Serum beta-2-microglobulin estimation as an indicator of the glomerular filtration rate

In 56 patients in whom the glomerular filtration rate (GFR) was estimated by the 51Cr-EDTA technique, serum creatinine and beta 2-microglobulin levels were also measured. In the 15 patients with a GFR of greater than or equal to 80 ml/min, both serum creatinine and beta 2-microglobulin levels were within the reference range. However, the beta 2-microglobulin level was elevated (greater than 2,3 mg/l) in all 41 patients with a GFR of less than 80 ml/min, while the serum creatinine level was increased (greater than 133 mumol/l) in only 35 patients. In the remaining 6 patients, the creatinine values ranged from 75 to 125 mumol/l. It would therefore seem that serum beta 2-microglobulin assay is a more sensitive test than creatinine assay for detecting impaired renal function.     

Renal toxicity of interleukin-2 administration in patients with metastatic renal cell cancer: effect of pre-therapy nephrectomy

Systemic administration of interleukin-2 and lymphokine-activated killer cells is a new approach to the immunotherapy of advanced cancer. Metastatic renal cell cancer is one of the histological types of tumors particularly susceptible to this treatment approach although renal toxicity often is a dose-limiting side effect. We compared the renal functional changes observed during interleukin-2 therapy in 52 consecutive patients with advanced renal cancer to that of 83 consecutive patients with metastatic nonrenal cancer. Of the 52 patients with renal cancer 41 had recently undergone nephrectomy. The over-all peak serum creatinine values and the percentage increase of serum creatinine over baseline for all patients studied were significantly higher in cycle 2 of interleukin-2 therapy than in cycle 1: 3.8 +/- 0.2 versus 2.6 +/- 0.1 mg. per dl. and 241.7 +/- 16.5 versus 140.3 +/- 11.0 per cent, respectively. In patients with pre-therapy serum creatinine values of 0.4 to 0.9 mg. per dl. there were no significant differences in the mean peak serum creatinine nor in the percentage increase over baseline between renal and nonrenal cancer patients during cycle 1. In cycle 2 of therapy these values were higher in the renal cancer group (3.6 +/- 0.8 versus 2.4 +/- 0.2 mg. per dl. and 310.4 +/- 103.5 versus 214 +/- 30.4 per cent, respectively) but they did not reach statistical significance (P2 = 0.08 and 0.25, respectively). Renal and nonrenal cancer patients with pre-therapy serum creatinine levels of 1.0 to 1.4 mg. per dl. achieved similar high values in cycle 2 of interleukin-2 therapy (3.9 +/- 0.3 versus 3.9 +/- 0.4 mg. per dl. and 222.7 +/- 23.2 versus 248.7 +/- 33.5 per cent, respectively), although the initial increase (cycle 1) was higher in the renal cancer patients (3.3 +/- 0.3 versus 2.4 +/- 0.2 mg. per dl. and 172.3 +/- 25.9 versus 116.1 +/- 18.0 per cent, respectively). Baseline serum creatinine greater than or equal to 1.5 mg. per dl. was associated with an over-all higher peak serum creatinine and higher percentage increase of serum creatinine over baseline than that below 1.5 mg. per dl. baseline: 4.4 mg.per dl. and 171.1 +/- 36.3 per cent in cycle 1 and 6.5 +/- 0.7 mg. per dl. and 296.1 +/- 44.0 per cent in cycle 2, respectively (p less than 0.01). There was no association between peak serum creatinine and interval from nephrectomy to interleukin-2 therapy.(ABSTRACT TRUNCATED AT 400 WORDS)     

Serum beta-2-microglobulin in the differential diagnosis of monoclonal gammopathies

Serum beta-2-microglobulin (B2m) concentrations were determined in 43 southern African black patients with multiple myeloma (MM), in 130 black patients with monoclonal gammopathy of undetermined significance (MGUS) and in 70 control subjects. The results showed median values for serum B2m in patients with MM, MGUS and the control group to be 8.10 mg/l, 3.05 mg/l, and 2.35 mg/l, respectively; these values differed significantly from one another (P less than 0.01), even when patients with normal renal function (serum creatinine value less than 110 mumol/l) were considered separately. The median serum B2m concentration for IgG MM (22 cases) was 4.3 mg/l, for IgA MM (8 cases) 7.3 mg/l, and 24.2 mg/l for Bence Jones MM (12 cases). These differences were also significant (P = 0.001), but not in the restricted group of MM patients with normal renal function. In the 43 MM patients serum B2m concentrations had a significant positive correlation with serum creatinine (r = 0.706; P less than 0.005) and a significant negative correlation with haemoglobin values (r = -0.459; P = 0.006). In 28 MM patients with normal renal function, serum B2m values had a significant negative correlation with serum albumin (r = -0.602, P = 0.003). Sixty-five per cent of the 43 MM patients and 18.5% of the MGUS patients had raised serum B2m values (greater than 4.7 mg/l). An optimum cut-off value for serum B2m of 6.9 mg/l for differentiating MM from MGUS was determined using a classification rule. Despite lacking specificity, serum B2m measurement was useful in differentiating MM from MGUS, and was the best second choice variable in relation to serum albumin and haemoglobin in patients with normal renal function.     

Prostatic specific antigen and prostatic acid phosphatase in the monitoring and staging of patients with prostatic cancer

Serum prostatic specific antigen and prostatic acid phosphatase levels were measured retrospectively and evaluated in 357 men with benign prostatic hypertrophy and in 209 men with various stages of prostatic carcinoma. Although prostatic specific antigen values were elevated in 21 per cent of the patients with benign prostatic hypertrophy, the elevations usually were low and did not interfere with clinical interpretation. Prostatic specific antigen was elevated in 98 per cent of 86 men with active stage D2 disease; in 22 per cent of the men prostatic specific antigen was the only elevated marker. In contrast, prostatic acid phosphatase was the only elevated marker in 1 per cent of the patients with stage D2 disease and neither marker was elevated in 2 per cent. Among 74 patients in whom prostatic specific antigen and prostatic acid phosphatase determinations were made before radical prostatectomy, prostatic specific antigen was elevated substantially (greater than 10 ng. per ml.) in 59 per cent (26 of 44) with extracapsular disease and in only 7 per cent (2 of 30) without extracapsular disease. More importantly, of those 28 patients with substantially elevated prostatic specific antigen levels 26 (93 per cent) had extracapsular disease. Serial serum measurements showed that prostatic specific antigen either reflected or predicted clinical status in more than 97 per cent of the patients. We conclude that prostatic specific antigen is an excellent serum tumor marker for monitoring patients with prostatic carcinoma and that it surpasses prostatic acid phosphatase in this regard. Prostatic specific antigen also may be useful in staging prostatic carcinoma and it may change our attitudes significantly about the therapeutic responses to this cancer.     

Estimation of renal function in diabetic nephropathy. Comparison of five methods

Plasma as well as renal clearance of 51Cr-EDTA, serum creatinine, plasma beta-2-microglobulin and endogenous creatinine clearance were compared and evaluated in patients with diabetic nephropathy and in control patients with renal disease of other origin. The difference between the plasma clearance and the renal clearance of 51Cr-EDTA, that is the extrarenal clearance, was found to be higher in diabetics than in control patients (7.0 vs. 3.5 ml/min; p less than 0.001). The serum creatinine correlated well with the glomerular filtration rate (GFR), but in the individual case the GFR was not at all predictable from serum creatinine. The plasma beta-2-microglobulin did not correlate better than serum creatinine to 51Cr-EDTA clearance, and did not permit an earlier diagnosis of renal insufficiency. Endogenous creatinine clearance overestimated GFR by 0-180%. Due to residual urine, the coefficient of variation was higher in diabetic patients than in controls, but the effect of this imperfection was reduced by using multiple collection periods. In conclusion, the renal clearance of 51Cr-EDTA was found to be preferable to the other methods.     

Optimal nutritional support in surgery for bladder cancer: preservation of visceral protein by amino acid infusions

Seventeen patients undergoing 19 major urological operations for bladder cancer or rectal leiomyosarcoma (1 case) were studied after randomization for 3 hypocaloric dietary regimens, preoperative keto-adaptation by a carbohydrate-free, oral protein diet continued in the postoperative period by isotonic amino acid infusions, postoperative amino acid infusions only and 5 per cent dextrose infusions. In these normally nourished patients serum transferrin (plus 13 mg./dl. minus 30 mg./dl., minus 69 mg./dl., p less than 0.05 for the first and combined amino acid groups against the third group) and 2 other short half-life hepatic secretory proteins, prealbumin and retinol-binding protein, represented sensitive indexes of visceral protein and nutritional support, superior to nitrogen balance, anthropometric assays, delayed hypersensitivity skin test reactivity and serum albumin. Near isotonic amino acid infusions were more effective in preserving visceral protein status than 5 per cent dextrose but preoperative keto-adaptation was not shown to have any increased benefit over protein-sparing therapy given only after an operation.     

Immunoreactive prostatic acid phosphatase in prostatic cancer: diagnosis and followup of patients

We compared the measurements of serum acid phosphatase activity to those obtained by radioimmunoassay of prostatic acid phosphatase in the sera of 126 untreated prostatic cancer patients. The catalytic activity of prostatic acid phosphatase was elevated in 32 per cent of the patients and the serum concentration of prostatic acid phosphatase was elevated in 66 per cent. Of these 126 patients 16 had stage T0-2M0N0-x disease, and enzyme activity and prostatic acid phosphatase concentration were increased in 0 and 38 per cent, respectively, in this group. Of the 110 patients with proved extracapsular cancer the corresponding figures were 36 and 70 per cent, respectively. We followed 109 of these 126 patients for 1 or more years after orchiectomy. A salient finding was that return of elevated serum prostatic acid phosphatase concentration to the health-associated reference interval within 7 days following castration indicated no progression of the disease at 1 year irrespective of the initial staging. The same was not detected by the measurement of catalytic activity of serum acid phosphatase. Our findings substantiate data showing that the measurement of circulating prostatic acid phosphatase is achieved better by immunological techniques than by measurements of catalytic activity of the enzyme. A novel aspect is the usefulness of immunological prostatic acid phosphatase measurements in evaluation of the prognosis of patients with metastatic prostatic carcinoma following ablative endocrine treatment.     

Renal handling of beta-2-microglobulin, amylase and albumin in acute pancreatitis.

The renal handling of beta-2-microglobulin, amylase and albumin was studied in patients with acute pancreatitis. The data were compared with results obtained from patients with glomerular proteinuria and from patients with tubular proteinuria. Initially during acute pancreatitis, the clearance ratio (clearance protein/clearance creatinine) for beta-2-microglobulin was increased dramatically (77-fold) compared to normals. After four to seven days this ratio had fallen and was elevated only 7-fold. The corresponding figures for amylase were 3.3 and 1.8 times and for albumin 9 and 5 times respectively. In glomerular disease, the clearance ratios for beta-2-microglobulin, amylase and albumin were increased 6, 1.1, and 154 times and in tubular disease 448, 1.1, and 28 times, respectively. The electrophoretic pattern of the urinary proteins during pancreatitis was mostly normal. In a few cases, slight tubular proteinuria was noticed. Amylase activity in serum and urine from patients with pancreatitis was found to sediment, (S20,W = 4.6) in a sucrose gradient, identical to amylase from normal serum and urine. The marked increase in the excretion of beta-2-microglobulin probably reflects interference of the kidney function at the proximal tubular level. Determinations of this protein in urine may be of value in studies of kidney dysfunction that can accompany pancreatitis.     

Serum low-molecular-weight proteins in haemodialysis patients: effect of residual renal function

Serum low-molecular-weight proteins, beta-2-microglobulin and alpha-1-microglobulin, were measured in 34 patients undergoing maintenance haemodialysis. There was a strong positive correlation between beta 2M and alpha 1M and predialysis serum creatinine and strong negative correlations between these proteins and 24-h urine volume and creatinine clearance. Good correlation was also demonstrated with total duration of haemodialysis, which also correlated with residual renal function. It is suggested that the elevated beta 2M and alpha 1M in haemodialysis patients merely reflect the severity of renal failure and are not directly influenced by the duration of dialysis or type of dialysis membrane.     

Usefulness of serum cystatin-C as a marker of the renal function: a comparative evaluation with beta 2-microglobulin, alpha 1-microglobulin and creatinine

We evaluated the usefulness of cystatin-C as a marker of renal function. Serum cystatin-C level was measured using latex agglutination tests in 885 patients with various forms of renal disease and 200 healthy subjects. In addition to cystatin-C, serum beta 2-microglobulin, alpha 1-microglobulin and serum creatinine (Scr) were measured concomitantly in the same sample. The serum cystatin-C level inversely correlated more closely with creatinine clearance (Ccr) (r = -0.90) than serum beta 2-microglobulin (r = -0.85), alpha 1-microglobulin (r = -0.74) and Scr (r = -0.78). In patients with mildly impaired renal function (defined as Ccr 71-90 ml/min), a significant increase in cystatin-C level was observed in 24% of patients, whereas elevated beta 2-microglobulin and Scr were seen in 8% and elevated alpha 1-microglobulin was seen in 17%. In patients with normal renal function (defined as Ccr > or = 100 ml/min), increased cystatin-C level was observed in 7% of patients, whereas beta 2-microglobulin was seen in 2%, Scr in 2% and alpha 1-microglobulin in 11%. These data suggest that cystatin-C is a better marker of glomerular filtration than beta 2-microglobulin, alpha 1-microglobulin and Scr. Moreover cystatin-C measurement offers improved clinical sensitivity as a screening test for early renal damage.     

Immune complexes in urine and serum of patients with bladder cancer

The urine and/or serum of 43 patients with bladder cancer was tested for the presence of immune complexes. Immune complexes were present more frequently in the urine (38 per cent) than in the serum (23 per cent). Urinary immune complexes were elevated in 10 per cent of the patients with no tumor (group 1), 25 per cent with superficial neoplasms (group 2) and 89 per cent with infiltrating or metastatic disease (group 3), which compared favorably to elevated serum immune complexes in 20, 25 and 33 per cent of the patients, respectively. The incidence of urinary immune complexes was statistically significant when compared in patients with and without active tumors (p less than 0.03), and when group 3 patients were compared to those in group 1 or 2 (p less than 0.01 and p less than 0.03, respectively). Unlike serum immune complexes urinary immune complexes appeared to correlate with the presence and stage of bladder cancer.     

Intraperitoneal rupture of the bladder causing the biochemical features of renal failure

A group of 20 patients with intraperitoneal rupture of the bladder was compared with a group of 20 patients with haematuria due to renal injury. In patients admitted to hospital within 24 h of sustaining an intraperitoneal bladder rupture, the mean serum levels of creatinine and potassium were increased and the mean serum sodium level was decreased. However, the individual serum creatinine values were within normal limits in six of the 11 patients in this group. Patients presenting more than 24 h after intraperitoneal bladder rupture had an increased mean serum urea, creatinine and potassium level and a decreased mean serum sodium and CO2 content. The individual serum urea and creatinine values on admission to hospital were higher than normal in all nine patients in this group but the serum urea/creatinine ratio was not significantly elevated. A dramatic decrease in serum urea and creatinine levels was seen within 24 h after laparotomy and suturing of the bladder rupture. In patients with abdominal symptoms and signs, haematuria and the biochemical features of renal failure (elevated serum urea, creatinine and potassium, decreased serum sodium and CO2 content), the clinician should suspect an intraperitoneal rupture of the bladder.     

Positive random iliac bone biopsy in advanced prostatic cancer

Forty-one patients with biopsy proved prostatic cancer and with biopsy proved bone metastases were retrospectively evaluated. In 16 per cent of the patients, bone biopsy was positive in spite of negative skeletal survey. Positive skeletal survey and increased serum acid phosphatase levels were found in 78 per cent of the patients, although bone marrow acid phosphatase was elevated in all patients. The determination of bone marrow acid phosphatase was found to be the most sensitive parameter in detection of bone metastases in patients with advanced prostatic cancer.     

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.     

Treatment of recurrent chronic bacterial prostatitis by local injection of thiamphenicol into prostate

Twenty-nine patients were treated for recurrent chronic bacterial prostatitis by an injection of 2 Gm. thiamphenicol glycinate via the perineal route directly into the prostate. Escherichia coli was identified as the pathogen responsible for this infection in 83 per cent of the cases. Using this medication locally, cure was obtained in 66 per cent of the patients. Thiamphenicol levels in prostatic fluid varied between l and 4,000 μg./ml. and were unrelated to the time after intraprostatic administration. However, in most cases they were high enough to inhibit most strains of gram-negative bacilli responsible for prostatitis. Serum levels were correlated with the time after injection and decreased over twenty-four-hour observation from 25 to 0.3 μg./ml. The pH of the prostatic fluid measured in 24 patients varied from 7.1 to 8.7 with a mean value of 7.9 and was markedly higher than the pH value of 6.5 reported for men without inflammatory prostatic disease. The elevated pH of prostatic fluid could explain the failure of short-term trimethoprim/sulfamethoxazole (Co-trimoxazole) treatment in our patients. The cure rate of the localized thiamphenicol treatment was higher than was reported with short- and long-term trimethoprim/sulfamethoxazole therapy. We concluded that direct injection into the prostate offers a good alternative for treatment of more resistant chronic infections of the prostate.     

Immunological assessment of renal cancer patients as evaluated by the lymphocyte adherence inhibition test

The lymphocyte adherence inhibition test was used to evaluate tumor immunity toward 2 types of soluble renal cancer antigens extracted from 3 different renal cancer specimens. These extractions were accomplished with either 3 molar potassium chloride or 2.5 per cent butanol, and were tested in 23 patients with renal cancer, 8 with benign renal disease and 9 with bladder cancer. In 62 tests of lymphocyte adherence inhibition reactivities toward 3 molar potassium chloride in renal cancer patients the mean value of lymphocyte adherence inhibition reactivity (32.7 +/- 15.4 per cent) was significantly greater compared to that observed in 20 examinations in patients with benign renal disease (17.6 +/- 9.4 per cent, p less than 0.001) and 24 tests in bladder cancer patients (15.4 +/- 4.4 per cent, p less than 0.001). With a lymphocyte adherence inhibition index of greater than 20 per cent as a positive response, there were 50 true positive findings (81 per cent) in the renal cancer group, while the combined benign renal disease and bladder tumor groups had 34 true negative responses (77 per cent). With the butanol extract the mean lymphocyte adherence inhibition reactivity of the 62 tests done on renal cancer patients (38.9 +/- 10.8 per cent) was significantly greater than either control group (7.1 +/- 6.2 per cent, p less than 0.001 for benign renal disease and 5.9 +/- 2.6 per cent, p less than 0.001 for bladder tumor). Moreover, of 62 tests done on renal cancer patients 59 (95 per cent) had true positive responses, while 43 of the 44 tests (98 per cent) in the combined control group showed true negative findings. These results suggest that immune responses in renal cancer can be assessed with the lymphocyte adherence inhibition test, and they may be useful in the diagnosis and management of renal cancer patients.     

Treatment of chronic prostatitis lowers serum prostate specific antigen

PURPOSE: We evaluated men with documented chronic prostatitis and elevated serum prostate specific antigen (PSA) to determine whether treatment with antibiotics and anti-inflammatory drugs lowers serum PSA. MATERIALS AND METHODS: We retrospectively reviewed the records of 95 men who presented with serum PSA greater than 4 ng./ml. and were subsequently diagnosed with chronic prostatitis with greater than 10 white blood cells per high power field in expressed prostatic excretions. Patients meeting these criteria were treated with a 4-week course of antibiotics and a nonsteroidal anti-inflammatory agent. In all patients followup PSA was determined within 2 months of treatment. RESULTS: Mean PSA decreased 36.4% from 8.48 ng./ml. before to 5.39 after treatment (p <0.001). In 44 patients (46.3%) serum PSA decreased to below 4 ng./ml. (mean 2.48) and these patients no longer had an indication for biopsy. In the remaining 51 patients serum PSA remained elevated at greater than 4 ng./ml. and they underwent double sextant transrectal ultrasound guided biopsy. Pathological study showed prostate cancer in 13 cases (25.5%), chronic inflammation in 37 (72.5%) and only benign prostatic hypertrophy in 1 (1.05%). PSA in the 13 patients with prostate cancer decreased with treatment only 4.8% from 8.32 to 7.92 ng./ml. (p >0.05). Followup PSA at a mean of 11.4 months was determined in 19 of the 44 men who responded to treatment. Mean PSA increased only 4.5% from 2.35 to 2.46 ng./ml. (p >0.05) during this followup interval. CONCLUSIONS: In almost half of the patients diagnosed with elevated PSA and chronic prostatitis serum PSA normalized with treatment and there was no longer an indication for transrectal ultrasound guided biopsy. Our study suggests that chronic prostatitis is an important cause of elevated PSA and when it is identified, treatment can decrease the percent of negative biopsies.     

Increased serum amylase levels in prostatic diseases

Serum amylase levels were found to be increased in 95 per cent of patients with benign prostatic hypertrophy and in 70 per cent of patients with prostatic cancer. No known causes for high serum amylase levels were present in these patients. Investigation of a possible relationship between amylase activity and prostatic diseases suggested that benign prostatic hypertrophy and prostatic cancer should be considered in the differential diagnosis of disorders associated with increased serum amylase levels.     

Tubule recovery after obstructive nephropathy relief: the value of enzymuria and microproteinuria

The recovery of tubules after relief of obstructive nephropathy may be investigated through serial assessment of the urinary excretion of tubular enzymes alpha-glucosidase, gamma-glutamyl-transferase and N-acetyl glucosaminidase as well as of the microprotein beta-2-microglobulin. We studied 21 patients in whom obstructive nephropathy was relieved by operative or nonoperative methods. Anuria persisted from 2 to 14 days. In these patients urinary excretion of alpha-glucosidase, gamma-glutamyl-transferase, N-acetyl glucosaminidase and beta-2-microglobulin, as well as the serum creatinine were assessed weekly. Serum creatinine was the earliest index to return to normal (within 9 to 26 days). Enzymuria returned to normal within 35 to 45 days, whereas normal urinary excretion of beta-2-microglobulin occurred more than 100 days after relief of obstructive nephropathy. N-acetyl glucosaminidase and gamma-glutamyl-transferase proved to be more reliable than alpha-glucosidase in detecting recovery of the luminal membrane of the proximal tubule. The return to normal of urinary beta-2-microglobulin levels has been shown to occur later, since more specific and complex intracellular functions underlie this index. The pathophysiological aspects of recovery of obstructive nephropathy may be considered similar to those observed in ischemic acute renal failure, since in both instances hemodynamic changes are involved.     

Outpatient irrigation of the renal collecting system with 10 per cent hemiacidrin: cumulative experience of 365 days in 13 patients

Despite Food and Drug Administration restrictions on its use above the ureterovesical junction, many investigators have used carefully monitored renal pelvic lavage with 10 per cent hemiacidrin for struvite calculi without serious side effects in hospitalized patients. We evaluated renal irrigations with hemiacidrin in 13 carefully selected patients (15 kidneys). In this high risk population (6 patients were paretic) initial treatment was done in the hospital but the remainder of 18 periods of extended renal perfusion (mean period 20 days) were performed at home. The total number of outpatient days of perfusion in this group was 365. All patients experienced external leakage around the perfusion catheter. Fever of greater than 101F occurred in 14 of 18 perfusions (78 per cent). Rehospitalization was necessary during 3 perfusions (17 per cent) and serum magnesium was elevated 3 times (17 per cent). Stones were dissolved successfully in 14 of 18 perfusions (78 per cent) but they recurred in 3 patients. No patient had altered post-perfusion serum creatinine levels. Outpatient perfusion of the renal pelvis with 10 per cent hemiacidrin under carefully controlled conditions appears to be a safe and cost-effective treatment for struvite or phosphate renal calculi.