Effect of elevated serum uric acid on cisplatin-induced acute renal failure

2007 ◽  
Vol 292 (1) ◽  
pp. F116-F122 ◽  
Author(s):  
Carlos A. Roncal ◽  
Wei Mu ◽  
Byron Croker ◽  
Sirirat Reungjui ◽  
Xiaosen Ouyang ◽  
...  

Marked hyperuricemia is known to cause acute renal failure via intrarenal crystal deposition. However, recent studies suggest mild hyperuricemia may have vasoactive and proinflammatory effects independent of crystal formation. We therefore tested the hypothesis that mild hyperuricemia might exacerbate renal injury and dysfunction in a model of cisplatin-induced acute renal failure in the rat. Cisplatin was administered to normouricemic and hyperuricemic rats (the latter generated by administering the urate oxidase inhibitor, oxonic acid). Recombinant urate oxidase (rasburicase) was administered in a third group to assess the effect of lowering uric acid on outcomes. Other control groups include normal rats and hyperuricemic rats without cisplatin-induced injury. Cisplatin induced injury of the pars recta (S3) segment of the proximal tubule in association with a mild monocyte infiltration. Hyperuricemic rats showed significantly greater tubular injury and proliferation with significantly greater macrophage infiltration and increased expression of monocyte chemoattractant protein-1. However, renal function was not different between normouricemic and hyperuricemic rats with cisplatin injury. Treatment with rasburicase reversed the inflammatory changes and lessened tubular injury with an improvement in renal function (relative to the hyperuricemic group). No intrarenal crystals were observed in any groups. These data provide the first experimental evidence that uric acid, at concentrations that do not cause intrarenal crystal formation, may exacerbate renal injury in a model of acute renal failure. The mechanism may relate to a proinflammatory pathway involving chemokine expression with leukocyte infiltration.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1142-1142
Author(s):  
Donovan Strader ◽  
Michael S. Oholendt ◽  
Uday Popat ◽  
George Carrum ◽  
Helen E. Heslop

Abstract Significant reduction in renal function secondary to protein deposition in the renal tubules is a common occurrence among patients with plasma cell dyscrasias such as Multiple Myeloma (MM) and Amyloidosis undergoing HSCT. Conditioning chemotherapy and uric acid release following cellular lysis may worsen already compromised renal function, leading to acute renal failure. Rasburicase, a recombinant urate oxidase enzyme, has been approved by the U.S. Food and Drug Administration for the treatment and prevention of hyperuricemia associated with tumor lysis syndrome in pediatric patients with leukemia, lymphoma, and solid tumor malignancies undergoing chemotherapy. We hypothesized that prompt treatment of hyperuricemia with rasburicase may prevent uric acid nephropathy and improve renal function, obviating the need for dialysis and improving the eventual outcome. Six adults, four with MM and two with amyloidosis, with rising uric acid levels after high dose Melphalan (200mg/m2) were given a single dose of rasburicase (0.15 mg/kg). At baseline, all patients had rising serum creatinine [mean: 2.1 mg/dL (range: 0.9–4.5 mg/dL)], rising BUN [mean: 27.6 mg/dL (range: 1.3–70 mg/dL)], and declining creatinine clearance (CrCL) [mean: 50.5 ml/min (range: 16–75 ml/min)]. After one dose of rasburicase, renal function significantly improved according to CrCL at 48 hours [mean: 55.2 ml/min (range: 17–82 ml/min)] and continued to improve at five days [mean: 68.2 ml/min (range: 18–109 mg/dL)]. Baseline uric acid was elevated [mean: 8.61 mg/dL (range: 7–9.9 mg/dL)] and improved 24 hours after treatment with rasburicase [mean: 0.2 mg/dL (range: 0–0.6 mg/dL)]. None of the patients required renal replacement therapy. There were no serious adverse events associated with rasburicase therapy. We therefore conclude that a single dose of rasburicase is promising in improving deteriorating renal function post high dose chemotherapy in patients with compromised renal function; further controlled studies are warranted.


2021 ◽  
Author(s):  
Trevor W Tobin ◽  
John S Thurlow ◽  
Christina M Yuan

ABSTRACT Creatine products and sports supplements are widely used by active duty soldiers. These products are associated with both acute renal failure and elevated serum creatinine levels without renal injury. We present a case involving an active duty, 26-year-old Caucasian soldier who was evaluated in our clinic for elevated creatinine levels. This patient had no active medical problems and was noted on repeat labs to have significantly elevated creatinine levels. Subsequent investigations led us to conclude these values were not associated with renal injury and were due to ingested supplements.


1989 ◽  
Vol 61 (03) ◽  
pp. 522-525 ◽  
Author(s):  
M P Gordge ◽  
R W Faint ◽  
P B Rylance ◽  
H Ireland ◽  
D A Lane ◽  
...  

SummaryD dimer and other large fragments produced during the breakdown of crosslinked fibrin may be measured by enzyme immunoassay using monoclonal antibodies. In 91 patients with renal disease and varying degrees of renal dysfunction, plasma D dimer showed no correlation with renal function, whereas FgE antigen, a fibrinogen derivative which is known to be cleared in part by the kidney, showed a significant negative correlation with creatinine clearance. Plasma concentrations of D dimer were, however, increased in patients with chronic renal failure (244 ± 3l ng/ml) (mean ± SEM) and diabetic nephropathy (308 ± 74 ng/ml), when compared with healthy controls (96 ± 13 ng/ml), and grossly elevated in patients with acute renal failure (2,451 ± 1,007 ng/ml). The results indicate an increase in fibrin formation and lysis, and not simply reduced elimination of D dimer by the kidneys, and are further evidence of activated coagulation in renal disease. D dimer appears to be a useful marker of fibrin breakdown in renal failure.


Author(s):  
Р.И. Айзман ◽  
А.П. Козлова ◽  
Е.И. Гордеева ◽  
М.С. Головин ◽  
Г.А. Корощенко ◽  
...  

Цель - исследование влияния куркумы длинной и галеги восточной на осмо- и ионорегулирующую функции почек крыс при аллоксан-индуцированном сахарном диабете и острой почечной недостаточности в эксперименте. Методика. Эксперименты выполнены на самцах крыс Wistar (n=70) с моделью сахарного диабета (1-я серия) и острой почечной недостаточности (2-я серия). В обеих сериях животные были поделены на 3 группы: крыс 1-й группы содержали на стандартном корме, крысам остальных групп в корм добавляли куркуму (2-я группа) или галегу (3-я группа) (2% от массы корма). На 7-е сут эксперимента проводили исследование диуретической и ионоуретической функций почек натощак и после 5% водной нагрузки. Концентрацию ионов в моче и плазме определяли методом пламенной фотометрии; осмотическую концентрацию биологических жидкостей - методом криоскопии; биохимические показатели крови - колориметрическим методом. Результаты. У животных с сахарным диабетом фоновый диурез, а также экскреция натрия и калия были статистически значимо выше, чем у контрольных животных. При острой почечной недостаточности наблюдался более низкий уровень диуреза и ионоуреза, особенно после водной нагрузки. Прием куркумы и галеги вызывал улучшение осмо- и ионорегулирующей функции почек у крыс с сахарным диабетом, и практически не влиял на эти функции почек при острой почечной недостаточности. Заключение. При сахарном диабете оба фитопрепарата вызывали понижение концентрации глюкозы, креатинина, мочевины и улучшение ионно-осмотических показателей плазмы крови, при этом эффект куркумы был выражен отчетливее. При острой почечной недостаточности эти фитопрепараты не давали описанного эффекта. Aim. To study effects of the phytomedicines, Curcuma longa and Galega orientalis, on osmosis- and ion-regulating renal functions in rats with experimental diabetes mellitus (DM) and acute renal failure (ARF). Methods. Experiments were performed in two series on Wistar male rats (n=70) with modeled diabetes mellitus (series 1) and acute renal failure (series 2). In each series, the animals were divided into 3 groups, 1) rats of group 1 receiving a standard diet; 2) rats of groups 2 and 3 receiving a standard diet supplemented with turmeric or galega (2% of food weight), respectively. On the 7th day of the experiment, the diuretic and ionuretic renal function was studied in fasting state and after 5% water loading. Concentrations of ions in urine and plasma were determined by flame photometry; osmotic concentrations of biological fluids were measured by cryoscopy; blood biochemical parameters were measured by colorimetry. Results. In diabetic rats, background diuresis and sodium and potassium excretion were significantly higher than in the control animals. In rats with acute renal failure, diuresis and ionuresis were significantly lower, particularly after the water loading. Turmeric and galega supplementation improved the osmotic and ion-regulating renal function in diabetic rats and left practically unchanged these functions in rats with acute renal failure. Conclusion. In rats with diabetes mellitus, both herbal remedies reduced concentrations of glucose, creatinine, and urea and improved ion-osmotic parameters of blood plasma with a more pronounced effect of turmeric. In acute renal failure, these phytomedicines did not produce the described effects.


1998 ◽  
Vol 94 (1) ◽  
pp. 57-64 ◽  
Author(s):  
Saburo Horikawa ◽  
Koji Ito ◽  
Satoru Ikeda ◽  
Toshikazu Shibata ◽  
Shino Ishizuka ◽  
...  

2007 ◽  
Vol 107 (6) ◽  
pp. 892-902 ◽  
Author(s):  
Sachin Kheterpal ◽  
Kevin K. Tremper ◽  
Michael J. Englesbe ◽  
Michael O’Reilly ◽  
Amy M. Shanks ◽  
...  

Background The authors investigated the incidence and risk factors for postoperative acute renal failure after major noncardiac surgery among patients with previously normal renal function. Methods Adult patients undergoing major noncardiac surgery with a preoperative calculated creatinine clearance of 80 ml/min or greater were included in a prospective, observational study at a single tertiary care university hospital. Patients were followed for the development of acute renal failure (defined as a calculated creatinine clearance of 50 ml/min or less) within the first 7 postoperative days. Patient preoperative characteristics and intraoperative anesthetic management were evaluated for associations with acute renal failure. Thirty-day, 60-day, and 1-yr all-cause mortality was also evaluated. Results A total of 65,043 cases between 2003 and 2006 were reviewed. Of these, 15,102 patients met the inclusion criteria; 121 patients developed acute renal failure (0.8%), and 14 required renal replacement therapy (0.1%). Seven independent preoperative predictors were identified (P < 0.05): age, emergent surgery, liver disease, body mass index, high-risk surgery, peripheral vascular occlusive disease, and chronic obstructive pulmonary disease necessitating chronic bronchodilator therapy. Several intraoperative management variables were independent predictors of acute renal failure: total vasopressor dose administered, use of a vasopressor infusion, and diuretic administration. Acute renal failure was associated with increased 30-day, 60-day, and 1-yr all-cause mortality. Conclusions Several preoperative predictors previously reported to be associated with acute renal failure after cardiac surgery were also found to be associated with acute renal failure after noncardiac surgery. The use of vasopressor and diuretics is also associated with acute renal failure.


1989 ◽  
Vol 35 (1) ◽  
pp. 84-89 ◽  
Author(s):  
Helen N. Georgaki-Angelaki ◽  
David B. Steed ◽  
Cyril Chantler ◽  
George B. Haycock

2002 ◽  
Vol 103 (s2002) ◽  
pp. 434S-437S ◽  
Author(s):  
Masanori TAKAOKA ◽  
Mikihiro YUBA ◽  
Toshihide FUJII ◽  
Mamoru OHKITA ◽  
Yasuo MATSUMURA

We investigated whether the treatment with 17β-oestradiol has renal protective effects in male rats with ischaemic acute renal failure (ARF). We also examined if the effect of 17β-oestradiol is accompanied by suppression of enhanced endothelin-1 production in postischaemic kidneys. Ischaemic ARF was induced by clamping the left renal artery and vein for 45min followed by reperfusion, 2 weeks after contralateral nephrectomy. Renal function parameters such as blood urea nitrogen, plasma creatinine and creatinine clearance were measured to test the effectiveness of the steroid hormone. Renal function in ARF rats markedly decreased 24h after reperfusion. The ischaemia/reperfusion-induced renal dysfunction was dose-dependently improved by pretreatment with 17β-oestradiol (20 or 100µg/kg, intravenously). Histopathological examination of the kidney of untreated ARF rats revealed severe lesions, such as tubular necrosis, proteinaceous casts in tubuli and medullary congestion, all of which were markedly improved by the higher dose of 17β-oestradiol. In addition, endothelin-1 content in the kidney after the ischaemia/reperfusion increased significantly by approx. 2-fold over sham-operated rats, and this elevation was dose-dependently suppressed by the 17β-oestradiol treatment. These results suggest that oestrogen exhibits protective effects against renal dysfunction and tissue injury induced by ischaemia/reperfusion, possibly through the suppression of endothelin-1 overproduction in postischaemic kidneys.


Sign in / Sign up

Export Citation Format

Share Document