The Management of Renal Scleroderma Experience with Dialysis, Nephrectomy and Transplantation
E. CARWILE LeROY, M.D. Charles ton, South Carolina ROY M. FLEISCHMANN,
M.D.
l
New York, New York
In 25 of 100 patients with scleroderma seen over a five year period irreversible renal failure developed; renal support was instituted in 17. Ten of I7 received peritoneal or hemodialysis, one survived. The remaining seven received hemodialysis plus nephrectomy; three survived. Two of these three underwent renal transplantation; one survived. This experience is presented to encourage improvement of these and other technics to increase the survival rate in the otherwise uniformly fatal renal failure associated with scleroderma (systemic
sclerosis).
Of the various manifestations
of scleroderma (systemic sclerosis), renal involvement is the most acute in onset and, without intervention, invariably fatal in outcome [ 1,2]. The structural basis for renal involvement is a distinctive microvascular lesion characterized by proliferation and fibrosis. This lesion is clinically undetectable prior to the onset of renal failure; therefore, prevention and early detection of renal involvement are not presently possible [3]. The therapy of renal failure has been directed at the prevention of renal vasoconstriction, inhibition of the renin-angiotensin system, peritoneal and hemodialysis, and renal transplantation. These attempts have, of necessity, been applied only to patients with fully developed renal failure in scleroderma. Successful therapy of renal failure in the acutely and chronically ill patient requires substantial multidisciplinary cooperation. Experience in the management of 25 patients with renal scleroderma over a five year period is the subject of this communication. From the Division of Rheumatic Diseases, Columbia Presbyterian Medical Center, New York, New York; and the Division of Rheumatology and Immunology, Department of Medicine, Medical University of South Carolina, Charleston, South Carolina.This study was supported by grants from the NIH (AM18904), RGK Foundation, S. & C. Lifschultz Foundation, T. R. Berner, S.C. State Appropriation for Research, Health Sciences Foundation, Medical University of South Carolina, and the Arthritis Foundation, New York and South Carolina Chapters. Requests for reprints should be addressed to Dr. E. Carwile LeRoy, Division of Rheumatology and Immunology, Department of Medicine, Medical University of South Carolina, 171 Ashley Avenue, Charleston, South Carolina 29403. Manuscript accepted January 11. 1978. Present address: Division of Rheumatology, St Paul’s Hospital, Dallas Texas 75234. l
974
June 1978
METHODS Patient Selection.
One hundred consecutive
by one or both of us between
patients
with scleroderma
seen
July 1, 1970, and June 30, 1975, were reviewed
for this report. The diagnosis of scleroderma was defined by the presence of indurated skin and involvement of one or more other organs with features characteristic of the disease. Renal failure developed in 25 of these 100 patients with scleroderma during the observation period. Highly selective patient referral patterns prevent any meaningful estimate of the incidence or prevalence of renal involvement in the population with scleroderma. Of the 25 patients with renal scleroderma, 22 were female (18 white, four black) and three were male (all white). The mean age of diagnosis was 42 years (range 19 to 61 years); the median age, 45 years. Age at onset of symptoms was indefinite due to the variable history of Raynaud’s syndrome prior to diagnosis. System Involvement. Renal involvement was defined as a creatinine clearance of less than 50 cc/min; azotemia was defined as a blood urea nitrogen of greater than 40 mg/dl on repeated determinations. Proteinuria (2+
The American Journal of Medlclne
Volume 64
MANAGEMENT OF RENAL SCLERODERMA-LeROY ET AL.
or greater on repeated determinations), hypertension (systolic > 140 mm Hg or diastolic >90 mm Hg on repeated determinations) and abnormal urinary, sediment (>5 white blood cells/hpf or >2 red blood cells/hpf on repeated determinations) were monitored as possible indicators of renal involvement. Pulmonary involvement was defined as one or more of the following: (1) the presence of pleurisy (pleuritic chest pain, pleural friction rub or pleural effusion not due to other causes), (2) interstitial infiltrates on chest roentgenogram, (3) decreased diffusion capacity by D,CO or arterial oxygen tension (~0~) at rest and exercise, (4) indirect (increased pulmonic second and/or right ventricular pattern on electrocardiogram or direct (by right heart catheterization) demonstration of pulmonary hypertension and (5) restrictive lung disease (vital capacity 80 per cent expected). Cardiac involvement was defined as (1) percarditis (pericardial friction rub, pericardial effusion (echo or angiocardiogram), cardiomegaly by chest roentgenogram or persistent electrocardiographic abnormalities not due to other causes. These criteria are similar to those of other investigators I41. Anemia was defined as a hemoglobin concentration of 5 per cent, a negative Coombs’ test and fragmented erythrocytes on peripheral blood smear. RESULTS
The prevalence of features suggestive of renal involvement in the 100 patients with scleroderma, shown in Table I, is similar to that previously published. With the exception of abnormal urinary sediment, these manifestations do not commonly occur alone. Moreover, the presence of any single feature could not be shown to be predictive of present or future renal involvement, since renal scleroderma did not develop in 40 per cent of patients with hypertension or proteinuria and 70 per cent with abnormal urinary sediment over the five year period of observation. It was distinctly unusual to observe patients with proteinuria alone (one of 100) hypertension alone (three of 100) or urinary sediment alone (seven of 100). No patient with azotemia alone was seen. Conversely, the presence of several or all of these features constitutes the syndrome of renal scleroderma and is not predictive. In the 25 patients with renal scleroderma, the appearance of proteinuria, hypertension, azotemia and abnormal urinary sediment was accompanied by clinically obvious renal failure within a period of several days to one month. These and associated features are shown in Table II. The frequency of organ involvement in these patients is higher than that in most previously published series of patients with scleroderma (cf. Table II and [3,5-71, due to the referral of many patients with major organ involvement.
TABLE I
Features of Renal Involvement in 100 Patients with Scleroderma Female:male = 6:l White:black = 4:l Patients (no.)
Features Proteinuria (2+ or >) Hypertension* Malignant hypertension+ Azotemia (blood urea nitrogen > 40 mg/dl) Abnormal urinary sedimentt
29 39 8 26 34 52
Any feature present
A value exceeding either 140 (systolic) or 90 (diastolic) mm Hg on repeated determinations was considered positive. t Defined as diastolic blood pressure > 140 mm Hg, papilledema or encephalopathy. t Defined as >2 red blood cells or 5 white blood cells/hpf or casts on repeated determinations. l
Definite renal involvement was most reliably defined as blood urea nitrogen greater than 40 mg/dl or a creatinine clearance less than 50 cc/min. In all 25 patients in whom these measurements were observed irreversible oliguric renal failure developed. Magnification renal arteriography was carried out in 18 of 25 patients and showed definite interlobular artery lesions in 16 [3]. In general, arteriographic changes were not observed early in the development of renal scleroderma and were not predictive. Cardiac and pulmonary involvement (as defined in “Methods”) was observed in 95 per cent and 80 per cent of the 25 patients with renal scleroderma, respectively. Thus, the clinical setting is in many ways analogous to that in accelerated hypertension. In many
TABLE II
Characteristics of 100 Patients with Scleroderma
Characteristic Cardiac involvement* Pulmonary involvement* Death Hypertension Anemia (hemoglobin
E. CARWILE LeROY, M.D. Charles ton, South Carolina ROY M. FLEISCHMANN,
M.D.
l
New York, New York
In 25 of 100 patients with scleroderma seen over a five year period irreversible renal failure developed; renal support was instituted in 17. Ten of I7 received peritoneal or hemodialysis, one survived. The remaining seven received hemodialysis plus nephrectomy; three survived. Two of these three underwent renal transplantation; one survived. This experience is presented to encourage improvement of these and other technics to increase the survival rate in the otherwise uniformly fatal renal failure associated with scleroderma (systemic
sclerosis).
Of the various manifestations
of scleroderma (systemic sclerosis), renal involvement is the most acute in onset and, without intervention, invariably fatal in outcome [ 1,2]. The structural basis for renal involvement is a distinctive microvascular lesion characterized by proliferation and fibrosis. This lesion is clinically undetectable prior to the onset of renal failure; therefore, prevention and early detection of renal involvement are not presently possible [3]. The therapy of renal failure has been directed at the prevention of renal vasoconstriction, inhibition of the renin-angiotensin system, peritoneal and hemodialysis, and renal transplantation. These attempts have, of necessity, been applied only to patients with fully developed renal failure in scleroderma. Successful therapy of renal failure in the acutely and chronically ill patient requires substantial multidisciplinary cooperation. Experience in the management of 25 patients with renal scleroderma over a five year period is the subject of this communication. From the Division of Rheumatic Diseases, Columbia Presbyterian Medical Center, New York, New York; and the Division of Rheumatology and Immunology, Department of Medicine, Medical University of South Carolina, Charleston, South Carolina.This study was supported by grants from the NIH (AM18904), RGK Foundation, S. & C. Lifschultz Foundation, T. R. Berner, S.C. State Appropriation for Research, Health Sciences Foundation, Medical University of South Carolina, and the Arthritis Foundation, New York and South Carolina Chapters. Requests for reprints should be addressed to Dr. E. Carwile LeRoy, Division of Rheumatology and Immunology, Department of Medicine, Medical University of South Carolina, 171 Ashley Avenue, Charleston, South Carolina 29403. Manuscript accepted January 11. 1978. Present address: Division of Rheumatology, St Paul’s Hospital, Dallas Texas 75234. l
974
June 1978
METHODS Patient Selection.
One hundred consecutive
by one or both of us between
patients
with scleroderma
seen
July 1, 1970, and June 30, 1975, were reviewed
for this report. The diagnosis of scleroderma was defined by the presence of indurated skin and involvement of one or more other organs with features characteristic of the disease. Renal failure developed in 25 of these 100 patients with scleroderma during the observation period. Highly selective patient referral patterns prevent any meaningful estimate of the incidence or prevalence of renal involvement in the population with scleroderma. Of the 25 patients with renal scleroderma, 22 were female (18 white, four black) and three were male (all white). The mean age of diagnosis was 42 years (range 19 to 61 years); the median age, 45 years. Age at onset of symptoms was indefinite due to the variable history of Raynaud’s syndrome prior to diagnosis. System Involvement. Renal involvement was defined as a creatinine clearance of less than 50 cc/min; azotemia was defined as a blood urea nitrogen of greater than 40 mg/dl on repeated determinations. Proteinuria (2+
The American Journal of Medlclne
Volume 64
MANAGEMENT OF RENAL SCLERODERMA-LeROY ET AL.
or greater on repeated determinations), hypertension (systolic > 140 mm Hg or diastolic >90 mm Hg on repeated determinations) and abnormal urinary, sediment (>5 white blood cells/hpf or >2 red blood cells/hpf on repeated determinations) were monitored as possible indicators of renal involvement. Pulmonary involvement was defined as one or more of the following: (1) the presence of pleurisy (pleuritic chest pain, pleural friction rub or pleural effusion not due to other causes), (2) interstitial infiltrates on chest roentgenogram, (3) decreased diffusion capacity by D,CO or arterial oxygen tension (~0~) at rest and exercise, (4) indirect (increased pulmonic second and/or right ventricular pattern on electrocardiogram or direct (by right heart catheterization) demonstration of pulmonary hypertension and (5) restrictive lung disease (vital capacity 80 per cent expected). Cardiac involvement was defined as (1) percarditis (pericardial friction rub, pericardial effusion (echo or angiocardiogram), cardiomegaly by chest roentgenogram or persistent electrocardiographic abnormalities not due to other causes. These criteria are similar to those of other investigators I41. Anemia was defined as a hemoglobin concentration of 5 per cent, a negative Coombs’ test and fragmented erythrocytes on peripheral blood smear. RESULTS
The prevalence of features suggestive of renal involvement in the 100 patients with scleroderma, shown in Table I, is similar to that previously published. With the exception of abnormal urinary sediment, these manifestations do not commonly occur alone. Moreover, the presence of any single feature could not be shown to be predictive of present or future renal involvement, since renal scleroderma did not develop in 40 per cent of patients with hypertension or proteinuria and 70 per cent with abnormal urinary sediment over the five year period of observation. It was distinctly unusual to observe patients with proteinuria alone (one of 100) hypertension alone (three of 100) or urinary sediment alone (seven of 100). No patient with azotemia alone was seen. Conversely, the presence of several or all of these features constitutes the syndrome of renal scleroderma and is not predictive. In the 25 patients with renal scleroderma, the appearance of proteinuria, hypertension, azotemia and abnormal urinary sediment was accompanied by clinically obvious renal failure within a period of several days to one month. These and associated features are shown in Table II. The frequency of organ involvement in these patients is higher than that in most previously published series of patients with scleroderma (cf. Table II and [3,5-71, due to the referral of many patients with major organ involvement.
TABLE I
Features of Renal Involvement in 100 Patients with Scleroderma Female:male = 6:l White:black = 4:l Patients (no.)
Features Proteinuria (2+ or >) Hypertension* Malignant hypertension+ Azotemia (blood urea nitrogen > 40 mg/dl) Abnormal urinary sedimentt
29 39 8 26 34 52
Any feature present
A value exceeding either 140 (systolic) or 90 (diastolic) mm Hg on repeated determinations was considered positive. t Defined as diastolic blood pressure > 140 mm Hg, papilledema or encephalopathy. t Defined as >2 red blood cells or 5 white blood cells/hpf or casts on repeated determinations. l
Definite renal involvement was most reliably defined as blood urea nitrogen greater than 40 mg/dl or a creatinine clearance less than 50 cc/min. In all 25 patients in whom these measurements were observed irreversible oliguric renal failure developed. Magnification renal arteriography was carried out in 18 of 25 patients and showed definite interlobular artery lesions in 16 [3]. In general, arteriographic changes were not observed early in the development of renal scleroderma and were not predictive. Cardiac and pulmonary involvement (as defined in “Methods”) was observed in 95 per cent and 80 per cent of the 25 patients with renal scleroderma, respectively. Thus, the clinical setting is in many ways analogous to that in accelerated hypertension. In many
TABLE II
Characteristics of 100 Patients with Scleroderma
Characteristic Cardiac involvement* Pulmonary involvement* Death Hypertension Anemia (hemoglobin
