A 5-year-old girl with impaired renal function after autologous bone marrow transplantation.

BONE MARROW TRANSPLANTATION (BMT) increasingly is used for the treatment of patients with hematologic malignancies, some metabolic and immunologic diseases, and depressed bone marrow after cancer treatment. Renal insufficiency after BMT is common and related to many causes. We present the case of a girl who had renal insufficiency 4 months after autologous BMT. A girl aged 5 years 3 months presented with fever and right posterior auricular and submandibular lymphadenopathy for 2 weeks when she was 3 years 4 months old. A lymph node biopsy was performed and showed malignant lymphoma, diffuse large cell type. Bone marrow biopsy showed minimal involvement by abnormal large mononuclear cells with increased histiocytes and hemophagocytic activity. Abdominal ultrasound showed mild hepatosplenomegaly, and chest radiograph and bone scan results were normal. A diagnosis of diffuse large cell lymphoma stage IV with hemophagocytic syndrome was made, and the patient was treated with chemotherapy adapted from the Berlin-Frankfurt-Munster-Non-Hodgkin lymphoma protocol.1Reiter A. Schrappe M. Parwaresch R. et al.Non-Hodgkin’s lymphomas of childhood and adolescence: Results of a treatment stratified for biologic subtypes and stage—A report of the Berlin-Frankfurt-Munster Group.J Clin Oncol. 1995; 13: 359-372Crossref PubMed Scopus (295) Google Scholar Chemotherapy consisted of prednisolone and cyclophosphamide in the induction phase and alternated intensive phase with dexamethasone, methotrexate, ifosfamide, etoposide, and cytosine arabinoside in course A and dexamethasone, methotrexate, cyclophosphamide, and doxorubicin (Adriamycin; Pharmacia Inc, Kalamazoo, MI) in course B for a total of 6 courses. Intrathecal methotrexate, hydrocortisone, and cytosine arabinoside also were administered. She had normal renal function throughout the course of chemotherapy. During the 6-month course of treatment, she experienced complications of febrile neutropenia, anemia, and thrombocytopenia. Unfortunately, the patient experienced a first relapse 1 month after finishing the intensive phase of chemotherapy. Because she had right cervical lymphadenopathy, a biopsy was performed and reported as malignant lymphoma, similar cell type. All metastatic workup results were negative. She was treated with the same chemotherapy protocol, and autologous BMT was planned after the intensive phase. Shortly after chemotherapy, lymphadenopathy resolved. Bone marrow aspiration after completion of chemotherapy was normal, without evidence of metastasis. Bone scan showed increased radiouptake at the fourth rib on the left side and second rib on the right side. Bony metastasis was suspected. The area of right cervical lymph node involvement was irradiated with 150 cGy for 10 fractions. Autologous peripheral-blood stem cell transplantation (SCT) was performed, although remission had not been achieved. The conditioning regimen consisted of fractionated total-body irradiation with 120 cGy twice a day for 4 days; cyclophosphamide, 60 mg/kg/d, for 2 days; and cytosine arabinoside, 3 g/m2/d, for 2 days. The post-SCT course was complicated by febrile neutropenia and Salmonella group B enteritis. The patient had neutrophil engraftment (absolute neutrophil count > 500/μL) on day 13 and platelet engraftment (platelet count > 20,000/μL) on day 41 after SCT. She was administered only sulfamethoxazole-trimethoprim for Pneumocystis carinii prophylaxis and folic acid before discharge. Bone marrow aspiration and bone scan at 4 weeks post-SCT were normal. Complete blood count (CBC) showed hematocrit of 35.8%, white blood cell count (WBC) of 4,400/μL, and platelet count of 29,000/μL. Renal function was normal throughout the course of SCT. Eight weeks after SCT, she was readmitted with respiratory distress. Radiation pneumonitis was diagnosed and responded well to prednisolone. At this time, CBC showed hematocrit of 31.3%, WBC count of 4,300/μL, and platelet count of 21,000/μL. Serum creatinine level remained normal at 0.3 mg/dL (27 μmol/L). During the next 3 to 4 months after SCT, hematocrit decreased to 19.8% to 26.4% and platelet count was in the range of 6,000 to 57,000/μL, for which she underwent transfusion with packed red blood cells and platelet concentrations occasionally. At 4½ months, serum creatinine level was 0.8 mg/dL (71 μmol/L), which increased to 1.7 mg/dL (150 μmol/L) at 5 months. Urinalysis results were normal except for trace albumin. CBC at that time showed hematocrit of 22.8% with reticulocyte count of 4%, WBC count of 4,800/μL, and platelet count of 86,000/μL. At 6 months after SCT, serum creatinine level was 2.4 mg/dL (212 μmol/L) and uric acid level was 8.5 mg/dL (506 μmol/L). She was admitted for investigation. Urine protein was 390 mg/d. Glomerular filtration rate was 33 mL/min/1.73 m2 (0.55 mL/s/1.73 m2). Blood smear did not show evidence of hemolysis, and direct and indirect Coombs test results were negative. Bone marrow aspiration showed normal cellularity with normal numbers of mature megakaryocytes and erythroid and myeloid series and no abnormal lymphoid cells. Because of renal insufficiency and significant proteinuria, renal biopsy was performed. The biopsy specimen contained 46 glomeruli. Most showed segmental mesangiolysis and congestion. Fragmented red blood cells were noted (Fig 1). Some glomeruli had aneurysmal dilatation caused by mesangiolysis. Endothelial cells were swollen. Capillary walls showed segmental splitting and corrugation. Several glomeruli showed fibrin thrombi in afferent arterioles (Fig 2). Tubules showed moderate (50%) atrophy proportional to interstitial fibrosis, with minimal mononuclear cell infiltrate. Interlobular arteries showed mild mucoid intimal thickening. Immunofluorescence studies showed 2 to 3+ mesangial and capillary loop staining for fibrinogen and trace arteriolar staining for C3. No staining for immunoglobulin G (IgG), IgA, IgM, or C4 was detected.Fig 2Glomerulus shows endothelial cell swelling and segmental capillary wall splitting and corrugation. There is a fibrin thrombus in afferent arteriole (periodic acid–Schiff; original magnification ×400).View Large Image Figure ViewerDownload (PPT) Electron microscopy showed widening of the subendothelial zone, containing electron-lucent material and fragmented red blood cells (Fig 3). New basement membrane formation was identified in a few capillary loops. There was marked dissolution of mesangial matrix, indicative of mesangiolysis. No immune complex–type deposits were found. Podocytes showed 70% foot-process effacement with microvillous transformation and cytoplasmic vacuolization. The renal biopsy diagnosis was thrombotic microangiopathy (TMA), consistent with BMT nephropathy. The patient was treated with prednisolone, 2 mg/kg/d, every 8 hours and dipyridamole, 1 mg/kg/dose, every 8 hours. Three weeks later, serum creatinine level decreased to 1.6 mg/dL (141 μmol/L) and thereafter increased to 2.8 mg/dL (248 μmol/L) at 7 weeks. Prednisolone dosage then was tapered. Although anemia improved with subcutaneous injection of erythropoietin, 1,000 unit, twice a week, proteinuria worsened and thrombocytopenia persisted. Dipyridamole therapy was changed to low-molecular-weight heparin. On last follow-up (9 months post-SCT), the patient had 3+ to 4+ proteinuria and serum creatinine level in the range of 2.3 to 2.5 mg/dL (203 to 221 μmol/L). CBC showed hematocrit of 31.7%, WBC count of 9,800/μL, and platelet count of 77,000/μL. She had normal serum electrolyte, calcium, and phosphate levels. Spot urine protein-creatinine ratio was 2.56. Acute renal failure in the first 3 months after BMT usually is associated with acute tubular necrosis, use of nephrotoxic drugs, hepatic veno-occlusive disease, and sepsis.2Zager R.A. Acute renal failure in the setting of bone marrow transplantation.Kidney Int. 1994; 46: 1443-1458Crossref PubMed Scopus (145) Google Scholar However, if patients can recover from these conditions, renal function will return to normal. BMT nephropathy is a less common condition, although the incidence is increasing because of increased use of BMT. The incidence is approximately 6% to 25%2Zager R.A. Acute renal failure in the setting of bone marrow transplantation.Kidney Int. 1994; 46: 1443-1458Crossref PubMed Scopus (145) Google Scholar, 3Rabinowe S.N. Soiffer R.J. Tarbell N.J. et al.Hemolytic-uremic syndrome following bone marrow transplantation in adults for hematologic malignancies.Blood. 1991; 77: 1837-1844PubMed Google Scholar, 4Pettitt A.R. Clark R.E. Thrombotic microangiopathy following bone marrow transplantation.Bone Marrow Transplant. 1994; 14: 495-504PubMed Google Scholar, 5Cohen E.P. Lawton C.A. Moulder J.E. Bone marrow transplant nephropathy: Radiation nephritis revisited.Nephron. 1995; 70: 217-222Crossref PubMed Scopus (87) Google Scholar and can be as high as 38% in children.6Tarbell N.J. Guinan E.C. Niemeyer C. Mauch P. Sallan S.E. Weinstein H.J. Late onset of renal dysfunction in survivors of bone marrow transplantation.Int J Radiat Oncol Biol Phys. 1988; 15: 99-104Abstract Full Text PDF PubMed Scopus (95) Google Scholar This onset of renal failure usually occurs at more than 3 months after initial irradiation, with peak incidence at 6 to 12 months.7Cohen E.P. Radiation nephropathy after bone marrow transplantation.Kidney Int. 2000; 58: 903-918Crossref PubMed Scopus (96) Google Scholar Adverse effects of radiation on the kidney were recognized 10 years after the advent of x-ray.8Alpers C.E. Irradiation injury.in: Jennette J.C. Olson J.L. Schwartz M.M. Silva F.G. Heptinstall’s Pathology of the Kidney. (ed 5). Lippincott-Raven, Philadelphia, PA1998: 1131-1148Google Scholar Most patients underwent irradiation in the abdominal areas for solid tumors. Luxton9Luxton R.W. Radiation nephritis.Q J Med. 1953; 22: 215-242PubMed Google Scholar classified patients into 5 groups according to clinical presentation: acute and chronic radiation nephritis, asymptomatic proteinuria, benign and malignant hypertension. Acute and chronic radiation nephritis later preferably were termed acute and chronic radiation nephropathy because of the lack of inflammatory changes.8Alpers C.E. Irradiation injury.in: Jennette J.C. Olson J.L. Schwartz M.M. Silva F.G. Heptinstall’s Pathology of the Kidney. (ed 5). Lippincott-Raven, Philadelphia, PA1998: 1131-1148Google Scholar Patients with acute radiation nephropathy usually had edema, hypertension, anemia, proteinuria, and renal insufficiency at 6 to 12 months after irradiation. A number of patients progressed to the chronic form with chronic renal insufficiency and persistent proteinuria. Poor prognostic indicators appeared to be generalized edema and hypertension. BMT nephropathy is a subset of radiation nephropathy and most likely corresponds to the acute form by the classification of Luxton.9Luxton R.W. Radiation nephritis.Q J Med. 1953; 22: 215-242PubMed Google Scholar However, the onset of BMT nephropathy can be as late as 3 months after initial irradiation. Clinical presentation includes proteinuria, microscopic hematuria, hypertension, anemia, and azotemia. Anemia usually is disproportionate to the degree of azotemia.7Cohen E.P. Radiation nephropathy after bone marrow transplantation.Kidney Int. 2000; 58: 903-918Crossref PubMed Scopus (96) Google Scholar The clinical course is variable. Approximately 20% of patients experienced acute loss of renal function, whereas the rest experienced a slow decline or initial decline followed by stable renal function.10Cohen E.P. Lawton C.A. Moulder J.E. Becker C.G. Ash R.C. Clinical course of late-onset bone marrow transplant nephropathy.Nephron. 1993; 64: 626-635Crossref PubMed Scopus (72) Google Scholar When BMT nephropathy initially was described, there was a question of whether this lesion was the result of radiation injury or associated with a nephrotoxic drug, especially cyclosporine, administered to patients.11Bergstein J. Andreoli S.P. Provisor A.J. Yum M. Radiation nephritis following total-body irradiation and cyclophosphamide in preparation for bone marrow transplantation.Transplantation. 1986; 41: 63-66Crossref PubMed Scopus (76) Google Scholar Accumulating evidence supports that this lesion is caused by radiation, rather than drugs or other conditions commonly found in patients undergoing BMT.2Zager R.A. Acute renal failure in the setting of bone marrow transplantation.Kidney Int. 1994; 46: 1443-1458Crossref PubMed Scopus (145) Google Scholar Histological findings of BMT nephropathy are those of TMA. Renal biopsy alone cannot distinguish BMT nephropathy from TMA from other causes. These include hemolytic uremic syndrome, thrombotic thrombocytopenic purpura, radiation nephropathy, and a multitude of other disorders affecting the glomerular endothelium. Therefore, the diagnosis of BMT nephropathy can be made from the patients’ history of exposure to total-body irradiation as a conditioning regimen for BMT, along with renal function impairment and renal biopsy findings of TMA. These findings are endothelial cell swelling, double contour of capillary walls, and mesangiolysis (disintegration of mesangium). Mesangiolysis causes confluence of capillary loops, forming aneurysms. Fibrin thrombi and fragmented red blood cells occasionally are identified in glomerular capillaries, arterioles, and interlobular arteries. Deposition of IgM and other complement components occasionally is observed by means of immunofluorescence study. Electron microscopy shows widening of the subendothelial zone with electron-lucent material and new basement membrane formation. Fibrin tactoids frequently are seen. Arterioles and large arteries show mucoid intimal thickening. These vascular lesions result in renal ischemia. Ischemic necrosis occurs if the arteries are severely occluded. Lesions, both glomerular and vascular, can be progressive, leading to end-stage kidney disease, although there is evidence that renal lesions in patients with BMT nephropathy are reversible.8Alpers C.E. Irradiation injury.in: Jennette J.C. Olson J.L. Schwartz M.M. Silva F.G. Heptinstall’s Pathology of the Kidney. (ed 5). Lippincott-Raven, Philadelphia, PA1998: 1131-1148Google Scholar There is no evidence of lesions in other organs.12George J.N. Selby G.B. Thrombotic microangiopathy after allogeneic bone marrow transplantation: A pathologic abnormality associated with diverse clinical syndromes.Bone Marrow Transplant. 2004; 33: 1073-1074Crossref PubMed Scopus (30) Google Scholar The primary site of renal injury from radiation appears to be the endothelium, both glomerular and extraglomerular.13Madrazo A. Schwarz G. Churg J. Radiation nephritis: A review.J Urol. 1975; 114: 822-827Abstract Full Text PDF PubMed Scopus (28) Google Scholar DNA of endothelial cells can be damaged by relatively low-dose radiation exposure.2Zager R.A. Acute renal failure in the setting of bone marrow transplantation.Kidney Int. 1994; 46: 1443-1458Crossref PubMed Scopus (145) Google Scholar These endothelial cells with damaged DNA are predisposed to thrombus formation, leading to TMA. Pigs irradiated with a single dose of 9.8 Gy gamma ray showed morphological changes in glomeruli 3 to 6 weeks after irradiation. Serial renal biopsy specimens showed leukocyte influx and attachment to the capillary endothelium, followed by endothelial swelling and occasional thrombus formation. Peritubular capillaries had similar changes. Mesangial expansion and sclerosis with decreased glomerular filtration rate ensued 12 weeks after irradiation.14Jaenke R.S. Robbins M.E. Bywaters T. Whitehouse E. Rezvani M. Hopewell J.W. Capillary endothelium Target site of renal radiation injury.Lab Invest. 1993; 68: 396-405PubMed Google Scholar In vitro study showed neutrophil chemotactic activity in irradiated endothelium that was related to dose and duration of radiation. The mechanisms include release of chemotactic factors from irradiated endothelial cells15Eldor A. Fuks Z. Matzner Y. Witte L.D. Vlodavsky I. Perturbation of endothelial functions by ionizing irradiation: Effects on prostaglandins, chemoattractants and mitogens.Semin Thromb Hemost. 1989; 15: 215-225Crossref PubMed Scopus (41) Google Scholar and synthesis and/or upregulation of such cell adhesion molecules as E-selectin16Hallahan D. Clark E.T. Kuchibhotla J. Gewertz B.L. Collins T. E-Selectin gene induction by ionizing radiation is independent of cytokine induction.Biochem Biophys Res Commun. 1995; 217: 784-795Crossref PubMed Scopus (115) Google Scholar and intercellular adhesion molecule.17Quarmby S. Hunter R.D. Kumar S. Irradiation induced expression of CD31, ICAM-1 and VCAM-1 in human microvascular endothelial cells.Anticancer Res. 2000; 20: 3375-3381PubMed Google Scholar Increased expression of plasminogen activator inhibitor 1 was shown in glomerular cells of the mouse radiation nephropathy model. Increased plasminogen activator inhibitor 1 expression promotes thrombosis by preventing fibrinolysis. In addition, it induces fibrosis by attenuation of extracellular matrix degradation by the plasminogen activator/plasmin system.18Oikawa T. Freeman M. Lo W. Vaughan D.E. Fogo A. Modulation of plasminogen activator inhibitor-1 in vivo: A new mechanism for the anti-fibrotic effect of renin-angiotensin inhibition.Kidney Int. 1997; 51: 164-172Crossref PubMed Scopus (216) Google Scholar Irradiation also affects mesangial cell and matrix. In vitro study of rat mesangial cells showed increased transforming growth factor β messenger RNA after irradiation,19Wang J. Robbins M.E. Radiation-induced alteration of rat mesangial cell transforming growth factor-beta and expression of the genes associated with the extracellular matrix.Radiat Res. 1996; 146: 561-568Crossref PubMed Scopus (35) Google Scholar but subsequent study failed to show increased transforming growth factor β expression.20Zhao W. O’Malley Y. Robbins M.E. Irradiation of rat mesangial cells alters the expression of gene products associated with the development of renal fibrosis.Radiat Res. 1999; 152: 160-169Crossref PubMed Scopus (32) Google Scholar Increased expression of tissue inhibitor of metalloproteinase in irradiated rat mesangial cells possibly could be important in triggering a scarring process in the mesangium.20Zhao W. O’Malley Y. Robbins M.E. Irradiation of rat mesangial cells alters the expression of gene products associated with the development of renal fibrosis.Radiat Res. 1999; 152: 160-169Crossref PubMed Scopus (32) Google Scholar Tubular epithelium also evidently is affected by irradiation. The radiosensitivity of different cell types can be compared by means of the dose-response curve of cell survival after irradiation (D0). D0 is the dose in centigrays that can decrease the cell population to 37%. Bone marrow stem cells have a D0 of approximately 100 cGy, whereas renal tubular cells have a D0 of 150 cGy. Therefore, the radiation dose used in BMT for marrow cell ablation has the potential to injure renal tubular epithelium.7Cohen E.P. Radiation nephropathy after bone marrow transplantation.Kidney Int. 2000; 58: 903-918Crossref PubMed Scopus (96) Google Scholar It generally is believed that tubular cell death is a relatively late phenomenon compared with radiation injury to glomerular cells.21Withers H.R. Mason K.A. Thames Jr, H.D. Late radiation response of kidney assayed by tubule-cell survival.Br J Radiol. 1986; 59: 587-595Crossref PubMed Scopus (79) Google Scholar However, recent data showed apoptosis of renal tubular cells within the first day after irradiation.22Gobe G. Schoch E. Leighton J. Molecular controls of radiation-induced apoptosis in the neonatal rat kidney.Kidney Int. 1999; 56: 1305-1309Crossref PubMed Scopus (7) Google Scholar Radiation injury to tubular cells could occur in both the acute and late stages. Interstitial fibroblasts are stimulated by tubular fibrin in irradiated pig kidneys. Fibrin from radiation-injured glomeruli passes into tubular lumens and crosses tubular basement membranes to activate fibroblasts.23Gray A.J. Bishop J.E. Reeves J.T. Laurent G.J. α and β chains of fibrinogen stimulate proliferation of human fibroblasts.J Cell Sci. 1993; 104: 409-413Crossref PubMed Google Scholar Transforming growth factor β expression is found in both tubular epithelial cells and interstitial fibroblasts. α-Smooth muscle actin, collagen III, and fibronectin also are expressed in irradiated rat kidneys.24Robbins M.E. O’Malley Y. Zhao W. Davis C.S. Bonsib S.M. The role of the tubulointerstitium in radiation-induced renal fibrosis.Radiat Res. 2001; 155: 481-489Crossref PubMed Scopus (31) Google Scholar This process can lead to increased extracellular matrix deposition and fibrosis in patients with BMT nephropathy and other renal diseases. There is evidence that cyclosporine, a drug commonly administered to patients after BMT, is unlikely to cause this renal lesion. Half the patients with BMT nephropathy never were administered this drug.2Zager R.A. Acute renal failure in the setting of bone marrow transplantation.Kidney Int. 1994; 46: 1443-1458Crossref PubMed Scopus (145) Google Scholar However, study in rats indicated that cytotoxic chemotherapeutic drugs can exacerbate radiation nephropathy.25Moulder J.E. Fish B.L. Influence of nephrotoxic drugs on the late renal toxicity associated with bone marrow transplant conditioning regimens.Int J Radiat Oncol Biol Phys. 1991; 20: 333-337Abstract Full Text PDF PubMed Scopus (26) Google Scholar Administration of cis-platinum or BCNU 3 months before irradiation and BMT significantly decreased survival rates of rats compared with the control group with irradiation and BMT only. This study supported the notion that chemotherapeutic drugs have a role in the pathogenesis of BMT nephropathy, at least in rodent models. These drugs may increase the radiosensitivity of glomerular cells. This could explain why patients after BMT with a less than nephrotoxic dose of radiation experience radiation injury to their kidneys in the form of BMT nephropathy. Before 1990, patients with radiation/BMT nephropathy inevitably progressed to end-stage renal disease. However, along with a renoprotective effect in patients with many renal diseases, angiotensin-converting enzyme (ACE) inhibitors, especially captopril, and angiotensin type II receptor antagonists slowed the progression of BMT nephropathy in experimental models.18Oikawa T. Freeman M. Lo W. Vaughan D.E. Fogo A. Modulation of plasminogen activator inhibitor-1 in vivo: A new mechanism for the anti-fibrotic effect of renin-angiotensin inhibition.Kidney Int. 1997; 51: 164-172Crossref PubMed Scopus (216) Google Scholar, 26Cohen E.P. Fish B.L. Moulder J.E. Treatment of radiation nephropathy with captopril.Radiat Res. 1992; 132: 346-350Crossref PubMed Scopus (61) Google Scholar, 27Moulder J.E. Fish B.L. Cohen E.P. Angiotensin II receptor antagonists in the treatment and prevention of radiation nephropathy.Int J Radiat Biol. 1998; 73: 415-421Crossref PubMed Scopus (44) Google Scholar These results indicated an important role of the renin-angiotensin system in the pathogenesis of radiation/BMT nephropathy. ACE inhibitors and angiotensin type II receptor antagonists do not prevent renal cell injury caused by irradiation, but they have effects on the pathogenetic process that are activated after radiation injury.7Cohen E.P. Radiation nephropathy after bone marrow transplantation.Kidney Int. 2000; 58: 903-918Crossref PubMed Scopus (96) Google Scholar Inhibition of the renin-angiotensin system has effects on hemodynamics. Injured capillaries can retain their normal permeability when the renin-angiotensin system is inhibited.28Fantone J.C. Schrier D. Weingarten B. Inhibition of vascular permeability changes in rats by captopril.J Clin Invest. 1982; 69: 1207-1211Crossref PubMed Scopus (47) Google Scholar In addition, the fibrotic process caused by irradiation is ameliorated by modulation of the plasminogen/plasmin system.18Oikawa T. Freeman M. Lo W. Vaughan D.E. Fogo A. Modulation of plasminogen activator inhibitor-1 in vivo: A new mechanism for the anti-fibrotic effect of renin-angiotensin inhibition.Kidney Int. 1997; 51: 164-172Crossref PubMed Scopus (216) Google Scholar Although the beneficial effect of ACE inhibitors and angiotensin type II receptor antagonists in patients with BMT nephropathy clearly has been established, the mechanism is not well elucidated.29Cohen E.P. Robbins M.E. Radiation nephropathy.Semin Nephrol. 2003; 23: 486-499Abstract Full Text Full Text PDF PubMed Scopus (166) Google Scholar In summary, we present the case of a child who underwent autologous peripheral-blood SCT and subsequently had BMT nephropathy. The pathogenesis is a complex and dynamic interaction between glomerular, tubular, and interstitial cells involving biological mediators, predominantly angiotensin II.29Cohen E.P. Robbins M.E. Radiation nephropathy.Semin Nephrol. 2003; 23: 486-499Abstract Full Text Full Text PDF PubMed Scopus (166) Google Scholar BMT nephropathy is an important cause of chronic renal failure leading to end-stage kidney disease in patients undergoing BMT, the number of which is increasing worldwide. It is crucial to recognize BMT nephropathy. Treatment with angiotensin inhibitors may help prevent or slow the progression of this condition.