Influence of body mass index on the association of weight changes with mortality in hemodialysis patients.

BACKGROUND AND OBJECTIVES: A high body mass index (BMI) is associated with lower mortality in patients undergoing hemodialysis. Short-term weight gains and losses are also related to lower and higher mortality risk, respectively. The implications of weight gain or loss may, however, differ between obese individuals and their nonobese counterparts. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: The Current Management of Secondary Hyperparathyroidism: A Multicenter Observational Study (COSMOS) is an observational study including 6797 European hemodialysis patients recruited between February 2005 and July 2007, with prospective data collection every 6 months for 3 years. Time-dependent Cox proportional hazard regressions assessed the effect of BMI and weight changes on mortality. Analyses were performed after patient stratification according to their starting BMI. RESULTS: Among 6296 patients with complete data, 1643 died. At study entry, 42% of patients had a normal weight (BMI, 20-25 kg/m(2)), 11% were underweight, 31% were overweight, and 16% were obese (BMI ≥ 30 kg/m(2)). Weight loss or gain (<1% or >1% of body weight) was strongly associated with higher rates of mortality or survival, respectively. After stratification by BMI categories, this was true in nonobese categories and especially in underweight patients. In obese patients, however, the association between weight loss and mortality was attenuated (hazard ratio, 1.28 [95% confidence interval (CI), 0.74 to 2.14]), and no survival benefit of gaining weight was seen (hazard ratio, 0.98 [95% CI, 0.59 to 1.62]). CONCLUSIONS: Assuming that these weight changes were unintentional, our study brings attention to rapid weight variations as a clinical sign of health monitoring in hemodialysis patients. In addition, a patient's BMI modifies the strength of the association between weight changes with mortality.

Use of phosphate-binding agents is associated with a lower risk of mortality.

Hyperphosphatemia has been associated with higher mortality risk in CKD 5 patients receiving dialysis. Here, we determined the association between the use of single and combined phosphate-binding agents and survival in 6797 patients of the COSMOS study: a 3-year follow-up, multicenter, open-cohort, observational prospective study carried out in 227 dialysis centers from 20 European countries. Patient phosphate-binding agent prescriptions (time-varying) and the case-mix-adjusted facility percentage of phosphate-binding agent prescriptions (instrumental variable) were used as predictors of the relative all-cause and cardiovascular mortality using Cox proportional hazard regression models. Three different multivariate models that included up to 24 variables were used for adjustments. After multivariate analysis, patients prescribed phosphate-binding agents showed a 29 and 22% lower all-cause and cardiovascular mortality risk, respectively. The survival advantage of phosphate-binding agent prescription remained statistically significant after propensity score matching analysis. A decrease of 8% in the relative risk of mortality was found for every 10% increase in the case-mix-adjusted facility prescription of phosphate-binding agents. All single and combined therapies with phosphate-binding agents, except aluminum salts, showed a beneficial association with survival. The findings made in the present association study need to be confirmed by randomized controlled trials to prove the observed beneficial effect of phosphate-binding agents on mortality.

Geographical variability of patient characteristics and treatment patterns affect outcomes for incident hemodialysis patients.

BACKGROUND: Geographical differences in disease prevalence and mortality have been described in the general population and in chronic kidney disease patients in Europe. In this secondary analysis of the Membrane Permeability Outcome (MPO) study, we addressed differences in patient and treatment patterns, and whether these affect patient outcomes. METHODS: Participating countries were grouped according to geographical location; thus study centers in France, Greece, Italy, Portugal and Spain were allocated to southern Europe (n=499), and those in all other countries (Belgium, Germany, Poland and Sweden) to northern Europe (n=148). Descriptive analysis of patient and treatment patterns at study start, as well as survival analysis, was performed. RESULTS: In patients from the northern European countries, a higher prevalence of diabetes mellitus and of cardiovascular disease was observed than in those from southern Europe (diabetes 35.1% vs. 21.0%, p=0.0007; cardiovascular disease 40.5% vs. 22.8%, p<0.0001). In northern Europe, 23% of patients started hemodialysis with a catheter for vascular access, while in southern European centers, only 13% did so (p=0.0042). Kaplan-Meier survival analysis revealed a lower probability for both all-cause and cardiovascular mortality in southern Europe (log-rank test p<0.001). In a Cox proportional hazards model, a higher mortality risk was estimated for the northern European patients after adjustment for age, sex, membrane permeability, comorbidity index and vascular access (hazard ratio = 1.831; 95% confidence interval, 1.282-2.615; p=0.0009). CONCLUSIONS: Our study patients from northern Europe showed a higher risk profile than those from southern Europe. However, only some of the factors can be modified in attempts to lower the mortality risk in this geographical area.

COSMOS: the dialysis scenario of CKD-MBD in Europe.

BACKGROUND: Chronic kidney disease-mineral and bone disorders (CKD-MBD) are important complications of CKD5D patients that are associated with mortality. METHODS: COSMOS is a multicentre, open cohort, prospective, observational 3-year study carried out in haemodialysis patients from 20 European countries during 2005-07. The present article describes the main characteristics of the European dialysis population, the current practice for the prevention, diagnosis and treatment of secondary hyperparathyroidism and the differences across different European regions. RESULTS: The haemodialysis population in Europe is an aged population (mean age 64.8±14.2 years) with a high prevalence of diabetes (29.5%) and cardiovascular disease (76.0%), and 28.7% of patients have been on haemodialysis more than 5 years. Patients from the former Eastern countries are younger (59.3±14.3 versus 66.0±13.9), having a lower proportion of diabetics (24.1 versus 30.7%). There were relevant differences in the frequency of measurement of the main CKD-MBD biochemical parameters [Ca, P and parathyroid hormone (PTH)] and the Eastern countries showed a poorer control of these biochemical parameters (K/DOQI and K/DIGO targets). Overall, 48.0% of the haemodialysis patients received active vitamin D treatment. Calcitriol use doubled that of alfacalcidiol in the Mediterranean countries, whereas the opposite was found in the non-Mediterranean countries. The criteria followed to perform parathyroidectomy were different across Europe. In the Mediterranean countries, the level of serum PTH considered to perform parathyroidectomy was higher than in non-Mediterranean countries; as a result, in the latter, more parathyroidectomies were performed in the year previous to inclusion to COSMOS. CONCLUSIONS: The COSMOS baseline results show important differences across Europe in the management of CKD-MBD.

Valproic acid attenuates proteinuria and kidney injury.

Inhibitors of histone deacetylase (HDAC) have anti-inflammatory and antifibrotic effects in several organs and tissues, but their effect on the progression of renal disease is unknown. Here, we studied the effect of valproic acid in adriamycin-induced nephropathy in mice. Administration of valproic acid before kidney injury prevented the development of proteinuria and the onset of glomerulosclerosis. Even after postponing treatment until the peak of adriamycin-induced proteinuria, valproic acid rapidly decreased the quantity of proteinuria and attenuated the progression of renal disease. Valproic acid abrogated the decrease in glomerular acetylation observed during adriamycin-induced nephropathy. Furthermore, valproic acid attenuated the significant upregulation of profibrotic and proinflammatory genes, the deposition of collagen, and the infiltration of macrophages into the kidney. Valproic acid decreased glomerular apoptosis and proliferation induced by adriamycin. Ultrastructural studies further supported the protective effect of valproic acid on podocytes in this model. Taken together, these data suggest that HDACs contribute to the pathogenesis of renal disease and that HDAC inhibitors may have therapeutic potential in CKD.

Gender and hypertension management: a sub-analysis of the I-inSYST survey.

Hypertension is a major risk factor for cardiovascular disease, which is the leading cause of death in women. Aim. To evaluate blood pressure control, prevalence of concomitant cardiovascular risk factors, subclinical and clinical organ damage, and treatment according to gender. Methods. 11,562 patients (49% women) from the cross-sectional I-inSyst survey in primary care were included. Results. Blood pressure control in women (21.8%) and men (21.2%) was similar, despite a slightly older age (64.9 vs 63 years, p<0.0001). Women had less concomitant cardiovascular risk factors and organ damage, with the exception of diabetes, cerebrovascular and renal disease, than men. They received more antihypertensive drugs than men (1.7 ± 0.9 vs 1.5 ± 0.9, p<0.0001). Diuretics were more (45% vs 36.5%, p<0.0001), calcium-channel blockers (26% vs 29%, p<0.003) and angiotensin-converting enzyme inhibitors (20% vs 22%, p<0.02) were less commonly prescribed in women than in men. Different clinical factors (i.e. age, duration of hypertension, smoking) in women and men were associated with blood pressure control, but gender itself was not. Conclusions. In this group of treated hypertensive patients, blood pressure control in women and men was not different. Women had a lower prevalence of most cardiovascular risk factors, subclinical and clinical organ damage. Antihypertensive drug treatment varied according to gender.

Fibrous intimal thickening at implantation adversely affects long-term kidney allograft function.

BACKGROUND: Kidneys from marginal and older donors are increasingly used to respond to the increasing demand for kidney transplants. This study evaluated the predictive value of intimal hyperplasia, as a marker of vasculopathy, in the renal allograft at the time of transplantation (transplantation) on the subsequent graft function (7 years). METHODS: The intima/media ratio of the arterial walls (I/M) was morphometrically determined by the sectorial elliptic method, in 51 implantation biopsies. Two study groups were determined. Group 1, with I/M less than or equal to 0.47, was considered as the group with minimal vascular damage at transplantation. Group 2, with I/M more than 0.47, was considered as having vasculopathy at transplantation. RESULTS: During the first 15 months, the estimated glomerular filtration rate improved in group 1 from 53+/-17 to 61+/-17 mL/min/1.73 m2, whereas it decreased from 51+/-21 to 46+/-14 mL/min/1.73 m2 in group 2. From 1 year posttransplantation, the estimated glomerular filtration rate (eGFR) was significantly higher in group 1 at all time points (6 month evaluation). The difference in graft function between the two groups (mean, 11 mL/min/1.73 m2) remained unchanged between 1 and 7 years posttransplantation. Among several clinical parameters investigated, blood pressure of the recipient significantly modulates the impact of preexisting vasculopathy on graft function. CONCLUSION: Our data provide evidence that donor-related vasculopathy, at the time of transplantation, has a persistent significant impact on the subsequent graft function. This effect becomes only apparent at 1 year posttransplantation and is increased in recipients with inadequately controlled blood pressure.

Age dependence of T1 perfusion MRI-based hemodynamic parameters in human kidneys.

PURPOSE: To determine the association between renal cortical perfusion parameters from T1-DCE magnetic resonance imaging (MRI) and age in human kidney. MATERIALS AND METHODS: Thirty-five patients (mean age: 53 years, SD = 15 years) were imaged using inversion recovery (IR)-prepared FLASH (pulse repetition time [TR] = 4.4 msec, echo time [TE] 2.2 msec, inversion time [TI] = 180 msec, FA 50 degrees , matrix 128 x 256, 0.3 sec/slice) during the injection of Gadolinium-DTPA. Tissue concentration-time courses were deconvolved. Renal blood flow (RBF), volume of distribution (RVD), and mean transit time (MTT) were derived from the resulting impulse response function. RESULTS: Mean RBF, RVD, and MTT were 127 mL/min/100 mL (SD = 81 mL/min/100 mL), 40 mL/100 mL (SD 23 mL/100 mL), and 22 sec (SD = 9 sec). A significant moderately negative correlation was found between RBF and age (R = -0.447, P = 0.007), RVD and age (R = -0.420, P = 0.012). MTT and age did not show a significant correlation (R = 0.017, P = 0.924). Repeating this analysis for each gender revealed a moderate age dependence of RBF (R = -0.600 with P = 0.009) and RVD (R = -0.540 with P = 0.021) in the male group only. CONCLUSION: T1-DCE quantitative perfusion MRI was sufficiently sensitive to demonstrate a significant negative correlation of RBF and RVD with patient age. This was due to a moderate age dependence of these quantities in males that seems to be absent in females.

Combined T1-based perfusion MRI and MR angiography in kidney: first experience in normals and pathology.

OBJECTIVES: To investigate the feasibility of implementing quantitative T1-perfusion in the routine MRA-protocol and to obtain a first experience in normals and pathology. MATERIALS AND METHODS: For perfusion imaging, IR-prepared FLASH (one 4 mm slice at mid-renal level, TR 4.4 ms, TE 2.2 ms, TI 180 ms, FA 50 degrees , matrix 128 x 256, bandwidth per pixel 300, 400 dynamics, temporal resolution 0.3 s, total measurement time 2 min) was applied during the injection of 10 ml of standard 0.5 mmol/ml Gadolinium-DTPA solution at 2 ml/s, followed by 3DCE-MRA with bolus tracking (TR 5.4, TE 1.4, FA 40 degrees , matrix 192 x 512, NSA 1, slice thickness 1.5 mm), using a second dose of 0.1 mmol Gadolinium-DTPA per kg body weight with a maximum of 20 ml. The T1-weighted signals (perfusion data) were converted to tissue tracer concentrations and deconvolved with an inflow corrected AIF; blood flow, distribution volume, mean transit time and blood flow heterogeneity were derived. RESULTS: MRA quality was uncompromised by the first bolus administered for perfusion purposes. In the normals, average cortical RBF, RVD and MTT were 1.2 ml/min/ml (S.D. 0.3 ml/min/ml), 0.4 ml/ml (S.D. 0.1 ml/ml) and 21s (S.D. 4s). These RBF values are lower than those found in the literature, probably due to residual AIF inflow effects. The sensitivity of the technique was sufficient to demonstrate altered perfusion in the examples of pathology. CONCLUSION: Combined quantitative T1-perfusion and MRA have a potential for noninvasive renovascular screening and may provide an anatomical and physiological evaluation of renal status.

Two-tier approach for the detection of alpha-galactosidase A deficiency in kidney transplant recipients.

BACKGROUND: Anderson-Fabry disease (AFD) is an X-linked condition originating from a deficiency in alpha-galactosidase, a lysosomal enzyme. Multi-organ involvement ensues in early adulthood and vital organs are affected: the kidneys, brain, heart. Several reports however suggest that AFD is underdiagnosed. METHODS: We screened a kidney transplant population using a two-tier approach. The first tier was the determination of alpha-galactosidase A (AGALA) activity using a dried blood spot on filter paper (DBFP); in the second tier, patients with the lowest alpha-galactosidase levels were further subjected to mutation analysis of the GLA gene. RESULTS: From the database of 2328 patients, 1233 subjects met the inclusion criteria. Finally, after informed consent, 673 patients were screened (54.5%-395 women and 278 men). DBFP analysis resulted in a mean AGALA of 2.63 +/- 2.48 micromol/L/h (2.5 and 97.5 percentile were 0.0001 and 5.07 micromol/L/h, respectively). Eleven patients were subjected to further genetic analysis. In a male patient a pathogenic missense mutation p.Ala143Thr (c.427A>G) was identified. CONCLUSIONS: Our results show that the proposed approach can detect AFD patients in a until now seldomly screened high-risk group: kidney transplant patients. We conclude that screening for AFD in high-risk populations is a cost-effective, technically feasible and clinically valuable objective.

Current management of secondary hyperparathyroidism: a multicenter observational study (COSMOS).

STUDY AIMS: To survey bone mineral disturbances in the hemodialysis (HD) population in Europe and current clinical practice in Europe for the prevention, diagnosis and treatment of secondary hyperparathyroidism (SHPT) in HD patients. PRIMARY OBJECTIVES: First, to estimate the prevalence of Kidney Disease Outcomes Quality Initiative (K/DOQI) guideline achievement in a representative sample of European hemodialysis subjects. As part of this objective, we will investigate the prevalence of achievement by type of dialysis, type of center and time on dialysis (less than or greater than 1 year). Among new dialysis subjects (less than 1 year), we will evaluate prevalence of K/DOQI target achievement until the end of the study. The study will run for 3 years. Second, to estimate the association of bone mineral markers (parathyroid hormone [PTH], calcium [Ca], serum phosphorus [P] and calcium phosphate product [CaxP]) classified by achievement of K/DOQI targets with mortality and overall cardiovascular hospitalization. Third, to characterize the longitudinal changes in bone mineral markers. As part of this objective, we will describe the patterns and predictors of bone mineral markers and achievement, with K/DOQI targets, using repeated measurements on individuals over time. SECONDARY OBJECTIVES: First, To estimate the association of bone mineral markers (PTH, Ca, P and CaxP) classified by achievement of K/DOQI targets with specific cardiovascular outcomes, parathyroidectomy, manifest bone disease (including incidence of symptomatic bone fractures), hospitalizations and vascular access. Second, to evaluate the additional value of albumin and hemoglobin levels in conjunction with bone mineral markers in the prediction of mortality and clinical events.

Vasculopathy in the kidney allograft at time of transplantation: impact on later function of the graft.

BACKGROUND: Older and marginal donors, increasingly used to overcome organ shortness, often have a cerebrovascular accident as cause of death and could have vascular lesions in their kidneys. METHODS: In this literature study, we evaluated the predictive value of vasculopathy in the renal allograft at the time of transplantation, on the subsequent graft function. RESULTS: Short-term graft survival rates do not seem to be diminished by suboptimal donor histology. When vasculopathy is clearly present at the time of transplantation, impaired kidney function is showed at 1-week posttransplantation, at hospital discharge, or at 3 months and an increased frequency of delayed graft function. The long-term graft survival rate, in the studies of Pokorna and Taub, was significantly lower in the group with arteriolosclerosis. Wang et al. concluded in their study that arterial fibrous intimal thickening is the single most important histological predictor of both graft loss and delayed graft function. However, Minakawa et al. observed no significant correlation between 1 or 2-year graft survival and vasculopathy score. Severe vascular lesions in the donor kidney do affect the level of kidney function in the later posttransplant period as described in different studies (follow-up till 7 years posttransplantation). CONCLUSIONS: Data obtained from the studies of donor biopsies sustain the notion that vasculopathy is a major determinant of the short-term and the long-term outcome of the kidney allograft.

CRBP-I in the renal tubulointerstitial compartment of healthy rats and rats with renal fibrosis.

BACKGROUND: Cellular retinol-binding protein I (CRBP-I), a member of the intracellular lipid-binding protein (iLBP) superfamily, is a specific marker of quiescent stellate cells in the healthy human liver. In the diseased fibrotic/cirrhotic liver, portal and septal myofibroblasts acquire CRBP-I expression, while activated hepatic stellate cells maintain their CRBP-I expression. Here, we investigate the distribution of CRBP-I in the renal cortex of healthy rats and rats with renal fibrosis. METHODS: Kidneys of healthy and adriamycin-treated rats were studied by immunohistochemistry, using antibodies against CRBP-I, desmin, vimentin and alpha-smooth muscle actin (alpha-SMA). Double stainings were done with immunofluorescence. Western blotting was performed to semi-quantify the expression levels of vimentin, desmin, alpha-SMA and CRBP-I. RESULTS: In the normal rat kidney, the convoluted proximal tubular epithelial cells express CRBP-I; no expression is found in the interstitium, nor in the glomeruli. In the adriamycin-induced fibrotic rat kidney, CRBP-I expression diminishes in the convoluted proximal tubular epithelial cells, whereas peritubular myofibroblasts in the interstitium acquire CRBP-I expression. CONCLUSIONS: In the tubulointerstitial compartment of the adriamycin-induced fibrotic rat kidney, CRBP-I is expressed in a different pattern than in the healthy rat kidney. As the convoluted proximal tubular epithelial cells dedifferentiate during fibrosis, CRBP-I expression decreases. Furthermore, de novo expression of CRBP-I is found in activated myofibroblast-like cells in the interstitium of adriamycin-treated rats. CRBP-I is therefore a useful marker to identify a subpopulation of activated/ myodifferentiated fibroblasts in the rat kidney.

Lanthanum carbonate possibly responsible for acute liver failure in a patient with Child-Pugh stage A liver cirrhosis.

The majority of patients with end-stage renal disease have hyperphosphataemia, which is associated with significant morbidity and mortality. Lanthanum carbonate has been introduced as a new treatment modality to lower serum phosphorus. But there has been ongoing concern about lanthanum accumulation in tissues, especially in liver. We describe the case of a woman with pre-existing liver disease, who presented with acute liver failure after introduction of lanthanum carbonate to her treatment. The condition was fully reversible after stopping lanthanum carbonate.

Two-tier approach for the detection of alpha-galactosidase A deficiency in a predominantly female haemodialysis population.

INTRODUCTION: Fabry's disease (AFD) is an X-linked lysosomal storage disease, resulting from a deficiency in alpha-galactosidase A (AGALA). Untreated, this leads to precocious failure of vital organ function and death. As enzyme replacement therapy is available, it is of vital importance that affected individuals can be traced. MATERIALS AND METHODS: We set up a screening in the Flemish haemodialysis population using a two-tier approach. The first tier was a determination of alpha-galactosidase A activity using a dried blood spot on filter paper, in the second tier, patients with the lowest alpha-galactosidase levels were further subjected to mutation analysis of the GLA gene. RESULTS: 1284 patients (1047 women, 237 men) were evaluated for inclusion, eliminating patients with definite renal diagnoses. Total 922 patients (71.8 %) were screened (742 women, 180 men). Fifty seven patients were subjected to further genetic analysis. Three GLA mutation carriers were identified: two apparently nonrelated female patients carry the missense mutation p.Ala143Thr (c.427G > A), a missense mutation p.Trp236Arg (c.706T > C) was identified in a man. While the male patient had been clinically diagnosed with AFD, the female patients had remained unrecognized. Additional family based screening resulted in the identification of nine mutation carriers (four males and five females). DISCUSSION: We demonstrated that the prevalence of GLA mutation carriers in our haemodialysis population is 0.3%. Our results show that the proposed approach accurately detects AFD patients. We conclude that screening for AFD in high risk populations is a cost-effective, technically feasible and clinically valuable objective.

Acute interstitial nephritis associated with salmonellosis.

Acute interstitial nephritis (AIN) is a common cause of acute renal failure. We report a case of AIN, confirmed by renal biopsy, that developed in a patient with typhoid fever due to a Salmonella hadar infection. AIN secondary to Salmonella infection is a rare complication that has only been described twice in the literature. Salmonella should be added to the list of possible causes of AIN.

Conversion from cyclosporine to sirolimus in stable renal transplant recipients.

BACKGROUND: Conversion from cyclosporine (CsA) to sirolimus (SRL) has mainly been done in clinical conditions warranting calcineurin inhibitor discontinuation. Little is known about the clinical outcome of conversion in renal transplant recipients without transplant dysfunction. METHODS: This prospective, open-label, multicentric pilot study evaluates the safety and efficacy of converting patients with stable renal function from CsA to SRL. RESULTS: Forty stable patients on CsA, mycophenolate mofetil (MMF) (1.5 g/day), and steroids (ST) were converted at 7.6+/-1.4 months after renal transplantation. At 1 year, graft and patient survival was 100% and the incidence of acute rejection 5%. Calculated glomerular filtration rate (GFR) increased from 54+/-18 to 66+/-16 ml/min (P<0.0001). Blood pressure remained unchanged. A gradual increase in the incidence and severity of proteinuria was observed from month 6 onwards with de novo proteinuria in 30% of the patients at 1 year. Protein excretion was below 1 g/day in 12.5%, between 1 and 3 g/day in 17.5% and above 3 g/day in 7.5% of the proteinuric cohort (P=0.0043, compared to baseline). No predictors could be identified for the development of proteinuria. All patients had a reduction in protein excretion following renin-angiotensin blockade and were continued on SRL. CONCLUSION: Conversion of stable renal transplant recipients from a CsA-MMF-ST to a SRL-MMF-ST regimen is safe and results in improved renal function but is associated with the development of proteinuria in 30% of the patients requiring renin-angiotensin blockade.

Increased oxidative stress in the mouse adriamycin model of glomerulosclerosis is accompanied by deposition of ferric iron and altered GGT activity in renal cortex.

Chronic renal failure evolves inevitable towards glomerular and tubulo-interstitial sclerosis. This pathological process involves a disturbed redox status of the kidney tissue, leading to irreversible damage. In this study we investigate in an adriamycin model of chronic renal failure in mice the evolution of in vivo hydrogen peroxide production, and the possible role of gamma-glutamyl transpeptidase and ferric iron in the process. Histological changes and ferric iron deposits are evaluated by histochemical staining. To evaluate oxidative stress residual catalase activity, TBARS formation and gamma-glutamyl transpeptidase activity are measured spectrophotometrically. While catalase activity remains the same, a decreased residual catalase activity indicates an increased formation of hydrogen peroxide. Both the activity of gamma-glutamyl transpeptidase and TBARS formation is increased at early stages of the disease. Ferric iron is clearly present in the proximal tubule. Twenty days after adriamycin injection all parameters decrease, probably due to the destruction of the tissue. Our data show the involvement of oxidative stress in the progression of adriamycin induced renal failure in mice. Both radical production and oxidative damage are measurable, while the altered activity of gamma-glutamyl transpeptidase and the deposition of ferric iron suggest the involvement of these factors in the development of a disturbed redox status in the kidney cortex.