Nephrol Dial Transplant (1992) 7: 173-177 £ 1992 European Dialysis and Transplant Association-European Renal Association
Nephrology Dialysis Transplantation
Letters Sarcoid-like granulomata in a renal transplant Sir, The course of a cardiac allograft recipient who developed granulomatous inflammation in the lungs has recently been reported. The liver from the multiorgan donor also snowed typical hepatic sarcoid granulomata [1]. We have recently cared for a renal transplant recipient who developed sarcoid-like granulomata in his graft. Our patient is a 25-year-old male who presented in endstage renal failure 2 years ago. The kidneys were small on ultrasound examination and were not biopsied. The serum calcium was normal and a chest X-ray showed only cardiomegaly. The patient had been deaf for 2 years but there was no family history of renal disease or premature deafness. Lenticonus was not present, but at presentation the patient had uveitis. After a period of treatment with haemodialysis, he received a cadaveric transplant in December 1989. The donor was a 15-year-old female who had died from a head injury after a road-traffic accident. The other kidney was transplanted locally and the recipient is doing well, with a normal serum creatinine (90 umol/1) and trivial proteinuria. The patient under discussion was initially treated with cyclosporin monotherapy and demonstrated primary function. At day 7 an episode of graft dysfunction was treated as for a rejection episode with methylprednisolone, and renal function improved. At day 15 a biopsy was performed because of a further episode of graft dysfunction; an interstitial infiltrate typical of cellular rejection was seen, and treatment was again with intravenous methylprednisolone, followed by prednisolone 20 mg/day orally. Four months post-transplant the serum creatinine was 108umoll ' and the prednisolone dose was reduced to 10 mg/day. Nine months after transplantation the serum creatinine was 135 umol/1 and prednisolone was withdrawn. Over the next 2 months the serum creatinine increased to 195 umol/1, and after investigation to rule out urinary obstruction the patient underwent a renal transplant biopsy. This revealed four separate, well-formed, non-caseating, sarcoid-like granulomata, and no evidence of rejection. Staining for fungi and tubercle bacilli was negative and subsequent early-morning urines have failed to grow mycobacteria. Serum angiotensin-converting enzyme was 121 IU r 1 (normal range 0-55). The patient was restarted on prednisolone 20 mg/day and 1 month later the serum creatinine was 113 umol'l and the serum angiotensin converting enzyme had declined to 10. Over the subsequent 4 months the serum creatinine has remained less than 120 umol 1 and angiotensin-converting enzyme less than 20. Renal sarcoid-like granulomata and steroid-responsive allograft dysfunction, in the absence of acute rejection or tuberculous infection, are strong evidence that this patient
had sarcoidosis affecting the transplanted kidney. Further support is provided by the raised angiotensin-converting enzyme, which returned to normal following steroid therapy. It is also possible that sarcoidosis was the cause of end-stage renal failure in this patient as chronic uveitis predated transplantation. Renal granulomata have been reported in 15-40% of patients with sarcoidosis [2,3], but have only been reported once previously in a renal transplant recipient [4]. The absence of type IV delayed hypersensitivity reactions, possibly representing a suppressed T cell defect, is common in sarcoidosis, and is often reversed by steroid therapy. Cyclosporin primarily suppresses helper T cell activity, but has little or no effect on suppressor T cells, whereas corticosteroids suppress the activity of all T cell subsets. It is striking that in this patient, cyclosporin was ineffectual in modifying the disease, whereas the addition of prednisolone led to a dramatic improvement in renal function. This tends to support the hypothesis that a defect in suppressor T cell function may be implicated in the pathogenesis of sarcoidosis. Renal Transplant Unit Manchester Royal Infirmary Oxford Road, Manchester M13 9WL.
J. H. Brown V. Jos C. G. Newstead
Department of Histopathology W. Lawler The Medical School, University of Manchester Oxford Road, Manchester 1. Burke WMJ, Keogh A, Maloney PJ, Delprado W, Bryant DH, Spratt P. Transmission of sarcoidosis via cardiac transplantation. Lancet 1990; 336: 1579 2. Ricker W, Clark M. Sarcoidosis: a clinicopathologic review of 300 cases including 22 autopsies. Am J Clin Pathol 1949; 19: 725-749 3. Lebacq E, Verhaegen H, Desmet V. Renal involvement in sarcoidosis. Postgrad Med J 1970; 46: 526-529 4. Shen SY, Hall-Craggs M, Posner JN, Shabazz B. Recurrent sarcoid granulomatous nephritis and reactive tuberculin skin test in a renal transplant recipient. Am J Med 1986; 80: 699 702
Low-dose recombinant human erythropoietin in dialysis patients living at high altitude Sir, In most recent studies the recommended starting dose of recombinant human erythropoietin (rHuEpo) for anaemic patients on regular haemodialysis has been 50 U kg i.v. with a maintenance dose ranging between 40 and 100 1)1 kg i.v. thrice weekly depending on the target haematocrit [1-3]. AH these studies, however, were on patients living at sea level. Anaemic patients on maintenance dialysis have been shown, when exposed to altitude hypoxia, to exhibit a smal! but significant increase in their plasma erythropoie-
Nephrology Dialysis Transplantation
Letters Sarcoid-like granulomata in a renal transplant Sir, The course of a cardiac allograft recipient who developed granulomatous inflammation in the lungs has recently been reported. The liver from the multiorgan donor also snowed typical hepatic sarcoid granulomata [1]. We have recently cared for a renal transplant recipient who developed sarcoid-like granulomata in his graft. Our patient is a 25-year-old male who presented in endstage renal failure 2 years ago. The kidneys were small on ultrasound examination and were not biopsied. The serum calcium was normal and a chest X-ray showed only cardiomegaly. The patient had been deaf for 2 years but there was no family history of renal disease or premature deafness. Lenticonus was not present, but at presentation the patient had uveitis. After a period of treatment with haemodialysis, he received a cadaveric transplant in December 1989. The donor was a 15-year-old female who had died from a head injury after a road-traffic accident. The other kidney was transplanted locally and the recipient is doing well, with a normal serum creatinine (90 umol/1) and trivial proteinuria. The patient under discussion was initially treated with cyclosporin monotherapy and demonstrated primary function. At day 7 an episode of graft dysfunction was treated as for a rejection episode with methylprednisolone, and renal function improved. At day 15 a biopsy was performed because of a further episode of graft dysfunction; an interstitial infiltrate typical of cellular rejection was seen, and treatment was again with intravenous methylprednisolone, followed by prednisolone 20 mg/day orally. Four months post-transplant the serum creatinine was 108umoll ' and the prednisolone dose was reduced to 10 mg/day. Nine months after transplantation the serum creatinine was 135 umol/1 and prednisolone was withdrawn. Over the next 2 months the serum creatinine increased to 195 umol/1, and after investigation to rule out urinary obstruction the patient underwent a renal transplant biopsy. This revealed four separate, well-formed, non-caseating, sarcoid-like granulomata, and no evidence of rejection. Staining for fungi and tubercle bacilli was negative and subsequent early-morning urines have failed to grow mycobacteria. Serum angiotensin-converting enzyme was 121 IU r 1 (normal range 0-55). The patient was restarted on prednisolone 20 mg/day and 1 month later the serum creatinine was 113 umol'l and the serum angiotensin converting enzyme had declined to 10. Over the subsequent 4 months the serum creatinine has remained less than 120 umol 1 and angiotensin-converting enzyme less than 20. Renal sarcoid-like granulomata and steroid-responsive allograft dysfunction, in the absence of acute rejection or tuberculous infection, are strong evidence that this patient
had sarcoidosis affecting the transplanted kidney. Further support is provided by the raised angiotensin-converting enzyme, which returned to normal following steroid therapy. It is also possible that sarcoidosis was the cause of end-stage renal failure in this patient as chronic uveitis predated transplantation. Renal granulomata have been reported in 15-40% of patients with sarcoidosis [2,3], but have only been reported once previously in a renal transplant recipient [4]. The absence of type IV delayed hypersensitivity reactions, possibly representing a suppressed T cell defect, is common in sarcoidosis, and is often reversed by steroid therapy. Cyclosporin primarily suppresses helper T cell activity, but has little or no effect on suppressor T cells, whereas corticosteroids suppress the activity of all T cell subsets. It is striking that in this patient, cyclosporin was ineffectual in modifying the disease, whereas the addition of prednisolone led to a dramatic improvement in renal function. This tends to support the hypothesis that a defect in suppressor T cell function may be implicated in the pathogenesis of sarcoidosis. Renal Transplant Unit Manchester Royal Infirmary Oxford Road, Manchester M13 9WL.
J. H. Brown V. Jos C. G. Newstead
Department of Histopathology W. Lawler The Medical School, University of Manchester Oxford Road, Manchester 1. Burke WMJ, Keogh A, Maloney PJ, Delprado W, Bryant DH, Spratt P. Transmission of sarcoidosis via cardiac transplantation. Lancet 1990; 336: 1579 2. Ricker W, Clark M. Sarcoidosis: a clinicopathologic review of 300 cases including 22 autopsies. Am J Clin Pathol 1949; 19: 725-749 3. Lebacq E, Verhaegen H, Desmet V. Renal involvement in sarcoidosis. Postgrad Med J 1970; 46: 526-529 4. Shen SY, Hall-Craggs M, Posner JN, Shabazz B. Recurrent sarcoid granulomatous nephritis and reactive tuberculin skin test in a renal transplant recipient. Am J Med 1986; 80: 699 702
Low-dose recombinant human erythropoietin in dialysis patients living at high altitude Sir, In most recent studies the recommended starting dose of recombinant human erythropoietin (rHuEpo) for anaemic patients on regular haemodialysis has been 50 U kg i.v. with a maintenance dose ranging between 40 and 100 1)1 kg i.v. thrice weekly depending on the target haematocrit [1-3]. AH these studies, however, were on patients living at sea level. Anaemic patients on maintenance dialysis have been shown, when exposed to altitude hypoxia, to exhibit a smal! but significant increase in their plasma erythropoie-
