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Purpose. Nephrotic syndrome and hypothyroidism are respectively reported to influence renal hemodynamic and hypercholesterolemia. However, the relationship of proteinuria-associated thyroid function with renal hemodynamics and cholesterol metabolism has yet to be determined in a simultaneous analysis of thyroid, renal and cholesterol variables. We investigated the hypothesis that the changes in thyroid hormones by proteinuria may contribute to changes in lipid metabolism and renal hemodynamics by proteinuria. Methods. Twenty-nine patients (17 men) with proteinuric kidney disease (mean age 46 years) were enrolled in a pilot study. Data for serum free triiodothyronine (FT3), free thyroxine (FT4), total cholesterol, and filtration fraction (FF; assessed by para-aminohippuric acid clearance) were used in variable-adjusted correlation analyses. Results. The patients had the following data (mean ± standard deviation): urinary protein 5.18 ± 3.28 g/day, FT3 2.18 ± 0.44 pg/mL, FT4 1.03 ± 0.26 ng/dL, FF 0.27 ± 0.07, and total cholesterol 327 ± 127 mg/dL. There was a significant positive correlation of FT3 with FF (β = 0.58, P = 0.01) and a significant inverse correlation of FT4 with total cholesterol (β = -0.40, P = 0.01). Conclusions. The proteinuria associated reduction in serum thyroid hormone levels may be involved in a part of hypercholesterolemia and the impaired glomerular function due to nephrotic syndrome. Further studies of these relationships are required.

Excessive intake of phosphate has been known to induce renal tubular damage and interstitial inflammation, leading to acute kidney injury or chronic kidney disease in rodents and humans. However, sensitive and early biomarkers for phosphate‐induced kidney damage remain to be identified. Our previous RNA sequencing analysis of renal gene expression identified interleukin‐36α (IL‐36α) as a gene significantly upregulated by dietary phosphate load in mice. To determine the time course and dose dependency of renal IL‐36α expression induced by dietary phosphate load, we placed mice with or without uninephrectomy on a diet containing either 0.35%, 1.0%, 1.5%, or 2.0% inorganic phosphate for 10 days, 4 weeks, or 8 weeks and evaluated renal expression of IL‐36α and other markers of tubular damage and inflammation by quantitative RT‐PCR, immunoblot analysis, and immunohistochemistry. We found that IL‐36α expression was induced in distal convoluted tubules and correlated with phosphate excretion per nephron. The increase in IL‐36α expression was simultaneous with but more robust in amplitude than the increase in tubular damage markers such as Osteopontin and neutrophil gelatinase‐associated lipocalin, preceding the increase in expression of other inflammatory cytokines, including transforming growth factor‐α, interleukin‐1β, and transforming growth factor‐β1. We conclude that IL‐36α serves as a marker that reflects the degree of phosphate load excreted per nephron and of associated kidney damage., An increase in dietary phosphate intake triggers renal tubular damage, followed by interstitial inflammation and fibrosis. Among several molecular markers indicative of these pathological changes, we identified induction of interleukin‐36α expression in distal tubules as an early and robust biomarker of phosphate‐induced tubular damage in mice.

IntroductionTakayasu arteritis (TA) is a chronic vasculitis associated with an increased cardiovascular risk. The measurement of pulse wave velocity (PWV), carotid artery intima-media thickness (CIMT) and flow-mediated dilatation (FMD) are generally used for evaluating the cardiovascular risk. The application of these measurements to TA patients remains undetermined.Material and methodsClinical studies that reported the PWV, CIMT and FMD levels in TA patients, which were published prior to 2021, were summarized using PubMed.ResultsFifteen studies were eligible. Overall, in TA patients, the PWV and CIMT levels were significantly higher and the FMD levels were significantly lower compared to controls. Part of the studies showed that the disease activity of TA was significantly associated with the PWV, CIMT or FMD levels.ConclusionsThe PWV, CIMT and FMD measurements could be useful for evaluating the cardiovascular risk in TA patients. Further studies to determine the proper use of these measurements are warranted.

The Western pattern diet is rich not only in fat and calories but also in phosphate. The negative effects of excessive fat and calorie intake on health are widely known, but the potential harms of excessive phosphate intake are poorly recognized. Here, we show the mechanism by which dietary phosphate damages the kidney. When phosphate intake was excessive relative to the number of functioning nephrons, circulating levels of FGF23, a hormone that increases the excretion of phosphate per nephron, were increased to maintain phosphate homeostasis. FGF23 suppressed phosphate reabsorption in renal tubules and thus raised the phosphate concentration in the tubule fluid. Once it exceeded a threshold, microscopic particles containing calcium phosphate crystals appeared in the tubule lumen, which damaged tubule cells through binding to the TLR4 expressed on them. Persistent tubule damage induced interstitial fibrosis, reduced the number of nephrons, and further boosted FGF23 to trigger a deterioration spiral leading to progressive nephron loss. In humans, the progression of chronic kidney disease (CKD) ensued when serum FGF23 levels exceeded 53 pg/mL. The present study identified calcium phosphate particles in the renal tubular fluid as an effective therapeutic target to decelerate nephron loss during the course of aging and CKD progression.

We examined whether fingolimod (FTY720), an S1PR (sphingosine-1-phosphate receptor) modulator, has beneficial or harmful effects on mineralocorticoid/salt-induced renal injury. Uninephrectomized rats on 0.9% NaCl/0.3% KCl drinking solution were randomly divided into control, control+FTY720, deoxycorticosterone acetate (DOCA), and DOCA+FTY720 groups and administered vehicle, vehicle+FTY720, DOCA+vehicle, and DOCA+FTY720 for 4 weeks, respectively. Only the DOCA+FTY720 group had reduced survival rates and showed hemolysis because of intravascular mechanical fragmentation of erythrocytes and thrombocytopenia. Both the DOCA+FTY720 and DOCA groups developed malignant hypertension, which was more severe in the DOCA+FTY720 group. In the DOCA+FTY720 group only, thrombotic microangiopathy involving severe renal arteriole endothelial cell injury was observed and was characterized by fibrinoid necrosis and onion-skin lesions in arterioles. There were fewer circulating endothelial progenitor cells in the DOCA+FTY720 group but more in the DOCA group compared with the control group. Expression levels of VEGF (vascular endothelial growth factor), S1PR1, and S1PR3 in renal arteriole endothelial cells were significantly greater in the DOCA+FTY720 and DOCA groups compared with the control group, with levels being similar between the 2 groups. Expression levels of endothelial nitric oxide synthase in renal arteriole endothelial cells were significantly lower in the DOCA+FTY720 group only. The control+FTY720 group showed reduced circulating endothelial progenitor cells but no significant functional or pathological changes in kidneys or changes in blood pressure. Exposure of uninephrectomized rats to DOCA/salt+FTY720 for 4 weeks induced renal arteriolar endothelial cell injury, resulting in the development of thrombotic microangiopathy. Consideration of this possibility is recommended when prescribing FTY720.

In patients with sarcoidosis, dysregulated calcium metabolism is one of the frequently observed complications. However, little attention has been paid to abnormal phosphate metabolism. Herein we present the case of a 42-year-old Japanese man with renal sarcoidosis who developed acute kidney injury due to hypercalcemia and nephrolithiasis. Laboratory data showed hypercalcemia with a normal serum phosphate level and high serum 1,25-hydroxyvitamin D3, fibroblast growth factor 23 (FGF23) and calciprotein particle (CPP) levels. After treatment with oral prednisone and bisphosphonate, the laboratory abnormalities and renal dysfunction were resolved. Thus increases in FGF23 and CPP may indicate disturbed phosphate metabolism in renal sarcoidosis.

The pathophysiology of sarcopenia is complex and must be further explored. While metabolic acidosis may be a risk factor for sarcopenia, it remains unclear whether acidic urine is related to sarcopenia. The purpose of the present study was to investigate the association between sarcopenia and urine pH in the elderly.An elderly population (n = 123 [male = 46]; mean age = 81.7 years) was classified into 2 groups based on the sarcopenia status according to their strength, requirement of assistance in walking, their ability to rise from a chair their ability to climb stairs, and their history of falls. Urinalysis was measured using dipstick tests.The sarcopenia group (n = 32) was significantly older, had less exercise habit and showed a lower urine pH (mean pH = 5.5) in comparison to the nonsarcopenia group (mean pH = 6.2, P

The ratio of oxidized lipoprotein(a) to native lipoprotein(a) (oxLp(a)/Lp(a)) may be a reasonable index for assessing endothelial dysfunction in type 2 diabetes mellitus (T2DM). The present study investigated whether the oxLp(a)/Lp(a) level is correlated with the endothelial function using the Endo-PATTM, a newly developed device, in patients with T2DM. A total of 63 patients with T2DM (mean age: 59 years old) were enrolled in the study. The patients&rsquo, serum Lp(a) and oxLp(a) levels were measured using an enzyme-linked immunosorbent assay. The reactive hyperemia index (RHI) level was measured using an Endo-PATTM 2000. A correlation analysis between the measured variables was conducted. Among the patients, the mean hemoglobin A1c was 7.8%. The median level of oxLp(a)/Lp(a) was 0.28 (interquartile range: 0.07&ndash, 0.54), and the mean RHI was 1.8 (standard deviation: 0.4). In a multiple linear regression analysis, the oxLp(a)/Lp(a) level was an independent, significant, and inverse variable for the RHI level (&beta, = &minus, 0.26, p &lt, 0.05), along with male gender. A high oxLp(a)/Lp(a) level may reflect endothelial dysfunction, as assessed by the Endo-PATTM, in patients with T2DM. Further studies are warranted to confirm the observed findings.

A case of acute kidney injury (AKI) strongly suspected to be drug-induced (oxaliplatin and non-steroidal anti-inflammatory drug) is discussed regarding the mechanism of a reduced glomerular filtration rate responsible for the development of AKI. Urinary biochemical tests are useful for the differential diagnosis of pre- renal (functional) AKI and intrinsic (structural) AKI(so-called acute tubular necrosis). In this case, although a comprehensive differential diagnosis using these parameters supported intrinsic AKI, only one pa- rameter, fractional excretion of urea (FEurea), indicated the existence of prerenal AKI. As a result of treatment with the appropriate management of body fluid in addition to avoiding nephrotoxic medications, AKI rapidly improved. FEurea revealed the underlying mechanism of AKI. [Review].

The avoidance of any form of anticoagulation is advised in cases of cholesterol embolization syndrome (CES). We herein describe a case of CES in a man with a history of unprovoked pulmonary embolism for which warfarinization was performed. Despite anecdotal reports of successful anticoagulation in CES patients with certain indications, irreversible renal failure, which was sufficiently severe to require chronic hemodialysis, eventually developed in our patient. Our results emphasize the pitfalls of this procedure, which imply its limited feasibility and safety. Several therapeutic concerns associated with this case are also discussed.

Bleeding from the gastrointestinal tract is one of the common determinants of morbidity and mortality in the ordinary clinical setting. The gastrointestinal involvement of Henoch-Schönlein purpura (HSP) has often been described as self-limiting, with no long-term morbidity. In this report, we describe our experience with a male HSP patient who presented with abdominal pain, loss of appetite and deteriorated renal function associated with nephrotic syndrome. Despite the use of aggressive immunomodulatory treatments, including corticosteroids and plasmapheresis, he developed lethal gastrointestinal hemorrhage. We believe that the accumulation of more experience with additional cases similar to ours is mandatory for the establishment of optimal management for HSP patients with severe gastrointestinal manifestations.

Mixed cryoglobulinemia is occasionally seen in patients with hepatitis B virus (HBV) infection. This report presents the case of a quiescent HBV carrier who had type II mixed cryoglobulinemia, protracted purpura, ulcerative skin lesions and advanced chronic kidney disease. The cutaneous manifestations of the patient improved along with a decrease in the serum cryoglobulin and HBV-deoxyribonucleic acid levels following the initiation of oral entecavir in combination with plasmapheresis. However, the patient ultimately required prednisolone due to the limited benefits of these treatments. We also discuss various concerns regarding steroid treatment in patients with mixed cryoglobulinemia complicated by HBV infection.

A 50-year-old female patient who presented with intermittent gross hematuria was referred to our hospital. Three-dimensional computed tomography (3D-CT) revealed a left renal arteriovenous malformation (AVM). Because she declined to undergo additional therapy including surgical treatment, we observed the clinical course of renal AVM for 7 years using 3DCT. When the 3D-CT showed gradual enlargement of the aneurysms concurrent with the onset of clinical symptoms (cardiomegaly and hypertension), we performed simple left nephrectomy. After the operation, the cardiomegaly and hypertension returned to normal, and gross hematuria did not recur. Based on the macro-anatomical findings of the resected kidney and the observation of the natural course, this case strongly supported the hypothesis that the renal AVM had existed from birth and enlarged gradually to eventually produce the typical signs and symptoms.

Kawasaki disease (KD) is an acute childhood febrile disease of unknown etiology. It exhibits not only coronary artery aneurysms in some cases but also systemic vasculitis. Whether KD is associated with accelerated atherosclerosis remains debatable. The measurement of pulse wave velocity (PWV) is useful as a simple, noninvasive measurement of arterial stiffness, an atherosclerotic manifestation. We herein present a systematic review of clinical studies that focused on PWV in patients with KD. A PubMed-based search identified 8 eligible studies published until June 2015. The PWV of patients with KD, regardless of antecedent coronary artery lesions, was high relative to controls, even though their blood pressure appeared to be similar. Although definitive conclusions cannot be made with the limited information, patients with KD may be at risk of systemic atherosclerosis in association with arterial stiffness. Further research, including longitudinal and outcome studies, is needed to determine the clinical significance of a potential increase in PWV in patients with KD.

Obstructive sleep apnea (OSA) is common in patients with renal disease, and an association between OSA and proteinuria has been proposed. However, the effect on proteinuria of OSA treatment with continuous positive airway pressure (CPAP) is unknown. We experienced a case of severe OSA, where proteinuria was clearly improved after CPAP initiation without any changes of medication or body weight. The remarkable reduction of repetitive apnea and hypopnea by CPAP might ameliorate proteinuria by lessening renal hypoxia and sympathetic nerve activation. This case suggests that CPAP is a promising option for OSA with proteinuria.

Klotho has been investigated as an anti-aging protein that is predominantly expressed in the distal convoluted tubules in the kidneys and in the choroid plexus of the brain. The purpose of the present study was to determine the relationship between the soluble form of Klotho and renal function in chronic peritoneal dialysis (PD) patients, a relationship which remains poorly understood. The soluble Klotho levels in the serum, urine, and peritoneal dialysate obtained from thirty-six PD patients were determined by a sandwich enzyme-linked immunosorbent assay system. The amount of urinary excreted soluble Klotho over 24 h ranged from 1.54 to 1774.4 ng/day (median 303.2 ng/day; interquartile range [IR] 84.1–498.5), while the serum soluble Klotho concentration ranged from 194.4 to 990.4 pg/ml (mean 553.7 ± 210.4 pg/ml). The amount of urinary Klotho excretion was significantly correlated with residual renal function. However, there was no apparent correlation between the serum soluble Klotho levels and the residual renal function. Klotho was also detected in the 24-h dialysate collections. There was a significant correlation between the peritoneal Klotho excretion and the amount of albumin contained in the dialysate collections (r = 0.798, p

Background Sleep-disordered breathing (SDB), characterized by repetitive apnea and hypopnea during sleep, is a risk factor for cardiovascular disease. However, the links between SDB and cardiovascular events in hemodialysis (HD) patients have not been clearly evaluated. Methods We followed the clinical outcome of 94 HD patients, who underwent overnight pulse oximetry on dialysis day. The SDB group was defined as 3% oxygen desaturation index (ODI) over five events per hour, and the others were the normal group. The primary outcome was cardiovascular events and death. We used Kaplan-Meier curve and Cox proportional hazard model for survival analyses. Results Forty-four patients (46.8%) were classified into the SDB group. Body mass index, diabetes mellitus, 3% ODI and Epworth sleepiness scale were significantly higher, and duration of dialysis, Kt/V, normalized protein catabolism rate and hemoglobin were lower in the SDB group than in the normal group. During a median 55 months of follow-up, Kaplan-Meier analysis revealed that the SDB group had a significantly higher rate of cardiovascular events and all-cause mortality than the normal group. Age, cardiothoracic ratio, serum albumin and 3% ODI were predictors of cardiovascular events and all-cause mortality at univariate Cox regression analysis. In the adjusted analysis, SDB is an independent predictor of increased cardiovascular events (hazard ratio 3.10; 95% confidence interval (CI), 1.35-7.12; P = 0.008) and all-cause mortality (hazard ratio 2.81; 95% CI, 1.07-7.41; P = 0.037). Conclusions SDB is an independent risk factor for cardiovascular events and mortality in HD patients. Effective and earlier treatment for these patients is needed to improve clinical outcome.

We herein describe an adult male patient who presented with tonsillitis, purpura, hematuria, and proteinuria. The serological analyses revealed elevated serum antistreptolysin, and the throat culture yielded Lancefield group A β-hemolytic streptococci. A renal biopsy revealed mild mesangial proliferation associated with granular mesangial depositions of IgA and C3, consistent with Henoch-Schönlein purpura nephritis (HSPN). Initially, the patient was treated with dipyridamole, which was followed by limited improvements in the proteinuria and hematuria. Nine months later, the tonsillitis relapsed due to GAS infection and deteriorated urinary abnormalities were noticed, which finally disappeared after monotherapeutic tonsillectomy. Although the impact of tonsillectomy on the treatment of HSPN remains to be characterized, our observations suggest that tonsillectomy in the present patient played a pivotal role in facilitating the recovery of the renal injuries. Because the arbitrary application of a tonsillectomy appears to be accompanied by ethical concerns, the evaluation of the clinical benefits of this procedure should be addressed more directly in the future.

We examined whether and how peritubular capillary (PTC) loss in the renal cortex contributes to the development of deoxycorticosterone acetate (DOCA)/salt-induced tubulointerstitial fibrosis. Uninephrectomized rats provided with 0.9% NaCl/0.3% KCl drinking solution ad libitum were divided into control, DOCA, and spironolactone groups, which were administered vehicle, DOCA alone, and DOCA plus spironolactone for 1 (initial phase) and 4 weeks (delayed phase), respectively. Exposure to DOCA initiated a sequence of events that initially involved reduced PTC density, followed by a delayed response that involved further reduced PTC density, development of tubulointerstitial fibrosis and hypertension, enhanced expression of transforming growth factor-β1 and connective tissue growth factor, and impaired renal function. Concomitant with the reduced PTC density, the 2 hypoxia-responsive angiogenic factors (vascular endothelial growth factor and hypoxia-inducible factor-1α) and the antiangiogenic factor (thrombospondin-1) were upregulated in cortical tubular cells of the DOCA group during the 2 phases and only in the delayed phase, respectively. In the DOCA group, PTC endothelial cell apoptosis was enhanced during the 2 phases, and PTC endothelial cell proliferation was inhibited in the delayed phase. In accordance with upregulation of thrombospondin-1, p53 expression was enhanced in the DOCA group in the delayed phase. The initial and delayed effects of DOCA were blocked in the spironolactone group. We conclude that exposure to DOCA initially caused the reduced PTC density associated with enhanced apoptosis independent of thrombospondin-1, which induced tubulointerstitial fibrosis via p53-mediated thrombospondin-1 activation, and spironolactone conversely corrected the effects of DOCA to prevent fibrosis.

A 63-year-old man was admitted to our hospital for evaluation of generalized edema. Coexistence of severe hypothyroidism and nephrotic syndrome was detected by laboratory examination. High titer of both antimicrosomal antibody and antithyroid peroxidase antibody indicated Hashimotoâs disease. Renal biopsy showed minimal change glomerular abnormality, but no findings of membranous nephropathy. A series of medical treatments, including steroid therapy, thyroid hormone and human albumin replacement therapy, were administered. However, acute renal failure accompanied by hypotension, was not sufficiently prevented. After 9 sessions of plasmapheresis therapy, the severe proteinuria and low serum albumin levels were improved. Even after resting hypotension was normalized, neither renal function nor thyroid function were fully recovered. After discharge, renal function gradually returned to normal, and the blood pressure developed into a hypertensive state concomitant with the normalization of thyroid function. This report is a rare case of autoimmune thyroid disease complicated with minimal change nephrotic syndrome. In most cases of nephritic syndrome, acute renal failure (ARF) has been reported to coexist with hypertension. Although pseudohypothyroidism is well-known in nephrotic pathophysiology, complications of actual hypothyroidism are uncommon. It is suggested that the development of hypotension and ARF could be enhanced not only by hypoproteinemia, but also by severe hypothyroidism.

A 66-year-old woman was admitted to our hospital because of vomiting and appetite loss. For the 2 days prior to admission, she had a cold, which had developed into acute viral bronchitis on admission. Because laboratory data on admission showed hyponatremia, intravenous infusion of Ringer's lactate solution was started. However, generalized seizures appeared, and she developed a coma on the day of admission. Her plasma antidiuretic hormone (ADH) level was high in the context of a low serum osmolality on the second hospital day. The infusion rate was increased, and the patient's consciousness level returned to normal. However, her normalized serum Na level declined again as she drank much water to reduce throat discomfort. As the throat discomfort caused by the throat inflammation improved with azulene gargling, her water intake was reduced, and the serum Na concentration returned to normal. Thus, polydipsia caused by a throat inflammation partially contributed to hyponatremia in this patient. We note that increased ADH secretion has been reported in adults with acute respiratory infection. Therefore, we concluded that polydipsia caused by the throat inflammation, plus increased ADH secretion, resulted in hyponatremia in this patient. We should pay attention to the behavior of drinking extra fluid in patients with acute respiratory infections.

Sir, Sleep apnoea syndrome (SAS) is characterized by repetitive nocturnal hypoxia, while it is also known to be a risk factor for cardiovascular disease [1]. The prevalence of SAS in dialysis patients has been shown to range from 20 to 50% in comparison to a range of 2–4% in the general population [2,3]. Although the main type of SAS in the general population is obstructive type, SAS in dialysis patients includes features of both central and obstructive types [3]. Moreover, uraemia and metabolic acidosis are good predictors of SAS in dialysis patients [3]. The gold standard diagnostic test for SAS is overnight polysomnography (PSG). However, PSG is costly in terms of both time and money. Pulse oximetry and Epworth Sleepiness Scale (ESS), a questionnaire about daytime sleepiness have been widely used to screen for obstructive SAS because these are simple and easy methods to perform [4,5]. However, no screening method for SAS in dialysis patients has yet been clearly evaluated. The purpose of this study is to evaluate the usefulness of pulse oximetry and ESS for screening SAS in dialysis patients. We studied 54 maintenance haemodialysis (HD) patients [male: 50%, age: 66.0 ± 24.2 years, diabetes mellitus: 39.9%, duration of HD: 5.7 ± 5.1 years and BMI: 22.7 ± 9.1] in Koga Red Cross Hospital during the period from April 2004 to March 2005. Patients with active malignancy and pulmonary disease were excluded. The validity of the pulse oximetry was confirmed by the synchronous recording of both PSG (Morpheus, Teijin Pharma Ltd, Japan) and pulse oximetry (PULSOX-Me300, Teijin Pharma Ltd, Japan) on dialysis day. We used the 3% oxygen desaturation index (ODI) and 4% ODI by pulse oximetry as a screening marker. In addition to pulse oximetry, ESS was used to investigate daytime sleepiness. We compared the apnoea–hypopnoea index (AHI) by PSG to 3% ODI, 4% ODI and ESS scores, respectively. Using a cutoff of AHI≥15 and 3% ODI (4% ODI) ≥15, the sensitivity and specificity were 100% (76.0%) and 55.2% (93.1%) respectively (Table ​(Table1).1). On the other hand, the sensitivity and specificity using a cutoff of AHI≥15 and ESS scores≥11 were 20.0% and 82.8% respectively (Table ​(Table11). Table 1 Sensitivity and specificity of pulse oximetry/ESS scores screening for SAS in dialysis patients (n = 54) Both 3% ODI and 4% ODI were significantly correlated with AHI (3% ODI: r = 0.657, P < 0.0001; 4% ODI: r = 0.618, P < 0.0001) (Figure ​(Figure1).1). However, no significant correlation was seen between ESS scores and AHI (r = 0.149, P = 0.283) (Figure ​(Figure11). Fig. 1 Correlation between AHI and 3% ODI (A)/ESS scores (B) in dialysis patients (n = 54). In dialysis patients, pulse oximetry is superior to ESS for detecting SAS. The less efficacy of ESS may be due to the unique characteristics of SAS in dialysis patients [2,3]. We therefore suggest that pulse oximetry is useful for screening SAS in dialysis patients. Conflict of interest statement. None declared.

Despite the crucial role of calcium in myocardial contractility, hypocalcemia has very rarely been reported as a reversible cause of heart failure. In this article, we describe a case of a 51-year-old woman with advanced stages of chronic renal failure after parathyroidectomy who exhibited congestive heart failure, severe hypocalcemia, hypomagnesemia and hypokalemia. Severe hypocalcemia resulted from discontinuation of taking calcium supplements after parathyroidectomy and from reduced 1.25(OH)2D3 synthesis by damaged kidneys. The patient presented with reduced left ventricular ejection fraction (EF) and ECG abnormalities (T wave alternans and increased QTc dispersion), both of which improved after correction of serum calcium levels. Her serum levels of total calcium corrected for serum albumin, but not serum levels of magnesium or potassium, positively and negatively correlated with EF and QTc dispersion, respectively. In the present case, both heart failure and the ECG abnormalities are directly associated with hypocalcemia.

睡眠呼吸障害 (sleep disordered breathing; SDB) は, 高血圧や虚血性心疾患, 脳血管障害など生命予後を左右する臓器疾患との関連があり, 腎不全患者では非常に高頻度であるといわれている. しかし, 国内では透析患者のSDBの検討は十分に行われていない. 今回われわれは, 維持透析患者におけるSDBの疫学および関連因子について検討した. 対象は, 維持透析中の101名 (男性51名, 女性50名), 透析法はHD 96名, HDF 3名, CAPD 2名, 原疾患は糖尿病41名 (40.6%), 非糖尿病60名, 平均BMIは22.4±5.2であった. 全対象患者に, 自宅での終夜パルスオキシメータを透析施行日から2日間連続で実施し, 合わせて睡眠アンケートも行った. この検査でSDBと診断した42名に簡易ポリソムノグラフィ (PSG) を追加施行した. パルスオキシメータの結果から, 原疾患別のSDB頻度, 測定日による違い, 肥満度・日中の自覚症状との相関について調べた. さらに, 貧血や心胸比などとの関連性も検討し, PSGによる型分類も行った. SDBの頻度は51.5%と高頻度で, 糖尿病では71%と極めて高い割合を示した. 測定日による差はなく, 肥満者の頻度は有意に高かったが, 中等症以上のSDBの頻度に有意な差はなかった. PSGの結果から71.1%で中枢型の無呼吸イベントが含まれていた. 関連因子についての検討では, 重症のSDBほど心胸比が大きく, 貧血が強い傾向にあったが, 透析間体重増加率, 尿素窒素, 血清Cr値, 血清Alb値, intact PTHとの関連はみられなかった.透析患者でのSDB有病率の高さと中枢型無呼吸イベントの多さが示され, 心胸比・貧血との関連もみられた. このことから, 透析患者でのSDBが一般人とは異なる機序により発症している可能性が示唆された.

塩酸イリノテカン (CPT-11) は, I型DNAトポイソメラーゼ阻害によりDNA合成を阻害し, 広い抗腫瘍スペクトラムを持つ. 血液透析療法中の患者ではCPT-11を減量し使用した報告は一例あるものの, その薬物動態, 透析性についての報告はない. われわれは, 維持血液透析中の大腸癌肝転移例にCPT-11を単回投与し, その薬物動態, 透析性について検討した.症例は58歳, 男性. インフォームドコンセントを得た後, CPT-11 50mg/m2を透析2時間前より90分かけて点滴静注し, 透析開始直後および0.5, 1, 2, 4, 8, 12, 24時間後にCPT-11およびその代謝物質 (SN-38およびSN-38G) の血漿中濃度を測定した. また, 透析開始0.5時間後のダイアライザー前後および透析液中の濃度も測定した.その結果, CPT-11およびSN-38Gは血液透析により除去された. 活性代謝物質であるSN-38は血液透析により直接的には除去されなかったが, CPT-11やSN-38Gが減少するため透析施行中に濃度低下を認めた.CPT-11は胆汁排泄が約80%, 腎排泄が約20%であり, 腎不全患者では投与量を調節する必要がある. 血液透析患者にCPT-11 60mg/m2 (週1回) は, 副作用をきたさず投与可能であった.

Rapidly progressive glomerulonephritis (RPGN) is characterized by the rapid deterioration of the renal function associated with crescent formation on renal biopsies. This report describes a case of RPGN caused by anti-glomerular basement membrane (GBM) glomerulonephritis in an elderly man with severe thrombocytopenia and a platelet count of 1.4 × 10(4)/µL. Thrombotic microangiopathy (TMA) and heparin-induced thrombocytopenia (HIT) were implicated in the severe decrease in platelets. This report also discusses the pathological background and clinical management of TMA and HIT among patients with anti-GBM glomerulonephritis.

We herein present a case of serial opportunistic infections that included disseminated nocardiosis and cryptococcal meningitis in a 67-year-old man who was diagnosed with ANCA-associated vasculitis and treated with corticosteroids. Upon admission, the initial manifestations of the disease included subcutaneous tumors and multiple lesions in the brain and lungs. Nocardia farcinica was identified in a culture of the aspirated pus. The patient was successfully treated for disseminated nocardiosis with antibiotics. However, three months after discharge, he was hospitalized with complaints of nuchal pain. Cryptococcus neoformans was identified on a culture of the cerebrospinal fluid. Anti-fungal treatment resulted in the remission of cryptococcal meningitis.

A large number of renal biopsy studies have shown the concurrent presence of non-diabetic renal disease in diabetics. This report describes one such diabetic female patient with nephrotic syndrome due to minimal change glomerular disease who was successfully treated with prednisolone. Despite the remission of her nephrotic syndrome, she had gradual development of malignant ascites, which was finally interpreted to be linked to primary peritoneal carcinoma. It is necessary to bear in mind that malignancies may not only be the underlying etiology for paraneoplastic glomerular injuries, but also can be an independent pathogenic process, regardless of their nephrotic status during the overall management of the patients with ascites.

Background Klotho, a single-pass transmembrane protein primarily expressed in the kidneys, parathyroid glands, and choroid plexus of the brain, has a short cytoplasmic tail and a long extracellular domain, which can be cleaved and released as a soluble form. However, information regarding the origins and kinetics of soluble serum Klotho remains poorly understood. We evaluated serial changes in serum Klotho levels among living donors before and after retroperitoneoscopic nephrectomy as well as in their renal transplant recipients. Methods The levels of soluble Klotho in serum obtained from 10 living donors and their renal transplant recipients were determined using a sandwich enzyme-linked immunosorbent assay system. Results Serum soluble Klotho was detectable in all subjects. The baseline serum Klotho concentrations in the living donors ranged from 726.4 to 1417.1 pg/mL (median, 909.8 pg/mL; interquartile ranges [IR], 754.8–1132.4), whereas that in the concomitant renal transplant recipients ranged from 397.5 to 1047.2 pg/mL (median, 613.0 pg/mL; IR, 445.9–750.8; P = .003). The levels of soluble serum Klotho measured 5 days after retroperitoneoscopic nephrectomy (median, 619.0 pg/mL; IR, 544.6–688.5; P = .001) were significantly lower than the baseline values. Among the renal transplant recipients, no significant changes in serum Klotho levels were observed during the observation period. Conclusion Our data regarding soluble serum Klotho levels obtained from living donors support the idea that the kidneys are a major source of soluble serum Klotho in human subjects without a deterioration of renal function. In recipients, concomitant acute kidney injuries and immunosuppressive protocols might modulate the release of soluble Klotho from the grafts into the circulation.

Glomerular crescents are most commonly associated with rapidly progressive crescentic glomerulonephritis; however, they also develop in response to a wide range of primary and secondary glomerular injuries. Since various kind of glomerulopathies occasionally overlay diabetic glomerular injuries, the presence of crescents in renal biopsy specimens of diabetics may have stimulated a search for etiologies other than diabetes. In this report, we describe an unusual case of diabetic glomerulosclerosis with peculiar extracapillary proliferation. Although such a relationship has so far been ignored in most of the literature, the etiological linkage between diabetic glomerulosclerosis and the development of crescents may not be exceptional. We have reviewed the previous literature and herein discuss the pathological implications of the development of crescents in patients with diabetic glomerulosclerosis. Virtual slides The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/3950457896920255.

To examine whether and how heart ANG II influences the coordination between cardiomyocyte hypertrophy and coronary angiogenesis and contributes to the pathogenesis of diabetic cardiomyopathy, we used Spontaneously Diabetic Torii (SDT) rats treated without and with olmesartan medoxomil (an ANG II receptor blocker). In SDT rats, left ventricular (LV) ANG II, but not circulating ANG II, increased at 8 and 16 wk after diabetes onset. SDT rats developed LV hypertrophy and diastolic dysfunction at 8 wk, followed by LV systolic dysfunction at 16 wk, without hypertension. The SDT rat LV exhibited cardiomyocyte hypertrophy and increased hypoxia-inducible factor-1α expression at 8 wk and to a greater degree at 16 wk and interstitial fibrosis at 16 wk only. In SDT rats, coronary angiogenesis increased with enhanced capillary proliferation and upregulation of the angiogenic factor VEGF at 8 wk but decreased VEGF with enhanced capillary apoptosis and suppressed capillary proliferation despite the upregulation of VEGF at 16 wk. In SDT rats, the phosphorylation of VEGF receptor-2 increased at 8 wk alone, whereas the expression of the antiangiogenic factor thrombospondin-1 increased at 16 wk alone. All these events, except for hyperglycemia or blood pressure, were reversed by olmesartan medoxomil. These results suggest that LV ANG II in SDT rats at 8 and 16 wk induces cardiomyocyte hypertrophy without affecting hyperglycemia or blood pressure, which promotes and suppresses coronary angiogenesis, respectively, via VEGF and thrombospondin-1 produced from hypertrophied cardiomyocytes under chronic hypoxia. Thrombospondin-1 may play an important role in the progression of diabetic cardiomyopathy in this model.

The patient was a 53-year-old woman who had bilateral renal arterial constriction due to Takayasu's arteritis, and developed end-stage renal failure. When transient loss of consciousness occurred in 2002, she was diagnosed with subclavian steal syndrome (SSS). The renal failure worsened in June 2004, and there was concern that the left SSS could become aggravated as a consequence of creating an arterio-venous (AV) shunt. Although peritoneal dialysis was strongly recommended, she elected to undergo hemodialysis. We confirmed that there was no reduction of cerebral blood flow using brain single photon emission computed tomography (SPECT). Right and left examinations indicated the site at which an AV shunt should be created and subsequently, the AV shunt was created on the left fore-arm. Brain SPECT findings were again confirmed after dialysis, at the time of hemodialysis induction, and again 2 years after hemodialysis induction, showing no reduction in cerebral blood flow. She has no apparent symptoms or signs of left SSS, to date. Although it is known that an SSS could arise after AV shunt creation, there has been no report of the creation of an AV shunt in a case of SSS. The present case suggests that cerebral blood flow measurement using brain SPECT is useful for evaluating cerebral hemodynamics before AV fistula creation among patients with Takayasu's arteritis.

Objectives Excess mineralocorticoids such as deoxycorticosterone acetate (DOCA) together with salt are known to cause tubulointerstitial fibrosis, but the mechanisms underlying fibrosis progression are unclear. Therefore, we investigated the role of matrix metalloproteinase 2 (MMP2) in the epithelial-mesenchymal transition and fibrosis progression. Methods Uninephrectomized rats drank 0.9% NaCl and 0.3% KCl solution and were treated with DOCA alone, DOCA + spironolactone, or vehicle for 1, 4, or 8 weeks. SBP, kidney function and morphology, and kidney and urine MMP2 activity were compared among the groups. Results At week 4, the DOCA-treated group exhibited hypertension, tubulointerstitial fibrosis, increased MMP2 activity in the kidney and urine, and overexpression of MMP2 in proximal tubule cells and MMP14 in apical membranes; these results were more pronounced at week 8. At week 8, the proximal tubule cell apicolateral surface proteins villin, claudin 2, and E-cadherin were downregulated, and the mesenchymal marker α-smooth muscle actin was upregulated in the tubulointerstitium of DOCA-treated rats. These DOCA/salt-induced changes (except for hypertension) and fibrosis progression observed at week 8 were reversed by TISAM (a selective MMP2 inhibitor), which was administered from week 4 to week 8. All of the effects of DOCA/salt at week 8 were attenuated by spironolactone. Conclusion Eight weeks of treatment with DOCA/salt activated MMP2, primarily on the apical surface of proximal tubule cells, which induced epithelial-mesenchymal transition from the luminal side and promoted tubulointerstitial fibrosis progression. These MMP2-induced changes occurred via downstream processes regulated by mineralocorticoid receptors.

Background. It has been well-recognized that cancer patients occasionally develop renal disorders independently of direct tumor invasion. However, the clinical entity of paraneoplastic glomerulopathy remains poorly understood, in part due to the lack of an animal model for basic research. In the present study, we investigated whether cancer-bearing rats develop features of glomerulopathy. Methods. RCN-9 rat colon cancer cells (1 3 10 7 ) were injected into F344 rats (n ¼ 13) and T cell-deficient F344 rats (nude rats; n ¼ 7) via the portal system. Urinalysis and histological examinations were performed in comparison with control rats (n ¼ 6) that received a vehicle injection. Results. Metastatic growth of RCN-9 cells exclusively in the liver was observed in the cancer-injected F344 rats, whereas direct invasion into the kidney was not evident even microscopically. Two of the cancer-injected F344 rats died within 2 days, but 9 of the 11 that avoided early death showed elevation of urinary protein (up to 158.0 mg/day) compared to controls (mean values: 60.8 6 12.9 versus 17.8 6 2.1 mg/day, P ¼ 0.0291). Although morphological changes were not evident in light microscopy, abundant IgG in the glomerular tufts of the proteinuric rats was shown immunohistochemically. Ultrastructure analysis revealed electron-dense deposits in the glomerular basement membrane zone and effacement of the podocytic foot process. Interestingly, none of the nude rats showed proteinuria despite of cancer growth, suggesting that a specific immune response was involved. Conclusions. The tumor-bearing rats developed features of glomerulopathy, as expected from the clinical perspective, and this animal model may provide new insights into the development of paraneoplastic glomerulopathies.

In ordinary settings, human immunodeficiency virus (HIV)-associated nephropathy should be considered when HIV infection is associated with heavy proteinuria. On the other hand, hepatitis B virus (HBV) may also play a role in the development of glomerular injury among patients with HIV infection, since HIV and HBV infections commonly occur together due to shared modes of transmission. We present here a case of nephrotic syndrome in an HIV-positive patient complicated with HBV infection. A renal biopsy revealed sparse granular deposits of immunoglobulin G in the subepithelial region, consistent with membranous nephropathy (MN) stage I. Moreover, immunostaining exhibited weak anti-hepatitis B core activity within glomeruli. These results led us to consider that HBV-associated MN might play a role in the development of nephrotic syndrome. Although anti-viral treatment for patients with HBV-associated MN has been suggested to be clinically effective, the use of two anti-HIV agents (tenofovir and emtricitabine), both of which have anti-HBV activities, was not effective for the patient’s nephrotic syndrome, despite obtaining a decrease in the serum HBV-DNA levels. A lack of prospective data suggests that many decisions on the treatment of glomerulopathies with HIV infections are potentially empirical. Obviously, further studies and accumulated clinical experience are required to better determine the pathogenesis and management of HBV-associated MN among patients with HIV infections.

症例は強直間代性痙攣および意識障害を主訴に入院した19歳女性. 腎血管性高血圧症による可逆性後部白質脳症と判明し, その他に漿液性網膜剥離, ネフローゼ症候群およびHyponatremic hypertensive syndromeを認めた. 経皮的腎動脈バルーン拡張術を施行後, 血圧は正常化し, 全ての症状は改善した. 多彩かつ稀な臨床症状を呈した腎血管性高血圧症を経験したので報告する.

be associated with the severity of nocturnal hypoxia, the direct relationship between CRP and nocturnal hypoxia has not yet been evaluated. Therefore, the relationship between CRP and nocturnal hypoxia diagnosed by average SaO2 using pulse oximetry was investigated. Moreover, pulse oximetry is a simple tool and is used for screening SAS in dialysis patients [6], while PSG is costly in terms of both time and money. In conclusion, this study demonstrated that nocturnal hypoxia is associated with elevated CRP levels in dialysis patients. These findings suggest that nocturnal hypoxia in dialysis patients may be an additional CVD risk and both a careful follow-up and good control of these patients are needed to prevent CVD.