Thin basement membrane disease and acute renal failure secondary to gross hematuria and tubular necrosis

doi:10.1016/S0272-6386(00)70209-5

American Journal of Kidney Diseases

Volume 35, Issue 3, March 2000, Pages 533-536

https://doi.org/10.1016/S0272-6386(00)70209-5 Get rights and content

Abstract

A patient with thin basement membrane disease (TBMD), macroscopic hematuria, and acute renal failure is described. A renal biopsy showed massive occlusion of renal tubules by red blood cells and casts. This was accompanied by tubular cell damage consistent with acute tubular necrosis. The patient was receiving warfarin because of a history of deep venous thrombosis at the time he developed the acute renal failure. The possible relationship of the warfarin therapy to the TBMD, intratubular hemorrhage, and acute renal failure are discussed.

Section snippets

Case report

A 59-year-old man with a long history of microscopic hematuria (thought to be secondary to benign prostatic hypertrophy) and a serum creatinine of 1.0 mg/dL in the past year presented to his family physician with complaints of flank pain and gross hematuria. He was treated with ciprofloxacin for a suspected urinary tract infection. When after 10 days, this failed to resolve, he was referred to a urologist whom he had previously seen for microscopic hematuria and prostatic hypertrophy.

His

Discussion

Thin basement membrane disease was first recognized by Rogers et al in 1973.⁷ They described a kindred with persistent microscopic hematuria and no evidence of deafness or nephritis. All members of the family were asymptomatic, and there was no morbidity. Dische et al⁸ described 14 patients with TBMD presenting with hematuria or proteinuria. Several had abnormal renal function, and one had end-stage renal failure. They concluded that TBMD can be a progressive disease. A study from the

References (13)

CMG Nieuwhof et al.
Thin GBM nephropathy: Premature glomerular obsolescence is associated with hypertension and late onset renal failure
Kidney Int
(1997)
LA Hebert et al.
Loin pain-hematuria syndrome associated with thin glomerular basement membrane disease and hemorrhage into renal tubules
Kidney Int
(1996)
HS Lee et al.
Acute renal failure associated with hematuria in IgA nephropathy
Am J Kidney Dis
(1988)
J Duflot et al.
Macroscopic hematuria as a presenting manifestation of oliguric acute tubular necrosis
Am J Kidney Dis
(1993)
SG Goodman et al.
Safety and anticoagulation effect of a low-dose combination of warfarin and aspirin in clinically stable coronary artery disease
Am J Cardiol
(1994)
FE Dische et al.
Incidence of thin membrane nephropathy: Morphometric investigation of a population sample
J Clin Pathol
(1990)

There are more references available in the full text version of this article.

Cited by (48)

Nonvalvular atrial fibrillation in patients undergoing chronic hemodialysis. Should dialysis patients with atrial fibrillation receive oral anticoagulation?
2022, Nefrologia
Chronic kidney disease (CKD) is an independent risk factor for presenting atrial fibrillation (AF), which conditions an increased risk already present in CKD of suffering a thromboembolic event. And this risk is even higher in the hemodialysis (HD) population. On the other hand, in CKD patients and even more so in HD patients, the probability of suffering serious bleeding is also higher. Therefore, there is no consensus on whether or not to anticoagulate this population.
Taking as a model what is advised for the general population, the most common attitude among nephrologists has been to opt for anticoagulation, even though there is no randomized studies to support it.
Classically, anticoagulation has been done with vitamin K antagonists, at high cost for our patients: severe bleeding events, vascular calcification, and progression of nephropathy, among other complications.
With the emergence of direct-acting anticoagulants, a hopeful outlook was opened in the field of anticoagulation, as they were postulated as more effective and safer drugs than antivitamin K. However, in clinical practice, this has not been the case.
In this paper we review various aspects of AF and its anticoagulant treatment in the HD population.
La enfermedad renal crónica (ERC) es un factor de riesgo independiente para presentar fibrilación auricular (FA) lo que condiciona un incremento del riesgo ya presente en la ERC de sufrir un evento tromboembólico; y este riesgo es mayor aún en la población en hemodiálisis (HD). Por otro lado, en estos pacientes también es mayor la probabilidad de sufrir una hemorragia grave. Por ello, decidir si se debe anticoagular o no a un paciente con FA en diálisis es motivo de controversia entre la comunidad nefrológica.
Tomando como modelo lo aconsejado para la población general, la actitud más común entre los nefrólogos ha sido la de optar por la anticoagulación, pese a que no haya estudios randomizados que lo apoyen.
Clásicamente la anticoagulación se ha hecho con antagonistas de la vitamina K, con alto coste para nuestros pacientes: eventos hemorrágicos graves, calcificación vascular y progresión de la nefropatía entre otras complicaciones.
Con el surgimiento de los anticoagulantes de acción directa, se abrió un panorama esperanzador en el campo de la anticoagulación, al postularse como fármacos más eficaces y seguros que los antivitamina K. Sin embargo, en la práctica clínica, esto no ha sido así.
En esta revisión repasamos diversos aspectos de la FA y de su tratamiento anticoagulante en la población en HD.
IgA Nephropathy Is the Most Common Underlying Disease in Patients With Anticoagulant-Related Nephropathy
2022, Kidney International Reports
Citation Excerpt :
Similar to preceding series, kidney survival was poor, with almost one-third of the patients remaining on chronic dialysis at the end of follow-up. To the best of our knowledge, at the present time, only 3 case series (n = 63)1,3,4 and 29 case reports have described histologic information on patients with ARN.2,9–35 Of note, 37 of 92 (40%) cases were compatible with IgAN, comprising by far the most common underlying kidney disease associated to ARN.
Anticoagulant-related nephropathy (ARN) is a relatively novel recognized entity characterized by hematuria-associated acute kidney injury (AKI) in the context of overanticoagulation. Preexisting or underlying kidney disease seems to be a predisposing factor; however, few studies have described histologic findings in patients with ARN. We aimed to evaluate underlying kidney pathology in patients on oral anticoagulation who presented an episode of AKI with hematuria in whom a kidney biopsy was performed.
Retrospective observational multicenter case study in patients treated with oral anticoagulants who developed macroscopic or intense hematuria followed by AKI. Only patients with available kidney biopsy specimens were included. Histologic findings and clinical data throughout follow-up were analyzed.
A total of 26 patients were included with a median age of 75 years (62–80) and a follow-up period of 10.1 months. Of the patients, 80% were male, and most cases (92%) were on anticoagulation with vitamin K antagonists (VKAs). At admission, median serum creatinine (SCr) level was 4.2 mg/dl (2.8–8.2), median international normalized ratio (INR) 2.4 (1.5–3.4), and 11 patients (42%) required acute dialysis during hospitalization. Kidney biopsy results revealed that all patients except 1 had an underlying nephropathy: IgA nephropathy (IgAN) in 19, probable IgAN in 1, diabetic nephropathy in 3, nephrosclerosis in 1, and idiopathic nodular glomerulosclerosis in 1. At 12 weeks after discharge, only 6 subjects (24%) attained complete kidney recovery whereas 7 (28%) remained on chronic dialysis.
IgAN was the most common underlying kidney disease in our biopsy-proven series of ARN, in which a significant percentage of patients did not achieve kidney function recovery.
The change of renal functions after nonvitamin K oral anticoagulants in patients with atrial fibrillation
2021, IJC Heart and Vasculature
Citation Excerpt :
Furthermore, emerging evidences suggested that profuse glomerular hemorrhage was one of the major factors that contributed to acute kidney injury and possibly progressed to chronic kidney disease[16]. Glomerular hemorrhage with worsening of renal function as a result of excessive anticoagulation was initially reported in the literature in the early 2000 s[17]. Non-vitamin K oral anticoagulants (NOACs) were increasingly prescribed because of their better profiles of stroke prevention and bleeding outcomes ,and in particular, the reduced intracranial hemorrhage aspect when compared to warfarin[18].
Oral anticoagulants decreased stroke and mortality in atrial fibrillation patients. There have been cumulative data suggesting that some oral anticoagulants may exert favorable renal outcomes.The aim of this study is to evaluate the renal outcomes in patients with atrial fibrillation who took oral anticoagulant.
A Retrospective cohort study using hospital electronic database. Serum creatinine and GFR were collected at baseline and at 1 and 2 years.
Authors identified 734 patients with non-valvular AF who took oral anticoagulants. At the end of 2-year, the cumulative risk of significant GFR decline (eGFR drop > 30%) was 10.94% in warfarin group and 9.69% in NOACs group.The incidence rate of significant eGFR decline were comparable between NOACs and warfarin group which were 4.82 and 5.34 per 100-patient year respectively(HR 1.01 CI 0.62–1.66 , p- value 0.964).However, the adjusted mean eGFR change per year was significantly lower in NOAC group, especially rivaroxaban (coefficient 7.83 ,CI 4.44 11.22 , p-value < 0.001) and dabigatran (coefficient 6.22 ,CI 2.67–9.77 , p-value = 0.001) at 2 years.
Significant GFR decline was not uncommon in non-valvular AF patients who received anticoagulant. Among these, the proportion of patients who had significant eGFR decline(>30%) were comparable between NOACs and warfarin at 2 years. However, there is a significantly less mean eGFR decline per year in patients who receive NOACs, notably with dabigatran and rivaroxaban, than those who receive warfarin.The findings of this study should be interpreted in the context of patients included in this study.
CKD Progression in Medicare Beneficiaries With Nonvalvular Atrial Fibrillation Treated With Apixaban Versus Warfarin
2021, American Journal of Kidney Diseases
Comparing kidney disease progression among patients treated with direct oral anticoagulants (DOACs) versus warfarin has not been well studied. We hypothesized that apixaban would be associated with lower risks of progression of chronic kidney disease (CKD) and progression to incident kidney failure than warfarin in patients with atrial fibrillation (AF).
Retrospective cohort study.
Medicare recipients with stage 3, 4, or 5 CKD and incident AF who received a new prescription for apixaban or warfarin from 2013 through 2017.
Apixaban or warfarin.
Progression to incident kidney failure or, separately, to a more advanced stage of CKD.
Marginal structural cause-specific proportional hazards models with inverse probability weighting to estimate marginal hazard ratios (HRs) for each outcome. HRs compared apixaban to warfarin in intention-to-treat and censored-at-drug-switch analyses.
12,816 individuals met inclusion criteria (50.3% received apixaban; 49.7% received warfarin). After weighting, the mean age of the cohort was 80 ± 7 years, 51% were women, and 88% were White. Approximately 84% had stage 3, 15% had stage 4, and 1% had stage 5 CKD. In the intention-to-treat analysis, apixaban, relative to warfarin, was associated with an HR of developing incident kidney failure of 0.98 (95% confidence interval [CI], 0.79-1.22) and of CKD stage progression of 0.90 (95% CI, 0.82-0.99). Corresponding HRs for censored-at-drug-switch analyses were 0.81 (95% CI, 0.56-1.17) and 0.81 (95% CI, 0.70-0.92). Results were similar for a series of subgroup and sensitivity analyses.
CKD was defined based on diagnosis codes from claims; findings may not be generalizable to non-Medicare CKD populations.
Apixaban, compared with warfarin, was associated with lower risk of CKD stage progression, but not with incident kidney failure.
Warfarin-related nephropathy: A case report
2015, Revue de Medecine Interne
La néphropathie liée à la warfarine (WRN), de description récente, se définit par une atteinte organique et aiguë du parenchyme rénal en contexte de surdosage en anti-vitamine K (AVK) (international normalized ratio, INR > 3).
Nous rapportons l’observation d’un homme de 70 ans, dont la fonction rénale était antérieurement normale, et qui développait une WRN lors d’un surdosage franc. La récupération de la fonction rénale était très incomplète.
Chez un patient présentant une insuffisance rénale aiguë dans un contexte de traitement par AVK, un INR > 3 doit faire envisager le diagnostic de WRN, surtout s’il existe une hématurie. Le diagnostic de certitude est histologique (congestion des tubules rénaux par des hématies). L’administration de vitamine K reste la seule stratégie thérapeutique reconnue pour cette entité de mauvais pronostic rénal et associée à une augmentation de la mortalité.
Warfarin-related nephropathy (WRN) is a newly recognized entity, which is characterized by the occlusion of renal tubules by red blood cells following glomerular hemorrhage in a patient overexposed to warfarin (international normalized ratio > 3).
We report a 70-year-old man with no previous renal condition who developed WRN when his INR was > 12. He did not fully recover his previous renal function.
The diagnosis of WRN should be considered whenever INR exceeds 3 in patients exposed to warfarin, particularly in the presence of hematuria. Vitamin K is the only therapeutic option.
Anticoagulants and acute kidney injury: Clinical and pathology considerations
2014, Kidney Research and Clinical Practice
Citation Excerpt :
It has been suggested that warfarin can cause AKI by inducing glomerular hematuria with subsequent widespread tubular obstruction. This was first reported in a patient with severe warfarin coagulopathy and thin glomerular basement membrane (GBM) disease [18]. Later, evidence of a similar syndrome in a patient with inactive systemic lupus erythematosus (SLE), with an abnormally thick GBM, was reported [19].
We have recently identified a new clinical syndrome in patients receiving warfarin for anticoagulation therapy. This syndrome has been named warfarin-related nephropathy (WRN), and patients with chronic kidney disease (CKD) appear to be particularly susceptible. WRN is defined as an acute increase in international normalized ratio (INR) to >3.0, followed by evidence of acute kidney injury (AKI) within 1 week of the INR increase. AKI was defined as a sustained increase in serum creatinine of greater than or equal to 0.3 mg/dL. The AKI cannot be explained by any other factors, and the kidney biopsy demonstrates extensive glomerular hemorrhage with tubular obstruction by red blood cells (RBCs). Beyond AKI, WRN is a significant risk factor for mortality within the first 2 months of diagnosis and it accelerates the progression of CKD. We demonstrated that 5/6 nephrectomy in rats is a suitable experimental model to study WRN. Animals treated with warfarin showed an increase in serum creatinine and morphologic findings in the kidney similar to those in humans with WRN. Our recent evidence suggests that novel oral anticoagulants may induce AKI. Diagnosis of WRN may be challenging for a renal pathologist. A few cases with suspected WRN and pathologic considerations are described.

View all citing articles on Scopus

: Address reprint requests to Arthur B. Abt, MD, Department of Pathology, H083, M.S. Hershey Medical Center, PO Box 850, Hershey, PA 17033. E-mail: [email protected]

View full text

Case ReportsThin basement membrane disease and acute renal failure secondary to gross hematuria and tubular necrosis

Abstract

Section snippets

Case report

Discussion

Kidney Int

Kidney Int

Am J Kidney Dis

Am J Kidney Dis

Am J Cardiol

Incidence of thin membrane nephropathy: Morphometric investigation of a population sample

J Clin Pathol

Case Reports
Thin basement membrane disease and acute renal failure secondary to gross hematuria and tubular necrosis