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The prognosis of lupus nephritis (LN) has improved following the introduction of effective immunosuppressive therapy and progress in supportive care. This study examined recent renal and patient prognosis for adults with LN in Japan.We conducted a nationwide retrospective cohort study of LN patients who received a renal biopsy between 2007 and 2012 that were registered in the Japan Renal Biopsy Registry. Of 623 registered adults with LN from 25 institutions and their affiliated or community hospitals, 489 were eligible for this study.The median age at renal biopsy was 39 years, and 82.2% of patients were female. Renal biopsies were performed in 348 patients with new-onset LN, 106 with relapse LN, and 35 with refractory LN. The distribution of ISN/RPS 2003 Classes was as follows: I 1.6%; II 5.3%; III (± V) 27.0%; IV (± V) 47.0%; V 18.4%; VI 0.6%. During the median observation period of 63.8 months, 36 patients (7.3%) reached a doubling of serum creatinine or end-stage kidney disease (ESKD), and 28 patients (5.7%) died. The 5 year renal and patient survival rates were 93.9% and 94.7%, respectively. Multivariate analysis revealed body mass index (BMI) and estimated glomerular filtration rate (eGFR) were independent risk factors for a doubling of serum creatinine in ESKD. Age and eGFR were independent risk factors for death.Recent prognosis for adults with LN are relatively good in Japan. Risk factors for impaired renal function are BMI and eGFR at renal biopsy, while age and eGFR are risk factors for death.

Objective: In our recent study, non-Gaussianity of heart rate variability (λ25s), an indicator of sympathetic nerve activity, did not change during two-day treatment with the angiotensin II type 1 receptor blocker (ARB) azilsartan. Coadministration of calcium channel blockers (CCBs) might affect the study results. Methods: In this subanalysis, 20 patients with chronic kidney disease (14 men; age 61±15 years) were divided into three groups: patients with coadministration of L-type CCB, patients without coadministration of CCB, and patients with coadministration of sympathoinhibitory (L/T- or L/T/N-type) CCB. λ25s was calculated separately in daytime and nighttime. Results: Daytime λ25s at baseline was higher in patients with L-type CCB coadministration (0.62±0.18, n = 5) compared with those without CCB (0.49±0.13, n = 11) and those with sympathoinhibitory CCB (0.46±0.06, n = 4). The relationship between the changes in daytime λ25s and systolic blood pressure was positive in patients with L-type CCB coadministration, whereas the relationship was inverse in the other two groups. A larger decrease in daytime λ25s was shown in patients with L-type CCB coadministration compared with those in the other two groups. Conclusions: CCBs, as well as diuretics, are recommended as second-line antihypertensive agents. Our results suggested that ARBs can overwhelm the activation of sympathetic nerve activity stimulated by coadministration of L-type CCBs.

Objective: Although percutaneous transluminal angioplasty is an effective therapy against vascular access failure in hemodialysis patients, recurrent stenosis imposes enormous burden for hemodialysis patients. A nitinol scoring element–equipped helical balloon catheter (AngioSculpt®) has been altered the landscape for treating several vascular diseases. It is not, however, fully elucidated whether AngioSculpt for advanced vascular access stenosis, difficult to expand by conventional balloons, successfully provides bailout angioplasty. Here, we report our cases whose intradialytic venous pressure significantly improved after percutaneous transluminal angioplasty without any serious adverse complications using AngioSculpt. Patients and Methods: Among patients undergoing hemodialysis in Masuko Memorial Hospital, 16 cases with resistant and recurrent vascular access stenosis underwent AngioSculpt (diameter 6 mm, total length 4 cm) angioplasty. We simultaneously measured the average venous pressures during hemodialysis before and after percutaneous transluminal angioplasty. Results: The average outflow vessel stenosis rate was 73.0 ± 11.3% before AngioSculpt intervention. Fully enlarged vessels were observed by expanding vessels at maximum pressure of 14 atm in all cases without any complications including vascular ruptures. Their intradialytic venous pressures decreased from 181.8 ± 39.2 mmHg to 150.5 ± 39.3 mmHg ( p Conclusion: AngioSculpt may provide a promising option for treating hemodialysis patients with severely advanced vascular access stenosis, who would otherwise need repeated vascular access surgeries and/or conventional percutaneous transluminal angioplasties.

We have revealed that even in humans, activated intrarenal renin–angiotensin–aldosterone system (RAAS) enhances tubular sodium reabsorption to facilitate salt sensitivity and nondipper rhythm of blood pressure (BP), and that angiotensin receptor blocker (ARB) could increase daytime urinary sodium excretion rate (U N a V) to produce lower sodium balance and restore nondipper rhythm. However, the sympathetic nervous system and intrarenal dopaminergic system can also contribute to renal sodium handling. A total of 20 patients with chronic kidney disease (61 ± 15 years) underwent 24‐h ambulatory BP monitoring before and during two‐day treatment with ARB, azilsartan. Urinary angiotensinogen excretion rate (U AGT V, μ g/gCre) was measured as intrarenal RAAS; urinary dopamine excretion rate (U DA V, pg/gCre) as intrarenal dopaminergic system; heart rate variabilities (HRV, calculated from 24‐h Holter‐ECG) of non‐Gaussianity index λ 25s as sympathetic nerve activity; and power of high‐frequency (HF) component or deceleration capacity (DC) as parasympathetic nerve activity. At baseline, glomerular filtration rate correlated inversely with U AGT V ( r = −0.47, P = 0.04) and positively with U DA V ( r = 0.58, P = 0.009). HF was a determinant of night/day BP ratio ( β = −0.50, F = 5.8), rather than DC or λ 25s . During the acute phase of ARB treatment, a lower steady sodium balance was not achieved. Increase in daytime U N a V preceded restoration of BP rhythm, accompanied by decreased U AGT V ( r = −0.88, P = 0.05) and increased U DA V ( r = 0.87, P = 0.05), but with no changes in HRVs. Diminished sodium excretion can cause nondipper BP rhythm. This was attributable to intrarenal RAAS and dopaminergic system and impaired parasympathetic nerve activity. During the acute phase of ARB treatment, cooperative effects of ARB and intrarenal dopaminergic system exert natriuresis to restore circadian BP rhythm.

Introduction: We have reported that the circadian rhythm of urinary potassium excretion (U K V) is determined by the rhythm of urinary sodium excretion (U Na V) in patients with chronic kidney disease (CKD). We also reported that treatment with an angiotensin receptor blocker (ARB) increased the U Na V during the daytime, and restored the non-dipper blood pressure (BP) rhythm into a dipper pattern. However, the circadian rhythm of U K V during ARB treatment has not been reported. Materials and methods: Circadian rhythms of U Na V and U K V were examined in 44 patients with CKD undergoing treatment with ARB. Results: Whole-day U Na V was not altered by ARB whereas whole-day U K V decreased. Even during the ARB treatment, the significant relationship persisted between the night/day ratios of U Na V and U K V ( r =0.56, p

Introduction:Increased sympathetic nerve activity has been suggested in patients with chronic kidney disease (CKD). Pathologic sympathetic activity can alter heart rate variability (HRV), and the altered HRV has prognostic importance, so that reducing sympathetic activity may be an important strategy. Novel nonlinear HRVs, including deceleration capacity (DC), have greater predictive power for mortality. We have recently proposed an increase in a non-Gaussianity index of HRV, λ25s, which indicates the probability of volcanic heart rate deviations of departure from each standard deviation level, as a marker of sympathetic cardiac overdrive. L/T-type calcium channel blocker (L/T-CCB), azelnidipine, decreases sympathetic nerve activity in experimental and clinical studies.Methods:In 43 hypertensive patients with CKD under treatment with an angiotensin receptor blocker (ARB), we investigated whether 8-week add-on L/T-CCB treatment could restore HRV.Results:Means of all normal-to-normal intervals over 24 h ( p25s( p=0.001) decreased regardless of gender, age, renal function or blood pressure, while no significant changes were observed in the other HRVs.Conclusions:Reduction of λ25sis useful to assess the effect of sympathoinhibitory treatment. Further studies are needed to investigate if the restoration of HRV is directly associated with the improvement of prognosis in patients with CKD.

High salt-sensitivity and nondipper blood pressure (BP) rhythm are highly associated with each other, because both are caused by impaired renal sodium excretion capability. We proposed that nocturnal hypertension and resultant pressure natriuresis could compensate for daytime sodium retention. If so, high BP may continue until sodium is sufficiently excreted at night. In fact, it takes longer for the night-time BP to fall in patients with more severe renal dysfunction. The time appears to be an essential component of the nondipper BP rhythm and, therefore, we defined the duration as the dipping time. Also, renal function was the sole determinant of a nocturnal BP dip other than age, sex, or BMI. Furthermore, we reported that diuretic therapy or dietary salt restriction, which can prevent sodium retention, restored the circadian BP rhythm into a dipper pattern. Large-scale studies are needed to explore whether these interventions can decrease the risks.

Recently, we found that an angiotensin II receptor blocker (ARB) restored the circadian rhythm of the blood pressure (BP) from a nondipper to a dipper pattern, similar to that achieved with sodium intake restriction and diuretics (Fukuda M, Yamanaka T, Mizuno M, Motokawa M, Shirasawa Y, Miyagi S, Nishio T, Yoshida A, Kimura G. J Hypertens 26: 583–588, 2008). ARB enhanced natriuresis during the day, while BP was markedly lower during the night, resulting in the dipper pattern. In the present study, we examined whether the suppression of tubular sodium reabsorption, similar to the action of diuretics, was the mechanism by which ARB normalized the circadian BP rhythm. BP and glomerulotubular balance were compared in 41 patients with chronic kidney disease before and during ARB treatment with olmesartan once a day in the morning for 8 wk. ARB increased natriuresis (sodium excretion rate; UNaV) during the day (4.5 ± 2.2 to 5.5 ± 2.1 mmol/h, P = 0.002), while it had no effect during the night (4.3 ± 2.0 to 3.8 ± 1.6 mmol/h, P = 0.1). The night/day ratios of both BP and UNaV were decreased. The decrease in the night/day ratio of BP correlated with the increase in the daytime UNaV ( r = 0.42, P = 0.006). Throughout the whole day, the glomerular filtration rate ( P = 0.0006) and tubular sodium reabsorption ( P = 0.0005) were both reduced significantly by ARB, although UNaV remained constant (107 ± 45 vs. 118 ± 36 mmol/day, P = 0.07). These findings indicate that the suppression of tubular sodium reabsorption, showing a resemblance to the action of diuretics, is the primary mechanism by which ARB can shift the circadian BP rhythm into a dipper pattern.

We reported a remarkable regional difference within Japan in the incidence of end-stage renal disease. Regional differences were also well-known for salt intake, blood pressure (BP), and mortality from stroke, which remains one of the leading causes of death. Noting these regional differences, we examined mutual relationships among salt intake, BP, and stroke mortality in 12 regions of Japan. Data of salt intake, BP, and stroke mortality in 12 regions were collected from National Nutrition Survey (NNS-J), reanalysis of NNS-J, and Vital Statistics of National Population Dynamic Survey (Ministry of Health, Labor and Welfare), respectively. Significant regional differences were found in salt intake (P < .0001), mean arterial BP (P = .0001), and stroke mortality (P < .0001). Although annual changes in these parameters were also significant, their regional differences persisted. Salt intake had positive relationships with both mean arterial BP (r = 0.26, P = .0009) and stroke mortality (r = 0.26, P < .0001) across 12 regions, whereas mean arterial BP was not correlated with stroke mortality. Multiple regression analysis further identified salt intake as an independent factor to increase stroke mortality, but mean arterial BP was not a determinant. Compared with the four regions with lowest salt intake, odds ratios of stroke mortality adjusted by mean arterial BP were 1.04 (95% CI, 1.03-1.06) for the intermediate four regions and 1.25 (95% CI, 1.23-1.27) for the four regions with highest salt intake. These findings suggest that salt intake may have an adverse effect on stroke mortality independently of BP.

We previously showed that there are marked geographic differences in the incidence of end-stage renal disease (ESRD) within Japan. In addition, the use of renin–angiotensin system inhibitors was found to be inversely correlated with the increasing ESRD rate. It was recently demonstrated that the incidence of ESRD due to diabetic nephropathy is declining in both Europe and USA. Therefore, we investigated the increasing ESRD rate and its geographic difference in Japan. Each year, the Japanese Society for Dialysis Therapy reports the numbers of patients initiating maintenance dialysis therapy in each prefecture of Japan. We used old (1984–1991) and recent (2001–2008) data to compare the increasing ESRD rate, which was estimated from the slope of the regression line of the annual incidence corrected for population, between the two periods in 11 regions of Japan. Increasing ESRD rate almost halved, from 11.1 ± 5.6 to 5.4 ± 0.7/million per year from the old to the recent period. Deceleration of the increasing ESRD rate from the old to the recent period was correlated with the incidence in the old period across 11 regions (r = 0.81, p < 0.003); i.e., the deceleration was greater in the regions where ESRD incidence had been higher. Whereas the increasing ESRD rate was significantly different among regions in the old period, this was not the case in the recent period, resulting in uniformity throughout Japan. The increasing ESRD rate is slowing in Japan, and its geographic differences, previously observed, have disappeared.

Some cardiovascular disorders disturb circadian variation of endothelial function. We investigated whether deterioration of renal function alters circadian variation of endothelial function in patients with hypertension. Endothelial function was assessed by the peak forearm blood flow (FBF) response to reactive hyperemia, and 24-hour ambulatory blood pressure monitoring was performed in 25 patients with essential hypertension (61 ± 17 years). Relationships among renal function, 24-hour blood pressure, and endothelial function were analyzed. The ratio of nighttime to daytime mean arterial pressure was inversely correlated with estimated glomerular filtration rate (eGFR) ( r = −0.43, P = .03). The FBF response to reactive hyperemia examined at 21:00, but not at 6:30 or 11:30, was significantly correlated with eGFR ( r = 0.44, P = .03). Furthermore, the ratio of FBF response measured at 21:00 to that measured at 6:30 was independently correlated with eGFR (β = 0.47, P = .02). Renal dysfunction is associated with the derangement of circadian variation of both endothelial function and blood pressure. Nocturnal blood pressure is elevated, and evening endothelial function deteriorates in parallel with a decline in renal function in hypertensive patients.

In healthy subjects, blood pressure (BP) drops by 10-20% during the night. Conversely, in patients with the salt-sensitive type of hypertension or chronic kidney disease, nighttime BP does not fall, resulting in an atypical pattern of circadian BP rhythm that does not dip. This pattern is referred to as the 'non-dipper' pattern. Loss of renal functional reserve, due to either reduced ultrafiltration capacity or enhanced tubular sodium reabsorption, induces the salt-sensitive type of hypertension. When salt intake is excessive in patients with salt-sensitive hypertension, the defect in sodium excretory capability becomes evident, resulting in elevated BP during the night. This nocturnal hypertension compensates for diminished natriuresis during the daytime and enhances pressure natriuresis during the night. Nocturnal hypertension and the non-dipper pattern of circadian BP rhythm cause cardiovascular events. When excess salt intake is loaded in patients who are in a salt-sensitive state, glomerular capillary pressure is also elevated, resulting in glomerular sclerosis and eventual renal failure. In this way, salt sensitivity and excess salt intake contribute to both cardiovascular and renal damage at the same time. We propose that salt sensitivity of BP and excess salt intake have important roles in the genesis of the cardiorenal connection. Salt sensitivity and circadian rhythm of BP are the keys to understanding the connections between cardiovascular and renal complications.

The Major Histocompatibility Complex (Mhc) class II DRB locus of vertebrates is highly polymorphic and some alleles may be shared between closely related species as a result of balancing selection in association with resistance to parasites. In this study, we developed a new set of PCR primers to amplify, clone, and sequence overlapping portions of the Mhc class II DRB-like gene from the 5'UTR end to intron 3, including exons 1, 2, and 3 and introns 1 and 2 in four species (20 Humboldt, six African, five Magellanic, and three Galapagos penguins) of penguin from the genus Spheniscus (Sphe). Analysis of gene sequence variation by the neighbor-joining method of 21 Sphe sequences and 20 previously published sequences from four other penguin species revealed overlapping clades within the Sphe species, but species-specific clades for the other penguin species. The overlap of the DRB-like gene sequence variants between the four Sphe species suggests that, despite their allopatric distribution, the Sphe species are closely related and that some shared DRB1 alleles may have undergone a trans-species inheritance because of balancing selection and/or recent rapid speciation. The new primers and PCR assays that we have developed for the identification of the DRB1 DNA and protein sequence variations appear to be useful for the characterization of the molecular evolution of the gene in closely related Penguin species and might be helpful for the assessment of the genetic health and the management of the conservation and captivity of these endangered species.

We have postulated that the diminished renal capacity to excrete sodium causes nocturnal blood pressure (BP) elevation, which enhances pressure natriuresis in compensation for impaired daytime natriuresis. If such a mechanism holds, high BP during sleep at night may continue until excess sodium is sufficiently excreted into urine. This study examined whether the duration, defined as “dipping time,” until nocturnal mean arterial pressure began to fall to cr ; ρ=−0.61; P P P cr (mean arterial pressure: r =−0.58, P r =−0.69, P cr (mL/min), hazard ratios of nocturnal BP dip adjusted for age, gender, and body mass index were 0.37 (95% CI: 0.17 to 0.79; P =0.01) for the second tertile (C cr : 50 to 90) and 0.20 (95% CI: 0.08 to 0.55; P =0.002) for the third tertile (C cr : 5 to 41) compared with the first tertile (C cr : 91 to 164). These findings demonstrate that patients with renal dysfunction require a longer duration until BP falls during the night. The prolonged duration until BP dip during sleep seems an essential component of the nondipper pattern of the circadian BP rhythm.

We have shown that as renal function deteriorated, night-time fall in both blood pressure and urinary sodium excretion were diminished. We have also reported that sodium intake restriction and diuretics both normalized circadian blood pressure rhythm from nondipper to dipper patterns. In this study, we investigated whether an angiotensin II receptor blocker, olmesartan, could restore night-time blood pressure fall.Twenty patients with chronic kidney disease (13 men, seven women; mean age 44.8 +/- 18.1 years; BMI 22.9 +/- 3.5 kg/m2) were studied. At baseline and 8 weeks after the treatment with olmesartan medoxomil (10-40 mg/day), 24-h blood pressure monitoring and urinary sampling for both daytime (0600-2100 h) and night-time (2100-0600 h) were repeated to compare the circadian rhythms of blood pressure and urinary sodium excretion.The 24-h mean arterial pressure was lowered by olmesartan, while urinary sodium excretion remained unchanged. On the other hand, daytime urinary sodium excretion was increased from 4.8 +/- 2.2 to 5.7 +/- 2.1 mmol/h, while night-time urinary sodium excretion tended to be reduced from 3.9 +/- 1.7 to 3.4 +/- 1.6 mmol/h. Night/day ratios of mean arterial pressure (0.98 +/- 0.1 to 0.91 +/- 0.08; P = 0.01) and urinary sodium excretion (0.93 +/- 0.5 to 0.68 +/- 0.4; P = 0.0006) were both decreased. Olmesartan enhanced night-time falls more in mean arterial pressure (r = 0.77; r2 = 0.59; P0.0001) and urinary sodium excretion (r = 0.59; r2 = 0.34; P = 0.007), especially in patients whose baseline night-time falls were more diminished.These findings demonstrated that olmesartan could restore night-time blood pressure fall, as seen with diuretics and sodium restriction, possibly by enhancing daytime sodium excretion. Since nocturnal blood pressure is a strong predictor of cardiovascular events, olmesartan could relieve cardiorenal load through normalization of circadian blood pressure rhythm besides having powerful ability to block the renin-angiotensin system.

Proportions of elderly aged ≥65 and ≥75 within Japan will increase to 30 and 20 %, respectively, in 2025, when “Baby-Boom Generations” will reach the age of 75 years. Okabayashi and colleagues report that even in elderly patients with IgA nephropathy (IgAN), immunosuppressive treatment can reduce proteinuria, with no adverse events. Their findings remind us of recent finding from STOP-IgAN study; additional immunosuppressive therapy to intensive supportive care [specifically renin–angiotensin system (RAS) inhibitors (RASi)] did not improve the outcome. If STOP-IgAN makes doctors believe that immunosuppression is not necessary, many patients could lose opportunity to eliminate their kidney disease. Indeed, we have experienced patients with IgAN, who despite hematuria, could not undergo renal biopsy or immunosuppressive treatment at another facility because of low proteinuria, and exhibited advanced lesions in their renal biopsy at our institution. The discrepancy between Okabayashi’s and STOP-IgAN study was derived not only from differences in population age (≥60 years vs. 18–70 years). STOP-IgAN excluded the crescentic IgAN, whereas Okabayashi et al. found active manifestations (hematuria, mesangial proliferation, and cellular/fibrocellular crescent). Therefore, immunosuppressive therapy is required even in elderly patients. In STOP-IgAN, RASi were used first, and then immunosuppressive agent was additionally used. RASi has important implications to reduce glomerular capillary pressure and to suppress the intrarenal RAS activity. However, immunosuppressant should be administered initially to cure hematuria. In fact, microscopic-hematuria was resolved in only 16 and 42 % of two-assigned groups in STOP-IgAN, respectively. Okabayashi et al. provided a timely message regarding the significance of immunosuppressive treatment of IgAN.

Patients with infective endocarditis (IE) often have renal complications which may include infarcts, abscesses and glomerulonephritis (GN). Furthermore, it is generally accepted that there is an association between IE and anti-neutrophil cytoplasmic antibody (ANCA). Here, we report the case of a 24-year-old man who developed rapidly progressive GN in the course of IE due to infection with alpha-streptococcus. The initial clinical manifestation of the condition was severe sacroiliitis without fever. Sandwich ELISA showed that the patient was positive for PR3-ANCA at low titer, and the classical complement pathway was also activated. Renal biopsy demonstrated several lesions: focal embolic GN, GN with immune deposits and focal and segmental crescentic necrotizing GN. Treatment with antibiotics and steroids led to eradication of the infection, and resolution of the renal disease was accompanied by immediate disappearance of PR3-ANCA and hypocomplementemia. During a 4-year follow-up period, no recurrence was observed. There have only been 7 case reports of GN associated with IE and PR3-ANCA in which the renal pathology has been described, and the current report is the first to document renal pathology in a patient with isolated pulmonic valve IE and PR3-ANCA. Moreover, this report is the first to show a change in renal biopsy findings in response to treatment. A review of the 7 literature cases and that of our patient showed that none involved pauci-immune GN. Hence, further studies are needed to clarify the prevalence of pauci-immune GN in ANCA-positive IE patients.

Background. Nocturnal polyuria has been well known in renal insufficiency. Recently, we found that as renal function deteriorated in chronic kidney disease (CKD), natriuresis was enhanced during the night with nocturnal blood pressure elevation. In the present study, we investigated whether nocturnal polyuria in CKD was due to the inability to concentrate urine, as previously proposed, or based on osmotic diuresis mainly by natriuresis. Methods. In 27 CKD patients, circadian rhythms of urinary sodium, potassium, urea and osmolar excretion rates (UNaV, UKV, UureaV, UosmV) as well as of urinary volume (V) and free-water clearance ðC H2O Þ were estimated during both daytime (6:00 to 21:00) and nighttime (21:00 to 6:00). Then, the night/day ratios of these parameters were analysed in relation to creatinine clearance (Ccr) as a marker of glomerular filtration rate. Results. Ccr had significantly negative relationships with night/day ratios of V (R ¼� 0.69; P < 0.0001), UosmV (R ¼� 0.54; P ¼ 0.004) and UNaV (R ¼� 0.63; P ¼ 0.0005), but no correlation with night/day ratios of CH2O (R ¼� 0.33; P ¼ 0.1), UKV (R ¼� 0.29; P ¼ 0.1) or UureaV (R ¼� 0.31; P ¼ 0.1). Linear and multiple regression analysis identified nocturnal natriuresis rather than urea excretion as an independent determinant of nocturia. Conclusion. As renal function deteriorated, nocturnal polyuria was seen, being consistent with classical recognition. Furthermore, this increase in nocturnal urine volume seemed related to osmotic diuresis mainly by natriuresis rather than to water diuresis or urea excretion.

SUMMARY: Background: We recently showed that there were clear regional differences in the dynamics of end-stage renal disease (ESRD) within Japan, which has an ethnically homogenous population. We speculate on the reason for these regional differences by correlating the regional distributions in the incidence of ESRD due to each of the following individual causes of ESRD: chronic glomerulonephritis (CGN), diabetic nephropathy (DMN) and polycystic kidney disease (PKD). Methods: The number of ESRD patients entering maintenance dialysis therapy due to individual causes of renal disease in each prefecture was reported annually for a 6-year period by the Japanese Society for Dialysis Therapy. After combining data from several prefectures into 11 geopolitical regions in Japan, the mean annual incidence of ESRD across the 11 regions was correlated among the three causes of ESRD. Results There were significant regional differences in the incidence of ESRD due to CGN (P

We present the case of a 69-year-old man with nephrotic syndrome and renal insufficiency, who developed lobular glomerulonephritis. An electron microscopy examination of a renal biopsy showed microtubular structures of 24 nm in diameter in the subendothelial space and the paramesangial area. These deposits were PAS-positive and Congo red-negative, and revealed predominantly positive staining for kappa light chain. There was no evidence of diseases with highly organized glomerular deposits, such as amyloidosis, cryoglobulinemia, systemic lupus erythematosus or paraproteinemia. Therefore, the patient was diagnosed to have immunotactoid glomerulopathy (ITG). During a seven-year course he has not developed any disease known to be associated with organized glomerular immune deposits. Hence, we believe ITG occurred as a primary glomerular disease in this case. We also highlight cases of ITG with microtubular deposits that have been reported in Japan, compare these cases to previous reports, and show that the characteristics of the Japanese cases are male predominance; a high incidence of membranoproliferative glomerulonephritis (MPGN); a low incidence of monoclonal gammopathy and hematological malignancies and a higher incidence of hypocomplementemia.

The Major Histocompatibility Complex (Mhc) genomic region of many vertebrates is known to contain at least one highly polymorphic class II gene that is homologous in sequence to one or other of the human Mhc DRB1 class II genes. The diversity of the avian Mhc class II gene sequences have been extensively studied in chickens, quails, and some songbirds, but have been largely ignored in the oceanic birds, including the flightless penguins. We have previously reported that several penguin species have a high degree of polymorphism on exon 2 of the Mhc class II DRB1-like gene. In this study, we present for the first time the complete nucleotide sequences of exon 2, intron 2, and exon 3 of the DRB1-like gene of 20 Humboldt penguins, a species that is presently vulnerable to the dangers of extinction. The Humboldt DRB1-like nucleotide and amino acid sequences reveal at least eight unique alleles. Phylogenetic analysis of all the available avian DRB-like sequences showed that, of five penguin species and nine other bird species, the sequences of the Humboldt penguins grouped most closely to the Little penguin and the mallard, respectively. The present analysis confirms that the sequence variations of the Mhc class II gene, DRB1, are useful for discriminating among individuals within the same penguin population as well those within different penguin population groups and species.

We recently illustrated a close relationship between glomerular filtration rate and circadian rhythm of blood pressure (BP) in patients with chronic kidney disease. However, it remains undetermined from such cross-sectional findings which occurs first, the loss of kidney function or the lack of nocturnal BP fall. In the present study, we examined whether circadian rhythm of BP is affected by unilateral nephrectomy for kidney donation to clarify this important issue. Fifteen healthy subjects (4 men, 11 women; aged 33 to 65 years; mean age 55 +/- 2 years) who underwent unilateral nephrectomy for kidney donation were studied. Ambulatory BP was monitored for 24 h, while serum and urinary samples were collected to estimate creatinine clearance before and on the 8th day after nephrectomy. Then, changes in the night/day ratios of mean arterial BP were analyzed in relation to the decrease in 24-h creatinine clearance as a marker of glomerular filtration rate by nephrectomy. Creatinine clearance was reduced by 29% in average from 84 +/- 6 to 60 +/- 4 ml/min by nephrectomy, while 24-h mean arterial BP values were 91 +/- 3 and 94 +/- 4 mmHg (p=0.08) before and after nephrectomy. Although mean BP (daytime, nighttime or night/day ratio) was not altered significantly by nephrectomy, the decrease in creatinine clearance was positively correlated with the increase in the night/ day ratio of mean BP (r=0.61, p=0.017). The decrease in creatinine clearance was not correlated with changes in either 24-h, daytime or nighttime mean BP. Our results suggest that unilateral nephrectomy disturbs the circadian rhythm of BP as a function of renal dysfunction without affecting absolute levels of BP. Non-dipping of BP seems the consequence of the loss of renal function, rather than the cause.

Nocturnal blood pressure is elevated with natriuresis and proteinuria as renal function deteriorates in nephropathy. Background We reported that patients with sodium sensitive type of hypertension exhibited the lack of nocturnal fall in blood pressure with enhanced natriuresis during night. Sodium sensitivity is caused by diminished glomerular filtration capability and/or augmented tubular reabsorption of sodium, and seems tightly linked with glomerular capillary hypertension. In the present study, we investigated the relationship between glomerular filtration rate and circadian rhythms of these parameters in patients with glomerulopathy. Methods Twenty six patients (15 men and 11 women; aged 17 to 72 years; mean age 47 ± 3 years), whose diagnosis was confirmed as glomerulopathy with renal biopsy, were studied during hospitalization. Ambulatory blood pressure for 24 hours was monitored, while urinary samples were collected for both daytime (6:00 a.m. to 9:00 p.m.) and nighttime (9:00 p.m. to 6:00 a.m.) to estimate circadian rhythms of urinary sodium and protein excretion rates (U Na V, U pro V). Then night/day ratios of mean arterial blood pressure (MAP), U Na V, and U pro V were analyzed in relation to 24-hour creatinine clearance as a marker of glomerular filtration rate. Results Serum creatinine and creatinine clearance were 1.1 ± 0.1 mg/dL and 89 ± 7 mL/min/1.73m2. There were significant day-night differences in MAP (96 ± 2 mm Hg vs. 92 ± 2 mm Hg; P = 0.006), U Na V (6.7 ± 0.9 mmol/hour vs. 3.6 ± 0.3mmol/hour; P = 0.003), and U pro V (161 ± 27 mg/hour vs. 128 ± 28 mg/hour; P = 0.02). Creatinine clearance had significantly negative relationships with night/day ratios of MAP ( r =-0.49; P = 0.01), U Na V ( r =-0.43; P = 0.03,) and U pro V ( r =-0.41; P = 0.04). In addition, night/day ratio of MAP had significantly positive relationships with night/day ratios of U Na V ( r = 0.49; P = 0.01) and U pro V ( r = 0.45; P = 0.02). Conclusion Our results show that as renal function deteriorates in glomerulopathy the nocturnal dip in blood pressure is lost, resulting in enhanced urinary sodium and protein excretions during night. These findings are compatible with our proposal that impaired natriuresis during daytime makes nocturnal blood pressure elevated to compensate for diminished natriuresis by pressure natriuresis. We speculate that nocturnal glomerular capillary hypertension contributes, at least in part, to enhanced urinary sodium and protein excretions during night.

Recently, Ruggajo et al.1 reported the Norwegian registration study regarding low birth weight (LBW) and end-stage renal disease (ESRD). They concluded that LBW, rather than familial factors, is a significant risk for future ESRD. We read the article1 with great interest because as they cited, we2 also reported a nationwide study showing strong associations between LBW and ESRD, and reaffirmed the significance of the article by Hosaka et al.,3 which was published in the journal, Hypertension Research.

The pathogenesis of antibody-mediated rejection has been investigated, but the precise mechanism of chronic glomerular rejection remains unclear. We have followed the clinicopathological course of a patient with pre-existing anti-donor antibody only detected by flow-cytometry crossmatch for over 3 years. Glomerular endothelial injuries and peculiar glomerular lesions were noted in biopsy specimen of postoperative year 3; however, both typical chronic vascular rejection lesions and peritubular capillary multilayered lesions were not revealed We consider that the presence of weak anti-donor antibody leading early onset of acute humoral rejection played a role in the pathogenesis of early onset of chronic transplant glomerulopathy.

日本におけるカワウの生息状況は,非常に劇的な変化を示した.1920年以前は北海道を除く全国各地で普通に見ることができた鳥であった.ところが,明治以降から戦前までの間は,無秩序な狩猟などによって急減したとみられる.戦後は水辺汚染や開発などによって減少したと考えられ, 1971年には全国3か所のコロニーに3,000羽以下が残るのみとなった.しかしながら,その後カワウは残存したコロニーで増加し始め,それらの近隣広がった.1980年代からは愛知,岐阜,三重の各県で始まった有害鳥獣駆除の捕獲圧による移動や分散で,各地に分布を拡大していったと考えら れる.増加の主な理由は,水辺の水質浄化が進み生息環境が改善したこと,人間によるカワウへの圧迫が減少して営巣地で追い払われることが少なくなったこと,そして姿を消した場所で食料資源である魚類が回復したことなどが考えられる.2000年末現在では,50,000～60,000羽が全国各地に生息するものと推定される.

Concentrations of organochlorines such as PCBs, DDTs, chlordanes (CHLs), HCHs and HCB were determined in the liver of common cormorants from two different colonies to understand the current status of contamination and geographical differences. The birds from Shinobazu pond, central Tokyo, exhibited significantly higher OC levels than those in the Lake Biwa. Residue level of PCBs was the highest followed by the DDTs regardless of the locations and growth stages. CHLs and HCB were also higher in the Shinobazu pond adults and juveniles, whereas HCHs were comparable with the Lake Biwa. The OC levels, excluding PCBs, were relatively higher in regurgitated fish in Lake Biwa than Tokyo Bay fish. The inverse relation of bioaccumulation between fish and birds emphasized that cormorants from both colonies, at least, would have seasonal and preferential feeding habits in a widely extended area. The calculated biomagnification values showed that DDTs and CHLs had lowest and highest metabolic capacities, respectively. This study also made evident that present OC contamination levels in common cormorants may not pose a serious threat to their reproduction. However, contaminant related risk in cormorants, if any, could be higher in Shinobazu pond than that in Lake Biwa.

Hypopotassemia with acid–base imbalance caused by laxative abuse is one of the disorders that nephrologists can be consulted for. Although laxatives are not supposed to form psychological dependence in themselves and their abuse should be cured theoretically by just finishing the overdose, the patients often resist treatment due to unpleasant symptoms such as edema and worsening constipation. Thus, chronic laxative abuse is often regarded as a drug addiction. We report a successfully treated case of chronic laxative abuse, where drastic reduction of laxatives was achieved by applying diuretics. After drastic reduction of laxatives, diuretics were added until they eased edema and bloating so that the patient could feel them to be tolerable, paying attention to lab data such as potassium and renal function. The diuretics, which substituted for laxatives in fluid control, could be tapered off over 3 months without any withdrawal symptoms or a need of additional laxatives. Our experience of simple but successful treatment of chronic laxative abuse emphasizes importance of physical management and suggests that there are cases where the two different kinds of drugs, laxatives and diuretics, can practically be regarded as swappable in the treatment of laxative abuse. This presentation should contribute to accumulation of knowledge in how to treat chronic laxative abuse where no standardized method is established yet.

Background Although genome-wide association studies (GWASs) have implicated several genes in the predisposition to chronic kidney disease (CKD) in Caucasian or African American populations, the genes that confer susceptibility to CKD in Asian populations remain to be identified definitively. We performed a GWAS to identify genetic variants that confer susceptibility to CKD in Japanese individuals. Methods 3851 Japanese individuals from three independent subject panels were examined. Subject panels A, B, and C comprised 252, 910, and 190 individuals with CKD and 249, 838, and 1412 controls, respectively. A GWAS for CKD was performed in subject panel A. Results Five single nucleotide polymorphisms (SNPs) at chromosome 3q28, ALPK1 , FAM78B , and UMODL1 were significantly (false discovery rate

Objective The sympathetic nervous system plays an important role in blood pressure regulation even in the early stages of chronic kidney disease (CKD). Methods To understand the role of the sympathetic system, we examined the relationship between day/night ratios of both heart rate (HR) and mean arterial pressure (MAP) as well as HR variability (HRV, SD) before and during an 8-week treatment with the angiotensin II receptor blocker (ARB), olmesartan, in 45 patients with CKD. Results The day/night HR ratio strongly correlated with the day/night MAP ratio before and during ARB treatment. The ratio of [day/night HR ratio] over [day/night MAP ratio] was increased as renal function deteriorated at baseline (r = -0.31, P = 0.04), and it was attenuated (1.10 ± 0.10 to 1.06 ± 0.10; P = 0.04) and became independent of renal function during ARB treatment (r = -0.04, P = 0.8). ARB increased both the day/night HR ratio (1.17 ± 0.09 to 1.21 ± 0.13; P = 0.04) and HRV (10.6 ± 2.9 to 11.7 ± 4.2; P = 0.04), which were lower when baseline renal function deteriorated. Conclusion The present study indicates that there exists a close correlation in circadian rhythms between HR and MAP in CKD. Synchronization between the two rhythms was progressively lost as renal function deteriorated, and ARB partly restored the synchronization. These findings suggest that the sympathetic nervous system is activated as renal function deteriorates, and ARB may suppress its activation.

Objective: Angiotensin receptor blockers (ARBs) produce a lower sodium (Na) balance, and the natriuretic effect is enhanced under Na deprivation, despite falls in blood pressure (BP) and glomerular filtration rate (GFR). Methods: The effect of additional hydrochlorothiazide (HCTZ; 12.5 mg/day) to ARB treatment (valsartan; 80 mg/day) on glomerulotubular Na balance was evaluated in 23 patients with chronic kidney disease. Results: Add-on HCTZ decreased GFR, tubular Na load, and tubular Na reabsorption (tNa), although 24-hour urinary Na excretion (UNaV) remained constant. Daily urinary angiotensinogen excretion (UAGTV, 152±10→82±17 μg/g Cre) reduced ( p=0.02). Changes in tubular Na load ( r2=0.26) and tNa ( r2=0.25) correlated with baseline 24-hour UAGTV. Changes in filtered Na load correlated with changes in nighttime systolic BP ( r2=0.17), but not with changes in daytime systolic BP. The change in the tNa to filtered Na load ratio was influenced by the change in daytime UNaV (β=−0.67, F=16.8), rather than the change in nighttime UNaV. Conclusions: Lower Na balance was produced by add-on HCTZ to ARB treatment without an increase of intra-renal renin-angiotensin system activity, leading to restoration of nocturnal hypertension. A further study is needed to demonstrate that the reduction of UAGTV by additional diuretics to ARBs prevents the progression of nephropathy or cardiovascular events.

各種の遊離皮弁による舌, 口底再建19症例を対象として術後会話機能, 咀嚼機能, 嚥下機能を切除範囲別に評価し, 遊離皮弁再建術が術後機能に及ぼす影響を検討した。会話機能は切除範囲や遊離皮弁による影響が少なく, 咀嚼機能は切除範囲や皮弁よりも下顎再建に影響を受けた。嚥下機能は舌亜全摘型および中咽頭合併切除型で低下し, videofluorographyにより咽頭通過時間の延長および誤嚥を認めた。また咽頭通過時間の分析より前腕皮弁は前外側大腿皮弁や腹直筋皮弁よりも残存舌運動への影響が大きいことが示唆された。皮弁の選択は残存舌運動の保持と大きな欠損の充填効果が期待できる前外側大腿皮弁や腹直筋皮弁が適応する。