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      Acute kidney injury due to glomerular haematuria and obstructive erythrocyte casts associated with thrombocytopaenia and thin basement membrane disease: a case report

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          Abstract

          Background

          Acute kidney injury due to glomerular bleeding has been described with IgA nephropathy and supratherapeutic warfarin anticoagulation. There is usually demonstrable tubular obstruction by erythrocyte casts associated with acute tubular injury. Although severe thrombocytopaenia increases the risk of bleeding, most cases of haematuria have been ascribed to non-glomerular or urological bleeding without a direct link to acute kidney injury. We describe a patient with acute kidney injury due to glomerular bleeding and tubular injury related to severe thrombocytopaenia, who was subsequently found to have thin basement membrane disease.

          Case presentation

          A 56 year old man presented with macroscopic haematuria, acute kidney injury and a platelet count of 35 × 10 9/L, in the absence of anticoagulation. Urinalysis demonstrated an active urinary sediment. His kidney biopsy demonstrated extensive intraluminal erythrocyte casts associated with acute tubular injury, along with haemosiderin deposition suggestive of recurrent glomerular bleeding. There was no histological evidence of glomerular pathology but electron microscopy analysis demonstrated thin basement membrane disease and effacement of podocyte foot processes. During long term follow-up, thrombocytopaenia and intermittent haematuria persisted. At 9 months, the patient progressed to Stage 5 chronic kidney disease with the development of gross renal atrophy.

          Conclusion

          Recurrent macroscopic haematuria may be a risk factor for progressive renal injury in patients with thin basement membrane. The mechanism may be due to recurrent acute kidney injury from glomerular bleeding leading to repeated tubular damage. In the absence of anticoagulation, severe thrombocytopaenia may be a risk factor for heavy glomerular bleeding and acute kidney injury in these patients.

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          Most cited references13

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          Acute kidney injury during warfarin therapy associated with obstructive tubular red blood cell casts: a report of 9 cases.

          Acute kidney injury (AKI) during warfarin therapy usually is hemodynamic secondary to massive blood loss. Here, we report pathological findings in kidney biopsy specimens from 9 patients with warfarin overdose, hematuria, and AKI. Kidney biopsy specimens from patients on warfarin therapy with AKI were identified in our database within a 5-year period. Each kidney biopsy specimen was evaluated by using semiquantitative morphometric techniques, and medical history was reviewed for conditions explaining AKI. Biopsy specimens with morphological findings of active glomerulonephritis and active inflammatory lesions were excluded from the study. Biopsy specimens from 9 patients were selected. At presentation with AKI, each patient had an abnormal international normalized ratio (mean 4.4 +/- 0.7 IU) and increased serum creatinine level (mean, 4.3 +/- 0.8 mg/dL). Morphologically, each biopsy specimen showed evidence of acute tubular injury and glomerular hemorrhage: red blood cells (RBCs) in Bowman space and numerous occlusive RBC casts in tubules. Each biopsy specimen showed chronic kidney injury. Six of 9 patients did not recover from AKI. These data suggest that warfarin therapy can result in AKI by causing glomerular hemorrhage and renal tubular obstruction by RBC casts. Our experience suggests that this may be a potentially serious complication of warfarin therapy, especially in older patients with underlying chronic kidney injury.
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            AKI associated with macroscopic glomerular hematuria: clinical and pathophysiologic consequences.

            Hematuria is a common finding in various glomerular diseases. This article reviews the clinical data on glomerular hematuria and kidney injury, as well as the pathophysiology of hematuria-associated renal damage. Although glomerular hematuria has been considered a clinical manifestation of glomerular diseases without real consequences on renal function and long-term prognosis, many studies performed have shown a relationship between macroscopic glomerular hematuria and AKI and have suggested that macroscopic hematuria-associated AKI is related to adverse long-term outcomes. Thus, up to 25% of patients with macroscopic hematuria-associated AKI do not recover baseline renal function. Oral anticoagulation has been associated with glomerular macrohematuria-related kidney injury. Several pathophysiologic mechanisms may account for the tubular injury found on renal biopsy specimens. Mechanical obstruction by red blood cell casts was thought to play a role. More recent evidence points to cytotoxic effects of oxidative stress induced by hemoglobin, heme, or iron released from red blood cells. These mechanisms of injury may be shared with hemoglobinuria or myoglobinuria-induced AKI. Heme oxygenase catalyzes the conversion of heme to biliverdin and is protective in animal models of heme toxicity. CD163, the recently identified scavenger receptor for extracellular hemoglobin, promotes the activation of anti-inflammatory pathways, opening the gates for novel therapeutic approaches.
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              Warfarin Therapy That Results in an International Normalization Ratio above the Therapeutic Range Is Associated with Accelerated Progression of Chronic Kidney Disease

              Background/Aims: We had previously reported that acute kidney injury (AKI) in warfarin-treated chronic kidney disease (CKD) patients may occur shortly after an acute increase in the International Normalization Ratio (INR) >3.0 with formation of occlusive red blood casts. Recovery from this warfarin-associated AKI is poor. Here we investigated whether excessive warfarin therapy could accelerate the progression of CKD. Methods: We analyzed serum creatinine (SC) and INR in 103 consecutive CKD patients on warfarin therapy in our Nephrology program from 2005 to the present. Results: Forty-nine patients experienced at least 1 episode of INR >3.0. Of these, 18 patients (37%, Group 1) developed an unexplained increase in SC ≧0.3 mg/dl coincident with INR >3.0 (mean SC increase 0.61 ± 0.44 mg/dl); 31 patients (63%, Group 2) showed stable SC (mean SC change 0.04 ± 0.19 mg/dl). Subsequent CKD progression was accelerated in Group 1, but not in Group 2. The 2 groups were not different with respect to demographics, comorbidities, blood pressure, or therapies. However, African Americans were overrepresented in Group 1 (p = 0.035). Conclusions: Overanticoagulation is associated with faster progression of CKD in a high percentage of patients. Our results indicate the need for prospective trials. Nevertheless, we suggest that our findings are sufficiently compelling at this point to justi- fy extra caution in warfarin-treated CKD patients to avoid overanticoagulation.
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                Author and article information

                Contributors
                +61 3 9594 6666 , Andy.lim@monash.edu
                Susan.brown@monashhealth.org
                Ian.simpson@monashhealth.org
                John.dowling@monashhealth.org
                Journal
                BMC Nephrol
                BMC Nephrol
                BMC Nephrology
                BioMed Central (London )
                1471-2369
                30 October 2015
                30 October 2015
                2015
                : 16
                : 180
                Affiliations
                [ ]Department of Nephrology, Monash Medical Centre, 246 Clayton Road, Clayton, VIC 3168 Australia
                [ ]Department of Haematology, Monash Medical Centre, 246 Clayton Road, Clayton, VIC 3168 Australia
                [ ]Department of General Medicine, Monash Medical Centre, 246 Clayton Road, Clayton, VIC 3168 Australia
                [ ]Department of Anatomical Pathology, Monash Medical Centre, 246 Clayton Road, Clayton, VIC 3168 Australia
                [ ]Department of Medicine, Monash University, Monash Health, 246 Clayton Road, Clayton, VIC 3168 Australia
                Author information
                http://orcid.org/0000-0001-7816-4724
                Article
                176
                10.1186/s12882-015-0176-4
                4628439
                26519297
                9eee1758-5fe9-4bfb-9374-488f0b1d13e7
                © Lim et al. 2015

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 15 July 2015
                : 22 October 2015
                Categories
                Case Report
                Custom metadata
                © The Author(s) 2015

                Nephrology
                acute kidney injury,thrombocytopaenia,haematuria,erythrocyte casts,thin basement membrane disease,chronic kidney disease

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