Normalization Of Creatinine Research Articles

Renoprotective immunosuppression by pioglitazone with low-dose cyclosporine in rat heart transplantation

The peroxisome proliferator-activated receptor gamma activator pioglitazone has recently been reported to possess pleiotropic cardioprotective and renoprotective actions. We hypothesized that pioglitazone would reduce a dose of the immunosuppressant cyclosporine after heart transplantation, resulting in beneficial protective effects for both cardiac allografts and recipient kidneys. Experiments were performed by using an allomismatched rat heterotopic heart transplantation model. Recipients were treated with cyclosporine with or without pioglitazone and were divided into one of 4 groups: group I, no treatment; group II, low-dose cyclosporine (2 mg x kg(-1) x d(-1)); group III, high-dose cyclosporine (5 mg x kg(-1) x d(-1)); and group IV, low-dose cyclosporine with pioglitazone (3 mg x kg(-1) x d(-1)). Cyclosporine-treated rats showed significantly longer graft survival and less graft rejection but severe renal damage in a dose-dependent manner. Compared with group II, treatment with pioglitazone with low-dose cyclosporine (group IV) significantly suppressed graft infiltration of CD4/CD8 T lymphocytes and serum concentrations of interleukin 2 and interferon gamma, leading to extended graft survival up to 60 days. These immunosuppressive effects in group IV were equivalent to those in group III. In addition, recipient kidneys in group IV had few apoptotic cells, possibly through upregulation of peroxisome proliferator-activated receptor gamma and downregulation of transforming growth factor beta1, and maintained stable renal functions, as evidenced by a normalization of blood urea nitrogen, creatinine, and creatinine clearance values. In vitro experiments also confirmed the renoprotective effects of pioglitazone on cyclosporine-induced toxicity. Collectively, pioglitazone can reduce a dose of cyclosporine with sufficient immunosuppressive effects. Pioglitazone treatment with low-dose cyclosporine has synergistic protective effects for cardiac allografts and recipient kidneys, leading to improvement of graft survival with a minimal cyclosporine-induced nephrotoxicity.

Vitamin D Deficiency as an Ignored Cause of Hypocalcemia in Acute Illness: Report of 2 Cases and Review of Literature

We describe the clinical and laboratory findings in 2 cases of hypocalcemia secondary to vitamin D deficiency in intensive care unit and the response of calcium to treatment. We also discuss the mechanism and review pertinent lit- erature. The first patient was admitted due to stroke. Laboratory data included serum calcium 7.6 mg/dl, intact parathyroid hormone (PTH) 891.6 pg/ml, 25-hydroxyvitamin D (25-OH-D) 7 ng/ml (17.5 nmol/l), 1,25-dihydroxyvitamin D (1,25- OH-D) 43 pg/ml (103.2 nmol/l), and corrected QT (QTc) interval 494 msec. After two weeks of treatment with oral cal- cium and ergocalciferol, serum calcium and intact PTH levels and QTc interval normalized. The second patient was trans- ferred for the management of disseminated cytomegalovirus infection. Laboratory work-up revealed serum calcium 7.7 mg/dl, creatinine 4.3 mg/dl, intact PTH 207.5 pg/ml, 25-OH-D <5 ng/ml (<12.5 nmol/l), 1,25-OH-D <10 pg/ml (<24 nmol/l), and QTc interval 505 msec. After treatment for vitamin D deficiency and infection, we observed normalization of creatinine, corrected calcium, intact PTH and QTc interval. The clinical courses were uneventful in both cases. In conclu- sion, we would like to emphasize that vitamin D status should be evaluated in patients with hypocalcemia in acute settings because vitamin D deficiency is common and readily treatable, and there may be clear life-threatening consequences if it is not treated.

Normalization of Urinary Drug Concentrations with Specific Gravity and Creatinine

Excessive fluid intake can substantially dilute urinary drug concentrations and result in false-negative reports for drug users. Methods for correction ("normalization") of drug/metabolite concentrations in urine have been utilized by anti-doping laboratories, pain monitoring programs, and in environmental monitoring programs to compensate for excessive hydration, but such procedures have not been used routinely in workplace, legal, and treatment settings. We evaluated two drug normalization procedures based on specific gravity and creatinine. These corrections were applied to urine specimens collected from three distinct groups (pain patients, heroin users, and marijuana/ cocaine users). Each group was unique in characteristics, study design, and dosing conditions. The results of the two normalization procedures were highly correlated (r=0.94; range, 0.78-0.99). Increases in percent positives by specific gravity and creatinine normalization were small (0.3% and -1.0%, respectively) for heroin users (normally hydrated subjects), modest (4.2-9.8%) for pain patients (unknown hydration state), and substantial (2- to 38-fold increases) for marijuana/cocaine users (excessively hydrated subjects). Despite some limitations, these normalization procedures provide alternative means of dealing with highly dilute, dilute, and concentrated urine specimens. Drug/metabolite concentration normalization by these procedures is recommended for urine testing programs, especially as a means of coping with dilute specimens.

Index of Suspicion

Index of Suspicion

Mitochondria-targeted plastoquinone derivatives as tools to interrupt execution of the aging program. 2. Treatment of some ROS- and Age-related diseases (heart arrhythmia, heart infarctions, kidney ischemia, and stroke)

Effects of 10-(6'-plastoquinonyl) decyltriphenylphosphonium (SkQ1) and 10-(6'-plastoquinonyl) decylrhodamine 19 (SkQR1) on rat models of H2O2- and ischemia-induced heart arrhythmia, heart infarction, kidney ischemia, and stroke have been studied ex vivo and in vivo. In all the models listed, SkQ1 and/or SkQR1 showed pronounced protective effect. Supplementation of food with extremely low SkQ1 amount (down to 0.02 nmol SkQ1/kg per day for 3 weeks) was found to abolish the steady heart arrhythmia caused by perfusion of isolated rat heart with H2O2 or by ischemia/reperfusion. Higher SkQ1 (125-250 nmol/kg per day for 2-3 weeks) was found to decrease the heart infarction region induced by an in vivo ischemia/reperfusion and lowered the blood levels of lactate dehydrogenase and creatine kinase increasing as a result of ischemia/reperfusion. In single-kidney rats, ischemia/reperfusion of the kidney was shown to kill the majority of the animals in 2-4 days, whereas one injection of SkQ1 or SkQR1 (1 micromol/kg a day before ischemia) saved lives of almost all treated rats. Effect of SkQR1 was accompanied by decrease in ROS (reactive oxygen species) level in kidney cells as well as by partial or complete normalization of blood creatinine and of some other kidney-controlled parameters. On the other hand, this amount of SkQ1 (a SkQ derivative of lower membrane-penetrating ability than SkQR1) saved the life but failed to normalize ROS and creatinine levels. Such an effect indicates that death under conditions of partial kidney dysfunction is mediated by an organ of vital importance other than kidney, the organ in question being an SkQ1 target. In a model of compression brain ischemia/reperfusion, a single intraperitoneal injection of SkQR1 to a rat (1 micromol/kg a day before operation) effectively decreased the damaged brain area. SkQ1 was ineffective, most probably due to lower permeability of the blood-brain barrier to this compound.

Pure Laparoscopic Donor Nephrectomy: 3-Year Experience and Analysis of a Refined Technique to Maximize Graft Function

Strategies for vascular control and limiting warm ischemia time (WIT) vary between institutions for laparoscopic live donor nephrectomy (LLDN). We refined our technique and retrospectively determined whether it safely provides an allograft of comparable quality to published series. Fifty consecutive LLDN between February 2003 and November 2006 were reviewed. Key technical aspects include placing the perfused kidney and transected ureter entirely within an endocatch bag, with the string externalized through an extended lateral port site incision. Vessels are then controlled with clips, or a Satinsky clamp for right sided veins. The extraction incision is completed and the bag immediately withdrawn and placed on ice. WIT ends with perfusion with cold UW solution. The series includes 42 left and 8 right kidneys. 13/50 (26%) demonstrated anatomical complexity (more than one artery, vein and/or ureter). Average operative time was 178 minutes. Average WIT was 128 seconds. Conversion to open surgery occurred in two patients, one to define challenging anatomy, and another for hemorrhage from the renal artery stump. Average blood loss was 76 ml. Average length of stay was 3.6 days. Average recipient creatinine was 1.26 mg/dl at discharge. Delayed graft function occurred in three recipients. ATN/slow normalization of creatinine occurred in four. Graft survival at one year was 96%. The refined technique of LLDN mimics important principles of open donor nephrectomy. Controllable variables which may impact graft function are optimized. WIT is amongst the lowest reported for pure laparoscopy, without increasing complication rates, blood loss, or operative time.

Porphyrinuria in childhood autistic disorder is not associated with urinary creatinine deficiency

Urinary metabolite measurements are often normalized to levels of the ubiquitous metabolite creatinine (CRT) to take account of variations in fluid export. Following CRT normalization, excesses of porphyrins and isoprostanes have been reported in the urines of children with neurodevelopmental disorders. It was suggested (Whiteley et al., 2006, Pediatr. Int. 2006; 48: 292-297) that urinary CRT levels may be depressed in children with autism spectrum disorders. This prompted re-evaluation of CRT levels in such children. First matinal urinary CRT levels were compared between subjects in different diagnostic categories including autistic disorder, pervasive developmental disorder not otherwise specified (PDD-NOS) and hyperactivity, before and after correction for age and gender. A larger reference group, consisting of subjects with unrelated disorders and Asperger disorder, with no reported porphyrin excess, was also compared to the group with autistic disorder, both for CRT and for porphyrin (coproporphyrin, COPRO) excess. No significant difference in CRT was observed between any of the categories analyzed, also when corrected for age and gender. In contrast, urinary COPRO levels were significantly higher in autistic disorder versus reference groups, either when expressed as absolute values (independent of CRT levels) or when normalized to CRT. These data do not support a systematic reduction in urinary CRT levels in subjects with autism spectrum disorders including autistic disorder and PDD-NOS. Urinary COPRO excess in autistic disorder was not associated with or consequent upon urinary CRT deficiency. Differences between affected and control subjects in age and sampling time, as reported by Whiteley et al., may underlie the apparent CRT reduction.

Successful Treatment of Catastrophic Antiphospholipid Antibody Syndrome (CAPS) Associated With Splenic Marginal-zone Lymphoma With Low-molecular Weight Heparin, Rituximab and Bendamustine

A 69-year-old woman with splenic marginal-zone lymphoma was admitted with progressive abdominal pain and splenomegaly as the suspected cause of pain. Rituximab treatment (375 mg/m) had been initiated on the day of admission. Abdominal computerized tomography revealed splenic infarction. Laboratory tests showed elevation of liver enzymes and creatinine, low platelet count, prolonged partial thromboplastin time, and lupus anticoagulant positivity. The diagnosis of catastrophic antiphospholipid antibody syndrome was made. Weight-adjusted low-molecular weight heparin therapy was initiated. Freedom from symptoms and normalization of liver enzymes and creatinine occurred within 4 weeks. Treatment was continued with 6 cycles of bendamustine monotherapy (90 mg/m) and heparin, leading to partial remission of lymphoma and lupus anticoagulant negativity. In case of multiorgan failure in patients suffering from lymphoma and showing features of disseminated intravascular coagulation, catastrophic antiphospholipid antibody syndrome should be considered. In our patient, rituximab followed by weight-adjusted low-molecular weight heparin and bendamustine therapy led to recovery.

CARBOHYDRATE-DEFICIENT TRANSFERRIN (CDT) AS A MARKER OF ALCOHOLDEPENDENCY

BACKGROUND Excessive alcohol consumption starts to change the structure of transferrin into thecarbohydrate-deficient transferrin (CDT). CDT is the only specific laboratory marker foralcohol dependency. However no one at all is sensitive enough.Method In our study we wanted to confirm the alcohol dependency by means of questionnairesand laboratory markers, particularly CDT. RESULTS Investigated were 68 (92.6 % males, 7.4 % females) general practice healthy patientsand blood donors and 186 (89.2 % males, 10.8 % females) inpatient alcoholics. A bloodsample was taken once from every healthy subject and three times from every alcoholic: onadmission to hospital, after 12 days and again after 42 days.In alcoholics we found statistically significantly elevated CDT, glutamate dehidrogenaze(GLDH), aspartate-aminotransferaze (AST), alanine-aminotransferaze (ALT), gamaglutamyltransferaze (GGT) and mean corpuscular volume (MCV) and decreased ureavalues. CDT was the most reliable marker with high specificity (91.2 %) and sensitivity(81.4 %). The area under ROC-curve was exceptional with 99.9 %.The kinetics of CDT, AST, ALT, GGT, MCV and creatinine normalization after 14 dayswere also statistically significant as well as kinetics of CDT, AST, GGT, MCV and creatininenormalization after 42 days. We estimated the course of CDT value normalization as themost applicable.The most important diagnostic marker combination was composed by CDT, MCV and AST.GGT had lower importance as expected. CONCLUSIONS In our population CDT was the most specific marker of all, attaining high sensitivity. But itwas not reliable enough as the sole marker or as the screening one for alcohol dependency.Its main applicability is in diagnostics of alcoholism, control of alcohol abstention andforensic cases but solely in combination with other laboratory markers of alcoholism

Low-Dose Aminophylline for the Treatment of Neonatal Non-Oliguric Renal Failure—Case Series and Review of the Literature

Aminophylline is a methylxanthine with multiple physiologic actions. At low doses, aminophylline can antagonize adenosine and improve renal function via increased glomerular filtration rate. Despite its clinical use, little data exists in neonates for this indication. Therefore, the objective of this report is to describe the impact of aminophylline on renal function indices in a series of neonates with acute renal failure. This was a retrospective chart review of 13 neonates with acute renal failure who received aminophylline during a 15-month study period. Aminophylline was administered at 1 mg/kg intravenously or orally every twelve hours. Forty-six percent (n = 6) of the patients received a 5 mg/kg loading dose before initiation of maintenance therapy. Most patients had already received other treatments for renal failure, including diuretics and dopamine. Resolution of acute renal failure (with normalization of serum creatinine and blood urea nitrogen) was documented in 10 patients (77%). Four of the thirteen patients died from complications due to their prematurity. Failure of low-dose aminophylline was observed in 3 of the 4 patients who died. Low-dose aminophylline in neonates with acute renal failure is associated with an improvement in renal function indices.

Long-term follow-up of Argentinean patients with hemolytic uremic syndrome who had not undergone dialysis

We examined the records of patients with hemolytic uremic syndrome, who had not undergone dialysis during the acute stage, with the aims of evaluating: (1) the outcome after at least 5 years of follow-up; (2) the value of peak serum creatinine as a prognostic marker; (3) the relationship between outcome and time to normalization of renal function. From 1968 to 2000, 1,179 patients were assisted. Forty-two patients (3.6%) died during the acute stage, 478 patients (40.5%) required dialysis and 659 patients (55.9%) did not undergo dialysis; 529 non-dialysis patients were lost to follow-up. The remaining 130 patients were classified into four groups: group I, complete recovery; group II, with two subgroups, IIa, microalbuminuria, and IIb, proteinuria and/or high blood pressure, both with normal renal function; group III, chronic renal failure; and group IV, end-stage renal disease. We analyzed the relationship between final outcome and: (1) peak creatinine (the highest of at least two determinations) during the acute stage and (2) time to normalization of urea and/or creatinine after the acute stage. After a mean follow-up time of 147.1 months (range 60-362 months), group I had 83 patients (63.9%), group IIa had 27 (20.8%), group IIb had 15 (11.5%) and group III had 5 (3.8%). The value of peak serum creatinine concentration was available for 57 patients. On the last clinical visit, eight out of 26 (30.7%) patients with peak serum creatinine equal to or higher than 1.5 mg/dl were in groups IIb and III versus one out of 31 (3.2%) patients with lower values (P < or = 0.007). Finally, six out of 28 patients (21%) whose renal function had normalized after 15 days from diagnosis were in groups IIb-III versus 8/82 (9.7%) whose renal function had normalized within 15 days (P = 0.18). After a mean period of follow-up of 12 years, 15% of a selected patient group had developed proteinuria, high blood pressure or chronic renal failure, and 21% had developed microalbuminuria. Peak serum creatinine during the acute stage was useful as a prognostic indicator. Patients whose renal function required more time to normalize did not have a worse outcome.

Acute poststaphylococcal glomerulonephritis superimposed on diabetic glomerulosclerosis

Acute poststaphylococcal glomerulonephritis superimposed on diabetic glomerulosclerosis

Clinical features and outcome of pediatric Wegener's granulomatosis

Wegener's granulomatosis (WG) is a predominantly small-vessel vasculitis associated with antineutrophil cytoplasmic antibodies (ANCAs). There are few reports describing its clinical features and outcome in children. We report on the experience at a single tertiary referral center over 21 years. We conducted a retrospective chart review of all patients diagnosed with WG at The Hospital for Sick Children between 1984 and 2005. Twenty-five patients were identified. Median age at diagnosis and median followup were 14.5 years and 32.7 months, respectively. Male-to-female ratio was 1:4. Median duration of symptoms before diagnosis was 2 months. Of 22 patients, 21 were ANCA positive during their disease course (classic ANCA 78.9%). Constitutional symptoms were the most common clinical feature at presentation (24 of 25). Glomerulonephritis was present in 22 patients at presentation. Only 1 of 11 patients who presented with or developed renal impairment had normalization of serum creatinine. Upper airway involvement occurred in 21 patients at presentation and 24 over followup; only 1 had subglottic stenosis. Twenty patients had initial pulmonary involvement, most commonly nodules (44%) and pulmonary hemorrhage (44%). Five patients required ventilation for pulmonary hemorrhage. Four patients (16%) had venous thrombotic events (VTEs). Treatment included prednisone (100%), cyclophosphamide (76%), azathioprine (40%), and methotrexate (32%). Pediatric WG typically presents in adolescence and has a female predominance. Glomerulonephritis and pulmonary disease are common at diagnosis and frequently present as a pulmonary-renal syndrome. Loss of renal function is common and rarely completely reversible. As in adults, children with WG are at risk of VTEs.

Kuwait Experience in Laparoscopic Donor Nephrectomy: First 80 Cases

Introduction Laparoscopic donor nephrectomy (LDN) has been adopted rapidly as it offers less postoperative pain, early recovery, and better cosmetic results compared with the open approach. This prospective study investigated the results of the first 80 LDN performed between May 2005 and May 2006, with regard to donor morbidity and effect on graft function. Patients and Methods LDN was attempted in 80 donors by one surgical team. Donors included 68 men and 12 women, ages 22 to 53 years, with body mass indices of 17.9 to 42.4. According to computed tomographic angiography, left nephrectomy was planned in 75 donors and right nephrectomy in 5. Results LDN was completed successfully in 74 (92.5%) and converted to open in 6 (7.5%) secondary to technical difficulties and operative bleeding. The mean operating time for LDN was 186.16 minutes (range, 95–260 minutes). Mean warm ischemia time (WIT) was 5.7 minutes (range 2–16 minutes). Mean hospital stay was 5.28 days (range, 3–14 days). Two donors (2.5%) were reexplored for postoperative bleeding. Renal function in all donors was satisfactory within 3 months of surgery. Immediate diuresis occurred in 76 (95%) recipients. Acute cellular rejection was diagnosed in 1 recipient. No association was observed between WIT, graft function, development of acute tubular necrosis (ATN), or rejection. Plasma creatinine normalization was clearly associated with donor age. Conclusions LDN was found to be a safe procedure with low postoperative morbidity and short recovery time for donors. It can potentially increase the donor pool.

Renal Function after Elective Infrarenal Aortic Aneurysm Repair in Patients with Pelvic Kidneys

Pelvic kidneys complicate aortic reconstructions because of increased risk of renal ischemia. Strategies for protection include shunting, cooling, and reliance on collaterals. A review identified two congenital pelvic kidney (not solitary) and five transplanted kidney patients who underwent elective abdominal aortic aneurysm repair. For congenital pelvic kidneys, topical cooling was used in one patient while no preservation was performed for the other patient. Three transplanted kidney patients were shunted, and one had endovascular repair. Postoperative creatinine values were compared to preoperative values. The two congenital pelvic kidney patients had no significant elevation of creatinine postoperatively. The transplanted kidney patient who underwent endovascular repair had no increase in creatinine postoperatively. All transplanted kidney patients who had open repair had significant but transient increase in creatinine postoperatively. Three patients who were shunted intraoperatively had normalization of creatinine. The patient who had persistent elevation of creatinine at discharge was not shunted. Aortorenal shunting or endovascular repair in transplanted pelvic kidney patients maintains renal function. For patients with congenital pelvic kidneys and adequate collaterals, cooling and collateral perfusion is usually sufficient. Though experience is limited, endovascular repair is likely to be superior to open repair in minimizing renal ischemia.

Reversibility of Renal Failure in Newly Diagnosed Patients with Multiple Myeloma Treated with High-Dose Dexamethasone Containing Regimens and the Impact of Novel Agents.

Introduction: Approximately 20% of patients with multiple myeloma present with renal failure (RF). It has been reported that with supportive measures and with antimyeloma treatment RF is reversible in 25 to 58% of patients. However, the impact of specific antimyeloma therapies on RF reversibility has not been clarified. Because high dose dexamethasone containing regimens are associated with a rapid myeloma control we performed a study to assess the impact of such regimens on RF reversibility.Patients and methods: Over the last decade 41 patients with RF, defined as a serum creatinine ≥2 mg/dL at the time of diagnosis, received primary treatment with high dose dexamethasone-based regimens in our Department. All patients were eligible fore assessment of reversibility of RF which was defined as a sustained decrease of serum creatinine to <1.5 mg/dl. Patients were separated into two groups. Group A: 26 patients who received VAD, VAD like regimens, Melphalan-high dose Dexamethasone or high-dose Dexamethasone alone and Group B: 15 patients who received high-dose Dexamethasone with thalidomide, with bortezomib or both.Results: Patients characteristics included: median age of 65 years, creatinine ≥4 mg/dL in 44%, Bence-Jones proteinuria ≥2 gr/day in 34%, ISS stage III in 76%, light chain only myeloma in 37%. Dialysis was required at presentation in 24% of patients. Response to treatment (EBMT criteria) was documented in 46% of patients of Group A and in 64% of patients of group B. The toxicity profile of novel agents-Dexamethasone combinations was similar to that seen in patients without RF. RF was reversed in 73% of all patients, in 69% of patients in group A and in 80% of patients in group B. After treatment only two patients initially requiring dialysis remained on renal replacement therapy. Multiple variables were assessed for their impact in RF reversibility: serum Creatinine ≥4 mg/dL and Bence-Jones proteinuria≥2 gr/day were associated with significantly lower probability of RF reversal (56% and 54% respectively). RF reversibility rate was 85% in patients who responded to treatment versus 56% in those who did not respond (p=0.046). The median time to RF reversal was 1.9 months for all patients, 2 months for patients of group A and 0.8 months for patients of group B (p=0.005).Conclusions: RF can be reversed in the majority of patients with newly diagnosed MM when they are treated with high-dose dexamethasone based regimens. Furthermore, normalization of serum creatinine occurs in one half of patients who do not meet criteria for objective response. Novel agents such as thalidomide and bortezomib or both can be safely combined with high dose dexamethasone for the treatment of Myeloma patients who present with RF and are associated with rapid rate of RF reversal.

A comparison of nicotine dose estimates in smokers between filter analysis, salivary cotinine, and urinary excretion of nicotine metabolites

RationaleNicotine uptake during smoking was estimated by either analyzing the metabolites of nicotine in various body fluids or by analyzing filters from smoked cigarettes. However, no comparison of the filter analysis method with body fluid analysis methods has been published.ObjectivesCorrelate nicotine uptake estimates between filter analysis, salivary cotinine, and urinary excretion of selected nicotine metabolites to determine the suitability of these methods in estimating nicotine absorption in smokers of filtered cigarettes.Materials and methodsA 5-day clinical study was conducted with 74 smokers who smoked 1–19 mg Federal Trade Commission tar cigarettes, using their own brands ad libitum. Filters were analyzed to estimate the daily mouth exposure of nicotine. Twenty-four-hour urine samples were collected and analyzed for nicotine, cotinine, and 3′-hydroxycotinine plus their glucuronide conjugates. Saliva samples were collected daily for cotinine analysis.ResultsEach method correlated significantly (p < 0.01) with the other two. The best correlation was between the mouth exposure of nicotine, as estimated by filter analysis, and urinary nicotine plus metabolites. Multiple regression analysis implies that saliva cotinine and urinary output are dependent on nicotine mouth exposure for multiple days. Creatinine normalization of the urinary metabolites degrades the correlation with mouth exposure.ConclusionsThe filter analysis method was shown to correlate with more traditional methods of estimating nicotine uptake. However, because filter analysis is less complicated and intrusive, subjects can collect samples easily and unsupervised. This should enable improvements in study compliance and future study designs.

Alcoholic cirrhosis-associated hepatorenal syndrome treated with vasoactive agents

A 35-year-old man with alcoholic cirrhosis, ascites and alcoholic hepatitis presented with new-onset renal insufficiency of unclear etiology after recovery from an episode of gastrointestinal bleeding. Renal function continued to worsen after cessation of diuretic therapy and initiation of volume resuscitation. Physical examination, abdominal ultrasound, liver tests, basic metabolic panel, abdominal paracentesis, renal function tests, 24-h urine collections. Type 1 hepatorenal syndrome (HRS). Intravascular volume resuscitation with normal saline and albumin followed by oral midodrine plus subcutaneous octreotide therapy. This regimen was continued until improvement and subsequent normalization of the serum creatinine.

Successful Treatment of Tumor Lysis Syndrome (TLS) with Low Doses of Rasburicase in Patients with Impaired Renal Function (IRF).

Background: TLS commonly occurs in patients with hematologic malignancies and is characterized by elevation of uric acid, potassium and phosphate and by hypocalcemia. A major complication is renal failure caused by precipitation of uric acid and / or calcium phosphate crystals. Standard treatment consists of hydration, correction of electrolyte disturbances and lowering of uric acid. Rasburicase, a recombinant urate oxidase, has proven to be highly effective in lowering serum uric acid levels, and its application is not restricted in patients with renal failure. Costs for a full seven-day course of rasburicase in the dosage recommended are high and amount to approximately 4800 €.Our question was whether patients with TLS and IRF can be treated cost-effectively with low doses of rasburicase.Patients and Methods: 26 patients (16 male, median age 65 yrs, range 16–76) with TLS and IRF were treated with 1–5 doses of rasburicase. Median number of rasburicase doses was 1, the median total dose given was 3 mg (range 1–15 mg) (0,038 mg/kg, range 0,016–0,19 mg/kg). 5 patients had acute leukemia, 13 had lymphoma, 5 had myeloproliferative disease and 3 had solid tumors. In 17 patients TLS was chemotherapy-induced, whereas 9 patients had spontaneous TLS. 10/26 patients had pre-existing chronic renal failure.TLS was classified and graded according to Cairo and Bishop. Laboratory TLS was diagnosed in 3 patients, 23 patients had clinical TLS (grade 1: n = 2, grade 2: n = 12, grade 3: n = 8, grade 4: n = 1).Results: The mean uric acid level before rasburicase administration was 15,35 mg/dl (range 10–22,2 mg/dl), the mean creatinine level was 3,29 mg/dl (range 1,41–8,61 mg/dl). The median rasburicase dose applied was 3,2 % of the dose recommended by the manufacturer (0,2 mg/kg for 5–7 days). Rasburicase was well tolerated by all patients without side effects. The mean serum uric acid level after rasburicase was 3,45 mg/dl (range 0,1–13 mg/dl). In 5 patients uric acid was above the upper limit of normal after rasburicase treatment; 3 of these patients had progressive malignant disease and died of disease progression, 2 of these patients had pre-existing chronic renal failure. Serum creatinine was within the normal range after rasburicase treatment in 16/26 patients. Of those patients without normalization of creatinine, 4 had progressive malignant disease and 5 had pre-existing chronic renal failure. No patient required renal replacement therapy.Conclusion: Treatment with low doses of rasburicase is effective in patients with TLS and IRF. Serum uric acid levels can be lowered effectively and renal function is improved in the majority of patients. Treatment costs can be reduced considerably (from 4800 € to approximately 160 €) by administering low doses of rasburicase. The effectiveness of low dose rasburicase was limited in patients with progressive malignant disease and ongoing tumor lysis and in patients with pre-existing chronic renal failure. Prospective studies with a standardized protocol for rasburicase administration are required to establish specific dosage regimens for subgroups of patients and to optimize cost-effective treatment.

URINE, HAIR, AND NAILS AS INDICATORS FOR INGESTION OF URANIUM IN DRINKING WATER

The concentration of uranium in urine, hair, and nails due to continuous exposure through ingestion of drinking water was studied. The study population consisted of 205 individuals living in 134 different households in southern Finland where drinking water is supplied from private drilled wells. The population was selected to include a broad range of uranium daily intake from drinking water (0.03-2,775 microg d). The uranium content in drinking water, urine (overnight collection), hair and nails was determined by ICPMS. Uranium in urine was corrected for the matrix effects by use of thallium as an internal standard and adjusted by creatinine normalization. Hair and toenail samples were rinsed to remove external contamination prior to acid digestion and analysis. The uranium content in all excretion pathways was correlated with the uranium intake, particularly at elevated levels (> or =10 microg d) where drinking water was the major source of exposure to uranium. The median of the individual uranium absorption factors for urine, hair, and toenails were fu=0.003, fh=0.003, and fn=4 x 10, respectively. The association between the different bioassays was examined. The absorption factor, f1, was calculated for the population with an intake above 10 microg d and was below 0.01 for 72% of the study persons (range 0.0002 to 0.070). No statistically significant difference in f1 values was found between women and men. However, the absorption factor was higher among younger (< 60 y) than older (> or =60 y) subjects and among people with a lower exposure (below 100 microg d) than among those that ingest over 100 microg d.