Detecting Proteomic Indicators to Distinguish Diabetic Nephropathy from Hypertensive Nephrosclerosis by Integrating Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry Imaging with High-Mass Accuracy Mass Spectrometry.

INTRODUCTION: Diabetic nephropathy (DN) and hypertensive nephrosclerosis (HN) represent the most common causes of chronic kidney disease (CKD) and many patients progress to -end-stage renal disease. Patients are treated primarily through the management of cardiovas-cular risk factors and hypertension; however patients with HN have a more favorable outcome. A noninvasive clinical approach to separate these two entities, especially in hypertensive patients who also have diabetes, would allow for targeted treatment and more appropriate resource allocation to those patients at the highest risk of CKD progression. Meth-ods: In this preliminary study, high-spatial-resolution matrix-assisted laser desorption/ion-ization (MALDI) mass spectrometry imaging (MSI) was integrated with high-mass accuracy MALDI-FTICR-MS and nLC-ESI-MS/MS analysis in order to detect tissue proteins within kidney biopsies to discriminate cases of DN (n = 9) from cases of HN (n = 9). RESULTS: Differences in the tryptic peptide profiles of the 2 groups could clearly be detected, with these becoming even more evident in the more severe histological classes, even if this was not evident with routine histology. In particular, 4 putative proteins were detected and had a higher signal intensity within regions of DN tissue with extensive sclerosis or fibrosis. Among these, 2 proteins (PGRMC1 and CO3) had a signal intensity that increased at the latter stages of the disease and may be associated with progression. DISCUSSION/CONCLUSION: This preliminary study represents a valuable starting point for a future study employing a larger cohort of patients to develop sensitive and specific protein biomarkers that could reliably differentiate between diabetic and hypertensive causes of CKD to allow for improved diagnosis, fewer biopsy procedures, and refined treatment approaches for clinicians.

Secondary Hypertension and Complications: Diagnosis and Role of Imaging.

Hypertension is a common problem; if left untreated, it can result in significant complications, including those involving the cardiovascular system and end organs. Approximately 10% of patients with hypertension are classified as having secondary hypertension, defined as hypertension attributable to a specific and potentially remediable cause. The evaluation for secondary hypertension typically begins with acquiring the patient history and performing a physical examination and screening laboratory tests. Directed imaging may be performed, on the basis of laboratory test results, to assess for potential causes of secondary hypertension. The causes can be broadly classified as endocrine (eg, hyperaldosteronism, pheochromocytoma, hyperparathyroidism) and nonendocrine (eg, aortic coarctation, renal vascular hypertension). In addition, patients with hypertension can develop significant complications that also are diagnosed with imaging, including conditions involving the cardiovascular system (eg, aortic aneurysm, acute aortic syndrome) and central nervous system (eg, stroke, subarachnoid hemorrhage, and posterior reversible encephalopathy syndrome). The imaging workup and imaging appearances of some of the causes of secondary hypertension are reviewed, treatment options are discussed, and the imaging appearances of hypertension-related complications are described. It is important for radiologists to accurately diagnose the secondary causes of hypertension, as many of them are treatable, and treatment may result in improved symptoms or resolution of hypertension. ©RSNA, 2019.

Diurnal variation of renal resistive index over 24-hour period in hypertensive patients and healthy controls.

PURPOSE: There are no data in the literature to our knowledge related to changes in renal resistive index (RRI) values over 24-h period and the importance of detecting these changes in patients who have hypertension (HT). In this study, we aimed to investigate the variation of RRI values over 24-h period and its usability in hypertensive patients. METHODS: A total of 118 subjects (80 with HT and 38 healthy controls) were included in the study. Morning, midday, evening, and midnight RRI, renal pulsatility index, and accelerated time were measured by Doppler ultrasonography (US). B-mode US and elastograpic assessment were performed only in the morning. RESULTS: Temporal RRI varied significantly (p < 0.001). The highest and lowest levels were found in the morning and evening, respectively. All temporal RRI levels were significantly higher in patients with HT (both p < 0.001). The absolute and relative increases in RRI (ΔRRI) levels were similar in two groups. All temporal RRI measurements positively correlated with the patient age, pulse pressure, renal cortical thickness, and cortical stiffness. However, absolute-ΔRRI and relative-ΔRRI positively correlated with the age. Absolute-ΔRRI positively correlated with the pulse pressure and cortical stiffness, and no correlation was observed between relative-ΔRRI and these variables. Of the four temporal measurements, morning RRI were found to be independently associated with cortical stiffness (p < 0.001). CONCLUSIONS: RRI measurements varied over 24-h period in patients with HT and/or healthy controls. Morning RRI was significantly higher than other day time, and it is also related to renal cortical stiffness.

Elevated pulse amplification in hypertensive patients with advanced kidney disease.

The progression of chronic kidney disease (CKD) inverts the arterial stiffness gradient. However, central hemodynamic pressure profiles in CKD have not been fully examined. A cross-sectional study was performed to assess the relationship between the CKD stage and central hemodynamic processes. The study enrolled 2020 hypertensive patients who had undergone echocardiography and measurement of their serum creatinine levels. Radial tonometry was applied to all patients to measure central blood pressure. Patients were classified according to six CKD stages based on their estimated glomerular filtration rate. Central (PP2) and brachial pulse pressure (PP) were elevated at stages 3a and 3b, respectively. Diastolic blood pressure (DBP) was higher at stage 1 compared to the other stages. The left ventricular mass index was greater at CKD stages 3b-5 than that at stage 1. Either PP or PP2 was sensitive for detecting the presence of left ventricular hypertrophy (LVH). Age, weight, pulse rate, brachial blood pressure, and antihypertensive medication differed among the six stages. Pulse amplification (PA) adjusted for these confounders was the lowest in CKD stages 3a and 3b. The present observations support that cardiovascular risk is higher in CKD stages 3b and later. Our findings indicate that PA is inverted in CKD stages 4 and 5. The present results suggest that aortic stiffening and the subsequent elevation in PA during CKD progression relate to a reduction in the ability of PP2 to predict LVH.

Renal denervation in a patient with unilateral ectopic kidney in the pelvis and refractory hypertension.

Ectopic kidney and inherent vascular abnormalities may result in renovascular hypertension. The case we report is peculiar as a left ectopic iliac kidney supplied by a superior and an inferior polar renal arteries was detected in a treatment-resistant hypertensive man. In conclusion, percutaneous renal artery denervation was successfully performed in the right renal artery and in both left accessory renal arteries, obtaining excellent blood pressure decrease at follow-up.

Simple Renal Cysts: Can They be Overlooked?

BACKGROUND / OBJECTIVE: The availability and use of abdominal ultrasonography and computed tomography for diagnostic purposes has led to frequent detection of asymptomatic renal cysts. Recent evidence suggests their association with hypertension. The aim of our study was to evaluate the presence of simple renal cysts in patients with hypertension and prehypertension. METHODS: In a hospital based cross-sectional study, all consecutive adult patients aged > 25 years were enrolled. Detailed medical history and physical examination was done in all the study participants. Abdominal ultrasonography and biochemical parameters were also performed. All the patients who had history or evidence of structural or functional kidney disease were excluded. RESULTS: A total of 6230 patients were enrolled and divided into three groups: normotension (n=3510), prehypertension (n=1850) and hypertension (n=870) groups. There were significant differences in age, gender, prevalence of diabetes, family history of hypertension, regular exercise, smoking, BMI, systolic blood pressure, diastolic pressure, fasting plasma glucose, total cholesterol, triglyceride, HDL cholesterol, creatinine, estimated glomerular filtration rate in three groups. Simple renal cysts (SRCs) were present in significantly greater numbers in patients with prehypertension and hypertension. SRCs ≥2 in number or ≥2 cm in size were significantly associated with both prehypertension and hypertension independent to other risk factors. CONCLUSIONS: The presence of SRCs should not be overlooked. In present study, SRCs ≥2 in number or ≥2 cm in size are important determinants of prehypertension and hypertension.

Diagnostic accuracy of Tc-99m DMSA scintigraphy and renal ultrasonography for detecting renal scarring and relative function in patients with spinal dysraphism.

AIMS: To study additional benefits of performing Tc-99m dimercaptosuccinic acid (Tc-99m-DMSA) scintigraphy as part of the follow-up of adults with spinal dysraphism (SD), compared with ultrasonography, with regard to finding renal scarring and difference in split renal function. METHODS: Between January 2011 and April 2013 every patient visiting our specialized outpatient clinic for adults with SD was invited to undergo both renal ultrasonography and Tc-99m-DMSA scintigraphy. Outcomes of both modalities were compared, with focus on renal scarring. The relation between renal scarring and hypertension was also assessed. RESULTS: In total, 122 patients (with 242 renal units) underwent both renal scintigraphy and ultrasonography. More scars were seen on DMSA scintigraphy than on ultrasonography: 45.9% vs. 10.3% of renal units; P < 0.001. Renal scarring seen on DMSA was associated with the presence of hypertension (P = 0.049) whereas scarring seen on ultrasonography was not (P = 0.10). If ultrasonography was difficult to interpret, many more scars were missed on ultrasonography (78.9%) compared with easily interpretable ultrasonographic images (30.6%; P < 0.001). CONCLUSIONS: In adults with SD, ultrasonography is of value to diagnose dilatation and stones of the upper urinary tract; however, compared with DMSA renography, renal scars are often missed, especially when the ultrasound is difficult to interpret.

Treatment of hypertension in patients with atherosclerotic renal artery stenosis, updated.

Atherosclerotic renal artery stenosis (ARAS) is a fairly common disease of elderly patients and is discovered incidentally in 6.3% to 38% in those undergoing diagnostic cardiac or abdominal angiography. Of those patients diagnosed with renal artery stenosis, in 90% it is due to ARAS and in 10% to fibromuscular dysplasia (FMD), which is a disease of younger persons, mostly females. Renal artery stenosis is frequently associated with hypertension and impaired renal function, and it is perceived by many physicians as the primary cause of hypertension and renal failure. For this reason, they believe that hypertension and renal failure can be significantly improved by performing percutaneous transluminal renal angioplasty (PTRA) with a stent placement as the preferred treatment instead of medical therapy. This practice has led to an increase in angioplasties, especially by interventional cardiologists who are familiar with the procedure. However, the results of several randomized studies comparing interventional therapy with medical therapy have shown no significant difference between the 2 treatment modalities in blood pressure reduction and prevention and in worsening of renal function. Similar results have been found by nonrandomized trials in patients treated selectively with PTRA. For this review, a Medline search was conducted of the English-language literature from January 1, 2006 to December 31, 2013, using the terms atherosclerotic renal artery stenosis and renal artery stenosis; 6 pertinent randomized studies were selected. These studies, with collateral literature, are discussed in this review. The data show that PTRA with stent plus medical therapy in patients with ARAS is not superior to medical therapy alone in lowering the blood pressure, in preventing renal function deterioration, and in reducing all-cause mortality, cardiovascular morbidity or mortality, and strokes.

Possible correlation among echocardiographic measures, serum brain natriuretic peptide, and angiotensin II levels in hypertensive kidney transplanted children.

OBJECTIVES: Ambulatory blood pressure monitoring is the standard for determining patients at risk of hypertension. Left ventricular hypertrophy is common in kidney transplant recipients. We evaluated the correlation between blood pressure measures achieved by ambulatory blood pressure monitoring and conventional (office) methods. MATERIALS AND METHODS: This cross-sectional study was done from December 2009 to October 2010 at Alzahra Hospital in Isfahan, Iran. Sixty five participants, 35 kidney transplant recipients under 20 years old, and 30 control subjects of the same age were recruited. Five kidney recipients did not complete the study and were excluded. Blood pressure was measured by ambulatory blood pressure monitoring and conventional methods. Echocardiographic study was done for kidney transplant recipients. Serum brain natriuretic peptide and angiotensin II levels were determined in case and control groups. RESULTS: Office-recorded systolic and/or diastolic hypertension was observed in 43.4% and 55.3% of patients. According to ambulatory blood pressure monitoring, 86% of kidney transplant recipients had systolic BP load. Left ventricular hypertrophy (defined according to the left ventricular mass index [left ventricular mass index/height]) was seen in 53.3% of the patients. The existence of left ventricular hypertrophy revealed a positive correlation with ambulatory blood pressure monitoring systolic and diastolic night blood pressure and systolic nondipper. Left ventricular mass index showed a positive correlation with brain natriuretic peptide level. Furthermore, the existence of left ventricular hypertrophy was positively correlated with angiotensin II level. CONCLUSIONS: Only ambulatory blood pressure monitoring systolic and diastolic blood pressures (nondippers) were positively correlated with left ventricular hypertrophy and higher left ventricular mass index. Serum levels of brain natriuretic peptide and angiotensin II had a positive relation with left ventricular hypertrophy. Measuring brain natriuretic peptide and angiotensin II in the clinical setting screens patients at risk of left ventricular hypertrophy.

Renal hypertension: an unusual cause for a common problem.

A 9-year-old girl with longstanding headaches presented acutely with rash, which disappeared quickly on treatment with oral phenoxymethylpenicillin. It was attributed to streptococcal infection as group A streptococcus was isolated from throat swab. She was incidentally found to have high blood pressure on routine screening on admission. Subsequently, 'fibromuscular dysplasia' was confirmed on renal angiogram, which showed a characteristic beaded appearance. It is a good clinical practice to check blood pressure in any child seen for whatever reason.

Long-term follow-up of patients with atherosclerotic renal artery disease.

Atherosclerotic renal artery stenosis (ARAS) is a predictor of increased morbidity and mortality. However, whether ARAS itself accelerates the arteriosclerotic process or whether ARAS is solely the consequence of atherosclerosis is unclear. We imaged renal arteries of 1561 hypertensive patients undergoing coronary angiography and followed this cohort for 9 years (range, 2.4-15.1 years; median, 31.2 months, interquartile range, 13.4/52.9 months). All patients received aspirin, renin-angiotensin system blockade, statins, and beta blockade as indicated. One hundred seventy-one patients had ARAS >50% diameter stenosis and 126 patients an arteriosclerotic plaque (ARAP) without significant stenosis. Blood pressures were not different in ARAS, ARAP, and non-ARAS patients. After adjustment for cardiovascular risk factors by propensity scores and matched pair analysis, ARAS patients had a lower ejection fraction and more coronary artery disease (CAD) than non-ARAS patients. The same was true for brain natriuretic peptide values, troponin I, and highly sensitive C-reative protein. Over 9 years, more ARAS patients died of any cause (34% vs 23%; P < .05). The prevalence of CAD in ARAP patients was higher than in non-ARAS patients and lower than in ARAS patients. The mortality of the ARAP patients at 9 years was 37%, not different from the ARAS patients. Atherosclerotic renal artery disease appears to be a marker for the severity of atherosclerosis rather than a causative factor for atherosclerosis progression.

Technical discussion of diagnostic angiography and intervention of atherosclerotic renal artery stenosis.

Renal artery stenting remains an important adjuvant treatment for true-resistant hypertension, although recent disappointing randomized trials highlight the importance of careful patient selection. Safe and successful renal interventions begin with critical core knowledge regarding renal artery anatomy and understanding the often hostile nature of the parent vessel (pararenal aorta). Armed with fundamental knowledge about anatomy and renal ostial disease pathology, it becomes easier to understand the advantages of less traumatic access techniques and how low-profile contemporary flexible stents have enhanced outcomes. In addition to suggested techniques based on detailed understanding of the vessel architecture and pathology, we will review the current available US Food and Drug Administration-approved balloon-expandable on-label renal stents and discuss the role of intravascular ultrasound for definition of lesion severity, stent sizing, and stent apposition. The durability of renal stenting will also be discussed, as will the velocity criteria for duplex surveillance. Lastly, the current empirical data related to renal embolic protection is provided, along with insight into technical issues in this domain.

Time course of hydronephrotic changes following unilateral pyeloplasty.

OBJECTIVES: The temporal pattern of hydronephrotic change following pyeloplasty has not been well defined. To address this issue, 23 years of postpyeloplasty follow-up data from a single surgeon were analyzed. PATIENTS AND METHODS: Records of dismembered pyeloplasty from 1986 to 2004 were retrospectively reviewed. Ultrasound follow-ups were conducted at 3-6-month intervals after surgery for up to 3 years, and were then extended to either annually or biannually until the completion of puberty. Overall outcome of hydronephrosis (HN), timing of initial improvement and normalization were determined. Factors associated with these changes were examined. RESULTS: Of 215 patients who completed follow-up of at least 5 years, about 80% experienced either normalization or improvement. Once they had shown improvement of HN during follow-up, no recurrence was observed. The median time for recognition of initial improvement and normalization of HN was 8 months and 41 months after surgery, respectively. Multivariate analysis revealed that the presence of immediate postoperative obstruction was a negative factor for initial improvement. Symptomatic presentation and no initial improvement until 6 months after pyeloplasty turned out to be negative factors for normalization. CONCLUSIONS: The results confirm the excellent long-term outcome of pyeloplasty, and highlight the importance of frequent ultrasound until initial improvement of HN, when subsequent ultrasound follow-ups may be safely omitted to focus on follow-up of renal function, proteinuria and hypertension.

Endovascular management of fusiform renal artery aneurysm in a patient with refractory hypertension using hydrocoils and embospheres.

We are reporting endovascular management of a renal artery aneurysm causing renal hypertension. The aneurysm by mass effect compressed the adjacent artery resulting in a hemodynamically significant stenosis. Endovascular management included embosphere embolization of the renal parenchyma distal to the stenosed segment and hydrocoil embolization of the aneurysm itself.