Kunimi Maeda

Glomerular changes in the KK‐Ay/Ta mouse: A possible model for human type 2 diabetic nephropathy

Background:  In type 2 diabetic nephropathy, there is no animal model which has been completely matched with humans. Advanced glycation end products (AGE) and transforming growth factor‐beta (TGF‐β) are closely related to hyperglycaemia and their pathobiochemistry could explain diabetic nephropathy. The objective of the present study was to evaluate the KK‐Ay/Ta mouse as a suitable model for type 2 diabetic nephropathy including pathological changes and immunohistochemical analyses of AGE and TGF‐β, compared with the non‐diabetic BALB/cA mouse.

Pioglitazone attenuates TGF-β1-induction of fibronectin synthesis and its splicing variant in human mesangial cells via activation of peroxisome proliferator-activated receptor (PPAR)γ

The peroxisome proliferator‐activated receptor (PPAR)γ is expressed not only in adipose tissue but also in macrophages/monocytes and plays important roles in acute/chronic inflammation. Transforming growth factor (TGF)‐β is a common pathogenic indicator of sclerosis because it induces the accumulation of extracellular matrix (ECM) in the glomerular mesangium of the kidney. Among components of the ECM, fibronectin (FN) is an acute reactant in inflammation, and isoforms of it produced by splicing of gene variants appear during abnormal conditions such as wound healing. In this study, we examined the effects of pioglitazone, a PPARγ agonist, on TGF‐β1‐induced FN synthesis in cultured mesangial cells using RT‐PCR and Western blot analysis. We also analyzed its splicing variant, extra domain (ED) A, containing FN (EDA+FN). TGF‐β1 enhanced the production of both FN and EDA+ FN and down‐regulated PPARγ expression. Pioglitazone reversed both these effects of TGF‐β1. These findings suggest that PPARγ activation by pioglitazone may affect the TGF‐β1‐induced FN accumulation observed in the glomerular mesangium in cases of glomerulosclerosis, although further in vivo experiments are needed to evaluate this inference.

Long-term effects of the oral adsorbent, AST-120, in patients with chronic renal failure.

The oral adsorbent AST-120 has been widely used in Japan to delay the initiation of dialysis therapy in patients with chronic renal failure. This study evaluated the long-term effects of AST-120 in patients with chronic renal failure who had not previously undergone dialysis. One hundred out-patients were prospectively enrolled and prescribed 6 g/day oral AST-120 for ≥ 1 year. The clinical effectiveness of AST-120 was evaluated by comparing changes in the slope of the reciprocal serum creatinine-time plot (1/sCr slope) before and after AST-120 administration. The 1/sCr slope improved significantly after ≥ 1 year of AST-120 treatment and greatest improvement was observed in patients with the longest AST-120 administration period (> 30 months). The results suggest that long-term treatment with AST-120 may be beneficial for chronic renal failure patients in the pre-dialysis stage.

USEFULNESS OF A BODY COMPOSITION ANALYZER, INBODY 2.0, IN CHRONIC HEMODIALYSIS PATIENTS

The objective of the present study was to investigate whether InBody 2.0 might be useful in measuring the dry weight of chronic hemodialysis (HD) patients. Thirty‐five HD patients (22 males and 13 females; mean age 62.6 ± 14.0 years; mean HD duration 101.0 ± 118.06 months) were examined. Multifrequency bioelectric impedance analysis was used to estimate the ratio of extracellular water (ECW) to total body water (TBW). The body resistance was measured at frequencies ranging from 1 kHz to 1 MHz. The impedance index was determined at a low frequency (5 kHz) and correlated closely with ECW, using sodium bromide dilution as standard comparison. The levels of serum albumin, prealbumin, total cholesterol (TC), triglycerides (TG), transferrin, and human atrial natriuretic peptide (hANP) were measured by routine methods in our hospital. The ECW/TBW ratio was significantly associated with the levels of hANP (p < 0.05). However, no associations between the levels of serum albumin, TC, TG, or transferrin and the ECW/TBW were observed. It appears that the body composition analyzer, InBody 2.0, may be useful for estimating the dry weight in chronic HD patients.

Severity of Alexithymia is Related to Psychosocial Factors in Patients with Peritoneal Dialysis

We examined the relationship between alexithymia and psychosocial factors in 72 peritoneal dialysis patients. The 72 patients had significantly higher scores on alexithymia and anxiety than did 73 healthy volunteers. The alexithymia scores were significantly and positively correlated with anxiety scores, suggesting that alexithymia may be related to anxiety derived from the stress associated with dialysis therapy. After 3 yr. of follow-up consultations, patients were still showing higher scores on alexithymia and anxiety; however, alexithymia scores were not correlated with anxiety scores but rather were significantly associated with poor social support. Alexithymic characteristics may be related to psychosocial factors such as the availability of social support.

Association of alexithymia with low utilization and perception on a measure of social support in patients on peritoneal dialysis.

This study examined the association of social support and alexithymia in 63 patients with end-stage renal failure on peritoneal dialysis. Scores on the Toronto Alexithymia Scale were significantly higher for the patient group than the control group. Social support was measured with the Stress and Coping Inventory. For scores on the Existence of social support there was no significant difference between the two groups; however, scores on the Utilization and Perception of social support were significantly lower for the patients than for the control group. The alexithymia scores were significantly and negatively correlated with the scores on the Utilization and Perception of social support Our findings suggest that patients with peritoneal dialysis score higher on a measure of alexithymia associated with low utilization and perception of social support.

Dose-response to a jelly preparation of calcium polystyrene sulfonate in patients with hyperkalemia--changes in serum potassium levels with or without a RAAS inhibitor.

AIMS In this study, dose-response of the serum potassium-lowering effect of a calcium polystyrene sulfonate (PS) preparation was investigated. Changes in the serum potassium level were also examined with or without application of a RAAS inhibitor, which is said to increase the serum potassium level. SUBJECTS AND METHODS 23 patients diagnosed to have hyperkalemia associated with chronic renal failure were enrolled in this study. The study drug, a PS-Ca jelly preparation (Argamate jelly), was started at a daily dose of 1 preparation (5 g as PS-Ca), and the dose was increased by 1 preparation every month to finally reach 3 preparations per day. Blood samples were collected once a month and serum levels of creatinine and electrolytes were measured. RESULTS PS-Ca jelly decreased serum potassium levels in a dose-dependent manner. Decreases were 0.67 mEq/l at 5 g of PS-Ca/day, 1.06 mEq/l at 10 g/d, and 1.33 mEq/l at 15 g/d. Irrespective of the use of the RAAS inhibitor, serum potassium levels decreased significantly in a dose-dependent manner. Furthermore, no major change in serum creatinine levels occurred in subjects in which the RAAS inhibitor was used, although in subjects in which the RAAS inhibitor was not used, serum creatinine level tended to gradually increase. CONCLUSION Serum potassium levels were reduced in a dose-dependent manner by administration of 5-15 g/d of PS-Ca, and it appeared that together with control of serum potassium levels, renal function should be maintained by continuous administration of RAAS inhibitor.

A case of primary immunoglobulin light chain amyloidosis with a delayed appearance of Bence Jones protein in urine.

SUMMARY:  We report here a case of a 58‐year‐old man who had nephrotic syndrome and immunoglobulin light chain (AL) amyloidosis. This patient underwent a renal biopsy to confirm the diagnosis. Treatment with permanganate before Congo red staining showed systemic secondary amyloidosis (AA) fibrils, which were sensitive to permanganate oxidation. Although this patient was initially diagnosed as having AA amyloidosis, he did not have any chronic inflammatory disease and/or malignancy. The level of amyloid A protein (7.9 µg/mL) in sera was within the normal range (0–8.0 µg/mL). Therefore, we performed an immunostaining of the precursor protein (amino terminus of constant region: κ and λ light chains, and AA protein) using duodenal biopsy specimens for a precise diagnosis. Immunostaining was positive for the amino terminus of constant region of the λ light chain, and negative for the amino terminus of constant region of the κ light chain and AA protein. No plasma cell proliferation in the bone marrow was observed. We finally diagnosed this patient as having primary AL amyloidosis. It appears that a pathological diagnosis must be performed by immunostaining the precursor proteins with the permanganate digestion technique in tissue of patients with amyloidosis. There were no abnormalities in serum and urine immunoelectrophoresis at the time of renal biopsy in this patient. During the follow‐up period, after discharge, Bence Jones protein appeared in the urine, but not in the serum. It is necessary to observe patients with primary AL amyloidosis carefully to determine if they their condition will progress to multiple myeloma.

Comparison Between the Fixation of Peritoneal Dialysis Catheters to the Peritoneal Wall and the Conventional Placement Technique: Clinical Experience and Follow-Up of a New Implant Technique for Peritoneal Dialysis Catheters

Peritoneal dialysis (PD) catheters often become severely dislocated, which may lead to malfunction. With the aim of preventing this complication, we have developed a simple method of fixing the catheter downwards in the peritoneal cavity (fixation technique), a technique that does not require a laparoscope. Sixteen patients were implanted using the conventional placement technique and 25 patients were implanted using the fixation technique. The location of the catheter tip was classified from grade 1 (downward, normal) to 5 (dislocated). The frequency of dislocation (defined as the extended time and/or decrease in volume when draining the PD solution) was measured for both the fixation technique and conventional placement technique. There was a significant difference in grade between the fixation technique (2.72 ± 1.01) and conventional technique (3.92 ± 1.31). The time until first dislocation was significantly different between the fixation technique (59.3 ± 48.1 days) and conventional technique (8.8 ± 14.6 days). The time until any dislocation was significantly different between the fixation technique (69.2 ± 41.9 days) and conventional technique (12.9 ± 13.7 days). Complications were not significantly different between the fixation technique and conventional technique. The fixation technique appears to be simple, safe, and useful for preventing severe dislocation and for lengthening the time until dislocation in PD patients.

Usefulness of Change in Estimated Glomerular Filtration Rate as a Predicting Factor of Progression of Chronic Kidney Disease

Purpose. To explore factors contributing to chronic kidney disease (CKD) progression and change in estimated glomerular filtration rate over time (ΔeGFR) as a risk factor in predialysis patients under multidisciplinary managements. Methods. Among 113 CKD patients, eGFR, serum creatinine, total protein, albumin, urea nitrogen, uric acid, calcium, inorganic phosphate, total cholesterol, urinary creatinine, urinary protein (UP), hemoglobin A1c, hemoglobin, and hematocrit were analyzed. Results. ΔeGFR analysis in the first six months presented a positive slope (remission group) in 43 patients (38%) and a negative slope (no-remission group) in 70 patients (62%). Three-year dialysis-free rate was 89.4% in the remission group and 39.3% in the no-remission group, with a significant difference (P < 0.0001). To explore factors contributing to dialysis initiation by stepwise Cox regression, baseline eGFR (HR 0.706, P < 0.0001) and ΔeGFR in the first six months of treatment (HR 0.075, P < 0.0001) were identified. To investigate factors affecting remission and no remission by stepwise logistic regression, age (odds ratio 1.06, P = 0.018) and UP excretion (odds ratio 1.223, P = 0.045) were identified. Conclusion. Monitoring of ΔeGFR and UP is not only useful in suppressing CKD 3 progression, but also in deciding strategies to achieve remission in individual patients.