Dietary acid intake and kidney disease progression in the elderly.

BACKGROUND/AIMS: Non-volatile acid is produced by metabolism of organic sulfur in dietary protein, and promotes kidney damage. We investigated the role of dietary acid load, in terms of net endogenous acid production (NEAP), in chronic kidney disease (CKD) progression. METHODS: 217 CKD patients on low-protein diet with a normal serum bicarbonate level were enrolled in this retrospective cohort study in Japan. The primary outcome was 25% decline in estimated glomerular filtration rate (eGFR) or start of dialysis. Their NEAP was measured every 3 months. The patients were categorized into four groups on the basis of quartiles of NEAP every 3 months. The groups were treated as time-dependent variables. RESULTS: The average age (SD) was 70.6 (7.1) years; eGFR 23.5 (14.2) ml/min/1.73 m(2). Analysis using extended Cox models for the NEAP groups adjusted for baseline characteristics (referring to group 1 showing the lowest NEAP) showed that high NEAP was associated with a high risk of CKD progression; group 2, adjusted hazard ratio (HR) 3.930 (95% confidence interval (CI) 1.914, 8.072); group 3, adjusted HR 4.740 (95% CI 2.196, 10.288); group 4, adjusted HR 4.303 (95% CI 2.103, 8.805). Logistic regression analysis adjusted for baseline characteristics showed that the occurrence of hypoalbuminemia or hyperkalemia was associated with low serum bicarbonate level and the presence of complications at baseline, but not with NEAP. CONCLUSION: In elderly CKD patients, our findings suggest that high NEAP is independently associated with CKD progression. The decrease in NEAP may be an effective kidney-protective therapy.

High serum bicarbonate level within the normal range prevents the progression of chronic kidney disease in elderly chronic kidney disease patients.

BACKGROUND: Metabolic acidosis leads to chronic kidney disease (CKD) progression. The guidelines recommend a lower limit of serum bicarbonate level, but no upper limit. For serum bicarbonate level to be clinically useful as a therapeutic target marker, it is necessary to investigate the target serum bicarbonate level within the normal range to prevent CKD progression. METHODS: One hundred and thirteen elderly CKD patients, whose serum bicarbonate level was controlled within the normal range, were enrolled in this retrospective cohort study in Ibaraki, Japan. Outcome was defined as a decrease of 25% or more in estimated glomerular filtration rate (eGFR) or starting dialysis. We used Cox proportional hazard models adjusted for patients' characteristics to examine the association between serum bicarbonate level and the outcome. RESULTS: Female patients were 36.3%: average age (SD), 70.4 (6.6) years; eGFR, 25.7 (13.6) ml/min/1.73 m(2); serum bicarbonate level, 27.4 (3.2) mEq/l. Patients with the lowest quartile of serum bicarbonate levels [23.4 (1.8) mEq/l] showed a high risk of CKD progression compared with patients with high serum bicarbonate levels [28.8 (2.3) mEq/l]: adjusted hazard ratio (HR), 3.511 (95% CI, 1.342-9.186). A 1 mEq/l increase in serum bicarbonate level was associated with a low risk of CKD progression: adjusted HR, 0.791 [95% confidence interval (CI), 0.684-0.914]. CONCLUSIONS: In elderly CKD patients, our findings suggest that serum bicarbonate level is independently associated with CKD progression, and that a high serum bicarbonate level is associated with a low risk of CKD progression. A high target serum bicarbonate level within the normal range may be effective for preventing CKD progression.

[Examination of activated charcoal preparations in chronic kidney disease: comparing Kremezin (K) and Merckmezin (M)].

BACKGROUND: Two activated charcoal preparations, Kremezin (K) and Merckmezin (M), are both available in Japan and derived from similar materials. However, their microstructures are distincty different, and possibly reflect differences in their properties of absorbance. To evaluate the difference between K and M, we investigated the effects of K and M on the clinical parameters related to uremia in pre-dialysis patients. METHODS: A prospective, randomized, open-label, two-arm, parallel-group comparative clinical trial was planned, as follows. After the 4-week observation period, twenty-two patients who were enrolled in this study were randomly distributed into two groups, K or M, for 8 weeks. RESULTS: There were no significant differences between the K and M groups in the characteristics of the patients. The rate of change of serum indoxyl sulfate was significantly reduced in the K group compared with the M group (p=0.002). Creatinine clearance was preserved in the K group, but decreased in the M group (p=0.045). CONCLUSIONS: K had more favorable effects in adsorbing uremic toxins and preserving renal function in the uremic patients than M.

Reversible brainstem hypertensive encephalopathy (RBHE): Clinicoradiologic dissociation.

We report two cases of reversible brainstem hypertensive encephalopathy (RBHE) with unusual magnetic resonance (MR) findings. Patient 1, an 85-year-old man without a history of hypertension, developed acute severe hypertension and mild consciousness disturbance as the only symptoms. Patient 2, a 46-year-old man with an untreated hypertension, presented with extremely high blood pressure and general fatigue, vertigo, and mild dysarthria as the initial manifestations. In these patients, fluid-attenuated inversion recovery (FLAIR) and T2-weighted MR images revealed diffuse hyperintensities in the brainstem. Diffusion-weighted imaging (DWI) findings were normal, and apparent diffusion coefficient (ADC) values were increased in the brainstem. The supratentorial regions were largely spared, and mildly diffuse hyperintensities were noted in the white matter. There were no accompanying changes in the occipital lobe and cerebellum. The lesions completely resolved after stabilization of blood pressure. The normal DWI findings and high ADC values were consistent with vasogenic edema due to severe hypertension. The characteristics of RBHE are a very high blood pressure, mild clinical and neurologic symptoms, rapidly improved MR findings after initial treatment with the control of hypertension, and a marked clinicoradiologic dissociation.

[Kidney disease improvement plan avoids dialysis for life].

Initially, chronic kidney disease (CKD) cases with no progression or remission are reported, those are experienced in our hospital and have a possibility relates to prevent dialysis through life. Considering the roadmap for treatment of CKD, misgivings of "clinical practice guidebook for diagnosis and treatment of CKD" are firstly noticed. In this guidebook, 24 hour urine collection method is almost ignored. We usually get very important various informations from this method. Moreover, it is necessary for practitioner and nephrologist to look education plan over again. For the spread of the CKD treatment, consultant and management fee is necessary, because the treatment takes a lot of time and is very complicated.

Pilot study in the identification of stability values for determining immediate and early loading of implants.

This pilot study assessed the impact of implant stability criteria on implant loading time. Insertion torque (IT) and baseline implant stability quotients (ISQ) from resonance frequency analysis were recorded for 41 tapered-screw implants placed in the mandibles of 20 patients. Immediate (IL), early (EL) (6 weeks postoperative), or delayed (DL) (12 weeks postoperative) prosthetic loading was performed based on results and study criteria. Postoperative ISQ values were also recorded at 6 time intervals for the IL and EL groups and after healing for the DL group. All implants were definitively restored after 6 weeks of provisionalization. There were no failures, complications, or stability differences based on loading time. At week 12 of follow-up, ISQ values were slightly higher for IL implants compared with EL implants. IL and EL implants showed significantly higher cumulative ISQ values compared with DL implants. High IT and baseline ISQ values in all groups corresponded to high implant survival. Postoperative ISQ values in the IL and EL groups were less certain indicators of implant survival because of fluctuations relative to baseline values. Small sample size and inequitable patient distribution across groups skewed results. More research is needed before definitive results can be drawn. IL and EL were safely performed within the IT and ISQ ranges in this study, but it is unknown whether EL criteria would have also sufficed for IL.

[Blood ionized calcium fraction in various serum albumin levels surveyed in non-dialysis patients].

Blood ionized calcium (iCa) fraction is affected by the serum albumin(Alb) level, even though this effect might not be appropriately estimated by the formulae proposed previously. To clarify a reasonable regimen for predicting iCa from serum total Ca (tCa), we investigated the relationship of blood iCa, tCa, and serum Alb levels through 124 samples from 116 non-dialysis patients requiring iCa measurement at the Nephrology Section of Toride Kyodo General Hospital. The patients comprised 61 males and 55 females with the mean age of 66.9 +/- 1.4 years, including 9 cases of hypercalcemia, 110 of normocalcemia, and 5 of hypocalcemia based on their iCa levels. Their background diseases were 25 cases of chronic glomerulonephritis, 17 of nephrotic syndrome, 40 of diabetes mellitus, 4 of collagen diseases, and 30 of others. Their mean serum Cr was 2.44 +/- 0.21 mg/dl, and 77 patients showed elevated Cr levels. Four adjustment formulae: one derived from Payne's, two from the proposal of K/DOQI Clinical Practice Guidelines, and a theoretical one based on the previous in vitro experiments, were compared with the non-adjusted value (tCa itself) with respect to their suitability for estimating iCa. The correlation coefficient of tCa with iCa was higher than the values adjusted by the above four formulae. The difference of iCa from tCa divided by eight, which concisely predicted iCa based on the assumption that half the serum Ca is bound to protein, was less than 1/8th of the other adjusted Ca levels. Hence none of the adjusted Ca by the above formulae was superior to nonadjusted tCa from the point of estimating the iCa level. Moreover, the sensitivity for predicting hypocalcemia was the highest in tCa, even though its specificity was lower than the other adjusted values. In conclusion, no adjustment formula is required to predict ionized Ca from tCa, and to screen hypo- or hypercalcemia.

[Flow cytometric analysis of mesothelial cells in peritoneal dialysis effluent].

According to recent reports, deformity and size of mesothelial cells reflect mesothelial condition. We applied flow cytometry (FCM) to the analyzation of mesothelial cells in peritoneal dialysis effluent (PDE) and the relationship between the period of peritoneal dialysis (PD) and peritoneal function. Eighteen patients treated for two to 89 months by PD were selected. Their dialysate: plasma creatinine ratio (D/P creatinine)was 0.67 +/- 0.086 (0.53 to 0.87). Overnight PDE was drained and centrifuged. The cell population of peritoneal cells identified by anti-cytokeratin, CD14 and 45 antibodies was studied by FCM. Cytokeratin positive cells were identified as mesothelial cells, distinct from macrophages, granulocytes or lymphocytes. The forward scatter (FSC) of cytokeratin positive cells, fluorescence intensity of cytokeratin and percentage of cytokeratin-positive cells in PDE were 395.6 +/- 55.5 (298.31 to 527.72), 333.9 +/- 272.9 (67.55 to 1,071.95), and 6.75 +/- 6.1% (0.44 to 21.14), respectively. There was a positive correlation between D/P creatinine and FSC, and a negative correlation between D/P creatinine and cytokeratin fluorescence intensity or the percentage of cytokeratin positive cells. However, there was no correlation between the period of PD and FSC, cytokeratin fluorescence intensity or the percentage of cytokeratin-positive cells. It was suggested that the alteration of mesothelial cells is not necessarily influenced by the period of PD, but influences peritoneal function. It was found that the analysis of cell population by FCM reflects the morphological and functional changes in the peritoneum of patients on PD.

[Estimation of glomerular filtration rate by inulin clearance: comparison with creatinine clearance].

Inulin clearance (Cin) is widely believed to be the gold standard of the glomerular filtration rate (GFR). However, in Japan, Cin has not been officially recognized by the Ministry of Health, Labour and Welfare of Japan for clinical use. Creatinine clearance (Ccr) has been used to estimate the renal function of patients, but there have been many studies in which Ccr estimates were GFR falsely high because the metabolism and tubular excretion of creatinine widely varied according to the pathophysiological state of the patient. In the present study, we determined Cin and Ccr simultaneously in 116 adult patients with renal diseases and diabetic mellitus. The clearance study was performed by the modified Wesson's method. The inulin preparation was FFI-1010 (Fuji Yakuhin Co. Ltd.). Inulin in serum and urine was determined by the newly devised enzymatic assay (Toyobo Co. Ltd.), which is specific for inulin. The mean Cin was 35.0 +/- 14.4 ml/min/1.73 m2. The mean Ccr(the enzyme assay) was 63.6 +/- 24.1 ml/min/1.73 m2 and that of the kinetic Jaffe assay was 55.3 +/- 19.3 ml/min/1.73 m2. Mean Ccr/Cin was 1.93 +/- 0.73, 1.69 +/- 0.62, respectively. This ratio was significantly different(p < 0.05) in the degree of reduction of Cin, with values of 2.07 +/- 0.82 (Cin < 40 ml/min/1.73 m2) and 1.64 +/- 0.32(40 < Cin < 80 ml/min/1.73 m2), respectively. Only 8 patients were classified into the same degree of reduced renal function (the Guideline of Japanese Society of Nephrology). The findings of this study suggest that the GFR determined by Ccr could misjudge the renal function of patient and delay the administration of proper treatment of the patient. Introduction of Cin into the clinical field is necessary to avoid this delay.

Renoprotective effect of losartan in comparison to amlodipine in patients with chronic kidney disease and hypertension--a report of the Japanese Losartan Therapy Intended for the Global Renal Protection in Hypertensive Patients (JLIGHT) study.

A 12-month, multicenter (57 clinical institutions), randomized, open-labeled trial was undertaken to compare the efficacy of the angiotensin II receptor antagonist losartan and the calcium channel blocker amlodipine in patients with proteinuric chronic kidney disease (CKD) and hypertension. A total of 117 patients (79, chronic glomerulonephritis; 14, diabetic nephropathy; 24, other CKD) were randomly allocated into two treatment groups. Losartan and amlodipine exerted the same efficacy for blood pressure (BP) control; however, losartan significantly reduced the 24-h urinary protein excretion at months 3, 6, and 12, with the reduction of 20.7%, 35.2%, 35.8%, whereas amlodipine did not change the amount of proteinuria over the 12-month study period. When patients were stratified into groups according to the level of BP control at 3 months, the reduction in urinary protein excretion by losartan was evident in the group for which a BP of <140/90 mmHg was achieved, as well as in the group for which the goal BP (<130/85 mmHg) for treatment of CKD was not achieved. When patients were stratified according to baseline urinary protein excretion, those with > or = 2 g/day showed a reduction in proteinuria by losartan of 23.3%, 39.4%, and 47.9% at months 3, 6, and 12, and those with <2 g/day showed a reduction of 18.5% and 31.2% at months 3 and 6, respectively. No fatal adverse events were experienced in either drug group. We conclude that losartan reduced proteinuria in patients with CKD and hypertension. This positive effect may contribute to the renal protective benefit of losartan, and is beyond the magnitude of BP control.

Survival-determining factors in patients with neurologic impairments who received home health care in Japan.

BACKGROUND: The Japanese have become the longest-lived nation population in the world, and numbers of elderly who require medical and nursing care are increasing. The capacity of nursing homes and nursing institutions is sharply limited in Japan; further, as a group, elderly Japanese patients prefer home care to institutional care. For these reasons, the home health care system in Japan has been increasingly important. OBJECTIVE: We sought to identify factors determining long-term survival in Japanese patients receiving home health care for neurologic disorders. PATIENTS AND METHODS: We retrospectively evaluated 180 patients with neurologic disease, who received home health care conducted by our hospital between 1992 and 2001. Factors considered were age; gender; illnesses; prognosis; follow-up period; activities of daily living (ADL); behavioral, cognitive, and communicative functions; swallowing function; feeding method; serum nutritional values (total protein, albumin, and total cholesterol); hemoglobin concentration; and social care services provided at home. RESULTS: Variables affecting long-term survival in 180 patients with neurologic disease were age (P<0.0002) and severity of dysphagia (P<0.04) by Cox's proportional hazard test. CONCLUSION: Maintenance of swallowing function and adequate nutrition through a variety of feeding methods that can be provided by a home health care program are important for long-term survival of patients with stroke and also that of patients with other neurologic diseases.

Polymyalgia rheumatica (PMR): clinical, laboratory, and immunofluorescence studies in 13 patients.

Thirteen elderly patients with polymyalgia rheumatica (PMR) are presented. The clinical and laboratory findings suggest that many progressive symptoms are due to the non-specific inflammatory changes in various organs of the body, especially in muscles and joints. An immunofluorescence study of muscle biopsy specimens revealed IgG, IgA, and fibrinogen deposits in the perifascicular area of the perimysium. This finding suggests that immune complexes play a role in the pathogenesis of this condition and that the pathophysiology of PMR is an interstitial inflammatory process. We think that the inflammatory findings affecting the interstitial tissue of muscles in the immunofluorescence study are relatively specific to PMR, and will be affected by steroid treatment.

[Dilution index as a candidate parameter reflecting dialysis dose in combined peritoneal dialysis and hemodialysis therapy].

Combined peritoneal dialysis and hemodialysis therapy (combined therapy) is recognized as an effective alternate in peritoneal dialysis patients with insufficient water and solute removal, but there is no appropriate index for dialysis dose, as two distinct dialysis procedures are utilized in the same patient. Among several candidate parameters, the dilution index proposed and defined by Yamada, et al as the solute generation rate divided by the distribution volume and time-averaged concentration of the solute might be applicable, because it is unrelated to the method of solute removal. Among 11 patients undergoing combined therapy at Toride Kyodo General Hospital, six patients who had transferred from peritoneal dialysis alone to combined therapy were recruited. All patients received peritoneal dialysis therapy for five consecutive days followed by one day off dialysis before a hemodialysis session on the seventh day every week. Total weekly creatinine and urea removal by residual renal function, peritoneal dialysis, and hemodialysis were measured, and their solute removal on the last(5th) day under peritoneal dialysis was ascertained and correlated with the averaged daily removal of solutes. Hence the value of solute removal obtained on the last day under peritoneal dialysis was multiplied seven times and defined as the weekly solute generation. The distribution volumes of creatinine and urea were defined as 58% of body weight. The time-averaged concentration was obtained from the mean level of a solute before and after a hemodialysis session. During the period followed solely by peritoneal dialysis, the dilution indices for creatinine and urea were 1.22 +/- 0.14 and 1.85 +/- 0.14, respectively. The dilution index after transferring to combined therapy, calculated by the above-mentioned method was increased to 1.72 +/- 0.29 and 2.28 +/- 0.31, respectively. Hence the dilution index may be useful for reflecting dialysis doses even in combined therapy.

[Protein restriction diet in the predialysis period does not decrease survival of uremic patients after the introduction of hemodialysis therapy].

To clarify whether a protein restriction diet in the pre-dialysis period affects the overall prognosis after initiating hemodialysis therapy, we compared the survival between patients with and without a protein restriction diet. Among 310 patients in whom hemodialysis was introduced between 1997 and 2000 at Toride Kyodo General Hospital, two hundred and ten patients were excluded due to an insufficient observation period (< 6 months) or the lack of records estimating their protein intake. One hundred patients were finally included in this study. All of these patients were followed at the hospital with their estimated protein intake using repeated (three times or more) urea nitrogen appearance in 24-hour collected urine samples over 6 months period to the initiation of dialysis therapy. The patients were divided into a protein restriction diet group (PRD 61 cases) and non-restriction diet group (NRD 39 cases), according to their estimated protein intake less or above 0.7 g/kg/day. Among the patient profile items, gender, cause of renal failure, and serum albumin did not differ between the two groups, but the age was higher in NRD (p < 0.01). Nineteen patients (PRD 8, NRD 11 cases) died during the observation period (0-65 months). On the analysis of their survival, PRD showed a better survival ratio by the Kaplan-Meier method (p < 0.01). Among the variables examined by Cox's proportional hazard test, age, PRD, and their combination showed significant risk ratios (1.06, 0.30, and 0.39 respectively) on survival after the initiation of hemodialysis. Hence a protein restriction diet in the pre-dialysis period does not deteriorate the prognosis even after the initiation of hemodialysis therapy.

Pseudoaldosteronism caused by combined administration of cilostazol and glycyrrhizin.

We report a case of obvious pseudoaldosteronism which occurred after the additional administration of cilostazol against arteriosclerosis obliterans (ASO) for bilateral legs in a 65 year-old man patient who had safely received glycyrrhizin for the previous ten years. Serum potassium level of the patient had been kept above 4 mEq/L until initiating cilostazol in November, 2006, then gradually decreased to 2.5 mEq/L for the following seven months. Both plasma renin activity and aldosterone were suppressed under co-administration of the angiotensin converting enzyme inhibitor, imidapril and the angiotensin II receptor blocker, olmesartan, both of which had been prescribed for longer than a year. Urinary potassium excretion was accelerated even in the critical level of hypokalemia. Because other drugs and supplements had not been changed at least for a year, pseudoaldosteronism caused by the combination of glycyrrhizin and another triggering factor, possibly cilostazol was highly suspected. By discontinuation of glycyrrhizin, potassium supplement, and the additional administration of the aldosterone blocker, spironolactone, the serum potassium level returned to the normal level two weeks later, even though cilostazol had been continued to avoid progression in his ASO. This is the first report of a case exhibiting pseudoaldosteronism induced by the interaction of glycyrrhizin with cilostazol, not by glycyrrhizin alone.

Diet therapy in diabetic nephropathy.

Although protein restriction has been suggested as a mainstay of therapy for patients with diabetic nephropathy, controversy exists regarding the exact dietary prescription and stage of disease for implementation. This chapter reviews the pathophysiology and stages of diabetic nephropathy, clinical studies of dietary therapy in diabetic nephropathy, and provides a framework for using diet in the treatment of diabetic renal disease.

Fulminant pneumatosis intestinalis in a patient with diabetes mellitus and minimal change nephrotic syndrome.

We report a case of pneumatosis intestinalis in a diabetic patient with minimal change nephrotic syndrome, receiving immunosuppressive drugs and an alpha-glucosidase inhibitor. The patient was a 72-year-old female, who suffered from right lower abdominal pain. Abdominal CT showed massive air in the intestinal wall, compatible with pneumatosis intestinalis. Her general condition rapidly deteriorated with systemic inflammatory response syndrome. The patient had received respiratory support for a week, along with antimicrobial therapy and continuous hemofiltration, and then recovered. Even though pneumatosis intestinalis is generally recognized as a mild disease, careful attention is necessary when it follows a serious condition.

Interim evidence of the renoprotective effect of the angiotensin II receptor antagonist losartan versus the calcium channel blocker amlodipine in patients with chronic kidney disease and hypertension: a report of the Japanese Losartan Therapy Intended for Global Renal Protection in Hypertensive Patients (JLIGHT) Study.

BACKGROUND: Insufficiency of renal function and high blood pressure influence each other and eventually result in life-threatening endstage renal disease. It has been proposed that proteinuria per se is a determinant of the progression of chronic kidney disease (CKD). The therapeutic strategy for patients with proteinuric CKD and hypertension should therefore be targeted with a view not merely toward blood pressure reduction but also toward renoprotection. METHODS: We examined the effect of the angiotensin (AT)1 receptor antagonist losartan and the calcium channel blocker amlodipine, throughout a period of 12 months, on reduction of blood pressure and renoprotection. This was done by assessing amounts of urinary protein excretion, serum creatinine (SCr), and creatinine clearance (CCr) in patients with hypertension (systolic blood pressure [SBP] > or = 140 mmHg or diastolic blood pressure [DBP] > or = 90 mmHg) and CKD (male, body weight [BW] > or = 60 kg: 1.5 < or = SCr < 3.0 mg/dl; female or male BW < 60 kg: 1.3 < or = SCr < 3.0 mg/dl), manifesting proteinuria of 0.5 g or more/day. Losartan was administered once daily at doses of 25 to 100 mg/day, and amlodipine was given once daily at 2.5 to 5 mg/day. No antihypertensive combination therapy was allowed during the first 3-month period. RESULTS: A 3-month interim analysis revealed that, despite there being no difference in blood pressure between the two groups, there was a significant reduction in 24-h urinary protein excretion in the losartan group ( n = 43), but there was no change in the amlodipine group ( n = 43). Analysis of stratified subgroups with proteinuria of 2 g or more/day and less than 2 g/day showed that losartan lowered proteinuria by approximately 24% in both subgroups, while amlodipine lowered proteinuria by 10%, but only in the subgroup of less than 2 g/day (NS). SCr and CCr did not change throughout the period of 3 months in either group. No severe or fatal adverse event was experienced in either group during the study period. CONCLUSIONS: Losartan appeared to be efficacious for renoprotection in patients with proteinuric CKD and hypertension, with the mechanism being independent of its antihypertensive action.