Excretion Of Beta 2-microglobulin Research Articles

Long-term outcome of kidney function after twin–twin transfusion syndrome treated by intrauterine laser coagulation

Twin-twin transfusion syndrome (TTTS) is caused by unbalanced shunting of blood between monochorionic twins. It is well known that chronic hypotension and hypovolemia may cause renal insufficiency in the donor twin. The long-term outcome of kidney function after TTTS has not previously been delineated in the literature, however. The aim of this study was to evaluate the long-term outcome of kidney function in children after intrauterine laser treatment for severe TTTS. Eighteen surviving twin pairs after intrauterine laser treatment for TTTS were involved in the study. Their gestational age at birth was 29-39 weeks, their median birth weight was 2050 g, and their median age at evaluation was 3 years 1 month, range 1 year 9 months to 4 years 5 months. Serum creatinine, cystatin C, and beta 2-microglobulin, sodium, potassium, and phosphate excretion, and urine albumin and alpha-1-microglobulin were measured. Creatinine clearance was calculated by use of the Schwartz formula. The laboratory findings for all 36 children were within normal limits. There were no significant differences between donors and recipients. Despite severe alteration of renal function before the laser treatment (anuria-polyuria) no long-term impairment of renal function could be detected in any of the 18 twin pairs.

Acute interstitial nephritis predisposed a six-year-old girl to minimal change nephrotic syndrome

A six-year-old girl was admitted to our hospital with acute renal failure. We made a clinical diagnosis of acute interstitial nephritis and oral corticosteroid therapy was started. Her renal failure soon recovered, and renal biopsy showed acute interstitial nephritis by light microscopy with glomerular foot process effacement by electron microscopy. Although her proteinuria was not heavy at the time of biopsy, her proteinuria subsequently increased to show nephrotic syndrome. We continued to give corticosteroids and her nephrotic syndrome went into remission 13 days after biopsy. Serological and bacteriological examination showed no evidence of known pathogen or drug hypersensitivity. The time changes in proteinuria were monitored by fractional total protein excretion (FETP) and fractional beta2 microglobulin excretion (FEbeta2MG) in order to evaluate the severity of proteinuria under different glomerular filtration rates and different proximal tubular functions. The results revealed that nephrotic syndrome had occurred during recovery from acute interstitial nephritis. This is the first case report to show the sequential occurrence of acute interstitial nephritis and nephrotic syndrome based on evidence from fractional protein excretion.

Secondary renal Fanconi syndrome caused by valproate therapy

Although renal Fanconi syndrome resulting from valproate (VPA) has occasionally been reported, the detailed clinical characteristics of this disease remain unclear. To clarify the clinical features of patients with VPA-induced Fanconi syndrome, we analyzed the clinical and laboratory data of seven affected patients. All patients were children, were severely disabled and required tube feeding. Five patients required treatment with multiple anticonvulsant agents. Hypophosphatemia and hypouricemia were found in all patients. Mild proteinuria, increased excretion of urinary beta2-microglobulin (beta2MG) and generalized hyperaminoaciduria were present in all patients. The renal biopsy of one patient exhibited tubulointerstitial nephritis without any structural abnormalities of the mitochondria in proximal renal tubular cells. All patients recovered from the Fanconi syndrome after the cessation of VPA therapy without any long-term renal sequellae. These results indicate that young age and being severely disabled with tube feeding and anticonvulsant polytherapy are contributory factors to the development of VPA-induced Fanconi syndrome. Serum phosphate and uric acid concentrations and urinary beta2MG levels in addition to serum electrolytes and urinalysis should be examined regularly in patients receiving VPA therapy, especially in those with the contributory factors outlined above. Patients with Fanconi syndrome caused by VPA have a favorable renal outcome.

Excretion of Urinary Cadmium, Copper, and Zinc in Cadmium-Exposed and Nonexposed Subjects, with Special Reference to Urinary Excretion of β<SUB>2</SUB>-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).

Renal dysfunction of cadmium-exposed workers residing in a cadmium-polluted environment

Human exposure to cadmium may occur in both occupational and general environments. We were interested in determining whether a combination of occupational and environmental exposure to cadmium results in different levels of severity of renal dysfunction relative to that arising from environmental or occupational exposure alone. We selected 44 residents, who once were employed in a smelter and lived in a cadmium-polluted area, as group A. Another 88 subjects, who never worked in the plant, but lived in the same area, were selected as group B. Group C consisted of 88 subjects who had no history of occupational exposure to cadmium and lived in a non-cadmium-polluted area. Statistical analysis demonstrated that there was no significant difference in age or gender among the three groups, nor were there significant differences in smoking habits. The prevalence of renal dysfunction as indicated by increased excretion of beta2-microglobulin (B2M), N-acetyl-beta-D-glucosaminidase (NAG) and albumin (ALB), was higher in group A than in group B. This finding suggests that exposure to cadmium both occupationally and environmentally results in a higher prevalence of renal dysfunction, relative to those who are exposed to cadmium only in the general environment. Therefore, this specific population, who once were occupationally exposed to cadmium and lived in polluted areas, should be identified. Furthermore, health examinations of this population should be conducted in time to prevent further health damage induced by cadmium exposure.

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.

A Study of Tubular Dysfunction in Indian Patients With Lupus Nephritis

Most reports mention isolated tubular dysfunction in active lupus nephritis and, hence, the present study was designed to investigate varied functional defects in Indian patients with stable lupus nephritis. Twenty patients with lupus nephritis were evaluated for evidence of renal tubular functional abnormalities. Disease activity was studied using the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). Renal histology was available for 12 patients, including six with WHO class IV disease and three each with class III and class V disease. Analysis of activity and chronicity indices as well as severity of tubulointerstitial involvement was also done on these biopsy specimens. Estimation of fractional excretion (FE) of beta-2 microglobulin (β 2 μg), 24-hour urinary excretion of alkaline phosphatase (ALP), leucine aminopeptidase (LAP) and gamma-glutamyltransferase (GGT), as well as the short ammonium chloride (NH 4 Cl) test, were performed in all patients. Ten healthy volunteers served as controls. The mean creatinine clearance (Ccr) was 58.9 ± 19.1 mL/min (range, 24.5-104.3 mL/min). Serum β 2 μg and FE-β 2 μg were elevated in all patients (mean, 5.5 ± 1.4 mg/L and 1.6 ± 0.9%, respectively). Urinary ALP excretion was elevated in 65% of patients, with a mean of 6.88 ± 5.08 μmol/L/min, and urinary GGT excretion was elevated in 50% of patients, with a mean of 59.43 ± 33.70 μmol/L/min. There was no significant correlation of serum β 2 μg, FE-β 2 μg, and urinary ALP levels with Ccr or severity of proteinuria. Urinary GGT levels were increased proportionately to the decrease in Ccr. Only 20% of patients were unable to acidify their urine (pH < 5.3); the minimum urinary pH was higher in the lupus nephritis patients compared to controls (5.17 ± 0.58 vs 4.65 ± 0.26; p < 0.05). The mean baseline and peak titratable acidity were not significantly lower in lupus nephritis patients. There was significant correlation of all renal functional abnormalities with the severity of SLEDAI and tubulo-interstitial involvement. Both proximal and distal tubular functional abnormalities were seen in patients with lupus nephritis and can co-exist. FE-β 2 μg is the most sensitive indicator of proximal tubal dysfunction. Assessment of urinary enzymes may give an early indication of tubular dysfunction. Disease activity and severity of tubulo-interstitial involvement influence these abnormalities. [ Hong Kong J Nephrol 2003;5(2):90-7]

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.

The Role Of Mannitol in Alleviating Renal Injury During Extracorporeal Shock Wave Lithotripsy

We determined the role of mannitol in preventing or alleviating renal injury during extracorporeal shock wave lithotripsy (ESWL, Dornier Medical Systems, Inc., Marietta, Georgia). Patients undergoing ESWL were randomized to receive mannitol or control. Change in the levels of urinary enzymes, beta 2-microglobulin and microalbumin were compared in the groups before and after the procedure. Mannitol treated patients had a statistically significant decrease in beta 2-microglobulin excretion after ESWL compared with the control group. Mannitol may serve a protective function by decreasing the amount of renal injury caused by ESWL for renal calculous disease.

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.

SHORT-TERM CHANGES IN RENAL FUNCTION AFTER EXTRACORPOREAL SHOCK WAVE LITHOTRIPSY IN CHILDREN

To our knowledge despite numerous studies the biological effect of extracorporeal shock wave lithotripsy (ESWL, Dornier Medical Systems, Inc., Marietta, Georgia) on the function of the immature kidney has not yet been evaluated. We determined the short-term effect of ESWL on renal function in children. In a 5-year period 65 children were treated for 77 kidney stones by ESWL and followed regularly at our department. In 16 children the short-term effect of shock wave energy was studied by measuring blood parameters (sodium, potassium, urea, creatinine and C-reactive protein), urinary electrolytes (sodium, potassium and creatinine), urinary enzyme activity (aspartate transaminase, alanine transferase, alkaline phosphatase and lactate dehydrogenase) and the excretion of beta 2-microglobulin. Samples were obtained immediately before and 2 hours after ESWL, and on days 1, 2, 8, 15, 30 and 90 after treatment. Morphological changes in the kidneys were not detected by ultrasound during followup. No significant changes were noted in overall renal function, serum parameters or urine electrolytes. A significant elevation in the excretion of aspartate transaminase, alkaline phosphatase, lactate dehydrogenase and beta 2-microglobulin was observed, indicating proximal tubular dysfunction and cell destruction. Enzyme levels returned to baseline within 15 days. Our results demonstrate that shock wave energy induces transient functional damage of tubular function in children. Minimizing the kV. and number of shocks may decrease the deleterious effect. When considering functional regeneration time, the minimal interval between 2 shock wave treatments should be at least 15 days. The long-term effect needs further investigation.

Enzymuria and beta2-mikroglobulinuria in the assessment of the influence of proteinuria on the progression of glomerulopathies.

The important role of the tubulo-interstitial system for the progression of glomerulonephritis (GN), is the cause of a continuous search for the proper markers of kidney tubules damage, which can be applied in clinical diagnosis. In the present work the activity of N-acetyl-beta-D-glucosamidase (NAG), its isoenzyme NAG-B, alanylaminopeptidase (AAP), gamma-glutamyltransferase (GGT), concentration of beta2-microglobulin (beta2M) and daily protein excretion in the urine of 37 patients with morphologically different glomerulopathies were measured. The serum creatinine was also controlled. The obtained results suggest that activity of NAG in the patients with GN has an intermediate connection with proteinuria and could be a cause of the inflammatory process of the kidney, but the activity of AAP is directly dependent on urine protein concentration. Systemic analysis of both partial and multiple correlation coefficients of the examined indicators creates new, additional possibilities in the estimation of activity and progress of GN.

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.

Isolated hypercalciuria with mutation in CLCN5: Relevance to idiopathic hypercalciuria

Isolated hypercalciuria with mutation in CLCN5: Relevance to idiopathic hypercalciuria. Idiopathic hypercalciuria (IH) is the most common risk factor for kidney stones and often has a genetic component. Dent's disease (X-linked nephrolithiasis) is associated with mutations in the CLCN5 chloride channel gene, and low molecular weight (LMW) proteinuria was universally observed in affected males. We sought to identify mutations in CLCN5 or abnormalities in LMW protein excretion in a large group of patients with IH and in a rat model of genetic hypercalciuria. One hundred and seven patients with IH (82 adults and 25 children) and one asymptomatic hypercalciuric man with a known inactivating mutation in CLCN5 were studied. Secondary causes of hypercalciuria were excluded in all. The excretion of retinol-binding protein and beta2-microglobulin was measured by immunoassay in 101 patients with IH. Mutation analysis of the CLCN5 gene was performed in 32 patients with IH and in the genetic hypercalciuric stone-forming (GHS) rat strain. LMW protein excretion was normal in 92 patients with IH, and only slight abnormalities were found in the other nine, none of whom had a mutation in CLCN5. One 27-year-old man who had a CLCN5 mutation was found to have isolated hypercalciuria without LMW proteinuria, renal failure, or other evidence of renal disease. Mutation analysis was normal in 32 patients with IH. The CLCN5 sequence was normal in the GHS rat. Inactivation of CLCN5 can be found in the setting of hypercalciuria without other features of X-linked nephrolithiasis. However, mutations in CLCN5 do not represent a common cause of IH.

PROTEINURIA AND RENAL FUNCTION DURING AND AFTER ACUTE URINARY RETENTION

Purpose Benign prostatic hyperplasia is the most common neoplasm as well as the main cause of bladder outlet obstruction in men. It may progress to involve a risk of urinary retention. We investigated the effects of acute urinary retention on renal function. Materials and Methods We evaluated renal function using biochemical markers in 25 men with a mean age of 69 years in whom an episode of acute urinary retention a mean of 31 hours in duration was due to bladder outlet obstruction. Patients were followed for 6 months after acute retention was relieved. Patients were not known to have had any renal disease previously. Results During acute urinary retention at presentation, and after 1 and 6 months we noted albuminuria in 100, 92 and 54% of patients, elevated alpha 1-microglobulin excretion in 54, 39 and 58%, and elevated beta 2-microglobulin excretion in 17, 19 and 9%. Serum creatinine or creatinine clearance did not predict proteinuria. All parameters became normal at 6 months in only 2 cases. Conclusions Acute urinary retention affects glomerular and tubular renal function. After acute urinary retention was relieved increased glomerular permeability and tubular damage persisted in the majority of patients. This condition may have been partially due to previous long-term bladder outlet obstruction. Our findings stress the importance of the rapid recognition and treatment of acute urinary retention.

DOES ALLOPURINOL AND/OR MANNITOL PROTECT THE RENAL TUBULE DURING CARDIOPULMONARY BYPASS?

Introduction. By inhibiting a step in the formation of oxygen free radicals, allopurinol attenuates or prevents the harmful effects of ischemia [1]. One of the protective effects of mannitol on the renal function is probably due to free radical scavenging [2]. An increase in urinary Beta 2 microglobulin (B2M) excretion rate is sensitive marker for renal tubular dysfunction [3]. We collected B2M data to evaluate the renal protective effects of mannitol and allopurinol during elective coronary artery bypass surgery with bypass pump (CPB). Methods. This is a prospective, randomized, double blind, placebo controlled design. After IRB approval and informed consent, 36 patients with a serum creatinine < 1.5 mg/dl undergoing elective coronary artery bypass surgery received one of the following: 1) placebo, 2) mannitol 0.5 g/kg in the CPB pump prime, 3) allopurinol 300 mg PO one hour before surgery, or 4) mannitol and allopurinol in the above dosage. The anesthetic management and assessment of the hemodynamic data were standardized. B2M and creatinine levels were measured from serum and from urine collected over 20 minutes following induction of anesthesia, 1, 6, and 24 hours post CPB. Data were analyzed with repeated measures analysis of variance, and post-hoc comparisons. A p < 0.05 was considered statistically significant. Results. All 4 groups were similar in demographics (age, weight, height), intraoperative characteristics (level of surgical trauma, duration of CPB and duration of aortic cross clamp) and B2M serum concentration (p > 0.20) during the period of the study. In all 4 groups B2M excretion rate increased at one hour post CPB and recovered to baseline within 24 hours post CPB (p < 0.000). The mannitol group tended to attenuate the renal tubular damage as reflected in the lower B2M excretion rate (p = 0.14), (Graph). The combination of mannitol/allopurinol and allopurinol/placebo did not differ significantly from each other or from the mannitol/placebo group in protecting the kidney (p > 0.54). (Figure 1)Figure 1Conclusion. Mannitol tends to attenuate the transient tubular dysfunction occurring at 1 hour post CPB. These preliminary data suggest that the controversial use of the free oxygen radical inhibitor allopurinol during cardiac surgery did not appear to add significantly to the kidney protection.

Atrial natriuretic peptide increases albuminuria in type I diabetic patients: evidence for blockade of tubular protein reabsorption.

It has been suggested that atrial natriuretic peptide (ANP) contributes to the glomerular hyperfiltration of diabetes mellitus. Infusion of ANP increases the urinary excretion of albumin in patients with type I diabetes mellitus (IDDM). Although the increased albuminuria is attributed to a rise in glomerular pressure, alterations in tubular protein handling might be involved. We have studied the effects of ANP in nine microalbuminuric IDDM patients. After obtaining baseline parameters, ANP was infused over a 1-h period (bolus 0.05 microgram kg-1, infusion rate 0.01 microgram kg-1 min-1). Renal haemodynamics, sodium and water clearance and tubular protein handling were studied. The glomerular filtration rate (GFR) increased from 116.4 +/- 8.9 to 128.3 +/- 8.8 mL min-1 1.73 m-2, whereas the effective renal plasma flow (ERPF) decreased from 534.3 +/- 44.3 to 484.9 +/- 33.3 mL min-1 1.73 m-2 (P < 0.05). As a result, the filtration fraction was significantly higher during infusion of ANP. ANP attenuated proximal tubular sodium reabsorption. Urinary albumin excretion rose from 87.57 +/- 21.03 to 291.40 +/- 67.86 micrograms min-1 (P < 0.01). Changes in the urinary excretion of beta 2-microglobulin and free kappa light chains were more marked, the excretion of beta 2-microglobulin increasing from 0.28 +/- 0.21 to 51.87 +/- 10.51 micrograms min-1 (P < 0.01), and of free kappa-light chains from 4.73 +/- 1.74 to 46.14 +/- 6.19 micrograms min-1 (P < 0.01). The observed rise in albuminuria during infusion of ANP does not simply reflect a change in glomerular pressure, but might at least partly result from an attenuation of tubular protein reabsorption.

Urinary excretion of ceruloplasmin is elevated in the subjects with "borderline glucose tolerance test".

To examine whether or not there are any renal alterations in subjects with borderline glucose tolerance and in patients with non-insulin dependent diabetes mellitus (NIDDM) classified by the criteria of Japan Diabetic Association, urinary excretions of plasma proteins including albumin, ceruloplasmin (Cerulo) and IgG were measured in timed overnight urine samples. Eighty middle-aged, non-obese, normotensive, untreated men with urinary albumin excretion rates below 20 microg/minutes, beta2-microglobulin excretion rates below 140 microg/minutes and creatinine clearance values exceeding 80 ml x min(-1) x (1.73 m2)(-1) were included in this study. Three groups were defined according to the results of 75 g oral glucose tolerance test (OGTT) as follows: D group, 10 subjects with NIDDM; B group, 40 subjects with "borderline glucose tolerance test" and N group, 30 subjects with normal glucose tolerance. The fractional clearance (theta) of Cerulo, but not albumin and IgG, was elevated in 37. 5% of the B group compared with the upper limit of that of the N group. Furthermore, theta-Cerulo and theta-IgG increased in the D group compared with those of the N and the B groups. Recently, we found that theta-Cerulo and theta-IgG increased in healthy volunteers when GFR was elevated by acute protein loading and that increase in theta-Cerulo is remarkable than increase in theta-IgG. The present result, taken together with our recent finding mentioned above, suggests that increases in theta-Cerulo and theta-IgG may not be due to an impairment of charge selectivity in the glomerular basement membrane, but due to an increase of intraglomerular hydraulic pressure.

The importance of tubulointerstitial injury in the early phase of primary glomerular disease.

As tubulointerstitial damage is regarded secondary to glomerular injury in primary glomerulopathies, we assessed lesions to renal tubulointerstitium in recently diagnosed primary glomerular diseases and evaluated their impact on progression of the disease during the first 2 years after diagnosis. A nonrandomized prospective study assessing tubulointerstitial morphometry at diagnosis, markers of tubular function within the next 6 months and progression of the disease (creatinine clearance) during 24 months' follow-up. Single tertiary referral centre. Forty-six patients with primary glomerular disease, the diagnostic oligobiopsy performed within 2 months of the onset of clinical symptoms. All patients were subjected to antiinflammatory/immunosuppressive treatment. Alterations in results of tubulointerstitial morphometry and tubular function tests, correlations between these variables and parameters of nephrosis/renal function, selection of the most accurate predictor of disease progression within 24 months after diagnostic biopsy. Function of proximal tubules, markedly deteriorated at the time of diagnosis, significantly improved 6 months later (urinary beta2-microglobulin: P < 0.0025), along with reduction in proteinuria (P < 0.00125). No appreciable alterations in function of distal tubules were noted. Morphometric indices revealing interstitial expansion and tubular atrophy significantly correlated with creatinine clearance at 6 months (P = 0.032) and were the best predictors of deteriorating renal function at 24 months. Excretion of beta2-microglobulin at the time of diagnosis was the best marker for impairment of glomerular filtration 6 months later. Significant damage to cortical tubulointerstitium occurs concurrently with glomerular injury in primary glomerulopathies and may predict the clinical course of the disease already in its initial phase.