Urinary Excretion Of Beta 2-microglobulin Research Articles

Role of beta 2 microglobulin in chronic kidney disease

The aim: to study the relationship of beta-2-microglobulin (beta-2 MG) with clinical and laboratory manifestations of chronic kidney disease (CKD).Patients and Methods. The results of a comprehensive examination of 284 people (118 males and 166 females) aged 18 to 86 years with various types of socially significant diseases were studied. All patients underwent thorough collection of clinical and anamnestic data, laboratory monitoring with the determination of the level of systolic and diastolic blood pressure (BP), body mass index, red blood, beta-2-microglobulin (B2M), lipid profile and proteinuria. Kidney function was assessed according to the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) formula using serum creatinine. The main group included 113 patients (55 men and 58 women, mean age 50.9±15.8 years), diagnosed with chronic kidney disease (CKD). The control group consisted of 171 people (63 men and 108 women) with various forms of socially significant diseases, but without signs of CKD. Statistical analysis was carried out using the programs Statistica 10.0 (StatSoft Inc., USA) and Microsoft Office Excel 2010 (Microsoft Corp., USA).Results. In the subgroup of patients with CKD, signs of renal failure were observed in 46 people in 40.7 % of cases. As CKD progressed, the signs of impaired metabolism of B2M were more severe: its serum level was 8.646 (7.892; 12.231) mg/l at C4 and 18.444 (11.225; 23.717) mg/l at C5 stages of CKD, and urinary excretion was 2.502 (0.305; 6.313) mg/l at C4 and 2.614 (1.535; 25.812) mg/l at C5 stages of CKD. Regardless of renal dysfunction, the median serum B2M level was clinically significantly higher in females (p>0.05). Single-factor one-way correlation analysis showed statistically highly significant relationship was between serum B2M and creatinine levels both in the subgroup of patients with CKD (r = 0.905; p = 0.001) and in the total sample (r = 0.749; p = 0.001). There was a strong negative relationship between serum B2M levels and estimated glomerular filtration rate (GFR) (r = -0.717; p = 0.001). In individuals without CKD, an increase in serum creatinine was closely associated with an increase in urinary excretion of B2M (r=0.252; p=0.005). Simultaneously, in this category of patients, there was a close correlation between estimated GFR with serum B2M level (r= -0.433; p=0.002) and its urinary excretion (r= -0.247; p=0.005). A direct relationship between an increase in serum B2M and an increase in diastolic blood pressure (r=0.274; p=0.034) among CKD patients was established. In the total sample, a direct relationship between the value of systolic BP and serum B2M level (r= 0.223; p=0.01) was registered, as well as between diastolic BP (r= 0.268; p=0.01) and urinary excretion of B2M.Conclusion. As a result of the study, metabolism of B2M and its relationship with the clinical and laboratory manifestations of CKD were evaluated. The data obtained show high prognostic potential of changes in metabolism of B2M in the population of patients with various forms of socially significant diseases, as well as CKD, which allows to identify among them groups of patients with high and/or very high renal and cardiovascular risk, in order to take timely targeted therapy.

Urinary Beta-2Microglobulin: An Indicator of Renal Tubular Damage after Extracorporeal Shock Wave Lithotripsy.

This study aims to determine extracorporeal shock wave lithotripsy (ESWL)-induced renal tubular damageand the affecting factors by measuring urinary beta2microglobulin (β2M) excretion. This is a cross-sectional study conducted on 91 patients with renal stones who underwentESWL during 2012. Urinary beta2microglobulin was measured immediately before and after the procedure foreach patient and analyzed based on different variables to evaluate factors affecting ESWL-induced renal tubularinjury. Mean ± SD urinary beta2-microglobulin values, before and after ESWL were 0.08 ± 0.07 and 0.22 ± 0.71mg/dL respectively, the average difference between which was equal to 0.14 ± 0.07 mg/dL. These figures exhibiteda 166.66% rise in the urinary β2M concentration after ESWL which was statistically significant (P < .001). Multivariateanalysis showed that hypertension (P = .05) and the history of ESWL (P = .02) were predictive factors ofhigher post-ESWL urinary beta2-microglobulin excretion. Urinary excretion of beta2-microglobulin increased significantly immediately after ESWL. Thesechanges could indicate that ESWL is a contributing factor to renal tubular damage. It also seems that in patientswith hypertension and a previous history of ESWL the likelihood of this injury is higher than others.

Urinary protein patterns in patients with Balkan endemic nephropathy

Urinary excretion of beta2-microglobulin (beta2-MG), albumin, immunoglobulin G (IgG) and protein was examined in patients with Balkan endemic nephropathy (BEN), glomerulonephritis (GN) and healthy controls. The proteins were measured in morning urine samples from 74 patients with BEN, 50 healthy persons and 22 patients with GN. In BEN patients, median values for albumin, beta2-MG and protein were above upper normal limits, but median IgG was inside normal range. All patients with GN had microalbuminuria (MAU) and half of them had increased urinary beta2-MG, which was also found in eleven patients with increased urinary IgG. In BEN patients, there were significant negative correlations between eGFR and all measured urinary proteins, the composition of which changed during the course of BEN. In patients with eGFR > 60 ml/min/1.73 m(2) isolated beta2-MG was the most frequent finding (10/12 patients), but MAU was present in 4/12 patients. In BEN patients with eGFR between 30 and 59 ml/min/1.73 m(2), beta2-MG appeared as often as the combination of beta2-MG and albumin and isolated MAU. Out of 49 BEN patients with eGFR > 30 ml/min/1.73 m(2) 15 had increased urinary IgG either alone (1) or together with beta2-MG (3) or albumin (3) or beta2-MG and albumin (8). In BEN patients with GFR < 30 ml/min/1.73 m(2) only 1/25 had isolated beta2-MG but increased urinary IgG with increased beta2-MG, and albumin was the most frequent. Although low-molecular weight proteinuria was the most frequent urinary finding in BEN patients, MAU was frequently detected in advanced stages of BEN but also in some patients with eGFR > 60 ml/min/1.73 m(2). IgG was increasingly found as eGFR decreased.

Randomized Comparison of Renal Effects, Efficacy, and Safety With Once-Daily Abacavir/Lamivudine Versus Tenofovir/Emtricitabine, Administered With Efavirenz, in Antiretroviral-Naive, HIV-1–Infected Adults: 48-Week Results From the ASSERT Study

Abacavir/lamivudine and tenofovir/emtricitabine fixed-dose combinations are commonly used first-line antiretroviral therapies, yet few studies have comprehensively compared their safety profiles. Forty-eight-week data are presented from this multicenter, randomized, open-label study comparing the safety profiles of abacavir/lamivudine and tenofovir/emtricitabine, both administered with efavirenz, in HLA-B*5701-negative HIV-1-infected adults. Three hundred eighty-five subjects were enrolled in the study. The overall rate of withdrawal was high (28%). Changes in estimated glomerular filtration rate from baseline were similar between arms [difference 0.953 mL.min.1.73 m (95% confidence interval: -1.445 to 3.351), P = 0.435]. Urinary excretion of retinol-binding protein and beta-2 microglobulin increased significantly more in the tenofovir/emtricitabine arm (+50%; +24%) compared with the abacavir/lamivudine arm (no change; -47%) (P < 0.0001). A lower proportion achieved viral load <50 copies per milliliter in the abacavir/lamivudine arm (114 of 192, 59%) compared with the tenofovir/emtricitabine arm (137 of 193, 71%) [difference 11.6% (95% confidence interval: 2.2 to 21.1)]. The overall virological failure rate was low. The adverse event rate was similar between arms (except drug hypersensitivity, reported more in the abacavir/lamivudine arm). The study showed no difference in estimated glomerular filtration rate between the arms, however, increases in markers of tubular dysfunction were observed in the tenofovir/emtricitabine arm, the long-term consequence of which is unclear. A significant difference in efficacy favoring tenofovir/emtricitabine was observed.

An expanded syndrome of dRTA with hearing loss, hyperoxaluria and beta2-microglobulinuria.

We describe a 7-month-old male with atypical features of autosomal recessive distal renal tubular acidosis (dRTA) with sensorineural hearing loss. Uncharacteristically, he presented with mild acidosis, hypokalaemia and hypocalciuria as well as unilateral sensorineural hearing loss. Subsequent investigations led to the discovery of both hyperoxaluria and beta2-microglobulinuria, thereby expanding the differential diagnosis to include both primary hyperoxaluria and Dent disease. Two mutations in the ATPV1B1 gene, one of which was novel, confirmed the diagnosis of dRTA. We consider the overlapping features of and diagnostic dilemmas involved in making a diagnosis of dRTA, primary hyperoxaluria and Dent disease in patients with infantile nephrocalcinosis. We highlight the occurrence of hyperoxaluria and low-molecular-weight proteinuria in patients with dRTA and propose that the phenotype of autosomal recessive dRTA with sensorineural hearing loss be broadened to include both hyperoxaluria and increased urinary excretion of beta2-microglobulin.

Tubular marker excretion in children from families with Balkan nephropathy

Balkan nephropathy (BN) has not been described in children; however, some previous studies in children from families with BN have revealed abnormalities of the urinary tract. In this study, urinary excretion of beta2-microglobulin, N-acetyl-beta-D-glucosaminidase (NAG) and gamma-glutamyl transpeptidase (GGT) was studied three times a year: spring, autumn, and winter, during a 3-year period, in 703 healthy children, initial age 9-13, from endemic and nonendemic settlements around the South Morava River. Beta-2-microglobulin excretion in urine, in all three seasons, was highest in children from families with BN compared with the excretion in children from the city, nonendemic villages, and those from nonendemic families. Increased urinary GGT excretion in children from endemic villages in October was higher than in children from the city and control villages, being the same in both endemic and nonendemic families. However, in February, it was similar in children from the city, endemic, and control villages. In conclusion, children from families with BN excreted significantly more beta2-microglobulin in all three seasons (spring, autumn, winter) of the study, in multivariate analysis significant for family status, gender, and the season (p < 0.001). NAG emerged as a potentially useful marker for seasonal exposure to an environmental nephrotoxin.

Renal tubular dysfunction in human visceral leishmaniasis (Kala-azar)

There are few studies about the functional tubular disturbances in human Kala-azar. The aim of this study was to investigate alterations in tubular reabsorption of urinary proteins, sodium, potassium, chloride, glucose, uric acid, inorganic phosphate and amino acids in patients with the chronic form of kala-azar. This is a cross-sectional study of 55 patients with visceral leishmaniasis (Kala-azar). The laboratorial investigation was: creatinine clearance and daily urinary excretion of total proteins, albumin, IgG, beta2-microglobulin, sodium, potassium, chloride, calcium, inorganic phosphate, uric acid and glucose. Plasma and urinary protein electrophoresis were performed in agarose gel. Urinary light chains were determined by the nephelometric method and amino acids by chromatography. All data were compared to those of a control group. Hypoalbuminemia, hypergammaglobulinemia as well as increased plasma levels of both IgG and beta2-microglobulins were found in all patients with Kala-azar. The mean urinary protein excretion was 277 +/- 66 mg/day. Increased albumin excretion was observed in 44% of patients accounting for 17% of the total urinary protein excretion. Proteinuria consisted predominantly of low molecular weight protein fractions that migrated with alpha1, alpha2, beta and especially gamma globulins. Urinary beta2-microglobulin excretion was elevated in all patients. Immune electrophoresis showed increased urinary excretion rates of kappa (27%) and lambda (42%) light chains. The Bence-Jones test was positive in 20% of patients. Immunofixation was negative for monoclonal peak. The principal alterations were hyponatremia 94.6%, hypokalemia 26%, hypochloremia 27.2%, hypocalcemia 32%, hypomagnesemia 41.8%, hypouricemia 14.3%, Increased urinary excretion fraction were: sodium 15%, potassium 26%, chloride 33.3%, calcium 32%, inorganic phosphate 27.2%, magnesium 100% with hypermagnesiuria, uric acid 44%. Glucosuria was found in one third of patients. There was evidence of renal proximal tubular damage with alterations in the reabsorption of proteins and light chains with characteristics of a tubular proteinuria, Disturbances of tubular reabsorption of uric acid, calcium, phosphate, glucose and magnesium were also observed.

Oxalate nephropathy with a granulomatous lesion due to excessive intake of peanuts

A 65-year-old Japanese male developed renal dysfunction, showing proteinuria and marked urinary excretion of beta2-microglobulin. He had consumed approximately 100-200 g peanuts and 750-1,000 ml beer every day for two or three months. He had previously been treated for hypertension with an angiotensin-converting enzyme inhibitor, enalapril. He then visited his primary-care doctor with mild fever, and renal dysfunction with mild diabetes mellitus were diagnosed. He was referred to our hospital, and because no diabetic retinopathy was observed by ophthalmological tests, renal biopsy examination was performed to clarify renal dysfunction. Renal biopsy specimens showed intimal thickening in the small arteries and interstitial nephritis with a granulomatous lesion, accompanied by oxalate crystals under polarized light. Glomeruli were unremarkable without any immunoglobulin deposition, and nodular lesions. Because he daily consumed a large amount of peanuts, oxalate nephropathy due to excessive intake of peanuts was strongly suspected. This case revealed that unusual food habits, including nuts, can cause oxalate nephropathy, and that close examination by renal biopsy was useful for clarifying the etiology of the unknown renal damage.

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.

Beta 2-microglobulinuria in cytomegalovirus infections following kidney transplantation

In a prospective study the occurrence of cytomegalovirus (CMV) infection was diagnosed by demonstrating CMV-immediate early antigen (IEA) in the blood in 13 out of 68 (19%) patients who had undergone renal transplantation (27 women, 41 men, mean age 46.3 [21-64] years). Twenty-four hour urine samples were collected at the same time for quantitative determination of selected marker proteins by immunoluminometric assays (IgG and transferrin as glomerular markers, alpha 1-microglobulin and beta 2-microglobulin as tubular markers). In all 13 confirmed cases of CMV infection there was an isolated rise in urinary beta 2-microglobulin excretion amounting to more than three times the normal. In 11 of the 13 cases the beta 2-microglobulinuria was noted before the CMV-IEA test became positive. This suggests that quantitative assay of beta 2-microglobulin in the urine may be of value in the early diagnosis of CMV infection--a matter of some prognostic importance--and may hence offer additional support for therapeutic decisions.

Dent disease

Dent disease is X-linked recessive proximal tubulopathy, due to mutations in the CLCN5 gene. It is characterized by low molecular weight proteinuria, hypercalciuria, nephrocalcinosis and progressive renal failure. A seven-year-old boy was referred after endocrinological examination where abdominal ultrasound showed nephrocalcinosis. There were anamnestic data neither of oedema, macrohaematuria, nor polyuria or hypertension. There were also no data of chronic renal failure in the family. We determined: proteinuria (1.8 g/day), elevated urinary excretion of Beta 2 microglobulin, microscopic haematuria, hypercalciuria (8-10 mg/kg/day), nephrocalcinosis, decreased tubular reabsorption phosphate (65%). Values of growth hormone, parathormone on thyroid hormone were normal. Except hypercalciuria, which was registered in the patient's mother, all other analyses performed in family members were between reference values. Diagnosis was finalized by mutation analysis, which showed S244L substitution on CNCL5. Mutation carrier was mother with normal phenotype. Dent disease is rare X-linked nephrocalcinosis. Definitive diagnosis of this proximal tubulopathy which leads to progressive renal damage is not possible without evidence of gene mutation in renal chlorine channel.

Changes in the Urinary Excretion of .BETA.2-Microglobulin (.BETA.2MG) and N-acety-.BETA.-D-glucosaminidase (NAG) during Treatment for Lupus Nephritis

Tubulointerstitial involvement in the kidneys is frequently found but it is a less emphasized feature of lupus nephritis (LN). Recent studies have shown increases in the urinary excretion of beta2-microglobulin (beta 2MG) and N-acetyl-beta-D-glucosaminidase (NAG), which are considered to indicate the presence of tubulointerstitial damage, particularly in cases of LN. However, the changes in these urinary parameters during the clinical course of LN have not yet been fully clarified. In this report, we describe the changes in the urinary excretion of beta 2MG and NAG during immunosuppressive treatment combined with double filtration plasmapheresis in a case of LN.

Correlation Between the Resistive Index by Doppler Ultrasound and Kidney Function and Histology

Although duplex Doppler ultrasonography has been used widely, it still is unknown whether resistive index could be related directly to vascular or tubulointerstitial changes in the kidney. Thirty-three patients who underwent renal biopsy were included in the present study. Clinical data, including sex; age; time from abnormal urinalysis result to biopsy; serum creatinine level; creatinine clearance; urinary excretion of protein, N-acetyl-beta-glucosaminidase, and urinary beta2-microglobulin; and presence of hypertension, were recorded at biopsy. Histopathologic data, including glomerular sclerosis, interstitial fibrosis/tubular atrophy, interstitial infiltration, and arteriolosclerosis, were evaluated separately by means of a quantitative or semiquantitative method. We examined whether resistive index at biopsy was related to these clinical and histopathologic parameters and, moreover, to renal outcome in patients followed up for more than 2 years. Age, creatinine clearance, urinary beta2-microglobulin excretion, and all histopathologic parameters showed statistically significant correlations with resistive index. However, stepwise multiple regression analysis showed that only arteriolosclerosis was chosen as an independent risk factor for increased resistive index. During the follow-up period of 57.5 +/- 15.6 months in 29 patients, 8 patients (27.6%) had progression of renal impairment, defined as an increase in serum creatinine level greater than 50%. They had a significantly increased resistive index at biopsy compared with patients without progression. We show a direct relationship between resistive index and arteriolosclerosis in damaged kidneys. Resistive index at renal biopsy may be useful as one of the prognostic markers for renal outcome.

Evaluation of Renal Functions in Asphyxiated Newborns

Renal injury due to perinatal asphyxia has not been systematically evaluated. The available studies have used variable definitions, incomplete investigations and none had a control group. The aim of this study was to evaluate systematically the renal functions in severely asphyxiated newborns and to find if abnormal renal function tests can predict adverse outcome (death or neurologic abnormality at discharge). In a prospective case-control design, 25 inborn babies>or=34 weeks gestation having asphyxia (5 min Apgar<or=6 or needing resuscitation>or=5 min) were enrolled as 'cases'. Simultaneously 25 gestation and weight matched babies with no asphyxia were enrolled as 'controls'. Renal function tests, calculated renal indices using timed urine collections and excretion of beta2-microglobulin and N-acetyl-beta-D-glucosaminidase (NAG) were monitored in both the groups for first 4 days of life. Fourteen (56 per cent) asphyxiated babies had acute renal failure (ARF) as compared to 1 (4 per cent) control (p=0.002). Blood urea and serum creatinine values were significantly higher in asphyxiated babies on day 4 but not on day 2. Renal failure index and FeNa were higher in asphyxiated babies on both day 2 and day 4, but creatinine clearance was not different. Urinary excretion of both beta2-microglobulin and NAG was higher in the asphyxiated babies on day 2 as well as day 4. Five minute Apgar<or=6 had the best sensitivity to predict renal failure. A combination of high serum creatinine and high blood urea had 100 per cent sensitivity and negative predictive value to predict adverse outcome while serum creatinine>1.5 mg/dl alone had the best specificity and positive predictive value. The renal parameters were however poorer predictors of adverse outcome in comparison to clinical markers like 5 min Apgar<or=3 and HIE stage II/III. Both glomerular and tubular involvement was seen commonly in babies with birth asphyxia. Clinical markers of asphyxia were better predictors of adverse outcome than renal function tests.

Excretion of Urinary Cadmium, Copper, and Zinc in Cadmium-Exposed and Nonexposed Subjects, with Special Reference to Urinary Excretion of β&lt;SUB&gt;2&lt;/SUB&gt;-microglobulin and Metallothionein

The objectives of this study were to examine the association between urinary excretion of cadmium (U-Cd), copper (U-Cu), and zinc (U-Zn) and the severity of two different indicators of renal toxicity (urinary excretion of beta2-microglobulin [U-beta2-MG] and metallothionein [U-MT]) in Cd-exposed subjects compared to controls, and to assess the physiologic mechanisms by which the exposure to environmental Cd affects U-Cd, U-Cu, and U-Zn. The target population included 3508 Cd-exposed and 294 nonexposed participants who received a health survey conducted among the population of the Kakehashi River basin. Increases of U-Cd, U-beta2-MG, and U-MT in the Cd-exposed population were observed relative to excretion of these substances in controls. Regression analysis using a general linear model revealed that the correlations between U-Cd or U-Cu, and U-beta2-MG and between U-Cd, U-Cu or U-Zn, and U-MT were statistically significant in both sexes, but the correlation between U-Zn and U-beta2-MG excretion was significant only in men. These results suggest U-Cd and U-Cu is affected by dysfunction in renal tubular absorption (indicated by U-beta2-MG), whereas not only U-Cd and U-Cu but also U-Zn appear to be a function of renal cellular desquamation (indicated by U-MT).

Low concentrations of intravenous polygelines promote low‐molecular weight proteinuria

Previously we observed that atrial natriuretic peptide (ANP)-induced albuminuria was accompanied by an increase in urinary excretion of the low-molecular weight protein (LMW protein) beta2-microglobulin (beta2-m), suggesting that the albuminuria may at least partly be the result of blockade of tubular protein reabsorption. However, in our experiments ANP was dissolved in the polygeline Haemaccel (Hoechst, Behring-Werke, Marburg Germany) to prevent adhesion of ANP to the infusion system. Anecdotal reports have shown that high dosages of polygelines such as Haemaccel or Gelofusine (Braun NPBI Oss, the Netherlands) may influence tubular protein handling. In the present study we have evaluated the effect of a low and high doses of the polygeline Haemaccel on proteinuria. In addition, we have reassessed the effects of ANP. We measured urinary beta2-microglobulin (beta2-m) and albumin excretion in healthy volunteers after infusion of a high-dose pure Haemaccel (0.04 mL kg(-1) min(-1) for 60 min), a low-dose Haemaccel (0.01 mL kg(-1) min(-1) for 60 min followed by infusion of 0.02 mL kg(-1) min(-1) for 60 min) and a low-dose Gelofusine (dose comparable to the low-dose Haemaccel). In addition we performed similar studies using ANP dissolved in saline and Haemaccel. Infusion of Haemaccel caused a dose-dependent increase in urinary excretion of beta2-m. There were no differences between Haemaccel and Gelofusine. After infusion of ANP dissolved in Haemaccel urinary beta2-m excretion increased from 0.05 +/- 0.03 microg min(-1) to 27 +/- 10 microg min(-1) and urinary albumin excretion increased from 4.5 +/- 1.1 microg min(-1) to 9.7 +/- 6.3 microg min(-1) (P<0.05). During ANP + saline infusion, urinary beta2-m excretion did not change, whereas the urinary albumin excretion increased from 5.3 +/- 1.5 microg min(-1) to 7.9 +/- 2.4 microg min(-1) (P<0.05). Our study demonstrates that even low doses of the polygelines Haemaccel and Gelofusine profoundly attenuate the tubular reabsorption of the low-molecular weight protein beta2-m. Atrial natriuretic peptide does not affect tubular protein reabsorption. Therefore, the rise in albuminuria during ANP infusion most likely reflects alterations in glomerular permeability.

Mediators of inflammation correlate with microalbuminuria in patients with non-Hodgkin's lymphoma.

Recent studies have demonstrated a high frequency of minor glomerular leakage of albumin in cancer patients. Pathogenic mechanisms of increased urinary albumin excretion (UAE) in malignancies remain to be clarified. We have attempted to identify whether microalbuminuria in lymphoma patients is associated with inflammatory mediators and the acute-phase response. UAE, urinary excretion of beta2-microglobulin and IgG, and serum levels of interleukin 6 (IL-6), tumour necrosis factor alpha (TNF-alpha) and C-reactive protein (CRP) were determined in 113 patients with newly diagnosed non-Hodgkin's lymphoma. We demonstrated a high frequency of microalbuminuria (>or= 20 microg/min) and UAE correlated strongly with serum levels of CRP, IL-6 and TNF-alpha. UAE, CRP, IL-6 and TNF-alpha were significantly higher in patients with advanced disease stage, B symptoms and in high-risk patients according to the International Prognostic Index. Urinary excretion of beta2-microglobulin was unaffected in patients with increased UAE. However, UAE was significantly correlated with urinary excretion of IgG, suggesting an altered size selectivity of the glomerular filtration barrier. This is the first study that shows a direct correlation between microalbuminuria and proinflammatory cytokines in malignancies, indicating a pathogenic relationship between inflammation and glomerular leakage of albumin. Future efforts should focus on the pathophysiological cause-effect mechanisms and larger studies are needed to confirm the clinical significance of UAE.

Impact of renal cryoablation on urine composition

Objectives. To examine prospectively serial urine biochemical parameters in 14 patients (9 men, 5 women) undergoing laparoscopic cryoablation of a small, exophytic solid renal mass. Prior studies have shown that various types of renal injury may predispose to the formation of urinary calculi. The metabolic effects of cryoenergy on the surrounding normal renal parenchyma are unknown. Methods. Timed 24-hour urine collections were obtained preoperatively and postoperatively on days 1, 30, and 60 to evaluate the following parameters: light microscopic findings, volume, pH, creatinine, protein, beta 2-microglobulin, calcium, citrate, oxalate, phosphate, uric acid, sodium, and potassium. Results. Urinary beta 2-microglobulin excretion increased from a preoperative baseline value of 114.8 to 1931.2 μg/L on postoperative day 1, an increase of more than 15-fold ( P = 0.05), thus confirming major renal injury. These values sharply decreased at 30 days and returned to near-baseline levels at 60 days postoperatively ( P = 0.76). Nevertheless, all lithogenic parameters remained within the normal range throughout the follow-up period, with no significant change in any value. Conclusions. Our findings suggest that renal cryoablation does not adversely alter urine composition with respect to lithogenic parameters for up to 2 months after surgery. Elevated beta 2-microglobulin levels indicating significant renal injury immediately postoperatively spontaneously revert to baseline levels within 2 months.

Prevention of diabetes-induced albuminuria in transgenic rats overexpressing human aldose reductase.

Studies using pharmacologic inhibitors have implicated the enzyme aldose reductase in the pathogenesis of albuminuria and diabetic renal disease. However, a clear conclusion is not easily drawn from such studies since these pharmacologic inhibitors have nonspecific properties. To examine further the role of aldose reductase, we have overexpressed the human enzyme in a transgenic rat model. Transgene expression in the kidney was predominantly localized to the outer stripe of the outer medulla, compatible with the histotopography of the straight (S3) proximal tubule. The effect of enzyme overexpression on diabetes-induced renal function and structure was then investigated. Contrary to what may have been anticipated from the previous enzyme inhibition studies, diabetes-induced albuminuria was completely prevented by the overexpression of aldose reductase. No effect of overexpression of aldose reductase on renal structure nor on urinary excretion of beta2-microglobulin and N-acetyl-beta-D-glucosaminidase was observed in this transgenic rat model. In conclusion, our study strongly suggests that multiple roles for aldose reductase may give it a more complex place in diabetic nephropathy than is currently recognized.

Lack of nephrotoxicity of new oral platinum drug JM216 in lung cancer patients.

The purpose of this study was to assess renal function in patients treated with the oral platinum drug JM216 [bisacetato-ammine-dichloro-cyclohexylamine-platinum(IV)], since the effects of JM216 on renal function have only partly been investigated using serum parameters or 51Cr-EDTA clearance. We used a sensitive method that assessed glomerular filtration rate (GFR), effective renal plasma flow (ERPF), and indicators of tubular and glomerular damage. A group of 24 patients with either non-small-cell lung cancer (NSCLC) stage IIIb/IV or small-cell lung cancer (SCLC), limited disease (LD) or extensive disease (ED), treated with JM216 were studied. All patients had no prior chemotherapy, a performance score < 2, a life expectancy of more than 3 months and normal liver, renal and bone marrow functions before treatment. All patients received oral JM216 120 mg/m2 per day for 5 consecutive days, repeated every 21 days with a maximum of six cycles. In six SCLC patients the dose was escalated to 140 mg/m2 per day after the first cycle. Prior to treatment, after the first cycle and after the end of treatment renal function was assessed by 125I-sodium thalamate and 131-hippurate clearances to determine acute and cumulative changes in GFR and ERPF, respectively. Furthermore, tubular and glomerular damage were assessed by urinary excretion of beta2-microglobulin, lactic dehydrogenase (LDH), alkaline phosphatase (ALP), gamma-glutamyltransferase (GT) and albumin. In 20 evaluable patients no significant acute impairment of renal function was observed. Median (range) GFR, ERPF and filtration fraction (FF) before treatment were 101 ml/min (53-164 ml/min), 417 ml/min (227-719 ml/min), and 0.25 (0.19-0.33), respectively. After the first cycle values were 117 ml/min (71-189 ml/min), 418 ml/min (228-709 ml/ min) and 0.28 (0.21-0.33), respectively. Also, no indications of tubular or glomerular damage were found. In four patients renal function was evaluated at the end of treatment (one after three cycles, one after five cycles and two after six cycles). Median (range) GFR, ERPF and FF were 99 ml/min (74-139 ml/min), 401 ml/min (277-496 ml/min) and 0.26 (0.23-0.30), respectively, revealing no delayed nephrotoxicity. We conclude that oral JM216 shows no nephrotoxicity.