Authors: Abdulrahim Al Zoubi, Mohammad Basheer Alameer, Anas Saad, Ibrahim Barghouth, Mohammad Ali Nahas
Categories: Case Report, Pediatric renovascular hypertension, Renal artery stenosis, Auto kidney transplantation, IgA-mediated vasculopathy
Source: Journal of Medical Case Reports
Authors: Abdulrahim Al Zoubi, Mohammad Basheer Alameer, Anas Saad, Ibrahim Barghouth, Mohammad Ali Nahas
Immunoglobulin A vasculitis (IgAV) is the most common cause of vasculitis among children. However, it is a very rare cause of large artery vasculitis. The histopathology of immunoglobulin A vasculitis typically involves IgA deposits in small vessels of the dermis, joints, kidneys, and gastrointestinal tract. These deposits induce an inflammatory response, activating the complement system, which explains the variety of symptoms and signs.
A 14-year-old Levantine Arab male with malignant refractory hypertension and prior left nephrectomy was referred for evaluation. The initial presentation at the age of 4 years revealed severe bilateral renal artery stenosis, left ventricular hypertrophy, and reduced ejection fraction (31%), which improved with medical therapy. Parents declined vascular interventions. At the age of 7 years, left kidney atrophy and total occlusion of the left renal artery led to nephrectomy. At the age of 14 years, hypertension worsened despite multiple antihypertensives. Imaging showed total occlusion of the right renal artery. A multidisciplinary team recommended autotransplantation of the solitary right kidney to the left iliac fossa. Postoperative recovery included transient anuria, followed by normalization of renal function and blood pressure. Histopathology revealed IgA-mediated vascular changes without amyloid deposition. The 1-month follow-up showed controlled blood pressure (130/80 mmHg) on reduced antihypertensive therapy.
This rare case sheds light on malignant renovascular hypertension in a young male, possibly due to IgA deposition in the right renal artery after a previous left nephrectomy. The surgical decision took into consideration the young age of the patient and the eventual characteristics of the renal artery, in addition to the size of the artery; therefore, we preferred and proceeded to an auto kidney transplant rather than aortorenal bypass, believing that the arterial anastomosis, which is the most important, could be more convenient from the hemodynamic point of view.
Immunoglobulin A vasculitis (IgAV) is a disorder that is usually diagnosed among children younger than 10 years old, and it represents their most common type of vasculitis [1]. The common presentation of IgAV includes palpable purpura, abdominal pain, joint pain, and renal injury, which ranges from hematuria and/or proteinuria to nephritic and nephrotic syndrome, and can progress to chronic kidney disease in some cases [1–3]. The diagnosis of IgAV is usually clinical, and histological confirmation is not required, especially among children [4].
The histopathology of IgAV typically involves IgA deposits in small vessels of the dermis, joints, kidneys, and gastrointestinal tract. These deposits induce an inflammatory response, activating the complement system, which explains the variety of symptoms and signs [1].
The deposition of immune complexes in large arteries is extremely rare, but it has been described in literature, and it is usually mediated by IgG or IgM antibodies [5, 6]. Moreover, atypical presentation of IgAV has been previously reported, such as pulmonary hemorrhage, orchitis, cerebral hemorrhage, and myocardial infarction [7].
In this case report, we describe bilateral renal artery ostial occlusion as a result of IgAV in a 14-year-old patient with malignant refractory hypertension.
A 14-year-old Levantine Arab male was referred because of malignant refractory hypertension. He had had a previous left nephrectomy at the age of 7 years.
The patient, at the age of 4 years, was referred to the pediatric university hospital in Damascus, complaining of vague abdominal pain and urinary tract infection-related symptoms. His arterial pressure was 220/120 mmHg, white blood cells (WBCs): 14,000 cells/μL, erythrocyte sedimentation rate (ESR): 1 h 40 mm/hr. Echocardiogram showed signs of left ventricular hypertrophy and an ejection fraction (EF) of 31%. The patient was treated with nitroglycerin, captopril, digoxin, and furosemide. Kidney color echo Doppler evidenced severe bilateral renal artery stenosis, which was later confirmed by digital subtraction angiography (DSA). After 2 weeks of treatment, the EF became 53%, and the blood pressure was well controlled. Digoxin and furosemide were suspended, and the patient continued the other antihypertensive drugs. We proposed, as a vascular treatment, to proceed with an endovascular approach by using a cutting balloon percutaneous transluminal angioplasty (PTA) or an auto kidney transplantation; both options were refused by the parents, who preferred to continue the antihypertensive therapy. After 3 years, at the age of 7 years, the patient was re-referred to the pediatric university hospital because of vague abdominal pain and arterial hypertension. A renal echogram evidenced a left kidney atrophy (5 cm) and total occlusion of the left renal artery, while the right kidney was normal in size and cortico-medullary differentiation. The previously observed right renal artery stenosis was stable. Glomerular filtration rate (GFR) of the left kidney was 7%, while GFR of the right kidney was 92.5% as observed by renal scintigraphy. Left nephrectomy was performed. There was no histopathological study after this procedure owing to financial difficulties, and the patient continued his antihypertensive drugs. At the age of 14 years, the patient was referred to the vascular surgery department because of uncontrolled malignant arterial pressure. The patient’s medical antihypertensive therapy, on admission, was nifedipine, methyldopa, atenolol, and hydrochlorothiazide.
No family history and no other significant medical history were signaled.
At admission, the physical examination was unremarkable, except for a blood pressure of 230/170. Renal function was normal as determined by creatinine level of 0.95 mg/dl (normal range 0.6–1.2), urea level of 35 mg/dl (normal range 18–45), and negative findings in urinalysis. The remaining laboratory values on admission are displayed in Table 1.Table 1Laboratory results upon admissionWhite blood cells7210 cells/μLN/L63/36Hematocrit44%Hemoglobin14.5 mg/dlPlatelets314,000 platelets per microliterUrea35 mg/dLCreatinine0.95 mg/dlNa145 mmol/LK4.37 mmol/LGlucose81 mg/dlLDH157 U/LTotal protein7.3 g/dLAlbumin4.2 g/dLSGPT13 U/LSGOT16 U/LCalcium9.2 mg/dLTotal cholesterol105 mg/dLTriglyceride81 mg/dLProthrombin activity94%INR1.04PTT27.2ESR9 mm/hrUrine colorYellowUrine specific gravity1.010Urine appearanceClearUrine pH5Urine leucocytes5 per hpfUrine erythrocyte5 per hpfAll other findings in the urine were negativeSGOT, serum glutamic-oxaloacetic transaminase; SGPT, serum glutamic pyruvic transaminase; INR, international normalized ratio; PTT, partial thromboplastin time; LDH, lactate dehydrogenase
The color echo Doppler of the right kidney and renal artery evidenced total occlusion of the ostial segment. A contrast multi-slice computed tomography scan was performed, which showed a single right kidney, normal in size and cortico-medullary differentiation, with no stones or hydronephrosis. The origin of the right renal artery from the abdominal aorta was totally occluded for 13 mm (Fig. 1).Fig. 1Contrast multislice computed tomography of the solo right kidney (A). A three-dimensional reconstruction of the aorta and its branches (B). The arrow shows the occluded right renal artery in both images
The patient was considered a renovascular hypertension patient. A multidisciplinary team (MDT) consisting of a cardiologist, pediatrician, urologist, and vascular surgeon discussed the patient’s case and concurred that to achieve better control of the refractory hypertension, a right kidney auto transplant must be done, relocating the solitary functioning kidney in the left iliac fossa by end to side anastomosis of the renal vein to the common iliac vein and end to end anastomosis of the renal artery to internal iliac artery.
Under general anesthesia, a left lower-quadrant paramedian incision was performed. The left internal iliac artery and common iliac vein were isolated and prepared, and then, via a right subcostal (Kocher) incision, the right kidney was exposed. A standard nephrectomy was performed. The kidney was perfused by the appropriate solution and prepared for an auto-transplantation. The venous outflow was established via an end-to-side 6/0 Prolene running suture anastomosis between the renal vein and the common iliac vein (12 min). An end-to-end noncontinuous 6/0 Prolene suture arterial anastomosis was done between the renal artery and the left internal iliac artery (8 min). The distal end of the left internal iliac artery was ligated. A specimen of the renal artery was harvested and sent for histopathological study. Ureteral continuity was restored using the Lich–Gregoir reimplantation technique into the bladder, followed by a DJ catheter insertion. A closed-suction drain was positioned in the left iliac fossa and in the right quadrant, and the abdominal wall was closed in layers. Figure 2 shows a postoperative computed tomography scan.Fig. 2The 1-month postoperative computed tomography scan. A Coronal computed tomography view demonstrating postoperative vascular anatomy and abdominal organ positioning. B Three-dimensional computed tomography reconstruction of the same view
The patient was admitted to the intensive care unit (ICU) to control his blood pressure with nitroglycerin infusion. His 3-day ICU follow-up was characterized by an initial 13-hour period of anuria and progressive elevation of creatinine and urea, while potassium levels were within the normal range. The venous central pressure was (6 mmHg), and the echo color Doppler ultrasound confirmed the good patency of the transplanted renal artery and vein with well-parenchymal perfusion. At hour 12 in the ICU, the patient started to have a urinary output reaching 100 mL/hour. Creatinine and urea levels also started to normalize gradually. The patient was later discharged back to the ward.
The clinical and laboratory follow-up in the ward were characterized by progressive normalization of his blood pressure values (Fig. 3) using the same previous antihypertensive regimen, reaching 140/90 mmHg. Creatinine, urea, and potassium follow-up are displayed in Figs. 4 and 5.Fig. 3Systolic and diastolic blood pressure values in mmHg during the patient’s stay. The 13th day’s value was recorded in the wardFig. 4Potassium values during the patient’s stay. Values are measured in mmol/LFig. 5Patient’s urea and creatinine levels mg/dL during his stay
After 1 month of follow-up, the average arterial pressure was 130/80 mmHg while on telmisartan 40 mg, amlodipine 5 mg, carvedilol 3125 mg, and methyldopa 250 mg. Note that the dose of these medications has been gradually decreased with follow-up by a cardiologist. The patient was referred for follow-up with a nephrologist to prevent vasculitis of the grafted kidney.
Histological examination with hematoxylin and eosin (H&E) staining revealed focal hyalinization of the arterial wall. Immunohistochemical staining for IgA demonstrated prominent deposition within the vascular walls, consistent with an IgA-mediated immune process. Congo red staining was negative, excluding amyloid deposition (Fig. 6). These findings suggest an IgA-related immune disorder affecting the renal vasculature.Fig. 6Histopathology. A hematoxylin and eosin 100×, B IgA by immunohistochemistry 100×, C hematoxylin and eosin 200×, D hematoxylin and eosin 200×, E IgA by immunohistochemistry 200×, F IgA by immunohistochemistry 200×
Types of vasculitis are usually classified according to the size of the affected vessels; for example, IgAV is classically a small vessel vasculitis, while giant cell arteritis (GCA) and Takayasu arteritis (TAK) are the major types of large vessel vasculitis [8]. The absence of a granulomatous inflammation and the presence of IgA deposits in this patient’s renal artery would most likely exclude GCA and TAK as the diagnosis [9], making this case the first case of IgAV with renal artery involvement with no evidence of glomerular disorder before the renal auto transplant. Moreover, this case reinforces what previous papers have that any vessel could be affected by any type of vasculitis [10, 11] . Furthermore, this case sheds light on an unusual treatment for IgAV, even though this type of treatment has been used before in treating bilateral renal artery stenosis caused by TAK [12].
A review of literature suggests that large-vessel involvement can occur in IgA vasculitis (IgAV). Kang et al. described coronary artery aneurysms as a complication of IgAV: 70.8% of patients in this paper had renal involvement alongside the coronary artery aneurysms, and the majority of them were males. It was also noted that older patients were more likely to show this presentation despite IgAV being a relatively rare disorder among them [7]. Harikrishnan et al. reported a case of a 15-year-old female with purpuric rash, episodic polyarthritis, melena, and large artery involvement represented by the cut-off of flow in the posterior tibial artery [10]. Sabzevari et al. reported a case of a 29-year-old male with IgAV diagnosed at the age of 14 years, which resulted in end-stage renal failure and was later complicated with critical limb ischemia. The interesting aspects of the aforementioned case were the positivity of lupus anticoagulant antibodies, the mildly raised C-reactive protein levels (10 mg/L), the positive IgA deposits in a punch biopsy, and the positive uptake in the subclavian, brachiocephalic, abdominal aortic, iliac, and femoral arteries on a positron emission tomography computed tomography (PET-CT), confirming large vessel involvement in this case [13].
It has been described that accumulation of immune complexes in the walls of arteries among patients with systemic lupus erythematosus (SLE) can lead to noninflammatory artery stenosis, which is similar to our case, with a difference in antibody type [14]. IgA deposits can contribute to the initiation and amplification of inflammation by triggering Fc alpha receptor 1, which can, in turn, synergize with other factors and receptors to amplify inflammation [15]. This inflammation causes endothelial damage, which causes plasma leakage into the vessel wall. This process is thought to be the cause of hyalinization [16], which was observed in the renal artery wall in this case.
We proceeded to an auto kidney transplantation rather than aorto–renal bypass or direct patch endarterectomy because we believed that it could be more appropriate from the hemodynamic point of view, with good future patency.
Future research should investigate large vessel IgAV in more detail to look into clinical, histopathological, genetic, or environmental characteristics that distinguish this disorder, as it can be the cause of idiopathic cases of large artery stenosis, especially among pediatric patients, possibly improving their prognosis.
This rare case sheds light on malignant renovascular hypertension in a young male due to IgA deposition in the right renal artery after a previous left nephrectomy. The surgical decision took into consideration the young age of the patient and the eventual characteristics of the renal artery, in addition to the size of the artery; therefore, we preferred and proceeded to an auto kidney transplant rather than aortorenal bypass, believing that the arterial anastomosis, which is the most important, could be more convenient from the hemodynamic point of view.
The arterial pressure values may take a long time before returning to normal because of the high peripheral resistance gained through the long-term morbidity, and this may require a long period of antihypertensive treatment, which can, contrary to before the surgery, control the blood pressure.