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.

Shear wave elastography accurately detects chronic changes in renal histopathology.

AIM: Renal biopsy is the gold standard for the histological characterization of chronic kidney disease (CKD), of which renal fibrosis is a dominant component, affecting its stiffness. The aim of this study was to investigate the correlation between kidney stiffness obtained by shear wave elastography (SWE) and renal histological fibrosis. METHODS: Shear wave elastography assessments were performed in 75 CKD patients who underwent renal biopsy. The SWE-derived estimates of the tissue Young's modulus (YM), given as kilopascals (kPa), were measured. YM was correlated to patients' renal histological scores, broadly categorized into glomerular, tubulointerstitial and vascular scores. RESULTS: Young's modulus correlates significantly with tubulointerstitial score (ρ = 0.442, P < .001) and glomerular score (ρ = 0.375, P = .001). Patients with no glomerular sclerosis showed lower mean YM measurements compared to those with glomerular sclerosis. The mean YM increased as the percentage of interstitial fibrosis and tubular atrophy increased. The area under the receiver operating characteristic curve (ROC) for SWE in differentiating between mildly and moderately impaired kidneys was 0.702. CONCLUSION: Shear wave elastography accurately detects chronic renal damage resulting from glomerular sclerosis, interstitial fibrosis and tubular atrophy, using the optimal cut-off YM value of ≥5.81 kPa.

Outcomes of STEMI patients with chronic kidney disease treated with percutaneous coronary intervention: the Malaysian National Cardiovascular Disease Database - Percutaneous Coronary Intervention (NCVD-PCI) registry data from 2007 to 2014.

BACKGROUND: Patients with renal impairment often left out from most major clinical trials assessing the optimal treatment for ST-elevation myocardial infarction (STEMI). Large body of evidence from various cardiovascular registries reflecting more 'real-world' experience might contribute to the knowledge on how best to treat this special cohort. We aim to analyze the outcomes of Malaysian STEMI patients with renal impairment treated with coronary angioplasty. METHODS: Utilizing the Malaysian National Cardiovascular Disease Database-Percutaneous Coronary Intervention (NCVD-PCI) registry data from 2007 to 2014, STEMI patients treated with percutaneous coronary intervention (PCI) were stratified into presence (GFR < 60 mls/min/1.73m2) or absence (GFR ≥ 60 mls/min/1.73m2) of chronic kidney disease (CKD). Patient's demographics, extent of coronary artery disease, procedural data, discharge medications, short (in-hospital) and long (1 year) term outcomes were critically assessed. RESULTS: A total of 6563 patients were included in the final analysis. STEMI CKD cohort was predominantly male (80%) with mean age of 61.02 ± 9.95 years. They had higher cardiovascular risk factors namely diabetes mellitus (54.6%), hypertension (79.2%) and dyslipidemia (68.8%) in contrast to those without CKD. There were notably higher percentage of CKD patients presented with Killip class 3 and 4; 24.9 vs 8.7%. Thrombolytic therapy remained the most commonly instituted treatment regardless the status of kidney function. Furthermore, our STEMI CKD cohort also was more likely to receive less of evidence-based treatment upon discharge. In terms of outcomes, patients with CKD were more likely to develop in-hospital death (OR: 4.55, 95% CI 3.11-6.65), MACE (OR: 3.42, 95% CI 2.39-4.90) and vascular complications (OR: 1.88, 95% CI 0.95-3.7) compared to the non-CKD patients. The risk of death at 1-year post PCI in STEMI CKD patients was also reported to be high (HR: 3.79, 95% CI 2.84-5.07). CONCLUSION: STEMI and CKD is a deadly combination, proven in our cohort, adding on to the current evidence in the literature. We noted that our STEMI CKD patients tend to be younger than the Caucasian with extremely high prevalence of diabetes mellitus. The poor outcome mainly driven by immediate or short term adverse events peri-procedural, therefore suggesting that more efficient treatment in this special group is imperative.

MDRD vs. CKD-EPI in comparison to 51Chromium EDTA: a cross sectional study of Malaysian CKD cohort.

BACKGROUND: Accurate measurement of renal function is important: however, radiolabelled gold standard measurement of GFR is highly expensive and can only be used on a very limited scale. We aim to compare the performance of Modification of Diet in Renal Disease (MDRD) and Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) equations in the multi-ethnic population attending University Malaya Medical Centre (UMMC). METHODS: This is a cross-sectional study recruiting patients, who attend UMMC Nephrology clinics on voluntary basis. 51-Chromium EDTA (51Cr-EDTA) plasma level was used to measure the reference GFR. The serum creatinine was determined by IDMS reference modified Jaffe kinetic assay (CrJaffe). The predictive capabilities of MDRD and CKD-EPI based equations were calculated. Data was analysed using SPSS version 20 and correlation, bias, precision and accuracy were determined. RESULTS: A total of 113 subjects with mean age of 58.12 ± 14.76 years and BMI of 25.99 ± 4.29 kg/m2 were recruited. The mean reference GFR was 66.98 ± 40.65 ml/min/1.73m2, while the estimated GFR based on MDRD and CKD-EPI formula were 62.17 ± 40.40, and 60.44 ± 34.59, respectively. Both MDRD and CKD-EPI were well-correlated with reference GFR (0.806 and 0.867 respectively) and statistically significant with p < 0.001. In the overall cohort, although MDRD had smaller bias than CKD-EPI (4.81 vs. 6.54), CKD-EPI was more precise (25.22 vs. 20.29) with higher accuracy within 30% of measured GFR (79.65 vs. 86.73%). CONCLUSION: The CKD-EPI equation appeared to be more precise and accurate than the MDRD equation in estimating GFR in our cohort of multi-ethnic populations in Malaysia.

Severe Plasmodium falciparum infection mimicking acute myocardial infarction.

This case report describes a case of presumed acute myocardial infarction in a returned traveler who was later diagnosed to have severe malaria. Emergency coronary angiography was normal and subsequent peripheral blood film was positive for Plasmodium falciparum.

Ultrasound shear wave elastography for the evaluation of renal pathological changes in adult patients.

OBJECTIVE: Many studies have conflicting findings in using shear wave elastography (SWE) to assess renal fibrosis. This study reviews the use of SWE to evaluate pathological changes in native kidneys and renal allografts. It also tries to elucidate the confounding factors and care taken to ensure the results are consistent and reliable. METHODS: The review was carried out according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Literature search was conducted in Pubmed, Web of Science and Scopus database up to 23 October 2021. To evaluate risk and bias applicability, the Cochrane risk-of bias tool and GRADE was used. The review was registered under PROSPERO CRD42021265303. RESULTS: A total of 2921 articles were identified. 104 full texts were examined and 26 studies included in systematic review. 11 studies performed on native kidneys and 15 studies on transplanted kidney. A wide range of impact factors was found that affect the accuracy of SWE of renal fibrosis in adult patients. CONCLUSIONS: Compared to point SWE, two-dimensional SWE with elastogram could enable better selection of the region of interest in kidneys, leading to reproducible results. Tracking waves were attenuated as the depth from skin to region of interest increased, therefore, SWE is not recommended for overweight or obese patients. Variable transducer forces might also affect SWE reproducibility, thus, training of operators to ensure consistent operator-dependent transducer forces may be helpful. ADVANCES IN KNOWLEDGE: This review provides a holistic insight on the efficiency of using SWE in evaluating pathological changes in native and transplanted kidneys, thereby contributing to the knowledge of its utilisation in clinical practice.

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 Role of Lymphocyte Subset in Predicting Allograft Rejections in Kidney Transplant Recipients.

BACKGROUND: Allograft rejection remains a significant challenge in managing post-transplant recipients despite the improvement in immunologic risk assessment and immunosuppressive therapy. Published literature including animal studies has demonstrated that the cells responsible for rejection are beyond the innate T and B cells, and other studies revealed evidence supporting natural killer (NK) cells' role in kidney allograft injury. This study aims to find the association between the peripheral blood lymphocyte subset counts, primarily NK cells, and the kidney allograft biopsy findings. METHODS: This is a prospective cross-sectional study among a total of 100 kidney allograft biopsies in 61 kidney transplant recipients. The peripheral blood for the lymphocyte subset was sent just before the allograft biopsy. The patients' immunosuppression and other laboratory investigations were managed as per clinical practices by the attending nephrologist. RESULTS: Overall, the mean age of our patients was 43.72 ± 10.68 years old, and 55.7% of recipients were male. Higher counts of T cells (CD4+; 658.8 ± 441.4 cells/µL; P = .043) and NK cells (CD3-CD16+CD56+; 188 [interquartile range = 133.0-363.0 cells/µL]; P = .002) were associated with higher risk of allograft rejection in the initial analysis. Patients with an allograft age <12 months had significantly higher total T cells, CD4+ T cells, and NK cells in the rejection groups. However, after assessing factors associated with rejection in the multivariate analysis, we only found that being ABO-incompatible and having >497 CD4+ cells/µL had a higher odds of allograft rejection. CONCLUSIONS: Higher CD4± counts were associated with a higher risk of allograft rejection. However, there was no significant increase in CD8±, CD19±, and NK cells count in our cohort with allograft rejection.

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.

Prevalence Rate of Proteinuria and Metabolic Acidosis Among Kidney Transplant Recipients in a Tertiary Teaching Hospital and Its Relationship to Dietary Intake.

BACKGROUND: Proteinuria and metabolic acidosis adversely affect long term renal allograft outcome and are highly prevalent in reported studies. The role of dietary intake in influencing proteinuria and metabolic acidosis remained uncertain. This study aims to determine the prevalence rate of proteinuria and metabolic acidosis among kidney transplant recipients (KTRs) and to study their relationship with dietary intake. METHODS: We performed a cross-sectional study on KTRs with functioning renal allograft and at least 3 months post transplant. Dietary protein, salt, and dietary acid load were estimated using 24-hour urine collection. Demographic characteristics, concomitant medications, medical history, and laboratory results were obtained from electronic medical records. RESULTS: A total of 204 KTRs were recruited with median age of 48 years (interquartile range [IQR], 18 years); male to female ratio was 61:39. A total of 79.9% (n = 163) were living related kidney transplants. The median duration after transplant was 71 months (IQR, 131 months), and median eGFR was 65 mL/min/1.73 m2 (IQR, 25 mL/min/1.73 m2). The prevalence rates of proteinuria (defined as ≥ 0.5 g/d) and metabolic acidosis (defined as at least 2 readings of serum bicarbonate ≤ 22 mmol/L in the past 6 months) were 17.7 % and 6.2%, respectively. High dietary protein of > 1.2 g/kg ideal body weight (adjusted odds ratio, 3.13; 95% CI, 1.35-7.28; P = .008) was significantly associated with proteinuria. Dietary protein, salt, and acid load did not correlate with chronic metabolic acidosis. CONCLUSIONS: The prevalence rate of proteinuria is consistent with published literature, but metabolic acidosis rate is extremely low in our cohort. High protein intake (> 1.2 g/kg ideal body weight) is a risk factor of proteinuria and may have negative impact on KTR outcome.

The Outcome of the Elderly Living Kidney Donors in a Single Tertiary Center in Malaysia.

Living-kidney transplantation increases with years, however, the rate is comparatively low to support local needs. Marginal living donors like the elderly were used to increase the donor pool. We retrospectively evaluate the outcome of 25 elderly living kidney donors (eLKDs) who were ≥60 years old at the time of donation in our center. Their medical history and laboratory results were analyzed retrospectively from e-medical records. There are 16 females (64.0%) with a median age of 63 (60.5-66.0). The mean follow-up duration was 4.36 ± 2.46 years. Their mean body mass index increased from 23.70 ± 3.07 kg/m2 to 24.21 ± 2.93 kg/m2 (t[14] = -2.176, P = .047) post donation. Systolic blood pressure (SBP) increased from 133.33 ± 11.65 mm Hg to 140.56 ± 17.78 mm Hg (t[17] = -2.124, P = .049). However, the prevalence of overweight and hypertension were not significant. Only 5.56% of the eLKDs developed proteinuria post nephrectomy (P =1.000). Serum creatinine increased from 62.33 ± 14.39 mmol/L to 104.63 ± 28.53 mmol/L post 1-month donation (t[23] = -9.720, P = .000) and decreased to 99.67 ± 22.39 mmol/L post 1-year donation (t[17] = -8.415, P = .006), and latest results were 94.28 ± 20.74mmol/L (t[17] = -6.630, P = .033). Fasting blood glucose and HbA1c level recorded no significant changes post donation. We noted that 47.62% of the eLKDs had dyslipidemia pre donation, which increased to 76.20% post donation (P = .031). eLKDs with hyperuricemia increased significantly from 5.88% to 52.94%; with uric acid level from 306.12 ± 68.67 umol/L to 412.24 ± 74.14 umol/L (t[16] = -7.726, P = .000). None of the eLKDs were diagnosed with metabolic syndrome pre and post kidney donation. Postdonation kidney function of the eLKDs compensated well and were stable in the short term. We noted statistically significant increments of weight, body mass index, SBP, uric acid, and lipid levels, which did not translate to clinical significance post donation. Elderly living-kidney donation can be done safely with close monitoring post donation.

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.

Prevalence of AT1R antibody (AT1R-Ab) among Malaysian multi-ethnic population.

BACKGROUND: Angiotensin II type 1 receptor antibody (AT1R-Ab) is a non-HLA antibody that has been reported to cause antibody-mediated rejection and graft loss in kidney transplantation. The prevalence of positive AT1R-Ab varies between 8% and 18% in different regions. Thus, this study aims to determine the prevalence of AT1R-Ab among the Malaysian population. METHODOLOGY: All sera for AT1R-Ab were collected at the University Malaya Medical Centre (UMMC), Kuala Lumpur, Malaysia. The sera were centrifuged and kept refrigerated at -80 °C before being transported to the South Australian Transplantation and Immunogenetics Laboratory (SATIS). Enzyme-linked immunosorbent assay kit (One Lambda) was used for the detection of AT1R-Ab, and it was performed according to the manufacturer's instructions. The level of >17.1 U/mL was considered to be AT1R-Ab positive; 10.0-17.1 U/mL at risk, and <10.0 U/mL negative. RESULTS: A total of 115 samples were collected from 99 patients pre and post-kidney transplant recipients. From the pre-transplant sera (n = 68) 17.7% were positive, 35.3% were at risk and 47.0% were negative. The positive AT1R-Ab cohort were relatively younger, with a mean age of 34.7 ± 8.3 years old and statistically significant, with a p-value of 0.028. Among the sera that were tested positive, 19.0% were from the Chinese ethnicity, 6.7% from Malay and 16.7% from Indian. There was no difference in the rejection episodes, persistent or de novo HLA-DSA, and graft function between the group (AT1R-Ab negative vs AT1R-Ab at risk and positive) and the results were consistent in a model adjusted for all potential confounders. CONCLUSION: The prevalence of positive (>17.1 U/mL) pre-transplant AT1R-Ab was 17.7% and 35.3% were at risk (10.0-17.1 U/mL) in our pre-transplant cohort.

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.

Stiffness and Anisotropy Effect on Shear Wave Elastography: A Phantom and in Vivo Renal Study.

Tissue elasticity is related to the pathologic state of kidneys and can be measured using shear wave elastography (SWE). However, SWE quantification has not been rigorously validated. The aim of this study was to evaluate the accuracy of SWE-measured stiffness and the effect of tissue anisotropy on SWE measurements. Point SWE (pSWE), 2-D SWE and dynamic mechanical analysis (DMA) were used to measure stiffness and evaluate the effect of tissue anisotropy on the measurements. SWE and DMA were performed on phantoms of different gelatin concentrations. In the tissue anisotropy study, SWE and DMA were performed on the outer cortex of sheep kidneys. In the in vivo study, 15 patients with different levels of interstitial fibrosis were recruited for pSWE measurements. Another 10 healthy volunteers were recruited for tissue anisotropy studies. SWE imaging revealed a non-linear increase with gelatin concentration. There was a significant correlation between pSWE and 2-D SWE, leading to the establishment of a linear regression equation between the two SWE ultrasound measurements. In the anisotropy study, the median difference in stiffness between shear waves oriented at 0° and 90° towards the pyramid axis was significant. In the in vivo study, there was a strong positive linear correlation between pSWE and the percentage of interstitial fibrosis. There was a significant difference in the Young's modulus (YM) between severities of fibrosis. The mean YM values were lower in control patients than in patients with mild, moderate and severe fibrosis. YM values were also significantly higher when shear waves were oriented at 0° toward the pyramid axis. Tissue stiffness and anisotropy affects SWE measurements. These factors should be recognized before applying SWE for the interpretation of measured values.

Clinical Significance of Renal Allograft Protocol Biopsies: A Single Tertiary Center Experience in Malaysia.

BACKGROUND: The role of protocol renal allograft biopsy in kidney transplantation is controversial due to the concern with procedural-related complications; however, its role is slowly evolving. Recent evidence suggests that protocol biopsy is useful in detecting subclinical renal pathology. Early recognition and treatment of renal pathologies can improve long-term outcomes of renal allografts. METHODOLOGY: A total of 362 renal allograft protocol biopsies were performed in adult recipients of kidney transplantation between 2012 and 2017. After excluding those with poor quality or those performed with a baseline serum creatinine level >200 umol/L, we analyzed 334 (92.3%) biopsies. Histology reports were reviewed and categorized into histoimmunological and nonimmunological changes. The immunological changes were subcategorized into the following: (1) no acute rejection (NR), (2) borderline changes (BC), and (3) subclinical rejection (SCR). Nonimmunological changes were subcategorized into the following: (1) chronicity including interstitial fibrosis/tubular atrophy (IFTA), chronic T-cell-mediated rejection (TCMR), unspecified chronic lesions, and arterionephrosclerosis, (2) de novo glomerulopathy/recurrence of primary disease (RP), and (3) other clinically unsuspected lesions (acute pyelonephritis, calcineurin inhibitors toxicity, postinfective glomerulonephritis, and BK virus nephropathy). Risk factors associated with SCR were assessed. RESULTS: For the histoimmunological changes, 161 (48.2%) showed NR, 145 (43.4%) were BC, and 28 (8.4%) were SCR. These clinical events were more pronounced for the first 5 years; our data showed BC accounted for 59 (36.4%), 64 (54.2%), and 22 (40.7%) biopsies within <1 year, 1-5 years, and > 5 years, respectively (p = 0.011). Meanwhile, the incidence for SCR was 6 (3.7%) biopsies in <1 year, 18 (15.3%) in 1-5 years, and 4 (7.4%) in >5 years after transplantation (p=0.003). For the nonimmunological changes, chronicity, de novo glomerulopathy/RP, and other clinically unsuspected lesions were seen in 40 (12%), 10 (3%), and 12 (3.6%) biopsies, respectively. Living-related donor recipients were associated with decreased SCR (p=0.007). CONCLUSIONS: Despite having a stable renal function, our transplant recipients had a significant number of subclinical rejection on renal allograft biopsies.

Comparison of Shear Wave Elastography and Conventional Ultrasound in Assessing Kidney Function as Measured Using 51Cr-ethylenediaminetetraacetic Acid and 99Tc-Dimercaptosuccinic Acid.

The purpose of this study was to assess the potential of shear wave elastography (SWE) as an indicator of abnormal kidney function defined by radiolabeled glomerular filtration rate (GFR). Fifty-seven patients referred for 51Cr-ethylenediaminetetraacetic acid GFR and 99mTc-dimercaptosuccinic acid renal scintigraphy were included. Young's modulus (YM) measured with SWE and kidney length, volume, cortical thickness and parenchymal echogenicity measured with conventional ultrasound were correlated with patients' GFR and renal scintigraphy results. Spearman correlation coefficients between SWE and GFR were negative for the right (r = -0.635, p < 0.0001) and left (r = -0.817, p < 0.0001) kidneys. Positive correlations between left renal cortical thickness (r = 0.381, p = 0.04) and left kidney volume (r = 0.356, p = 0.019) with GFR were reported. SWE correctly predicted the dominant functioning kidney in 94.7% of cases. The area under the receiver operating characteristic curve for SWE (0.800) was superior to that for conventional ultrasound (0.252-0.415). The cutoff value of ≥5.52 kPa suggested a kidney function ≤60 mL/min/1.73 m2 (82.4% sensitivity and 76.2% specificity). SWE has advantages over conventional ultrasound in assessing kidney function and distinguishing the dominant functioning kidney.

Proactive treatment of angiotensin receptor antibodies in kidney transplantation with plasma exchange and/or candesartan is safe and associated with excellent graft survival at 4 years: A single centre Australian experience.

High levels of angiotensin receptor antibodies (ATRab) are associated with acute cellular and humoral rejection, vascular occlusion, de novo human leucocyte antigen donor specific antibody (HLA DSA) and poor graft survival in kidney transplant recipients (KTR). Since 2015 we proactively managed patients "at risk" (AR) with ATRab >17 U/ml with perioperative plasma exchange (PLEX) and/or angiotensin receptor blockade (ARB). 44 patients were treated with this protocol. 265 KTR with ATRab ≤17 U/ml deemed "low risk" (LR) were transplanted under standard conditions. PLEX and ARB were not associated with increased risk of: delayed graft function requiring haemodialysis (HDx), hyperkalaemia >5.5 mmol/l requiring HDx, and the combined clinical end-point of severe hypotension, blood transfusion and re-operation for bleeding. Rejection rates were similar at 90 days: 8/44 (18%) in the AR group and 36/265 (14%) in the LR group (p = 0.350). Death censored graft survival was the same between the AR and LR groups with a 94% 48-month graft survival - hazard ratio (log-rank) 1.16 [95% CI 0.2-5.8] p = 0.844. Proactive treatment of ATRab >17 U/ml with PLEX and/or ARB is not associated with increased rates of perioperative complications and comparable rates of rejection and death censored graft survival at 4 years compared to KTR <17 U/ml ATRab.

Estimating Renal Function in the Elderly Malaysian Patients Attending Medical Outpatient Clinic: A Comparison between Creatinine Based and Cystatin-C Based Equations.

BACKGROUND: To assess the performance of different GFR estimating equations, test the diagnostic value of serum cystatin-C, and compare the applicability of cystatin-C based equation with serum creatinine based equation for estimating GFR (eGFR) in comparison with measured GFR in the elderly Malaysian patients. METHODS: A cross-sectional study recruiting volunteered patients 65 years and older attending medical outpatient clinic. 51 chromium EDTA (51Cr-EDTA) was used as measured GFR. The predictive capabilities of Cockcroft-Gault equation corrected for body surface area (CGBSA), four-variable Modification of Diet in Renal Disease (4-MDRD), and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations using serum creatinine (CKD-EPIcr) as well as serum cystatin-C (CKD-EPIcys) were calculated. RESULTS: A total of 40 patients, 77.5% male, with mean measured GFR 41.2 ± 18.9 ml/min/1.73 m2 were enrolled. Mean bias was the smallest for 4-MDRD; meanwhile, CKD-EPIcr had the highest precision and accuracy with lower limit of agreement among other equations. CKD-EPIcys equation did not show any improvement in GFR estimation in comparison to CKD-EPIcr and MDRD. CONCLUSION: The CKD-EPIcr formula appears to be more accurate and correlates better with measured GFR in this cohort of elderly patients.