- Email: [email protected]
Renal amyloidosis followed more than 5 years: Report of 12 cases
Renal Amyloidosis Followed More Than 5 Years: Report of 12 Cases H. Kaaroud, K. Boubaker, S. Béji, E. Abderrahim, F. Ben Moussa, S. Turki, R. Goucha, H. Hedri, F. El Younsi, A. Kheder, and H. Ben Maiz ABSTRACT Renal involvement with amyloidosis is common but causes patient survival to be poor, rarely reaching 5 years. In this study, we retrospectively reviewed clinical and biological characteristics as well as treatments and outcomes of patients with renal amyloidosis followed for more than 5 years. Between 1975 and 2003, 485 patients were diagnosed with renal amyloidosis including only 12 patients who were followed more than 5 years. The six men and six women of mean age 42.4 years (range 18 to 66 years) displayed renal signs of lower limb edema in all cases; hypertension in four cases, proteinuria on urinalysis in all cases with microscopic hematuria in five cases. Biological tests showed nephrotic syndrome in 11 patients, normal renal function in nine patients, and renal failure in three patients whose mean creatinine was 481.6 mol/L (range 294 to 726). The amyloidosis was AA type in 11 cases and non-AA in one case. An etiologic survey revealed spondylarthropathy in one patient, pulmonary tuberculosis in two patients, chronic bronchitis in three patients, hepatic hydatic cyst in one patient, Mediterranean familial fever in two patients, Crohn’s disease in one patient, Hodgkin’s lymphoma in one patient, and multiple myeloma in one patient. Specific treatment was initiated with colchicine in seven patients. At a 110-month mean follow-up (range 53 to 153 months), remission of nephrotic syndrome was observed in four cases, progression to chronic renal failure in two patients, and to end-stage renal failure in five cases (range 53 to 196 months), with stabilization of renal function in seven patients. In conclusion, primary amyloid disease should be optimally suppressed in patients with renal involvement. The role of this treatment in remission of renal amyloidosis is not well established. This efficacy of the treatment has been demonstrated in some patients with improved survival.
A
MYLOID NEPHROPATHY (AN) is common in our country due to the frequency of infections, especially tuberculosis. AN is characterized by a poor prognosis with progression to end-stage renal failure. Despite treatment of systemic amyloidosis, overall prognosis is poor with patients dead at an average of 13 months after diagnosis.1 The survival of hemodialysis patients is lower than that of patients with primary renal diseases or even diabetic nephropathy.2,3 We report our experiences with AN patients who have survived more than 5 years to analyze their clinical, biological, histological, and etiologic characteristics. MATERIALS AND METHODS During the period from 1975 to 2003, 485 patients underwent kidney or salivary gland biopsy. Twelve of patients survived more than 5 years (Table 1). We studied the clinical signs of edema,
blood pressure, urinalysis, and extrarenal signs, biological tests for nephrotic syndrome, creatinine, histology, kidney biopsy, amyloidosis type, etiology, treatment, and follow-up.
RESULTS
The six men and six women mean age of 42.4 years (range 18 to 66) showed clinical signs of edema in 12 cases, high blood pressure in three cases, hypotension in six cases, macroscopic hematuria in one case, and microscopic hematuria in four cases. We noted macroglossia in three cases, From the Department of Nephrology and Internal Medicine, Charles Nicolle Hospital, Tunis, Tunisia. Address reprint requests to A. Kheder, Department of Nephrology and Internal Medicine, Charles Nicolle Hospital, Boulevard 9 Avril 1938, Tunis BS 1006, Tunisia. E-mail: [email protected]
0041-1345/04/$–see front matter doi:10.1016/j.transproceed.2004.07.022
© 2004 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
1796
Transplantation Proceedings, 36, 1796 –1798 (2004)
RENAL AMYLOIDOSIS
1797 Table 1. Clinical Characteristics of Patients.
Etiology
Cases
Treatment
Follow-up (months)
Pulmonar tuberculosis
2
Colchicine tuberculosis treatment
Chronic bronchitis
3
Colchicine in two cases
103
Familial Mediterranean fever Crohn’s disease Spondylarthropathy Hodgkin’s lymphoma Multiple myeloma Hydatic cyst
2 1 1 1 1 1
Colchicine Colchicine salazopyrine NSAD Colchicine chemotherapy Colchicine steroid melphalan Surgery colchicine
153 122 144 60 87 128
85.2
State at last news
HD: two Death in one case Remission: one HD: two HD: two HD HD ⫹ death Remission Remission Remission
HD, haemodialysis; NSAD, non–steroid antiinflammatory drugs.
splenomegaly in two cases, hepatomegaly in one case, goiter in one case, lower limb neuropathy in two cases, orthostatic hypotension in one case, carpal tunnel syndrome in one case, and thrombocytosis in five cases. The underlying causes of amylodosis were pulmonary tuberculosis in two cases, chronic bronchitis in three case, familial Mediterranean fever in two cases, Crohn’s disease in one case, spondylarthropathy in one case, Hodgkin’ lymphoma in one case, multiple myeloma in one case, and hydatic cyst in one case. Laboratory investigations showed normal renal function in nine cases and chronic renal failure in three-cases with a mean serum creatinine of 481 mol/L (294 to 726), mean 24-hour protein excretion 8.6 g (1.25 to 20), and mean albuminemia 14.9 g/L (6.5 to 20.5). A nephrotic syndrome was observed in 11 cases. Amyloid deposits were detected in glomerula in 12 cases, in the tubulointerstitium in four cases, and in the vessels in 12 cases. Causal disease was treated if possible associated with colchicine therapy in nine patients. The mean follow-up was 110 months (53 to 196). The interval between diagnosis of amyloidosis and dialysis was 83 months (0 to 132). Remission of nephrotic syndrome was observed in four cases, namely, with normal renal function in three cases and with moderate renal insufficiency in one case. End-stage renal failure was observed in eight cases including one who had the disorder at renal biopsy. All end-stage patients were treated with hemodialysis. DISCUSSION
A long follow-up of patients with AN can be observed after clinical remission, which is rare occuring after treatment of the cause. Colchicine represents the only specific preventive treatment of AN secondary to familial Mediterranean fever (FMF). A curative effect of colchicine has been postulated by some authors. These benefits of colchicine in FMF have led to its use alone or in association with specific treatment for AN secondary to other causes among patients with normal renal function. Clinical and biological remission was obtained in four patients after specific treatment of the causal disease asso-
ciated with colchicine (chronic bronchitis: one case; Hodgkin’s lymphoma: one case; multiple myeloma: one case; hydatic cyst: one case). Despite the poor prognosis of AL amyloidosis, remission of clinical symptoms was observed in a patient with multiple myeloma treated with melphalan and prednisone.4 Remission of AN after surgical removal of the amyloid focus has rarely been reported. This remission can be explained by suppression of antigenic stimulation. In one of our patients, surgical removal of a hydatic cyst and treatment with colchicine led to remission, as previously described in the literature.5,6 Progression of renal amyloidosis was associated with severe proteinuria, nephrotic syndrome, amyloid deposition producing tubulointerstitial and vascular damage on biopsy and serum creatinine level greater than 2 mg/dL at presentation.7,8 Three of our patients showed serum creatinine levels greater than 2 mg/dL. Renal replacement therapy is required for 1.6% and 5% to 10% ESRD patients with secondary amyloidosis.2,9 Hemodialysis is established for the treatment of ESRD due to systemic amyloidosis9,10 because peritoneal dialysis can worsen the depletion caused by heavy proteinuria.2 Renal replacement therapy is poorly tolerated in patients with AN; mortality occurred in 52% during the first month. The patients died from cardiac complications or septicemia.2,11 The survival of dialysis patients exceeding 5 years is better among patients less than 45 years of age. Survival on dialysis was better at 1 year than transplantation (82% vs 70%) and worsen at 2 and 3 years (46% and 37% vs 62% and 62%, respectively).2 In conclusion, during long follow-up of patients with AN clinical remission may be observed. However remission remains rare, independent of etiology and type of amyloidosis. Treatment of causal disease, especially infection, is imperative. Surgical removal of an amyloid focus must be discussed with care because of the risk of acute renal failure. Hemodialysis remains the method of choice for renal replacement therapy despite the poor survival.1
1798
REFERENCES 1. Brunner FP, Fassbinder W, Broyer M, et al: Survival on renal replacement therapy: data from the EDTA registry. Nephrol Dial Transplant 2:109, 1988 2. Ylinen K, Gröhagen-Riska C, Honkanen E, et al: Outcome of patients with secondary amyloidosis in dialysis treatment. Nephrol Dial Transplant 7:908, 1992 3. Boyle J, Johnston B: Acute upper gastrointestinal hemorrhage in patients with chronic renal disease. Am J Med 75:409, 1983 4. Hetzel GR, Heering GP, Grabensee B: Systemic A1-amyloidosis. Clinical course and limits of melphalan therapy. Med Klin 94:549, 1999 5. Kaaroud H, Ben Moussa F, Béji S, et al: Amylose rénale secondaire à un kyste hydatique du foie. Rémission clinique après exérèse chirurgicale. Néphrologie 23:213, 2002
KAAROUD, BOUBAKER, BÉJI ET AL 6. Ben Maiz H, Ben Moussa F, Goucha R, et al: Association of renal amyloidosis and hydatid disease: study of 11 cases. Abstract— XIII international congress of Nephrology. Madrid, July 282, 1995 7. Sasatomi Y, Kiyoshi Y, Uesugi N, et al: Prognosis of renal amyloidosis: a clinicopathologic study using cluster analysis. Nephron 87:42, 2001 8. Gertz MA, Kyle RA: Secondary systemic amyloidosis: response and survival in 64 patients. Medicine (Baltimore) 70:246, 1991 9. Fassbinder W, Brunner FP, Brynger H, et al. Combined report on regular dialysis and transplantation in Europe, XX, 1989. Nephrol Dial Transplant 6(Suppl 1):31, 1991 10. Gurland HJ, Brunner FP, Chantler C, et al. Combined report on regular dialysis and transplantation in Europe, VI, 1975. Proc Eur Dial Transplant Assoc 13:3, 1976 11. Pasternack A, Ahonen J, Kuhlbäck B: Renal transplantation in 45 patients with amyloidosis. Transplantation 42:598, 1986
A
MYLOID NEPHROPATHY (AN) is common in our country due to the frequency of infections, especially tuberculosis. AN is characterized by a poor prognosis with progression to end-stage renal failure. Despite treatment of systemic amyloidosis, overall prognosis is poor with patients dead at an average of 13 months after diagnosis.1 The survival of hemodialysis patients is lower than that of patients with primary renal diseases or even diabetic nephropathy.2,3 We report our experiences with AN patients who have survived more than 5 years to analyze their clinical, biological, histological, and etiologic characteristics. MATERIALS AND METHODS During the period from 1975 to 2003, 485 patients underwent kidney or salivary gland biopsy. Twelve of patients survived more than 5 years (Table 1). We studied the clinical signs of edema,
blood pressure, urinalysis, and extrarenal signs, biological tests for nephrotic syndrome, creatinine, histology, kidney biopsy, amyloidosis type, etiology, treatment, and follow-up.
RESULTS
The six men and six women mean age of 42.4 years (range 18 to 66) showed clinical signs of edema in 12 cases, high blood pressure in three cases, hypotension in six cases, macroscopic hematuria in one case, and microscopic hematuria in four cases. We noted macroglossia in three cases, From the Department of Nephrology and Internal Medicine, Charles Nicolle Hospital, Tunis, Tunisia. Address reprint requests to A. Kheder, Department of Nephrology and Internal Medicine, Charles Nicolle Hospital, Boulevard 9 Avril 1938, Tunis BS 1006, Tunisia. E-mail: [email protected]
0041-1345/04/$–see front matter doi:10.1016/j.transproceed.2004.07.022
© 2004 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
1796
Transplantation Proceedings, 36, 1796 –1798 (2004)
RENAL AMYLOIDOSIS
1797 Table 1. Clinical Characteristics of Patients.
Etiology
Cases
Treatment
Follow-up (months)
Pulmonar tuberculosis
2
Colchicine tuberculosis treatment
Chronic bronchitis
3
Colchicine in two cases
103
Familial Mediterranean fever Crohn’s disease Spondylarthropathy Hodgkin’s lymphoma Multiple myeloma Hydatic cyst
2 1 1 1 1 1
Colchicine Colchicine salazopyrine NSAD Colchicine chemotherapy Colchicine steroid melphalan Surgery colchicine
153 122 144 60 87 128
85.2
State at last news
HD: two Death in one case Remission: one HD: two HD: two HD HD ⫹ death Remission Remission Remission
HD, haemodialysis; NSAD, non–steroid antiinflammatory drugs.
splenomegaly in two cases, hepatomegaly in one case, goiter in one case, lower limb neuropathy in two cases, orthostatic hypotension in one case, carpal tunnel syndrome in one case, and thrombocytosis in five cases. The underlying causes of amylodosis were pulmonary tuberculosis in two cases, chronic bronchitis in three case, familial Mediterranean fever in two cases, Crohn’s disease in one case, spondylarthropathy in one case, Hodgkin’ lymphoma in one case, multiple myeloma in one case, and hydatic cyst in one case. Laboratory investigations showed normal renal function in nine cases and chronic renal failure in three-cases with a mean serum creatinine of 481 mol/L (294 to 726), mean 24-hour protein excretion 8.6 g (1.25 to 20), and mean albuminemia 14.9 g/L (6.5 to 20.5). A nephrotic syndrome was observed in 11 cases. Amyloid deposits were detected in glomerula in 12 cases, in the tubulointerstitium in four cases, and in the vessels in 12 cases. Causal disease was treated if possible associated with colchicine therapy in nine patients. The mean follow-up was 110 months (53 to 196). The interval between diagnosis of amyloidosis and dialysis was 83 months (0 to 132). Remission of nephrotic syndrome was observed in four cases, namely, with normal renal function in three cases and with moderate renal insufficiency in one case. End-stage renal failure was observed in eight cases including one who had the disorder at renal biopsy. All end-stage patients were treated with hemodialysis. DISCUSSION
A long follow-up of patients with AN can be observed after clinical remission, which is rare occuring after treatment of the cause. Colchicine represents the only specific preventive treatment of AN secondary to familial Mediterranean fever (FMF). A curative effect of colchicine has been postulated by some authors. These benefits of colchicine in FMF have led to its use alone or in association with specific treatment for AN secondary to other causes among patients with normal renal function. Clinical and biological remission was obtained in four patients after specific treatment of the causal disease asso-
ciated with colchicine (chronic bronchitis: one case; Hodgkin’s lymphoma: one case; multiple myeloma: one case; hydatic cyst: one case). Despite the poor prognosis of AL amyloidosis, remission of clinical symptoms was observed in a patient with multiple myeloma treated with melphalan and prednisone.4 Remission of AN after surgical removal of the amyloid focus has rarely been reported. This remission can be explained by suppression of antigenic stimulation. In one of our patients, surgical removal of a hydatic cyst and treatment with colchicine led to remission, as previously described in the literature.5,6 Progression of renal amyloidosis was associated with severe proteinuria, nephrotic syndrome, amyloid deposition producing tubulointerstitial and vascular damage on biopsy and serum creatinine level greater than 2 mg/dL at presentation.7,8 Three of our patients showed serum creatinine levels greater than 2 mg/dL. Renal replacement therapy is required for 1.6% and 5% to 10% ESRD patients with secondary amyloidosis.2,9 Hemodialysis is established for the treatment of ESRD due to systemic amyloidosis9,10 because peritoneal dialysis can worsen the depletion caused by heavy proteinuria.2 Renal replacement therapy is poorly tolerated in patients with AN; mortality occurred in 52% during the first month. The patients died from cardiac complications or septicemia.2,11 The survival of dialysis patients exceeding 5 years is better among patients less than 45 years of age. Survival on dialysis was better at 1 year than transplantation (82% vs 70%) and worsen at 2 and 3 years (46% and 37% vs 62% and 62%, respectively).2 In conclusion, during long follow-up of patients with AN clinical remission may be observed. However remission remains rare, independent of etiology and type of amyloidosis. Treatment of causal disease, especially infection, is imperative. Surgical removal of an amyloid focus must be discussed with care because of the risk of acute renal failure. Hemodialysis remains the method of choice for renal replacement therapy despite the poor survival.1
1798
REFERENCES 1. Brunner FP, Fassbinder W, Broyer M, et al: Survival on renal replacement therapy: data from the EDTA registry. Nephrol Dial Transplant 2:109, 1988 2. Ylinen K, Gröhagen-Riska C, Honkanen E, et al: Outcome of patients with secondary amyloidosis in dialysis treatment. Nephrol Dial Transplant 7:908, 1992 3. Boyle J, Johnston B: Acute upper gastrointestinal hemorrhage in patients with chronic renal disease. Am J Med 75:409, 1983 4. Hetzel GR, Heering GP, Grabensee B: Systemic A1-amyloidosis. Clinical course and limits of melphalan therapy. Med Klin 94:549, 1999 5. Kaaroud H, Ben Moussa F, Béji S, et al: Amylose rénale secondaire à un kyste hydatique du foie. Rémission clinique après exérèse chirurgicale. Néphrologie 23:213, 2002
KAAROUD, BOUBAKER, BÉJI ET AL 6. Ben Maiz H, Ben Moussa F, Goucha R, et al: Association of renal amyloidosis and hydatid disease: study of 11 cases. Abstract— XIII international congress of Nephrology. Madrid, July 282, 1995 7. Sasatomi Y, Kiyoshi Y, Uesugi N, et al: Prognosis of renal amyloidosis: a clinicopathologic study using cluster analysis. Nephron 87:42, 2001 8. Gertz MA, Kyle RA: Secondary systemic amyloidosis: response and survival in 64 patients. Medicine (Baltimore) 70:246, 1991 9. Fassbinder W, Brunner FP, Brynger H, et al. Combined report on regular dialysis and transplantation in Europe, XX, 1989. Nephrol Dial Transplant 6(Suppl 1):31, 1991 10. Gurland HJ, Brunner FP, Chantler C, et al. Combined report on regular dialysis and transplantation in Europe, VI, 1975. Proc Eur Dial Transplant Assoc 13:3, 1976 11. Pasternack A, Ahonen J, Kuhlbäck B: Renal transplantation in 45 patients with amyloidosis. Transplantation 42:598, 1986