Tsuyoshi Miyagi

An association between uric acid levels and renal arteriolopathy in chronic kidney disease : a biopsy-based study

Uric acid (UA) can induce renal arteriolopathy in animal models. Whether there is an association between UA and renal arteriolopathy in patients with chronic kidney disease (CKD) is unknown. Here, we examined the cross-sectional association of serum UA levels with renal arteriolar hyalinosis and wall thickening. Arteriolar parameters were assessed by semiquantitative grading (max: grade 3) of arterioles in 167 patients with CKD (mean age, 42.4 years; 86 men and 81 women) who underwent renal biopsy. The mean serum UA level was 6.4 mg dl−1. We observed hyalinosis in 94 patients (56%) and wall thickening in 119 patients (71%). As the UA level tertile increased, the proportion of higher-grade (grade 2 and 3) hyalinosis and wall thickening increased (hyalinosis, P<0.0001 and wall thickening, P=0.0002, for trend). Multiple logistic analysis adjusted for age ⩾40 years, sex, hypertension status, diabetes mellitus status and estimated glomerular filtration rate <60 ml min−1 per 1.73 m2 showed that hyperuricemia (UA ⩾7 mg dl−1) was significantly associated with a higher risk of hyalinosis (adjusted odds ratio: 3.13; 95% confidence interval: 1.23–7.94; P=0.02) and higher-grade (equal to or higher than the mean value) wall thickening (adjusted odds ratio: 2.66; 95% confidence interval: 1.11–6.38; P=0.03). Hence, these results suggest that hyperuricemia may be related to renal arteriolar damage in patients with CKD.

Quantitation of the Level of Hepatitis Delta Virus RNA in Serum, by Real-Time Polymerase Chain Reaction—and Its Possible Correlation with the Clinical Stage of Liver Disease

Some hepatitis B virus (HBV) carriers with chronic hepatitis delta virus (HDV) superinfection show progressive chronic hepatitis, whereas others show no apparent signs of liver disease. In the present study, we established a sensitive method for the quantitation of the level of HDV RNA in serum on the basis of real-time reverse-transcription polymerase chain reaction (RT-PCR), to clarify the role that the level of HDV RNA in serum plays in the diverse natural course of clinical manifestation. In 48 subjects who were positive for hepatitis B surface antigen and for anti-hepatitis delta antibody, the levels of HDV RNA in serum were quantitated by RT-PCR. The levels of HBV DNA in serum were determined by a transcription-mediated amplification assay. The levels of HDV RNA in serum of subjects with chronic hepatitis and of subjects with liver cirrhosis were significantly higher than those in asymptomatic carrier subjects. The levels of HBV DNA in serum did not differ significantly among these 3 groups. In conclusion, HDV RNA quantification by real-time RT-PCR is possibly a useful tool for understanding the pathophysiology of HDV infection.

Alcoholic liver cirrhosis complicated with torsade de pointes during plasma exchange and hemodiafiltration

A 36-year-old man with severe alcoholic hepatitis was treated with plasma exchange combined with hemodiafiltration to remove endotoxins and inflammatory cytokines. During the treatment, he had critical arrhythmia (torsade de pointes [TdP]). His laboratory data showed hypomagnesemia, which was suspected to be responsible for the development of TdP. Patients with alcoholic liver disease tend to have hypomagnesemia and Q-T interval prolongation. Furthermore, hemodiafiltration may cause hypomagnesemia. Careful observation for electrolytic imbalance is necessary when clinicians treat patients with alcoholic liver failure with a liver support system.

A patient with primary biliary cirrhosis associated with autoimmune hemolytic anemia.

Abstract: Primary biliary cirrhosis is often associated with autoimmune conditions, such as thyroid disease, sicca complex, and rheumatoid arthritis. However, an association with autoimmune hemolytic anemia has rarely been reported. We present a case of primary biliary cirrhosis associated with warm type autoimmune hemolytic anemia, and we review prior reports.

Interrelationship between brachial artery function and renal small artery sclerosis in chronic kidney disease

Chronic kidney disease (CKD), characterized by senile inflammation, is a risk factor for cardiovascular disease. Conduit artery function and small artery structure relate to cardiovascular disease. We examined the correlations, determinants and interrelationships of arterial indices in association with CKD in a cross-sectional study of 139 patients (60% male; mean age 44 years) with CKD (stages 3–5, 39%) who underwent a renal biopsy. Conduit artery function and small artery sclerosis were assessed by brachial artery flow-mediated dilatation (FMD) and semiquantitative evaluation of small artery intimal thickening (SA-IT), respectively. The estimated glomerular filtration rate correlated with FMD (r=0.31, P=0.0002) and inversely correlated with SA-IT (r=−0.54, P<0.0001). Multiple regression analysis showed that FMD was inversely correlated with SA-IT and vice versa. In addition, high-sensitivity C-reactive protein (hs-CRP) was significantly correlated with SA-IT, but not FMD. Multiple logistic analysis revealed that higher hs-CRP concomitant with decreased FMD was further associated with the risk of severe SA-IT compared with their individual effects. These findings suggest that both conduit artery and small artery disease develop with mutual interaction in parallel with decreased kidney function. Coexistence of inflammation and conduit artery dysfunction may be closely related to renal small artery sclerosis in patients with CKD.

The major low molecular weight apolipoprotein from normal and hyperlipidemia atherosclerosis-prone (LAP) Japanese quail.

The low molecular weight (LMW) apolipoprotein of apo C plays an important role in the metabolism of triglyceride-rich lipoproteins. This study aimed at a characterization of the major LMW apolipoproteins from normal quail strain, and also from LAP (hyperlipidemia atherosclerosis-prone) strain to identify its genetic disorder. The major LMW apoprotein cDNA clone from normal quail comprised of approximately 500 bp, and encoded polypeptide of 78 amino acid residues containing 57 amino acids as a mature apolipoprotein. Although the quail LMW apoprotein showed a low homology to either apo C-I, C-II, or C-III of other animals, it retained a well-developed amphipathic alpha-helix structure. There was no difference in the deduced primary structure of the quail LMW apoprotein between LAP and normal strain. An analysis of the mRNA expression showed that the quail LMW apoprotein was only expressed in the liver of both LAP and normal Japanese quail. No difference was noted in the hepatic expression of the quail LMW apoprotein mRNA between normal and LAP strains with neither normal nor atherogenic dietary conditions. The structure and expression of the major LMW apoprotein thus had no relevance to higher susceptibility of LAP strain to the experimental atherosclerosis.

Modification of the impact of hypertension on proteinuria by renal arteriolar hyalinosis in nonnephrotic chronic kidney disease.

Objective: Morphological analysis suggests that afferent arteriole hyalinosis reflects disturbed autoregulation of glomerular hemodynamics. However, the effect of arteriolar hyalinosis on the correlation between blood pressure (BP) levels and proteinuria is unknown in patients with chronic kidney disease (CKD). Therefore, we conducted a cross-sectional study to determine this correlation. Methods: A total of 109 patients with nonnephrotic CKD (55 men and 54 women) who underwent renal biopsy were recruited. Arteriolar hyalinosis was semiquantitatively assessed via arteriole grading. We examined the correlation between BP and urine protein levels (g/gCr) according to the presence of arteriolar hyalinosis. Result: Patients had a mean age, BP, estimated glomerular filtration rate, and urine protein level of 40 years, 126/75 mmHg, 86 ml/min per 1.73 m2, and 1.3 g/gCr, respectively. Patients with hyalinosis (n = 59) exhibited significant increases in median proteinuria (g/gCr) because the SBP increased (<130, 130–140, and ≥140 mmHg: 1.0, 1.3, and 2.3, respectively; P = 0.045); however, median proteinuria was comparable in patients without hyalinosis (n = 50), regardless of SBP. Multiple logistic analysis revealed that combined high BP and hyalinosis were significantly associated with increased proteinuria, defined as equal to or greater than the median value (odds ratio: 5.99, 95% confidence interval: 1.13–31.70, P < 0.05 vs. high BP−/hyalinosis−). Moreover, this combination was associated with the largest glomerular diameter. Conclusion: Renal arteriolar hyalinosis may potentiate susceptibility to BP-related glomerular damage in patients with nonnephrotic CKD. Dysregulated afferent arteriolar resistance via arteriolar sclerosis may affect hypertensive renal damage.

Augmented Association Between Blood Pressure and Proteinuria in Hyperuricemic Patients With Nonnephrotic Chronic Kidney Disease

BACKGROUND Hyperuricemia (HU) may enhance susceptibility to hypertensive renal damage via disrupted autoregulation of glomerular hemodynamics. The effect of HU on the association between blood pressure (BP) and proteinuria remains unknown in patients with chronic kidney disease (CKD). METHODS In total, 109 patients with nonnephrotic CKD (55 men and 54 females) who underwent renal biopsy were recruited. Arteriolar hyalinosis was semiquantitatively assessed via arteriole grading. Correlation between BP and urine protein (UP) level was examined based on the presence of HU, which was defined as the use of urate-lowering drugs or serum uric acid levels of ≥7 and ≥5 mg/dl in males and females, respectively, which were associated with increased risks of hyalinosis in our previous study. RESULTS Median age, BP, estimated glomerular filtration rate, and UP level were 38 years, 124/74 mm Hg, 82 ml/min/1.73 m2, and 0.8 g/gCr, respectively. In patients with HU (n = 59), log-transformed systolic BP (SBP) was significantly correlated with log-transformed UP level (r = 0.49, P < 0.0001); this was not observed in patients without HU (n = 50). Multiple regression analysis (R2 = 0.21, P = 0.0001) revealed that the interaction between HU and log-transformed SBP with respect to proteinuria was significantly correlated with log-transformed UP level (β = 7.0, P = 0.03), independent of age, sex, and potential confounding factors; however, this statistical significance was completely eliminated after adjustment for the arteriolar hyalinosis index. CONCLUSIONS HU potentiates susceptibility to hypertensive glomerular damage via disrupted autoregulation in patients with nonnephrotic CKD.

PS 08-56 ASSOCIATION BETWEEN SERUM URIC ACID LEVEL AND HYPOTENSIVE EFFECTS OF SUPPLEMENTAL THIAZIDE DIURETIC THERAPY FOR HYPERTENSION PATIENTS WITH SEVERE RENAL DYSFUNCTION TREATED WITH RENIN ANGIOTENSIN SYSTEM INHIBITORS

Objective: The hypotensive effects caused by thiazide diuretics (TZ) may be reduced in the group of patients with severe renal dysfunction and elevated uric acid levels after starting treatment. We investigated whether there is an association between hypotensive effects induced by TZ and changes in uric acid levels after starting TZ administration. Design and Method: Subjects comprised 20 hypertension patients (13 males) with eGFR levels < 30 mL/min/1.73 m2 who were on renin angiotensin system inhibitor (RAS-I) therapy and had recently started supplemental TZ therapy. We retrospectively investigated clinical indices before TZ administration and after 2 months of administration. We then divided subjects into two groups depending on whether uric acid levels were elevated or not after TZ administration, and we compared hypotensive effects in the two groups. Results: The group that exhibited uric acid level elevation after TZ administration comprised 13 cases (65%). Significant decrease in mean value of mean blood pressure after TZ administration was noted in 15 cases (75%), from 99 mmHg before administration to 88 mmHg after 2 months of administration. The amount of decrease in mean blood pressure was significantly lower in the uric acid elevation group than in the non-elevation group. In addition to the tendency of eGFR to decrease more in the uric acid elevation group after TZ administration than in the non-elevation group, we noted a tendency of urinary protein to decrease in the uric acid elevation group. Conclusions: A significant increase in hypotensive effects can be expected with the supplemental TZ administration for patients already taking RAS-Is, even for cases of severe renal dysfunction. However, although somewhat weak effects can be expected for patients with increased serum uric acid levels following TZ administration, protective effects for the kidneys can be expected over the long-term as decreases in overall levels of urinary protein were noted in these patients.

746 ANTIHYPERTENSIVE AND RENOPROTECTIVE EFFECTS OF ADDING THIAZIDE DIURETICS TO RENIN-ANGIOTENSIN SYSTEM INHIBITOR IN THE ADVANCED STAGE OF CHRONIC KIDNEY DISEASE

Objectives: Loop diuretics are recommended-diureticsfor hypertension in renal failure.Theantihypertensive effect ofthiazide diuretics (TZ) was unknown in advanced renal failure, who treated withrenin-angiotensin system inhibitor (RAS-I).We examinedthe effectofadding TZ to RAS-Iin the patients with advance stage of chronic kidney disease (CKD). Methods: We retrospectively examined antihypertensive and renoprotective effects of adding TZ to RAS-I in 105 hypertensive patients (62% male), whose estimated GFR (eGFR, ml/min/1.73 m2) was ≦60. We compared those effects in the group of eGFR 30-60 (group A) with those in less than 30 (group B). Results: Mean age, blood pressure (BP, mmHg) and eGFR were 61.9y.o, 145/76 and 37.4at just before adding TZ respectively. In the group A, BP is significantly decreasing from 146 to 126, 128, 126at 2, 6 and 12 months after adding TZ and from 148 to 132, 131, 126 in the groupB, respectively. In the group B, eGFRwas reduced from 23.7 to 21.5 at 2 months, but had been remained stable thereafter. On the other hand, urinary protein was reduced from 3.9 to 2.3 at 2 months and had been still suppressed at 12 months. Conclusion: These findings suggested that additional use of TZ to RAS-I could be effective for lowering BP even in advanced stage of CKD and it might retard the progression of CKD by reducing proteinuria. The improvement of glomerular hypertension might be involved in itsantiproteinuric effect.