Obinutuzumab in Kidney Transplantation: Effect on B-cell Counts and Crossmatch Tests.

BACKGROUND: Resistance to the action of rituximab (RTX) has been documented in several diseases. More recently, obinutuzumab (OBZ) has shown promise where RTX has failed in oncology and lupus nephritis. Unlike RTX, OBZ is a weak activator of complement, which may avoid the false-positive complement-dependent cytotoxicity (CDC) crossmatch tests after RTX infusions. METHODS: The aim of this study was to explore the effect of OBZ on B-cell depletion in kidney-transplant candidates and its impact on crossmatch test results. We included 12 patients, who were either highly sensitized kidney-transplant candidates or kidney-transplant recipients presenting with antibody-mediated rejection. Six received OBZ, and 6 received RTX. CD-19 counts, flow cytometry, and CDC crossmatch tests were run immediately before and at 2 wk after drug infusion. RESULTS: OBZ reduced CD-19 counts: median reduction was 98%. B-cell CDC crossmatch test results became positive following RTX infusion but were not affected by OBZ infusion. CONCLUSIONS: OBZ effectively depleted B-cell counts in sensitized kidney-transplant candidates and, unlike RTX, had no effect on CDC crossmatch results.

Transplantation in the era of the Covid-19 pandemic: How should transplant patients and programs be handled?

Due to the Covid-19 pandemic caused by SARS-CoV-2, transplant programs worldwide have been severely impacted with dwindling numbers of transplantations performed and a complete halt in several areas. In this review we examine whether SARS-CoV-2 infection presents differently in transplant recipients, whom and how we should test, how susceptible the transplant population is to overt infection and describe the range of outcomes. From retrieved published reports on SARS-CoV-2infections in 389solid organ transplant recipients reported in the literature, the overall mortality rate was 16.7% (n = 65); however for those with mild or moderate Covid-19 disease this was 2.9% and 2.3% respectively; conversely, for those with severe infection the mortality rate was 52.2%.We then address questions regarding halting transplantation programs during this pandemic, whether all human tissues being considered for transplantation are capable of transmitting the infection, and if we should alter immunosuppressive medications during the pandemic.

Comparing different calcification scores to detect outcomes in chronic kidney disease patients with vascular calcification.

BACKGROUND: There is no consensus on the most appropriate technique to diagnose vascular calcification in chronic kidney disease. This is primarily because of the absence of direct comparisons of predictive values of the various calcification scores, especially outside the coronary vascular beds, to detect clinical outcomes. METHODS: We included 93 haemodialysis patients and performed 6 vascular calcification scores: two scores utilised simple X-rays of abdominal aorta and peripheral vessels. CT scans of the thoracic, upper abdominal and lower abdominal aorta were performed to calculate the aortic calcification index and CT of the pelvis for calcification of iliac vessels. Patients were followed for 63months (mean 46.8months) for first major cardiovascular events and mortality. RESULTS: Nineteen cardiovascular events and 28 deaths occurred. Calcification was detected more sensitively in central and peripheral beds using CT scans compared to X-rays (p<0.001). CT scans detected calcification more frequently in distal than proximal vascular beds (p<0.001). Calcification of the pelvic vessels and lower abdominal aorta were most predictive of events including pre-existing cardiovascular disease O.R. 6.5 (95% C.I. 2-22; p=0.001) and O.R. 3 (95% C.I. 1.1-9; p=0.035); new major cardiovascular events H.R. 4.2 (95% C.I. 1.5-11; p=0.006) and H.R. 2 (95% C.I. 0.8-5.3; p=0.1) as well as mortality H.R. 2.8 (95% C.I. 1.3-6; p=0.01) and H.R. 2.2 (95% C.I. 1.04-5; p=0.04) respectively. CONCLUSIONS: CT based techniques are more sensitive than plain X-rays at detecting peripheral and aortic vascular calcifications. Distal CT scans of the aorta and pelvic vessels have the highest predictive value for cardiovascular events and mortality.

Complementary and Alternative Medicine Use Among Patients With Chronic Kidney Disease and Kidney Transplant Recipients.

OBJECTIVE: To explore and compare complementary and alternative medicine (CAM) practice among subsets of patients with chronic kidney disease (CKD) and renal allograft recipients. DESIGN: Cross-sectional survey questionnaire. SETTING: Three outpatient nephrology clinics and dialysis centers in Egypt. SUBJECTS: A total of 1005 subjects were included in the study (560 predialyis patients with CKD 3-4, 245 patients on hemodialysis, and 200 transplant recipients). INTERVENTION: Face to face interview with CKD patients. The survey inquired about epidemiological data, types, sources, and patterns of CAM used as well as the effect of CAM use on the patients' interaction with modern medicine and clinical caregivers. MAIN OUTCOME MEASURE: (1) Prevalence and types of CAM used by CKD patients; (2) Associations and correlates of CAM use including epidemiological features, impact of CAM use on adherence to conventional treatment and interaction of the users with modern medical systems; (3) Differences in CAM practice between subsets of CKD patients viz. hemodialysis patients, CKD 3-4, and transplant recipients. RESULTS: Overall, 522 patients (52%) were using CAM (64% of predialyis patients, 33% of dialysis patients, and 40.5% of transplant recipients, P < .001). Herbal and natural products were the most commonly used type of CAM (78%), followed by mind and body procedures (21.6%). CAM users were more likely to be males (odds ratio [OR] 1.4; 95% confidence interval [CI] 1.1-1.6); employed (OR 1.6; 95% CI 1.2-2); urban residents (OR 1.3; 95% CI 1.2-1.5); have higher income (OR 2.6; 95% CI 2-3.6); and higher education (OR 1.6; 95% CI 1.2-2). Seventy nine percent of CAM users did not report their practices to their caregivers mainly because they were not asked; however, transplant recipients were more likely to report P < .02. Compliance to medical treatment was affected in 4.2% of users. Thirty natural products were identified as well as 4 body and mind procedures. The most commonly used herbs were Nigella sativa, Hibiscus sabdariffa, and Cymbopogon proximus. Potentially harmful CAM included intake of licorice and vinegar. CONCLUSIONS: Use of traditional medicine is highly prevalent among CKD patients. Some of these practices are potentially harmful and may affect patient compliance to modern medicine. Physicians commonly ignore to inquire about these practices, which frequently reflect patient frustration with modern medicine efficacy and/or price.

Fasting during the month of Ramadan among patients with chronic kidney disease: renal and cardiovascular outcomes.

BACKGROUND: Fasting during the month of Ramadan is a religious obligation for Muslims who represent 20% of the world population. This study explores the safety of fasting for a whole month among patients with chronic kidney disease (CKD) with the possible risk of dehydration and hyperviscosity leading to deterioration of kidney functions and vascular thrombosis. METHODS: We followed CKD patients with stable kidney function who chose to fast during the month of Ramadan. A group of nonfasting CKD patients served as controls. Serum creatinine was recorded at the beginning of the month, after 1 week of fasting, at the end of the month and 3 months later. Patients were followed for major adverse cardiovascular events (MACE). RESULTS: A total of 131 CKD patients were recruited and included in two groups: fasting and nonfasting (mean baseline estimated glomerular filtration rate 27.7, SD 13 and 21.5, SD 11.8 mL/min/1.73 m2, respectively). A rise of serum creatinine was noted during fasting in 60.4% of patients by Day 7 and was associated with intake of renin angiotensin aldosterone system antagonists [relative risk (RR) 2, P = 0.002]. Adverse cardiovascular events were observed in six patients in the fasting cohort and were associated with a rise of serum creatinine after 1 week of fasting (P = 0.009) and the presence of pre-existing cardiovascular disease (RR 15, P = 0.001); the latter association was confirmed by logistic regression analysis. Only one event was recorded in the nonfasting group, P = 0.036. CONCLUSIONS: MACE occurred more frequently among fasting CKD patients with pre-existing cardiovascular disease and were predicted by an early rise of serum creatinine.

The Association between Fibroblast Growth Factor-23 and Vascular Calcification Is Mitigated by Inflammation Markers.

BACKGROUND: Fibroblast growth factor-23 (FGF-23) has been linked to vascular calcification, ventricular hypertrophy and mortality in chronic kidney disease (CKD), although these links may not be direct and independent. Similar grave outcomes are associated with inflammation and oxidative stress in CKD. Recently, accumulating evidence has linked components of phosphate homeostasis to inflammation and oxidative stress. The interaction between the triad of inflammation, FGF-23 and cardiovascular outcomes is underinvestigated. METHODS: We studied 65 patients with stage 5 CKD on hemodialysis. Serum levels of FGF-23, high-sensitivity C-reactive protein (hsCRP), endogenous soluble receptor of advanced glycation end products (esRAGE), advanced oxidation protein products (AOPP), parathormone, lipids, calcium and phosphorous were measured. The aortic calcification index (ACI) was determined using non-contrast CT scans of the abdominal aorta. RESULTS: FGF-23 was elevated (mean: 4,681 pg/ml, SD: 3,906) and correlated with hsCRP, esRAGE, AOPP, dialysis vintage and phosphorus in univariate analysis. In multiple regression analysis, hsCRP, AOPP and phosphorus but not esRAGE were all significantly correlated to FGF-23 (R2 = 0.7, p < 0.001). In univariate analysis, ACI correlated with hsCRP, esRAGE, FGF-23, dialysis vintage, systolic blood pressure (BP) and serum cholesterol. In multiple regression analysis not including inflammation markers, ACI was associated with FGF-23. However, inclusion of inflammation markers in another multiple regression analyses showed that ACI correlated with hsCRP, BP, dialysis vintage and esRAGE but not with FGF-23 (R2 = 0.65, p < 0.001). CONCLUSION: FGF-23 is strongly correlated to various markers of inflammation and oxidative stress in hemodialysis patients. The association between FGF-23 and vascular calcification was mitigated when corrected for inflammation markers.

Insulin resistance and metabolic syndrome in primary gout: relation to punched-out erosions.

OBJECTIVES: To verify the relation of gout to insulin resistance (IR) and metabolic syndrome (MetS) and find any association of metatarsophalangeal (MTP) joint erosions to the features of MetS and IR. METHODS: Forty-six primary gout male patients with a mean age of 41.96 ± 5.77 years were grouped according to the presence of MetS. Twenty-seven age and sex matched healthy volunteers served as controls. Insulin sensitivity was estimated using the homeostatic model assessment index (HOMA-B) for beta cell function and HOMA-IR for peripheral tissue IR. RESULTS: Gout patients had significantly higher HOMA-IR and HOMA-B compared to controls. Those with MetS (n = 27) had significantly higher serum uric acid (SUA) than those without (n = 19; 11.51 ± 3.72 mg/dL vs. 9.15 ± 2.34 mg/dL; P = 0.012). Gout patients with MTP erosions had notable higher insulin levels and more IR as shown by the higher levels of HOMA-IR and HOMA-B compared to those without. HOMA-IR and HOMA-B significantly correlated with the presence of erosions. Moreover, the presence of erosions significantly correlated with SUA (r = 0.64, P < 0.0001). CONCLUSIONS: The level of SUA is closely related to IR in patients with and without MetS. There is an association of the severity of gout and presence of MTP erosions to IR. Metabolic syndrome forms an important marker for those who develop more punched-out erosions.

Subclinical renal involvement in essential cryoglobulinemic vasculitis and classic polyarteritis nodosa.

OBJECTIVE: Renal vasculitis is usually associated with anti-neutrophil cytoplasmic antibodies (ANCAs). However, non-ANCA patients constitute a rarely studied variant of renal vasculitis. The aim of the present study was to demonstrate the features of renal involvement in patients with primary systemic non-ANCA associated vasculitis (NAAV) and compare essential cryoglobulinemic vasculitis (ECV) with classic polyarteritis nodosa (PAN). METHODS: The study included 30 patients with primary systemic non-ANCA associated vasculitis (NAAV). Fifteen with ECV and another 15 patients with classic PAN. The patients were recruited from the Rheumatology and Internal medicine departments and outpatient clinics of Cairo University Hospitals. The patients had no or mild renal involvement at entry and the ANCA was negative as tested by immunoflourescence and ELISA. Renal biopsy was performed for all the patients and histopathologically studied. RESULTS: Renal biopsy abnormalities were seen in six females. One patient with PAN showed renal vasculitis and membranoproliferative glomerulonephritis (MPGN) and was HBV and ANA positive. The patient had negative HCV and cryoglobulins. Five patients with ECV-associated HCV had findings; one had chronic interstitial nephritis and was HBV positive. The other four were HBV negative with MPGN in two, focal proliferative and crescentic GN in one patient each. CONCLUSIONS: Increased understanding of the manifestations of systemic vasculitis is likely to provide the basis for the use of more selective immunomodulatory therapies in the future. It is our hope that this study will raise awareness of the non ANCA-associated vasculitic renal involvement.

Endogenous soluble receptor of advanced glycation end-products (esRAGE) is negatively associated with vascular calcification in non-diabetic hemodialysis patients.

BACKGROUND: Advanced glycation end-products (AGE) accumulate in CKD and may predispose to cardiovascular disease by inducing inflammatory and oxidant stress in the vascular endothelium. Soluble forms of the receptor for AGE (RAGE) may be protective against these effects by binding AGE in the soluble phase. Accumulating evidence suggests a protective role of soluble RAGE against vascular calcification. This study investigates the association between endogenous soluble RAGE (esRAGE) and vascular calcification in hemodialysis patients. METHODS: We studied 65 non-diabetic hemodialysis patients, on 3 × 4 h dialysis schedule, and 19 controls. Serum levels of esRAGE, hsCRP, parathormone, lipids, calcium, and phosphorus were measured. Aortic calcification index (ACI) was measured using non-contrast CT of the abdominal aorta. RESULTS: Aortic calcification was detected in 64 out of 65 hemodialysis patients. Levels of esRAGE were lower in hemodialysis patients (278 pg/ml, SD 101.1) than in controls (443 ± 109 pg/ml; P = 0.001). ACI correlated negatively in stepwise multivariate analysis with esRAGE (P = 0.002) and positively with hsCRP (<0.0001), systolic blood pressure (P < 0.0001) and dialysis vintage (P = 0.05); R (2) = 0.65. CONCLUSION: Levels of esRAGE were low among hemodialysis patients and correlated negatively with ACI.

Fibroblast growth factor-23 (FGF-23) is independently correlated to aortic calcification in haemodialysis patients.

BACKGROUND: Vascular calcification has detrimental consequences on chronic kidney disease (CKD) patients, yet its pathogenesis is not fully understood. Fibroblast growth factor-23 (FGF-23) is involved in the regulation of mineral metabolism which may in turn affect vascular calcification. Data on the relationship between FGF-23 and peripheral vascular calcification, using conventional radiographs, are conflicting, and less is known about its relation to aortic calcification. We conducted this study to investigate the relationship between FGF-23 and aortic calcification in a standard haemodialysis setting. METHODS: The study included 65 haemodialysis patients (46 prevalent and 19 incident) on a three times 4-h dialysis schedule as well as 15 controls. Those with diabetes, oral anticoagulation or parathyroidectomy were excluded. Intact FGF-23, parathormone, lipids, calcium and phosphorus were measured. Aortic calcification index (ACI) was assessed by a non-contrast computerized tomography (CT) of the abdominal aorta. RESULTS: FGF-23 levels were higher among haemodialysis patients (4681.3 +/- 3906.1 pg/mL) compared to controls (98.2 +/- 51.9 pg/mL), P = 0.005. ACI was higher in haemodialysis patients (14.1 +/- 12) than controls (3.2 +/- 3.6), P = 0.009. FGF-23 (P < 0.0001) and systolic blood pressure (BP) (P < 0.0001) were independently related to ACI in stepwise multiple regression analysis of pooled analysis of haemodialysis patients, R(2) = 0.476; in subgroup analysis, the independent factors relating to ACI among prevalent dialysis patients were systolic BP (P < 0.0001), FGF-23 (P = 0.002) and age (P = 0.012), R(2)=0.48; whereas in incident patients, only FGF-23 was associated with ACI (P = 0.007), R(2) = 0.37. CONCLUSIONS: In haemodialysis patients, FGF-23 and ACI were significantly increased, and FGF-23 was independently associated with aortic calcification.