Structural changes in renal arterioles are closely associated with central hemodynamic parameters in patients with renal disease.

Although central hemodynamics are known to be closely associated with microvascular damage, their association with lesions in the small renal arteries has not yet been fully clarified. We focused on arterioles in renal biopsy specimens and analyzed whether their structural changes were associated with noninvasive vascular function parameters, including central blood pressure (BP) and brachial-ankle pulse wave velocity (baPWV). Forty-four nondiabetic patients (18-50 years of age) with preserved renal function underwent renal biopsy. Wall thickening of arterioles was analyzed based on the media/diameter ratio, and hyalinosis was analyzed by semiquantitative grading. Associations of these indexes (arteriolar wall remodeling grade index (RG index) and arteriolar hyalinosis index (Hyl index)) with clinical variables were analyzed. Multiple regression analyses demonstrated that the RG index was significantly associated with central systolic BP (ß = 0.97, p = 0.009), serum cystatin C-based estimated glomerular filtration rate (ß = -0.36, p = 0.04), and high-density lipoprotein cholesterol levels (ß = -0.37, p = 0.02). The Hyl index was significantly associated with baPWV (ß = 0.75, p = 0.01). Our results indicate that aortic stiffness and abnormal central hemodynamics are closely associated with renal microvascular damage in young to middle-aged, nondiabetic kidney disease patients with preserved renal function.

[Two cases of incidentally detected renal arteriovenous fistula over ten years after renal biopsy].

CASE 1: The case was a 66-year-old Japanese woman. A renal biopsy had been carried out at 53 years of age, and she was diagnosed as IgA nephropathy. Her renal function had been stable at around 0.7 mg/dL of serum creatinine. At 66 years of age, macrohematuria was found and she was admitted to hospital. Enhanced abdominal computed tomography showed left renal arteriovenous fistula (AVF) (21 mm x 10 mm), and hydronephrosis. Her renal AVF was successfully treated with coil embolization, and hydronephrosis was improved with stable renal function. Her AVF was cirsoid type, which is usually congenital, although it was not recognized before the renal biopsy. CASE 2: A 48-year-old Japanese woman was referred to a nephrologist for proteinuria and an elevated serum creatinine level. She had undergone two renal biopsies when she was 14 and 18 years of age and her condition had been diagnosed as chronic glomerulonephritis. However, she had not received any special treatment. Upon abdominal ultrasonography, a right renal AVF (18 mm x 23 mm) was detected. Her aneurysmal type AVF was successfully treated with coil embolization. In these 2 cases, renal biopsy might be a cause of renal AVF. Regular screening test using ultrasonography is recommended to avoid missing remote complications of renal biopsy.

Dietary intake in Japanese patients with kidney transplantation.

BACKGROUND: Kidney transplantation may release the patient receiving dialysis therapy in their life style, especially in restriction of dietary intake. However, their renal functions are not enough to take daily diet without any restriction. In Japan, we have neither standard of diet intake for them, nor data to build it. METHODS: Dietary intake and its satisfaction were surveyed in 62 outpatients who received kidney transplantation in Keio University Hospital using brief-type self-administered diet history questionnaire. RESULTS: Cross-sectional research was carried out in 2013. Estimated GFR of the object was 42 ± 16 ml/min/1.73 m2. One patient was CKD G1 stage, five in G2, 17 in G3a, 24 in G3b, 14 in G4, and one in G5. Urinary protein was shown in 30 % of patients. Their daily intake was 29 ± 8 kcal/kg of energy, 1.1 ± 0.4 g/kg of protein, 9.9 ± 3.6 g of salt. Protein and salt intakes were over comparing the respective standards for CKD in Japan. The patient who have dissatisfaction for their daily diet was significantly decreased from 79 to 4 % after their kidney transplantation. Attentions to overtake were significantly reduced after kidney transplantation from 56 to 8 % for potassium, 55 to 21 % for salt, 50 to 16 % for protein, 35 to 3 % for calcium/phosphate. CONCLUSIONS: Changes in daily diet of the patients with dialysis and kidney transplantation were recognized. The patients who received kidney transplantation would take daily diet according to their renal function although they do not have specific standards.

Relationship between dietary protein intake and the changes in creatinine clearance and glomerular cross-sectional area in patients with IgA nephropathy.

BACKGROUND: Dietary protein intake (PI) induces glomerular hyperfiltration and reduced dietary PI can be effective in preserving kidney function. However, there is limited information regarding the relationship between dietary PI and glomerular histological changes in chronic kidney disease. We investigated the relationship between changes in dietary PI and both the changes in creatinine clearance and glomerular histomorphometry in adult patients with IgA nephropathy (IgAN). METHODS: A total of 24 consecutive adult patients with biopsy-confirmed IgAN were enrolled and glomerular histomorphometric variables and clinical variables were investigated. The main clinical variables were differences in creatinine clearance (Ccr) (dCcr) and in PI (dPI) which were calculated by subtracting PI and Ccr values in patients on a controlled diet during hospitalization for kidney biopsy from the respective values in patients on daily diets as outpatients. These values of PI were estimated from urinary urea excretion measured by 24-h urine collection. The main renal histomorphometric variable was glomerular tuft area (GTA) (µm(2)). RESULTS: dCcr positively correlated with dPI (r = 0.726, P < 0.001). GTA correlated positively with dPI (r = 0.556, P = 0.013). Multiple regression analysis showed that dPI was independently associated with both dCcr and GTA. Additionally, GTA positively correlated with dietary PI as outpatients (r = 0.457, P = 0.043). CONCLUSION: Changes in dietary PI were associated with the changes in glomerular filtration rate. Furthermore, histomorphometric findings suggested that a greater dietary PI can affect the glomerular size at the time of the initial diagnostic biopsy for IgAN.

Clinical significance of microscopic haematuria in diabetic nephropathy in type 2 diabetes patients with overt proteinuria.

AIM: Although some patients with diabetic nephropathy with overt proteinuria have microscopic haematuria, the pathological characteristics and clinical significance related to microscopic haematuria have not yet been clarified. The aim of the present study was to clarify the pathological characteristics and clinical significance of microscopic haematuria. METHODS: Eighty-four type 2 diabetes patients with overt proteinuria and biopsy-confirmed diabetic nephropathy were enrolled. The clinical and histological findings were compated between the patients with persistent haematuria (group 1, n=25) and those with persistent non-haematuria (group 2, n=23) after renal biopsy. The association between persistent haematuria and renal outcome at 5 years was examined. Histological scoring was made according to the original system and that of Tervaert et al. RESULTS: Thirty-six patients (43%) had microscopic haematuria at the time of renal biopsy. Age was significantly smaller and blood pressure was significantly greater in group 1 than in group 2 (age: group 1, 56 ± 10 years; group 2, 62 ± 9 years; P=0.03, systolic blood pressure: group 1, 152 ± 16 mm Hg; group 2, 140 ± 16 mm Hg; P=0.01). There were no significant differences in histological parameters between the two groups. A logistic regression model demonstrated that arteriolar hyalinosis was significantly associated with persistent haematuria (OR=2.81; P=0.04). There were no significant differences in changes in reciprocal serum creatinine and rates of doubling of serum creatinine after renal biopsy between the two groups. CONCLUSION: Although arteriolar hyalinosis was associated with persistent haematuria, the clinical significance of microscopic haematuria was minor in diabetic nephropathy in type 2 diabetes patients with overt proteinuria.

Histological predictors for renal prognosis in diabetic nephropathy in diabetes mellitus type 2 patients with overt proteinuria.

AIM: Although several clinical risk factors for end-stage renal disease in diabetic nephropathy are known, the pathological findings that may help predict renal prognosis have not yet been defined. METHODS: We enrolled 69 diabetes mellitus type 2 patients with overt proteinuria and biopsy-confirmed diabetic nephropathy with mesangial expansion, and retrospectively examined the association of histological and clinical findings with renal outcome. The median follow-up duration was 52 months. Histological scoring was made according to that of Tervaert et al. Patients were divided into four groups according to glomerular classification (class 2a, mild mesangial expansion, n=11; class 2b, severe mesangial expansion without nodular sclerosis, n=15; class 3, nodular sclerosis, n=36; class 4, global glomerulosclerosis observed in more than 50% of glomeruli, n=7). Interstitial and vascular lesions were scored for each patient. A renal event was defined as a condition requiring the initiation of chronic dialysis or doubling of the serum creatinine level. RESULTS: Cox proportional hazard analysis showed that the glomerular classes were not significant variables, while interstitial fibrosis, tubular atrophy and interstitial inflammation were independent variables associated with renal end-point (HR: 3.36 (95% confidence interval: 1.21-9.32), 4.74 (1.26-17.91)). There were no significant differences in the renal survival rates between the glomerular classes 2a and 2b combined group and the glomerular class 3 group (P=0.17, log-rank test). CONCLUSION: Interstitial lesions but not glomerular lesions were a significant predictor for renal prognosis in diabetic nephropathy in type 2 diabetes patients with overt proteinuria.

Triple therapy with single daily dose of cyclosporine in Japanese patients with idiopathic membranous nephropathy.

OBJECTIVE: The optimal therapeutic approach to patients with idiopathic membranous nephropathy (IMN) remains controversial. In this study, we assessed the efficacy of single daily dose cyclosporine (CsA) combined with low-dose prednisolone (PSL) and an angiotensin II receptor blocker (ARB) in patients with IMN. METHODS: We studied 13 nephrotic patients (8 men, 5 women) with IMN diagnosed on biopsy. An initial single daily dose of 2 mg/kg, but not exceeding 150 mg, CsA was given for 12 months, tapered by a 25 mg reduction every 2 months. An initial twice-daily dose of 0.5 mg/kg PSL was given for 2 months and was also tapered. An ARB was given to all patients and the same dosage was used throughout the study. Patients were followed up for 6 to 66 months. RESULTS: Nine patients achieved complete remission at 6.7±2.9 months, and incomplete remission was obtained in the remaining patients. After a follow-up period of 32.7±20.0 months, their serum creatinine and estimated glomerular filtration rate values were similar to baseline levels. The 9 patients who completed the treatment course have not relapsed. Moreover, there were no adverse effects requiring discontinuation of this triple therapy. CONCLUSION: A single daily dose of CsA combined with a low dose of PSL and an ARB in new-onset nephrotic patients with IMN induced a high remission rate of nephrotic syndrome, with a low incidence of relapse and a low risk of adverse effects. The triple therapy and prospective follow-up shows potential as a treatment approach for patients with IMN.

[A pregnant woman with nephrotic syndrome and focal segmental lesions].

A 32-year-old woman was admitted at 36 weeks' gestation because of increasing proteinuria and generalized edema. At the time of admission, serum creatinine was 1.3 mg/dl, and urinalysis demonstrated 4+ protein and 2+ occult blood. During her pregnancy, her blood pressure had been in the normal range. A normal healthy female neonate was delivered by caesarean section at 38 weeks' gestation. After delivery, the woman's 24-hour urine protein excretion was 11 g/day and serum albumin was 1.4 g/dl , hence nephrotic syndrome was diagnosed. Eleven days after delivery, a renal biopsy showed focal segmental lesions with glomerular epithelial cell injury. She was given 50 mg/day prednisolone and after a month, her 24-hour urinary protein excretion decreased to 2 g/day. One year later, she achieved complete remission. Although she had a relapse of nephrotic syndrome after twenty-one months, steroid therapy again achieved a good response.

Insulin resistance contributes to obesity-related proteinuria.

OBJECTIVE: Proteinuria is a recognized complication of obesity, but the pathogenesis remains unclear. We undertook the present study to clarify the factors contributing to proteinuria associated with obesity. METHODS: We studied 12 obese patients with proteinuria. Twenty-seven age-matched obese subjects without proteinuria served as controls. A glucose tolerance test and renal biopsy were performed in all patients. Fasting serum insulin and homeostasis model assessment-insulin resistance (HOMA-IR) were regarded as reflecting insulin resistance. To delineate the relation between insulin resistance and proteinuria, troglitazone, which acts an insulin sensitizer was given to 6 of 12 patients with a regular diet for 8 weeks. The 6 others were observed without receiving troglitazone. RESULTS: The 12 patients showed the presence of a cluster of insulin resistance factors: higher blood pressure, higher body mass index, higher fasting plasma glucose, higher fasting serum insulin, and higher HOMA-IR than controls. The renal biopsy specimens exhibited no histological abnormalities in 7, focal segmental glomerulosclerosis in 3 and benign nephrosclerosis in 2. Troglitazone attenuated HOMA-IR and ameliorated proteinuria, but did not affect body weight, creatinine clearance, or blood pressure. In contrast, the parameters in the patients not given troglitazone did not change. CONCLUSION: Insulin resistance is a factor contributing to obesity-related proteinuria. The role of insulin resistance as a factor reducing proteinuria remains to be clarified.

[Nephrotic syndrome and malignancy].

The patients with nephrotic syndrome frequently associate with solid tumors as well as hematologic malignancies, although the presence of nephrotic syndrome in patients with malignancy is rare. The association cannot be explained by chance alone, because it occurs at a rate. Theoretically, malignancy-associated glomerulopathy should be explained by at least two clinical criteria. First, a remission of proteinuria achieves after surgical removal of tumor or disappearance of tumor by chemotherapy. Second, relapse of proteinuria occurs after recurrence of malignancy. However, pathophysiologic link which is the third important criteria has not been established between the two diseases.

[Henoch-Schönlein purpura nephritis in a patient infected with the human immunodeficiency virus].

There are various forms of renal lesions in patients with human immunodeficiency virus(HIV), however reported cases of immune-complex glomerulonephritis are scarce. Here we describe an HIV-positive patient with Henoch-Schönlein purpura nephritis(HSPN), which presented as nephrotic syndrome. In addition to therapy combined with glucocorticosteroid and inhibition of the renin-angiotesin system(RAS), plasmapheresis and antiretroviral therapy produced a favorable outcome. A 26-year-old HIV positive man was admitted for purpura on both lower limbs. Despite glucocorticosteroid treatment, purpura recurred and urinary protein increased to 5-10 g daily. HSPN was diagnosed based on the skin and renal biopsies. During 2 months of treatment with combined glucocorticosteroid and RAS inhibition, nephrotic syndrome persisted. He received double filtration plasmapheresis(DFPP). Soon after, urine protein decreased to 2-3 g daily and macrohematuria decreased. The second renal biopsy showed a decrease in IgA deposition and improvement of acute inflammatory changes. In addition, highly active antiretroviral therapy was started to reduce the high viral load. After 3 weeks, HIV-1-RNA rapidly decreased and urine protein decreased to 1 g daily. After a year, urinary protein was negative, but mild microhematuria persisted. We speculate that the refractory nephrotic syndrome in this patient might be associated with the abnormal immunological condition due to HIV infection.