warfarin and Proteinuria

Warfarin is widely prescribed for patients with atrial fibrillation. In addition to unexpected bleeding, allergic skin reaction is one of its uncommon adverse effects. We herein report an 89-year-old man who, after taking warfarin for 4 years, suffered extensive skin eruptions. The skin biopsy disclosed leukocytoclastic vasculitis. The causal relationship between skin lesions and warfarin was confirmed after re-challenge of warfarin. A literature review revealed only 13 such cases reported from 1980 to 2011. Clinicians should be aware of this potential adverse effect of warfarin.

Topics: Acute Kidney Injury; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Coronary Disease; Drug Eruptions; Heart Failure; Humans; Hypertension; Male; Proteinuria; Taiwan; Thrombophilia; Vasculitis, Leukocytoclastic, Cutaneous; Warfarin

Children with IgA nephropathy showing diffuse (>80%) mesangial proliferation are at high risk for end-stage renal failure (ESRF). A previous controlled trial showed that combination therapy consisting of prednisolone, azathioprine, heparin-warfarin, and dipyridamole early in the course of disease reduces immunologic renal injury and prevents the progression of sclerosed glomeruli. The objective of this study was to evaluate the long-term effectiveness of combination therapy in children with IgA nephropathy showing diffuse mesangial proliferation.. A secondary analysis of a multicenter, randomized, controlled trial involving 78 children with IgA nephropathy who received either 2-year combination therapy or heparin-warfarin and dipyridamole (control) therapy was conducted.. The median duration of observation was 10 years (range, 0.5 to 18). Two of 40 patients (5%) who received combination therapy and five of 34 patients (14.7%) who received control therapy developed ESRF. A Kaplan-Meier plot of renal survival showed that the outcomes of patients in the combined therapy group were better than those in the control therapy group (log-rank P = 0.03). The 10-year renal survival probability of each group was 97.1% (95% confidence interval, 81.4 to 99.6%) and 84.8% (95% confidence interval, 55.4 to 95.5%), respectively. The Cox proportional hazards model showed that the 2-year combination therapy was significantly associated with renal survival in both univariate and multivariate analyses.. Two-year combination therapy not only ameliorated the activity of the acute phase of nephritis but also improved the long-term outcome of severe childhood IgA nephropathy.

Topics: Adolescent; Anticoagulants; Azathioprine; Cell Proliferation; Child; Dipyridamole; Disease Progression; Drug Therapy, Combination; Female; Glomerulonephritis, IGA; Heparin; Humans; Immunosuppressive Agents; Japan; Kaplan-Meier Estimate; Kidney Failure, Chronic; Kidney Glomerulus; Male; Prednisolone; Proportional Hazards Models; Prospective Studies; Proteinuria; Risk Assessment; Risk Factors; Severity of Illness Index; Time Factors; Treatment Outcome; Warfarin

Two previous randomized controlled trials showed that treatment of severe childhood immunoglobulin A (IgA) nephropathy using prednisolone with azathioprine, heparin-warfarin, or dipyridamole prevented the increase of sclerosed glomeruli. Prednisolone alone, however, did not prevent further increase. These studies indicated the importance of immunosuppressants in the treatment. An additional pilot study using mizoribine instead of azathioprine enabled us to complete 2 years of combined regimen. It showed non-numerical inferior effectiveness compared with the azathioprine regimen. Further examination of the additional efficacy of warfarin and dipyridamole was required.. A randomized control trial of prednisolone and mizoribine with (group 1) or without (group 2) warfarin and dipyridamole was administered for treatment of 71 children with severe IgA nephropathy to evaluate the efficacy of additional warfarin and dipyridamole.. Thirty of 34 patients (88.2%) in group 1, and 27 of 36 patients (75.0%) showed the disappearance of proteinuria as defined by early morning urinary protein to creatinine ratio of < 0.2 during the 2-year treatment period. The cumulative disappearance rate of proteinuria determined by the Kaplan-Meier method showed that the disappearance rate of proteinuria was significantly higher in group 1 than in group 2 (log-rank P = 0.04). There was no significant difference in pathological findings, but there was a tendency of increase of global sclerosis in group1 which might be related to warfarin. Most of the adverse effects were related to prednisolone, but fortunately transient.. The balance between minimal benefits of warfarin/dipyridamole and potential adverse effects may be in favor of avoiding them in children with IgA nephropathy.

Topics: Adolescent; Biopsy; Child; Dipyridamole; Drug Therapy, Combination; Female; Glomerular Mesangium; Glomerulonephritis, IGA; Humans; Immunosuppressive Agents; Male; Prednisolone; Prospective Studies; Proteinuria; Ribonucleosides; Severity of Illness Index; Treatment Outcome; Warfarin

Children with IgA nephropathy showing diffuse (>80%) mesangial proliferation are at high risk for end-stage renal failure (ESRF). A previous controlled trial showed that combination therapy consisting of prednisolone, azathioprine, heparin-warfarin, and dipyridamole early in the course of disease reduces immunologic renal injury and prevents the progression of sclerosed glomeruli. The objective of this study was to evaluate the long-term effectiveness of combination therapy in children with IgA nephropathy showing diffuse mesangial proliferation.. A secondary analysis of a multicenter, randomized, controlled trial involving 78 children with IgA nephropathy who received either 2-year combination therapy or heparin-warfarin and dipyridamole (control) therapy was conducted.. The median duration of observation was 10 years (range, 0.5 to 18). Two of 40 patients (5%) who received combination therapy and five of 34 patients (14.7%) who received control therapy developed ESRF. A Kaplan-Meier plot of renal survival showed that the outcomes of patients in the combined therapy group were better than those in the control therapy group (log-rank P = 0.03). The 10-year renal survival probability of each group was 97.1% (95% confidence interval, 81.4 to 99.6%) and 84.8% (95% confidence interval, 55.4 to 95.5%), respectively. The Cox proportional hazards model showed that the 2-year combination therapy was significantly associated with renal survival in both univariate and multivariate analyses.. Two-year combination therapy not only ameliorated the activity of the acute phase of nephritis but also improved the long-term outcome of severe childhood IgA nephropathy.

Topics: Adolescent; Anticoagulants; Azathioprine; Cell Proliferation; Child; Dipyridamole; Disease Progression; Drug Therapy, Combination; Female; Glomerulonephritis, IGA; Heparin; Humans; Immunosuppressive Agents; Japan; Kaplan-Meier Estimate; Kidney Failure, Chronic; Kidney Glomerulus; Male; Prednisolone; Proportional Hazards Models; Prospective Studies; Proteinuria; Risk Assessment; Risk Factors; Severity of Illness Index; Time Factors; Treatment Outcome; Warfarin

No satisfactory treatment exists for IgA nephropathy (IgAN), especially in patients with severe histologic damage. Several trials using steroids combined with other therapies such as warfarin have demonstrated unremarkable results. We investigated the renoprotective effects of warfarin and steroids in IgAN patients with crescent formation.. Fifteen Japanese patients with IgAN were followed for up to 3 years. Crescent formation was recognized in over half of their glomeruli from renal biopsy specimens. Treatments consisted of either 0.5 mg/kg per day of prednisolone, or warfarin monotherapy. Blood pressure was controlled with long-acting calcium channel blockers and alpha-beta blockers. Serum creatinine and urinary protein excretion were evaluated at least every 2 months for 36 months.. Ten of the 15 patients completed the study. The serum creatinine levels had increased in both groups by 3 years, but significantly more so in the group treated with warfarin. However, they were not significantly different between the two groups as measured at the beginning and end of the study. Blood pressure for all patients in the study was maintained below 130/85 mmHg. Excluded from the study were 5 patients who experienced either peptic ulcers (n = 2, steroid group) or bleeding problems (n = 3, warfarin group).. These results suggest that corticosteroid therapy may assist in preventing deterioration of renal function in patients with IgAN accompanied by crescent formation. However, further study would be required to decide its usefulness.

Topics: Adolescent; Adult; Aged; Anticoagulants; Biopsy; Blood Pressure; Child; Creatinine; Female; Glomerulonephritis, IGA; Glucocorticoids; Humans; Kidney; Male; Middle Aged; Prednisolone; Proteinuria; Warfarin

The most appropriate treatment for patients with IgA nephropathy is controversial. Treatment with prednisolone, azathioprine, heparin-warfarin, and dipyridamole early in the course of disease may prevent immunologic renal injury in children with severe IgA nephropathy. To determine whether similar results can be obtained with a combination of just heparin-warfarin and dipyridamole, the effects of such treatment were compared to those of treatment with prednisolone, azathioprine, heparin-warfarin, and dipyridamole in 78 children with newly diagnosed IgA nephropathy showing diffuse mesangial proliferation. The patients were randomly assigned to receive either prednisolone, azathioprine, heparin-warfarin, and dipyridamole for 2 yr (group 1) or heparin-warfarin and dipyridamole for 2 yr (group 2). All of the 40 patients in group 1 and 34 of the 38 patients in group 2 completed the trial. The mean urinary protein excretion fell in group 1 patients (P < 0.0001), but remained unchanged in group 2 patients. The mean serum IgA concentration was reduced in group 1 patients (P = 0.0002), but was unchanged in group 2 patients. BP and creatinine clearance were normal at the end of the trial in all but one group 2 patient, who developed chronic renal insufficiency. The percentage of glomeruli showing sclerosis was unchanged in group 1 patients, but increased in group 2 patients (P = 0.006). The intensity of mesangial IgA deposits decreased in group 1 patients (P = 0.02), but remained unchanged in group 2 patients. In conclusion, the present study shows that treatment of children with severe IgA nephropathy with prednisolone, azathioprine, heparin-warfarin, and dipyridamole for 2 yr early in the course of disease reduces immunologic renal injury and prevents increase of sclerosed glomeruli.

Topics: Adolescent; Azathioprine; Blood Urea Nitrogen; Child; Dipyridamole; Drug Therapy, Combination; Glomerular Mesangium; Glomerulonephritis, IGA; Hematuria; Heparin; Humans; Immunoglobulin A; Microscopy, Fluorescence; Prednisolone; Proteinuria; Warfarin

Nine patients with biopsy-proven primary focal and segmental hyalinosis and sclerosis (FSHS) and steroid-resistant nephrotic syndrome were randomly allocated to either a period of 4-6 months of treatment (ciclosporin; (CS); 5-8 mg/kg/24 h and warfarin) or to a control period (warfarin alone) and then crossed over to the alternative for a further 4-6 months. Serum creatinine levels increased at a similar rate during treatment and control periods of observation. Serum albumin levels increased (p less than 0.05) and urinary protein excretion decreased (p less than 0.01) in association with the CS therapy compared to the control period of observation. No patient had complete resolution of the nephrotic syndrome. In primary FSHS, CS treatment is unlikely to produce complete resolution of nephrotic-range proteinuria but does significantly decrease urinary protein excretion.

Topics: Adolescent; Adrenal Cortex Hormones; Adult; Creatinine; Cyclosporins; Drug Resistance; Drug Therapy, Combination; Female; Glomerulonephritis; Glomerulosclerosis, Focal Segmental; Humans; Male; Middle Aged; Nephrotic Syndrome; Proteinuria; Randomized Controlled Trials as Topic; Serum Albumin; Warfarin

Topics: Anticoagulants; Heparin; Humans; Male; Middle Aged; Proteinuria; Renal Veins; Severity of Illness Index; Tomography, X-Ray Computed; Treatment Outcome; Venous Thrombosis; Warfarin

A wide variety of treatments, including tonsillectomy and steroid pulse therapy (TSP), are performed for the various stages of IgA nephropathy (IgAN) in Japan. However, the current status of treatments for IgAN patients in Japan is still unclear. The objective of the present study was to investigate the current status of treatments for IgAN patients.. A nationwide survey was conducted in 2008 by sending questionnaires to the 1,194 teaching hospitals of the Japanese Society of Nephrology (JSN) via Progressive Renal Diseases Research, Research on intractable disease, from the Ministry of Health, Labour and Welfare of Japan.. Among the total 376 hospitals (31.4 %) that responded, 188 hospitals (66.2 % in the internal medicine departments) performed TSP, out of which 137 hospitals (61.4 %) had begun to perform TSP in the period from 2004 to 2008. The following two major steroid pulse protocols in TSP were used: (1) three cycles over 3 consecutive weeks and (2) three cycles every 2 months. Approximately 68 % of pediatric hospitals (68 hospitals) performed combination therapy with prednisolone, azathioprine, heparin-warfarin and dipyridamole. The clinical remission rates for hematuria and proteinuria after TSP tended to be higher than those following other corticosteroid therapies. Almost all hospitals prescribed antiplatelet agents and renin angiotensin system inhibitor (RAS-I).. In addition to popular treatments such as antiplatelet agents and RAS-I, TSP is becoming a standard treatment for adult IgAN patients in Japan.

Topics: Adult; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Azathioprine; Child; Combined Modality Therapy; Glomerulonephritis, IGA; Heparin; Humans; Japan; Platelet Aggregation Inhibitors; Prednisolone; Proteinuria; Renin-Angiotensin System; Surveys and Questionnaires; Tonsillectomy; Warfarin

Atrial fibrillation (AF) substantially increases the risk of ischemic stroke, but this risk varies among individual patients with AF. Existing risk stratification schemes have limited predictive ability. Chronic kidney disease is a major cardiovascular risk factor, but whether it independently increases the risk for ischemic stroke in persons with AF is unknown.. We examined how chronic kidney disease (reduced glomerular filtration rate or proteinuria) affects the risk of thromboembolism off anticoagulation in patients with AF. We estimated glomerular filtration rate using the Modification of Diet in Renal Disease equation and proteinuria from urine dipstick results found in laboratory databases. Patient characteristics, warfarin use, and thromboembolic events were ascertained from clinical databases, with validation of thromboembolism by chart review. During 33,165 person-years off anticoagulation among 10,908 patients with AF, we observed 676 incident thromboembolic events. After adjustment for known risk factors for stroke and other confounders, proteinuria increased the risk of thromboembolism by 54% (relative risk, 1.54; 95% CI, 1.29 to 1.85), and there was a graded, increased risk of stroke associated with a progressively lower level of estimated glomerular filtration rate compared with a rate > or =60 mL x min(-1) x 1.73 m(-2): relative risk of 1.16 (95% CI, 0.95 to 1.40) for estimated glomerular filtration rate of 45 to 59 mL x min(-1) x 1.73 m(-2) and 1.39 (95% CI, 1.13 to 1.71) for estimated glomerular filtration rate <45 mL x min(-1) x 1.73 m(-2) (P=0.0082 for trend).. Chronic kidney disease increases the risk of thromboembolism in AF independently of other risk factors. Knowing the level of kidney function and the presence of proteinuria may improve risk stratification for decision making about the use of antithrombotic therapy for stroke prevention in AF.

Topics: Adult; Aged; Anticoagulants; Atrial Fibrillation; California; Chronic Disease; Comorbidity; Creatinine; Female; Fibrinolytic Agents; Follow-Up Studies; Glomerular Filtration Rate; Humans; Kidney Diseases; Male; Middle Aged; Proteinuria; Risk Factors; Stroke; Thromboembolism; Warfarin

Renal tubulointerstitial injury plays an important role in the development of IgA nephropathy (IgAN), the most common form of glomerulonephritis. Few currently in use biomarkers can sensitively detect the earliest signs of renal tubular injury, hindering our efforts to launch preventive and therapeutic measures for this disorder in a timely manner. Neutrophil gelatinase-associated lipocalin (NGAL) is an acute phase protein that is rapidly released from not only neutrophils but also a variety of cell types upon inflammation and tissue injury. Its small molecular size and protease resistance could render it an excellent biomarker of renal injury in IgAN. In this study, we tested this hypothesis by measuring urinary levels of NGAL, creatinine and N-acetyl-beta-D-glucosaminidase (NAG) in 40 healthy individuals and 70 IgAN patients with various disease severities. The urinary NGAL levels and NGAL/creatinine values were significantly upregulated in Lee grade III IgAN patients, in correlation with progressive glomerular mesangial proliferation and tubulointerstitial injury. Compared with urinary NAG levels, the urinary NGAL levels elevated much more drastically and can be readily detected even in Lee grade II IgAN patients when their NAG levels showed almost no change. Our findings suggest the promising use of urinary NGAL as an early biomarker for tubulointerstitial injury of IgA nephropathy and perhaps other types of renal disease in general.

Topics: Acetylglucosaminidase; Acute-Phase Proteins; Adolescent; Adult; Angiotensin-Converting Enzyme Inhibitors; Anticoagulants; Benzazepines; Biomarkers; Female; Glomerulonephritis, IGA; Humans; Kidney Tubules; Lipocalin-2; Lipocalins; Male; Mesangial Cells; Middle Aged; Phytotherapy; Plant Extracts; Predictive Value of Tests; Proteinuria; Proto-Oncogene Proteins; ROC Curve; Tripterygium; Warfarin

A 30-year-old woman with primary antiphospholipid syndrome (PAPS) presented with cerebral ischemia, thrombocytopenia, anemia and proteinuria. Administration of warfarin potassium, without concomitant corticosteroid administration, significantly improved all of these symptoms along with a decrease in the titers of antiCL-beta2-GP-I antibodies and a shortening of prolonged APTT. Therefore, the antiphospholipid antibodies in this patient could have been evoked by vitamin-K-dependent coagulation factors or plasma proteins which are assumed to undergo conformational changes exposing cryptic epitopes. This case report provides clues to the mechanisms underlying the production of antiphospholipid antibodies in patients with PAPS.

Topics: Adult; Anemia; Anticoagulants; Antiphospholipid Syndrome; beta 2-Glycoprotein I; Brain Ischemia; Cardiolipins; Female; Glycoproteins; Humans; Partial Thromboplastin Time; Proteinuria; Thrombocytopenia; Warfarin

Female Sprague-Dawley rats underwent right nephrectomy and 40 min left renal artery occlusion (RAO). After 15 min of reflow, polyethylene glycol 1000 (PEG1000) was infused to induce osmotic diuresis and to enable glomerular filtration rate (GFR) measurements. Urine was collected during a 90 min period, and the concentrations of PEG1000, albumin, IgG, IgM and fibrin(ogen)/degradation products (FIB) were assessed both in plasma and urine by radial immuno diffusion technique Groups of rats were subjected to saline + RAO, warfarin + RAO or sham-operation. GFR as measured by PEG1000 clearance averaged 0.61, 0.036 and 0.094 mL/min/100g BW/kidney in sham-operated, saline + RAO and warfarin + RAO rats, respectively. Urinary excretion of albumin and IgG increased substantially in both ischemic groups. IgM was not detected in any of the urine samples. FIB excretion was lowest in the saline + RAO group, possibly due to retention of FIB-containing obstructions in the tubules. Rats subjected to warfarin + RAO had significantly higher excretion of FIB. This result suggests that warfarin does not prevent the glomerular sieving of macromolecules in the glomerular filter, but reduces tubular obstruction by preventing fibrin formation, which may explain its positive effect on GFR.

Topics: Acute Kidney Injury; Animals; Anticoagulants; Female; Fibrin Fibrinogen Degradation Products; Glomerular Filtration Rate; Kidney; Proteinuria; Rats; Rats, Sprague-Dawley; Renal Artery Obstruction; Warfarin

The authors describe a 46-year-old Japanese woman who had Takayasu's arteritis associated with nephrotic syndrome due to mesangial proliferative glomerulonephritis with crescent. Although a few cases of focal and segmental mesangial proliferative glomerulonephritis associated with Takayasu's arteritis have been reported, nephrotic syndrome has not been reported previously in this situation.

Topics: Anti-Inflammatory Agents; Anticoagulants; Carotid Artery Diseases; Female; Glomerulonephritis, Membranoproliferative; Heparin; Humans; Middle Aged; Nephrotic Syndrome; Prednisolone; Proteinuria; Takayasu Arteritis; Warfarin

To achieve clinical remission, intensive therapy in active IgA nephropathy was conducted on a trial basis. Forty-five patients with active IgAN in which cellular crescents were present were divided into two groups. The patients in one group (Group A, N = 19) were treated with a combined regimen of steroid pulse, cyclophosphamide (4 months), dipyridamole (36 months) and warfarin. The patients in the other group (Group B, N = 26) were treated with tonsillectomy in addition to the same regimen as Group A. Three years after the initiation of treatment, proteinuria and hematuria had significantly decreased in both groups, and the renal function in Group B was significantly improved. Remission of proteinuria and hematuria was achieved in five patients (26.3%) and eight patients (42.1%), respectively, in Group A, and 14 patients (53.8%) and 20 patients (76.9%), respectively, in Group B. These results indicate that early intensive therapy combined with tonsillectomy in active IgAN is potentially of great benefit from both the medical and socioeconomic points of view.

Topics: Adolescent; Adult; Cyclophosphamide; Dipyridamole; Drug Therapy, Combination; Female; Follow-Up Studies; Glomerulonephritis, IGA; Hematuria; Humans; Male; Middle Aged; Proteinuria; Remission Induction; Tonsillectomy; Warfarin

Topics: Azathioprine; Blood Coagulation; Cadaver; Creatinine; Drug Evaluation; Fibrin; Graft Rejection; Hemoglobins; Humans; Immunosuppression Therapy; Kidney Function Tests; Kidney Transplantation; Prednisone; Proteinuria; Transplantation, Homologous; Urea; Warfarin

Topics: Aspirin; Blood Coagulation; Complement System Proteins; Diabetic Nephropathies; Dipyridamole; Fibrin; Fibrinogen; Glomerulonephritis; Hemolytic-Uremic Syndrome; Heparin; Humans; Iodine Radioisotopes; Kidney; Kidney Diseases; Kidney Glomerulus; Kidney Transplantation; Plasminogen; Proteinuria; Thrombosis; Transplantation, Homologous; Uremia; Warfarin

Topics: Adult; Blood Urea Nitrogen; Female; Heparin; Humans; Kidney Transplantation; Male; Middle Aged; Phlebography; Postoperative Complications; Proteinuria; Pulmonary Embolism; Renal Veins; Thrombosis; Transplantation, Homologous; Warfarin

Topics: Adult; Aged; Anticoagulants; Azathioprine; Blood Urea Nitrogen; Creatinine; Dipyridamole; Diuresis; Fibrinolytic Agents; Fluorescent Antibody Technique; Glomerulonephritis; Hemorrhage; Heparin; Humans; Kidney; Middle Aged; Phenindione; Prednisone; Proteinuria; Sulfinpyrazone; Warfarin

Topics: Adolescent; Anticoagulants; Child; Complement System Proteins; Female; Glomerulonephritis; Granulomatosis with Polyangiitis; Heparin; Humans; Kidney Diseases; Male; Nephrosis; Nephrotic Syndrome; Proteinuria; Purpura; Warfarin

Topics: Animals; Antigen-Antibody Reactions; Blood Coagulation; Electrons; Fibrin; Fluorescent Antibody Technique; Glomerulonephritis; Microscopy; Microscopy, Electron; Pathology; Proteinuria; Rabbits; Research; Warfarin