Discharging patients from the nephrology clinic to primary care--will they get appropriate monitoring of renal function?

BACKGROUND: Chronic kidney disease (CKD) guidelines have been produced to allow affected individuals to be identified early and managed more effectively, thereby reducing cardiovascular risk and slowing the progression of CKD. The guidelines allow patients with stable early CKD, who were previously followed in nephrology clinics, to be discharged back to primary care for monitoring of their CKD. AIM: To determine if patients discharged from the nephrology clinic have appropriate monitoring of renal function in primary care according to the UK CKD guidelines, and if patients are being referred back to the clinic appropriately. METHODS: All patients discharged from a weekly satellite unit general nephrology clinic over a 2-year period were identified (n = 160). Clinic letters, the local laboratory system and direct contact with the general practice were used to determine if the timing of tests of renal function were consistent with the UK CKD guidelines. RESULTS: Most subjects (88%) had CKD Stages 1-3 at the time of discharge (i.e. eGFR > 30 ml/min). After exclusion of patients with an incomplete management plan or insufficient time since discharge (n = 50), 85% of eligible patients (n = 110) had at least one measure of eGFR after discharge. In 65% (n = 84) of these patients, measurement occurred within 1 month of the correct timing according to the guidelines. Four patients were re-referred appropriately. There were no other patients who should have been re-referred due to deteriorating renal function. CONCLUSION: Patients with stable early CKD get appropriate monitoring of renal function after discharge from the nephrology clinic to primary care and are also referred back to the renal clinic appropriately.

Tacrolimus combined with two different dosages of sirolimus in kidney transplantation: results of a multicenter study.

Tacrolimus combined with mycophenolate mofetil (MMF) is an effective regimen in kidney transplantation. This study compared the efficacy of combining tacrolimus and two different dosages of sirolimus with an established tacrolimus-MMF regimen. Each day in addition to tacrolimus, 325 patients received 2 mg sirolimus (TAC-SRL2 mg), 325 patients received 0.5 mg sirolimus (TAC-SRL0.5 mg) and 327 patients 1 g MMF (TAC-MMF). The initial tacrolimus dose was 0.2 mg/kg/day. Sirolimus patients received loading doses of 6 or 1.5 mg, and daily doses of 2 or 0.5 mg thereafter. Steroid administration was identical for all groups. The incidence of biopsy-proven acute rejection was lower in the TAC-SRL2 mg group (15.7%) compared with the TAC-SRL0.5 mg (25.2%, p = 0.003) and the TAC-MMF groups (22.3%, p = 0.036). Six-month graft survival was 91.0% (TAC-SRL2 mg), 92.6% (TAC-SRL0.5 mg) and 92.4% (TAC-MMF); the respective values for patient survival were 98.1%, 97.8% and 97.9%. Thirty-four patients (10.5%), 19 patients (5.8%) and 16 patients (4.9%) in the TAC-SRL2 mg, TAC-SRL0.5 mg and TAC-MMF groups, respectively, discontinued the study because of adverse events. Hyperlipemia was reported more often in the TAC-SRL2 mg group (24.0%) compared with 19.4% (TAC-SRL0.5 mg) and 11.0% (TAC-MMF; p < 0.05). Combining 2 mg sirolimus/day with tacrolimus results in lower rates of acute rejection, but a higher incidence of adverse events.

Lobar nephronia in a transplanted kidney.

We report a patient who presented with a solid mass in her graft 15 years after renal transplantation. The appearances by ultrasound were consistent with either malignancy or lobar nephronia (focal acute bacterial nephritis). Biopsy confirmed the diagnosis of a lobar nephronia with marked inflammatory infiltrate and frank pus formation. Treatment with antibiotics was associated with resolution of the mass. Lobar nephronia is a diagnosis based upon renal ultrasonography and must be considered in a patient with a solid mass in the kidney.

Hypertension, antihypertensive agents and outcomes following renal transplantation.

UNLABELLED: Hypertension is common following renal transplantation and adversely affects graft and patient survival. However, strategies for antihypertensive drug therapy and target blood pressure have not been clearly defined. AIM: To assess the influence of achieved blood pressure and antihypertension drug therapy on graft and patient survival with the aim of identifying targets and event rates for future intervention studies. METHODS: We undertook a longitudinal follow up study of 634 renal transplant patients. Patients were surveyed in December 1994 and followed up after 102 months. Blood pressure (BP) was determined from the mean of three clinic readings and antihypertensive drug therapy recorded. RESULTS: Complete follow up data were available for analysis on 622 patients (57.2% male; mean age: 45.2 +/- 13.0 yr. There were 158 (25.4%) deaths and 115 (18.5%) death-censored graft failures. Lower systolic and diastolic blood pressure were associated with better graft survival in the Kaplan-Meier analysis. Univariate analysis showed serum creatinine (HR 1.012, p < 0.001), duration of renal replacement therapy (HR 0.946, p = 0.012), age (HR 0.979, p = 0.014) and pulse pressure (HR 1.017, p = 0.044) to be predictors of graft survival with serum creatinine and duration of renal replacement therapy as the only significant factors in the multivariate analysis. Lower systolic and pulse pressure were associated with better patient survival in the Kaplan-Meier analysis. Age (HR) 1.062, p < 0.0001), serum creatinine (HR 1.002, p = 0.021), diabetes (HR 3.371, p < 0.0001), and pulse pressure (HR 1.013, p = 0.036) were significant predictors of patient survival in the univariate and multivariate analysis. Patient survival was reduced with increasing number of antihypertensives (p < 0.05), as was graft survival (p < 0.05). Reduced patient and graft survival were seen in patients prescribed calcium channel antagonists (p < 0.01). There was no increased patient mortality in those patients on beta-blockers or angiotensin converting enzyme (ACE) inhibitors. CONCLUSION: Hypertension is a risk factor, which remains despite the use of anti-hypertensives, for reduced patient and graft survival. The risk was not significant when blood pressure was entered together with serum creatinine in the multivariate analysis. Beta-blockers may have a beneficial effect on cardiovascular mortality, and ACE inhibitors a beneficial effect on both patient and graft survival. There is a pressing need for interventional studies to assess the impact of blood pressure targets on patient and graft survival and the effect of individual agents on these outcomes.

Partial nephrectomy used to treat renal cell carcinoma arising in a live donor transplant kidney.

There are few reported cases of renal cell carcinoma (RCC) arising in kidney allografts. Whether these tumours occur due to post-transplant malignant transformation or are present at the time of transplantation is unclear. The influence of immunosuppression must be considered in their development, progression and treatment. We report a case of a RCC presenting asymptomatically in a functioning live donor renal allograft 173 months after transplantation. In an attempt to avoid return to dialysis treatment, a partial nephrectomy was carried out. To optimise the procedure, and to assure cancer clearance, combined intraoperative ultrasound and frozen section analysis were used. Our patient remains disease free and dialysis independent at 22 months follow up. To our knowledge, this patient represents the only live donor organ transplant tumour reported to be treated using nephron-sparing surgery and remain dialysis independent. Partial nephrectomy should be considered as a treatment option in such cases.

Biocompatible membranes do not promote graft recovery following cadaveric renal transplantation.

BACKGROUND: Controversy surrounds the role of biocompatible membrane dialyzers in treatment of acute renal failure. Studies that have shown a benefit have involved critically ill patients where renal recovery and patient mortality are influenced by other comorbid disease. The aim of the present work is to clarify this issue in a more homogeneous population of patients with acute renal failure following cadaveric renal transplantation. METHODS: All patients with delayed graft function between January 1996 and February 1998 were randomized to receive either a biocompatible (BCM, polysulfone) membrane or bioincompatible (BICM, cuprophane) membrane for dialysis until onset of graft function. RESULTS: Forty-one patients were randomized, 23 to receive BCM and 18 BICM. Five patients (2 BCM, 3 BICM; p = NS) with primary non-function of graft were excluded from analysis, leaving 36 cases of acute tubular necrosis (ATN). Patient and donor characteristics were similar in both groups. The BCM group had significantly longer periods of dialysis dependency compared to the BICM group (14 vs 10 days; p = 0.03). There was a tendency towards higher serum creatinine levels in the short term in the BCM group (318 vs 164 micromol/l at 1 month (p = 0.1), 190 vs 169 micromol/l at latest visit (p = 0.07)) and a greater number of acute rejection episodes in the BCM group (3.7 vs 1.7 episodes per 100 days of dialysis dependency, p = 0.1). With an intention-to-treat analysis of all 41 patients originally randomized, there was no significant difference in time to graft recovery between the 2 groups (p = 0.18). CONCLUSIONS: In the setting of ARF posttransplantation, we have found no evidence to support the use of biocompatible membranes for dialysis. Rather, our study provides argument against a large benefit for the use of BCM in the recovery of ARF, as suggested by earlier studies.

Cardiac and vascular abnormalities in renal transplant patients: differential effects of cyclosporin and azathioprine.

Renal transplant patients die prematurely of cardiovascular disease and LV hypertrophy is now recognised as an important adverse prognostic indicator. This study investigated the factors implicated in the development of echocardiographic abnormalities (including LV hypertrophy) and the possible differential effects of treatment with cyclosporin and azathioprine. A cross-sectional study was undertaken in 46 patients randomly assigned to immunosuppressant treatment with either cyclosporin or azathioprine at 1 year post-transplantation: patients were studied not less than 5 years after assignment to cyclosporin (CyA) - or azathioprine (Aza)-based treatment regimens. Although clinic blood pressure control was not different in the two treatment groups, 24 hour ambulatory BP (ABP), particularly night-time BP, was significantly higher in the CyA group. There was a trend for both left ventricular hypertrophy (61 vs. 43%) and carotid wall thickening (43 vs. 26%) to be more common in the CyA group though this failed to achieve statistical significance. Left ventricular mass was determined by ABP, rather than clinic BP, and was also associated with increased QT dispersion. Multivariate analysis identified that 24 hour ambulatory systolic blood pressure (ASBP) and time on renal replacement therapy (RRT) were the major determinants of LV mass. Thus, despite the absence of differences in clinic BP measurements, CyA treatment was associated with higher rates of cardiovascular functional and structural abnormalities. This small scale study has identified cardiovascular functional and structural abnormalities in renal transplant patients, particularly in those receiving CyA-based immunosuppressive therapy. However, rather than reflecting a direct effect of CyA they are related to increased 24 ABP (but not clinic BP). These data suggest that ABP should be used to monitor and target antihypertensive therapy in this high risk patient group. Moreover, the future use of non-calcineurin inhibitor immunosuppressant therapy may have benefits on blood pressure control and LV mass.

Impaired endothelium-dependent vasodilatation in uraemia.

BACKGROUND: Patients with chronic renal failure (CRF) have a substantially increased risk of cardiovascular death, the proposed mechanisms being arrhythmias (left ventricular hypertrophy) and accelerated atherosclerosis. The vascular endothelium protects against the development of atherosclerosis principally by releasing vasoactive substances such as nitric oxide (NO) and endothelium-derived hyperpolarizing factor. In CRF there is accumulation of endogenous inhibitors of NO synthesis. In this present study we assessed endothelium-dependent vasodilatation in patients with advanced uraemia. METHODS: Sixteen uraemic patients (pre-dialysis and continuous ambulatory peritoneal dialysis) and 18 controls were studied. Forearm plethysmography was used to measure forearm blood flow and the changes induced by carbachol (endothelium-dependent vasodilator) and sodium nitroprusside (SNP; endothelium-independent vasodilator). The order of drugs infused was randomized between subjects. Dose response curves were constructed for each agent and area under the curve (AUC) calculated (arbitrary units). RESULTS: Overall, vasodilatation to SNP and carbachol was similar between uraemic patients and controls. However, it became apparent that there was a marked order effect for the drugs infused, such that infusion of SNP as the first agent blunted the subsequent response to carbachol. When only those patients and controls who received carbachol followed by SNP were studied (10 in each group), the response to carbachol in uraemic patients was attenuated compared to controls: AUC (median(range)) for uraemic patients 529.0 (150.9-834.7) compared to AUC for controls 703.9 (583.5-1576.6); P=0. 028. Vasodilatation to SNP was, however, similar between groups: AUC for uraemic patients 1475.0 (857.8-4717.1) compared to AUC for controls 1328.1 (216.6-3311.4); P=0.545. CONCLUSIONS: This study has demonstrated a marked drug order effect not previously described for forearm plethysmography. When the order effect was taken into account, this study demonstrated reduced vasodilatation to carbachol in uraemic patients with a preserved response to SNP. This pattern indicates impaired endothelium-dependent vasodilatation in uraemic patients, a defect that may predispose this group to accelerated atherosclerosis.

Endothelial dysfunction in renal transplant recipients maintained on cyclosporine.

BACKGROUND: Hypertension is almost universal following renal transplantation and may contribute to the already poor cardiovascular prognosis of this group. Cyclosporine-induced hypertension is a particular problem and has variously been attributed to increased sympathetic nerve activity, salt and water retention, and increased circulating endothelin levels. However, the effects of cyclosporine on the L-arginine/nitric oxide (NO) system in vivo in humans are unknown. In this present study, we examined basal and stimulated NO production from the vascular endothelium in cyclosporine-treated renal transplant recipients using the technique of forearm venous plethysmography. METHODS: In study 1, stimulated NO production was assessed in 9 cyclosporine-treated renal transplant recipients (CsA), 7 azathioprine-treated renal transplant recipients (AZA), and 12 controls, using carbachol (an endothelium-dependent vasodilator) and sodium nitroprusside (an endothelium-independent vasodilator). In study 2, basal NO production was assessed in 9 cyclosporine-treated patients and 11 controls using L-NMMA (inhibits NO synthase), with norepinephrine as a control vasoconstrictor. Drugs were infused into the nondominant forearm through a sterile 27-gauge needle, and changes in forearm blood flow (FBF) were measured using venous occlusion plethysmography. RESULTS: In study 1, sodium nitroprusside caused a similar dose-dependent increase in FBF in all groups. However, the median (range) percentage increase FBF to carbachol (3 micrograms/min) was markedly reduced in the CsA patients (188.8; 72.5 to 385.1) compared with AZA patients (378.1; 124.0 to 548.9; P = 0.042) and to controls (303.8; 124.8 to 813.3; P = 0.028). In study 2, the maximum percentage reduction in FBF to L-NMMA (4 mumol/min) was less pronounced in CsA patients (-19.5; -4.7 to -63.1) compared with controls (-39.5; -15.7 to -52.8; P = 0.056), and while controls vasoconstricted to the maximum dose of norepinephrine (240 pmol/min) as expected (-26.9; -1.4 to -38.6), CsA patients as a group tended to vasodilate (7.9; -36.8 to 92.6; P = 0.02). CONCLUSION: These data demonstrate impaired stimulated and basal NO production in CsA patients, indicating endothelial dysfunction. This may predispose patients to atherosclerosis and may be involved in the etiology of post-transplant hypertension.

Early echocardiographic changes and survival following renal transplantation.

BACKGROUND: Left ventricular hypertrophy, ventricular dilatation and poor systolic function prior to renal transplantation are associated with increased mortality. However, whether the improvement in these echocardiographic indices that is reported to follow renal transplantation improves patient survival has not been investigated. METHODS: We studied 67 patients who underwent renal transplantation in our unit between 1988 and 1990 and in whom echocardiography was performed immediately prior to transplant surgery and 4 months later. Pre- and post-transplantation echocardiographic parameters were compared between the 20 patients who have since died and surviving patients and a descriptive survival analysis was performed. RESULTS: Following transplantation there was no significant change in left ventricular mass index (LVMI) or end diastolic diameter (EDD). End systolic diameter (ESD) improved in 60% of patients (median 3.3 vs 3. 7 cm; P=0.031) as did fractional shortening in 67% (0.33 vs 0.29; P=0.001). However, improvement was not associated with survival benefits. We also found that prior to transplantation, fractional shortening, ESD and EDD were strongly associated with outcome; this was no longer the case following transplantation. In contrast, LVMI provided a stronger association with adverse outcome (albeit of limited statistical significance) following transplantation. CONCLUSIONS: In this Preliminary Report, we conclude that echocardiographic parameters are associated with adverse outcome in patients receiving renal replacement therapy (RRT). Different echocardiographic parameters are associated with adverse outcome before and after renal transplantation and improvement of pre-transplant abnormalities (e.g. poor LV systolic function) following transplantation does not necessarily confer survival benefits. Whether this is a genuine observation or a reflection of the interpretation of echocardiographic measurements in dialysis patients requires further investigation.

Echocardiography overestimates left ventricular mass in hemodialysis patients relative to magnetic resonance imaging.

UNLABELLED: Echocardiography overestimates left ventricular mass in hemodialysis patients relative to magnetic resonance imaging. BACKGROUND: Left ventricular hypertrophy (LVH) is a common finding and a strong adverse prognostic factor in patients with chronic renal failure. An accurate method of measuring left ventricular mass (LV mass) is therefore a prerequisite in the management of these patients. Recent evidence has suggested that echocardiography overestimates LV mass in patients with essential hypertension, and this error increases with increasing LV mass. METHODS: We studied 35 patients on maintenance hemodialysis within 24 hours of their last dialysis. LV mass was measured by both echocardiography and magnetic resonance imaging (MRI) performed less than three hours apart. Clinic and ambulatory blood pressure (ABPM), resting echocardiogram, and blood sampling were performed at the same visit. RESULTS: Thirty-two patients had results from both methods. Clinic blood pressure, ABPM, and QT dispersion all correlated with LV mass, with a stronger correlation observed for MRI values. Intraobserver and interobserver variability were significantly greater for echocardiography (although similar to other published data). Comparing the two methods, the difference in LV mass values (echo minus magnetic resonance) increased in a linear fashion with an increasing mean mass and chamber diameter. CONCLUSIONS: Echocardiography significantly overestimates LV mass relative to MRI in the presence of LVH and dilation. This overestimation is the result of assumptions made in the calculation of mass from echocardiography M-mode images, which are invalid when LV geometry is abnormal. This error is therefore amplified in dialysis patients, the majority of whom have LVH and in whom intravascular volume is constantly changing.

Early graft function and patient survival following cadaveric renal transplantation.

BACKGROUND: The influence of events that occur early following renal transplantation such as delayed graft function (DGF) and acute rejection on long-term graft survival has been widely reported, but its association with patient survival has received less attention. METHODS: We studied 589 patients who received their first cadaveric transplants between 1984 and 1993, all of whom received cyclosporine-based immunosuppression and who had a median follow-up of seven years. The following factors were identified, and both univariate and multivariate analyses were used to determine their association with long-term patient and graft survival: age, sex, duration of pretransplant dialysis, primary renal disease, immediate graft function (IGF), DGF, primary nonfunction (PNF), acute rejection, and serum creatinine at 3, 6, and 12 months. RESULTS: Patients with PNF had a poorer survival than those with DGF and IGF (P = 0.01), but there was no difference in survival between DGF and IGF (P = 0.54). Good graft function (serum creatinine of less than 200 mumol/liter) at three months was predictive of better long-term patient survival (P = 0.03). Other factors associated with poor patient outcome were older age, diabetes, adult polycystic kidney disease, male gender, and acute rejection. Cardiovascular disease was the most common cause of death (51.8%). Good graft function at three months (P < 0.001) and an absence of rejection episodes (P = 0.01) were associated with better graft survival. CONCLUSION: Patients with poor levels of early graft function (but not DGF) and those with either acute rejection episodes or early graft loss are at an increased risk of early death. These high-risk groups should be targeted for interventional studies in an attempt to improve patient survival.

QT dispersion before and after hemodialysis.

Sudden cardiac death is common in patients on hemodialysis, and may occur in the immediate postdialysis period, when ventricular premature complexes are common. Elevated QT dispersion (Maximum - Minimum QT interval on standard 12-lead electrocardiogram) is associated with increased risk of ventricular arrhythmias following myocardial infarction, but has not previously been assessed in patients with chronic renal failure. We studied electrocardiograms recorded in 50 patients before and after a single hemodialysis session, and in 20 control subjects. QT dispersion was significantly higher in patients (63.1 +/- 20.6 ms) compared with control subjects (36.0 +/- 13.7 ms; P < 0.001) and rose significantly after hemodialysis to levels comparable to those seen following myocardial infarction (76.6 +/- 27.0 ms; P < 0.01). Because QT dispersion reflects nonhomogeneous recovery of ventricular excitability, hemodialysis patients may be at significantly greater risk of reentrant arrhythmias and sudden death in the postdialysis period.

Long-term outcome of a prospective randomized trial of conversion from cyclosporine to azathioprine treatment one year after renal transplantation.

BACKGROUND: Since the introduction of cyclosporine (CsA), 1-year renal allograft survival has improved, but concern persists about the long-term adverse effects of CsA, especially with respect to renal function and blood pressure. This randomized controlled trial was set up to establish whether withdrawal of CsA would alter long-term outcome. METHODS: Adult patients who, at 1 year after renal transplantation, had a stable serum creatinine of less than 300 micromol/L and who had not had acute rejection within the last 6 months were eligible for entry. Patients were randomized either to continue on CsA (n=114) or to stop CsA and start azathioprine (Aza, n=102). All patients remained on prednisolone. Median follow-up was 93 months after transplantation (range: 52-133 months). RESULTS: There was no significant difference in actuarial 10-year patient or graft survival (Kaplan-Meier), despite an increased incidence of acute rejection within the first few months after conversion. Median serum creatinine was lower in the Aza group (Aza: 119 micromol/L; CsA. 153 micromol/L at 5 years after randomization, P=0.0002). The requirement for antihypertensive treatment was also reduced after conversion to Aza; 75% of patients required antihypertensive treatment at the start of the study, decreasing to 55% from 1 year after randomization in the Aza group and increasing to >80% in the CsA group (55% (Aza) and 84% (CsA) at 5 years after randomization, P<0.005). CONCLUSIONS: Conversion from CsA to Aza at 1 year after renal transplantation results in improvement in both blood pressure control and renal allograft function, and is not associated with significant adverse effects on long-term patient or graft survival.

Pre-operative echocardiographic abnormalities and adverse outcome following renal transplantation.

BACKGROUND: Premature cardiovascular disease is now the leading cause of death in renal transplant recipients. Although patients with progressive renal disease have many of the conventional risk factors for cardiovascular disease these do not have the same predictive power as they do in the general population. Echocardiographic abnormalities, notably left ventricular hypertrophy, have been shown to be associated with adverse outcome in patients on dialysis. METHODS: The echocardiograms were studied from 141 patients who were examined on the eve of renal transplantation between 1988 and 1990 to try to identify factors predicting outcome. Thirty-four patients have since died, 22 of cardiovascular disease. Ninety-three of the survivors and 27 of the dead patients had echocardiographic traces suitable for analysis. RESULTS: Left ventricular mass index was increased in those patients who died (median 167 vs 134 g/m2; P=0.03), as were end-systolic (4.3 vs 3.4 cm; P<0.01) and end-diastolic (5.8 vs 5.2 cm; P<0.01) diameters. Systolic function was also more severely impaired (fractional shortening, 27 vs 33%; P<0.01). Apart from age, only systolic function and end systolic diameter were independent predictors of outcome in multivariate analysis. CONCLUSIONS: This pattern of echocardiographic abnormality is similar to that reported in long-term dialysis populations, despite the adverse effects on survival. Moreover, despite potential benefits of transplantation on cardiac function, left ventricular hypertrophy, ventricular dilatation and systolic dysfunction were all associated with adverse outcome following transplantation. We conclude that echocardiography identifies markers for premature death following transplantation and provides targets for therapeutic intervention.