Creatinine clearance in selection of living kidney donor among the Malaysian population: is it safe?

BACKGROUND: Assessment of donor renal function is made by the measurement of Glomerular Filtration Rate (GFR). Exogenous markers are preferred over creatinine clearance and are widely used for measuring GFR. However, they are difficult to obtain, costly and laborious. This is a study to look into the safety and accuracy of creatinine clearance for renal assessment among the living kidney donors in the Malaysian population. METHODS: This is a retrospective, single-centre study comprising 105 living kidney donor candidates from the year 2007 to 2020. By comparing against 51-Chromium ethylenediamine-tetraacetic acid (51Cr-EDTA), we analysed creatinine clearance for correlation, bias, precision and accuracy. RESULTS: The study group had a mean age of 45.68 ± 10.97 years with a mean serum creatinine of 64.43 ± 17.68 µmol/L and a urine volume of 2.06 ± 0.83 L. Mean measured GFR from 51Cr-EDTA was 124.37 ± 26.83 ml/min/1.73m2 whereas mean creatinine clearance was 132.35 ± 38.18 ml/min/1.73m2. Creatinine clearance overestimated 51Cr-EDTA significantly with a correlation coefficient of 0.48 (p < 0.001) and an accuracy of 78.10% and 64.0% within 30% and 20% respectively of 51Cr-EDTA. CONCLUSION: Creatinine clearance is an acceptable and affordable alternative for donor renal assessment in the absence of exogenous markers with an emphasis on adequate urine collection followed by using measured GFR in selected cases.

Utility of Estimated Glomerular Filtration Rate Equations in Assessing Renal Allograft Function: Are They Accurate?

Creatinine clearance (CrCl) is more accurate than other methods when assessing renal allograft function, but it is inconvenient for patients. In clinical practice, renal allograft function is often estimated using estimated glomerular filtration rate (GFR) equations. This cross-sectional study compared agreement between CrCl and serum creatinine-based equations among renal transplant recipients (RTRs) attending a transplant clinic in a tertiary center. Six equations (Cockcroft-Gault, Walser's, Nankivell, abbreviated Modification of Diet in Renal Disease [MDRD], Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI], and European Kidney Function Consortium[EKFC]) were included in the analysis. The bias, precision, and accuracy of each equation were determined. Correlation analysis was performed by determining the correlation coefficient and plotting Bland-Altmann plots. A total of 165 subjects were included in this study. Mean serum creatinine was 112.03 ± 38.67 µmol/L, and mean CrCl was 58.44 ± 21.24 mL/min/1.73 m2. Walser's equation showed strongest correlation, lowest bias, and highest accuracy of the proportion of estimated GFR falling within ±30% of CrCl, followed by the 4-variable MDRD equation. All 6 equations systematically underestimated GFR among RTRs. Walser's equation showed the best estimation of GFR, suggesting that it may be the formula of choice to estimate GFR among RTRs.

The Utility of Combined Urine Urea and Creatinine Clearance for Pretransplant Renal Function Assessment.

BACKGROUND: Evaluation of donor renal function as glomerular filtration rate (GFR) is a crucial part of pretransplant workup. Most guidelines recommend measured GFR (mGFR) using exogenous markers with creatinine clearance (CrCl) as an alternative. However, exogenous markers are difficult to obtain and perform, and CrCl may overestimate GFR. OBJECTIVE: We explore the use of CrCl and combined urea and creatinine clearance as an alternative for GFR assessment. METHODS: A retrospective study involving 81 kidney donors from 2007 to 2020, with mGFR collected by chromium 51-labeled ethylenediaminetetraacetic acid (51Cr-EDTA) and CrCl and combined urea and creatinine clearance. We analyzed the performance of CrCl and combined urea and creatinine clearance against 51Cr-EDTA. Adequacy of urine volume was taken into consideration. RESULTS: A total of 81 candidates with a mean age of 44.80 ± 10.77 years were enrolled. Mean mGFR from 51Cr-EDTA was 123.66 ± 26.91 mL/min/1.73 m2, and combined urea and creatinine clearance and CrCl were 122.13 ± 47.07 and 133.40 ± 36.32 mL/min/1.73 m2, respectively. CrCl overestimated 51Cr-EDTA. Though combined urea and creatinine clearance had minimal bias, it had a lower correlation coefficient (0.25 vs 0.43), lower precision (49.51 vs 38.10), and slightly lower accuracy within 30% of 51Cr-EDTA (74.07% vs 76.54%). CONCLUSIONS: Combined urea and creatinine clearance did not improve the performance of CrCl. Nevertheless, it can potentially be used as first-line GFR assessment, followed by mGFR in selected donors, to ascertain threshold of safe kidney donation. A stringent urine collection method is essential to ensure accurate measurement.

The Effects of Different Induction Regimes on Serial Lymphocyte Subsets in Kidney Transplant Recipients: A Single Tertiary Center Experience.

BACKGROUND: Immunosuppressive therapy is the backbone of kidney transplantation in preventing acute rejection. T-cell depletion after doses of thymoglobulin is dose-dependent, as are their side effects. At the same time, basiliximab and other maintenance immunosuppressive drugs act at different signals on T lymphocytes. Therefore, studying the pattern of lymphocyte subset depletion depending on the induction regime given at transplantation could be an added tool in managing post-transplant recipients. METHODOLOGY: This prospective observational study recruited kidney transplant recipients from August 2019 through April 2021 at the University of Malaya Medical Centre. Blood tests for lymphocyte subsets were taken at pre-transplant, 1 week, 1 month, 3 months, and 6 months post-transplantation. At transplantation, recipients received either basiliximab, low-dose thymoglobulin (cumulative dose: 1.5 mg/kg), or standard-dose thymoglobulin (cumulative dose: 5 mg/kg). RESULTS: A total of 39 patients were recruited: 38.5% received basiliximab (15 of 39), 15.4% received low-dose thymoglobulin (6 of 39), and 46.2% received standard-dose thymoglobulin (18 of 39). Absolute lymphocyte counts 1 week post-transplantation were 1.5 ± 0.84 × 109/L for basiliximab, 0.7 ± 0.57 × 109/L for low-dose thymoglobulin, and 0.1 ± 0.08 × 109/L for standard-dose thymoglobulin (P < .001). The CD4+ and CD8+ counts were severely depleted in the standard-dose thymoglobulin group, with a statistically significant differenceup to 6 months post-transplantation. In the low-dose thymoglobulin group, the CD4+ and CD8+ counts were depleted at 1 week post-transplantation and recovered at 1 month post-transplantation. There was no difference in allograft function and incidence of allograft rejection across groups. CONCLUSIONS: The effects on lymphocyte counts, CD4+ and CD8+, vary depending on the type and dose of induction immunosuppression. This could be a guiding tool in managing immunosuppression post-transplantation depending on the patient's immunologic risk.

Metabolic Changes In Living Kidney Donors After Donation In University Malaya Medical Centre.

The short- and long-term outcome of donations from living donors of kidneys (LKDs) remains controversial. Information regarding metabolic changes after donation in Malaysia remains limited despite Malaysia having the highest record prevalence of diabetes, obesity, and hypertension in Asia. There were 159 LKDs in our center from 2010 to 2020. We analyzed pre and post donation clinical data and laboratory results from 140 LKDs, retrospectively, from electronic medical records and looked for any metabolic changes. Among these 140 LKDs, 99 were women (70.7%), with a mean age of 47.23 ± 11.67 before donation. The median follow-up was 4 years (range, 2-6 years). Median body mass index increased from 24.35 kg/m2 (range, 22.11-26.93) to 25.56 kg/m2 (range, 22.78-28.57; Z=-3.934, P = .000) after donation. Prevalence of obesity increased from 24.18% to 30.77%. Only 2.8% of LKDs developed proteinuria postnephrectomy (P = .250). Serum creatinine increased from 60 mmol/L (range, 52-74) to 87 mmol/L (range, 74-108) 1 year after donation (P = .000), and the latest results decrease to 83 mmol/L (range, 73-101; P = .000). Systolic blood pressure increased from 127.83 ± 12.25 mm Hg to 131.30 ± 18.16 mm Hg, (t[97] = -2.012; P = .047); and prevalence of hypertension increased from 19.81% to 23.58% (P = .125), with 22.64% requiring treatment. We noted that 22.54% of the LKDs had dyslipidemia before donation, a number that increased to 50% after donation (P = .000). LKDs with hyperuricemia increased significantly from 7.92% to 34.65%, with uric acid level increasing from 311.94 ± 78.51umol/L to 381.87 ± 86.96 umol/L (t[94] = -10.805; P = .000). Fasting blood glucose and glycated hemoglobin level recorded no significant changes after donation. Post donation kidney function of LKDs compensated well and stable in short term. We noted statistically significant increment of weight, post donation body mass index, systolic blood pressure, uric acid, and lipids. We suggest prospective studies with longer follow-up and more subjects for clinical correlation.

Synchronous online learning during movement control order in higher education institutions: a systematic review.

Background: Higher education institutions (HEI) are not spared from the coronavirus disease 2019 (COVID-19) pandemic. The closure of campuses because of the movement control order (MCO) to mitigate the spread of the COVID-19 has forced HEIs to adopt online learning, especially synchronous online learning (SOL). Although teaching and learning can be continued via SOL, retaining students' interest and sustaining their engagement have not been sufficiently explored. This study presents a systematic review of the research pertaining to SOL associated with students' interest and engagement in HEIs during the MCO environment. Methods: Five major online databases, i.e., EBSCOhost, Science Direct, Emerald, Scopus and Springer were searched to collect relevant papers published between 1st January 2010 to 15th June 2021 including conference proceedings, peer-reviewed papers and dissertations. Papers written in the English language, based in full-fledged universities, and with these five keywords: (i) synchronous online learning, (ii) engagement, (iii) interest, (iv) MCO/Covid-19 and (v) HEI, were included. Papers focussing on synchronous and asynchronous online learning in schools and colleges were excluded. Each paper was reviewed by two reviewers in order to confirm the eligibility based on the inclusion and exclusion criteria. Results: We found 31 papers of which six papers were related to SOL, engagement and interest in HEIs in the MCO environment. Our review presents three major findings: (i) limited research has been conducted on SOL associated with students' engagement and interest, (ii) studies related to the context of HEIs in the MCO environment are limited, and (iii) the understanding of the new phenomena through qualitative research is insufficient. We highlight the SOL alignment with students' engagement, interest, style preference, learner interaction effectiveness, behavior and academic performance. Conclusions: We believe that the findings of this study are timely and require attention from the research community.

Genomic analysis revealed a novel genotype of methicillin-susceptible Staphylococcus aureus isolated from a fatal sepsis case in dengue patient.

Staphylococcus aureus (S. aureus) is an opportunistic pathogen capable of causing serious health implications in susceptible individuals once it invades the host's protective barriers. Methicillin-susceptible S. aureus (MSSA) often receives lesser attention although it has been frequently associated with serious infections in human. We aim to investigate the genomic features of a highly virulent yet pan susceptible MSSA strain (coded as HS-MSSA) which caused concurrent bacteraemia in a dengue patient, ultimately resulted in sepsis death of the patient. Whole genome sequence analysis was performed. The draft genome of HS-MSSA is approximately 2.78 Mb (GC content = 32.7%) comprising of 2637 predicted coding sequences. In silico genotyping of the HS-MSSA strain revealed a novel combined genotype (t091/ST2990). The HS-MSSA carries a SaPIn1-like pathogenicity island that harbours the staphylococcal enterotoxin and enterotoxin-like genes (sec3 and selL). The strain-specific ß-lactamase (blaZ)-bearing plasmid region was identified in HS-MSSA. Core genome phylogeny showed that the HS-MSSA strain shared a common ancestry with the European MRSA clone. We report herein the genomic features of an MSSA lineage with novel genotype previously not reported elsewhere.

Low Immunologic Risk Living Related Renal Transplant Using Very Low-Dose Antithymocyte Globulin as Induction Therapy: A Single Tertiary Hospital Experience.

The aim of induction therapy in the management of kidney transplant is to reduce the incidence of acute rejection and delayed graft function after kidney transplant. The agent for induction therapy differs depending on the recipient risks. The regimen can be either polyclonal (rabbit antithymocyte globulin [rATG]) or monoclonal antibody (basiliximab). Basiliximab is commonly used in patients with low immunologic risk. However, to date we know that the use of rATG on T cell depletion is dose dependent and more potent antirejection therapy. Therefore, we would like to look at 1-year graft function of very low-dose rATG in low immunologic risk recipients. All low immunologic risk patients who received low-dose rATG (0.5 mg/kg of body weight daily) during transplant (day 0) and on days 1 and 2 were recruited. Their renal function, HLA donor-specific antibodies, lymphocyte counts, protocol biopsy results, and cytomegalovirus (CMV) polymerase chain reaction were monitored as per clinical practice. All 10 patients had immediate graft function. Low-dose rATG caused lymphocyte counts to deplete immediately on day 0, and the effect lasted about 1 month post-transplant. All the patients had stable graft function without any significance episode of rejection. Only one patient had de novo HLA-DQ antibody. It is good to know that without prophylaxis antiviral in CMV+ donor to CMV+ recipient, the incidence of CMV viremia is considerably low in our cohort. Very low-dose rATG is an effective induction immunosuppression in low immunologic risk patients with acceptable infection risk.

One-Year Outcomes of Living Related Kidney Transplant in Patients With Preformed HLA Donor-Specific Antibodies: A Single-Center Experience in Malaysia.

The shortage of deceased donors led to an increase of living related renal transplant performed in the presence of donor-specific antibodies (DSAs) or ABO incompatibilities. There are various desensitization protocols that have been proposed. Here, we describe the outcome of these sensitized patients. This is a prospective cohort study recruiting all kidney transplant recipients from August 2016 until June 2018. Deceased donations, ABO incompatible patients, and sensitized patients who were not prescribed on our desensitization protocol were excluded. Recipients were screened for the presence of HLA-antibodies 1 month before transplant. Those with positive DSA will undergo flow cytometry (risk stratification). We are using a protocol that consisted of intravenous rituximab 200 mg (day -14), intravenous antithymocyte globulin 5mg/kg (day 0-4), plasma exchange post transplant for patients with mean fluorescent intensity (MFI) < 3000, and negative flow cytometry. Those patients with MFI ≥ 3000 or positive flow cytometry need extra cycles pretransplant. A total of 40 patients were recruited, and 20 were sensitized patients. Among the sensitized group 4 of 20 had flow cytometry crossmatch positive, while all had preformed HLA-DSA. A total of 8 of 20 had class I HLA-DSA, 11 of 20 had class II HLA-DSA, and 1of 20 was positive for both class I and II HLA-DSA. Mean immunodominant MFI was 2133.4 (standard deviation [SD], 4451.24) and 1383.7 (SD, 2979.02) for class I and class II, respectively. At 1 year, mean serum creatinine was 108.90 (SD, 25.95) and 118.42 (SD, 31.68) in sensitized and unsensitized patients, respectively. One of 20 unsensitized patients had Banff 1B rejection at 3 months, and there was no significant rejection in sensitized patients at 6 months and 1 year. There was no difference in the occurrence of de novo HLA-DSA between the groups. Desensitization protocols may help to overcome incompatibility barriers in living donor renal transplant. The combination of low-dose rituximab, antithymocyte globulin, and judicious use of plasma exchange has worked well for our cohort.

Atypical Presentation of Methicillin-Susceptible Staphylococcus aureus Infection in a Dengue-Positive Patient: A Case Report with Virulence Genes Analysis.

Concurrent bacteraemia in patients with dengue fever is rarely reported. We report a case of a patient who initially presented with symptoms typical of dengue fever but later succumbed to septic shock caused by hypervirulent methicillin-susceptible Staphylococcus aureus (MSSA). A 50-year-old female patient with hypertension and diabetes mellitus presented with typical symptoms of dengue fever. Upon investigation, the patient reported having prolonged fever for four days prior to hospitalization. Within 24 hours post-admission, the patient developed pneumonia and refractory shock, and ultimately succumbed to multiple-organs failure. Microbiological examination of the blood culture retrieved a pan susceptible MSSA strain. Genomic sequence analyses of the MSSA strain identified genes encoding staphylococcal superantigens (enterotoxin staphylococcal enterotoxin C 3 (SEC3) and enterotoxin-like staphylococcal enterotoxins-like toxin L (SElL)) that have been associated with toxic shock syndrome in human hosts. Genes encoding important toxins (Panton-Valentine leukocidins, alpha-haemolysin, protein A) involved in the development of staphylococcal pneumonia were also present in the MSSA genome. Staphylococcus aureus co-infections in dengue are uncommon but could be exceptionally fatal if caused by a toxin-producing strain. Clinicians should be aware of the risks and signs of sepsis in dengue fever, thus allowing early diagnosis and starting of antibiotic treatment in time to lower the mortality and morbidity rates.