Urinary excretion of dipeptidyl aminopeptidase i.v. in patients with renal diseases

Enzymuria is a frequent finding in patients suffering from various kidney diseases. The present study was undertaken to evaluate the clinical value of the determination of tubule-brush-border-associated dipeptidyl aminopeptidase IV (DAP IV) in the urine of patients with acute and chronic tubulointerstitial nephritis (n = 12), chronic glomerulonephritis (n = 15), essential arterial hypertension (n = 30), after kidney transplantation (n = 20), and of healthy control persons (n = 68). DAP IV was measured in spontaneously voided mid-stream morning urine ("second morning urine"), and was expressed as enzyme activity in units/liter. In order to account for variations due to urine concentration without collecting 24-hour specimens, a urinary DAP IV/creatinine ratio (DCR) was calculated. Furthermore, patterns of proteinuria were assayed by SDS-polyacrylamide gel electrophoresis. Urinary DAP IV activity of healthy controls was 4.94 +/- 0.12 U/l (DCR: 0.46 +/- 0.30 U/mmol creatinine) with only small day to day variations. Urinary DAP IV activity in patients with tubulointerstitial nephritis was significantly higher (15.5 +/- 15.6 U/l, p less than 0.05 vs controls; DCR: 1.67 +/- 0.97 U/mmol creatinine, p less than 0.001 vs controls). In patients with chronic glomerulonephritis urinary DAP IV activity was 9.6 +/- 5.6 U/l, p less than 0.05 (DCR: 1.22 +/- 0.75 U/mmol creatinine, p less than 0.05 vs controls). Increased urinary DAP IV activity in patients with chronic glomerulonephritis was associated with a mixed glomerulo-tubular pattern of proteinuria (as determined by SDS-PAGE).(ABSTRACT TRUNCATED AT 250 WORDS)     

Urinary excretion of ten plasma proteins in patients with renal carcinoma.

Urinary and serum proteins were studied preoperatively in 48 patients with renal carcinoma, using an automated immunoprecipitin reaction. The 24 h excretion and the renal clearance of albumin, transferrin, haptoglobin, IgG, IgA, and IgM and the 24 h excretion of the immunoglobulin lambda and kappa free light chains and beta2-microglobulin were significantly increased compared with a control group. The excretion of lysozyme was also increased, but not significantly. Increased protein excretion was the most common urinary finding in patients with renal carcinoma. The protein excretion was predominantly of the glomerular type, implying a glomerular injury. The serum concentrations of albumin and transferrin were significantly decreased and the serum concentration of haptoglobin significantly increased in patients with stage III and IV tumours compared with patients with stage I and II tumours. Abnormal serum concentrations of albumin, transferrin, and haptoglobin were indicative for advanced renal carcinoma.     

Urinary N-acetyl-beta-D-glucosaminidase and gamma-glutamyl-transpeptidase activities for evaluation of renal disturbance in patients with multiple myeloma]

The activities of N-acetyl-beta-D-glucosaminidase (NAG), gamma-glutamyl-transpeptidase (gamma-GTP) and NAG isoenzyme were measured in the urine of 20 patients with multiple myeloma (IgG/IgA type/Bense Jones type; 15/1/4 cases) and 25 healthy controls to evaluate these activities as indicators of renal disturbance in multiple myeloma. NAG isoenzyme fractions in urine were measured by agarose electrophoresis-m-cresol sulfonphthaleinyl-NAG reaction. Mean urinary NAG activity in the patients with myeloma was significantly higher than that in the controls (20.1 +/- 3.3 vs 4.3 +/- 0.3U/g. cr; p < 0.001). Urinary NAG activity in these patients correlated positively with the dose (mg/g. cr) of urinary protein (r = 0.755; p < 0.01), most of which were considered to be light chain protein, but not with creatinine clearance. Each urinary NAG isoenzyme fraction (NAG-1, -2, -3) was higher in the patients than that in the controls, and especially NAG-2 fraction (A form) showed a highly positive correlation with the dose of urinary protein. Urinary gamma-GTP activity in the patients did not differ from that in the controls, but urinary NAG/gamma-GTP ratio was higher in the patients, and reversely correlated with creatinine clearance (r = -0.721; p < 0.01). It is suggested that the elevation of urinary NAG activity results from the damage of lysosome in proximal tubular cells by urinary light chain protein and its degradation products. Therefore, urinary NAG activity may be a good index for proximal tubular disturbance, and NAG/gamma-GTP ratio may be an index for the extensive damage of nephrons in addition to the damage of tubular cells in multiple myeloma.     

Urinary citrate excretion in patients with renal calculi

Urinary citrate excretion was measured with a specific enzymatic technique in normal subjects and in an unselected group of patients with recurrent calcium oxalate stones. Hypocitraturia (citrate levels less than those present in 95 per cent of the normal population) was detected in 7 of 46 patients with stones (15 per cent). Hypocitraturia was the only metabolic abnormality in 6 patients.     

Urinary excretion of N-acetyl-beta-D-glucosaminidase in patients with urological disease: with special reference to hydronephrosis

Activity of urinary N-acetyl-beta-D-glucosaminidase (NAG) has been studied in patients with urological diseases. In most patients with benign prostatic hyperplasia, prostate cancer and bladder cancer, activity of urinary NAG was elevated (92.9%), especially in cases of indwelling catheterization or poor visualization of IVU. Urinary NAGs were also elevated for all patients with renal stones, ureter stones, uretero-cutaneous stomy or a single kidney. In hydronephrosis or hydronephrosis with hydroureter patients, urinary NAG level was low pre-operatively, but increased post-operatively. Urinary beta 2-microglobulin (BMG) showed a similar tendency in patients with hydronephrosis or hydronephrosis with hydroureter. Electronmicroscopic observations of the kidney in such patients revealed many primary and secondary lysosomes.     

Urinary protein excretion and renal function in young people with diabetes mellitus.

To detect early renal involvement in young diabetic patients (IDDM), urinary protein excretion and renal function were examined in 110 patients aged 5.9-25.0 years. Clearances of inulin and PAH were determined as well as albumin (Alb), IgG, N-acetyl-beta-D-glucosaminidase (NAG) and creatinine (Cr) excretion rates (UV). The patients were grouped according to IDDM duration (2- less than 5, 5-10 and greater than 10 years) and albumin excretion rate (non-albuminuria less than 20, microalbuminuria 20-200, and albuminuria greater than 200 micrograms/min per 1.73 m2). Four patients had overt albuminuria, 17 microalbuminuria (equally distributed among the duration groups). Grouped according to albumin excretion rate, the mean GFR was increased in those without albuminuria but 'normalized' in patients with microalbuminuria/albuminuria. Grouped according to albumin excretion rate and the duration of the disease, the non-albuminuric patients with IDDM for greater than 10 years had a lower GFR than those with a shorter duration of IDDM. The patients with microalbuminuria/albuminuria and IDDM for less than 5 years had a reduced GFR. Patients with increased NAG excretion rate had lower Na excretion rate, lower fractional Na excretion and greater creatinine excretion than those with normal NAG excretion. Albumin excretion correlated with IgG excretion, but also with NAG excretion. Our results suggest that early albuminuria in IDDM is of both glomerular and tubular origin. The hyperfiltration declines with increasing albumin excretion but also with the duration of the disease.     

Urinary excretion of low molecular weight proteins in patients with pure monoclonal light chain proteinuria

BACKGROUND: Because urinary low molecular weight protein (LMWP) measurement shows changes in renal integrity at an early stage, beta2-microglobulin (B2m), retinol-binding protein (RBP) and alpha1-microglobulin (A1m) were evaluated in 24-hour urine collection of 65 patients with pure monoclonal light chain (MLC) proteinuria and in 47 patients with different kidney diseases (DKDs) for comparison.METHODS AND RESULTS: Albumin, kappa, lambda, A1m and B2m were measured by immunonephelometry. RBP was determined by ELISA. The mean values of LMWP quantitation were significant for origin of the disease (MLC and DKD) (p<0.05) and renal failure (RF) (p<0.001) (MANOVA). Tukey HSD test only showed significant differences for LMWP between MLC patients with RF and DKD patients without RF. The mean value of A1m was different between patients with and without RF in each group (p<0.05 for MLC, and p<0.01 for DKD). In the group without RF, the frequency of A1m excretion above 12 mg/L differed between MLC patients and DKD patients (p<0.01). CONCLUSION: A tubular dysfunction occurred in a great number of patients excreting pure MLC even in those with well-preserved renal function, as it did in patients with DKDs. In patients with MLC without RF, A1m might be measured for the early recognition of tubular involvement.     

Urinary protein excretion and renal function in children with IgA nephropathy

Renal haemodynamics and the pattern of urinary protein excretion were studied in 38 children (21 boys, 17 girls) with biopsy-proven IgA nephropathy (IgAN), 0.4–16.8 (median 5.3) years after onset of the disease. Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were evaluated by clearances of inulin and para-aminohippuric acid. Serum and urinary albumin, IgG and beta₂-microglobulin (2) were determined and the excretion rates, clearances, and fractional clearances were calculated. The patients were grouped according to the type and the amount of proteinuria. Mean GFR and ERPF were significantly decreased (107±3 and 580±17 ml/min per 1.73 m², respectively) versus controls (119±2 and 627±14 ml/min per 1.73 m², respectively). Grouped according to albumin excretion rates, non-albuminuric patients had normal GFR, while mean GFR was reduced in patients with micro-albuminuria (106±3 ml/min per 1.73 m²) and albuminuric patients (92±7 ml/min per 1.73 m²). IgG excretion increased with increasing albuminuria, but the selectivity index was lower in albuminuric patients than in patients with micro-albuminuria. Albuminuric patients had also higher blood pressure than those with micro-albuminuria. 2 excretion did not discriminate between patients with impaired renal function. The results suggest that childhood IgAN is not a benign kidney disease. After a median duration of 5 years of the disease a number of children had impaired renal function. Mean GFR was reduced most in the albuminuric patients but was also decreased in micro-albuminuric patients, indicating that micro-albuminuria may be a predictor of more severe disease.     

Urinary excretion of N-acetyl-beta-D-glucosaminidase in newly diagnosed essential hypertensive patients and its changes with effective antihypertensive therapy

International Urology and Nephrology -     

Urinary albumin excretion in patients with diabetes after renal transplantation

BACKGROUND: Many studies support microalbuminuria screening as the cornerstone of early detection of nephropathy in patients with diabetes mellitus (DM), but there are no studies that address its utility in the follow-up of renal transplant recipients with DM. MATERIALS AND METHODS: We retrospectively studied 104 subjects with DM who had undergone renal transplantation. Sixty three had a history of preexisting DM and 41 developed posttransplant diabetes (PTDM). We collected data on random urine albumin/creatinine (A/C) ratio, systolic blood pressure (SBP), serum creatinine concentration (Cr), and HBA1C. RESULTS: Mean subject age was 58 +/- 9.8 years; 63% received cadaveric grafts while 37% received living donor grafts. Mean follow-up was 7 years (range 1.6 to 15.6). Seventy percentage developed proteinuria over time; of these 62% developed microalbuminuria (A/C ratio 30 to 300 microg albumin/mg creatinine) and 38% developed macroalbuminuria (A/C ratio >300 microg/mg). Subjects with preexisting DM were as likely to develop an elevated A/C ratio as those with PTDM. Higher A/C ratios correlated with higher SBP (P < .01), with higher HBA1C (P < .036), and with higher Cr (P < .01). Lower A/C ratios correlated with more stable Cr over time (P < .01). CONCLUSIONS: Strict SBP and glycemic control are associated with a significantly lower A/C ratio in patients with DM after renal transplantation. Annual monitoring of A/C ratio in patients with DM after renal transplantation can identify candidates for stricter glycemic and blood pressure control, similar to current recommendations for all other patients with DM.     

Urinary excretion of ten plasma proteins in patients with extrarenal epithelial carcinoma.

Urinary and serum proteins were studied in 55 patients with extrarenal epithelial carcinoma, using an automated immunopreciptin reaction. The 24 h excretion and renal clearance of 6 high molecular weight proteins: albumin, transferrin, haptoglobin, IgG, IgA, and IgM were significantly increased compared with a control group, implying a glomerular injury. The 24 h excretion of 4 low molecular weight proteins: free lambda and kappa light chains of immunoglobulin, lysozyme, and beta2-microglobulin was significantly increased in patients with disseminated carcinoma compared with patients with localized carcinoma. The serum concentrations of albumin and transferrin were significantly decreased and the serum concentration of haptoglobin significantly increased in patients with disseminated carcinoma compared with patients with localized tumours.     

Urinary excretion of arylsulfatases A and B in patients with renal transplants

Arylsulfatase A and B activities have been determined in urine samples from four patients who received a Kidney allograft from living donors as a treatment for terminal uraemia. The values have been compared with those obtained in the urine of the respective donors. Two patients, with optimal renal functionality, the enzymatic activities were in the order of that observed in the urine of the donor in one case and lower than that of the donor in the other case. A patient showing kidney rejection episodes, reversed by the specific therapy, had the enzymatic activities higher than those shown by the donor. Another patient who suffered for two rejections, the last one irreversible, showed a constant higher value of the two enzymatic activities compared with those of the donor and a further increase during the rejection period. In the light of these preliminary results it seems that the determination of the arylsulfatase activities in the urine of transplanted subjects could contribute to establishing the functional activity of the transplanted kidney and also in establishing the tendency of the kidney to undergo rejection.     

Prognostic factors in a patients with renal cell carcinoma]

PURPOSE: The purpose of this study is to evaluate prognostic factors of renal cell carcinoma using univariate statistics. Materials and methods: Materials are 182 patients treated from 1976 to 1992. Kaplan-Meier method and generalized wilcoxon test were used for statistical analysis. RESULTS: Seventy cases were found incidentally without any symptoms. The overall 5- and 10-year survival rates by Kaplan-Meier method were 73.8% and 66.2%, respectively. In the univariate analysis, sex, chief complaints, tumor sizes, T-Stages, venous invasions and grades were statistically significant prognostic factors. The prognosis of males more than 60 years of age was significantly poor. The prognosis of patients with incidentalomas was far better than that of symptomatic patients. CONCLUSION: Sex and chief complaints were pointed out as significant prognostic factors for renal cell carcinoma.     

Urinary Tamm-Horsfall protein excretion in patients with primary vesicoureteral reflux

The excretion of urinary Tamm-Horsefall protein (THP) was determined by enzyme-linked immunosorbent assay and glomerular filtration rate (GFR) was calculated with technetium-99m diethylenetriamine pentacetic acid (99mTc-DTPA) renal scintigraphy in 26 consecutive patients with primary vesicoureteral reflux (VUR) before and after antireflux surgery. Wide variations of urinary THP excretion and GFR were seen in all grades of VUR. On the basis of the relationship between urinary THP excretion and GFR before the surgery, patients were divided into three groups. The first group (group A, n = 8) had normal urinary THP values and normal values of GFR. The second group (group B, n = 11) had high THP excretion and moderately decreased GFR, the third group (group C, n = 7) had normal urinary THP excretion and severely decreased GFR. In group A, urinary THP values remained normal and GFR improved in all patients after surgery. In group B, GFR improved when urinary THP dropped immediately, but GFR did not improve when urinary THP remained high after surgery. In group C, GFR did not improve and urinary THP continued to be low or tended to drop again after the surgery. The results suggested that serial measurements of urinary THP excretion and GFR by 99mTc-DTPA renal scintigraphy before and after antireflux surgery are useful for the evaluation of renal function in patients with primary VUR.     

Urinary nuclear matrix protein 22 for diagnosis of renal cell carcinoma

OBJECTIVE: To determine the incidence of positive urinary nuclear matrix protein 22 (NMP22) values, which are currently used to detect transitional cell carcinoma of the bladder, in renal cell carcinoma (RCC). MATERIAL AND METHODS: Urinary NMP22 values were determined preoperatively in 41 patients in whom a solid renal mass had been detected using CT and who were scheduled for radical nephrectomy; 38 of these patients were diagnosed with RCC. Two patients had xanthogranulomatous pyelonephritis and one had metastasis of a small cell adenocarcinoma to the kidney; these patients were excluded from the study. A total of 30 patients with kidney stones and simple renal cysts were used as controls. RESULTS: The urinary NMP22 values of the RCC patients were significantly higher than those of the controls. Of the 38 patients with RCC, 23 (60.5%) had positive urinary NMP22 values > or =10 U/ml. There were four measurements above this cut-off level in the control group. Urinary NMP22 values increased with an increase in pathologic tumor stage, but the correlation was not statistically significant. There was no correlation between grade and urinary NMP22 or between tumor burden and urinary NMP22. CONCLUSIONS: The urinary NMP22 test may help to diagnose RCC and may also result in an increase in the incidental discovery of RCC. As elevated urinary NMP22 levels have also been found to occur in RCC, patients with suspected bladder cancer and positive urinary NMP22 levels should be more broadly evaluated. Specific NMP assays for renal tumor cells may increase the utility of the test for RCC.     

Relationship of renal lesions with urinary protein excretion in patients with overt diabetic nephropathy]

We investigated the relationship of renal lesions with the degrees of proteinuria in 57 type 2 diabetic patients with overt proteinuria (urinary protein excretion rate (UP) > 0.5 g/day). Creatinine clearance (Ccr) ranged from 25.4 to 131.0 ml/min/1.73 m2. Kidney specimens were obtained and the diagnosis of diabetic nephropathy was made in all patients. The degree of each of the following histologic changes were evaluated: diffuse or nodular lesion, the type of nodular change, mesangiolysis, arteriolar hyalinosis and interstitial damage. We divided the patients into the following 4 groups according to Ccr and UP: group A with Ccr > 60 and UP > 3 g/day (n = 10), group B with Ccr > 60 and UP < 3 g/day (n = 10), group C with Ccr < 60 and UP > 3 g/day (n = 23) and group D with Ccr < 60 and UP < 3 g/day (n = 14), and compared the histologic parameters among the 4 groups. Diffuse index in group A was greater than those in group B (p = 0.05), while those in groups C and D were not different. Nodular index, percentage of patients with nodular lesion did not differ among the 4 groups, however the percentage of glomeruli with complicated nodules (nodular lesion with mesangiolysis and/or microaneurysm) in group C was greater than those in group D (p < 0.05). Hyalinosis index did not differ between group A and B, nor between group C and D, respectively. Interstitial index in group A and B did not differ, however that in group C was greater than in group D (p < 0.05). In addition, the rate of Ccr decrease between renal biopsy and after 12 months was significantly greater in group A and C than in group B and D, respectively (both p < 0.01). These results suggest that 1) mesangial expansion was associated with the degree of proteinuria in patients with slight impaired renal function, 2) tubulointerstitial involvement was associated with the degree of proteinuria in patients with advanced impaired renal function, and 3) these structural changes might be associated with decrease in renal function in diabetic nephropathy.