Dyslipidaemia and the progression of renal disease in chronic renal failure patients.

BACKGROUND: Dyslipidaemia is common in patients with chronic renal failure (CRF), and there is increasing evidence to support the role of dyslipidaemia as a contributing factor in the progression of chronic renal disease. However, few prospective studies have been carried out which address the possible relationship between dyslipidaemia and the rate of progression of renal disease in patients with renal failure. METHODS: Between January 1985 and December 1997, we prospectively assessed the risk of CRF progression to dialysis in a cohort of 138 patients. Forty CRF patients reached end-stage renal disease (ESRD) and had to start supportive therapy during the follow-up period [group ESRD(+)]. The remaining 98 CRF patients served as controls [group ESRD(-)]. Potential clinical and laboratory risk factors for more rapid CRF decline to dialysis, including lipid abnormalities and baseline creatinine clearance were determined at the start of the follow-up period. RESULTS: Several significant differences were found in univariate analysis between the two groups of CRF, ESRD(+) and ESRD(-), namely a shorter follow-up period, a lower level of baseline creatinine clearance, a faster rate of creatinine clearance decline, a higher level of serum triglycerides, fibrinogen, total homocyst(e)ine and proteinuria, and a lower level of serum high-density lipoprotein in the ESRD(+) group than in the ESRD(-) group. However, by multivariate Cox analysis proteinuria [relative risk (95% confidence interval) 1.32 (1.16-1.50) for each g/day P = 0.001], baseline creatinine clearance [0.53 (0.40-0.70) for each 10 ml/min, P = 0.001] and chronic interstitial nephritis and hypertensive nephrosclerosis [0.38 (0.17-0.84) for presence, P = 0.005] were the only significant risk factors for CRF progression to dialysis. Hypertriglyceridaemia and male gender were selected in the final model, but were of borderline significance. CONCLUSIONS: These results suggest a limited role for dyslipidaemia in the progression of chronic renal disease to dialysis in CRF patients, in contrast with the powerful influence of proteinuria, baseline creatinine clearance and nephropathy type in predicting this progression.     

Effects of current smoking and smoking discontinuation on renal function and proteinuria in the general population

BACKGROUND: Smoking may adversely affect the progression of renal diseases. However, it is unknown whether smoking affects renal function in subjects without nephropathy. METHODS: In 1998, 28,409 volunteers from the general population were examined at the Institut Régional pour la Santé (IRSA). Renal function was estimated with creatinine clearance using the Cockcroft formula. Dipstick proteinuria was assessed on an overnight urine sample by a trained technician. RESULTS: Adjusted creatinine clearance was higher in current smokers than in former smokers and never smokers (100.6 +/- 13.6 vs. 98.8 +/- 13.9 mL/min/1.73 m2, P < 0.0001, and vs. 98.5 +/- 14.0 mL/min/1. 73 m2, P < 0.0001, respectively). This difference was predominant in men and weak in women, and was associated with the number of cigarettes smoked daily. The slope of the projected age-related decline in the creatinine clearance accelerated with age, but it was similar in current smokers, former smokers, and never smokers. Creatinine clearance was associated with a relative risk of proteinuria [for each mL/min/1.73 m2, the relative risk was 1.007 (95% CI, 1.000 to 1.015), P = 0.056, for 1+ or higher proteinuria; and 1.018 (1.004 to 1.030), P = 0.0078, for 2+ or higher proteinuria]. Current and former smokers had a marked risk of 2 or higher proteinuria [adjusted RR (95% CI), 3.26 (1.66 to 6.80), P = 0. 0009, and 2.69 (1.24 to 5.99), respectively, P = 0.013, vs. never smoking], which was independent of the daily or cumulative cigarette consumption. CONCLUSIONS: In the general population, smokers do not exhibit lower creatinine clearance than never smokers. In fact, creatinine clearance is slightly higher in current smokers at least in men, even when normotensive and hypertensive subjects are analyzed separately, but the difference is small, especially in women. This effect seems reversible upon smoking discontinuation. Chronic smoking results in a marked risk of irreversible proteinuria that may occur despite moderate smoking.     

Smoking--a renal risk factor

One of the most important tasks of clinical and experimental nephrology is to identify the risk factors of progression of renal failure. A major renal risk factor which has not been sufficiently acknowledged despite increasing evidence is cigarette smoking. Diabetologists were the first to recognize the adverse effects of smoking on the kidney: both in type 1 and in type 2 diabetes smoking (i) increases the risk of development of nephropathy and (ii) nearly doubles the rate of progression to end-stage renal failure. Until recently it was not known whether smoking also increases the risk to progress to end-stage renal failure in patients with primary renal disease. A retrospective multicenter European case-control study showed that smoking is an independent risk factor for end-stage renal failure in patients with inflammatory and noninflammatory renal disease, i.e. IgA glomerulonephritis and polycystic kidney disease. The pathogenesis of the smoking-related renal damage is largely unknown. The intermittent increase in blood pressure during smoking seems to play a major role in causing renal damage, but further potential pathomechanisms are presumably also operative. Smoking as a renal risk factor is of great interest to diabetologists as well as nephrologists, but unfortunately so far this information has had little impact on patient management. The present article reviews the current knowledge about the renal risks of smoking and discusses the potential mechanisms of smoking-mediated renal injury.     

Cigarette smoking and vascular pathology in renal biopsies

BACKGROUND: In recent years cigarette smoking has been identified as a progression factor in chronic nephropathies such as glomerulonephritis or diabetic nephropathy. The exact pathomechanism of nicotine-induced renal damage is, however, unknown. Autopsy studies and functional investigations suggest that the renal vasculature is primarily affected by smoking. METHODS: Renal vascular pathology, that is, glomerulosclerosis, hyalinosis of arterioles and myointimal hyperplasia of small arteries, was determined in 135 biopsies of patients over thirty years of age. A questionnaire about smoking habits was returned by 107 of the patients. For glomerular sclerosis the percentage of sclerotic glomeruli was determined, whereas arteriolar hyalinosis and myointimal hyperplasia of small arteries were described as present or absent without further quantification. A univariate analysis was performed for existence of vascular changes and ever-smoking status. In addition, a multivariate analysis for glomerular sclerosis and logistic regression analysis for arteriolar hyalinosis and myointimal hyperplasia and the variables ever-smoking, age, body mass index, creatinine clearance, blood pressure and lipids were performed. RESULTS: Creatinine clearance was comparable for nonsmokers, ex-smokers and smokers. Frequency of myointimal hyperplasia of small arteries was twice as high in ever-smokers as compared to nonsmokers (50% vs. 25.5%, P < 0.01). Arteriolar hyalinosis was detected in 23.5% of nonsmokers and in 35.7% of smokers, showing a trend toward hyalinosis in ever-smokers (P=0.20). Glomerular sclerosis was found in 62.7% of nonsmokers and in 69.6% of ever-smokers. Logistic regression analysis confirmed an association between ever-smoking and myointimal hyperplasia (P < 0.01). This association also was present in males and patients over fifty years of age, but not in younger patients and females. CONCLUSION: In patients with renal, especially glomerular disease, cigarette smoking exhibits its deleterious effect on the kidneys primarily through damage of small interlobular arteries.     

Creatinine measurements often yielded false estimates of progression in chronic renal failure

In 9 of 22 observation periods (lasting an average of 15 months) in 17 patients with moderate to severe chronic renal failure (GFR 4 to 23 ml/min), rates of progression as estimated from the linear regression on time of 24-hour creatinine clearance (b1) differed significantly from rates of progression as estimated from the regression on time of urinary clearance of 99mTc-DTPA (b2), during all or part of the period of observation. b1 exceeded b2 in four cases and was less than b2 in the other five. Thus there were gradual changes in the fractional tubular secretion of creatinine in individual patients, in both directions. Owing to these changes, measurements of creatinine clearance gave erroneous impressions of the rate or existence of progression during all or a portion of the period of observation in nearly half of these patients. In the 22 studies as a group, using the entire periods of observation, b1 indicated significantly more rapid progression (by 0.18 +/- 0.06 ml/min/month, P less than 0.01) than did b2, and had a significantly greater variance. Measurements of progression based on the rate of change of reciprocal plasma creatinine (multiplied by an average rate of urinary creatinine excretion in each study) were equally misleading, even though less variable. We conclude that sequential creatinine measurements are often misleading as measures of progression and should, when feasible, be replaced by urinary clearance of isotopes in following patients with chronic renal failure.     

Disease progression and outcomes in chronic kidney disease and renal transplantation

BACKGROUND: It is unknown whether renal transplant recipients (RTR) have better outcomes and disease progression rates compared to patients with chronic kidney disease (CKD) when matched for the level of kidney function. METHODS: We analyzed data on 1762 patients with CKD (N = 872) and RTR (N = 890) over 16 years, applying the new Kidney/Disease Outcomes Quality Initiative (K/DOQI) staging system for CKD in a single center retrospective study. Patients were further divided based their native kidney disease. We determined disease progression by the slope of creatinine clearance decline and patient and kidney survival rates adjusted for age, gender and stage of kidney function, using Cox proportional hazards models. RESULTS: The overall rate of creatinine clearance decline in patients with CKD was -6.6 +/- 8.7 mL/min/year compared to -1.9 +/- 4.7 mL/min/year in RTR (P < 0.0001). The rate of decline per stage of CKD was also significantly lower in RTR. Whereas overall kidney survival was higher in RTR compared to patients with CKD (49.6% vs. 17.2%, respectively, P < 0.001), patient survival was not statistically different between the two groups (74.7% vs. 80.3%, respectively, P = 0.25). CONCLUSION: RTR had similar mortality rates compared to patients with CKD despite enjoying slower rates of disease progression and better kidney survival rates. These data suggest that RTR are a unique subset of patients with CKD whose comorbid conditions likely offset the potential benefits of slower rates of progression.     

Influence of pregnancy on progression of diabetic nephropathy and subsequent requirement of renal replacement therapy in female type I diabetic patients with impaired renal function.

The influence of pregnancy on the progression of diabetic nephropathy in diabetic women with pre-existing moderate renal insufficiency is a subject of considerable controversy in the literature. In four of five female patients with type I diabetes mellitus with pre-existing impaired renal function (creatinine clearance less than 80 ml/min), significant proteinuria (greater than 2 g/24 h urine) and hypertension we have found a further decline in renal function during pregnancy, with an increased deterioration rate of creatinine clearance in comparison to the time before and after pregnancy. The mean decline of the glomerular filtration rate was 1.8 ml/min per month during pregnancy and 1.4 ml/min per month postpartum until the start of dialysis treatment. The difference in the progression of diabetic nephropathy during and after pregnancy can be explained by increased hypertension during pregnancy, especially in the third trimester, despite an intensified antihypertensive therapy. The long-term effect of pregnancy on renal function in our patients was therefore an earlier requirement for renal replacement therapy than would have been expected without pregnancy.     

Impairment of renal function following liver transplantation

BACKGROUND: Although renal insufficiency following liver transplantation is not infrequent, only limited reports describe the incidence and progression of the kidney disease. METHODS: This single-centre retrospective analysis after successful liver transplantation between January 1985 and March 2002 defined the baseline serum creatinine at 50 days after liver transplantation to represent the renal function. The primary end-point was an increase of serum creatinine by more than 50% above the baseline. RESULTS: Long-term data were available for 162 patients (84 women, 78 men) who received 167 liver transplants. The median serum creatinine level at 50 days after liver transplantation was 1.0 mg/dL (range 0.5-3.5 mg/dL). The median serum creatinine increased to 1.2 mg/dL (0.4-9.8 mg/dL) at the end of follow-up. Six patients (4%) experienced end-stage renal failure. Forty-one patients (25%) showed a 50% increase in the serum creatinine. Kaplan-Meier analysis revealed that 43% and 48% of patients had a deterioration of renal function at 10 and 15 years after liver transplantation, respectively. Patients at risk showed an increase of serum creatinine by 0.25 mg/dL/y. Only the recipient age was an independent risk factor for deterioration of renal function. CONCLUSIONS: Although there is a high risk for the impairment of renal function after liver transplantation, progression of renal disease is slow and rarely results in end-stage renal failure within 10-15 years. However, patients at risk should be identified early to prevent further decline in renal function.     

How valuable for prognosis is the perioperative assessment of serum creatinine values with reference to postoperative renal complications in risk patients?

Renal function is not considered to be as important as cardiovascular or respiratory function during the perioperative period. Nevertheless, recent studies demonstrate a significant correlation between preoperative levels of creatinine and postoperative disturbances of kidney function. METHOD AND RESULTS: In a retrospective study 250 patients with the ASA physical status classification III and IV were investigated. All patients had a preoperative creatinine level greater than 1.0 mg/dl. For further investigations patients were divided into two groups; group I consisted of patients with preoperative creatinine level of 1.0-1.19 mg/dl; group II patients had preoperative creatinine levels greater than 1.2 mg/dl. Postoperatively these parameters were monitored on the 1st, 3rd and 5th days. A deterioration of renal function was seen postoperatively in all high risk patients (Tables 3, 4). Group II patients showed significant changes in kidney function on the 3rd and 5th postoperative days (p less than 0.005). During the study period the creatinine levels in this group did not return to normal values. In this group four patients suffered acute postoperative kidney failure, and two of these died. DISCUSSION AND CONCLUSION: In a recent study Hou et al. [5] could show that 5% of all patients suffer renal insufficiency during their hospital stay. Mortality for acquired renal failure is still 40-70%. The most important factor in the development of disturbances of kidney function is pre-existing kidney disease. The patients investigated in this study were high-risk patients. Cardiovascular complications during the perioperative phase are common, and hemodynamically mediated renal failure is the most frequent form of kidney failure.(ABSTRACT TRUNCATED AT 250 WORDS)     

Treatment of severe hypothyroidism in a patient with progressive renal failure leads to significant improvement of renal function

The case of a 41-year-old patient with end-stage renal failure and diabetes mellitus Type 1 who was being prepared for renal replacement therapy is described. After severe hypothyroidism was diagnosed, thyroid hormone substitution therapy was started. Subsequently, a substantial decline in serum creatinine was observed. Creatinine clearance rose from 19 to 40 ml/min and renal replacement therapy was no longer imminent. Several studies have described the pathophysiology of diminished renal function in hypothyroidism. Few studies or case reports have shown amelioration of end-stage renal failure as seen in our patient. The etiology is presumed to be multifactorial, in which hemodynamic effects and a direct effect of thyroid hormone on the kidney play an important role. Diagnosing signs of hypothyroidism and therapy with thyroid hormone in progressive renal failure could be very important in delaying the need for renal replacement therapy.     

Progression of chronic renal failure in patients given ketoacids following amino acids

Twelve patients with chronic renal failure who exhibited a progressive decline in 24-hour creatinine clearance, despite being given for 2 to 10 months a diet containing 0.3 g per kg ideal weight of protein and 7 to 9 g mg per kg ideal weight of phosphorus, supplemented with vitamins, CaCO3, and 10 g per day of essential amino acids, were changed to a supplement containing predominantly ketoacids. In six patients whose serum creatinine was 7.5 mg/dl or greater at changeover, progression continued unabated. In six patients with serum creatinine levels at changeover of 6.6 to 7.4 mg/dl, one was non-compliant with the diet and progressed to dialysis. In the other five, progression, measured as the rate of change of a bimonthly radioisotope clearance, has been undetectable during the ensuing one to two years. There has been no change in urea appearance, blood pressure, phosphaturia or proteinuria. Nutrition has been maintained. Thus this ketoacid supplemented regimen apparently halted the progression of moderately-severe chronic renal failure for at least a year in a small group of patients in whom restriction of protein and phosphate intake without ketoacids failed to halt progression. In more severe renal failure, no effect on progression was seen.     

The influence of donor age on renal function in transplant recipients

To the extent that age-related declines in kidney function are caused by intrarenal alterations, donor age should affect glomerular filtration rate (GFR) after renal transplantation. Although some investigations have suggested that transplantation of aging kidneys may cause an increased incidence of primary allograft failure, the effects of donor age on GFR are unknown. In the present study, 201 patients who had allografts that survived for at least 24 months were investigated. The age range of the donors was 7 to 61 years. Multivariate regression analysis demonstrated that both donor and recipient age had significant, independent effects on creatinine clearance at 1 year, and at last follow-up, 5.0 +/- 1.9 years (mean +/- SD) after transplantation. The effect of donor age on renal function could not be attributed to differences in the number of rejection episodes, the frequency or duration of posttransplant acute tubular necrosis, age of the recipient, or other factors. Donor age had no effect on allograft survival, and did not affect the rate of decline in creatinine clearance between 1 year and last follow-up. Thus, these results suggest that donor age is associated with intrarenal alterations that lead to reductions in renal function after transplantation, but donor age may not affect long-term prognosis or allograft survival in the late posttransplant period.     

Rapidly progressive renal failure in type 2 diabetes in the tropical environment: a clinico-pathological study

BACKGROUND: Rapid decline of renal function in a diabetic suggests the presence of a nondiabetic kidney disease (NDKD). We designed a prospective study to evaluate the factors associated with a rapid decline in renal function in patients with type 2 diabetes. METHODS: Over a 2 and a half year period, all patients with type 2 diabetes who presented with documented doubling of serum creatinine in less than 4 weeks or recently diagnosed advanced renal failure were identified. Patients with prerenal causes, urinary tract obstruction, or systemic disease causing renal failure were not included. Renal histology was studied in all cases. RESULTS: A total of 26 patients satisfied the inclusion criteria. Over 75% had serum creatinine >4 mg/dL at presentation and 62% were dialysis dependent. Renal histology showed mixed lesions of diabetic nephropathy (DN) and NDKD in 11 cases, only DN in nine, and pure NDKD in six. Diffuse proliferative glomerulonephritis (DPGN) was the commonest NDKD (27% cases), all on a background of DN. History of preceding cutaneous or pharyngeal infection was available in five cases. The proportion of postinfectious glomerulonephritis in diabetics with rapidly progressive renal failure was over six times that of the nondiabetic adult RPRF population during the study period. Four patients had acute interstitial nephritis and three showed crescentic glomerulonephritis. Other lesions included amyloidosis, atheroembolic disease, and renal papillary necrosis (one each). The frequency of microscopic hematuria and retinopathy was similar in those with pure DN and NDKD. Four out of seven cases with DPGN showed partial recovery whereas the other three remained unchanged. CONCLUSIONS: About two-thirds of patients with type 2 diabetes presenting with rapid decline of renal function in a tropical environment show NDKD. The high incidence of postinfectious glomerulonephritis in this group is possibly related to the high prevalence of skin and soft tissue infections; and could contribute to progressive kidney disease.     

The decline of renal function slowed by very low phosphorus intake in chronic renal patients following a low nitrogen diet

The rate of progression of renal failure has been evaluated in two homogenous groups of chronic renal patients with early insufficiency. In both groups the diet supplied the same amount of calories (approximately 35 Kcal/kg/day) and the protein intake was equally restricted (approximately, 0.6 g/kg/day); however, in Group 1 the phosphorus intake was lower (6.5 mg/kg/day) than in Group 2 (12 mg/kg/day). In both groups the rate of decline of creatinine clearance decreased when patients changed from a free mixed diet to the specially controlled diets, but in Group 1 (lower phosphorus intake) this change was much more marked than in Group 2. Elevated mean levels of serum phosphate and of urinary output of phosphate per unit of creatinine clearance, and elevated mean levels of serum iPTH were found in the patients of Group 2, whereas Group 1 patients had normal mean levels of serum phosphate and of iPTH, and the phosphaturia per unit of creatinine clearance was almost normal. The role of such abnormalities in urinary and serum phosphate, and of secondary hyperparathyroidism, on the progression of renal failure is discussed.     

Cigarette smoking accelerates progression of renal failure in primary renal disease. A prospective study in parallel group design with matched groups

There is substantial evidence for the adverse impact of smoking on deterioration of renal function in diabetic nephropathy but very little information is available concerning effects of smoking on the evolution of other renal diseases. In a prospective study in parallel group design with matched groups, 45 cigarette smoking patients (≥ 1 pack/day) with glomerular or tubulointerstitial lesions were compared with 45 non‐smoking patients matched for age, gender, cause and severity of renal disease as well as presence of hypertension. The monthly decline of creatinine clearance was significantly faster in smoking patients than in non‐smoking patients (follow‐up period 2 years) (1.25 mL/min vs 0.67 mL/min, P < 0.001). Smoking promoted progression of both glomerular and tubulointerstitial nephropathy. This effect occurred independently of changes in blood pressure, proteinuria or lipid concentration. The results of this investigation indicate that cigarette smoking is an independent risk factor not only for diabetic but also for non‐diabetic nephropathies.     

Comparison of methods for determining renal function decline in early autosomal dominant polycystic kidney disease: the consortium of radiologic imaging studies of polycystic kidney disease cohort

A decline in renal function suggests progression of chronic kidney disease. This can be determined by measured GFR (e.g., iothalamate clearance), serum creatinine (SCr)-based GFR estimates, or creatinine clearance. A cohort of 234 patients with autosomal dominant polycystic kidney disease and baseline creatinine clearance>70 ml/min were followed annually for four visits. Iothalamate clearance, SCr, and creatinine clearance were obtained at each visit. Estimated GFR (eGFR) was determined with the Modification of Diet in Renal Disease (MDRD) and Cockcroft-Gault equations. Renal function slopes had a mean residual SD of 10.7% by iothalamate clearance, 8.2% by MDRD equation, 7.7% by Cockcroft-Gault equation, and 14.8% by creatinine clearance. By each method, a decline in renal function (lowest quintile slope) was compared among baseline predictors. Hypertension was associated with a decline in iothalamate clearance (odds ratio [OR] 5.8; 95% confidence interval [CI] 2.3 to 14), eGFR (OR [MDRD] 2.0 [95% CI 1.0 to 4.2] or OR [Cockcroft-Gault] 1.9 [95% CI 0.9 to 3.9]), and creatinine clearance (OR 2.0; 95% CI 1.0 to 4.2). Each doubling of kidney volume at baseline was associated with a decline in iothalamate clearance (OR 2.4; 95% CI 1.5 to 3.7), eGFR (OR 1.7 [95% CI 1.1 to 2.6] or 2.1 [95% CI 1.4 to 3.3]), and creatinine clearance (OR 1.7; 95% CI 1.1 to 2.5). Predictor associations were strongest with measured GFR. Misclassification from changes in non-GFR factors (e.g., creatinine production, tubular secretion) conservatively biased associations with eGFR. Misclassification from method imprecision attenuated associations with creatinine clearance.     

Predicting postoperative renal insufficiency in patients undergoing nephrectomy for renal malignancy: assessment by renal scintigraphy using 99mtechnetium-mercaptoacetyltriglycine

PURPOSE: We performed Tc-mercaptoacetyltriglycine (MAG3) renal scintigraphy in patients with renal malignancy to evaluate the function of each renal unit before and after nephrectomy to see if postoperative functional deterioration could be predicted based on scintigraphy results and creatinine clearance. MATERIALS AND METHODS: A total of 22 men and 13 women with renal malignancy, including 32 with renal cell carcinoma and 3 with urothelial cancer, were prospectively enrolled in this study. Average patient age was 64.3 years (median 65, range 43 to 88). All patients underwent MAG3 renal scintigraphy before and after unilateral nephrectomy. At the same time serum creatinine and endogenous creatinine clearance were determined. RESULTS: Mean serum creatinine was 0.93 mg/dl before and 1.31 after nephrectomy (p <0.0001). Preoperative endogenous creatinine clearance was 70.8 ml per minute per 1.73 m, which decreased to 49.0 ml per minute per 1.73 m after nephrectomy (p <0.0001). Mean MAG3 clearance of the remaining kidney increased 35.1% above baseline from 156.5 to 211.5 ml per minute per 1.73 m following nephrectomy. Spearman rank core analysis revealed that preoperative MAG3 clearance of the remaining kidney significantly correlated with postoperative creatinine clearance (r = 0.596, p = 0.0005). Preoperative MAG3 clearance of the remaining kidney more than 130 ml per minute per 1.73 m coincided with postoperative creatinine clearance above 40 ml per minute per 1.73 m. CONCLUSIONS: MAG3 renal scintigraphy may be useful for predicting renal insufficiency after nephrectomy. The findings in this study suggest that preoperative MAG3 clearance of the remaining kidney less than 130 ml per minute per 1.73 m is a risk factor for postoperative renal insufficiency.     

Is gender a determinant for evolution of renal failure? A study in autosomal dominant polycystic kidney disease

More males than females enter renal replacement therapy programs. This may reflect greater propensity of men to acquire renal disease, faster progression of renal disease, or a combination of both. In order to address this problem, autosomal dominant polycystic kidney disease (ADPKD), a well-defined genetically homogenous hereditary disorder, was studied. One hundred fifty-eight cases of the disease in adults were diagnosed by sonography and studied (73 men, 85 women); 58 of the patients had reached end-stage renal failure. Survival analysis of age at renal death revealed a significant gender difference (log-rank test, P = 0.0072): median age at renal death was 52.5 years in men and 58.0 years in women. In 64 patients with adequate sequential measurements of serum creatinine, progression of renal failure was followed retrospectively. When serum creatinine was greater than 3 mg/dL, the average rate of progression was similar in both sexes. In contrast to ADPKD, a sex difference for the age at renal death was not found in prepubertal individuals with hereditary renal diseases, ie, cystinosis or nephronophthisis. The data suggest that sex (hormones) influences evolution of renal failure.     

Long-term renal allograft function under maintenance immunosuppression with cyclosporin A or azathioprine: A single center, five-year follow-up study

Abstract. In order to evaluate long-term renal graft function, 149 cyclosporin A and prednisolone (CyA/P)-treated renal transplant recipients were compared with 119 azathioprine and prednisolone (Aza/P)-treated patients. Only patients who had a functioning graft for at least 1 year and who were maintained on their initial immunosuppressive protocol were included. The minimum follow-up period was 4 years. Renal graft function was estimated by yearly determinations of serum creatinine and creatinine clearance. The CyA/P-treated patients had a significantly higher serum creatinine and a significantly lower creatinine clearance at every point in time post-transplantation than Aza/P-treated patients ( P < 0.001). The evolution of renal graft function, as reflected in the line of regression for serum creatinine and creatinine clearance versus time, was estimated for each individual patient. There was an almost stable renal function, as assessed by the median of the slopes of the regression line for serum creatinine versus time in both groups. The median increase in serum creatinine was only 1.4 μmol/l per year for Aza/P-treated patients and 2.4 μmol/l per year for CyA/P-treated patients (difference NS). The median decline in creatinine clearance was 2.18 ml/min per 1.73 m²/year in the Aza/P group and 1.07 ml/min per 1.73 m²/year in the CyA/P group ( P = 0.05). In patients with a functioning graft for at least 5 years, creatinine clearance remained unchanged in both groups during the study period. In conclusion, renal graft function, as assessed by measurements of serum creatinine and creatinine clearance, remained essentially unchanged for at least 5 years after transplantation, regardless of the immunosuppressive protocol used. Thus, these data do not indicate a progression with time of the nephrotoxicity observed in CyA-treated patients.     

Evolution of the renal function is a better predictor of long-term survival than serum creatinine

BACKGROUND: In recent years acute rejection has decreased to 10% to 20%. Therefore it is necessary to look for new endpoints in renal transplantation. Serum creatinine and changes in creatinine have been reported to be powerful predictors of long-term kidney transplant survival. Chronic renal allograft nephropathy is the primary cause of long-term graft failure but may appear at any stage in the evolution. METHODS: Data from 315 patients receiving cadaver donor renal transplants between February 1987 and March 2001 that functioned for 1 year were examined for the influence of demographic characteristics and transplant variables. Creatinine clearance was estimated using the Cockroft-Gault formula. Survival was assessed with the actuarial method. The multivariate analyses were performed using Cox proportional hazard models. RESULTS: The 10-year graft survival showed a relative risk of 2.5 in the univariate analysis when there was more than 10% decrease in renal function at 3 months compared with nadir values. When the decrease was more than 25% of creatinine clearance at the third month, during the evolution and serum creatinine at 3 months introduced in the multivariate model, the latter was not significant, while the other variables had a RR of 4.4 and 10, respectively. CONCLUSION: The evolution of renal function at 3 months and throughout the evolution were better predictors of graft failure than an isolated serum creatinine value.