Acute Renal Failure Following High Dose Excretory Urography in Dehydrated Patients

Previous studies (Vaidya VS, Shankar K, Lock EA, Bucci TJ, Mehendale HM. Toxicol Sci 74: 215–227, 2003; Korrapati MC, Lock EA, Mehendale HM. Am J Physiol Renal Physiol 289: F175–F185, 2005; Korrapati MC, Chilakapati J, Lock EA, Latendresse JR, Warbritton A, Mehendale HM. Am J Physiol Renal Physiol 291: F439–F455, 2006) demonstrated that renal repair stimulated by a low dose of S-(1,2-dichlorovinyl)l-cysteine (DCVC; 15 mg/kg ip) 72 h before administration of a normally lethal dose (75 mg/kg ip) protects mice from acute renal failure (ARF) and death (autoprotection). The present study identified the proteins indicative of DCVC-induced ARF and autoprotection in male Swiss Webster mice. Renal dysfunction and injury were assessed by plasma creatinine and histopathology, respectively. Whole-kidney homogenates were run on two-dimensional gel electrophoresis gels, and the expression of 18 common proteins was maximally changed (≥10-fold) in all the treatment groups and they were conclusively identified by liquid chromatography tandem mass spectrometry. These proteins were mildly downregulated after low dose alone and in autoprotected mice in contrast to severe downregulation with high dose alone. Glucose-regulated protein 75 and proteasome α-subunit type 1 were further investigated by immunohistochemistry for their localization in the kidneys of all the groups. These proteins were substantially higher in the proximal convoluted tubular epithelial cells in the low-dose and autoprotected groups compared with high-dose alone group. Proteins involved in energetics were downregulated in all the three groups of mice, leading to a compromise in cellular energy. However, energy is recovered completely in low-dose and autoprotected mice. This study provides the first report on proteomics of DCVC-induced ARF and autoprotection in mice and reflects the application of proteomics in mechanistic studies as well as biomarker development in a variety of toxicological paradigms.

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Editorials: ACUTE RENAL FAILURE AFTER EXCRETORY UROGRAPHY IN MULTIPLE MYELOMA

American Journal of Roentgenology ◽

10.2214/ajr.113.3.583 ◽

1971 ◽

Vol 113 (3) ◽

pp. 583-588 ◽

Cited By ~ 51

Author(s):

GEORGE H. MYERS ◽

DAVID M. WITTEN

Keyword(s):

Multiple Myeloma ◽

Renal Failure ◽

Acute Renal Failure ◽

Excretory Urography

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High-dose intravenous IgG treatment and acute renal failure

Intensive Care Medicine ◽

10.1007/bf01701493 ◽

1995 ◽

Vol 21 (3) ◽

pp. 288-289 ◽

Cited By ~ 5

Author(s):

B. Veber ◽

I. Mohammedi ◽

B. Gachot ◽

J. P. Bédos ◽

M. Wolff

Keyword(s):

Renal Failure ◽

Acute Renal Failure ◽

High Dose

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Effect of Severe Hypoalbuminemia on Myelosuppression and Other Toxicities of High Dose Melphalan and Autologous Stem Cell Transplantation in AL Amyloidosis Patients

Blood ◽

10.1182/blood.v126.23.5499.5499 ◽

2015 ◽

Vol 126 (23) ◽

pp. 5499-5499

Author(s):

Shin Yin Lee ◽

Robert Meehan ◽

John Mark Sloan ◽

Karen Quillen ◽

Dina Brauneis ◽

...

Keyword(s):

Renal Failure ◽

Acute Renal Failure ◽

Stem Cell ◽

Serum Albumin ◽

Albumin Level ◽

Control Group ◽

High Dose ◽

Al Amyloidosis ◽

Grade 3 ◽

High Dose Melphalan

Abstract Background: High-dose melphalan with autologous peripheral blood stem cell transplantation (HDM/SCT) has been shown to extend survival as well as to induce hematologic and clinical responses in selected patients with light chain (AL) amyloidosis. The most frequent toxicities of HDM are profound myelosuppression and gastrointestinal (GI) side effects. Studies have shown that 80% of melphalan is bound to plasma proteins (60% albumin bound) with ~20% free. We hypothesized that AL amyloidosis patients with severe nephrotic syndrome and profound hypoalbuminemia might have greater free melphalan fraction and more treatment-related toxicity. Methods: Patients with AL amyloidosis treated with HDM/SCT between 2011 and 2014 with severe hypoalbuminemia (SH), defined as a pre-transplant serum albumin of ≤2g/dL, were studied retrospectively. The stem cell transplant database was queried for patient demographic information, pre-transplant albumin level, HDM dose, renal function, pre-transplant 24-hour urine protein level, time to neutrophil and platelet engraftment, and treatment-related complications. Patients with AL amyloidosis treated between 2011 and 2012 without severe hypoalbuminemia, defined as serum albumin level of > 2g/dL (WSH), served as a control group. Results: Of the 84 patients with AL amyloidosis treated with HDM/SCT in this 4 year period, 16 (19%) with SH were identified. 41 patients were identified in the control group (WSH). There was no difference in the proportion of patients with all non-hematologic grade 3 or 4 adverse events between the groups. All patients suffered from expected grade 4 myelosuppression. The only statistically different non-hematologic grade 4 toxicity in SH was acute renal failure requiring temporary hemodialysis (n=4/16, 25% SH vs n=2/41, 5% WSH; p=0.05), with 1 subject eventually needing long term dialysis. There were no grade 4 mucositis or GI toxicities in either groups. The only statistically different grade 3 non-hematologic toxicity was lightheadedness (n=3/16, 19% SH vs n=0/41, 0% WSH; p=0.02). Conclusion: These data suggest that patients with severe hypoalbuminemia do not have more prolonged myelosuppression or GI toxicities when treated with HDM/SCT compared to those with higher serum albumin levels in AL amyloidosis. Grade 4 renal toxicity with acute renal failure requiring temporary hemodialysis (p=0.05) and grade 3 lightheadedness (p=0.02) occurred more commonly in SH than WSH group. In this retrospective study, we did not measure free melphalan concentrations in the blood. However, these data suggest that patients with severe hypoalbuminemia do not require adjustment of melphalan dosing. Figure 1. Figure 1. Disclosures No relevant conflicts of interest to declare.

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Successful rescue with leucovorin and thymidine in a patient with high-dose methotrexate induced acute renal failure

Cancer Chemotherapy and Pharmacology ◽

10.1007/s002800000269 ◽

2001 ◽

Vol 47 (6) ◽

pp. 537-540 ◽

Cited By ~ 19

Author(s):

Desirée van den Bongard ◽

Ron Mathôt ◽

Willem Boogerd ◽

Jan Schornagel ◽

Marcel Soesan ◽

...

Keyword(s):

Renal Failure ◽

Acute Renal Failure ◽

High Dose ◽

High Dose Methotrexate ◽

Dose Methotrexate

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Letter: High dose frusemide in established acute renal failure.

BMJ ◽

10.1136/bmj.4.5895.784-b ◽

1973 ◽

Vol 4 (5895) ◽

pp. 784-784 ◽

Cited By ~ 2

Author(s):

Y K Seedat

Keyword(s):

Renal Failure ◽

Acute Renal Failure ◽

High Dose

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Molecular mechanisms of enhanced renal cell division in protection against S-1,2-dichlorovinyl-l-cysteine-induced acute renal failure and death

AJP Renal Physiology ◽

10.1152/ajprenal.00418.2004 ◽

2005 ◽

Vol 289 (1) ◽

pp. F175-F185 ◽

Cited By ~ 15

Author(s):

Midhun C. Korrapati ◽

Edward A. Lock ◽

Harihara M. Mehendale

Keyword(s):

Renal Failure ◽

Acute Renal Failure ◽

Cell Division ◽

Cyclin D1 ◽

Renal Cell ◽

Low Dose ◽

Lethal Dose ◽

S Phase ◽

High Dose ◽

Priming Dose

Sustained activation of ERK 1/2 by a low dose (15 mg/kg ip) of S-1,2-dichlorovinyl-l-cysteine (DCVC) 72 h before administration of a lethal dose of DCVC (75 mg/kg ip) enhances renal cell division and protects mice against acute renal failure (ARF) and death (autoprotection). The objective of this study was to determine correlation among extent of S-phase DNA synthesis, activation of transcription factors, expression of G1/S cyclins, cyclin-dependent kinases (CDKs), and CDK inhibitors downstream of ERK 1/2 following DCVC-induced ARF in autoprotection. Administration of the lethal dose alone caused a general downregulation or an unsustainable increase, in transcriptional and posttranscriptional events thereby preventing G1-S transition of renal cell cycle. Phosphorylation of IκBα was inhibited resulting in limited nuclear translocation of NF-κB. However, cyclin D1 expression was high probably due to transcriptional cooperation of AP-1. Cyclin D1/cyclin-dependent kinase 4 (cdk4)-cdk6 system-mediated phosphorylation of retinoblastoma protein was downregulated due to overexpression of p16 at 24 h after exposure to the lethal dose alone. Inhibition of S-phase stimulation was confirmed by proliferating cell nuclear antigen assay (PCNA). This inhibitory response was prevented if the lethal dose was administered 72 h after the low priming dose of DCVC due to promitogenic effect of the low dose. NF-κB-DNA binding is not limited if mice were pretreated with the priming dose. Cyclin D1/cdk4-cdk6 expression stimulated by the priming dose of DCVC was unaltered even after the lethal dose in the autoprotected group, explaining higher phosphorylated-pRB and S-phase stimulation found in this group. These results were corroborated with PCNA immunohistochemistry. These findings suggest that the priming dose relieves the block on compensatory tissue repair by upregulation of promitogenic mechanisms, normally blocked by the high dose when administered without the prior priming dose.

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