Renal tubule function in beta-thalassemia after hematopoietic stem cell transplantation

Advances in hematopoietic stem cell transplantation (HSCT) for beta-thalassemia major make the long-term outcome of these patients very important. Few data on long-term renal function of thalassemia patients are available. We evaluated the renal function in children after successful allogeneic HSCT for beta-thalassemia. Twenty-nine patients were included; the mean age at HSCT was 4.9 years. Mean follow-up time was 7.6 years. After HSCT, two patients developed acute renal failure and two had graft versus host disease. At last follow up, height standard deviation score (SDS) remained the same, but weight SDS had improved. Mean hemoglobin was 12.5 g/dl, and serum ferritin level was 545 ng/ml. All children had normal estimated glomerular filtration rate (GFR). One patient had hypertension and proteinuria, 10 years after HSCT. When comparing 39 children of the same age with beta-thalassemia of similar disease severity but who had not experienced HSCT, we found that the parameters of renal tubule function were better in patients that had undergone HSCT, as demonstrated by urine protein level (0.36 mg/mg creatinine vs 3.03 mg/mg creatinine, P < 0.001), osmolality (712 mosmol/kg vs 573 mosmol/kg, P = 0.006), N-acetyl-beta-D: -glucosaminidase (17.7 U/g creatinine vs 42.9 U/g creatinine, P = 0.045), and beta 2 microglobulin (0.09 microg/mg creatinine vs 0.13 microg/mg creatinine, P = 0.029). This study showed a low incidence of long-term renal impairment after HSCT and indicated that renal tubule function may be better in beta-thalassemia patients after HSCT.     

The influence of urinary flow rate in children on excretion of markers used for assessment of renal damage: albumin, gamma-glutamyl transpeptidase, N-acetyl-beta-D -glucosaminidase, and alpha1-microglobulin

The aim of the present study was to examine the influence of urinary flow rate on markers of renal function in children. A sub-study of the New England Children’s Amalgam Trial collected 82 pairs of urine samples from children aged 10–16 years: a timed overnight collection and a spot daytime sample collected the following day. These samples were analyzed for albumin, γ-glutamyl transpeptidase (γ-GT), N-acetyl-β-D-glucosaminidase (NAG), alpha1-microglobulin (A1M), and creatinine concentration. Regression analysis was used to model the effect of urinary flow rate in the timed overnight samples. A paired t-test compared concentrations and creatinine-corrected renal markers between overnight and daytime samples. Albumin, γ-GT, NAG, and A1M excretion rates increased significantly with urinary flow rate. Their corresponding creatinine-corrected markers did not vary significantly with urinary flow rate, but the creatinine-corrected excretions of albumin, γ-GT, and NAG were significantly higher in daytime samples than in overnight samples, with the same (non-significant) trend for A1M. The influence of urinary flow rate on creatinine-corrected markers of renal function was markedly less than its influence on excretion rates. Therefore, the use of creatinine-corrected markers seems to be a good choice in practice, with the caveat that daytime and overnight samples are not comparable. This study was supported by a cooperative agreement (U01 DE11886) between the New England Research Institutes and the National Institute of Dental and Craniofacial Research, National Institutes of Health.     

Functional parameters and99mtechnetium-dimercaptosuccinic acid scan in acute pyelonephritis

The diagnostic value of^99mtechnetium-dimercaptosuccinic acid (DMSA) scintigraphy, ultrasonography and renal functional parameters [urineN-acetyl--d-glucosaminidase (NAG)/creatinine and urine albumin/creatinine quotients] in acute pyelonephritis (APN) were studied in 39 children (28 girls, 11 boys, median age 9 months, range 2 weeks to 9.4 years, 28 patients <1 year, 11 patients >1 year) with first-time urinary tract infection. Ultrasonography of the urinary tract was performed on admission and together with DMSA scintigraphy (<10 days from admission). Urine NAG/creatinine and urine albumin/creatinine quotients were measured daily and after 6–8 weeks. Ultrasonography revealed abnormalities in 12 of 39 (31%) patients [11/32 patients (34%) with positive DMSA scintigraphy], while DMSA uptake defects were present in 32 of 39 (82%) patients [21/28<1 year (75%), 11/11 >1 year (100%),P=0.08]. Urine NAG/creatinine and urine albumin/creatinine quotients were significantly higher in children <1 year with APN, as well as in non-renal fever controls, than in older children. However, in both age groups the urine NAG/creatinine and urine albumin/creatinine quotients were significantly higher in APN than in non-renal fever. The urine NAG and albumin excretion decreased rapidly after the initiation of antimicrobial therapy and had normalized at 6–8 weeks. The size and grade of the DMSA uptake defect (DMSA score) did not correlate with duration of disease at admission, maximum C-reactive protein or maximum fever. The urine NAG/creatinine quotient in the children <1 year showed, however, a significant correlation with the DMSA score (r=0.58,P<0.05), while no correlation was found in the older children. We conclude that DMSA scintigraphy is a sensitive method to confirm the clinical diagnosis of APN, although a substantial number of infants appear to have normal scans. Early determination of the urine NAG/creatinine and albumin/creatinine quotients may further improve the diagnostics in the infant.     

Serial renal biopsies in three girls with tubulointerstitial nephritis and uveitis syndrome

Tubulointerstitial nephritis and uveitis (TINU) syndrome is considered to have a good prognosis even without any immunosuppressive therapy, although there is no histological evidence to support this. The objective of this study was to evaluate, retrospectively, serial renal biopsy findings in three girls with TINU syndrome who were treated with prednisolone. At presentation, all patients had significantly elevated urinary β₂-microglobulin levels (7583–19,313 μg/l) and high serum creatinine levels (0.93–1.3 mg/dl). The elevated β₂-MG and creatinine levels persisted for 1 month, and renal biopsies were performed to establish a definitive diagnosis. The initial biopsy specimens of all patients revealed marked interstitial enlargement consisting of infiltration of lymphocytes; there was also notable tubulitis and infiltration of eosinophils. All patients received prednisolone therapy following the diagnosis. A second renal biopsy was performed 9 months after the first biopsy for two of three patients, and 2 years later for the third patient. The biopsy specimens taken at 9 months still showed histological changes of acute inflammation; in contrast, that taken at 2 years showed a lower degree of acute inflammation, but scar formation was observed in some regions. Based on these results, we conclude that selected TINU syndrome patients require some immunosuppressive therapy.     

Renal function in children with β-thalassemia major and thalassemia intermedia

In beta-thalassemia, profound anemia and severe hemosiderosis cause functional and physiological abnormalities in various organ systems. In recent years, there have been few published studies demonstrating proteinuria, aminoaciduria, low urine osmolality, and excess secretion of the tubular damage markers, such as urinary N-acetyl-D-glucosaminidase (U(NAG)) and beta2 microglobulin, in patients with thalassemia. The object of this study was to analyze renal tubular and glomerular function in pediatric patients with beta-thalassemia and to correlate the renal findings to iron overload. Thirty-seven patients with beta-thalassemia major and 11 with thalassemia intermedia were studied. Twelve children without iron metabolism disorders or renal diseases served as a control group. No difference in blood urea nitrogen (BUN), serum creatinine, creatinine clearance, electrolytes, fractional excretion of sodium and potassium, and tubular phosphorus reabsorption was found. Serum uric acid was equal in the two groups, but its urine excretion was significantly higher in the thalassemic group. U(NAG) and U(NAG) to creatinine ratio (U(NAG/CR)) were elevated in all patients with thalassemia compared with the control group (p < 0.001) and were directly correlated to the amount of transfused iron but not to actual ferritin level. We found that renal tubular function is impaired in children with beta- thalassemia major and intermedia. It is not known whether these functional abnormalities would have any long-term effects on the patients. Further studies are needed, and means of preventing these disturbances should be sought.     

Nephrotic syndrome associated with interferon-β-1b therapy for multiple sclerosis

A 43-year-old woman with multiple sclerosis (MS) had nephrotic syndrome 21 months after starting treatment with interferon (IFN)-β-1b (subcutaneous administration). She had taken no drug except for the IFN-β-1b. Because nephrotic syndrome may be induced by IFN therapy, the IFN was stopped. Percutaneous renal biopsy revealed that she had minimal change nephrotic syndrome. As nephrotic-range proteinuria, hypoalbuminemia, and general edema were worsening even 2 weeks after cessation of the drug, oral corticosteroid therapy (prednisolone 40 mg/day) was started. The nephrotic syndrome was treated successfully with prednisolone. The dosage of prednisolone was tapered, without a relapse, and then the corticosteroid therapy was stopped. IFN-β-1b therapy was then resumed, and the patient is in remission for both nephrotic syndrome and MS. Though proteinuria and nephrotic syndrome is a rare adverse effect of IFN-β-1b therapy, physicians treating MS patients with this agent should pay careful attention to new clinical symptoms and laboratory findings.     

Diclofenac, a nonsteroidal anti-inflammatory drug, decreases proteinuria in some glomerular diseases: a controlled study

Treatment with nonsteroidal anti-inflammatory drugs (NSAIDs) was first used in glomerulonephritis (GN) in 1966 but its efficiency is still debated. We studied the antiproteinuric effect of such a treatment in a double-blind study. 29 GN patients with normal renal function (17 membranoproliferative GN, 12 IgA GN) were randomly assigned to receive 100 mg/day of diclofenac or placebo for at least 2 months. There was a significant antiproteinuric effect of diclofenac versus placebo with a fall of 70% in the diclofenac group versus 6% in the placebo group (p less than 0.001 with the Mann-Whitney test). The median was 3 mg/min at onset and 2.45 mg/min after 2 months treatment with the placebo. In the diclofenac group, it was 2.2 and 0.95 mg/min, respectively (p less than 0.01). Diclofenac did not significantly increase creatinine levels. Gastric irritation was noted only once. This study establishes the short-term antiproteinuric action of diclofenac. Whether this action affects the final outcome is not yet determined.     

Urinary uranium and kidney function parameters in professional assistance workers in the Epidemiological Study Air Disaster in Amsterdam (ESADA).

BACKGROUND: The Epidemiological Study Air Disaster in Amsterdam (ESADA) aimed to assess long-term health effects in professional assistance workers involved in the 1992 air disaster in Amsterdam. As part of ESADA indications of nephrotoxicity due to exposure to uranium from the balance weights of the crashed aircraft were assessed. METHODS: Data of a historically defined cohort of 2499 (exposed and non-exposed) firefighters, police officers and hangar workers were collected 8.5 years after the disaster. Urinary uranium concentrations were determined by sector field inductively coupled plasma mass spectrometry. Urine albumin-creatinine ratio and fractional excretion of beta(2)-microglobulin were calculated from a single-spot urine specimen and simultaneous blood sample. Exposed assistance workers were compared with their non-exposed colleagues, and associations between uranium and kidney function parameters were explored. RESULTS: Median uranium concentrations were around 2 ng/g creatinine. Median values of albumin-creatinine ratio and fractional excretion of beta(2)-microglobulin were well below the level for microalbuminuria and for tubular damage, respectively. No statistically significant differences between exposed and non-exposed workers were found in uranium concentrations and kidney function parameters, although exposed hangar workers had lower uranium concentrations. No statistically significant associations were found between uranium concentrations and kidney function parameters in the total cohort. CONCLUSIONS: Occupational exposure to the air disaster in Amsterdam was neither significantly associated with higher uranium concentrations, nor with disturbed kidney function parameters. In this large cohort of professional assistance workers, urinary uranium concentrations were in the low range compared with previously published reference populations. No indications of nephrotoxicity were found at urinary uranium concentrations around 2 ng/g creatinine.     

Protective Effect of Oral <Emphasis Type="SmallCaps">L</Emphasis>-arginine Supplementation on Cyclosporine Induced Nephropathy in Rats

Background: One of the major adverse effects of long term cyclosporine A (CyA) administration is chronic nephrotoxicity. Several studies have suggested that alterations of the L-arginine (L-Arg) nitric oxide (NO) pathway may be involved in the pathogenesis of CyA-induced kidney damage. Aim: We postulated that in vivo activation of L-Arg-NO pathway might have a beneficial effect on CyA-induced renal damage. Conditions of chronic NO enhancement was established with L-Arg supplementation and chronic NO blockade with N-nitro-L-Arg methyl ester (L-NAME). We tested the hypothesis that, if CyA administration alters intrarenal NO synthesis, then exogenous L-Arg supplementation could limit renal injury, on the contrary, L-NAME, a potent competitive inhibitor of NO synthesis, could enhance CyA nephrotoxicity. Harmful effect of NO blockade indirectly supports the beneficial effect of NO in a model of CyA nephrotoxicity. Methods: Rats were administered vehicle (VH), CyA (7.5 mg/kg/day), CyA + L-Arg (2g/kg/day), CyA + L-NAME (5 mg/100 ml/day), CyA + L-Arg + L-NAME, VH + L-Arg, VH + L-NAME and were sacrificed at the end of the experiment. Body weight, serum creatinine, blood urea nitrogen (BUN) and NO levels were determined. Tubular injury and interstitial fibrosis were evaluated semiquantitatively using scoring systems on paraffin sections stained with hematoxylin/eosin (H/E), Masson’s trichromic and periodic acid-Schiff (PAS). Results: The CyA group developed marked renal injury, characterized by a significant increase in serum creatinine and BUN, and histopathological alterations including tubular dilatation, vacuolization, necrosis, interstitial cell infiltration and tubulointerstitial fibrosis. CyA reduced serum NO level. L-Arg treatment significantly enhanced NO biosynthesis and protected animals from CyA-induced kidney damage. In contrast L-NAME strikingly reduced serum NO level, and worsened biochemical and histopathological alterations. Conclusion: Chronic CyA nephrotoxicity can be aggravated by NO blockade and ameliorated by NO enhancement suggesting that L-Arg supplementation may be protective in CyA nephrotoxicity.     

Repeat renal biopsy in children with severe idiopathic tubulointerstitial nephritis

Idiopathic (primary) tubulointerstitial nephritis (TIN) of childhood is relatively rare. Four children, two with concomitant uveitis, aged 8–14 years, with idiopathic TIN who underwent repeat renal biopsy were retrospectively evaluated. At presentation, all had a significant elevation of the urinary ₂-microglobulin/creatinine ratio (2MG ratio), ranging from 10,100 to 44,550, with increased histological indices of tubulointerstitial scores (TI scores) in excess of 6 points. Three of the children received prednisolone (PSL) therapy following diagnosis, while the remaining child received the therapy 30 months after the first renal biopsy. In the children that received prompt PSL therapy, a rapid decrease in urinary 2MG ratio was observed and the TI scores obtained at a mean interval of 16 months after the first biopsy decreased to less than 5, while preserving renal function. In the remaining child that received delayed PSL therapy, persistent elevations of urinary 2MG ratio and TI scores were observed. He subsequently progressed to chronic renal insufficiency. These clinical findings suggest that persistent elevations of urinary 2MG ratio and TI scores are indicators of progression of renal failure in TIN. For successful treatment, early therapeutic intervention should be deployed in selected patients with severe idiopathic TIN.     

Ifosfamide nephrotoxicity in pediatric cancer patients

The renal functions in pediatric cancer patients who received ifosfamide (IFO) treatment were evaluated and the risk factors related to IFO nephrotoxicity were determined. The medical records of all children treated with IFO were reviewed, and 62 with normal renal function before IFO treatment were selected. Nephrotoxicity was diagnosed by measuring urine β₂-microglobulin and glucose, and serum phosphate, bicarbonate, and creatinine. Forty-eight (77.4%) had a history of previous cisplatin treatment. Nephrotoxicity was detected in 20 patients (32.3%). β₂-Microglobulinuria was observed in all 20, hypophosphatemia in 10 (16.1%), hypocarbia in 2 (3.2%), glucosuria in 5 (8.1%), and decreased creatinine clearance in 7 (11.3%). The cumulative dose of IFO and a history of previous cisplatin therapy were related to nephrotoxicity. Among the 20 patients with nephrotoxicity, the median cumulative dose of IFO in patients with a low (<500 mg/m²) and high (>500 mg/m²) cumulative dose of previous cisplatin was 80 g/m² (73–102 g/m²) and 45 g/m² (11–76 g/m²), respectively. Most of the nephrotoxicity persisted after cessation of IFO treatment. In conclusion, close monitoring of IFO nephrotoxicity should be started earlier in patients with high-dose cisplatin pretreatment. Tubular proteinuria, as indicated by β₂-microglobulinuria, was the most-sensitive marker for IFO nephrotoxicity. Long-term follow-up study for reversibility of IFO nephrotoxicity is in progress. Received: 19 February 2001 / Revised: 15 May 2001 / Accepted: 18 May 2001     

Acute changes in renal function following extracorporeal shock wave lithotripsy in patients with a solitary functioning kidney

Twelve consecutive patients with a solitary functioning kidney were treated for renal stone by extracorporeal shock wave lithotripsy (ESWL*) with the modified Dornier HM3 lithotriptor and studied for 3 days after treatment. Urinary excretion of electrolytes, N-acetyl-beta-glucosaminidase (NAG), alkaline phosphatase, kallikrein, glycosaminoglycans, albumin and beta 2-microglobulin, and clearances of creatinine, inulin and para-aminohippuric acid were determined, as were serum levels of creatinine, urea, beta 2-microglobulin and aldosterone, and plasma renin activity. Urinary flow rate, free water clearance, and urinary excretion of NAG, kallikrein and beta 2-microglobulin were significantly increased 0 to 24 hours after ESWL. The urinary excretions of alkaline phosphatase, albumin and glycosaminoglycans were unchanged. Glomerular filtration rate was significantly decreased and effective renal plasma flow was unchanged. Filtration fraction was stable. Serum lactic dehydrogenase increased significantly after ESWL and remained high through the period of observation. Serum levels of creatinine, beta 2-microglobulin and aldosterone were unaltered. A decrease in plasma renin activity immediately after treatment is explained by the water immersion and the extracellular volume expansion during treatment.     

Early markers of renal dysfunction in patients with beta-thalassemia major

Studies of renal involvement in thalassemia syndromes have been varied and few. The most important cause of mortality and morbidity in these patients is organ failure due to iron deposition. We report here a cross-sectional study carried out between February 2005 and February 2006 on all beta-thalassemia major patients being treated in Mofid Children’s hospital, Tehran. The aim of the study was to detect renal dysfunction in these patients. The patient cohort consisted of 103 patients with various disease severities. Fresh first morning urine samples were collected and analyzed for sodium (Na), potassium (K), calcium (Ca), creatinine (Cr), phosphate, uric acid (UA), N-acetyl beta-D-glucosaminidase (NAG) and amino acids. We also carried out a complete blood count evaluation and assayed fasting blood sugar and serum ferritin, sodium, potassium, creatinine, uric acid and amino acids in all patients. The mean age of our patient cohort was 12.5 ± 5.53 years and 53.4% were female. Abnormal levels of urinary NAG were detected in 35.9% of patients (confidence interval  26–45%). Abnormal levels of fractional excretion (FE)-Na, FE-K and FE-UA and abnormal urine protein Pr/Cr and urine Ca/Cr ratios were present in 29.1, 7.8, 52.4, 0.3 and 22.3% of the patients, respectively. There was a significant relationship between urinary NAG and the age of the patient (R = 0.35), duration of deferoxamine therapy (R = 0.31), duration of receiving blood transfusions (R = 0.34) and level of fasting blood sugar (R = 0.2). We concluded that renal disorders are not rare in patients with beta-thalassemia major and that they may increase in terms of frequency with age, increased duration of transfusion and deferoxamine usage and high levels of blood sugar.     

Treatment-related changes in urinary excretion of high and low molecular weight proteins in patients with idiopathic membranous nephropathy and renal insufficiency.

BACKGROUND: In patients with idiopathic membranous nephropathy, an increased urinary excretion of high (IgG) and low [beta(2)-microglobulin (beta(2)M), alpha(1)-microglobulin (alpha(1)M)] molecular weight proteins predicts prognosis and precedes renal insufficiency. We have studied the changes in the urinary excretion of these proteins in patients with idiopathic membranous nephropathy and renal insufficiency during and after treatment with cyclophosphamide and steroids, and investigated their value in predicting long-term outcome. METHODS: Standardized measurements of urinary IgG, albumin, beta(2)M and alpha(1)M were performed at 0, 2, 6 and 12 months in 11 patients, at 12 months in 25 patients and in 17 of these last patients after 2-5 years. RESULTS: We observed a rapid improvement of glomerular permselectivity and tubular protein reabsorption within 2 months after the start of therapy. Despite a partial remission of proteinuria within 12 months in most patients, evidence of tubulo-interstitial injury remained apparent. Neither absolute levels of urinary IgG, beta(2)M or alpha(1)M at baseline or at 12 months nor the percentage reduction between baseline and 12 months clearly predicted the occurrence of a remission or a relapse to nephrotic range proteinuria. In the case of a persistent stable remission, we observed a gradual decrease of urinary beta(2)M towards normal values. CONCLUSIONS: In patients with idiopathic membranous nephropathy and renal insufficiency, treatment with cyclophosphamide and steroids resulted in an improvement of glomerular permeability and tubular proteinuria. Tubular proteinuria remained present for many years, even in patients with stable remission of proteinuria. Measurements of urinary proteins at 12 months after treatment start lacked predictive accuracy.     

Pain treatment with a COX-2 inhibitor after coronary artery bypass operation: a randomized trial

BACKGROUND: Adequate analgesic medication is mandatory after cardiac operations. Cyclooxygenase-2 inhibitors represent a new therapeutic option, acting primarily on the response to inflammation. METHODS: We compared a cyclooxygenase-2 inhibitor (etodolac) with two traditional drugs: a nonselective cyclooxygenase inhibitor (diclofenac) and a weak opioid (tramadol) on postoperative pain and renal function in patients undergoing coronary artery bypass operations. Sixty consecutive patients were randomized into three groups: (1) group A patients who received tramadol; (2) group B patients who received diclofenac; and (3) group C patients who received etodolac. For measurement of analgesic effect, the visual analogue scale was assessed up to postoperative day 4. Creatinine-clearance was determined before and at the end of study medication, and serum creatinine and urea were monitored daily for renal effects. Study medication was given on postoperative days 2 and 3. Side effects and additional pain medication were recorded. RESULTS: The visual analogue scale was lower in group C (p < 0.05) from postoperative days 2 to 4 and in group B (p < 0.05) from postoperative days 3 to 4 compared with group A. Amount of additional pain medication and incidence of side effects were significantly less in group C compared with group A. We observed a short-lasting elevation of serum creatinine and urea in groups B and C compared with group A (p < 0.05). CONCLUSIONS: At the doses analyzed, etodolac and diclofenac produced better postoperative pain relief with less side-effects than tramadol. A short-lasting impairment of renal function was found in patients treated with etodolac and diclofenac.     

Comparison of the new polyethersulfone high-flux membrane DIAPES HF800 with conventional high-flux membranes during on-line haemodiafiltration.

BACKGROUND: Current modalities of renal replacement therapy allow only a limited removal of larger, possibly toxic molecules, which accumulate in uraemia. Recently, a haemodiafilter has been made available with the new, high-flux, polyethersulfone-based membrane DIAPES HF800. We performed a study to compare DIAPES HF800 with two conventional high-flux membranes in on-line haemodiafiltration (HDF), with respect to the removal properties for the two marker proteins, beta(2)-microglobulin (beta(2)m, 11.8 kDa) and albumin (66.5 kDa). METHODS: In a prospective, controlled study 10 stable end-stage renal disease patients were randomly allocated to 30 sessions of post-dilutional on-line HDF with three types of steam-sterilized membranes: DIAPES HF800, polysulfone and polyamide. Blood flow rate was 250 ml/min and treatment time was 240 min. Pre-treatment beta(2)m and albumin plasma concentrations did not differ between the three groups. The concentration of the two proteins was determined before and after treatment in plasma as well as in the continuously collected haemodiafiltrate. RESULTS: Tolerance of all treatments was very good, without any side-effects for all filters. The mean plasma reduction rate of beta(2)m was 77 +/- 1% for DIAPES HF800 and polysulfone whereas it was 71 +/- 1% for polyamide (P < 0.05). The mean beta(2)m amount removed and found in the haemodiafiltrate per session was 230 +/- 14 mg for DIAPES HF800, 186 +/- 13 mg for polysulfone and 147 +/- 13 mg for polyamide (P < 0.05 between each pair of membranes). The same ranking was obtained for albumin removed and found in haemodiafiltrate per session for the three membranes: 5.7 +/- 0.4, 3.5 +/- 0.4 and 1.0 +/- 0.4 g, respectively. Although DIAPES HF800 showed the highest value for albumin in haemodiafiltrate the mean post-treatment plasma albumin was higher after the treatment with DIAPES HF800 compared with the other membranes (P < 0.05). CONCLUSIONS: On-line HDF has shown to achieve plasma reduction rates for beta(2)m of up to 77% for the DIAPES HF800 membrane and for polysulfone. The amounts of beta(2)m and albumin in haemodiafiltrate were much higher for DIAPES HF800 than for the other two membranes indicating a greater permeability for molecules up to a molecular weight of 66.5 kDa. This could, at least theoretically, offer the advantage also to remove uraemic toxins in the molecular weight range of albumin or of albumin-bound toxins. The future must show whether this will counterbalance the loss of albumin.     

青藤碱对梗阻性黄疸大鼠急性肾损伤的保护作用

目的：探讨青藤碱对梗阻性黄疸（OJ）大鼠急性肾损伤的保护作用及机制。 方法：将24只大鼠随机分均为假手术组、模型组与青藤碱干预组,后两组大鼠行胆总管结扎切断制作OJ模型。青藤碱干预组大鼠于术后第1天起给予青藤碱（80 mg/kg）灌胃,每天1次,而假手术组与模型组大鼠以同样方式给予等量生理盐水代替。术后第8天处死各组大鼠,取血检测血清尿素氮（SUN）、血清肌酐（Scr）含量,取肾组织行病理学检查,检测肾组织丙二醛（MDA）、髓过氧化物酶（MPO）水平和总抗氧化能力（T-AOC）以及转化生长因子（TGF-β1）蛋白与mRNA的表达。 结果：除假手术组外,其余两组大鼠术后均出现OJ表现以及明显的肾损伤病理学改变,但青藤碱干预组的肾损伤轻于模型组。与假手术组比较,其余两组大鼠SUN、Scr水平均明显升高;肾组织MDA、MPO含量、TGF-β1蛋白和mRNA表达明显升高,T-AOC明显降低（均P<0.05）,但青藤碱干预组以上指标的改变程度均明显低于模型组（均P<0.05）。 结论：青藤碱对OJ大鼠急性肾损伤具有保护作用,其机制可能与其抗氧化作用以及抑制TGF-β1的表达有关。

     

Oral supplement of six selective amino acids arrest progression renal failure in uremic patients

Certain amino acids such as glycine, L-aspartic acid, L-glutamic acid, L-glutamine, L-histidine and L-arginine taken orally by normal adults or patients with renal failure increase glomerular filtration rate (GFR). Twelve nondiabetic patients suffering from glomerulonephritis confirmed by renal biopsy previously, with creatinine clearances ranging from 15 to 24 ml minute/1.73, and on low protein diet 0.6 g/kg/day, received an amino acid supplement daily in 2 or 3 doses for 1 year. At 4, 8 and 12 months creatinine clearance increased slightly (NS, NS, NS), 24 hour urine volume increased (P 0.001, 001, 0.001), 24 hour albuminuria decreased (P<0.001, 0.001, 0.001), serum urea increased (NS, NS, NS) serum albumin increased (NS, 0.05, 0.05), total cholesterol decreased slightly (NS, NS, 0.01), HDL increased slightly (0.05, 0.05, 0.05), LDL decreased (NS, 0.001, 0.001) triglycerides decreased (0.001, 0.001, 0.001), Apo B remained unchanged (NS, NS, NS), ROS/H₂O₂ decreased (0.001, 0,001, 0.001), Hct increased (NS, 0.01, 0.01) Hb increased (0.05, 0.05, 0.05) and serum phosphate decreased (0.01, 0.01, 0.01). After removal of supplements at the end of the year all parameters remained unchanged. We believe that a large controlled study should be undertaken to confirm these most encouraging findings.     

Prediction of residual total renal function before nephron-sparing surgery using99mTc-DMSA renal scintigraphy

Background Although radical nephrectomy is the standard treatment for renal cell carcinoma, nephron-sparing surgery is the preferred treatment in patients with a single functioning kidney. It is important before surgery to evaluate the level of residual renal function likely after the operation. In this study, we investigated the prediction of residual renal function, using technetium Tc 99m dimercaptosuccinic acid (^99mTc-DMSA) renal scintigraphy, before nephron-sparing surgery for renal tumors. Methods Preoperative and postoperative evaluation of renal function was done in 11 patients with renal cell carcinoma or renal angiomyolipoma, using^99mTc-DMSA scintigraphy. Nine patients had renal cell carcinoma and 2 had renal angiomyolipoma. Partial nephrectomy was performed in 4 patients and surgical enucleation in 7 patients. Both the predicted total DMSA renal uptake rate prior to surgery and the actual postoperative total^99mTc-DMSA renal uptake rate were obtained. Endogenous creatinine clearance and serum creatinine levels were also obtained. Results There was a good relationship between the predicted and postoperative total^99mTc-DMSA renal uptake rates. The ratio of the postoperative total DMSA renal uptake rate to the predicted total^99mTc-DMSA renal uptake rate was 85% after partial nephrectomy, and 101% after surgical enucleation. There was also a significant correlation between the postoperative total^99mTc-DMSA renal uptake rate and creatinine clearance, and postoperative total^99mTc-DMSA renal uptake rate levels above 11.4% coincided with serum creatinine levels below 2.0 mg/dL. Conclusion Preoperative assessment with^99mTc-DMSA renal scintigraphy is clinically useful for predicting residual renal function after nephron-sparing surgery.     

COX-2 inhibitors and acute interstitial nephritis: case report and review of the literature

We report a case of biopsy-proven acute interstitial nephritis (AIN) in a 50-year-old diabetic woman, who had been treated with celecoxib for 4 weeks before presentation. She presented with clinical findings of renal proximal tubulopathy, aseptic leukocyturia and acute renal failure. A kidney biopsy specimen showed AIN with intense tubuli and eosinophilic infiltrate in the interstitium. She recovered normal renal function two weeks after cessation of celecoxib and use of a corticosteroid. A review of the literature yielded eight cases of COX-2 inhibitor-associated AIN with a biopsy-proven diagnosis. Among the reported cases, AIN was diagnosed after an average of 8.3 months of therapy (SD 12 months, range 3 days - 3 years) with 25 mg rofecoxib or 200 mg celecoxib daily. Common symptoms included asthenia, anorexia, nausea and vomiting. The classic triad of fever, rash and eosinophilia was uncommon. Typical laboratory features included hematuria, proteinuria, eosinophilia. Renal failure was common at the time of diagnosis. Mean serum creatinine levels were 0.86 +/- 0.11 mg/dl, 5.66 +/- 3.50 mg/dl and 1.15 +/- 0.24 before treatment, at time of diagnosis and 1 - 2 months after COX-2 inhibitor withdrawal, respectively. Three patients required emergency hemodialysis. After cessation of COX-2 inhibitor treatment, patients recovered completely with a normalized serum creatinine level after one to two months. Management consisted of withdrawal of the COX-2 inhibitor drug and in four patients, corticosteroid therapy was well-tolerated and may have been beneficial.