Reduced endothelial factor VIII staining in renal microcirculation correlates with hemodynamic alteration in nephrosis

Endothelial factor VIII staining in renal microcirculation was performed in eight nephrotic patients associated with mesangial proliferation (MesP) and six nephrotic patients associated with focal segmental glomerulosclerosis (FSGS). The result in MesP revealed a greater staining for glomerular endothelial factor VIII (35 +/- 15%) and for postglomerular capillary endothelial factor VIII (65 +/- 21%) than that observed in FSGS, which revealed a 11 +/- 8% staining for glomerular endothelial factor VIII and 19 +/- 15% staining for postglomerular capillary endothelial factor VIII. This finding implies that there is a greater loss of endothelial cell in renal microcirculation in FSGS. Such a finding correlates with the intrarenal hemodynamics which illustrated (Futrakul, P.; Sitprija, V.; Yenrusi, S. Glomerular endothelial dysfunction determines disease progression: a hypothesis. Am. J. Nephrol. 1997, 17, 533-540.) a mild reduction in renal plasma flow (535 +/- 106 mL/min/1.73 m2, normal 600 mL/min/1.73 m2) and in peritubular capillary flow (422 +/- 80 mL/min/1.73 m2, normal 480 mL/min/1.73 m2) in MesP and (Futrakul, P. Coagulation in glomerulonephritis and nephrotic symdrome: Its therapeutic intervention. In Asian Manual of Nephrology, Takeuchi, T.; Sugino, N.; Ota, K., Eds.; SEAMIC Publication, Tokyo, 1981; pp. 89-95.) a greater reduction in renal plasma flow (108 +/- 50 mL/min/1.73 m2) and in peritubular capillary flow (87 +/- 42 mL/min/1.78 m2) in FSGS. Therefore the study has emphasized both the structural and functional defects of endothelium in renal microcirculation in particular in FSGS.     

Hemodynamic Maladjustment and Disease Progression in Nephrosis with FSGS

Idiopathic nephrotic syndrome (NS) associated with focal segmental glomerulosclerosis (FSGS) and severe renal function impairment is usually refractory to the conventional treatment and progresses to end‐stage renal disease. Herein, we reported 10 patients with NS‐FSGS who had initially had CCr 34 ± 12 mL/min/1.73m² (normal 120 mL/min/1.73m²), FE Mg 7.8 ± 2.6% (normal 2.2%), 24‐h urinary protein 3.1 g (normal < 200 mg) and been followed up for over 10 years. The initial intrarenal hemodynamic study revealed a marked elevation of efferent arteriolar resistance (RE 17289 ± 8636 dyne.s.cm^{? 5}; normal 3000 dyne.s.cm^{? 5}), intraglomerular hypertension (PG 57 ± 1 mm Hg; normal 52 mm Hg), hyperfiltration (FF 0.24; normal 0.2), marked reductions in GFR 35 ± 17 mL/min/1.73m², renal plasma flow (RPF 159 ± 61 mL/min/1.73m²; normal 600 mL/min/1.73m²) and peritubular capillary flow (PTCF 123 ± 57 mL/min/1.73m²; normal 480 mL/min/1.73m²). Such a hemodynamic alteration indicated a hemodynamic maladjustment with a preferential constriction at RE. Treatment consists of multidrugs, namely angiotensin converting enzyme inhibitor, calcium channel blocker, antiplatelet and anticoagulant, with or without angiotensin II receptor antagonist. Following the treatment, correction of hemodynamic maladjustment has been achieved which is characterized by reductions in RE 6046 ± 2191 dyne.s.cm^{? 5}, PG 52 ± mm Hg, FF 0.19 ± 0.1 and increments in RPF 341 ± 118 mL/min/1.73m², PTCF 280 ± 106 mL/min/1.73m² and GFR 64 ± 17 mL/min/1.73m². Coinciding with hemodynamic improvement, there has been a steadily increased creatinine clearance and improvement in FE Mg 4.3 ± 2.6% and suppression of proteinuria 0.29 ± 0.4g/24 h after the period of follow‐up of greater than 10 years.     

Glomerular Endothelial Dysfunction and Hemodynamic Maladjustment in Vesicoureteric Reflux

A structural defect of the non-vascular component of a nephron namely vesicoureteric reflex (VUR) can induce injury to the vascular component, which is reflected by the alteration in intrarenal hemodynamics. A mild alteration in intrarenal hemodynamics was observed in grades I–II VUR which revealed (a) mild reductions in renal plasma flow (RPF) 543 ± 104 mL/min/1.73 m²; in peritubular capillary flow (PTCF) 438 ± 103 mL/min/1.73 m²; in glomerular filtration rate (GFR) 105 ± 19 mL/min/1.73 m² and in ultrafiltration coefficient (KFG) 0.04 ± 0.01 mL/s/mmHg; (b) normal values of filtration fraction (FF) 0.2 ± 0.04, of intraglomerular hydrostatic pressure (PG) 50 ± 0.3 mmHg, and of afferent arteriolar resistance (RA) 2261 ± 718 dyne s cm^?5; and (c) a slight elevation of efferent arteriolar resistance (RE) 3914 ± 962 dyne s cm^?5. In contrast, a moderately severe alteration in intrarenal hemodynamics was observed in severe VUR (grades III up) which revealed greater reductions in RPF 267 ± 114 mL/min/1.73 m², in PTCF 195 ± 90 mL/min/1.73 m², in GFR 72 ± 34 mL/min/1.73 m² and in KFG 0.03 ± 0.01 mL/s/mmHg; and elevation of PG 53 ± 2 mmHg, of filtration fraction 0.27 ± 0.07, of RA 4557 ± 2340 dyne s cm^?5 and of RE 9417 ± 4163 dyne s cm^?5. Such an alteration in intrarenal hemodynamics observed in severe VUR induces both intraglomerular hypertension (elevated PG) and an exaggeratedly reduced PTCF. This intrarenal hemodynamic defect is due to the glomerular endothelial dysfunction and its hemodynamic maladjustment. In accordance with the preceding information, treatment to correct the hemodynamic maladjustment is likely to improve renal function and prevent renal disease progression.     

Frequently relapsing nephrotic syndrome: treatment with mycophenolate mofetil

Long-term treatment with cyclosporin A (CyA) of children with frequently relapsing steroid-sensitive nephrotic syndrome (SSNS) carries the risk of nephrotoxicity. We have analyzed renal function in 23 children with SSNS during CyA therapy. Repeated measurements of glomerular filtration rate (single-shot ⁵¹Cr-EDTA clearance) showed a decline from 131±21 ml/min per 1.73 m² to 116±27 ml/min per 1.73 m² at last follow-up. Similarly, effective renal plasma flow (simultaneous ¹²³I-hippurate clearance) was correlated with duration of CyA treatment, and showed a decline from 980±318 ml/min per 1.73 m² to 724±242 ml/min per 1.73 m². In a pilot study we investigated the effect of mycofenolate mofetil (MMF) in 7 children with a median age of 12.7 years [6 with minimal change nephrotic syndrome (MCNS), 1 with focal segmental glomerulosclerosis (FSGS)] with signs of nephrotoxicity because of long-term CyA therapy. Only 1 patient with SSNS showed a relapse during MMF therapy. In the patient with FSGS, MMF was started in addition to CyA, resulting in complete remission for a follow-up of 28 months. This preliminary study demonstrates that children with MCNS treated with CyA may be successfully converted to MMF without major side effects. In all cases, including FSGS, MMF had a beneficial effect on renal function. These data should be confirmed by a prospective randomized clinical trial.     

Treatments of Hemodynamic Maladjustment and Oxidative Stress Prevent Renal Disease Progression in Chronically Severe Glomerulonephritides

Hemodynamic maladjustment is a unique observation in chronically severe glomerulonephritides. It is characterized by a markedly elevated efferent arteriolar resistance (RE), an elevated intraglomerular hydrostatic pressure (PG) and a markedly decreased renal plasma flow (RPF), and peritubular capillary flow (PTCF). A correction of such hemodynamic maladjustment can be accomplished by administering a combination of vasodilators (angiotensin receptor antagonist, angiotensin converting enzyme inhibitor, and calcium channel blocker) in 14 chronic glomerulonephritides with severe renal function impairment (mean serum creatinine 3.6 + 1.3 mg/dL). Doses titration aim for maximal renal perfusion effect (increased RPF, PTCF) or maximal renal function improvement (increased CCr, reduced FE Mg) usually higher than needed for maximal blood pressure reduction. Evidence of oxidative stress is also corrected with high doses of vitamins C and E. After a mean period of treatment for 13.5 months, improvements in CCr (pre R_x 22 ± 10 vs. post R_x 32 ± 13 mL/min/1.73 m²), and FE Mg (pre R_x 11.9 ± 4% vs. post R_x 10 ± 3%) were observed in conjunction with the improvement in intrarenal hemodynamics namely RPF (pre R_x 201 ± 71 vs. post R_x 288 ± 99 mL/min/1.73 m²), PTCF (pre R_x 161 ± 57 vs. post R_x 242 ± 90 mL/min/1.73 m²), PG (pre R_x 56.7 ± 0.5 vs. post R_x 51 ± 0.1 mm Hg), and RE (pre R_x 12085 ± 6503 vs. post R_x 6550 ± 1872 dyne.s.cm^?5).     

Histological Features of Acute Tubular Necrosis in Native Kidneys and Long-Term Renal Function

There are few studies on the relationship between the morphology of acute tubular necrosis (ATN) in native kidneys and late functional recovery. Eighteen patients with acute renal failure (ARF) who had undergone renal biopsy were studied. All had the histological diagnosis of ATN and were followed for at least six months. Clinical characteristics of ARF were analyzed, and histological features were semi-quantitatively evaluated (tubular atrophy, interstitial inflammatory infiltrate, interstitial fibrosis, and ATN). According to the maximal GFR achieved during the follow-up, patients were divided into two groups: complete recovery (GFR ≥ 90 mL/min/1.73 m²) and partial recovery (GFR < 90 mL/min/1.73 m²). Only 39% of the patients achieved complete recovery. Patients with partial recovery achieved their maximal GFR (63 ± 9 mL/min/1.73 m²) 37 ± 14 months after ARF, a period of time similar to those patients with complete recovery (i.e., 54 ± 22 months). Patients with partial recovery had more severe ARF: oliguria was more frequent (90 versus 17%, p < 0.01), and they had higher peak creatinine (13.85 ± 1.12 versus 8.95 ± 1.30 mg/dL, p = 0.01), and longer hospitalization (45 ± 7 versus 20 ± 4 days, p = 0.03). No single histological parameter was associated with partial recovery, but the sum of all was when expressed as an injury index [4.00 (2.73–5.45) versus 2.00 (1.25–3.31), p < 0.05]. In conclusion, among patients with atypical ATN course, those with more severe ARF and tubule-interstitial lesions are more prone to partial recovery.     

Transforming Growth Factor-β1 Gene Polymorphism in Renal Transplant Recipients

Background. Cytokine transforming growth factor (TGF) is involved in regulation of tissue repair after injury. More recently, TGF–β1 codon 10 gene polymorphism has been shown to be associated with circulating TGF-β levels. We tested whether TGF-β1 genotype polymorphism was predictive of renal allograft function decline. Patients and Methods. The study population consisted of 129 consecutive cadaveric or living related renal transplant recipients at our center between 1985 and 2001. The recipient TGF-β1 genotype polymorphism was determined from peripheral blood leucocytes DNA. The primary endpoint was rate of glomerular filtration rate decline between the first year and the third year of transplant. Results. Baseline glomerular filtration rate as estimated by MDRD study equation at 1 year measured 50 ± 17 mL/min/1.73 m². At the end of the 3-year follow-up period, 52 patients (40%) experienced biopsy-confirmed acute rejections. Frequency and severity of allograft rejection did not differ with TGF-β genotypes. However, the decline in glomerular filtration rate was significantly greater in Leu/Leu (TT) than Leu/Pro (CT) recipients, 6.3 ± 16.9 mL/min/1.73 m² versus 0.1±10.2 mL/min/1.73 m², p = 0.04. Conclusion. Our results demonstrate that recipient TGF-β1 codon 10 Leu/Leu homozygosity is a potential risk factor of kidney allograft function decline.     

Baseline living‐donor kidney volume and function associate with 1‐year post‐nephrectomy kidney function

Living donors may develop kidney dysfunction more often than equally healthy populations. The purpose of this study was to determine whether computed tomography‐assessed remaining kidney volume indexed to body surface area (RKV/BSA) was associated with 1‐year post‐nephrectomy renal function independent of baseline renal function. Using multivariable regression, we modeled 1‐year estimated glomerular filtration rate (eGFR) and eGFR <60 mL /min/1.73 m² and considered pre‐determined baseline eGFR subgroups in 151 consecutive donors. Mean ± SD baseline age, eGFR, RKV, BSA, and RKV/BSA were 38 ± 11 years, 97 ± 16 mL/min/1.73 m², 153 ± 29 mL, 1.9 ± 0.2 m², and 80.0 ± 12.8 ml/m², respectively; 50% were female and 94% were white. Mean baseline eGFR was greater with increasing RKV/BSA tertiles (92 ± 14, 97 ± 16, 107 ± 16 mL/min/1.73 m²; P < 0.001). Post‐nephrectomy eGFR remained separated by RKV/BSA tertiles. At baseline, each SD greater RKV/BSA and eGFR was independently associated with higher adjusted 1‐year eGFR by 2.4 and 9.2 mL/min/1.73 m². Each SD greater age associated with 2.2 mL/min/1.73 m² lower adjusted 1‐year eGFR. Adjusted odds of 1‐year eGFR <60 increased significantly for donors with RKV/BSA <80 mL/m². With baseline eGFR <90, probability of 1‐year eGFR <60 increased to >80% with decreasing RKV/BSA values below 80 mL/m². Those with baseline eGFR >100 rarely developed 1‐year eGFR <60 if RKV/BSA remained >60 mL/m². RKV/BSA independently associated with 1‐year eGFR <60, especially with lower baseline eGFRs. Additional studies should evaluate the predictive utility of this measure and its potential role in donor evaluations and informed consent.     

Long-term plasmapheresis and protein A column treatment of recurrent FSGS

Transient or intermittent plasmapheresis with concurrent immunosuppressive therapy is thought to be beneficial in the treatment of recurrent focal segmental glomerulosclerosis (FSGS) in the early post-transplant period. The results of long-term (6-year) plasmapheresis therapy, in a 9-year-old female with an immediate recurrence of FSGS [urinary protein/urinary creatinine (UP/UC)=17.7] after cadaveric renal transplant, are presented. A 4-week plasmapheresis course induced a decline in the proteinuria, but a relapse occurred after cessation of plasmapheresis. Addition of protein A column therapy led to a further decrease in the proteinuria, to a non-nephrotic range. Long-term control of the nephrotic syndrome was established using a chronic treatment regimen consisting of a single-volume plasmapheresis, followed by a protein A column treatment, performed on sequential days every 3–4 weeks. Mean UP/UC values decreased to 1.15±0.9. A course of cyclophosphamide was successfully used to control a worsening of proteinuria 4 years post transplant. Although sequential renal biopsies demonstrated progressive glomerular sclerosis, the patient’s mean calculated creatinine clearance only modestly declined from 78.3 ml/min per 1.73 m², at the time of transplantation, to 62.7 ml/min per 1.73 m², 6 years later. This patient demonstrated dependence on plasmapheresis/protein A column therapy to maintain a clinical remission of her FSGS recurrence. While long-term plasmapheresis and protein A column therapy in combination with immunosuppressive therapy reversed the effects of uncontrolled nephrosis and possibly facilitated long-term renal allograft survival, the glomerular sclerosis continued to progress. Received: 4 April 2001 / Revised: 15 June 2001 / Accepted: 15 June 2001     

Renal function during and after childhood acute poststreptococcal glomerulonephritis

It is still debatable whether acute poststreptococcal glomerulonephritis (APSGN) can lead to permanent renal impairment. The clinical, immunological, and histological findings during the acute disease have been described thoroughly, however, the hemodynamic events are still poorly understood. In this retrospective study, the inulin and p-aminohippurate clearances were measured to evaluate glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) within a month of onset of the disease (acute stage) in 26 children, and 2–12 months after onset (follow-up) in 22 children with APSGN. During the acute stage, the mean GFR was 77±23 (SD) ml/min per 1.73 m², the mean ERPF 537±138 ml/min per 1.73 m², and the filtration fraction (FF) 14%±3%, compared with values for controls of 115±11 ml/min per 1.73 m², 607±72 ml/min per 1.73 m², and 19%±2%, respectively (n=42). At follow-up, GFR was 114±15 ml/min per 1.73 m², ERPF 600±68 ml/min per 1.73 m², and FF 19%±3%. Thus, during the disease both GFR and ERPF fell below values for controls, but later were restored. The GFR, however, was more reduced than the ERPF, as indicated by the reduced FF. This might reflect a relative hyperperfusion of individual nephrons, which might start processes later deleterious to the nephrons. This finding, however, needs to be further investigated and we have therefore started a long-term follow-up of these patients. Received: 24 June 1998 / Revised: 4 December 1998 / Accepted: 7 December 1998     

Peritubular capillary flow determines tubulointerstitial disease in idiopathic nephrotic syndrome

The spatial relationship between renal perfusion and nephronal structure was determined in 51 nephrotic patients consisting of 11 patients with steroid sensitive, minimal change (MC) nephrosis, 12 patients with steroid resistant, mesangial proliferative (MesP) nephrosis and without tubulointerstitial fibrosis (TIF), 11 patients with steroid resistant, MesP nephrosis and with low grade TIF and 17 patients with focal segmental glomerulosclerosis (FSGS). The intrarenal hemodynamic study revealed a unique correlation between renal perfusion and nephronal structure. A normal or slight reduction in peritubular capillary flow observed in MC or mild MesP nephrosis correlates with an intact tubulointerstitial structure. A moderate reduction in peritubular capillary flow observed in steroid resistant, MesP nephrosis induces a low incidence of TIF. A severe reduction in peritubular capillary flow denotes a higher incidence of TIF as that observed in nephrosis with FSGS. Thus, it is of notion that the reduction in renal perfusion precedes the development of tubulo-interstitial fibrosis and thereby supports the concept of renal perfusion as a crucial determinant of nephronal structure.     

Differential risk of remission and ESRD in childhood FSGS

Focal segmental glomerulosclerosis (FSGS) is the leading cause of steroid-resistant nephrotic syndrome in childhood and the most common form of end stage renal disease (ESRD) from glomerular disease. In order to assess the risk of progression of children with primary FSGS and the impact of proteinuria remission status on disease progression, we undertook this study to describe a cohort of 60 children and adolescents from the Glomerular Disease Collaborative Network. Of the 60 patients included in the cohort, 58% were African American. Median age was 16 years. Proteinuria ranged from 1.0–24.0 g/day/1.73 m²; 57% were hypertensive, and the median estimated glomerular filtration rate (eGFR) was 90.2 ml/min/1.73 m². Complete remission was achieved in 20%, partial remission in 33%, and 47% have not achieved remission during follow-up with all prescribed therapy. Only ACE-I/ARB therapy was predictive of proteinuria remission in multivariate analysis (hazard ratio [HR] 3.35; 95% confidence interval [CI] 1.42–7.92). Renal survival was much improved in patients with complete or partial remission compared with no remission in univariate analysis. In multivariate analysis comparing no remission status, complete remission was associated with a 90% decreased risk of ESRD (HR 0.10, 95% CI 0.01–0.79, p =0.03). In summary, proteinuria remission status is a valid predictor of long-term renal survival in children with FSGS.     

Living-Donor Kidney Transplantation: Donor-Recipient Function Correlation

Background

With the rising prevalence of living-donor kidney transplantation, evaluation of factors correlated with renal function in the donor-recipient pair constitutes a main goal for kidney transplantation clinicians. Our objective was to analyze the more relevant donor characteristics that contribute to donor and recipient estimated glomerular filtration rates (eGFR) after 1 year.

Febuxostat for treating allopurinol-resistant hyperuricemia in patients with chronic kidney disease

Background: Availability of the novel xanthine oxidase inhibitor febuxostat, which has multiple excretion pathways, enables investigation of the significance of serum uric acid control on renal function in patients with chronic kidney disease (CKD). Methods: This was an exploratory, retrospective, observational study conducted at a single Japanese center. Serum uric acid concentrations and serum creatinine levels in the 6 months before and after the start of febuxostat treatment were collected for CKD patients switched from allopurinol after failing to achieve serum uric acid concentrations ≤6.0?mg/dL. Results: Evaluable data were available for 60 patients, 67% of whom had advanced CKD (eGFR <30?mL/min/1.73?m²). Mean dose of febuxostat was 15.9 (±?8)?mg/day. Mean serum uric acid concentration decreased from 8.4 (±1.4) mg/dL at baseline to 6.2 (±1.2)?mg/dL at 6 months; 47.5% of patients achieved a level ≤6.0?mg/dL. The change from baseline in eGFR was positive at all time points during febuxostat treatment and the increase of 2.3 (±5.6)?mL/min/1.73?m² at 6 months was significant (p?=?0.0027). Whereas the eGFR slope was negative during allopurinol treatment, it became positive after the switch to febuxostat. The change in eGFR slope before and after febuxostat treatment was significant for all patients (p?p?2 (p?Conclusions: In patients with CKD, febuxostat reduces serum uric acid concentrations effectively and may suppress the progressive decline in renal function.     

Pulse methylprednisolone treatment of idiopathic steroid-resistant nephrotic syndrome

Although much of the interest in pulse methylprednisolone therapy (PMT) has centered around its use in children with focal segmental glomerulosclerosis, PMT has also been shown to be effective in the treatment of other proteinuric renal diseases. We hypothesized that a PMT-based treatment protocol, derived from the Tune-Mendoza protocol, would effectively induce a more rapid remission in young children with idiopathic steroid-resistant nephrotic syndrome (SRNS). A retrospective analysis was conducted of 11 consecutive SRNS patients (mean age 3.6±1.5 years) that received PMT between 1 August 1992 and 1 May 1998. The initial mean urinary protein/urinary creatinine ratio (UP/UC, mg/mg) was 8.3±9.7 and mean estimated creatinine clearance (C _Cr) 137.7±47.0 ml/min per 1.73 m². An average of 24.8±10.5 PMT doses were given. The mean duration of PMT therapy until remission was 23.4±29.9 days (median 12 days). Cyclosporine and cyclophosphamide were used to maintain and extend remissions in 5 and 4 patients, respectively. At the conclusion of the study, the mean UP/UC was 0.12±0.22 and mean C _Cr 151.8± 39.8 ml/min per 1.73 m² (no C _Cr≤100 ml/min per 1.73 m²). Of the 11 patients, 9 attained complete remission. Adverse effects were mild and infrequent. This PMT protocol appears to safely and effectively induce remission in young children with SRNS. A future prospective trial that evaluates the efficacy of PMT in young children with SRNS is warranted. Received: 15 March 2000 / Revised: 14 August 2000 / Accepted: 18 August 2000     

Kidney outcomes in patients with liver cirrhosis and chronic kidney disease receiving an orthotopic liver transplant alone

Kidney transplant in patients with liver cirrhosis and nondialysis chronic kidney disease (CKD) is controversial. We report 14 liver cirrhotic patients who had persistently low MDRD‐6 estimated glomerular filtration rate (e‐GFR) <40 mL/min/1.73 m² for ≥3 months and underwent either liver transplant alone (LTA; n=9) or simultaneous liver‐kidney transplant (SLKT; n=5). Pretransplant, patients with LTA compared with SLKT had lower serum creatinine (2.5±0.73 vs 4.6±0.52 mg/dL, P=.001), higher MDRD‐6 e‐GFR (21.0±7.2 vs 10.3±2.0 mL/min/1.73 m², P=.002), higher 24‐hour urine creatinine clearance (34.2±8.8 vs 18.0±2.2 mL/min, P=.002), lower proteinuria (133.2±117.7 vs 663±268.2 mg/24 h, P=.0002), and relatively normal kidney biopsy and ultrasound findings. Post‐LTA, the e‐GFR (mL/min/1.73 m²) increased in all nine patients, with mean e‐GFR at 1 month (49.8±8.4), 3 months (49.6±8.7), 6 months (49.8±8.1), 12 months (47.6±9.2), 24 months (47.9±9.1), and 36 months (45.1±7.3) significantly higher compared to pre‐LTA e‐GFR (P≤.005 at all time points). One patient developed end‐stage renal disease 9 years post‐LTA and another patient expired 7 years post‐LTA. The low e‐GFR alone in the absence of other markers or risk factors of CKD should not be an absolute criterion for SLKT in patients with liver cirrhosis.     

Renal Transplantation in Obese Patients: Experience in an Argentine Center

Possible complications of renal transplants in obese patients have raised concerns among nephrologists. We describe the outcomes of 110 renal transplant patients according to body mass index (BMI). Recipient BMI was calculated by using height and weight at time of transplantation and categorized according to World Health Organization guidelines. The patients' BMI values were as follows: underweight, n = 8 (7.27%); normal weight, n = 55 (50%); overweight, n = 30 (27.27%); and obese, n = 17 (15.45%). Mean age was significantly different among groups: underweight, 27.62 ± 7.57 years; normal weight, 44.98 ± 15.55 years; overweight, 50.53 ± 13.90 years; and obese, 52.11 ± 10.41 years (P < .05). Donor age and mean time of dialysis treatment were comparable in all groups. Underweight patients had a significantly larger proportion of living donors than those with higher BMIs. Calculated glomerular filtration rate (using the Modification of Diet in Renal Disease equation) were significantly different among the groups at 30, 60, and 90 days' posttransplantation. At 180 days, however, it was comparable: underweight, 62.96 ± 40.77 mL/min/1.73 m²; normal weight, 53.55 ± 26.23 mL/min/1.73 m²; overweight, 47.52 ± 16.37 mL/min/1.73 m²; and obese, 46.19 ± 17.56 mL/min/1.73 m² (P = .34). Incidence of delayed graft function was as follows: underweight, 0%; normal weight, 30.4%; overweight, 53.3%; and obese, 64.1% (P < .05). The incidence of surgical complications, incidence of rejection within the first 6 months' posttransplantation, and graft and patient survival rates over 6 months did not differ among the groups. Because transplantation in obese patients may be associated with higher risks and costs, the evaluation of each center experience is imperative. Longer term assessments are warranted, but our short-term results show that outcomes in overweight or obese renal transplant patients are comparable to those in patients with lower BMI.     

Efficacy and Safety of Early Cyclosporine Conversion to Sirolimus with Continued MMF—Four‐Year Results of the Postconcept Study

Calcineurin inhibitor (CNI) withdrawal has been used as a strategy to improve renal allograft function. We previously reported that conversion from cyclosporine A (CsA) to sirolimus (SRL) 3 months after transplantation significantly improved renal function at 1 year. In the Postconcept trial, 77 patients in the SRL group and 85 in the CsA group were followed for 48 months. Renal function (Cockcroft and Gault) was significantly better at month 48 (M48) in the SRL group both in the intent‐to‐treat population (ITT): 62.6 mL/min/1.73 m² versus 57.1 mL/min/1.73 m² (p = 0.013) and in the on‐treatment population (OT): 67.5 mL/min/1.73 m² versus 57.4 mL/min/1.73 m² (p = 0.002). Two biopsy proven acute rejection episodes occurred after M12 in each group. Graft and patient survival were comparable (graft survival: 97.4 vs. 100%; patient survival: 97.4 vs. 97.6%, respectively). The incidence of new‐onset diabetes was numerically increased in the SRL group (7 vs. 2). In OT, three cancers occurred in the SRL group versus nine in the CsA group and mean proteinuria was increased in the SRL group (0.42 ± 0.44 vs. 0.26 ± 0.37; p = 0.018). In summary, the renal benefits associated with conversion of CsA to SRL, at 3 months posttransplantation, in combination with MMF were maintained for 4 years posttransplantation.     

Comparison of Cystatin C,Creatinine and Creatinine Clearance vs. GFR for Detection of Renal Failure in Renal Transplant Patients

Background: Serum cystatin C (Scyst) has been suggested as an alternative index of glomerular filtration rate (GFR) and could be useful in renal transplant patients. Methods: In a 60‐subject cohort (40 ± 12 years old), we compared the simultaneous measurements of Scyst, serum creatinine (Screat), creatinine clearance (Ccreat), Cockcroft and Gault's estimated clearance (Ccg) and GFR measured using inulin clearance (Cin). Receiver operating characteristic (ROC) analysis was performed using two Cin cut‐off (60 and 90 mL/min/1.73 m²). Results: A significant correlation was found among Cin on one hand and 1/Scyst, Ccreat, 1/Screat and Ccg on the other hand. Best fits (sensitivity/specificity) at 90 mL/min/1.73 m² were 1.18 mg/L (0.72/0.80) for Scyst, 1.32 mg/dL (0.67/0.90) for Screat, 77 mL/min (0.80/0.70) for Ccg and 104 mL/min (0.88/0.80) for Ccreat. The areas under the ROC curves were not significantly different. Conclusions: This study provides cut‐off values for Screat and Ccg for detection of renal failure in renal transplant patients. However, the results also suggest that Scyst is not a more sensitive marker than Screat or Ccg for detecting renal failure in renal transplant patients.     

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 m², 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.