative effect of protein intake on creatinine clearance. A standard 24-h urine collection and blood sample at the end of the collection were obtained for creatinine and urea concentrations. Correlations between creatinine clearance and urinary urea nitrogen excretion (r = 0.8; P less than 0.0001) and calculated protein intake (r = 0.8; P less than 0.0001) were observed. A significant relationship between creatinine clearance and urea nitrogen excretion was also demonstrated in 28 elderly healthy subjects and 33 patients with renal disease. To demonstrate a cause and effect between urea nitrogen excretion and creatinine clearance in healthy subjects, 18 of the 37 healthy subjects repeated the 24-h urine collection and blood sample after ingesting 5 g of urea in addition to their usual diet. Mean urinary urea nitrogen excretion increased from a mean value of 9.8 +/- 4.0 to 11.8 +/- 4.0 g/day. There was a strong correlation between the changes in urea nitrogen excretion and the changes in creatinine clearance. In acute studies with oral protein loading, there was a significant correlation between creatinine clearance and urinary urea nitrogen excretion. It was concluded that protein intake has a direct and quantitative effect on creatinine clearance in healthy subjects. In normal humans, it is likely that GFR is not a fixed function. Thus, a low creatinine clearance is not a categorical sign of renal disease. A low creatinine clearance adjusted for urea nitrogen excretion may be a useful clinical tool to assess renal function.     

Creatinine excretion rates for evaluation of kidney function in children

A protein load protocol for evaluation of kidney function was tested in normal children and pediatric renal patients. An overnight, timed urine collection was used for calculation of the baseline cretinine clearance and creatinine excretion rate. One hour following ingestion of a standardized protein meal (baked chicken), a 2–3 h urine collection was begun. The post-protein meal changes in creatinine clearance showed considerable variation in both the normal children and those with renal disorders. In contrast, the rate of excretion of creatinine was consistently increased in the normal children following the protein meal (73.4±18%; range 48.2%–122.4%). Of 33 renal patients, 14 showed less than a 48% increase in creatinine excretion rate, even though 9 of these children had baseline creatinine clearances within the normal range. These 9 patients have evidence of less than normal quantities of functioning renal tissue. Serial studies over a year on 2 children who presented with acute renal failure showed a progressive increase in creatinine clearance with scant increases in creatinine excretion rate. These studies provide indirect evidence that a less than normal enhancement of the rate of creatinine excretion following a protein load reflects the presence of adaptive glomerular hyperfiltration and hyperperfusion.     

慢性肾小球肾炎患者尿液TNFR1检测的临床意义

目的探讨慢性肾小球肾炎患者尿液肿瘤坏死因子a特异性的膜受体1（TNFR1）在评价。肾脏损伤程度中的价值以及对。肾功能损害的预测价值。方法选择在我院经病理检查确诊的原发性慢性肾小球肾炎患者50例,另选择20名健康体检者为对照组。检测2组24h尿蛋白定量,血清和尿液的肌酐浓度,计算肌酐清除率。酶联免疫法（ELISA）检测尿液TNFR1浓度。所有研究对象随访2年,每6个月1次,随访时检测肾功能。结果不同病理类型的慢性。肾小球肾炎患者尿液TN—FR1浓度均较对照组升高（P〈0．05）;病情恶化者肌酐清除率低于病情稳定患者（P〈0．05）,尿液TNFRI浓度高于病情稳定者（P〈0．05）,2组24h尿蛋白定量无明显差异（P〉O．05）;尿液TNFRl浓度与肌酐清除率呈负相关（P〈0．05）,与24h尿蛋白定量呈正相关（P〈0．05）;年龄、24h尿蛋白定量和尿液TNFR1浓度是基线肌酐清除率的影响因素（P〈0．05）;尿液TNFRl浓度是病情恶化者肌酐清除率下降的独立影响因素（P〈0．05）。结论尿液TNFRl浓度可以评价和预测慢性肾小球肾炎患者肾功能损害。     

Assessment of renal function in surgical patients by urine osmolality concentration tests

Evaluation of renal function by urine concentration induced by fluid deprivation (thirteen to fifteen hours) or exogenous ADH (aqueous Pitressin, 10 units intramuscularly) has been carried out in 196 patients. These studies indicate that in comparison with the endogenous creatinine clearance test, the urine osmolality concentration test is simpler, is less subject to error, and appears to be a reliable method of identifying the majority of cases with significant impairment of renal function.A small proportion of patients with elevation of serum creatinine above 1.5 mg per cent may not have diminished concentrating ability; however, a combination of serum creatinine and urine osmolality tests would identify a wide span of renal functional abnormalities.Urine osmolality concentration tests deserve further definitive evaluation and currently are worthy of clinical application for the recognition of disorders of renal function.Under the conditions of an active general surgical ward, estimation of endogenous creatinine clearance is an unreliable measure of renal function.     

Urinary epidermal growth factor excretion in children with chronic renal failure.

To investigate the excretion of urinary epidermal growth factor (EGF) in children with chronic renal failure (CRF), we have measured the urinary EGF/creatinine ratio (EGF/Cr) and the 24-hour urine EGF concentration in 19 children with CRF, 11 children with kidney disease and normal creatinine clearance, and 12 healthy children. Children with CRF had a significantly lower daily urine EGF concentration as well as urinary EGF/Cr. In contrast, children with kidney disease and normal renal function had normal daily urine EGF levels and urinary EGF/Cr. Accompanied by no difference in serum EGF between these two groups of patients, these data provide indirect evidence of the kidney as a source of human urinary EGF. There was a positive correlation of urinary EGF/Cr with creatinine clearance in all renal patients (r = 0.608, n = 30, p < 0.001). A much better correlation was found between daily urine EGF and creatinine clearance (r = 0.855, n = 30, p < 0.001). Our results implicate that there is a functional relationship between glomerular filtration and urinary EGF excretion, and that the urinary EGF/Cr may be a reliable indicator of urinary EGF excretion in children with CRF.     

Influence of pregnancy on progression of diabetic nephropathy and subsequent requirement of renal replacement therapy in female type I diabetic patients with impaired renal function.

The influence of pregnancy on the progression of diabetic nephropathy in diabetic women with pre-existing moderate renal insufficiency is a subject of considerable controversy in the literature. In four of five female patients with type I diabetes mellitus with pre-existing impaired renal function (creatinine clearance less than 80 ml/min), significant proteinuria (greater than 2 g/24 h urine) and hypertension we have found a further decline in renal function during pregnancy, with an increased deterioration rate of creatinine clearance in comparison to the time before and after pregnancy. The mean decline of the glomerular filtration rate was 1.8 ml/min per month during pregnancy and 1.4 ml/min per month postpartum until the start of dialysis treatment. The difference in the progression of diabetic nephropathy during and after pregnancy can be explained by increased hypertension during pregnancy, especially in the third trimester, despite an intensified antihypertensive therapy. The long-term effect of pregnancy on renal function in our patients was therefore an earlier requirement for renal replacement therapy than would have been expected without pregnancy.     

Timed-urine collections for renal clearance studies

The purpose of this study was to describe the reproducibility of timed-urine collections for renal clearance studies and the effect variations in urine collection has on measurement of glomerular filtration rate (GFR). Data from 222 cimetidine clearance studies (GFR-Cim) were obtained from 32 pediatric renal patients over a period of 8 years. There were three to 18 studies per child aged 4.8 years to 21 years at the time of a study. The urinary creatinine excretion rate is measured during supervised urine collection periods. The creatinine excretion rates in each child were compared to obtain data on the reproducibility of the urine collections. The coefficient of variation (CV) of the creatinine excretion rate is approximately 10% in both children and adults. The variation in GFR to be expected during repeated renal clearance studies in subjects with stable GFR, using voided urine collections, was similar in children and adults, with a CV of 12% to 14%.     

Glomerular expression of biglycan and decorin and urinary levels of decorin in primary glomerular disease

AIMS: Recent studies have suggested that small leucine-rich proteoglycans (SLRP) of the extracellular matrix play a major role in modulating the activity of growth factors and in regulating the deposition of collagens. In this study, the expression of the SLRPs biglycan and decorin in the glomeruli of patients with primary glomerular disease (minimal change disease, IgA nephropathy, and membranous nephropathy) and urine immunoreactive levels examined. METHODS: Renal biopsy specimens were obtained from patients with minimal change disease, IgA nephropathy and membranous nephropathy. Immunohistochemical staining was performed on fresh-frozen samples using anti-biglycan and anti-decorin antibodies. Examination of urine proteoglycan excretion from a total of 26 patients and 8 normal volunteers was performed by indirect ELISA. RESULTS: In normal kidney samples, biglycan and decorin expression was found predominantly in the intrarenal arteries and tubulointerstitium, with only minimal expression in the glomeruli. Glomerular expression of these proteoglycans in glomerular disease was unchanged in all of the 4 patients examined with minimal change disease. In the case of IgA nephropathy or membranous nephropathy, some of the patients showed minimally increased immunostaining of either biglycan or decorin, but there were no signs of simultaneous upregulation of both proteoglycans. To further examine the changes in proteoglycan expression, ELISA was performed on urine samples. Urine biglycan levels were below detection levels, but high values of urine decorin immunoreactivity were found in the patients with glomerular disease. A significant negative correlation was found between urine decorin and creatinine clearance. CONCLUSION: These results suggest that distinct changes in the expression of the SLRPs biglycan and decorin may be seen in patients with primary glomerular disease. Moreover, the negative relationship between urine decorin levels and renal function supports the hypothesis that decorin may be involved in the pathophysiology of renal dysfunction in humans.     

Effect of postural change on urine volume and urinary sodium excretion in diabetic nephropathy

Fluid retention develops relatively early in the renal insufficiency of patients with diabetic nephropathy. The objective of this study was to clarify the effect of postural change on urine volume and urinary sodium excretion in diabetic nephropathy. Subjects consisted of 16 patients with non-insulin-dependent diabetes mellitus (five with diabetic nephrotic syndrome [DNS], five with nonnephrotic overt diabetic nephropathy [NNODN], and six without overt diabetic nephropathy [ODN]) and 11 patients with nondiabetic renal diseases (five with nondiabetic nephrotic syndrome [NDNS] and six without nephrotic syndrome). Patients were studied during 60 minutes of recumbency, followed by 60 minutes of standing. Mean blood pressure decreased in the standing posture only in patients with DNS and nondiabetic renal diseases. Urine volume decreased in the standing posture in the three groups of diabetic patients. Urine volume showed no changes in the standing posture in nondiabetic patients with and without nephrotic syndrome. The decreases in mean blood pressure and urine volume and the percentage decrease in creatinine clearance were significantly larger in patients with DNS than in those with NDNS and NNODN. The increase in free water clearance was significantly smaller in patients with DNS than in those with NDNS and NNODN. Urinary sodium excretion decreased in the standing posture in diabetic and nondiabetic patients, while no differences in the magnitude of changes were noted among patients with NDNS, NNODN, and DNS. It is concluded that the standing posture causes a greater decrease in urine volume due to orthostatic hypotension in patients with DNS compared with those with NDNS and NNODN, and that the presence of orthostatic hypotension in patients with DNS is likely responsible for the greater fluid retention of this group compared with other nephrotic patients with similar degrees of hypoalbuminemia.     

Creatinine clearance in critically ill surgical patients.

Standard tests of renal function (urine output, BUN, and serum creatinine) were compared with creatinine clearance values and with outcome in 131 critically ill surgical patients. There was a strong negative relationship between creatinine clearance and mortality. Of the 23 patients with a severe reduction of creatinine clearance (less than 20 mL/min), 17 died. In contrast, 23 of the 24 patients with a creatinine clearance of 100 mL/min or more survived. Urine output, BUN, and serum creatinine levels correlated poorly with creatinine clearance. A urine output of less than 30 mL/hr, a BUN level greater than 40 mg/dL, and a serum creatinine level greater than 2.0 mg/dL in all instances were associated with reduced creatinine clearances. However, more than half of all the patients with a normal urine output, BUN, or serum creatinine levels also had a reduced creatinine clearance.     

Detection of renal tubular lesions after abdominal aortography and selective renal arteriography by quantitative measurements of brush-border enzymes in the urine

Quantitative determination of brush-border enzyme excretion in the 24-hour urine is a much more sensitive index of renal tubular damage after aortography and selective renal arteriography than the conventional renal function tests such as serum creatinine and clearance determinations. Among the five brush-border enzymes which we investigated, alkaline phosphatase (AP) was the most sensitive diagnostic pointer. In 90% of hypertensive patients without detectable pre-existing renal parenchymal damage, abnormal levels of AP excretion in the urine were found on the same day as or on the day after the intra-arterial injection of contrast medium. Measurement of other brush-border enzymes does not provide any further diagnostic information. Provided there is no pre-existing renal parenchymal damage, the lesion caused by the contrast medium is transient and is usually reversed within 48 h. For the early detection of tubular lesions caused by tri-iodinated benzoic acid derivatives, AP excretion in the 24-hour urine should be measured at least twice--on the day of the contrast medium injection and on the following day.     

Myoglobin release and renal function in polytraumatized patients in intensive care

The excessive release of myoglobin following extensive skeletal muscle trauma, burns, and myopathies may result in renal dysfunction. Due to its molecular size, myoglobin is filtered through the glomerulus and is in part reabsorbed by the tubular system. intraluminal deposition of myoglobin following renal hypoperfusion and the impact of endogenous mediators on cell function contribute to the pathogenesis of acute renal failure. The present study was aimed to investigate the relation between myoglobin and renal function in polytraumatized patients. Thirty-four patients with an Injury Severity Score (ISS) of 28 +/- 3.1 (SEM) and a mean age of 39.5 years (range 18-70) were studied prospectively. Myoglobin, sodium, and creatinine concentrations in plasma and urine were determined 8-hourly. Myoglobin excretion, fractional myoglobin excretion, myoglobin clearance, creatinine clearance, and fractional excretion of sodium were calculated. The mean concentration of plasma myoglobin on the 1st day post-trauma was 3087 ng/ml. A continuous decrease in plasma myoglobin concentration could be observed, with a mean value of 497 ng/ml on day 7. The myoglobin concentration in urine showed marked fluctuations: the mean values were 3.37-4.12 mg/ml on day 1 and 0.78-1.34 mg/ml on day 7. There was no correlation between plasma and urine myoglobin concentrations. The myoglobin concentration increased during the period of observation, but there was no correlation with the creatinine clearance. The fractional excretion of myoglobin was in the range of 1% to 14%. There was no correlation between the fractional excretions of myoglobin and sodium.(ABSTRACT TRUNCATED AT 250 WORDS)     

Uromucoid excretion in normal subjects,calcium stone formers and in patients with chronic renal failure

Summary Using an electroimmunoassay technique for uromucoid in urine, the excretion of this protein has been studied in normal subjects, calcium stone formers and in patients with chronic renal failure. In the normal subjects there was no significant difference in daily excretion between males and females, but a positive correlation with urine volume was demonstrated for this group. No significant difference in daily uromucoid excretion was found between normal and stone forming subjects. In the presence of chronic renal failure uromucoid excretion was found to be reduced and correlated with overall renal function as assessed by creatinine clearance.     

Treatment of IgA nephropathy with eicosapentanoic acid (EPA): a two-year prospective trial

Thirty-seven patients with biopsy proven mesangial IgA nephropathy were prospectively allocated to either two years of treatment with eicosapentanoic acid (EPA) 10 g per day or no treatment. At entry treated and untreated patients with renal dysfunction (Group A) or patients with normal serum creatinine less than 0.12 mmol/l (Group B) did not differ in serum creatinine, creatinine clearance, urinary protein excretion, or quantitative urinary red cell counts. Compliance with EPA therapy was excellent as assessed by plasma fatty acid profiles. At the end of the trial creatinine clearance in treated patients had gone from 80 +/- 16 to 57 +/- 17 ml/min (p less than 0.05) and in untreated patients from 76 +/- 18 to 55 +/- 14 (p less than 0.05). There were no beneficial effects in either Group A or Group B patients. The only two patients who had improvement in renal function were in the EPA treatment group. Although no side effects of treatment were noted, EPA does not alter the course of established mesangial IgA nephropathy.     

Successful relatively low-dose corticosteroid therapy for diclofenac-induced acute interstitial nephritis with severe renal failure

We report a case of nephrotic syndrome and acute renal failure that developed in a 73-year-old woman after six months of treatment with the non-steroidal anti-inflammatory drug (NSAID) diclofenac. Renal biopsy revealed interstitial nephritis and minimal change nephropathy. Despite discontinuation of treatment with diclofenac, she subsequently became anuric and required hemodialysis for progressive azotemia. Since her anuria was persistent, treatment with prednisone at a dose of 30 mg/day was started. With progressive increase in urine output after the initiation of corticosteroid treatment, a constant decrease in serum creatinine was observed along with improvement of creatinine clearance. In addition, the increased urinary excretion of beta2-microglobulin (beta2MG) and N-acetyl-beta-D-glucosaminidase (NAG) on admission was also improved during the treatment. Our findings suggest that corticosteroid treatment should be reserved for patients with the protracted deterioration of renal function even after discontinuation of offending trigger agents.     

Myoglobinuria in chronic renal failure

Serum and urine myoglobin levels were determined on 14 patients with stable chronic renal failure. Serum myoglobin ranged from 38 to 350 ng/mL. Eleven patients had myoglobinuria between 15 and 250 ng/mL; none developed myoglobinuric renal failure. Fractional excretion of myoglobin in the myoglobinuric patients increased as creatinine clearance decreased, although there was no correlation between filtered load and excretion rate of myoglobin. This confirms that renal failure leads to hypermyoglobinemia and usually to myoglobinuria. Surviving nephrons tend to reabsorb less of the filtered load of myoglobin as renal function diminishes.     

Creatinine excretion rates for renal clearance studies

A total of 637 timed-urine collections for creatinine excretion rates obtained from 295 children over 14 years have been analyzed. The children ranged in age from 2.8 to 21.7 years at the time of the clearance study. The data analyzed included only one study from a child during any 6-month period. The objective is to provide data defining the expected range of creatinine excretion for renal clearance studies. One hundred forty-two studies were conducted on children not pretreated with cimetidine and 495 on those pretreated with cimetidine. Analysis showed that pretreatment with cimetidine for creatinine clearance studies does not alter creatinine excretion rates (P=0.080; 95% CI –0.03 to 1.61). Creatinine excretion rates in urine collections obtained at home (roughly 24-h collections) were compared with 2-h supervised collections in the Children’s Kidney Center. The supervised urine collections resulted in creatinine excretion rates 1.38 mg/kg/24 h greater than home collections (P=0.001; 95% CI 0.76–2.00). Using regression equations for creatinine excretion rate with age, tables have been prepared showing the expected rate of creatinine excretion for renal clearance studies in children 3–21 years of age. Received: 7 December 2000 / Revised: 20 March 2001 / Accepted: 22 March 2001     

Creatinine clearance after cimetidine administration: is it useful in the monitoring of the function of transplanted kidney?

BACKGROUND: Determination of clearance of endogenous creatinine using its plasma and urinary concentration (standard clearance), Cockroft and Gault formula, or MDRD formula (estimated clearance) is commonly performed for assessment of glomerular filtration rate. Although the evaluation of renal function in this way is useful, it is biased with an error resulting from secretion of creatinine in tubules. This error can be reduced by determining the clearance after administration of cimetidine, which competitively blocks creatinine tubular transport. METHODS: The study was performed in the group of 87 patients after renal transplantation. In this group, estimated clearance and creatinine clearance after cimetidine administration (1000 mg in 75 patients and then 1600 mg in 12 patients with plasma creatinine above 3 mg/dL) were determined. RESULTS: Analysis of mean percentage differences between clearance values after cimetidine administration and estimated clearance shows increasing contribution of creatinine tubular secretion along with plasma creatinine increase in renal transplant recipients. A higher dose of cimetidine resulted in lower clearance values in renal transplant recipients with plasma creatinine above 3 mg/dL. CONCLUSIONS: Creatinine clearance after administration of 1000 mg cimetidine seems to be a useful measure of glomerular filtration rate in renal graft recipients with plasma creatinine concentration below 2.5 mg/L. Higher dose of cimetidine would be needed to effectively block tubular excretion at higher concentrations of creatinine. Establishing an efficient but safe dose of cimetidine for such patients needs further investigations. As we have noticed that creatinine clearance calculated according to MDRD formula was similar to the clearance after administration of cimetidine, we propose a strategy of one GFR measurement at baseline using 24h urine collection after cimetidine administration and follow-up with creatinine clearance calculated from MDRD formula during standard check-up visits.     

Renal and liver function tests in surgical septicemia

The prognostic value of conventional renal and liver function tests was evaluated during surgical septicemia. Changes in renal function variables were associated with the development of septic shock. Creatinine clearance was the most sensitive variable in predicting the outcome of septic shock, but serum creatinine and urine output were also of some value in this respect. Significantly lower creatinine clearance and urine output values, as well as significantly higher serum creatinine concentrations, were thus observed during septic shock with fatal outcome compared to non-fatal septic shock. In septicemia not complicated with shock, the variables of renal function remained in the normal range irrespective of final outcome. Among the liver function tests, serum albumin and total protein concentration revealed significant differences in behaviour between survivors and patients dying with persistent septicemia. However, due to the small differences and considerable overlap observed between the two groups of patients during the first 2 weeks of septicemia, these two variables are of limited practical value as prognostic predictors. The other liver function tests gave no information as regards the outcome of septicemia in the present study.     

Beta 2-microglobulin excretion and urinary cytology in analgesic nephropathy

Patients with analgesic nephropathy are at risk from uro-epithelial malignancy. Enhanced secretion of beta 2-microglobulin occurs from epithelial cancer cells. In order to find a screening test for malignancy in analgesic nephropathy, urinary levels of this protein were measured in patients with analgesic nephropathy with urine cytological abnormalities and were compared to a control group with glomerulonephritis. Mean fractional excretion of beta 2-microglobulin was higher (8.61 +/- 1.76 SEM) in patients with analgesic nephropathy than in those with glomerulonephritis (1.13 +/- 0.76) (P less than 0.025). Those patients with analgesic nephropathy who had malignant cells in the urine had higher mean fractional excretion (18.56 +/- 5.77) than those with only atypical cells (8.5 +/- 2.0) (P less than 0.05) who in turn had higher mean values than those with normal cytology (2.12 +/- 0.62) (P less than 0.0025). It is suggested that the increased beta 2-microglobulin excretion in analgesic nephropathy is due to secretion from abnormal urothelial cells as well as reduced tubular catabolism. Beta 2-microglobulin may be of use as a screening test for malignancy in analgesic nephropathy.