Renal artery stenosis following nilotinib administration in a patient with chronic myelogenous leukemia.

A 63-year-old male was diagnosed as having chronic phase CML in 2001. He obtained a major molecular response with imatinib (IM). In 2012, amulodipin was started for hypertension. In January 2013, IM was switched to nilotinib (NIL) in a clinical trial, and in February 2015, NIL was discontinued because MR4.5 had been maintained for two years. One month later, he was admitted to our hospital because of headache and high blood pressure (194/108 mmHg). His urine test showed protein 3+ and occult blood 2+. His eGFR rapidly deteriorated from 45.6 to 28.5 after admission. MR angiography showed left renal artery stenosis. He thus underwent angioplasty of the left renal artery with a stent implantation. His renal function subsequently improved. Cardiovascular events such as PAOD (peripheral artery occlusive disease) during NIL treatment were recently reported. However, to date, only four cases including our present patient with renal artery stenosis associated with NIL have been reported. These observations suggest assessment of risk factors for cardiovascular events at the start of NIL and careful monitoring to be important during tyrosine kinase inhibitor treatment of CML patients.

Does this patient have hypertensive encephalopathy?

A 63-year-old man was admitted to our hospital for further investigation and management of brain metastases. The patient was initially presented with a 4-day history of confusion. On the day of admission, the patient was confused, agitated, disorientated in place and time, and had visual disturbances. His blood pressure was repeatedly recorded high, with levels of systolic blood pressure between 170-210 mm Hg. A brain magnetic resonance imaging showed areas of high signal on T2 and fluid-attenuated inversion recovery images, located bilaterally in the white matter of the occipital regions and unilateral in the left frontal lobe, suggestive of posterior reversible encephalopathy syndrome. Aggressive treatment of hypertension resulted in complete resolution of the clinical and radiologic features of the syndrome.

Unilateral renal artery stenosis with renal atrophy in a patient with metastatic papillary thyroid carcinoma treated with sorafenib.

Tyrosine kinase inhibitors (TKIs) have been recently introduced for treatment of different malignancies. Various cardiovascular toxicities have been reported with TKIs with hypertension being the most common adverse cardiovascular event. We report a case of a 60-year-old woman who developed left renal artery stenosis associated with renal atrophy in the context of metastatic papillary thyroid carcinoma treated with sorafenib. Renal atrophy was noticed during serial imaging studies to monitor cancer therapy. Clinically, she was asymptomatic without significant change in blood pressure. The glomerular filtration rate dropped from 88 ml/min/1.73 m(2) at baseline to 56 ml/min/1.73 ml/min and partially recovered to 71 ml/min/1.73 m(2) after renal artery stenting. To our knowledge, this will be the first known case of renal artery stenosis associated with TKI use. Physicians may need to investigate the possibility of developing renal artery stenosis in patients with unexplained worsening in kidney functions while on TKIs.

Endothelial progenitor cells homing and renal repair in experimental renovascular disease.

Tissue injury triggers reparative processes that often involve endothelial progenitor cells (EPCs) recruitment. We hypothesized that atherosclerotic renal artery stenosis (ARAS) activates homing signals that would be detectable in both the kidney and EPCs, and attenuated on renal repair using selective cell-based therapy. Pigs were treated with intrarenal autologous EPC after 6 weeks of ARAS. Four weeks later, expression of homing-related signals in EPC and kidney, single kidney function, microvascular (MV) density, and morphology were compared with untreated ARAS and normal control pigs (n = 7 each). Compared with normal EPC, EPC from ARAS pigs showed increased stromal cell-derived factor (SDF)-1, angiopoietin-1, Tie-2, and c-kit expression, but downregulation of erythropoietin (EPO) and its receptor. The ARAS kidney released the c-kit-ligand stem cell factor, uric acid, and EPO, and upregulated integrin beta2, suggesting activation of corresponding homing signaling. However, angiopoietin-1 and SDF-1/CXCR4 were not elevated. Administration of EPC into the stenotic kidney restored angiogenic activity, improved MV density, renal hemodynamics and function, decreased fibrosis and oxidative stress, and attenuated endogenous injury signals. The ARAS kidney releases specific homing signals corresponding to cognate receptors expressed by EPC. EPC show plasticity for organ-specific recruitment strategies, which are upregulated in early atherosclerosis. EPC are renoprotective as they attenuated renal dysfunction and damage in chronic ARAS, and consequently decreased the injury signals. Importantly, manipulation of homing signals may potentially allow therapeutic opportunities to increase endogenous EPC recruitment.

Renal failure and concurrent RAAS blockade in older CKD patients with renal artery stenosis: an extended Mayo Clinic prospective 63-month experience.

Concerns have been raised regarding a possible link between the increasing utilization of RAAS blocking strategies in the United States and the increasing ESRD epidemic. Most reports of accelerated renal failure in CKD patients with renal artery stenosis on RAAS blockade are retrospective. We hypothesized that this syndrome is therefore poorly understood, may be under-recognized, and demanded prospective analysis. As part of a larger cohort of 100 CKD patients on RAAS blockade presenting with worsening renal failure (>25% increased serum creatinine from baseline) while concurrently on an ACE inhibitor and/or an angiotensin receptor blocker, 26 patients (26%) enrolled between September 2002 and February 2005 had hemodynamically significant renal artery stenosis. RAAS blockade was discontinued, standard nephrology care applied, and eGFR by MDRD monitored. They consisted of 26 Caucasian patients, M:F = 10:16, age 75.3 +/- 6.4 (63-87) years. Mean follow-up was 26.4 +/- 16.4 (1-49) months. Duration of RAAS blockade prior to enrollment was 20.2 +/- 16.4 (0.5-48) months. Contrary to previous reports, precipitating factors were often absent (15/26), unilateral RAS lesions in patients with dual kidneys was common (19/26), and progression to ESRD was frequent (5/26). Four-fifths of the ESRD patients were dead after 5.5 +/- 4.1 (1-11) months. A fifth patient with improved eGFR died after 14 months from metastatic gastric cancer. Excluding five patients who progressed to ESRD and two patients lost early to follow-up, in 19 patients, eGFR increased from 27.8 +/- 9.5 (11-47) to 36.7 +/- 16 (14-68) mL/min/1.73 m(2) BSA (p = 0.014) after 34.8 +/- 10.1 (14-49) months of follow-up. This improvement in eGFR was evident after weeks to months of stopping RAAS blockade in these patients with and without renal PTA and stenting. Nevertheless, renal PTA/stenting further improved eGFR in selected patients. We conclude that renal failure/ESRD associated with concurrent RAAS blockade in older CKD patients with renal stenosis remains poorly understood and mostly unrecognized. Unilateral lesions in patients with dual kidneys, absent precipitating factors, and progression to ESRD with high mortality, despite discontinuation of RAAS blockade, are more common than previously thought. Lower baseline eGFR (<35) predicted ESRD. Our findings call for a larger prospective study, especially given growing concerns of iatrogenic renal failure from RAAS blockade in the aging U.S. population. An aging U.S. population further raises the probability of the presence of increasing and unrecognized renal artery stenosis in our CKD patient population.

Worsening renal failure in older chronic kidney disease patients with renal artery stenosis concurrently on renin angiotensin aldosterone system blockade: a prospective 50-month Mayo-Health-System clinic analysis.

BACKGROUND: The current US chronic kidney disease (CKD)/end stage renal disease (ESRD) epidemic, coincident with the increasing application of renin angiotensin aldosterone system (RAAS) blockade, has raised concerns of iatrogenic renal failure. The US population is an ageing one, further raising the possibility of increasing renal artery stenosis (RAS) in our patients. Current literature regarding worsening renal failure in CKD patients with RAS is based almost wholly on retrospective studies, and therefore may be poorly understood. AIM: To prospectively examine the syndrome of worsening renal failure in CKD patients with hemodynamically significant RAS concurrently on RAAS blockade. DESIGN: Prospective cohort study. METHODS: Between September 2002 and February 2005, CKD patients, concurrently on RAAS blockade, with RAS >70% by magnetic resonance angiography, who presented with accelerated azotemia (> or =25% increase in baseline serum creatinine) were consecutively enrolled. In addition to standard nephrology care, RAAS blockade was discontinued and renal percutaneous transluminal angioplasty (PTA)/stenting performed according to standard guidelines. Renal function as measured by MDRD-derived eGFR (estimated glomerular filtration rate) was monitored. RESULTS: Twenty-six Caucasian patients were enrolled-M:F = 10:16, mean age 75.3 years. Prior duration of RAAS blockade was 20.2 months. Known risk factors were absent in 15/26. Unilateral RAS with dual kidneys was common-19/26. Five patients, with higher baseline creatinine-2.1 +/- 0.6 vs. 1.5 +/- 0.4 mg/dl, P = 0.013, progressed to ESRD; 4/5 ESRD patients died after 6.3 months. Excluding the 5 with ESRD, and 2 lost to follow-up, in 19 patients, eGFR increased from 27.8 +/- 9.5 to 39.7 +/- 14.9 ml/min/1.73 m(2) BSA (P = 0.001), 26.4 months after stopping RAAS blockade. In these same 19 patients, mean arterial blood pressure improved from 100 +/- 9 to 92 +/- 10 mmHg, with 8 patients requiring additional antihypertensive substitutions. Renal PTA/stenting further improved eGFR in 7/9 patients. CONCLUSION: Contrary to previous retrospective reports, we observed that renal failure/ESRD in this older CKD patient population is common in patients with unilateral RAS lesions with dual kidneys; precipitating risk factors are often absent, and progression to ESRD with increased mortality is not infrequent. Older age, higher baseline creatinine (>2.0) and/or lower eGFR (<35) predicted ESRD. eGFR improved following discontinuation of RAAS blockade, generally. Furthermore, in selected patients, renal PTA and stent placement led to additional improvements in eGFR. Our observations call for further studies.

Degradable gelatin microspheres as an embolic agent: an experimental study in a rabbit renal model.

OBJECTIVE: To investigate the basic characteristics of degradable gelatin microspheres (GMSs), including their embolic behavior and degradation periods when they are used as embolic materials in the renal arteries of rabbit models. MATERIALS AND METHODS: Based on the GMS particle size, 24 kidneys were divided into 3 groups of eight kidneys, and each group was embolized with a different GMS particle size (group 1: 35-100 microm, group 2: 100-200 microm, and group 3: 200-300 microm). From each group, two rabbits were sacrificed immediately after embolization (day 0), and a pair of rabbits from each group underwent an angiogram and were sacrificed on days 3, 7, and 14, respectively, after embolization. The level of arterial occlusion, the pathological changes in the renal parenchyma, and the degradation of the GMSs were evaluated angiographically and histologically. RESULTS: A follow-up angiogram on days 0, 3, 7, and 14 revealed the presence of wedge-shaped poorly-enhanced areas in the parenchymal phase as seen in all groups. The size of these areas tended to increase with the particle diameter, and persisted up to day 14. On days 3, 7, and 14, parenchymal infarctions were observed histologically in all cases, and this observation corresponded with the parenchyma being supplied by the embolized arteries. GMSs of group 1 mainly reached the interlobular arteries, while those of group 3 mainly reached the interlobar arteries. In all but two cases, the GMSs were identified histologically even on day 14, and sequential degradation was histologically identified in all GMS groups. CONCLUSION: GMSs can be used as degradable embolic materials which can control the level of embolization.

Degradable Gelatin Microspheres as an Embolic Agent: an Experimental Study in a Rabbit Renal Model

OBJECTIVE: To investigate the basic characteristics of degradable gelatin microspheres (GMSs), including their embolic behavior and degradation periods when they are used as embolic materials in the renal arteries of rabbit models. MATERIALS AND METHODS: Based on the GMS particle size, 24 kidneys were divided into 3 groups of eight kidneys, and each group was embolized with a different GMS particle size (group 1: 35-100 micrometer, group 2: 100-200 micrometer, and group 3: 200-300 micrometer). From each group, two rabbits were sacrificed immediately after embolization (day 0), and a pair of rabbits from each group underwent an angiogram and were sacrificed on days 3, 7, and 14, respectively, after embolization. The level of arterial occlusion, the pathological changes in the renal parenchyma, and the degradation of the GMSs were evaluated angiographically and histologically. RESULTS: A follow-up angiogram on days 0, 3, 7, and 14 revealed the presence of wedge-shaped poorly-enhanced areas in the parenchymal phase as seen in all groups. The size of these areas tended to increase with the particle diameter, and persisted up to day 14. On days 3, 7, and 14, parenchymal infarctions were observed histologically in all cases, and this observation corresponded with the parenchyma being supplied by the embolized arteries. GMSs of group 1 mainly reached the interlobular arteries, while those of group 3 mainly reached the interlobar arteries. In all but two cases, the GMSs were identified histologically even on day 14, and sequential degradation was histologically identified in all GMS groups. CONCLUSION: GMSs can be used as degradable embolic materials which can control the level of embolization.

Renal artery stenosis emerged after angiotensin-converting enzyme inhibitor treatment for myocardial infarction: a case report.

A 76-year-old woman with acute myocardial infarction underwent percutaneous coronary angioplasty followed by treatment with an angiotensin-converting enzyme (ACE) inhibitor, lisinopril. Her renal function deteriorated after the administration of lisinopril, so it was changed to another ACE inhibitor, temocapril. Renography suggested a complication of severe right renal artery stenosis, and renal angiography revealed bilateral renal artery stenoses. Her renal hemodynamics were assessed by (99m)Tc-Mercaptoacetyltriglycine ((99m)Tc-MAG(3))-renography before and after withdrawal of temocapril. The authors concluded the patient had essential hypertension complicated by atherosclerotic renovascular disease. In the treatment of elderly patients with heart disease, hypertension, or both, with ACE inhibitor, the possibility of coexisting renal artery stenosis should be considered. Renography is recommended as a reliable tool for detecting renal artery stenosis.

Arterial embolization using poly-N-acetyl glucosamine gel in a rat kidney model.

Aqueous solutions of poly-N-acetyl glucosamine (p-GlcNAc) exhibit a liquid-gel transition at physiological pH and temperature. This feature inspired the authors to conduct a study to evaluate the macro- and histological changes of rat kidneys after embolization using either p-GlcNAc gel injection into the renal artery or ligation of the renal artery. The procedures were performed in 46 rats through open abdominal surgeries. Animals were sacrificed at 3 days and at 1, 3, 5, and 8 weeks postoperatively. The results of both macro-observation and histological study showed that p-GlcNAc gels were effective in causing necrosis and subsequent fibrosis in all embolized kidneys. The data indicate that p-GlcNAc gel may have promise as an effective agent for therapeutic embolization.

Cocaine-induced renal artery dissection and thrombosis leading to renal infarction.

We present the case history of a 40-year-old man who developed renal artery dissection and thrombosis, probably due to cocaine use. The patient underwent exploratory laparotomy and thrombectomy. He remained asymptomatic and cocaine-free, and warfarin was discontinued 9 months after discharge. Approximately 12 months after discharge he returned to the hospital with symptoms very similar to previous episodes. He was found to have recurrent clot formation in the right renal artery. Further workup revealed a double heterozygous methyltetrahydrofolate reductase A1298C/C677T thermolabile polymorphism with an elevated serum homocysteine.

Coingestion of cyclooxygenase inhibitors can worsen severe paracetamol poisoning by middle-sized and small arteries vasoconstriction.

OBJECTIVE: We report fatal cases of multifocal ischemic injuries occurring in patients awaiting liver transplantation after severe concomitant paracetamol and cyclooygenase inhibitors self-poisoning. DESIGN AND SETTING: Case report in an intensive care unit. PATIENTS: In addition to signs of acute liver failure with a systemic inflammatory response syndrome, these three previously healthy young women demonstrated cutaneous vasoconstriction. One patient displayed a sudden ST-segment elevation with ventricular fibrillation. INTERVENTIONS: Angiography, plasma endothelin concentrations measurements, and autopsy. RESULTS: Radiography showed diffuse vasospasm on mesenteric and renal arteries, transiently reversed by vasodilators. We measured tenfold higher plasma endothelin concentrations than in healthy controls. Autopsy revealed no atherosis (including coronary arteries); organs showed multifocal ischemic injuries without thrombosis. CONCLUSIONS: Such injuries subsequent to dramatic vasoconstriction suggest that cyclooygenase inhibition has specific deleterious vascular side effects once systemic inflammatory response syndrome is in progress during paracetamol poisoning.

[Acute renal failure, renal artery stenosis and angiotensin-converting enzyme (ACE) inhibitor]. / Akutt nyresvikt, nyrearteriestenose og angiotensinkonvertase (ACE)-hemmer.

BACKGROUND: Acute renal failure is a well-known complication in patients with renal artery stenosis during treatment with ACE inhibitor. Renal artery thrombosis after withdrawal of ACE inhibitor has not been reported previously. MATERIAL AND METHODS: We describe a patient with acute renal failure with an unexpected course. RESULTS: A 67-year-old man was admitted with acute anuric renal failure during treatment with hydrochlorothiazide and enalapril. His blood pressure was 165/60 mm Hg. Renal ultrasound was normal. After initial rehydration and dialysis, diuresis resumed until a sudden unexpected anuric renal failure recurred on day 12. Angiography disclosed bilateral renal artery occlusion. The right renal artery was successfully opened and a stenosis was blocked and stented, and brisk diuresis ensued. Two days later hypertension accelerated, and a new invasive procedure on day 24 succeeded in opening, blocking and stenting a proximal stenosis in the left artery; a mobile thrombus was located behind the stenosis and successfully treated with intraarterial thrombolysis. Blood pressure rapidly normalized, and serum creatinine was normal on visits 1.5 and 4 months later. INTERPRETATION: General aspects and prevention of acute renal failure during ACE inhibitor therapy are discussed. Acute renal thrombosis after withdrawal of ACE inhibitor in patients with stimulated renin angiotensin system and significant renal artery stenosis may be causally related to the antifibrinolytic effects of angiotensin II and aldosterone. Endovascular reconstruction of renal artery occlusion may completely restore the kidney function.