Patients with biopsy-proven nephrosclerosis and moderately impaired renal function have a higher risk for cardiovascular disease: 15 years' experience in a single, kidney disease center.

BACKGROUND: Nephrosclerosis progresses slowly to end-stage renal disease (ESRD) in only a small percentage of patients. However, because hypertension and nephrosclerosis are normally found simultaneously, nephrosclerosis is a risk factor for cardiovascular disease (CVD). In turn, the onset of CVD may progress to further renal impairment. AIM: To evaluate clinical outcomes and the association between nephrosclerosis and CVD in the long term. DESIGN: Prospective study METHODS: We prospectively assessed 35 patients (male/female: 19/16) with nephrosclerosis aged >30 years at disease onset, attending the Kidney Disease Center, Saitama Medical University, in a single teaching hospital center between 1995 and 2014. Nephrosclerosis was diagnosed in accordance with the criteria outlined in the World Health Organization (WHO) monograph of renal diseases. All patients were followed by means of registries for 10 years to record subsequent events, if any. OUTCOMES: The primary study outcome was correlating the occurrence of CVD, defined as a composite of cardiovascular deaths, nonfatal and fatal myocardial infarction, and stroke, with the development of ESRD or death. RESULTS: The mean age of patients at the time of biopsy was 54.8 ± 12.7 years (range 33-72 years). Of these patients, seven were affected by nonfatal CVD and two died due to CVD. Only one patient developed ESRD during the follow-up period. Using Kaplan-Meier analysis, risk factors for the primary study outcome were estimated to include an estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73 m(2), systolic blood pressure > 130 mmHg and proteinuria > 1 g/g creatinine. Univariate analysis was used for the assessment of the relative risk for the primary study endpoint of several covariates: age, systolic blood pressure, eGFR and proteinuria at time of renal biopsy. eGFR was found to be the strongest factor determining an event-free period [relative risk (RR) =1.931, p = 0.014]. CONCLUSIONS: Patients with nephrosclerosis are at high risk of CVD when they have moderately advanced renal impairment.

Successful prednisolone therapy in elderly patients with severe forms of henoch-schönlein purpura nephritis.

INTRODUCTION: Recently, Henoch-Schönlein purpura (HSP) has been observed in elderly people, although it was believed to be uncommon in these subjects. The increased risks of developing end-stage renal disease (ESRD) in adults in comparison with children were highlighted by different studies; however, limited data are available on the treatment of HSP nephritis in adults. METHODS: Between 2002 and 2008, five elderly Japanese patients (>65 years old) (mean age, 68 years, ranging from 65 to 72) with severe forms of HSP nephritis were entered into a prospective study to evaluate prednisolone therapy on the outcome of nephropathy in terms of clinical symptoms and histopathological changes. The patients were considered at risk of developing chronic renal failure when they presented with a nephrotic syndrome and crescentic glomeruli. RESULTS: At the last follow-up, 4-10 years after initiation of the therapy, four patients had clinically recovered and one died of lung cancer. No patients developed ESRD. The clinical outcome seemed to be correlated with glomerular activity (massive proteinuria and crescent formation). In spite of a relatively large dose of prednisolone, a few adverse effects, such as insomnia and skin lesions, were observed. DISCUSSION: Our preliminary small study suggests that renal outcome as well as survival of elderly patients with severe forms of HSP might be altered by aggressive prednisolone therapy.

Time to re-evaluate effects of renin-angiotensin system inhibitors on renal and cardiovascular outcomes in diabetic nephropathy.

The use of renin-angiotensin system (RAS) inhibitors, such angiotensin converting enzyme inhibitors/angiotensin-II receptor blockers, to slow progression of chronic kidney disease (CKD) in a large group dominated by elderly people in the real world is not supported by available evidence. Large-scale clinical trials had many faults, among them a lack of focus on the elderly. However, it would be difficult to conduct clinical trials of a similar scale in elderly CKD patients. Besides, progression of kidney disease is often slow in elderly persons, and the vast majority of older adults with CKD will die before reaching end stage renal disease. Moreover, since it is not clear that progression of kidney disease, and even of proteinuric diabetic nephropathy, is not inhibited through the use of RAS inhibitors, the most patient-centric goal of therapy for many elderly individuals should be individualized.

Long-term survival benefits of combined hemodialysis and peritoneal dialysis.

Recently, it was reported that concomitant hemodialysis (HD) in peritoneal dialysis (PD) patients facilitated continuation of PD treatment and mitigated the deterioration of peritoneal function in patients with uremic symptoms and excess body fluid associated with loss of residual renal function. To determine the effect of combined HD and PD on patient and technique survival, we undertook a retrospective cohort study of patients who underwent PD at Saitama Medical University Hospital between 1995 and 2010. We compared patients who started PD during 1995 2002 with those who started during 2003- 2010. Because our center started a new strategy of supplementing PD with once-weekly HD in 2000, the effects of combination therapy could be determined by comparing the data obtained during the two periods. The 440 patients (274 men, 166 women) who started PD during the study period had a mean age of 60.2 +/- 73 years. The mean age was significantly higher in the 2003 - 2010 group than in the 1995 - 2002 group. Using a Kaplan-Meier plot, we observed a significant difference in technique survival (p < 0.001). The technique survival rate at 3 and 5 years was, respectively, 89% and 74% in the 2003-2010 group and 68% and 35% in the 1995 - 2002 group (p < 0.05). Cumulative patient survival at 3 and 5 years was, respectively, 87% and 72% in the 2003 - 2010 group and 69% and 51% in the 1995 - 2003 group (p < 0.01). Patient and technique survival were significantly improved in PD patients receiving the combination of HD and PD.

Role of Pulse Wave Velocity in Patients with Chronic Kidney Disease Stages 3-5 on Long-Term Follow-Up.

BACKGROUND: The relationship between arterial stiffness and kidney function has not been clearly demonstrated although observations of higher arterial stiffness in patients with advanced stages of chronic kidney disease (CKD) were reported. In longitudinal analyses, there was no close association between basal arterial stiffness and progression of kidney function in the general population. In the present study, we assessed the relationship between arterial stiffness and progression of renal dysfunction in patients with CKD stages 3-5 using two types of measures of arterial stiffness, i.e., carotid-femoral pulse wave velocity (cfPWV) and brachial-ankle pulse wave velocity (baPWV), over a 10-year period. METHODS: 110 patients with CKD stages 3-5 (aged 57.8 ± 10.6 years; female/male: 72/38) were followed for 10 years. Before and at the end of the 10-year period, cfPWV and baPWV were measured using form PWV/ABI (Omron Colin Co. Ltd.). RESULTS: Throughout the study, systolic blood pressure was well-controlled in all patients. Twenty-nine patients (26%) received renal replacement therapy, 12 patients (11%) developed cardiovascular diseases (CVDs), 5 patients were found to have neoplasm, and 9 patients dropped out of the study during the 10-year observation period. In patients who developed end-stage renal disease, the baseline estimated glomerular filtration rate (eGFR) was significantly lower, and in patients who developed CVD, the basal value of baPWV was significantly higher (p < 0.05). Throughout the study, blood pressures were controlled (136.1/77.0 ± 15.6/7.1 to 137.5/77.6 ± 14.9/11.2), kidney function worsened (eGFR, 30.8 ± 16.5 to 22.9 ± 17.6 ml/min/1.73 m(2); p < 0.01), and baPWV but not cfPWV showed a significant change [1, 672.2 ± 209.6 vs. 1,753.1 ± 333.2 cm/s (p = 0.04) and 918.9 ± 153.2 vs. 939.4 ± 133.2 cm/s]. Moreover, the difference in PWV between the start and the end of the 10-year observation period was positively correlated with the difference in eGFR. CONCLUSION: With moderate progression of renal dysfunction and under well-controlled blood pressure, peripheral but not central arterial stiffness is possibly one of the strongest predictors of CVD in patients with CKD stages 3-5.

Decline of Renal Function and Progression of Left Ventricular Hypertrophy Are Independently Determined in Chronic Kidney Disease Stages 3-5.

UNLABELLED: Invasive and noninvasive methods for evaluating the effects of hemodynamics on progression of left ventricular hypertrophy (LVH) in patients with chronic kidney disease (CKD) have been proposed. Central aortic pressure (CAP) has been reported to be the best among selected measures of hemodynamics for predicting LVH. However, there are few studies examining the relation between longitudinal changes in CAP and renal dysfunction in patients with CKD. METHODS: Sixty-seven patients with CKD stages 3-5 (female/male ratio: 26/41, age: 61.5 ± 13.1 years) were followed for 5 years. Before and at the end of the 5-year period, CAP was recorded by an automated tonometric system (HEM-9000 AI; Omron Healthcare, Kyoto, Japan). Second systolic aortic blood pressure (SBP2) was employed as an index of CAP. RESULTS: Throughout the study, systolic blood pressure (SBP) was well controlled. Renal function followed by estimated glomerular filtration rate (eGFR) gradually worsened as a whole. Ten patients had renal replacement therapy, 3 patients developed cardiovascular diseases and 2 patients were found to have a neoplasm during the 5-year observation period. SBP2 increased from 120 ± 19 to 125 ± 33 mm Hg and eGFR decreased from 38.2 ± 18.2 to 29.5 ± 16.3 ml/min/1.73 m(2); however, these differences did not achieve significance. The left ventricular mass (LVM) index significantly increased from 115.5 ± 10.5 to 131.2 ± 11.7 g/m(2) (p < 0.05). Although the changes in SBP2 and eGFR looked like a mirror image, there was no significant correlation between the two factors. Moreover, multivariate regression analysis did not reveal a close correlation between SBP2 and CKD progression. In contrast to the decline of renal function, the baseline value of SBP2 predicted an increase in the LVM index. CONCLUSION: Worsening of renal dysfunction is not solely dependent on hemodynamics. Other factors might be involved in a complex manner.

Aliskiren reduces morning blood pressure in hypertensive patients with diabetic nephropathy on hemodialysis.

Our previous study indicated that the exchange from an angiotensin receptor blocker (ARB) to aliskiren reduced morning blood pressure and albuminuria in hypertensive patients with diabetic nephropathy. We extended the above study and assessed the effects of exchanging from an ARB to aliskiren on home blood pressure in hypertensive patients with diabetic nephropathy on chronic hemodialysis. The patients who were persistently hypertensive despite antihypertensive therapy, including ARB, were considered as candidates for the exchange from the ARB to aliskiren. Patients' age and durations of diabetes and hemodialysis were averaged as 62 ± 9 years old, 15 ± 8 and 7 ± 3 years, respectively. Aliskiren decreased morning systolic blood pressure (149 ± 14 to 144 ± 13 mm Hg, n = 30, P < .01) and plasma renin activity (3.5 ± 1.1 to 1.2 ± 0.6 ng/mL/h, P < .01) without changes in serum potassium. Aliskiren also reduced interdialytic weight gain (2.7 ± 0.6 to 2.5 ± 0.5 kg/interval, P < .05) and attenuated the magnitude of intradialytic declines in systolic (-20 ± 11 to -17 ± 10 mm Hg, P < .05) and diastolic blood pressure (-9 ± 6 to -5 ± 5 mm Hg, P < .01). The exchange from an ARB to aliskiren is safe and useful to control home blood pressure in hypertensive hemodialysis patients with diabetic nephropathy. Aliskiren reduced both intradialytic blood pressure drops and interdialytic weight gain in patients with DN.

Statin improves flow-mediated vasodilation in chronic kidney diseases.

Background. Numbers of drugs are required to manage patients with chronic kidney disease (CKD). Drug adherence is relatively poor in this population. Methods. In 36 CKD patients with hypertension and dyslipidemia, who were prescribing amlodipine 5 mg and atorvastatin 10 mg daily, the influences of exchanging to a combination drug containing equivalent doses of amlodipine and atorvastatin were observed for 6 months. Results. At the baseline, flow-mediated dilation (FMD) was reduced (2.4 ± 0.3%), and proteinuria was significantly contributed to decrements of FMD (R (2) = 0.38, F = 3.7, df (6,29), and P < 0.01). Six months later from exchanging to combination drug, total cholesterol (TC, 197 ± 5 to 183 ± 3 mg/dL, P < 0.01) and triglycerides (142 ± 14 to 129 ± 10 mg/dL, P < 0.05) were decreased, but high density lipoprotein cholesterol (53 ± 3 to 56 ± 3 mg/dL, P < 0.05) was increased. FMD was slightly albeit significantly improved to 2.7 ± 0.3% (P < 0.05). No serious adverse effects were seen by the combination drug. Subanalysis for the patients with considerable reductions of TC demonstrated that the combination drug decreased proteinuria and high sensitive CRP (P < 0.05 for both). Conclusion. Our data indicate that proteinuria constitutes a determinant of a reduced FMD. The present results implicate that combination drug is useful to improve adherence and suggest that atorvastatin refines endothelium function as well as lipid profiles in CKD patients.

Combination therapy with hemodialysis and peritoneal dialysis.

Both continuous ambulatory peritoneal dialysis (CAPD) and hemodialysis (HD) have their advantages regarding the treatment of patients with renal failure. In CAPD, solute removal is sometimes insufficient in patients who have a relatively large muscle mass that produces high levels of creatinine. To compensate for this deficiency, frequent exchanges and large peritoneal dialysate volumes are required. Alternatively, CAPD and HD as a combined modality of treatment for patients needing dialysis therapy has been proposed. Our experiences with three groups of patients are described. First, in 2003, 7 cases (6 males and 1 female; average age 54.3 ± 4.5 years; mean duration of CAPD therapy 4.3 ± 1.1 years; average weekly creatinine clearance (WCC) was 45.2 ± 1.7 l/1.73 m(2)) were treated with once-a-week HD therapy (3.5 h; 200 ml/h). Addition of once-a-week HD therapy improved WCC to 66 ± 7.1 liters/1.73 m(2). This improvement was due not only to the addition of HD therapy but also to an increase in creatinine clearance for 3 consecutive days after the completion of once-a-week HD therapy. Both creatinine clearance and ultrafiltration were significantly increased. Other clinical parameters such as blood pressure control, weight control, and dosage of erythropoietin were significantly improved after introducing this therapy. Second, we followed 9 CAPD patients who underwent an additional weekly HD for more than 3 years. Similar improvements were obtained in this long-term study as seen in the short-term study. Besides, the incidence of peritonitis decreased dramatically from 0.13 to 0.09 episodes/patient-year (p < 0.05) during the 3-year study. These data suggest that the combined use of CAPD and HD improves solute clearance in CAPD patients who are insufficiently dialyzed. Third, based on these data, we examined the efficacy of an early start of combination therapy and found that it stabilized dialysis therapy and prolonged the duration of CAPD. Combined with several of the previous several reports and our present experience, it is suggested that an early start of HD therapy will prolong the survival rate in patients on CAPD with physically stable conditions.

Long-term effects of calcium antagonists on augmentation index in hypertensive patients with chronic kidney disease: a randomized controlled study.

BACKGROUND: Our previous retrospective study showed that benidipine was superior to amlodipine (AM) for reducing proteinuria and preserving the augmentation index (AI) in patients with chronic kidney disease (CKD). METHODS: The present study enrolled CKD patients whose blood pressure was not well controlled by an angiotensin receptor blocker (ARB) and a calcium channel blocker other than AM or azelnidipine (AZ). Either AM (5 mg) or AZ (16 mg) was prescribed randomly. Clinical parameters, including proteinuria, serum creatinine, and AI, were measured before initiation of AM or AZ and 1 year later to assess the long-term effect on renal function and central blood pressure. RESULTS: Brachial and central blood pressures were similarly reduced in both groups. However, pulse rate increased in the AM group, but decreased in the AZ group (+3 ± 1 vs. -2 ± 1 bpm, p < 0.0001). The reduction of proteinuria was greater in the AZ group (-29 ± 2 vs. -38 ± 3%, p < 0.01). Improvement of AI adjusted for a pulse rate of 75 bpm was larger in the AZ group than in the AM group (-4 ± 1 vs. -9 ± 1%, p < 0.05). In both groups, estimated GFR remained unchanged throughout the observation period. CONCLUSION: In hypertensive patients with CKD, combined treatment with AZ and an ARB decreases proteinuria and preferentially improves arterial reflection.

Early start of combination therapy with hemodialysis and peritoneal dialysis prolongs survival and reduces cardiovascular events in male patients.

Although peritoneal dialysis (PD) has been recommended for initial dialysis therapy, a larger proportion of patients with end-stage renal disease choose hemodialysis (HD) instead. Several previous studies comparing the outcomes of these two therapies, including survival rates and cardiovascular events, have not clearly demonstrated the superiority of one over the other. Our recent study indicated that, compared with HD or PD alone, renal replacement therapy with HD and PD in combination prolongs survival and reduces cardiovascular events. However, the use of combination dialysis therapy is not widely accepted. We set out to analyze the efficacy of combination dialysis therapy with PD and HD in patients who started with PD as initial dialysis therapy. Our single-center retrospective cohort study included 401 patients (165 women, 236 men; 61 +/- 12 and 62 +/- 9 years of age respectively) who started PD during 1995-2005. Chart and electronic databases were used to obtain information on the course of dialysis therapy, including mortality and cardiovascular events. Treatment with HD and PD in combination was used in 103 patients. During 5 years of follow-up after the start of PD, 80 patients died. We observed no differences in cumulative mortality between the men (49, 200%) and women (31, 18%) and no difference in the cumulative incidence of catheter removal for various reasons (35% vs. 31%). There was a significant difference (p < 0.05) in the time of HD start between men and women. In men on PD, HD therapy was started 22 +/- 2 months after the start of PD; in women, it was started 38 +/- 7 months after PD start. Although women have a survival advantage in both the general and the dialysis patient population, women on PD experience mortality similar to that in men. The reasons for those findings have not been fully explained. The present analysis suggests that an early start to HD therapy will prolong the survival of patients on PD, especially men.

New modality of dialysis therapy: peritoneal dialysis first and transition to home hemodialysis.

Recent studies have clearly demonstrated that start ing treatment with peritoneal dialysis (PD) is superior to starting with conventional hemodialysis (HD) because PD preserves residual renal function for a longer period. Similarly, because of the frequency of treatments, home HD (HHD) is also superior to conventional HD. The accumulated evidence suggests that a combination of PD and HHD might be a new and effective method for patients receiving dialysis therapy. We analyzed 10 patients who, over the past 10 years, were started on PD and who were then transferred to HHD. Electronic databases were used to examine changes in their health status. Mean age was 58 +/- 8 years in these 2 female and 8 male patients. Mean duration of PD was 6.9 +/- 2.4 years. The average total duration of dialysis therapy was 9.7 +/- 1.9 years. The main reason for the transition from PD to HHD was loss of residual renal function. To the time of writing, no serious complications (including cardiovascular events and calcium homeostasis) had occurred. All patients continue to receive dialysis therapy and have been able to lead a nearly normal social life. Major laboratory findings include serum albumin 4.2 +/- 0.2 g/dL, hemoglobin 10.2 +/- 1.4 g/dL (half the patients were not using erythropoiesis-stimulating agents), serum creatinine 7.5 +/- 2.5 mg/dL, blood urea nitrogen 36 +/- 17 mg/dL, serum phosphate 4.3 mg/dL. In two thirds of the patients, blood pressure was controlled without antihypertensive agents. No patient had left ventricular hypertrophy. In this analysis, we found that relatively young subjects preferred PD first, with later transfer to HHD; that PD is superior as an introduction to dialysis therapy; that patients starting with PD prefer self medical treatment; and that all patients were free from the various complications that are encountered during long-term dialysis therapy. We suggest that patients who need dialysis therapy consider this new dialysis approach of "PD first and transfer to HHD."

Testing a single monthly dose of darbepoetin alpha to maintain hemoglobin levels in continuous ambulatory peritoneal dialysis patients.

The newly developed erythropoiesis agent darbepoetin alpha (DA) allows for once-monthly dosing in the treatment of anemia in patients on dialysis. This dosing schedule has prompted some studies to examine the efficacy of DA in patients on continuous ambulatory peritoneal dialysis (CAPD). In the present study, we assessed whether intravenous (IV) administration of DA once monthly is effective for maintaining hemoglobin levels near 10.5 g/dL in patients on CAPD. This single-center prospective cohort study included 52 clinically stable patients (25 men, 27 women; mean age: 59 +/- 10 years). All patients had been on a stable weekly or twice monthly regimen of recombinant human erythropoietin (rHuEPO) before initiation of the study. To determine the monthly dose of DA, the previously used mean weekly dose of rHuEPO was divided by 200 to determine the equivalent weekly dose of DA in micrograms; that number was then multiplied by 4 to generate the monthly dose requirement. For example, if 3000 IUrHuEPO was being administered weekly, then the monthly dose of DA was calculated to be 60 microg (3000/200 x 4). All patients received a monthly dose of DA the first month, and hemoglobin and other routine laboratory tests were performed monthly for 24 consecutive weeks. In 26 patients, the calculated monthly DA dose remained stable. The monthly dose was increased by 25% in 22 patients and by 50% in 4 patients. With regard to iron stores and iron availability for erythropoiesis, no significant differences were observed in the patients on various doses of DA. Nonsignificant differences in weekly creatinine clearance as determined using the PD Adequest software (Baxter Healthcare, Tokyo, Japan) were observed between the groups. No clinically meaningful differences in other laboratory values between the groups were observed. Once-monthly administration of DA is not always sufficient to maintain hemoglobin levels in patients on CAPD when adequate dialysis therapy is not achieved.

Clinical presentation in patients more than 80 years of age at the start of peritoneal dialysis.

The age of new dialysis patients is rapidly increasing. In the present study, we examined clinical presentation in new peritoneal dialysis (PD) patients 80 years of age or older at our hospital. Data were collected from the records of patients newly starting continuous ambulatory PD (CAPD) therapy between January 2005 and July 2010. During that period, 11 patients 80 years of age or older (average age: 83.1 +/- 3.8 years) were introduced to PD therapy. The reason for dialysis was hypertensive nephrosclerosis in 8 patients, and chronic glomerulonephritis, chronic tubulointerstitial nephritis, and an unknown primary disease in 1 patient each; there were no cases of diabetic nephropathy. At dialysis start, average serum creatinine was 6.1 +/- 1.4 mg/dL, arterial wall calcification was found by computed tomography or chest radiography in 10 of 11 patients (90.9%), and aortic or mitral valve calcification, or both, was found by echocardiography in 3 patients (27.3%). By the end of January 2011, 8 patients had died. Average survival after the start of PD was 31.9 +/- 22.3 months. Hypertensive nephrosclerosis, a cause less often seen in younger patients, was the most common primary disease among our elderly dialysis patients. As we previously reported, vascular and valvular calcification are important factors for determining prognosis; however, no significant relationships were observed in the present study, probably because almost all the patients had such calcifications.

Removal of the peritoneal dialysis catheter because of gastrointestinal disease in patients on continuous ambulatory peritoneal dialysis: a single-center case series.

We previously reported that peritoneal dialysis (PD)-associated peritonitis is a major cause of PD catheter removal. Another major cause is disease of the gastrointestinal tract, including neoplasm and perforation. In the present study, we reviewed the records of patients who underwent catheter removal at our hospital for reasons other than peritoneal infection--and for gastrointestinal disease in particular. Data were collected from the records of patients who received continuous ambulatory PD (CAPD) therapy between 2004 and 2010 at the Department of Nephrology, Saitama Medical University. Mean duration of CAPD was 6.2 +/- 4.7 years, and mean age at onset was 64.5 +/- 9.6 years. During the investigation period, catheters were removed from 13 patients (4 men, 9 women) because of gastrointestinal disease: gastric cancer in 3 cases, colon cancer in 3 cases, perforation of the lower gastrointestinal tract in 3 cases, and other reasons in 4 cases. Examination of pathology specimens obtained from 6 patients-including 1 in whom contrast-enhanced computed tomography indicated the presence of encapsulating peritoneal sclerosis (EPS)-revealed mild fibrosis in the subserous layer. No patient died of infection after a surgical procedure. Moreover, throughout the observation period, no patient developed new EPS or postoperative ileus. The present study suggests that CAPD itself seems to be free of untoward effects during the postoperative course in these patients.

Does cinacalcet HCl, an oral calcimimetic agent for the treatment of secondary hyperparathyroidism, improve arterial stiffness in patients on continuous ambulatory peritoneal dialysis?

Vascular calcification (VC) and arterial stiffness (AS) are major contributors to cardiovascular disease, and in chronic kidney disease, VC and AS are correlated. Disorders of calcium and phosphate metabolism contribute to the progression of VC and to increases in AS. The efficacy of cinacalcet (CIN) in reducing AS in patients on continuous ambulatory peritoneal dialysis (CAPD) has not been determined. The present study enrolled 19 CAPD patients (12 women, 7 men; mean age: 62.2 +/- 3.6 years) with serum intact parathyroid hormone (iPTH) greater than 500 ng/dL (mean value: 675 +/- 106 ng/dL) in whom daily oral treatment with CIN 25 mg was started. If administration of CIN for 3 months failed to reduce the level of iPTH to less than 300 ng/dL, the dose of CIN was increased to 50 mg daily. Before the start of CIN and at 3 years after the start of CIN, pulse wave velocity (PWV) was determined. In 11 patients, levels of iPTH were reduced to less than 300 ng/dL; levels in the rest of the patients remained high. We observed no significant differences in PWV before CIN and at 3 years after CIN start (1856 +/- 198 cm/s vs. 1726 +/- 187 cm/s). Multivariate regression analysis of PWV demonstrated that both systolic blood pressure and changes in serum levels of phosphate contributed to decreases in PWV In patients receiving CAPD, VC and AS might be the result of higher systolic blood pressure and increased serum levels of phosphate.

Noninvasive evaluation of kidney hypoxia and fibrosis using magnetic resonance imaging.

Interstitial fibrosis and hypoxia accelerate the progression of CKD, but clinical tools to quantitate these factors in patients are lacking. Here, we evaluated the use of two magnetic resonance imaging (MRI) techniques, diffusion-weighted (DW)-MRI and blood oxygen level-dependent (BOLD)-MRI, to assess kidney fibrosis and hypoxia of the cortex in 142 patients with either diabetic nephropathy (n = 43), CKD without diabetes (n = 76), or acute kidney injury (AKI) (n = 23). Apparent diffusion coefficient (ADC) values of DW-MRI correlated with estimated glomerular filtration rates (eGFR) in the diabetic nephropathy and CKD groups (r(2) = 0.56 and r(2) = 0.46, respectively). Although the T2* values of BOLD-MRI and eGFR displayed good correlation in the CKD group (r(2) = 0.38), we did not observe a significant correlation between these values in the diabetic nephropathy group, suggesting that factors other than tubulointerstitial alteration determine the degree of hypoxia in the renal cortex. In the AKI group, neither the T2* nor ADC values correlated with eGFR. Renal biopsies from patients with CKD demonstrated that the T2* and ADC MRI values correlated with renal pathology. Taken together, ADC and T2* values appear to serve as accurate indices for evaluating renal tubulointerstitial alterations and parenchymal hypoxia, respectively, in the cortex. Functional MRI can thus contribute to multilateral, noninvasive, in vivo assessment of kidney function.

[Association between long-term smoking and hypertension and early-onset nodular glomerulosclerosis].

Diabetic nodular glomerulosclerosis, also known as Kimmelstiel-Wilson syndrome, is a specific pathological variant of diabetic nephropathy ; however, histological findings similar to diabetic nephropathy are observed occasionally without glucose intolerance. Therefore, such nodular glomerulosclerosis is called idiopathic nodular glomerulosclerosis. Several case reports that have been published recently indicate that smoking and hypertension, which are classical renal risk factors, may be attributed to this form of glomerular degeneration. Accordingly smoking- and hypertension-associated nodular glomerulosclerosis has been considered to be different from the idiopathic form. This novel form of nodular glomerulosclerosis is associated with a history of long-term smoking and hypertension, and the age of onset of this disease is more than 60 years. We present the case of a 27-year-old Japanese male who was admitted to our hospital with nephrotic syndrome, hypertension, and renal impairment. He had a smoking history of at least 13 years, and had been exposed to passive smoking for several years because his parents were smokers. Renal biopsy revealed diffuse and global nodular glomerulosclerosis, although the patient did not have any primary diseases such as diabetes mellitus or paraproteinemia, that can cause this condition. We diagnosed smoking- and hypertension-associated nodular glomerulosclerosis. Cessation of smoking and the administration of an angiotensin II receptor blocker decreased his proteinuria and showed recovery of kidney function. This case report suggests that long-term smoking is closely associated with nodular glomerulosclerosis. Further, in our case, the age of the patient was lower than that of patients with the same disease among cases that have been reported previously.

Granulomatous interstitial nephritis in chronic lymphocytic leukaemia.

We present a case of granulomatous interstitial nephritis (GIN) associated with chronic lymphocytic leukaemia (CLL). GIN is a rare pathological finding noted in renal biopsy specimens. Furthermore, CLL does not usually cause GIN. In this case, acute renal injury probably resulted from GIN, and urgent dialysis was required, despite sufficient chemotherapy. Immunohistochemical analyses of a biopsy specimen revealed invasion of CD20( +) CLL cells, surrounded by reactive T cells, and granuloma formation. Thus, CLL may induce secondary interstitial nephritis as a granulomatous reaction.