Efficacy of add-on therapy of aliskiren to an angiotensin II receptor blocker on renal outcomes in advanced-stage chronic kidney disease: a prospective, randomized, open-label study.

BACKGROUND: Combination therapy of aliskiren and an angiotensin II receptor blocker (ARB) has been reported to be effective for reducing the level of proteinuria. However, it remains unclear whether this combination therapy contributes to suppression of kidney disease progression. The aim of this study was to investigate the effect of aliskiren on hard renal endpoints, when added to an ARB, in patients with advanced chronic kidney disease (CKD). METHODS: The study design was a prospective, randomized open-label design. 83 CKD patients (52 men and 31 women) were enrolled and assigned randomly to an aliskiren add-on group (n = 42) or control group (n = 41). Entry criteria included elevated serum creatinine ≥ 1.5 mg/dl, urine protein excretion (≥ 1+ on urine dipstick test), and hypertension. All participants were treated with an ARB. The follow-up period was 12 months. 12 participants were withdrawn during the study period and the study was terminated in January 2012 as a consequence of the results of the interim analysis of the ALTITUDE study. RESULTS: Nine patients in the aliskiren group and seven patients in the control group started dialysis. Doubling of the serum creatinine level occurred in one patient in the control group. A Cox proportional hazards test showed that dual blockade of the renin-angiotensin-aldosterone system with aliskiren and ARB was not associated with improvement in hard renal endpoints. CONCLUSION: We conclude that aliskiren add-on therapy to an ARB may not give any benefit and, therefore, should not be recommended in CKD patients.

An autopsy case of clinically un-diagnosed autosomal recessive polycystic kidney disease in 77-year-old male.

Autosomal recessive polycystic kidney disease (ARPKD) is caused by genetic mutations of the gene encoding fibrocystin, and is characterized by the collecting duct cysts and congenital hepatic fibrosis. We report an autopsy-proven case of ARPKD in a 77-year-old male who presented with rapidly progressive renal and liver dysfunction. He had refused hemodialysis, and died 4 months later. At autopsy, both kidneys were enlarged with numerous small cysts throughout the cortex, which were revealed immunohistochemically to be the collecting ducts. Liver involvement was characterized by ductal plate malformation accompanied with portal fibrosis. The morphological appearances were compatible with ARPKD and the negative immunostaining for fibrocystin in the collecting ducts and bile ducts confirmed the diagnosis. ARPKD is known to occur in the neonatal period or in infancy with a high mortality rate. Although some patients who survive infancy are expected to live longer into young adulthood, most patients with ARPKD die of renal and hepatic failure in their childhood. The present case is extremely exceptional, in that no clinical symptoms suggestive of ARPKD were noticed until old age, and suggests that the disease spectrum of ARPKD is variable, and that a slowly progressive form of ARPKD may not be diagnosed until old age.

[Case of MMF monotherapy for membranous nephropathy].

We report the case of a 58-year-old male patient who visited our hospital for the management of edema and proteinuria. He was diagnosed as having nephrotic syndrome, with serum total protein and albumin levels of 4.6 g/dL and 2.1 g/dL, respectively, and a urinary protein excretion level of 6.0 g/day. A percutaneous renal biopsy showed features of membranous glomerulonephritis, with capillary-wall granular deposits of IgG and C3 on immunofluorescence and subepithelial immune complex deposits on electron microscopy. No other secondary cause of membranous glomerulopathy was found even after extensive investigations. The patient was started on mycophenolate mofetil (MMF) monotherapy (1,500 mg/day), and 18 months after the start of this therapy, the proteinuria decreased to 0.5 g/day, with return to a normal serum albumin level. No digestive symptoms, kidney function worsening or increase in blood pressure were noted during treatment. These findings suggest that MMF monotherapy is effective and safe for the treatment of membranous nephropathy.

A case of Mikulicz's disease complicated with severe interstitial nephritis associated with IgG4.

A 48-year-old woman who had bilateral swelling in the eyelids and submandibular region was admitted. Clinical findings suggested that her renal function had deteriorated. Laboratory data showed renal insufficiency (2.52 mg/dl), hypergammaglobulinemia (IgG 3,729 mg/dl, IgA 124 mg/dl, IgM 73 mg/dl). Gallium-67 scintigram indicated abnormal uptake in bilateral lacrimal glands, submandibular glands, and kidneys. A diagnosis of Mikulicz's disease and interstitial nephritis was made, since biopsy specimens of her lacrimal gland and minor salivary gland showed diffuse infiltration of lymphocytes. In addition, renal biopsy specimens showed diffuse severe interstitial infiltration of IgG4-positive mononuclear cells. Symptoms and laboratory data normalized in response to methylprednisolone semi-pulse therapy and prednisolone 50 mg/day. Mikulicz's disease was recently reported to be IgG4 associated disease. In our case, Mikulicz's disease complicated with diffuse severe interstitial nephritis was successfully treated by corticosteroid. The present case supports the hypothesis that IgG4-related autoimmune disease could be causes of Mikulicz's disease and interstitial nephritis.

[Effects of steroid therapy on membranous nephropathy].

BACKGROUND: Although membranous nephropathy is a common cause of nephrotic syndrome in adults, its treatment remains under debate. METHODS: To clarify the effects of steroid therapy, the data of 51 Japanese adult patients with idiopathic membranous nephropathy who received treatment at our department were analyzed retrospectively. We divided the patients with nephrotic syndrome and a serum creatinine level <1.7 mg/dL, into two groups: the steroid therapy group (n=20) and the non-steroid therapy group (n=7), and compared the clinical characteristics between the two groups. RESULTS: Significantly decreased proteinuria levels (p<0.05) after 2 and 5 years were observed in the steroid therapy group as compared to the non-steroid therapy group. There was no significant difference in the serum creatinine levels after 2 and 5 years between the steroid therapy group and the non-steroid therapy group. CONCLUSION: Steroid therapy in idiopathic membranous nephropathy showed good efficacy in patients with nephrotic syndrome.

Characteristics of patients on hemodialysis therapy for more than 30 years.

Since its experimental introduction in 1960, hemodialysis has become a widely performed and relatively safe procedure. Therapeutic strategies have been developed, and the numbers of long-term survivors of hemodialysis therapy have been increasing. Hemodialysis therapy was introduced at Sangenjaya Hospital in October 1970, and the 16 patients who have survived for more than 30 years on hemodialysis therapy since its introduction at the hospital were enrolled in this study to investigate the characteristics of long-term hemodialysis patients. For comparison, 50 patients on hemodialysis for less than 30 years were also studied (21 patients with <10 years hemodialysis, 13 with 10-20 years hemodialysis and 16 with 20-30 years hemodialysis). Background information (age, gender, and cause of renal disease), dialysis dose (single pool [sp.] Kt/V), mineral metabolism (serum phosphate), anemia management (serum hemoglobin), and nutrition (serum albumin and reduced interdialytic weight gain) were assessed. Hemodialysis was instituted at 28.7 +/- 6.4 years of age. The primary cause of end-stage renal disease was chronic glomerulonephritis in all of the patients except one, and in that patient it was polycystic kidney disease. As an index of the dialysis dose, sp. Kt/V was 1.2 +/- 0.11. As an index of mineral metabolism, serum phosphate was 5.4 +/- 0.9 mg/dL. As an index of anemia management, serum hemoglobin was 10.2 +/- 1.2 g/dL. As indexes of nutrition, serum albumin was 4.0 +/- 0.2 g/dL and interdialytic weight gain was 4.43 +/- 1.36%. The sp. Kt/V-value, serum phosphate, serum hemoglobin and interdialytic weight gain did not differ between the four different hemodialysis duration groups. Serum albumin was lower in the >30 group (4.0 +/- 0.2 g/dL) than in the <10 group (4.2 +/- 0.3 g/dL) (P = 0.046). As the duration of hemodialysis has increased, the age at hemodialysis induction has become younger. The cause of the renal failure was chronic glomerulonephritis in most of the cases. None had diabetic nephropathy. Improvement of the prognosis of patients with diabetic nephropathy is required. Most of the indexes of these patients nearly satisfied the recommended values.

Abscisic acid related compounds and lignans in prunes (Prunus domestica L.) and their oxygen radical absorbance capacity (ORAC).

Four new abscisic acid related compounds (1-4), together with (+)-abscisic acid (5), (+)-beta-D-glucopyranosyl abscisate (6), (6S,9R)-roseoside (7), and two lignan glucosides ((+)-pinoresinol mono-beta-D-glucopyranoside (8) and 3-(beta-D-glucopyranosyloxymethyl)-2- (4-hydroxy-3-methoxyphenyl)-5-(3-hydroxypropyl)-7-methoxy-(2R,3S)-dihydrobenzofuran (9)) were isolated from the antioxidative ethanol extract of prunes (Prunus domestica L.). The structures of 1-4 were elucidated on the basis of NMR and MS spectrometric data to be rel-5-(3S,8S-dihydroxy-1R,5S-dimethyl-7-oxa-6-oxobicyclo[3,2,1]oct-8-yl)-3-methyl-2Z,4E-pentadienoic acid (1), rel-5-(3S,8S-dihydroxy-1R,5S-dimethyl-7-oxa-6-oxobicyclo[3,2,1]oct-8-yl)-3-methyl-2Z,4E-pentadienoic acid 3'-O-beta-d-glucopyranoside (2), rel-5-(1R,5S-dimethyl-3R,4R,8S-trihydroxy-7-oxa-6-oxobicyclo[3,2,1]oct-8-yl)-3-methyl-2Z,4E-pentadienoic acid (3), and rel-5-(1R,5S-dimethyl-3R,4R,8S-trihydroxy-7-oxabicyclo[3,2,1]- oct-8-yl)-3-methyl-2Z,4E-pentadienoic acid (4). The antioxidant activities of these isolated compounds were evaluated on the basis of oxygen radical absorbance capacity (ORAC). The ORAC values of abscisic acid related compounds (1-7) were very low. Two lignans (8 and 9) were more effective antioxidants whose ORAC values were 1.09 and 2.33 micromol of Trolox equiv/micromol, respectively.

Antioxidant properties of prunes (Prunus domestica L.) and their constituents.

Prunes contain large amounts of phenolics and show high antioxidant activity. The aim of this study is to clarify the contents of caffeoylquinic acid (CQA) isomers, and to estimate the contribution of these isomers to the antioxidant activity of prunes. Furthermore, structural elucidation and evaluation of antioxidant activity of prune components were also performed. CQA isomers in prunes were quantified by HPLC analysis, and it has become apparent that prunes contain relatively high amount of 4-O-caffeoylquinic acid. The contribution of CQA isomers to the antioxidant activity of prunes was revealed to be 28.4% on the basis of oxygen radical absorbance capacity (ORAC); hence, it was indicated that residual ORAC is dependent on unknown antioxidant components. Total 28 compounds were isolated and their structures were elucidated by NMR and MS analyses. Four abscisic acid related compounds, a chromanon, and a bipyrrole were novel. Each CQA isomer in prunes showed high antioxidant activities when measured by the oil stability index (OSI) method, O2- scavenging activity, and ORAC. Other isolated compounds such as hydroxycinnamic acids, benzoic acids, coumarins, lignans, and flavonoid showed high ORAC values. Furthermore, a novel chromanon indicated a remarkable synergistic effect on ORAC of CQA isomers.