Association between physical activity and mortality in the Japanese general population with mild to moderate impaired renal function: the Jichi Medical School (JMS) cohort study.

BACKGROUND: The association between physical activity volume or intensity and mortality in general population with impaired renal function is unclear. We assessed these relationships among Japanese residents with impaired renal function. METHODS: We analyzed 638 individuals with estimated creatinine clearance below 60 ml/min in the Jichi Medical School cohort study. Exposures included the daily amount of physical activity converted to the physical activity index (PAI) used in the Framingham study and the activity time for each intensity. Physical activity intensity was classified into sedentary and nonsedentary. Nonsedentary activity was further divided into light-intensity and moderate-to-vigorous physical activity (MVPA). The outcome was all-cause mortality. Quartiles of the exposures were created, and hazard ratios (HRs) were calculated using the Cox proportional hazards model. RESULTS: The mean age of the subjects was 63.3 years, and 72.4% were female. In total, 172 deaths were registered during 11,567 person-years. No significant association was found between PAI and mortality. A significant association was found between long sedentary time and increased mortality (p = 0.042). Regarding nonsedentary activity, the HRs [95% confidence intervals (CIs)] for Q2, Q3, and Q4 versus Q1 were 0.85 (0.55-1.31), 0.67 (0.41-1.08), and 0.90 (0.54-1.45), respectively. In the subdivided analysis for light-intensity activity, the HRs (95% CIs) of Q2, Q3, and Q4 versus Q1 were 0.53 (0.33-0.84), 0.51 (0.34-0.82), and 0.57 (0.34-0.96), respectively. No significant association was found between MVPA and mortality. CONCLUSIONS: Nonsedentary activity, especially light-intensity activity, significantly reduced mortality among residents with impaired renal function.

The Urinary Angiotensinogen to Urinary Albumin Ratio Reflects Whether the Renin-angiotensin System in the Kidney Is Activated due to Filtration of Plasma Angiotensinogen through the Damaged Glomeruli or the Production of Angiotensinogen in the Proximal Tubules.

Objective Urinary angiotensinogen (AGT) is a surrogate marker for intrarenal renin-angiotensin system (RAS) activity that plays an important role in the development of renal damage. Urinary AGT levels are determined by the filtration of plasma AGT through the damaged glomeruli and production of AGT in the proximal tubules. However, the relative merits of the filtration and production of urinary AGT levels in chronic kidney diseases (CKD) have not been clarified. Therefore, we investigated them in CKD patients. Methods We recruited 41 biopsy-proven patients diagnosed with IgA nephropathy (IgAN) in 31, membranous nephropathy (MN) in 5, and tubulointerstitial nephritis (TIN) in 5. The patients taking RAS blockers were excluded. Results The urinary albumin levels in MN patients were significantly higher and those in TIN patients significantly lower than in IgAN patients, and the urinary AGT levels in the MN and TIN patients were significantly higher than those in IgAN patients. Conversely, the urinary AGT-to-urinary albumin (urinary AGT/Alb) ratios were the same for IgAN and MN patients, and those of TIN patients were significantly higher than those of IgAN and MN patients. A multiple linear regression analysis revealed that the urinary AGT/Alb ratios had a significant positive association with IgAN and TIN after adjustments (ß=0.75, and p<0.01). Conclusion These data suggest that the origins of urinary AGT may differ according to the etiology of renal damage [i.e. glomerular damage (such as IgAN and MN) or tubulointerstitial damage (such as TIN)], and a higher urinary AGT/Alb ratio, as in TIN, may reflect AGT production in the kidney.

A Rare Case of Lupus Nephritis Presenting as Thrombotic Microangiopathy with Diffuse Pseudotubulization Possibly Caused by Atypical Hemolytic Uremic Syndrome.

A 31-year-old woman was admitted to our hospital for thrombotic microangiopathy (TMA). She was diagnosed with systemic lupus erythematosus (SLE) and class V lupus nephritis. She had no aggravated SLE activity, Shiga toxin positivity, ADAMTS13 abnormality, or other causes of secondary TMA. Plasma exchange partially improved TMA, and eculizumab was introduced for suspected atypical hemolytic uremic syndrome (aHUS), as eculizumab was effective in suppressing the TMA activity. A kidney biopsy revealed diffusely organized crescents (pseudotubulization) with glomerular and arteriolar endothelial injury and subepithelial immune deposits. Thus, this was a rare case of lupus nephritis presenting as TMA with pseudotubulization possibly caused by aHUS.

Focal segmental glomerulosclerosis associated with cutaneous and systemic plasmacytosis.

Cutaneous and systemic plasmacytosis (CSP) is a rare lymphoproliferative disorder that mainly affects middle-aged Asian individuals. Although Castleman disease is often complicated with various renal involvements, glomerulonephritis associated with CSP, which is considered as a variant of Castleman disease, is rare. This report presents the case of a 41-year-old Japanese man with nephrotic syndrome associated with CSP. Renal biopsy findings showed focal segmental glomerulosclerosis (FSGS) and diffusely mild segmental mesangial proliferation. Plasma cell infiltration in the interstitium was not observed. Electron microscopic findings showed diffuse foot process effacement, localized involvement of subendothelial space widening with amorphous materials, and endothelial cell swelling. Lymph node biopsy findings denied Castleman disease. His skin regions and proteinuria were successfully treated with prednisolone and cyclosporine. The causal relationship between CSP and FSGS is unknown. However, increased serum levels of IL-6 and VEGF and decreased VEGF expression in the podocyte may contribute to renal lesions in patients with CSP. To our best knowledge, this is the first case of a patient with FSGS associated with CSP.

Membranous Nephropathy with an Enhanced Granular Expression of Thrombospondin Type-1 Domain-containing 7A in a Pregnant Woman.

A 30-year-old woman with proteinuria first noted at 26 weeks of gestation was admitted to undergo further evaluation. A renal biopsy revealed membranous nephropathy (MN). There was no evidence of any secondary MN. Prednisolone was initiated 6 months after delivery. Four months later, her urine protein became negative. Enhanced granular staining for thrombospondin type-1 domain-containing 7A (THSD7A) in the glomeruli was retrospectively detected in a biopsy specimen. A literature review revealed that 60% of cases of THSD7A-related MN occurred in women of childbearing age. Therefore, THSD7A-related MN should be considered in female patients presenting with idiopathic MN in childbearing age.

Caffeine intoxication successfully treated by hemoperfusion and hemodialysis.

Caffeine is an easily available drug which is generally regarded as being safe. However, it can lead to a lethal outcome in severe cases of caffeine intoxication. We herein report a case of a 32-year-old man who ingested approximately 15.6 g of caffeine in a suicide attempt. He suffered from sustained ventricular tachycardia despite conservative treatment. Therefore, we performed a combined therapy of hemoperfusion and hemodialysis which resulted in rapid improvement of the patient's ventricular tachycardia as well as a reduction of the patient's plasma caffeine level. To the best of our knowledge, this combination has not been previously reported to treat caffeine intoxication.

Plasma levels of fibroblast growth factor-23 are associated with muscle mass in haemodialysis patients.

AIM: Malnutrition is highly prevalent in haemodialysis (HD) patients, and it contributes to morbidity and mortality. Fibroblast growth factor-23 (FGF-23) and Klotho contribute to chronic kidney disease-mineral and bone disorder (CKD-MBD) in HD patients, but the role that these molecules play in determining nutritional status is currently unknown. METHODS: A cross-sectional study examining 77 HD patients was performed. The plasma concentrations of FGF-23 and soluble Klotho (s-Klotho) were studied to evaluate their association with muscle mass, which was investigated by abdominal muscle areas measured using computed tomography and by creatinine (Cr) production estimated using the Cr kinetic model. RESULTS: Plasma FGF-23 concentrations were significantly and positively correlated with abdominal muscle areas and Cr production (rho = 0.301, P < 0.01 and rho = 0.345, P < 0.01, respectively). In contrast, s-Klotho was not significantly correlated with these muscle mass indices and plasma FGF-23 concentrations. Multiple regression analyses showed that FGF-23 was a significant independent predictor of both muscle mass indices (P < 0.01 and P < 0.05, respectively). CONCLUSION: Plasma FGF-23 concentrations were associated with muscle mass indices in HD patients. Our findings suggest that FGF-23 and nutritional status are linked and this link is most likely independent of s-Klotho.

Plasma levels of the pro-inflammatory protein S100A12 (EN-RAGE) are associated with muscle and fat mass in hemodialysis patients: a cross-sectional study.

BACKGROUND: Malnutrition is highly prevalent and contributes to mortality in hemodialysis (HD) patients. Although the receptor for advanced glycation end products (RAGE) system also contributes to the morbidity and mortality of these patients, the role that the RAGE system plays in determining nutritional status is currently unknown. METHODS: A cross-sectional study examining 79 HD patients was performed. The plasma concentrations of the soluble RAGE (sRAGE) and S100A12 (also known as EN-RAGE) were studied to evaluate their association with nutritional status, which was assessed by measuring the mid-thigh muscle mass and subcutaneous fat mass with computed tomography. RESULTS: Plasma S100A12 concentrations were shown to be significantly and negatively correlated with muscle mass and with fat mass (r = -0.237, P < 0.05 and r = -0.261, P < 0.05, respectively). In contrast, sRAGE was not shown to significantly correlate with either of these factors. Multiple regression analyses demonstrated that S100A12 is a significant independent predictor of both muscle mass and fat mass (P < 0.01 and P < 0.05, respectively). CONCLUSIONS: Our findings suggest that plasma S100A12 levels could play an important role in determining muscle mass and fat mass in HD patients. TRIAL REGISTRATION: Study number; UMIN000012341.

Acquired Fanconi syndrome in patients with Legionella pneumonia.

BACKGROUND: Hyponatremia is often observed in patients with Legionella pneumonia. However, other electrolyte abnormalities are uncommon and the mechanism remains to be clarified. CASE PRESENTATION: We experienced two male cases of acquired Fanconi syndrome associated with Legionella pneumonia. The laboratory findings at admission showed hypophosphatemia, hypokalemia, hypouricemia and/or hyponatremia. In addition, they had the generalized dysfunction of the renal proximal tubules presenting decreased tubular reabsorption of phosphate (%TRP), increased fractional excretion of potassium (FEK) and uric acid (FEUA), low-molecular-weight proteinuria, panaminoaciduria and glycosuria. Therefore, they were diagnosed as Fanconi syndrome. Treatment for Legionella pneumonia with antibiotics resulted in the improvement of all serum electrolyte abnormalities and normalization of the %TRP, FEK, FEUA, low-molecular-weight proteinuria, panaminoaciduria and glycosuria, suggesting that Legionella pneumophila infection contributed to the pathophysiology of Fanconi syndrome. CONCLUSION: To the best of our knowledge, this is the first report demonstrating Fanconi syndrome associated with Legionella pneumonia.