Lupus Anticoagulant in Systemic Lupus Erythematosus: A Clinical and Renal Pathological Study Emanuel Farrugia, MD, Vicente E. Torres, MD, Dennis Gastineau, MD, Clement J. Michet, MD, and Keith E. Holley, MD • Circulating lupus anticoagulant (LA) is associated with thrombosis in large and small vessels. To determine how often the presence of LA is associated with thrombosis within the renal microcirculation, 33 patients with systemic lupus erythematosus (SLE), renal dysfunction, and LA were identified over a 25-year period (LA group) and 32 patients with renal SLE but with normal gross coagulation screen were matched for age, sex, and biopsy timing (C group). Prevalences of serositis, neuropsychiatric illness, leukopenia, thrombocytopenia, hemolysis, anti-OS-DNA elevation, and complement reduction were similar. Arthritis was less and biologic false-positive (BFP) syphilis serology more common in LA. More LA patients had thrombotic events (LA 39% "C 13%; P = 0.014); bleeding episodes, including postbiopsy, were similar. At biopsy, hypertension (LA 55%, C 41%), serum creatinine (mean ± SO: LA 186 ± 168 /.Imol/ L [2.1 ± 1.9 mg/dL]" C 150 ± 168 /.Imol/L [1.7 ± 1.9 mg/dL)) and proteinuria (LA 2.6 ± 3.1 g/24 h" C 3.1 ± 2.7) were similar. Lesions by World Health Organization (WHO) class, activity, and chronicity indices, as well as immunofluorescence (IF) and electron microscopy (EM) findings, were not significantly different. Occlusive glomerular, arteriolar, and arterial fibrin thrombi, along with varying degrees of renal thrombotic microangiopathy, were seen in five of 33 patients with LA, but zero of 32 C patients (P = 0.053); three of these five patients died soon after biopsy. Overall, mortality was not different between LA and C. We conclude that the majority of patients with SLE, renal dysfunction, and LA exhibit renal morphologic findings indistinguishable from patients without LA. However, a significant minority of LA patients have thrombotic microangiopathy in their biopsy, which is accompanied by a worse prognosis. © 1992 by the National Kidney Foundation, Inc. INDEX WORDS: Systemic lupus erythematosus; lupus anticoagulant; renal thrombotic microangiopathy.
C
IRCULATING or endogenous lupus anticoagulants (LA) are a group of immunoglobulins, usually IgG or IgM, that interfere to a variable extent in various phospholipid-dependent coagulation reactions. Circulating LA immunoglobulins are directed toward portions of the prothrombin activator complex, specifically recognizing epitopes on anionic phospholipids and a complex oflipid-bound human prothrombin. I ,2 Circulating LA or the distinct but closely related anticardiolipin antibodies can be detected in a variety of clinical situations, including up to 34% of systemic lupus erythematosus (SLE) patients.3,4 The presence of LA in vivo has been associated with certain clinical features, in particular, a predisposition to venous and arterial thrombotic vascular disorders in multiple organ systems and, in women, to recurrent miscarriage. 4 ,j The thrombotic effects of LA may also extend into the renal circulation. Renal artery and renal vein thrombosis, glomerular capillary thrombosis, and pregnancy-related acute renal failure caused by thrombotic microangiopathy have been reported in patients with circulating LA. 6- 10 Because these studies involved only small numbers of highly selected patients, we wanted to determine in a controlled fashion how often the presence of circulating LA is associated with thrombosis within the renal microcirculation in
a large group of patients with systemic lupus erythematosus (SLE) and renal dysfunction. PATIENTS AND METHODS
Patient Selection Included in the study were all patients meeting the following criteria: ( I) American Rheumatologic Association revised criteria for diagnosis of SLE, II (2) documented circulating LA, and (3) renal biopsy performed at the Mayo Clinic. Thirtythree such patients were identified over a 25-year period from 1964 to 1989 and comprised the LA group. This represented 6.9% of 478 biopsy-proven lupus nephritis patients at Mayo Clinic during this time period. All patients had adequate renal biopsy tissue for light microscopic analysis. Three patients each had more than one renal biopsy; however, only the biopsy performed at time of diagnosis of the LA was analyzed. Thirtytwo patients meeting criteria (I) and (3) listed above but withFrom the Division of Nephrology and Internal Medicine, Division of Hematology and Internal Medicine, Division of Rheumatology and Internal Medicine, and Section ofMedical Pathology, Mayo Clinic and Mayo Foundation, Rochester,
MN. Received April 7, 1992; accepted in revised form June 30, 1992. Supported by the Mayo Clinic/Mayo Foundation. Presented at the American Society ofNephrology, 23rd Annual Meeting, Washington, DC, 1990. Address reprint requests to Vicente E. Torres, MD, Division ofNephrology, Mayo Clinic, 200 First St, SW, Rochester, MN 55905. © 1992 by the National Kidney Foundation, Inc. 0272-6386/92/2005-0004$3.00/0
American Journal of Kidney Diseases, Vol XX, No 5 (November), 1992: pp 463-471
463
464
out evidence for a circulating LA were matched for age, sex, and timing of renal biopsy (C group). All LA and C patients met the revised criteria for SLE, even though several study patients were diagnosed with SLE before the criteria were formulated. Patients with lupus-like disease or drug-associated lupus syndromes were excluded. In all patients, the indication for renal biopsy was the presence of clinically evident renal dysfunction (eg, proteinuria, abnormal urinary sediment, and/ or elevated serum creatinine). The medical records were reviewed thoroughly and all data recorded and tabulated. Followup data were obtained via clinical records, telephone call follow-ups, autopsy reports, and death certificates.
Coagulation Studies All patients with circulating LA had a full coagulation profile performed at the Special Coagulation Laboratory at the Mayo Oinic as previously described. 12 In almost all of these patients, an abnormal gross coagulation screen was the clue that ultimately led to the diagnosis of LA. The latter was established according to previously described criteria, II including (I) prolongation of the plasma clot time (PCT) more than 5 seconds above the normal range (70 to 90 seconds), and the lack of correction to normal with a I : I mixture with normal plateletrich plasma; and (2) similar prolongation of the partial thromboplastin time (activated [APTT] or nonactivated [PTT]) with a similar lack of correction with a 1: 1 mixture of normal and test platelet-poor plasma. An additional criterion for the diagnosis of LA was lack of inhibition directed against a single coagulation factor. 13 Since 1982, the platelet neutralization procedure was also used to diagnose the LA. All patients in the control group had a normal gross coagulation screen (APTT, prothrombin time [PT]), although only seven of these patients also had a full coagulation profile. Serum anticardiolipin antibodies were measured in only a minority of study patients (LA group = 5, C group = 4). All of the latter patients presented to us after 1985.
Renal Histology Tissue specimens obtained by percutaneous or open renal biopsy were prepared for light microscopy and when available for immunofluorescent microscopy (IF) and electron microscopy (EM) as described elsewhere. 14 For light microscopy, sections were stained with hematoxylin and eosin, silver methenamine, Masson's trichrome, and periodic acid-Schiff. All sections were analyzed "blindly" by semiquantitative methods without knowledge of the clinical findings. On light microscopy, the following features were noted and tabulated: number of obsolescent and viable glomeruli, glomeruli with crescents, adhesions, polymorphonuclear exudation, intraglomerular thrombosis, capillary wall thickening, and subepithelial "spikes." Biopsies were classified using a modification of the International Study of Kidney Disease in Childhood and the World Health Organization (lSKDC-WHO) classification of glomerular involvement in SLE.IS To facilitate analysis of light microscopical findings, activity and chronicity indices were computed for each biopsy. The activity index comprised glomerular cell proliferation, leukocyte exudation, karyorrhexis/fibrinoid necrosis, cellular crescents, hyaline deposits, and interstitial cell infiltration (maximum score = 16). The chronicity index comprised glomerular sclerosis, fibrous
FARRUGIA ET AL
crescents, tubular atrophy, and interstitial fibrosis (maximum score = 8). The severity of intimal sclerosis, medial hypertrophy, arteriolar sclerosis, vasculitis, and thrombosis was graded on a scale of 0 to 3 (0 = absent, 1 = mild, 2 = moderate, 3 = severe). Intraglomerular thrombosis was only considered present if total or near total occlusion of a glomerular capillary lumen by fibrin was present.
Statistics The two-sample t test was used to compare continuous variables. Dichotomous variables were assessed by the chiSQuare test or the Fischer's exact test for small numbers. AP value less than 0.05 was considered statistically significant. Survival following biopsy was estimated using Kaplan-Meier curves. Comparison between groups was made using a twosample log-rank test.
RESULTS
Clinical Features
Patient characteristics in both the LA and C group are summarized in Table 1. With the exception of joint manifestations (LA 73%, C 97%, P = 0.013), the prevalence of serositis (pleuritis and/or pericarditis), mucocutaneous features (malar rash, discoid rash, oral ulceration, photosensitivity), and neuropsychiatric features (seizures and/or psychoses) were not different between patients with or without the circulating LA. Selected laboratory manifestations commonly associated with SLE at any time during the disease course were not statistically different between the LA and control groups: antinuclear antibody (ANA) positivity (LA 79%, C 94%), anti-DNA antibodies (LA 90%, C 89%), leukopenia (LA 30%, C 38%), thrombocytopenia (LA 42%, C 25%), and Coombs positive hemolytic anemia (LA 30%, C 19%). However, patients with LA were significantly more likely to possess a biologic false-positive Venereal Disease Reference LaboTable 1. Patient Characteristics
Study Group
LA
C
No. of patients Sex (M/F) Age at time of diagnosis (yr) Age at time of biopsy (yr) Follow-up period (mo)
33 21/12 30 ± 13 (15-63) 31 ± 14 (15-63) 60 ± 60 (1-241)
32 20/12 28 ± 12 (13-62) 30 ± 12 (14-64) 48 ± 53 (1-201)
NOTE. Values are mean
± SO (range).
PValue
NS NS NS NS NS
LUPUS ANTICOAGULANT AND RENAL DYSFUNCTION Table 2. Thromboembolic and Bleeding Events P
No. of Patients With:
LA
Thrombosis Bleeding
13/33 (39%)* 7/33 (21%)t
C
4/32 (13%):1: 6/32 (19%)§.
Value
0.014 NS
, Includes deep vein thrombosis lower extremities (9), cerebrovascular accident (3), pulmonary embolus (1), axillary artery occlusion (1), anterior spinal artery thrombosis (1). t Includes bleeding from ear, nose, and throat (2), gut (1), skin (2), and postrenal biopsy (3). :I: Includes deep vein thrombosis, lower extremities (3), pulmonary embolus (1), cerebrovascular accident (3). § Includes bleeding from gut (2), uterus (2), ear, nose, and throat (2), and postrenal biopsy (3).
ratory (BFP-VDRL) test than were control patients (LA 52%, C 11 %, P = 0.001). All patients with circulating LA had prolonged recalcification times of platelet-rich plasma (PCT). In the LA group of patients, mean values for the PCT, PTT, and PT were 169 seconds, 57 seconds, and 19 seconds, respectively. In C patients, mean values for the PTT and PT were 29 seconds and 14 seconds, respectively. Three patients with LA and a prolonged PT were on oral anticoagulants. The average value for the bleeding time was 6 minutes in the LA patients and 4 minutes in the C subjects. The prevalence of thromboembolic vascular events was significantly increased in the LA group as compared with the C group (Table 2). Thrombosis occurred in both large arteries and veins, with recurrent deep venous thrombophlebitis of the lower extremity being particularly common. In contrast to thrombotic events, the prevalence of bleeding episodes was not increased in patients with circulating LA compared with C patients without LA. Predisposing factors such as anticoagulant therapy, uremia, thrombocytopenia, or steroid therapy were identified in all patients that had a bleeding problem, regardless of the presence or absence of LA. Patients with LA underwent more open renal biopsies than C patients (7/33 v 1/32; P = 0.054). In all instances, open kidney biopsies were performed either when the percutaneous method had failed or when it was contraindicated because of severe hypertension, impaired kidney function, or thrombocytopenia. With the exception of one patient with circulating LA who was pretreated with 2 U of fresh frozen
465
plasma before the biopsy, no special therapy or maneuver was employed in LA patients to forestall postbiopsy bleeding complications. No difference between the two groups was noted with regard to the number and severity of bleeding complications following either percutaneous or open renal biopsy. Clinical data at the time of the kidney biopsy for the two groups of patients is summarized in Table 3. Findings on urine microscopy, serum creatinine levels, degree of proteinuria, and complement levels, as well as lupus serology at the time of biopsy, were similar in patients with or without LA. The LA group had a lower absolute platelet count than the C group; otherwise, the two groups were indistinguishable. Overall, both groups of patients were treated in a similar fashion with no difference noted in the proportion of patients receiving steroids or cytotoxic therapy. Only one patient (in the LA group) received plasmapheresis therapy. In the LA group, five patients died and three patients were alive on renal replacement therapy at the end of follow-up. In the C group, eight patients were dead and four patients were alive on dialysis or with a functioning allograft. Both groups experienced worse mortality than would be expected for individuals of like age and gender in Table 3. Clinical Data at Time of Kidney Biopsy LA
(n
= 33)
C (n
= 32)
PValue
18 (55%) 24(78%) 13 (39%)
13 (41%) 22 (72%) 18 (56%)
CHso < 25 U C3 < 70 U C. < 10 U
7/25 (28%) 7/16 (44%) 7/18 (39%)
9/20 (45%) 8/9 (89%) 7/9 (78%)
NS 0.04 NS
Proteinuria (g/24 h) Serum creatinine (J'mol/L) Platelet count (mm 3)
2.6 ± 3.1:1: (0-12.1) 186 ± 274 (0-1,070) 190 ± 96 (64-456)
3.1 ± 2.7 (0.2-11.3) 150 ± 168 (62-981) 274 ± 113 (125-496)
NS
Hypertension' Hematuriat RBC casts
NS NS NS
NS
C
IRCULATING or endogenous lupus anticoagulants (LA) are a group of immunoglobulins, usually IgG or IgM, that interfere to a variable extent in various phospholipid-dependent coagulation reactions. Circulating LA immunoglobulins are directed toward portions of the prothrombin activator complex, specifically recognizing epitopes on anionic phospholipids and a complex oflipid-bound human prothrombin. I ,2 Circulating LA or the distinct but closely related anticardiolipin antibodies can be detected in a variety of clinical situations, including up to 34% of systemic lupus erythematosus (SLE) patients.3,4 The presence of LA in vivo has been associated with certain clinical features, in particular, a predisposition to venous and arterial thrombotic vascular disorders in multiple organ systems and, in women, to recurrent miscarriage. 4 ,j The thrombotic effects of LA may also extend into the renal circulation. Renal artery and renal vein thrombosis, glomerular capillary thrombosis, and pregnancy-related acute renal failure caused by thrombotic microangiopathy have been reported in patients with circulating LA. 6- 10 Because these studies involved only small numbers of highly selected patients, we wanted to determine in a controlled fashion how often the presence of circulating LA is associated with thrombosis within the renal microcirculation in
a large group of patients with systemic lupus erythematosus (SLE) and renal dysfunction. PATIENTS AND METHODS
Patient Selection Included in the study were all patients meeting the following criteria: ( I) American Rheumatologic Association revised criteria for diagnosis of SLE, II (2) documented circulating LA, and (3) renal biopsy performed at the Mayo Clinic. Thirtythree such patients were identified over a 25-year period from 1964 to 1989 and comprised the LA group. This represented 6.9% of 478 biopsy-proven lupus nephritis patients at Mayo Clinic during this time period. All patients had adequate renal biopsy tissue for light microscopic analysis. Three patients each had more than one renal biopsy; however, only the biopsy performed at time of diagnosis of the LA was analyzed. Thirtytwo patients meeting criteria (I) and (3) listed above but withFrom the Division of Nephrology and Internal Medicine, Division of Hematology and Internal Medicine, Division of Rheumatology and Internal Medicine, and Section ofMedical Pathology, Mayo Clinic and Mayo Foundation, Rochester,
MN. Received April 7, 1992; accepted in revised form June 30, 1992. Supported by the Mayo Clinic/Mayo Foundation. Presented at the American Society ofNephrology, 23rd Annual Meeting, Washington, DC, 1990. Address reprint requests to Vicente E. Torres, MD, Division ofNephrology, Mayo Clinic, 200 First St, SW, Rochester, MN 55905. © 1992 by the National Kidney Foundation, Inc. 0272-6386/92/2005-0004$3.00/0
American Journal of Kidney Diseases, Vol XX, No 5 (November), 1992: pp 463-471
463
464
out evidence for a circulating LA were matched for age, sex, and timing of renal biopsy (C group). All LA and C patients met the revised criteria for SLE, even though several study patients were diagnosed with SLE before the criteria were formulated. Patients with lupus-like disease or drug-associated lupus syndromes were excluded. In all patients, the indication for renal biopsy was the presence of clinically evident renal dysfunction (eg, proteinuria, abnormal urinary sediment, and/ or elevated serum creatinine). The medical records were reviewed thoroughly and all data recorded and tabulated. Followup data were obtained via clinical records, telephone call follow-ups, autopsy reports, and death certificates.
Coagulation Studies All patients with circulating LA had a full coagulation profile performed at the Special Coagulation Laboratory at the Mayo Oinic as previously described. 12 In almost all of these patients, an abnormal gross coagulation screen was the clue that ultimately led to the diagnosis of LA. The latter was established according to previously described criteria, II including (I) prolongation of the plasma clot time (PCT) more than 5 seconds above the normal range (70 to 90 seconds), and the lack of correction to normal with a I : I mixture with normal plateletrich plasma; and (2) similar prolongation of the partial thromboplastin time (activated [APTT] or nonactivated [PTT]) with a similar lack of correction with a 1: 1 mixture of normal and test platelet-poor plasma. An additional criterion for the diagnosis of LA was lack of inhibition directed against a single coagulation factor. 13 Since 1982, the platelet neutralization procedure was also used to diagnose the LA. All patients in the control group had a normal gross coagulation screen (APTT, prothrombin time [PT]), although only seven of these patients also had a full coagulation profile. Serum anticardiolipin antibodies were measured in only a minority of study patients (LA group = 5, C group = 4). All of the latter patients presented to us after 1985.
Renal Histology Tissue specimens obtained by percutaneous or open renal biopsy were prepared for light microscopy and when available for immunofluorescent microscopy (IF) and electron microscopy (EM) as described elsewhere. 14 For light microscopy, sections were stained with hematoxylin and eosin, silver methenamine, Masson's trichrome, and periodic acid-Schiff. All sections were analyzed "blindly" by semiquantitative methods without knowledge of the clinical findings. On light microscopy, the following features were noted and tabulated: number of obsolescent and viable glomeruli, glomeruli with crescents, adhesions, polymorphonuclear exudation, intraglomerular thrombosis, capillary wall thickening, and subepithelial "spikes." Biopsies were classified using a modification of the International Study of Kidney Disease in Childhood and the World Health Organization (lSKDC-WHO) classification of glomerular involvement in SLE.IS To facilitate analysis of light microscopical findings, activity and chronicity indices were computed for each biopsy. The activity index comprised glomerular cell proliferation, leukocyte exudation, karyorrhexis/fibrinoid necrosis, cellular crescents, hyaline deposits, and interstitial cell infiltration (maximum score = 16). The chronicity index comprised glomerular sclerosis, fibrous
FARRUGIA ET AL
crescents, tubular atrophy, and interstitial fibrosis (maximum score = 8). The severity of intimal sclerosis, medial hypertrophy, arteriolar sclerosis, vasculitis, and thrombosis was graded on a scale of 0 to 3 (0 = absent, 1 = mild, 2 = moderate, 3 = severe). Intraglomerular thrombosis was only considered present if total or near total occlusion of a glomerular capillary lumen by fibrin was present.
Statistics The two-sample t test was used to compare continuous variables. Dichotomous variables were assessed by the chiSQuare test or the Fischer's exact test for small numbers. AP value less than 0.05 was considered statistically significant. Survival following biopsy was estimated using Kaplan-Meier curves. Comparison between groups was made using a twosample log-rank test.
RESULTS
Clinical Features
Patient characteristics in both the LA and C group are summarized in Table 1. With the exception of joint manifestations (LA 73%, C 97%, P = 0.013), the prevalence of serositis (pleuritis and/or pericarditis), mucocutaneous features (malar rash, discoid rash, oral ulceration, photosensitivity), and neuropsychiatric features (seizures and/or psychoses) were not different between patients with or without the circulating LA. Selected laboratory manifestations commonly associated with SLE at any time during the disease course were not statistically different between the LA and control groups: antinuclear antibody (ANA) positivity (LA 79%, C 94%), anti-DNA antibodies (LA 90%, C 89%), leukopenia (LA 30%, C 38%), thrombocytopenia (LA 42%, C 25%), and Coombs positive hemolytic anemia (LA 30%, C 19%). However, patients with LA were significantly more likely to possess a biologic false-positive Venereal Disease Reference LaboTable 1. Patient Characteristics
Study Group
LA
C
No. of patients Sex (M/F) Age at time of diagnosis (yr) Age at time of biopsy (yr) Follow-up period (mo)
33 21/12 30 ± 13 (15-63) 31 ± 14 (15-63) 60 ± 60 (1-241)
32 20/12 28 ± 12 (13-62) 30 ± 12 (14-64) 48 ± 53 (1-201)
NOTE. Values are mean
± SO (range).
PValue
NS NS NS NS NS
LUPUS ANTICOAGULANT AND RENAL DYSFUNCTION Table 2. Thromboembolic and Bleeding Events P
No. of Patients With:
LA
Thrombosis Bleeding
13/33 (39%)* 7/33 (21%)t
C
4/32 (13%):1: 6/32 (19%)§.
Value
0.014 NS
, Includes deep vein thrombosis lower extremities (9), cerebrovascular accident (3), pulmonary embolus (1), axillary artery occlusion (1), anterior spinal artery thrombosis (1). t Includes bleeding from ear, nose, and throat (2), gut (1), skin (2), and postrenal biopsy (3). :I: Includes deep vein thrombosis, lower extremities (3), pulmonary embolus (1), cerebrovascular accident (3). § Includes bleeding from gut (2), uterus (2), ear, nose, and throat (2), and postrenal biopsy (3).
ratory (BFP-VDRL) test than were control patients (LA 52%, C 11 %, P = 0.001). All patients with circulating LA had prolonged recalcification times of platelet-rich plasma (PCT). In the LA group of patients, mean values for the PCT, PTT, and PT were 169 seconds, 57 seconds, and 19 seconds, respectively. In C patients, mean values for the PTT and PT were 29 seconds and 14 seconds, respectively. Three patients with LA and a prolonged PT were on oral anticoagulants. The average value for the bleeding time was 6 minutes in the LA patients and 4 minutes in the C subjects. The prevalence of thromboembolic vascular events was significantly increased in the LA group as compared with the C group (Table 2). Thrombosis occurred in both large arteries and veins, with recurrent deep venous thrombophlebitis of the lower extremity being particularly common. In contrast to thrombotic events, the prevalence of bleeding episodes was not increased in patients with circulating LA compared with C patients without LA. Predisposing factors such as anticoagulant therapy, uremia, thrombocytopenia, or steroid therapy were identified in all patients that had a bleeding problem, regardless of the presence or absence of LA. Patients with LA underwent more open renal biopsies than C patients (7/33 v 1/32; P = 0.054). In all instances, open kidney biopsies were performed either when the percutaneous method had failed or when it was contraindicated because of severe hypertension, impaired kidney function, or thrombocytopenia. With the exception of one patient with circulating LA who was pretreated with 2 U of fresh frozen
465
plasma before the biopsy, no special therapy or maneuver was employed in LA patients to forestall postbiopsy bleeding complications. No difference between the two groups was noted with regard to the number and severity of bleeding complications following either percutaneous or open renal biopsy. Clinical data at the time of the kidney biopsy for the two groups of patients is summarized in Table 3. Findings on urine microscopy, serum creatinine levels, degree of proteinuria, and complement levels, as well as lupus serology at the time of biopsy, were similar in patients with or without LA. The LA group had a lower absolute platelet count than the C group; otherwise, the two groups were indistinguishable. Overall, both groups of patients were treated in a similar fashion with no difference noted in the proportion of patients receiving steroids or cytotoxic therapy. Only one patient (in the LA group) received plasmapheresis therapy. In the LA group, five patients died and three patients were alive on renal replacement therapy at the end of follow-up. In the C group, eight patients were dead and four patients were alive on dialysis or with a functioning allograft. Both groups experienced worse mortality than would be expected for individuals of like age and gender in Table 3. Clinical Data at Time of Kidney Biopsy LA
(n
= 33)
C (n
= 32)
PValue
18 (55%) 24(78%) 13 (39%)
13 (41%) 22 (72%) 18 (56%)
CHso < 25 U C3 < 70 U C. < 10 U
7/25 (28%) 7/16 (44%) 7/18 (39%)
9/20 (45%) 8/9 (89%) 7/9 (78%)
NS 0.04 NS
Proteinuria (g/24 h) Serum creatinine (J'mol/L) Platelet count (mm 3)
2.6 ± 3.1:1: (0-12.1) 186 ± 274 (0-1,070) 190 ± 96 (64-456)
3.1 ± 2.7 (0.2-11.3) 150 ± 168 (62-981) 274 ± 113 (125-496)
NS
Hypertension' Hematuriat RBC casts
NS NS NS
NS
