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.

Evaluation of the efficacy of granulocyte and monocyte adsorption apheresis on skin manifestation and joint symptoms of patients with pustulotic arthro-osteitis.

Pustulotic arthro-osteitis, occasionally complicated with palmoplantar pustulosis, affects patients' activities of daily living. Granulocyte and monocyte adsorption apheresis selectively removes activated granulocytes and monocytes by means of extracorporeal circulation. Although the efficacy of granulocyte and monocyte adsorption apheresis in the treatment of generalized pustular psoriasis has been proved, very few reports have assessed its efficacy in the treatment of palmoplantar pustulosis and pustulotic arthro-osteitis. Ten pustulotic arthro-osteitis patients with five palmoplantar skin manifestations were treated with weekly granulocyte and monocyte adsorption apheresis over 5 weeks. Skin manifestations were assessed using palmoplantar pustulosis area and severity index, and joint symptoms were assessed using a visual analog scale of joint pain, tender joint count, swollen joint count and C-reactive protein immediately before, after and at the 3-month follow up of the five granulocyte and monocyte adsorption apheresis sessions. Two out of five patients with skin manifestations achieved more than 50% improvement in their score (remarkably improved). However, in two patients, deterioration was noted, in one of whom the skin manifestations remained unchanged at the 3-month follow up. In five out of the 10 patients, the joint symptoms were assessed as better than improved at the 3-month follow up. No deterioration was noted at the 3-month follow up. In three patients, reduction or cessation of medication for arthralgia was possible. We concluded that granulocyte and monocyte adsorption apheresis is a therapeutic option to consider when pustulotic arthro-osteitis is recalcitrant to conventional therapy.

The effect of small dose of topiroxostat on serum uric acid in patients receiving hemodialysis.

INTRODUCTION: Topiroxostat, a recently developed xanthine oxidase inhibitor, is expected to have fewer adverse effects than allopurinol because it has different mechanism of action from alloprinol. However, its dosage, usage and safety have not been established in patients with impaired renal function or those undergoing dialysis at the development since no studies was conducted in these patients. METHODS: Cross over clinical trial using 3 months of allopurinol and topiroxostat on 27 maintain Japanese HD patients were carried out. The effects on oxidative stress status of both drugs were also evaluated by measuring oxidation reduction potential. FINDINGS: Twenty-five of twenty-seven patients completed study. The mean serum uric acid levels in the topiroxostat-treated arm was significantly lower than it in the allopurinol-treated arm time-dependently (P < 0.0001). Corrected oxidative stress ratio defined as biological antioxidant potential/diacron reactive oxygen metabolites was significantly increased in topiroxostat-arm (*P = 0.0035), but not in allopurinol-arm (P = 0.1429). No significant difference was seen in diacron reactive oxygen metabolites, biological antioxidant potential, static oxidation-reduction potential, and capacity oxidation-reduction potential between pre and post treatment of both drugs. DISCUSSION: It is suggested that a low dose of topiroxostat decreased serum uric acid sufficiently to maintain it below 7.0 mg/dL in patients receiving hemodialysis.

[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.

Association between visit-to-visit clinic blood pressure variability and home blood pressure variability in patients with chronic kidney disease.

Although both clinic blood pressure (BP) variability and home BP variability are associated with the risk of cardiovascular disease, the relationship between both BP variabilities remain unclear. We evaluated the association between visit-to-visit variability of clinic BP (VVV) and day-by-day home BP variability (HBPV) in patients with chronic kidney disease (CKD). We recruited 143 CKD patients in whom we performed HBP measurements every morning and evening over seven consecutive days. We obtained clinic BP data during 9.6 ± 1.0 consecutive visits within 24 months. The associations between the variables of VVV and HPBV were examined. The CV values of clinic systolic BP (CSBP) was significantly correlated with the mean values of morning systolic BP (MSBP) and those of evening systolic BP (ESBP) (r = 0.23, 0.20; p = 0.007, 0.02, respectively). The CV values of CSBP was significantly correlated with the CV values of MSBP and those of ESBP (r = 0.19, 0.31; p = 0.02, <0.001, respectively). On the multivariate regression analysis, the CV values of CSBP was significantly correlated with the CV values of MSBP and those of ESBP [standardized regression coefficient (ß) = 0.19, 0.34; p = 0.03, <0.001, respectively]. In conclusion, VVV showed a weak but significant association with HBPV, especially the CV values of ESBP in CKD patients. Further studies are necessary to clarify whether these different BPV elements will be alternative marker of BPV.

Clinical Practice of Two Measurements of Home Blood Pressure on Each Occasion in Patients with Chronic Kidney Disease.

BACKGROUND/AIMS: Although several guidelines propose two or three measurements of home blood pressure (HBP) on each occasion, the actual status of multiple measurements is not clear in the practical management of hypertension. We surveyed the details regarding two measurements of HBP in patients with chronic kidney disease (CKD). METHODS: HBP was measured twice every morning and evening over 7 consecutive days in 175 CKD patients. The distribution of the differences between two BP values (2nd - 1st BP) and their association with BP parameters were evaluated. RESULTS: The 2nd - 1st morning systolic BP (SBP) and diastolic BP (DBP) differences were -2.3 ± 4.1 and -0.4 ± 2.6 mm Hg, respectively. The proportion of 2nd - 1st morning SBP differences >0 mm Hg was 31.7% in a total of 1,195 measurements. Eighty patients (45.7%) had days with a difference ≤-5 mm Hg and days with a difference ≥5 mm Hg in morning SBP during 7 days. The multivariate regression analysis of the SD values of 2nd - 1st morning SBP as a dependent variable showed that the SD value of the 1st morning SBP (ß = 0.65, p < 0.001) was a significant determinant. CONCLUSION: Although the 2nd SBP was 2-3 mm Hg lower than the 1st SBP in the population as a whole, various differences were found for each subject during 7 days. 2nd - 1st BP variability might be associated with day-by-day 1st BP variability.

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.

[Validity of the assessment of urinary protein excretion by spot urine in patients with chronic kidney disease].

AIM: We investigate the validity of the assessment of urinary protein excretion by spot urine samples collected by different methods in outpatients with chronic kidney disease (CKD). SUBJECTS AND METHODS We obtained 24-hour urine and two spot urine samples, including the first morning urine and daytime urine in 159 CKD patients. Urinary protein excretion was assessed by the protein/creatinine ratio from spot urine samples (morning: m-UP (g/gCr), daytime: d-UP (g/gCr) ]. We examined the correlations and the differences among m-UP, d-UP and the actual urinary protein excretion obtained by 24-hour urine (a-UP(g/day) . RESULTS: Significant correlations were found between m-UP and a-UP, and between d-UP and a-UP (r = 0.88, 0.85; p < 0.001). Correlations between m-UP and a-UP were greater relative to those between d-UP and a-UP in patients with less than 3.5 g/day of a-UP and in patients with CKD stages 1 to approximately 3. The percent difference between m-UP and a-UP was--16.0 +/- 40.5%, and that between d-UP and a-UP was 27.1 +/- 72.9%. The absolute value of the percent difference between d-UP and a-UP tended to be greater than that between m-UP and a-UP (34.9 +/- 25.9% vs. 49.9 +/- 59.9%, p = 0.06). CONCLUSION: Urinary protein/creatinie ratio of the first morning urine is better approximate the urinary protein excretion obtained by 24-hour urine compared with that of spot urine in the daytime.

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.

Phosphate handling by end-stage kidneys and benefits of residual renal function on phosphate removal in patients on haemodialysis.

AIM: We investigated the handling of phosphate by end-stage kidneys and the contribution of residual renal function (RRF) to phosphate homeostasis in haemodialysis patients. METHODS: Blood and 24 h urinary specimens were obtained from 79 consecutive chronic haemodialysis patients with a urinary output greater than 100 mL/day. Thirty-five patients with a glomerular filtration rate (GFR) ≥ 3.0 mL/min were included as group A, and 44 patients with GFR < 3.0 mL/min as group B. Additionally, the whole dialysed fluids during a session of haemodialysis were collected from another nine patients. Concentrations of phosphate, creatinine, urea nitrogen, intact parathyroid hormone (iPTH) and fibroblast growth factor 23 (FGF-23) were measured. RESULTS: Twenty-four hour urinary phosphate excretion (UPE) was 283 ± 115 and 139 ± 57 mg/day (9.1 ± 3.5 and 4.5 ± 1.8 mmol/day) in groups A and B, respectively. Tubular reabsorption of phosphate (TRP) was 39.2 ± 13.3 and 31.7 ± 13.6% in groups A and B, respectively (P = 0.02). UPE significantly correlated with GFR (r = 0.85, P < 0.001) and PTH (r = 0.44, P < 0.001), but not with FGF-23, in the entire patient population. The correlation between UPE and intact PTH levels was absent in group B. Weekly UPE in group A was significantly greater (P < 0.001), while that in group B was similar to the amount of phosphate removed by a haemodialysis session. CONCLUSIONS: Urinary phosphate excretion by end-stage kidneys depends more on GFR than diminishing TRP. The action of PTH on the kidneys remains until GFR decreases to as low as 3 mL/min. Residual renal function plays a significant role in phosphate elimination, and it is possible that FGF-23 no longer acts effectively to excrete phosphate in the urine in these patients.

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.

Association of home blood pressure variability with progression of chronic kidney disease.

OBJECTIVE: Home blood pressure (HBP) has been found to be a predictor of the progression of chronic kidney disease (CKD). The objective of this study is to clarify the clinical significance of day-by-day HBP variability on the progression of CKD. METHODS: We recruited 135 patients with stage 3-5 CKD, who performed daily HBP measurements, every morning and evening over 7 consecutive days and recorded every 6 months, with a follow-up of 36 months. We examined the associations between the variables of blood pressure (BP) variability [SD, coefficient of variation (CV), average real variability (ARV)], and renal outcomes. RESULTS: No significant correlations were found between the SD values, the CV values, the ARV values of each BP measurement, and the change in estimated glomerular filtration rate on multivariate regression analysis (ß of SD, CV, and ARV of morning systolic BP: 0.04, 0.04, and 0.02; P=0.69, 0.63, and 0.20, respectively). None of these variables of each BP measurement showed a significant risk of renal events on multivariate Cox proportional hazards analysis (hazard ratios of SD, CV, and ARV of morning systolic BP: 0.99 (95% confidence intervals: 0.80-1.23), 0.97 (0.72-1.31), and 1.01 (0.83-1.24); P=0.94, 0.86, and 0.92, respectively). CONCLUSION: Day-by-day BP variability as assessed by HBP measurements had no significant association with the progression of CKD.

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.

Ratio of urinary potassium to urinary sodium and the potassium and edema status in nephrotic syndrome.

OBJECTIVE: This study aimed to evaluate the relevance of ratios of urinary potassium to urinary sodium + potassium (U(K)/U(Na + K)) to edema status in minimal-change nephrotic syndrome (MCNS). METHODS: We retrospectively studied 26 adults with newly diagnosed MCNS with significant pitting edema. On the basis of mean value (0.46±0.21) of U(K)/U(Na + K) determined from spot urine samples on admission, patients were classified into 2 groups. RESULTS: On admission, 12 of 26 patients had U(K)/U(Na + K) >0.46 (0.65±0.16, Group H), 14 patients had U(K)/U(Na + K) <0.46 (0.29±0.08, Group L). The level of serum albumin was similarly decreased in these 2 groups. Noteworthy were lower urine volume, fractional excretion of sodium (FENa), serum sodium, and higher hematocrit in the group H as compared with the group L. The group H had a shorter mean time required from onset of edema to hospitalization, and tended to have a longer mean time to complete remission than group L. High U(K)/U(Na + K) levels in group H decreased significantly after remission, eventually becoming equal to those of group L (0.24±0.05 vs. 0.25±0.05). CONCLUSION: U(K)/U(Na + K) determined from spot urine sample on admission relates to laboratory or clinical indices to distinguish edema status in adult patients with MCNS.

Influence of proteinuria on glycated albumin values in diabetic patients with chronic kidney disease.

BACKGROUND: Glycated albumin (GA), which is an alternative glycemic marker, is influenced by factors associated with albumin turnover, and it is not clear whether proteinuria influences GA values in diabetic patients with chronic kidney disease (CKD). METHODS: We enrolled 94 diabetic patients with CKD stages 3 to 5. GA, glycated hemoglobin, and urinary protein excretion (UP) levels were consecutively obtained in each patient. The correlations between GA and UP and those between changes in GA and UP were examined. RESULTS: There was a significant correlation between GA and UP in all cases (r=-0.46, p<0.0001), however no significant correlation was found in cases with UP of 0-3.49 g/day (r=0.01). GA values in cases with UP ≥3.5 g/day were significantly lower than those in cases with UP <3.5 g/day [UP ≥3.5 g/day and serum albumin (Alb) ≤3 g/dL; 12.0 ± 1.3%, UP ≥3.5 g/day and Alb >3 g/dL; 17.8 ± 4.3%, 0≥ UP <3.5 g/day; 21.2 ± 4.2%], while no significant difference in HbA(1c) or glucose levels was found. In cases with a minimum of UP ≥0.5 g/day, no significant correlation was found between the difference in GA and the difference in UP at the point of maximum UP and minimum UP (r=0.04). CONCLUSION: Nephrotic-range proteinuria decreases GA values independent of the glycemic state, while non-nephrotic range proteinuria has no significant influence on GA values in diabetic CKD patients.

Benefits of staple food restriction for Japanese obese patients with chronic kidney disease: a pilot study.

OBJECTIVE: We conducted a pilot study to assess the effects of dietary intervention on metabolic risk factors and renal parameters in obese patients with chronic kidney disease (CKD). METHODS: We studied 19 obese patients with CKD at our outpatient clinic. The diet selected for this study restricted only their staple food intake, with no change in the side dish component of their meals. We studied neither the lifestyles of the patients nor the activities that they were involved in. We examined changes in clinical and laboratory parameters at baseline and after consumption of the diet. RESULTS: After 2 and 6 months of staple food restriction, changes in body weight were found to be -3.6% ± 3.9% and -3.4% ± 4.7%, respectively. Of the 19 patients, the body weights of 9 decreased by >3% (range: 3.4% to 17.1%) from baseline to follow-up at 6 months. After 6 months of following the diet, these 9 patients showed marked reductions in blood pressure, homeostasis model assessment insulin resistance, and triglycerides, when compared with the remaining 10 patients with stable body weights; however, for proteinuria and estimated glomerular filtration rate they reported having values similar to the 10 patients with stable body weights. CONCLUSIONS: Weight reduction associated with a lowered insulin resistance was reported in obese patients with CKD after 6 months of staple food restriction; however, further studies need to be conducted to confirm the presence of other possible renal benefits.

Clinical evaluation of chronic nephrotoxicity of long-term cyclosporine A treatment in adult patients with steroid-dependent nephrotic syndrome.

AIM: Chronic nephrotoxicity of long-term cyclosporine A (CsA) treatment is a matter of concern in patients with steroid-dependent nephrotic syndrome (SDNS). METHODS: Twenty-eight adult NS patients (25, minimal-change nephrotic syndrome (NS); three, focal-segmental glomerulosclerosis) were divided into three groups. Group A was continuously treated with CsA for more than 5 years (143 ± 40 months, 1.3 ± 0.4 mg/kg per day at final analysis, n = 12); group B had been previously treated with CsA (70 ± 27 months, n = 6); and group C had been treated with corticosteroids alone (n = 10). The clinical variables related to chronic CsA nephrotoxicity were examined. RESULTS: In groups A and B, estimated glomerular filtration rate decreased from 86 ± 22 and 107 ± 17 to 83 ± 23 and 88 ± 13 mL/min per 1.73 m(2) , respectively, at final analysis (both P < 0.05). Serum magnesium levels in group A were significantly lower than those in group B or C (A, 1.78 ± 0.16 mg/dL; B, 2.00 ± 0.14 mg/dL; C, 2.03 ± 0.10 mg/dL; A vs B, C, P < 0.01), and a significant correlation between these and the duration of CsA treatment was found (r = -0.68, P < 0.001). There was a trend towards a correlation between the duration of CsA administration and urinary α1-microglobulin (r = 0.38, P = 0.07). CONCLUSION: Mild decrease in renal function and hypomagnesemia were found in adult SDNS patients with long-term CsA treatment. Careful monitoring of renal function, blood pressure and serum magnesium levels is necessary.