Structured clinical follow-up for CKD stage 5 may safely postpone dialysis.

BACKGROUND AND OBJECTIVES: The optimal timing of dialysis initiation is still unclear. We aimed to ascertain whether a strict clinical follow-up can postpone need for dialysis in chronic kidney disease (CKD) stage 5 patients. DESIGN, SETTING, PARTICIPANTS AND MEASUREMENTS: We reviewed records of all consecutive adult patients attending our conservative CKD stage 5 outpatient clinic from 2001 to 2010. Chronicity was defined as two consecutive estimated glomerular filtration rate (eGFR) measurements below 15 ml/min/1.73 m(2). Characteristics of subjects, including comorbidities, were assessed at baseline; blood pressure and serum markers of uremia were assessed both at first and last visit. GFR was estimated by the 4-variable Modification of Diet in Renal Disease (MDRD) formula. RESULTS: In the 312 patients analyzed baseline eGFR was 9.7 ± 2.7 ml/min, which declined by 1.93 ± 4.56 ml/min after 15.6 ± 18.2 months. Age was inversely related to eGFR decline (r -0.27, p = 0.000). During conservative follow-up 55 subjects (18%) died. In comparison with those eventually entering dialysis, deceased subjects were older and had a longer follow-up with no CKD progression. Multivariate analysis identified age, proteinuria and lower baseline K values as the only independent determinants of death. One hundred ninety-four subjects (66%) started dialysis with an average eGFR of 6.1 ± 1.9 ml/min. During 35.8 ± 24.7 months of dialysis follow-up, 84 patients died. Multivariate analysis identified age as the main determinant of death (hazard ratio [HR] for every year 1.07, 95% confidence interval [CI] 1.04-1.11, p 0.000). Patients starting dialysis with eGFR below the median, e.g. <5.7 ml/min, showed a better survival (HR for mortality 0.52, 95% CI 0.30-0.89, p 0.016) than the other group. CONCLUSIONS: A well-organized nephrological outpatient clinic for conservative follow-up of CKD stage five patients can delay dialysis entry as long as 1 year. Starting dialysis with eGFR lower than 6 ml/min does not confer any increased risk of death in selected early-referral patients.

Is left ventricular hypertrophy a powerful predictor of progression to dialysis in chronic kidney disease?

BACKGROUND: The role of cardiovascular factors in predicting renal outcome has not been extensively elucidated. Herein, we report a prospective evaluation of the impact of left ventricular hypertrophy (LVH) on outcome in non-diabetic patients with chronic kidney disease (CKD). METHODS: We studied 144 patients (99 men; age 62±14 years) with stage 3-4 CKD, with baseline assessment of left ventricular mass index (LVMi) by echocardiography, estimated glomerular filtration rate (eGFR) by MDRD equation, 24-h blood pressure profile and 24-h proteinuria. Combined end point was progression to ESRD requiring dialysis, or death within 5 years. RESULTS: Forty-nine patients (34%) progressed to dialysis, 24 (17%) died, 57 (39%) were dialysis-free after 5 years and 14 were lost to follow-up. Multivariate Cox proportional hazards analysis showed that increased LVMi (HR 1.28, 95% CI 1.17-1.40 for each 10-g/m2 increase, P<0.0001) and reduced eGFR (5% risk increase for each 1-mL/min reduction, P=0.027) were the significant predictors of the combined end point in stage 3 CKD patients, whereas LVMi proved to be the only significant predictor of the combined end point in patients with stage 4 CKD (HR 1.19, 95% CI 1.09-1.31, P<0.0001). The same analysis showed that LVMi was the only significant predictor of progression to dialysis in stage 3 CKD patients (HR 1.42, 95% CI 1.23-1.64 for each 10-g/m2 increase, P<0.0001), while a 20% increase in the risk of progression to ESRD was observed for each 10-g/m2 increase in LVMi (P<0.0001), and a 10% increase for each 1-mL/min reduction in eGFR (P=0.046) in patients with stage 4 CKD. When evaluating the predictive role of LVMi on outcome using AUC-ROC curves, the overall performance of the model including LVMi (AUC 0.877, 95% CI 0.8-0.954) was superior to the model including eGFR (AUC 0.737, 95% CI 0.656-0.817) for the end point of progression to dialysis (P=0.026, Hanley test). CONCLUSIONS: LVH proved to be the strongest predictor of the risk of progression to dialysis in non-diabetic CKD, especially among patients with less advanced renal dysfunction. Regardless of whether it is a simple marker or a pathogenetic factor, LVH encompasses all factors possibly affecting renal and general outcome in CKD patients.

Association of arterial hypertension with renal target organ damage in kidney transplant recipients: the predictive role of ambulatory blood pressure monitoring.

BACKGROUND: Although arterial hypertension is a powerful predictor of graft failure, only few studies have evaluated 24-hr blood pressure (BP) profile in renal transplant recipients (RTRs). METHODS: We performed ambulatory blood pressure monitoring (ABPM) in 94 RTRs (65 men; age 28-71 years) with 1-year functioning grafts. Serum biochemical parameters, daily proteinuria, and transplantation-related data were evaluated in all subjects. RESULTS: ABPM showed that only 5% of RTRs were normotensives (BP<130/80 mm Hg) and identified 29% of patients with nocturnal hypertension. A strong, direct correlation was shown between each set of both systolic BP and diastolic BP measured by ABPM and serum creatinine, daily proteinuria, and serum triglycerides (P at least <0.025 for each). Serum creatinine immediately after transplantation and 1-yr asleep diastolic BP were the only significant predictors of 1-yr creatinine (P<0.0001; r=0.49), whereas awake systolic BP was the only predictor of daily proteinuria (r=0.39; P=0.005) by multiple regression analysis. CONCLUSIONS: BP assessed by ABPM proved to be a stronger predictor of renal graft damage than traditional immunologic factors. ABPM improved the diagnostic accuracy of arterial hypertension in RTRs and was the only effective tool in disclosing the association of BP with 1-year renal transplant outcome.

Effect of sirolimus on left ventricular hypertrophy in kidney transplant recipients: a 1-year nonrandomized controlled trial.

BACKGROUND: Left ventricular hypertrophy (LVH) after renal transplantation may be affected by immunosuppressive therapy. STUDY DESIGN: Nonrandomized controlled trial evaluating the effect of sirolimus (SRL) on LVH of renal transplant recipients (RTRs). SETTING & PARTICIPANTS: 13 RTRs without diabetes who had received a single-kidney transplant from a deceased donor with chronic allograft dysfunction and biopsy-proven allograft nephropathy who were converted from calcineurin-inhibitor (CNI) to SRL treatment; 26 controls matched for age and year of transplantation who were not converted from CNI to SRL treatment. INTERVENTION: Conversion from CNI to SRL therapy. OUTCOMES & MEASUREMENTS: Left ventricular mass determination by using echocardiography at baseline and again 1 year later. Blood pressure (BP), hemoglobin level, serum creatinine level, uric acid level, lipid levels, trough levels of immunosuppressive drugs, and daily proteinuria were assessed at least twice monthly. Conventional antihypertensive therapy was used to achieve BP of 130/80 mm Hg or less. RESULTS: The study population included 26 men and 13 women (age, 25 to 66 years). Changes in BP were similar in the 2 groups (between-group difference, -4 +/- 5 mm Hg; P = 0.5 for systolic BP; -2 +/- 3; P = 0.6 for diastolic BP), whereas left ventricular mass significantly decreased in the SRL group alone (between-group difference, 8.6 +/- 2.4 g/m(2.7); P < 0.001) because of a decrease in both the interventricular septum and left ventricular posterior wall. LVH regressed in 12 of 13 patients on SRL therapy and 10 of 26 controls (P = 0.002). LIMITATIONS: Nonrandomized design. Single-center study with small sample size. CONCLUSIONS: Conversion from CNI to SRL therapy may regress LVH in RTRs regardless of BP changes, mainly by decreasing left ventricular wall thickness, thus suggesting nonhemodynamic-effect mechanisms of SRL on left ventricular mass.

ACE inhibitors and persistent left ventricular hypertrophy after renal transplantation: a randomized clinical trial.

BACKGROUND: Interventional studies of left ventricular hypertrophy (LVH) in renal transplant recipients are scarce and to date evaluated only patients immediately after renal transplantation. STUDY DESIGN: Randomized controlled trial that assessed the effectiveness of angiotensin-converting enzyme (ACE) inhibitors in regressing persistent LVH after successful transplantation. SETTING & PARTICIPANTS: 70 renal transplant recipients (47 men; age, 30 to 68 years) without diabetes previously randomly assigned to either cyclosporine or tacrolimus therapy, with LVH persisting 3 to 6 months after transplantation. INTERVENTION: Subjects were randomly assigned to either lisinopril (ACE-inhibitor group; 36 patients) or no therapy (control group; 34 subjects). OUTCOMES: Main outcome was change in left ventricular mass index (LVMi) at month 18. RESULTS: A consistent decrease in both systolic (SBP) and diastolic blood pressure (DBP) was observed in both groups (between-group differences, -1.7 +/- 3.3 mm Hg; 95% confidence interval [CI], -4.8 to 8.2; P = 0.6 for SBP; 0.3 +/- 2.2 mm Hg; 95% CI, -4.8 to 4.1; P = 0.9 for DBP), whereas LVMi regressed more in the ACE-inhibitor group (between-group difference, 10.1 +/- 16.3 g/m(2.7); 95% CI, 4.2 to 16.1; P < 0.01). A significant interaction of ACE inhibitors with cyclosporine in affecting LVMi change was shown by means of post hoc multiple regression analysis (P < 0.01; differences between cyclosporine and tacrolimus group, 13.3 +/- 3.9 g/m(2.7); 95% CI, 5.3 to 21.2; P < 0.01 in the ACE-inhibitor group; 3.7 +/- 4.2 g/m(2.7); 95% CI, -4.7 to 12.2; P = 0.4 in the control group). LIMITATIONS: Single-center study with small sample size. Interaction of ACE inhibitors with cyclosporine treatment emerged from post hoc analysis. CONCLUSION: A prolonged course of ACE-inhibitor therapy is effective in regressing the persistent LVH of renal transplant recipients by mechanisms independent of effects on BP. This regression seems to be at least in part the effect of an interaction between ACE inhibitors and cyclosporine.

Relationship between arterial hypertension and renal damage in chronic kidney disease: insights from ABPM.

BACKGROUND: To date, few studies have used ambulatory pressure monitoring (ABPM) in patients with chronic kidney disease (CKD) before the start of dialysis treatment. The aim of this study was therefore to ascertain the correlates of arterial hypertension assessed by ABPM in CKD patients at their first referral to a nephrologist. METHODS: We studied 244 (164 men; mean age 63 years) nondiabetic patients with CKD. Each patient had blood pres-sure (BP) measured by 24-hour ABPM, creatinine clearance (CrCl) estimated according to the Cockcroft-Gault formula, and Hgb concentration, serum lipids, iPTH, daily urinary protein (Uprot) and sodium (UNa) excretion assessed using routine methods. RESULTS: According to ABPM data analysis, 81 patients were normotensives, 78 were stable hypertensives, 26 had day-time hypertension and 59 had nocturnal hypertension. ANOVA showed both lower CrCl (p=0.0033), and higher Uprot (p<0.0001) in stable and nighttime hypertensives as compared with normotensives and daytime hypertensives. In the whole group each set of both systolic (SBP) and pulse pressure (PP) readings was directly associated with both age and Uprot (p<0.05), and inversely with both CrCl and Hgb (p<0.05). In multivariate analysis, however, Uprot emerged among modifiable risk factors, as the most significant predictor of both SBP and PP; the strength of this association was in the order nighttime PP > nighttime SBP > 24-hour PP > daytime PP > daytime SBP > 24-hour SBP. CONCLUSION: In CKD patients, proteinuria is the strongest correlate of arterial hypertension and particularly of increased nocturnal PP, possibly as an expression of vascular damage. On the basis of these results, ABPM appears to be the most reliable tool for detecting the associations between raised BP (particularly nighttime hypertension) and renal damage in CKD patients not yet on renal replacement therapy (RRT).