COVID-19 and kidney: role of SARS-CoV-2 infection in the induction of renal damage.

OBJECTIVE: SARS-CoV-2 causes acute respiratory disease, interstitial and alveolar pneumonia, and involves numerous organs and systems such as the kidney, heart, digestive tract, blood, and nervous system. We aimed to evaluate the incidence of renal manifestations in patients diagnosed with COVID-19 infection. PATIENTS AND METHODS: We performed a monocentric, cross-sectional, observational study, conducted on 114 patients with SARS-CoV-2. Clinical and laboratory parameters [renal function, serum electrolytes, inflammatory state, blood gas analysis, Interleukin 6 (IL-6) and urinalysis] were evaluated. The same values were checked out after two months (T1), however after negativization. RESULTS: We enrolled 114 patients (59 males) with a mean age of 63.8 ± 13.9 years. We found hematuria in 48 patients (55.8%), proteinuria in 33 patients (38.4%), leukocyturia in 61 patients (70.9%), acute kidney injury (AKI) in 28 patients (24.6%), AKI in chronic kidney disease (CKD) in 24 patients (21.1%). Moreover, we found a significant increase of inflammatory indexes as C Reactive Protein (CRP), lactic dehydrogenase (LDH), alpha 1 and alpha 2 globulins with a subsequent reduction at T1 (p = 0.016, p < 0.001, p = 0.005, p = 0.007; respectively). Hemoglobin and erythrocyte values significantly decreased (p < 0.001, p = 0.003, respectively), and we found lymphopenia (p < 0.001). Also, we found elevated levels of the D-Dimer (p < 0.001) and a significant increase in the International Normalized Ratio (INR) (p = 0.038). We also showed a significant improvement after negativization in oxygen partial pressure (p = 0.001) and oxygen saturation (p < 0.001) and a significant increase in pH (p = 0.018) and bicarbonate concentration (p = 0.042). Moreover, we found a significant increase in IL-6 (p = 0.004). Also, we reported mild hyponatremia and hypokalemia with subsequent significant recovery (p < 0.001, p < 0.001, respectively) and mild hypochloremia with a recovery to the limits of statistical significance (p = 0.053). At the entrance, we found an increase in serum glucose with a significant reduction during recovery (p < 0.001). CONCLUSIONS: The prevalence of AKI and/or CKD and/or abnormal urinalysis in patients diagnosed with COVID-19 on admission seems to be high and appears as a negative prognostic factor. Urinalysis appears to be very useful in unveiling the potential kidney impairment of COVID-19 patients; therefore, urinalysis could be used to reflect and predict the disease severity. We also recommend a careful evaluation of metabolic alterations, inflammatory states, and electrolytic disorders in COVID-19 patients.

Liver transplantation: role of immunosuppression, renal dysfunction and cardiovascular risk factors.

In the past decades, advances in immunosuppression, organ preservation, surgical techniques and better management of post-transplantation complications have led to improvement in survival of liver transplant patients. Such extended survival of liver graft recipients in their fifties and sixties has resulted in a greater prevalence of complications, in particular chronic kidney (CKD) and cardiovascular diseases (CVD). Renal failure and cardiovascular complications in the setting of liver transplantation are associated to an increase of morbidity and mortality. A 4-fold increased risk of death is reported among patients developing post-transplant CKD, and CVD is the leading cause of death with a functioning allograft, accounting for as much as 30% of post-transplant mortality. The onset is multifactorial, with pre-transplant conditions involved, including pre-transplant renal insufficiency, hepatitis C virus infection and pretransplant diabetes. Acute renal dysfunction in the setting of transplantation is also responsible of post-transplant CKD. Immunosuppressive therapy is primarily responsible for the development of CKD. Metabolic syndrome and its individual components, including diabetes mellitus, systemic hypertension, dyslipidemia, and obesity, are increasingly being identified as closely related to immunosuppressive therapy and actively contribute to cardiovascular morbidity and mortality in transplant patients. Treatment of modifiable risk factors is mandatory aiming to prevent the development and progression of serious complications. Early recognition, prevention and treatment of these conditions may further improve long-term survival after liver transplantation.

Literature review on the cross-link between ocular and renal disease: renin angiotensin aldosterone system is a main actor.

OBJECTIVE: Chronic kidney disease (CKD) and ocular disease share several cardiovascular risk factors as well as pathogenetic mechanisms having Renin-Angiotensin-Aldosterone System (RAAS) as main actor. Moreover, kidney and eyes have common genetic and embryonic origin. In this literature review, we present main evidence supporting this association for early identifying diseases affecting both systems and evaluating potential multi-target therapeutic strategies. MATERIALS AND METHODS: We performed a literature review of the current peer-reviewed English-language randomized controlled studies (RCTs), reference lists of nephrology or ophthalmology textbooks, review articles and relevant studies with ocular or eye and kidney or renal diseases as keywords until March 2020. Prospective and retrospective studies as well as meta-analyses and latest systematic reviews were included. RESULTS: We evaluated a total of 683 records, finally selecting 119 articles related to ocular and renal diseases. Records were divided into two areas: chronic and acute kidney disease and ocular or eye diseases. Some of the examined studies were discarded for population biases/intervention or deemed unfit. CONCLUSIONS: Based on our results, we conclude that there is evidence of a clear association between kidney and eye diseases, being this cross-link mainly based on RAAS dysregulation. Our review suggests that it may be useful to screen CKD patients for associated ocular diseases, such as cataract, glaucoma, diabetic retinopathy and age-related macular degeneration. A comprehensive study of CKD and proteinuric patients should include careful eye examination. Renal impairment in young patients should prompt a search for ocular disease, such as TUNA syndrome or oculo-renal syndrome, in particular if family history of concurrent ocular and renal disease is present. Anti-RAAS agents are mostly recommended in patients with renal and ocular impairment.

Screening of QTc interval and global autonomic activity in autosomal dominant polycystic kidney disease and atherosclerotic renal artery stenosis hypertensive patients.

OBJECTIVE: Arterial hypertension (AH) represents a major risk factor for cardiovascular disease and is associated to several complications, such as prolonged corrected QT (QTc) interval and impaired heart rate variability (HRV). Secondary causes of AH include autosomal dominant polycystic kidney disease (ADPKD) and atherosclerotic renal artery stenosis (ARAS), both known to be related to arrhythmic risk and autonomic imbalance. The aim of the study is to evaluate whether global autonomic activity and QTc interval differently affect ADPKD and ARAS hypertensive patients. PATIENTS AND METHODS: An observational study was performed on 59 patients: 16 ADPKD patients and 19 diagnosed with ARAS, compared to 24 healthy controls (HC). All patients underwent clinical evaluation, biochemical lab tests, 24-hour electrocardiogram (ECG) and renal Doppler ultrasound. HRV was assessed through the analysis of 24-hour ECG to detect standard deviation of normal-to-normal RR intervals (SDNN). QTc interval was defined as prolonged when > 440 msec. RESULTS: SDNN was significantly lower in ADPKD and ARAS patients than HC (p < 0.0001) and no significant differences were found between ADPKD and ARAS patients (p > 0.05). QTc was found significantly higher in ARAS patients than HC (p = 0.001) and in ARAS patients than ADPKD patients (p = 0.004). CONCLUSIONS: The pathogenesis of hypertension in ADPKD and ARAS patients is related to the activation of the renin angiotensin aldosterone system (RAAS). In ADPKD, cyst enlargement leads to kidney ischemia and renin release, associated to endothelial dysfunction, low nitric oxide and sympathetic tone activation. Differently, reduction in renal perfusion pressure activates RAAS and renal adrenergic nerves in ARAS patients. We can speculate that prolonged QTc interval is more present in ARAS vs. ADPKD hypertensive patients due to a greater activation of RAAS. We suggest adding 24-hour HRV evaluation in association with traditional risk factors in course of ADPKD and ARAS hypertension to better stratify cardiovascular risk in these groups of patients.

Effects of non-invasive ventilation on renal and endothelial function in patients with respiratory failure.

OBJECTIVE: Non-invasive positive pressure ventilation (NIV) is now an indispensable safeguard in the management of many pathologies. However, sometimes the positive end-expiratory pressure (PEEP) showed harmful effects on renal function, although effects on renal hemodynamic are unclear. We aimed at evaluating the effects of NIV on renal and endothelial function, in patients with chronic or acute respiratory failure. PATIENTS AND METHODS: We performed a longitudinal, prospective, interventional study. We enrolled 17 hospitalized and non-hospitalized patients (11 males) with indication to NIV and stable hemodynamic parameters. Patients were treated with NIV and followed up at T0, at T1 (at the end of the NIV cycle) and at T2 (fifteen days after). RESULTS: 17 patients (11 males) with a mean age of 71.94 ± 14.89 years were enrolled. A significant increase in flow mediated dilation (FMD) was found (p = 0.004). We showed a significant improvement, after NIV, in the values of pH (p = 0.0002), pCO2 (p = 0.0001), pO2 (p = 0.04), lactates (p = 0.04), sO2 (p = 0.02) and in the P/F Ratio (p = 0.004). We also showed a significant reduction of serum glucose (p = 0.01) and a significant increase of serum chlorine (p = 0.047), while we did not report a significant increase of creatinine (p = 0.297) or a significant change in diuresis. CONCLUSIONS: In our study NIV has no significant effects on renal function in patients with respiratory failure. Probably these patients required low PEEP values, which were less harmful to lung parenchyma and not effective on systemic hemodynamic. Furthermore, NIV has improved endothelial function in the short term, likely by reducing oxidative stress, as improvements of the gas-analysis parameters showed. Therefore, NIV could help to reduce cardiovascular risk of patients improving endothelial function.

Long-term Glomerular Filtration Rate and Kidney Disease: Improving Global Outcomes Stage Stability After Conversion to Once-Daily Tacrolimus in Kidney Transplant Recipients.

Close monitoring of estimated glomerular filtration rate (eGFR) is important for early recognition of worsening renal function to prevent further deterioration. Safe conversion from twice-daily tacrolimus (TD-Tac) to once-daily tacrolimus (OD-Tac) has been reported, but the effects on eGFR are contrasting. The aim of our study is to evaluate long-term stability of eGFR after 1:1 conversion from TD-Tac to OD-Tac and the effects on serum cytokine blood levels. Forty-six consecutive kidney transplant recipients treated with TD-Tac 3 to 5 years post-transplant, with stable renal function, were enrolled in the study (2009-2011). Clinical and biochemical parameters were evaluated for 12 months before conversion up to 6 years after conversion. The patients served as their own controls. A panel of cytokines was evaluated repeatedly during the first year after conversion. Mean values of eGFR were not different long-term after conversion (P = .11) compared with baseline, and the majority of patients remained stable on Kidney Disease: Improving Global Outcomes stage during the study period; eGFR was stable in 30.0% after 5 years, decreased > 1 mL/min/1.73 m2/y in 13.3%, and improved > 1 mL/min/1.73 m2/y in 56.7%. Cytokine levels and C-reactive protein did not show any significant deterioration. Metabolic parameters were stable during the 6 years of follow-up. OD-Tac therapy can preserve an effective immunosuppressive state together with a safe profile of eGFR.

DNA microarrays for identifying fishes.

In many cases marine organisms and especially their diverse developmental stages are difficult to identify by morphological characters. DNA-based identification methods offer an analytically powerful addition or even an alternative. In this study, a DNA microarray has been developed to be able to investigate its potential as a tool for the identification of fish species from European seas based on mitochondrial 16S rDNA sequences. Eleven commercially important fish species were selected for a first prototype. Oligonucleotide probes were designed based on the 16S rDNA sequences obtained from 230 individuals of 27 fish species. In addition, more than 1200 sequences of 380 species served as sequence background against which the specificity of the probes was tested in silico. Single target hybridisations with Cy5-labelled, PCR-amplified 16S rDNA fragments from each of the 11 species on microarrays containing the complete set of probes confirmed their suitability. True-positive, fluorescence signals obtained were at least one order of magnitude stronger than false-positive cross-hybridisations. Single nontarget hybridisations resulted in cross-hybridisation signals at approximately 27% of the cases tested, but all of them were at least one order of magnitude lower than true-positive signals. This study demonstrates that the 16S rDNA gene is suitable for designing oligonucleotide probes, which can be used to differentiate 11 fish species. These data are a solid basis for the second step to create a "Fish Chip" for approximately 50 fish species relevant in marine environmental and fisheries research, as well as control of fisheries products.

Hypokalemic rhabdomyolysis: a rare manifestation of primary aldosteronism.

Rhabdomyolysis is a rare presentation of hypokalemia, although muscle weakness is a well-known manifestation of hypokalemia. Primary aldosteronism is characterized by hypertension, suppressed plasma renin activity, increased aldosterone excretion and hypokalemia with metabolic alkalosis. Rhabdomyolysis is not common in primary aldosteronism. We present here a 40-year-old woman presenting with rhabdomyolysis accompanied by severe hypokalemia as heralding symptom of primary aldosteronism.

Mitochondrial DNA variation, phylogenetic relationships, and evolution of four mediterranean genera of soles (soleidae, pleuronectiformes).

To increase knowledge about the systematics and evolution of Mediterranean soles, we assessed mitochondrial DNA variation, molecular phylogeny, and evolution in eight species from the genera Solea, Microchirus, Monochirus, and Buglossidium by large ribosomal subunit (16S) and cytochrome b (cytb) sequence analysis. Relevant molecular features are the great variation of base composition among species at the third codon in cytb and the heterogeneity of the nucleotide substitution rate. Phylogenies recovered using 16S nucleotide and cytb amino acid sequences agree with those based on morphology in assessing monophyly of Solea species and ancestry of Buglossidium luteum, but they are against the intergeneric differentiation of Microchirus and Monochirus. Conversely, phylogenetic trees based on cytb nucleotide sequences yielded relationships among taxa regardless of their evolutionary histories. The incongruities between morphological and molecular issues suggest the need for reassessing the systematic value of some morphological characters. Approximate estimates of the divergence time of Mediterranean soleid lineages range from 40 to 13 Mya (Oligocene-Miocene), indicating an ancient origin for the group.

Species recognition of congeneric acanthocephalans in slider turtles by random-amplified polymorphic DNA (RAPD) markers.

Species recognition of acanthocephalans of the genus Neoechinorhynchus (Hamann, 1892) found in the freshwater turtle Trachemys scripta (Wied, 1838) has previously been based primarily on female body and egg morphology. Observed morphological plasticity within and among species may lead to the misclassification of female specimens and leaves males of different species completely indistinguishable. Here, random-amplified polymorphic DNA (RAPD) analysis was used to genetically characterize samples of Neoechinorhynchus pseudemydis (Cable and Hopp, 1954), Neoechinorhynchus emydis (Leidy, 1851), and Neoechinorhynchus emyditoides (Fisher, 1960). Amplifications performed with 3 decamer oligonucleotides showed banding patterns with a few diagnostic fragments that allowed the recognition of N. pseudemydis specimens from those of the N. emydis-N. emyditoides group. No primer gave a species-specific locus that allowed the differentiation of N. emydis from N. emyditoides specimens, suggesting that they could belong to a sole taxon. The species assignment of females of uncertain classification and of males is fully reliable using RAPD markers. Thus, identification of acanthocephalan species by RAPD in the helminth infracommunities could potentially be very useful to determine community structure. RAPD and other polymerase chain reaction-based methods have some practical advantages over multilocus discriminant analysis, such as the ability to use ethanol-stored specimens and small tissue samples of parasites.

Rapid assessment of maturation stage and reproductive mode in centrolecytic eggs of stick insects (Phasmatodea) using DAPI stain.

A rapid three-step DAPI technique is proposed for detecting meiotic stages and sperm head evolution in yolky, fertilized stick insect eggs, which were difficult to analyze with other methods. Fixed eggs were freed from chorionic envelopes and stained directly in DAPI/PBS solution. After rinsing, eggs were singly squashed in a drop of mounting buffer and examined under a microscope with incident fluorescent illumination. The method was almost uniformly successful, and direct observation of nuclear structures, coupled with fluorometry, allowed easy recognition of bivalents, diads, pronuclei and their DNA content. The DAPI method proposed here appears particularly helpful for investigating unusual reproductive modes in eggs with large amounts of yolk.

From listing to transplant: nephrologic monitoring in cirrhotic patients awaiting liver transplantation.

Nephrologic monitoring of end-stage liver disease (ESLD) patients is part of evaluation for orthotopic liver transplantation (OLT). The numerous causes of renal dysfunction in ESLD patients sometimes relate to the extent of liver damage or sometimes more closely to organic nephropathy. The aim of this study was to evaluate renal function through a specific nephrologic form applied in our outpatient clinic to optimize nephrologic monitoring in ESLD patients awaiting OLT. We enrolled 69 cirrhotic patients (56 men, 13 women) awaiting OLT from April 2008 to January 2012. All patients were evaluated at listing and every 3 months until OLT. The most interesting result was the stable values of serum creatinine from listing to transplantation. We think that dedicated liver transplant nephrologic evaluation is important in the follow-up of ESLD patients awaiting OLT, because the presence of renal dysfunction may represent an important criterion for specific therapeutic interventions to minimize pre-OLT renal injuries that limit the effect of impaired renal function on patient outcomes.

Resistive index and MELD-Na: nephrologic monitoring in cirrhotic patients awaiting liver transplantation.

Renal dysfunction in cirrhotic patients is primarily related to disturbances in circulatory function. In decompensated cirrhosis, ascites and water retention are associated with development of dilutional hyponatremia. The arterial resistive index (RI) is a measure of resistance to arterial flow within the renal vascular bed. Hyponatremia is an independent predictor of mortality in patients with ascites. The aim of this study was to evaluate intrarenal RI in end-stage liver disease (ESLD) patients awaiting liver transplantation (LT) and its association with renal and hepatic function as assessed by Model for End-Stage Liver Disease (MELD) and MELD-Na scores. We evaluated 40 cirrhotic patients (23 males, 17 females) awaiting LT from January 2009 to January 2012. Twenty-six of the 40 patients (65%) showed a renal RI ≥ 0.70, the normal value according to standard reported evaluations. Patients with RI ≥ 0.70 showed significantly higher MELD and MELD-Na scores as well as greater higher serum creatinine and lower serum sodium concentrations compared with subject displaying RI <0.70. The most relevant result of our study was the strong association between elevated renal RI in ESLD patients and advanced liver dysfunction, as demonstrated by MELD and MELD-Na scores, hyponatremia, ascites, and acute renal failure episodes. In conclusion, this study suggested that intrarenal RI assessment should be considered in the clinical and nephrologic monitoring of cirrhotic patients awaiting LT.

Stages of early acute renal dysfunction in liver transplantation: the influence of graft function.

The development of early acute renal dysfunction (eARD) occurring in the first week after orthotopic liver transplantation (OLT) is mainly influenced by more severe degrees of pre-OLT hepatic insufficiency and liver graft dysfunction. The aim of our study was to evaluate the incidence of eARD post-OLT as well as its association with pre- and post-OLT hepatic dysfunction. We selected 54 end-stage liver disease patients who underwent OLT from 2008 to 2011. The prevalence of eARD was 53.7% (29/54) classified according to AKIN criteria in ARD-Risk (55.2%), ARD-Injury (27.6%) and ARD-Failure (17.2%). The worst stage of post-OLT eARD (eARD-Failure) seems to be influenced by the poor pre-OLT hepatic function as well as by early suboptimal recovery of graft function.

Polyomavirus BK infection in end-stage renal disease: analysis of viral replication in patients on hemodialysis or peritoneal dialysis.

Patients in end-stage renal disease undergoing renal replacement treatment (ESRD-RRT) are considered immunocompromised. The hemodialysis (HD) or peritoneal dialysis (PD) procedures seem to produce alterations of the immune status. Interest in immunosuppression has increased due to the poliomavirus BK (BKV) infection. Our study evaluated the prevalence of BKV infection in ESRD-RRT patients and viral replication on HD or PD. From 2006 to 2011 we selected 58 patients (34 males) in ESRD-RRT for inclusion in our study. BKV replication was evaluated by qualitative real-time polymerase chain reaction. In ESRD-RRT patients, the prevalence of BKV replication on plasma was 21%. We identified two groups of patients according to the dialysis procedure: 36 patients on HD (HD group) and 22 on PD (PD group). BKV replication in the HD group was 33% (12 of 36) versus 0% (0 of 22) in the PD group. Different age, number of months on RRT, and preserved diuresis was observed in the HD versus PD groups. With our results we can speculate that BKV infection in ESRD-RRT patients is linked to factors involved in the uremia-related immune dysfunction but also to specific mechanisms related to the different RRTs. PD is an option that could be associated with a better transplant outcome for patients undergoing kidney transplantation.

Long-term interleukin-2 assessment after conversion from a twice-daily to once-daily tacrolimus regimen in stable kidney recipients.

Conversion to tacrolimus (Tac) to once daily (Tac-O) formulation is commonly followed by a 20% reduction in Tac trough levels in the first month. It is not associated with modifications of renal function but there is the issue of its effects on inflammatory cytokines and on subclinical rejection. The aim of our study was to evaluate long-term interleukins (IL)-2 profiles in stable renal transplant patients after Tac-O conversion. We enrolled 10 stable kidney transplant patients converted to Tac-O. Tac trough levels, serum creatinine concentrations, glomerular filtration rate using the Modification of Diet in Renal Disease formula, C-reactive protein, IL-2 levels, and clinical assessments were performed monthly for 6 months before and 12 months after conversion. Despite the significant reduction in Tac trough levels, we did not observe alterations suggestive of clinical or subclinical acute rejection.

Polyomavirus BK infection before liver transplantation in patients with chronic kidney disease.

End-stage liver disease (ESLD) and chronic kidney disease (CKD) patients are both immunocompromised populations but polyomavirus BK (BKV) replication before liver transplantation is rare. We evaluated BKV prevalence among liver transplant recipients with renal dysfunction and the possible role of CKD as a risk factor for BKV replication in ESLD. From 2010 to 2011 we selected 31 ESLD patients awaiting liver transplantation to identify, the presence of CKD: No CKD (n = 22; 18 males) and CKD group (n = 9; 5 males). BKV infection was defined on the basis of viremia evaluated using quantitative real-time polymerase chain reactions. The prevalence of viremia among the No CKD group was 14% versus 56% in the CKD group (Fisher test; P = .027). We hypothesized that the presence of CKD may represent an additional condition of immunologic dysfunction regarding antiviral surveillances other than the antibacterial one that characterizes ESLD immunodysfunction, which could have promoted BKV replication. The specific immunologic mechanisms involved in pretransplantation diseases may have a role in BKV reactivation that could become responsible for nephropathy after transplantation.

Occurrence of chronic renal failure in liver transplantation: monitoring of pre- and posttransplantation renal function.

The aim of our study was to evaluate the occurrence of middle and long-term chronic renal failure (CRF) after orthotopic liver transplantation (OLT) in relation to acute renal failure (ARF). We prospectively monitored 75 patients, studying renal function on the basis of serum creatinine and glomerular filtration rate as estimated using the Modification of Diet in Renal Disease formula before as well as 1,6, and 12 months after OLT. The prevalence of ARF was 56% classified by the Acute Kidney injury Network criteria (52% stage 1, 29% stage 2, and 19% stage 3). The occurrences of CRF were 18.6% (11/59), 11.5% (6/52), and 14% (6/43) at 1, 6, and 12 months after OLT, respectively. The occurrence of CRF before OLT was 14.7%. We did not find any association between ARF and post-OLT CRF. The most relevant result of our study was the association between CRF at 6 and 12 months after transplantation with pre-OLT CRF on univariate and multivariate analysis. We suggest that evaluation of pre-OLT renal function should always be considered in the follow-up of liver transplant patients. Pre-OLT renal dysfunction must be recognized to be a risk factor for post-OLT CRF, representing important criterion to define specific therapeutic interventions to reduce patient morbidity and mortality.

Interleukin-2 profiles shortly after tacrolimus conversion from a twice-daily to once-daily regimen.

A number of studies have indicated that kidney recipients can be safely converted from the twice-daily formulation (Tac-T) to the same dose of a once-daily tacrolimus (TAC) regimen (Tac-O) based upon monitoring of renal function. Conversion from Tac-T to Tac-O is commonly followed by a reduction in Tac trough levels, estimated by some authors to be about 20%. These alterations seem to not be associated with a modification of graft function, but study of inflammatory cytokines would be useful. The aims of our study were to monitor Tac, C-reactive protein (CRP), and interleukin (IL)-2 levels as well as to evaluate renal function among stable renal transplant patients converted from a Tac-T to a Tac-O regimen. We enrolled 10 consecutive stable kidney transplanted patients. Tac trough levels, serum creatinine concentrations, glomerular filtration rates using the Modification of Diet in Renal Disease formula (MDRD), CRP, and clinical assessment were performed monthly for 6 months before and 3 months after the conversion. After conversion we observed a slight but not significant reduction in Tac trough level. Renal function evaluated by serum creatinine and MDRD as well as CRP were not significantly different after conversion. IL-2 levels remained stable after conversion. We identified a group of patients showing reduced Tac trough levels below the therapeutic range and a group with stable Tac levels. No significant differences were observed among the two groups before versus after the conversion. Our results did not show a modification of IL-2, CRP and renal function levels, at 3 months after conversion despite the lower Tac trough concentrations. The clinical meaning of Tac trough alterations is not clear. They might reflect inter- and intraindividual differences in the clearance of Tac as recently described. They did not seem to be associated with activation of an inflammatory pathway.

Tacrolimus trough levels and level-to-dose ratio in stable renal transplant patients converted to a once-daily regimen.

Numerous evidence has been reported to support a safe 1:1 conversion from the twice-daily tacrolimus (Tac-T) to the once-daily tacrolimus regimen (Tac-O), but frequently there is a reduction in drug trough levels, which has been estimated by some authors to be about 20%. The relationship between Tac-O dosage and trough levels after conversion is not clear. The tacrolimus trough levels-to-dose ratio has been applied to better define the wide variability in doses and blood levels of tacrolimus. The aim of this study was to evaluate tacrolimus trough levels, tacrolimus daily dosage, and tacrolimus level-to-dose ratio during 1 year pre-postconversion follow-up in 31 stable kidney transplant patients who had received Tac-T therapy for over 6 months with stable renal function. They were converted to the same dosage of Tac-O. Patients before and after conversion were their own controls. The trough levels of tacrolimus showed a slight albeit significant reduction after conversion, remaining in the therapeutic range. Nineteen percent underwent an adjustment in total daily dosage after conversion versus 39% before conversion with no significant difference. No significant differences were detected in the total daily dose administered either by tacrolimus level-to-dose ratio before or after conversion. Kidney transplant recipients under Tac-O therapy were safely maintained using the same therapeutic monitoring as when receiving Tac-T.