|Year : 2021 | Volume
| Issue : 1 | Page : 69-72
Renal transplantation in a patient with polyarteritis nodosa - A case report
K Vinod Kumar1, V Narayanan Unni1, Nanda Kachare2, R Anil Kumar3, Bipi Prasannan1, Vishnu Dev Urs1
1 Department of Nephrology, Aster Medcity, Kochi, Kerala, India
2 Department of Pathology, Aster Medcity, Kochi, Kerala, India
3 Department of Cardiology, Aster Medcity, Kochi, Kerala, India
|Date of Submission||10-Sep-2020|
|Date of Acceptance||08-Jan-2021|
|Date of Web Publication||31-Mar-2021|
Dr. K Vinod Kumar
Department of Nephrology, Aster Medcity, Cheranalloor, Kochi - 682 027, Kerala
Source of Support: None, Conflict of Interest: None
Polyarteritis nodosa (PAN) is a systemic necrotizing vasculitis, predominantly affecting medium-sized arteries, and usually involving the kidneys, heart, gastrointestinal tract, and nervous system. The common clinical presentation is renovascular hypertension due to renal artery stenosis. We report a 38-year-old man, who presented with secondary hypertension and progressive renal failure leading on to end-stage renal disease (ESRD). He had renal artery stenosis on evaluation which caused ischemic damage to the kidneys resulting in ESRD. He also had multivessel coronary artery disease requiring percutaneous transluminal angioplasty. Coronary angiogram and renal angiogram showed areas of ectatic segments and aneurysms along with stenotic segments, which was consistent with medium-vessel vasculitis. We had challenges in considering him for kidney transplantation due to significant coronary artery disease, and he required coronary angioplasty on two occasions 6 months apart. He underwent bilateral nephrectomy prior to the transplantation as he had refractory hypertension requiring five antihypertensive medications. Histology of the nephrectomy specimen confirmed the diagnosis of PAN. Our patient did not show evidence of hepatitis B infection which is commonly associated with PAN. Renal failure and progression to ESRD are rare in PAN and are due to ischemic damage to the kidneys. He underwent kidney transplantation and had a smooth perioperative period and normal graft functions 6 months after the transplant surgery. To the best of our knowledge, this is the second reported case of PAN, who underwent successful kidney transplantation. Significant coronary artery disease is a rare manifestation in PAN.
Keywords: Coronary artery disease, end-stage renal disease, polyarteritis nodosa, renal transplantation, vasculitis
|How to cite this article:|
Kumar K V, Unni V N, Kachare N, Kumar R A, Prasannan B, Urs VD. Renal transplantation in a patient with polyarteritis nodosa - A case report. Indian J Transplant 2021;15:69-72
|How to cite this URL:|
Kumar K V, Unni V N, Kachare N, Kumar R A, Prasannan B, Urs VD. Renal transplantation in a patient with polyarteritis nodosa - A case report. Indian J Transplant [serial online] 2021 [cited 2021 Apr 15];15:69-72. Available from: https://www.ijtonline.in/text.asp?2021/15/1/69/312746
| Introduction|| |
Polyarteritis nodosa (PAN) is a systemic necrotizing vasculitis, predominantly affecting medium-sized arteries. It may affect any organ, but for unknown reasons, it spares the pulmonary arteries and glomerular capillaries. The presence of glomerular involvement is classified as microscopic polyangiitis (MPA) as per the new classification for vasculitis. Renal failure due to PAN reported in the past is mainly due to MPA which presents with glomerulonephritis overlapping with necrotizing vasculitis involving the medium-sized arteries. End-stage renal disease (ESRD) is rarely seen in patients with classical PAN in contrast to MPA. Renal involvement in PAN manifests as stenotic lesions and aneurysmal dilatation of main renal arteries and its segmental branches. Progression to ESRD is rarely reported (few case reports) in PAN after the new classification and is predominantly due to ischemic damage to the kidneys., We report a patient with PAN, progressing to ESRD, who underwent successful kidney transplantation.
| Case Report|| |
A 38-year-old man was evaluated for breathlessness 6 years back, and was found to have accelerated hypertension, mild renal failure (serum creatinine: 1.9 mg/dL), and severe left ventricular (LV) dysfunction (ejection fraction of 32%). Urine routine examination was bland except for mild proteinuria. He had proteinuria of 1.3 g in 24 h; kidney biopsy was not done in view of the small and echogenic kidneys on ultrasonogram. Renal artery Doppler showed left main renal artery stenosis which was confirmed by magnetic resonance (MR) angiogram. He had constitutional symptoms in the form of intermittent low-grade fever, malaise, and myalgia lasting for 6 months before the diagnosis of kidney disease. He received steroids empirically for a few months at another hospital; he stopped steroids, following which he had progressive worsening of renal functions and reached ESRD. He was started on maintenance hemodialysis and worked up for renal transplantation. Echocardiogram 3 years after the initial presentation showed global LV hypokinesia with moderate LV dysfunction; exercise stress test was positive for inducible ischemia, however, he had no history of chest pain. He underwent coronary angiogram which showed multivessel coronary artery disease with evidence of ectasia and aneurysms [Figure 1]a and [Figure 1]b. Thoracic and abdominal aortas were normal; there was evidence of bilateral renal artery stenosis (left 90% and right 99%) [Figure 2]a and [Figure 2]b. Computed tomography (CT) aortogram showed similar findings; in addition to narrowing of renal arteries, it showed the involvement of the right phrenic artery. He had no other extrarenal manifestations other than the heart: no joint pains, abdominal pain, skin rashes, eye manifestations, or any other organ involvement. Since he was keen for transplantation, he underwent percutaneous transluminal angioplasty of the left anterior descending (LAD) and diagonal arteries [Figure 1]c and [Figure 1]d and was started on dual antiplatelet drugs and was continued on dialysis for 6 months. Treadmill test (TMT) repeated after 6 months was positive for inducible ischemia. Redo angioplasty was done to LAD. The patient had to wait for 6 more months before considering transplantation. In view of involvement of renal arteries and coronary arteries, with multiple ectatic segments and aneurysmal dilatation in the arteries, a diagnosis of medium-vessel vasculitis, PAN was made. Hepatitis B infection is commonly associated with this condition, however, serum hepatitis B surface antigen was negative. Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were normal. Antineutrophil cytoplasmic antibody (ANCA) test was negative. The cause for chronic kidney disease is probably ischemic nephropathy secondary to bilateral renal artery stenosis. The patient was considered for transplantation after explaining the risk due to coronary artery disease. Since he had uncontrolled hypertension, requiring five antihypertensive medications including diuretics, it was decided to do bilateral nephrectomy at the time of transplantation.
|Figure 1: (a) Proximal left circumflex artery shows large aneurysm (white arrow) followed by 50% stenosis (yellow arrow), (b) distal left anterior descending artery shows 100% occlusion (yellow arrow), (c) balloon dilatation of distal left anterior descending (arrow), (d) good blood flow restored after stenting in distal left anterior descending (arrow)|
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|Figure 2: (a) Left renal artery shows proximal 90% stenosis (yellow arrow) followed by aneurysmal dilatation and ectatic segments (white arrow), (b) right renal artery shows distal 90% stenosis (yellow arrow)|
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The patient underwent live related robotic kidney transplantation, with wife as the donor (1/6 human leukocyte antigen match). It was combined with bilateral nephrectomy. He was continued on ecosprin; clopidogrel was stopped 5 days before the surgery and was restarted 5 days after the surgery. Injection basiliximab 20 mg was given as an induction agent on days 0 and 4. He was started on tacrolimus, mycophenolate mofetil, and prednisolone as maintenance immunosuppression. He was given low-molecular-weight heparin for 5 days in the postoperative period. He had a smooth postoperative course and was discharged from the hospital 6 days after the surgery. All his antihypertensive medicines were stopped as the current blood pressure is 120/80 mm Hg. He has completed 6 months after transplant. His graft function is remaining stable (present creatinine is 1.0 mg/dL), and no complications were noted during this period. Nephrectomy specimen was sent for histopathology. The bilateral nephrectomy specimen showed grossly shrunken kidneys with adherent capsule, and cut sections of both kidneys showed thrombosed renal arteries and few interlobular arteries with gritty hard cut surface [Figure 3]a. The histopathology of both kidneys showed severe glomerulosclerosis, periglomerular fibrosis with thyroidization of tubules [Figure 3]b, and dense chronic interstitial inflammatory infiltrates consistent with ESRD. The sections of bilateral renal arteries showed thrombosis with hyalinization occluding the lumina completely with calcification and cholesterol clefts with giant cell reaction [Figure 3]c, [Figure 3]d, [Figure 3]e, [Figure 3]f. The renal arteries showed disruption of internal elastic lamina [Figure 3]f, elastic van Gieson stain] and thinned out muscular layer with pseudoaneurysm formation [Figure 3]d and transmural chronic inflammatory infiltrate [Figure 3]c. The histopathological features confirmed the healed stage of PAN. Repeat TMT, 3 months after the transplant surgery, was negative.
|Figure 3: (a) Nephrectomy specimen with thrombus in renal artery (red arrow); (b) glomerulosclerosis with thyroidization of tubules and hypertensive vascular changes (H and E, ×200); (c) renal artery with extensive intimal fibroplasia and chronic inflammatory infiltrate in the wall (H and E, ×400); (d) thrombosed renal artery with pseudoaneurysm formation and disrupted internal elastic lamina (H and E, ×200); (e) thrombosed renal artery with pseudoaneurysm formation and disrupted internal elastic lamina (elastic van Gieson stain, ×200); (f) thrombosed renal artery with calcification (H and E, ×200)|
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| Discussion|| |
The kidneys are targets for a variety of systemic vasculitides, especially those that affect small vessels. Based on 2012 Chapel Hill Consensus Conference definitions, vasculitides can be categorized as large-vessel vasculitis, medium-vessel vasculitis, and small-vessel vasculitis. ANCA-associated vasculitis is small-vessel vasculitis that predominantly affects the kidneys resulting in renal failure and ESRD. Although any arteries in the kidney can be affected by PAN, interlobular and arcuate arteries are the most common; main renal arteries can also be involved, as in our case. The presence of glomerulonephritis overlapping with involvement of medium-sized arteries is now classified as MPA according to the newer classification. Medium-vessel vasculitis like PAN usually present with hypertension, rarely resulting in renal failure.
PAN is a systemic necrotizing vasculitis that predominantly affects medium-sized muscular arteries and occasionally involves small muscular arteries. The prevalence of PAN ranges from 2 to 33 per million population.,, Thirty percent of patients with PAN have chronic hepatitis B infection. The marked reduction in hepatitis B virus infection has been associated with the reduction in the prevalence of PAN. It is commonly described in middle-aged or older adults, and males are more commonly affected. Most cases of PAN are idiopathic. Secondary causes include hepatitis B virus infection, hepatitis C infection, human immunodeficiency virus infection, cytomegalovirus infection, and hairy cell leukemia.,, Our patient was a middle-aged male and had no specific triggers.
PAN was initially considered as an immune complex-related disease based on the development of necrotizing arteritis in animal models of immune complex-mediated injury. The presence of dendritic cells and the abundance of CD4 T-lymphocytes in vascular inflammatory infiltrates suggest that antigen-specific T-cell-mediated immune responses may also play a role in the pathogenesis of vascular inflammation in PAN.
Clinical features include nonspecific constitutional symptoms such as malaise, weight loss, fever, arthralgia and myalgia (seen in 60% of the patients), and symptoms derived from dysfunction or damage of the target organs. Our patient had constitutional symptoms for more than 6 months before the diagnosis was made.
Polyarteritis nodosa and kidney
Based on autopsy reports, kidney is the most common organ involved in PAN. Thickening of the inflamed vessel wall and intimal proliferation can cause luminal narrowing, reducing blood flow and predisposing to thrombosis of affected vessels. The resulting ischemia or infarction causes acute kidney injury which can progress to ESRD later. Involvement of branches of the renal arteries or intrarenal vessels such as the interlobular or arcuate arteries causes renal ischemia, activation of the renin–angiotensin system, and hypertension., Inflammation can cause weakening of the vessel wall that leads to aneurysm formation. Aneurysmal rupture may result in life-threatening bleeding (perinephric hematoma). It causes glomerular ischemia but not inflammation or necrosis of the glomerular capillary tuft. Thus, the urinalysis shows only subnephrotic-range proteinuria and modest hematuria. Red blood cell casts are usually absent. Our patient had uncontrolled hypertension with minimal proteinuria and no hematuria. PAN leading to ESRD was reported in the past (prior to the new classification), but most of those cases were classified under MPA. Although prognosis of kidney disease is more favorable than many other systemic vasculitides with renal involvement, development of ESRD has only been rarely reported (few cases) in different series of PAN.
There are currently no diagnostic serologic tests for PAN, and the diagnosis is mainly based on the characteristic findings of vasculitis in biopsy specimens of the involved organs, as well as findings on renal angiogram. Although ESR and CRP are elevated in active disease, they are neither sensitive nor specific. Conventional renal arteriography or less invasive techniques such as CT/MR angiography show multiple aneurysms and irregular constrictions in the larger vessels with occlusion of smaller penetrating arteries. Confirmation of the diagnosis can be established by renal histology which shows inflammation in the medium-sized arteries and ischemic damage in the kidneys; often, this is not possible due to sampling error. It is characterized by segmental transmural inflammation of muscular arteries. PAN does not involve veins. The cellular infiltrate contains polymorphonuclear leukocytes and mononuclear cells. Fragments of white blood cells (leukocytoclasis) may be noted. Necrosis of the arterial wall results in a homogeneous, eosinophilic appearance referred to as fibrinoid necrosis. Disruption of the internal and external elastic lamina is noted and may contribute to the development of aneurysmal dilation. Lesions that appear to be of different ages are typically found within a single sample. Granulomatous inflammation does not occur in PAN. In our case, renal biopsy showed ischemic changes and features of vasculitis affecting the main renal arteries and interlobular arteries.
Polyarteritis nodosa and heart
Although overt acute myocardial infarction is uncommon, myocardial ischemia may result from narrowing or occlusion of the coronary arteries. Heart failure may result from either vasculitis of the coronary arteries, resulting in ischemic cardiomyopathy, or from uncontrolled hypertension caused by renal disease. Coronary arteries, though rarely involved, can manifest with multiple aneurysmal formation (typical), intraluminal thrombosis, and segmental luminal narrowing. Usually, it responds to immunosuppressive medications in the active stage. Our patient was detected to have multivessel coronary artery disease, for which angioplasty was done and stents were placed. New lesions were found 6 months later, and new stents were placed in those vessels.
Other system involvements include cutaneous manifestations (livedo reticularis, subcutaneous nodules, and necrotic ulcers), neurological manifestations (mononeuritis multiplex, polyneuropathy and stroke), gastrointestinal involvement (mesenteric ischemia), and testicular pain and tenderness. Our patient did not have other organ involvement except for the kidney and heart. The American College of Rheumatology has established ten criteria for the classification of PAN in a patient with a vasculitis. Six out of ten criteria for the diagnosis of PAN was fulfilled in our case.
Although he was treated with steroids initially, it was stopped in view of rapid progression of kidney disease to ESRD, and he had no other clinical features of activity of the disease. Although there is no literature mentioning about coronary angioplasty in PAN, since there was critical stenosis, we proceeded with coronary stenting in preparation for transplant surgery. He was on hemodialysis for 15 months prior to the transplant. First successful kidney transplantation in a patient with PAN was reported in the year 1980, with favorable outcomes. No further cases are reported after that our patient underwent successful live related kidney transplantation and received basiliximab induction followed by maintenance immunosuppression (tacrolimus/mycophenolate mofetil/prednisolone). He has completed 6 months after transplantation. He has normal graft functions, and repeat TMT done at the end of 3 months is negative. His blood pressure is normal, and all his antihypertensives (five medications) could be stopped after transplant. He is on dual antiplatelet drugs at present.
To the best of our knowledge, this is probably the second reported case of PAN who presented with ESRD and underwent successful kidney transplantation. PAN presenting with ESRD and significant coronary artery disease is rare. Kidney transplantation offers better quality of life and keeps the disease activity under check as the patient receives immunosuppressive medications following the transplant surgery.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
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Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3]