The Associations of Malnutrition and Aging with Fluid Volume Imbalance between Intra- and Extracellular Water in Patients with Chronic Kidney Disease.

OBJECTIVES: Fluid imbalance due to sodium retention and malnutrition can be characterized by the ratio of extracellular water (ECW) to intracellular water (ICW). We investigated whether the ECW/ICW ratio is a risk factor for adverse outcomes. DESIGN: Retrospective cohort study. SETTING AND PARTICIPANTS: 149 patients with chronic kidney disease from 2005 to 2009, who were followed until August 2013. MEASUREMENTS: Body fluid composition was measured by bioelectrical impedance analysis. Patients were categorized according to the ECW/ICW ratio tertile. Daily nutrient intake was estimated from 24-h dietary recall and analyzed using standard food composition tables. The main outcomes were adverse renal outcomes, as defined by a decline of 50% or more from the baseline glomerular filtration rate or initiation of renal replacement therapy, cardiovascular events, and all-cause mortality. RESULTS: The ECW/ICW ratio increased with downward ICW slope with age and renal dysfunction besides ECW excess with massive proteinuria. Sodium intake, protein intake, and calorie intake were negatively correlated with the ECW/ICW ratios due to the steeper decreasing ICW content with the decreased dietary intake than the decreasing ECW content. During a median 4.9-year follow up, patients in the highest tertile had the worst adverse renal outcomes (15.9 vs. 5.1 per 100 patient-years, P < 0.001), cardiovascular events (4.1 vs. 0.3 per 100 patient-years, P = 0.002), and mortality (11.2 vs. 1.3 per 100 patient-years, P < 0.001). The adjusted hazard ratio (95% confidence intervals) for adverse renal outcomes, cardiovascular events, and mortality were 1.15 (1.03 - 1.26), 1.12 (0.93 - 1.31), and 1.29 (1.11 - 1.50), respectively. CONCLUSIONS: Fluid imbalance between ICW and ECW occurring in malnourished and elderly patients with chronic kidney disease may explain the reserve capacity for volume overload and is associated with adverse renal outcomes and all-cause mortality.

The pathologic impact of tacrolimus on protocol biopsy in renal transplant patients with basiliximab-based immunosuppression.

Forty-two ESRD patients underwent renal transplantation using basiliximab (mean age: 30.6 +/- 18.6 years at transplantation; male: 50%; ESRD duration: 51.6 +/- 13.0 months) between February, 2000 and July, 2003. All patients had a protocol biopsy on the day of transplant, on discharge from the hospital (35.5 +/- 13.2 days), and at 1 year after transplant. The immunosuppression included a calcineurin inhibitor, basiliximab, mycophenolate mofetil (MMF), and methylprednisolone. While 16 patients used tacrolimus (FK group: 29.4 +/- 16.6 years old), 26 patients used cyclosporine (CsA group: 31.4 +/- 20.1 years old). Protocol biopsies were graded according to the Banff 97 classification. The incidence of acute rejection episodes within 1 year was greater in the CsA (15%) than the FK group (6%). Serum creatinine at hospital discharge was similar (CsA: 1.01 +/- 0.59 mg/dL, FK: 0.97 +/- 0.49, p = .18); however creatinine at 1 year differed significantly (CyA: 1.22 +/- 0.88 mg/dL, FK: 0.92 +/- 0.39, P = .03). There was a trend toward an increase in the score of interstitial inflammations in the CsA group, while it remained constant in the FK cohort (P = .05 at 1 year between the two groups). Other pathologic scores (t, ci, ct, cv, ah) did not differ between the groups at 1 year. Although there were no differences in the demographics between the two groups, there were several trends toward better renal function in the FK group.

Baseline glomerular sclerosis influences morphological changes, but not level of serum creatinine.

The aim of this study was to investigate whether glomerular sclerosis (GS) at the time of engraftment affects subsequent morphology and clinical course of renal allografts. Eighty-one renal transplant recipients were recruited for this study. Protocol biopsies of the renal allografts were performed at engraftment, as well as at 1, 3, 5, and 7 years after transplantation. All cases were divided into 2 groups based on the presence of GS at engraftment, namely, non-GS and GS groups. Morphological changes in the renal allografts were graded from 0 to 3+ based on the severity of chronic allograft nephropathy (CAN) of the Banff classification based on 5 factors: percentage of GS, extent of interstitial fibrosis, tubular atrophy, arterial intimal thickening, and arteriolar hyalinosis. Furthermore, the level of serum creatinine (s-Cr) at each year was examined by recipient age and gender, donor age and gender, type of donor (living/cadaver), delayed graft function, acute rejection within 1 year after transplantation, mean blood pressure, and use of calcineurin inhibitors as well as the presence of GS at engraftment. The extent of GS at engraftment significantly correlated with donor age (P = .0038) but with a weak correlation coefficient. Although the severity of CAN developed gradually in both non-GS and GS groups, differences in morphological changes at engraftment between the 2 groups persisted throughout 7 years. Donor age and recipient gender influenced s-Cr significantly. In conclusion, the presence of GS at engraftment aggravates subsequent morphological changes and affects short-term but not long-term allograft prognosis.

BK virus nephropathy in a patient with ABO-incompatible renal transplantation.

A 43-year-old woman with end-stage renal disease originating from IgA nephropathy entered chronic haemodialysis therapy. She then received an ABO-incompatible living related renal transplantation. Initial immunosuppression consisted of azathioprine, methylprednisolone and tacrolimus. At 155 days after transplantation, the azathioprine was changed to mycophenolate mofetil for continuous graft dysfunction. Furthermore, a total of three courses of anti-rejection therapy was given. At 665 days after transplantation, diagnosis of BK-virus nephropathy was made by immunohistochemical analysis and viral DNA assay. Therefore the immunosuppression therapy was reduced for graft dysfunction. All five renal biopsy specimens were examined retrospectively in order to determine when the BK virus nephropathy had developed. The expressions of SV40 large T antigens were detected from the third (117 days) to the fifth (665 days) biopsies, with increasing numbers of SV40 large T antigen positive cells. In addition, many cells contained inclusion bodies which were already present in the urinary sediment for 3 months post-transplantation. Although it is difficult to make a diagnosis of early stage of BKVN, we have to consider with caution if urinary cells with inclusion body are seen. Awareness of BKVN at the earliest opportunity is important in order to avoid over-immunosuppression.

Angiotensin-converting enzyme (ACE) I/D genotype and renal ACE gene expression.

BACKGROUND: The angiotensin-converting enzyme (ACE) I/D genotype affects serum ACE levels and the onset and progression of renal disease, but little is known about the mechanism. We investigated a possible association between the ACE I/D genotype and renal ACE mRNA levels in healthy subjects. METHODS: Renal biopsy samples were obtained from 50 healthy kidney donors. The ACE I/D genotype was determined by polymerase chain reaction (PCR). Renal ACE mRNA quantification was performed by competitive RNA-PCR. In situ hybridization (ISH) for ACE mRNA on renal biopsy specimens was also performed. RESULTS: The number of ACE transcripts in 100 ng of total RNA was significantly (P < 0.01) lower in subjects with II genotype (5.6 +/- 5.3 x 10(5), N = 20) compared with those with the ID (17.9 +/- 13.6 x 10(5), N = 23) or the DD genotype (36.9 +/- 14.6 x 10(5), N = 7) in healthy donors. The ISH studies showed that both tubular and glomerular ACE mRNA expressions were weak in subjects with the II genotype, intermediate in subjects with ID genotype, and strong in subjects with DD genotype. CONCLUSIONS: It is suggested that renal ACE gene expression is associated with the ACE I/D genotype in healthy Japanese subjects.

Successful transplantation of a cadaveric kidney with post-infectious glomerulonephritis.

This report describes a successful renal Tx in a patient with chronic renal failure, caused by dysplastic kidneys, who received a cadaveric kidney with post-infectious glomerulonephritis. Sequential renal biopsies were performed at 12 h before Tx, and at 1 h and on days 8 and 58 post-Tx. Post-operative hematuria disappeared on day 9 and proteinuria on day 13. Normal graft function was observed within 1 month, with histologic resolution. Our study suggests that while the donor kidney facilitates deposition of certain immune reactants, this is a host (environmental) problem and when transplanted into a new host (new environment), the problem is no longer sustained.

Effect of intraperitoneal administration of heparin on advanced glycation end-products in CAPD.

OBJECTIVE: To evaluate the effect of intraperitoneal (IP) administration of heparin on clearance of advanced glycation end-products (AGEs) and peritoneal dialysis efficiency. DESIGN: Sequential self-controlled intervention study. SETTING: University hospital, Department of Nephrology. PATIENTS AND METHODS: Pyrraline, urea, and creatinine levels in plasma and dialysate, along with AGE-derived fluorescence intensity (excitation, 370 nm; emission, 440 nm) in dialysate were measured 0, 30, and 60 days after IP administration of heparin in 11 patients on continuous ambulatory peritoneal dialysis (CAPD). Pyrraline levels were determined by ELISA. RESULTS: Heparin induced a significant decrease in plasma pyrraline levels; the values on days 0, 30, and 60 were 162.0+/-89.8 micromol/L, 101.1+/-32.1 micromol/L (p < 0.01), and 94.0+/-19.8 micromol/L (p < 0.001), respectively. Heparin also induced a tendency of increased dialysate pyrraline levels and a significant increase in AGE-derived fluorescence intensity in the dialysate. The values for the latter on days 0, 30, and 60 were 51.0+/-9.3 AU (arbitrary units/ mg of collagen), 73.5+/-16.0 AU (p < 0.001), and 65.6+/-15.5 AU (p < 0.01), respectively. Furthermore, heparin administration resulted in a significant (p < 0.01) increase in the dialysate/plasma ratio of urea (means 0.80, 0.90, and 0.94 on days 0, 30, and 60, respectively). CONCLUSION: These results suggest that a beneficial effect of IP administration of heparin is in part due to its action on AGE kinetics, supporting a potential preventive strategy for peritoneal membrane distortion in CAPD.

Primary Shewanella alga septicemia in a patient on hemodialysis.

We report the first Japanese case of primary septicemia with Shewanella alga and also describe the bacteriological characteristics of and results of antibiotic susceptibility tests of the isolate. S. alga was repeatedly isolated, at times simultaneously with Escherichia coli, from the blood of a 64-year-old female undergoing hemodialysis. The isolated organism was determined to be S. alga based on recently published identification criteria, such as hemolysis on sheep blood agar, no acid production from carbohydrates, and growth on agar containing 6. 5% NaCl. Results of antibiotic susceptibility tests demonstrated that the isolate was sensitive to levofloxacin and cefpirome (MICs, 128, 64, and 8 microg/ml, respectively). Although the role of S. alga as a human pathogen has not been fully determined, accumulating data suggest that this organism may be a potential pathogen, especially in compromised hosts.

A case of ABO-incompatible renal transplant patient with non-insulin-dependent diabetes mellitus; long-standing observation of serial glomerular change by protocol biopsy.

A 41-yr-old patient with non-insulin-dependent diabetes mellitus (NIDDM), before and after ABO-incompatible renal transplant, is reviewed using serial protocol biopsy. Although she recovered from delayed hyperacute rejection (DHAR) immediately post-transplantation, her graft function deteriorated gradually. A mild acute transplant glomerulitis, noted at the 155th day post-transplantation, progressed to pronounced chronic transplant glomerulopathy over 5 yr. In the specimen of the last biopsy, at 5 yr post-transplantation, glomeruli demonstrated an exudative hyaline lesion, which was characteristic of diabetic nephropathy in addition to chronic transplant glomerulopathy. Therefore, we made a diagnosis of this glomerular lesion as chronic transplant glomerulopathy complicated by diabetic glomerulopathy. Considering the result of this case, the protocol biopsy is a useful procedure to diagnose an accurate cause of graft dysfunction in individual cases. It is concluded that the protocol biopsy is apparently useful for the detection of various pathological processes occurring in allograft and may contribute to a strategy for improvement of graft survival.

Renal ACE immunohistochemical localization in NIDDM patients with nephropathy.

A role of renal angiotensin-converting enzyme (ACE) in diabetic nephropathy has been suggested. Immunohistochemical localization of ACE was studied in 20 non-insulin-dependent diabetes mellitus patients with diabetic nephropathy and 17 healthy kidney transplant donors, with ACE gene insertion/deletion (I/D) polymorphism also examined in the latter. Immunohistochemical studies indicated that ACE staining was significantly (P < 0.01) enhanced in glomeruli and slightly decreased in proximal tubules in diabetic patients. Glomeruli positive for ACE immunostaining were observed in 23.5% of the healthy subjects and in 80% of the diabetic patients. All patients with nodular lesions had ACE-positive glomeruli and showed significantly (P < 0.01) more intense glomerular ACE immunostaining than patients without nodular lesions. Among healthy controls, subjects with the DD genotype had ACE-positive glomeruli more frequently and tended to show slightly increased intensity on proximal tubule ACE immunostaining compared with subjects with other genotypes. These observations suggest that increased ACE localization in glomeruli is likely to be one of the factors in the increased renin-angiotensin system activity in glomeruli in patients with diabetic nephropathy. There is a possibility that ACE gene I/D polymorphism may be related to renal ACE immunohistochemical localization.

Renal effects of alcohol withdrawal in five-week alcohol-treated rats.

OBJECTIVE: The effects of alcohol withdrawal on renal function following renal ischemia was examined in rats fed a liquid containing ethanol for 5-week alcohol treatment. METHOD: For alcohol-treated rats, animals were fed with an ethanol-containing diet for 5 weeks. In withdrawal studies, the alcoholic diet was replaced by a regular diet following 5-week alcohol treatment. Renal ischemia was induced by clamping the renal artery for 20 minutes and renal function was evaluated 24 hours later. RESULTS: Alcohol ingestion for 5 weeks did not alter the renal function in the absence of renal ischemia. Mean (+/- SD) glomerular filtration rate (GFR) and renal plasma flow rate (RPFR) measured 24 hours after ischemia in control rats were 430 +/- 29.6 microliters/min/g/kidney weight (gKW) and 1.4 +/- 0.17ml/min/gKW, whereas in alcohol-treated rats, they were 117.2 +/- 35.2 microliters/min/gKW and 0.31 +/- 0.12ml/min/gKW, which values were significantly lower than controls (p < .05). However, when alcohol was withdrawn for 1 week, the renal function of rats after ischemia was no different from that of control rats (GFR = 413.9 +/- 66.3 microliters/min/gKW and RPFR = 2.14 +/- 0.7 ml/min/gKW). As for renal histopathology, tubular damage was milder 1 week after alcohol withdrawal compared to that observed in rats fed the alcohol-containing diet for 5 weeks. CONCLUSIONS: The findings suggest renal damage induced in rats by exposure to alcohol for 5 weeks was reversed when alcohol was withdrawn for 1 week before renal ischemia.

Renal hemodynamic changes induced by captopril and angiotensin-converting enzyme gene polymorphism.

We studied the relationship between renal hemodynamic changes induced by a single acute administration of captopril (50 mg p.o.) and angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism in 27 healthy human volunteers, 7 with DD genotype, 10 with ID, and 10 with II genotype. The increase in effective renal plasma flow (p < 0.02) and the fall in renal vascular resistance (p < 0.01) in response to captopril were significantly less in subjects with the DD genotype than in subjects with the other genotypes. These data suggest that intrarenal ACE inhibition by captopril differs according to ACE gene ID polymorphism in healthy humans.

Renal angiotensin-converting enzyme localization in diabetic rats and the effect of low protein diet.

Recent evidence suggests a role of angiotensin-converting enzyme (ACE) in diabetic nephropathy. The effect of diabetes and low protein diet on renal immunohistochemical ACE localization was studied in streptozotocin-induced DM rats. Immunohistochemical ACE localization was reduced in DM rats, and a low protein diet partially resolved this abnormality while inhibiting the progression of diabetic nephropathy.

Evaluation of gamma camera-based measurement of individual kidney function using iodine-123 orthoiodohippurate.

Gamma camera-based clearance techniques which use the renal uptake ratio (RUR) of the radiotracer are available to estimate the effective renal plasma flow (ERPF) and glomerular filtration rate. To evaluate the accuracy of these techniques, we measured RUR by an optimized procedure and compared it with standard ERPF. Iodine-123 orthoiodohippurate (OIH) scintigraphy and simultaneous para-aminohippurate clearance study for measuring standard ERPF were performed in three hospitals in 24 patients with normal or mildly impaired renal function. 123I-OIH was injected intravenously and 10-s consecutive imaging of the kidneys was started when the abdominal aorta was seen. The attenuation coefficient for 123I was measured in each hospital using the same water-equivalent absorption materials and used for the attenuation correction. After subtracting background radioactivity, RURs were defined as the count ratios of fractional renal uptakes based on the integral from 1 to 2, 2 to 3, 1.5 to 2.5 and 1 to 3 min after the injection of 123I-OIH in relation to injected doses using the following three procedures in respect of attenuation correction: (1) RUR without attenuation correction, (2) RUR with fractional renal uptake corrected by the measured attenuation coefficient, (3) RUR with the total injected dose corrected by the absorption material. To decide upon the appropriate correction method and time interval, RURs were compared with standard ERPF. Among the three correction methods, procedure 2 showed the highest correlation between RUR and standard ERPF, but the correlation coefficient was low (r=0.75). No significant difference was observed among the RURs of each time interval. Individual kidney function measured from early renal uptake may be inaccurate even when appropriate correction is made for attenuation, background activity or time lag between injection and data acquisition. Gamma camera-based measurement of renal function using 123I-OIH is limited with regard to accuracy and reproducibility, though it is convenient and non-invasive.

Angiotensin-converting enzyme polymorphism and development of diabetic nephropathy in non-insulin-dependent diabetes mellitus.

We determined the distribution frequency of angiotensin-converting enzyme insertion/deletion (I/D) polymorphism in 111 Japanese patients with non-insulin-dependent diabetes mellitus (NIDDM) of at least 10 years duration (80 patients with diabetic nephropathy and 31 patients without nephropathy) and 76 healthy Japanese controls. Patients with diabetic nephropathy showed an excess of the ID genotype compared with patients without nephropathy (p < 0.02) and less of the II genotype compared with healthy controls (p < 0.01) and patients without nephropathy (p < 0.01). NIDDM patients with the II genotype have a decreased risk for the development of diabetic nephropathy.