Search

Worldwide, the number of patients with diabetes is increasing. Adults with diabetes have a two- to threefold increased risk of heart attack and stroke, and diabetic nephropathy is a leading cause of end-stage renal failure. Salt sensitivity of blood pressure is reported to be elevated in patients with diabetes. Hyperinsulinemia, hyperglycemia, and an activated sympathetic nervous system play key roles in the genesis of salt-sensitive blood pressure in individuals who are obese and/or have type 2 diabetes. In this review, I summarize previous research performed to improve our understanding of the relationship between salt and hypertension in diabetic patients. [ABSTRACT FROM AUTHOR]

Background: Several studies have demonstrated that spironolactone has an anti-albuminuric property in diabetic nephropathy. As an adverse event, spironolactone often induces the elevation of creatinine levels with hypotension and hyperkalemia. Therefore, we aimed to evaluate the efficacy and safety of spironolactone in Japanese patients with type 2 diabetes treated with either angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. Methods: Fifty-two Japanese patients with diabetic nephropathy and albuminuria (100 mg/gCr-2000 mg/gCr) treated with renin-angiotensin system (RAS) blockade were enrolled in a prospective, randomized, open-label study. The patients were subjected to add-on treatment with spironolactone 25 mg once daily and compared with matched controls for 8 weeks. The primary outcome was a reduction in the rate of albuminuria at 8 weeks compared with the baseline value. This study was registered with UMIN Clinical Trials Registry (000008016). Results: Albuminuria was reduced by 33 % (95 % confidence interval: 22-54; P = 0.0002) at 8 weeks with spironolactone. In the spironolactone group, blood pressure tended to lower and the estimated glomerular filtration rate (eGFR) was significantly decreased compared to those in the control group. When adjusted by systolic blood pressure and eGFR, spironolactone treatment still showed a significant effect on albuminuria reduction in a linear mixed model (coefficient ± standard error; 514.4 ± 137.6 mg/gCr, P < 0.0005). No patient was excluded from the study because of hyperkalemia. Conclusions: Spironolactone reduced albuminuria along with conventional RAS inhibitors in patients with diabetic nephropathy. Our study suggests that spironolactone exerts anti-albuminuric effects independent of systemic hemodynamic alterations. [ABSTRACT FROM AUTHOR]

Background: Because oral nonsteroidal anti-inflammatory drugs (NSAIDs) have adverse effects on kidney function, patients with kidney diseases are administered these drugs as transdermal patches. Little is known about the effects of NSAID patches on renal function. We therefore assessed the effects of topical loxoprofen sodium on kidney function in type 2 diabetic patients with overt nephropathy. Methods: Twenty patients with type 2 diabetes and overt proteinuria and with knee and/or low back pain were treated with skin patches containing 100 mg loxoprofen on the knee or back for 24 h per day for 5 consecutive days. The degree of pain was assessed using a visual analogue scale (VAS). Blood and 24-h urine samples were obtained at baseline and at the end of the study. Glomerular filtration rate (GFR) was estimated from serum creatinine and cystatin C concentrations. Results: The 20 patients consisted of 11 males and 9 females, of mean age 61.6 ± 13.9 years. Loxoprofen-containing patches significantly reduced VAS pain without affecting blood pressure, GFR or urinary prostaglandin E concentration. Serum concentrations of loxoprofen and its active trans-OH metabolite did not correlate with GFR. Conclusions: Loxoprofen-containing patches do not affect renal function in type 2 diabetic patients with overt nephropathy over a short-term period. Long-term studies are needed to clarify the safety of loxoprofen-containing patches in patients with chronic kidney diseases. [ABSTRACT FROM AUTHOR]

Background: A recent genome-wide association study for diabetic nephropathy in European type 1 diabetes identified 3 candidate loci for diabetic nephropathy. In this study, we examined the association of the 3 single nucleotide polymorphism (SNP) loci with susceptibility to diabetic nephropathy in Japanese subjects with type 2 diabetes. Methods: We genotyped 3 SNPs, rs7583877 in AFF3, rs12437854 in the RGMA- MCTP2 locus and rs7588550 in ERBB4, for 2,300 Japanese patients with type 2 diabetes [initial study, 1,055 nephropathy cases with overt proteinuria or with end-stage renal disease (ESRD) and 1,245 control patients with normoalbuminuria]. The association of these SNPs with diabetic nephropathy was examined by using a logistic regression analysis. Results: We observed a significant association of rs7588550 in ERBB4 with diabetic nephropathy in the Japanese patients with type 2 diabetes, although the effect direction was not consistent with that in the European study [ p = 0.0126, odds ratio (OR) = 0.79, 95 % confidence interval (CI): 0.65–0.95]. We further examined the association of rs7588550 with diabetic nephropathy in an independent Japanese cohort (596 nephropathy cases and 311 controls) and observed the same trend of the association with the initial study. We did not observe any association of the remaining 2 SNP loci with diabetic nephropathy in the present Japanese sample. Conclusion: The association of SNP loci derived from GWAS in European type 1 diabetes with diabetic nephropathy was not replicated in the Japanese patients with type 2 diabetes, although the ERBB4 locus may have some effect also in Japanese type 2 diabetes. [ABSTRACT FROM AUTHOR]

Autophagy meaning 'self-eating' in Greek, is a large-scale mechanism of intracellular degradation that seeks to maintain homeostasis in cells of all eukaryotes, from yeast to humans. Over the past several decades, autophagy research has actively proceeded both at home and abroad. As a result, studies have reported the physiological role of autophagy in different organs of mammals and of the role that impairment of its activation plays in the development of age-related diseases, abnormal glucose-lipid metabolism, and neurodegenerative disorders. Currently, new therapies targeting the regulation of activation of autophagy are anticipated, and research is continuing. In recent years, the role of autophagy in the kidneys has gradually been elucidated, and reports are indicating an association between autophagy and the development of various kidney diseases. This paper reviews the molecular mechanisms regulating autophagy and discusses new findings from autophagy research on the kidney and issues that have yet to be resolved. [ABSTRACT FROM AUTHOR]

Background: Sirtuin is a member of the nicotinamide adenine dinucleotide (NAD)-dependent deacetylases, and has been reported to play a pivotal role in energy expenditure, mitochondrial function and pathogenesis of metabolic diseases, including aging kidneys. In this study, we focused on the genes encoding sirtuin families, and examined the association between single nucleotide polymorphisms (SNPs) within genes encoding sirtuin families and diabetic nephropathy. Methods: We examined 52 SNPs within the SIRT genes (11 in SIRT1, 7 in SIRT2, 14 in SIRT3, 7 in SIRT4, 9 in SIRT5, and 4 in SIRT6) in 3 independent Japanese populations with type 2 diabetes (study 1: 747 cases (overt proteinuria), 557 controls; study 2: 455 cases (overt proteinuria) and 965 controls; study 3: 300 cases (end-stage renal disease) and 218 controls). The associations between these SNPs were analyzed by the Cochran-Armitage trend test, and results of the 3 studies were combined with a meta-analysis. We further examined an independent cohort (195 proteinuria cases and 264 controls) for validation of the original association. Results: We identified 4 SNPs in SIRT1 that were nominally associated with diabetic nephropathy ( P < 0.05), and subsequent haplotype analysis revealed that a haplotype consisting of the 11 SNPs within SIRT1 locus had a stronger association ( P = 0.0028). Conclusion: These results indicate that SIRT1 may play a role in susceptibility to diabetic nephropathy in Japanese subjects with type 2 diabetes. [ABSTRACT FROM AUTHOR]

The importance of sleep disturbance and depression in patients with type 2 diabetes is unclear. Our objective was to evaluate their effects on the quality of life (QOL) of patients with type 2 diabetes. For the study, 270 patients were recruited from the Shiga Prospective Observational Follow-up Study for Diabetic Complications. Depressive symptoms, sleep disturbance, and QOL were assessed by use of the Zung Self-Rating Depression Scale (SDS), the Pittsburgh Sleep Quality Index (PSQI), and SF-8, respectively, after evaluation of their metabolic control and complications. Furthermore, 141 patients were recruited to repeat the same study after 6-12 (mean 7.3) months. Significant correlations were found among sleep disturbance, depression, and QOL in patients with type 2 diabetes. Patients undergoing insulin therapy had significantly higher SDS scores, meaning more depressive symptoms, than those not undergoing insulin therapy. Patients with painful neuropathy had higher PSQI and SDS scores and lower physical component of the QOL score than patients without painful neuropathy. In the follow-up observation it was found that the presence of neuropathy and elevated HbA1c level were predictors of increasing PSQI score and SDS score, respectively. It was found that the presence of painful neuropathy was a risk factor for sleep disturbance for type 2 diabetic patients. Sleep disturbance and depressive symptoms correlated significantly with the QOL scores of patients with type 2 diabetes, suggesting the importance of these indices for better management of diabetic patients. [ABSTRACT FROM AUTHOR]

Background: Interleukin-18 (IL-18), a pro-inflammatory cytokine, is a predictor of cardiovascular and renal disease in diabetic patients. Postprandial hyperglycemia is one of the important factors contributing to an increase in the circulating pro-inflammatory cytokine levels. This study investigated the effect of miglitol, an α-glucosidase inhibitor, on postprandial hyperglycemia and IL-18 levels in diabetic patients with nephropathy. Methods: Fifteen Japanese diabetic patients with persistent proteinuria and preserved renal function were recruited. The patients received 50 mg miglitol thrice daily after the baseline examinations and were followed up for 12 weeks. A meal tolerance test was performed on eight patients at baseline and week 12. The fasting miglitol concentration was measured in seven patients just before the meal tolerance test. Results: There were no changes in the body weight, blood pressure, liver and renal function, and proteinuria from baseline to week 12. However, the levels of glycated hemoglobin and interleukin 18 significantly decreased from baseline to week 12. During the meal tolerance test, plasma glucose was significantly decreased 60 min after treatment with miglitol, whereas the serum concentration of insulin was not changed. Fasting and postprandial levels of IL-18 were significantly decreased from baseline to week 12. Serum miglitol concentrations showed a significantly negative correlation with eGFR ( r = −0.82, p = 0.02). However, the serum miglitol concentrations did not changed during the course of this study. Conclusion: Miglitol improved postprandial hyperglycemia and reduced serum IL-18 levels in patients with stage 3 diabetic nephropathy. Miglitol may therefore prevent atherosclerotic diseases and diabetic micro-vascular complications through decreasing glucose swings and/or the circulating IL-18 level. [ABSTRACT FROM AUTHOR]

The inhibition of the renin-angiotensin system in the diabetic condition was reported to enhance the sodium sensitivity of blood pressure. In patients with sodium-sensitive hypertension, high sodium intake reduces the nocturnal fall in blood pressure. Therefore, we examined the effects of the amount of sodium intake or diuretics in patients with diabetes treated with an angiotensin receptor blocker. We recruited 32 Japanese type 2 diabetic patients with base line blood pressure ≥130/80 mmHg and treated with valsartan (80 mg daily). At baseline, 24-h ambulatory blood pressure and 24-h urinary excretion of sodium were measured. The patients were then randomly assigned to take either combination therapy with 50 mg of losartan plus 12.5 mg of hydrochlorothiazide or monotherapy with 160 mg of valsartan for 24 weeks. At baseline, 22 of 32 (69%) patients were classified as non-dippers, and the night/day ratio of mean arterial pressure was significantly correlated with 24-h urinary sodium excretion. The combination therapy resulted in a significantly higher fall than the monotherapy in 24-h mean, daytime, night-time and morning blood pressures. The night/day ratio of mean arterial pressure was significantly reduced from the baseline at the end of the study in the combination therapy group, but not in the monotherapy group. In non-dipper patients, the diminished nocturnal fall in blood pressure was restored by the combination therapy. Excessive intake of salt causes non-dipping and diuretics restored nocturnal BP fall in type 2 diabetic patients treated with angiotensin 2 receptor blockers. [ABSTRACT FROM AUTHOR]

To elucidate the role of the renin–angiotensin system (RAS) in diabetic nephropathy, we examined the association between diabetic nephropathy in a large cohort of Japanese type 2 diabetic patients and polymorphisms within the genes that encode angiotensin-converting enzyme ( ACE), angiotensinogen ( AGT) and angiotensin II receptor type 1 ( AGTR1). Single nucleotide polymorphisms (SNPs) within these genes were genotyped using invader assay in 747 nephropathy cases and 557 control subjects. Eight SNPs within the ACE gene were significantly associated with diabetic nephropathy ( P<0.05), including five SNPs in almost complete linkage disequilibrium to the insertion/deletion polymorphism in the 16th intron ( P=0.01, odds ratio =1.34, 95% CI 1.07–1.69). Three SNPs within the AGT, including M235T and one SNP in the AGTR1, were also significantly associated with nephropathy (M235T P=0.01, odds ratio =0.74, 95% CI 0.59–0.94). In addition, we found that the allelic mRNA expression corresponding to the 235M allele was significantly higher than that for the 235T allele in normal kidney tissues. Furthermore, we found a significant additional effect of these three genes by a step-wise logistic regression analysis (final empirical P value =0.00005). We concluded that RAS gene polymorphisms may contribute to the susceptibility to diabetic nephropathy in type 2 diabetes. [ABSTRACT FROM AUTHOR]

On April 25, 2003, a 62-year-old Japanese man had been admitted to a hospital because of heavy proteinuria and elevated serum creatinine level, and purpura on the lower extremities. On May 15, 2003, he was referred to our hospital for evaluation and treatment. Serum immunoglobulin and complements were within normal ranges. Immune serology was negative for antinuclear antibody, antiglomerular basement membrane antibody, and antineutrophil cytoplasmic antibodies. Histological examination of a percutaneous renal biopsy specimen revealed that all of the glomeruli had severe crescent formation without deposits of immunoreactants. A diagnosis of antineutrophil cytoplasmic antibody-negative pauci-immune crescentic glomerulonephritis was made. The patient was treated with one cycle of steroid pulse therapy (1000 mg methylprednisolone daily, given on 3 consecutive days), and subsequently with prednisolone (60 mg/day). Despite this treatment, renal failure progressed rapidly and hemodialysis was started 1 month after the acute presentation. On May 30, 2003, he suddenly developed massive hematochezia. A technetium-targeted red-blood-cell scan suggested bleeding in the small intestine. On June 11, he presented with massive melena. A bleeding ulcer was found in the third part of the duodenum, and was treated successfully with endoscopy, using a heater probe. On June 19, he presented with massive hematochezia again. Mesenteric angiography revealed active bleeding from the iliac branch of the superior mesenteric artery. He was treated with continuous intraarterial vasopressin infusion by a catheter seated in the branch artery. The majority of patients with pauci-immune crescentic glomerulonephritis, one of the most common causes of rapidly progressive glomerulonephritis, have glomerular disease as part of a systemic vasculitis. Massive gastrointestinal bleeding, although rare, should be considered one of the serious complications in these patients. [ABSTRACT FROM AUTHOR]

We report a case of a 41-year-old Japanese man who presented with rapidly progressive glomerulonephritis, chronic sinusitis, and positive cytoplasmic-antineutrophil cytoplasmic antibody (c-ANCA). Renal biopsy showed crescentic glomerulonephritis, and he was diagnosed as having Wegener’s granulomatosis. During the clinical course, he suffered from pulmonary bleeding, and combination therapy of steroid, immunosuppressant, and double filtration plasmapheresis (DFPP) was started. He rapidly entered remission after assistance through DFPP, suggesting the potential efficacy of DFPP for Wegener’s granulomatosis, especially with pulmonary bleeding. [ABSTRACT FROM AUTHOR]

Background Methods. We analyzed renal biopsy findings from 10 patients with rheumatoid arthritis and concomitant bucillamine-induced nephropathy. Each patient was followed up until proteinuria had resolved. Results. Proteinuria appeared 2–11 months after the initiation of the treatment with bucillamine. Nine patients, who stopped bucillamine treatment immediately (within 3 months) after the onset of proteinuria, were diagnosed as having stage I membranous nephropathy. Only one patient, who used bucillamine for 9.5 months after the onset of proteinuria, was diagnosed as having stage II membranous nephropathy. In all patients with stage I membranous nephropathy, the proteinuria disappeared within 7 months after they stopped bucillamine treatment. On the other hand, in the patient with stage II membranous nephropathy, the proteinuria persisted for 14 months after the use of bucillamine was stopped. In all the patients, the proteinuria resolved completely without deterioration of renal function. None of the patients has experienced recurrence of proteinuria. Conclusions. In patients with proteinuria induced by treatment with bucillamine, membranous nephropathy is the most common disorder. Immediate withdrawal of bucillamine results in prompt and complete resolution of proteinuria without deterioration of renal function. Bucillamine, a disease-modifying antirheumatic drug widely prescribed in Japan, is reported to be a cause of proteinuria. However, to date, the clinical course of the nephropathy associated with the use of bucillamine has not been described in detail. [ABSTRACT FROM AUTHOR]

Background. In patients with heavy proteinuria, corticosteroid therapy has been shown to have favorable effects on the progression of IgA nephropathy. However, the efficacy of corticosteroids on the progression of IgA nephropathy with moderate proteinuria is still controversial. Methods. We assessed 45 adult (age, 18–50 years) patients with moderate proteinuria (0.5–2.0 g daily) and preserved renal function, (serum creatinine concentration, ≦106 µmol/l) who were diagnosed as having primary IgA nephropathy between December 1993 and July 1998. Twenty-three of the patients were treated with corticosteroids (steroid group), and the remaining 22 patients had no steroid treatment (control group). All patients were followed up for more than 3 years. Results. There were no differences in baseline characteristics between the two groups, except for proteinuria. In the steroid group, urinary protein excretion was significantly higher than that in the control group. During the follow-up period, urinary protein excretion was not changed in the control group. On the other hand, in the steroid group, mean urinary protein excretion decreased significantly. Seven patients in the control group and 2 patients in the steroid group reached the endpoint, which was defined as a 50% increase in serum creatinine concentration from baseline. Renal survival curves were significantly different between the two groups. A second biopsy was performed in 20 patients who received steroid therapy. Mesangial cell proliferation, mesangial matrix increase, and cellular crescents were significantly reduced in the second compared with the first biopsy specimens. Conclusions. Steroid therapy is effective in reducing the progression of IgA nephropathy with moderate proteinuria. [ABSTRACT FROM AUTHOR]

Background. Glomerular mesangial cells were found to have a considerable number of receptors for insulin-like growth factor I (IGF-I) and to proliferate in response to IGF-I. However, the mechanism of the metabolic actions of IGF-I in mesangial cells has not yet been fully elucidated. Methods. In order to clarify the effect of IGF-I on glucose metabolism in mesangial cells, we performed a kinetic analysis of 2-deoxyglucose (2-DOG) uptake, the first step of glucose metabolism, and examined the gene and protein expression of glucose transporter 1 (GLUT 1), a major facilitative glucose transporter in mesangial cells. Results. IGF-I was able to increase 2-DOG uptake significantly after 12 h, and the kinetic analysis of 2-DOG uptake revealed that IGF-I increased maximum velocity (Vmax) without changing Michaelis constant (Km). The expression of GLUT 1 mRNA was increased after the exposure to IGF-I and reached the maximal level at 6 h, followed by an increase in its protein expression. Conclusions. These results suggest that IGF-I plays an important role in glucose metabolism in glomerular mesangial cells by enhancing glucose transport through an increase in the expression of GLUT 1. [ABSTRACT FROM AUTHOR]

We describe 2 patients with autosomal dominant polycystic kidney disease associated with aortic dissection. Both patients presented with chronic renal failure arising from autosomal dominant polycystic kidney disease, as well as with aortic dissection, DeBakey type IIIb. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented that describes the case of a patient with diffuse lupus nephritis complicated with severe thrombocytopenia and hemolytic anemia, whose hematological manifestations have been related to cytomegalovirus reactivation.

A letter to the editor that discusses the prevalence of sensorineural hearing loss in patients with myeloperoxidase-anti-neutrophil cytoplasmic antibody-related microscopic polyangitis is presented.

A letter to the editor is presented which cites a case of post-streptococcal reactive arthritis and acute nephritis following a bacterial infection caused by Streptococcus pyogenes.

We encountered an adult patient with rheumatoid arthritis who developed acute interstitial nephritis associated with an anti-tumor necrosis factor alpha agent, etanercept. [ABSTRACT FROM AUTHOR]

We encountered an adult patient with Henoch-Schönlein purpura. He had been infected with human immunodeficiency virus (HIV) and antiretroviral therapy improved his nephritis, indicating that HIV infection might have contributed to the development of Henoch-Schönlein purpura in our case. [ABSTRACT FROM AUTHOR]

We encountered an adult patient with acute parvovirus B19 infection who presented with transient lupus-like symptoms (i.e., polyarthritis, fever, myalgia, pancytopenia, hypocomplementemia, and nephritis). Our case is characterized by the demonstration of acute nephritis as a complication of this infection, making it difficult to distinguish between a viral infection and the first episode of systemic lupus erythematosus. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article about wegener's granulomatosis initial manifestation.

A 73-year-old man who was being treated with corticosteroids for nonsystemic vasculitic neuropathy developed small-bowel hemorrhage after ileostomy for ileus. Immunohistochemical staining for cytomegalovirus (CMV) antigen in the ulcer in the resected ileum was positive; thus, cytomegalovirus infection of the small intestine caused his gastrointestinal manifestations. Cytomegalovirus infection should be considered in the differential diagnosis of gastrointestinal diseases in patients with collagen vascular diseases receiving immunosuppressive agents. [ABSTRACT FROM AUTHOR]

Presents a response by Mie Obayashi, Takashi Uzu and Atsushi Yamauchi to a letter to the editor about their article on treatment of patients suffering from rheumatoid arthritis with bucillamine in the September 2004 issue.