Management of immunosuppressive therapy in kidney transplant recipients with COVID-19. A multicentre national study derived from the Spanish Society of Nephrology COVID registry.

INTRODUCTION: SARS CoV2 infection has had a major impact on renal transplant patients with a high mortality in the first months of the pandemic. Intentional reduction of immunosuppressive therapy has been postulated as one of the cornerstone in the management of the infection in the absence of targeted antiviral treatment. This has been modified according to the patient`s clinical situation and its effect on renal function or anti-HLA antibodies in the medium term has not been evaluated. OBJECTIVES: Evaluate the management of immunosuppressive therapy made during SARS-CoV2 infection, as well as renal function and anti-HLA antibodies in kidney transplant patients 6 months after COVID19 diagnosis. MATERIAL AND METHODS: Retrospective, national multicentre, retrospective study (30 centres) of kidney transplant recipients with COVID19 from 01/02/20 to 31/12/20. Clinical variables were collected from medical records and included in an anonymised database. SPSS statistical software was used for data analysis. RESULTS: renal transplant recipients with COVID19 were included (62.6% male), with a mean age of 57.5 years. The predominant immunosuppressive treatment prior to COVID19 was triple therapy with prednisone, tacrolimus and mycophenolic acid (54.6%) followed by m-TOR inhibitor regimens (18.6%). After diagnosis of infection, mycophenolic acid was discontinued in 73.8% of patients, m-TOR inhibitor in 41.4%, tacrolimus in 10.5% and cyclosporin A in 10%. In turn, 26.9% received dexamethasone and 50.9% were started on or had their baseline prednisone dose increased. Mean creatinine before diagnosis of COVID19, at diagnosis and at 6 months was: 1.7 ±â€¯0.8, 2.1 ±â€¯1.2 and 1.8 ±â€¯1 mg/dl respectively (p < 0.001). 56.9% of the patients (N = 350) were monitored for anti-HLA antibodies. 94% (N = 329) had no anti-HLA changes, while 6% (N = 21) had positive anti-HLA antibodies. Among the patients with donor-specific antibodies post-COVID19 (N = 9), 7 patients (3.1%) had one immunosuppressant discontinued (5 patients had mycophenolic acid and 2 had tacrolimus), 1 patient had both immunosuppressants discontinued (3.4%) and 1 patient had no change in immunosuppression (1.1%), these differences were not significant. CONCLUSIONS: The management of immunosuppressive therapy after diagnosis of COVID19 was primarily based on discontinuation of mycophenolic acid with very discrete reductions or discontinuations of calcineurin inhibitors. This immunosuppression management did not influence renal function or changes in anti-HLA antibodies 6 months after diagnosis.

Best practices during COVID-19 pandemic in solid organ transplant programs in Spain.

Clinical management of transplant patients abruptly changed during the first months of COVID-19 pandemic (March to May 2020). The new situation led to very significant challenges, such as new forms of relationship between healthcare providers and patients and other professionals, design of protocols to prevent disease transmission and treatment of infected patients, management of waiting lists and of transplant programs during state/city lockdown, relevant reduction of medical training and educational activities, halt or delays of ongoing research, etc. The two main objectives of the current report are: 1) to promote a project of best practices in transplantation taking advantage of the knowledge and experience acquired by professionals during the evolving situation of the COVID-19 pandemic, both in performing their usual care activity, as well as in the adjustments taken to adapt to the clinical context, and 2) to create a document that collects these best practices, thus allowing the creation of a useful compendium for the exchange of knowledge between different Transplant Units. The scientific committee and expert panel finally standardized 30 best practices, including for the pretransplant period (n = 9), peritransplant period (n = 7), postransplant period (n = 8) and training and communication (n = 6). Many aspects of hospitals and units networking, telematic approaches, patient care, value-based medicine, hospitalization, and outpatient visit strategies, training for novelties and communication skills were covered. Massive vaccination has greatly improved the outcomes of the pandemic, with a decrease in severe cases requiring intensive care and a reduction in mortality. However, suboptimal responses to vaccines have been observed in transplant recipients, and health care strategic plans are necessary in these vulnerable populations. The best practices contained in this expert panel report may aid to their broader implementation.

Anti-Glutathione S Transferase T1 Antibodies After Renal Transplant and Their Impact on Graft Outcome.

OBJECTIVES: Anti-glutathione S transferase T1 (GSTT1) antibodies, a type of non-HLA antibody, have been associated with chronic hepatic graft rejection. Despite the presence of this enzyme in the kidney, there are not enough studies on the development of anti-GSTT1 antibodies and their impact on renal grafts. Our objective was to evaluate the presence of anti-GSTT1 antibodies after renal transplant and their impact on graft outcomes. MATERIALS AND METHODS: We conducted an ambispective cohort study. We performed real-time polymerase chain reaction to screen for GSTT1 alleles in 293 recipients and their donors. In null GSTT1 (GSTT1*0) genotype recipients of GSTT1-positive donors, the presence of anti-GSTT1 antibodies was evaluated using indirect immunofluorescence and Luminex assays, and their effects on graft function were evaluated. The median follow-up period was 54.3 months. RESULTS: Of the 293 patients studied, 42 recipients (14.4%) with GSTT1-positive donors did not have the GSTT1 allele (GSTT1-positive donor/GSTT1*0 recipient). Using Luminex assay, we detected antibodies in 16 patients (38.1%), 12 of which were already present at the time of transplant. Of these cases, 37.5% with antibodies had undergone a previous renal transplant. Using indirect immunofluorescence, we found that only 12 patients tested positive, 4 at the time of transplant. Antibody presence did not effect graft glomerular filtration rates or graft loss at 1 year, at 2 years, or end of follow-up. CONCLUSIONS: The presence of anti-GSTT1 antibodies is frequent in renal transplant GSTT1*0 recipients of GSTT1-positive donors but has no effects on graft outcome.

[Management of immunosuppressive therapy in kidney transplant recipients with COVID19. A multicentre national study derived form the S.E.N. COVID registry.] / Manejo de la inmunosupresión en pacientes trasplantados de riñón con COVID19. Estudio multicéntrico nacional derivado del registro COVID de la S.E.N.

INTRODUCTION: SARS CoV2 infection has had a major impact on renal transplant patients with a high mortality in the first months of the pandemic. Intentional reduction of immunosuppressive therapy has been postulated as one of the cornerstone in the management of the infection in the absence of targeted antiviral treatment. This has been modified according to the patient`s clinical situation and its effect on renal function or anti-HLA antibodies in the medium term has not been evaluated. OBJECTIVES: Evaluate the management of immunosuppressive therapy made during SARS-CoV2 infection, as well as renal function and anti-HLA antibodies in kidney transplant patients 6 months after COVID19 diagnosis. MATERIAL AND METHODS: Retrospective, national multicentre, retrospective study (30 centres) of kidney transplant recipients with COVID19 from 01/02/20 to 31/12/20. Clinical variables were collected from medical records and included in an anonymised database. SPSS statistical software was used for data analysis. RESULTS: 615 renal transplant recipients with COVID19 were included (62.6% male), with a mean age of 57.5 years.The predominant immunosuppressive treatment prior to COVID19 was triple therapy with prednisone, tacrolimus and mycophenolic acid (54.6%) followed by m-TOR inhibitor regimens (18.6%). After diagnosis of infection, mycophenolic acid was discontinued in 73.8% of patients, m-TOR inhibitor in 41.4%, tacrolimus in 10.5% and cyclosporin A in 10%. In turn, 26.9% received dexamethasone and 50.9% were started on or had their baseline prednisone dose increased.Mean creatinine before diagnosis of COVID19, at diagnosis and at 6 months was: 1.7±0.8, 2.1±1.2 and 1.8±1 mg/dl respectively (p<0.001).56.9% of the patients (N=350) were monitored for anti-HLA antibodies. 94% (N=329) had no anti-HLA changes, while 6% (N=21) had positive anti-HLA antibodies. Among the patients with donor-specific antibodies post-COVID19 (N=9), 7 patients (3.1%) had one immunosuppressant discontinued (5 patients had mycophenolic acid and 2 had tacrolimus), 1 patient had both immunosuppressants discontinued (3.4%) and 1 patient had no change in immunosuppression (1.1%), these differences were not significant. CONCLUSIONS: The management of immunosuppressive therapy after diagnosis of COVID19 was primarily based on discontinuation of mycophenolic acid with very discrete reductions or discontinuations of calcineurin inhibitors. This immunosuppression management did not influence renal function or changes in anti-HLA antibodies 6 months after diagnosis.

Effect of weight change after renal transplantation on outcomes of graft survival.

BACKGROUND AND OBJECTIVE: After kidney transplantation, there is an overall increase in weight, which may increase the risk of chronic kidney disease (CKD) and graft loss. But, not all patients gain weight, and the impact on the graft of this different evolution has not been well studied. The objective was to determine the causes of this different evolution and its effect on the graft. PATIENTS AND METHODS: Retrospective single-center cohort study of 201 patients followed up after transplantation, analyzing the determinants of the variation in weight at one year using logistic regression, and its effect on graft survival at the end of follow-up using Cox regression. RESULTS: Globally, there was an average weight gain of 4.5 kg in the first year, but 26.6% lost weight. 37.2% increased their BMI, while 9.5% decreased it. The determinants of the different evolution of weight were age (OR for every 10 years: 0.6, p = 0.002), previous dialysis modality (ref. hemodialysis) (OR 0.3, p = 0.003), and BMI before transplantation (OR 0.9, p = 0.017). The different evolution of weight did not influence the final situation of the graft. The BMI at one year did influence as a continuous variable (HR 1.3, p = 0.003), and obesity, with a worse evolution (HR 7.0, p = 0.025). CONCLUSIONS: Although not all patients gain weight after kidney transplantation, the different evolution of weight does not influence graft survival.

Effect of weight change after renal transplantation on outcomes of graft survival. / Efecto del cambio en el peso tras el trasplante renal en la supervivencia del injerto.

BACKGROUND AND OBJECTIVE: After kidney transplantation, there is an overall increase in weight, which may increase the risk of chronic kidney disease (CKD) and graft loss. But, not all patients gain weight, and the impact on the graft of this different evolution has not been well studied. The objective was to determine the causes of this different evolution and its effect on the graft. PATIENTS AND METHODS: Retrospective single-center cohort study of 201 patients followed up after transplantation, analyzing the determinants of the variation in weight at one year using logistic regression, and its effect on graft survival at the end of follow-up using Cox regression. RESULTS: Globally, there was an average weight gain of 4.5kg in the first year, but 26.6% lost weight. 37.2% increased their BMI, while 9.5% decreased it. The determinants of the different evolution of weight were age (OR for every 10 years: 0.6, P=.002), previous dialysis modality (ref. hemodialysis) (OR 0.3, P=.003), and BMI before transplantation (OR 0.9, P=.017). The different evolution of weight did not influence the final situation of the graft. The BMI at one year did influence as a continuous variable (HR 1.3, P=.003), and obesity, with a worse evolution (HR 7.0, P=.025). CONCLUSIONS: Although not all patients gain weight after kidney transplantation, the different evolution of weight does not influence graft survival.

Risk factors for unfavorable outcome and impact of early post-transplant infection in solid organ recipients with COVID-19: A prospective multicenter cohort study.

The aim was to analyze the characteristics and predictors of unfavorable outcomes in solid organ transplant recipients (SOTRs) with COVID-19. We conducted a prospective observational cohort study of 210 consecutive SOTRs hospitalized with COVID-19 in 12 Spanish centers from 21 February to 6 May 2020. Data pertaining to demographics, chronic underlying diseases, transplantation features, clinical, therapeutics, and complications were collected. The primary endpoint was a composite of intensive care unit (ICU) admission and/or death. Logistic regression analyses were performed to identify the factors associated with these unfavorable outcomes. Males accounted for 148 (70.5%) patients, the median age was 63 years, and 189 (90.0%) patients had pneumonia. Common symptoms were fever, cough, gastrointestinal disturbances, and dyspnea. The most used antiviral or host-targeted therapies included hydroxychloroquine 193/200 (96.5%), lopinavir/ritonavir 91/200 (45.5%), and tocilizumab 49/200 (24.5%). Thirty-seven (17.6%) patients required ICU admission, 12 (5.7%) suffered graft dysfunction, and 45 (21.4%) died. A shorter interval between transplantation and COVID-19 diagnosis had a negative impact on clinical prognosis. Four baseline features were identified as independent predictors of intensive care need or death: advanced age, high respiratory rate, lymphopenia, and elevated level of lactate dehydrogenase. In summary, this study presents comprehensive information on characteristics and complications of COVID-19 in hospitalized SOTRs and provides indicators available upon hospital admission for the identification of SOTRs at risk of critical disease or death, underlining the need for stringent preventative measures in the early post-transplant period.

Alpha-1-microglobulin: Prognostic value in chronic kidney disease. / Alfa-1-microglobulina: valor pronóstico en la enfermedad renal crónica.

OBJECTIVES: α1-microglobulin (α1M) is a tubular protein used for detecting acute lesions of proximal tubules. This study evaluated the use of urine α1M excretion as a marker of chronic kidney disease (CKD) progression and life survival. DESIGN AND METHODS: In all 163 patients were recruited (90 men), mean age 61.6±16.4 years. Urinary α1M was evaluated using an immunonephelometric assay. Patients were divided into 2 groups according to urinary α1M excretion (cut-off value: 32.85mg/24h). RESULTS: End stage renal disease-free survival was 94.2% at 5 years for patients with lower α1M. For patients in the highest percentile, renal function survival was 72.7% (P=.011). Life survival was 94.4% for patients with α1M in the lower percentiles. For patients in the upper percentile, live survival was 54.2% (P=.001). The Cox regression analysis showed an independent association of CKD progression with high α1M excretion (P=.043). CONCLUSIONS: α1M urinary excretion was associated with faster CKD progression and higher mortality. Further studies are needed to determine whether the association between α1M urinary excretion and excess mortality risk represents a causal link.

Successful treatment of invasive aspergillosis caused by Aspergillus parafelis in a kidney transplant recipient.

Invasive aspergillosis (IA) is associated with a high mortality rate in kidney-transplant recipients. Azole-resistance is increasing in Aspergillus fumigatus. We report a clinical case of a kidney-transplant recipient with cerebellar and pulmonary aspergillosis caused by azole-resistant Aspergillus parafelis (molecular identification through ß-tubulin sequence). The patient experienced an effective resolution after three surgical procedures and associated antifungal therapy. This case highlights that azole-resistant aspergillosis should be considered in every patient with IA as long as susceptibility testing results are not known. Therefore, in selected patients with IA and central nervous system involvement, empirical combination antifungal therapy could be considered.

Use of tocilizumab in kidney transplant recipients with COVID-19.

Acute respiratory distress syndrome associated with coronavirus infection is related to a cytokine storm with large interleukin-6 (IL-6) release. The IL-6-receptor blocker tocilizumab may control the aberrant host immune response in patients with coronavirus disease 2019 (COVID-19) . In this pandemic, kidney transplant (KT) recipients are a high-risk population for severe infection and showed poor outcomes. We present a multicenter cohort study of 80 KT patients with severe COVID-19 treated with tocilizumab during hospital admission. High mortality rate was identified (32.5%), related with older age (hazard ratio [HR] 3.12 for those older than 60 years, P = .039). IL-6 and other inflammatory markers, including lactic acid dehydrogenase, ferritin, and D-dimer increased early after tocilizumab administration and their values were higher in nonsurvivors. Instead, C-reactive protein (CRP) levels decreased after tocilizumab, and this decrease positively correlated with survival (mean 12.3 mg/L in survivors vs. 33 mg/L in nonsurvivors). Each mg/L of CRP soon after tocilizumab increased the risk of death by 1% (HR 1.01 [confidence interval 1.004-1.024], P = .003). Although patients who died presented with worse respiratory situation at admission, this was not significantly different at tocilizumab administration and did not have an impact on outcome in the multivariate analysis. Tocilizumab may be effective in controlling cytokine storm in COVID-19 but randomized trials are needed.

Anemia as very late-onset cytomegalovirus disease after kidney transplantation.

Very late-onset cytomegalovirus (CMV) disease after solid organ transplantation is not associated with classic risk factors; therefore, it does not follow a pattern of predictable appearance. A high index of suspicion is necessary to make an accurate diagnosis. Anemia has multiple etiologies among kidney transplanted recipients, and CMV could be one of them. We report the case of a kidney recipient with anemia refractory to treatment which proved to be secondary to extremely late CMV digestive disease.

Does a blood pressure J curve exist for patients with chronic kidney disease?

Aggressive reduction of blood pressure may increase cardiovascular events (the J-curve phenomenon) in certain populations. In this regard, most studies in patients with chronic kidney disease have shown a J curve for cardiovascular morbidity and mortality, and this phenomenon persists after adjusting for confounding factors. Since there is no evidence that a straighter blood pressure target (<130/70 mm Hg) could improve renal outcomes, the increased cardiovascular risk associated with extreme blood pressure reduction should be seen as undesirable. Moreover, the intensive control of blood pressure may induce an unintended reduction of renal function and this decrease, in turn, may increase cardiovascular risk.

Renin-angiotensin system blocking drugs.

The two major classes of drugs that target the RAS are the angiotensin-converting enzyme (ACE) inhibitors and the selective AT1 receptor blockers (ARBs). Although both of these drug classes target angiotensin II, the differences in their mechanisms of action have implications for their effects on other pathways and receptors that may have therapeutic implications. Both ACEIs and ARBs are effective antihypertensive agents that have been shown to reduce the risk of cardiovascular and renal events. Direct inhibition of renin -the most proximal aspect of the RAS -became clinically feasible from 2007 with the introduction of aliskiren. This latter drug has been shown to be efficacious for the management of hypertension. Combined therapy of direct renin-inhibitors with ACEIs or ARBs has been tested in some clinical situations as congestive HF and proteinuria with diverse results. This article tries to offer an updated review of current knowledge on the use of RAS blocking drugs in clinical settings.

Blood pressure in renal disease: how to accomplish the goal?

The Avoiding Cardiovascular Events through Combination Therapy in Patients Living with Systolic Hypertension (ACCOMPLISH) trial showed that initial antihypertensive therapy with benazepril plus amlodipine was superior to benazepril plus hydrochlorothiazide in reducing progression of chronic kidney disease as well as cardiovascular morbidity and mortality in renal patients. The renal results of the ACCOMPLISH trial strongly support the recommendation of using calcium channel blockers as second antihypertensive agent added to renin-angiotensin axis-blocking drugs. This review discusses the validity of these data and their relationship with the cumulative evidence on the effects of calcium antagonists on renal disease progression.

Congestive heart failure in patients with advanced chronic kidney disease: association with pre-emptive vascular access placement.

INTRODUCTION: Congestive heart failure (CHF) is a common complication in patients with chronic kidney disease (CKD). In addition to classical risk factors (e.g. age and pre-existing cardiac diseases), other potential reversible abnormalities linked to CKD such as anaemia, volume overload, or vascular access placement may also influence the incidence and severity of acute exacerbations of CHF. OBJECTIVE: This study aims to determine the incidence and main determinants of CHF in a cohort of patients with stage 4-5 pre-dialysis CKD. PATIENTS AND METHOD: The study group consisted of 562 patients (mean age: 65 +/- 15 years, 260 females, 31% diabetics). Native arteriovenous fistulas (AVF) were created in 160 patients who chose haemodialysis as the initial technique for renal replacement therapy. The main outcome variables were: acute decompensated CHF (defined by standard criteria), dialysis initiation (planned and unplanned), and death before dialysis initiation. In addition to demographics, comorbidities, and clinical and biochemical data, AVF creation was also included as a potential determinant of CHF in multiple logistic regression models. RESULTS: Ninety-five patients (17%) developed at least one episode of acute decompensated CHF, and the incidence rate was 19 episodes per 1000 patient-years. In addition to classical risk factors (age, female sex, obesity, diabetes, and previous history of CHF or coronary artery disease), creation of a successful AVF significantly increased the risk of CHF (OR=9.54, 95% CI: 4.84-18.81, P<.0001). In 47 out of 95 patients who developed CHF, a functioning AVF had previously been created, 92% of which were upper arm native AVF, with a median of 51 days between the surgical procedure and CHF episode. The mortality of patients with CHF was similar to that of the rest of the study patients, although unplanned dialysis initiation was significantly more frequent in those who developed CHF. CONCLUSIONS: Acute decompensated CHF episodes are common in pre-dialysis CKD patients. In addition to classical risk factors, pre-emptive AVF placement was strongly associated with the development of CHF.

[Impact of advanced kidney disease on transplanted patients and their return to dialysis]. / Impacto de la enfermedad renal avanzada del trasplantado renal y su vuelta a diálisis.

Although long-term outcomes also improved, graft loss caused by chronic allograft nephropathy remains an important obstacle. This situation, together with the progressive increase in the number of renal transplant patients, means that the population of transplant patients readmitted to a dialysis program will be progressively greater. The mortality rate in patients starting dialysis after graft loss has been reported as variable, though higher than that observed in patients with a functioning graft and that observed in patients on dialysis treatment. However, it is not known how the management of chronic kidney disease patients in the transplant setting differs from that of patients with native kidney disease with a similar degree of renal dysfunction. Many patients in stages 4T-5T have chronic kidney disease related complications that fall below targets established for nontransplant chronic kidney disease patients. A limited number of studies have evaluated patients returning to dialysis after graft failure and the different guidelines in the setting of transplantation have not analyzed this crucial aspect so important. Parting from this premise, a working group of the Spanish Society of Nephrology in the field of kidney transplantation and dialysis has reviewed in-depth each of the clinical aspects of care of patients with kidney transplant failure coming back to dialysis and drawn up a consensus document in order to optimize the management of this condition.

[Progression factors in chronic kidney disease. Immunological mechanisms]. / Factores de progresión de la enfermedad renal crónica. Mecanismos inmunológicos.

In kidney transplantation patient and graft survival are excellent in short-term and mid-term, although they remain stable in the long-term.The incidence of acute rejection has decreased to 8%-15%.Despite marked progress in understanding immunologic mechanisms involved in transplantation, new tools are required to detect early changes that could affect allograft function allowing us to anticipate histological lesions and providing a more accurate use of immunosuppressive drugs.From an immunologic point of view, efforts should be directed to avoid interstitial fibrosis and tubular atrophy (IF/TA) and to prevent antibody-mediated rejection.The most frequent cause of late graft loss is IF/TA.Improvement in kidney transplant results have been achieved with calcineurin inhibitors -CNI- (cyclosporin and tacrolimus), antiproliferative agents (mycophenolate mofetil and enteric-coated mycophenolic acid) and T-cell depleting antibodies. The combination of tacrolimus + mycophenolate mofetil + steroids has been the gold standard in kidney transplant immunosuppression. An adequate balance in order to maintain the appropriate immune response is essential to the patient to avoid infections or neoplasias as well to prevent rejection.In renal transplant recipients with chronic kidney disease stage 4T in which renal function remains stable,immuno-suppressive drugs can be continued at the usual maintenance doses. As GFR declines, CNI and antiproliferative drugs should be reduced.

[Definitive removal of immunosuppressors]. / Retirada definitiva de la inmunosupresión.

There's no controlled and prospective studies which show the safest and most effective way to reduce or suspend immunosuppression drugs dosage, and only few groups have published their own protocols. There are reasons to discontinue the immunosuppression therapy; the high incidence of infections is the most important. However, a fast withdrawal is not free of problems, like are residual renal function decline and graft intolerance signs, which could take to nephrectomy, a high risk intervention. Most recommended guidelines for immunosuppression use are: - Antimetabolites immediately cancellation and corticoesteroids slow drop (level C recommendation). - Calcineurin inhibitors could be discontinued but if residual renal function is still significant, it is recommended to maintain a low dosage over three to six months; then, withdrawal may be done slowly (level C recommendation). We have not found information supporting the immunosuppression use beyond six months.

Do inflammatory markers add predictive information of death beyond that provided by age and comorbidity in chronic renal failure patients?

BACKGROUND: Elevated levels of inflammatory markers have been shown to be associated with increased mortality in chronic kidney disease (CKD) patients. Comorbid indexes are also helpful clinical instruments for predicting mortality. At present, it is unknown whether inflammatory markers add predictive information of death beyond that provided by comorbid indexes. METHODS: This observational single-centre study included 404 patients (mean age 63+/-16 years) with CKD stage 4 and 5 predialysis who were prospectively followed-up. Data obtained at baseline: demographics, grade of comorbidity by Davies index, serum albumin, creatinine clearance, total white blood cell (WBC), polymorphonuclear leukocyte (PMN) counts, and high-sensitivity C-reactive protein (CRP) were analysed as potential determinants of the subsequent all-cause mortality. Receiver-operating characteristic (ROC) curves were used to determine the values of CRP, WBC and PMN most closely related to mortality. These cut-off values were used to define subgroups with high or low inflammatory markers. Uni- and multivariate Cox regression models were performed. RESULTS: Median follow-up time was 583 days, with a mortality of 26%, and overall survival rate of 47%. In unadjusted Cox models, inflammatory markers (CRP, WBC and PMN) were all significantly associated with all-cause mortality. Age (HR 1.05; 95% CI 1.03-1.07, P<0.0001) and comorbid index (HR 2.15; 95% CI 1.54-3.00, P<0.0001) were strongly associated with mortality. The introduction of inflammatory markers into the multivariate Cox regression model did not add significant predictive power. In a stepwise Cox model, the age, comorbid index, serum albumin levels and creatinine clearance were the best predictive variables of mortality. CONCLUSIONS: Although elevated inflammatory markers are associated with a worse outcome in CKD patients, they did not add predictive information of all-cause mortality beyond that provided by age and the comorbid index.