Factors Associating with Non-Dipping Pattern of Nocturnal Blood Pressure in Patients with Essential Hypertension.

Background: In patients with essential hypertension, a non-dipping blood pressure pattern is a strong risk factor for cardiovascular diseases. However, background factors associating with such a blood pressure pattern remain unknown. Methods: Untreated essential hypertensive patients without chronic kidney diseases who were admitted to our outpatient clinic were included. Blood sampling and 24 h ambulatory blood pressure monitoring were mandatorily performed. Non-dipper status was defined as a maximum decrease in nocturnal systolic blood pressure within 10%. Clinical factors associating with non-dipper status were investigated. Results: A total of 154 patients (56 ± 12 years old, 86 men) were included. Among baseline characteristics, a higher serum uric acid level was independently associated with non-dipper status (odds ratio 1.03, 95% confidence interval 1.00−1.05, p < 0.05). Among those with non-dipper status, a higher high-sensitivity C-reactive protein level tended to be associated with incremental nighttime systolic blood pressure levels (p = 0.065). Conclusions: Hyperuricemia and micro-inflammation might be associated with attenuated nocturnal blood pressure dipping and incremental nighttime systolic blood pressure levels.

Pubertal administration of antiserum against nerve growth factor regresses renal vascular remodeling in spontaneously hypertensive rats.

To investigate the role of nerve growth factor (NGF) in the development of hypertensive renal vascular remodeling, antiserum against NGF (anti-NGF) or vehicle was injected at 3 weeks of age in spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats (n = 9 for each treatment in each strain). Flow-pressure (F-P) and pressure-glomerular filtration rate (P-GFR) relationships at vasodilated perfused kidneys were determined at 10 weeks of age. In the vehicle rats, blood pressure, renal noradrenaline content, the gradient of F-P (minimal vascular resistance at pre- and post-glomerular vasculature) and the X-intercept of P-GFR (preglomerular : postglomerular vascular resistance ratio) were greater in SHR than in WKY rats, although the gradient of P-GFR (glomerular filtration capacity) did not differ significantly between the strains. Blood pressure and renal noradrenaline content were lower in SHR receiving anti-NGF than in SHR receiving vehicle, although such difference was not observed in WKY rats. The gradient of F-P was less but the gradient of P-GFR was greater in SHR receiving anti-NGF compared with SHR receiving vehicle, although the similar differences did not occur in WKY rats. Blood pressure and renal noradrenaline content remained greater in SHR treated with anti-NGF compared with WKY rats treated with vehicle; however, the gradient of F-P did not differ significantly between them. Contrary, anti-NGF did not affect the X-intercept of P-GFR in either strain. In conclusion, NGF could contribute to the genesis of renal vascular remodeling, at least in part, through modification of renal sympathetic activity and blood pressure in SHR.

Imbalance of renal production between 5-hydroxytryptamine and dopamine in patients with essential hypertension complicated by microalbuminuria.

BACKGROUND: In the kidney, 5-hydroxytryptamine (5-HT) and dopamine (DA) are formed by the same enzyme, l-aromatic amino acid decarboxylase, but act on renal function and glomerular structure in an opposite direction. The present study was designed to explore whether rates of renal production of 5-HT relative to that of DA are altered in patients with essential hypertension and microalbuminuria. METHODS: We measured urinary levels of 5-HT and DA, reflecting renal production of 5-HT and DA as well as 24-hour ambulatory blood pressure and urinary albumin excretion in 82 consecutive untreated, essential hypertensives without overt proteinuria. RESULTS: Urinary 5-HT excretion and the ratio of urinary 5-HT to DA were significantly higher in 22 patients with microalbuminuria than in the remaining patients with normoalbuminuria, although urinary DA levels did not differ between the groups. The 24-hour systolic and diastolic blood pressures were also higher in the microalbuminuric group than in the normoalbuminuric group. Multiple regression analysis revealed that urinary 5-HT excretion and 24-hour systolic blood pressure were independently associated with urinary albumin excretion. Furthermore, urinary 5-HT excretion was positively correlated with creatinine clearance as well as blood pressure but tended to be negatively correlated with fractional excretion of sodium. CONCLUSIONS: Renal production of 5-HT is enhanced compared with that of DA in essential hypertensives with microalbuminuria. This imbalance may contribute to the genesis of hypertensive glomerular damage.

Increased blood viscosity is associated with reduced renal function and elevated urinary albumin excretion in essential hypertensives without chronic kidney disease.

Increased blood viscosity reduces blood flow and elevates vascular resistance in the cardiovascular system. The aim of this study was to elucidate how blood viscosity could affect renal function and eventually contribute to renal damage in essential hypertensives (EHT). In 164 untreated EHT without apparent renal damage (96 men, 56±12 years old, creatinine clearance 123±33 ml min(-1) per 1.73 m(2) and urinary albumin excretion 19±19 mg per day), blood and plasma viscosity was determined using a falling ball microviscometer. Blood viscosity correlated negatively with creatinine clearance (r=-0.185, P=0.018) and positively with urinary albumin excretion (r=0.253, P=0.001). This indicated that increased blood viscosity is associated with reduced renal function and worsening of albuminuria in EHT. Stepwise multiple regression analysis identified blood viscosity as an independent determinant of creatinine clearance (R(2)=0.058) and urinary albumin excretion (R(2)=0.216). In conclusion, increased blood viscosity may be a risk for development of renal disease in EHT.

[Case of distal renal tubular acidosis complicated with renal diabetes insipidus, showing aggravation of symptoms with occurrence of diabetes mellitus].

We report herein a 27-year-old male case of inherited distal renal tubular acidosis complicated with renal diabetes insipidus, the symptoms of which were aggravated by the occurrence of diabetes mellitus. At 2 months after birth, he was diagnosed as having inherited distal renal tubular acidosis and thereafter supplementation of both potassium and alkali was started to treat his hypokalemia and metabolic acidosis. At the age of 4 years, calcification of the bilateral renal medulla was detected by computed tomography. Subsequently his urinary volume gradually increased and polyuria of approximately 4 L/day persisted. At the age of 27 years, he became fond of sugar-sweetened drinks and also often forgot to take the medicine. He was admitted to our hospital due to polyuria of more than 10 L day, muscle weakness and gait disturbance. Laboratory tests disclosed worsening of both hypokalemia and metabolic acidosis in addition to severe hyperglycemia. It seemed likely that occurrence of diabetes mellitus and cessation of medications can induce osmotic diuresis and aggravate hypokalemia and metabolic acidosis. Consequently, severe dehydration, hypokalemia-induced damage of his urinary concentration ability and enhancement of the renin angiotensin system occurred and thereby possibly worsened his hypokalemia and metabolic acidosis. As normalization of hyperglycemia and metabolic acidosis might have exacerbated hypokalemia further, dehydration and hypokalemia were treated first. Following intensive treatment, these abnormalities were improved, but polyuria persisted. Elevated plasma antidiuretic hormone (12.0 pg/mL) and deficit of renal responses to antidiuretic hormone suggested that the polyuria was attributable to the preexisting renal diabetes insipidus possibly caused by bilateral renal medulla calcification. Thiazide diuretic or nonsteroidal anti-inflammatory drugs were not effective for the treatment of diabetes insipidus in the present case.

[Autopsy case of Henoch-Schönlein purpura nephritis complicated with intestinal cytomegalovirus infection].

A 55-year-old man was admitted to our hospital because of arthralgia, purpura, abdominal pain, melena and leg edema. Laboratory findings showed an increased serum creatinine level (2.4 mg/dL), hematuria and massive proteinuria (10.7 g/day). Renal biopsy revealed diffuse endocapillary proliferation and focal mesangial proliferation with IgA deposition predominantly in the glomerular capillary walls. Based on these findings, he was diagnosed as having Henoch-Schönlein purpura nephritis and steroid therapy was started. Following steroid therapy, his nephrotic state remained unchanged, although his renal function improved concomitantly with the disappearance of arthralgia, purpura and abdominal symptoms. Therefore, cyclosporine was added to the steroid therapy to enhance immunosuppression. However, melena recurred and anemia progressed. Endoscopy revealed multiple ulcers in the duodenum and jejunum, and clipping was performed at some bleeding sites. However, he died of hemorrhagic shock. The autopsy revealed that hemorrhagic lesions having cytomegalovirus infection spread widely in the stomach, duodenum and jejunum. Recurrence of gastrointestinal bleeding during the treatment of Henoch-Schönlein purpura nephritis is usually due to severe vasculitis or steroid ulcer. However, in patients receiving strong immunosuppressive therapy, cytomegalovirus infection needs to be considered as cause of gastrointestinal bleeding.