Primary Malignant Hypertension Research Articles

Urinary complement factor D is increased in primary malignant hypertension: a single-center, cross-sectional study

Kidney injury is one of the detrimental consequences of primary malignant hypertension (pMHTN). There is a paucity of non-invasive biomarkers to enhance diagnosis and elucidate the underlying mechanisms. This study aims to explore urine protein biomarkers for pMHTN associated renal damage. In the discovery phase, urine samples were collected from 8 pMHTN, 19 disease controls (DCs), and 5 healthy controls (HCs). In-gel digestion combined with liquid chromatography–tandem mass spectrometry (LC–MS/MS) approach was used for identification of proteins associated with pMHTN. In the validation phase, the differentially expressed proteins were validated by ELISA assay in cohort with 10 pMHTN patients, 37 DCs, and 30 HCs. Compared to DCs and HCs, a specific band between 15 and 25 kDa was found in 7 out of 8 patients with pMHTN. Further LC–MS/MS analysis revealed 5 differentially expressed proteins. ELISA validation demonstrated that urinary complement factor D (CFD) was significantly up regulated in pMHTN. By receiver operating characteristic curve analysis, urinary CFD/Cr showed moderate potential in discriminating pMHTN from DCs (the area under curve: 0.822, 95% CI 0.618–0.962). Urinary CFD may be a potential biomarker for pMHTN with its elevation indicative of the activation of the alternative complement pathway in pMHTN.

CD4(+)CD25(+) T Cells in primary malignant hypertension related kidney injury.

CD4+CD25+ T cells are critical for maintenance of immunologic self-tolerance. We measured the number of CD4+CD25+ cells in the patients with primary malignant hypertension related kidney injury, to explore the molecular pathogenesis of this disease. We selected 30 patients with primary malignant hypertension related kidney injury and 30 healthy volunteers. Information on clinical characteristics and laboratory tests was obtained from each subject. The number of CD4+CD25+ cells and glomerular injury were assessed by flow cytometry and histopathology, respectively. Both serum IL-2, IL-4, and IL-6 and endothelial cell markers were analyzed by ELISA. ADAMTS13 antibody was detected by Western blotting. CD4+CD25+ cells were significantly reduced in patients with primary malignant hypertension related kidney injury compared to controls (P < 0.05). The number of CD4+CD25+ cells was negatively related to blood urea nitrogen, serum uric acid, proteinuria, and supernatant IL-4; whereas positively associated with estimated glomerular filtration rate in patients. Gradually decreasing CD4+CD25+ cells were also found as increasing renal injury. Additionally, patients exhibited increasing supernatant IL-4, serum IL-2 and IL-6, endothelial cell markers, and anti-ADAMTS13 antibody compared with controls (all P < 0.05). CD4+CD25+ cells may play a key role in the pathogenesis of primary malignant hypertension related kidney injury.

A case of secondary focal segmental glomerulosclerosis associated with malignant hypertension.

Focal segmental glomerulosclerosis (FSGS) is associated with various clinicopathological conditions, including hypertension. We report here a case of secondary FSGS associated with malignant hypertension. A 33-year-old man with a 1-month history of visual impairment and headache visited the Department of Ophthalmology at our hospital and was found to have hypertensive retinopathy and severe hypertension (230/160mmHg). He was referred to our department based on suspected renal dysfunction. His blood pressure on admission was 250/130mmHg. Physical examination and laboratory tests revealed hypertensive cardiac dysfunction, focal brain edema, renal dysfunction (serum creatinine, Cr 7.07mg/dl, blood urea nitrogen, BUN 49.9mg/dl), massive proteinuria (10.7g/day), and thrombotic microangiopathy. Funduscopy showed exudate, hemorrhage, and papilledema. The cause of secondary hypertension could not be identified. He was treated for primary malignant hypertension, but required hemodialysis 3days after admission due to anuria. Treatment with antihypertensive agents resulted in the gradual recovery of renal function, although heavy proteinuria continued with nephrotic syndrome. Renal biopsy performed 1month after admission showed features of malignant nephrosclerosis with secondary FSGS. Hemodialysis was discontinued following further improvement in renal function and the most recent laboratory tests showed proteinuria 1.8g/day and persistent renal dysfunction (BUN 36.5mg/dl, Cr 3.14mg/dl). Malignant hypertension may cause various injuries, including glomerular endothelial and epithelial cell injuries in glomerular hypertension and hyperfiltration, increase of the renin-angiotensin-aldosterone system, and endothelial-epithelial interaction, resulting in the development of secondary FSGS and heavy proteinuria.

Common Genetic Variants in the Chromogranin A Promoter Are Associated with Renal Injury in IGA Nephropathy Patients with Malignant Hypertension

The present study aimed to investigate whether genetic variants in the chromogranin A (CHGA) promoter were associated with malignant hypertension (MHT) and renal functional damage. The polymorphisms of CHGA promoter in 39 patients with malignant hypertension secondary to idiopathic IgA nephropathy (IgAN-MHT), 23 patients with primary malignant hypertension and 63 controls were genotyped by sequencing. Four diploid genotypes with minor allele frequencies of approximately ≥10% for individual CHGA SNP loci or haplotypes were compared among the patient with IgAN-MHT, primary MHT and healthy control. Polymorphisms and haplotypes of CHGA promoter were not associated with primary MHT and IgAN-MHT. Within 39 IgAN-MHT patients whose clinical and histological data were available, patients carrying −415TT genotype tended to present with higher serum creatinine (Scr) level than those carrying −415TC/CC genotype (636.94 ± 524.07 μmol/L vs 277.84 ± 196.39 μmol/L, P = 0.014). Consistent with this statistic, we found the haplotype-specific score value of haplotype ATC was 2.25046 (p = 0.024), and by permutation testing, the empirical p value was 0.014. The present study suggested the genetic variants in the chromogranin A promoter may not involve in the onset of malignant hypertension, but the variants might play a role in the renal dysfunction in patients with IgAN-MHT.

Malignant Hypertension in Patients with Idiopathic IgA Nephropathy

Background: Idiopathic IgA nephropathy is one of the main causes of secondary malignant hypertension, especially in Chinese population. But little information has been available about malignant hypertension secondary to IgA nephropathy (IgANMHT). The purpose of this study is to evaluate the clinico-pathological features and outcomes of IgANMHT patients. Methods: A case control retrospective study was carried out in 45 cases of IgANMHT and 26 cases of primary malignant hypertension (PMHT) diagnosed by renal biopsy. Their clinical features and pathological findings were investigated. Their average follow-up time was 37.4 months. Univariate analysis and multivariate Cox regression analysis were performed to select variables to predict renal survival. Results: In the study, 1.2% of all the IgA nephropathy patients presented malignant hypertension. The amounts of urine protein excretion and red blood cells in IgANMHT patients were significantly higher, while the levels of serum creatinine were significantly lower than those in PMHT patients. The glomerular injury in IgANMHT patients was more severe than that in PMHT patients. The two characteristic vascular lesions of primary malignant hypertension, proliferative endoarteritis and fibrinoid necrosis were also found in IgANMHT patients but with less severity. Renal survival of IgANMHT patients was significantly higher than that of PMHT patients (p = 0.0043). However, log-rank test showed no significant difference in the renal survival between IgANMHT and PMHT patients with similar SCr levels at admission. Multivariate Cox regression analysis revealed that a high amount of urine protein excretion(≧1.5 g/24 h), mesangial proliferation and elevated serum creatinine (≧2 mg/dl) were statistically independent risk factors for renal prognosis (RR = 1.90, 2.72, 2.84, respectively). Conversely, strict blood pressure control had a favorable effect on renal prognosis. Conclusion: The clinico-pathological features and outcomes of IgANMHT patients were different from those of PMHT patients. The renal survival of IgANMHT patients was poor, which was determined by many factors. Early control of proteinuria, early monitoring and strictly controlling blood pressure may contribute to the renal survival.

Recovery of Renal Function in Black South African Patients with Malignant Hypertension: Superiority of Continuous Ambulatory Peritoneal Dialysis over Hemodialysis

To describe recovery of renal function (RC) in Black South African patients with primary malignant hypertension (MHT) and end-stage renal failure, according to the type of dialysis provided. A retrospective analysis of the records of 31 patients with MHT. A university-based, large tertiary-care hospital and its community-based satellite continuous ambulatory peritoneal dialysis (CAPD) clinics. Only patients with renal failure caused by MHT and who were on dialysis between January 1997 and June 2000. There were 11 patients on peritoneal dialysis (PD) that regained renal function; 11 patients on hemodialysis (HD), none of whom recovered renal function; and 9 patients on PD who did not recover renal function during the same time period. The groups were investigated for variables that might predict RC. Peritoneal dialysis compared with HD was highly significant as an indicator of RC (p < 0.0001), with 60% of patients on PD regaining renal function, versus 0% on HD. Median time to recovery was 300 (150 -365) days. There was no significant difference in decline of mean arterial pressure (MAP) between the groups; MAP declined significantly in all groups (p = 0.00002). All groups received similar drug therapy. In the RC group, initial MAP, kidney size, and urine output tended to be higher and creatinine lower (p = not significant). Dialysis adequacy was similar in the different groups. This retrospective study suggests there may be benefit from PD as the primary form of dialysis when patients have MHT as a cause of their renal failure. Possible predictors of RC include blood pressure control, initial MAP, initial serum creatinine, initial urine output, and kidney size. Time should be allowed for RC before transplantation is undertaken. Prospective studies are needed to confirm the benefit of CAPD in patients with MHT.

Half-life of truth in surgical literature

The hypothetico-deductive model of Karl Popper contends that “An assertion is true if it corresponds to, or agrees with, the facts”. Because “the facts” change over time, truth is relative. In this view of events, science progresses via a series of theories (paradigms) that are held to be true until they are replaced by a better approximation of reality. It follows that some “truths” will last longer than others. We decided to estimate the half-life of dogma relating to the practice of surgery. The journal Surgery Gynecology and Obstetrics had a section entitled International Surgical Abstracts that concluded at the end of 1994. We obtained copies of all of the abstracts for the even numbered months for each fifth year after 1935. The first 20 abstracts about general surgery from each of the 13 review periods were selected for study. The one sentence from each abstract that best summarised the conclusion was copied to a database. Editing of these sentences was restricted to the rephrasing of outdated terminology and the elimination of redundant words. The form, which contained the 260 selected sentences in a random order, was assessed by seven general surgeons. They were asked to mark each question as being either true or false. We explored the relation between time and the number of positive responses from the questionnaire using scatter plots and regression analyses. The linear model detailed in the figure was found to be most appropriate (R=0·86, p<0·001). It suggests that the rate of loss of truth is 0·75% per year and that the estimated half-life of truth for clinical statements in the surgical literature is 45 years. This seems appropriate; 45 years ago it was suggested that: prefrontal lobotomy usefully altered patients’ reactions so that “no anxiety, fear, or concern over their impending death from cancer was manifest”; “in primary malignant hypertension the malignant phase may disappear” after lumbodorsal sympathectomy; and, the detection of a gastric ulcer was “a strong indication for immediate operation”. Extrapolation of the regression line can be used to hypothesise that the current era of surgery extends between 1904 and 2038. From an historical perspective, 1904 is a reasonable estimate of the commencement of the era of “open” surgery. Gauze masks and rubber gloves had just been introduced into operating theatres and abdominal surgery gained public respectability in the UK in 1902 when Edward VII’s coronation was delayed by the need to drain his appendiceal abscess. More contentious is extrapolation of the regression line to predict the future. However, a nexus point for the present era of surgery in the second quartile of the next century is consistent with the current trend towards the ascendancy of minimally invasive procedures and medical treatments over open surgery.

Partial recovery of renal function in black patients with apparent end-stage renal failure due to primary malignant hypertension.

We report the largest series in which 12 out of 54 patients with primary malignant hypertension requiring dialysis recovered sufficient renal function to allow withdrawal of dialysis. The patients were divided into recovery (RC; n = 12) and non-recovery (N-RC; n = 42) groups. The two groups were compared for variables which might predict RC. They were also assessed for survival. Nine of the RC and 6 of the N-RC patients presented with acute oliguria (p = 0.01). The initial mean arterial pressure was significantly higher in the RC than the N-RC group (178 +/- 17 vs. 160 +/- 27 mm Hg; p = 0.03). Although not statistically significant, more females recovered (8 of 12 vs. 16 of 42; p < 0.1). More patients presenting with serum creatinine concentrations < 1,000 mumol/l (11 mg/dl) recovered (p = 0.09), while the presence of microangiopathic-haemolytic anaemia occurred more frequently in the RC (7 of 10) than in the N-RC (15 of 35) group (p = 0.16)> Age, kidney size, and the presence of hypertensive retinopathy did not distinguish between the two groups. RC patients had a greater long-term survival (Mantel-Cox chi2 = 4.48; p = 0.03). The renal function RC may be related to the type of dialysis provided (intermittent peritoneal dialysis) and to the use of modern potent peripheral vasodilator antihypertensive agents. Potential renal function RC should always be considered in patients being dialyzed for primary malignant hypertension.

Preservation of renal function in chronic renal failure.

Mechanisms of progression of chronic renal failure (CRF) have been well documented in the rat but may not be relevant in man. Factors which may modify clinical CRF include underlying disease, diet, hypertension, intercurrent events, and adverse or beneficial effects of drug therapy. It has been argued that progression in many forms of renal disease is inexorable below a certain level of renal function. In other diseases, eg primary malignant hypertension, analgesic nephropathy, function frequently improves in both the short and long term with appropriate management. Thus knowledge of the nature of the underlying disease is essential in assessing progression. The value of diet in preserving renal function has been debated, particularly the relative roles of protein and phosphate control. In our own unit, a prospective randomized study showed a benefit of protein restriction. Development of accelerated hypertension is an important cause of progression of renal disease and clinical and experimental evidence supports the view that non-accelerated hypertension is also a factor in progression, amenable to treatment. Various intercurrent events may accelerate progression and function may be lost permanently following sepsis, urinary tract obstruction, renal arterial or venous obstruction, hypotension and in some cases pregnancy. Numerous drugs can have deleterious effects on the kidney. The possibility that converting enzyme inhibitors might preserve renal function is attracting attention but in view of their side effects their place in therapy should be determined by prospective controlled studies in which the above factors are carefully considered.

Protracted Anuria Due to Active Vasoconstriction in Primary or Secondary Malignant Hypertension

Anuria complicated the malignant phase of hypertension in twelve patients (ten males and two females). Five were black; five had primary hypertension; one had HBs virus angiitis; the six remaining cases suffered from previously documented renal disease, including two with Berger's disease. Renal angiography showed interruption of renal blood flow as far as the main branches of the renal artery and/or a false impression of 'cortical necrosis' and of 'renal infarcts'. In contrast, renal biopsy did not show irreversible vascular damage. Thus, anuria was mainly functional and due to active renal vasoconstriction. This was confirmed by the subsequent course; diuresis resumed after 1 week to 24 months of dialysis. Repeat angiography in six cases showed recovery of renal circulation and disappearance of 'cortical infarcts', even when plasma renin activity remained elevated and hypertension was not controlled. In one case captopril induced a new reversible episode of anuria. These observations suggest that active vasoconstriction with prolonged anuria might be due to some vasoconstrictive substance other than angiotensin II.

Malignant hypertension: aetiology and outcome in 83 patients.

To evaluate the current pattern of aetiology and outcome in malignant hypertension, we reviewed all medical records of patients presenting between 1979 and 1985 who fulfilled WHO criteria for malignant hypertension. There were 83 patients, 43 males (52%) and 40 females (48%). Primary malignant hypertension was diagnosed in 17 cases (20%) and secondary lesions in 66 cases (80%). Overall one year survival was 94%, and 5 year survival 75%, which is similar to recent reports. Initial serum creatinine was a prognostic indicator.

Lysosomal and brush border membrane enzymes in urine of patients with renal artery stenosis and with essential hypertension

A urinary enzyme pattern consisting of three lysosomal enzymes ( β -galactosidase, N-acetyl- β -glucosaminidase, β -glucuronidase) and three enzymes originating from kidney tubular brush border membrane ( α -glutamyl-transferase, alkaline phosphatase, leucine arylamidase) was studied in 16 patients with renal artery stenosis, 84 with benign essential and 13 with malignant essential hypertension. N-acetyl- β -glucosaminidase showed the greatest diagnostic sensitivity. This enzyme was increased in more than 88% of cases with primary malignant or renovascular hypertension, and in 23% of patients with benign essential hypertension. The urinary enzyme pattern in the three patient groups differed considerably and application of discriminant analysis to the data resulted in an overall correct classification of 86% of patients according to the clinical diagnosis. Results suggest that different morphological alterations of the kidney may be reflected by typical urinary enzyme patterns. Analyses of these patterns may be a helpful adjunct to the differential diagnosis of hypertensive disease.

Blood Pressure Behaviour in Patients with Malignant Hypertension Submitted to Kidney Transplantation

The authors investigated post-renal transplantation hypertension behaviour in 20 patients with primary malignant hypertension (PMH), in 42 patients with secondary malignant hypertension (SMH) and in 62 controls (without malignant hypertension). All cases of malignant hypertension required removal of primary kidneys, either before or after transplantation. Hypertension was noticed at different periods of the post-renal transplantation phase, in 93% of PMH cases, 90% of SMH cases and in only 31% of the controls. After a period of time following transplantation, a decrease of hypertension incidence in the SMH and control groups was noticed, and persistence of hypertension was observed in the PMH group. The long-term development of PMH patients was worse than that of the other two groups.

Bilateral nephrectomy and renal homotransplantation for malignant nephrosclerosis.

The effects of hemodialysis, bilateral nephrectomy, and renal homotransplantation were evaluated in 12 patients with renal failure due to primary malignant hypertension. The blood pressure was difficult to control with hemodialysis, moderately high doses of antihypertensives, and dietary restriction. Bilateral nephrectomy resulted in significant reduction of diastolic blood pressure and reduction in the number and quantities of antihypertensive medication. Fourteen renal homografts were performed. Patient survival and transplant function compare favorably with other patients transplanted by us and those reported to the Human Transplant Registry. In the posttransplant period, hypertension was a problem in only two patients. The mean diastolic blood pressure was similar to that achieved by bilateral nephrectomy. Renal transplantation is an acceptable therapy for patients who have been treated by bilateral nephrectomy for malignant nephrosclerosis.