Hypercalcemia Owing to Overproduction of 1,25-Dihydroxyvitamin D3 in Fetal Lung Adenocarcinoma: Case Report.

Hypercalcemia is a common electrolyte abnormality in malignancy and is largely caused by activation of parathyroid hormone (PTH) pathways. We report the case of a 76-year-old man with hypercalcemia primarily owing to 1,25-dihydroxyvitamin D3 overproduction from a high-grade fetal lung adenocarcinoma. Histologically, the tumor itself and tumor-adjacent macrophages were positive for the CYP27B1 protein, a key enzyme that generates 1,25-dihydroxyvitamin D3. Suppression was observed in serum PTH and PTH-related hormone levels, suggesting hypercalcemia is independent of the PTH pathway. Serum calcium level returned to normal after surgical resection of the lung cancer, supporting extrarenal overproduction of 1,25-dihydroxyvitamin D3 elicited by the tumors is the cause of hypercalcemia in this patient.

Determinants of the Change in Arterial Stiffness in Peritoneal Dialysis Patients.

Arterial stiffness is an important risk factor for cardiovascular disease (CVD) in patients with end-stage renal failure. However, little is known about the factors that contribute to arterial rigidity in peritoneal dialysis (PD) patients. The aim of this study was to define the pattern and determinants of the longitudinal change in arterial stiffness after PD initiation.Arterial stiffening was estimated for 46 PD patients by using brachial-ankle pulse wave velocity (baPWV) and carotid intima-media thickness (cIMT). The cross-sectional relationship between the arterial markers and their clinical determinants was studied. The longitudinal effects of blood pressure (BP), body fluid status, and glucose were studied over the two years after initiating PD.Multivariate analysis showed that higher baPWV was associated positively with urinary protein excretion (P < 0.001), systolic BP (P = 0.001), and hemoglobin A1c (P = 0.003). In contrast, increased cIMT correlated with smoking (P = 0.004) and hypoalbuminemia (P = 0.04), suggesting that endothelial dysfunction is implicated in the atherogenic process. Neither cIMT nor baPWV correlated significantly with other PD-related covariates of volume overload, peritoneal solute transport, kidney function, and C-reactive protein. Longitudinal observation demonstrated that BP had a greater influence on baPWV changes than hyperglycemia or fluid status.Our study indicates that 1) baPWV represent an arterial marker that integrates multifactorial interaction between modifiable variables including BP and plasma glucose; and 2) intervention aimed at controlling BP as well as nutritional conditions (glucose and albumin) may reduce CVD risk in PD patients.

Monoclonal immunoglobulin-associated proliferative glomerulonephritis characterized by organized deposits of striated ultra-substructures: A case report.

We herein report the case of a 64-year-old male who presented with progressive glomerulonephritis notable for organized and striated ultra-substructures. The patient was diagnosed with hypertension and proteinuria 3 years prior to admission and subsequently developed nephrotic syndrome and impairment of renal function. Laboratory tests did not reveal any evidence of infections or autoimmune diseases. Monoclonal gammopathy was not detected in serum or urine, although a small population of abnormal plasma cell clones was detected by flow cytometry. A renal biopsy showed mesangial and endocapillary proliferative glomerulonephritis with lobular accentuation, accompanied with focal and segmental double-contour formation. Additionally, moderate tubulointerstitial scarring and arteriosclerosis were noted. Immunofluorescence staining revealed positive staining for IgG, IgM, C3, C1q, and fibrinogen. IgG subclass and light chain staining showed restricted positivity for IgG1κ. Electron microscopy demonstrated massive amounts of subendothelial deposits with a fibrillary and branching profile. At higher magnification, a periodic striated pattern was observed within the microfilament-like structures. Immunohistochemical staining was negative for myoglobin, laminin, and collagens (type III and IV). Steroid and antihypertensive therapy did not show improvement in renal function. The second biopsy performed 2 years later revealed a similar lobular proliferative glomerulonephritis pattern with more extensive tubulointerstitial damage, indicating poor response to immunosuppressive therapy. The patient progressed to end-stage renal disease and required hemodialysis. We discuss the possible origins of the deposits with unusual substructures observed in this case.

The relationships between visit-to-visit blood pressure variability and renal and endothelial function in chronic kidney disease.

Visit-to-visit blood pressure variability has been shown to be an independent risk factor for cardiovascular diseases. High visit-to-visit blood pressure variability and endothelial dysfunction are observed in patients with chronic kidney disease. It is therefore assumed that high variability in visit-to-visit blood pressure measurements may be associated with endothelial dysfunction in these patients. The present study investigated the associations between visit-to-visit blood pressure variability and renal and endothelial function in patients with chronic kidney disease. We analyzed 150 consecutive patients with predialysis chronic kidney disease who visited our outpatient clinic from January 2006 to December 2010. The study examined the relationships between variability in visit-to-visit systolic blood pressure levels or mean systolic blood pressure (M SBP) and estimated glomerular filtration rate (eGFR) and flow-mediated dilation, an index of endothelial function. Variability in visit-to-visit systolic blood pressure showed a significant negative association with eGFR, independent of age, hemoglobin A1c, low-density lipoprotein (LDL) cholesterol and uric acid, whereas M SBP did not. Similarly, variability in SBP showed a significant negative association with flow-mediated dilation, independent of age, eGFR, HbA1c, LDL cholesterol and M SBP. These data indicate that variability in visit-to-visit blood pressure measurements is associated with impaired renal and endothelial function in patients with chronic kidney disease. This finding suggests that reducing blood pressure fluctuations might have beneficial effects in patients with chronic kidney disease, although this point needs to be addressed by future studies.

Renal and vascular protective effects of ezetimibe in chronic kidney disease.

OBJECTIVE: Dyslipidemia is a risk factor for not only cardiovascular diseases (CVD), but also chronic kidney disease (CKD). Ezetimibe, a cholesterol absorption inhibitor, lowers cholesterol levels by inhibiting both extrinsic and intrinsic cholesterol absorption via the gastrointestinal duct. However, very few studies have examined its efficacy and safety for patients with dyslipidemia complicated with CKD. METHODS: Thirty-seven dyslipidemic patients (low density lipoprotein cholesterol (LDL-C) levels ≥120 mg/dL) complicated with CKD were given ezetimibe (10 mg/day) for twenty-four weeks. The efficacy and safety of the therapy, including the anti-atherosclerotic and renal protective effects, were then examined. RESULTS: Significant decreases were observed in the levels of LDL-C (158.9 ± 26.9 mg/dL→123.0 ± 31.8 mg/dL; p<0.0001), remnant-like lipoprotein cholesterol (9.3 ± 5.3 mg/dL→7.3 ± 3.8 mg/dL; p<0.05) and lipoprotein (a) (22.0 ± 16.1 mg/dL→16.4 ± 11.0 mg/dL; p<0.01). The estimated glomerular filtration rate did not change, but the urine protein to creatinine ratio decreased significantly (1,107.3 ± 1,454.2 mg/gCre→732.1 ± 1,237.8 mg/gCre; p<0.05). No changes were observed in the carotid intima media thickness, but the brachial-ankle pulse wave velocity decreased significantly (1,770.4 ± 590.3 cm/sec→1,702.5 ± 519.9 cm/sec; p<0.05). No adverse events were observed. CONCLUSION: Ezetimibe can be safely administered even to patients with CKD. The results of this study indicate that ezetimibe may provide some renal protection and suppress the complications of CVD in CKD patients.

Peritoneopericardial communication after aortic valve replacement in a peritoneal dialysis patient.

A 73-year-old male undergoing peritoneal dialysis (PD) for end-stage renal disease due to diabetic nephropathy was diagnosed with aortic stenosis and was admitted to our hospital in September, 2009. The patient underwent replacement of the ascending aorta with an artificial blood vessel plus aortic valve replacement without any notable complications. PD was restarted 3 days after the surgery and large amounts of light red fluid from the drain placed in the pericardium were observed just after resumption of PD solution. The patient was diagnosed with peritoneopericardial communication. PD was discontinued and hemodialysis was performed only with intermittent lavage of the peritoneal cavity. The amount of drainage was spontaneously decreased, and on the 17th day after surgery, PD was resumed. The patient is undergoing PD without recurrence of peritoneopericardial communication, 59 months after the onset of symptoms. Peritoneopericardial communication in a patient with PD developing after open-heart surgery is rare because such a case has been documented in only one case report. However, since massive pericardial effusion may cause severe cardiac problems, we consider that the communication between the peritoneal cavity and the pericardium needs to be checked for in patients with PD after cardiac surgery.

Olmesartan induces renoprotective effects by stimulating angiotensin type 2 receptors and reducing oxidative stress in diabetic nephropathy.

BACKGROUND: Angiotensin receptor blockers reduce the progression of diabetic nephropathy primarily by inhibiting angiotensin type 1 (AT(1)) receptors. In the present study, we investigated the role of angiotensin type 2 (AT(2)) receptors on the renoprotective effects of olmesartan in diabetic nephropathy. METHODS: Six-week-old mice were treated with streptozotocin and divided into four groups: the OLM group (mice treated with olmesartan), the OLM+Ang II group (mice treated with olmesartan and angiotensin II), the OLM+PD group (mice treated with olmesartan and the AT(2) antagonist PD 123319), and the vehicle group. Nondiabetic mice were used as controls. We measured blood glucose levels and urinary excretions of albumin and 8-hydroxy-2'-deoxyguanosine (8-OHdG), which is a marker for oxidative stress. RESULTS: Although urinary albumin excretion in the OLM and OLM+Ang II groups showed a tendency to be reduced compared to the vehicle group, it was significantly lower compared to the OLM+PD group. Urinary excretion of 8-OHdG was also significantly lower in the OLM and OLM+Ang II groups compared to the OLM+PD group. CONCLUSIONS: In diabetic nephropathy, the renoprotective effects of olmesartan are due not only to the blockade of AT(1) receptors, but also to a reduction in oxidative stress via stimulation of AT(2) receptors.

A Japanese case of proteinase 3 antineutrophil cytoplasmic autoantibody-associated pauci-immune-type crescentic glomerulonephritis without valvular endocarditis.

A 74-year-old male without recent medical treatment visited our hospital complaining of fever and lack of appetite. Upon examination severe azotemia, proteinuria, and urinary occult blood were noted, and the patient was admitted. Results of a blood test showed that his proteinase 3 antineutrophil cytoplasmic autoantibody (PR3-ANCA) level was high. A transthoracic echocardiogram indicated normal cardiac function and no valvular regurgitation or stenosis. Necrotizing glomerulonephritis accompanied by cellular crescentic bodies, but not granuloma, was noted on renal biopsy. An immunofluorescence study demonstrated no immunofluorescence staining in the glomerulus or in the tubulointerstitial or vascular compartments. No lesion was present in the lung or upper respiratory tract. The patient was diagnosed with PR3-ANCA-associated pauci-immune-type crescentic glomerulonephritis and treated with steroids. This treatment resulted in rapid normalization of C-reactive protein, and the PR3-ANCA level slowly decreased and converted to negative. The renal function, however, did not improve, and maintenance dialysis was introduced. No pulmonary or upper airway lesion has developed during 18 months of follow-up. PR3-ANCA-positive crescentic glomerulonephritis accompanied by valvular endocarditis has been described by several reports in Japan; however, this case was not complicated by valvular endocarditis. To our knowledge, this is the 4th case report describing PR3-ANCA-associated crescentic glomerulonephritis in Japan.

Characteristics of 20-year survivors undergoing maintenance hemodialysis.

Hemodialysis techniques have improved remarkably in recent decades and the number of long-term survivors among patients with end-stage renal disease has increased. The mortality rate of hemodialysis patients has been reported to be low in Japan. However, the long-term survival rate of dialysis patients is still low: 23.6% for 15 years and 17.4% for 20 years, even in Japan, and background information on patients undergoing hemodialysis therapy for more than 20 years is scarce in this country. In the present study, we investigated the characteristics of 20-year survivors undergoing maintenance hemodialysis at our medical center. We compared the characteristics of hemodialysis patients who had survived for more than 20 years after the initiation of hemodialysis with those of patients who started hemodialysis at the same time and had already died. No patient among those who were still alive had diabetes mellitus while 15% of patients who had died had diabetes mellitus at the time of initiation of hemodialysis. Age, cardiothoracic ratio, and serum levels of total cholesterol and triglyceride 6 months after the initiation of hemodialysis, as well as decreases in body weight per year were significantly lower in those who had survived than in those who had died. These results suggest that long-term hemodialysis survivors are characterized by (i) initiation of hemodialysis at a young age (ii) being free of diabetes mellitus (iii) a well-controlled cardiothoracic ratio (iv) small successive change in body weight, and (v) being free of hypercholesterolemia and hypertriglyceridemia.